Photochemical systems and methods for preparing cyanobenzamides

Abstract

Described herein is a loop reactor system for carrying out photochemical reactions. The loop reactor system is particularly advantageous for preparing cyanobenzamides. Also disclosed are photochemical methods for preparing cyanobenzamides and compositions containing cyanobenzamides.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 449,694, filed March 3, 2023, all of which are incorporated herein by reference in their entirety.

[0002] The present disclosure relates to methods and apparatus for preparing cyanobenzamides. Compounds prepared by the methods disclosed herein are useful for preparing certain anthranilamide compounds of interest as pesticides, such as the insecticides chlorantraniliprole and cyantraniliprole. [Background technology]

[0003] Photochemical reactions are known to be useful as an alternative method for carrying out certain chemical reactions. For example, the synthesis of electron-donating substituted benzonitriles by photolysis of phenyl halides and esters has been described by Dichiarante et al. (Chem. Commun., 2006, 3001-3003). However, these reactions are often limited by the photochemical reactor systems used to carry them out. As a result, these known photochemical reactions often have suboptimal yields and incomplete reactions.

[0004] The present disclosure provides a loop reactor system for carrying out photochemical reactions. The loop reactor system is particularly advantageous for preparing cyanobenzamides. The loop reactor system provides high yields and optimized reactions by continuously circulating the reaction mixture until satisfactory conversion is achieved. Summary of the Invention [Means for solving the problem]

[0005] In one aspect, provided herein is a photochemical reaction system comprising: 1. A loop reactor system comprising: a container configured to contain the mixture; and a photochemical reaction vessel configured to subject the mixture to irradiation from at least one light source; a precipitation vessel configured to contain the irradiated mixture; a loop reactor system comprising: Optionally, additional reaction system components selected from the group of a fluid transfer system, a stripping system, a filtration system, a drying system, an agitation system, a temperature control system, and combinations thereof; A photochemical reaction system is provided, comprising:

[0006] In another embodiment, a compound of formula II [ka] (In the formula, R 12 and R 13 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C3-C6 branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers thereof; R 14 are amines, amides, carbamides, NH2, NR 17 R 18 , and NR 21 COR 22 is selected from the group R 15 is an amide, C(O)NR 19 R 20 and C(O)NHCH3; R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , and R 22are each independently selected from the group consisting of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C3-C6 branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers thereof; and Y is selected from the group of cyano-containing substituents and CN. Provided herein is a method for preparing The method is: I) a) a compound of formula I [ka] (In the formula, R 1 and R 2 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C3-C6 branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers; R 3 are amines, amides, carbamides, NH2, NR 6 R 7 , and NR 8 COR 9 is selected from the group R 4 is an amide, C(O)NR 10 R 11 and C(O)NHCH3; R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , and R 11are each independently selected from the group consisting of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, and substituted or unsubstituted C3-C6 branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers thereof; and X is a leaving group, trifluoromethanesulfonate (TfO), tosylate (TsO), p-tosylate (p-TsO), mesylate (MsO), diethyl phosphate (POEt), sulfonate (-OSOR 23 ), carboxylate (-OCOR 24 ), diazonium, halogen, fluoride, chloride, bromide, and iodide; R 23 and R 24 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C3-C6 branched alkyl, C1-C6 haloalkyl, and C1-C6 fluoroalkyl; b) a cyano-containing compound; and c) forming a mixture comprising, optionally, a solvent; II) subjecting the mixture to irradiation from at least one light source; Includes:

[0007] In another aspect, provided herein are compositions comprising: (a) a compound of formula II; and (b) a compound of formula I. [Brief explanation of the drawings]

[0008] [Figure 1] 1 is an exemplary photochemical reaction system according to the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0009] Unless otherwise indicated, the drawings provided herein are intended to illustrate features of embodiments of the present disclosure. These features are believed to be applicable to a wide variety of systems incorporating one or more embodiments of the present disclosure. Thus, the drawings are not intended to include all conventional features known to those skilled in the art that are required for the practice of the embodiments disclosed herein.

[0010] The photochemical reaction system of the present disclosure includes a containment vessel configured to contain a mixture, a photochemical reaction vessel configured to subject the mixture to irradiation from at least one light source, and a precipitation vessel configured to contain the irradiated mixture. The photochemical reaction system optionally further includes additional reaction system components selected from the group consisting of a fluid transfer system, a stripping system, a filtration system, a drying system, an agitation system, a temperature control system, and combinations thereof.

[0011] FIG. 1 illustrates an exemplary photochemical reaction system 110. In this exemplary embodiment, the photochemical reaction system 110 includes a loop reactor system 112 including a storage vessel 114 configured to receive a mixture, a photochemical reaction vessel 116 configured to receive the mixture from the storage vessel 114 and then subject the mixture to irradiation from at least one light source, and a precipitation vessel 118 configured to receive the irradiated mixture from the photochemical reaction vessel 116. Arrows indicate the flow of the mixture. As can be seen, the mixture can flow from the precipitation vessel 118 to the storage vessel 114. A reaction cycle can be achieved in this embodiment. The photochemical reaction system 110 optionally further includes one or more additional reaction system components, as shown in dashed box outlines. These components include a fluid transfer system 120, a stripping system 122, a filtration system 124, a drying system 126, an agitation system 128, and a temperature control system 130. Among these optional components, the agitation system 128, the filtration system 124, and the temperature control system 130 are included in the loop reactor system 112, while the remainder of these components are separate from the loop reactor system 112 and are used for post-reaction work-up.

[0012] In some embodiments, the loop reactor system 112 is configured to circulate the mixture through the receiving vessel 114, the photochemical reactor vessel 116, and the precipitation vessel 118 at least once.

[0013] In some embodiments, the photochemical reaction system includes at least one fluid transfer system configured to transfer the mixture from the storage vessel 114 to the photochemical reaction vessel 116, to transfer the mixture from the photochemical reaction vessel 116 to the precipitation vessel 118, and / or to transfer the mixture from the precipitation vessel 118 to the storage vessel 114. In some embodiments, the at least one fluid transfer system includes at least one pump.

[0014] In some embodiments, the photochemical reaction system includes a stripping system 122, an agitation system 128, a filtration system 124, a drying system 126, and / or a temperature control system 130.

[0015] In many embodiments, the photochemical reaction vessel is configured to subject the mixture to irradiation from at least one light source. In some embodiments, the photochemical reaction vessel is configured to subject the mixture to irradiation from multiple light sources. In some embodiments, the photochemical reaction vessel is configured to subject the mixture to irradiation from two light sources. In some embodiments, the photochemical reaction vessel is configured to subject the mixture to irradiation from three light sources. In some embodiments, the photochemical reaction vessel is configured to subject the mixture to irradiation from four light sources. In some embodiments, the photochemical reaction vessel is configured to subject the mixture to irradiation from five or more light sources.

