1,4,2-oxathiazoles, analogs thereof, and methods of making and using thereof

Abstract

Provided herein are 1,4,2-oxathiazoles, oxidized analogs thereof, as well as methods of making these compounds. The compounds can exhibit antifungal activity, insecticidal activity, and / or herbicidal activity. Accordingly, also provided are compositions comprising the 1,4,2-oxathiazoles and analogs thereof described herein as well as methods of using these compounds and compositions as pesticides (i.e., herbicides, insecticides, fungicides, or a combination thereof).

Description

[0001] Attorney Docket No. 10620-164W01

[0002] NCSU Ref.: 2025-138-03

[0003] 1,4,2-Oxathiazoles, Analogs thereof, and Methods of Making and Using Thereof

[0004] STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0005] This invention was made with government support under GM139583 awarded by the National Institutes of Health, and 1454845 awarded by the National Science Foundation. The government has certain rights in the invention.

[0006] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims benefit of priority of U. S. Provisional Application No.

[0007] 63 / 778,322, filed March 26, 2025, and U. S. Provisional Application No. 63 / 891,146, filed September 30, 2025, each of which is hereby incorporated by reference herein in its entirety.

[0008] BACKGROUND

[0009] Heterocycles are ubiquitous in agrochemical and therapeutic agents, and they are found in more than 90% of the current drugs being developed, with N, O, and 5 being the three most common heteroatoms present within. Five-membered / V- and O- containing heterocycles represent a significant population of recently FDA approved pharmaceuticals and crop protections agents, with thiazoles and isoxazoles each being among the top 25 most frequent N-containing heterocycles in U. S. FDA approved agents. Additionally, heterocyclic five-membered rings displaying denser population of heteroatoms (2+) such as 1,3,4- and 1,2,4-oxadiazoles have been commonly used to improve the pharmacokinetics and dynamics of the native compounds.

[0010] The 2-isoxazoline class of five-membered heterocycles exists as the core scaffold for numerous marketed fungicides and insecticides focused on crop protections and in veterinary medicine. By a similar fashion, 1,2,4-oxadiazoles have been widely used as nematocidal agents for crop protection. Fungicidal agents such as oxathiapiprolin, approved in 2015 by US EP A, fluoxapiprolin, approved in 2018 and pyrisoxazole, approved in the EU in 2019 have been widely used for crop protection. Other 2-isoxazoles have several applications, such as insecticides and insecticidal agents for veterinary use Additionally, other 1,2,4-oxadiazoles such as tioxazaphen has been used as nematicidal agents.Attorney Docket No. 10620-164W01

[0011] NCSU Ref.: 2025-138-03

[0012] Deep-seated modifications of these scaffolds could lead to newer molecular entities with broader antimicrobial spectrum, improved pharmacokinetic properties, or bioactivity enhancement. However, new methods to access heteroatom rings and bio-isosteres with single atom modifications to known, underrepresented heterocycles are scarce, yet would provide new avenues of exploration about SAR by providing new classes of chemical probes.

[0013] SUMMARY

[0014] 1,4,2-Oxathiazoles are a highly underreported class of N, O, S- containing heterocycles. When disregarding the 5- heteroatom within this motif, this scaffold represents an alternative to the heavily prevalent N- and O- containing five-membered heterocycles. Regarding crop protecting agents, the 3,5-biaryl substituted 2-isoxazolines exist as the core scaffold for numerous marketed fungicides, nematicides (e.g. fluxametamide, thioxazafen, etc.) and insecticides. To that end, a method to access similar molecules containing sulfur would represent a potentially valuable deep-seated modification to the core of numerous bioactive molecules.

[0015] Accordingly, described herein are methods for preparing 1,4,2-oxathiazoles and oxidized analogs thereof. These methods can comprise contacting a thiohydroximic acid defined by Formula II below

[0016]

[0017] Formula II

[0018] or a salt or ester thereof, wherein R1is chosen from alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, hetercycloalkyl, alkylcycloalkyl, alkylhetercycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxycarbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, and heterodialkylaminocarbonyl, each optionally substituted with one or more substituents individually chosen from RA; R2is chosen from alkenyl, alkynyl, cycloalkyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxycarbonyl, thioalkylcarbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, thioamido, aryl, and heteroaryl, each optionally substituted with one or more substituents individually chosen from RA; R3is chosen from hydrogen, alkyl, and haloalkyl, wherein the alkyl and haloalkyl groups are optionally substituted with one or more substituents individually chosen from RA; and RAis chosen from hydroxy, halogen, -CN, -NO2, amino, alkylamino, dialkylamino, alkyl,Attorney Docket No. 10620-164W01

[0019] NCSU Ref.: 2025-138-03

[0020] haloalkyl; alkylthio; haloalkylthio; alkoxy, haloalkoxy, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, nitrone, sulfonic acid, sulfonamido, thiol, phosphonate, phosphinyl, aldehyde, trimethylsilyl, hydrazino, azido, isocyanate, aryl, and heteroaryl; with a heterogeneous catalyst under conditions effective to form a 1,4,2-oxathiazole or an analog thereof defined by Formula I below

[0021]

[0022] Formula I

[0023] or a salt or ester thereof, wherein R1is chosen from alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, hetercycloalkyl, alkylcycloalkyl, alkylhetercycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxycarbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, and heterodialkylaminocarbonyl, each optionally substituted with one or more substituents individually chosen from RA; R2is chosen from alkenyl, alkynyl, cycloalkyl, alkylcarbonyl, haloalkylcarbonyl, alkoxycarbonyl, haloalkoxycarbonyl, thioalkylcarbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, thioamido, aryl, and heteroaryl, each optionally substituted with one or more substituents individually chosen from RA; R3is chosen from hydrogen, alkyl, and haloalkyl, wherein the alkyl and haloalkyl groups are optionally substituted with one or more substituents individually chosen from RA; and RAis chosen from hydroxy, halogen, -CN, -NO2, amino, alkylamino, dialkylamino, alkyl, haloalkyl; alkylthio; haloalkylthio; alkoxy, haloalkoxy, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, nitrone, sulfonic acid, sulfonamido, thiol, phosphonate, phosphinyl, aldehyde, trimethylsilyl, hydrazino, azido, isocyanate, aryl, and heteroaryl; and optionally oxidizing the 1,4,2-oxathiazole defined by Formula I to generate a sulfoxide or sulfone analog of the 1,4,2-oxathiazoles defined by Formula I.

[0024] Also provided herein are 1,4,2-oxathiazoles and analogs thereof defined by Formula I belowAttorney Docket No. 10620-164W01

[0025] NCSU Ref.: 2025-138-03

[0026]

[0027] Formula I

[0028] or a salt or ester thereof, wherein Y is chosen from S, S=O, and S(=O)2; R1is chosen from alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, hetercycloalkyl, alkylcycloalkyl, alkylhetercycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, and heterodialkylaminocarbonyl, each optionally substituted with one or more substituents individually chosen from RA; R2is chosen from alkenyl, alkynyl, cycloalkyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxycarbonyl, thioalkylcarbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, thioamido, aryl, and heteroaryl, each optionally substituted with one or more substituents individually chosen from RA; R3is chosen from hydrogen, alkyl, and haloalkyl, wherein the alkyl and haloalkyl groups are optionally substituted with one or more substituents individually chosen from RA; and RAis chosen from hydroxy, halogen, -CN, -NO2, amino, alkylamino, dialkylamino, alkyl, haloalkyl; alkylthio; haloalkylthio; alkoxy, haloalkoxy, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, nitrone, sulfonic acid, sulfonamido, thiol, phosphonate, phosphinyl, aldehyde, trimethylsilyl, hydrazino, azido, isocyanate, aryl, and heteroaryl.

[0029] In certain embodiments, at least one of R1and R2is chosen from aryl and heteroaryl, each optionally substituted with one or more substituents individually chosen from RA.

[0030] In certain embodiments, when R2is unsubstituted phenyl, R1is not unsubstituted phenyl,

[0031] unsubstituted pyridyl, thiazolyl, or

[0032]

[0033] In certain embodiments, when R2is unsubstituted pyridyl, R1is not unsubstituted phenyl. Also described herein are compounds defined by Formula III belowAttorney Docket No. 10620-164W01

[0034] NCSU Ref.: 2025-138-03

[0035]

[0036] Formula III

[0037] wherein RAis chosen from hydroxy, halogen, -CN, -NO2, amino, alkylamino, dialkylamino, alkyl, haloalkyl; alkylthio; haloalkylthio; alkoxy, haloalkoxy, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, nitrone, sulfonic acid, sulfonamido, thiol, phosphonate, phosphinyl, aldehyde, trimethylsilyl, hydrazino, azido, isocyanate, aryl, and heteroaryl; n is 0, 1, 2, or 3; and m is 0, 1, or 2. For example, in some embodiments, the compound can comprise one of the following:

[0038]

[0039] Also described herein are agrichemical compositions comprising a 1,4,2-oxathiazoles or analog thereof described herein, as well as methods of using these compounds and compositions as fungicides, herbicides, and insecticides.

[0040] BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1. Illustration of various heterocycles of interest, including in FDA approved pharmaceuticals.Attorney Docket No. 10620-164W01

[0042] NCSU Ref.: 2025-138-03

[0043] Figure 2. Panel a) Reported synthetic procedure to access 1,4,2-oxathiazoles; Panel b) Synthetic approach previously reported; Panel c) New in-flow oxidative cyclization of thiohydroximic acids to access 1,4,2-oxathiazoles.

[0044] Figure 3. Reaction setup and MnCh column preparation.

[0045] Figure 4. Percentages of detected 12b formation and 12a recovery during a column efficiency assay, using a 7.0 g MnCh column, and a 14 mM, 3.34 mg / mL dichloromethane solution of 12a.

[0046] Figure 5. Synthesis of 1,4,2-oxathiazoles via flow. All reactions were performed using a 14 mM dichloromethane solution of the thiohydroximic acids 12a-37a, and pumped through the 7.0 g MnCh column at a fixed rate of 45 mL / h. Isolated yields reported.

[0047] Figure 6. Inaccessible 1,4,2-oxathiazole scaffolds using the MnCh-mediated cyclization.

[0048] Figure 7. Schematic illustration of the in-flow synthesis of 1,4,2-oxathiazoles.

[0049] Figure 8. Summary of the antifungal and herbicidal activity of example 1,4,2-oxathiazoles.

[0050] Figure 9. Summary of the insecticidal activity of example 1,4,2-oxathiazoles.

[0051] Figure 10. Example synthetic strategy for the preparation of a 1,4,2-oxathiazole analog of fluoxapiprolin.

[0052] Figure 11. Example synthetic strategy for the preparation of a 1,4,2-oxathiazole analog of oxathiapiprolin.

[0053] Figure 12. Illustration of the anti-oomycete activity of three example 1,4,2-oxathiazole analogs (AV-1241, AV-1242, and AV-1243).

[0054] Figure 13. Illustration of the anti-oomycete activity of three example 1,4,2-oxathiazole analogs (AV-1253, AV-1254, and AV-1255).

[0055] Figure 14. Illustration of the anti-oomycete activity of three example 1,4,2-oxathiazole analogs (AV-1324, AV-1349, and AV-1350).

[0056] Figure 15. Illustration of the anti-oomycete activity of three example 1,4,2-oxathiazole analogs (AV-1351, AV-1352, and AV-1353).

[0057] DETAILED DESCRIPTION

[0058] Definitions

[0059] Terms used herein will have their customary meaning in the art unless specified otherwise. The organic moieties mentioned when defining variable positions within the general formulae described herein (e.g., the term “halogen”) are collective terms for the individualAttorney Docket No. 10620-164W01

[0060] NCSU Ref.: 2025-138-03

[0061] substituents encompassed by the organic moiety. The prefix Cn-Cmindicates in each case the possible number of carbon atoms in the group.

[0062] The term “alkyl,” as used herein, refers to saturated straight, branched, cyclic, primary, secondary or tertiary hydrocarbons, including those having 1 to 20 atoms. In some embodiments, alkyl groups will include C1-C12, C1-C10, Ci-Cs, Ci-C6, C1-C5, C1-C4, C1-C3, C1-C2, or Ci alkyl groups. Examples of C1-C10 alkyl groups include, but are not limited to, methyl, ethyl, propyl, 1-methylethyl, butyl, 1 -methylpropyl, 2-methylpropyl, 1,1 -dimethylethyl, pentyl, 1 -methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1 -ethylpropyl, hexyl, 1,1 -dimethylpropyl, 1,2-dimethylpropyl, 1 -methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1 -ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1 -methylpropyl, l-ethyl-2 -methylpropyl, heptyl, octyl, 2-ethylhexyl, nonyl and decyl groups, as well as their isomers. Examples of Ci-C4-alkyl groups include, for example, methyl, ethyl, propyl, 1 -methylethyl, butyl, 1 -methylpropyl, 2-methylpropyl and 1,1 -dimethylethyl groups.

[0063] Cyclic alkyl groups or “cycloalkyl” groups, which are encompassed alkyl, include cycloalkyl groups having from 3 to 10 carbon atoms. Cycloalkyl groups can include a single ring, or multiple condensed rings. In some embodiments, cycloalkyl groups include C3-C4, C4-C7, C5-C7, C4-C6, or Cs-Ce cyclic alkyl groups. Non-limiting examples of cycloalkyl groups include adamantyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like.

[0064] Alkyl groups can be unsubstituted or substituted with one or more moieties selected from the group consisting of alkyl, halo, haloalkyl, hydroxyl, carboxyl, acyl, acyloxy, amino, alkyl- or dialkylamino, amido, arylamino, alkoxy, aryloxy, nitro, cyano, azido, thiol, imino, sulfonic acid, sulfate, sulfonyl, sulfanyl, sulfinyl, sulfamonyl, ester, phosphonyl, phosphinyl, phosphoryl, phosphine, thioester, thioether, acid halide, anhydride, oxime, hydrazine, carbamate, phosphoric acid, phosphate, phosphonate, or any other viable functional group that does not inhibit the biological activity of the compounds of the invention, either unprotected, or protected as necessary, as known to those skilled in the art, for example, as described in Greene, et al., Protective Groups in Organic Synthesis, John Wiley and Sons, Third Edition, 1999, hereby incorporated by reference.

[0065] Terms including the term “alkyl,” such as “alkylcycloalkyl,” “cycloalkylalkyl,” “alkylamino,” or “dialkylamino,” will be understood to comprise an alkyl group as defined above linked to another functional group, where the group is linked to the compound through the last group listed, as understood by those of skill in the art.Attorney Docket No. 10620-164W01

[0066] NCSU Ref.: 2025-138-03

[0067] The term “alkenyl,” as used herein, refers to both straight and branched carbon chains which have at least one carbon-carbon double bond. In some embodiments, alkenyl groups can include C2-C20 alkenyl groups. In other embodiments, alkenyl can include C2-C12, C2-C10, C2-C8, C2-C6 or C2-C4 alkenyl groups. In one embodiment of alkenyl, the number of double bonds is 1 -3, in another embodiment of alkenyl, the number of double bonds is one or two. Other ranges of carbon-carbon double bonds and carbon numbers are also contemplated depending on the location of the alkenyl moiety on the molecule. “C2-Cio-alkenyl” groups may include more than one double bond in the chain. The one or more unsaturations within the alkenyl group may be located at any position(s) within the carbon chain as valence permits. In some embodiments, when the alkenyl group is covalently bound to one or more additional moieties, the carbon atom(s) in the alkenyl group that are covalently bound to the one or more additional moieties are not part of a carbon-carbon double bond within the alkenyl group. Examples of alkenyl groups include, but are not limited to, ethenyl, 1 -propenyl, 2-propenyl, 1 -methyl-ethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1 -methyl- 1 -propenyl, 2-methyl-l -propenyl, 1 -methyl-2-propenyl, 2-methyl- 2-propenyl; 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1 -methyl- 1-butenyl, 2-methyl-l-butenyl, 3-methyl- 1-butenyl, l-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, l,l-dimethyl-2-propenyl, 1,2-dimethyl-1 -propenyl, 1,2-dimethyl-2-propenyl, 1 -ethyl- 1 -propenyl, l-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1 -methyl- 1-pentenyl, 2-methyl-l -pentenyl, 3-methyl-l -pentenyl, 4-methyl-l -pentenyl, l-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2 -pentenyl, 1-methy 1-3 -pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3 -pentenyl, l-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, l,l-dimethyl-2-butenyl, l,l-dimethyl-3-butenyl, 1,2-dimethyl- 1-butenyl, 1.2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl- 1 -butenyl, 1,3-dimethyl-2-butenyl, 1.3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl- 1-butenyl, 2,3-dimethyl-2-butenyl, 2.3-dimethyl-3-butenyl, 3,3-dimethyl-l-butenyl, 3,3-dimethyl-2-butenyl, 1 -ethyl- 1-butenyl, 1-ethyl-2-butenyl, l-ethyl-3 -butenyl, 2-ethyl- 1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, l,l,2-trimethyl-2-propenyl, 1 -ethyl- 1-methy 1-2-propenyl, l-ethyl-2 -methyl- 1 -propenyl and 1-ethyl-2-methyl-2-propenyl groups.

[0068] The term “alkynyl,” as used herein, refers to both straight and branched carbon chains which have at least one carbon-carbon triple bond. In one embodiment of alkynyl, the number of triple bonds is 1-3; in another embodiment of alkynyl, the number of triple bonds is one or two. In some embodiments, alkynyl groups include from C2-C20 alkynyl groups. In other embodiments, alkynyl groups may include C2-C12, C2-C10, C2-C8, C2-C6 or C2-C4 alkynyl groups.Attorney Docket No. 10620-164W01

[0069] NCSU Ref.: 2025-138-03

[0070] Other ranges of carbon-carbon triple bonds and carbon numbers are also contemplated depending on the location of the alkenyl moiety on the molecule. For example, the term ”C2-Cio-alkynyl” as used herein refers to a straight-chain or branched unsaturated hydrocarbon group having 2 to 10 carbon atoms and containing at least one triple bond, such as ethynyl, prop-l-yn-l-yl, prop-2 -yn-1-yl, n-but-l-yn-l-yl, n-but-l-yn-3-yl, n-but-l-yn-4-yl, n-but-2-yn-l-yl, n-pent-l-yn-l-yl, n-pent-l-yn-3-yl, n-pent-l-yn-4-yl, n-pent-l-yn-5-yl, n-pent-2-yn-l-yl, n-pent-2-yn-4-yl, n-pent-2-yn-5-yl, 3-methylbut-l-yn-3-yl, 3-methylbut-l-yn-4-yl, n-hex-l-yn-l-yl, n-hex-l-yn-3-yl, n-hex-l-yn-4-yl, n-hex-l-yn-5-yl, n-hex-l-yn-6-yl, n-hex-2-yn-l-yl, n-hex-2-yn-4-yl, n-hex-2-yn-5-yl, n-hex-2-yn-6-yl, n-hex-3-yn-l-yl, n-hex-3-yn-2-yl, 3-methylpent-l-yn-l-yl, 3-methylpent-l-yn-3-yl, 3 -methylpent- l-yn-4-yl, 3 -methylpent- l-yn-5-yl, 4-methylpent-l-yn-l-yl, 4-methylpent-2-yn-4-yl, and 4-methylpent-2-yn-5-yl groups.

[0071] The term “haloalkyl,” as used herein refers to an alkyl group, as defined above, which is substituted by one or more halogen atoms. In some instances, the haloalkyl group can be an alkyl group substituted by one or more fluorine atoms. In certain instances, the haloalkyl group can be a perfluorinated alkyl group. For example, Ci-C4-haloalkyl includes, but is not limited to, chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, di chlorofluoromethyl, chlorodifluoromethyl, 1 -chloroethyl, 1 -bromoethyl, 1 -fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, and pentafluoroethyl.

[0072] The term “haloalkenyl,” as used herein, refers to an alkenyl group, as defined above, which is substituted by one or more halogen atoms.

[0073] The term “haloalkynyl,” as used herein, refers to an alkynyl group, as defined above, which is substituted by one or more halogen atoms.

[0074] The term “alkoxy,” as used herein, refers to alkyl-O-, wherein alkyl refers to an alkyl group, as defined above. Similarly, the terms “alkenyloxy,” “alkynyloxy,” “haloalkoxy,” “haloalkenyloxy,” “haloalkynyloxy,” “cycloalkoxy,” “cycloalkenyloxy,” “halocycloalkoxy,” and “halocycloalkenyloxy” refer to the groups alkenyl-O-, alkynyl-O-, haloalkyl-O-, haloalkenyl-O-, haloalkynyl-O-, cycloalkyl-O-, cycloalkenyl-O-, halocycloalkyl-O-, and halocycloalkenyl-O-, respectively, wherein alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, cycloalkenyl, halocycloalkyl, and halocycloalkenyl are as defined above. Examples of Ci-Ce-alkoxy include, but are not limited to, methoxy, ethoxy, C2H5-CH2O-, (CHsECHO-. n-butoxy, C2HS-CH(CH3)O-, (CFh CH-CFEO-, (CFh^CO-, n-pentoxy, 1 -methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1,1 -dimethylpropoxy, 1,2-dimethylpropoxy, 2,2-dimethyl-propoxy, 1-Attorney Docket No. 10620-164W01

[0075] NCSU Ref.: 2025-138-03

[0076] ethylpropoxy, n-hexoxy, 1 -methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methylpentoxy, 1,1 -dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1 -ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1 -ethyl- 1 -methylpropoxy, and l-ethyl-2-methylpropoxy.

[0077] The term “alkylthio,” as used herein, refers to alkyl-S-, wherein alkyl refers to an alkyl group, as defined above. Similarly, the terms “haloalkylthio,” “cycloalkylthio,” and the like, refer to haloalkyl-S- and cycloalkyl-S- where haloalkyl and cycloalkyl are as defined above.

[0078] The term “alkylsulfinyl,” as used herein, refers to alkyl-S(O)-, wherein alkyl refers to an alkyl group, as defined above. Similarly, the term “haloalkylsulfinyl” refers to haloalkyl-S(O)-where haloalkyl is as defined above.

[0079] The term “alkylsulfonyl,” as used herein, refers to alkyl-S(O)2-, wherein alkyl is as defined above. Similarly, the term “haloalkylsulfonyl” refers to haloalkyl-S(O)2- where haloalkyl is as defined above.

[0080] The terms “alkylamino” and “dialkylamino,” as used herein, refer to alkyl-NH- and (alkyl)2N- groups, where alkyl is as defined above. Similarly, the terms “haloalkylamino” and “halodialkylamino” refer to haloalkyl-NH- and (haloalkyl)2-NH-, where haloalkyl is as defined above.

[0081] The terms “alkylcarbonyl,” “alkoxycarbonyl,” “alkylaminocarbonyl,” and “dialkylaminocarbonyl,” as used herein, refer to alkyl-C(O)-, alkoxy-C(O)-, alkylamino-C(O)-and dialkylamino-C(O)- respectively, where alkyl, alkoxy, alkylamino, and dialkylamino are as defined above. Similarly, the terms “haloalkylcarbonyl,” “haloalkoxy carbonyl,” “haloalkylaminocarbonyl,” and “dihaloalkylaminocarbonyl,” as used herein, refer to the groups haloalkyl-C(O)-, haloalkoxy-C(O)-, haloalkylamino-C(O)-, and dihaloalkylamino-C(O)-, where haloalkyl, haloalkoxy, haloalkylamino, and dihaloalkylamino are as defined above.

[0082] The term “aryl,” as used herein, refers to a monovalent aromatic carbocyclic group of from 6 to 14 carbon atoms. Aryl groups can include a single ring or multiple condensed rings. In some embodiments, aryl groups include Ce-Cio aryl groups. Aryl groups include, but are not limited to, phenyl, biphenyl, naphthyl, tetrahydronaphtyl, phenylcyclopropyl and indanyl. Aryl groups may be unsubstituted or substituted by one or more moieties selected from halogen, cyano, nitro, hydroxy, mercapto, amino, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, halocycloalkenyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, haloalkenyloxy, haloalkynyloxy, cycloalkoxy, cycloalkenyloxy, halocycloalkoxy, halocycloalkenyloxy, alkylthio, haloalkylthio, cycloalkylthio,Attorney Docket No. 10620-164W01

[0083] NCSU Ref.: 2025-138-03

[0084] halocycloalkylthio, alkylsulfinyl, alkenylsulfinyl, alkynyl-sulfinyl, haloalkylsulfinyl, haloalkenylsulfinyl, haloalkynylsulfinyl, alkylsulfonyl, alkenylsulfonyl, alkynylsulfonyl, haloalkyl-sulfonyl, haloalkenylsulfonyl, haloalkynylsulfonyl, alkylamino, alkenylamino, alkynylamino, di(alkyl)amino, di(alkenyl)-amino, di(alkynyl)amino, or trialkylsilyl.

[0085] The term “alkylaryl,” as used herein, refers to an aryl group that is bonded to a parent compound through a diradical alkylene bridge, (-CH2-)n, where n is 1-12 and where “aryl” is as defined above.

[0086] The term “alkylcycloalkyl,” as used herein, refers to a cycloalkyl group that is bonded to a parent compound through a diradical alkylene bridge, (-CH2-)n, where n is 1-12 and where “cycloalkyl” is as defined above. The term “cycloalkylalkyl,” as used herein, refers to a cycloalkyl group, as defined above, which is substituted by an alkyl group, as defined above.

[0087] The term “heteroalkyl,” as used herein, refers to an alkyl group, as described above, which includes one or more heteroatoms (e.g., from one to four heteroatoms) within the carbon backbone. In some cases, the heteroatom(s) incorporated into the carbon backbone are oxygen, nitrogen, sulfur, or combinations thereof. The terms “heteroalkenyl” and “heteroalkynyl,” as used herein, likewise refer to alkenyl and alkynyl groups respectively which include one or more heteroatoms (e.g., from one to four heteroatoms, such as oxygen, nitrogen, sulfur, or combinations thereof) within their carbon backbone.

[0088] The term “heteroaryl,” as used herein, refers to a monovalent aromatic group of from 1 to 15 carbon atoms (e.g., from 1 to 10 carbon atoms, from 2 to 8 carbon atoms, from 3 to 6 carbon atoms, or from 4 to 6 carbon atoms) having one or more heteroatoms within the ring. The heteroaryl group can include from 1 to 4 heteroatoms, from 1 to 3 heteroatoms, or from 1 to 2 heteroatoms. In some cases, the heteroatom(s) incorporated into the ring are oxygen, nitrogen, sulfur, or combinations thereof. When present, the nitrogen and sulfur heteroatoms may optionally be oxidized. Heteroaryl groups can have a single ring (e.g., pyridyl or furyl) or multiple condensed rings provided that the point of attachment is through a heteroaryl ring atom. Preferred heteroaryls include pyridyl, piridazinyl, pyrimidinyl, pyrazinyl, triazinyl, pyrrolyl, indolyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinnyl, furanyl, thiophenyl, furyl, pyrrolyl, imidazolyl, oxazolyl, isoxazolyl, isothiazolyl, pyrazolyl benzofuranyl, and benzothiophenyl. Heteroaryl rings may be unsubstituted or substituted by one or more moieties as described for aryl above.

[0089] The term “alkylheteroaryl,” as used herein, refers to a heteroaryl group that is bonded to a parent compound through a diradical alkylene bridge, (-CH2-)n, where n is 1-12 and where “heteroaryl” is as defined above.Attorney Docket No. 10620-164W01

[0090] NCSU Ref.: 2025-138-03

[0091] The terms “cycloheteroalkyl,” “heterocyclyl,” “heterocyclic,” and “heterocyclo” are used herein interchangeably, and refer to fully saturated or unsaturated, cyclic groups, for example, 3 to 7 membered monocyclic or 4 to 7 membered monocyclic; 7 to 11 membered bicyclic, or 10 to 15 membered tricyclic ring systems, having one or more heteroatoms within the ring. The heterocyclyl group can include from 1 to 4 heteroatoms, from 1 to 3 heteroatoms, or from 1 to 2 heteroatoms. In some cases, the heteroatom(s) incorporated into the ring are oxygen, nitrogen, sulfur, or combinations thereof. When present, the nitrogen and sulfur heteroatoms may optionally be oxidized, and the nitrogen heteroatoms may optionally be quatemized. The heterocyclyl group may be attached at any heteroatom or carbon atom of the ring or ring system and may be unsubstituted or substituted by one or more moieties as described for aryl groups above.

[0092] Exemplary monocyclic heterocyclic groups include, but are not limited to, pyrrolidinyl, pyrrolyl, pyrazolyl, oxetanyl, pyrazolinyl, imidazolyl, imidazolinyl, imidazolidinyl, oxazolyl, oxazolidinyl, isoxazolinyl, isoxazolyl, thiazolyl, thiadiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, furyl, tetrahydrofuryl, thienyl, oxadiazolyl, piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolodinyl, 2-oxoazepinyl, azepinyl, 4-piperidonyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, tetrahydropyranyl, morpholinyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, 1,3-di oxolane and tetrahydro- 1,1-dioxothienyl, triazolyl, triazinyl, and the like.

[0093] Exemplary bicyclic heterocyclic groups include, but are not limited to, indolyl, benzothiazolyl, benzoxazolyl, benzodioxolyl, benzothienyl, quinuclidinyl, quinolinyl, tetra-hydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, indolizinyl, benzofuryl, chromonyl, coumarinyl, benzopyranyl, cinnolinyl, quinoxalinyl, indazolyl, pyrrolopyridyl, furopyridinyl (such as furo[2,3-c]pyridinyl, furo[3,2-b]pyridinyl]or furo[2,3-b]pyridinyl), dihydroisoindolyl, dihydroquinazolinyl (such as 3,4-dihydro-4-oxo-quinazolinyl), tetrahydroquinolinyl and the like.

[0094] Exemplary tricyclic heterocyclic groups include carbazolyl, benzidolyl, phenanthrolinyl, acridinyl, phenanthridinyl, xanthenyl, and the like.

[0095] The term “alkylheterocyclyl” and “alkylcycloheteroalkyl” are used herein interchangeably, and refer to a heterocyclyl group that is bonded to a parent compound through a diradical alkylene bridge, (-CH2-)n, where n is 1-12 and where “heterocyclyl” is as defined above. The term “heterocyclylalkyl,” as used herein, refers to a heterocyclyl group, as defined above, which is substituted by an alkyl group, as defined above.Attorney Docket No. 10620-164W01

[0096] NCSU Ref.: 2025-138-03

[0097] The term “halogen,” as used herein, refers to the atoms fluorine, chlorine, bromine and iodine. The prefix halo- (e.g., as illustrated by the term haloalkyl) refers to all degrees of halogen substitution, from a single substitution to a perhalo substitution (e.g., as illustrated with methyl as chloromethyl (-CH2CI), dichloromethyl (-CHCh), trichloromethyl (-CCI3)).

[0098] As used herein, the term “substituted” is contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, and aromatic and nonaromatic substituents of organic compounds. Illustrative substituents include, for example, those described below. The permissible substituents can be one or more and the same or different for appropriate organic compounds. For purposes of this disclosure, the heteroatoms, such as nitrogen, can have hydrogen substituents and / or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms. This disclosure is not intended to be limited in any manner by the permissible substituents of organic compounds. Also, the terms “substitution” or “substituted with” include the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, e.g, a compound that does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc.

[0099] As used herein, herbicide and herbicidal active ingredient mean a compound that controls undesirable vegetation when applied in an appropriate amount.

[0100] As used herein, control of or controlling undesirable vegetation means killing or preventing the vegetation, or causing some other adversely modifying effect to the vegetation e.g., deviations from natural growth or development, regulation, desiccation, retardation, and the like.

[0101] As used herein, a herbicidally effective or vegetation controlling amount is an amount of herbicidal active ingredient the application of which controls the relevant undesirable vegetation.

[0102] As used herein, applying a herbicide or herbicidal composition means delivering it directly to the targeted vegetation or to the locus thereof or to the area where control of undesired vegetation is desired. Methods of application include, but are not limited to pre-emergently contacting soil or water, post-emergently contacting the undesirable vegetation or area adjacent to the undesirable vegetation.

[0103] As used herein, plants and vegetation include, but are not limited to, dormant seeds, germinant seeds, emerging seedlings, plants emerging from vegetative propagules, immature vegetation, and established vegetation.Attorney Docket No. 10620-164W01

[0104] NCSU Ref.: 2025-138-03

[0105] As used herein, agriculturally acceptable salts and esters refer to salts and esters that exhibit herbicidal activity, or that are or can be converted in plants, water, or soil to the referenced herbicide. Exemplary agriculturally acceptable esters are those that are or can by hydrolyzed, oxidized, metabolized, or otherwise converted, e.g., in plants, water, or soil, to the corresponding carboxylic acid which, depending on the pH, may be in the dissociated or undissociated form.

[0106] Suitable salts include those derived from alkali or alkaline earth metals and those derived from ammonia and amines. Preferred cations include sodium, potassium, magnesium, and aminium cations of the formula:

[0107] R13R14R15R16N+

[0108] wherein R13, R14, R15and R16each, independently represents hydrogen or C1-C12 alkyl, C3-C12 alkenyl or C3-C12 alkynyl, each of which is optionally substituted by one or more hydroxy, C1-C4 alkoxy, C1-C4 alkylthio or phenyl groups, provided that R13, R14, R15and R16are sterically compatible. Additionally, any two R13, R14, R15and R16together may represent an aliphatic difunctional moiety containing one to twelve carbon atoms and up to two oxygen or sulfur atoms. Salts of the compounds of Formula I can be prepared by treatment of compounds of Formula I with a metal hydroxide, such as sodium hydroxide, with an amine, such as ammonia, trimethylamine, diethanolamine, 2-methylthiopropylamine, bisallylamine, 2-butoxyethylamine, morpholine, cyclododecylamine, or benzylamine or with a tetraalkylammonium hydroxide, such as tetramethylammonium hydroxide or choline hydroxide. Amine salts are often preferred forms of the compounds of Formula I because they are water-soluble and lend themselves to the preparation of desirable aqueous based herbicidal compositions.

[0109] Compounds of the Formula I can include N-oxides. Pyridine N-oxides can be obtained by oxidation of the corresponding pyridines. Suitable oxidation methods are described, for example, in Houben-Weyl, Methoden der orgcmischen Chemie [Methods in organic chemistry], expanded and subsequent volumes to the 4th edition, volume E 7b, p. 565 f.

[0110] Compounds

[0111] Provided herein are 1,4,2-oxathiazoles that can exhibit activity as antifungal agents, herbicidal agents, and / or insecticidal agents.

[0112] For example, provided herein are 1,4,2-oxathiazoles and analogs thereof defined by Formula I belowAttorney Docket No. 10620-164W01

[0113] NCSU Ref.: 2025-138-03

[0114]

[0115] Formula I

[0116] or a salt or ester thereof, wherein Y is chosen from S, S=O, and S(=O)2; R1is chosen from alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, hetercycloalkyl, alkylcycloalkyl, alkylhetercycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, and heterodialkylaminocarbonyl, each optionally substituted with one or more substituents individually chosen from RA; R2is chosen from alkenyl, alkynyl, cycloalkyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxycarbonyl, thioalkylcarbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, thioamido, aryl, and heteroaryl, each optionally substituted with one or more substituents individually chosen from RA; R3is chosen from hydrogen, alkyl, and haloalkyl, wherein the alkyl and haloalkyl groups are optionally substituted with one or more substituents individually chosen from RA; and RAis chosen from hydroxy, halogen, -CN, -NO2, amino, alkylamino, dialkylamino, alkyl, haloalkyl; alkylthio; haloalkylthio; alkoxy, haloalkoxy, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, nitrone, sulfonic acid, sulfonamido, thiol, phosphonate, phosphinyl, aldehyde, trimethylsilyl, hydrazino, azido, isocyanate, aryl, and heteroaryl.

[0117] In some embodiments, at least one of R1and R2is chosen from aryl and heteroaryl, each optionally substituted with one or more substituents individually chosen from RA.

[0118] In some embodiments, when R2is unsubstituted phenyl, R1is not unsubstituted phenyl, o

[0119] unsubstituted pyridyl, thiazolyl, or

[0120]

[0121] <- In some embodiments, when R2is unsubstituted pyridyl, R1is not unsubstituted phenyl. In some embodiments, Y is S.

[0122] In some embodiments, R1is chosen from aryl and heteroaryl, each optionally substituted with one or more substituents individually chosen from RA. In certain embodiments, R1isAttorney Docket No. 10620-164W01

[0123] NCSU Ref.: 2025-138-03

[0124] phenyl, optionally substituted with one or more substituents individually chosen from RA. In other embodiments, R1is pyridyl, optionally substituted with one or more substituents individually chosen from RA. In other embodiments, R1is thiophenyl, optionally substituted with one or more substituents individually chosen from RA.

[0125] In some embodiments, R2is chosen from aryl and heteroaryl, each optionally substituted with one or more substituents individually chosen from RA. In certain embodiments, R2is phenyl, optionally substituted with one or more substituents individually chosen from RA. In other embodiments, R2is pyridyl, optionally substituted with one or more substituents individually chosen from RA. In other embodiments, R2is thiophenyl, optionally substituted with one or more substituents individually chosen from RA. In other embodiments, R2is benzothiazole, optionally substituted with one or more substituents individually chosen from RA. In other embodiments, R2is pyrimidinyl, optionally substituted with one or more substituents individually chosen from RA. In other embodiments, R2is cyclopropyl, crotyl, allyl, propargyl, acyl, or thioacyl.

[0126] In some embodiments R1, R2, or a combination thereof is substituted with one or more substituents individually chosen from RA. In certain embodiments R1and R2are each substituted with one or more substituents individually chosen from RA.

[0127] In some embodiments, RAis chosen from halogen, -CN, -NO2, alkyl, haloalkyl, alkoxy, and haloalkoxy. In certain embodiments, RAis chosen from halogen and -CF3. In some embodiments, RAis aryl or heteroaryl (e.g., phenyl, naphthyl, pyridyl, furyl, thienyl, indolyl, imidazolyl).

[0128] In some embodiments, R3is hydrogen. In other embodiments, R3is trifluoromethyl. In other embodiments, R3is chosen from -C(R4)F2, -C(R4)HF, or C(R4)H2, where R4is chosen from hydrogen and RA.

[0129] In some embodiments, the compound can comprise one of the following:Attorney Docket No. 10620-164W01

[0130] NCSU Ref.: 2025-138-03

[0131] AV-2421

[0132]

[0133] Attorney Docket No. 10620-164W01

[0134] NCSU Ref.: 2025-138-03

[0135]

[0136] Attorney Docket No. 10620-164W01

[0137] NCSU Ref.: 2025-138-03

[0138]

[0139] Attorney Docket No. 10620-164W01

[0140] NCSU Ref.: 2025-138-03

[0141]

[0142] Attorney Docket No. 10620-164W01

[0143] NCSU Ref.: 2025-138-03

[0144] AV-2465 AV-2466 AV-2565 AV-2566

[0145] AV-2509

[0146] AV-2506

[0147]

[0148] Attorney Docket No. 10620-164W01

[0149] NCSU Ref.: 2025-138-03

[0150] AV-2508

[0151]

[0152] 1,4,2-Oxathiazole Analogs of Oxathiapiprolin and Fluoxapiprolin

[0153] In some examples, described herein are 1,4,2-oxathiazole analogs of oxathiapiprolin. Oxathiapiprolin and related compounds are described for example in International Publication No. W02009 / 094445, which is incorporated by reference in its entirety. Described herein are analogs of these compounds which include a 1,4,2-oxathiazole ring or an oxidized analog thereof.

[0154] For example, described herein are compounds defined by Formula III below

[0155]

[0156] Formula III

[0157] wherein RAis chosen from hydroxy, halogen, -CN, -NO2, amino, alkylamino, dialkylamino, alkyl, haloalkyl; alkylthio; haloalkylthio; alkoxy, haloalkoxy, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, nitrone, sulfonic acid, sulfonamido, thiol, phosphonate, phosphinyl, aldehyde, trimethylsilyl, hydrazino, azido,Attorney Docket No. 10620-164W01

[0158] NCSU Ref.: 2025-138-03

[0159] isocyanate, aryl, and heteroaryl; n is 0, 1, 2, or 3; and m is 0, 1, or 2. For example, in some embodiments, the compound can comprise one of the following:

[0160]

[0161] Also described herein are compounds defined by Formula V

[0162] A-q ^(A-G) / A,<A'J

[0163] / ^(A-X) ^(A-Z^

[0164] A-E-\>\JA-r

[0165]

[0166] (A-R2)n

[0167] Formula V

[0168] or an N-oxide or salt thereof, wherein

[0169] A-E is a radical selected from the group consisting of

[0170] (A-R1a)^ (A-R1b)\ ^A-A^x (A-R1c)\ x-A'A-e /

[0171] (A-Z5) Td(A-Z6) I (A-Z7)

[0172] A-W1A-W II (O)A-d A-E-1 A-E-2 A-E-3

[0173] 5 5, and

[0174] (A-R1d)^

[0175]

[0176] (A-Z"’ O A A-R.6

[0177] A-E-4

[0178] A-A is CH- A-R15, N-A-R16or C(=O);

[0179] A-G is an optionally substituted 5-membered heterocyclic ring;

[0180] A-J is a 5-membered ring, an 8- to 11-membered bicyclic ring system or a 7- to 11-membered spirocyclic ring system, each ring or ring system comprising a 1,4,2-oxathiazole ring or an oxidized analog thereof, and optionally further comprising additional ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N, and up to 3 ring members selected from C(=O), C(=S), S(=O)A-S(=N-A-Attorney Docket No. 10620-164W01

[0181] NCSU Ref.: 2025-138-03

[0182] R23)A-f and Si-A-R17-A-R18, and optionally substituted with up to 5 substituents independently selected from A-R5;

[0183] A-W1is O-A-R30, S-A-R31, N- A-R32- A-R33, or A-R28;

[0184] A-W is O or S;

[0185] A-X is a radical selected from

[0186]

[0187] wherein the bond of A-X1, A-X2, A-X3, A-X4, A-X5, A-X6, A-X7, A-X8, or A-X9which is identified with " A-t" is connected to the carbon atom identified with " A-q" of Formula V, the bond which is identified with " A-u" is connected to the carbon atom identified with " A-r" of Formula V, and the bond which is identified with " A-v" is connected to A-G of

[0188] Formula V;

[0189] A-Z1is a direct bond, O, C(=O), S(O)A-m, CH- A-R20, or N-A-R21;

[0190] A-Z5, A-Z6, A-Z7and A-Z8independently are a direct bond, C(=O) or S(O)2;

[0191] A-Rla, A-Rlb, A-Rlcand A-Rldindependently are an optionally substituted phenyl, an optionally substituted naphthalenyl or an optionally substituted 5- to 6-membered heteroaromatic ring; or cyano, Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 alkynyl, Ci-Cs haloalkyl, C2-C8 haloalkenyl, C2-C8 haloalkynyl, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C4-C10 alkylcycloalkyl, C4-C10 cycloalkylalkyl, C4-C10 halocycloalkylalkyl, C5-C10 alkylcycloalkylalkyl, C2-C8 alkoxyalkyl, C2-Cs haloalkoxyalkyl, C4-C10 cycloalkoxyalkyl, C3-C10 alkoxyalkoxyalkyl, C2-C8 alkylthioalkyl, C2-C8 haloalkylthioalkyl, C2-C8 alkylsulfinylalkyl, C2-C8 alkylsulfonylalkyl, C3-C8

[0192] alkoxy carbonylalkyl, C3-C8 haloalkoxy carbonylalkyl, C2-C8 alkylaminoalkyl, C3-C10 dialkylaminoalkyl, C2-C8 haloalkylaminoalkyl, C4-C10 cycloalkylaminoalkyl, Ci-Cs alkoxy, Ci-Cs haloalkoxy, C3-C8 cycloalkoxy, C3-C8 halocycloalkoxy, C4-C10 cycloalkylalkoxy, C2-C8 alkenyloxy, C2-C8 haloalkenyloxy, C2-C8 alkynyloxy, C3-C8 haloalkynyloxy, C2-C8Attorney Docket No. 10620-164W01

[0193] NCSU Ref.: 2025-138-03

[0194] alkoxyalkoxy, C2-C8 alkylcarbonyloxy, C2-C8 haloalkylcarbonyloxy, C1-C8 alkylthio, C1-C8 haloalkylthio, C3-C8 cycloalkylthio, C3-C10 trialkylsilyl, C1-C8 alkylamino, C2-C8 dialkylamino, C1-C8 haloalkylamino, C2-C8 halodialkylamino, C3-C8 cycloalkylamino, C2-C8 alkylcarbonylamino, C2-C8 haloalkylcarbonylamino, C1-C8 alkylsulfonylamino, C1-C8 haloalkylsulfonylamino, pyrrolidinyl, piperidinyl or morpholinyl;

[0195] each A-R2is independently halogen, cyano, hydroxy, C1-C4 alkyl, C1-C4 alkenyl, Ci-C4 haloalkyl or C1-C4 alkoxy; or

[0196] two A-R2groups are taken together as C1-C4 alkylene or C2-C4 alkenylene to form a bridged bicyclic or fused bicyclic ring system; or

[0197] two A-R2groups attached to adjacent ring carbon atoms joined by a double bond are taken together as -CH=CH-CH=CH- optionally substituted with up to 3 substituents independently selected from halogen, cyano, hydroxy, amino, nitro, C1-C4 alkyl, Ci-C4 haloalkyl, C1-C4 alkoxy and C1-C4 haloalkoxy;

[0198] A-R6is C1-C4 alkyl, C1-C4 haloalkyl, or C2-C4 alkoxyalkyl;

[0199] each A-R5is independently H, halogen, cyano, hydroxy, amino, nitro, -CHO, -C(=O)OH, -C(=O)NH2, -N-A-R25-A-R26, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Ci-C6haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C4-C10 alkylcycloalkyl, C4-C10 cycloalkylalkyl, C6-C14 cycloalkylcycloalkyl, C4-C10 halocycloalkylalkyl, C5-C10 alkylcycloalkylalkyl, C3-C8 cycloalkenyl, C3-C8 halocycloalkenyl, C2-C6 alkoxy alkyl, C4-C10 cycloalkoxyalkyl, C3-C8 alkoxyalkoxyalkyl, C2-C6 alkylthioalkyl, C2-C6 alkylsulfinylalkyl, C2-C6 alkylsulfonylalkyl, C2-C6 alkylaminoalkyl, C3-C8 dialkylaminoalkyl, C2-C6 haloalkylaminoalkyl, C4-C10 cycloalkylaminoalkyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C4-C8 cycloalkylcarbonyl, C2-C6 alkoxycarbonyl, C4-C8 cycloalkoxycarbonyl, C5-C10 cycloalkylalkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, C4-C8 cycloalkylaminocarbonyl, C2-C6 haloalkoxyalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C8 cycloalkoxy, C3-C8 halocycloalkoxy, C4-C10 cycloalkylalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy,

