Molecules with pesticidal utility and methods related thereto

Abstract

The present disclosure relates to the field of molecules having pesticidal utility on pests in Nematoda's Phyla, as well as methods of using such molecules on such pests. The pesticidal molecules may be used in pesticidal compositions, such as, for example, nematicidal compositions.

Description

Background Art

[0001] The present disclosure relates to the field of molecules having pesticidal efficacy against pests in the phylum Nematoda, and methods of using such molecules on such pests. The pesticidal molecules can be used in pesticidal compositions, such as, for example, nematocidal compositions.

[0002] “Many of the most dangerous human diseases are transmitted by insect vectors” (Rivero et al., Insect Control of Vector-Borne Diseases: When is Insect Resistance a Problem? Public Library of Science Pathogens, Vol. 6, No. 8, pp. 1-9, 2010). “Historically, malaria, dengue, yellow fever, plague, filariasis, louse-borne typhus, trypanosomiasis, leishmaniasis, and other vector-borne diseases caused more human illness and death from the 17th to the early 20th centuries than all other causes combined” (Gubler, D., Resurgent Vector-Borne Diseases as a Global Health Problem, Emerging Infectious Diseases, Vol. 4, No. 3, pp. 442-450, 1998). Vector-borne diseases account for approximately 17% of parasitic and infectious diseases worldwide. Malaria alone kills over 800,000 people annually, 85% of which occur in children under five years old. There are approximately 50 to 100 million cases of dengue fever each year. There are also 250,000 to 500,000 cases of dengue hemorrhagic fever each year (Matthews, Integrated Vector Management: Controlling Vectors of Malaria and Other Insect Vector Borne Diseases, Chapter 1, page 1, 2011). Vector control plays a vital role in the prevention and control of infectious diseases. However, resistance to insecticides, including resistance to multiple insecticides, has emerged in all insect species that are major vectors of human diseases (Rivero et al.).Recently, more than 550 arthropod species have developed resistance to at least one pesticide (Whalon et al., Analysis of Global Pesticide Resistance in Arthropods, Global Pesticide Resistance in Arthropods, Chapter 1, pp. 5-33, 2008). Furthermore, cases of insect resistance continue to outnumber cases of herbicide and fungicide resistance by far (Sparks et al., IRAC: Mode of action classification and insecticide resistance management, Pesticide Biochemistry and Physiology (2014), available online December 4, 2014).

[0003] Every year, insects, plant pathogens, and weeds destroy more than 40% of all food produced. This loss occurs despite the application of pesticides and the use of a variety of non-chemical control measures (such as crop rotation) and biological control measures. If only a portion of this food could be saved, it could be used to feed the world's more than 3 billion malnourished people (Pimental, D., Pest Control in World Agriculture, Agricultural Sciences - Volume II, 2009).

[0004] Plant parasitic nematodes are among the most prevalent pests and often the most insidious and costly, causing over $100 billion in yield losses annually worldwide (Abad et al., Root-knotnematode parasitism and host response: Molecular basis of a sophisticated interaction. Mol. Plant Pathol. 4, 217-224. doi: 10.1046 / j.1364-3703.2003.00170.x). It is estimated that losses attributable to nematodes range from about 9% in developed countries to about 15% in underdeveloped countries. However, surveys of various crops in 35 states in the United States have shown losses as high as 25% due to nematodes (Nicol et al., Current Nematode Threats to World Agriculture, Genomic and Molecular Genetics of Plant-Nematode Interactions, pp. 21-43, 2011).

[0005] Globally, approximately 2,000 plant species are susceptible to root-knot nematodes, and they are responsible for approximately 5% of global crop losses (Haydock et al.: Haydock PJ, Woods SR, Grove G, Hare MC. Chemical control of nematodes. In: Perry RN, Moens M, eds. Plant Nematology. Wallingford, Cambridge: CAB International; 2006: 392-408. http: / / dx.doi.org / 10.1079 / 9781845930561.0392 Accessed 14.11.16). Root-knot nematodes (RKN), species of the genus Meloidogyne, are one of the three most economically destructive plant-parasitic nematodes in agriculture. Root-knot nematodes are distributed worldwide. The genus includes more than 90 species. Four root-knot nematode species (M. javanica, M. arenaria, M. incognita, and M. hapla) are major pests globally, and seven additional species are locally important. If root-knot nematodes become established in deep-rooted perennial crops, control is difficult and options are limited.

