A sulfonic acid functionalized molecule and its preparation method and application

Abstract

The present invention provides a sulfonic acid-functionalized molecule, its preparation method, and application. Through systematic optimization, design, synthesis, and activity screening, the sulfonic acid-functionalized molecule of the present invention constructs a class of functional derivatives containing sulfonic acid groups. These derivatives exhibit good water solubility and significant bactericidal or insecticidal activity, and can be widely used in the integrated prevention and control of agricultural and forestry pests and diseases, effectively improving bioavailability. The present invention can also reduce the use of large amounts of adjuvants and fillers in agricultural pharmaceutical formulations.

Description

Technical Field

[0001] The present invention relates to the technical field of functional drug preparation and application, and in particular to a sulfonic acid functionalized molecule and a preparation method and application thereof. Background Art

[0002] Agrochemicals are important agricultural inputs, playing a crucial role in the comprehensive management of agricultural pests, diseases, weeds, rodents, and other biological disasters. They are widely used in a variety of fields, including plant protection, forestry, aquaculture, animal husbandry, and pest control. Growing environmental awareness and the guidance for China's agricultural development outlined in the 14th Five-Year Plan for Green Agricultural Development are driving the development of comprehensive technologies to reduce the use of agrochemical inputs and increase their efficiency.

[0003] It's reported that the effective utilization rate of existing agrochemicals for my country's three major grain crops is only approximately 41%. The quality and performance of formulations play a crucial role in the efficient use and efficacy of existing agricultural chemicals. With the continuous evolution of factors such as pest species and occurrence patterns, planting structures, and plant protection strategies, the development of new agricultural drug formulations and their efficient utilization have become key research areas in agrochemical application technology. Most existing functional agricultural drugs, such as insecticides, fungicides, herbicides, and plant growth regulators, are lipophilic and generally have poor solubility. To improve their bioavailability, they must be processed into appropriate agricultural dosage forms. This formulation process requires a large number of adjuvants and fillers, such as wetting agents, dispersants, thickeners, emulsifiers, antifreeze agents, and defoaming agents. The addition of these adjuvants inadvertently increases the amount of chemical inputs released into the environment.

[0004] Therefore, in order to reduce the use of a large number of adjuvants and fillers in agricultural drug formulations and improve the effective utilization rate of functional drugs, it is necessary to develop a new water-soluble drug. Summary of the Invention

[0005] In view of this, the present invention proposes a sulfonic acid functionalized molecule and a preparation method and application thereof to solve or at least partially solve the defects in the prior art.

[0006] In a first aspect, the present invention provides a sulfonic acid functionalized molecule, wherein the sulfonic acid functionalized molecule is selected from any one of the following formulas (I), (II), (III), and (IV);

[0007] Wherein, the sulfonic acid functionalized molecular structure shown in formula (I) is:

[0008]

[0009] The sulfonic acid functionalized molecular structure shown in formula (II) is:

[0010]

[0011] The sulfonic acid functionalized molecular structure shown in formula (III) is:

[0012]

[0013] The sulfonic acid functionalized molecular structure shown in formula (IV) is:

[0014]

[0015] Among them, R 1 Any one selected from CH2CN, 4-CF3OPhCH2CH2, 4-CF3PhCH2CH2, 4-FPhCH2CH2, 4-CF3OPhCH2, CH2CO2Me, CH2CONH2, CH(CH3)CO2Me, CH(CH3)CONH2;

[0016] R 2 One or two selected from H, 2-CF3, 4-CF3, 2-F, 2-CF3O;

[0017] R 3 One or two selected from H, F, Cl, Br, CF3, CF3O;

[0018] R 4 Any one selected from CH3, CH2CH3;

[0019] R 5 Any one selected from CH3, CH2CH3, Ph, 4-ClPh, 4-FPh, 4-CF3Ph;

[0020] R 6 Selected from H, COCH3, COCH2CH3, COCF3, CO2CH3, CO2CH2CH3, CO2 t Any of Bu;

[0021] R 7 One or two selected from H, F, Cl, Br, CF3, CH3, CF3O, and CN;

[0022] n is 1 or 2.

[0023] In a second aspect, the present invention further provides a method for preparing the sulfonic acid functionalized molecule, the method for preparing the sulfonic acid functionalized molecule shown in formula (I), comprising the following steps:

[0024] Alkylation reaction of a substituted 4-trifluoromethyl nicotinamide derivative with a substituted sultone to obtain a sulfonic acid functionalized molecule represented by formula (I);

[0025] The preparation method of the sulfonic acid functionalized molecule represented by formula (II) comprises the following steps:

[0026] Alkylation reaction of a substituted benzamide derivative with a substituted sultone yields a sulfonic acid functionalized molecule represented by formula (II);

[0027] The preparation method of the sulfonic acid functionalized molecule represented by formula (III) comprises the following steps:

[0028] Alkylation reaction of a benzimidazole derivative with a substituted sultone yields a sulfonic acid functionalized molecule represented by formula (III);

[0029] The preparation method of the sulfonic acid functionalized molecule represented by formula (IV) comprises the following steps:

[0030] Alkylation reaction of a triazine heterocyclic imine derivative with a substituted sultone to obtain a sulfonic acid functionalized molecule represented by formula (IV);

[0031] The structural formula of the substituted 4-trifluoromethyl nicotinamide derivative is as follows:

[0032]

[0033] The structural formula of the substituted benzamide derivative is shown below:

[0034]

[0035] The structural formula of the benzimidazole derivative is shown below:

[0036]

[0037] The structural formula of the triazine heterocyclic imine derivative is shown below:

[0038]

[0039] In a third aspect, the present invention further provides a composition comprising a solvate or a soluble salt formed by the sulfonic acid functionalized molecule and a pharmaceutically acceptable solvent.