[0200] C2-C6 haloalkynyloxy, C2-C6 alkoxyalkoxy, C2-C6 alkylcarbonyloxy, C2-C6 haloalkylcarbonyloxy, C4-C8 cycloalkylcarbonyloxy, C3-C6 alkylcarbonylalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C3-C8 cycloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C3-C8 cycloalkylsulfonyl, C3-C10 trialkylsilyl, C1-C6 alkylsulfonylamino, C1-C6 haloalkylsulfonylamino, or -A-Z2-A-Q;

[0201] each A-Z2is independently a direct bond, -O, -C(=O), -S(O)A-m, -CH-A-R20or -N-A-R21;Attorney Docket No. 10620-164W01

[0202] NCSU Ref.: 2025-138-03

[0203] each A-Q is independently phenyl, benzyl, naphthalenyl, a 5- to 6-membered heteroaromatic ring or an 8- to 11 -membered heteroaromatic bicyclic ring system, each optionally substituted with up to 2 substituents independently selected from A-R7aon carbon atom or nitrogen atom ring members, and each optionally substituted with up to 5 substituents independently selected from A-R7on carbon atom ring members and A-R12on nitrogen atom ring members; or

[0204] a 3- to 7-membered nonaromatic carbocyclic ring, a 5-, 6- or 7-membered nonaromatic heterocyclic ring or an 8- to 11 -membered nonaromatic bicyclic ring system, each optionally including ring members selected from the group consisting of C(=O), C(=S), S(=O)A-S(=N-A-R23)A-f and Si-A-R17-A-R18, and each ring or ring system optionally substituted with up to 2 substituents independently selected from A-R7aon carbon atom or nitrogen atom ring members, and each optionally substituted with up to 5 substituents independently selected from A-R7on carbon atom ring members and A-R12on nitrogen atom ring members;

[0205] each A-R7ais independently -A-Z3-A-TA, -A-Z3-A-TNor -A-Z3-A-Tp;

[0206] each A-Z3is independently a direct bond, O, N-A-R22, C(=O), C(=S), S(O)A-m, CH-A-R20, -CH-A-R2O-CH-AR20-, -C-A-R24=C-A-R27-, -OCH-A-R20-, or -CH-A-R20O-;

[0207] each A-TAis independently phenyl, phenylethynyl, or a 5- to 6-membered heteroaromatic ring, each optionally substituted with up to 5 substituents independently selected from A-R29on carbon atom ring members, and each optionally substituted with up to 2 substituents independently selected from A-R22on nitrogen atom ring members;

[0208] each A-TNis independently a 3- to 7-membered nonaromatic ring including ring members selected from the group consisting of C(A-R29)2, O, S, N-A-R22, -C(A-R29)=CC(A-R29)-, -C(A-R29)=N-, -N=N-, C(=O), C(=S), -C=C-, C(=N-A-R23), S(=O)A-s(=N-A-R23)A-f and Si-A-R17-A-R18;

[0209] each A-Tpis independently an 8- to 10-membered aromatic or a 7- to 11 -membered nonaromatic bicyclic ring system, said ring system including ring members selected from the group consisting of C(A-R29)2, O, S, N-A-R22, -C(A-R29)=CC(A-R29)-, -C(A-R29)=N-, -N=N-, C(=O), C(=S), -C=C-, C(=N-A-R23), S(=O)A-s(=N-A-R23)A-f and Si-A-R17-A-R18;

[0210] each A-R7is independently halogen, cyano, hydroxy, amino, nitro, Ci-Ce alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C6 cycloalkyl, C4-C10 cycloalkylalkyl, C4-C10 alkylcycloalkyl, C5-C10 alkylcycloalkylalkyl, C6-C14 cycloalkylcycloalkyl, Ci-Ce haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C6 halocycloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 haloalkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylsulfinyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylamino, C2-C8 dialkylamino, C3-C6 cycloalkylamino, C2-C4Attorney Docket No. 10620-164W01

[0211] NCSU Ref.: 2025-138-03

[0212] alkoxyalkyl, C1-C4 hydroxyalkyl, C2-C4 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylcarbonyloxy, C2-C6 alkylcarbonylthio, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, or C3-C6 trialkylsilyl; or

[0213] A-R5and A-R7are taken together with the atoms linking A-R5and A-R7to form an optionally substituted 5- to 7-membered ring containing ring members selected from carbon atoms and optionally up to 3 heteroatoms selected from up to 1 O, up to 1 S, and up to 1 N, and up to 3 ring members selected from C(=O), C(=S), S(=O)A-s(=N-A-R23)A-f and Si-A-R17-A-R18;

[0214] each A-R12is independently H, C1-C3 alkyl, C1-C3 alkylcarbonyl, C1-C3 alkoxy, or Ci-C3 alkoxy carbonyl;

[0215] A-R15is H, halogen, cyano, hydroxy, -CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C2-C4 alkoxyalkyl, C2-C4 alkylthioalkyl, C2-C4 alkylsulfinylalkyl, C2-C4 alkylsulfonylalkyl, C2-C4 alkylcarbonyl, C2-C4 haloalkylcarbonyl, C2-C5 alkoxycarbonyl, C3-C5 alkoxycarbonylalkyl, C2-C5 alkylaminocarbonyl, C3-C5 dialkylaminocarbonyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 haloalkylthio, C1-C4 alkylsulfinyl, C1-C4 haloalkylsulfinyl, C1-C4 alkylsulfonyl, or C1-C4 haloalky Isulfonyl;

[0216] A-R16is H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C2-C4 alkoxyalkyl, C2-C4 alkylthioalkyl, C2-C4 alkylsulfinylalkyl, C2-C4 alkylsulfonylalkyl, C2-C4 alkylcarbonyl, C2-C4 haloalkylcarbonyl, C2-C5 alkoxycarbonyl, C3-C5 alkoxycarbonylalkyl, C2-C5 alkylaminocarbonyl, C3-C5 dialkylaminocarbonyl, C1-C4 alkylsulfonyl or C1-C4 haloalkylsulfonyl;

[0217] each A-R17and A-R18is independently C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, C3-C5 cycloalkyl, C3-C6 halocycloalkyl, C4-C10 cycloalkylalkyl, C4-C7 alkylcycloalkyl, C5-C7 alkylcycloalkylalkyl, C1-C5 haloalkyl, C1-C5 alkoxy, or C1-C5 haloalkoxy;

[0218] each A-R20, A-R22, A-R24and A-R27is independently H, C1-C4 alkyl or C1-C4 haloalkyl; each A-R21is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C2-C6 alkoxycarbonyl or C2-C6 haloalkoxycarbonyl; each A-R23is independently H, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylamino, C2-C8 dialkylamino, C1-C6 haloalkylamino, or phenyl;

[0219] each A-R25is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C2-C6 alkoxycarbonyl, or C2-C6 haloalkoxycarbonyl;Attorney Docket No. 10620-164W01

[0220] NCSU Ref.: 2025-138-03

[0221] each A-R26is independently Ci-Ce alkyl, Ci-Ce haloalkyl, C3-C8 cycloalkyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 haloalkoxycarbonyl or -A-Z4-A-Q;

[0222] each -A-Z4is independently O, C(=O), S(O)A-m or CH-A-R20;

[0223] A-R28is H, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkoxyalkyl, C2-C4 alkylcarbonyl, C2-C4 alkoxy carbonyl, C2-C3 alkylaminocarbonyl or C3-C6 dialkylaminocarbonyl;

[0224] each A-R29is independently H, halogen, cyano, hydroxy, amino, nitro, -CHO, -C(=O)OH, -C(=O)NH2, -SO2NH2, -C(=S)NH2, -C(=O)NHCN, -C(=O)NHOH, -SH, -SO2NHCN, -SO2NHOH, -OCN, -SCN, -SF5, -NHCHO, -NHNH2, -N3, -NHOH, -NHCN, -NHC(=0)NH2, -N=C=O, -N=C=S, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Ci-Ce haloalkyl, C2-C8 alkylcarbonyl, C2-C8 haloalkylcarbonyl, C2-C8 alkoxy carbonyl, C4- C10 cycloalkoxycarbonyl, C5-C12 cycloalkylalkoxycarbonyl, C2-C8 alkylaminocarbonyl, C3-C10 dialkylaminocarbonyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C4-C10 alkylcycloalkyl, C4-C10 cycloalkylalkyl, C6-C14 cycloalkylcycloalkyl, C4-C10 halocycloalkylalkyl, C5-C12 alkylcycloalkylalkyl, C3-C8 cycloalkenyl, C3-C8 halocycloalkenyl, C2-C8 alkoxyalkyl, C4-C10 cycloalkoxyalkyl, C3-C10 alkoxyalkoxyalkyl, C2-C8 alkylthioalkyl, C2-C8 alkylsulfinylalkyl, C2-C8 alkylsulfonylalkyl, C2-C8 alkylaminoalkyl, C3-C10 dialkylaminoalkyl, C2-C8 haloalkylaminoalkyl, C4-C10 cycloalkylaminoalkyl,

[0225] C4-C10 cycloalkylcarbonyl, C4-C10 cycloalkylaminocarbonyl, C2-C7 cyanoalkyl, Ci-Ce hydroxy alkyl, C4-C10 cycloalkenylalkyl, C2-C8 haloalkoxyalkyl, C2-C8 alkoxyhaloalkyl, C2-C8 haloalkoxyhaloalkyl, C4-C10 halocycloalkoxyalkyl, C4-C10 cycloalkenyloxyalkyl, C4-C10 halocycloalkenyloxyalkyl, C3-C10 dialkoxyalkyl, C4-C12 trialkoxyalkyl, C3-C8 alkoxyalkenyl, C3-C8 alkoxyalkynyl, C3-C10 halodialkylaminoalkyl, C5-C12 cycloalkyl(alkyl)aminoalkyl, C2-C8 alkyl(thiocarbonyl), C3-C10 alkoxyalkylcarbonyl, C3-C10 alkoxycarbonylalkyl, C2-C8 haloalkoxycarbonyl, C3-C10 alkoxyalkoxycarbonyl, C2-C8 (alkylthio)carbonyl, C2-C8 alkoxy(thiocarbonyl), C2-C8 alkylthio(thiocarbonyl), C2-C8 alkylamino(thiocarbonyl), C3-C10 dialkylamino(thiocarbonyl), C3-C10 alkoxy (alkyl)aminocarbonyl, C2-C8 alkylsulfonylaminocarbonyl, C2-C8 haloalkylsulfonylaminocarbonyl, C2-C8 alkylamidino, C3-C10 dialkylamidino, Ci-Ce alkoxy, Ci-Ce haloalkoxy, C2-C8 alkylcarbonyloxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, Ci-Ce alkylaminosulfonyl, C2-C8 dialkylaminosulfonyl, C3-C10 trialkylsilyl, C3-C8 cycloalkoxy, C3-C8 halocycloalkoxy, C4-C10 cycloalkylalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C3-C6 haloalkynyloxy, C2-C8 alkoxyalkoxy, C2-C8 haloalkylcarbonyloxy, C4-C10 cycloalkylcarbonyloxy, C3-C10 alkylcarbonylalkoxy, C3-C8Attorney Docket No. 10620-164W01

[0226] NCSU Ref.: 2025-138-03

[0227] cycloalkylthio, C3-C8 cycloalkylsulfonyl, Cs-Cs cycloalkenyloxy, Cs-Cs halocycloalkenyloxy, C2-C8 haloalkoxyalkoxy, C2-C8 alkoxyhaloalkoxy, C2-C8 haloalkoxyhaloalkoxy, C3-C10 alkoxycarbonylalkoxy, C2-C8 alkyl(thiocarbonyl)oxy, C2-C8 alkylcarbonylthio, C2-C8 alkyl(thiocarbonyl)thio, C3-C8 cycloalkylsulfinyl, C3-C10 halotrialkylsilyl, C1-C6 alkylamino, C2-C8 dialkylamino, C2-C8 alkylcarbonylamino, C1-C6 alkylsulfonylamino, C1-C6 haloalkylamino, C2-C8 halodialkylamino, C3-C8 cycloalkylamino, C2-C8 haloalkylcarbonylamino, C1-C6 haloalkylsulfonylamino, C4-C10 cycloalkylalkylamino, C4-C10 cycloalkyl(alkyl)amino, C3-C10 alkoxycarbonylalkylamino, Ci-Ce alkoxyamino, Ci-Ce haloalkoxyamino, C4-C12 dialkylimido, C2-C8 alkoxy carbonylamino, C2-C8 haloalkoxy carbonylamino, C2-C8 alkylaminocarbonylamino, C3-C10 dialkylaminocarbonylamino, C3-C10 alkylaminocarbonyl(alkyl)amino, C4-C12 dialkylaminocarbonyl(alkyl)amino, C2-C8 alkylamino(thiocarbonyl)amino, C3-C10 dialkylamino(thiocarbonyl)amino, C3-C10 alkylamino(thiocarbonyl)alkylamino or C4-C12 dialkylamino(thiocarbonyl)alkylamino;

[0228] each A-R30and A-R31is independently C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C1-C6 haloalkyl, C3-C6 haloalkenyl, C3-C6 haloalkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C4-C8 alkylcycloalkyl, C4-C8 cycloalkylalkyl, C4-C8 halocycloalkylalkyl, C5-C8 alkylcycloalkylalkyl, C2-C6 alkoxyalkyl, C4-C8 cycloalkoxyalkyl, C3-C6 alkoxyalkoxyalkyl, C2-Ce alkylthioalkyl, C2-C6 alkylsulfinylalkyl, C2-C6 alkylsulfonylalkyl, C2-C6 alkylaminoalkyl, C3-C6 dialkylaminoalkyl, C2-C6 haloalkylaminoalkyl, C4-C8 cycloalkylaminoalkyl,

[0229] C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C4-C8 cycloalkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl or C4-C8 cycloalkylaminocarbonyl;

[0230] A-R32is H, cyano, hydroxy, amino, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C1-C6 haloalkyl, C3-C6 haloalkenyl, C3-C6 haloalkynyl, C3-C6 cycloalkyl, C4-C8 cycloalkylalkyl, C2-C6 alkoxyalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, Ci-Ce alkylamino, C2-C8 dialkylamino, Ci-Ce haloalkylamino or C2-C8 halodialkylamino;

[0231] A-R33is H, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C1-C6 haloalkyl or C3-C6 cycloalkyl; or

[0232] A-R32and A-R33are taken together as -(CH2)4-, -(CH2)5- or -(CH2)2O(CH2)2-;

[0233] A-d is 1 or 2;

[0234] each A-m is independently 0, 1 or 2;

[0235] A-n is 0, 1 or 2; and

[0236] A-s and A-f are independently 0, 1 or 2 in each instance of S(=O)A-s(=N-A-R23)A-f, provided that the sum of A-s and A-f is 1 or 2.Attorney Docket No. 10620-164W01

[0237] NCSU Ref.: 2025-138-03

[0238] In some embodiments, A-J comprises A-J-29:

[0239] / (A-R5)A. X

[0240]

[0241] A-J-29

[0242] wherein the bond shown projecting to the left is bonded to A-Z1in Formula V and to an available carbon or nitrogen atom ring member in the A-J ring;

[0243] A-x is 0, 1, or 2; and

[0244] Y is chosen from S, S=O, and S(=O)2.

[0245] In some embodiments, A-J comprises one of A-J-29- 1 to A-J-29-40:Attorney Docket No. 10620-164W01

[0246] NCSU Ref.: 2025-138-03

[0247] A-J-29-11 A-J-29-12

[0248] A-J-29-13

[0249] A-J-29-19 A-J-29-23 A-J-29-24

[0250] A-J-29-25

[0251] A-J-29-32 A-J-29-33 A-J-29-34 A-J-29-35 A-J-29-36

[0252]

[0253] A-J-29-37 A-J-29-40 wherein Y is chosen from S, S=O, and S(=O)2.

[0254] In some embodiments, A-E is A-E-l or A-E-2;

[0255] A-G is a 5-membered heterocyclic ring optionally substituted with up to 2 substituents selected from A-R3on carbon ring members and selected from A-R11on nitrogen ring members;

[0256] each A-R3is independently halogen, C1-C3 alkyl or C1-C3 haloalkyl;

[0257] each A-R11is independently C1-C3 alkyl;

[0258] A- J comprises A-J-29:Attorney Docket No. 10620-164W01

[0259] NCSU Ref.: 2025-138-03

[0260] O^X(A-R5)A. X

[0261]

[0262] A-J-29

[0263] wherein the bond shown projecting to the left is bonded to A-Z1in Formula V and to an available carbon or nitrogen atom ring member in the A-J ring; A-x is 0, 1, or 2; and Y is chosen from S, S=O, and S(=O)2;

[0264] A-X is A-X1, A-X2, A-X3, A-X4, A-X5. A-X6A-X7, or A-X8;

[0265] A-Z1is a direct bond, CH-A-R20, or N-A-R21;

[0266] each A-R21is independently H, C1-C3 alkyl, C1-C3 alkylcarbonyl or C2-C3

[0267] alkoxy carbonyl;

[0268] A-Rla, A-Rlb, and A-Rlcindependently are optionally substituted phenyl, optionally substituted naphthalenyl or an optionally substituted 5- or 6-membered heteroaromatic ring; or cyano, Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 alkynyl, Ci-Cs haloalkyl, C2-C8 haloalkenyl, C2-C8 haloalkynyl, C2-C8 haloalkylthioalkyl, C3-C8 cycloalkyl, C2-C8 alkoxyalkyl, C2-C8 haloalkoxyalkyl, C3-C8 alkoxycarbonylalkyl, C3-C8 haloalkoxycarbonylalkyl, C2-C8 alkylthioalkyl, C2-C8 alkylsulfinylalkyl, C2-C8 alkylsulfonylalkyl, C2-C8 alkylaminoalkyl, C2-C8 alkylcarbonyloxy, C2-C8 haloalkylcarbonyloxy, C3-C10 dialkylaminoalkyl, Ci-Cs alkoxy, Ci-Cs haloalkoxy, Ci-Cs alkylthio, C3-C10 trialkylsilyl, Ci-Cs alkylamino, C2-C8 dialkylamino, C2-C8 alkylcarbonylamino, pyrrolidinyl, piperidinyl or morpholinyl;

[0269] each A-R2is independently halogen, cyano, hydroxy, C1-C2 alkyl, C1-C2 haloalkyl or Ci-C2 alkoxy;

[0270] A-R5is independently H, halogen, cyano, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Ci-Ce haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C4-C10 alkylcycloalkyl, C4-C10 cycloalkylalkyl, C2-C6 alkoxyalkyl, C4-C10 cycloalkoxyalkyl, C3-C8 alkoxyalkoxyalkyl, C2-C6 alkylthioalkyl, C2-C6 alkoxycarbonyl, Ci-Ce alkoxy, Ci-Ce haloalkoxy, C3-C8 cycloalkoxy, C3-C8 halocycloalkoxy, C4-C10 cycloalkylalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C2-C6 haloalkynyloxy, C2-C6 alkoxyalkoxy, C2-C6 alkylcarbonyloxy, C2-C6 haloalkylcarbonyloxy, C4-C8 cycloalkylcarbonyloxy, C3-C6 alkylcarbonylalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C3-C8 cycloalkylthio, C3-C10 trialkylsilyl, -N-A-R25-A-R26or -A-Z2-A-Q;

[0271] each A-R26is independently C1-C3 alkyl or -A-Z4-A-Q;

[0272] each A-Z4is independently C(=O) or S(=O)2;

[0273] each A-Z2is independently a O, C(=O), S(O)2, CH-A-R20or N-A-R21;Attorney Docket No. 10620-164W01

[0274] NCSU Ref.: 2025-138-03

[0275] each A-Q is independently phenyl, benzyl, naphthalenyl, a 5- to 6-membered heteroaromatic ring or an 8- to 11 -membered heteroaromatic bicyclic ring system, each optionally substituted with up to 1 substituent independently selected from A-R7aon carbon atom or nitrogen atom ring members, and each optionally substituted with up to 5 substituents independently selected from A-R7on carbon atom ring members and A-R12on nitrogen atom ring members; or a 3- to 7-membered nonaromatic carbocyclic ring, a 5-, 6- or 7-membered nonaromatic heterocyclic ring or an 8- to 11 -membered nonaromatic bicyclic ring system, each optionally including ring members selected from the group consisting of C(O), C(=S), S(=O)A-s(=N-A-R23)A-f and Si-A-R17-A-R18, and each ring or ring system optionally substituted with up to 1 substituent independently selected from A-R7aon carbon atom or nitrogen atom ring members, and each optionally substituted with up to 5 substituents independently selected from A-R7on carbon atom ring members and A-R12on nitrogen atom ring members;

[0276] each A-R7is independently halogen, cyano, hydroxy, amino, nitro, C1-C3 alkyl, C1-C3 haloalkyl, C1-C2 alkoxy or C1-C2 haloalkoxy; or A-R5and A-R7are taken together with the atoms linking A-R5and A-R7to form an optionally substituted 5- to 7-membered ring containing ring members selected from carbon atoms and optionally up to 3 heteroatoms selected from up to 1 O, up to 1 S and up to 1 N, and up to 2 ring members selected from C(=O), C(=S), S(=O)A-s(=N-A-R23)A-f and Si-A-R17-A-R18, the ring optionally substituted with substituents selected from A-R8;

[0277] each R8is independently halogen, cyano, hydroxy, amino, nitro, Ci-Ce alkyl, C2-Ce alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C10 cycloalkylalkyl, C4-C10 alkylcycloalkyl, Cs-C10 alkylcycloalkylalkyl, Ci-Ce haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C6 halocycloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulftnyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylthio, C1-C4 haloalkylsulftnyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylamino, C2-C8 dialkylamino, C3-C6 cycloalkylamino, C2-C4 alkoxyalkyl, C1-C4 hydroxyalkyl, C2-C4 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylcarbonyloxy, C2-C6 alkylcarbonylthio, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, or C3-Ce trialkylsilyl;

[0278] each A-R7ais independently -A-Z3-A-TA;

[0279] each A-R29is independently H, halogen, cyano, hydroxy, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy or C1-C2 haloalkoxy;

[0280] each A-TAis independently selected from A-TA-18 and A-TA-49 wherein the bond shown projecting to the left is bonded to A-Z3in Formula V and A-r is 0, 1, 2, 3, 4 or 5Attorney Docket No. 10620-164W01

[0281] NCSU Ref.: 2025-138-03

[0282] F^JHA-R29)^ (A-R29)A-r

[0283]

[0284] A-TA-18 A-TA-49

[0285] A-R15is H, halogen, cyano, hydroxy, -CHO, C1-C4 alkyl, C1-C4 haloalkyl,

[0286] C1-C4 alkoxy or C2-C5 alkoxy carbonyl; and

[0287] A-R16is H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkylcarbonyl, C2-C4 haloalkylcarbonyl or C2-C4 alkoxy carbonyl.

[0288] In some embodiments, A-G is one of A-G-l through A-G-59 wherein the bond projecting to the left is bonded to A-X, and the bond projecting to the right is bonded to Z1in Formula 1

[0289] (A-R3a) (A-R11),, JL

[0290] A-G-6 (A-R3a)

[0291] / A o3ax<A-R3a> (A-R3a) (A-R3a),A o3ai(A-R3a) (A-R3a)((A-R3a) n-sk (A-R3a)N< A-R3a) NN, N (A-R A

[0292] / z'" N L 'N—NA- z^N A-G-25 (A-R3a) A-G-26 A-G-27 (A-R3a)A-G-28 (X-RSajA. G.29 A. G-30 (A-R3a) A-G-31 (X-R^) A-G-32 (A-R3a)

[0293] (A-R3a) (A-R3a) / / (A. Ri1a) / / N N (A-R3a) 1 ' N—A KN— ~T N— V U y— (A-R3a) I A— (A-R3a) L V<A-R3a) JL / y— (A-R3a) »3a- z^^N z^^N z*^^. >,(A'R3a)A-G-34 (A-R3a) A-G-35 A-G-36 A-G-37 A-G-38 A-G-39 A-G-40 A-lj-OO (A-R3a)

[0294] wherein

[0295]

[0296] Attorney Docket No. 10620-164W01

[0297] NCSU Ref.: 2025-138-03

[0298] each A-R3ais independently selected from H and A-R3;

[0299] A-Rllais selected from H and A-R11;

[0300] A-x is 0, 1, or 2;

[0301] A-X is A-X1, A-X2, or A-X3;

[0302] A-Z1is a direct bond or CH-A-R20;

[0303] each A-R21is independently H or methyl;

[0304] A-Z5and A-Z6independently are each a direct bond;

[0305] A-Rlaand A-Rlbindependently are phenyl, naphthalenyl or a 5- or 6-membered heteroaromatic ring, each optionally substituted with up to 3 substituents selected from A-R4aon carbon ring members and A-R4bon nitrogen ring members; or cyano, Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 alkynyl, Ci-Cs haloalkyl, C2-C8 haloalkenyl, C2-C8 haloalkynyl, C2-C8 haloalky Ithioalkyl, C3-C8 cycloalkyl, C2-C8 alkoxyalkyl, C2-C8 haloalkoxyalkyl, C3-C8 alkoxycarbonylalkyl, C3-C8 haloalkoxycarbonylalkyl, C2-C8 alkylthioalkyl, C2-C8 alkylsulfinylalkyl, C2-C8 alkylsulfonylalkyl, C2-C8 alkylaminoalkyl, C2-C8 alkylcarbonyloxy, C2-C8 haloalkylcarbonyloxy, C3-C10 dialkylaminoalkyl, Ci-Cs alkoxy, Ci-Cs haloalkoxy, Ci-Cs alkylthio, C3-C10 trialkylsilyl, Ci-Cs alkylamino, C2-C8 dialkylamino, C2-C8 alkylcarbonylamino, pyrrolidinyl, piperidinyl or morpholinyl;

[0306] each A-R4ais independently halogen, cyano, hydroxy, amino, nitro, Ci-Cg alkyl, C2-Ce alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C10 cycloalkylalkyl, C4-C10 alkylcycloalkyl, Cs-C10 alkylcycloalkylalkyl, Ci-Ce haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C6 halocycloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylthio, C1-C4 haloalkylsulfinyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylamino, C2-C8 dialkylamino, C3-C6 cycloalkylamino, C2-C4 alkoxyalkyl, C1-C4 hydroxyalkyl, C2-C4 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylcarbonyloxy, C2-Ce alkylcarbonylthio, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl or C3-Ce trialkylsilyl;

[0307] each A-R4bis independently Ci-Ce alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, Ci-Ce haloalkyl, C3-C6 haloalkenyl, C3-C6 haloalkynyl, C3-C6 halocycloalkyl or C2-C4 alkoxy alkyl;

[0308] each A-R2is independently cyano, hydroxy, methyl or methoxy;

[0309] each A-R5is independently H, halogen, cyano, Ci-Ce alkyl, Ci-Ce haloalkyl,

[0310] C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C2-C6 alkoxy alkyl, Ci-Ce alkoxy, Ci-Ce haloalkoxy, C3-Cs cycloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C2-C6Attorney Docket No. 10620-164W01

[0311] NCSU Ref.: 2025-138-03

[0312] alkoxyalkoxy, C2-C6 alkylcarbonyloxy, C2-C6 haloalkylcarbonyloxy, Ci-Ce alkylthio, Ci- Ce haloalky Ithio, C3-C10 trialkylsilyl, -N-A-R25-A-R26or -A-Z2-A-Q;

[0313] each A-Z2is independently a direct bond or N-A-R21;

[0314] A-Q is one of A-Q-1 through A-Q-106 wherein p is an integer from 0 to 5 and q is an integer from 0 to 2

[0315] rt<A-R7)p ^-(A-R7)P 4^-<A-R7)P r^(A-R7)p^^-(A-R7)p ^^-(A-R7)p O-<A-R)P 'S^(A-R7a)q%^(A-R7a)q'^N^(A-R7a)qS7x(A-R7a)< TxO^(A-R7a)t|'^XS^(A-R7a)qSX(A-R7a)qA-Q-1 A-Q-2 R12A-Q-3 A-Q-4 A-Q-5 A-Q-6 A-Q-8 r^<A-R7>p %^(A-R7a)qA-Q-16 y^-^pXO^(A-R7a)qA-Q-24 P^(A-R7)PVX(A-R7a)qA-Q-32 IN3'(A’R7)PJC<< A’R7)PJ^< A’R7)PJO‘(A’R7)PJ|N?r(A-R7)p JO<A-R7)P |fNV<A-R7>p r | *' -nf-(A-R 77)p^■(A-R7a)q(A-R7a)q^NN(A. R7a)q^N^(A. R7a)q^NN(A. R7a)qX<NX(A-R7a)q^X(A-R A-Q-33 A-Q-34 A-Q-35 A-Q-36 A-Q-37 A-Q-38 A-Q-V7a)qA-Q-40 J|^JJ-(A-R7)Pif. Jr(A R7)P. J“(A'R7)PJL •^(A'R7)px^0^-(A R7)P^JC''-1 jT^J“(A-R7)p -^(A-R7)PN’*A-R7a)q^NAA-R7a)q^~N(A-R7’)qN' (A-R7a)q(A'R?a|qI ^fA-R^L C ^(A. R7^ ^(A-R7a)qA-Q-41 A-Q-42 A-Q-43 A-Q-44 A-Q-45 I A-Q-462A-Q-47 A-Q-48<<^(A-R7)p _A^(A-R7)P_AJ-(A-R7)P— ^ J-(A-R7)p— < QJ-(A-R7)P(A-R7)P_ / 7^-(A-R7)p ^-(A-R7a)q~ \A(A. R7a)^ \^(A-R7a)qX(A-R7a)qX(A-R7a)q(A-R7a)q~ V2>(A-R7a)q

[0316]

[0317] A-Q-49 A-Q-50 A-Q-51 A-Q-52 A-Q-53 A-Q-54 A-Q-55Attorney Docket No. 10620-164W01

[0318] NCSU Ref.: 2025-138-03

[0319] o o O o <R12-A)'N? JT J-< A-R7)P I [ J-(A-R7)PI jf J-(A-R7)PY Ji0 NJ-(A-R <^ ^j^(A. R7a)ci7)PN'^^fA-R7’), CT' N^^(A-R7a)qN^^(A-R7a)qA-Q-76 A-Q-77 A-Q-78R12A-Q-79

[0320] O

[0321] V,(A-R7a)q-N t-(A-R7)p-N J-(A-R7)p— N J-(A-R7)p^(A-R73) y "(A-R12) ^(A-R7%,

[0322] 000A-Q-86 A-Q-89 A-Q-90

[0323] 0<J?S''NsT'(~A(-A'R7)PR7a)q(A-R12) A-Q-92 S

[0324] A-Q-98

[0325] — N / =J-(A-R7)P-N J-(A-R7)P^(A-R7a)qN^(A-R7a)qA-Q-105 A-Q-106

[0326]

[0327] each A-R7is independently halogen, cyano, hydroxy, C1-C3 alkyl, C1-C3 haloalkyl, Ci-C2 alkoxy or C1-C2 haloalkoxy;

[0328] each A-R29is independently H, halogen, C1-C2 alkyl, C1-C2 haloalkyl or C1-C2 alkoxy; A-R15is H, halogen, cyano, hydroxy, methyl, methoxy or methoxy carbonyl;

[0329] A-R16is H, methyl, methylcarbonyl or methoxy carbonyl;

[0330] A-R28is H, halogen, cyano or C1-C4 alkyl;

[0331] each A-R30and A-R31is independently selected from Ci-Ce alkyl, C3-C4 alkenyl, C3-C4 alkynyl, C1-C4 haloalkyl, C3-C6 haloalkenyl, C3-C6 haloalkynyl, C2-C6 alkoxyalkyl and C3-Ce cycloalkyl;

[0332] A-R32is H, cyano, hydroxy, amino, Ci-Ce alkyl or Ci-Ce alkoxy; and

[0333] R33is H or Ci-Ce alkyl.Attorney Docket No. 10620-164W01

[0334] NCSU Ref.: 2025-138-03

[0335] In some embodiments, A-Gis selected from A-G-I, A-G-2, A-G-7, A-G-8, A-G-14, A-G- 15, A-G-23, A-G-24, A-G-26, A-G-27, A-G-36, A-G-37, A-G-38, A-G-49, A-G-50 and A-G-55, wherein A-G is unsubstituted;

[0336] A-W is O;

[0337] A-X is A-X1or A-X2;

[0338] A-Z1is a direct bond;

[0339] A-Rlaand A-Rlbindependently are selected from A-U-l through A-U-50 wherein when A-R4is attached to a carbon ring member, said A-R4is selected from A-R4a, and when A-R4is attached to a nitrogen ring member, said A-R4is selected from A-R4b, and k is 0, 1 or 2; or C2-Cs alkyl, C2-C5 alkenyl, C2-C5 haloalkyl, C2-C5 haloalkenyl, C2-C5 haloalkylthioalkyl, C2-Cs alkoxyalkyl, C2-C5 haloalkoxyalkyl, C2-C5 alkylthioalkyl, C2-C5 alkylaminoalkyl, C2-Cs alkylcarbonyloxy, C2-C5 haloalkylcarbonyloxy, C2-C5 alkoxy, C2-C5 haloalkoxy, C2-Cs alkylthio, C2-C5 alkylamino or C2-C5 alkylcarbonylamino

[0340] n, A R4|‘ N' ' "s' O' N - "s' -"xX I A-U-1 A-U-2 A-U-3 A-U-4 A-U-5 A-U-6 A-U-7 ° A-ll-R >41

[0341] N^(A-R4)kN-N *-(A-R4)k / / ^(A-Rhk N,’N A-U-10 A-U-1 N A-U-9 1 A-U-12 N •o < A-R4)kA-U-13 A-U-14 A-U-15 A-U-16 (A-R4)k(A-R4)kN-N N"?r(A-R4)k(A-R4)k(A-R4)kN' S'

[0342] | A-U-21 A-U-24 | A-U-20 A-U-23 A-U-17 A-U-19 A-U-18 A-U-22 br(A-R4)kM

[0343] & A-U-29 A-U-30 A-U-31 A-U-32

[0344] v-< A. R-lkA-U-33 I A-U-34 A-U-35 I A-U-36 A-U-37 A-U-38 A-U-39 A-U-40 jO~(A'R4)kJl 3_(A-R4? Jr^L(A-R4b^^(AR4ML-^(A-R4)iJ> Jr^r< A-R4ML ^<A-R4)jOL(A-R4)kA-U-41 A-U-42 A-U-43 A-U-44 A-U-45 A-U-46 A-U-47 A-U-48

[0345] A-U-49 A-U-50

[0346]

[0347] each A-R5is independently H, halogen, cyano, Ci-Ce alkyl, Ci-Ce haloalkyl,

[0348] Ci-Ce alkoxy, Ci-Ce haloalkoxy, -N- A-R25-A-R26or -A-Z2-A-Q;

[0349] each A-Z2is a direct bond;Attorney Docket No. 10620-164W01

[0350] NCSU Ref.: 2025-138-03

[0351] each A-Q is independently A-Q-l, A-Q-20, A-Q-32 through A-Q-34, A-Q-45 through A-Q-47, A-Q-60 through A-Q-73, A-Q-76 through A-Q-79, A-Q-84 through A-Q-94 and A-Q-98 through A-Q-l 06;

[0352] p is an integer from 0 to 3;

[0353] q is an integer from 0 to 1;

[0354] each A-R7is independently F, Cl, cyano, hydroxy, methyl or methoxy;

[0355] A-R28is H, halogen or cyano;

[0356] each A-R30and A-R31is independently selected from Ci-Ce alkyl, C3-C4 alkenyl, C3-C4 alkynyl and C1-C4 haloalkyl;

[0357] R32is selected H, cyano, hydroxy, amino, C1-C3 alkyl or C1-C3 alkoxy;

[0358] R33is selected from H or methyl; and

[0359] n is 0.

[0360] In some embodiments, A-G is selected from A-G-l, A-G-2, A-G-15, A-G-26, A-G-27, A-G-36, A-G-37 and A-G-38;

[0361] A-X is A-X1or A-X2; and the ring comprising A-X is saturated;

[0362] A-Rlaand A-Rlbindependently are selected from A-U-l through A-U-3, A-U-ll, A-U-13, A-U-20, A-U-22, A-U-23, A-U-36 through A-U-39, and A-U-50 wherein when A-R4is attached to a carbon ring member, said A-R4is selected from A-R4a, and when A-R4is attached to a nitrogen ring member, said A-R4is selected from A-R4b, and k is 0, 1 or 2; or C3-C5 alkyl, C3-C5 alkenyl, C3-C5 haloalkyl, C3-C5 haloalkenyl, C2-C4 haloalkylthioalkyl, C2-C4 alkoxyalkyl, C2-C4 haloalkoxyalkyl, C2-C4 alkylthioalkyl, C2-C4 alkylaminoalkyl, C2-C3 alkylcarbonyloxy, C2-C3 haloalkylcarbonyloxy, C2-C4 alkoxy, C2-C4 haloalkoxy, C2-C4 alkylthio, C2-C4 alkylamino or C2-C3 alkylcarbonylamino;

[0363] each A-R5is independently H, halogen, cyano, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce alkoxy, Ci-Ce haloalkoxy or -A-Z2-A-Q;

[0364] A-Q is selected from A-Q-l, A-Q-45, A-Q-63, A-Q-64, A-Q-65, A-Q-68, A-Q-69, A-Q-70, A-Q-71, A-Q-72, A-Q-73, A-Q-76, A-Q-78, A-Q-79, A-Q-84, A-Q-85, A-Q-98, A-Q-99, A-Q-100, and A-Q-l 01 through A-Q-l 06;

[0365] A-R28is Cl, F or cyano;

[0366] each A-R30and A-R31is independently selected from C1-C4 alkyl;

[0367] A-R32is H, cyano, hydroxy, C1-C2 alkyl or C1-C2 alkoxy; and

[0368] A-R33is H.

[0369] In some embodiments, A-G is selected from A-G-l, A-G-2, A-G-15, A-G-26 and A-G- 36;Attorney Docket No. 10620-164W01

[0370] NCSU Ref.: 2025-138-03

[0371] A- J is any one of A-J-29-1 to A-J-29-40

[0372] A-J-29-25

[0373] A-J-29-36

[0374]

[0375] A-J-29-37 A-J-29-40 wherein Y is chosen from S, S=O, and S(=O)2;

[0376] A-X is A-X1;

[0377] A-Rlaand A-Rlbare each selected from A-U-l, A-U-20 and A-U-50 wherein when A-R4is selected from A-R4a, and k is O, 1 or 2; or C3-C5 haloalkyl, C3-C5 haloalkenyl, C3-C5 haloalkylthioalkyl, C3-C5 haloalkoxyalkyl, C2-C3 haloalkylcarbonyloxy or C2-C4 haloalkoxy; each R5is independently cyano, Ci-Ce alkyl, Ci-Ce alkoxy or -A-Z2-A-Q;Attorney Docket No. 10620-164W01

[0378] NCSU Ref.: 2025-138-03

[0379] A-Q is selected from -A-Q-45, -A-Q-63, -A-Q-64, -A-Q-65, -A-Q-68, -A-Q-69, -A-Q-70, -A-Q-71, -A-Q-72, -A-Q-84 and -A-Q-85; and

[0380] each -A-R30and -A-R31is independently ethyl or methyl.

[0381] In some embodiments, A-A is C(=O).

[0382] In some embodiments, A-A is CH-A-R15or N-A-R16.

[0383] In some embodiments, the compound is defined by Formula VA

[0384] / (A-TT)

[0385]

[0386] (A-TT)

[0387] Formula V A

[0388] wherein

[0389] Y is chosen from S, S=O, and S(=O)2;

[0390] each A-R is individually chosen from halogen, cyano, hydroxy, amino, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy and C1-C4 haloalkoxy;

[0391] each A-Z3is independently absent, a direct bond, O, N-A-R22, C(=O), C(=S), S(O)A-m, CH-A-R20, -CH-A-R2O-CH-AR20-, -C-A-R24=C-A-R27-, -OCH-A-R20-, or -CH-A-R20O-;

[0392] each A-TTis individually chosen from halogen, cyano, hydroxy, amino, nitro, Ci-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, A-TA-1 through A-TA-49, A-TN-1 through A-TN-28, or A-Tp-1 through A-Tp-35;Attorney Docket No. 10620-164W01

[0393] NCSU Ref.: 2025-138-03

[0394] 7^R29)L-Z$'< A'R29)r^-^'< A-R29)r / / -^-(A-R29), ^“^.(A-R29),. xZ s ''y /

[0395] A-T -5

[0396] N-N ff~3,(A-R29)rtf-^A-R29), n-(A. R2s)r7^(A-R29)r 4"!t(A-R29)r / =3r-(A-R29)rN-jt-(A-R29)r. N ^4' > ft 2>(A-R29)r-v N, 4

[0397] R22 A-T”15^~a-(A-R29)r,N=2-(A-R29), N-N N-N <A-R29)r --N^N (A-R29)

[0398] ^ ''Ss-^A-R29)^ ”Nh «N, O^'(A-R29)r 7 R22-23 ^y< A-R29)rZ*-(A-R29)rJ

[0399] [j 4— (A-R29)rJj J-(A-R29)r^■^.(A-R29), ^r(A-R29),

[0400] OL< A’R29)rjOr(A-R29)rT%(A-R29)r •zZls‘N^ •J22A-TA-35

[0401] A’7*45A-7*46[| 4— (A-R29)r

[0402] — N^J-(A-R29)r— N — N O A-TNO O A-TN-6 0 -2 Q o Q Q Q — NZ7-(A-R29)r— N N •N J"(A-R29),— N -n-(A-R29)r-N — N 4-(A-R29)r-N 4-(A-R29)r- N Y '(A-R22)

[0403] V" '(A-R22) V_>(A-R29)r0A-TN-9 O O O z0A-TN-15 '

[0404] (A-R22) — N 3=0 — N29O^N ■ V j-(A-R29)r7 J-(A-R V_> A R9,29) ( -2)rO' s A-TN-18 g - <^j-(A-R29)r— < Qj-(A-R29)

[0405] (A-R29) -HA-R29),

[0406] ^^(A-R29)r(A-R29)

[0407]

[0408] Attorney Docket No. 10620-164W01

[0409] NCSU Ref.: 2025-138-03

[0410]

[0411] r is 0, 1, 2, 3, 4, or 5; and

[0412] R29is chosen from halogen, cyano, hydroxy, amino, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy and C1-C4 haloalkoxy.

[0413] In some embodiments, the compound is chosen from one of the following:

[0414]

[0415] Attorney Docket No. 10620-164W01

[0416] NCSU Ref.: 2025-138-03

[0417]

[0418] wherein Y is chosen from S, S=O, and S(=O)2.

[0419] In some embodiments, the 1,4,2-oxathiazole analog of oxathiapiprolin can be a compound defined by the formula belowAttorney Docket No. 10620-164W01

[0420] NCSU Ref.: 2025-138-03

[0421] 3 JA-R7: 'A-RX\, N / 4 (A-Z5)

[0422] N-0 6

[0423]

[0424] (A-W) wherein

[0425] Y is chosen from S, S=O, and S(=O)2;

[0426] A-Z5is a direct bond;

[0427] and A-Rla, A-W, and (A-R7)j are as defined below.

[0428] Compound A-Rla A-Wl (A-R7)A-j A-l (Ex.l) 2,5-di-Me-Ph Sme - A-2 (Ex.2) 2,5-di-Me-Ph H - A-3 (Ex.3) 2,5-di-Me-Ph Ome - A-2 la 2,5-di-Me-Ph H - A-22 2,5-di-Me-Ph Cl - A-23 (Ex.9) 2,5-di-Me-Ph NH2 - A-24 2,5-di-Me-Ph NMe2 - A-25 2,5-di-Me-Ph NHOH 2,6-di-F A-26b 2,5-di-Me-Ph SMe 2,6-di-F A-27 2,5-di-Me-Ph NHC(=O)Me - A-28 2,5-di-Me-Ph NHMe - A-29 2,5-di-Me-Ph OEt - A-30 2,5-di-Me-Ph 4-morpholinyl - A-31 2,5-di-Me-Ph NH2 2,6-di-F A-32 2,5-di-Me-Ph CN - A-34 2,5-di-Me-Ph NHOMe 2,6-di-F A-35 2,5-di-Me-Ph NHMe 2,6-di-F A-38 2,5-di-Me-Ph NMe2 2,6-di-F A-39 2,5-di-Me-Ph NHOEt 2,6-di-F A-42 2,5-di-Me-Ph NHCN 2,6-di-F A-44 2,5-di-Me-Ph OMe 2,6-di-F a. HC1 salt.

[0429] b. HI salt.

[0430]

[0431] Attorney Docket No. 10620-164W01

[0432] NCSU Ref.: 2025-138-03

[0433] In some embodiments, the 1,4,2-oxathiazole analog of oxathiapiprolin can be a compound defined by the formula below

[0434] (R1b-A) S 2 LA / (A'R7;

[0435] (*■<

[0436]

[0437] (A-W) wherein

[0438] Y is chosen from S, S=O, and S(=O)2;

[0439] A-Z5is a direct bond;

[0440] and A-Rlb, A-A, A-W, and (A-R7)j are as defined below.

[0441] Compound A-Rlb A-A A-W (A-R7)A-j A-4 (Ex.4) CH3(CH2)4 NH 0 - A-5 (Ex.5) CH2=CHCH2 NH s - A-6 (Ex.6) CF3CH(Me) CH2 0 2-F A- 7 (Ex.7) C1CH2(CH2)2 CH2 0 2-F A-8 (Ex.8) CH=CCH2 CH2 0 2-F A-9 c-hexyl NH 0 - A-10 Ph-CH2 NH 0 - A-ll CH3 NMe 0 - A-12 CH3CH2 N-Et 0 - A-13 CH3CH2 NH 0 - A-14 n-Pr NH 0 - A-15 i-Pr NH 0 - A-16 t-Bu NH 0 - A-17 CH3CH2CH(Me) NH 0 - A-18 EtOC(=O)CH2 NH 0 - A-19 c-pentyl NH 0 - A-20 c-hexyl-CH2 NH 0 - A-40 2,5-di-Me-Ph C(=O) 0 2-F

[0442]

[0443] Attorney Docket No. 10620-164W01

[0444] NCSU Ref.: 2025-138-03

[0445] A-41 5-Me-3-CF 3-pyrazol-l-yl C(=O) 0 2-F A-43 5-Me-3-CF 3-pyrazol-l-yl C(=O) 0 2,6-di-F A-45 Ph C(=O) 0 2-F A-46 2-thienyl C(=O) 0 2-F A-47 2-furanyl C(=O) 0 2-F A-48 Et CH(OH) 0 2,6-di-F A-49 i-Pr CH(OH) 0 2,6-di-F A-50c PhCH2 CH(OH) 0 2,6-di-F A-51 2,4,6-tri-Me-Ph C(=O) 0 2-F A-52 (Ex.10) 2,5-di-Me-Ph C(=O) 0 2,6-di-F A-53 CF3 CH(OH) 0 2,6-di-F A-54d i-Pr CH(OH) 0 2,6-di-F A-55c i-Pr CH(OH) 0 2,6-di-F A-56c i-Bu CH(OH) 0 2,6-di-F A-57 i-Bu CH(OH) 0 2,6-di-F A-58 n-Bu CH(OH) 0 2,6-di-F A-59c c-hexyl CH(OH) 0 2,6-di-F A-60d c-hexyl CH(OH) 0 2,6-di-F A-61 n-hexyl CH(OH) 0 2,6-di-F A-63 CN CH2 0 2,6-di-F A-64 MeC(=O)O CH2 0 2,6-di-F A-65 Me C(=O) 0 2,6-di-F A-66 Et C(=O) 0 2,6-di-F A-67 n-Pr C(=O) 0 2,6-di-F A-68 i-Pr C(=O) 0 2,6-di-F A-69 i-Bu C(=O) 0 2,6-di-F A-70 s-Bu C(=O) 0 2,6-di-F A-71 2-thienyl C(=O) 0 2,6-di-F A-72 2-furanyl C(=O) 0 2,6-di-F A-73 CH3(CH2)4 CH2 0 2,6-di-F A-74 CF3CH2O CH2 0 2,6-di-F A-75 CF3CH2CH2O CH2 0 2,6-di-F

[0446]

[0447] Attorney Docket No. 10620-164W01

[0448] NCSU Ref.: 2025-138-03

[0449] A-76 3-CF3-c-hex-l-yl CH2 O 2,6-di-F

[0450] A-77 CF3CH2OCH2 CH2 O 2,6-di-F c. S-isomer at the carbon atom denoted by the asterisk"*" in the structure above.

