Molecules with insecticidal activity and related methods

Abstract

The present disclosure relates to the field of molecules having insecticidal activity against pests of the phylum Nematoda, and methods of using such molecules against such pests. The insecticidal molecules may be used in insecticidal compositions, such as nematicidal compositions.

Description

[Technical Field]

[0001] The present disclosure relates to the field of molecules having insecticidal activity against pests of the phylum Nematoda, and methods of using such molecules against such pests. The insecticidal molecules may be used in insecticidal compositions, such as nematicidal compositions. [Background technology]

[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 fever, yellow fever, plague, filariasis, louse-borne typhus, trypanosomiasis, leishmaniasis, and other vector-borne diseases caused more human illness and death than all other causes combined from the 17th to the early 20th centuries" (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 all parasitic and infectious diseases worldwide. Malaria alone causes more than 800,000 deaths annually, 85% of which occur in children under the age of five. Approximately 50 million to 100 million cases of dengue fever occur annually. Another 250,000 to 500,000 cases of dengue hemorrhagic fever occur annually (Matthews, Integrated Vector Management: Controlling Vectors of Malaria and Other Insect Vector Borne Diseases, Ch. 1, p. 1, 2011). Vector control plays a major role in preventing and controlling infectious diseases. However, insecticide resistance (including resistance to multiple insecticides) has emerged in all insect species that are major vectors of human disease (Rivero et al.). In recent years, more than 550 arthropod species have developed resistance to at least one insecticide (Whalon et al. Analysis of Global Pesticide Resistance in Arthropods, Global Pesticide Resistance in Arthropods, Ch. 1, p. 5-33, 2008).Furthermore, examples of insect resistance continue to far exceed those of herbicide and fungicide resistance (Sparks et al., IRAC: Mode of action classification and insecticide resistance management, Pesticide Biochemistry and Physiology (2014) available online 4 December 2014).

[0003] Each year, insects, plant pathogens, and weeds destroy over 40% of all food production. This loss occurs despite the application of pesticides and the use of various non-chemical controls, such as crop rotation and biological controls. If even a portion of this food could be saved, it could be used to feed the more than 3 billion undernourished people worldwide (Pimental, D., Pest Control in World Agriculture, Agricultural Sciences - Vol. II, 2009).

[0004] Plant-parasitic nematodes are among the most widespread and often the most insidious and damaging pests, causing an estimated annual yield loss of over $100 billion worldwide (Abad et al., Root-knot nematode 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). Estimates of losses due to nematodes range from approximately 9% (in developed countries) to approximately 15% (in developing countries). However, in the United States, a study of various crops in 35 states showed that losses due to nematodes could be as high as 25% (Nicol, et al., Current Nematode Threats to World Agriculture, Genomic and Molecular Genetics of Plant-Nematode Interactions, pp. 21–43, 2011).

[0005] Approximately 2,000 plant species worldwide are susceptible to infection by root-knot nematodes, which cause 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), Meloidogyne spp., are one of the three most economically damaging genera of plant-parasitic nematodes in agriculture. Root-knot nematodes are distributed worldwide. This genus contains more than 90 species. Four Meloidogyne species (M. javanica, M. arenaria, M. incognita, and M. hapla) are major pests worldwide, with seven other species of local importance. Once 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 devastating pest of soybean crop yield in the United States, targeting the roots of soybeans and other legumes with estimated annual yield losses exceeding $1 billion (Wrather et al.: Soybean disease loss estimates for the top ten soybean-producing countries in 1998. Canadian J. Plant Pathol. 23:115-121). Symptoms caused by SCN may not be easily recognized by farmers, and in some cases, there are no symptoms to warn before 30% of the yield is lost.

[0007] Above-ground symptoms of root-lesion nematodes in plants with severe root infections can include chlorosis, stunted growth, and poor vigor. Infected roots are stunted and may have small brownish-black lesions. Root-lesion nematodes are migratory endoparasites.