[0040] In a fourth aspect, the present invention further provides an insecticide comprising the sulfonic acid functionalized molecule and a diluent.

[0041] In a fifth aspect, the present invention also provides a use of the sulfonic acid functionalized molecule, the composition or the insecticide in the preparation of drugs for killing biological insects and in the preparation of drugs for preventing and controlling plant diseases.

[0042] Compared with the prior art, the present invention has the following technical effects:

[0043] 1. The sulfonic acid functionalized molecules of the present invention have constructed a class of functional derivatives containing sulfonic acid groups through systematic optimization design, synthesis and activity screening research. These derivatives have good water solubility and obvious bactericidal or insecticidal activity. They can be widely used in the integrated prevention and control of agricultural and forestry pests and diseases, effectively improving bioavailability. DETAILED DESCRIPTION

[0044] To make the purpose, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments.

[0045] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0046] It should be noted that the order of description of the following embodiments is not intended to limit the preferred order of the embodiments. In addition, in the description of this application, the term "including" means "including but not limited to". Various embodiments of the present invention may be in the form of a range; it should be understood that the description in the form of a range is merely for convenience and brevity and should not be understood as a rigid limitation on the scope of the invention; therefore, it should be considered that the range description has specifically disclosed all possible sub-ranges and single numerical values ​​within the range. For example, the range description from 1 to 6 should be considered to have specifically disclosed sub-ranges, such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well as single numbers within the numbered ranges, such as 1, 2, 3, 4, 5 and 6, regardless of the range. In addition, whenever a numerical range is indicated herein, it is meant to include any cited numbers (fractions or integers) within the indicated range.

[0047] The present invention provides a sulfonic acid functionalized molecule selected from any one of the following formulas (I), (II), (III), and (IV);

[0048] Wherein, the sulfonic acid functionalized molecular structure shown in formula (I) is:

[0049]

[0050] The sulfonic acid functionalized molecular structure shown in formula (II) is:

[0051]

[0052] The sulfonic acid functionalized molecular structure shown in formula (III) is:

[0053]

[0054] The sulfonic acid functionalized molecular structure shown in formula (IV) is:

[0055]

[0056] Among them, R 1 Any one selected from CH2CN, 4-CF3OPhCH2CH2 (4-CF3OPh indicates that the 4th position of the benzene ring is CF3O), 4-CF3PhCH2CH2 (4-CF3Ph indicates that the 4th position of the benzene ring is CF3), 4-FPhCH2CH2 (4-FPh indicates that the 4th position of the benzene ring is F), 4-CF3OPhCH2 (4-CF3OPh indicates that the 4th position of the benzene ring is CF3O), CH2CO2Me, CH2CONH2, CH(CH3)CO2Me, and CH(CH3)CONH2;

[0057] R 2 One or two selected from the group consisting of H, 2-CF3 (indicating that the 2nd position of the benzene ring is CF3), 4-CF3 (indicating that the 4th position of the benzene ring is CF3), 2-F (indicating that the 2nd position of the benzene ring is F), and 2-CF3O (indicating that the 2nd position of the benzene ring is CF3O);

[0058] R 3 One or two selected from H, F, Cl, Br, CF3, CF3O;

[0059] R 4 Any one selected from CH3, CH2CH3;

[0060] R 5 Any one selected from CH3, CH2CH3, Ph, 4-ClPh (indicating that the 4th position of the benzene ring is Cl), 4-FPh (indicating that the 4th position of the benzene ring is F), and 4-CF3Ph (indicating that the 4th position of the benzene ring is CF3);

[0061] R 6Selected from H, COCH3, COCH2CH3, COCF3, CO2CH3, CO2CH2CH3, CO2 t Any of Bu;

[0062] R 7 One or two selected from H, F, Cl, Br, CF3, CH3, CF3O, and CN;

[0063] n is 1 or 2.

[0064] Specifically, t Bu represents a tert-butyl group, the group represented by Ph is a phenyl group, Me represents a methyl group, Et represents an ethyl group, and Py represents a pyridyl group.

[0065] Nitrogen heterocyclic compounds are common molecular skeletons widely present in natural products and synthetic drugs. They usually have important physiological and biochemical functions and have very important applications in pharmaceutical chemistry, agricultural and food chemistry, biochemistry and polymer materials. The present application uses nitrogen-containing heterocyclic molecules as a guide to carry out sulfonic acid functionalized molecular design to obtain a class of functional derivatives containing sulfonic acid groups, which have obvious bactericidal or insecticidal activity and can be used as potential functional drugs in the comprehensive prevention and control of agricultural and forestry pests and diseases. The present application has constructed a class of functional derivatives containing sulfonic acid groups through systematic optimization design synthesis and activity screening research. This class of derivatives has good water solubility and has obvious bactericidal or insecticidal functional activity. It can be widely used in the comprehensive prevention and control of agricultural and forestry pests and diseases, and effectively improves bioavailability. The preparation process of this class of compounds is simple and easy, and it is a functional active substance with broad application prospects.