[0451] d. R-isomer at the carbon atom denoted by the asterisk" *"in the structure above.

[0452]

[0453] In some examples, the 1,4,2-oxathiazole analog of oxathiapiprolin can be the compound shown below

[0454]

[0455] wherein Y is chosen from S, S=O, and S(=O)2.

[0456] In certain examples, the 1,4,2-oxathiazole analog of oxathiapiprolin can be the compound shown below.

[0457]

[0458] In some examples, described herein are 1,4,2-oxathiazole analogs of fluoxapiprolin. Fluoxapiprolin and related compounds are described for example in International Publication No. WO 2012 / 025557 and U. S. Patent Nos. 8,759,527, 9,006,266, 9,434,723, 9,770,027, 9,930,890, and 10,499,641, each of which is incorporated by reference in its entirety. Described herein are analogs of these compounds which include a 1,4,2-oxathiazole ring or an oxidized analog thereof.

[0459] For example, described herein are compound of Formula VI and / or a salt, metal complex and / or N-oxides thereofAttorney Docket No. 10620-164W01

[0460] NCSU Ref.: 2025-138-03

[0461] (B-R2)

[0462] (B-Y) /

[0463] (B-A). JJ- ■X)— (B-G)-(B-Q)-(B-L2)-(B-R1)

[0464]

[0465] (B-R10)p

[0466] Formula VI

[0467] wherein

[0468] B-A is pyrazol-l-yl which may contain up to two substituents, where the substituents are each independently selected from the following list:

[0469] substituents on carbon: halogen, cyano, hydroxyl, nitro, — N-B-R3-B-R4, Ci-Ce-alkyl, C2-Ce-alkenyl, C2-Ce-alkenyl, Cs-Ce-cycloalkyl, Ci-Ce-haloalkyl, C2-Ce-haloalkenyl, C2-C6-haloalkynyl, Cs-Ce-halocycloalkyl, Ci-C4-alkoxy, Ci-C4-haloalkoxy, Ci-C4-alkylthio, C1-C4-alkylsulphonyl, Ci-C4-haloalkylthio, Ci-C4-haloalkylsulphonyl, Ci-C4-alkoxy-Ci-C4-alkyl, hydroxy-Ci-C4-alkyl, Ci-Ce-alkylcarbonyl, Ci-Ce-alkoxycarbonyl, Ci-Ce-alkylcarbonyloxy or phenyl,

[0470] substituents on nitrogen: Ci-Ce-alkyl, C2-Ce-alkenyl, C2-Ce-alkynyl, Ci-Ce-haloalkyl, C2-Ce-haloalkenyl, C2-Ce-haloalkynyl, Cs-Cio-cycloalkyl-Ci-Ce-alkyl, Ci-Ce-haloalkylcarbonyl, phenyl, benzyl, Ci-C4-alkylsulphonyl, Ci-C4-haloalkylsulphonyl, phenylsulphonyl, — C(C=O)H, or Ci-Ce-alkylcarbonyl,

[0471] B-RG1is the same or different and is independently hydrogen, halogen, hydroxyl, thiol, nitro, cyan, — C(C=O)H, — C(C=O)OH, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, halocycloalkyl, hydroxyalkyl, formylalkyl, alkoxyalkyl, alkylcarbonylalkyl, alkylcycloalkyl, alkoxy, alkylcycloalkylalkyl, alkylthio, aloalkylthio, alkynylthio, alkenyloxy, alkynyloxy, haloalkoxy, alkoxyalkoxy, alkylcarbonyloxy, haloalkylcarbonyloxy, cycloalkylcarbonylamino, alkylsulphonylamino, haloalkylsulphonylamino, phenylsulphonylamino, cycloalkylalkyl, halocycloalkylalkyl, cycloalkylcycloalkyl, alkoxycarbonyloxy, alkylcarbonylthio, alkylsulphinyl, haloalkylsulphinyl, alkylsulphonyl, haloalkylsulphonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, alkylaminocarbonyloxy, — C(C=O)N-B-R3-B-R4or — N-B-R3-B-R4,

[0472] B-R3and B-R4are the same or different and are each independently hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, benzyl or phenyl,

[0473] B-LHS C(B-RL11)2,

[0474] B-RL11is the same or different and is independently hydrogen, halogen, hydroxyl, cyano, — C(C=O)H, — C(C=O)OH, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl,Attorney Docket No. 10620-164W01

[0475] NCSU Ref.: 2025-138-03

[0476] alkoxyalkyl, alkylthioalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxy, alkylthio, haloalkylthio, haloalkoxy, alkylcarbonyloxy, alkylcarbonylamino, alkylcarbonylthio, alkylsulphonyl, haloalkylsulphonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxycarbonyl, trialkylsilyloxy, — N-B-R3-B-R4or — C(C=O)N-B-R3-B-R4, or the two B-RL11radicals, together with the carbon atom to which they are bonded, form a cyclopropyl ring, or the two B-RL11radicals are =CH2, =CO-B-R3, =NO-B-R3or =CHN(B-R9)2,

[0477] B-R9is alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, benzyl or phenyl,

[0478] B-Y is sulphur or oxygen,

[0479] B-X is carbon,

[0480] B-R2is hydrogen,

[0481] B-R10is oxo, alkyl, alkenyl, haloalkyl, alkoxy, halogen, cyano or hydroxyl,

[0482] B-p is 0 or 1,

[0483] B-G is chosen from B-G-l through B-G-l 1

[0484] (B-RB G1) B-G-1 B-G-2 B-G-3 B-G-5

[0485] B-G-6 B-G-7 B-G-8 B-G-9

[0486]

[0487] B-G-11

[0488] where the bond identified by u is bonded directly to B-X and where the bond identified by co is bonded directly to B-Q;

[0489] B-Q is

[0490]

[0491] where the bond is identified by % is bonded directly to B-G and the bond is identified by % bonded directly to B-L2, or the bond is identified by % is bonded directly to B-L2and the bond is identified by % bonded directly to B-G;Attorney Docket No. 10620-164W01

[0492] NCSU Ref.: 2025-138-03

[0493] B-R5is the same or different and is independently:

[0494] bonded to carbon of B-Q: hydrogen, oxo, halogen, cyano, hydroxyl, nitro, — CHO, — C(C=O)OH, — C(C=O)NH2, — C(C=O)N-B-R3-B-R4, — N-B-R3-B-R4, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, halocycloalkylalkyl, alkylcycloalkylalkyl, cycloalkenyl, halocycloalkenyl, alkoxyalkyl, haloalkoxyalkyl, cycloalkoxyalkyl, alkoxyalkoxyalkyl, alkylthioalkyl, formylalkyl, alkylcarbonylalkyl, alkylsulphinylalkyl, alkylsulphonylalkyl, alkylaminoalkyl, dialkylaminoalkyl, haloalkylaminoalkyl, cycloalkylaminoalkyl, alkylcarbonyl, haloalkylcarbonyl, cycloalkylcarbonyl, alkoxycarbonyl, cycloalkoxycarbonyl, cycloalkylalkoxy carbonyl, cycloalkylaminocarbonyl, hydroxyalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkoxy, cycloalkylalkoxy, alkenyloxy, haloalkenyloxy, alkynyloxy, haloalkynyloxy, alkoxyalkoxy, alkylcarbonyloxy, haloalkylcarbonyloxy, cycloalkylcarbonyloxy, alkylcarbonylalkoxy, alkylthio, haloalkylthio, cycloalkylthio, alkylsulphinyl, haloalkylsulphinyl, alkylsulphonyl, haloalkylsulphonyl, cycloalkylsulphonyl, trialkylsilyl, alkylsulphonylamino, haloalkylsulphonylamino,

[0495] bonded to nitrogen of B-Q: hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl, cycloalkylalkyl, phenyl, benzyl, alkylsulphonyl, — C(C=O)H, alkoxy carbonyl or alkylcarbonyl;

[0496] B-L2is a direct bond;

[0497] B-m is 0, 1 or 2;

[0498] B-R20is hydrogen, alkyl or haloalkyl;

[0499] B-R1is unsubstituted phenyl or a phenyl ring substituted by one or more substituents chosen from B-Z1and B-Z4;

[0500] B-Z1is hydrogen, halogen, hydroxyl, — SH, nitro, cyano, C(=O)H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, cycloalkenyl, halocycloalkyl, halocycloalkenyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, cycloalkoxyalkyl, alkylthioalkyl, alkylsulphinylalkyl, alkylaminoalkyl, haloalkylaminoalkyl, cycloalkylaminoalkyl, dialkylaminoalkyl, alkylsulphonylalkyl, alkylcycloalkyl, alkoxy, alkylcycloalkylalkyl, halocycloalkoxy, alkylthio, haloalkylthio, cycloalkylthio, alkenyloxy, alkynyloxy, haloalkoxy, haloalkenyloxy, haloalkynyloxy, cycloalkoxy, alkoxyalkoxy, cycloalkylalkoxy, alkylcarbonyloxy, haloalkylcarbonyloxy, cycloalkylcarbonyloxy, cycloalkylamino, alkylsulphonylamino, haloalkylsulphonylamino, cycloalkylalkyl, halocycloalkylalkyl, cycloalkylcycloalkyl, alkoxyalkoxyalkyl, alkylcarbonylalkoxy, cycloalkylaminocarbonyl, cycloalkylalkoxycarbonyl, alkylcarbonylthio, alkylsulphinyl, haloalkylsulphinyl, alkylsulphonyl,Attorney Docket No. 10620-164W01

[0501] NCSU Ref.: 2025-138-03

[0502] haloalkylsulphonyl, cycloalkylsulphonyl, alkylcarbonyl, haloalkylcarbonyl, cycloalkylcarbonyl, alkoxy carbonyl, cycloalkoxy carbonyl, trialkylsilyl, — N-B-R3-B-R4, — C(C=O)N-B-R3-B-R4or -B-L3-B-Z3,

[0503] B-L3is a direct bond, — CH2 —, — C(C=O) —, sulphur, oxygen, — C(C=O)O —, — C(C=O)NH—, — OC(=O)—, — NHC(=O)—, — N-B-R20—, — C(=S)—, — S(O)B-m—, -CH-B-R20—, — CH-B-R20— CH-B-R20—, — C-B-R20=C-B-R20, — OCH-B-R20—, — CH-B-R20O—, B-Z3is a phenyl radical, naphthalenyl radical or a 5- or 6-membered heteroaryl radical, each of which may contain 0, 1, 2 or 3 substituents, where the substituents are each independently selected from the following list:

[0504] substituents on carbon: halogen, cyano, nitro, hydroxyl, amino, — SH, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkoxyalkyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkoxy, alkenyloxy, alkynyloxy, alkoxyalkoxy, alkylamino, dialkylamino, alkylthio, haloalkylthio, alkylsulphinyl, haloalkylsulphinyl, alkylsulphonyl, haloalkylsulphonyl, trisilylalkyl or phenyl,

[0505] substituents on nitrogen: hydrogen, — C(C=O)H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl, cycloalkylalkyl, alkoxyalkyl, alkylsulphonyl, haloalkylsulphonyl, cycloalkylsulphonyl, phenylsulphonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxycarbonyl, haloalkoxycarbonyl, cycloalkoxycarbonyl, — C(C=O)NR3R4, phenyl or benzyl; and

[0506] B-Z4is alkylsulphonyloxy.

[0507] In some embodiments, B-R5is hydrogen, cyano, — NR3R4, Ci-Ce-alkyl, C2-Ce-alkenyl, C2-Ce-alkynyl, Ci-Ce-haloalkyl, C2-Ce-haloalkenyl, C2-Ce-haloalkynyl, Cs-Cs-cycloalkyl, C3-C8-halocycloalkyl, Cs-Cs-halocycloalkyl, Ci-C4-alkyl-C3-C8-cycloalkyl, C3-C8-cycloalkyl-Ci-C4-alkyl, Ci-C4-alkoxy-Ci-C4-alkyl, C3-C8-cycloalkoxy-Ci-C4-alkyl, Ci-C4-alkoxy-Ci-C4-alkoxy-Ci-C4-alkyl, Ci-C4-alkylthio-Ci-C4-alkyl, Ci-Ce-alkoxy, Ci-Ce-haloalkoxy, Cs-Cs-cycloalkoxy, Cs-Cs-halocycloalkoxy, C3-C8-cycloalkyl-Ci-C4-alkoxy, C2-Ce-alkenyloxy, C2-C6-haloalkenyloxy, C2-Ce-alkynyloxy, C2-Ce-haloalkynyloxy, Ci-C6-alkoxy-Ci-C4-alkoxy, Ci-Ce-alkylcarbonyloxy, Ci-Ce-haloalkylcarbonyloxy, Cs-Cs-cycloalkylcarbonyloxy, Ci-Ce-alkylcarbonyl-Ci-Ce-alkoxy, Ci-Ce-alkylthio, Ci-Ce-haloalkylthio, or Cs-Cs-cycloalkylthio.

[0508] In some embodiments, B-A is chosen from 3,5-bis(difluoromethyl)-lH-pyrazol-l-yl and 5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl.

[0509] In some embodiments, B-L1is chosen from -CH2- and -NH-.

[0510] In some embodiments, B-Y is O, B-X is -CH- and B-R5is hydrogen.

[0511]

[0512] Attorney Docket No. 10620-164W01

[0513] NCSU Ref.: 2025-138-03

[0514] In some embodiments, B-G is B-G-l.

[0515] In some embodiments, the compound can be defined by the formula below

[0516] (B-R2)

[0517] (B-AN ■X)— (B-G)-(B-Q)-(B-L2)-(B-R1

[0518] > B-L1)

[0519]

[0520] wherein p is 0, B-R2is H, B-L2is a direct bond, B-Y is O, B-X is CH, B-G is B-G-l, B-RG1is H, B-R5is H, B-Q is

[0521]

[0522] where the bond is identified by % is bonded directly to B-G and the bond is identified by % bonded directly to B-L2, or the bond is identified by % is bonded directly to B-L2and the bond is identified by % bonded directly to B-G, B-R1is as defined above, and B-A and B-L1are as defined in the table below.

[0523] Ex B-A B-Ll

[0524] B-I-l 3,5-bis(difluoromethyl)-J H-pyrazol-l-yl CH2

[0525] B-I-2 3,5-bis( difluoromethyl)-! H-pyrazol-l-yl CH2

[0526] B-I-3 5 -methyl-3 -(trifluoromethyl)- 1 H-pyrazol- 1 -yl CH2

[0527] B-I-4 3,5-bis(difluoromethyl)-lH-pyrazol-l-yl CH2

[0528] B-I-5 3,5-bis(difluoromethyl)-lH-pyrazol-l-yl CH2

[0529] B-I-6 3,5-bis(difluoromethyl)-lH-pyrazol-l-yl CH2

[0530] B-I-7 5 -methyl-3 -(trifluoromethyl)- 1 H-pyrazol- 1 -yl CH2

[0531] B-I-8 5-methyl-3-(trifluoromethyl)- IH-pyrazol- 1-yl CH2

[0532] B-I-9 5-methyl-3-(trifluoromethyl)- IH-pyrazol- 1-yl CH2

[0533] B-I-10 5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl CH2

[0534] B-I-l 1 5 -methyl-3 -(trifluoromethyl)- IH-pyrazol- 1 -yl CH2

[0535] B-I-12 5-chloro-2-methylphenyl NH

[0536] B-I-13 5-chloro-2-methylphenyl NH

[0537]

[0538] Attorney Docket No. 10620-164W01

[0539] NCSU Ref.: 2025-138-03

[0540] B-I-14 5-chloro-2-methylphenyl NH B-I-15 5 -methyl-3 -(trifluoromethyl)- IH-pyrazol- 1 -yl CH2 B-I-16 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-17 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-18 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-19 5-chloro-2-methylphenyl NH B-I-20 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-21 3,5-bis (difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-22 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-23 5-chloro-2-methylphenyl NH B-I-24 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-25 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-26 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-27 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-28 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-29 5 -methyl-3 -(trifluoromethyl)- IH-pyrazol- 1 -yl CH2 B-I-30 5 -methyl-3 -(trifluoromethyl)- IH-pyrazol- 1 -yl CH2 B-I-31 5 -methyl-3 -(trifluoromethyl)- IH-pyrazol- 1 -yl CH2 B-I-32 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-33 5-chloro-2-methylphenyl NH B-I-34 5 -methyl-3 -(trifluoromethyl)- IH-pyrazol- 1 -yl CH2 B-I-35 3,5-bis(d ifluoromethyl)-lH-pyrazol-l-yl CH2 B-I-36 5-chloro-2-methylphenyl NH B-I-37 5-chloro-2-methylphenyl NH B-I-38 5-methyl- 3-(trifluoromethyl)-lH-pyrazol-l-yl CH2 B-I-39 5 -methyl-3 -(trifluoromethyl)- IH-pyrazol- 1 -yl CH2 B-I-40 5 -methyl-3 -(trifluoromethyl)- IH-pyrazol- 1 -yl CH2 B-I-41 5-chloro-2-methylphenyl NH B-I-42 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-43 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-44 3-( difluoromethyl)-5-methyl-lH-pyrazol-l -yl CH2 B-I-45 5 -methyl-3 -(trifluoromethyl)- 1 H-pyrazol- 1 -yl CH2

[0541]

[0542] Attorney Docket No. 10620-164W01

[0543] NCSU Ref.: 2025-138-03

[0544] B-I-46 5 -methyl-3 -(trifluoromethyl)- IH-pyrazol- 1 -yl CH2 B-I-47 5 -methyl-3 -(trifluoromethyl )- IH-py razol- 1 -y 1 CH2 B-I-48 3,5-bis(difluoromethyl)-I H-pyrazol-l-yl CH2 B-I-49 3-( difluoromethyl)-5-methyl-lH-pyrazol-l -yl CH2 B-I-50 3,5-bis( difluoromethyl)- IH-pyrazo 1-1-yl CH2 B-I-51 3-(difluoromethyl)-5-methyl-lH-pyrazol-l-yl CH2 B-I-52 2,5-dimethylphenyl CH2 B-I-53 3,5-bis(difluoromethyl)-I H-pyrazo 1-1-yl CH2 B-I-54 5-chloro-2-methylphenyl NH B-I-55 3,5-bis( difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-56 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-57 3,5-bis( difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-58 3,5-bis( difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-59 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-60 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-61 5 -methyl-3 -(trifluoromethyl)- IH-pyrazol- 1 -yl CH2 B-I-62 5-methyl- 3-(trifluoromethyl)-lH-pyrazol-l-yl CH2 B-I-63 3,5-bis( difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-64 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-65 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-66 5 -methyl-3 -(trifluoromethyl)- IH-pyrazol- 1 -yl CH2 B-I-67 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-68 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-69 3,5-bis( difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-70 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-71 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-72 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-73 5-(difluoromethyl)-3-methyl-lH-pyrazol-l-yl CH2 B-I-74 2,5-dimethylphenyl NH B-I-75 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-76 3-(difluoromethyl)-5-methyl-lH-pyrazol-l-yl CH2 B-I-77 3,5-bis(difluoromethyl)-lH-pyrazol-l-yI CH2

[0545]

[0546] Attorney Docket No. 10620-164W01

[0547] NCSU Ref.: 2025-138-03

[0548] B-I-78 5 -methyl-3 -(trifluoromethyl)- IH-pyrazol- 1 -yl CH2 B-I-79 5 -methyl-3 -(trifluoromethyl)- IH-pyrazol- 1 -yl CH2 B-I-80 3,5 -bis (difluoromethyl)- IH-py razol- 1 -yl CH2 B-I-81 3,5 -bis (difluoromethyl)- IH-pyrazol- 1 -yl CH2 B-I-82 3,5 -bis (difluoromethyl)- IH-pyrazol- 1 -yl CH2 B-I-83 3,5-bis( difluoromethyl)-lH-pyrazol-l-yI CH2 B-I-84 3,5 -bis (difluoromethyl)- IH-pyrazol- 1 -yl CH2 B-I-85 3,5 -bis (difluoromethyl)- IH-pyrazol- 1 -yl CH2 B-I-86 5 -methyl-3 -(trifluoromethyl)- IH-pyrazol- 1 -yl CH2 B-I-87 3,5-bis(difluoromethyl)-lH-pyrazol-l -yl CH2 B-I-88 3,5-bis( difluoromethyl)- IH-pyrazol- 1-yl CH2 B-I-90 5 -methyl-3 -(trifluoromethyl)- IH-pyrazol- 1 -yl CH2 B-I-91 3,5-bis(difluoromethyl)-lH-pyrazo 1-1-yl CH2 B-I-92 3,5-bis( difluoromethyl)- IH-pyrazo 1-1-yl CH2 B-I-93 5 -methyl-3 -(trifluoromethyl)- IH-pyrazol- 1 -yl CH2 B-I-94 3,5-bis( difluoromethyl)- IH-pyrazo 1-1-yl CH2 B-I-95 5 -methyl-3 -(trifluoromethyl)- 1 H-py razol- 1 -yl CH2 B-I-96 5 -methyl-3 -(trifluoromethyl)- 1 H-py razol- 1 -yl CH2 B-I-97 5 -methyl-3 -(trifluoromethyl)- 1 H-py razol- 1 -yl CH2 B-I-98 5 -methyl-3 -(trifluoromethyl)- 1 H-py razol- 1 -yl CH2 B-I-99 5 -methyl-3 -(trifluoromethyl)- 1 H-py razol- 1 -yl CH2 B-I-100 3,5-bis( difluoromethyl )- IH-pyrazo 1-1 -yl CH2 B-I-101 5 -methyl- 3 -(trifluoromethyl)- 1 H-pyrazol- 1 -yl CH2 B-I-102 3,5-bis( difluoromethyl )- IH-pyrazo 1-1 -yl CH2 B-I-103 5-methyl-3-(trifluoromethyl)-l H-py razol- 1-yl CH2 B-I-104 5-methyl-3-(trifluoromethyl)-l H-py razol- 1-yl CH2 B-I-105 3,5-bis( difluoromethyl)- IH-pyrazo 1-1-yl CH2 B-I-106 3,5-bis( difluoromethyl)- IH-pyrazo 1-1-yl CH2 B-I-107 3,5-bis( difluoromethyl)- IH-pyrazo 1-1-yl CH2 B-I-108 3,5-bis( difluoromethyl)- IH-pyrazo 1-1-yl CH2 B-I-109 5 -methyl- 3 -(trifluoromethyl)- 1 H-pyrazol- 1 -yl CH2 B-I-110 3, 5 -bis (difluoromethyl)- 1 H-py razo 1- 1 -y 1 CH2

[0549]

[0550] Attorney Docket No. 10620-164W01

[0551] NCSU Ref.: 2025-138-03

[0552] B-I-lll 5-methyl-3-(trifluoromethyl)-l H-pyrazol-l-yl CH2 B-I-112 3,5-bis(difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-113 3,5-bis(difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-114 5-methyl-3-(trifluoromethyl)-l H-pyrazol-l-yl CH2 B-I-115 3,5-bis(difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-116 3,5-bis(difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-117 3,5-bis(difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-118 5 -methyl-3 -(tri fluoromethyl)-! H-pyrazol-l-yl CH2 B-I-119 5 -methyl-3 -(tri fluoromethyl)-! H-pyrazol-l-yl CH2 B-I-120 5 -methyl-3 -(tri fluoromethyl)-! H-pyrazol-l-yl CH2 B-I-121 3,5-bis(difluoromethyl)- IH-pyrazol-l-yl CH2 B-I-122 2,5-bis(difluoromethyl)phenyl CH2 B-I-123 2,5-bis(difluoromethyl)phenyl NH B-I-124 3,5-bis( difluoromethyl)- IH-pyrazol-l-yl CH2 B-I-125 5 -methyl-3 -(trifluoromethyl)- IH-py razol- 1 -yl CH2 B-I-127 3,5-bis( difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-128 3,5-bis( difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-129 3,5-bis( difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-130 3,5-bis( difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-131 3,5-bis( difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-132 3,5-bis( difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-133 3,5-bis( difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-134 3,5-bis( difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-135 3,5-bis( difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-136 3,5-bis( difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-137 3,5-bis( difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-138 3,5-bis( difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-139 3,5-bis( difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-140 5 -methyl-3 -(trifluoromethyl)- IH-py razol- 1 -yl CH2 B-I-141 3,5-bis(difluoromethyl)-lH-pyrazo 1-1 -yl CH2 B-I-142 5 -methyl-3 -(trifluoromethyl-lH-py razol- 1 -yl CH2 B-I-143 5-( difluoromethyl)-3-methyl-lH-pyrazol-l-yl CH2

[0553]

[0554] Attorney Docket No. 10620-164W01

[0555] NCSU Ref.: 2025-138-03

[0556] B-I-144 3,5-bis(difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-145 3,5-bis(difluoromethyl)-lH-pyrazol-l-yl CH2 B-I-146 3,5-bis(difluoromethyl)-lH-pyrazol-l-yl CH2

[0557]

[0558] In some embodiments, the compound comprises one of the following

[0559]

[0560] Attorney Docket No. 10620-164W01

[0561] NCSURef: 2025-138-03

[0562] wherein Y is chosen from S, S=O, and S(=O)2.

[0563] In some embodiments, the compound can be defined by the formula below

[0564] (B-R2)

[0565] (B-Y) I

[0566] (B-A). JJ-N B-X)— (B-G)~(B-Q)— (B-L2)— (B-R1)

[0567] > B-L1)

[0568]

[0569] (B P

[0570] wherein p is 0, B-R2is H, B-L2is a direct bond, B-Y is O, B-X is CH, B-G is B-G-l, B-RG1is H, B-R5is H, B-Q is

[0571]

[0572] where the bond is identified by is bonded directly to B-G and the bond is identified by bonded directly to B-L2, or the bond is identified by is bonded directly to B-L2and the bond is identified by bonded directly to B-G, and B-A, B-L1, and B-R1are as defined in the table below.

[0573] Ex B-A B-Ll B-R1

[0574] B-I-l 3,5-bis(difluoromethyl)- J H-pyrazol- 1 - CH2 2- { [3 -(trimethy Isily l)prop-2-yn- 1 - yi yl)oxy{ phenyl

[0575] B-I-2 3,5-bis( difluoromethyl)- 1 H-pyrazol- 1 - CH2 2- { [3 -(naphthalen- 1 -y l)prop-2-yn- 1 -y l)oxy yi {phenyl

[0576] B-I-3 5-methyl-3-(trifluoromethyl)- 1 H- CH2 3 - [N-methoxyethanimidoy l]phenyl pyrazol-l-yl

[0577] B-I-4 3,5-bis(difluoromethy 1)- 1 H-pyrazol- 1 - CH2 2- [(hydroxy imino )methyl)phenyl

[0578] yi

[0579] B-I-5 3,5-bis(difluoromethy 1)- 1 H-pyrazol- 1 - CH2 3-[N-ethoxyethanimidoyl]phenyl

[0580] yi

[0581] B-I-6 3,5-bis(difluoromethy 1)- 1 H-pyrazol- 1 - CH2 3- { [(propan-2-yloxy)imino]methyl}phenyl yi

[0582] B-I-7 5-methyl-3-(trifluoromethyl)- 1 H- CH2 3 - [N-hy droxyethanimidoyl)phenyl pyrazol-l-yl

[0583] B-I-8 5-methyl-3-(trifluorom ethyl)- 1 H- CH2 3- { [(propan-2-yloxy) imino]methyl}phenyl pyrazol-l-yl

[0584] B-I-9 5-methyl-3-(trifluorom ethyl)- 1 H- CH2 3-[N-(propan-2-yloxy)ethanimidoyl)phenyl pyrazol-l-yl

[0585]

[0586] Attorney Docket No. 10620-164W01

[0587] NCSURef: 2025-138-03

[0588] B-I-10 5-methyl-3-(trifluorom ethyl)- 1 H- CH2 3-[(hydroxy imino )methyl)phenyl pyrazol-l-yl

[0589] B-I-ll 5-methyl-3-(trifluoromethyl)- 1 H- CH2 3- [(ethoxy imino)m ethyl] phenyl pyrazol-l-yl

[0590] B-I-12 5-chloro-2-methylphenyl NH 3 - [(ethoxy imino )methy l)pheny 1

[0591] B-I-13 5-chloro-2-methylphenyl NH 3 - { [(Propan-2-yloxy )imino)methy 1 } phenyl B-I-14 5-chloro-2-methylphenyl NH 3 - [(hydroxy imino )methy l)pheny 1 B-I-15 5-methyl-3-(trifluoromethyl)- 1 H- CH2 3-[(methoxy imino )methyl)phenyl pyrazol-l-yl

[0592] B-I-16 3,5-bis(difluoromethy 1)- 1 H-pyrazol- 1 - CH2 3-[(methoxy imino )methyl)phenyl

[0593] yi

[0594] B-I-17 3,5-bis(difluoromethy 1)- 1 H-pyrazol- 1 - CH2 4-[(tert-butoxycarbonyl)amino]phenyl yi

[0595] B-I-18 3,5-bis(difluoromethy 1)- 1 H-pyrazol- 1 - CH2 3 - [N-hy droxyethanimidoyl)phenyl yi

[0596] B-I-19 5-chloro-2-methylphenyl NH 3- [(methoxyimino )methyl)phenyl B-I-20 3,5-bis(difluoromethy 1)- 1 H-pyrazol- 1 - CH2 3-[N-(propan-2-yloxy)ethanimidoyl]phenyl yi

[0597] B-I-21 3,5-bis (difluoromethyl)- 1 H-pyrazol- 1 - CH2 3 - [N-methoxyethanimidoy l)phenyl yi

[0598] B-I-22 3,5-bis(difluoromethy 1)- 1 H-pyrazol- 1 - CH2 3-[(hydroxy imino )methyl]phenyl

[0599] yi

[0600] B-I-23 5-chloro-2-methylphenyl NH 3-[N-methoxyethanimidoyl)phenyl B-I-24 3,5-bis(difluoromethy 1)- 1 H-pyrazol- 1 - CH2 3-[(ethoxyimino )methyl)phenyl

[0601] yi

[0602] B-I-25 3,5-bis(difluoromethy 1)- 1 H-pyrazol- 1 - CH2 4-(Acetylamino)phenyl

[0603] yi

[0604] B-I-26 3,5-bis(difluoromethy 1)- 1 H-pyrazol- 1 - CH2 2- [(methoxy imino )methy l)pheny 1

[0605] yi

[0606] B-I-27 3,5-bis(difluoromethy 1)- 1 H-pyrazol- 1 - CH2 2- [(ethoxy imino)methyl)phenyl

[0607] yi

[0608] B-I-28 3,5-bis(difluoromethy 1)- 1 H-pyrazol- 1 - CH2 2-[N-(propa.n-2-yloxy)ethanimidoyl)phenyl yi

[0609] B-I-29 5-methyl-3-(trifluoromethyl)- 1 H- CH2 2- [(ethoxy imino)methyl)phenyl pyrazol-l-yl

[0610] B-I-30 5-methyl-3-(trifluoromethyl)- 1 H- CH2 2-[N-(propan-2-yloxy)ethanimidoyl]phenyl pyrazol-l-yl

[0611] B-I-31 5-methyl-3-(trifluoromethyl)- 1 H- CH2 2-[N-methoxyetha.nimidoyl)phenyl pyrazol-l-yl

[0612]

[0613] Attorney Docket No. 10620-164W01

[0614] NCSU Ref.: 2025-138-03

[0615] B-I-32 3,5-bis(difluoromethy 1)- 1 H-pyrazol- 1 - CH2 2- [N-methoxyethanimidoy l)phenyl yi

[0616] B-I-33 5-chloro-2-methylphenyl NH 2-[(ethoxyimino )methyl)phenyl

[0617] B-I-34 5-methyl-3-(trifluoromethyl)- 1 H- CH2 2- [(methoxy imino )methy l)pheny 1 pyrazol-l-yl

[0618] B-I-35 3,5-bis(d ifluoromethy 1)- 1 H-pyrazol- 1 - CH2 2-[N-hydroxyethanimidoyl]phenyl

[0619] yi

[0620] B-I-36 5-chloro-2-methylphenyl NH 2- [(hydroxy imino )methy l)pheny 1

[0621] B-I-37 5-chloro-2-methylphenyl NH 2-{[(propa.n-2-yloxy)imino]methyl}phenyl B-I-38 5-methyl- 3 -(trifluoromethyl)- 1H- CH2 2-[(hydroxy imino )methyl]phenyl pyrazol-l-yl

[0622] B-I-39 5-methyl-3-(trifluoromethyl)- 1 H- CH2 2- { [(propan-2-yloxy)imino]methyl}phenyl pyrazol-l-yl

[0623] B-I-40 5-methyl-3-(trifluoromethyl)- 1 H- CH2 2- [hydroxy ethanimidoy l)pheny 1 pyrazol-l-yl

[0624] B-I-41 5-chloro-2-methylphenyl NH 2- [(methoxyimino)methy l)pheny 1

[0625] B-I-42 3,5-bis(difluoromethy 1)- 1 H-pyrazol- 1 - CH2 2- { [(propan-2-yloxy)imino]methyl}phenyl yi

[0626]

[0627] In some examples, the 1,4,2-oxathiazole analog of fluoxapiprolin can be the compound shown below

[0628]

[0629] wherein Y is chosen from S, S=O, and S(=O)2.

[0630] In some examples, the 1,4,2-oxathiazole analogs of fluoxapiprolin can be the compound shown below.

[0631]

[0632] Attorney Docket No. 10620-164W01

[0633] NCSU Ref.: 2025-138-03 Other example analogs of interest include the following:

[0634]

[0635] Attorney Docket No. 10620-164W01

[0636] NCSU Ref.: 2025-138-03

[0637]

[0638] Attorney Docket No. 10620-164W01

[0639] NCSU Ref.: 2025-138-03

[0640]

[0641] Attorney Docket No. 10620-164W01

[0642] NCSU Ref.: 2025-138-03

[0643]

[0644] 1,4,2-Oxathiazole Analogs of Isoxadifen

[0645] Described herein are 1,4,2-oxathiazole analogs of isoxadifen as well as agriculturally acceptable salts and esters thereof. For example, provided herein are 1,4,2-oxathiazole analogs of isoxadifen defined by the formula below

[0646]

[0647] or an agriculturally acceptable salt or ester thereof, wherein

[0648] Y is chosen from S, S=O, and S(=O)2; and

[0649] RAis chosen from hydrogen, Ci-Ce alkyl, and Ci-Ce haloalkyl.

[0650] These compounds can be used as safener compounds. In some embodiments, the safener compound can be one of the following:

[0651]

[0652] In certain embodiments, the safener compound can

[0653]

[0654] These compounds can be as safeners, for example, in place of the existing commercial safener isoxadifen-ethyl.

[0655] Accordingly, provided herein are methods of protecting a cultivated crop plant from injury caused by application of an herbicide. These methods can comprise applying to the cropAttorney Docket No. 10620-164W01

[0656] NCSU Ref.: 2025-138-03

[0657] plant, to seed of the crop plant, or to soil in which the crop plant is growing or is to be grown, an effective safening amount of a safener compound defined by the formula below

[0658]

[0659] or an agriculturally acceptable salt or ester thereof, wherein

[0660] Y is chosen from S, S=O, and S(=O)2; and

[0661] RAis chosen from hydrogen, Ci-Ce alkyl, and Ci-Ce haloalkyl,

[0662] in combination with the herbicide, thereby reducing herbicidal injury to the crop plant without substantially reducing herbicidal activity against undesired vegetation.

[0663] The herbicide can comprise any suitable herbicide known to be safened by isoxadifen-ethyl. For example, the herbicide can comprise an herbicide that inhibits acetolactate synthase (ALS), acetyl-CoA carboxylase (ACCase), and / or 4-hydroxyphenylpyruvate dioxygenase (HPPD), including, for example, sulfonylurea herbicides such as foramsulfuron, rimsulfuron, iodosulfuron, and nicosulfuron, phenoxypropionate herbicides such as fenoxaprop-p-ethyl, and HPPD inhibitors such as mesotrione, isoxaflutole, sulcotrione, and tembotrione. In certain embodiments, herbicide can comprise one or more of dicamba, dicamba / diflufenzopyr mixtures, metribuzin, S-metolachlor, dimethenamide, dimethenamide-P, or flufenacet, optionally together with further herbicidal active ingredients.

[0664] The safened compositions can be applied pre-emergence or post-emergence to the locus of the crop, to foliage, to soil, or as a seed treatment, using methods and application rates conventional for the respective herbicide actives. Suitable crops include monocot and dicot crop plants such as maize (field, sweet, and popcorn types), cereals such as wheat, barley, rye, oats, and triticale, rice, soybean, cotton, canola, oilseed rape, sugar beet, potato, tobacco, and teff, as well as other agronomically important cereals and broadleaf crops. In some embodiments, application of the safened compositions to maize or rice provides selective control of grassy and broadleaf weeds with reduced crop injury relative to the corresponding unsafened herbicide treatment.

[0665] Method of Making

[0666] Also provided herein are methods for preparing 1,4,2-oxathiazoles and oxidized analogs thereof. These methods can comprise contacting a thiohydroximic acid defined by Formula II belowAttorney Docket No. 10620-164W01

[0667] NCSU Ref.: 2025-138-03

[0668] . OH

[0669]

[0670] Formula II

[0671] or a salt or ester thereof, wherein R1is chosen from alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, hetercycloalkyl, alkylcycloalkyl, alkylhetercycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxycarbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, and heterodialkylaminocarbonyl, each optionally substituted with one or more substituents individually chosen from RA; R2is chosen from alkenyl, alkynyl, cycloalkyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxycarbonyl, thioalkylcarbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, thioamido, aryl, and heteroaryl, each optionally substituted with one or more substituents individually chosen from RA; R3is chosen from hydrogen, alkyl, and haloalkyl, wherein the alkyl and haloalkyl groups are optionally substituted with one or more substituents individually chosen from RA; and RAis chosen from hydroxy, halogen, -CN, -NO2, amino, alkylamino, dialkylamino, alkyl, haloalkyl; alkylthio; haloalkylthio; alkoxy, haloalkoxy, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, nitrone, sulfonic acid, sulfonamido, thiol, phosphonate, phosphinyl, aldehyde, trimethylsilyl, hydrazino, azido, isocyanate, aryl, and heteroaryl; with a heterogeneous catalyst under conditions effective to form a 1,4,2-oxathiazole defined by Formula I below

[0672] N

[0673]

[0674] Formula I

[0675] or a salt or ester thereof, wherein R1is chosen from alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, hetercycloalkyl, alkylcycloalkyl, alkylhetercycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxycarbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, and heterodialkylaminocarbonyl, each optionally substituted with one or more substituentsAttorney Docket No. 10620-164W01

[0676] NCSU Ref.: 2025-138-03

[0677] individually chosen from RA; R2is chosen from alkenyl, alkynyl, cycloalkyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxycarbonyl, thioalkylcarbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, thioamido, aryl, and heteroaryl, each optionally substituted with one or more substituents individually chosen from RA; R3is chosen from hydrogen, alkyl, and haloalkyl, wherein the alkyl and haloalkyl groups are optionally substituted with one or more substituents individually chosen from RA; and RAis chosen from hydroxy, halogen, -CN, -NO2, amino, alkylamino, dialkylamino, alkyl, haloalkyl; alkylthio; haloalkylthio; alkoxy, haloalkoxy, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, nitrone, sulfonic acid, sulfonamido, thiol, phosphonate, phosphinyl, aldehyde, trimethylsilyl, hydrazino, azido, isocyanate, aryl, and heteroaryl and optionally oxidizing the 1,4,2-oxathiazole defined by Formula I to generate a sulfoxide or sulfone analog of the 1,4,2-oxathiazole defined by Formula I.

[0678] In some embodiments, contacting the thiohydroximic acid defined by Formula II with the heterogeneous catalyst comprises flowing the thiohydroximic acid defined by Formula II over or through a stationary phase comprising the heterogeneous catalyst. In some examples, the stationary phase can be composed solely of a heterogeneous catalyst (e.g., MnCh powder) for example packaged in a cartridge or disposed in a fixed bed or column. In other examples, the stationary phase can comprise an inert filler and the heterogeneous catalyst. The inert filler can be, for example, a non-porous or a porous solid or filtering aid agent, such as Celite®, bentonite, talc, sand, sodium sulfate, diatomaceous earth, CaO, CaCOs, chalk, MgSC, clay, silica gel, or combinations thereof.

[0679] In certain embodiments, the cyclization of the starting material (SM) defined by Formula II can be performed under continuous flow conditions using a heterogeneous oxidant catalyst, wherein the catalyst is optionally combined with one or more inert filler materials. The incorporation of such fillers can improve flow characteristics within the packed column by reducing back pressure, enhancing permeability, and enabling more uniform distribution of the reaction mixture across the catalytic bed. In some embodiments, the presence of an inert filler further enables operation under simplified conditions, including manual pushing of the reaction mixture through the column (e.g., via syringe or gravity-assisted flow), thereby reducing or eliminating the need for automated pumping systems.Attorney Docket No. 10620-164W01

[0680] NCSU Ref.: 2025-138-03

[0681] The inert filler may be selected from materials that are chemically compatible with the reaction conditions and do not substantially interfere with the oxidation or cyclization process. Suitable fillers include, but are not limited to, celite, sand, diatomaceous earth, silica gel, montmorillonite, alumina, and inorganic salts such as sodium sulfate, calcium carbonate, and sodium chloride, as well as desiccants such as molecular sieves. In certain embodiments, the filler material may also serve secondary roles, such as moisture control, dispersion of the oxidant, or stabilization of reactive intermediates.

[0682] In some embodiments, the heterogeneous oxidant is physically mixed or co-packed with the inert filler within the stationary phase. The proportion of filler relative to the oxidant can vary depending on the desired flow properties and reactivity profile. For example, the filler may be present in an amount ranging from about 2% to about 90% by weight relative to the total packed material. In certain embodiments, the filler is present in an amount of from about 5% to about 50%, and in more preferred embodiments from about 5% to about 30%. Adjustment of the filler ratio can allow fine-tuning of parameters such as residence time, pressure drop across the column, and effective contact between the SM and the oxidant.

[0683] In particular implementations, lower filler loadings may favor higher catalytic density and shorter reaction times, whereas higher filler loadings may facilitate improved flow, reduced clogging, and scalability of the process. The optimal balance between oxidant and filler can be determined empirically based on the nature of the SM, the oxidant employed, solvent system, and desired throughput

[0684] In certain embodiments, flowing the thiohydroximic acid defined by Formula II over or through a stationary phase comprising the heterogeneous catalyst comprises flowing a solution of the thiohydroximic acid defined by Formula II over or through a stationary phase comprising the heterogeneous catalyst at a flow rate of from 0.1 mL / min to 1 L / min. In certain embodiments, the thiohydroximic acid defined by Formula II exhibits a residence time with the heterogeneous catalyst of from 5 minutes to 4 hours, such as from 5 minutes to 2 hours.

[0685] The flow rate can be varied from 10 mL / h to 90 mL / h when using a laboratory syringe pump. Further scaling of the reaction (e.g., larger pumps, larger volumes of stationary phase) will necessarily increase the flowrate). In some embodiments, the reaction can be performed with a flowrate / (column volume) ratio ranging from 1.5 to 25, and up to 50 when using a concentration of 0.014 M of the thiohydroximic acid defined by Formula II. The concentration can be increased from 14 mM to 3.0 M, yet optimal concentration could even be determined or limited by the starting material’s own solubility in the carrier solvent.Attorney Docket No. 10620-164W01

[0686] NCSU Ref.: 2025-138-03

[0687] In some embodiments, the heterogeneous catalyst comprises an oxidant. Oxidants used for benzylic position oxidations are suitable for this cyclization, and the optimal catalyst for a particular cyclization is determined by the chemical compatibility or chemical stability of the starting material being used. Examples of suitable catalysts include, for example, potassium permanganate, chromium dichromate, chromium chromate, chromic acid, hydrogen peroxide, oxone, peracetic acid, and mCPBA. In certain embodiments, the heterogeneous catalyst comprises a metal oxide, such as manganese oxide.

[0688] In some embodiments, the thiohydroximic acid defined by Formula II is contacted with the heterogeneous catalyst at a temperature of from 0 °C to 50 °C, such as from 15 °C to 50 °C or from 15 °C to 30 °C. However, the temperature can be as high as the boiling point of a carrier solvent in which the reaction is performed. In the examples below, reactions were performed in dichloromethane. However, other organic non-protic solvents such as THF, Methyl-THF, DCE, ethyl acetate, and ethyl acetate-heptanes are suitable.

[0689] In some embodiments, the method further comprises regenerating the heterogeneous catalyst.

[0690] Compositions and Methods of Use

[0691] In some embodiments, the 1,4,2-oxathiazoles provided herein are employed in mixtures containing an effective amount of the compound along with at least one agriculturally acceptable adjuvant or carrier. Exemplary adjuvants or carriers include those that are not phytotoxic or significantly phytotoxic to valuable crops, e.g., at the concentrations employed in applying the compositions for selective weed control in the presence of crops, and / or do not react or significantly react chemically with the compounds provided herein or other composition ingredients. Such mixtures can be designed for application directly to weeds or their locus or can be concentrates or formulations that are \diluted with additional carriers and adjuvants before application. They can be solids, such as, for example, dusts, granules, water dispersible granules, or wettable powders, or liquids, such as, and for example, emulsifiable concentrates, solutions, emulsions or suspensions. They can also be provided as a pre-mix or tank-mixed.