[0008] Thus, for many reasons, including those mentioned above, the development of new pesticides continues to be costly (estimated at approximately US$286 million per pesticide in 2014), time-consuming (on average, approximately 11.3 years per pesticide), and difficult (Phillips McDougall, "The Cost of New Agrochemical Product Discovery, Development, and Registration in 1995, 2000, 2005-2008, and 2010-2014; R&D expenditure in 2014 and expectations for 2019, 2016").

[0009] Definitions for this disclosure The examples provided herein are not exhaustive and should not be construed as limiting. It should be understood that a substituent must comply with the chemical bonding rules and steric compatibility constraints of the particular molecule to which it is attached. These definitions are used solely for the purposes of this disclosure.

[0010] The term "area" means a habitat, breeding ground, plant, seed, soil, material, or environment in which a pest is growing, can grow, or can move about. For example, an area can be: where crops, trees, fruits, grains, forage seeds, vines, lawns, and / or ornamental plants are growing; where livestock live; interior or exterior surfaces of a building (e.g., where grain is stored); construction materials used in a building (e.g., impregnated wood); and the soil around a building.

[0011] The term "pest" means an organism that is harmful to humans or human concerns (crops, food, livestock, etc.), wherein said organism is of the phylum Nematoda, such as Aphelenchoides spp., Belonolaimus spp., Criconemella spp., Ditylenchus spp., Globodera spp., Heterodera spp., Hirschmanniella spp., Hoplolaimus spp., Meloidogyne spp., Pratylenchus spp. and Radopholus spp. 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.

[0012] The phrase "pesticidally effective amount" refers to the amount of pesticide required to achieve an observable effect on pests, such as necrosis, death, suppression, prevention, elimination, destruction, or otherwise reducing the occurrence and / or activity of pests in an area. This effect can occur when pest populations are eliminated from an area, when pests are incapacitated in or around an area, and / or when pests are eradicated in or around an area. Of course, a combination of these effects can occur. Generally, it is desirable to reduce pest populations, activity, or both by more than 50 percent, preferably by more than 90 percent, and most preferably by more than 99 percent. Generally, an amount effective as a pesticide for agricultural purposes is from about 0.0001 grams / hectare to about 5000 grams / hectare, preferably from about 0.0001 grams / hectare to about 500 grams / hectare, and even more preferably from about 0.0001 grams / hectare to about 50 grams / hectare.

[0013] All references, including publications, patent applications, and patents, cited in this specification are herein incorporated by reference to the same extent as if each individual reference was individually and specifically indicated to be incorporated by reference and was set forth in its entirety.

[0014] In the context of this disclosure (particularly in the context of the claims below), use of the terms "a," "an," "the," and "at least one," and similar referents, should be construed to encompass both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The use of the term "at least one" followed by a list of one or more items (e.g., "at least one of A and B") should be construed to mean one item (A or B) selected from the listed items or any combination of two or more of the listed items (A and B), unless otherwise indicated herein or clearly contradicted by context. The terms "comprise," "have," "include," and "containing" should be construed as open-ended terms (i.e., meaning "including, but not limited to"), unless otherwise indicated. The recitation of ranges of values ​​herein is merely intended to serve as a shorthand method of referring individually to each of the separate values ​​falling within the range, and each separate value is incorporated herein as if it were individually set forth herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or clearly contradicted by context. Any examples or use of exemplary language (e.g., "etc.") provided herein are intended merely to better clarify the disclosure and do not limit the scope of the disclosure unless specifically claimed. No language herein should be construed as indicating any non-claimed element as essential to the practice of any embodiment herein. In this disclosure, the terms "molecule" and "compound" can be used interchangeably. DETAILED DESCRIPTION OF THE INVENTION

[0015] This document discloses the following molecules: [ka]

[0016] The chemical name of this molecule is (S)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide (also known as "S1" for the purposes of this disclosure).