[0006] The soybean cyst nematode (SCN), Heterodera glycines, is the most destructive pest to soybean crop yields in the United States, with estimated yield losses exceeding $1 billion annually. It targets the roots of soybeans and other legumes (Wrather et al.: Soybean disease loss estimates for the top ten soybean producing countries in 1998. Canadian J. Plant Pathol. 23:115-121). The symptoms caused by SCN can be easily recognized by farmers - in some cases there are no warning symptoms until yields have been lost by 30%.

[0007] Aboveground symptoms of root rot nematodes in plants with severe root infestation can include chlorosis, stunted growth, and poor vigor. Infested roots may be stunted and have small brown-black lesions. Rot nematodes are migratory internal parasites.

[0008] Thus, for many reasons, including those mentioned above, the demand for the expensive (estimated at approximately $286 million per pesticide in 2014), time-consuming (average of approximately 11.3 years per pesticide), and difficult development of new pesticides persists (Phillips McDougall, The Cost of New Agrochemical Product Discovery, Development and Registration in 1995, 2000, 2005-8 and 2010-2014. R&D expenditure in 2014 and expectations for 2019, 2016).

[0009] Definitions of the Disclosure

[0010] The examples provided herein are not exhaustive and should not be construed as limiting. It is understood that substituents should comply with chemical bonding rules and steric compatibility constraints relative to the specific molecule to which they are attached. These definitions are for the purposes of this disclosure only.

[0011] The term "locus" means a habitat, breeding ground, plant, seed, soil, material, or environment where a pest is growing, may grow, or may pass through. For example, a locus can be: where crops, trees, fruits, cereals, forage species, vines, turf, and / or ornamental plants are growing; where livestock live; interior or exterior surfaces of buildings (such as where grain is stored); building materials used in buildings (such as impregnated wood); and the soil surrounding buildings.

[0012] The term "pest" means an organism that is harmful to humans or objects of human concern (e.g., crops, food, livestock, etc.), wherein the organism is from the phylum Nematoda, such as, for example, and including, but not limited to, Aphelenchoides spp., Belonolaimus spp., Criconemella spp., Ditylenchus spp., Globodera spp., Heterodera spp., Hirschmanniella spp., Hoplolaimus spp., Meloidogyne spp., Pratylenchus spp., and Radopholus spp. A non-exhaustive list of specific species includes, but is not limited to, Dirofilaria immitis, Globodera pallida, Heterodera glycines, Heterodera zeae, Meloidogyne incognita, Meloidogyne javanica, Onchocerca volvulus, Pratylenchus penetrans, Radopholus similis, and Rotylenchulus reniformis.

[0013] Phrase " killing harmful organisms effective dose " means harmful organism is realized the amount of the required pesticide of observable effect, this effect for example is bad, dead, retards, prevents, eliminates, destroys or otherwise reduces the appearance and / or active effect of harmful organism in the place.When the harmful organism colony is expelled from the place, harmful organism loses ability in the place or around and / or harmful organism is eradicated in the place or around, this effect can occur.Certainly, the combination of these effects can occur.Usually, harmful organism colony, activity or both reduce and exceed 50 percent-points, preferably exceed 90 percent-points and most preferably exceed 99 percent-points desirably.Usually, for agricultural purposes killing harmful organism effective dose be about 0.0001 gram / hectare to about 5000 grams / hectare, preferably about 0.0001 gram / hectare to about 500 grams / hectare and it even more preferably about 0.0001 gram / hectare to about 50 grams / hectares.

[0014] All references, including publications, patent applications, and patents, cited herein are hereby incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein.

[0015] Unless otherwise indicated herein or clearly contradicted by context, the terms "a / an," "the," "at least one," and similar designators used in the context of this disclosure (particularly in the context of the following claims) should be interpreted as including both the singular and the plural. Unless otherwise indicated herein or clearly contradicted by context, the term "at least one" used followed by a list of one or more items (e.g., "at least one of A and B") should be interpreted as meaning any combination of one item selected from the listed items (A or B) or two or more of the listed items (A and B). Unless otherwise indicated herein, the terms "comprising," "having," "including," and "containing" should be interpreted as open-ended terms (i.e., meaning "including but not limited to"). Unless otherwise indicated herein, the recitation of ranges of values herein is intended merely to serve as a shorthand method of individually referencing each individual value falling within the range, and each individual value is incorporated into this specification as if it were individually recited herein. Unless otherwise indicated herein or otherwise clearly contradictory to the context, all methods described herein can be performed in any suitable order. Unless otherwise indicated, the use of any and all examples or exemplary language (e.g., "such as") provided herein is intended only to better illustrate the present disclosure and is not intended to limit the scope of the present disclosure. No language in this specification should be construed as indicating that any unclaimed element is essential for the practice of any embodiment herein. In this disclosure, the terms "molecule" and "compound" are used interchangeably. DETAILED DESCRIPTION

[0016] This document discloses the following molecules.