[0692] Suitable agricultural adjuvants and carriers that are useful in preparing the compositions described herein are well known to those skilled in the art. Some of these adjuvants include, but are not limited to, crop oil concentrate (mineral oil (85%) + emulsifiers (15%)); nonylphenol ethoxylate; benzylcocoalkyldimethyl quaternary ammonium salt; blend of petroleum hydrocarbon, alkyl esters, organic acid, and anionic surfactant; C9-C11 alkylpolyglycoside; phosphated alcohol ethoxylate; natural primary alcohol (C12-C16) ethoxylate; di-scc-butylphenolAttorney Docket No. 10620-164W01

[0693] NCSU Ref.: 2025-138-03

[0694] EO-PO block copolymer; polysiloxane-methyl cap; nonylphenol ethoxylate + urea ammonium nitrate; emulsified methylated seed oil; tridecyl alcohol (synthetic) ethoxylate (8EO); tallow amine ethoxylate (15 EO); PEG(400) dioleate-99.

[0695] Liquid carriers that can be employed include water and organic solvents. The organic solvents typically used include, but are not limited to, petroleum fractions or hydrocarbons such as mineral oil, aromatic solvents, paraffinic oils, and the like; vegetable oils such as soybean oil, rapeseed oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cottonseed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; esters of the above vegetable oils; esters of monoalcohols or dihydric, trihydric, or other lower polyalcohols (4-6 hydroxy containing), such as 2-ethylhexyl stearate, / 7-butyl oleate, isopropyl myristate, propylene glycol dioleate, di-octyl succinate, di-butyl adipate, di-octyl phthalate and the like; esters of mono-, di- and poly-carboxylic acids and the like. Specific organic solvents include toluene, xylene, petroleum naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol monomethyl ether and diethylene glycol monomethyl ether, methyl alcohol, ethyl alcohol, isopropyl alcohol, amyl alcohol, ethylene glycol, propylene glycol, glycerine, A-methyl-2-pyrrolidinone, N,N-dimethyl alkylamides, dimethyl sulfoxide, liquid fertilizers, and the like. In some embodiments, water is the carrier for the dilution of concentrates.

[0696] Suitable solid carriers include talc, pyrophyllite clay, silica, attapulgus clay, kaolin clay, kieselguhr, chalk, diatomaceous earth, lime, calcium carbonate, bentonite clay, Fuller's earth, cottonseed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell flour, lignin, and the like.

[0697] In some embodiments, one or more surface-active agents are utilized in the compositions of the present disclosure. Such surface-active agents are, in some embodiments, employed in both solid and liquid compositions, e.g, those designed to be diluted with carrier before application. The surface-active agents can be anionic, cationic or nonionic in character and can be employed as emulsifying agents, wetting agents, suspending agents, or for other purposes. Surfactants conventionally used in the art of formulation and which may also be used in the present formulations are described, inter alia, in McCutcheon ’s Detergents and Emulsifiers Annual, MC Publishing Corp., Ridgewood, New Jersey, 1998, and in Encyclopedia of Surfactants, Vol. I-III, Chemical Publishing Co., New York, 1980-81. Typical surface-active agents include salts of alkyl sulfates, such as diethanolammonium lauryl sulfate; alkylarylsulfonate salts, such as calcium dodecylbenzenesulfonate; alkylphenol-alkylene oxide addition products, such as nonylphenol-C₁₅ ethoxylate; alcohol-alkylene oxide addition products,Attorney Docket No. 10620-164W01

[0698] NCSU Ref.: 2025-138-03

[0699] such as tridecyl alcohol-C₁₆ ethoxylate; soaps, such as sodium stearate; alkylnaphthalenesulfonate salts, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2-ethylhexyl) sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryl trimethyl ammonium chloride; polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; salts of mono- and dialkyl phosphate esters; vegetable or seed oils such as soybean oil, rapeseed / canola oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cottonseed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; and esters of the above vegetable oils, e.g., methyl esters.

[0700] Oftentimes, some of these materials, such as vegetable or seed oils and their esters, can be used interchangeably as an agricultural adjuvant, as a liquid carrier or as a surface active agent.

[0701] Other adjuvants commonly used in agricultural compositions include compatibilizing agents, antifoam agents, sequestering agents, neutralizing agents and buffers, corrosion inhibitors, dyes, odorants, spreading agents, penetration aids, sticking agents, dispersing agents, thickening agents, freezing point depressants, antimicrobial agents, and the like. The compositions may also contain other compatible components, for example, other herbicides, plant growth regulants, fungicides, insecticides, and the like and can be formulated with liquid fertilizers or solid, particulate fertilizer carriers such as ammonium nitrate, urea and the like.

[0702] The concentration of the active ingredients in the compositions of this disclosure is generally from about 0.001 to about 98 percent by weight. Concentrations from about 0.01 to about 90 percent by weight are often employed. In compositions designed to be employed as concentrates, the active ingredient is generally present in a concentration from about 5 to about 98 weight percent, preferably about 10 to about 90 weight percent. Such compositions are typically diluted with an inert carrier, such as water, before application. The diluted compositions usually applied to a crop, a field, to weeds or the locus of weeds generally contain about 0.0001 to about 1 weight percent active ingredient and preferably contain about 0.001 to about 0.05 weight percent.

[0703] The present compositions can be applied to crops, a field, weeds or their locus by the use of conventional ground or aerial dusters, sprayers, and granule applicators, by addition to irrigation or flood water, and by other conventional means known to those skilled in the art.

[0704] In some embodiments, the compounds and compositions described herein are applied as a post-emergence application, pre-emergence application, in-water application to flooded paddy rice or water bodies (e.g., ponds, lakes and streams), or bum-down application.Attorney Docket No. 10620-164W01

[0705] NCSU Ref.: 2025-138-03

[0706] In some embodiments, the compounds and compositions provided herein are utilized to control undesirable vegetation, insects, and / or fungus in crops, including but not limited to citrus, apple, rubber, oil, palm, forestry, direct-seeded, water-seeded and transplanted rice, wheat, barley, oats, rye, sorghum, com / maize, pastures, grasslands, rangelands, fallowland, turf, tree and vine orchards, aquatics, or row-crops, as well as non-crop settings, e.g., industrial vegetation management (IVM) or rights-of-way. In some embodiments, the compounds and compositions are used to control woody plants, broadleaf and grass weeds, or sedges.

[0707] In some embodiments, the compounds and compositions provided herein are utilized to control undesirable vegetation, insects, and / or fungus in rice. In certain embodiments, the undesirable vegetation is Brachiaria platyphylla (Groseb.) Nash (broadleaf signal grass, BRAPP), Digitaria sanguinalis (L.) Scop, (large crabgrass, DIGSA), Echinochloa crus-galli (L.) P. Beauv. (barnyardgrass, ECHCG), Echinochloa colonum (L.) LINK (junglerice, ECHCO), Echinochloa oryzoides (Ard.) Fritsch (early watergrass, ECHOR), Echinochloa oryzicola (Vasinger) Vasinger (late watergrass, ECHPH), Ischaemum rugosum Salisb. (saramollagrass, ISCRU), Leptochloa chinensis (L.) Nees (Chinese sprangletop, LEFCH), Leptochloa fascicularis (Lam.) Gray (bearded sprangletop, LEFFA), Leptochloa panicoides (Presl.) Hitchc. (Amazon sprangletop, LEFPA), Panicum dichotomiflorum (L.) Michx. (fall panicum, PANDI), Paspalum dilatatum Poir. (dallisgrass, PASDI), Cyperus difformis L. (smallflower flatsedge, CYPDI), Cyperus esculentus L. (yellow nutsedge, CYPES), Cyperus iria L. (rice flatsedge, CYPIR), Cyperus rotundus L. (purple nutsedge, CYPRO), Eleocharis species (ELOSS), Fimbristylis miliacea (L.) Vahl (globe fringerush, FIMMI), Schoenoplectus juncoides Roxb. (Japanese bulrush, SPCJU), Schoenoplectus maritimus L. (sea clubrush, SCPMA), Schoenoplectus mucronatus L. (ricefield bulrush, SCPMU), Aeschynomene species, (jointvetch, AESSS), Alternanthera philoxeroides (Mart.) Griseb. (alligatorweed, ALRPH), Alisma plantago-aquatica L. (common waterplantain, ALSPA), Amaranthus species, (pigweeds and amaranths, AMASS), Ammannia coccinea Rottb. (redstem, AMMCO), Eclipta alba (L.) Hassk. (American false daisy, ECLAL), Heteranthera limosa (Sw.) Willd. / Vahl (ducksalad, HETLI), Heteranthera reniformis R. & P. (roundleaf mudplantain, HETRE), Ipomoea hederacea (L.) Jacq. (ivyleaf morningglory, IPOHE), Lindernia dubia (L.) Pennell (low false pimpernel, LIDDU), Monochoria korsakowii Regel & Maack (monochoria, MOOKA), Monochoria vaginalis (Burm. F.) C. Presl ex Kunth, (monochoria, MOOVA), Murdannia nudiflora (L.) Brenan (doveweed, MUDNU), Polygonum pensylvanicum L., (Pennsylvania smartweed, POLPY), Polygonum persicaria L. (ladysthumb, POLPE), Polygonum hydropiperoides Michx. (POLHP, mild smartweed), Rotala indica (Willd.) Koehne (Indian toothcup, ROTIN), Sagittaria

[0708] 13Attorney Docket No. 10620-164W01

[0709] NCSU Ref.: 2025-138-03

[0710] species, (arrowhead, SAGSS), Sesbania exaltata (Raf.) Cory / Rydb. Ex Hill (hemp sesbania, SEBEX), or Sphenoclea zeylanica Gaertn. (gooseweed, SPDZE).

[0711] In some embodiments, the compounds and compositions provided herein are utilized to control undesirable vegetation, insects, and / or fungus in cereals. In certain embodiments, the undesirable vegetation is Alopecurus myosuroides Huds. (blackgrass, ALOMY), Apera spica-venti (L.) Beauv. (windgrass, APESV), Avena fatua L. (wild oat, AVEFA), Bromus tectorum L. (downy brome, BROTE), Lolium multiflorum Lam. (Italian ryegrass, LOLMU), Phalaris minor Retz. (littleseed canarygrass, PHAMI), Poa annua L. (annual bluegrass, POANN), Setaria pumila (Poir.) Roemer & J. A. Schultes (yellow foxtail, SETLU), Setaria viridis (L.) Beauv. (green foxtail, SETVI), Cirsium arvense (L.) Scop. (Canada thistle, CIRAR), Galium aparine L. (catchweed bedstraw, GALAP), Kochia scoparia (L.) Schrad. (kochia, KCHSC), Lamium purpureum L. (purple deadnettle, LAMPU), Matricaria recutita L. (wild chamomile, MATCH), Matricaria matricarioides (Less.) Porter (pineappleweed, MATMT), Papaver rhoeas L.

[0712] (common poppy, PAPRH), Polygonum convolvulus L. (wild buckwheat, POLCO), Salsola tragus L. (Russian thistle, SALTR), Stellaria media (L.) Vill. (common chickweed, STEME), Veronica persica Poir. (Persian speedwell, VERPE), Viola arvensis Murr. (field violet, VIOAR), or Viola tricolor L. (wild violet, VIOTR).

[0713] In some embodiments, the compounds and compostions provided herein are utilized to control undesirable vegetation, insects, and / or fungus in range and pasture. In certain embodiments, the undesirable vegetation is Ambrosia artemisiifolia L. (common ragweed, AMBEL), Cassia obtusifolia (sickle pod, CASOB), Centaurea maculosa auct. non Lam.

[0714] (spotted knapweed, CENMA), Cirsium arvense (L.) Scop. (Canada thistle, CIRAR), Convolvulus arvensis L. (field bindweed, CONAR), Euphorbia esula L. (leafy spurge, EPHES), Lactuca serriola L. / Tom. (prickly lettuce, LACSE), Plantago lanceolata L. (buckhom plantain, PLALA), Rumex obtusifolius L. (broadleaf dock, RUMOB), Sida spinosa L. (prickly sida, SIDSP), Sinapis arvensis L. (wild mustard, SINAR), Sonchus arvensis L. (perennial sowthistle, SONAR), Solidago species (goldenrod, SOOSS), Taraxacum officinale G. H. Weber ex Wiggers (dandelion, TAROF), Trifolium repens L. (white clover, TRFRE), or Urtica dioica L. (common nettle, URTDI).

[0715] In some embodiments, the compounds and compositions provided herein are utilized to control undesirable vegetation, insects, and / or fungus found in row crops. In certain embodiments, the undesirable vegetation is Alopecurus myosuroides Huds. (blackgrass, ALOMY), Avena fatua L. (wild oat, AVEFA), Brachiaria platyphylla (Groseb.) Nash (broadleaf signalgrass, BRAPP), Digitaria sanguinalis (L.) Scop, (large crabgrass, DIGSA), EchinochloaAttorney Docket No. 10620-164W01

[0716] NCSU Ref.: 2025-138-03

[0717] crus-galli (L.) P. Beauv. (bamyardgrass, ECHCG), Echinochloa colonum (L.) Link (junglerice, ECHCO), Lolium multiflorum Lam. (Italian ryegrass, LOLMU), Panicum dichotomiflorum Michx. (fall panicum, PANDI), Panicum miliaceum L. (wild-proso millet, PANMI), Setaria faberi Herrm. (giant foxtail, SETFA), Setaria viridis (L.) Beauv. (green foxtail, SETVI), Sorghum halepense (L.) Pers. (Johnsongrass, SORHA), Sorghum bicolor (L.) Moench ssp. Arundinaceum (shattercane, SORVU), Cyperus esculentus L. (yellow nutsedge, CYPES), Cyperus rotundus L. (purple nutsedge, CYPRO), Abutilon theophrasti Medik. (velvetleaf, ABUTH), Amaranthus species (pigweeds and amaranths, AMASS), Ambrosia artemisiifolia L. (common ragweed, AMBEL), Ambrosia psilostachya DC. (western ragweed, AMBPS), Ambrosia trifida L. (giant ragweed, AMBTR), Asclepias syriaca L. (common milkweed, ASCSY), Chenopodium album L. (common lambsquarters, CHEAL), Cirsium arvense (L.) Scop. (Canada thistle, CIRAR), Commelina benghalensis L. (tropical spiderwort, COMBE), Datura stramonium L. (jimsonweed, DATST), Daucus carota L. (wild carrot, DAUCA), Euphorbia heterophylla L. (wild poinsettia, EPHHL), Erigeron bonariensis L. (hairy fleabane, ERIBO), Erigeron canadensis L. (Canadian fleabane, ERICA), Helianthus annuus L. (common sunflower, HELAN), Jacquemontia tamnifolia (L.) Griseb. (smallflower morningglory, JAQTA), Ipomoea hederacea (L.) Jacq. (ivyleaf morningglory, IPOHE), Ipomoea lacunosa L. (white morningglory, IPOLA), Lactuca serriola L. / Tom. (prickly lettuce, LACSE), Portulaca oleracea L. (common purslane, POROL), Sida spinosa L. (prickly sida, SIDSP), Sinapis arvensis L. (wild mustard, SINAR), Solanum ptychanthum Dunal (eastern black nightshade, SOLPT), Xanthium strumarium L. (common cocklebur, XANST).

[0718] In some embodiments, application rates of about 1 to about 5,000 grams / hectare (g / ha) are employed in post-emergence operations. In some embodiments, rates of about 1 to about 5,000 g / ha are employed in pre-emergence operations.

[0719] In some embodiments, the compounds, compositions, and methods provided herein are used in conjunction with one or more other herbicides to control a wider variety of undesirable vegetation. When used in conjunction with other herbicides, the presently claimed compounds can be formulated with the other herbicide or herbicides, tank-mixed with the other herbicide or herbicides or applied sequentially with the other herbicide or herbicides. Some of the herbicides that can be employed in conjunction with the compounds of the present disclosure include: 4- CPA, 4-CPB, 4-CPP, 2,4-D, 2,4-D choline salt, 2,4-D esters and amines, 2,4-DB, 3,4-DA, 3,4- DB, 2,4-DEB, 2,4-DEP, 3,4-DP, 2,3,6-TBA, 2,4,5-T, 2,4,5-TB, acetochlor, acifluorfen, aclonifen, acrolein, alachlor, allidochlor, alloxydim, allyl alcohol, alorac, ametridione, ametryn, amibuzin, amicarbazone, amidosulfuron, aminocyclopyrachlor, aminopyralid, amiprofos-methyl,Attorney Docket No. 10620-164W01

[0720] NCSU Ref.: 2025-138-03

[0721] amitrole, ammonium sulfamate, anilofos, anisuron, asulam, atraton, atrazine, azafenidin, azimsulfuron, aziprotryne, barban, BCPC, beflubutamid, benazolin, bencarbazone, benfluralin, benfuresate, bensulfuron-methyl, bensulide, benthiocarb, bentazon-sodium, benzadox, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzoylprop, benzthiazuron, bicyclopyrone, bifenox, bilanafos, bispyribac-sodium, borax, bromacil, bromobonil, bromobutide, bromofenoxim, bromoxynil, brompyrazon, butachlor, butafenacil, butamifos, butenachlor, buthidazole, buthiuron, butralin, butroxydim, buturon, butylate, cacodylic acid, cafenstrole, calcium chlorate, calcium cyanamide, cambendichlor, carbasulam, carbetamide, carboxazole, chlorprocarb, carfentrazone-ethyl, CDEA, CEPC, chlomethoxyfen, chloramben, chloranocryl, chlorazifop, chlorazine, chlorbromuron, chlorbufam, chloreturon, chlorfenac, chlorfenprop, chlorflurazole, chlorflurenol, chloridazon, chlorimuron, chlomitrofen, chloropon, chlorotoluron, chloroxuron, chloroxynil, chlorpropham, chlorsulfuron, chlorthal, chlorthiamid, cinidon-ethyl, cinmethylin, cinosulfuron, cisanilide, clethodim, cliodinate, clodinafop-propargyl, clofop, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, cloransulam-methyl, CMA, copper sulfate, CPMF, CPPC, credazine, cresol, cumyluron, cyanatryn, cyanazine, cycloate, cyclosulfamuron, cycloxydim, cycluron, cyhalofop-butyl, cyperquat, cyprazine, cyprazole, cypromid, daimuron, dalapon, dazomet, delachlor, desmedipham, desmetryn, di-allate, dicamba, dichlobenil, dichloralurea, dichlormate, dichlorprop, dichlorprop-P, diclofop, diclosulam, diethamquat, diethatyl, difenopenten, difenoxuron, difenzoquat, diflufenican, diflufenzopyr, dimefuron, dimepiperate, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimexano, dimidazon, dinitramine, dinofenate, dinoprop, dinosam, dinoseb, dinoterb, diphenamid, dipropetryn, diquat, disul, dithiopyr, diuron, DMPA, DNOC, DSMA, EBEP, eglinazine, endothal, epronaz, EPTC, erbon, esprocarb, ethalfluralin, ethbenzamide, ethametsulfuron, ethidimuron, ethiolate, ethobenzamid, etobenzamid, ethofumesate, ethoxyfen, ethoxy sulfuron, etinofen, etnipromid, etobenzanid, EXD, fenasulam, fenoprop, fenoxaprop, fenoxaprop-P-ethyl, fenoxaprop-P-ethyl + isoxadifen-ethyl, fenoxasulfone, fenteracol, fenthiaprop, fentrazamide, fenuron, ferrous sulfate, flamprop, flamprop-M, flazasulfuron, florasulam, fluazifop, fluazifop-P-butyl, fluazolate, flucarbazone, flucetosulfuron, fluchloralin, flufenacet, flufenican, flufenpyr-ethyl, flumetsulam, flumezin, flumiclorac-pentyl, flumioxazin, flumipropyn, fluometuron, fluorodifen, fluoroglycofen, fluoromidine, fluoronitrofen, fluothiuron, flupoxam, flupropacil, flupropanate, flupyrsulfuron, fluridone, flurochloridone, fluroxypyr, flurtamone, fluthiacet, fomesafen, foramsulfuron, fosamine, furyloxyfen, glufosinate, glufosinate-ammonium, glyphosate, halosafen, halosulfuron-methyl, haloxydine, haloxyfop-methyl, haloxyfop-P-methyl, halauxifen-methyl, hexachloroacetone, hexaflurate,Attorney Docket No. 10620-164W01

[0722] NCSU Ref.: 2025-138-03

[0723] hexazinone, imazamethabenz, imazamox, imazapic, imazapyr, imazaquin, imazethapyr, imazosulfuron, indanofan, indaziflam, iodobonil, iodomethane, iodosulfuron, iofensulfuron, ioxynil, ipazine, ipfencarbazone, iprymidam, isocarbamid, isocil, isomethiozin, isonoruron, isopolinate, isopropalin, isoproturon, isouron, isoxaben, isoxachlortole, isoxaflutole, isoxapyrifop, karbutilate, ketospiradox, lactofen, lenacil, linuron, MAA, MAMA, MCPA esters and amines, MCPA-thioethyl, MCPB, mecoprop, mecoprop-P, medinoterb, mefenacet, mefluidide, mesoprazine, mesosulfuron, mesotrione, metam, metamifop, metamitron, metazachlor, metazosulfuron, metflurazon, methabenzthiazuron, methalpropalin, methazole, methiobencarb, methiozolin, methiuron, methometon, methoprotryne, methyl bromide, methyl isothiocyanate, methyldymron, metobenzuron, metobromuron, metolachlor, metosulam, metoxuron, metribuzin, metsulfuron, molinate, monalide, monisouron, monochloroacetic acid, monolinuron, monuron, morfamquat, MSMA, naproanilide, napropamide, napropamide-M, naptalam, neburon, nicosulfuron, nipyraclofen, nitralin, nitrofen, nitrofluorfen, norflurazon, noruron, OCH, orbencarb, ortho-dichlorobenzene, orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxapyrazon, oxasulfuron, oxaziclomefone, oxyfluorfen, paraflufen-ethyl, parafluron, paraquat, pebulate, pelargonic acid, pendimethalin, penoxsulam, pentachlorophenol, pentanochlor, pentoxazone, perfluidone, pethoxamid, phenisopham, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenylmercury acetate, picloram, picolinafen, pinoxaden, piperophos, potassium arsenite, potassium azide, potassium cyanate, pretilachlor, primisulfuron-methyl, procyazine, prodiamine, profluazol, profluralin, profoxydim, proglinazine, prohexadione-calcium, prometon, prometryn, propachlor, propanil, propaquizafop, propazine, propham, propisochlor, propoxy carbazone, propyrisulfuron, propyzamide, prosulfalin, prosulfocarb, prosulfuron, proxan, prynachlor, pydanon, pyraclonil, pyraflufen, pyrasulfotole, pyrazogyl, pyrazolynate, pyrazosulfuron-ethyl, pyrazoxyfen, pyribenzoxim, pyributicarb, pyriclor, pyridafol, pyridate, pyriftalid, pyriminobac, pyrimisulfan, pyrithiobac-methyl, pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quinoclamine, quinonamid, quizalofop, quizalofop-P-ethyl, rhodethanil, rimsulfuron, saflufenacil, S-metolachlor, sebuthylazine, secbumeton, sethoxydim, siduron, simazine, simeton, simetryn, SMA, sodium arsenite, sodium azide, sodium chlorate, sulcotrione, sulfallate, sulfentrazone, sulfometuron, sulfosate, sulfosulfuron, sulfuric acid, sulglycapin, swep, TCA, tebutam, tebuthiuron, tefuryltrione, tembotrione, tepraloxydim, terbacil, terbucarb, terbuchlor, terbumeton, terbuthylazine, terbutryn, tetrafluron, thenylchlor, thiazafluron, thiazopyr, thidiazimin, thidiazuron, thiencarbazone-methyl, thifensulfuron, thiobencarb, tiocarbazil, tioclorim, topramezone, tralkoxydim, triafamone, tri-allate, triasulfuron, triaziflam, tribenuron, tricamba, triclopyr esters and amines,Attorney Docket No. 10620-164W01

[0724] NCSU Ref.: 2025-138-03

[0725] tridiphane, trietazine, trifloxysulfuron, trifluralin, triflusulfuron, trifop, trifopsime, trihydroxytriazine, trimeturon, tripropindan, tritac, tritosulfuron, vernolate and xylachlor.

[0726] The compounds and compositions of the present disclosure can generally be employed in combination with known herbicide safeners, such as benoxacor, benthiocarb, brassinolide, cloquintocet (e.g, mexyl), cyometrinil, daimuron, dichloromid, dicyclonon, dimepiperate, disulfoton, fenchlorazole-ethyl, fenclorim, flurazole, fluxofenim, furilazole, harpin proteins, isoxadifen-ethyl, mefenpyr-di ethyl, MG 191, MON 4660, naphthalic anhydride (NA), oxabetrinil, R29148 and / V-phenylsulfonylbenzoic acid amides, to enhance their selectivity.

[0727] The compounds, compositions, and methods described herein be used to control undesirable vegetation, insects, and / or fungus on glyphosate-tolerant-, glufosinate-tolerant-, dicamba-tolerant-, phenoxy auxin-tolerant-, pyridyloxy auxin-tolerant-, aryloxyphenoxypropionate-tolerant-, acetyl CoA carboxylase (ACCase) inhibitor-tolerant-, imidazolinone-tolerant-, acetolactate synthase (ALS) inhibitor-tolerant-, 4-hydroxyphenyl-pyruvate dioxygenase (HPPD) inhibitor -tolerant-, protoporphyrinogen oxidase (PPO) inhibitor -tolerant-, triazine-tolerant-, and bromoxynil-tolerant- crops (such as, but not limited to, soybean, cotton, canola / oilseed rape, rice, cereals, com, turf, etc), for example, in conjunction with glyphosate, glufosinate, dicamba, phenoxy auxins, pyridyloxy auxins, aryloxyphenoxypropionates, ACCase inhibitors, imidazolinones, ALS inhibitors, HPPD inhibitors, PPO inhibitors, triazines, and bromoxynil. The compositions and methods may be used in controlling undesirable vegetation in crops possessing multiple or stacked traits conferring tolerance to multiple chemistries and / or inhibitors of multiple modes-of-action. The compounds and compositions provided herein may also be employed to control herbicide resistant or tolerant weeds. Exemplary resistant or tolerant weeds include, but are not limited to, biotypes resistant or tolerant to acetolactate synthase (ALS) inhibitors, photosystem II inhibitors, acetyl CoA carboxylase (ACCase) inhibitors, synthetic auxins, photosystem I inhibitors, 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase inhibitors, microtubule assembly inhibitors, lipid synthesis inhibitors, protoporphyrinogen oxidase (PPO) inhibitors, carotenoid biosynthesis inhibitors, very long chain fatty acid (VLCFA) inhibitors, phytoene desaturase (PDS) inhibitors, glutamine synthetase inhibitors, 4-hydroxyphenyl-pyruvate-dioxygenase (HPPD) inhibitors, mitosis inhibitors, cellulose biosynthesis inhibitors, herbicides with multiple modes-of-action such as quinclorac, and unclassified herbicides such as arylaminopropionic acids, difenzoquat, endothall, and organoarsenicals. Exemplary resistant or tolerant weeds include, but are not limited to, biotypes with resistance or tolerance to multiple herbicides, multiple chemical classes, and multiple herbicide modes-of-action.Attorney Docket No. 10620-164W01

[0728] NCSU Ref.: 2025-138-03

[0729] By way of non-limiting illustration, examples of certain embodiments of the present disclosure are given below.

[0730] EXAMPLES

[0731] Example 1. In-Flow Synthesis of 1,4,2-Oxathiazoles

[0732] Summary

[0733] 1,4,2-Oxathiazoles represent a unique and underexplored class of heterocycle, with potential agrochemical applications similar to the 1,2,4-oxadiazole and 1, 4, 2-di oxazole classes of 5-membered heterocycles. In this example, we report a facile, mild, efficient, and convenient in-flow synthesis of the 1,4,2-oxathiazole scaffold utilizing a manganese dioxide-mediated oxidative cyclization of thiohydroximic acids as an alternative to previous approaches. This method affords 3-, or 5- substituted pyridinyl-, 5-pyrimidinyl-, 5-ethynyl- and 5-benzothiazolyl-substituted 1,4,2-oxathiazole scaffolds which were previously inaccessible due to the harsh reaction conditions. Additionally, the efficiency of the manganese dioxide columns was evaluated for use in gram-scale synthesis.

[0734] Introduction

[0735] Heterocycles are ubiquitous in agrochemical and therapeutic agents and can be found in more than 90% of drugs under development, with nitrogen, oxygen, and sulfur being the three most common heteroatoms. Five-membered N- and (9-containing heterocycles are a prominent class in recently FDA-approved pharmaceuticals and agrochemical agents. Additionally, heterocyclic five-membered rings containing more than two heteroatoms, such as 1,3,4- and 1,2,4-oxadiazoles (1-2), and thiadiazoles (3-4) (Figure 1, panel a) have been commonly used to improve the pharmacokinetics and dynamics of bioactive lead compounds.2 4Additionally, 1,3,4-thiadiazole scaffolds have been reported to have antiviral activity, anticancer and antimalarial activity.5 8Additionally, these scaffolds are structural components of FDA-approved drugs such as cefazolin,9,10megazol,11methazolamide,12,13and azetepa.14,15

[0736] In the updated ranking of the most common nitrogen-containing heterocycles in approved drugs (2013-2023), structures bearing more than two heteroatoms are largely dominated by polyaza heterocycles (5a-h), with thiadiazole being a notable sulfur-containing exception (Figure 1, panel b).16Although sulfur remains the sixth most common atom in FDA-approved drugs (-23% of compounds),16classic sulfur-rich scaffolds like cephems (6a), thiazoles (6b), penams (6c), and phenothiazines (6d) (Figure 1, panel c) have significantly declined in prominence fromAttorney Docket No. 10620-164W01

[0737] NCSU Ref.: 2025-138-03

[0738] 2013¹⁷ to 2023, replaced mainly by nitrogen-containing or simpler heterocyclic systems. While the structural reasons behind this trend are not always explicitly stated, improved synthetic accessibility, broader tunability, and changing therapeutic priorities likely contribute. This shift highlights a key opportunity: developing new synthetic methods to access various sulfur-containing heterocycles could revitalize this important class and expand chemical space for future drug discovery.

[0739] 1,4,2-Oxathiazoles are a highly underreported class of N, O, S- containing heterocycles. This scaffold represents an alternative to the heavily prevalent N- and O- containing five-membered heterocycles lacking the additional sulfur atom. There are limited reports of the reactivity and methods for preparation of 1,4,2-oxathiazoles. Among such available strategies, the [3+2] cycloaddition of benzonitrile A-oxides and phenyl trimethyl silyl thioketone18has been reported, although this approach requires a highly reactive thioketone surrogate (Figure 2, panel a).

[0740] Another method reported for the synthesis of these 1,4,2-oxathiazoles utilizes the corresponding 3,5-diphenyl thiohydroximic acids with A-bromosuccinimide or iodine and a base to promote the oxidative cyclization (Figure 2, panel a).19Other reported methods have used 5-glucosyl-thiohydroximic acids to access the corresponding 1,4,2-oxathiazole via a radical pathway.20

[0741] We have also reported the synthesis of 1,4,2-oxathiazoles from thiohydroximic acids via oxidative cyclization using DDQ under acidic conditions and high temperatures (Figure 2, panel b).21Although this method provides ease of access to these unique heterocycles and other related heterocycles like the 1,2,4-oxadiazoles,22’23the use of p-TsOH acid, excessive temperatures necessary for conversion, and harsh oxidative environment hindered the scope of this reaction.21Results and Discussion

[0742] Accordingly, we desired to find milder conditions to perform this oxidative cyclization. The potential of heterogeneous catalysis for this process particularly caught our attention as several metal oxides have been reported to promote the generation of C-centered radicals in benzylic systems and (9-centered radicals in oximes.24 28Batch processes have been a traditional approach to synthesis since the origin of organic synthesis; however, with an increased focus towards more sustainable alternatives and better process mass intensity (PMI) scores on total processes,29flow chemistry has become of great interest to industrial applications due to its ability to generate large quantities of material while minimizing the consumption of reagents, catalysts, and solvents. Cartridge-based heterogeneous catalysis is one of the most commonAttorney Docket No. 10620-164W01

[0743] NCSU Ref.: 2025-138-03

[0744] applications of flow chemistry and we envisioned that heterogeneous catalysts such as MnCh could be suitable for flow applications with our thiohydroximic acid substrates.

[0745] To explore the potential of this approach we accessed the thiohydroximic acid precursors through a procedure previously reported,21accessing a total of 24 thiohydroximic acids bearing different substituents to expand on our previously reported substrate scope (Figures 5-6). We began exploring different conditions using heterogeneous catalysis with MnCh in a traditional round bottom fashion, which has been widely used for benzylic, allylic, and propargylic oxidation reactions30 32and oxime radical generation.28We proceeded to explore and optimize the reaction (Table 1), and initial screening of the reaction at equimolar amounts of oxidant and substrate (12a) did not yield 12b, but we observed trace amounts of a byproduct.

[0746] Further increase of the equivalents of MnCh led to elevated yields of 12b and the formation of smaller amounts of the byproduct. We found that a reduction of the reaction duration and an increase in the amount of MnCh up to 30 equivalents improved the formation of 12b, while the byproduct formation was reduced. Optimal results using a batch setup to obtain 12b were found in to be the use of 30 equivalents of Mn02 with dichloromethane as the solvent for 30 minutes. Other metal oxides, such as Ag2O, known to generate benzylic-centered radicals, failed to convert thiohydroxamic acids into the desired product 12b.Attorney Docket No. 10620-164W01

[0747] NCSU Ref.: 2025-138-03

[0748] Table 1. Optimization of oxidative cyclization.

[0749] N'OHoxidant

[0750]

[0751] + byproduct Ph S Ph solvent, Pti ^$

[0752] 12a rt, time 12b

[0753]

[0754] Yield* (%) entry oxidant solvent time 12b byproduct 1 1 equiv MnO2Heptane 2 hours 0

[0755]

[0756] 2 5 equiv MnO2Heptane 2 hours 0 4 3 10 equiv MnO2Heptane 2 hours 7 8 4 15 equiv MnO2Heptane 2 hours 15 11 5 30 equiv MnO2Heptane 30 min 25 10 6 30 equiv MnO2CH2CI230 min 45 11 7 30 equiv MnO2CHCI330 min 42 15 8 30 equiv MnO2CCI430 min 29 10 9 30 equiv MnO2DCE 30 min 45 12 10 30 equiv MnO2Benzene 30 min 37 10 11 30 equiv MnO2MeCN 30 min 33 8 12 30 equiv MnO2DMF 30 min 22 9 13 3 equiv Ag2O Benzene 4 hours 0 0 *Yields reported are NMR yields

[0757] Having demonstrated successful cyclization, we envisioned using similar reaction conditions in a flow-chemistry setup, hoping that the reduced reaction times would allow us to reduce the amount of byproduct formed; an established approach to produce dimerization sensitive products like diazo compounds.33,34To evaluate the potential of this approach, we decided to use an in-house assembled MnCh column using a syringe pump to ensure constant flow through the MnCh column (Figure 3).Attorney Docket No. 10620-164W01

[0758] NCSU Ref.: 2025-138-03

[0759] We first explored the effects of different flow rates in the conversion of the substrate into product and byproduct generation, and found that 0.5 to 1.0 mL / min resulted in optimal conversion to the product and elimination of the byproduct formation. We were pleased to observe that the inflow approach allowed us to increase the yields from 45% to 80%.

[0760] With these results in hand, we decided to explore the cyclization of similar substrates to those reported with the DDQ cyclization and with mono- and di-functionalized thiohydroximic acids. The cyclization of phenyl-, mono- and dihalogenated, methoxy-, thiophene-, trifluoromethyl-, or nitro-substituted thiohydroximic acid derivatives (12b-22b and 26b-32b) resulted in isolated yields up to 80% (Figure 5), comparable to the yields obtained with our previous method.

[0761] Next, we focused on scaffolds found to be inaccessible using the DDQ method. Initially, we explored the cyclization of the vinyl thiohydroximic acid 37a. In our previous report, the oxidation of different vinylogous positions resulted in low yields. Under our optimized flow conditions the vinyl oxathiazole 37b was obtained in a slightly higher yield of 26% compared to the 16% previously reported. Propargyl oxathiazole (36b) which was previously inaccessible, was now synthesized in a modest 25% yield. Similar results were obtained for other N-containing n-deficient heterocycles, highlighting the broader scope of this flow-based method. We observed that if the 7i-deficient moiety was at the 3-position of the oxathiazole (23b and 24b), it resulted in lower yields than when the ^-containing moiety was in the 5-position of the oxathiazole heterocycle (33-35b). Surprisingly, the 5-(pyrimidin-5-yl) analog resulted in 73% yield, while all the other ^-containing derivatives resulted in modest yields ranging 13-37%. Though modest, these yields highlight the challenges of accessing novel heterocycles and underscore our method's significance in their synthesis.

[0762] Even though this cyclization strategy was improved with respect to our other methods, due to milder reaction conditions, faster reaction times, flow-chemistry approach, and expanded analog scope, it also had some limitations. For example, the nature of the substituent in the 5-position of the oxathiazole influenced whether the reaction would proceed. Cyclization attempts proved unsuccessful when / 7-al ky 1 or carbonyl moieties were present in the 5-position of the oxathiazole (Figure 6). Mechanistically, it is not certain whether the reaction proceeds via an oxime-type radical or benzylic oxidation as the initiating step; however, studies suggest that either mechanistic paradigm could be operative.28,35’36

[0763] To evaluate the efficiency of our new flow chemistry method, we conducted an assay using thiohydroximic acid 12a as the substrate. A total of 1.0 g of 12a was passed through a 7.0 g MnCE column, with all other parameters consistent with previous cyclization procedures. DuringAttorney Docket No. 10620-164W01

[0764] NCSU Ref.: 2025-138-03

[0765] the experiment, we observed partial retention of the product on the column, causing a delay between the injection of 12a and the collection of the oxathiazole (Figure 4). Initially, product formation followed an almost linear increase, eventually stabilizing at a product formation rate of 80-90%. However, after 500 mg of 12a were injected into the column (150 mL, 14 mM), unreacted starting material began eluting from the column, leading to a reduction in product formation and indicating that column saturation was occurring. Throughout the entire duration of the experiment, the flow was maintained at a constant rate between 0.75 to 1.0 mL / min, although a consistent increase in the system's pressure was detected. We hypothesized that this increase in pressure was due to the formation of amorphous manganese hydroxide (II), which clogged the column and produced the pressure increase, which ultimately caused the syringe pump to stop before the experiment was completed. Based on our results, the setup using the 7.0 g MnCh columns appears well-suited for reactions on a 500 mg scale (equivalent to 150 mL injected into the column). Scaling beyond this level would require either a larger column or additional measures to mitigate backpressure buildup. Further developments in scaling up this process will be reported in due course.

[0766] Overall, the column efficiency assay resulted in 61% yield and 11% of 12a recovered from pumping 900 mg of 12a (270 mL) through the 7 g column. If we consider that no starting material was detected until after the first 500 mg were injected into the column, we estimate that these 7 g Mn02 columns are suitable for carrying out this transformation in 500 mg scale.

[0767] Additionally, we confirmed that the used column filling can be regenerated in the oven overnight at 140 °C, thereby regenerating its oxidative capacity.

[0768] Conclusion

[0769] In summary, we have reported an improved, operationally simpler, and milder (oxidant used and temperature) MnCh-mediated oxidative cyclization of thiohydroximic acids into 1,4,2-oxathiazoles via flow. This procedure enabled access to an expanded library of heterocycles, including A-containing aromatic and propargylic analogs that were too sensitive to be cyclized under harsher oxidative conditions. Moreover, our flow-based approach enables improved handling and potential for scalability of this process, while using a more environmentally benign and reusable oxidizing agent.

[0770] Materials and Methods

[0771] General experimental procedures: All reactions were carried out under an inert atmosphere with anhydrous solvents in a flame-dried apparatus unless otherwise stated. Organic solvents were removed under reduced pressure at or below 40 °C. Yields refer to isolated yields following chromatography unless otherwise stated. Flash chromatography on SiO2 was used toAttorney Docket No. 10620-164W01

[0772] NCSU Ref.: 2025-138-03

[0773] purify the crude reaction mixtures and performed on a Biotage Isolera utilizing Biotage cartridges and linear gradients. Reactions were monitored by thin layer chromatography (TLC) analysis (pre-coated silica gel 60 F254 plates, 250 mm layer thickness) and by LC-MS (2.6 mm Cl 8 x 2.10 mm column).

[0774] Materials: Dichloromethane (CH2CI2) was obtained by passing the previously degassed solvents through activated alumina columns under nitrogen atmosphere. Extra dry N, N-Dimethylformamide (DMF, 99.8%) was purchased from Fischer Scientific. Deuterated solvents were purchased from Cambridge Isotopes. Technical grade (90%) manganese dioxide (MnCh) was activated in a 61 L Thermo Fischer oven overnight at 140 °C prior to use. All other reagents were purchased from commercial chemical companies and used without further modification, unless otherwise stated.

[0775] Instrumentation:JH and13C NMR spectra were obtained on a 500 or 600 MHz instrument in CDCh or (CD3)2SO. Chemical shifts (5) were reported in parts per million (ppm) with the residual solvent peak used as an internal standard (CDCh 'H NMR = 7.26 ppm,13C NMR = 77.16 ppm; (CD3)2SO 1H NMR = 2.50 ppm, 13C NMR = 39.52 ppm) and multiplicities are reported as observed. The following abbreviations were used to report NMR peak multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, p = pentet, m = multiplet, dd = doublet of doublets, dt = doublet of triplets, td = triplet of doublets, ddt = doublet of doublets of triplets, ddd = doublet of doublets of doublets. Infrared spectra were determined on the Agilent Cary 630 FTIR spectrometer and data are represented as frequency of absorption (cm-1). High-resolution mass spectra were obtained on the Thermo Fisher Scientific Exploris 480 MS, a benchtop full-scan OrbitrapTM mass spectrometer using Heated Electrospray Ionization (HESI). Melting points were obtained using Digimelt MPA160 melting point apparatus.

[0776] General Procedure A for the Synthesis of Thiohydroximic Acids: To a 1 M solution of the benzaldehyde oxime derivative in dry dimethylformamide at 0 °C was added one-fifth of the total N-chlorosuccinimide, followed by portion-wise addition of the reagent over one hour. During this time, the reaction was allowed to warm slowly to room temperature and stir at this temperature for three hours. The reaction mixture was then diluted with diethyl ether to a concentration of 0.1 M and cooled back to 0 °C. Benzyl mercaptan was then added, followed by triethylamine, and the reaction was allowed to stir overnight while warming to room temperature. The reaction was quenched by the addition of saturated ammonium chloride and diluted with deionized water. The aqueous layer was extracted with ethyl acetate. The combined organic fractions were washed with saturated lithium chloride (5% w / v), water, brine, dried overAttorney Docket No. 10620-164W01

[0777] NCSU Ref.: 2025-138-03

[0778] anhydrous sodium sulfate, fdtered, and concentrated in vacuo. The crude mixture was purified via flash chromatography to afford the desired product.

[0779] General Procedure B for the Synthesis of Thiohydroximic Acids: To a 0.1 M solution of A-hydroxy benzothioamide in diethyl ether was added successively the corresponding benzyl chloride / bromide derivative, tetra-n-butyl ammonium iodide, and triethyl amine at room temperature, and the reaction mixture was allowed to stir for three hours. The reaction was quenched with saturated ammonium chloride and left stirring for fifteen minutes. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with water, 1 M hydrochloric acid, and brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude mixture was purified via flash chromatography.

[0780] General Procedure C for the Synthesis of Thiohydroximic Acids: To a 1 M solution of benzaldehyde oxime in dry dimethylformamide at 0 °C was added one- fifth of the total N-chlorosuccinimide, followed by portion-wise addition of the reagent over one hour. During this time, the reaction was allowed to warm slowly to room temperature and stir at this temperature for three hours. The reaction mixture was then diluted with diethyl ether to a concentration of 0.1 M and cooled back to 0 °C. The mercaptan derivative was then added, followed by triethylamine, and the reaction was allowed to stir overnight while warming to room temperature. The reaction was quenched by the addition of saturated ammonium chloride and diluted with deionized water. The aqueous layer was extracted with ethyl acetate. The combined organic fractions were washed with saturated lithium chloride (5% w / v), water, brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude mixture was purified via flash chromatography to afford the desired product

[0781]

[0782] 5-(2,6-dichlorophenyl)-3-phenyl-l,4,2-oxathiazole was synthesized following Procedure A in 80% yield (3.45 g) as a white solid.

[0783]

[0784] Benzyl / V-hydroxy-4-(trifluoromethyl)benzimidothioate was synthesized following Procedure A in 72% yield (118 mg) as a white crystalline solid. R / = 0.43 (20% EtOAc in hexanes). NMR (500 MHz, CDCk) 87.63 (d, J= 8.1 Hz, 2H), 7.56 (d, J= 8.1 Hz, 2H), 7.24Attorney Docket No. 10620-164W01

[0785] NCSU Ref.: 2025-138-03

[0786] - 7.19 (m, 3H), 7.09 - 7.04 (m, 2H), 3.91 (s, 2H).13C NMR (126 MHz, CDCh) 8 154.00, 137.20, 136.69, 131.82 (q, J= 32.6 Hz), 129.14, 128.78, 128.73, 127.69, 125.68 (q, J= 3.7 Hz), 123.93 (q, J= 272.4 Hz), 36.49. IR (Diamond-ATR, neat) vmax: 3315, 3042, 2948, 2879, 1605, 1478, 1431, 1346, 1180, 1111, 1079 cm’1. HRMS (m / z)-. calculated for C15H13F3NOS [M+H]+312.0665, found 312.0655. Melting Point: 108 °C

[0787]

[0788] Benzyl 4-chloro- / V-hydroxy-2-(trifliioromethyl)benzimidothioate was synthesized following Procedure A in 73% yield (378 mg) as a white powder. R = 0.51 (20% EtOAc in hexanes). NMR (500 MHz, CDCh) 88.53 (s, 1H), 7.71 (d, J= 2.2 Hz, 1H), 7.49 (dd, J= 8.3, 2.2 Hz, 1H), 7.26 - 7.20 (m, 4H), 7.06 - 7.02 (m, 2H), 3.61 (s, 2H).13C NMR (126 MHz, CDCh) 8 152.91, 136.18, 135.73, 133.17, 132.04, 131.13 (q, J= 31.8 Hz), 129.53, 128.90, 128.70, 127.75, 127.22 (q, J= 5.1 Hz), 122.75 (q, J = 274.7 Hz), 35.75. IR (Diamond-ATR, neat) vmax: 3219, 3086, 2954, 2766, 1502, 1420, 1413, 1298, 1234 cm HRMS (m / z)-. calculated for C15H12CIF3NOS [M+H]+346.0275, found 346.0266. Melting Point: 147 - 148

[0789]

[0790] Benzyl 4-chloro-2-fluoro- / V-hydroxybenzimidothioate was synthesized following Procedure A in 91% yield (724 mg) as a white powder. R = 0.43 (20% EtOAc in hexanes). 'H NMR (500 MHz, CDCh) 87.24 - 7.19 (m, 3H), 7.17 - 7.11 (m, 3H), 7.07 - 7.04 (m, 2H), 3.76 (s, 2H).13C NMR (126 MHz, CDCh) 8 160.85, 158.82, 151.17, 136.98 (d, J= 9.7 Hz), 136.17, 132.03, 128.70 (d, J= 11.9 Hz), 127.62, 125.01 (d, J= 3.7Hz), 119.80 (d, J= 15.0 Hz), 117.04 (d, J= 24.4 Hz), 35.54. IR (Diamond-ATR, neat) vmax: 3278, 3099, 3043, 2973, 1620, 1502, 1428, 1200 cm’1. HRMS (m / z)-. calculated for C14H12CIFNOS [M+H]+296.0307, found 296.0298. Melting Point: 97 °C.