[0017] This molecule can be prepared using a variety of methods known in the art, such as those described in WO 2017116646, U.S. Patent Application Publication No. 20200397000, WO 2007039615, and U.S. Patent No. 8,148,538. Additionally, a variety of separation techniques are available for isolating a specific enantiomer, such as S1, from a racemic mixture, such as B. For example, chiral chromatography can be used to isolate enantiomers, and this method can be used to determine enantiomeric purity (Journal of Pharmaceutical and Biomedical Analysis, 2013 and "Principles and Practice of Modern Chromatographic Methods (Second Edition), 2022). [Example]

[0018] Preparation of (S)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide (S1) (S)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide (S1) can be prepared by direct condensation of (S)-3-ethylpentan-2-amine hydrochloride (2) with 2-chlorofuran-3-carbonic acid (1) or via 2-chlorofuran-3-carbonyl chloride (1b), as illustrated in Scheme 1. Scheme 1. Preparation of (S)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide. [ka]

[0019] The synthesis of (S)-3-ethylpentan-2-amine hydrochloride (2) from 2-ethylbutanal (3) and (R)-2-methylpropane-2-sulfinamide in three steps is outlined in Scheme 2. Scheme 2. Preparation of (S)-3-ethylpentan-2-amine (HCl salt) [ka]

[0020] experiment (R,E)-N-(2-ethylbutylidene)-2-methylpropane-2-sulfinamide (5) [ka] A 3-liter, three-necked round-bottom flask equipped with an overhead stirrer, temperature probe, and nitrogen bubbler was charged with (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 (approximately 2 days), as monitored by HPLC. The resulting mixture was filtered through a plug of Celite (approximately 300 g), and the wet cake was rinsed with dichloromethane (2 × 750 mL). The filtrate was concentrated by rotary evaporation under reduced pressure. The residue was dried under high vacuum overnight to give the desired product 5 (104.70 g, 489 mmol, 99% yield) as a clear, pale yellow oil. 1 H-NMR(400MHz,CDCl3)δ 7.90(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). 13C-NMR(101MHz,CDCl3)δ 173.46,56.65,48.94,24.96,24.72,22.59,11.82,11.73.

[0021] (R)-N-((S)-3-ethylpentan-2-yl)-2-methylpropane-2-sulfinamide (6) [ka] A 2-L, three-necked round-bottom flask equipped with an overhead stirrer, addition funnel, temperature probe, and nitrogen bubbler was charged with (R,E)-N-(2-ethylbutylidene)-2-methylpropane-2-sulfinamide (5, 21.5 g, 100 mmol) and dichloromethane (700 mL). The mixture was cooled to below -50 °C. A 3 M solution of methylmagnesium bromide (90 mL, 270 mmol) in 2-MeTHF was added to the addition funnel at a rate that maintained the reaction temperature below -45 °C (this took approximately 30 min). After the addition was complete, the reaction mixture was stirred at -50 °C for 3 h and then allowed to warm to ambient temperature (18-22 °C) overnight. The reaction mixture was cooled to 0 °C, and a solution of saturated ammonium chloride (1 L) was slowly added. The resulting mixture was allowed to separate. The aqueous phase was extracted with ethyl acetate (2 × 750 mL). The combined organics were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure by rotary evaporation. The residual oil was dried in vacuo overnight to give the desired title product 6 (39.37 g, 179 mmol, 90% yield) as a pale yellow oil. 1 H NMR(300MHz,CDCl3)δ 3.52-3.35(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)δ 55.89,53.98,47.47,22.80,22.09,21.89,20.16,11.99,11.98.

[0022] (S)-3-Ethylpentan-2-amine hydrochloride (2) [ka] A 1-liter, four-necked round-bottom flask equipped with an overhead stirrer, temperature probe, addition funnel, and nitrogen bubbler was charged with (R)-N-((S)-3-ethylpentan-2-yl)-2-methylpropane-2-sulfinamide (7, 35.9 g, 164 mmol) and methanol (205 mL). The mixture was cooled to 0 °C, and a solution of 4.0 M HCl in dioxane (205 mL, 818 mmol) was added to the addition funnel at a rate that maintained the reaction temperature below 10 °C. After the addition was complete, the reaction mixture was warmed to ambient temperature (20 °C) and continued stirring at ambient temperature until the reaction was complete (2 h), as monitored by TLC. The reaction mixture was concentrated under reduced pressure to give a light brown oil that gradually solidified. The residue was triturated with heptane (55 mL) for 3 h. The precipitated solid was collected by filtration, washed with cold heptane (55 mL), and dried in vacuo to give the desired product as a white solid (21.9 g, 144 mmol, 88% yield). 1 H NMR(400MHz,CDCl3)δ 8.31(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)δ 50.11,44.58,21.99,21.31,15.67,11.48,11.40.