[0066] In some embodiments, the sulfonic acid functionalized molecule of formula (I) comprises any one of the following structural formulas: (No. I-1), (No. I-2), (No. I-3), (No. I-4), (No. I-5), (No. I-6).

[0067] In some embodiments, the sulfonic acid functionalized molecule represented by formula (II) comprises any one of the following structural formulas: (No. II-1), (No. II-2), (No. II-3), (No. II-4), (No. II-5).

[0068] In some embodiments, the sulfonic acid functionalized molecule of formula (III) comprises any one of the following structural formulas: (No. III-1), (No. III-2), (No. III-3).

[0069] In some embodiments, the sulfonic acid functionalized molecule of formula (IV) comprises any one of the following structural formulas: (No. IV-1), (No. IV-2), (No. IV-3), (No. IV-4), (No. IV-5), (No. IV-6), (No. IV-7), (No. IV-8), (No. IV-9).

[0070] Based on the same inventive concept, the present invention also provides a method for preparing the above-mentioned sulfonic acid functionalized molecule. Specifically, the method for preparing the sulfonic acid functionalized molecule represented by formula (I) comprises the following steps:

[0071] Alkylation reaction of a substituted 4-trifluoromethyl nicotinamide derivative with a substituted sultone to obtain a sulfonic acid functionalized molecule represented by formula (I);

[0072] The preparation method of the sulfonic acid functionalized molecule represented by formula (II) comprises the following steps:

[0073] Alkylation reaction of a substituted benzamide derivative with a substituted sultone yields a sulfonic acid functionalized molecule represented by formula (II);

[0074] The preparation method of the sulfonic acid functionalized molecule represented by formula (III) comprises the following steps:

[0075] Alkylation reaction of a benzimidazole derivative with a substituted sultone yields a sulfonic acid functionalized molecule represented by formula (III);

[0076] The preparation method of the sulfonic acid functionalized molecule represented by formula (IV) comprises the following steps:

[0077] Alkylation reaction of a triazine heterocyclic imine derivative with a substituted sultone to obtain a sulfonic acid functionalized molecule represented by formula (IV);

[0078] The structural formula of the substituted 4-trifluoromethyl nicotinamide derivative is shown below:

[0079]

[0080] The structural formula of the substituted benzamide derivatives is shown below:

[0081]

[0082] The structural formula of the benzimidazole derivative is shown below:

[0083]

[0084] The structural formula of triazine heterocyclic imine derivatives is shown below:

[0085]

[0086] In some embodiments, the substituted sultone includes any one of 1,3-propane sultone, 1,4-butane sultone, 1,3-propene sultone, 3-hydroxypropane sultone, 3-chloropropane sultone, and 3-fluoropropane sultone.

[0087] In some embodiments, the general conditions for the alkylation reaction are to suspend a suitable substrate in a reaction solvent, then add a catalyst under stirring, slowly raise the temperature to a certain level for reaction, and monitor the reaction progress using thin layer chromatography and liquid chromatography-mass spectrometry equipment.

[0088] In some embodiments, in the process of preparing the sulfonic acid functionalized molecule of any one of formulas (I) to (IV), the solvent used includes at least one of tetrahydrofuran, toluene, 1,4-dioxane, xylene, 1,2-dichloroethane, o-dichlorobenzene, and heptane;

[0089] The catalyst used includes at least one of sodium hydride, potassium tert-butoxide, sodium methoxide, and N,N-diisopropylethylamine;

[0090] The reaction temperature is 40-120°C.

[0091] Specifically, in the process of preparing the sulfonic acid functionalized molecule of any one of formulas (I) to (IV), the alkylation reaction conditions are: using tetrahydrofuran as solvent, sodium hydride as catalyst, and the reaction temperature at 40-80°C; or, using tetrahydrofuran as solvent, potassium tert-butoxide as catalyst, and the reaction temperature at 40-80°C; or, using toluene as solvent, sodium hydride as catalyst, and the reaction temperature at 40-110°C; or, using 1,4-dioxane as solvent, sodium hydride as catalyst, and the reaction temperature at 40-110°C; or, using xylene as solvent, sodium hydride as catalyst, and the reaction temperature at 40-120°C; or, using tetrahydrofuran as solvent, sodium methoxide as catalyst, and the reaction temperature at 40-80°C; or, using toluene as solvent, no catalyst, and the reaction temperature at 80-110°C; or, using toluene as solvent, N,N-diisopropylethylamine as catalyst, and the reaction temperature at The reaction temperature is 80-110°C; or, using 1,4-dioxane as solvent, without catalyst, the reaction temperature is 80-110°C; or, using 1,4-dioxane as solvent, N,N-diisopropylethylamine as catalyst, the reaction temperature is 80-110°C; or, using 1,2-dichloroethane as solvent, without catalyst, the reaction temperature is 80-90°C; or, using xylene as solvent, without catalyst, the reaction temperature is 80-120°C ; or, using xylene as solvent, the catalyst is N,N-diisopropylethylamine, and the reaction temperature is 80-120°C; or, using o-dichlorobenzene as solvent, without catalyst, the reaction temperature is 80-120°C; or, using o-dichlorobenzene as solvent, the catalyst is N,N-diisopropylethylamine, and the reaction temperature is 80-120°C; or, using heptane as solvent, the catalyst is N,N-diisopropylethylamine, and the reaction temperature is 80-110°C.