[0791]

[0792] Attorney Docket No. 10620-164W01

[0793] NCSU Ref.: 2025-138-03

[0794] Benzyl.4-diclil()r()- \-liydr()xybenziinidothioate was synthesized following Procedure A in 27% yield (230 mg) as a white powder. R / ’= 0.42 (20% EtOAc in hexanes).JH NMR (600 MHz, CDCh) 87.53 (d, J =2.1 Hz, 1H), 7.44 (d, J= 8.3 Hz, 1H), 7.31 (dd, J = 8.3, 2.1 Hz, 1H), 7.28 - 7.20 (m, 3H), 7.12 - 7.10 (m, 2H), 3.94 (s, 2H).13C NMR (151 MHz, CDCh) 8 152.90, 136.69, 134.31, 133.69, 133.06, 130.64, 130.53, 128.81, 128.77, 127.83, 127.77, 36.65. IR (Diamond-ATR, neat) vmax: 3302, 3701, 2987, 2907, 1588, 1543, 1454, 1372, 1260, 1223, 1126 cm HRMS (m / z)-. calculated for C14H12CI2NOS [M+H]+312.0011, found 312.0003. Melting Point: 102- 104 °C.

[0795]

[0796] Benzyl 2.6-dichloro-\-hydro\ybenziniidothioate was synthesized following Procedure A in 41% yield as a white solid. R = 0.28 (20% EtOAc in hexanes). 'H NMR (500 MHz, CDCk) 87.35 (d, J= 2.0 Hz, 1H), 7.34 (d, J= 0.7 Hz, 1H), 7.30 (dd, J= 9.3, 6.5 Hz, 1H), 7.22 -7.18 (m, 3H), 7.10 - 7.06 (m, 2H), 3.64 (s, 2H).13C NMR (151 MHz, CDCh) 8 153.05, 135.93, 135.58, 131.40, 130.81, 128.98, 128.61, 128.33, 127.66, 35.03. IR (Diamond-ATR, neat) vmax: 3168, 3101, 2967, 2818, 1580, 1476, 1439, 1409, 1282 cm’1. HRMS (m / z)-. calculated for C14H12CI2NOS [M+H]+312.0017, found 312.0014. Melting Point: 165 - 167 °C.

[0797]

[0798] Benzyl 3-bromo-5-chloro- / V-hydroxybenzimidothioate was synthesized following Procedure A in 86% yield (572 mg) as a white powder. R = 0.51 (20% EtOAc in hexanes). 'H NMR (600 MHz, CDCh) 87.56 (t, J= 1.9 Hz, 1H), 7.47 (t, J= 1.6 Hz, 1H), 7.37 (t, J= 1.7 Hz, 1H), 7.29 - 7.22 (m, 3H), 7.17 - 7.08 (m, 2H), 3.96 (s, 2H).13C NMR (151 MHz, CDCh) 8 152.52, 136.82, 136.61, 135.45, 132.64, 129.96, 128.81, 128.79, 127.80, 127.59, 122.94, 36.62.

[0799] IR (Diamond-ATR, neat) vmax: 3192, 3064, 3008, 1567, 1461, 1426, 1342, 1250 cm’1. HRMS (m / z)'. calculated for CuH BrCINOS [M+H]+355.9506, found 355.9498. Melting Point: 114 — 115°C.Attorney Docket No. 10620-164W01

[0800] NCSU Ref.: 2025-138-03

[0801]

[0802] a

[0803] Benzyl 2-bromo-5-chloro- / V-hydroxybenzimidothioate was synthesized following Procedure A in 39% yield (290 mg) as an off-white powder. R = 0.41 (20% EtOAc in hexanes).

[0804] 'H NMR (500 MHz, CDCh) 87.54 (d, J= 8.5 Hz, 1H), 7.24 (dd, J= 8.6, 2.7 Hz, 1H), 7.22 (dd, J= 4.9, 1.9 Hz, 3H), 7.07 (d, J= 2.5 Hz, 1H), 7.05 - 7.03 (m, 2H), 3.69 (s, 2H).13C NMR (126 MHz, CDCh) 8 155.00, 136.00, 135.29, 134.14, 133.84, 131.60, 131.20, 128.80, 128.65, 127.70, 121.31, 35.42. IR (Diamond-ATR, neat) vmax: 3122, 2981, 2816, 1557, 1374, 1270, 1226 cm HRMS (m / z)-. calculated for CuH BrCINOS [M+H]+355.9506, found 355.9496. Melting Point: 153 - 155 °C

[0805]

[0806] Benzyl 2-bromo-6-chloro- / V-hydroxybenzimidothioate was synthesized following Procedure A in 39% yield (300 mg) as a white powder. R = 0.30 (20% EtOAc in hexanes). 'H NMR (500 MHz, CDCh) 87.53 (dd, J= 8.1, 1.1 Hz, 1H), 7.39 (dd, J= 8.1, 1.1 Hz, 1H), 7.24-7.18 (m, 4H), 7.12 - 7.07 (m, 2H), 3.63 (s, 2H).13C NMR (126 MHz, CDCh) 8 154.40, 135.82, 135.53, 132.58, 131.68, 131.52, 129.05, 128.90, 128.61, 127.66, 125.24, 35.11. IR (Diamond-ATR, neat) vmax: 3153, 3019, 2945, 1551, 1454, 1424, 1245, 1193 cm’1. HRMS (m / z)-. calculated for CuH BrCINOS [M+H]+355.9506, found 355.9495. Melting Point: 154 - 155 °C

[0807]

[0808] Benzyl 3-biomo- / V-hydioxy-4-methoxybenzimidothioate was synthesized following Procedure A in 84% yield (547 mg) as an off-white solid. R / = 0.21 (20% EtOAc in hexanes).

[0809] 'H NMR (500 MHz, CDCh) 87.70 (d, J= 2.2 Hz, 1H), 7.45 (dd, J= 8.5, 2.2 Hz, 1H), 7.33 -7.24 (m, 3H), 7.19 - 7.13 (m, 2H), 6.92 (d, J= 8.6 Hz, 1H), 3.98 (s, 2H), 3.97 (s, 3H).13C NMR (151 MHz, CDCh) 8 157.34, 154.09, 136.86, 133.62, 129.21, 128.88, 128.73, 127.67, 127.02, 111.94, 111.67, 56.53, 36.74. IR (Diamond-ATR, neat) vmax: 3119, 3012, 2825, 2020, 1833, 1495, 1450, 1275, 1251, 1000 cm’1. HRMS (m / z)-. calculated for Ci5Hi5BrNO2S [M+H]+ 352.0007, found 352.0003. Melting Point: 90 - 93 °C.Attorney Docket No. 10620-164W01

[0810] NCSU Ref.: 2025-138-03

[0811] BenzylN-hydroxy-3-methylthiophene-2-carbimidothioate was synthesized following Procedure A in 66% yield (620 mg) as an off-white powder. R / ’= 0.46 (20% EtOAc in hexanes).

[0812] NMR (500 MHz, CDCh) 87.31 (d, J= 5.1 Hz, 1H), 7.22 (td, J= 7.0, 3.5 Hz, 3H), 7.12 -7.07 (m, 2H), 6.86 (d, J= 5.1 Hz, 1H), 3.85 (s, 2H), 2.14 (s, 3H).13C NMR (126 MHz, CDCh) 8 150.07, 138.95, 136.88, 130.37, 128.91, 128.59, 128.23, 127.49, 126.89, 36.11, 14.52. IR (Diamond-ATR, neat) vmax: 3116, 3073, 3034, 2941, 2825, 1459, 1388, 1223 cm4HRMS (m / z)-. calculated for C13H14NOS2 [M+H]+264.0511, found 264.0505. Melting Point: 108 - 110

[0813]

[0814] BenzyIN-hydroxypyridine-2-carbimidothioate was synthesized following Procedure A in 20% yield (100 mg) as an off-white powder. Rf= 0.13 (20% EtOAc in hexanes).

[0815]

[0816] NMR (500 MHz, DMSO) 811.90 (s, 1H), 8.68 (dt, J= 3.9, 0.9 Hz, 1H), 7.81 (td, J=7.7, 1.8 Hz, 1H), 7.44 (ddd, J= 7.6, 4.9, 1.2 Hz, 1H), 7.38 (d, J= 7.8 Hz, 1H), 7.24 - 7.13 (m, 3H), 6.98 (dd, J = 7.7, 1.8 Hz, 2H), 4.07 (s, 2H).13C NMR (126 MHz, DMSO) 8 152.36, 151.34, 148.84, 137.93, 137.07, 128.45, 128.28, 126.96, 123.96, 123.28, 34.06. IR (Diamond-ATR, neat) vmax: 3168, 3101, 2967, 2818, 1580, 1476, 1439, 1409, 1282 cm’1. HRMS (m / z)-. calculated for C13H13N2OS [M+H]+245.0743, found 245.0735. Melting Point: 165 - 167 °C.

[0817]

[0818] Benzyl \-hydroxy py ridine-3-carbiniidothioate was synthesized following Procedure A in 56% yield (280 mg) as a yellow crystalline solid. R / = 0.10 (20% EtOAc in hexanes). 'H NMR (600 MHz, CDCh) 8 10.02 (s, 1H), 8.77 (dd, J =2.2, 0.8 Hz, 1H), 8.61 (dd, J=4.9, 1.7 Hz, 1H), 7.79 (dt, J=7.9, 2.0 Hz, 1H), 7.31 (ddd, J= 7.9, 4.9, 0.9 Hz, 1H), 7.22 (ddd, J= 11.9, 7.7, 6.0 Hz, 3H), 7.13 - 7.10 (m, 2H), 3.99 (s, 2H).13C NMR (151 MHz, CDCh) 8 149.99, 149.63, 148.92, 137.05, 136.76, 131.08, 128.81, 128.72, 127.60, 123.55, 36.40. IR (Diamond-Attorney Docket No. 10620-164W01

[0819] NCSU Ref.: 2025-138-03

[0820] ATR, neat) vmax: 3086, 2758, 2682, 2093, 1547, 1502, 1442, 1415, 1266 cm HRMS (m / z)-. calculated for C13H13N2OS [M+H]+245.0743, found 245.0734. Melting Point: 115 - 116 °C.

[0821] S

[0822]

[0823] Benzyl \-hydro\ythiazole-4-carbiniidothioate was synthesized following Procedure A in 40% yield as a white crystalline solid.

[0824] Me

[0825]

[0826] Ethyl 2-(benzylthio)-2-(hydroxyimino)acetate was synthesized following Procedure A in 92% yield (185 mg) as a yellow crystalline solid.

[0827]

[0828] 4-(trifluoromethyl)benzyl \-hydro\ybenziinido thioate (4.58a) was synthesized following Procedure B in 60% yield (243 mg) as a white powder. R = 0.40 (20% EtOAc in hexanes). NMR (500 MHz, CDCh) 87.46 (d, J= 8.2 Hz, 2H), 7.43 - 7.37 (m, 5H), 7.14 (d, J = 8.0 Hz, 2H), 3.91 (s, 2H).13C NMR (126 MHz, CDCh) 8 155.11, 141.30, 133.01, 130.16, 129.72 (q, J= 32.5 Hz), 129.16, 128.85, 128.85, 125.55 (q, J= 3.8 Hz), 124.13 (q, J = 272.2 Hz), 35.75. HRMS (m / z): [M+H]+calculated for C15H13F3NOS [M+H]+312.0670, found 312.0655. Melting Point: 104- 105 °C.

[0829]

[0830] 4-chlorobenzyl / V-hydroxybenzimidothioate was synthesized following Procedure B in 67% yield (365 mg) as a white crystalline solid. R / = 0.34 (20% EtOAc in hexanes).JH NMR (500 MHz, CDCh) 88.71 (s, 1H), 7.46 - 7.36 (m, 5H), 7.17 (dd, J= 8.3, 1.6 Hz, 2H), 6.97 (dd, J = 8.5, 1.8 Hz, 2H), 3.83 (s, 2H).13C NMR (126 MHz, CDCh) 8 155.02, 135.69, 133.31, 133.29, 130.19, 129.98, 128.83, 128.80, 128.74, 35.60. IR vmax: 3265, 3045, 2879, 2736, 1491, 1415, 1206 cm4. HRMS (m / z)-. calculated for C14H13CINOS [M+H]+278.0401, found 278.0393. Melting Point: 165 - 167 °CAttorney Docket No. 10620-164W01

[0831] NCSU Ref.: 2025-138-03

[0832]

[0833] 2-nitrobenzyl A'-hydroxybenzimidothioate was synthesized following Procedure B in 66% yield (375 mg) as a light yellow powder. Rf = 0.23 (20% EtOAc in hexanes).JH NMR (500 MHz, CDCh) 88.10 (s, 1H), 7.95 (dd, J= 8.1, 1.4 Hz, 1H), 7.50 - 7.34 (m, 7H), 7.13 (dd, J = 1.1, 1.5 Hz, 1H), 4.26 (s, 2H).13C NMR (126 MHz, CDC13) 8150.17, 148.11, 133.71, 133.58, 132.68, 131.80, 129.40, 128.86, 128.54, 128.34, 125.02, 32.06. IR (Diamond-ATR, neat) vmax: 3176, 3064, 3019, 2900, 1521, 1439, 1409, 1349, 1237, 1163 cm HRMS (m / z)-. calculated for C14H13N2O3S [M+H]+289.0641, found 289.0633. Melting Point: 166 - 168 °C.

[0834]

[0835] 4-methoxybenzyl A-hydroxybenzimidothioate was synthesized following Procedure C in 77% yield (351 mg) as a white powder. Rf= 0.28 (20% EtOAc in hexanes). 'H NMR (500 MHz, CDCh) 87.50 - 7.35 (m, 5H), 6.99 (d, J= 8.6 Hz, 2H), 6.75 (d, J= 8.7 Hz, 2H), 3.82 (s, 2H), 3.76 (s, 3H).13C NMR (151 MHz, CDCh) 8 158.98, 155.92, 133.38, 130.07, 129.93, 128.86, 128.83, 128.74, 114.03, 55.37, 36.01. IR (Diamond-ATR, neat) vmax: 3525, 3021, 2984, 2868, 1620, 1530, 1478, 1290, 1275, 1187 cm’1. HRMS (m / z)-. calculated for C15H16NO2S [M+H]+274.0896, found 274.0890. Melting Point: 85 - 88 °C.

[0836]

[0837] 2,6-difluorobenzyl A-hydroxybenzimidothioate was synthesized following Procedure B in 61% yield (331 mg) as an off-white crystalline solid. Rf = 0.28 (20% EtOAc in hexanes).

[0838] 'H NMR (600 MHz, CDCh) 87.63 - 7.55 (m, 2H), 7.44 (d, J= 2.3 Hz, 3H), 7.19 (p, J= 7.4 Hz, 1H), 6.83 (t, J=7.8 Hz, 2H), 3.93 (s, 2H).13C NMR (151 MHz, CDCh) 8 162.16 (d, J= 7.5 Hz), 160.50 (d, J=7.6Hz), 155.18, 133.24, 130.07, 129.53 (t, J= 10.3 Hz), 128.85, 113.24 (t, J = 19.2 Hz), 111.45 (dd, J=20.8, 4.5 Hz), 23.59. IR (Diamond-ATR, neat) vmax: 3183, 3049, 2922, 1618, 1588, 1469, 1230 cm4. HRMS (m / z)-. calculated for C14H12F2NOS [M+H]+280.0602, found 280.0594. Melting Point: 113 - 114 °C.Attorney Docket No. 10620-164W01

[0839] NCSU Ref.: 2025-138-03

[0840]

[0841] 3,4-dichlorobenzyl (Z)-N-hydroxybenzimidothioate was synthesized following Procedure C in 48% yield (337 mg) as a white powder. Rf = 0.35 (20% EtOAc in hexanes).JH NMR (600 MHz, CDCh) 87.47 - 7.43 (m, 1H), 7.42 - 7.36 (m, 4H), 7.27 (d, J= 8.3 Hz, 1H), 6.99 (d, J=2.1 Hz, 1H), 6.89 (dd, J= 8.3, 2.1 Hz, 1H), 3.81 (s, 2H).13CNMR (151 MHz, CDCh) 8 155.02, 137.45, 132.84, 132.44, 131.55, 130.76, 130.53, 130.23, 128.89, 128.85, 128.16, 35.09. IR (Diamond-ATR, neat) vmax: 3213, 3034, 2922, 2987, 1489, 1394, 1237 cm’1.

[0842] HRMS (m / z) calculated for C14H12CI2NOS [M+H]+312.0011, found 312.0004. Melting Point:

[0843] 106- 109 °C.

[0844] S

[0845]

[0846] Pyridin-4-ylmethyl A-hydroxybenzimidothioate was synthesized following Procedure B in 67% yield (530 mg) as a bright yellow crystalline solid. Rf = 0.07 (20% EtOAc in Hexanes).JH NMR (500 MHz, DMSO) 8 11.91 (s, 1H), 8.39 (d, J = 6.1 Hz, 2H), 7.58 - 7.31 (m, 5H), 7.01 (d, J = 6.0 Hz, 2H), 3.94 (s, 2H).13C NMR13C NMR (126 MHz, DMSO) 8 150.24, 149.50, 146.97, 133.67, 129.32, 128.51, 128.44, 123.58, 33.53. IR (Diamond-ATR, neat) vmax: 3267, 3069, 2982, 2892, 2723, 1620, 1564, 1480, 1424, 1275, 1221 cm’1. HRMS (m / z): calculated for C13H13N2OS [M+H]+245.0743, found 245.0736. Melting Point: 151 - 154

[0847]

[0848] Pyrimidin-5-ylmethyl / V-hydroxybenzimidothioate was synthesized following Procedure B in 21% yield (100 mg) as an off-white crystalline solid. Rf = 0.05 (20% EtOAc in hexanes). NMR (500 MHz, DMSO) 8 11.95 (s, 1H), 8.98 (s, 1H), 8.37 (s, 2H), 7.46 - 7.39 (m, 3H), 7.39 - 7.35 (m, 2H), 4.01 (s, 2H).13C NMR (126 MHz, DMSO) 8 156.88, 156.69, 149.61, 133.72, 132.29, 129.44, 128.61, 128.30, 29.37. IR (Diamond-ATR, neat) vmax: 3086, 2973, 2621, 2495, 1533, 1362, 1237, 1170 cm HRMS (m / z): calculated for C12H12N3OS [M+H]+246.0696, found 246.0690. Melting Point: 160 - 161 °C.Attorney Docket No. 10620-164W01

[0849] NCSU Ref.: 2025-138-03

[0850]

[0851] Benzo [d]thiazol-2-ylmethyl \-hydroxybenzimidothioate was synthesized following Procedure B in 59% yield (170 mg) as a bright yellow oil. R / = 0.17 (20% EtOAc in hexanes).

[0852] 'H NMR (500 MHz, CDCh) 87.94 (d, J= 8.2 Hz, 1H), 7.82 (d, J= 8.0 Hz, 1H), 7.56 - 7.46 (m, 2H), 7.44 (ddd, J= 8.3, 7.2, 1.2 Hz, 1H), 7.41 - 7.30 (m, 4H), 4.47 (s, 2H).13C NMR (151 MHz, CDCh) 8 169.10, 152.44, 152.24, 135.48, 133.18, 130.12, 128.82, 128.80, 126.45, 125.51, 123.06, 121.78, 34.03. IR (Diamond-ATR, neat) vmax: 3056, 2974, 2810, 1498, 1431, 1237 cm’J. HRMS (m / z)-. calculated for C15H13N2OS2 [M+H]+301.0469, found 301.0462.

[0853] N'0H

[0854]

[0855] Prop-2-yn-l-yl / V-hydroxybenzimidothioate was synthesized following Procedure B in 55% yield (275 mg) as a deep yellow solid. R / = 0.31 (20% EtOAc in hexanes).JH NMR (500 MHz, CDCh) 89.00 (s, 1H), 7.56 (dd, J= 7.6, 2.0 Hz, 2H), 7.46 - 7.41 (m, 2H), 3.40 (d, J= 2.7 Hz, 2H), 2.19 (t, J= 2.7 Hz, 1H).13C NMR (126 MHz, CDCh) 8207.62, 154.11, 132.86, 130.10, 128.93, 128.79, 79.08, 72.22, 31.05, 20.18 (Reported as Observed). IR (Diamond-ATR, neat) vmax: 3280, 3064, 2980, 2915, 1483, 1439, 1401, 1230 cm HRMS (m / z)-. calculated for C10H10NOS [M+H]+192.0478, found 192.0471. Melting Point: 92 °C.

[0856]

[0857] Allyl / V-hydroxybenzimidothioate was synthesized following Procedure C in 27% yield (127 mg) as a light green oil. R = 0.35 (20% EtOAc in hexanes). 'H NMR (600 MHz, CDC13) 57.54 > 7.49 (m, 2H), 7.44 - 7.38 (m, 3H), 5.68 (ddt, J= 17.0, 10.0, 7.0 Hz, 1H), 4.97 (dd, J = 10.0, 1.2 Hz, 1H), 4.87 (dd, J= 16.9, 1.4 Hz, 1H), 3.29 (dd, J= 7.0, 1.2 Hz, 2H).13C NMR (151 MHz, CDCh) 8 155.68, 133.27, 133.11, 129.98, 128.87, 128.71, 118.36, 34.94. IR (Diamond-ATR, neat) vmax: 3213, 3079, 2964, 2890, 1595, 1491, 1424, 1230 cm4. HRMS (m / z)-. calculated for C10H12NOS [M+H]+194.0634, found 194.0627.

[0858] General Procedure D for the Synthesis of 1,4,2-Oxathiazoles: From a 5-gram FlashPure Buchi silica column, all the silica was expelled. 200 mg of celite was placed into theAttorney Docket No. 10620-164W01

[0859] NCSU Ref.: 2025-138-03

[0860] bottom of the container and compacted. In the same fashion, 7 grams of Mn02 was placed on top of the celite and the system was sealed with the same glass fiber frit the column contained originally. The vessel was conditioned by passing through 10 mL of dry di chloromethane. A 14 mM solution of the corresponding thiohydroximic derivative was then prepared in dry dichloromethane and loaded into a 25 mL syringe. A New Era Syringe Pump was fixed at 45 mL / hour, and the loaded syringe was passed through the column. After all the solution had been passed, an additional 45 mL (9 CV) was utilized to wash the container. The obtained solution was then concentrated in vacuo to afford the desired 1,4,2- oxathiazole derivative.

[0861] N-Q _

[0862]

[0863] 3,5-diphenyl-l,4,2-oxathiazole was synthesized following General Procedure D in 80% yield (57 mg) as a white solid.

[0864]

[0865] NMR (500 MHz, CDCk) 87.76-7.72 (m, 2H), 7.60-7.57 (m, 2H), 7.49-7.39 (m, 6H), 7.18 (s, 1H).

[0866]

[0867] 4-phenyl-3-(4-(trifluoromethyl)phenyl)-l,4,2-oxathiazole was synthesized following the General Procedure D in 80% yield (95 mg) as a white powder. R / ’= 0.68 (20% EtOAc in hexanes). NMR (500 MHz, CDCk) 87.84 (d, J= 8.1 Hz, 2H), 7.69 (d, J= 8.2 Hz, 2H), 7.59 - 7.55 (m, 2H), 7.47 - 7.41 (m, 3H), 7.23 (s, 1H).13C NMR (126 MHz, CDCk) 8 155.45, 137.12, 132.90 (q, J= 32.6 Hz), 131.49, 130.01, 129.00, 128.50, 126.76, 125.94 (q, J=3.7Hz), 123.74 (q, J= 272.5 Hz), 95.02. IR (Diamond-ATR, neat) vmax: 3053, 2904, 2769, 1631, 1523, 1439, 1390, 1316 cm HRMS (m / z)-. calculated for C15H11F3NOS [M+H]+310.0580, found 310.0501. Melting Point: 83 - 86 °C.

[0868]

[0869] 3-(4-chloro-2-(trifluoromethyl)phenyl)-5-phenyl- 1,4,2-oxathiazole was synthesized following General Procedure D in 51% yield (102 mg) as a yellow oil. R = 0.63 (20% EtOAc in hexanes). NMR (500 MHz, CDC13) 87.77 (d, J= 2.1 Hz, 1H), 7.63 - 7.53 (m, 4H), 7.47 -Attorney Docket No. 10620-164W01

[0870] NCSU Ref.: 2025-138-03

[0871] 7.40 (m, 3H), 7.30 (s, 1H).13C NMR (126 MHz, CDCh) 8 152.26, 137.22, 137.15, 132.99, 132.25, 131.14 (q, JC-F= 32.6 Hz), 129.95, 128.97, 127.66 (q, JC-F= 5.4 Hz), 126.70, 124.56, 122.63 (q, JC-F= 274.4 Hz), 95.94. IR (Diamond-ATR, neat) vmax: 3086, 2987, 2330, 1562, 1379, 1290, 1113 cm'1. HRMS (m / z): calculated for C15H10CIF3NOS [M+H]+344.01182, found 344.0119.

[0872]

[0873] 3-(4-chloro-2-fluorophenyl)-5-phenyl-l,4,2-oxathiazole was synthesized following General Procedure D in 55% yield (109 mg) as a white crystalline solid. R / = 0.69 (20% EtOAc in hexanes).JH NMR (500 MHz, DMSO) 87.80 (t, J= 8.2 Hz, 1H), 7.70 (dd, J= 11.0, 2.1 Hz, 1H), 7.54 (dd, J= 7.8, 1.8 Hz, 2H), 7.50 (s, 1H), 7.47 - 7.38 (m, 4H).13C NMR (126 MHz, DMSO) 8 159.90, 157.85, 149.41, 149.37, 138.29, 137.01, 136.93, 131.06, 131.03, 129.49, 128.77, 126.16, 125.69, 125.67, 117.57, 117.37, 114.47, 114.37, 92.77, 92.75 (Reported as Observed). IR (Diamond-ATR, neat) vmax: 3096, 3042, 2946, 1588, 1485, 1433, 1383 cm'1HRMS (m / z) C14H10CIFNOS [M+H]+294.01502, found 294.0153. Melting Point: 84 °C.

[0874]

[0875] 3-(3,4-dichlorophenyl)-5-phenyl-l,4,2-oxathiazole was synthesized following General Procedure D in 15% yield (19 mg) as a white powder. R = 0.68 (20% EtOAc in hexanes). 'H NMR (500 MHz, CDCh) 87.82 (d, J = 2.0 Hz, 1H), 7.57-7.53 (m, 3H), 7.50 (d, J = 8.4 Hz, 1H), 7.42 (dd, J = 5.2, 2.1 Hz, 3H), 7.21 (s, 1H).13C NMR (126 MHz, CDCh) 8 154.67, 137.05, 135.51, 133.39, 130.96, 130.01, 129.83, 129.00, 127.99, 127.17, 126.74, 95.13. IR (Diamond-ATR, neat) vmax: 3086, 3034, 2922, 1528, 1454, 1387, 1282, 1230, 1133, 1021 cm'1HRMS (in z): calculated for C14H10CI2NOS [M+H]+309.9860, found 309.9858. Melting Point: 66 - 68

[0876]

[0877] Attorney Docket No. 10620-164W01

[0878] NCSU Ref.: 2025-138-03

[0879] 3-(2,6-dichlorophenyl)-5-phenyl-l,4,2-oxathiazole was synthesized following General Procedure D in 41% yield (53 mg) as an off-white powder. Rf = 0.61 (20% EtOAc in hexanes).

[0880] 'H NMR (500 MHz, CDCh) 87.65 (dd, J= 7.8, 1.8 Hz, 2H), 7.47 - 7.41 (m, 3H), 7.40 (d, J = 1.6 Hz, 1H), 7.38 (s, 1H), 7.35 (s, 1H), 7.33 (dd, J=9.1, 6.9 Hz, 1H).13CNMR (151 MHz, CDCh) 8 151.02, 137.41, 135.90, 131.99, 129.89, 128.89, 128.47, 126.96, 126.03, 95.91. IR (Diamond-ATR, neat) vmax: 3071, 2922, 1558, 1431, 1260, 1193, 1103 cm4HRMS (m / z): calculated for C14H10CI2NOS [M+H]+309.9860, found 309.9856. Melting Point: 89 - 90 °C.

[0881]

[0882] 3-(3-bromo-5-chlorophenyl)-5-phenyl-l,4,2-oxathiazole was synthesized General Procedure D in 41% yield (82 mg) as a white crystalline solid. Rf = 0.78 (20% EtOAc in hexanes).JH NMR (500 MHz, CDCh) 87.75 (t, J= 1.6 Hz, 1H), 7.65 (t, J= 1.7 Hz, 1H), 7.60 (t, J= 1.8 Hz, 1H), 7.58 - 7.52 (m, 2H), 7.42 (dd, J= 5.1, 2.1 Hz, 3H), 7.22 (s, 1H).13C NMR (126 MHz, CDCh) 8 154.15, 136.91, 135.65, 133.71, 130.95, 129.93, 129.13, 128.90, 126.76, 126.58, 123.12, 95.08. IR (Diamond-ATR, neat) vmax: 3088, 2892, 1547, 1502, 1416, 1240, 1215 cm HRMS (m / z): calculated for CuHioBrCINOS [M+H]+353.9350, found 353.9357. Melting Point: 69 °C.

[0883]

[0884] 3-(2-bromo-5-chlorophenyl)-5-phenyl-l,4,2-oxathiazole was synthesized following General Procedure D in 51% yield (76 mg) as a white crystalline solid. R =0.41 (20% EtOAc in hexanes). NMR (500 MHz, CDCh) 87.62 - 7.57 (m, 4H), 7.48 - 7.39 (m, 3H), 7.29 (dd, J = 8.6, 2.6 Hz, 1H), 7.26 (s, 1H).13C NMR (151 MHz, CDCh) 8 154.15, 137.23, 135.09, 133.87, 131.90, 131.38, 130.63, 129.94, 128.98, 126.76, 120.52, 95.68. IR (Diamond-ATR, neat) vmax: 3082, 3022, 2921, 1558, 1533, 1453, 1380, 1285 cm4HRMS (m / z): calculated for CuHioBrCINOS [M+H]+353.9359, found 353.9355. Melting Point: 98 - 100 °C.Attorney Docket No. 10620-164W01

[0885] NCSU Ref.: 2025-138-03

[0886]

[0887] 3-(2-bromo-6-chlorophenyl)-5-phenyl-l,4,2-oxathiazole was synthesized following General Procedure D in 48% yield (19 mg) as an off-white solid. Rf = 0.61 (20% EtOAc in hexanes). ‘HNMR (500 MHz, CDCh) 87.65 (dd, J= 7.8, 1.7 Hz, 2H), 7.57 (dd, J= 8.1, 1.1 Hz, 1H), 7.47 - 7.40 (m, 4H), 7.36 (s, 1H), 7.26 (t, J= 8.1 Hz, 1H).13C NMR (151 MHz, CDCh) 8 152.65, 137.33, 135.83, 132.31, 131.70, 129.90, 129.06, 128.89, 127.83, 127.06, 124.91, 96.02.

[0888] IR (Diamond-ATR, neat) vmax: 3042, 2995, 2878, 2801, 1573, 1461, 1390, 1284, 1224, 1135 cm HRMS (m / z) calculated for CuHioBrCINOS [M+H]+353.9355, found 353.9353. Melting Point: 86 - 87 °C

[0889]

[0890] 3-(3-bromo-4-methoxyphenyl)-5-phenyl-l,4,2-oxathiazole was synthesized following General Procedure D in 48% yield (95 mg) as a white powder. Rf = 0.54 (20% EtOAc in hexanes). NMR (500 MHz, CDCh) 87.94 (d, J= 2.2 Hz, 1H), 7.63 (dd, J= 8.6, 2.2 Hz, 1H), 7.57 - 7.54 (m, 2H), 7.45 - 7.34 (m, 3H), 7.16 (s, 1H), 6.91 (d, J= 8.6 Hz, 1H), 3.94 (s, 3H).13C NMR (126 MHz, CDCh) 8 158.17, 155.15, 137.33, 133.00, 129.81, 128.92, 128.82, 126.73, 121.76, 112.20, 111.72, 94.49, 56.57. IR (Diamond-ATR, neat) vmax: 3012, 2937, 2885, 1491, 1267, 1230, 1051 cm’1HRMS (m / z): calculated for Ci5Hi3BrNO2S [M+H]+349.9850, found 349.9846. Melting Point: 111 - 113 °C.

[0891]

[0892] 3-(3-methylthiophen-2-yl)-5-phenyl-l,4,2-oxathiazole was synthesized following General Procedure D in 32% yield (32 mg) as a light green oil. Rf= 0.78 (20% EtOAc in hexanes). NMR (500 MHz, CDCh) 87.57 (dd, J= 7.5, 2.1 Hz, 2H), 7.43 - 7.38 (m, 3H), 7.34 (d, J=5.1 Hz, 1H), 7.13 (s, 1H), 6.92 (d, J=5.1 Hz, 1H), 2.49 (s, 3H).13CNMR (126 MHz, CDCh) 8 150.92, 140.64, 137.07, 131.97, 129.79, 128.90, 128.06, 126.82, 123.87, 94.26,Attorney Docket No. 10620-164W01

[0893] NCSU Ref.: 2025-138-03

[0894] 16.36. IR (Diamond-ATR, neat) vmax: 3064, 3027, 2915, 1521, 1454, 1416, 1223 cm HRMS (m / z) calculated for C13H12NOS2 [M+H]+262.0360, found 262.0357.

[0895]

[0896] 5-phenyl-3-(pyridin-2-yl)-l,4,2-oxathiazole was synthesized following General Procedure D in 26% yield (26 mg) as an off-white solid. / = 0.45 (20% EtOAc in hexanes).JH NMR (600 MHz, CDCh) 88.65 - 8.62 (m, 1H), 8.04 (d, J= 1.2 Hz, 1H), 7.77 (td, J= 7.9, 2.5 Hz, 1H), 7.60 - 7.54 (m, 2H), 7.40 (qd, J= 13, 3.3 Hz, 3H), 7.37 - 7.32 (m, 1H), 7.18 (s, 1H).

[0897] 13C NMR (151 MHz, CDCh) 8 158.74, 149.62, 147.79, 137.97, 136.79, 129.70, 128.88, 126.82, 125.26, 121.70, 94.07. IR (Diamond-ATR, neat) vmax: 3084, 2922, 1580, 1551, 1461, 1431, 1305, 1245, 1200 cm4HRMS (m / z)-. calculated for C13H11N2OS [M+H]+243.0592, found 243.0589. Melting Point: 79 - 80 °C.

[0898]

[0899] 5-phenyl-3-(pyridin-3-yl)-l,4,2-oxathiazole was synthesized following General Procedure D in 40% yield (41 mg) as a yellow crystalline solid. / = 0.25 (20% EtOAc in hexanes). 'H NMR (500 MHz, CDCh) 88.91 (d, J= 2.4Hz, 1H), 8.70 (dd, J=4.9, 1.6 Hz, 1H), 8.08 (dt, J= 8.0, 1.9 Hz, 1H), 7.59 - 7.55 (m, 2H), 7.46 - 7.37 (m, 4H), 7.24 (s, 1H).13C NMR (126 MHz, CDCh) 8 153.78, 151.56, 148.62, 136.97, 135.54, 130.04, 129.02, 126.76, 124.81, 123.91, 95.02. IR (Diamond-ATR, neat) vmax: 3092, 3017, 2986, 1595, 1461, 1306, 1211 cm’1HRMS (m / z)'. calculated for C13H13N2OS [M+H]+243.0587, found 243.0586. Melting Point: 68

[0900]

[0901] 5-phenyl-3-(thiazol-4-yl)-l,4,2-oxathiazole was synthesized following General Procedure D in 24% yield (25.2 mg) as a pale-yellow oil. 'H NMR (500 MHz, CDCh) S 8.85 (d, J= 2.0 Hz, 1H), 7.95 (d, J= 2.0 Hz, 1H), 7.62-7.53 (m, 2H), 7.46-7.35 (m, 3H), 7.19 (s, 1H).Attorney Docket No. 10620-164W01

[0902] NCSU Ref.: 2025-138-03

[0903] Me

[0904]

[0905] Ethyl 5-phenyl-l,4,2-oxathiazole-3-carboxylate was synthesized following General Procedure D in 25% yield as a white solid.

[0906]

[0907] 3-phenyl-5-(4-(trifluoromethyl)phenyl)-l,4,2-oxathiazole was synthesized following General Procedure D in 46% yield (138 mg) as a white powder. Rf = 0.63 (20% EtOAc in hexanes). NMR (500 MHz, CDCh) 87.71 (dd, J= 8.0, 1.4 Hz, 2H), 7.67 (s, 4H), 7.50 - 7.46 (m, 1H), 7.43 (dd, J= 8.3, 6.6 Hz, 2H), 7.20 (s, 1H).13C NMR (126 MHz, CDCh) 8 156.31, 142.14, 132.37 - 131.21 (q, JC-F= 32.6 Hz), 131.55, 129.03, 128.32, 127.63, 126.78, 125.93 (q, JC-F= 3.8 Hz), 127.38 - 120.42 (q, JC-F= 272.5 Hz), 92.86. IR (Diamond-ATR, neat) vmax: 3073, 2900, 1826, 1711, 1631, 1554, 1502, 1448, 1431, 1366, 1338, 1133 cm HRMS (m / z) calculated for C15H11F3NOS [M+H]+310.0508, found 310.0508. Melting Point: 74 °C.

[0908]

[0909] 5-(4-chlorophenyl)-3-phenyl-l,4,2-oxathiazole was synthesized following General Procedure D in 61% yield (121 mg) as a white powder. Rf = 0.68 (20% EtOAc in hexanes). 'H NMR (500 MHz, CDC13) 87.74 - 7.69 (m, 2H), 7.52 - 7.49 (m, 2H), 7.48 - 7.40 (m, 3H), 7.41 - 7.36 (m, 2H), 7.14 (s, 1H).13C NMR (126 MHz, CDCh) 8 156.54, 136.31, 135.64, 131.44, 129.12, 128.99, 128.26, 128.06, 127.81, 93.38. IR (Diamond-ATR, neat) vmax: 3112, 3073, 3042, 2945, 2876, 1502, 1454, 1390, 1333, 1269, 1098 cm4HRMS (m / z): calculated for C14H11CINOS [M+H]+276.0244, found 276.0248. Melting Point: 58 - 60 °C.

[0910]

[0911] 5-(2-nitrophenyl)-3-phenyl-l,4,2-oxathiazole was synthesized following General Procedure D in 27% yield (33 mg) as an off-white crystalline solid. Rf = 0.60 (20% EtOAc inAttorney Docket No. 10620-164W01

[0912] NCSU Ref.: 2025-138-03

[0913] hexanes).1H NMR (500 MHz, CDCh) 88.24 (d, J= 7.0 Hz, 1H), 7.93 (d, J= 6.4 Hz, 1H), 7.75 - 7.70 (m, 2H), 7.67 - 7.63 (m, 2H), 7.54 (t, J= 8.5 Hz, 1H), 7.47 - 7.42 (m, 1H), 7.39 (t, J= 7.4 Hz, 2H).13C NMR (126 MHz, CDCh) 8156.70, 144.90, 137.25, 134.90, 131.52, 129.83, 128.96, 128.19, 127.89, 127.53, 125.83, 90.18. IR (Diamond-ATR, neat) vmax: 3019, 2915, 1550, 1342, 1275, 1200 cm’1HRMS (m / z): calculated for C14H11N2O3S [M+H]+287.0485, found 287.0485. Melting Point: 109 - 110 °C.

[0914]

[0915] 5-(4-methoxyphenyl)-3-phenyl-l,4,2-oxathiazole was synthesized following General Procedure D in 49% yield (60 mg) as an off-white solid. = 0.55 (20% EtOAc in hexanes). 'H NMR (600 MHz, CDCh) 87.73 (dd, J= 8.3, 1.4 Hz, 2H), 7.52 (d, J= 8.7 Hz, 2H), 7.48 - 7.45 (m, 1H), 7.44 - 7.41 (m, 2H), 7.14 (s, 1H), 6.93 (d, J= 8.7 Hz, 2H), 3.82 (s, 3H).13C NMR (126 MHz, CDCh) 8 160.85, 156.94, 131.24, 129.03, 128.92, 128.55, 128.23, 128.19, 114.25, 94.51, 55.51. IR (Diamond-ATR, neat) vmax:3088, 3042, 2987, 2930, 2861, 2809, 1621, 1547, 1495, 1428, 1312, 1251, 1206, 1185 cm HRMS (m / z): calculated for C15H14NO2S [M+H]+272.0740, found 272.0740. Melting Point: 61 - 62 °C.

[0916]

[0917] 5-(2,6-difluorophenyl)-3-phenyl-l,4,2-oxathiazole was synthesized following General Procedure D in 37% yield (78 mg) as a white crystalline solid. / = 0.66 (20% EtOAc in hexanes). NMR (500 MHz, CDCh) 87.75 - 7.70 (m, 2H), 7.55 (s, 1H), 7.50 - 7.41 (m, 3H), 7.36 (tt, J= 8.4, 6.2 Hz, 1H), 6.95 (t, J= 8.4 Hz, 2H).13C NMR (126 MHz, CDCh) 8 162.08, 162.02, 160.05, 160.00, 155.12, 131.77, 131.68, 131.60, 131.10, 128.85, 128.03, 127.68, 114.62, 114.50, 114.38, 112.24, 112.20, 112.07, 112.04, 83.86, 83.83, 83.80 (Reported as Observed). IR (Diamond-ATR, neat) vmax: 3064, 2922, 2796, 1722, 1618, 1588, 1551, 1460, 1275, 1237, 1193 cm’1HRMS (m / z): calculated for C14H10F2NOS [M+H]+278.0451, found 278.0447. Melting Point: 55 - 57 °CAttorney Docket No. 10620-164W01

[0918] NCSU Ref.: 2025-138-03

[0919]

[0920] 5-(3.4-dichlorophenyl)-3-phenyl-l.4.2-oxathiazole was synthesized following General Procedure D in 38% yield (66 mg) as a white solid. Rf = 0.70 (20% EtOAc in hexanes).1H NMR (500 MHz, CDCh) 87.73 - 7.68 (m, 2H), 7.65 (d, J= 2.1 Hz, 1H), 7.53 - 7.46 (m, 2H), 7.43 (dd, J= 8.3, 6.6 Hz, 2H), 7.38 (dd, J= 8.3, 2.1 Hz, 1H), 7.10 (s, 1H).13C NMR (126 MHz, CDCh) 8 156.33, 138.37, 133.82, 133.19, 131.60, 130.95, 129.05, 128.53, 128.33, 127.56, 125.77, 92.39. IR (Diamond-ATR, neat) vmax: 2922, 2270, 1528, 1489, 1237, 1133 cm HRMS (m / z)'. calculated for C14H10CI2NOS [M+H]+309.9855, found 309.9859. Melting Point:

[0921] 63 - 64 °C.

[0922]

[0923] 3-phenyl-5-(pyridin-4-yl)-l,4,2-oxathiazole was synthesized following General Procedure D in 30% yield (68 mg) as a dark orange solid. Rf = 0.18 (20% EtOAc in hexanes).

[0924] 'H NMR (500 MHz, CDCh) 88.71 - 8.64 (m, 2H), 7.72 - 7.66 (m, 2H), 7.53 - 7.46 (m, 3H), 7.45 - 7.40 (m, 2H), 7.13 (s, 1H).13C NMR (126 MHz, CDCh) 8 155.98, 150.13, 147.87, 131.68, 129.06, 128.38, 127.32, 120.58, 91.44. IR (Diamond-ATR, neat) vmax: 3040, 2917, 1603, 1502, 1454, 1433, 1292, 1183 cm4HRMS (m / z): calculated for C13H11N2OS [M+H]+243.0587, found 243.0584. Melting Point: 68 - 70 °C.

[0925] -o

[0926]

[0927] 3-phenyl-5-(pyrimidin-5-yl)-l,4,2-oxathiazole (4.65b) was synthesized following General Procedure D in 73% yield as an off-white crystalline solid. Rf= 0.15 (20% EtOAc in hexanes). NMR (500 MHz, CDCh) 89.25 (s, 1H), 8.93 (s, 2H), 7.77 - 7.61 (m, 2H), 7.54 -7.47 (m, 1H), 7.47 - 7.39 (m, 2H), 7.18 (s, 1H).13C NMR (126 MHz, CDCh) 8 159.48, 156.33, 155.12, 132.33, 131.89, 129.14, 128.42, 127.10, 89.21. IR (Diamond-ATR, neat) vmax: 3055, 3032, 2953, 1558, 1408, 1271, 1181, 1100 cm4HRMS (m / z): calculated for C12H10N3OS [M+H]+244.0539, found 244.0539. Melting Point: 96 - 99 °C.Attorney Docket No. 10620-164W01

[0928] NCSU Ref.: 2025-138-03

[0929]

[0930] 5-(benzo[d]thiazol-2-yl)-3-phenyl-1,4,2-oxathiazole was synthesized following General Procedure D in 37% yield (73 mg) as a yellow crystalline solid. / = 0.53 (20% EtOAc in hexanes).1H NMR (600 MHz, CDCh) 88.05 (d, J= 8.2 Hz, 1H), 7.90 (d, J= 7.5 Hz, 1H), 7.75 - 7.71 (m, 2H), 7.52 (ddd, J= 8.4, 7.2, 1.3 Hz, 1H), 7.48 (d, J= 7.0 Hz, 2H), 7.43 (td, J= 7.6, 1.4 Hz, 3H).13C NMR (151 MHz, CDCh) 8 169.72, 156.38, 153.13, 135.44, 131.80, 129.10, 128.50, 127.12, 126.69, 126.13, 123.81, 122.15, 89.92. IR (Diamond-ATR, neat) vmax: 3075, 2946, 2822, 2301, 1552, 1495, 1450, 1323, 1292, 1217, 1174 cm HRMS (m / z. calculated for C15H11N2OS2 [M+H]+299.0307, found 299.0310. Melting Point: 77 - 80 °C.

[0931]

[0932] 5-ethynyl-3-phenyl-l,4,2-oxathiazole was synthesized following General Procedure D in 25% yield (13 mg) as a yellow solid. R / ’= 0.57 (20% EtOAc in hexanes).1H NMR (500 MHz, CDCh) 87.78 - 7.65 (m, 2H), 7.53 - 7.46 (m, 1H), 7.46 - 7.40 (m, 2H), 6.66 (d, J= 2.0 Hz, 1H), 2.91 (d, J= 2.0 Hz, 1H).13C NMR (151 MHz, CDCh) 8 156.43, 131.64, 129.04, 128.45, 127.47, 79.30, 78.91, 78.31. IR (Diamond-ATR, neat) vmax: 3399, 3288, 2922, 2117, 1692, 1349, 1319, 1267, 1237 cm’1HRMS (m / z. calculated for CioHsNOS [M+H]+190.0327, found 190.0321. Melting Point: 93 - 95 °C.