[0023] (S)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide (S1) Example A: [ka] In a 22 L four-neck round-bottom flask equipped with an overhead stirrer, temperature probe, and N2 inlet, 2-chlorofuran-3-carboxylic acid (1) (400 g, 2.73 mol) and (S)-3-ethylpentan-2-amine hydrochloride (2) (455.4 g, 3.00 mol) were dissolved in EtOAc (5.4 L). The solution was cooled to 5 °C. To this solution, triethylamine (1.90 L, 13.64 mol) was added via addition funnel over 20 minutes. The reaction mixture was stirred at 5 °C for 10 minutes. Propylphosphonic anhydride solution (50 wt % in ethyl acetate) (2.43 L, 4.09 mol) was added dropwise over 1 hour via addition funnel. The reaction mixture was stirred at room temperature for 2 hours. Completion of the reaction was confirmed by HPLC. The reaction mixture was diluted with water (2 L) and transferred to a separatory funnel. The layers were separated. The aqueous layer was extracted with EtOAc (2 L). The organic layers were combined and washed with a saturated aqueous solution of NaHCO3 (3 L × 1), 2 M HCl (2 L × 1), and then brine (2 L × 1). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude compound was purified by silica gel chromatography using 5-30% EtOAc:hexanes to give the desired compound as a pale yellow oil (550 g). The pale yellow oil was triturated with hexanes (500 mL) in an acetone-dry ice bath, and the resulting solid was filtered, washed with cold hexanes (400 mL), and finally dried under vacuum (525 g, 79% yield with a 99:1 S:R enantiomer 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.

[0024] Example B: [ka] Formation of 1b: A 500 mL four-neck round-bottom flask equipped with an overhead stirrer, condenser, nitrogen bubbler, addition funnel, and temperature probe was charged with 2-chlorofuran-3-carboxylic acid (33.79 g, 231 mmol) and toluene (50 mL). The mixture was heated to 40 °C, and thionyl chloride (50.2 mL, 692 mmol) was added through the addition funnel at a rate that maintained the temperature near 40-50 °C. The mixture was continued to stir at 40 °C until the reaction was complete, as monitored by H-NMR. The reaction mixture was concentrated to give 65.2 g of a brown oil (98% yield, 57% by weight in toluene).

[0025] Preparation of S1 (labeled "3" in the above schematic): A 1 L, four-necked, round-bottom flask equipped with an overhead stirrer, condenser, nitrogen bubbler, and temperature probe was charged with (S)-3-ethylpentan-2-amine hydrochloride (2, 42.7 g, 225 mmol) and ethyl acetate (EtOAc, 451 mL). The mixture was cooled to 10°C. Triethylamine (676 mmol, 94 mL) was added at a rate to maintain the temperature below 20°C. After stirring for 30 minutes, a solution of 2-chlorofuran-3-carbonyl chloride (1b, 65.2 g, 225 mmol, 57 wt% in toluene) was added via syringe while maintaining the temperature below 20°C. After the addition was complete, the resulting mixture was stirred at ambient temperature for 2 hours. Water (100 mL) was added. The mixture was partitioned between hexane (500 mL) and 1 N HCl (200 mL). The organic portion was separated, washed with brine, dried, and concentrated to give a brown oil (57.05 g). The crude material was purified by silica gel chromatography eluting with 10-30% EtOAc / hexanes to give a pale yellow oil that solidified upon standing after concentration (44.9 g, 82% yield with a 99:1 S:R enantiomer ratio). 1H NMR(400MHz,chloroform-d)δ 7.31(d,J=2.1Hz,1H),6.83(d,J=2.1Hz,1H),6.12(d,J=8.6Hz,1H),4.30(dqd,J=13.4,6.8, 4.0Hz,1H),1.49-1.25(m,5H),1.17(d,J=6.8Hz,3H),0.95(dt,J=8.5,7.2Hz,6H).ESI[M+H] + :244.2. R1 was similarly prepared from 2-chlorofuran-3-carboxylic acid and the corresponding (R)-3-ethylpentan-2-amine hydrochloride in a 99:1 R:S enantiomeric ratio.