[0092] The substituted 4-trifluoromethylnicotinamide derivatives, 4-trifluoromethylnicotinamide derivatives, substituted benzamide derivatives, benzimidazole derivatives, and triazine heterocyclic imine derivatives described herein can all be prepared using a variety of basic chemical raw materials via conventional organic synthesis methods. Through systematic optimization design, synthesis, and activity screening, the present invention has constructed a class of functional derivatives containing sulfonic acid groups. These derivatives exhibit good water solubility and significant bactericidal or insecticidal activity, effectively enhancing their bioavailability and enabling widespread application in the integrated control of agricultural and forestry pests and diseases. The preparation process for these compounds is simple and easy, making them promising functional active substances with broad application prospects.

[0093] Based on the same inventive concept, the present invention also provides a composition comprising a solvate or a soluble salt formed by the above-mentioned sulfonic acid functionalized molecule and a pharmaceutically acceptable solvent.

[0094] Based on the same inventive concept, the present invention also provides an insecticide comprising the above-mentioned sulfonic acid functionalized molecule and a diluent.

[0095] In some embodiments, the diluent includes at least one of kaolin, clay, bentonite, clay, diatomaceous earth, montmorillonite, attapulgite, dolomite, quartz, calcium carbonate, talc, and attapulgite.

[0096] In some embodiments, the diluent includes one or more of polyvinyl alcohol, carboxymethyl cellulose, gum arabic, and natural and synthetic polymers in powder, granular, or emulsion form, or one or more of trace nutrients.

[0097] Specifically, in some embodiments, the pesticide can be made into different formulations such as aqueous emulsions, suspensions, wettable powders, and water-dispersible granules.

[0098] Based on the same inventive concept, the present invention also provides the use of the above-mentioned sulfonic acid functionalized molecule, the above-mentioned composition or the above-mentioned insecticide in the preparation of drugs for killing biological pests and in the preparation of drugs for preventing and controlling plant diseases.

[0099] In some embodiments, biological pests include but are not limited to vegetable aphids, bean aphids, corn aphids, alfalfa aphids, cotton aphids, wheat aphids, wheat macrosiphum, peach aphids, cabbage aphids, Bemisia tabaci, rice planthoppers, rice gray planthoppers, rice brown planthoppers, greenhouse whiteflies, whiteback planthoppers, citrus psyllids, Chinese pear psyllids, black-tailed leafhoppers, small green leafhoppers, large green leafhoppers, beet leafhoppers, potato green leafhoppers, tea net stink bugs, blind stink bugs, diamondback moths, beet armyworms, Spodoptera litura, cotton bollworms, tobacco budworms, root-knot nematodes, greenhouse thrips, rice thrips, etc.

[0100] In some embodiments, the plant diseases include at least one of cotton verticillium wilt, wheat ergot, watermelon wilt, rice sheath blight, wheat glumen blight, gray mold, rapeseed black shank, pear black spot, tomato coryneform leaf spot, damping-off, rice blast, gloeosporium anthracnose, citrullus rot, Fusarium oxysporum, watermelon damping-off, apple ring rot, pepper phytophthora, Fusarium graminearum, Alternaria alternata, bacterial wilt, soft rot, and Enterobacter.

[0101] The following further illustrates the sulfonic acid functionalized molecules of the present application, their preparation methods, and applications using specific examples. This section further illustrates the present invention in conjunction with specific examples, but should not be construed as limiting the present invention. Unless otherwise specified, the techniques employed in the examples are conventional techniques well known to those skilled in the art. Unless otherwise specified, the reagents, methods, and equipment employed in the present invention are conventional in the art.

[0102] Example 1

[0103] The present embodiment provides a sulfonic acid functionalized molecule (numbered I-1), the preparation reaction formula of which is:

[0104]

[0105] The specific preparation method is as follows: the intermediate N-(cyanomethyl)-5-(trifluoromethyl)nicotinamide 1a (1 mmol) is dissolved in 10 mL of toluene, 1.1 mmol of 1,3-propane sultone is added with stirring, and the reaction is heated to 110-120°C and maintained at this temperature. TLC is followed until the substrate is completely converted. The reaction system is then cooled to room temperature, and the solvent is evaporated under reduced pressure. After the system is cooled, a solid precipitates, which is filtered under reduced pressure, washed with a small amount of cold methanol, and dried under vacuum to obtain the target compound I-1 in a yield of 74%. The mass spectrometric analysis of the target compound is: MS (ESI) m / z 352.27 (M+H). + ,calcd.for C 12 H 12 F3N3O4S m / z=351.05.

[0106] Example 2

[0107] The present embodiment provides a sulfonic acid functionalized molecule (numbered I-2), the preparation reaction formula of which is:

[0108]

[0109] The specific preparation method is as follows: the intermediate N-(cyanomethyl)-5-(trifluoromethyl)nicotinamide 1a (1 mmol) is weighed and suspended in 15 mL of toluene. 1.1 mmol of propene sultone is added with stirring, followed by 0.1 mmol of N,N-diisopropylethylamine (DIPEA). The reaction is slowly heated to 100-110°C and maintained at this temperature. TLC is performed until the substrate is completely converted. The reaction is then cooled to room temperature, and the toluene is evaporated under reduced pressure. After cooling, a solid precipitates, which is filtered under reduced pressure, washed with a small amount of cold methanol, and dried under vacuum to obtain the target compound I-2 in a 68% yield. The mass spectrometric analysis of the target compound is: MS (ESI) m / z 350.20 (M+H). + ,calcd.for C 12 H 10 F3N3O4S m / z=349.03.

