Triazole-containing compounds, methods of synthesis, and uses thereof

Abstract

The present application discloses a triazole-containing compound, a synthesis method and an application thereof, and belongs to the field of pesticides. The method uses a heterocyclic molecule with a carboxyl functional group as a raw material, and is subjected to an amide reaction with aminoacetylene to generate an intermediate shown in formula (I). The intermediate (I) is subjected to a reaction with an azide compound to obtain an amide-containing triazole compound, such as formula (II). Substituted benzaldehyde, sodium azide and 2-(phenylsulfonyl)acetonitrile are used as raw materials to generate a cyano-containing triazole compound shown in formula (III). The method is simple in operation, mild in conditions and strong in functional group tolerance. The prepared intermediate and final product have certain insecticidal and fungicidal activity, and have potential application prospect.

Description

Technical Field

[0001] This invention relates to the field of pesticides, and in particular to triazole compounds, their synthesis methods, and their applications. Background Technology

[0002] Outbreaks of crop diseases and pests pose a serious threat to food security. Globally, losses due to diseases and pests account for approximately 40% of total crop losses annually, with disease and pest losses accounting for 14% of these losses. Agricultural pests are diverse, and hemiptera stinging insects have become one of the major threats to crops in my country. With the extensive use of pesticides, some pests have developed resistance, leading to increased dosages and a rapidly growing environmental impact, making the development of new insecticides imperative. Heterocyclic compounds, due to their similarity to certain parts of organisms (such as pyrimidine cells or amino acids), are more effective. Therefore, fluorine-containing and heterocyclic compounds have become the target for new pesticide development. According to incomplete statistics, about 70% of the new pesticides developed in the 1990s were fluorine-containing or heterocyclic pesticides, while 5% were pesticides containing both fluorine and heterocyclic compounds. Fluorine-containing and heterocyclic pesticides will remain the main focus of research in chemical pesticides.

[0003] In summary, this invention utilizes a bioisosteric and active substructure splicing method to develop a new series of triazole compounds and has conducted insecticidal and fungicidal activity assays. In the future, with continuous technological advancements and innovations, these pesticides will provide more efficient and environmentally friendly solutions for agricultural production. Summary of the Invention

[0004] To address the aforementioned problems, this invention provides a series of synthetic methods for triazole compounds, which can produce them with high yield and high purity, and are simple, safe, and environmentally friendly.

[0005] To achieve the above objectives, the present invention adopts the following technical solution:

[0006] Triazole compounds, including amide triazole compounds (Formula II) and cyano triazole compounds (Formula III), have the following structural formulas:

[0007]

[0008] In the formula, R 1 Ar is any one of methyl, methoxy, trifluoromethyl, hydroxy, nitro, or halogen; Ar is a benzene ring, furan ring, pyridine ring, thiazole ring, pyrazole ring, pyrazine ring, or imidazothiazole ring; R 2 It is hydrogen, methyl, or dimethyl; R 3 It is benzylbenzene, ethyl acetate, or p-toluenesulfonyl.

[0009] A method for synthesizing triazole compounds, the method comprising the following steps:

[0010] S1, add heterocyclic compound 1 with carboxyl functional group and aminoacetylene 2 to solvent, react under the action of condensing agent, and elute the fully reacted solution to obtain intermediate formula (I).

[0011] S2, intermediate (I) reacts with azide compound 3 under the action of a catalyst to prepare an amide compound containing a triazole structure as shown in formula (II). The reaction equation is as follows:

[0012]

[0013] S3, substituted benzaldehyde 4 with cyano functional group, sodium azide 5, and 2-(benzenesulfonyl)acetonitrile 6 are added to a solvent and reacted fully to prepare a triazole compound containing a cyano functional group as shown in formula (III). The reaction equation is as follows:

[0014]

[0015] Further, the condensing agent mentioned in step S1 is one or two of the following: dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI), 4-dimethylaminopyridine (DMAP), 1-hydroxybenzotriazole (HOBT), carbonyl diimidazole (CDI), triethylamine (TEA), diphenylphosphine chloride (DPP-Cl), diethyl cyanophosphate (DECP), diphenyl phosphate azide (DPPA), and thiodimethylphosphoazide (MPTA).

[0016] Furthermore, the conditions for a complete reaction described in step S1 are a reaction temperature of 0-60℃ and a reaction time of 8-24h.

[0017] Furthermore, the molar ratio of compound 1 and compound 2 in step S1 is (1-2):1.

[0018] Furthermore, the concentration of compound 1 in the solvent in step S1 is 0.05-0.2 mol / L.