[0017]

[0018] The chemical name of this molecule is (S)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide. (For the purposes of this disclosure, it is also referred to as "S1").

[0019] Various methods known in the art can be used to prepare the molecule, such as, for example, WO 2017116646, US 20200397000, WO 2007039615, and US 8148538. In addition, various separation techniques can be used to separate specific enantiomers, such as separating S1 from a racemic mixture such as B. For example, chiral chromatography can be used to separate enantiomers and the enantiomeric purity can be determined using this method (Journal of Pharmaceutical and Biomedical Analysis, 2013 and "Principles and Practice of Modern Chromatographic Methods" (Second Edition), 2022).

[0020] Examples

[0021] Preparation of (S)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide (S1)

[0022] As shown in Scheme 1, (S)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide (S1) was prepared from (S)-3-ethylpentane-2-amine hydrochloride (2) and 2-chlorofuran-3-carboxylic acid (1) by direct condensation of 2-chlorofuran-3-carbonyl chloride (1b).

[0023] Scheme 1. Preparation of (S)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide.

[0024]

[0025] Scheme 2 outlines the three-step synthesis of (S)-3-ethylpentane-2-amine hydrochloride (2) from 2-ethylbutanal (3) and (R)-2-methylpropane-2-sulfenamide.

[0026] Scheme 2. Preparation of (S)-3-ethylpentane-2-amine (HCl salt)

[0027]

[0028] experiment

[0029] (R,E)-N-(2-Ethylbutylidene)-2-methylpropane-2-sulfenamide (5)

[0030]

[0031] Into a 3-liter, 3-necked round-bottom flask equipped with an overhead stirrer, a temperature probe, and a nitrogen bubbler was charged (R)-2-methylpropane-2-sulfinamide (4, 60.0 g, 495.0 mmol), 2-ethylbutanal (3, 220 mL, 1788 mmol), pyridinium p-toluenesulfonate ("PPST," 6.25 g, 24.87 mmol), anhydrous magnesium sulfate (298.0 g, 2475 mmol), and dichloromethane (1000 mL). The mixture was stirred at ambient temperature under a nitrogen atmosphere until (R)-2-methylpropane-2-sulfinamide (4) was consumed as monitored by HPLC (approximately 2 days). The resulting mixture was filtered through a plug of celite (approximately 300 g) and the wet cake was rinsed with dichloromethane (2 x 750 mL). The filtrate was concentrated by rotary evaporation under reduced pressure. The residue was dried under high vacuum overnight to afford the desired product 5 (104.70 g, 489 mmol, 99% yield) as a clear, light yellow oil. 1 H-NMR (400MHz, CDCl3) δ7.90 (d, J = 6.2Hz, 1H), 2.37 (h, J = 6.6Hz, 1H), 1.64-1.53 (m, 4H), 1.21 (s, 9H), 0.91 (td, J = 7.6, 2.7Hz, 6H). 13 C-NMR (101MHz, CDCl3) δ173.46,56.65,48.94,24.96,24.72,22.59,11.82,11.73.

[0032] (R)-N-((S)-3-Ethylpentan-2-yl)-2-methylpropane-2-sulfenamide (6)

[0033]

[0034] (R, E)-N-(2-ethylbutylidene)-2-methylpropane-2-sulfinamide (5,21.5g, 100mmol) and dichloromethane (700mL) are loaded into 2 liters of 3-neck round-bottom flasks equipped with an overhead stirrer, an addition funnel, a temperature probe and a nitrogen bubbler. The mixture is cooled to below-50°C. A solution of 3M methylmagnesium bromide (90mL, 270mmol) in 2-MeTHF is added to the addition funnel at a rate maintaining the reaction temperature below-45°C (spending about 30min). After completion of the addition, the reaction mixture is stirred for 3h at-50°C, and is warming up to ambient temperature (18°C-22°C) and spends the night. The reaction mixture is cooled to 0°C and saturated ammonium chloride solution (1L) is slowly added. The resulting mixture is phase separated. The aqueous phase is extracted with ethyl acetate (2x 750mL). The combined organic matter is dried over anhydrous sodium sulfate, filtered, and concentrated by rotary evaporation under reduced pressure. The residual oil was dried in vacuo overnight to afford the desired title product 6 (39.37 g, 179 mmol, 90% yield) as a pale yellow oil. 1 H NMR (300MHz, CDCl3) δ3.52-3.35 (m, 1H), 2.79 (d, J = 7.8Hz, 1H), 1.48-1.11 (m, 17H), 0.88 (td, J = 7.2, 5.5Hz, 6H). 13 C NMR (75MHz, CDCl3) δ55.89,53.98,47.47,22.80,22.09,21.89,20.16,11.99,11.98.