[0110] Example 3

[0111] The present embodiment provides a sulfonic acid functionalized molecule (numbered I-3), the preparation reaction formula of which is:

[0112]

[0113] The specific preparation method is as follows: Take an appropriate amount of N-(cyanomethyl)-5-(trifluoromethyl)nicotinamide 1a (1 mmol), dissolve it in 10 mL of xylene, add 1.1 mmol of 1,4-butane sultone with stirring, and then add 0.1 mmol of N,N-diisopropylethylamine (DIPEA). Slowly raise the temperature to 90-100°C and keep the reaction warm. TLC is monitored until the substrate is completely converted. Then cool to room temperature, and evaporate two-thirds of the solvent under reduced pressure. After cooling the system, a solid precipitates, which is filtered under reduced pressure, washed with a small amount of cold ethanol, and dried under vacuum to obtain the target compound I-3 in a 70% yield. The mass spectrometric analysis of the target compound is: MS (ESI) m / z 366.22 (M+H). + ,calcd.for C 13 H 14 F3N3O4S m / z=365.07.

[0114] Example 4

[0115] The present invention provides a sulfonic acid functionalized molecule (numbered I-4) whose preparation reaction formula is:

[0116]

[0117] The specific preparation method is as follows: 1 mmol of the intermediate N-(4-(trifluoromethoxy)phenethyl)-4-(trifluoromethyl)nicotinamide 1b is dissolved in 15 mL of dioxane, 1.1 mmol of 1,3-propane sultone is added with stirring, and the mixture is slowly heated to 100-110°C and kept warm for reaction. TLC is performed until the substrate is completely converted. The mixture is then cooled to room temperature, and half of the solvent is evaporated under reduced pressure. After cooling, a solid precipitates, which is filtered under reduced pressure, washed with a small amount of cold isopropanol, and dried under vacuum to obtain the target compound I-4 in a yield of 78%. The mass spectrometric analysis of the target compound is: MS (ESI) m / z 501.45 (M+H). + ,calcd.for C 19 H 18 F6N2O5S m / z=500.08.

[0118] Example 5

[0119] The present invention provides a sulfonic acid functionalized molecule (numbered II-1) whose preparation reaction formula is:

[0120]

[0121] The specific preparation method is as follows: The intermediate N-(2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethyl)-2-(trifluoromethyl)benzamide 2a (1 mmol) is dissolved in 20 mL of toluene, 1.1 mmol of 1,3-propane sultone is added with stirring, and the mixture is slowly heated to 110°C and kept warm for reaction. TLC is followed until the substrate is completely converted. The mixture is then cooled to room temperature, and the solvent is evaporated under reduced pressure. After cooling, the mixture is filtered under reduced pressure, washed with a small amount of cold acetonitrile, and dried under vacuum to obtain the target compound II-1 in a yield of 56%. The mass spectrometric analysis of the target compound is: MS (ESI) m / z 519.46 (M+H). + ,calcd.for C 19 H 17 ClF6N2O4S m / z=518.05.

[0122] Example 6

[0123] The present invention provides a sulfonic acid functionalized molecule (numbered II-2) whose preparation reaction formula is:

[0124]

[0125] The specific preparation method is as follows: 1 mmol of the intermediate N-(2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethyl)-2-(trifluoromethyl)benzamide 2a is dissolved in 20 mL of heptane. 1.1 mmol of propene sultone is added with stirring, followed by 0.1 mmol of N,N-diisopropylethylamine (DIPEA). The reaction is slowly heated to 100°C and maintained at this temperature. TLC is used to monitor complete conversion of the substrate. The mixture is then cooled to room temperature, and two-thirds of the solvent is removed by vacuum distillation. After cooling, the mixture is filtered under reduced pressure, washed with a small amount of cold ethanol, and dried under vacuum to obtain the target compound II-2 in a 63% yield. The mass spectrometric analysis of the target compound is: MS (ESI) m / z 517.32 (M+H). + ,calcd.for C 19 H 15 ClF6N2O4S m / z=516.03.

[0126] Example 7

[0127] The present invention provides a sulfonic acid functionalized molecule (numbered III-1) whose preparation reaction formula is:

[0128]

[0129] The specific preparation method is as follows: 1 mmol of the intermediate N-(2-benzimidazolyl)carbamic acid methyl ester 3a is dissolved in 1,2-dichloroethane (15 mL), and 1.1 mmol of 1,3-propane sultone is added with stirring. The mixture is slowly heated to 80-90°C and then kept warm for reaction. TLC is performed until the substrate is completely converted. The mixture is then cooled to room temperature, and half of the solvent is evaporated under reduced pressure. After cooling, the mixture is filtered under reduced pressure, washed with a small amount of cold ethanol, and dried under vacuum to obtain the target compound III-1 in an 85% yield. The mass spectrometric analysis of the target compound is: MS (ESI) m / z 314.09 (M+H). + ,calcd.for C 12 H 15 N3O5S m / z=313.07.