[0016] In many embodiments, the photochemical reactor is configured to subject the mixture to irradiation. Generally, the irradiation can be of any suitable wavelength known in the art. In some embodiments, the irradiation comprises ultraviolet light, visible light, or a combination thereof.

[0017] In some embodiments, the radiation is at 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 150 nm, 160 nm, 170 nm, 180 nm, 190 nm, 200 nm, 210 nm, 220 nm, 230 nm, 240 nm, 250 nm, 260 nm, 270 nm, 280 nm, 290 nm, 300 nm, 310 nm, 320 nm, 330 nm, 340 nm, 350 nm, 360 nm, 370 nm, 380 nm, 390 nm, 400 nm, 410 nm, 420 nm, 430 nm, 440 nm, 450 nm, m, and has a minimum wavelength selected from 460 nm, 470 nm, 480 nm, 490 nm, 500 nm, 510 nm, 520 nm, 530 nm, 540 nm, 550 nm, 560 nm, 570 nm, 580 nm, 590 nm, 600 nm, 610 nm, 620 nm, 630 nm, 640 nm, 650 nm, 660 nm, 670 nm, 680 nm, 690 nm, 700 nm, 710 nm, 720 nm, 730 nm, 740 nm, 750 nm, 760 nm, 770 nm, 780 nm, 790 nm, and 800 nm.

[0018] In some embodiments, the radiation is at 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 150 nm, 160 nm, 170 nm, 180 nm, 190 nm, 200 nm, 210 nm, 220 nm, 230 nm, 240 nm, 250 nm, 260 nm, 270 nm, 280 nm, 290 nm, 300 nm, 310 nm, 320 nm, 330 nm, 340 nm, 350 nm, 360 nm, 370 nm, 380 nm, 390 nm, 400 nm, 410 nm, 420 nm, 430 nm, 440 nm, 450 nm, m, and has a maximum wavelength selected from 460 nm, 470 nm, 480 nm, 490 nm, 500 nm, 510 nm, 520 nm, 530 nm, 540 nm, 550 nm, 560 nm, 570 nm, 580 nm, 590 nm, 600 nm, 610 nm, 620 nm, 630 nm, 640 nm, 650 nm, 660 nm, 670 nm, 680 nm, 690 nm, 700 nm, 710 nm, 720 nm, 730 nm, 740 nm, 750 nm, 760 nm, 770 nm, 780 nm, 790 nm, and 800 nm.

[0019] In some embodiments, the photochemical reaction vessel is configured to subject the mixture to light irradiation having a wavelength in the range of about 180 nm to about 450 nm, preferably about 180 nm to about 420 nm, more preferably about 360 nm to about 420 nm, and even more preferably about 360 nm to about 400 nm.

[0020] In some embodiments, at least one of the receiving vessel 114 and the settling vessel 118 includes a filter.

[0021] Embodiments of the present disclosure include:

[0022] Embodiment 1. A photochemical reaction system comprising: 1. A loop reactor system comprising: a container configured to contain the mixture; and a photochemical reaction vessel configured to subject the mixture to irradiation from at least one light source; a precipitation vessel configured to contain the irradiated mixture; a loop reactor system comprising: Optionally, additional reaction system components selected from the group of a fluid transfer system, a stripping system, a filtration system, a drying system, an agitation system, a temperature control system, and combinations thereof; A photochemical reaction system comprising:

[0023] Embodiment 2. The photochemical reaction system of embodiment 1, wherein the loop reactor system is configured to circulate the mixture through the containment vessel, the photochemical reaction vessel, and the precipitation vessel at least once.

[0024] Embodiment 3. The photochemical reaction system is transferring the mixture from the containment vessel to a photochemical reactor; Transferring the mixture from the photochemical reactor to a precipitation vessel, and / or Transfer the mixture from the settling vessel to a receiving vessel 2. The photochemical reaction system of embodiment 1, comprising at least one fluid transfer system configured to:

[0025] Embodiment 4. The photochemical reaction system of embodiment 1, wherein the photochemical reaction system includes a stripping system, an agitation system, a filtration system, a drying system, a temperature control system, or a combination thereof.

[0026] Embodiment 5. The photochemical reaction system of embodiment 1, wherein the photochemical reaction vessel is configured to subject the mixture to irradiation from a plurality of light sources.

[0027] Embodiment 6. The photochemical reaction system of embodiment 1, wherein the photochemical reaction vessel is configured to subject the mixture to light irradiation having a wavelength in the range of about 180 nm to about 450 nm, preferably about 180 nm to about 420 nm, more preferably about 360 nm to about 420 nm, and even more preferably about 360 nm to about 400 nm.

[0028] Embodiment 7. The photochemical reaction system of embodiment 1, wherein at least one of the containment vessel and the precipitation vessel includes a filter.

[0029] Embodiment 8. The photochemical reaction system of embodiment 1 is used to produce a compound of formula II [ka] (In the formula, R 12 and R 13 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C3-C6 branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers thereof; R 14 are amines, amides, carbamides, NH2, NR 17 R 18 , and NR 21 COR 22 is selected from the group R 15 is an amide, C(O)NR 19 R20 and C(O)NHCH3; R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , and R 22 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C3-C6 branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers thereof; and Y is selected from the group of cyano-containing substituents and CN. 1. A method for preparing The method is: I) A container for containing a photochemical reaction system, a) a compound of formula I [ka] (In the formula, R 1 and R 2 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C3-C6 branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers; R 3 are amines, amides, carbamides, NH2, NR 6 R 7 , and NR 8 COR 9 is selected from the group R 4 is an amide, C(O)NR 10 R 11 and C(O)NHCH3; R 5 , R 6 , R 7 , R 8 , R 9, R 10 , and R 11 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, and substituted or unsubstituted C3-C6 branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers thereof; and X is a leaving group, trifluoromethanesulfonate (TfO), tosylate (TsO), p-tosylate (p-TsO), mesylate (MsO), diethyl phosphate (POEt), sulfonate (-OSOR 23 ), carboxylate (-OCOR 24 ), diazonium, halogen, fluoride, chloride, bromide, and iodide; R 23 and R 24 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C3-C6 branched alkyl, C1-C6 haloalkyl, and C1-C6 fluoroalkyl; b) a cyano-containing compound; and c) optionally a solvent; providing a mixture comprising: II) reacting the mixture in a photochemical reaction system to produce a compound of formula II; A method comprising:

[0030] Embodiment 8A. R 12 and R 13 are each independently selected from the group of hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, and n-pentyl; R 14 is NH2, R 15 is C(O)NR 19 R 20 and C(O)NHCH3, R 16 , R 19 , and R 20 are each independently selected from the group of hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, and n-pentyl; Y is CN, R 1 and R 2 are each independently selected from the group of hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, and n-pentyl; R 3 is NH2, R 4 is C(O)NR 10 R 11 and C(O)NHCH3, R 5 , R 10 , and R 11 are each independently selected from the group of hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, and n-pentyl; X is a leaving group, trifluoromethanesulfonate (TfO), tosylate (TsO), p-tosylate (p-TsO), mesylate (MsO), diethyl phosphate (POEt), sulfonate (-OSOR 23 ), carboxylate (-OCOR 24 ), diazonium, halogen, fluoride, chloride, bromide, and iodide; and R 23 and R 24 is each independently selected from the group of methyl and ethyl.