[0933]

[0934] 3-phenyl-5-vinyl-l,4,2-oxathiazole was synthesized following General Procedure D in 26% yield (11 mg) as a light green oil. R = 0.65 (20% EtOAc in hexanes).1H NMR (600 MHz, CDCh) 87.72 - 7.68 (m, 2H), 7.48 - 7.39 (m, 3H), 6.57 (dd, J= 6.8, 1.1 Hz, 1H), 6.10 (ddd, J = 17.0, 10.3, 6.8 Hz, 1H), 5.50 (dd, J= 17.0, 1.1 Hz, 1H), 5.32 (d, J= 10.2 Hz, 1H).13C NMR (151 MHz, CDCh) 8 156.34, 133.87, 131.25, 128.90, 128.22, 128.08, 119.08, 93.04. IR (Diamond-ATR, neat) vmax: 3056, 2922, 1538, 1491, 1448, 1416, 1267 cm4HRMS (m / z): calculated for C10H10NOS [M+H]+192.0483, found 192.0481.Attorney Docket No. 10620-164W01

[0935] NCSU Ref.: 2025-138-03

[0936] Example 2. Evaluation of the Activity of 1,4,2-Oxathiazoles

[0937] The antifungal, herbicidal, and insecticidal activity of 19 example 1,4,2-oxathiazoles, prepared as described in Example 1, was evaluated. The structure of the example 1,4,2-oxathiazoles evaluated are shown below.

[0938] s AV-2481

[0939] AV-2411

[0940] O-N

[0941] AV-2421

[0942]

[0943] Attorney Docket No. 10620-164W01

[0944] NCSU Ref.: 2025-138-03

[0945]

[0946] Methods

[0947] Disease control: Each active ingredient was tested on four relevant fungal pathogens, BOTRCI for Botrytis cinerea, SEPTTR for Septoria tritici, FUSACU for Fusarium culmorum & PHAKPA for Phakopsora pachyrhizi in a microscopic-based assay in a 384-microtiter plate. Each active ingredient was tested in a dose-response curve from 20 to 0.015 ppm - unless PHAKPA from 12 to 0.047 ppm, by adding 0.5pL of a DMSO-solution of the active ingredient in a final growth culture volume of 50 pL for BOTRCI, FUSACU, SEPTTR. The growth medium used in this assay was a synthetic-based medium mainly composed of KH2PO4, K2HPO4, KNO3, MgSO47H2O, CaCh, Saccharose, Urea & micro-elements. A water-based medium with Tween & MOPs was used for PHAKPA - final volume 85 pL.

[0948] For all pathogens, transmitted light images were generated after 4h for PHAKPA, 24h FUSACU & 48h for BOTRCI, SEPTTR (4X, one image per well). An in-house image analysis solution permitted to quantify the growth inhibition effect at each concentration to edit dedicated doseresponse curve.

[0949] Spodoptera frugiperda (SPODFR) - spray test: Maize (Zea mays) leaf sections are sprayed with a preparation of the active ingredient of the desired concentration. Once dry, the leaf sections are infested with fall army worm larvae (Spodoptera frugiperda).

[0950] After 7 days mortality in % is determined. 100 % means all caterpillars have been killed and 0 % means none of the caterpillars have been killed.

[0951] Diabrotica balteata (DIABBA)- spray test: Soaked wheat seeds (Triticum aestivum) are placed in a multiple well plate filled with agar and some water and are incubated for 1 day to germinate (5 seeds per well). The germinated wheat seeds are sprayed with a test solution containing the desired concentration of the active ingredient. Afterwards each unit is infected with 10-20 larvae of the banded cucumber beetle (Diabrotica balteata). After 7 days efficacy in % is determined. 100 % means all the seedlings have grown up like in the untreated, uninfected control; 0 % means none of the seedlings have grown.

[0952] Myzus persicae (MYZUPE) - spray test: Chinese cabbage (Brassica pekinensis) leaf discs infected with all instars of the green peach aphid (Myzus persicae), are sprayed with a preparation of the active ingredient of the desired concentration. After 5 days mortality in % isAttorney Docket No. 10620-164W01

[0953] NCSU Ref.: 2025-138-03

[0954] determined. 100 % means all aphids have been killed and 0 % means none of the aphids have been killed.

[0955] Frankliniella occidentalis (FRANOC) - spray test: Common bean (Phaseolus vulgaris) leaf discs are sprayed with a preparation of the active ingredient of the desired concentration. Once dry, leaf discs are infected with mixed population of Frankliniella occidentalis. After 7 days plant protection in % is determined. 100 % means all insects have been killed and the leaf disk is still green; 0 % means the leaf disc has massive leaf damage.

[0956] Euschistus heros (EUSCHE) - Spray TestBarley seedlings (Hordeum vulgare) are sprayed with a test solution containing the desired concentration of the active ingredient and are infested with Euschistus heros. After 4 days mortality in % is determined. 100 % means all the Euschistus heros have been killed; 0 % means none of the Euschistus heros have been killed.

[0957] Nilaparvata lugens (NILALU) - spray test Rice seedlings (Oryza sativa) are sprayed with a preparation of the active ingredient of the desired concentration and the plants are infested with the brown planthopper (Nilaparvata lugens). After 4 days mortality in % is determined. 100 % means all planthoppers have been killed and 0 % means none of the planthoppers have been killed

[0958] Results

[0959] The antifungal activity of the 19 example 1,4,2-oxathiazoles was evaluated against BOTRCI (Botrytis cinerea, grey mold disease), SEPTTR (Zymoseptoria tritici, septoria tritici blotch (STB)), FUSACU (Fusarium culmorum, seedling blight, foot rot, or head blight (FHB)), and PHAKPA (Phakopsora pachyrhizi, soybean rust). The results are shown in Figure 8.

[0960] Notably, many of the example compounds exhibited strong antifungal activity, with many of the example compounds exhibiting an IC50 against PHAKPA of less than 1 ppm.

[0961] As shown in Figure 8, many of the 19 example 1,4,2-oxathiazoles also exhibited herbicidal activity against representative weed / plant species, including AGSTE (agrostis capillaris, common bent, colonial bent, browntop), DIPTE (Diplotaxis tenuifolia, perennial wallrocket), MATCH (Matricaria chamomilla, German chamomile), and POAAN (Poa annua, annual bluegrass).

[0962] The insecticidal activity of the 19 example 1,4,2-oxathiazoles was evaluated against MYZUPE (Myzus persicae, green peach aphid), AEDSAE (Aedes aegypti, yellow fever mosquito), SPODFR (Spodoptera frugiperda, fall armyworm), DIABBA (Diabrotica balteata, cucumber beetle), NILALU (Nilaparvata lugens, brown planthopper), EUSCHE (Euschistus heros, brown stink bug), and FRANOC (Frankliniella occidentalis, western flower thrips). TheAttorney Docket No. 10620-164W01

[0963] NCSU Ref.: 2025-138-03

[0964] results are shown in Figure 9. Notably, many of the example compounds exhibited strong insecticidal activity against representative aphid and mosquito species.

[0965] Example 3. Oxidation of 1,4,2-Oxathiazoles to Form Oxidized Analogs of 1,4,2-Oxathiazoles

[0966] As shown in the scheme below, oxidized analogs of 1,4,2-oxathiazoles (sulfoxide and sulfone analogs of 1,4,2-oxathiazoles) can be accessed via subsequent oxidation of 1,4,2-oxathiazoles prepared as described above.

[0967] [Oxidant]

[0968]

[0969] Oxidant Examples:

[0970] m-CPBA, Oxone, Peracetic 1,4,2-oxathiazole 4-oxide 1,4,2-oxathiazole 4,4-dioxide acid, H2O2, SeO2 + oxidant

[0971] Examples of oxidized analogs of 1,4,2-oxathiazoles that can be prepared using these methods include the compounds shown below.Attorney Docket No. 10620-164W01

[0972] NCSU Ref.: 2025-138-03

[0973] Ek

[0974] AV-2501

[0975] AV-2509 Ek

[0976] AV-2510

[0977] Ek

[0978]

[0979] AV-2506Attorney Docket No. 10620-164W01

[0980] NCSU Ref.: 2025-138-03

[0981] Cl

[0982] AV-2508

[0983]

[0984] AV-2555

[0985] Example 4. Synthesis of 1,4,2-oxathiazole analogs of existing pesticides.

[0986] The methods described herein can be used to generate 1,4,2-oxathiazole analogs of existing pesticides, including analogs of fungicides in the piperidinyl thiazole isoxazoline class (e.g., 1,4,2-oxathiazole analogs of fluoxapiprolin and oxathiapiprolin).

[0987] The structure of example 1,4,2-oxathiazole analogs prepared herein are shown below.

[0988] F2C

[0989]

[0990] Attorney Docket No. 10620-164W01

[0991] NCSU Ref.: 2025-138-03

[0992]

[0993] Attorney Docket No. 10620-164W01

[0994] NCSU Ref.: 2025-138-03

[0995]

[0996] Attorney Docket No. 10620-164W01

[0997] NCSU Ref.: 2025-138-03

[0998] Synthesis of methyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)thiazole-4-carboxylate (AV-1190). Tert-butyl 4-carbamothioylpiperidine-l -carboxylate (1.8 g,Me1 equiv.) was dissolved in anhydrous N, N-dimethylformamide (DMF)

[0999]

[1000] (1 M) and cooled to 0 °C in an ice bath. A solution of ethyl bromopyruvate (2.30 g, 1 equiv.) in anhydrous DMF (1 M) was added dropwise with stirring. The reaction mixture allowed to warm slowly to room temperature (R, T.) and stirred overnight. Triethylamine (TEA) was added dropwise at a rate of 1 mL / gram of thioamide used. The mixture then was suspended in brine and extracted with ethyl acetate (3X). Organic layers were washed with LiCl 5% (2X), brine and dried over Na2SO4. Mixture was purified using flash chromatography. Desired product obtained as a yellow solid (2.15 g, 73%). 1H NMR (600 MHz, CDCh) 88.10 (d, J = 0.9 Hz, 1H), 4.22 (s, 2H), 3.94 (d, J = 1.0 Hz, 3H), 3.24 (tt, J = 11.9, 3.8 Hz, 1H), 2.85 (s, 2H), 2.12 (d, J = 13.0 Hz, 2H), 1.72 (qd, J = 12.5, 4.3 Hz, 2H), 1.47 (d, J = 1.0 Hz, 9H). m.p.= 81-83 °C. LCMS (ESI-APCI): 327 m / z (M+H).

[1001] Synthesis of tert-butyl 4-(4-formylthiazol-2-yl)piperidine-l-carboxylate (AV-1191).qIn a flame dried round bottom (RB) was added AV-1190 (1.1 g, 1 equiv.) and dissolved in di chloromethane (DCM, 0.15 M). The resulting solution

[1002]

[1003] was cooled to -78 °C and diisobutylaluminium hydride (1.0 M in toluene, 1.04 equiv.) was added dropwise. Upon completion of the addition, the reaction mixture was stirred for 2.5 hours at -78 °C (monitored by TLC). Temperature was controlled using a thermometer in the dry ice bath. (-78 all the time). Then saturated Rochelle’s salt solution (100 mL) was freshly prepared with saturated solution of sodium potassium tartrate. It was added slowly at this temperature, and the mixture was stirred at room temperature until there were two clear layers (after around 1.5 hours later). The mixture was extracted using DCM (250 mL), dryed with anhydrous Na2SO4, then concentrated in vacuo, the crude was carried forward for the next step. Crude DP was a yellow oil, rendering 80% crude yield. Small portion was purified for characterization, to afford a pale yellow solid. 1H NMR (600 MHz, CDCh) 89.99 (s, 1H), 8.08 (s, 1H), 4.21 (s, 2H), 3.21 (tt, J = 11.7, 3.8 Hz, 1H), 2.89 (s, 2H), 2.16 - 2.09 (m, 2H), 1.76 (tdd, J = 13.1, 10.7, 4.8 Hz, 2H), 1.46 (s, 9H). LC-MS (ESI, APCI, m / z) 297 (M+H).

[1004] Synthesis of tert-butyl 4-(4-((hydroxyimino)methyl)thiazol-2-yl)piperidine-l- 30 carboxylate (AV-1194): To a solution of aldehyde AV-1191 (3.58 g, 1 equiv.) OH

[1005] in absolute EtOH (0.5 M) was added hydroxylamine HC1 (1.5 equiv.) and pyridine (3 equiv.) successively at R. T. The reaction was allowed to stir

[1006]

[1007] overnight or until consumption of the SM, and followed by TLC and LCMS. The reaction was quenched by the addition of IN HC1 and the bulk of the EtOH was removed byAttorney Docket No. 10620-164W01

[1008] NCSU Ref.: 2025-138-03

[1009] rotovap. The aqueous layer was extracted with EtOAc (3X) and the combined organic layers were washed with brine (IX), dried over MgSO4, filtered, and concentrated to yield the crude mixture of E / Z oximes as an off-white solid. Mixture was purified using flash chromatography. Desired product obtained as a white solid (3.2 g, 85%). 1H NMR (600 MHz, DMSO) 5 11.24 (s, 1H), 8.13 (s, 1H), 7.77 (s, 1H), 4.00 (d, J = 11.9 Hz, 2H), 3.20 (tt, J = 11.5, 3.8 Hz, 1H), 2.89 (s, 3H), 2.05 - 1.97 (m, 2H), 1.54 (qd, J = 12.2, 4.2 Hz, 2H), 1.41 (s, 9H). LC-MS (ESI, APCI, m / z) 312 (M+H).

[1010] General Procedure A for the Synthesis of Thiohydroximic Acids. To a 1 M solution of the benzaldehyde oxime derivative in dry dimethylformamide at 0 °C was added one-fifth of the total N-chlorosuccinimide, followed by portion-wise addition of the reagent over one hour. During this time, the reaction was allowed to warm slowly to room temperature and stir at this temperature for three hours. The reaction mixture was then diluted with diethyl ether to a concentration of 0.1 M and cooled back to 0 °C. Benzyl mercaptan was then added, followed by triethylamine, and the reaction was allowed to stir overnight while warming to room temperature. The reaction was quenched by the addition of saturated ammonium chloride and diluted with deionized water. The aqueous layer was extracted with ethyl acetate (3X). The combined organic fractions were washed with lithium chloride (5% w / v), water, brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude mixture was purified via flash chromatography to afford the desired product.

[1011] General Procedure B for the Synthesis of Thiohydroximic Acids. To a 1 M solution of the benzaldehyde oxime derivative in dry dimethylformamide at 0 °C was added one-fifth of the total N-chlorosuccinimide, followed by portion-wise addition of the reagent over one hour. During this time, the reaction was allowed to warm slowly to room temperature and stir at this temperature for three hours. The mixture was poured on 10 volumes of ice and allowed to melt over time. Once all the ice has melted, the mixture was extracted with diethyl ether (3X).

[1012] Combined organic layers were washed with lithium chloride (5% w / v), brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo and used crude for next reaction. The resulting chloroxime derivative was dissolved with diethyl ether (0.01-0.1 M) and cooled to 0 °C. Benzyl mercaptan was then added at this temperature, followed by triethylamine, and the reaction was allowed to stir overnight while warming to room temperature. The reaction was quenched by the addition of saturated ammonium chloride and diluted with deionized water. The aqueous layer was extracted with ethyl acetate (3X). The combined organic fractions were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude mixture was purified via flash chromatography to afford the desired product.Attorney Docket No. 10620-164W01

[1013] NCSU Ref.: 2025-138-03

[1014] Synthesis of tert-butyl 4-(4-((benzylthio)(hydroxyimino)methyl)thiazol-2- yl)piperidine-l-carboxylate (AV- 1246). The target compound was synthesized using General procedures A and / or B for the synthesis of

[1015]

[1016] thiohydroximic acids. Chloroxime of AV-1194 (180 mg, 1 equiv), benzyl mercaptan (1 equiv.) and triethylamine (1 equiv.). Desired product was obtained as a white solid (200 mg, 93%). m.p.= 121-123 °C. 'H NMR (600 MHz, DMSO) 8 11.75, 11.74, 7.59, 7.59, 7.23, 7.21, 7.20, 7.19, 7.17, 7.16, 7.02, 7.01, 4.15, 4.03, 4.02, 4.02, 3.32, 3.29, 3.29, 3.28, 3.27, 3.27, 3.26, 3.26, 3.25, 3.25, 3.24, 2.91, 2.08, 2.07, 2.05, 2.05, 1.62, 1.61, 1.60, 1.59, 1.58, 1.57, 1.56, 1.55, 1.41. HRMS (ESI, m / z) calculated for C21H28N3O3S2, 434.15721 (M+H), found 434.15646.

[1017] Synthesis of tert-butyl tert-butyl 4-(4-(((4-fluorobenzyl)thio)(hydroxyimino)

[1018] OHmethyl)thiazol-2-yl)piperidine-l-carboxylate (AV-1220). The target N'

[1019] compound was synthesized using General procedures A and / or B for the

[1020]

[1021] 15 synthesis of thiohydroximic acids. Chloroxime of AV- 1194 (360 mg, 1 equiv), 4-fluorobenzyl mercaptan (1 equiv.) and triethylamine (1 equiv.). Desired product was obtained as an off-white solid (308 mg, 69%). *HNMR (600 MHz, DMSO) 8 11.77, 7.58, 7.04, 7.03, 7.03, 7.02, 7.02, 5.75, 4.04, 4.03, 4.02, 4.02, 4.01, 3.32, 3.30, 3.29, 3.28, 3.27, 3.27, 3.26, 3.25, 3.25, 3.24, 3.24, 2.07, 2.07, 2.07, 2.05, 2.05, 2.04, 1.99, 1.61, 1.60, 1.59, 1.59, 1.58, 1.57, 1.57, 1.57, 1.56, 1.55, 1.54, 1.41. HRMS (ESI, m / z) calculated for C21H27FN3O3S2 452.14779 (M+H), found 452.14685.

[1022] Synthesis of tert-butyl 4-(4-(((2-fluorobenzyl)thio)(hydroxyimino)methyl)thiazol-2- yl)piperidine-l-carboxylate (AV-1319). The target compound was synthesized using General procedures A and / or B for the synthesis of

[1023]

[1024] thiohydroximic acids. Chloroxime of AV-1194 (250 mg, 1 equiv), 2- fluorobenzyl mercaptan (1 equiv.) and triethylamine (1 equiv.). Desired product was obtained as a colorless oil (257 mg, quant.). 'H NMR (600 MHz, CDCh) 87.91, 7.41, 7.21, 7.21, 7.20, 7.20, 7.19, 7.19, 7.19, 7.18, 7.17, 7.17, 7.03, 7.03, 7.02, 7.02, 7.01, 7.01, 6.98, 6.96, 6.96, 6.96, 6.95, 4.20, 3.24, 3.23, 3.22, 3.21, 3.21, 3.20, 3.19, 3.19, 3.18, 3.17, 3.17, 2.87, 2.12, 2.10, 2.10, 1.77, 1.77, 1.75, 1.75, 1.73, 1.73, 1.71, 1.71, 1.47, 1.31, 1.30, 1.29, 1.27, 1.27, 1.26, 1.25, 0.89, 0.88, 0.87, 0.87, 0.86, 0.85, 0.84, 0.84. HRMS (ESI, m / z) calculated for C21H27FN3O3S2 452.14779 (M+H), found 452.14578.Attorney Docket No. 10620-164W01

[1025] NCSU Ref.: 2025-138-03

[1026] Synthesis of tert-butyl 4-(4-(((2-chlorobenzyl)thio)(hydroxyimino)methyl)thiazol-2-OHyl)piperidine-l-carboxylate (AV-1314). The target compound was H'

[1027] synthesized using General procedures A and / or B for the synthesis of

[1028]

[1029] thiohydroximic acids. Chloroxime of AV-1194 (250 mg, 1 equiv), 2- chlorobenzyl mercaptan (1 equiv.) and triethylamine (1 equiv.). Desired product was obtained as a light yellow oil (204 mg, 77%). 'H NMR (600 MHz, CDCh) 88.51, 7.45, 7.44, 7.43, 7.33, 7.32, 7.32, 7.31, 7.31, 7.31, 7.29, 7.19, 7.19, 7.19, 7.18, 7.18, 7.17, 7.17, 7.16, 7.16, 7.15, 7.15, 7.14, 7.14, 7.13, 7.12, 7.12, 4.28, 4.25, 4.20, 4.16, 4.14, 4.13, 4.11, 3.95, 3.22, 3.21, 3.20, 3.20, 3.19, 3.18, 3.18, 3.17, 3.16, 3.16, 2.86, 2.13, 2.12, 2.12, 2.11, 2.11, 2.10, 2.09, 2.09, 2.09, 2.08, 1.76, 1.75, 1.74, 1.73, 1.72, 1.71, 1.70, 1.69, 1.69, 1.48, 1.47, 1.47, 1.46, 1.45, 1.28, 1.27, 1.26, 1.26, 1.25, 1.24. HRMS (ESI, m / z) calculated for C21H27C1N3O3S2 468.11824 (M+H), found 468.11633.

[1030] Synthesis of tert-butyl 4-(4-(((2,6- difluorobenzyl)thio)(hydroxyimino)methyl)thiazol-2-yl)piperidine-l- carboxylate (AV- 1230). The target compound was synthesized using

[1031]

[1032] General procedures A and / or B for the synthesis of thiohydroximic acids. Chloroxime of AV-1194 (575 mg, 1 equiv), 2,6-difluorobenzyl mercaptan (1 equiv.) and triethylamine (1 equiv.). Desired product was obtained as a off-white waxy solid (557 mg, 75%).XH NMR (600 MHz, DMSO) 8 11.86, 11.86, 11.85, 7.78, 7.77, 7.77, 7.39, 7.37, 7.37, 7.36, 7.36, 7.36, 7.35, 7.35, 7.34, 7.08, 7.07, 7.07, 7.06, 7.06, 7.05, 7.05, 7.04, 7.04, 7.03, 7.03, 7.03, 3.82, 3.29, 3.28, 3.28, 3.27, 3.26, 3.26, 3.26, 3.25, 3.25, 3.25, 3.24, 3.24, 3.24, 3.23, 3.23, 3.22, 3.21, 2.90, 1.40, 1.40, 1.39. HRMS (ESI, m / z) calculated for C21H26F2N3O3S2, 470.13837 (M+H); found 470.13757.

[1033] Synthesis of tert-butyl 4-(4-(((2-chloro-6-((methylsulfonyl)oxy)benzyl)thio)

[1034] §5 (hydroxyimino)methyl)thiazol-2-yl)piperidine-l-carboxylate (AV- 'VCHj

[1035] 1325). The target compound was synthesized using General procedures A

[1036]

[1037] and / or B for the synthesis of thiohydroximic acids. Chloroxime of AV- 1194 (302 mg, 1 equiv.), 2-chloro-6-methylsulfonylbenzyl mercaptan (1 equiv.) and triethylamine (1 equiv.). Desired product was obtained as a light yellow waxy solid (256 mg, 56%). 'H NMR (600 MHz, CDCh) 88.52, 7.60, 7.35, 7.35, 7.34, 7.34, 7.34, 7.34, 7.33, 7.33, 7.27, 7.25, 7.24, 4.39, 4.21, 3.31, 3.30, 3.25, 3.24, 3.23, 3.23, 3.22, 3.21, 3.21, 3.20, 3.20, 3.19, 2.87, 2.15, 2.14, 2.13, 2.12, 2.11, 2.11, 1.77, 1.77, 1.75, 1.74, 1.73, 1.72, 1.71, 1.70, 1.48, 1.46. HRMS (ESI, m / z) calculated for C22H29C1N3O6S3 562.09070 (M+H), found 562.08843.Attorney Docket No. 10620-164W01

[1038] NCSU Ref.: 2025-138-03

[1039] General procedure for the preparation of 1,4,2-oxathiazoles: A 10-gram Biotage Sfar Silica silica column, all the silica was removed. 500 mg of celite was placed into the bottom of the container and compacted. In the same fashion, 12 grams of MnCh was placed on top of the celite and the system was closed using the same glass fiber frit the column contained originally. The Mn02 column was pressed using a Biotage dry load plunger until packed tightly. The vessel was conditioned by passing through 20 mL of dry dichloromethane. A 14 mM solution of the corresponding thiohydroximic derivative was then prepared in dry dichloromethane and loaded into a 20 mL syringe. A New Era Syringe Pump was fixed at 30 mL / hour, and the loaded syringe was passed through the column. After all the solution had been passed, an additional 45 mL was utilized to wash the container. The obtained solution was then concentrated in vacuo to afford the desired 1,4,2-oxathiazole derivative.

[1040]

[1041] Synthesis of tert-butyl 4-(4-(5-phenyl-l,4,2-oxathiazol-3-yl)thiazol-2-yl)piperidine-l- carboxylate (AV-1247): The target compound was synthesized using General procedure for the preparation of 1,4,2-oxathiazoles.

[1042]

[1043] Thiohydroximic acid of AV-1246 (180 mg, 0.014 M). Desired product was obtained as a yellow oil (100 mg, 55%). 'H NMR (600 MHz, CDCh) 87.75, 7.74, 7.74, 7.56, 7.55, 7.40, 7.39, 7.16, 7.16, 7.15, 4.20, 3.21, 3.20, 3.19, 3.18, 2.87, 2.12, 2.10, 1.76, 1.74, 1.72, 1.70, 1.56, 1.56, 1.55, 1.47, 1.47, 1.47. HRMS (ESI, m / z) calculated for C21H26N3O3S2, 432.14156 (M+H), found 432.14056.

[1044] Synthesis of tert-butyl 4-(4-(5-(4-fluorophenyl)-l,4,2-oxathiazol-3-yl)thiazol-2-yl)piperidine-l-carboxylate (AV- 1228): The target compound was synthesized using General procedure for the preparation of 1,4,2-oxathiazoles. Thiohydroximic

[1045]

[1046] acid of AV-1220 (308 mg, 0.014 M). Desired product was obtained as a clear oil (160 mg, 55%). 'HNMR (600 MHz, CDCh) 87.74, 7.56, 7.56, 7.55, 7.55, 7.55,Attorney Docket No. 10620-164W01

[1047] NCSU Ref.: 2025-138-03

[1048] 7.54, 7.54, 7.53, 7.53, 7.13, 7.10, 7.10, 7.10, 7.09, 7.09, 7.08, 7.08, 7.08, 7.07, 7.07, 7.07, 4.20, 3.22, 3.21, 3.21, 3.20, 3.19, 3.19, 3.18, 3.17, 3.17, 2.87, 2.12, 2.11, 2.10, 2.09, 1.76, 1.75, 1.74, 1.73, 1.72, 1.71, 1.70, 1.69, 1.47, 1.46, 1.45. LC-MS (ESI, APCI, m / z) 450 (M+H).

[1049] Synthesis of tert-butyl 4-(4-(5-(2-fluorophenyl)-l,4,2-oxathiazol-3-yl)thiazol-2- yl)piperidine-l-carboxylate (AV-1327): The target compound was (2 / synthesized using General procedure for the preparation of 1,4,2- '(J

[1050]

[1051] oxathiazoles. Thiohydroximic acid of AV-1319 (165 mg, 0.014 M). Desired product was obtained as a clear semisolid (72 mg, 43%). LC-MS (ESI, APCI, m / z) 450 (M+H).

[1052] Synthtesis of tert-butyl 4-(4-(5-(2-chlorophenyl)-l,4,2-oxathiazol-3-yl)thiazol-2- ci yl)piperidine-l-carboxylate (AV-1318) The target compound was ItA )=\

[1053] o synthesized using General procedure for the preparation of 1,4,2-

[1054]

[1055] A-d ' — / S'"

[1056] ' oxathiazoles. Thiohydroximic acid of AV-1314 (200 mg, 0.014 M). Desired product was obtained as a light yellow wax (60 mg, 30%). LC-MS (ESI, APCI, m / z) 466 (M+H).

[1057] Synthesis of tert-butyl 4-(4-(5-(2,6-difluorophenyl)-l,4,2-oxathiazol-3-yl)thiazol-2- yl)piperidine-l-carboxylate (1236) The target compound was synthesized using General procedure for the preparation of 1,4,2- oxathiazoles. Thiohydroximic acid of AV-1230 (500 mg, 0.014 M). Desired product was obtained as a waxy solid (190 mg, 38%). 'H NMR (600 MHz, CDCh) 5 8.10, 8.10, 8.10, 7.26, 7.26, 7.26, 4.23, 3.95, 3.95, 3.95, 3.94, 2.85, 2.13, 2.11, 1.76, 1.75, 1.74, 1.73, 1.73, 1.72, 1.71, 1.70, 1.69, 1.50, 1.47, 1.47, 1.47. LC-MS (ESI, APCI, m / z) 468 (M+H).

[1058] Synthesis of tert-butyl 4-(4-(5-(2-chloro-6-((methylsulfonyl)oxy)phenyl)-l,4,2- oxathiazol-3-yl)thiazol-2-yl)piperidine-l-carboxylate (AV- 1335).

[1059] O' PH'

[1060] <25° The target compound was synthesized using General procedure for the NA Z=\

[1061] s' preparation of 1,4, 2-oxathiazoles. Thiohydroximic acid of AV-1325 cr

[1062]

[1063] (256 mg, 0.014 M). Desired product was obtained as a milky wax (55 mg, 22%). 'H NMR (600 MHz, CDCh) 88.04, 7.75, 7.75, 7.75, 7.43, 7.42, 7.42, 7.41, 7.41, 7.39, 7.39, 7.39, 7.38, 7.38, 7.37, 7.37, 7.37, 7.37, 7.36, 7.36, 7.36, 7.35, 7.35, 7.35, 7.35, 7.34, 7.33, 7.32, 7.31, 7.29, 7.29, 7.28, 7.27, 7.27, 7.27, 7.25, 7.25, 7.24, 4.57, 4.45, 4.19, 3.44, 3.43, 3.42, 3.41, 3.41, 3.40, 3.38, 3.37, 3.36, 3.35, 3.34, 3.29, 3.26, 3.21, 3.20, 3.19, 3.19, 3.18, 3.17, 3.17, 3.16, 3.15, 3.15, 3.14, 3.13, 3.13, 2.87, 2.11, 2.09, 2.04, 1.75, 1.74, 1.73, 1.72, 1.71, 1.70, 1.69, 1.68, 1.66, 1.64, 1.55, 1.48, 1.47, 1.47, 1.47, 1.46, 1.46, 1.27, 1.26, 1.26, 1.25, 1.25. LC- MS (ESI, APCI, m / z) 560 (M+H).Attorney Docket No. 10620-164W01

[1064] NCSU Ref.: 2025-138-03

[1065] Boc-deprotection of 1,4,2-oxathiazole derivatives: In certain embodiments, Boc-carbamate deprotection is carried out by treating the protected 1,4,2-oxathiazole intermediate with trifluoroacetic acid (TFA, 20 equiv.) in DCM (0.1-0.5 M) and stirring the reaction mixture overnight, or until full conversion is observed (4-16 hours). After completion of the reaction, the solvent is removed under reduced pressure to provide the deprotected residue. Residual TFA is then removed by resuspending the residue in DCM followed by evaporation under reduced pressure, and this process may be repeated, for example two or more times, until traces of TFA are substantially eliminated. The resulting crude product can then be used directly in the subsequent synthetic step without further purification.

[1066] N'°> H R N-°> s Z~C TFA sRCH2CI2

[1067] , Me Cl Examples of Cl AV- 1251 AV-1238 AV-1327 AV-1320 AV-1250 AV-1341

[1068]

[1069] Synthesis of 5-phenyl-3-(2-(piperidin-4-yl)thiazol-4-yl)-l,4,2-oxathiazole (AV-1251):

[1070] The corresponding 1,4,2-oxathaizole AV- 1247 (17 mg, 1 equiv.) is dissolved in DCM (0.02 M) and added at R. T. trifluoroacetic acid (20

[1071]

[1072] equiv.). Desired product was obtained as a clear oil. Used without further purification. LC-MS (ESI, APCI, m / z) 332 (M+H).

[1073] Synthesis of 5-(4-fluorophenyl)-3-(2-(piperidin-4-yl)thiazol-4-yl)-l,4,2-oxathiazole (AV-1238) The corresponding 1,4,2-oxathaizole AV-1228 (52 mg, 1

[1074]

[1075] equiv.) is dissolved in DCM (0.05 M) and added at R. T. trifluoroacetic acid (20 equiv.). Desired product was obtained as a clear oil. Used without further purification. LC-MS (ESI, APCI, m / z) 350 (M+H).

[1076] Synthesis of 5-(2-fluorophenyl)-3-(2-(piperidin-4-yl)thiazol-4-yl)- 1.4.2-0 xa thiazole (AV-1348). The corresponding 1,4,2-oxathaizole AV-1327 (53 mg, 1 equiv.) is dissolved in DCM (0.01 M) and added at R. T. trifluoroacetic acid

[1077]

[1078] 25 (20 equiv.). Desired product was obtained as a clear oil. Used without further purification. LC-MS (ESI, APCI, m / z) 350 (M+H).Attorney Docket No. 10620-164W01

[1079] NCSU Ref.: 2025-138-03

[1080] Synthesis of 5-(2-chlorophenyl)-3-(2-(piperidin-4-yl)thiazol-4-yl)- 1.4.2-0 xa thiazole (AV- 1320). The corresponding 1,4,2-oxathaizole AV-1318 (60 mg, 1 equiv.) is dissolved in DCM (0.01 M) and added at R. T. trifluoroacetic acid

[1081]

[1082] (20 equiv.). Desired product was obtained as a clear oil. Used without further purification. LC-MS (ESI, APCI, m / z) 366 (M+H).

[1083] Synthesis of 5-(2,6-difhiorophenyI)-3-(2-(piperidin-4-yI)thiazol-4-yI)- 1,4,2- oxathiazole (AV- 1250). The corresponding 1,4,2-oxathaizole AV- 1236 (69

[1084]

[1085] mg, 1 equiv.) is dissolved in DCM (0.03 M) and added at R. T. trifluoroacetic acid (20 equiv.). Desired product was obtained as a clear oil. Used without further purification. LC-MS (ESI, APCI, m / z) 368 (M+H).

[1086] Synthesis of 3-chloro-2-(3-(2-(piperidin-4-yl)thiazol-4-yl)- l,4,2-oxathiazol-5- yl)phenyl methanesulfonate (AV-1341). The corresponding 1,4,2- oxathaizole AV-1335 (55 mg, 1 equiv.) is dissolved in DCM (0.02 M) and added at R. T. trifluoroacetic acid (20 equiv.). Desired product was

[1087]

[1088] obtained as a clear oil. Used without further purification. LC-MS (ESI, APCI, m / z) 460 (M+H).

[1089] General procedure for the synthesis of 1,4,2-oxathiazole piprolins:

[1090] In certain embodiments, amide bond formation is carried out by dissolving the carboxylic acid coupling partner in dry dimethylformamide (DMF, 0.01-0.05 M) and cooling the solution to 0 °C. A coupling reagent such as l-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI HC1, 1.1 equivalents) and a nucleophilic catalyst such as 4-dimethylaminopyridine (DMAP) (0.1 equivalents, optionally also supplemented to neutralize acidic counterions) are added, followed by addition of the amine component (1 equiv.). The reaction mixture is then allowed to warm to room temperature and stirred, for example overnight. Upon completion, the reaction mixture is diluted with water and brine, and extracted with an organic solvent such as ethyl acetate (3X). The combined organic layers may be washed with aqueous lithium chloride (5% w / v) and brine, dried over sodium sulfate, and concentrated under reduced pressure. The crude product may be purified, for example, by flash chromatography to afford the desired product.Attorney Docket No. 10620-164W01

[1091] NCSU Ref.: 2025-138-03

[1092]

[1093] 'uV'C# Synthesis of 2-(3,5-bis(difluoro-13-methyl)-lH-pyrazol-l-yl)- \N~~ \s

[1094] = l-(4-(4-(5-(4-fluorophenyI)-l,4,2-oxathiazol-3-yI)thiazol-2-

[1095]

[1096] F*c5 yl)piperidin-l-yl)ethan- 1-one (AV-1241). The corresponding 1,4,2- oxathaizole piprolin was synthesized using the general procedure reported for the amide coupling. The corresponding 1,4,2-oxathiazole amine trifluoroacetic salt (19 mg, 1 equiv.) was added to a DMF solution containing the acetic acid derivative (1.1 equiv.), EDCI HC1 (1.1 equiv.), and DMAP (3 equiv.). After purification, desired product was obtained as a white solid (20.1 mg, 66%). 1H NMR (600 MHz, CDC13) 87.77, 7.77, 7.56, 7.55, 7.55, 7.54, 7.14, 7.12, 7.11, 7.09, 7.08, 7.08, 6.87, 6.78, 6.76, 6.66, 5.18, 5.15, 5.14, 5.11, 4.57, 4.55, 3.92, 3.90, 3.36, 3.36, 3.35, 3.34, 3.33, 3.32, 3.30, 2.95, 2.93, 2.91, 2.28, 2.26, 2.21, 2.18, 1.90, 1.89, 1.88, 1.87, 1.85, 1.83, 1.81, 1.79, 1.77. HRMS (ESI, m / z) calculated for C23H21F5N5O2S2, 558.10568 (M+H), found 558.10510.

[1097] Synthesis of l-(4-(4-(5-(2,6-difluorophenyl)- l,4,2-oxathiazol-3-yl)thiazol-2- yl)piperidin-l-yl)-2-(5-methyl-3-(trifluoromethyl)-lH-pyrazol-l- yl)ethan-l-one (AV-1242). The corresponding 1,4,2-oxathaizole piprolin was synthesized using the general procedure reported for the

[1098]

[1099] amide coupling. The corresponding 1,4,2-oxathiazole amine trifluoroacetic salt (25 mg, 1 equiv.) was added to a DMF solution containing the acetic acid derivative (1.1 equiv.), EDCI HC1 (1.1 equiv.), and DMAP (3 equiv.). After purification, desired product was obtained as a white solid (27.3 mg, 72%). 1H NMR (600 MHz, CDC13) 88.05, 8.04, 7.80, 7.79, 7.53, 7.37, 7.35, 7.34, 7.33, 7.26, 7.26, 7.23, 7.22, 7.21, 6.95, 6.94, 6.93, 6.90,Attorney Docket No. 10620-164W01

[1100] NCSU Ref.: 2025-138-03

[1101] 6.88, 6.33, 5.02, 4.99, 4.98, 4.95, 4.57, 4.55, 4.37, 4.13, 4.12, 4.11, 4.11, 4.10, 4.10, 3.32, 3.30, 3.28, 2.92, 2.90, 2.88, 2.32, 2.32, 2.31, 2.24, 2.24, 2.22, 2.20, 2.17, 2.04, 2.04, 1.80, 1.78, 1.76, 1.74, 1.27, 1.27, 1.26, 1.25, 1.25, 1.24. HRMS (ESI, m / z) calculated for C23H21F5N5O2S2, 558.10568 (M+H), found 558.10455.

[1102] Synthesis of 2-(3,5-bis(difluoro-13-methyl)-lH-pyrazol-l-yl)-l-(4-(4-(5-(2,6- difhiorophenyl)-l,4,2-oxathiazol-3-yl)thiazol-2-yl)piperidin-l- yl)ethan-l-one (AV-1243). The corresponding 1,4,2-oxathaizole

[1103]

[1104] piprolin was synthesized using the general procedure reported for the amide coupling. The corresponding 1,4,2-oxathiazole amine trifluoroacetic salt (25 mg, 1 equiv.) was added to a DMF solution containing the acetic acid derivative (1.1 equiv.), EDCI HC1 (1.1 equiv.), and DMAP (3 equiv.). After purification, desired product was obtained as a white solid (28.3 mg, 72%). 1H NMR (600 MHz, CDC13) 87.81, 7.81, 7.80, 7.53, 7.38, 7.37, 7.36, 7.35, 7.34, 7.33, 7.26, 7.26, 7.26, 6.97, 6.96, 6.94, 6.93, 6.90, 6.89, 6.87, 6.76, 6.66, 6.66, 6.66, 5.17, 5.15, 5.14, 5.13, 5.11, 4.57, 4.54, 4.51, 3.92, 3.90, 3.34, 3.33, 3.31, 2.96, 2.94, 2.92, 2.29, 2.26, 2.21, 2.21, 2.19, 2.05, 2.04, 2.04, 1.90, 1.90, 1.88, 1.88, 1.86, 1.84, 1.81, 1.79, 1.27, 1.27, 1.26, 1.26, 1.25, 1.25, 1.24. HRMS (ESI, m / z) calculated for C23H20F6N5O2S2, 576.09626 (M+H), found 576.09460.

[1105] Synthesis of l-(4-(4-(5-(4-fluorophenyl)- l,4,2-oxathiazol-3-yl)thiazol-2-yl)piperidin- l-yl)-2-(5-methyl-3-(trifhioromethyl)-lH-pyrazol-l-yl)ethan-l- 5"e 20 one(AV- 1240). The corresponding 1,4,2-oxathaizole piprolin was

[1106]

[1107] synthesized using the general procedure reported for the amide coupling. The corresponding 1,4,2-oxathiazole amine trifluoroacetic salt (19 mg, 1 equiv.) was added to a DMF solution containing the acetic acid derivative (1.1 equiv.), EDCI HC1 (1.1 equiv.), and DMAP (3 equiv.). After purification, desired product was obtained as a white solid (18 mg, 61%). 1H NMR (600 MHz, CDC13) 87.77, 7.77, 7.76, 7.76, 7.55, 7.54, 7.14, 7.14, 7.13, 7.11, 7.09, 7.08, 6.33, 5.03, 5.00, 4.97, 4.95, 4.58, 4.56, 4.13, 4.13, 4.13, 4.12, 4.11, 4.11, 4.06, 4.04, 3.34, 3.32, 3.30, 3.28, 2.91, 2.89, 2.87, 2.33, 2.32, 2.32, 2.24, 2.21, 2.19, 2.17, 2.05, 2.05, 2.04, 2.04, 1.80, 1.78, 1.58, 1.28, 1.27, 1.26, 1.25, 1.25, 0.88, 0.84. HRMS (ESI, m / z) calculated for C23H22F4N5O2S2, 540.11510 (M+H), found 540.11389.Attorney Docket No. 10620-164W01

[1108] NCSU Ref.: 2025-138-03

[1109] Synthesis of 2-(5-methyl-3-(trifluoromethyl)- IH-pyrazol- 1-yl)- l-(4-(4-(5-phenyl- 4? l,4,2-oxathiazol-3-yl)thiazol-2-yl)piperidin-l-yl)ethan-l-one MBCVN / ^S> (AV-1253). The corresponding 1,4,2-oxathaizole piprolin was J=N, Nsynthesized using the general procedure reported for the amide F3C

[1110]

[1111] 5 coupling. The corresponding 1,4,2-oxathiazole amine trifluoroacetic salt (12.6 mg, 1 equiv.) was added to a DMF solution containing the acetic acid derivative (1.1 equiv.), EDCI HC1 (1.1 equiv.), and DMAP (3 equiv.). After purification, desired product was obtained as a white solid (6.7 mg, 33%). 1H NMR (600 MHz, CDC13) 87.77, 7.76, 7.76, 7.57, 7.55, 7.41, 7.40, 7.26, 7.26, 7.17, 7.16, 7.16, 6.34, 6.33, 6.33, 5.02, 5.00, 4.99, 4.99, 4.98, 4.98, 4.97, 4.95, 4.57, 4.55, 4.55, 4.06, 4.03, 3.32, 3.29, 3.27, 2.91, 2.89, 2.87, 2.32, 2.32, 2.23, 2.21, 2.19, 2.16, 1.80, 1.78, 1.77, 1.76, 1.75, 1.73, 1.58, 1.26. HRMS (ESI, m / z) calculated for C23H23F3N5O2S2, 522.12453 (M+H), found 522.12347.

[1112] Synthesis of l-(4-(4-(5-(2,6-difhiorophenyl)-l,4,2-oxathiazol-3-yl)thiazol-2-oyl)piperidin-l-yl)-2-(lH-pyrazol-l-yl)ethan- 1-one (AV-1254).

[1113] The corresponding 1,4,2-oxathaizole piprolin was synthesized using the general procedure reported for the amide coupling. The

[1114]

[1115] corresponding 1,4,2-oxathiazole amine trifluoroacetic salt (25 mg, 1 equiv.) was added to a DMF solution containing the acetic acid derivative (2 equiv.), EDCI HC1 (2.2 equiv.), and DMAP (5 equiv.). After purification, desired product was obtained as a white solid (17.6 mg, 54%). 1H NMR (600 MHz, CDC13) 87.79, 7.54, 7.54, 7.53, 7.52, 7.38, 7.37, 7.36, 7.35, 7.34, 7.34, 7.33, 6.95, 6.94, 6.92, 6.33, 6.33, 6.33, 5.07, 5.04, 5.03, 5.00, 4.61, 4.59, 4.07, 4.04, 3.31, 3.31, 3.30, 3.30, 3.29, 3.28, 3.28, 3.27, 3.26, 3.25, 3.22, 2.90, 2.89, 2.88, 2.87, 2.85, 2.18, 2.16, 1.79, 1.78, 1.77, 1.76, 1.74, 1.74, 1.73, 1.72, 1.68, 1.67, 1.66, 1.65, 1.64. HRMS (ESI, m / z) calculated for C21H20F2N5O2S2, 476.10265 (M+H), found 476.10131.

[1116] Synthesis of l-(4-(4-(5-(2,6-difhiorophenyl)-l,4,2-oxathiazol-3-yl)thiazol-2- N'f>' yl)piperidin- l-yl)-2-(3,5-dimethyl- lH-pyrazol-l-yl)ethan- 1-one (AV-1255). The corresponding 1,4,2-oxathaizole piprolin was synthesized using the general procedure reported for the amide

[1117]

[1118] coupling. The corresponding 1,4,2-oxathiazole amine trifluoroacetic salt (25 mg, 1 equiv.) was added to a DMF solution containing the acetic acid derivative (2 equiv.), EDCI HC1 (2.2 equiv.), and DMAP (5 equiv.). After purification, desired product was obtained as a white solid (11.9 mg, 35%). 1HNMR(6OO MHz, CDC13) 87.80, 7.79, 7.79, 7.53, 7.52, 7.52, 7.35, 6.96, 6.94, 6.92, 5.85, 5.85, 5.85, 4.91, 4.88, 4.88, 4.86, 4.85, 4.83, 4.60, 4.58,Attorney Docket No. 10620-164W01

[1119] NCSU Ref.: 2025-138-03

[1120] 4.08, 4.06, 3.29, 3.24, 3.22, 2.88, 2.85, 2.85, 2.83, 2.23, 2.23, 2.22, 2.21, 2.21, 2.18, 1.76, 1.74, 1.72. HRMS (ESI, m / z) calculated for C23H24F2N5O2S2, 504.13395 (M+H), found 504.13247.