[0035] (S)-3-Ethylpentane-2-amine hydrochloride (2)

[0036]

[0037] (R)-N-((S)-3-ethylpentane-2-yl)-2-methylpropane-2-sulfinamide (7,35.9g, 164mmol) and methanol (205mL) are packed into 1 liter 4 neck round bottom flask equipped with overhead stirrer, temperature probe, addition funnel and nitrogen bubbler.Mixture is cooled to 0 ℃, with the speed that reaction temperature is maintained at below 10 ℃, add the solution of 4.0M HCl in dioxane (205mL, 818mmol) in addition funnel.After addition is complete, reaction mixture is warming up to environment temperature (20 ℃) and continues to stir at environment temperature, until as monitored by TLC reaction completion (2h).Reaction mixture is concentrated under reduced pressure to obtain light brown oily thing, and it solidifies gradually.Resistates is ground 3h with heptane (55mL). The precipitated solid was collected by filtration, washed with cold heptane (55 mL), and dried in vacuo to give the desired product (21.9 g, 144 mmol, 88% yield) as a white solid. 1 H NMR (400MHz, CDCl3) δ8.31 (s, 3H), 3.46-3.31 (m, 1H), 1.65-1.41 (m, 5H), 1.34 (d, J = 6.8Hz, 3H), 0.93 (td, J = 7.4, 2.3Hz, 6H). 13 C NMR (101MHz, CDCl3) δ50.11, 44.58, 21.99, 21.31, 15.67, 11.48, 11.40.

[0038] (S)-2-Chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide (S1)

[0039] Example A:

[0040]

[0041] In a 22L 4-neck round-bottom flask equipped with an overhead stirrer, a temperature probe, and an N2 inlet, 2-chlorofuran-3-carboxylic acid (1) (400g, 2.73mol) and (S)-3-ethylpentane-2-amine hydrochloride (2) (455.4g, 3.00mol) were dissolved in EtOAc (5.4L). The solution was cooled to 5°C. Triethylamine (1.90L, 13.64mol) was added to the solution via an addition funnel over a period of 20 minutes. The reaction mixture was stirred at 5°C for 10 minutes. Propylphosphonic anhydride solution (50wt.% in ethyl acetate) (2.43L, 4.09mol) was added dropwise via an addition funnel over a period of 1 hour. The reaction mixture was stirred at RT for 2 hours. The reaction was checked for completion by HPLC. The reaction mixture was diluted with water (2L) and transferred to a separating funnel. The layers were separated. The aqueous layer was extracted with EtOAc (2L). The organic layers are merged and washed with saturated NaHCO the aqueous solution (3L x 1), 2M HCl (2L x 1), and then washed with salt water (2L x 1). The combined organic layer is through Na sO dried, filtered and concentrated under vacuum. The crude compound is purified by silica gel chromatography (5%-30% EtOAc: hexane) to provide the target compound (550g) in a light yellow oil. The light yellow oil is ground with hexane (500mL) in an acetone-dry ice bath, and the gained solid is filtered, washed with cold hexane (400mL), and finally dried under vacuum (525g, 79% yield, with 99:1S:R enantiomeric ratio). 1H NMR(CDCl3):7.30(d,J=2.2Hz,1H),6.83(d,J=2.1Hz,1H),6.12(d,J=7.8Hz,1H),4.30(dtd,J =8.8, 4.0, 2.0Hz, 1H), 1.51-1.26 (m, 5H), 1.17 (d, J = 6.8Hz, 3H), 0.94 (dt, J = 8.4, 7.2Hz, 6H). 13C NMR (CDCl3): 160.03, 141.77, 135.12, 117.05, 112.80, 46.50, 46.12, 22.31, 22.20, 17.77, 11.89, 11.72. ESI[M+H]+:243.86.