[0031] Embodiment 8B. R 12 and R 13 are each independently selected from the group: hydrogen and methyl; R 14 is NH2, R 15is C(O)NR 19 R 20 and C(O)NHCH3, R 16 is selected from the group of hydrogen and methyl; R 19 and R 20 are each independently selected from the group of hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, and n-pentyl; Y is CN, R 1 and R 2 are each independently selected from the group: hydrogen and methyl; R 3 is NH2, R 4 is C(O)NR 10 R 11 and C(O)NHCH3, R 5 is selected from the group of hydrogen and methyl; R 10 and R 11 are each independently selected from the group of hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, and n-pentyl; X is a leaving group, trifluoromethanesulfonate (TfO), tosylate (TsO), p-tosylate (p-TsO), mesylate (MsO), diethyl phosphate (POEt), sulfonate (-OSOR 23 ), carboxylate (-OCOR 24 ), diazonium, halogen, fluoride, chloride, bromide, and iodide; and R 23 and R 24 is each independently selected from the group of methyl and ethyl.

[0032] Embodiment 8C. R 12 is hydrogen, R 13 is methyl, R 14 is NH2, R 15 is C(O)NR 19 R 20 and C(O)NHCH3, R 16 is hydrogen, R 19 and R 20 are each independently selected from the group of hydrogen, methyl, ethyl, n-propyl, and iso-propyl; Y is CN, R 1 is hydrogen, R 2 is methyl, R 3 is NH2, R 4 is C(O)NR 10 R 11 and C(O)NHCH3, R 5 is hydrogen, R 10 and R 11 are each independently selected from the group of hydrogen, methyl, ethyl, n-propyl, and iso-propyl; X is a leaving group, trifluoromethanesulfonate (TfO), tosylate (TsO), p-tosylate (p-TsO), mesylate (MsO), diethyl phosphate (POEt), sulfonate (-OSOR 23 ), carboxylate (-OCOR 24 ), diazonium, halogen, fluoride, chloride, bromide, and iodide; and R 23 and R 24 and n is independently methyl.

[0033] Embodiment 9. A compound of formula II is [ka] 9. The method of embodiment 8, wherein

[0034] Embodiment 10. A compound of Formula I is [ka] 9. The method of embodiment 8, wherein

[0035] Embodiment 11. Compound of Formula II [ka] (In the formula, R 12 and R 13 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C3-C6 branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers thereof; R 14 are amines, amides, carbamides, NH2, NR 17 R 18 , and NR 21 COR 22 is selected from the group R 15 is an amide, C(O)NR 19 R 20 and C(O)NHCH3; R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , and R 22 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C3-C6 branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers thereof; and Y is selected from the group of cyano-containing substituents and CN. 1. A method for preparing The method is: I) a) a compound of formula I [ka] (In the formula, R 1 and R 2 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C3-C6 branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers; R 3 are amines, amides, carbamides, NH2, NR 6 R 7 , and NR 8 COR 9 is selected from the group R 4 is an amide, C(O)NR 10 R 11 and C(O)NHCH3; R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, and substituted or unsubstituted C3-C6 branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers thereof; and X is a leaving group, trifluoromethanesulfonate (TfO), tosylate (TsO), p-tosylate (p-TsO), mesylate (MsO), diethyl phosphate (POEt), sulfonate (-OSOR 23 ), carboxylate (-OCOR 24 ), diazonium, halogen, fluoride, chloride, bromide, and iodide; R23 and R 24 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C3-C6 branched alkyl, C1-C6 haloalkyl, and C1-C6 fluoroalkyl; b) a cyano-containing compound; and c) forming a mixture comprising, optionally, a solvent; II) subjecting the mixture to irradiation from at least one light source; A method comprising:

[0036] Embodiment 11A. R 12 and R 13 are each independently selected from the group of hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, and n-pentyl; R 14 is NH2, R 15 is C(O)NR 19 R 20 and C(O)NHCH3, R 16 , R 19 , and R 20 are each independently selected from the group of hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, and n-pentyl; Y is CN, R 1 and R 2 are each independently selected from the group of hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, and n-pentyl; R 3 is NH2, R 4 is C(O)NR 10 R 11 and C(O)NHCH3, R5 , R 10 , and R 11 are each independently selected from the group of hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, and n-pentyl; X is a leaving group, trifluoromethanesulfonate (TfO), tosylate (TsO), p-tosylate (p-TsO), mesylate (MsO), diethyl phosphate (POEt), sulfonate (-OSOR 23 ), carboxylate (-OCOR 24 ), diazonium, halogen, fluoride, chloride, bromide, and iodide; and R 23 and R 24 is each independently selected from the group of methyl and ethyl.

[0037] Embodiment 11B. R 12 and R 13 are each independently selected from the group: hydrogen and methyl; R 14 is NH2, R 15 is C(O)NR 19 R 20 and C(O)NHCH3, R 16 is selected from the group of hydrogen and methyl; R 19 and R 20 are each independently selected from the group of hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, and n-pentyl; Y is CN, R 1 and R 2 are each independently selected from the group: hydrogen and methyl; R 3 is NH2, R 4 is C(O)NR 10 R 11and C(O)NHCH3, R 5 is selected from the group of hydrogen and methyl; R 10 and R 11 are each independently selected from the group of hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, and n-pentyl; X is a leaving group, trifluoromethanesulfonate (TfO), tosylate (TsO), p-tosylate (p-TsO), mesylate (MsO), diethyl phosphate (POEt), sulfonate (-OSOR 23 ), carboxylate (-OCOR 24 ), diazonium, halogen, fluoride, chloride, bromide, and iodide; and R 23 and R 24 is each independently selected from the group of methyl and ethyl.

[0038] Embodiment 11C. R 12 is hydrogen, R 13 is methyl, R 14 is NH2, R 15 is C(O)NR 19 R 20 and C(O)NHCH3, R 16 is hydrogen, R 19 and R 20 are each independently selected from the group of hydrogen, methyl, ethyl, n-propyl, and iso-propyl; Y is CN, R 1 is hydrogen, R 2 is methyl, R 3 is NH2, R 4 is C(O)NR10 R 11 and C(O)NHCH3, R 5 is hydrogen, R 10 and R 11 are each independently selected from the group of hydrogen, methyl, ethyl, n-propyl, and iso-propyl; X is selected from the group of halogen, fluoride, chloride, bromide, and iodide; and R 23 and R 24 and n is independently methyl.