[1121] 2-(3,5-bis(difluoro-13-methyl)-lH-pyrazol- 1-yl)- l-(4-(4-(5-(2-chlorophenyl)-l, 4,2- ct, « ° oxathiazol-3-yl)thiazol-2-yl)piperidin-l-yl)ethan- 1-one (AV-rro51324). The corresponding 1,4, 2-oxathaizole piprolin was synthesized A 'susing the general procedure reported for the amide coupling. The

[1122]

[1123] r2C’ corresponding 1,4,2-oxathiazole amine trifluoroacetic salt (4.4 mg, 1 equiv.) was added to a DMF solution containing the acetic acid derivative (2.0 equiv.), EDCI HC1 (2.2 equiv.), and DMAP (4.5 equiv.). After purification, desired product was obtained as a white solid (4.2 mg, 61%). 1H NMR (600 MHz, CDC13) 88.06, 7.77, 7.76, 7.69, 7.69, 7.68, 7.68, 7.68, 7.68, 7.41, 7.41, 7.41, 7.40, 7.39, 7.38, 7.33, 7.32, 7.32, 7.31, 7.31, 7.31, 7.31, 7.30, 7.30, 7.29, 7.29, 6.97, 6.96, 6.96, 6.91, 6.89, 6.87, 6.87, 6.86, 6.78, 6.78, 6.77, 6.76, 6.75, 6.67, 6.66, 6.57, 5.17, 5.15, 5.14, 5.13, 5.12, 5.11, 5.09, 4.55, 4.53, 4.36, 3.91, 3.89, 3.35, 3.34, 3.34, 3.33, 3.33, 3.32, 3.31, 3.30, 3.29, 2.94, 2.93, 2.92, 2.89, 2.26, 2.24, 2.18, 2.17, 2.16, 1.88, 1.86, 1.84, 1.82, 1.81, 1.80, 1.79, 1.78, 1.77, 1.75, 1.74, 1.73, 1.71, 1.35, 1.35, 1.34, 1.33, 1.32, 1.32, 1.31, 1.30, 1.29, 1.29, 1.28, 1.28, 1.27, 1.27, 1.26, 1.26, 1.25, 1.25, 1.25, 1.23, 1.22, 1.21. HRMS (ESI, m / z) calculated for C23H21C1F4N5O2S2, 574.07613 (M+H), found 574.07354.

[1124] Synthesis of 3-chloro-2-(3-(2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH-pyrazol-l- yl)acetyl)piperidin-4-yI)thiazol-4-yI)- l,4,2-oxathiazol-5-yI)phenyI methanesulfonate (AV- 1349). The corresponding 1,4, 2-oxathaizole JX+7piprolin was synthesized using the general procedure reported for the

[1125]

[1126] amide coupling. The corresponding 1,4,2-oxathiazole amine trifluoroacetic salt (14.3 mg, 1 equiv.) was added to a DMF solution containing the acetic acid derivative (1.1 equiv.), EDCI HC1 (1.2 equiv.), and DMAP (2 equiv.). After purification, desired product was obtained as a white solid (13.0 mg, 64%). 1H NMR (600 MHz, CDC13) 88.05, 8.05, 7.41, 7.40, 7.40, 7.38, 7.37, 7.37, 7.37, 7.37, 7.36, 7.36, 7.35, 7.35, 7.29, 7.27, 7.26, 7.25, 6.33, 5.02, 5.00, 4.99, 4.98, 4.96, 4.95, 4.94, 4.57, 4.55, 4.54, 4.53, 4.06, 4.03, 3.50, 3.49, 3.48, 3.47, 3.46, 3.39, 3.38, 3.36, 3.31, 3.31, 3.30, 3.30, 3.29, 3.29, 3.28, 3.27, 3.27, 3.26, 3.26, 2.90, 2.33, 2.33, 2.32, 2.32, 2.32, 2.32, 2.30, 2.29, 2.17, 2.16, 1.82, 1.82, 1.80, 1.78, 1.78, 1.76, 1.76, 1.74, 1.73, 1.72, 1.72. LC-MS (ESI, APCI, m / z) 650 (M+H).Attorney Docket No. 10620-164W01

[1127] NCSU Ref.: 2025-138-03

[1128] Synthesis of 2-(3-(2-(l-(2-(3,5-bis(difhioro-13-methyI)-lH-pyrazol-l-N,cy_^==^ yl)acetyl)piperidin-4-yI)thiazol-4-yI)-l,4,2-oxathiazol-5-yI)-3- o / " V-Z'TiS Ms0chlorophenyl methanesulfonate (AV-1350). The corresponding >n'n1,4, 2-oxathaizole piprolin was synthesized using the general

[1129]

[1130] procedure reported for the amide coupling. The corresponding 1,4,2-oxathiazole amine trifluoroacetic salt (14.3 mg, 1 equiv.) was added to a DMF solution containing the acetic acid derivative (1.1 equiv.), EDCI HC1 (1.2 equiv.), and DMAP (2 equiv.). After purification, desired product was obtained as a white solid (12.5 mg, 62%). 1H NMR (600 MHz, CDC13) 58.06, 7.41, 7.40, 7.40, 7.39, 7.37, 7.37, 7.37, 7.36, 7.36, 7.28, 7.26, 7.26, 7.25, 7.25, 6.97, 6.96, 6.87, 6.87, 6.79, 6.78, 6.78, 6.75, 6.75, 6.67, 6.66, 6.66, 6.57, 6.57, 5.17, 5.16, 5.15, 5.14, 5.13, 5.12, 5.11, 4.57, 4.57, 3.92, 3.90, 3.50, 3.49, 3.48, 3.47, 3.46, 3.45, 3.39, 3.38, 3.37, 3.35, 3.35, 3.35, 3.34, 3.34, 3.33, 3.32, 3.32, 3.31, 3.30, 2.95, 2.93, 2.91, 2.28, 2.25, 2.23, 2.22, 2.20, 2.18, 2.17, 1.90, 1.89, 1.87, 1.85, 1.84, 1.83, 1.82, 1.81, 1.80, 1.79, 1.78, 1.76, 1.75, 1.25. LC-MS (ESI, APCI, m / z) 668 (M+H).

[1131] Synthesis of 3-chloro-2-(3-(2-(l-(2-(3-(trifluoromethyl)-lH-pyrazol-l- Cl

[1132] n,0>=\ yl)acetyl)piperidin-4-yl)thiazol-4-yl)-l,4,2-oxathiazol-5-yl)phenyl0Ms° methanesulfonate (AV-1351). The corresponding 1,4, 2-oxathaizole O1piprolin was synthesized using the general procedure reported for the

[1133]

[1134] amide coupling. The corresponding 1,4,2-oxathiazole amine trifluoroacetic salt (14.3 mg, 1 equiv.) was added to a DMF solution containing the acetic acid derivative (1.1 equiv.), EDCI HC1 (1.2 equiv.), and DMAP (2 equiv.). After purification, desired product was obtained as a white solid (9.0 mg, 44%). 1H NMR (600 MHz, CDC13) 58.06, 8.05, 8.05, 7.61, 7.60, 7.60, 7.60, 7.59, 7.59, 7.37, 7.37, 7.36, 7.36, 7.28, 7.27, 7.26, 7.25, 7.25, 6.59, 6.59, 6.59, 5.13, 5.12, 5.09, 5.08, 5.07, 5.07, 5.06, 5.03, 4.57, 4.54, 4.54, 4.01, 3.99, 3.50, 3.49, 3.48, 3.47, 3.46, 3.38, 3.38, 3.35, 3.33, 3.33, 3.32, 3.32, 3.31, 3.31, 3.30, 3.30, 3.29, 3.28, 3.27, 3.27, 3.26, 3.26, 2.95, 2.94, 2.93, 2.91, 2.89, 2.89, 2.22, 2.20, 2.18, 2.17, 2.16, 1.81, 1.81, 1.79, 1.78, 1.77, 1.76, 1.75, 1.75, 1.73, 1.72, 1.25. LC-MS (ESI, APCI, m / z) 636 (M+H).

[1135] Synthesis of 2-(4-chlorophenyl)-l-(4-(4-(5-(4-fluorophenyl)-l,4,2-oxathiazol-3- yl)thiazol-2-yl)piperidin-l-yl)ethan-l-one (AV-1352). TheNJ-Z corresponding 1,4, 2-oxathaizole piprolin was synthesized using the VW

[1136] / V-' general procedure reported for the amide coupling. The

[1137]

[1138] corresponding 1,4,2-oxathiazole amine trifluoroacetic salt (10.0 mg, 1 equiv.) was added to a DMF solution containing the acetic acid derivative (1.1 equiv.), EDCIAttorney Docket No. 10620-164W01

[1139] NCSU Ref.: 2025-138-03

[1140] HC1 (1.2 equiv.), and DMAP (2 equiv.). After purification, desired product was obtained as a white solid (10.1 mg, 71%). 1H NMR (600 MHz, CDC13) 87.74, 7.56, 7.55, 7.55, 7.55, 7.54, 7.54, 7.54, 7.53, 7.53, 7.31, 7.31, 7.30, 7.30, 7.29, 7.29, 7.28, 7.20, 7.20, 7.19, 7.18, 7.18, 7.13, 7.11, 7.10, 7.10, 7.09, 7.09, 7.09, 7.08, 7.08, 7.08, 7.07, 7.07, 4.68, 4.65, 3.94, 3.92, 3.72, 3.27, 3.27, 3.26, 3.25, 3.25, 3.24, 3.23, 3.23, 3.22, 3.18, 3.17, 3.16, 3.15, 3.15, 3.13, 3.13, 2.81, 2.17, 2.16, 2.14, 2.09, 2.07, 1.75, 1.75, 1.74, 1.73, 1.73, 1.71, 1.71, 1.69, 1.69. LC-MS (ESI, APCI, m / z) 502 (M+H).

[1141] Synthesis of l-(4-(4-(5-(4-fluorophenyl)- l,4,2-oxathiazol-3-yl)thiazol-2-yl)piperidin- l-yl)-2-(4-(trifluoromethoxy)phenyl)ethan- 1-one (AV- 1353). The O Jj

[1142] s 10corresponding 1,4, 2-oxathaizole piprolin was synthesized using the

[1143]

[1144] 3'o-yj /

[1145] general procedure reported for the amide coupling. The corresponding 1,4,2-oxathiazole amine trifluoroacetic salt (10.0 mg, 1 equiv.) was added to a DMF solution containing the acetic acid derivative (1.1 equiv.), EDCI HC1 (1.2 equiv.), and DMAP (2 equiv.). After purification, desired product was obtained as a white solid (8.2 mg, 57%). 1H NMR (600 MHz, CDC13) 87.74, 7.74, 7.56, 7.55, 7.55, 7.55, 7.54, 7.54, 7.53, 7.53, 7.53, 7.30, 7.29, 7.29, 7.28, 7.28, 7.27, 7.21, 7.19, 7.19, 7.19, 7.18, 7.18, 7.18, 7.17, 7.17, 7.17, 7.13, 7.11, 7.10, 7.10, 7.09, 7.09, 7.09, 7.08, 7.08, 7.08, 7.07, 7.07, 4.68, 4.66, 3.97, 3.94, 3.78, 3.75, 3.75, 3.75, 3.72, 3.71, 3.29, 3.28, 3.27, 3.27, 3.26, 3.25, 3.25, 3.24, 3.23, 3.20, 3.20, 3.18, 3.18, 3.17, 3.16, 3.15, 2.82, 2.14, 2.11, 2.09, 1.76, 1.76, 1.74, 1.74, 1.74, 1.72, 1.71, 1.70, 1.69, 1.64, 1.61, 1.61, 1.59, 1.59, 1.55, 1.55, 1.54. LC-MS (ESI, APCI, m / z) 552 (M+H).

[1146] Synthesis of 2-(3,5-bis(difluoro-13-methyl)-lH-pyrazol-l-yl)-l-(4-(4-(5-(2- fhiorophenyl)-l,4,2-oxathiazol-3-yl)thiazol-2-yl)piperidin-l- yl)ethan-l-one (AV-1354). The corresponding 1,4, 2-oxathaizole piprolin was synthesized using the general procedure reported for

[1147]

[1148] 25 the amide coupling. The corresponding 1,4,2-oxathiazole amine trifluoroacetic salt (3.9 mg, 1 equiv.) was added to a DMF solution containing the acetic acid derivative (1.1 equiv.), EDCI HC1 (1.2 equiv.), and DMAP (2 equiv.). After purification, desired product was obtained as a white solid (1.5 mg, 24%). LC-MS (ESI, APCI, m / z) 558 (M+H).

[1149] Synthesis of piperazin-containing 1,4,2-oxathiazole piprolin analogs

[1150] Piperazin-containing analogs of 1,4,2-oxathiazole piprolin were synthesized according to the following scheme.Attorney Docket No. 10620-164W01

[1151] NCSU Ref.: 2025-138-03

[1152] NH2OH Pyridine EtOH

[1153] AV-1340 (2-Chloro-6-OMsPhenyl);

[1154] TBSCI

[1155] Imidazole 1 TBAF CH2CI2TEA, DMF 2 MnO2

[1156] CH2CI2AV-1347 AV-1383 1 TFA, CH2CI2EDCI-HCI, DMAP AV-1388 DMF, 0 °C - R T AV-1389 AV-1393 AV-1395 AV-1395

[1157]

[1158] Synthesis of 2-chlorothiazole-4-carbaldehyde oxime (AV-1331): To a solution of N'0Haldehyde (4.0 g, 1 equiv.) in absolute EtOH (0.5 M) was added hydroxylamine HC1 7r n

[1159]

[1160] (1.5 equiv.) and pyridine (3 equiv.) successively at R. T. The reaction was allowed to stir overnight or until consumption of the SM, and followed by TLC and LCMS. The reaction was quenched by the addition of IN HC1 and the bulk of the EtOH was removed by rotovap. The aqueous layer was extracted with EtOAc (3X) and the combined organic layers were washed with brine (IX), dried over MgSO4, filtered, and concentrated to yield the crude mixture of E / Z oximes as a light yellow solid. Mixture was purified using flash chromatography. Desired product obtained as a white solid (2.99 g, 72%). 'H NMR (600 MHz, DMSO) 5 11.45 (s, 1H), 8.11 (s, 1H), 7.88 (s, 1H). HRMS (ESI) found 162.97229.

[1161] Synthesis of 2-chloro-N-hydroxythiazole-4-carbimidoyl chloride (AV-1337). To a 1 „OH

[1162] ’j'l M solution of the corresponding oxime (2.99 g, 1 equiv.) in dry dimethylformamide d_ 'ifCl

[1163] " (0.5 M) at 0 °C was added one-fifth of the total N-chlorosuccinimide, followed by portion-wise addition of the reagent over one hour (1.2 equiv.). During this time, the reaction was allowed to warm slowly to room temperature and stir at this temperature for three hours. The mixture was poured on 10 volumes of ice and allowed to melt over time. Once all the ice has melted, the mixture was extracted with diethyl ether (3X). Combined organic layers were washedAttorney Docket No. 10620-164W01

[1164] NCSU Ref.: 2025-138-03

[1165] with lithium chloride (5% w / v), brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to afford the desired product. Crude used for next reaction.

[1166] Synthesis of 2,6-difluorobenzyl 2-chloro-N-hydroxythiazole-4-carbimidothioate OH

[1167] N' F (AV-1339). The corresponding chloroxime AV-1337 derivative (350 mg, 1CI~Cjr15j equiv.) was dissolved with diethyl ether (0.2 M) and cooled to 0 °C. Benzyl

[1168]

[1169] S p'

[1170] mercaptan derivative (1 equiv.) was then added at this temperature, followed by triethylamine (1 equiv.), and the reaction was allowed to stir overnight while warming to room temperature. The reaction was quenched by the addition of saturated ammonium chloride and diluted with deionized water. The aqueous layer was extracted with ethyl acetate (3X). The combined organic fractions were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude mixture was purified via flash chromatography to afford the desired product as a white solid (290 mg, 71%).JH NMR (600 MHz, DMSO) 5 12.10 (s, 1H), 7.89 (s, 1H), 7.37 (tt, J= 8.3, 6.6 Hz, 1H), 7.10 - 7.03 (m, 2H), 4.10 (s, 2H). LC-MS 321 m / z (M+H).

[1171] Synthesis of 2,6-difluorobenzyl 2-chloro-N-hydroxythiazole-4-carbimidothioate N'OHOMS (AV-1340). The corresponding chloroxime AV-1337 derivative (350 mg, 1Cl~\ J II J equiv.) was dissolved with diethyl ether (0.2 M) and cooled to 0 °C. Benzyl

[1172]

[1173] mercaptan derivative (1 equiv.) was then added at this temperature, followed by triethylamine (1 equiv.), and the reaction was allowed to stir overnight while warming to room temperature. The reaction was quenched by the addition of saturated ammonium chloride and diluted with deionized water. The aqueous layer was extracted with ethyl acetate (3X). The combined organic fractions were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude mixture was purified via flash chromatography to afford the desired product as a white solid (302 mg, 58%). 'H NMR (600 MHz, DMSO) 5 12.11 (s, 1H), 7.95 (s, 1H), 7.50 (dd, J= 8.0, 1.3 Hz, 1H), 7.44 (t, J= 8.1 Hz, 1H), 7.40 (dd, J= 8.2, 1.4 Hz, 1H), 4.18 (s, 2H), 3.53 (s, 3H). LC-MS 414 m / z (M+H).

[1174] Synthesis of 2-chloro-6-((methylsulfonyl)oxy)benzyl-N-((tert- N'OTBSOMS butyldimethylsilyl)oxy)-2-chlorothiazole-4-carbimidothioate (AV- 1347). h

[1175] Cl~<g Thiohydroximic acid AV-1340 was dissolved in dichloromethane, and TBSC1

[1176]

[1177] and imidazole were added at R. T. The reaction mixture was stirred overnight. Upon completion, solvent was removed under vacuo, and the residue was treated with 1 M HC1 solution and extracted with ethyl acetate, washed with brine, and dried over Na2SO4, and reduced in vacuo.Attorney Docket No. 10620-164W01

[1178] NCSU Ref.: 2025-138-03

[1179] Purified using flash chromatography to afford the desired product s a light yellow oil (465 mg, quant.).XH NMR (600 MHz, CDCh) 87.53 (s, 1H), 7.38 (dd, J= 8.3, 1.2 Hz, 1H), 7.32 (dd, J= 8.1, 1.3 Hz, 1H), 7.28 - 7.23 (m, 2H), 4.28 (s, 2H), 3.39 (s, 3H), 0.95 (s, 9H), 0.21 (s, 6H). LC- MS 528 m / z (M+H).

[1180] Synthesis of 2,6-difluorobenzyl N-((tert-butyldimethylsilyl)oxy)-2-chlorothiazole-4- f carbimidothioate (AV-1383). Thiohydroximic acid AV-1339 was dissolved

[1181]

[1182] ct— jFA. J in dichloromethane, and TBSC1 and imidazole were added at R. T. The reaction mixture was stirred overnight. Upon completion, solvent was removed under vacuo, and the residue was treated with 1 M HC1 solution and extracted with ethyl acetate, washed with brine, and dried over Na2SO4, and reduced in vacuo. Purified using flash chromatography to afford the desired product as a clear wax (340 mg, quant.). LC-MS 435 m / z (M+H).

[1183]

[1184] Ethyl (Z)-2-(benzhydrylthio)-2-(hydroxyimino)acetate (AV-2465-SM) was synthesized following Procedure A in 73% yield (277 mg) as a white powder. 1H NMR (700 MHz, CDC13) 87.43 - 7.38 (m, 4H), 7.31 (dd, J = 8.5, 6.9 Hz, 4H), 7.25 - 7.22 (m, 2H), 6.24 (s, 1H), 4.01 (q, J = 7.2 Hz, 2H), 1.08 (t, J = 7.2 Hz, 3H). 13C NMR (176 MHz, CDC13) 8 160.80, 148.08, 139.99, 128.87, 128.73, 127.90, 62.65, 53.52, 13.88. Rf (30% EtOAc) = 0.43. m.p.= 121-122 °C.

[1185]

[1186] Ethyl 5,5-diphenyl-l,4,2-oxathiazole-3-carboxylate (AV-2465) was synthesized following the General Procedure D in 45% yield (55 mg) as a clear oil. 1H NMR (700 MHz, CDC13) 87.54 - 7.48 (m, 4H), 7.41 - 7.34 (m, 6H), 4.36 (q, J = 7.1 Hz, 2H), 1.36 (t, J = 7.1 Hz, 3H). 13C NMR (176 MHz, CDC13) 8 158.36, 150.61, 140.60, 129.15, 128.34, 126.98, 111.08, 63.24, 14.03. RF (30% EtOAc) = 0.68.

[1187] Inhibition against Oomycetes

[1188] The anti-oomycete activity of the disclosed compounds is evaluated using an in vitro agar-based assay against Phytophthora nicotianae (black shank). Test compounds are prepared in acetone at a concetration of 10,000 ppm, and aliquot and incorporated into molten potatoAttorney Docket No. 10620-164W01

[1189] NCSU Ref.: 2025-138-03

[1190] dextrose agar (PDA) to achieve desired concentrations (ppm), followed by pouring into Petri dishes. After solidification, an agar plug (e.g., about 10 mm in diameter) of actively growing P. nicotianae is placed at the center of each plate. The plates are incubated under conditions suitable for growth, such as at approximately 25 °C, and monitored for up to 9 days or until the colony reaches the edge of the plate. In some embodiments, each condition is tested in quintuplicate. Growth inhibition is assessed by measuring colony expansion and / or the presence of an inhibition zone (halo), with halo diameters recorded along two perpendicular axes to account for non-uniform growth.

[1191] The anti-oomycete activity of example 1,4,2-oxathiazole analogs AV-1241, AV-1242, and AV- 1243 is summarised in Figure 12.

[1192] The anti-oomycete activity of example 1,4,2-oxathiazole analogs AV-1253, AV-1254, and AV-1255 is summarised in Figure 13.

[1193] The anti-oomycete activity of example 1,4,2-oxathiazole analogs AV- 1324, AV- 1349, and AV-1350 is summarised in Figure 14.

[1194] The anti-oomycete activity of example 1,4,2-oxathiazole analogs AV-1351, AV-1352, and AV-1353 is summarised in Figure 15.

[1195] The compounds, compositions, and methods of the appended claims are not limited in scope by the specific compounds, compositions, and methods described herein, which are intended as illustrations of a few aspects of the claims. Any compounds, compositions, and methods that are functionally equivalent are intended to fall within the scope of the claims. Various modifications of the compounds, compositions, and methods in addition to those shown and described herein are intended to fall within the scope of the appended claims. Further, while only certain representative compounds, compositions, and method steps disclosed herein are specifically described, other combinations of the compounds, compositions, and method steps also are intended to fall within the scope of the appended claims, even if not specifically recited. Thus, a combination of steps, elements, components, or constituents may be explicitly mentioned herein or less, however, other combinations of steps, elements, components, and constituents are included, even though not explicitly stated.

[1196] The term “comprising” and variations thereof as used herein is used synonymously with the term “including” and variations thereof and are open, non-limiting terms. Although the terms “comprising” and “including” have been used herein to describe various embodiments, the terms “consisting essentially of’ and “consisting of’ can be used in place of “comprising” andAttorney Docket No. 10620-164W01

[1197] NCSU Ref.: 2025-138-03

[1198] “including” to provide for more specific embodiments of the invention and are also disclosed. Other than where noted, all numbers expressing geometries, dimensions, and so forth used in the specification and claims are to be understood at the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, to be construed in light of the number of significant digits and ordinary rounding approaches.

[1199] Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of skill in the art to which the disclosed invention belongs. Publications cited herein and the materials for which they are cited are specifically incorporated by reference.

Claims

1. Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03WHAT IS CLAIMED IS:

1. A compound defined by Formula I belowFormula Ior a salt or ester thereof, whereinY is chosen from S, S=O, and S(=O)2;R1is chosen from alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, hetercycloalkyl, alkylcycloalkyl, alkylhetercycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, and heterodialkylaminocarbonyl, each optionally substituted with one or more substituents individually chosen from RA;R2is chosen from alkenyl, alkynyl, cycloalkyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, thioalkylcarbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, thioamido, aryl, and heteroaryl, each optionally substituted with one or more substituents individually chosen from RA;R3is chosen from hydrogen, alkyl, and haloalkyl, wherein the alkyl and haloalkyl groups are optionally substituted with one or more substituents individually chosen from RA; and RAis chosen from hydroxy, halogen, -CN, -NO2, amino, alkylamino, dialkylamino, alkyl, haloalkyl; alkylthio; haloalkylthio; alkoxy, haloalkoxy, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, nitrone, sulfonic acid, sulfonamido, thiol, phosphonate, phosphinyl, aldehyde, trimethylsilyl, hydrazino, azido, isocyanate, aryl, and heteroaryl;with the proviso that at least one of R1and R2is chosen from aryl and heteroaryl, each optionally substituted with one or more substituents individually chosen from RA;Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03with the proviso that when R2is unsubstituted phenyl, R1is not unsubstituted phenyl, ounsubstituted pyridyl, thiazolyl, or; andwith the proviso that when R2is unsubstituted pyridyl, R1is not unsubstituted phenyl.

2. The compound of claim 1, wherein R1is chosen from aryl and heteroaryl, each optionally substituted with one or more substituents individually chosen from RA.

3. The compound of any one of claims 1-2, wherein R1is phenyl, optionally substituted with one or more substituents individually chosen from RA.

4. The compound of any one of claims 1-2, wherein R1is pyridyl, optionally substituted with one or more substituents individually chosen from RA.

5. The compound of any one of claims 1-2, wherein R1is thiophenyl, optionally substituted with one or more substituents individually chosen from RA.

6. The compound of any one of claims 1-5, wherein R2is chosen from aryl and heteroaryl, each optionally substituted with one or more substituents individually chosen from RA.

7. The compound of any one of claims 1-6, wherein R2is phenyl, optionally substituted with one or more substituents individually chosen from RA.

8. The compound of any one of claims 1-6, wherein R2is pyridyl, optionally substituted with one or more substituents individually chosen from RA.

9. The compound of any one of claims 1-6, wherein R2is thiophenyl, optionally substituted with one or more substituents individually chosen from RA.

10. The compound of any one of claims 1-6, wherein R2is benzothiazole, optionally substituted with one or more substituents individually chosen from RA.Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-0311. The compound of any one of claims 1-6, wherein R2is pyrimidinyl, optionally substituted with one or more substituents individually chosen from RA.

12. The compound of any one of claims 1-11, wherein RAis chosen from halogen, -CN, -NO2, alkyl, haloalkyl, alkoxy, and haloalkoxy.

13. The compound of any one of claims 1-12, wherein R1, R2, or a combination thereof is substituted with one or more substituents individually chosen from RA.

14. The compound of any one of claims 1-13, wherein R3is hydrogen.

15. The compound of any one of claims 1-14, wherein the compound comprises one of the followingAttorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03AV-2465 AV-2466 AV-2565 AV-2566AV-2509AV-2506Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03AV-250816. A composition comprising an agriculturally acceptable adjuvant or carrier and an herbicidally, insecticidally, and / or fungicidally effective amount of a compound defined by Formula I belowFormula Ior a salt or ester thereof, whereinY is chosen from S, S=O, and S(=O)2;R1is chosen from alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, hetercycloalkyl, alkylcycloalkyl, alkylhetercycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, and heterodialkylaminocarbonyl, each optionally substituted with one or more substituents individually chosen from RA;R2is chosen from alkenyl, alkynyl, cycloalkyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, thioalkylcarbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, thioamido, aryl,Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03and heteroaryl, each optionally substituted with one or more substituents individually chosen from RA;R3is chosen from hydrogen, alkyl, and haloalkyl, wherein the alkyl and haloalkyl groups are optionally substituted with one or more substituents individually chosen from RA; and RAis chosen from hydroxy, halogen, -CN, -NO2, amino, alkylamino, dialkylamino, alkyl, haloalkyl; alkylthio; haloalkylthio; alkoxy, haloalkoxy, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, nitrone, sulfonic acid, sulfonamido, thiol, phosphonate, phosphinyl, aldehyde, trimethylsilyl, hydrazino, azido, isocyanate, aryl, and heteroaryl.

17. The composition of claim 16, wherein at least one of R1and R2is chosen from aryl and heteroaryl, each optionally substituted with one or more substituents individually chosen from RA.

18. The composition of any one of claims 16-17, wherein when R2is unsubstituted phenyl, oR1is not unsubstituted phenyl, unsubstituted pyridyl, thiazolyl, or19. The composition of any one of claims 16-18, wherein when R2is unsubstituted pyridyl, R1is not unsubstituted phenyl.

20. The composition of any one of claims 16-19, wherein R1is chosen from aryl and heteroaryl, each optionally substituted with one or more substituents individually chosen from RA.

21. The composition of any one of claims 16-20, wherein R1is phenyl, optionally substituted with one or more substituents individually chosen from RA.

22. The composition of any one of claims 16-20, wherein R1is pyridyl, optionally substituted with one or more substituents individually chosen from RA.Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-0323. The composition of any one of claims 16-20, wherein R1is thiophenyl, optionally substituted with one or more substituents individually chosen from RA.

24. The composition of any one of claims 16-23, wherein R2is chosen from aryl and heteroaryl, each optionally substituted with one or more substituents individually chosen from RA.

25. The composition of any one of claims 16-24, wherein R2is phenyl, optionally substituted with one or more substituents individually chosen from RA.

26. The composition of any one of claims 16-24, wherein R2is pyridyl, optionally substituted with one or more substituents individually chosen from RA.

27. The composition of any one of claims 16-24, wherein R2is thiophenyl, optionally substituted with one or more substituents individually chosen from RA.

28. The composition of any one of claims 16-24, wherein R2is benzothiazole, optionally substituted with one or more substituents individually chosen from RA.

29. The composition of any one of claims 16-24, wherein R2is pyrimidinyl, optionally substituted with one or more substituents individually chosen from RA.

30. The composition of any one of claims 16-29, wherein RAis chosen from halogen, -CN, -NO2, alkyl, haloalkyl, alkoxy, and haloalkoxy.

31. The composition of any one of claims 16-30, wherein R1, R2, or a combination thereof is substituted with one or more substituents individually chosen from RA.

32. The compound of any one of claims 16-31, wherein R3is hydrogen.

33. The composition of any one of claims 16-32, wherein the compound defined by Formula I comprises one of the followingAttorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03AV-2413AV-242142Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03AV-2465 AV-2466 AV-2565 AV-2566AV-2509AV-2506Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03AV-250834. The composition of any one of claims 16-33, wherein the composition further comprises an additional pesticide.

35. The composition of any one of claims 16-34, wherein the composition further comprises a herbicidal safener.

36. A method of controlling a pest chosen from a fungus, an insect, undesirable vegetation, or a combination thereof, the method comprising applying to vegetation or an area adjacent the vegetation or applying to soil or water to prevent the emergence or growth of a pest the compound of any of claims 1-15 or the composition of any of claims 16-35.

37. A method for preparing a 1,4,2-oxathiazole or an analog thereof, the method comprising contacting a thiohydroximic acid defined by Formula II below. OHl\F R3R1SFormula IIAttorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03or a salt or ester thereof, whereinR1is chosen from alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, hetercycloalkyl, alkylcycloalkyl, alkylhetercycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, and heterodialkylaminocarbonyl, each optionally substituted with one or more substituents individually chosen from RA;R2is chosen from alkenyl, alkynyl, cycloalkyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, thioalkylcarbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, thioamido, aryl, and heteroaryl, each optionally substituted with one or more substituents individually chosen from RA;R3is chosen from hydrogen, alkyl, and haloalkyl, wherein the alkyl and haloalkyl groups are optionally substituted with one or more substituents individually chosen from RA; and RAis chosen from hydroxy, halogen, -CN, -NO2, amino, alkylamino, dialkylamino, alkyl, haloalkyl; alkylthio; haloalkylthio; alkoxy, haloalkoxy, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, nitrone, sulfonic acid, sulfonamido, thiol, phosphonate, phosphinyl, aldehyde, trimethylsilyl, hydrazino, azido, isocyanate, aryl, and heteroaryl;with a heterogeneous catalyst under conditions effective to form a 1,4,2-oxathiazole defined by Formula I belowFormula Ior a salt or ester thereof, whereinR1is chosen from alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, hetercycloalkyl, alkylcycloalkyl, alkylhetercycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, and heterodialkylaminocarbonyl, each optionally substituted with one or more substituents individually chosen from RA;Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03R2is chosen from alkenyl, alkynyl, cycloalkyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, thioalkylcarbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, thioamido, aryl, and heteroaryl, each optionally substituted with one or more substituents individually chosen from RA;R3is chosen from hydrogen, alkyl, and haloalkyl, wherein the alkyl and haloalkyl groups are optionally substituted with one or more substituents individually chosen from RA; and RAis chosen from hydroxy, halogen, -CN, -NO2, amino, alkylamino, dialkylamino, alkyl, haloalkyl; alkylthio; haloalkylthio; alkoxy, haloalkoxy, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, nitrone, sulfonic acid, sulfonamido, thiol, phosphonate, phosphinyl, aldehyde, trimethylsilyl, hydrazino, azido, isocyanate, aryl, and heteroaryl; andoptionally oxidizing the 1,4,2-oxathiazole defined by Formula I to generate a sulfoxide or sulfone analog of the 1,4,2-oxathiazole defined by Formula I.

38. The method of claim 37, wherein contacting the thiohydroximic acid defined by Formula II with the heterogeneous catalyst comprises flowing the thiohydroximic acid defined by Formula II over or through a stationary phase comprising the heterogeneous catalyst.

39. The method of claim 38, wherein flowing the thiohydroximic acid defined by Formula II over or through a stationary phase comprising the heterogeneous catalyst comprises flowing a solution of the thiohydroximic acid defined by Formula II over or through a stationary phase comprising the heterogeneous catalyst at a flow rate of from 0.1 mL / min to 1 L / min.

40. The method of claim 39, wherein the thiohydroximic acid defined by Formula II exhibits a residence time with the heterogeneous catalyst of from 5 minutes to 4 hours, such as from 5 minutes to 2 hours.

41. The method of any one of claims 37-40, wherein the heterogeneous catalyst comprises an oxidant.Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-0342. The method of any one of claims 37-41, wherein the heterogeneous catalyst comprises a metal oxide, such as manganese oxide, potassium permanganate, chromium dichromate, chromium cromate, chromic acid, hydrogen peroxide, oxone, peracetic acid, mCPBA, or a combination thereof.

43. The method of any one of claims 37-42, wherein the thiohydroximic acid defined by Formula II is contacted with the heterogeneous catalyst at a temperature of from 0 °C to 50 °C, such as from 15 °C to 30 °C.

44. The method of any one of claims 37-43, wherein the method further comprises regenerating the heterogeneous catalyst.

45. A compound defined by Formula III belowFormula IIIwhereinRAis chosen from hydroxy, halogen, -CN, -NO2, amino, alkylamino, dialkylamino, alkyl, haloalkyl; alkylthio; haloalkylthio; alkoxy, haloalkoxy, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, haloalkoxy carbonyl, alkylaminocarbonyl, heteroalkylaminocarbonyl, dialkylaminocarbonyl, heterodialkylaminocarbonyl, nitrone, sulfonic acid, sulfonamido, thiol, phosphonate, phosphinyl, aldehyde, trimethylsilyl, hydrazino, azido, isocyanate, aryl, and heteroaryl;n is 0, 1, 2, or 3; andm is 0, 1, or 2.

46. The compound of claim 45, wherein the compound comprises one of the followingAttorney Docket No. 10620-164W01NCSU Ref.: 2025-138-0347. A method of protecting a cultivated crop plant from injury caused by application of an herbicide, the method comprising applying to the crop plant, to seed of the crop plant, or to soil in which the crop plant is growing or is to be grown, an effective safening amount of a safener compound defined by the formula below,0-Nor an agriculturally acceptable salt or ester thereof, whereinY is chosen from S, S=O, and S(=O)2; andRAis chosen from hydrogen, Ci-Ce alkyl, and Ci-Ce haloalkyl,in combination with the herbicide, thereby reducing herbicidal injury to the crop plant without substantially reducing herbicidal activity against undesired vegetation.

48. The method of claim 47, wherein the safener compound is one of the following:wherein the herbicide is chosen from herbicides that inhibit acetolactate synthase (ALS), acetyl-CoA carboxylase (ACCase), and 4-hydroxyphenylpyruvate dioxygenase (HPPD);wherein the herbicide is chosen from foramsulfuron, rimsulfuron, nicosulfuron, iodosulfuron-methyl-sodium, fenoxaprop-p-ethyl, mesotrione, isoxaflutole, sulcotrione,Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03tembotrione, dicamba, diflufenzopyr, metribuzin, S-metolachlor, dimethenamide, dimethenamide-P, flufenacet, and combinations thereof;or any combination thereof.

49. A compound defined by Formula V(A-R2)nFormula Vor an N-oxide or salt thereof, whereinA-E is a radical selected from the group consisting of(A-R1b)~^ ^A-A (A-R1c)>^ A-A.s / (A-Z6)A-W II (O)A-d A-E-1 A-E-2 A-E-3, andA-E-4A-A is CH- A-R15, N-A-R16or C(=O);A-G is an optionally substituted 5-membered heterocyclic ring;A-J is a 5-membered ring, an 8- to 11-membered bicyclic ring system or a 7- to 11-membered spirocyclic ring system, each ring or ring system comprising a 1,4,2-oxathiazole ring or an oxidized analog thereof, and optionally further comprising additional ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N, and up to 3 ring members selected from C(=O), C(=S), S(=O)A-S(=N-A-R23)A-f and Si-A-R17-A-R18, and optionally substituted with up to 5 substituents independently selected from A-R5;A-W1is O-A-R30, S-A-R31, N-A-R32- A-R33, or A-R28;A-W is O or S;A-X is a radical selected fromA-X A-X2A-X4Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03A-* A-u?and A-uA-X8A-X9wherein the bond of A-X1, A-X2, A-X3, A-X4, A-X5, A-X6, A-X7, A-X8, or A-X9which is identified with " A-t" is connected to the carbon atom identified with " A-q" of Formula V, the bond which is identified with " A-u" is connected to the carbon atom identified with " A-r" of Formula V, and the bond which is identified with " A-v" is connected to A-G ofFormula V;A-Z1is a direct bond, O, C(=O), S(O)A-m, CH- A-R20, or N-A-R21;A-Z5, A-Z6, A-Z7and A-Z8independently are a direct bond, C(=O) or S(O)2;A-Rla, A-Rlb, A-Rlcand A-Rldindependently are an optionally substituted phenyl, an optionally substituted naphthalenyl or an optionally substituted 5- to 6-membered heteroaromatic ring; or cyano, Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 alkynyl, Ci-Cs haloalkyl, C2-C8 haloalkenyl, C2-C8 haloalkynyl, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C4-C10 alkylcycloalkyl, C4-C10 cycloalkylalkyl, C4-C10 halocycloalkylalkyl, C5-C10 alkylcycloalkylalkyl, C2-C8 alkoxyalkyl, C2-Cs haloalkoxyalkyl, C4-C10 cycloalkoxyalkyl, C3-C10 alkoxyalkoxyalkyl, C2-C8 alkylthioalkyl, C2-C8 haloalkylthioalkyl, C2-C8 alkylsulfinylalkyl, C2-C8 alkylsulfonylalkyl, C3-C8alkoxy carbonylalkyl, C3-C8 haloalkoxy carbonylalkyl, C2-C8 alkylaminoalkyl, C3-C10 dialkylaminoalkyl, C2-C8 haloalkylaminoalkyl, C4-C10 cycloalkylaminoalkyl, Ci-Cs alkoxy, Ci-Cs haloalkoxy, C3-C8 cycloalkoxy, C3-C8 halocycloalkoxy, C4-C10 cycloalkylalkoxy, C2-C8 alkenyloxy, C2-C8 haloalkenyloxy, C2-C8 alkynyloxy, C3-C8 haloalkynyloxy, C2-C8 alkoxyalkoxy, C2-C8 alkylcarbonyloxy, C2-C8 haloalkylcarbonyloxy, C1-C8 alkylthio, C1-C8 haloalkylthio, C3-C8 cycloalkylthio, C3-C10 trialkylsilyl, C1-C8 alkylamino, C2-C8 dialkylamino, C1-C8 haloalkylamino, C2-C8 halodialkylamino, C3-C8 cycloalkylamino, C2-C8 alkylcarbonylamino, C2-C8 haloalkylcarbonylamino, C1-C8 alkylsulfonylamino, C1-C8 haloalkylsulfonylamino, pyrrolidinyl, piperidinyl or morpholinyl;each A-R2is independently halogen, cyano, hydroxy, C1-C4 alkyl, C1-C4 alkenyl, Ci-C4 haloalkyl or C1-C4 alkoxy; orAttorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03two A-R2groups are taken together as C1-C4 alkylene or C2-C4 alkenylene to form a bridged bicyclic or fused bicyclic ring system; ortwo A-R2groups attached to adjacent ring carbon atoms joined by a double bond are taken together as -CH=CH-CH=CH- optionally substituted with up to 3 substituents independently selected from halogen, cyano, hydroxy, amino, nitro, C1-C4 alkyl, Ci-C4 haloalkyl, C1-C4 alkoxy and C1-C4 haloalkoxy;A-R6is C1-C4 alkyl, C1-C4 haloalkyl, or C2-C4 alkoxyalkyl;each A-R5is independently H, halogen, cyano, hydroxy, amino, nitro, -CHO, -C(=O)OH, -C(=O)NH2, -N-A-R25-A-R26, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Ci-C6haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C4-C10 alkylcycloalkyl, C4-C10 cycloalkylalkyl, C6-C14 cycloalkylcycloalkyl, C4-C10 halocycloalkylalkyl, C5-C10 alkylcycloalkylalkyl, C3-C8 cycloalkenyl, C3-C8 halocycloalkenyl, C2-C6 alkoxy alkyl, C4-C10 cycloalkoxyalkyl, C3-C8 alkoxyalkoxyalkyl, C2-C6 alkylthioalkyl, C2-C6 alkylsulfinylalkyl, C2-C6 alkylsulfonylalkyl, C2-C6 alkylaminoalkyl, C3-C8 dialkylaminoalkyl, C2-C6 haloalkylaminoalkyl, C4-C10 cycloalkylaminoalkyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C4-C8 cycloalkylcarbonyl, C2-C6 alkoxycarbonyl, C4-C8 cycloalkoxycarbonyl, C5-C10 cycloalkylalkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, C4-C8 cycloalkylaminocarbonyl, C2-C6 haloalkoxyalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C8 cycloalkoxy, C3-C8 halocycloalkoxy, C4-C10 cycloalkylalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy,C2-C6 haloalkynyloxy, C2-C6 alkoxyalkoxy, C2-C6 alkylcarbonyloxy, C2-C6 haloalkylcarbonyloxy, C4-C8 cycloalkylcarbonyloxy, C3-C6 alkylcarbonylalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C3-C8 cycloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C3-C8 cycloalkylsulfonyl, C3-C10 trialkylsilyl, C1-C6 alkylsulfonylamino, C1-C6 haloalkylsulfonylamino, or -A-Z2-A-Q;each A-Z2is independently a direct bond, -O, -C(=O), -S(O)A-m, -CH-A-R20or -N-A-R21; each A-Q is independently phenyl, benzyl, naphthalenyl, a 5- to 6-membered heteroaromatic ring or an 8- to 11 -membered heteroaromatic bicyclic ring system, each optionally substituted with up to 2 substituents independently selected from A-R7aon carbon atom or nitrogen atom ring members, and each optionally substituted with up to 5 substituents independently selected from A-R7on carbon atom ring members and A-R12on nitrogen atom ring members; orAttorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03a 3- to 7-membered nonaromatic carbocyclic ring, a 5-, 6- or 7-membered nonaromatic heterocyclic ring or an 8- to 11 -membered nonaromatic bicyclic ring system, each optionally including ring members selected from the group consisting of C(=O), C(=S), S(=O)A-S(=N-A-R23)A-f and Si-A-R17-A-R18, and each ring or ring system optionally substituted with up to 2 substituents independently selected from A-R7aon carbon atom or nitrogen atom ring members, and each optionally substituted with up to 5 substituents independently selected from A-R7on carbon atom ring members and A-R12on nitrogen atom ring members;each A-R7ais independently -A-Z3-A-TA, -A-Z3-A-TNor -A-Z3-A-Tp;each A-Z3is independently a direct bond, O, N-A-R22, C(=O), C(=S), S(O)A-m, CH-A-R20, -CH-A-R2O-CH-AR20-, -C-A-R24=C-A-R27-, -OCH-A-R20-, or -CH-A-R20O-;each A-TAis independently phenyl, phenylethynyl, or a 5- to 6-membered heteroaromatic ring, each optionally substituted with up to 5 substituents independently selected from A-R29on carbon atom ring members, and each optionally substituted with up to 2 substituents independently selected from A-R22on nitrogen atom ring members;each A-TNis independently a 3- to 7-membered nonaromatic ring including ring members selected from the group consisting of C(A-R29)2, O, S, N-A-R22, -C(A-R29)=CC(A-R29)-, -C(A-R29)=N-, -N=N-, C(=O), C(=S), -C=C-, C(=N-A-R23), S(=O)A-s(=N-A-R23)A-f and Si-A-R17-A-R18;each A-Tpis independently an 8- to 10-membered aromatic or a 7- to 11 -membered nonaromatic bicyclic ring system, said ring system including ring members selected from the group consisting of C(A-R29)2, O, S, N-A-R22, -C(A-R29)=CC(A-R29)-, -C(A-R29)=N-, -N=N-, C(=O), C(=S), -C=C-, C(=N-A-R23), S(=O)A-s(=N-A-R23)A-f and Si-A-R17-A-R18;each A-R7is independently halogen, cyano, hydroxy, amino, nitro, Ci-Ce alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C6 cycloalkyl, C4-C10 cycloalkylalkyl, C4-C10 alkylcycloalkyl, C5-C10 alkylcycloalkylalkyl, C6-C14 cycloalkylcycloalkyl, Ci-Ce haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C6 halocycloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 haloalkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylsulfinyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylamino, C2-C8 dialkylamino, C3-C6 cycloalkylamino, C2-C4 alkoxyalkyl, C1-C4 hydroxyalkyl, C2-C4 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylcarbonyloxy, C2-C6 alkylcarbonylthio, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, or C3-C6 trialkylsilyl; orA-R5and A-R7are taken together with the atoms linking A-R5and A-R7to form an optionally substituted 5- to 7-membered ring containing ring members selected from carbonAttorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03atoms and optionally up to 3 heteroatoms selected from up to 1 O, up to 1 S, and up to 1 N, and up to 3 ring members selected from C(=O), C(=S), S(=O)A-s(=N-A-R23)A-f and Si-A-R17-A-R18;each A-R12is independently H, C1-C3 alkyl, C1-C3 alkylcarbonyl, C1-C3 alkoxy, or Ci-C3 alkoxy carbonyl;A-R15is H, halogen, cyano, hydroxy, -CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C2-C4 alkoxyalkyl, C2-C4 alkylthioalkyl, C2-C4 alkylsulfinylalkyl, C2-C4 alkylsulfonylalkyl, C2-C4 alkylcarbonyl, C2-C4 haloalkylcarbonyl, C2-C5 alkoxycarbonyl, C3-C5 alkoxycarbonylalkyl, C2-C5 alkylaminocarbonyl, C3-C5 dialkylaminocarbonyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 haloalkylthio, C1-C4 alkylsulfinyl, C1-C4 haloalkylsulfinyl, C1-C4 alkylsulfonyl, or C1-C4 haloalky Isulfonyl;A-R16is H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C2-C4 alkoxyalkyl, C2-C4 alkylthioalkyl, C2-C4 alkylsulfinylalkyl, C2-C4 alkylsulfonylalkyl, C2-C4 alkylcarbonyl, C2-C4 haloalkylcarbonyl, C2-C5 alkoxycarbonyl, C3-C5 alkoxycarbonylalkyl, C2-C5 alkylaminocarbonyl, C3-C5 dialkylaminocarbonyl, C1-C4 alkylsulfonyl or C1-C4 haloalkylsulfonyl;each A-R17and A-R18is independently C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, C3-C5 cycloalkyl, C3-C6 halocycloalkyl, C4-C10 cycloalkylalkyl, C4-C7 alkylcycloalkyl, C5-C7 alkylcycloalkylalkyl, C1-C5 haloalkyl, C1-C5 alkoxy, or C1-C5 haloalkoxy;each A-R20, A-R22, A-R24and A-R27is independently H, C1-C4 alkyl or C1-C4 haloalkyl; each A-R21is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C2-C6 alkoxycarbonyl or C2-C6 haloalkoxycarbonyl; each A-R23is independently H, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylamino, C2-C8 dialkylamino, C1-C6 haloalkylamino, or phenyl;each A-R25is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C2-C6 alkoxycarbonyl, or C2-C6 haloalkoxycarbonyl; each A-R26is independently Ci-Ce alkyl, Ci-Ce haloalkyl, C3-C8 cycloalkyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 haloalkoxycarbonyl or -A-Z4-A-Q;each -A-Z4is independently O, C(=O), S(O)A-m or CH-A-R20;A-R28is H, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkoxyalkyl, C2-C4 alkylcarbonyl, C2-C4 alkoxy carbonyl, C2-C3 alkylaminocarbonyl or C3-C6 dialkylaminocarbonyl;Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03each A-R29is independently H, halogen, cyano, hydroxy, amino, nitro, -CHO, -C(=O)OH, -C(=O)NH2, -SO2NH2, -C(=S)NH2, -C(=O)NHCN, -C(=O)NHOH, -SH, -SO2NHCN, -SO2NHOH, -OCN, -SCN, -SF5, -NHCHO, -NHNH2, -N3, -NHOH, -NHCN, -NHC(=O)NH2, -N=C=O, -N=C=S, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Ci-Ce haloalkyl, C2-C8 alkylcarbonyl, C2-C8 haloalkylcarbonyl, C2-C8 alkoxy carbonyl, C4- C10 cycloalkoxycarbonyl, C5-C12 cycloalkylalkoxycarbonyl, C2-C8 alkylaminocarbonyl, C3-C10 dialkylaminocarbonyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C4-C10 alkylcycloalkyl, C4-C10 cycloalkylalkyl, C6-C14 cycloalkylcycloalkyl, C4-C10 halocycloalkylalkyl, C5-C12 alkylcycloalkylalkyl, C3-C8 cycloalkenyl, C3-C8 halocycloalkenyl, C2-C8 alkoxyalkyl, C4-C10 cycloalkoxyalkyl, C3-C10 alkoxyalkoxyalkyl, C2-C8 alkylthioalkyl, C2-C8 alkylsulfinylalkyl, C2-C8 alkylsulfonylalkyl, C2-C8 alkylaminoalkyl, C3-C10 dialkylaminoalkyl, C2-C8 haloalkylaminoalkyl, C4-C10 cycloalkylaminoalkyl,C4-C10 cycloalkylcarbonyl, C4-C10 cycloalkylaminocarbonyl, C2-C7 cyanoalkyl, Ci-Ce hydroxy alkyl, C4-C10 cycloalkenylalkyl, C2-C8 haloalkoxyalkyl, C2-C8 alkoxyhaloalkyl, C2-C8 haloalkoxyhaloalkyl, C4-C10 halocycloalkoxyalkyl, C4-C10 cycloalkenyloxyalkyl, C4-C10 halocycloalkenyloxyalkyl, C3-C10 dialkoxyalkyl, C4-C12 trialkoxyalkyl, C3-C8 alkoxyalkenyl, C3-C8 alkoxyalkynyl, C3-C10 halodialkylaminoalkyl, C5-C12 cycloalkyl(alkyl)aminoalkyl, C2-C8 alkyl(thiocarbonyl), C3-C10 alkoxyalkylcarbonyl, C3-C10 alkoxycarbonylalkyl, C2-C8 haloalkoxycarbonyl, C3-C10 alkoxyalkoxycarbonyl, C2-C8 (alkylthio)carbonyl, C2-C8 alkoxy(thiocarbonyl), C2-C8 alkylthio(thiocarbonyl), C2-C8 alkylamino(thiocarbonyl), C3-C10 dialkylamino(thiocarbonyl), C3-C10 alkoxy (alkyl)aminocarbonyl, C2-C8 alkylsulfonylaminocarbonyl, C2-C8 haloalkylsulfonylaminocarbonyl, C2-C8 alkylamidino, C3-C10 dialkylamidino, Ci-Ce alkoxy, Ci-Ce haloalkoxy, C2-C8 alkylcarbonyloxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, Ci-Ce alkylaminosulfonyl, C2-C8 dialkylaminosulfonyl, C3-C10 trialkylsilyl, C3-C8 cycloalkoxy, C3-C8 halocycloalkoxy, C4-C10 cycloalkylalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C3-C6 haloalkynyloxy, C2-C8 alkoxyalkoxy, C2-C8 haloalkylcarbonyloxy, C4-C10 cycloalkylcarbonyloxy, C3-C10 alkylcarbonylalkoxy, C3-C8 cycloalkylthio, C3-C8 cycloalkylsulfonyl, C3-C8 cycloalkenyloxy, C3-C8 halocycloalkenyloxy, C2-C8 haloalkoxyalkoxy, C2-C8 alkoxyhaloalkoxy, C2-C8 haloalkoxyhaloalkoxy, C3-C10 alkoxycarbonylalkoxy, C2-C8 alkyl(thiocarbonyl)oxy, C2-C8 alkylcarbonylthio, C2-C8 alkyl(thiocarbonyl)thio, C3-C8 cycloalkylsulfmyl, C3-C10 halotrialkylsilyl, Ci-Ce alkylamino, C2-C8 dialkylamino, C2-C8 alkylcarbonylamino, Ci-Ce alkylsulfonylamino, Ci-Ce haloalkylamino,Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03C2-C8 halodialkylamino, C3-C8 cycloalkylamino, C2-C8 haloalkylcarbonylamino, Ci-Ce haloalkylsulfonylamino, C4-C10 cycloalkylalkylamino, C4-C10 cycloalkyl(alkyl)amino, C3-C10 alkoxycarbonylalkylamino, Ci-Ce alkoxyamino, Ci-Ce haloalkoxyamino, C4-C12 dialkylimido, C2-C8 alkoxy carbonylamino, C2-C8 haloalkoxy carbonylamino, C2-C8 alkylaminocarbonylamino, C3-C10 dialkylaminocarbonylamino, C3-C10 alkylaminocarbonyl(alkyl)amino, C4-C12 dialkylaminocarbonyl(alkyl)amino, C2-C8 alkylamino(thiocarbonyl)amino, C3-C10 dialkylamino(thiocarbonyl)amino, C3-C10 alkylamino(thiocarbonyl)alkylamino or C4-C12 dialkylamino(thiocarbonyl)alkylamino;each A-R30and A-R31is independently C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C1-C6 haloalkyl, C3-C6 haloalkenyl, C3-C6 haloalkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C4-C8 alkylcycloalkyl, C4-C8 cycloalkylalkyl, C4-C8 halocycloalkylalkyl, C5-C8 alkylcycloalkylalkyl, C2-C6 alkoxyalkyl, C4-C8 cycloalkoxyalkyl, C3-C6 alkoxyalkoxyalkyl, C2-Ce alkylthioalkyl, C2-C6 alkylsulfinylalkyl, C2-C6 alkylsulfonylalkyl, C2-C6 alkylaminoalkyl, C3-C6 dialkylaminoalkyl, C2-C6 haloalkylaminoalkyl, C4-C8 cycloalkylaminoalkyl,C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C4-C8 cycloalkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl or C4-C8 cycloalkylaminocarbonyl;A-R32is H, cyano, hydroxy, amino, Ci-Ce alkyl, C3-C6 alkenyl, C3-C6 alkynyl, Ci- Ce haloalkyl, C3-C6 haloalkenyl, C3-C6 haloalkynyl, C3-C6 cycloalkyl, C4-C8 cycloalkylalkyl, C2-C6 alkoxyalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, Ci-Ce alkylamino, C2-C8 dialkylamino, Ci-Ce haloalkylamino or C2-C8 halodialkylamino;A-R33is H, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C1-C6 haloalkyl or C3-C6 cycloalkyl; orA-R32and A-R33are taken together as -(CH2)4-, -(CH2)5- or -(CH2)2O(CH2)2-;A-d is 1 or 2;each A-m is independently 0, 1 or 2;A-n is 0, 1 or 2; andA-s and A-f are independently 0, 1 or 2 in each instance of S(=O)A-s(=N-A-R23)A-f, provided that the sum of A-s and A-f is 1 or 2.