[0026] Example 1 S1 (99:1 S:R enantiomer ratio) from Example B herein was compared with the following molecules: [ka] (R)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide; and [ka] 2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide (CAS Registry Number 1876009-19-6)

[0027] B1 is a racemic mixture of S1 and R1, where S1 and R1 are enantiomers with relative purities as described herein.

[0028] Part 1 The following root-knot nematode (RKN) test was performed to compare the activities of S1, R1, and B1.

[0029] Test Procedure We conducted an experiment to evaluate the relative bioactivity of S1, R1, and B1 against the root-knot nematode (RKN), Meloidogyne incognita. S1, R1, and B1 were each tested at six concentrations: 125, 62.5, 31.25, 15.6, 7.8, 3.9, and 2 ppm. Cucumber seeds (Cucumis sativus) were planted in 3-inch pots in sandy loam soil. Six days after germination, the seedlings were treated with the test compound dissolved in 5% acetone in water. Treated plants were inoculated with 4,000 second-stage larvae (J2s) of M. incognita. Each experimental unit was replicated three times. Inoculated plants were kept in a greenhouse (approximately 27 °C) for 14 days, after which the amount of root damage (galls), called the Galling Index (GI), was assessed on a scale of 0 to 10, where 0 = no galls (100% control) and 10 = maximum galls (no control). GI was converted to % control using the formula (10 - GI) x 10, where GI = Galling Index. Effective concentration (EC) values ​​based on % control of nematodes by S1, R1, and B1 were calculated by probit analysis.

[0030] Test results and conclusions.

[0031] [Table 1]

[0032] These data show that S1 is clearly and unexpectedly far superior to R1 and B1 when considering the magnitude of the delta percent (Delta%).

[0033] Part 2 The following soybean cyst nematode (SCN) test was conducted to compare the activities of S1, R1, and B1.

[0034] Test Procedure We conducted an in vitro experiment to compare the activity of S1, R1, and B1 against second-stage (J2) larvae of the soybean cyst nematode (SCN): Heterodera glycines. S1, R1, and B1 were each tested at six concentrations: 62.5, 15.6, 4, 1, 0.25, and 0 ppm (untreated control, UTC), with each treatment replicated three times. An equal volume of nematode suspension was added to an equal volume of compound dissolved in 0.5% DMSO (dimethyl sulfoxide) in water. The nematodes and compound were incubated on a shaker at 95 revolutions per minute (RPM) at room temperature (approximately 25°C). A 0.5 milliliter (mL) aliquot of the nematode suspension was evaluated under a microscope for mortality after 48 hours of incubation. SCN J2s were counted and the number of dead and active nematodes was used to calculate % SCN mortality, which was used to generate lethal concentration (LC) values ​​by probit analysis.

[0035] Test results and conclusions.

[0036] [Table 2]

[0037] These data show that S1 is clearly and unexpectedly far superior to R1 and B1 when considering the magnitude of the delta percent (Delta%).

[0038] Part 3 The following root-lesion nematode (RLN) test was carried out to compare the activities of S1, R1, and B1.

[0039] Test Procedure We conducted an in vitro experiment to compare the activity of S1, R1, and B1 against the root lesion nematode (RLN), Pratylechus penetrans. S1, R1, and B1 were each tested at six concentrations: 62.5, 15.6, 4, 1, 0.25, and 0 ppm (UTC), with each treatment replicated three times. 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 in a 25 mL vial. The treated nematode suspension was incubated on a shaker (95 RPM) at room temperature (approximately 25°C). A 1 mL aliquot of the nematode suspension was evaluated under a microscope for mortality after 48 hours. RLNs were counted and the numbers of dead and active nematodes were used to calculate % mortality, from which lethal concentration (LC) values ​​were obtained.