[0039] Embodiment 12. The method of embodiment 11, wherein subjecting the mixture to irradiation from at least one light source comprises subjecting the mixture to light irradiation having a wavelength in the range of about 180 nm to about 450 nm, preferably about 180 nm to about 420 nm, more preferably about 360 nm to about 420 nm, and even more preferably about 360 nm to about 400 nm.

[0040] Embodiment 12A. The method of embodiment 11 or embodiment 12, wherein subjecting the mixture to irradiation from at least one light source comprises subjecting the mixture to light irradiation having a wavelength in the range of about 360 nm to about 420 nm.

[0041] Embodiment 12B. The method of embodiment 11 or embodiment 12, wherein subjecting the mixture to irradiation from at least one light source comprises subjecting the mixture to light irradiation having a wavelength in the range of about 360 nm to about 400 nm.

[0042] Embodiment 13 The method of embodiment 11, wherein the solubility of the compound of Formula II in the solvent is lower than the solubility of the compound of Formula I in the solvent.

[0043] Embodiment 14 The method of embodiment 11, wherein the cyano-containing compound is soluble in the solvent.

[0044] Embodiment 15. The method of embodiment 11, wherein subjecting the mixture to irradiation from at least one light source comprises subjecting the mixture to light irradiation having a power in the range of about 1 W to about 1000 W.

[0045] Embodiment 16. The method of embodiment 11, wherein subjecting the mixture to irradiation from at least one light source comprises subjecting the mixture to irradiation from at least one light source for a time period ranging from 1 second to about 12 hours.

[0046] Embodiment 17. The method of embodiment 11, wherein the cyano-containing compound is selected from the group consisting of cyanide salts, NaCN, KCN, metal cyanide salts, K3[Fe(CN)6], Na3[Fe(CN)]6, CuCN, Zn(CN)2, acetonitrile, HCN, tetrabutylammonium cyanide, tetraethylammonium cyanide, trimethylsilyl cyanide, acetone cyanohydrin, and combinations thereof.

[0047] Embodiment 18. The method of embodiment 11, wherein the solvent is selected from the group consisting of aqueous solvents, organic solvents, water, acetonitrile, dimethylformamide (DMF), acetone, dimethylacetamide (DMAc), dimethyl sulfoxide (DMSO), N-methylpyrrolidone (NMP), alcohol, methanol, ethanol, n-propanol, isopropanol, n-butanol, 2-butanol, t-butanol, and combinations thereof; preferably, the solvent is a mixture of water and acetonitrile or a mixture of water and t-butanol.

[0048] Embodiment 19. A compound of formula II is [ka] 12. The method of embodiment 11, wherein

[0049] Embodiment 20. A compound of Formula I is [ka] 12. The method of embodiment 11, wherein

[0050] Embodiment 21 The method of any one of Embodiments 11-20, wherein the photochemical reaction system of any one of Embodiments 1-7 is used to prepare a compound of Formula II.

[0051] Embodiment 22. 2-Amino-5-cyano-N,3-dimethyl-benzamide [ka] 1. A method for preparing The method is: I) a) 2-amino-5-chloro-N,3-dimethyl-benzamide [ka] and, b) a cyano-containing compound; and c) forming a mixture comprising, optionally, a solvent; II) subjecting the mixture to irradiation from at least one light source; A method comprising:

[0052] Embodiment 23. The method of embodiment 22, wherein the cyano-containing compound is selected from the group consisting of cyanide salts, NaCN, KCN, metal cyanide salts, K3[Fe(CN)6], Na3[Fe(CN)]6, CuCN, Zn(CN)2, acetonitrile, HCN, tetrabutylammonium cyanide, tetraethylammonium cyanide, trimethylsilyl cyanide, acetone cyanohydrin, and combinations thereof.

[0053] Embodiment 23A. The method of embodiment 22, wherein the cyano-containing compound is selected from the group of NaCN, KCN, K3[Fe(CN)6], Na3[Fe(CN)]6, CuCN, and Zn(CN)2.

[0054] Embodiment 23B. The method of embodiment 22, wherein the cyano-containing compound is selected from the group of NaCN, KCN, CuCN, and Zn(CN)2.

[0055] Embodiment 23C. The method of Embodiment 22, wherein the cyano-containing compound is NaCN.

[0056] Embodiment 24. The method of any one of embodiments 22-23C, wherein the solvent is selected from the group consisting of aqueous solvents, organic solvents, water, acetonitrile, dimethylformamide (DMF), acetone, dimethylacetamide (DMAc), dimethyl sulfoxide (DMSO), N-methylpyrrolidone (NMP), alcohol, methanol, ethanol, n-propanol, isopropanol, n-butanol, 2-butanol, t-butanol, and combinations thereof; preferably, the solvent is a mixture of water and acetonitrile or a mixture of water and t-butanol.

[0057] Embodiment 24A. The method of Embodiment 24, wherein the solvent is a mixture of water and acetonitrile or a mixture of water and t-butanol.

[0058] Embodiment 25. The method of any one of Embodiments 22-24A, wherein subjecting the mixture to irradiation from at least one light source comprises subjecting the mixture to light irradiation having a wavelength in the range of about 360 nm to about 400 nm.

[0059] Embodiment 26. The method of any one of embodiments 22 to 25, using the photochemical reaction system of any one of embodiments 1 to 7.

[0060] Embodiment C1. A composition comprising: (a) a compound of formula II [ka] (In the formula, R 12 and R 13are each independently selected from the group consisting of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C3-C6 branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers thereof; R 14 are amines, amides, carbamides, NH2, NR 17 R 18 , and NR 21 COR 22 is selected from the group R 15 is an amide, C(O)NR 19 R 20 and C(O)NHCH3; R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , and R 22 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C3-C6 branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers thereof; and Y is selected from the group of cyano-containing substituents and CN; (b) a compound of formula I [ka] (In the formula, R 1 and R 2 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C3-C6 branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers; R 3are amines, amides, carbamides, NH2, NR 6 R 7 , and NR 8 COR 9 is selected from the group R 4 is an amide, C(O)NR 10 R 11 and C(O)NHCH3; R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, and substituted or unsubstituted C3-C6 branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers thereof; and X is a leaving group, trifluoromethanesulfonate (TfO), tosylate (TsO), p-tosylate (p-TsO), mesylate (MsO), diethyl phosphate (POEt), sulfonate (-OSOR 23 ), carboxylate (-OCOR 24 ), diazonium, halogen, fluoride, chloride, bromide, and iodide; and R 23 and R 24 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C3-C6 branched alkyl, C1-C6 haloalkyl, and C1-C6 fluoroalkyl; A composition comprising:

[0061] Embodiment C2. The composition of Embodiment C1, optionally comprising: (c) a compound of Formula III [ka] (In the formula, R 1 a and R 2 each a is independently selected from the group consisting of hydrogen, substituted or unsubstituted linear alkyl, substituted or unsubstituted C1-C6 linear alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C3-C6 branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and an isomer; R 3 a is amine, amide, carbamide, NH2, NR 6 R 7 , and NR 8 COR 9 is selected from the group R 4 a is amide, C(O)NR 10 R 11 and C(O)NHCH3, and R 5 a, R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are each independently selected from the group of hydrogen, substituted or unsubstituted straight chain alkyl, substituted or unsubstituted C1-C6 straight chain alkyl, substituted or unsubstituted branched alkyl, and substituted or unsubstituted C3-C6 branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers thereof.