[0042] Example B:

[0043]

[0044] 1b forms: into the 500mL 4-necked round-bottom flask equipped with overhead stirrer, condenser, nitrogen bubbler, addition funnel and temperature probe, 2-chlorofuran-3-formic acid (33.79g, 231mmol) and toluene (50mL) are packed.Mixture is heated at 40 ℃, and thionyl chloride (50.2ml, 692mmol) is added by addition funnel so that temperature is maintained at about 40 ℃-50 ℃.Mixture is continued to stir at 40 ℃ until reaction is completed as monitored by H-NMR.Reaction mixture is concentrated to provide brown oil (65.2g, 98% productive rate, 57wt% in toluene).

[0045] Preparation of S1 (labeled as " 3 " in the above figure): (S) -3- ethylpentane -2- amine hydrochloride (2, 42.7 g, 225 mmol) and ethyl acetate (EtOAc, 451 mL) are loaded into a 1L 4-neck round-bottom flask equipped with an overhead stirrer, condenser, nitrogen bubbler and temperature probe. The mixture is cooled to 10 ° C. Triethylamine (676 mmol, 94 mL) is added at a rate maintaining the temperature below 20 ° C. After stirring for 30 min, a solution of 2- chlorofuran -3- carbonyl chloride (1b, 65.2 g, 225 mmol, 57 wt % in toluene) is added by syringe while maintaining the temperature at < 20 ° C. After the addition is complete, the resulting mixture is stirred for 2 h at ambient temperature. Water (100 mL) is added. The mixture is distributed between hexane (500 mL) and 1N HCl (200 mL). The organic portion was separated, washed with brine, dried and concentrated to afford a brown oil (57.05 g). The crude product was purified by silica gel chromatography (eluting with 10%-30% EtOAc / hexanes) to afford a light yellow oil which solidified upon standing (44.9 g, 82% yield, with an enantiomeric ratio of 99:1 S:R). 1 H NMR (400 MHz, chloroform-d) δ 7.31 (d, J = 2.1 Hz, 1H), 6.83 (d, J = 2.1 Hz, 1H), 6.12 (d, J = 8.6 Hz, 1H), 4.30 (dqd, J = 13.4, 6.8, 4.0 Hz, 1H), 1.49-1.25 (m, 5H), 1.17 (d, J = 6.8 Hz, 3H), 0.95 (dt, J = 8.5, 7.2 Hz, 6H). ESI [M+H] + :244.2.

[0046] R1 was prepared similarly from 2-chlorofuran-3-carboxylic acid and the corresponding (R)-3-ethylpentane-2-amine hydrochloride in a 99:1 R:S enantiomeric ratio.

[0047] Example 1

[0048] S1 (99:1 S:R enantiomeric ratio), produced from Example B herein, was compared to the following molecules.

[0049] R1

[0050]

[0051] (R)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide; and

[0052] B1

[0053]

[0054] 2-Chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide (CAS Reg. No. 1876009-19-6)

[0055] B1 is a racemic mixture of S1 and R1, and S1 and R1 are enantiomers having relative purities as described herein.

[0056] Part 1

[0057] The following root knot nematode (RKN) test was performed to compare the activities of S1, R1 and B1.

[0058] Test Procedure

[0059] Experiments were conducted to evaluate the comparative bioactivity of S1, R1, and B1 against the root-knot nematode (RKN), Meloidogyne incognita. Each of S1, R1, and B1 was tested at six application rates: 125, 62.5, 31.25, 15.6, 7.8, 3.9, and 2 ppm. Cucumber seeds (Cucumis sativus) were planted in sandy loam in 3-inch pots. After 6 days of germination, the seedlings were treated with the test compound dissolved in 5% acetone in water. The treated plants were inoculated with 4,000 second-instar larvae (J2) of the southern root-knot nematode. Each experimental unit was replicated three times. The inoculated plants were kept in a greenhouse for 14 days (approximately 27° C.) and the amount of root damage (galls) was assessed on a scale of 0-10, termed the Gall Index (GI); where 0 = no galls (100% control) and 10 = maximum galls (no control). The GI was converted to % control using the formula (10-GI) x 10; where GI = Gall Index. The effective concentration (EC) values for % control of nematodes for S1, R1, and B1 were calculated by probit analysis.

[0060] Test results and conclusions.