[0040] Test results and conclusions

[0041] [Table 3]

[0042] These data show that S1 is clearly and unexpectedly far superior to R1 and B1 when considering the magnitude of the delta percent (Delta%).

[0043] In summary, the experimental data are unexpected and surprising, especially considering that comparing S1 with R1, the average Delta % was over 2202, and comparing S1 with B1, the average Delta % was 564. The magnitude of these changes prompted further investigation.

[0044] Example 2 The following molecules were compared: [ka] [ka]

[0045] Test Procedure We conducted an experiment to evaluate the relative bioactivity of compounds S1, C1, C2, C3, C4, and C5 against the root-knot nematode, Meloidogyne incognita. Each compound was tested at 600 grams of active ingredient per hectare (g ai / ha) with three replicates. Cucumber seeds (Cucumis sativus) were planted in 3-inch pots in sandy loam soil. Six days after planting, seedlings were treated by drench application with the test compound dissolved in 5% acetone in water. The plants were inoculated with 4,000 second-stage larvae (J2s) of M. incognita. Inoculated plants were kept in a greenhouse for 14 days (temperature 27 °C), after which the amount of root damage (galls), called the Galling Index (GI), was assessed on a scale of 0 to 10, where 0 = no galls (100% nematode control) and 10 = maximum galls (no nematode control). GI was converted to % nematode control using the formula ((10 - GI) x 10), where GI = Galling 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).

[0046] Test results and conclusions

[0047] [Table 4]

[0048] The results show that only S1 has an acceptable and statistically superior level of control than the other molecules tested. At a planned field rate of 600 g ai / ha, the threshold root-knot nematode control is set at ≥ 75%.

[0049] Example 3 The molecules of Example 2 were compared in a residual test.

[0050] Test Procedure Residual studies were conducted to compare residual control or persistence of S1, R1, C1, C2, C3, C4, and C5 in soil. Each compound was applied at 1250 g ai / ha to bare sandy loam soil (containing no plants or nematodes) in 3-inch pots. The treated soil was kept in a greenhouse (27°C) under normal irrigation for 4 weeks. After 4 weeks, 6-day-old cucumber (Cucumis sativus) seedlings were transplanted into the treated soil and inoculated with 4000 second-stage larvae of M. incognita. Each treatment was replicated four times. Inoculated plants were kept in a greenhouse for 14 days (temperature 27 °C), after which the amount of root damage (galls), called the Galling Index (GI), was assessed on a scale of 0 to 10, where 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 = Galling 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).

[0051] Test results and conclusions

[0052] [Table 5]

[0053] The results show that only S1 has a surprising and unexpected level of persistence compared to the other molecules. In summary, based on the above, S1 has unexpected and surprising properties that are statistically far superior to the other molecules.

[0054] Compositions containing S1 can be prepared by techniques known in the art. A currently preferred example is a nematicidal composition containing S1 as the only nematicidal active substance. However, other active substances, such as R1, may also be present. When R1 and S1 are present in the composition, it is preferred that the composition be enantiomerically enriched with 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 A.D. McNaught and A. Wilkinson. Blackwell Scientific Publications, Oxford (1997). Online version (2019-) created by S.J. Chalk. ISBN0-9678550-9-8. https: / / doi.org / 10.1351 / goldbook). Generally, depending on the manufacturing process, 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 situations where the composition will be used in a particular environment, an enantiomeric ratio of S1 to R1 of 100:0 is preferred.

[0055] Additional details are provided below.

[0056] 1d. Molecule (S)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide (hereinafter referred to as "S1") [ka]

[0057] 2d. A composition comprising: (a) a molecule as described in Detail 1d, (b) A molecule that is not (R)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide (hereinafter referred to as "R1") [ka] A composition comprising: In other words, the enantiomeric ratio of S1 to R1 is 100:0.

[0058] 3d. A composition comprising: (a) a molecule described in detail in Detail 1d (hereinafter "S1"); and (b) (R)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide (hereinafter referred to as "R1") A composition comprising (wherein the enantiomeric ratio of S1 to R1 is greater than 50:50 but less than 100:0).