[0062] Embodiment C2A.(c) The composition of any one of Embodiments C1-C2 further comprising a compound of Formula III.

[0063] Embodiment C3. A compound of Formula II is [ka] The composition of any one of embodiments C1 through C2A, wherein

[0064] Embodiment C3A. A compound of Formula I is [ka] The composition of any one of embodiments C1-C3, wherein

[0065] Embodiment C3B. A compound of Formula III is [ka] The composition of any one of embodiments C1 through C3A, wherein

[0066] Embodiment C4. A composition comprising: (a) 2-amino-5-cyano-N,3-dimethyl-benzamide [ka] and, (b) 2-amino-5-chloro-N,3-dimethyl-benzamide [ka] and a composition comprising:

[0067] Embodiment C5. A composition comprising: (a) 2-amino-5-cyano-N,3-dimethyl-benzamide [ka] and, (b) 2-amino-5-chloro-N,3-dimethyl-benzamide [ka] and, (c) 2-amino-N,3-dimethyl-benzamide [ka] and a composition comprising:

[0068] Embodiment C6. The composition of any one of Embodiments C1 through C5, wherein the molar ratio of the compound of Formula II to the compound of Formula I is from about 1:1 to about 99.9:0.1.

[0069] Embodiment C7. The composition of any one of Embodiments C1 through C6, wherein the molar ratio of the compound of Formula II to the compound of Formula I is from about 2:1 to about 99.9:0.1.

[0070] Embodiment C8. The composition of any one of Embodiments C1 through C7, wherein the molar ratio of the compound of Formula II to the compound of Formula I is from about 5:1 to about 99.9:0.1.

[0071] Embodiment C9. The composition of any one of Embodiments C1 through C8, wherein the molar ratio of the compound of Formula II to the compound of Formula I is from about 5:1 to about 99:1.

[0072] Embodiment C10. The composition of any one of Embodiments C1 through C9, wherein the molar ratio of the compound of Formula II to the compound of Formula I is from about 5:1 to about 50:1.

[0073] Embodiment C11. The composition of any one of Embodiments C1 through C10, wherein the molar ratio of the compound of Formula II to the compound of Formula I is from about 5:1 to about 30:1.

[0074] Embodiment C12. The composition of any one of Embodiments C2 through C11, wherein the molar ratio of the compound of Formula II to the compound of Formula III is from about 1:1 to about 99.9:0.1.

[0075] Embodiment C13. The composition of any one of Embodiments C2 through C12, wherein the molar ratio of the compound of Formula II to the compound of Formula III is from about 2:1 to about 99.9:0.1.

[0076] Embodiment C14. The composition of any one of Embodiments C2 through C13, wherein the molar ratio of the compound of Formula II to the compound of Formula III is from about 5:1 to about 99.9:0.1.

[0077] Embodiment C15. The composition of any one of Embodiments C2 through C14, wherein the molar ratio of the compound of Formula II to the compound of Formula III is from about 5:1 to about 99:1.

[0078] Embodiment C16. The composition of any one of Embodiments C2 through C15, wherein the molar ratio of the compound of Formula II to the compound of Formula III is from about 5:1 to about 50:1.

[0079] Embodiment C17. The composition of any one of Embodiments C2 through C16, wherein the molar ratio of the compound of Formula II to the compound of Formula III is from about 5:1 to about 30:1.

[0080] Embodiment C18. The composition of any one of embodiments C1-C17, wherein the composition is prepared by the method of any one of embodiments 11-20.

[0081] In one aspect, compounds of Formula II are prepared according to the method represented by Scheme 1. The R group is as defined anywhere in this disclosure. [ka]

[0082] This embodiment includes containing a mixture comprising a compound of Formula I, a cyano-containing compound, and optionally a solvent in a containment vessel of a photochemical reaction system, and then reacting the mixture in the photochemical reaction system to produce a compound of Formula II.

[0083] In many embodiments, reacting the mixture in the photochemical reaction system includes subjecting the mixture to irradiation from at least one light source. Generally, the irradiation can be of any suitable wavelength known in the art. In some embodiments, the irradiation includes ultraviolet light, visible light, or a combination thereof.

[0084] In some embodiments, the radiation is at 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 150 nm, 160 nm, 170 nm, 180 nm, 190 nm, 200 nm, 210 nm, 220 nm, 230 nm, 240 nm, 250 nm, 260 nm, 270 nm, 280 nm, 290 nm, 300 nm, 310 nm, 320 nm, 330 nm, 340 nm, 350 nm, 360 nm, 370 nm, 380 nm, 390 nm, 400 nm, 410 nm, 420 nm, 430 nm, 440 nm, 450 nm, m, and has a minimum wavelength selected from 460 nm, 470 nm, 480 nm, 490 nm, 500 nm, 510 nm, 520 nm, 530 nm, 540 nm, 550 nm, 560 nm, 570 nm, 580 nm, 590 nm, 600 nm, 610 nm, 620 nm, 630 nm, 640 nm, 650 nm, 660 nm, 670 nm, 680 nm, 690 nm, 700 nm, 710 nm, 720 nm, 730 nm, 740 nm, 750 nm, 760 nm, 770 nm, 780 nm, 790 nm, and 800 nm.

[0085] In some embodiments, the radiation is at 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 150 nm, 160 nm, 170 nm, 180 nm, 190 nm, 200 nm, 210 nm, 220 nm, 230 nm, 240 nm, 250 nm, 260 nm, 270 nm, 280 nm, 290 nm, 300 nm, 310 nm, 320 nm, 330 nm, 340 nm, 350 nm, 360 nm, 370 nm, 380 nm, 390 nm, 400 nm, 410 nm, 420 nm, 430 nm, 440 nm, 450 nm, m, and has a maximum wavelength selected from 460 nm, 470 nm, 480 nm, 490 nm, 500 nm, 510 nm, 520 nm, 530 nm, 540 nm, 550 nm, 560 nm, 570 nm, 580 nm, 590 nm, 600 nm, 610 nm, 620 nm, 630 nm, 640 nm, 650 nm, 660 nm, 670 nm, 680 nm, 690 nm, 700 nm, 710 nm, 720 nm, 730 nm, 740 nm, 750 nm, 760 nm, 770 nm, 780 nm, 790 nm, and 800 nm.

[0086] In some embodiments, the radiation has a wavelength in the range of about 180 nm to about 450 nm. In some embodiments, the radiation has a wavelength in the range of about 180 nm to about 400 nm. In some embodiments, the radiation has a wavelength in the range of about 360 nm to about 420 nm. In some embodiments, the radiation has a wavelength in the range of about 380 nm to about 400 nm.