[0061]

[0062] These data show that S1 is significantly and unexpectedly much better than R1 and B1 considering the magnitude of the delta percentage (δ%).

[0063] Part 2

[0064] The following soybean nematode (SCN) test was performed to compare the activities of S1, R1 and B1.

[0065] Test Procedure

[0066] In vitro experiments were conducted to compare the activity of S1, R1, and B1 against soybean Heterodera glycines (SCN): second instar larvae (J2) of soybean cyst nematode. Each of S1, R1, and B1 was tested at six application rates: 62.5, 15.6, 4, 1, 0.25, and 0 ppm (untreated control, UTC), with three replicates per treatment. An equal volume of nematode suspension was added to an equal volume of 0.5% DMSO (dimethyl sulfoxide) compound dissolved in water. The nematodes plus compound were incubated on an oscillator at 95 revolutions per minute (RPM) at room temperature (approximately 25°C). 0.5 milliliters (mL) of aliquots of the nematode suspension were evaluated under a microscope for mortality after incubation for 48 hours. SCN J2 were counted, and the number of dead and active nematodes was used to calculate % SCN mortality for the generation of lethal concentration (LC) values by probabilistic analysis.

[0067] Test results and conclusions.

[0068]

[0069] These data show that S1 is significantly and unexpectedly much better than R1 and B1 considering the magnitude of the delta percentage (δ%).

[0070] Part 3

[0071] The following root rot nematode (RLN) test was performed to compare the activities of S1, R1 and B1.

[0072] Test Procedure

[0073] An in vitro experiment was conducted to compare the activity of S1, R1, and B1 against the root rot nematode (RLN), Pratylechus penetrans. Each of S1, R1, and B1 was tested at six application rates: 62.5, 15.6, 4, 1, 0.25, and 0 ppm (UTC), with three replicates for each treatment. In a 25 mL vial, an equal volume of nematode suspension was added to an equal volume of each of S1, R1, and B1 dissolved in 0.5% DMSO (dimethyl sulfoxide) in water. The treated nematode suspension was incubated on a shaker (95 RPM) at room temperature (approximately 25° C.). Aliquots of 1 mL of the nematode suspension were evaluated for mortality after 48 hours under a microscope. RLN were counted, and the number of dead and active nematodes was used to calculate the % mortality, thereby generating a lethal concentration (LC) value.

[0074] Test results and conclusions

[0075]

[0076] These data show that S1 is significantly and unexpectedly much better than R1 and B1 considering the magnitude of the delta percentage (δ%).

[0077] Overall, the experimental data were unexpected and surprising, especially considering that, comparing S1 to R1, the δ% averaged >2202, and comparing S1 to B1, the δ% averaged 564. The magnitude of this variation prompted additional investigation.

[0078] Example 2

[0079] Compare the following molecules.

[0080] S1

[0081]

[0082] C1

[0083]

[0084] C2

[0085]

[0086] C3

[0087]

[0088] C4

[0089]

[0090] C5

[0091]

[0092] Test Procedure

[0093] Experiments were conducted to evaluate the comparative bioactivity of S1, C1, C2, C3, C4, and C5 against root-knot nematodes (Meloidogyne incognita). Each compound was tested at 600 grams of active ingredient per hectare (g ai / ha) and replicated three times. Cucumber seeds (Cucumis sativus) were planted in sandy loam in 3-inch pots. Six (6) days after planting, the seedlings were treated with a drench of the test compound dissolved in 5% acetone in water. Plants were inoculated with 4,000 second-instar larvae (J2) of the southern root-knot nematode. The inoculated plants were kept in a greenhouse for 14 days (temperature 27°C) and the amount of root damage (galls) was then assessed on a scale of 0-10, referred to as the Gall Index (GI); wherein 0 = no galls (100% nematode control) and 10 = maximum galls (no nematode control). The GI was converted to % nematode control using the formula ((10-GI) x 10); wherein GI = Gall Index. Data were analyzed by analysis of variance using JMP (John's Macintosh Project) statistical software, and means were separated using Tukey's HSD (α=0.05).

[0094] Test results and conclusions

[0095] molecular Statistics Group Average Percentage Control S1 A 84 C1 BC 54 C2 BC 54 C3 B 67 C4 D 25 C5 C 50 comparison E 0

[0096] The results showed that only S1 had acceptable and statistically superior levels of control to the other molecules tested.At the projected field application rate of 600 g ai / ha, the threshold root-knot nematode control was set to >= 75%.