[0130] Example 8

[0131] The present invention provides a sulfonic acid functionalized molecule (numbered III-2) whose preparation reaction formula is:

[0132]

[0133] The specific preparation method is as follows: an appropriate amount of the intermediate methyl N-(2-benzimidazolyl)carbamate 3a (1 mmol) is dissolved in 20 mL of toluene, 1.1 mmol of propene sultone is added with stirring, and the mixture is slowly heated to 110°C and kept warm for reaction. TLC is performed to monitor complete conversion of the substrate. The mixture is then cooled to room temperature, and a large amount of toluene is evaporated under reduced pressure. After cooling, the mixture is filtered under reduced pressure, washed with an appropriate amount of cold acetonitrile, and dried under vacuum to obtain the target compound III-2 in an 88% yield. The mass spectrometric analysis of the target compound is: MS (ESI) m / z 312.20 (M+H). + ,calcd.for C 12 H 13 N3O5S m / z=311.06.

[0134] Example 9

[0135] The present invention provides a sulfonic acid functionalized molecule (numbered III-3) whose preparation reaction formula is:

[0136]

[0137] The specific preparation method is as follows: 1 mmol of the intermediate N-(2-benzimidazolyl)carbamic acid methyl ester 3a is dissolved in 20 mL of dioxane, 1.1 mmol of 1,4-butane sultone is added with stirring, and the mixture is slowly heated to 100-105°C and kept warm for reaction. TLC is performed until the substrate is completely converted. The mixture is then cooled to room temperature, and two-thirds of the solvent is evaporated under reduced pressure. After cooling, the mixture is filtered under reduced pressure, washed with a small amount of cold acetonitrile, and dried under vacuum to obtain the target compound III-3 in a yield of 91%. The mass spectrometric analysis of the target compound is: MS (ESI) m / z 328.23 (M+H). + ,calcd.for C 13 H 17 N3O5S m / z=327.09.

[0138] Example 10

[0139] The present invention provides a sulfonic acid functionalized molecule (numbered IV-1) whose preparation reaction formula is:

[0140]

[0141] The specific preparation method is as follows: The intermediate 6-methyl-4-((pyridin-3-methylene)amino)-4,5-dihydro-1,2,4-triazine-3(2H)-one 4a (1 mmol) is suspended in 20 mL of o-dichlorobenzene, 1.1 mmol of 1,3-propane sultone is added with stirring, and the mixture is slowly heated to 110-120°C and kept warm for reaction. TLC is performed until the substrate is completely converted. The mixture is then cooled to room temperature, filtered under reduced pressure, washed with a small amount of cold ethanol, and dried under vacuum to obtain the target compound IV-1 in an 83% yield. The mass spectrometric analysis of the target compound is: MS (ESI) m / z 340.38 (M+H). + ,calcd.for C 13 H 17 N5O4S m / z=339.10.

[0142] Example 11

[0143] The present invention provides a sulfonic acid functionalized molecule (numbered IV-2) whose preparation reaction formula is:

[0144]

[0145] The specific preparation method is as follows: 1 mmol of the intermediate 6-methyl-4-((pyridin-3-methylene)amino)-4,5-dihydro-1,2,4-triazin-3(2H)-one 4a is suspended in 20 mL of toluene. 1.1 mmol of propene sultone is added with stirring, followed by 0.1 mmol of N,N-diisopropylethylamine (DIPEA). The mixture is slowly heated to approximately 110°C and maintained for reaction. TLC is performed until the substrate is completely converted. The mixture is then cooled to room temperature, and 2 / 3 of the solvent is removed under reduced pressure. After cooling, the mixture is filtered under reduced pressure, washed with an appropriate amount of cold ethanol, and dried under vacuum to obtain the target compound IV-2 in an 86% yield. The mass spectrometric analysis of the target compound is: MS (ESI) m / z 338.22 (M+H). + ,calcd.for C 13 H 15 N5O4S m / z=337.08.

[0146] Example 12

[0147] The present invention provides a sulfonic acid functionalized molecule (numbered IV-3) whose preparation reaction formula is:

[0148]

[0149] The specific preparation method is as follows: 1 mmol of the intermediate 6-methyl-4-((pyridin-3-methylene)amino)-4,5-dihydro-1,2,4-triazin-3(2H)-one 4a is suspended in 15 mL of xylene. 1.1 mmol of 1,4-butane sultone is added with stirring, followed by 0.1 mmol of N,N-diisopropylethylamine (DIPEA). The mixture is slowly heated to 110-120°C and then kept warm for reaction. TLC is performed until the substrate is completely converted. The mixture is then cooled to room temperature, filtered under reduced pressure, washed with a small amount of cold ethanol, and dried under vacuum to obtain the target compound IV-3 in an 85% yield. The mass spectrometric analysis of the target compound is: MS (ESI) m / z 354.25 (M+H). + ,calcd.for C 14 H 19 N5O4S m / z=353.12.

[0150] Example 13

[0151] The present invention provides a sulfonic acid functionalized molecule (numbered IV-4) whose preparation reaction formula is:

[0152]

[0153] The preparation method comprises the following steps: suspending the intermediate 2-acetyl-6-methyl-4-((pyridin-3-methylene)amino)-4,5-dihydro-1,2,4-triazine-3(2H)-one 4b (1 mmol) in 20 mL of toluene, adding 1.1 mmol of 1,3-propane sultone with stirring, slowly heating to 100-110°C and then maintaining the temperature for reaction. TLC is performed until the substrate is completely converted, followed by cooling to room temperature, vacuum filtration, washing with a small amount of cold ethanol, and vacuum drying to obtain the target compound IV-4 in an 88% yield. The specific physical and chemical properties of the target compound are: MS (ESI) m / z 382.43 (M+H). + ,calcd.for C 15 H 19 N5O5S m / z=381.11.