[0087] Generally, the radiation can be of any suitable power known in the art. In many embodiments, the power output depends on various factors and is not required. In some embodiments, the radiation output is in the range of about 1 W to about 1000 W.

[0088] Generally, irradiation can be applied for any suitable period of time known in the art. In many embodiments, the period of time depends on various factors and is not required. In some embodiments, irradiation is applied for a period of time ranging from 1 second to about 12 hours.

[0089] Generally, the cyano-containing compound can be any suitable cyano-containing compound known in the art. In some embodiments, the cyano-containing compound is selected from the group consisting of cyanide salts, NaCN, KCN, metal cyanide salts, K3[Fe(CN)6], Na3[Fe(CN)]6, CuCN, Zn(CN)2, acetonitrile, HCN, tetrabutylammonium cyanide, tetraethylammonium cyanide, trimethylsilyl cyanide, acetone cyanohydrin, and combinations thereof.

[0090] Generally, the solvent can be any suitable solvent known in the art. In some embodiments, the solvent is selected from the group consisting of aqueous solvents, organic solvents, water, acetonitrile, dimethylformamide (DMF), acetone, dimethylacetamide (DMAc), dimethyl sulfoxide (DMSO), N-methylpyrrolidone (NMP), alcohol, methanol, ethanol, n-propanol, isopropanol, n-butanol, 2-butanol, t-butanol, and combinations thereof. In some preferred embodiments, the solvent is a mixture of water and acetonitrile or a mixture of water and t-butanol.

[0091] In some embodiments, when the reaction occurs in a loop reactor system, the solubility of the compound of Formula II in the solvent is lower than the solubility of the compound of Formula I in the solvent. In these embodiments, the difference in solubility allows for cycling of the reaction by precipitating and recovering the compound of Formula II from solution. Such recovery can be carried out using a filter.

[0092] In some embodiments, when the reaction occurs in a loop reactor system, the cyano-containing compound is soluble in the solvent. In these embodiments, the solubility of the cyano-containing compound allows for cycling of the reaction by avoiding precipitation of the cyano-containing compound.

[0093] Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. Therefore, the following examples are intended to be merely illustrative and in no way limit the present disclosure. The starting materials in the following examples may not necessarily have been prepared by the specific preparation procedures described in other examples. Furthermore, any numerical range recited herein is understood to include all values ​​from the lower value to the upper value. For example, if a range is recited as 10 to 50, it is intended that values ​​such as 12 to 30, 20 to 40, or 30 to 50 are expressly recited herein. These are merely examples of what is specifically intended, and all possible combinations of values ​​between the lowest and highest recited values ​​should be considered to be expressly stated in this application. Ambient or room temperature is defined as approximately 20 to 25°C. The term HPLC refers to high-performance liquid chromatography.

[0094] Example 1 Preparation of 2-amino-5-cyano-N,3-dimethyl-benzamide To a 25 mL reactor was added 0.3 g of 2-amino-5-chloro-N,3-dimethyl-benzamide, 0.3 g of sodium cyanide (NaCN), 7.5 g of acetonitrile, and 7.5 g of water at ambient temperature. The mixture was stirred for 5 hours under 370 nm light irradiation. HPLC analysis indicated 94.9% 2-amino-5-cyano-N,3-dimethyl-benzamide and 2.4% 2-amino-5-cyano-N,3-dimethyl-benzamide. Gravimetric analysis indicated a reaction yield of 80%.

[0095] Example 2 Preparation of 2-amino-5-cyano-N,3-dimethyl-benzamide To a 25 mL reactor, 0.8 g of 2-amino-5-chloro-N,3-dimethyl-benzamide, 0.8 g of sodium cyanide (NaCN), 7.5 g of acetonitrile, and 7.5 g of water were added at 60° C. The mixture was stirred for 5 hours under 370 nm light irradiation. HPLC analysis showed 95.5% 2-amino-5-cyano-N,3-dimethyl-benzamide and 1.2% 2-amino-5-cyano-N,3-dimethyl-benzamide. Gravimetric analysis showed a reaction yield of 76%.

[0096] Example 3 Preparation of 2-amino-5-cyano-N,3-dimethyl-benzamide using various irradiation wavelengths To a 25 mL reactor at ambient temperature, 0.3 g of 2-amino-5-chloro-N,3-dimethyl-benzamide, 0.3 g of sodium cyanide (NaCN), 7.5 g of acetonitrile, and 7.5 g of water were added. The mixture was stirred for 4 hours under irradiation with light of various wavelengths. HPLC analysis showed various conversion rates depending on the irradiation wavelength, as shown in Table 1 below.

[0097] [Table 1]

[0098] Example 4 Preparation of 2-amino-5-cyano-N,3-dimethyl-benzamide using various irradiation wavelengths To a 25 mL reactor at ambient temperature, 0.3 g of 2-amino-5-chloro-N,3-dimethyl-benzamide, 0.3 g of sodium cyanide (NaCN), 7.5 g of acetonitrile, and 7.5 g of water were added. The mixture was stirred for 3 hours under irradiation with light of various wavelengths. HPLC analysis showed various conversion rates depending on the irradiation wavelength, as shown in Table 2 below.

[0099] [Table 2]

[0100] Example 5 Preparation of 2-amino-5-cyano-N,3-dimethyl-benzamide using various irradiation wavelengths To each quartz vessel of the parallel UV reactor, 0.3 g of 2-amino-5-chloro-N,3-dimethyl-benzamide, 0.3 g of sodium cyanide (NaCN), 7.5 g of acetonitrile, and 7.5 g of water were added at ambient temperature. The mixture was stirred for 3 hours under irradiation with light of various wavelengths. HPLC analysis showed various conversion rates depending on the irradiation wavelength, as shown in Table 2 below.

[0101] [Table 3]

[0102] Example 6 Preparation of 2-amino-5-cyano-N,3-dimethyl-benzamide using a loop reactor system A first 500 mL reactor equipped with a filter plate was charged with 50 g of 2-amino-5-chloro-N,3-dimethyl-benzamide, 36 g of sodium cyanide (NaCN), 228 g of t-butanol, and 686 g of water at room temperature. The solution below the filter plate was pumped into a photoreactor by the first pump. The reaction was carried out under 370 nm light irradiation. The resulting warm reaction liquid was cooled to room temperature and transferred to a second 500 mL reactor equipped with a filter plate. 2-amino-5-cyano-N,3-dimethyl-benzamide was precipitated in the second reactor. The mother liquid (i.e., the filtrate) was transferred to the first reactor by the second pump. This system was run until all 2-amino-5-cyano-N,3-dimethyl-benzamide had disappeared. HPLC analysis showed a conversion of 2-amino-5-cyano-N,3-dimethyl-benzamide of greater than 98%. Gravimetric analysis indicated a reaction yield of 82%.