50. The compound of claim 49, wherein A-J comprises A-J-29:Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03A-J-29wherein the bond shown projecting to the left is bonded to A-Z1in Formula V and to an available carbon or nitrogen atom ring member in the A-J ring;A-x is 0, 1, or 2; andY is chosen from S, S=O, and S(=O)2.

51. The compound of any one of claims 49-50, wherein A-J comprises one of A-J-29-1 to A- J-29-40:Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03A-J-29-11 A-J-29-12A-J-29-18A-J-29-19 A-J-29-23 A-J-29-24A-J-29-25A-J-29-32 A-J-29-34 A-J-29-35 A-J-29-36A-J-29-38 A-J-29-40 wherein Y is chosen from S, S=O, and S(=O)2.

52. The compound of claim 49, wherein A-E is A-E-l or A-E-2;A-G is a 5-membered heterocyclic ring optionally substituted with up to 2 substituents selected from A-R3on carbon ring members and selected from A-R11on nitrogen ring members;each A-R3is independently halogen, C1-C3 alkyl or C1-C3 haloalkyl;each A-R11is independently C1-C3 alkyl;Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03A- J comprises A-J-29:A-J-29wherein the bond shown projecting to the left is bonded to A-Z1in Formula V and to an available carbon or nitrogen atom ring member in the A-J ring; A-x is 0, 1, or 2; and Y is chosen from S, S=O, and S(=O)2;A-X is A-X1, A-X2, A-X3, A-X4, A-X5. A-X6A-X7, or A-X8;A-Z1is a direct bond, CH-A-R20, or N-A-R21;each A-R21is independently H, C1-C3 alkyl, C1-C3 alkylcarbonyl or C2-C3alkoxy carbonyl;A-Rla, A-Rlb, and A-Rlcindependently are optionally substituted phenyl, optionally substituted naphthalenyl or an optionally substituted 5- or 6-membered heteroaromatic ring; or cyano, Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 alkynyl, Ci-Cs haloalkyl, C2-C8 haloalkenyl, C2-C8 haloalkynyl, C2-C8 haloalkylthioalkyl, C3-C8 cycloalkyl, C2-C8 alkoxyalkyl, C2-C8 haloalkoxyalkyl, C3-C8 alkoxycarbonylalkyl, C3-C8 haloalkoxycarbonylalkyl, C2-C8 alkylthioalkyl, C2-C8 alkylsulfinylalkyl, C2-C8 alkylsulfonylalkyl, C2-C8 alkylaminoalkyl, C2-C8 alkylcarbonyloxy, C2-C8 haloalkylcarbonyloxy, C3-C10 dialkylaminoalkyl, Ci-Cs alkoxy, Ci-Cs haloalkoxy, Ci-Cs alkylthio, C3-C10 trialkylsilyl, Ci-Cs alkylamino, C2-C8 dialkylamino, C2-C8 alkylcarbonylamino, pyrrolidinyl, piperidinyl or morpholinyl;each A-R2is independently halogen, cyano, hydroxy, C1-C2 alkyl, C1-C2 haloalkyl or Ci-C2 alkoxy;A-R5is independently H, halogen, cyano, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Ci-Ce haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C4-C10 alkylcycloalkyl, C4-C10 cycloalkylalkyl, C2-C6 alkoxyalkyl, C4-C10 cycloalkoxyalkyl, C3-C8 alkoxyalkoxyalkyl, C2-C6 alkylthioalkyl, C2-C6 alkoxycarbonyl, Ci-Ce alkoxy, Ci-Ce haloalkoxy, C3-C8 cycloalkoxy, C3-C8 halocycloalkoxy, C4-C10 cycloalkylalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C2-C6 haloalkynyloxy, C2-C6 alkoxyalkoxy, C2-C6 alkylcarbonyloxy, C2-C6 haloalkylcarbonyloxy, C4-C8 cycloalkylcarbonyloxy, C3-C6 alkylcarbonylalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C3-C8 cycloalkylthio, C3-C10 trialkylsilyl, -N-A-R25-A-R26or -A-Z2-A-Q;each A-R26is independently C1-C3 alkyl or -A-Z4-A-Q;each A-Z4is independently C(=O) or S(=O)2;Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03each A-Z2is independently a O, C(=O), S(O)2, CH-A-R20or N-A-R21;each A-Q is independently phenyl, benzyl, naphthalenyl, a 5- to 6-membered heteroaromatic ring or an 8- to 11 -membered heteroaromatic bicyclic ring system, each optionally substituted with up to 1 substituent independently selected from A-R7aon carbon atom or nitrogen atom ring members, and each optionally substituted with up to 5 substituents independently selected from A-R7on carbon atom ring members and A-R12on nitrogen atom ring members; or a 3- to 7-membered nonaromatic carbocyclic ring, a 5-, 6- or 7-membered nonaromatic heterocyclic ring or an 8- to 11 -membered nonaromatic bicyclic ring system, each optionally including ring members selected from the group consisting of C(O), C(=S), S(=O)A-s(=N-A-R23)A-f and Si-A-R17-A-R18, and each ring or ring system optionally substituted with up to 1 substituent independently selected from A-R7aon carbon atom or nitrogen atom ring members, and each optionally substituted with up to 5 substituents independently selected from A-R7on carbon atom ring members and A-R12on nitrogen atom ring members;each A-R7is independently halogen, cyano, hydroxy, amino, nitro, C1-C3 alkyl, C1-C3 haloalkyl, C1-C2 alkoxy or C1-C2 haloalkoxy; or A-R5and A-R7are taken together with the atoms linking A-R5and A-R7to form an optionally substituted 5- to 7-membered ring containing ring members selected from carbon atoms and optionally up to 3 heteroatoms selected from up to 1 O, up to 1 S and up to 1 N, and up to 2 ring members selected from C(=O), C(=S), S(=O)A-s(=N-A-R23)A-f and Si-A-R17-A-R18, the ring optionally substituted with substituents selected from A-R8;each R8is independently halogen, cyano, hydroxy, amino, nitro, Ci-Ce alkyl, C2-Ce alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C10 cycloalkylalkyl, C4-C10 alkylcycloalkyl, Cs-C10 alkylcycloalkylalkyl, Ci-Ce haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C6 halocycloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulftnyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylthio, C1-C4 haloalkylsulftnyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylamino, C2-C8 dialkylamino, C3-C6 cycloalkylamino, C2-C4 alkoxyalkyl, C1-C4 hydroxyalkyl, C2-C4 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylcarbonyloxy, C2-C6 alkylcarbonylthio, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, or C3-Ce trialkylsilyl;each A-R7ais independently -A-Z3-A-TA;each A-R29is independently H, halogen, cyano, hydroxy, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy or C1-C2 haloalkoxy;Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03each A-TAis independently selected from A-TA-18 and A-TA-49 wherein the bond shown projecting to the left is bonded to A-Z3in Formula V and A-r is 0, 1, 2, 3, 4 or 5A-rNA-TA-18 A-TA-49A-R15is H, halogen, cyano, hydroxy, -CHO, C1-C4 alkyl, C1-C4 haloalkyl,C1-C4 alkoxy or C2-C5 alkoxy carbonyl; andA-R16is H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkylcarbonyl, C2-C4 haloalkylcarbonyl or C2-C4 alkoxy carbonyl.

53. The compound of claim 52, whereinA-G is one of A-G-l through A-G-59 wherein the bond projecting to the left is bonded to A-X, and the bond projecting to the right is bonded to Z1in Formula 1Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03(A-R3a) (A-R11),, JLA-G-6 (A-R3a)(A-R3a)(A-R3a) (A-R3a) / / (A-R11a)^ / / , N (A-R3a) N— £ (A-R3a) | V- (A-R3a7u y-(A-R3a) L / ?— (A-R3a) * \ s N >- ■ Z^N Z A A-G-33A R3a)A-G-34(A'R3a) A’G’35 A’G’36A-G-37 A-G-38 A-G-39 A-G-40 < A-R3a)(A-R11a)A-G-58 (A-RJa) whereineach A-R3ais independently selected from H and A-R3;A-Rllais selected from H and A-R11;A-x is 0, 1, or 2;A-X is A-X1, A-X2, or A-X3;A-Z1is a direct bond or CH-A-R20;each A-R21is independently H or methyl;A-Z5and A-Z6independently are each a direct bond;A-Rlaand A-Rlbindependently are phenyl, naphthalenyl or a 5- or 6-membered heteroaromatic ring, each optionally substituted with up to 3 substituents selected from A-R4aonAttorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03carbon ring members and A-R4bon nitrogen ring members; or cyano, Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 alkynyl, Ci-Cs haloalkyl, C2-C8 haloalkenyl, C2-C8 haloalkynyl, C2-C8 haloalky Ithioalkyl, C3-C8 cycloalkyl, C2-C8 alkoxyalkyl, C2-C8 haloalkoxyalkyl, C3-C8 alkoxycarbonylalkyl, C3-C8 haloalkoxycarbonylalkyl, C2-C8 alkylthioalkyl, C2-C8 alkylsulfinylalkyl, C2-C8 alkylsulfonylalkyl, C2-C8 alkylaminoalkyl, C2-C8 alkylcarbonyloxy, C2-C8 haloalkylcarbonyloxy, C3-C10 dialkylaminoalkyl, Ci-Cs alkoxy, Ci-Cs haloalkoxy, Ci-Cs alkylthio, C3-C10 trialkylsilyl, Ci-Cs alkylamino, C2-C8 dialkylamino, C2-C8 alkylcarbonylamino, pyrrolidinyl, piperidinyl or morpholinyl;each A-R4ais independently halogen, cyano, hydroxy, amino, nitro, Ci-Cg alkyl, C2-Ce alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C10 cycloalkylalkyl, C4-C10 alkylcycloalkyl, Cs-C10 alkylcycloalkylalkyl, Ci-Ce haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C6 halocycloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylthio, C1-C4 haloalkylsulfinyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylamino, C2-C8 dialkylamino, C3-C6 cycloalkylamino, C2-C4 alkoxyalkyl, C1-C4 hydroxyalkyl, C2-C4 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylcarbonyloxy, C2-Ce alkylcarbonylthio, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl or C3-Ce trialkylsilyl;each A-R4bis independently Ci-Ce alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, Ci-Ce haloalkyl, C3-C6 haloalkenyl, C3-C6 haloalkynyl, C3-C6 halocycloalkyl or C2-C4 alkoxy alkyl;each A-R2is independently cyano, hydroxy, methyl or methoxy;each A-R5is independently H, halogen, cyano, Ci-Ce alkyl, Ci-Ce haloalkyl,C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C2-C6 alkoxy alkyl, Ci-Ce alkoxy, Ci-Ce haloalkoxy, C3-Cs cycloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C2-C6 alkoxyalkoxy, C2-C6 alkylcarbonyloxy, C2-C6 haloalkylcarbonyloxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C3-C10 trialkylsilyl, -N- A-R25-A-R26or -A-Z2-A-Q;each A-Z2is independently a direct bond or N-A-R21;A-Q is one of A-Q-l through A-Q-106 wherein p is an integer from 0 to 5 and q is an integer from 0 to 2Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03^-(A-R7)P^^-(A-R7)P r^(A-R7)pN-^-(A-R7)PN-^.(A. R7)PO-<A-R)P^SX(A-R7a)q\?> A-R7a)q'NX(A-R7’), S^(A-R7a)q\r-(A-R7a)q'^XS>'(A-R7a)qS^(A-R7a)qA-Q-1 A-Q-2 R12A-Q-3 A-Q-4 A-Q-5 A-Q-6 A-Q-8lp^N-^(A-R7)p^^-(A-R7)pO-<A-R )r, ^^(A-R7)P ^^<A-R7)p^-^<A-R7)fr^<A-R7) < \NtO'X(A-R7a),, C(A-R7a)q ^(A-R^P ^VR73) %XA-R73),>, A-Q-9 <■ ^< A - AA-R A>« -5 - 0 QA- Q 1R R7^- -7A-Q-1611RA-Q-12RA-Q-13RA-Q-14 N-Dr-(A-R7)pn-<A-R7)p\? NA-R7a)q\> XA-R A-Q-177a)qA-Q-24 W-<A-R7)P | ^-(A-R7)P V"(A-R7i% VX(A-R7a)qA-Q-25 A-Q-32 jQr(A-R7)pAm 1>A-R7)pJ[N>(A-R7)P X^r(A-R7)p ^^^fA-R^^N^A-RTa^ ^N^(A. R7a)q^" N^A-R7’), ^NX(A-R7a)qA-Q-34 A-Q-35 A-Q-36 A-Q-37 A-Q-38 JCJT(A-R7)P X,}r(A-N’X(A-R7a)qR7)pJ; J-<A-R7)JL ^(A'R7)UL><(A'R7)PLA-0 A^~(A'R7)P_<^(A-R7)P 7A-R7a)qN'(A-R7a)qN'(A-R7a)q<A’R7a)q ^ ^^(A-R73)^^^ (A-R7a)q^(A-R7a)qA-Q-41 A-Q-42 A-Q-43 A-Q-44 A-Q-451A-O-462A-Q-47 A-Q-48(A-R7)P_ / ^-(A-R7)P<>-(A-R7)P_y^(A-R7)p_z>5'<A-R7>p— O<A-R7)P- ^J-(A-R7)P\3>(A-R7a)q(A-R7a)q^(A-R7a)q'^(A-R7a)T^s<(A-R7a)qX(A-R7a)qX(A-R7a)qA-Q-55 A-Q-54 A-Q-49 A-Q-52 A-Q-53 A-Q-50 A-Q-51Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03o o O o <R12-A)'N? JT J-< A-R7)P I [ J-(A-R7)PI jf J-(A-R7)PY Ji0 NJ-(A-R <^ ^j^(A. R7a)ci7)PN'^^fA-R7’), CT' N^^(A-R7a)qN^^(A-R7a)qA-Q-76 A-Q-77 A-Q-78R12A-Q-79o V,(A-R7a)q-N t-(A-R7)p-N J-(A-R7)p— N J-(A-R7)p^(A-R73) y "(A-R12) ^(A-R7%,000A-Q-86 A-Q-89 A-Q-900<J?S''NsT'(~A(-A'R7)PR7a)q(A-R12) A-Q-92 SA-Q-98— N / =J-(A-R7)P-N J-(A-R7)P^(A-R7a)qN^(A-R7a)qA-Q-105 A-Q-106each A-R7is independently halogen, cyano, hydroxy, C1-C3 alkyl, C1-C3 haloalkyl, Ci-C2 alkoxy or C1-C2 haloalkoxy;each A-R29is independently H, halogen, C1-C2 alkyl, C1-C2 haloalkyl or C1-C2 alkoxy; A-R15is H, halogen, cyano, hydroxy, methyl, methoxy or methoxy carbonyl;A-R16is H, methyl, methylcarbonyl or methoxy carbonyl;A-R28is H, halogen, cyano or C1-C4 alkyl;each A-R30and A-R31is independently selected from Ci-Ce alkyl, C3-C4 alkenyl, C3-C4 alkynyl, C1-C4 haloalkyl, C3-C6 haloalkenyl, C3-C6 haloalkynyl, C2-C6 alkoxyalkyl and C3-Ce cycloalkyl;A-R32is H, cyano, hydroxy, amino, Ci-Ce alkyl or Ci-Ce alkoxy; andR33is H or Ci-Ce alkyl.Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-0354. The compound of claim 53 whereinA-Gis selected from A-G-I, A-G-2, A-G-7, A-G-8, A-G-14, A-G-15, A-G-23, A-G-24, A-G-26, A-G-27, A-G-36, A-G-37, A-G-38, A-G-49, A-G-50 and A-G-55, wherein A-G is unsubstituted;A-W is O;A-X is A-X1or A-X2;A-Z1is a direct bond;A-Rlaand A-Rlbindependently are selected from A-U-l through A-U-50 wherein when A-R4is attached to a carbon ring member, said A-R4is selected from A-R4a, and when A-R4is attached to a nitrogen ring member, said A-R4is selected from A-R4b, and k is 0, 1 or 2; or C2-Cs alkyl, C2-C5 alkenyl, C2-C5 haloalkyl, C2-C5 haloalkenyl, C2-C5 haloalkylthioalkyl, C2-Cs alkoxyalkyl, C2-C5 haloalkoxyalkyl, C2-C5 alkylthioalkyl, C2-C5 alkylaminoalkyl, C2-Cs alkylcarbonyloxy, C2-C5 haloalkylcarbonyloxy, C2-C5 alkoxy, C2-C5 haloalkoxy, C2-Cs alkylthio, C2-C5 alkylamino or C2-C5 alkylcarbonylaminoN' O' N' - "s' I A-U-1 A-U-2 A-U-3 A-U-4 A-U-5 A-U-6 A-U-7 ° A-ll-R >41 ’Jt-(A-R4)k."“^(A-R4), N-N N (A-R A-U-9 A-U-10 A-U-11 A-U- N'4)12kA-U-13 A-U-14 A-U-15 A-U-16 (A-R4)k(A-R4)kN-N N-2HA-R4), (A-R4)k(A-R4)kS' N' A-U-17 A-U-18 A-U-19 | A-U-20 | A-U-21 A-U-22 A-U-23 A-U-24(A-R4)kN ‘O 'S S'N" OZ^< A-R4)kA-U-25 A-U-26 A-U-27 A-U-28 A-U-29 A-U-30 A-U-31 A-U-32%K(A-R4)k^(A'R4)kf^~^(A'R4)k A’R4)> X^-< A’R2i^^^(A’R4]jJL^r< A’R4)kA-U-33 I A-U-34 A-U-35 I A-U-36 A-U-37 A-U-38 A-U-39 A-U-40jO fsj ~(A'R4)XkJ^iN >A-R4^O<A-^^^ X^ N' •''^N ^' -<A-R4>Zj'O^NL(A-R4)kA-U-41 A-U-42 A-U-43 A-U-44 A-U-45 A-U-46 A-U-47 A-U-48A-U-49 A-U-50 each A-R5is independently H, halogen, cyano, Ci-Ce alkyl, Ci-Ce haloalkyl,Ci-Ce alkoxy, Ci-Ce haloalkoxy, -N- A-R25-A-R26or -A-Z2-A-Q;Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03each A-Z2is a direct bond;each A-Q is independently A-Q-l, A-Q-20, A-Q-32 through A-Q-34, A-Q-45 through A-Q-47, A-Q-60 through A-Q-73, A-Q-76 through A-Q-79, A-Q-84 through A-Q-94 and A-Q-98 through A-Q-l 06;p is an integer from 0 to 3;q is an integer from 0 to 1;each A-R7is independently F, Cl, cyano, hydroxy, methyl or methoxy;A-R28is H, halogen or cyano;each A-R30and A-R31is independently selected from Ci-Ce alkyl, C3-C4 alkenyl, C3-C4 alkynyl and C1-C4 haloalkyl;R32is selected H, cyano, hydroxy, amino, C1-C3 alkyl or C1-C3 alkoxy;R33is selected from H or methyl; andn is 0.

55. The compound of claim 54 whereinA-Gis selected from A-G-l, A-G-2, A-G-15, A-G-26, A-G-27, A-G-36, A-G-37 and A-G-38;A-X is A-X1or A-X2; and the ring comprising A-X is saturated;A-Rlaand A-Rlbindependently are selected from A-U-l through A-U-3, A-U-ll, A-U-13, A-U-20, A-U-22, A-U-23, A-U-36 through A-U-39, and A-U-50 wherein when A-R4is attached to a carbon ring member, said A-R4is selected from A-R4a, and when A-R4is attached to a nitrogen ring member, said A-R4is selected from A-R4b, and k is 0, 1 or 2; or C3-C5 alkyl, C3-C5 alkenyl, C3-C5 haloalkyl, C3-C5 haloalkenyl, C2-C4 haloalkylthioalkyl, C2-C4 alkoxyalkyl, C2-C4 haloalkoxyalkyl, C2-C4 alkylthioalkyl, C2-C4 alkylaminoalkyl, C2-C3 alkylcarbonyloxy, C2-C3 haloalkylcarbonyloxy, C2-C4 alkoxy, C2-C4 haloalkoxy, C2-C4 alkylthio, C2-C4 alkylamino or C2-C3 alkylcarbonylamino;each A-R5is independently H, halogen, cyano, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce alkoxy, Ci-Ce haloalkoxy or -A-Z2-A-Q;A-Q is selected from A-Q-l, A-Q-45, A-Q-63, A-Q-64, A-Q-65, A-Q-68, A-Q-69, A-Q-70, A-Q-71, A-Q-72, A-Q-73, A-Q-76, A-Q-78, A-Q-79, A-Q-84, A-Q-85, A-Q-98, A-Q-99, A-Q-100, and A-Q-l 01 through A-Q-l 06;A-R28is Cl, F or cyano;each A-R30and A-R31is independently selected from C1-C4 alkyl;Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03A-R32is H, cyano, hydroxy, C1-C2 alkyl or C1-C2 alkoxy; andA-R33is H.

56. The compound of Claim 55 whereinA-G is selected from A-G-l, A-G-2, A-G-15, A-G-26 and A-G-36;A- J is any one of A-J-29-1 to A-J-29-40A-J-29-10 A-J-29-11 A-J-29-12A-J-29-13 A-J-29-17 A-J-29-18A-J-29-19 A-J-29-23 A-J-29-24A-J-29-25A-J-29-31A-J-29-37 A-J-29-40 wherein Y is chosen from S, S=O, and S(=O)2;Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03A-X is A-X1;A-Rlaand A-Rlbare each selected from A-U-l, A-U-20 and A-U-50 wherein when A-R4is selected from A-R4a, and k is O, 1 or 2; or C3-C5 haloalkyl, C3-C5 haloalkenyl, C3-C5 haloalkylthioalkyl, C3-C5 haloalkoxyalkyl, C2-C3 haloalkylcarbonyloxy or C2-C4 haloalkoxy; each R5is independently cyano, Ci-Ce alkyl, Ci-Ce alkoxy or -A-Z2-A-Q;A-Q is selected from -A-Q-45, -A-Q-63, -A-Q-64, -A-Q-65, -A-Q-68, -A-Q-69, -A-Q-70, -A-Q-71, -A-Q-72, -A-Q-84 and -A-Q-85; andeach -A-R30and -A-R31is independently ethyl or methyl.

57. The compound of any one of claims 49-56, wherein the compound is chosen from one of the following:Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03wherein Y is chosen from S, S=O, and S(=O)2.

58. The compound of claim 49, wherein A-A is C(=O).

59. The compound of claim 49, wherein A-A is CH-A-R15or N-A-R16.

60. The compound of claim 49, wherein the compound is defined by Formula VA(A-TT)Formula V AAttorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03whereinY is chosen from S, S=O, and S(=O)2;each A-R is individually chosen from halogen, cyano, hydroxy, amino, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy and C1-C4 haloalkoxy;each A-Z3is independently absent, a direct bond, O, N-A-R22, C(=O), C(=S), S(O)A-m, CH- A-R20, -CH-A-R2O-CH-AR20-, -C-A-R24=C-A-R27-, -OCH-A-R20-, or -CH-A-R20O-;each A-TTis individually chosen from halogen, cyano, hydroxy, amino, nitro, Ci-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, A-TA-1 through A-TA-49, A-TN-1 through A-TN-28, or A-Tp-1 through A-Tp-35;N / 3'(A’R29)^"^(A-R29)r7 / A’< A'R29)r#’^-(A-R29)r SxJXA-R®!, P-(A-Ra)r / ^(A-R29)^! L(A-R29)r^ASJN _4O; N -XN, N -V.NH;< A’R29)J3'(A’R29)rJl(A-R29)''NA 'NA A-T -14 R22R22N-N(A-R29)rN-?_.(A-R29)r,N=2>(A-R29)rM (A-R29)r\ _ _, N -N NA-T'M7 °(A‘R )rH o'(A-R29)rR22yy< A-R29)rv^(A_R29)ry><A-R29>‘ v^< A-R29)rH(A-R29)rv< A_R29)r^ £ > ^*^A-R29^r (A-R29)r^z^^^^— (A"R29)r^[C*^^^(A" R29)r NxNx'hr N^ jOL(A’R29)rxJt^r(A-R29)1- jC^(A'R29),^N^r< A R29)rxXN^r(A'R29)>ilN-?’< A’R29)rJL(A'R29)r^-(A-R29). — N ^-(A-R — N ~HA-R29)r— N29)r— / X(A-R29)r— N 4-(A-R29)r-o ' k° v-sy-sO OO 0. o O O — N 7-(A-R29)r— N Z T Z ”l Z T T<A-R2M ><A-R29)r-N ^(A-R29)r-N +<A-R29)r _N' A(A-R29) O )r — N a )T '(A-R22) Y YSV>(A-R29)rO O 0 O (A-R22) — N:0 — N O — N V j-(A-R29)r7 j-(A-R29)r7 X cr 'cr o^isrA-R29)r A-TN-19 H - <^j-(A-R29)rV> A-R29)r— 6 X-dJr<A-R29)i— -|-(A-R V^<(A. R29)r-!-(A-R29)r29)r^^(A-R29)r(A-R29)rA-TN-25Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03r is 0, 1, 2, 3, 4, or 5; andR29is chosen from halogen, cyano, hydroxy, amino, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy and C1-C4 haloalkoxy.

61. A compound of Formula VI and / or a salt, metal complex and / or N-oxides thereof(B-R10)pFormula VIwhereinB-A is pyrazol-l-yl which may contain up to two substituents, where the substituents are each independently selected from the following list:substituents on carbon: halogen, cyano, hydroxyl, nitro, — N-B-R3-B-R4, Ci-Ce-alkyl, C2-Ce-alkenyl, C2-Ce-alkenyl, Cs-Ce-cycloalkyl, Ci-Ce-haloalkyl, C2-Ce-haloalkenyl, C2-C6-Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03haloalkynyl, Cs-Ce-halocycloalkyl, Ci-C4-alkoxy, Ci-C4-haloalkoxy, Ci-C4-alkylthio, C1-C4-alkylsulphonyl, Ci-C4-haloalkylthio, Ci-C4-haloalkylsulphonyl, Ci-C4-alkoxy-Ci-C4-alkyl, hydroxy-Ci-C4-alkyl, Ci-Ce-alkylcarbonyl, Ci-Ce-alkoxycarbonyl, Ci-Ce-alkylcarbonyloxy or phenyl,substituents on nitrogen: Ci-Ce-alkyl, C2-Ce-alkenyl, C2-Ce-alkynyl, Ci-Ce-haloalkyl, C2-Ce-haloalkenyl, C2-C6-haloalkynyl, Cs-Cio-cycloalkyl-Ci-Ce-alkyl, Ci-Ce-haloalkylcarbonyl, phenyl, benzyl, Ci-C4-alkylsulphonyl, Ci-C4-haloalkylsulphonyl, phenylsulphonyl, — C(C=O)H, or Ci-Ce-alkylcarbonyl,B-RG1is the same or different and is independently hydrogen, halogen, hydroxyl, thiol, nitro, cyan, — C(C=O)H, — C(C=O)OH, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, halocycloalkyl, hydroxyalkyl, formylalkyl, alkoxyalkyl, alkylcarbonylalkyl, alkylcycloalkyl, alkoxy, alkylcycloalkylalkyl, alkylthio, aloalkylthio, alkynylthio, alkenyloxy, alkynyloxy, haloalkoxy, alkoxyalkoxy, alkylcarbonyloxy, haloalkylcarbonyloxy, cycloalkylcarbonylamino, alkylsulphonylamino, haloalkylsulphonylamino, phenylsulphonylamino, cycloalkylalkyl, halocycloalkylalkyl, cycloalkylcycloalkyl, alkoxycarbonyloxy, alkylcarbonylthio, alkylsulphinyl, haloalkylsulphinyl, alkylsulphonyl, haloalkylsulphonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, alkylaminocarbonyloxy, — C(C=O)N-B-R3-B-R4or — N-B-R3-B-R4,B-R3and B-R4are the same or different and are each independently hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, benzyl or phenyl,B-LHS C(B-RL11)2,B-RL11is the same or different and is independently hydrogen, halogen, hydroxyl, cyano, — C(C=O)H, — C(C=O)OH, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxyalkyl, alkylthioalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxy, alkylthio, haloalkylthio, haloalkoxy, alkylcarbonyloxy, alkylcarbonylamino, alkylcarbonylthio, alkylsulphonyl, haloalkylsulphonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxycarbonyl, trialkylsilyloxy, — N-B-R3-B-R4or — C(C=O)N-B-R3-B-R4, or the two B-RL11radicals, together with the carbon atom to which they are bonded, form a cyclopropyl ring, or the two B-RL11radicals are =CH2, =CO-B-R3, =NO-B-R3or =CHN(B-R9)2,B-R9is alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, benzyl or phenyl,B-Y is sulphur or oxygen,B-X is carbon,B-R2is hydrogen,Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03B-R10is oxo, alkyl, alkenyl, haloalkyl, alkoxy, halogen, cyano or hydroxyl,B-p is 0 or 1,B-G is chosen from B-G-l through B-G-l 1(B-RB G1)B-G-1 B-G-2 B-G-3 B-G-5B-G-6B-G-11where the bond identified by u is bonded directly to B-X and where the bond identified by co is bonded directly to B-Q;B-Q isY,0where the bond is identified by % is bonded directly to B-G and the bond is identified by % bonded directly to B-L2, or the bond is identified by % is bonded directly to B-L2and the bond is identified by % bonded directly to B-G;B-R5is the same or different and is independently:bonded to carbon of B-Q: hydrogen, oxo, halogen, cyano, hydroxyl, nitro, — CHO, — C(C=O)OH, — C(C=0)NH2, — C(C=O)N-B-R3-B-R4, — N-B-R3-B-R4, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, halocycloalkylalkyl, alkylcycloalkylalkyl, cycloalkenyl, halocycloalkenyl, alkoxyalkyl, haloalkoxyalkyl, cycloalkoxyalkyl, alkoxyalkoxyalkyl, alkylthioalkyl, formylalkyl, alkylcarbonylalkyl, alkylsulphinylalkyl, alkylsulphonylalkyl, alkylaminoalkyl, dialkylaminoalkyl, haloalkylaminoalkyl, cycloalkylaminoalkyl, alkylcarbonyl, haloalkylcarbonyl, cycloalkylcarbonyl, alkoxycarbonyl, cycloalkoxycarbonyl, cycloalkylalkoxy carbonyl, cycloalkylaminocarbonyl, hydroxyalkyl, alkoxy, haloalkoxy,Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03cycloalkoxy, halocycloalkoxy, cycloalkylalkoxy, alkenyloxy, haloalkenyloxy, alkynyloxy, haloalkynyloxy, alkoxyalkoxy, alkylcarbonyloxy, haloalkylcarbonyloxy, cycloalkylcarbonyloxy, alkylcarbonylalkoxy, alkylthio, haloalkylthio, cycloalkylthio, alkylsulphinyl, haloalkylsulphinyl, alkylsulphonyl, haloalkylsulphonyl, cycloalkylsulphonyl, trialkylsilyl, alkylsulphonylamino, haloalkylsulphonylamino,bonded to nitrogen of B-Q: hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl, cycloalkylalkyl, phenyl, benzyl, alkylsulphonyl, — C(C=O)H, alkoxy carbonyl or alkylcarbonyl;B-L2is a direct bond;B-m is 0, 1 or 2;B-R20is hydrogen, alkyl or haloalkyl;B-R1is unsubstituted phenyl or a phenyl ring substituted by one or more substituents chosen from B-Z1and B-Z4;B-Z1is hydrogen, halogen, hydroxyl, — SH, nitro, cyano, C(=O)H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, cycloalkenyl, halocycloalkyl, halocycloalkenyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, cycloalkoxyalkyl, alkylthioalkyl, alkylsulphinylalkyl, alkylaminoalkyl, haloalkylaminoalkyl, cycloalkylaminoalkyl, dialkylaminoalkyl, alkylsulphonylalkyl, alkylcycloalkyl, alkoxy, alkylcycloalkylalkyl, halocycloalkoxy, alkylthio, haloalkylthio, cycloalkylthio, alkenyloxy, alkynyloxy, haloalkoxy, haloalkenyloxy, haloalkynyloxy, cycloalkoxy, alkoxyalkoxy, cycloalkylalkoxy, alkylcarbonyloxy, haloalkylcarbonyloxy, cycloalkylcarbonyloxy, cycloalkylamino, alkylsulphonylamino, haloalkylsulphonylamino, cycloalkylalkyl, halocycloalkylalkyl, cycloalkylcycloalkyl, alkoxyalkoxyalkyl, alkylcarbonylalkoxy, cycloalkylaminocarbonyl, cycloalkylalkoxycarbonyl, alkylcarbonylthio, alkylsulphinyl, haloalkylsulphinyl, alkylsulphonyl, haloalkylsulphonyl, cycloalkylsulphonyl, alkylcarbonyl, haloalkylcarbonyl, cycloalkylcarbonyl, alkoxy carbonyl, cycloalkoxy carbonyl, trialkylsilyl, — N-B-R3-B-R4, — C(C=O)N-B-R3-B-R4or -B-L3-B-Z3,B-L3is a direct bond, — CH2 —, — C(C=O) —, sulphur, oxygen, — C(C=O)O —, — C(C=O)NH—, — OC(=O)—, — NHC(=O)—, — N-B-R20—, — C(=S)—, — S(O)B-m—, -CH-B-R20—, — CH-B-R20— CH-B-R20—, — C-B-R20=C-B-R20, — OCH-B-R20—, — CH-B-R20O—, B-Z3is a phenyl radical, naphthalenyl radical or a 5- or 6-membered heteroaryl radical, each of which may contain 0, 1, 2 or 3 substituents, where the substituents are each independently selected from the following list:Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-03substituents on carbon: halogen, cyano, nitro, hydroxyl, amino, — SH, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkoxyalkyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy carbonyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkoxy, alkenyloxy, alkynyloxy, alkoxyalkoxy, alkylamino, dialkylamino, alkylthio, haloalkylthio, alkylsulphinyl, haloalkylsulphinyl, alkylsulphonyl, haloalkylsulphonyl, trisilylalkyl or phenyl,substituents on nitrogen: hydrogen, — C(C=O)H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl, cycloalkylalkyl, alkoxyalkyl, alkylsulphonyl, haloalkylsulphonyl, cycloalkylsulphonyl, phenylsulphonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxycarbonyl, haloalkoxycarbonyl, cycloalkoxycarbonyl, — C(C=O)NR3R4, phenyl or benzyl; andB-Z4is alkylsulphonyloxy.

62. The compound according to claim 61, in which B-R5is hydrogen, cyano, — NR3R4, Ci-Ce-alkyl, C2-Ce-alkenyl, C2-Ce-alkynyl, Ci-Ce-haloalkyl, C2-Ce-haloalkenyl, C2-C6-haloalkynyl, Cs-Cs-cycloalkyl, Cs-Cs-halocycloalkyl, Cs-Cs-halocycloalkyl, Ci-C4-alkyl-C3-C8-cycloalkyl, C3-C8-cycloalkyl-Ci-C4-alkyl, Ci-C4-alkoxy-Ci-C4-alkyl, C3-C8-cycloalkoxy-Ci-C4-alkyl, C1-C4-alkoxy-Ci-C4-alkoxy-Ci-C4-alkyl, Ci-C4-alkylthio-Ci-C4-alkyl, Ci-Ce-alkoxy, Ci-Ce-haloalkoxy, Cs-Cs-cycloalkoxy, Cs-Cs-halocycloalkoxy, C3-C8-cycloalkyl-Ci-C4-alkoxy, C2-Ce-alkenyloxy, C2-C6-haloalkenyloxy, C2-Ce-alkynyloxy, C2-Ce-haloalkynyloxy, Ci-Ce-alkoxy-Ci-C4-alkoxy, Ci-Ce-alkylcarbonyloxy, Ci-Ce-haloalkylcarbonyloxy, Cs-Cs-cycloalkylcarbonyloxy, Ci-Ce-alkylcarbonyl-Ci-Ce-alkoxy, Ci-Ce-alkylthio, Ci-Ce-haloalkylthio, or Cs-Cs-cycloalkylthio.

63. The compound according to any one of claims 61-62, wherein B-A is chosen from 3,5-bis(difluoromethyl)- IH-pyrazol- 1 -yl and 5-methyl-3-(trifluoromethyl)-lH-pyrazol- 1 -yl.

64. The compound according to any one of claims 61-63, wherein B-L1is chosen from -CH2-and -NH-.

65. The compound according to any one of claims 61-64, wherein B-Y is O, B-X is -CH- and B-R5is hydrogen.

66. The compound according to any one of claims 61-65, wherein B-G is B-G-l.Attorney Docket No. 10620-164W01NCSU Ref.: 2025-138-0367. The compound according to any one of claims 61-65, wherein the compounds comprises one of the following68. A compound selected from any one of the followingAttorney Docket No. 10620-164W01NCSU Ref.: 2025-138-0369. A composition comprising an agriculturally acceptable adjuvant or carrier and an herbicidally, insecticidally, and / or fungicidally effective amount of a compound defined by any one of claims 45-68.

70. The composition of claim 69, wherein the composition further comprises an additional pesticide.

71. The composition of any one of claims 69-70, wherein the composition further comprises a herbicidal safener.

72. A method of controlling a pest chosen from a fungus, an insect, undesirable vegetation, or a combination thereof, the method comprising applying to vegetation or an area adjacent the vegetation or applying to soil or water to prevent the emergence or growth of a pest the compound of any of claims 45-68 or the composition of any of claims 69-71.

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