[0154] Example 14

[0155] The present invention provides a sulfonic acid functionalized molecule (numbered IV-5) whose preparation reaction formula is:

[0156]

[0157] The preparation method comprises the following steps: dissolving the intermediate 2-propionyl-6-methyl-4-((pyridin-3-methylene)amino)-4,5-dihydro-1,2,4-triazine-3(2H)-one 4c (1 mmol) in 20 mL of xylene, adding 1.1 mmol of 1,3-propane sultone with stirring, slowly heating to 100-110°C and then maintaining the temperature for reaction. TLC is performed until the substrate is completely converted, followed by cooling to room temperature, partially removing the solvent under reduced pressure, cooling, and precipitating a solid. The solid is filtered under reduced pressure, washed with a small amount of cold ethanol, and dried under vacuum to obtain the target compound IV-5 in an 81% yield. The specific physical and chemical properties of the target compound are: MS (ESI) m / z 396.35 (M+H). + ,calcd.for C 16 H 21 N5O5S m / z=395.13.

[0158] Example 15

[0159] The present invention provides a sulfonic acid functionalized molecule (numbered IV-6) whose preparation reaction formula is:

[0160]

[0161] The preparation method comprises the following steps: suspending the intermediate 2-acetyl-6-methyl-4-((pyridin-3-methylene)amino)-4,5-dihydro-1,2,4-triazine-3(2H)-one 4b (1 mmol) in 20 mL of toluene, adding 1.1 mmol of propene sultone with stirring, slowly heating to 100-110°C and then maintaining the temperature for reaction. TLC is followed until the substrate is completely converted, followed by cooling to room temperature, evaporating the solvent under reduced pressure, cooling and filtering, washing with a small amount of cold ethanol, and vacuum drying to obtain the target compound IV-6 in a yield of 92%. Specific physical and chemical properties of the target compound: MS (ESI) m / z 380.36 (M+H) + ,calcd.for C 15 H 17 N5O5Sm / z=379.10.

[0162] Example 16

[0163] The present invention provides a sulfonic acid functionalized molecule (numbered IV-8) whose preparation reaction formula is:

[0164]

[0165] The preparation method comprises the following steps: 1 mmol of the intermediate 2-acetyl-6-methyl-4-((pyridin-3-methylene)amino)-4,5-dihydro-1,2,4-triazine-3(2H)-one 4b is suspended in 20 mL of xylene, 1.1 mmol of 1,4-butane sultone is added with stirring, and the mixture is slowly heated to 100-110°C and kept warm for reaction. TLC is performed until the substrate is completely converted, followed by cooling to room temperature, and the appropriate solvent is evaporated under reduced pressure. The mixture is then cooled, filtered, washed with a small amount of cold acetone, and dried under vacuum to obtain the target compound IV-8 in an 86% yield. The specific physical and chemical properties of the target compound are: MS (ESI) m / z 396.29 (M+H). + ,calcd.for C 16 H 21 N5O5S m / z=395.13.

[0166] The preparation of the remaining compounds can refer to the basic synthesis methods described in Examples 1 to 16. At the same time, appropriate chemical raw materials are selected in combination with the different structural characteristics of the compounds described in the embodiments to facilitate the preparation of the other sulfonic acid functional compounds and their pesticide-acceptable salts listed.

[0167] Activity test

[0168] The sulfonic acid functionalized molecules in the above embodiment were subjected to agricultural biological function evaluation, wherein the insecticidal activity test targets were cotton bollworm (Heliothis armigera), diamondback moth (Plutella xylostella) and aphid (Aphis craccivora).

[0169] When the test targets are cotton bollworm and diamondback moth, the screening method is a conventional artificial feed surface coating method, specifically using 24-well cell culture plates for activity screening, adding 300 microliters of artificial feed to each well, and adding 20 microliters of liquid to each well. The screening liquid adopts two repetitions of different concentrations (Rep1 and Rep2), which are 500mg / L, 250mg / L, and 125mg / L respectively. The aphid-killing activity test adopts a conventional immersion method, specifically accurately weighed samples (i.e., sulfonic acid functionalized molecules of the present invention) are dissolved in ethanol and mixed with a certain concentration of mother liquor, and diluted to a certain concentration with an aqueous solution containing 0.1mL / L of emulsifier (Tween-80) as needed, which are 500mg / L, 250mg / L, and 125mg / L respectively. The screening liquid adopts two repetitions of different concentrations (Rep1 and Rep2). Blank controls were set up, and the activity results were compared with the blank controls. Statistics were divided into different levels, with a mortality rate of 0-30% being 0, a mortality rate of 30-50% being 3, a mortality rate of 50-70% being 5, a mortality rate of 70-90% being 7, and a mortality rate of 90-100% being 9. Some of the test results are shown in Table 1 below (the compound numbers in Table 1 correspond to the compound numbers in the specific embodiments):

[0170] Table 1 - Insecticidal activity of different sulfonic acid functionalized molecules

[0171]

[0172]

[0173] In Table 1, a) insecticide test target; b) test concentration (unit: mg / L)

[0174] As shown in Table 1, some of the tested sulfonic acid-functionalized molecules exhibited varying degrees of insecticide activity against lepidopteran pests such as cotton bollworm and diamondback moth, as well as Homoptera aphids, at the tested concentrations. In particular, some of the sulfonic acid-functionalized molecules exhibited significant insecticide activity against aphids at all three tested concentrations, achieving pest mortality rates exceeding 90%. These results demonstrate that the sulfonic acid-functionalized molecules of the present invention possess significant insecticidal activity, and the prepared compounds demonstrated excellent water solubility during testing. This provides a promising foundation for the development of application technologies for these compounds. The discovery of these novel sulfonic acid-functionalized derivatives could also serve as a means of addressing resistance to existing insecticides.