[0103] This specification uses examples to illustrate the disclosure, including the best mode, and to enable those skilled in the art to practice the disclosure, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the disclosure is defined by the claims, and may include other examples that occur to those skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements that do not differ substantially from the literal language of the claims.

[0104] As used herein, the terms "comprises," "comprising," "includes," "including," "has," "having," "contains," "containing," "characterized by," or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitations expressly stated. For example, a composition, mixture, process, or method that includes a list of elements is not necessarily limited to only those elements and may include other elements not expressly listed or inherent in such composition, mixture, process, or method.

[0105] The transitional phrase "consisting of" excludes any unspecified element, step, or ingredient. In a claim, such a transitional phrase closes the claim to the inclusion of materials other than those recited, apart from impurities normally associated with the recited materials. When the phrase "consisting of" appears in a clause in the body of a claim rather than immediately before the preamble, it limits only the elements set forth in that clause and does not exclude other elements from the claim as a whole.

[0106] The transitional phrase "consisting essentially of" is used to define compositions or methods that include materials, steps, features, components, or elements in addition to those literally disclosed, provided that these additional materials, steps, features, components, or elements do not materially affect the basic and novel characteristics of the claimed invention. The term "consisting essentially of" occupies a middle ground between "comprising" and "consisting of."

[0107] It should be readily understood that where the invention or any portion thereof is defined in open-ended terms such as "comprising," the statement should also be construed as describing such inventions using the terms "consisting essentially of" or "consisting of" (unless otherwise stated).

[0108] Furthermore, unless expressly stated to the contrary, "or" refers to an inclusive "or" and not an exclusive "or." For example, a condition A or B is satisfied by any one of the following: A is true (or exists) and B is false (or does not exist), A is false (or does not exist) and B is true (or exists), and both A and B are true (or exist).

[0109] Furthermore, the indefinite articles "a" and "an" preceding an element or component of the invention are intended to be open-ended regarding the number of instances (i.e., occurrences) of that element or component. Thus, "a" or "an" should be read to include one or at least one, and singular forms of elements or components also include the plural, unless the number is clearly intended to be singular.

[0110] As used herein, the term "about" means ±10% of a value.

[0111] The term "halogen," alone or in compound words such as "haloalkyl," includes fluorine, chlorine, bromine, or iodine. Furthermore, when used in compound words such as "haloalkyl," the alkyl may be partially or fully substituted with halogen atoms, which may be the same or different.

[0112] A group may have a substituent that may be hydrogen, e.g., R 4 and that substituent is then taken to be hydrogen, this is considered to be equivalent to the group being unsubstituted.

[0113] The term "cyano-containing compound" includes, but is not limited to, compounds that contain a functional group that contains a nitrile bond (-C≡N).

[0114] Certain compounds of the present invention can exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers, atropisomers, and geometric isomers. As will be appreciated by those skilled in the art, one stereoisomer may be more active and / or exhibit advantageous effects when enriched or separated from other stereoisomers. Furthermore, those skilled in the art will recognize methods for separating, enriching, and / or selectively preparing such stereoisomers.

Claims

1. Compound of Formula II 【Chemistry 1】 (In the formula, R １２ and R １３ are each independently hydrogen, substituted or unsubstituted linear alkyl, substituted or unsubstituted C １ -C ６ Straight-chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C ３ -C ６ selected from the group consisting of branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers thereof; R １４ is an amine, amide, carbamide, NH ２ , N.R. １７ R １８ , and N.R. ２１ COR ２２ is selected from the group R １５ is an amide, C(O)NR １９ R ２０ , and C(O)NHCH ３ is selected from the group R １６ , R １７ , R １８ , R １９ , R ２０ , R ２１ , and R ２２ are each independently hydrogen, substituted or unsubstituted linear alkyl, substituted or unsubstituted C １ -C ６ Straight-chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C ３ -C ６ selected from the group consisting of branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers thereof; and Y is selected from the group of cyano-containing substituents and CN.

1. A method for preparing The method comprises: I) a) a compound of formula I 【Chemistry 2】 (In the formula, R １ and R ２ are each independently hydrogen, substituted or unsubstituted linear alkyl, substituted or unsubstituted C １ -C ６ Straight-chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C ３ -C ６ selected from the group consisting of branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl and isomers thereof; R ３ is an amine, amide, carbamide, NH ２ , N.R. ６ R ７ , and N.R. ８ COR ９ is selected from the group R ４ is an amide, C(O)NR １０ R １１ , and C(O)NHCH ３ is selected from the group R ５ , R ６ , R ７ , R ８ , R ９ , R １０ , and R １１ are each independently hydrogen, substituted or unsubstituted linear alkyl, substituted or unsubstituted C １ -C ６ Straight-chain alkyl, substituted or unsubstituted branched alkyl, and substituted or unsubstituted C ３ -C ６ selected from the group consisting of branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl and isomers thereof; X is a leaving group, trifluoromethanesulfonate (TfO), tosylate (TsO), p-tosylate (p-TsO), mesylate (MsO), diethylphosphate (PO ４ Et ２ ), sulfonate (-OSO ２ R ２３ ), carboxylate (-OCOR ２４ ), selected from the group of diazonium, halogen, fluoride, chloride, bromide, and iodide; R ２３ and R ２４ are each independently hydrogen, substituted or unsubstituted linear alkyl, substituted or unsubstituted C １ -C ６ Straight-chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C ３ -C ６ Branched alkyl, C １ -C ６ Haloalkyl, and C １ -C ６ fluoroalkyl) and b) a cyano-containing compound; and c) forming a mixture comprising, optionally, a solvent; II) subjecting said mixture to irradiation from at least one light source; A method comprising:

2. 10. The method of claim 1, wherein subjecting the mixture to irradiation from at least one light source comprises subjecting the mixture to light irradiation having a wavelength in the range of from about 180 nm to about 450 nm, preferably from about 180 nm to about 420 nm, more preferably from about 360 nm to about 420 nm, and even more preferably from about 360 nm to about 400 nm.

3. 10. The method of claim 1, wherein the solubility of the compound of formula II in the solvent is lower than the solubility of the compound of formula I in the solvent.

4. The method of claim 1 , wherein the cyano-containing compound is soluble in the solvent.

5. 10. The method of claim 1, wherein subjecting the mixture to irradiation from at least one light source comprises subjecting the mixture to light irradiation having a power in the range of about 1 W to about 1000 W.

6. 10. The method of claim 1, wherein subjecting the mixture to irradiation from at least one light source comprises subjecting the mixture to irradiation from at least one light source for a time period ranging from 1 second to about 12 hours.

7. The cyano-containing compounds include cyanide salts, NaCN, KCN, metal cyanide salts, K ３ [Fe(CN) ６ ], Na ３ [Fe(CN)] ６ , CuCN, Zn(CN) ２ 2. The method of claim 1, wherein the solvent is selected from the group consisting of acetonitrile, HCN, tetrabutylammonium cyanide, tetraethylammonium cyanide, trimethylsilyl cyanide, acetone cyanohydrin, and combinations thereof.