[0059] 4d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 51:49 but less than 100:0.

[0060] 5d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 52:48 but less than 100:0.

[0061] 6d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 53:47 but less than 100:0.

[0062] 7d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 54:46 but less than 100:0.

[0063] 8d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 55:45 but less than 100:0.

[0064] 9d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 56:44 but less than 100:0.

[0065] 10d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 57:43 but less than 100:0.

[0066] 11d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 58:42 but less than 100:0.

[0067] 12d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 59:41 but less than 100:0.

[0068] 13d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 60:40 but less than 100:0.

[0069] 14d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 61:39 but less than 100:0.

[0070] 15d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 62:38 but less than 100:0.

[0071] 16d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 63:37 but less than 100:0.

[0072] 17d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 64:36 but less than 100:0.

[0073] 18d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 65:35 but less than 100:0.

[0074] 19d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 66:34 but less than 100:0.

[0075] 20d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 67:33 but less than 100:0.

[0076] 21d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 68:32 but less than 100:0.

[0077] 22d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 69:31 but less than 100:0.

[0078] 23d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 70:30 but less than 100:0.

[0079] 24d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 71:29 but less than 100:0.

[0080] 25d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 72:28 but less than 100:0.

[0081] 26d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 73:27 but less than 100:0.

[0082] 27d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 74:26 but less than 100:0.

[0083] 28d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 75:25 but less than 100:0.

[0084] 29d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 76:24 but less than 100:0.

[0085] 30d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 77:23 but less than 100:0.

[0086] 31d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 78:22 but less than 100:0.

[0087] 32d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 79:21 but less than 100:0.

[0088] 33d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 80:20 but less than 100:0.

[0089] 34d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 81:19 but less than 100:0.

[0090] 35d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 82:18 but less than 100:0.

[0091] 36d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 83:17 but less than 100:0.

[0092] 37d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 84:16 but less than 100:0.

[0093] 38d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 85:15 but less than 100:0.

[0094] 39d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 86:14 but less than 100:0.

[0095] 40d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 87:13 but less than 100:0.

[0096] 41d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 88:12 but less than 100:0.

[0097] 42d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 89:11 but less than 100:0.

[0098] 43d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 90:10 but less than 100:0.

[0099] 44d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 91:9 but less than 100:0.

[0100] 45d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 92:8 but less than 100:0.

[0101] 46d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 93:7 but less than 100:0.

[0102] 47d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 94:6 but less than 100:0.

[0103] 48d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 95:5 but less than 100:0.

[0104] 49d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 96:4 but less than 100:0.

[0105] 50d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 97:3 but less than 100:0.

[0106] 51d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 98:2 but less than 100:0.

[0107] 52d. The composition of detail 3d, wherein the enantiomeric ratio of S1 to R1 is greater than 99:1 but less than 100:0.

[0108] 53d. A method for controlling pests in an area, comprising the step of: (a) a molecule as described in detail in Detail 1d; or (b) By using 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. Molecule (S)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide 【Chemistry 1】 。

2. 1. A composition comprising: (a) A molecule according to claim 1, (b) A composition containing a molecule other than (R)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide (hereinafter "R1"). 【Chemistry 2】 。

3. 1. A composition comprising: (a) a molecule according to claim 1 (hereinafter "S1"); and (b) (R)-2-chloro-N-(3-ethylpentan-2-yl)furan-3-carboxamide (hereinafter referred to as "R1"); A composition comprising A composition in which the enantiomeric ratio of S1 to R1 is greater than 50:50 but less than 100:

0.

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

0.

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

0.

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

0.

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

0.

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

0.

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

0.

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

0.

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

0.

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

0.

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

0.

14. 10. A method of controlling pests in an area by using an insecticidally effective amount of a molecule of claim 1.

15. 10. A method of controlling pests in an area by using an insecticidally effective amount of a molecule of claim 2.

16. 14. A method of controlling pests in an area by using an insecticidally effective amount of a molecule of claim 13.

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