[0175] The representative sulfonic acid functionalized molecules obtained in the above specific embodiments were evaluated for their fungicidal biological functions, wherein the plant pathogenic fungi targets used in the fungicidal activity test were cotton Verticillium dahliaekieb., wheat fusarium culmorum, watermelon wilt (Fusarium oxysporumf.sp.Niveum), rice sheath blight (Thanatephorus cucumeris), wheat glumen blight (Septoria nodorum Berk.), gray mold (Botrytis cinerea), rapeseed black shank (Leptosphaeria biglobosa), pear black spot (Alternaria kikuchiana), tomato corynespora leaf spot (Corynespora leaf spot of tomato), damping-off (Rhizoctonia solani), rice blast (Magnaporthe oryzae), gloeobosporioids (Colletotrichum gloeobosporioids) and citrullus fusarium (Pythium aphanidematum).

[0176] The bactericidal activity test was conducted using the microwell dilution method in a 96-well sterile plate. The test compound (i.e., the sulfonic acid functionalized molecule of the present invention) was dissolved in DMSO and diluted to the specified concentrations (100 μg / mL, 50 μg / mL, 25 μg / mL, and 12.5 μg / mL) using a two-fold serial dilution method. The final DMSO concentration did not exceed 5%. The bactericidal activity assay used inoculated culture medium and sterile water containing 5% DMSO as negative controls. The fungi were cultured at 28°C for 48-96 hours. The growth of the pathogen was observed, and the bactericidal activity data were statistically analyzed. The activity results were compared with the blank control. Evaluation criteria: if the target showed essentially normal growth, consistent with the blank control, an inhibition rate of 0-30% was scored as 3; if the target showed partial growth, an inhibition rate of 30-70% was scored as 5; if the target showed minimal growth, an inhibition rate of 70-90% was scored as 7; if the target showed no growth at all, an inhibition rate of 90-100% was scored as 9. The fungicidal activity results are shown in Table 2 below (only the activity data of some highly active compounds III-1, III-2, and III-3 are listed).

[0177] Table 2 - Bactericidal activity of sulfonic acid functionalized molecules III-1, III-2, and III-3

[0178]

[0179]

[0180] In Table 2, a is compound number; b is test concentration (unit: μg / mL).

[0181] As shown in Table 2, some test compounds, such as III-1, III-2, and III-3, exhibited significant fungicidal activity against a variety of pathogenic targets at various test concentrations, achieving inhibition rates exceeding 90%. In particular, at a relatively low test concentration of 12.5 μg / mL, even at a concentration of almost complete inactivation of several pathogens, the fungicidal inhibition rate remained above 90%. These results suggest that the discovery of these novel sulfonic acid-functionalized derivatives offers a novel approach to the integrated prevention and control of crop diseases and could also serve as a means of addressing resistance to existing fungicides.

[0182] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A sulfonic acid functionalized molecule, characterized in that: The structural formula of the sulfonic acid functionalized molecule is any one of the following structural formulas:

2. The method for preparing a sulfonic acid functionalized molecule according to claim 1, wherein: The following steps are involved: Alkylation reaction of substituted 4-trifluoromethylnicotinamide derivatives with substituted sultones yields sulfonic acid functionalized molecules; The structural formula of the substituted 4-trifluoromethyl nicotinamide derivative is as follows: Among them, R 1 Any one selected from CH2CN, 4-CF3OPhCH2CH2; The substituted sultone is any one of 1,3-propane sultone, 1,4-butane sultone, and 1,3-propene sultone.

3. The method for preparing a sulfonic acid functionalized molecule according to claim 2, wherein: In the process of preparing the sulfonic acid functionalized molecules, the solvent used is at least one of tetrahydrofuran, toluene, 1,4-dioxane, xylene, 1,2-dichloroethane, o-dichlorobenzene, and heptane; In the process of preparing the sulfonic acid functionalized molecule, a catalyst is added, wherein the catalyst used is at least one of sodium hydride, potassium tert-butoxide, sodium methoxide, and N,N-diisopropylethylamine; The reaction temperature is 40-120°C.

4. An insecticide, characterized in that The method comprises the sulfonic acid functionalized molecule as claimed in claim 1 and a diluent.

5. The insecticide according to claim 4, wherein The diluent is at least one of kaolin, clay, bentonite, clay, diatomaceous earth, montmorillonite, activated clay, dolomite, quartz, calcium carbonate, talc, attapulgite, polyvinyl alcohol, carboxymethyl cellulose, gum arabic, polymer, and trace nutrients.

6. Use of the sulfonic acid functionalized molecule according to claim 1 or the insecticide according to any one of claims 4 to 5 in the preparation of a drug for killing biological pests; The biological pest is at least one of cotton bollworm, diamondback moth and aphid.

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