8. 2. The method of claim 1, wherein the solvent is selected from the group consisting of aqueous solvents, organic solvents, water, acetonitrile, dimethylformamide (DMF), acetone, dimethylacetamide (DMAc), dimethylsulfoxide (DMSO), N-methylpyrrolidone (NMP), alcohols, methanol, ethanol, n-propanol, isopropanol, n-butanol, 2-butanol, t-butanol, and combinations thereof, and preferably, the solvent is a mixture of water and acetonitrile or a mixture of water and t-butanol.

9. 10. The method of preparing a compound of formula II according to claim 1, wherein said compound of formula II is 2-amino-5-cyano-N,3-dimethyl-benzamide 【Transformation 3】 and The method comprises: I) a) A compound of formula I, wherein said compound of formula I is 2-amino-5-chloro-N,3-dimethyl-benzamide 【Chemistry 4】 and a compound b) a cyano-containing compound; and c) forming a mixture comprising, optionally, a solvent; II) subjecting said mixture to irradiation from at least one light source, said light irradiation having a wavelength in the range of about 360 nm to about 400 nm.

10. The step of subjecting the mixture to irradiation from at least one light source comprises subjecting the mixture to a photochemical reaction system, the photochemical reaction system comprising:

1. A loop reactor system comprising: a container configured to contain the mixture; and a photochemical reactor configured to subject the mixture to irradiation from at least one light source; a precipitation vessel configured to contain the irradiated mixture; a loop reactor system comprising: Optionally, additional reaction system components selected from the group of a fluid transfer system, a stripping system, a filtration system, a drying system, an agitation system, a temperature control system, and combinations thereof; 10. The method of claim 1, wherein the method is carried out using a photochemical reaction system comprising:

11. 11. The method of claim 10, wherein the loop reactor system is configured to circulate the mixture through the holding vessel, the photochemical reactor vessel, and the precipitation vessel at least once.

12. The photochemical reaction system includes: transferring the mixture from the storage vessel to the photochemical reaction vessel; transferring the mixture from the photochemical reactor to the precipitation vessel; and / or Transferring the mixture from the settling vessel to the receiving vessel. The method of claim 10 , comprising at least one fluid transfer system configured to:

13. 11. The method of claim 10, wherein the photochemical reaction system comprises a stripping system, an agitation system, a filtration system, a drying system, a temperature control system, or a combination thereof.

14. 11. The method of claim 10, wherein the photochemical reactor is configured to subject the mixture to irradiation from multiple light sources.

15. 11. The method of claim 10, wherein the photochemical reactor is configured to subject the mixture to light irradiation having a wavelength in the range of about 180 nm to about 450 nm, preferably about 180 nm to about 420 nm, more preferably about 360 nm to about 420 nm, and even more preferably about 360 nm to about 400 nm.

16. The method of claim 10 , wherein at least one of the receiving vessel and the settling vessel includes a filter.

17. 1. A composition comprising: (a) a compound of formula II 【Transformation 5】 (In the formula, R １２ and R １３ are each independently hydrogen, substituted or unsubstituted linear alkyl, substituted or unsubstituted C １ -C ６ Straight-chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C ３ -C ６ selected from the group consisting of branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers thereof; R １４ is an amine, amide, carbamide, NH ２ , N.R. １７ R １８ , and N.R. ２１ COR ２２ is selected from the group R １５ is an amide, C(O)NR １９ R ２０ , and C(O)NHCH ３ is selected from the group R １６ , R １７ , R １８ , R １９ , R ２０ , R ２１ , and R ２２ are each independently hydrogen, substituted or unsubstituted linear alkyl, substituted or unsubstituted C １ -C ６ Straight-chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C ３ -C ６ selected from the group consisting of branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers thereof; and Y is selected from the group of cyano-containing substituents and CN; (b) a compound of formula I 【Transformation 6】 (In the formula, R １ and R ２ are each independently hydrogen, substituted or unsubstituted linear alkyl, substituted or unsubstituted C １ -C ６ Straight-chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C ３ -C ６ selected from the group consisting of branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl and isomers thereof; R ３ is an amine, amide, carbamide, NH ２ , N.R. ６ R ７ , and N.R. ８ COR ９ is selected from the group R ４ is an amide, C(O)NR １０ R １１ , and C(O)NHCH ３ is selected from the group R ５ , R ６ , R ７ , R ８ , R ９ , R １０ , and R １１ are each independently hydrogen, substituted or unsubstituted linear alkyl, substituted or unsubstituted C １ -C ６ Straight-chain alkyl, substituted or unsubstituted branched alkyl, and substituted or unsubstituted C ３ -C ６ selected from the group consisting of branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers thereof; and X is a leaving group, trifluoromethanesulfonate (TfO), tosylate (TsO), p-tosylate (p-TsO), mesylate (MsO), diethylphosphate (PO ４ Et ２ ), sulfonate (-OSO ２ R ２３ ), carboxylate (-OCOR ２４ ), selected from the group of diazonium, halogen, fluoride, chloride, bromide, and iodide; and R ２３ and R ２４ are each independently hydrogen, substituted or unsubstituted linear alkyl, substituted or unsubstituted C １ -C ６ Straight-chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C ３ -C ６ Branched alkyl, C １ -C ６ Haloalkyl, and C １ -C ６ fluoroalkyl) and A composition comprising:

18. (c) a compound of formula III 【Transformation 7】 (In the formula, R １ a and R ２ a each independently represents hydrogen, substituted or unsubstituted linear alkyl, substituted or unsubstituted C １ -C ６ Straight-chain alkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted C ３ -C ６ selected from the group consisting of branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl and isomers thereof; R ３ a is an amine, amide, carbamide, NH ２ , N.R. ６ R ７ , and N.R. ８ COR ９ is selected from the group R ４ a is an amide, C(O)NR １０ R １１ , and C(O)NHCH ３ is selected from the group R ５ a, R ６ , R ７ , R ８ , R ９ , R １０ , and R １１ are each independently hydrogen, substituted or unsubstituted linear alkyl, substituted or unsubstituted C １ -C ６ Straight-chain alkyl, substituted or unsubstituted branched alkyl, and substituted or unsubstituted C ３ -C ６ branched alkyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, and isomers thereof.

20. The composition of claim 17, further comprising:

19. The compound of formula II is 2-amino-5-cyano-N,3-dimethyl-benzamide; 18. The composition of claim 17, wherein said compound of formula I is 2-amino-5-chloro-N,3-dimethyl-benzamide.

20. The compound of formula II is 2-amino-5-cyano-N,3-dimethyl-benzamide; The compound of formula I is 2-amino-5-chloro-N,3-dimethyl-benzamide; 19. The composition of claim 18, wherein the compound of formula III is 2-amino-N,3-dimethyl-benzamide.

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