[0097] Example 3

[0098] The molecules of Example 2 were compared in a residue test.

[0099] Test Procedure

[0100] Residue testing was performed to compare the residual control or persistence of S1, R1, C1, C2, C3, C4, and C5 in soil. Each compound was applied to bare sandy loam (without plants or nematodes) at 1250g ai / ha in a 3-inch pot. The treated soil was kept for four weeks in a greenhouse (temperature 27°C) under regular irrigation. At the end of the four weeks, six-day-old cucumber (Cucumis sativus) seedlings were transplanted into the treated soil and inoculated with 4,000 second-instar larvae of southern root-knot nematodes. Each treatment was repeated four times. The inoculated plants were kept in a greenhouse for 14 days (temperature 27°C), and the amount of root damage (galls) was then assessed on a scale of 0-10, referred to as the Gall Index (GI); wherein 0 = no galls (100% nematode control) and 10 = maximum galls (no nematode control). GI was converted to % control using the formula ((10-GI) x 10); where GI = gall index. Data were analyzed by ANOVA using JMP (John's Macintosh Project) statistical software, and means were separated using Tukey's HSD (α = 0.05).

[0101] Test results and conclusions

[0102] molecular Statistics Group Average percentage control S1 A 77.5 R1 C 7.5 C1 B 27.5 C2 B 25.0 C3 B 22.5 C4 C 2.5 C5 B 22.5 comparison C 2.5

[0103] The results show that only S1 has surprising and unexpected residual levels when compared to the other molecules.In conclusion, based on the above, S1 has surprising and unexpected properties that are statistically far superior to the other molecules.

[0104] Compositions comprising S1 can be prepared by techniques known in the art. A currently preferred example is a nematicide composition comprising S1 as the sole nematicidal active substance. However, other active substances may also be present, such as, for example, R1. If R1 and S1 are present in the composition, it is preferred that the composition is enantiomerically enriched in S1; in other words, the enantiomeric ratio of S1 to R1 is greater than 50:50 but less than 100:0 (see "enantiomerically enriched" IUPAC. Compendium of Chemical Terminology, 2nd ed. (the "Gold Book"). Compiled by AD McNaught and A. Wilkinson. Blackwell Scientific Publications, Oxford (1997). Online version created by SJ Chalk (2019-). ISBN 0-9678550-9-8. https: / / doi.org / 10.1351 / goldbook). Generally, depending on the production method, an enantiomeric ratio of S1 to R1 of greater than 90:10 is preferred, an enantiomeric ratio of S1 to R1 of greater than 95:5 is more preferred, and an enantiomeric ratio of S1 to R1 of greater than 97:3 is even more preferred. However, in some cases where the composition is to be used in a specific environment, an enantiomeric ratio of S1 to R1 of 100:0 is preferred.

[0105] Additional details are provided below.

[0106] 1d. A molecule, (S)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide (hereinafter, "S1")

[0107]

[0108] 2d. A composition comprising:

[0109] (a) a molecule according to detail 1d; but not

[0110] (b) (R)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide (hereinafter, "R1")

[0111]

[0112] In other words, the enantiomeric ratio of S1 to R1 is 100:0.

[0113] 3d. A composition comprising:

[0114] (a) a molecule according to Detail 1d (hereinafter, "S1"); and

[0115] (b) (R)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide (hereinafter, "R1");

[0116] The enantiomeric ratio of S1 to R1 is greater than 50:50 but less than 100:0.

[0117] 4d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 51:49 but less than 100:0.

[0118] 5d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 52:48 but less than 100:0.

[0119] 6d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 53:47 but less than 100:0.

[0120] 7d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 54:46 but less than 100:0.

[0121] 8d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 55:45 but less than 100:0.

[0122] 9d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 56:44 but less than 100:0.

[0123] 10d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 57:43 but less than 100:0.

[0124] 11d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 58:42 but less than 100:0.

[0125] 12d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 59:41 but less than 100:0.

[0126] 13d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 60:40 but less than 100:0.

[0127] 14d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 61:39 but less than 100:0.

[0128] 15d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 62:38 but less than 100:0.

[0129] 16d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 63:37 but less than 100:0.

[0130] 17d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 64:36 but less than 100:0.

[0131] 18d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 65:35 but less than 100:0.

[0132] 19d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 66:34 but less than 100:0.

[0133] 20d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 67:33 but less than 100:0.

[0134] 21d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 68:32 but less than 100:0.

[0135] 22d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 69:31 but less than 100:0.

[0136] 23d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 70:30 but less than 100:0.

[0137] 24d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 71:29 but less than 100:0.

[0138] 25d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 72:28 but less than 100:0.

[0139] 26d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 73:27 but less than 100:0.

[0140] 27d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 74:26 but less than 100:0.

[0141] 28d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 75:25 but less than 100:0.

[0142] 29d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 76:24 but less than 100:0.

[0143] 30d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 77:23 but less than 100:0.

[0144] 31d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 78:22 but less than 100:0.

[0145] 32d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 79:21 but less than 100:0.

[0146] 33d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 80:20 but less than 100:0.

[0147] 34d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 81:19 but less than 100:0.

[0148] 35d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 82:18 but less than 100:0.

[0149] 36d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 83:17 but less than 100:0.

[0150] 37d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 84:16 but less than 100:0.

[0151] 38d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 85:15 but less than 100:0.

[0152] 39d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 86:14 but less than 100:0.

[0153] 40d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 87:13 but less than 100:0.

[0154] 41d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 88:12 but less than 100:0.

[0155] 42d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 89:11 but less than 100:0.

[0156] 43d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 90:10 but less than 100:0.

[0157] 44d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 91:9 but less than 100:0.

[0158] 45d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 92:8 but less than 100:0.

[0159] 46d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 93:7 but less than 100:0.

[0160] 47d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 94:6 but less than 100:0.

[0161] 48d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 95:5 but less than 100:00.

[0162] 49d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 96:4 but less than 100:0.

[0163] 50d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 97:3 but less than 100:0.

[0164] 51d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 98:2 but less than 100:0.

[0165] 52d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 99:1 but less than 100:0.

[0166] 53d. A method of controlling pests in a locus by administering a pesticidally effective amount of:

[0167] (a) a molecule according to detail 1d; or

[0168] (b) A composition according to one of details 2d, 3d, 4d, 5d, 6d, 7d, 8d, 9d, 10d, 11d, 12d, 13d, 14d, 15d, 16d, 17d, 18d, 19d, 20d, 21d, 22d, 23d, 24d, 25d, 26d, 27d, 28d, 29d, 30d, 31d, 32d, 33d, 34d, 35d, 36d, 37d, 38d, 39d, 40d, 41d, 42d, 43d, 44d, 45d, 46d, 47d, 48d, 49d, 50d, 51d, or 52d.

Claims

1. A molecule, (S)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide 2. A composition comprising: (a) a molecule according to claim 1; but not (b) (R)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide (hereinafter, "R1") 3. A composition comprising: (a) the molecule according to claim 1 (hereinafter, "S1"); and (b) (R)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide (hereinafter, "R1"); in, The enantiomeric ratio of S1 to R1 is greater than 50:50 but less than 100:

0.

4. The composition according to claim 3, wherein The enantiomeric ratio of S1 to R1 is greater than 90:10 but less than 100:

0.

5. The composition according to claim 3, wherein The enantiomeric ratio of S1 to R1 is greater than 91:9 but less than 100:

0.

6. The composition according to claim 3, wherein The enantiomeric ratio of S1 to R1 is greater than 92:8 but less than 100:

0.

7. The composition according to claim 3, wherein The enantiomeric ratio of S1 to R1 is greater than 93:7 but less than 100:

0.

8. The composition according to claim 3, wherein The enantiomeric ratio of S1 to R1 is greater than 94:6 but less than 100:

0.

9. The composition according to claim 3, wherein The enantiomeric ratio of S1 to R1 is greater than 95:5 but less than 100:

0.

10. The composition according to claim 3, wherein The enantiomeric ratio of S1 to R1 is greater than 96:4 but less than 100:

0.

11. The composition according to claim 3, wherein The enantiomeric ratio of S1 to R1 is greater than 97:3 but less than 100:

0.

12. The composition according to claim 3, wherein The enantiomeric ratio of S1 to R1 is greater than 98:2 but less than 100:

0.

13. The composition according to claim 3, wherein The enantiomeric ratio of S1 to R1 is greater than 99:1 but less than 100:

0.

14. A method of controlling pests in a locus by using a pesticidally effective amount of a molecule according to claim 1.

15. A method of controlling pests in a locus by using a pesticidally effective amount of a molecule according to claim 2.

16. A method of controlling pests in a locus by using a pesticidally effective amount of a molecule according to claim 13.

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