[0019] Furthermore, the solvent in step S1 is any one of acetonitrile, N,N-dimethylformamide, dimethyl sulfoxide, acetone, ethyl acetate, dichloromethane, dichloroethane, methanol, ethanol, 1,4-dioxane, toluene, tetrahydrofuran, or n-hexane.

[0020] Furthermore, the eluent used in step S1 is dichloromethane and methanol in a volume ratio of (20-100):1.

[0021] Furthermore, the catalyst mentioned in step S2 is one or two of copper sulfate, sodium ascorbate, copper acetate, cuprous iodide, and triethylamine.

[0022] Furthermore, the reaction conditions in step S2 are a reaction temperature of 0-60℃ and a reaction time of 0.25-3h.

[0023] Furthermore, the molar ratio of the intermediate (I) to the azide compound 3 in step S2 is (1-2):1.

[0024] Furthermore, the concentration of intermediate (I) in the solvent in step S2 is 0.05-0.2 mol / L.

[0025] Furthermore, the solvent mentioned in step S2 is any one of pure water, acetonitrile, N,N-dimethylformamide, dimethyl sulfoxide, tert-butanol, acetone, ethyl acetate, dichloromethane, dichloroethane, methanol, ethanol, 1,4-dioxane, toluene, tetrahydrofuran, or n-hexane.

[0026] Furthermore, in step S2, the solution after the reaction is separated and purified, and the eluent used is dichloromethane and methanol in a volume ratio of (20-100):1.

[0027] Furthermore, the conditions for a complete reaction in step S3 are a reaction temperature of 0-100℃ and a reaction time of 3-24h.

[0028] Furthermore, the molar ratio of the reaction of compounds 4, 5 and 6 in step S3 is 1:(1-2):(1:2).

[0029] Furthermore, the concentration of compound 4 in the solvent in step S3 is 0.05-0.2 mol / L.

[0030] Furthermore, the solvent mentioned in step S3 is any one of distilled water, acetonitrile, N,N-dimethylformamide, dimethyl sulfoxide, acetone, ethyl acetate, dichloromethane, dichloroethane, methanol, ethanol, 1,4-dioxane, toluene, tetrahydrofuran, or n-hexane.

[0031] Furthermore, in step S3, the solution after the reaction is fully purified by separating and purifying it, using petroleum ether and ethyl acetate in a volume ratio of (1-10):1.

[0032] Insecticidal applications of intermediate formula (I) and triazole-containing compound formula (II) against whiteflies, peach aphids, and spider mites; fungicidal applications of compound formula (III) against Phytophthora, Acer rubrum, Fusarium graminearum, and Botrytis cinerea.

[0033] The beneficial effects of this invention are:

[0034] 1. This invention employs a bioisosteric and active substructure splicing method, using aminoacetylene compounds as raw materials to undergo an amide reaction with heterocyclic molecules containing carboxyl groups, yielding an intermediate structure as shown in formula (I). Then, intermediate (I) is used as a raw material to undergo a click reaction with an azide compound, generating an amide compound (II) with a triazole structure. This reaction is simple to operate, operates under relatively mild conditions, exhibits strong functional group tolerance, and requires only a certain amount of raw materials, catalyst, and solvent, demonstrating high step economy. Simultaneously, the atom utilization rate reaches 80-100%, making it a typical example of green synthesis. Furthermore, the prepared nitrogen-containing heterocyclic amide compound (II) enriches the molecular library of this class of compounds.

[0035] 2. This invention employs a bioisosteric and active substructure splicing method, using sodium azide and 2-(benzenesulfonyl)acetonitrile as raw materials, to react with substituted benzaldehyde to obtain the structure shown in formula (III). This reaction is simple to operate, operates under relatively mild conditions, exhibits strong functional group tolerance, requires no catalyst, uses distilled water as a solvent, and only requires the addition of a certain amount of raw materials. This reaction demonstrates high step economy, while achieving an atom utilization rate of 40-98%, making it a typical example of green synthesis. Furthermore, the prepared cyanotriazole-containing compound of formula (III) enriches the molecular library of this class of compounds.

[0036] 3. The insecticidal activity of the intermediate (I) and the amide-triazole compound (II) prepared in this invention was determined. Both intermediate (I) and the amide-triazole compound (II) showed certain insecticidal activity against the whitefly. Specifically, intermediates I-5, I-6, I-7 and the amide-triazole compound II-7 showed significant LC-reactivity against the whitefly. 50 The LC50 values ​​of compounds I-1, II-16, and II-14 against the peach aphid reached 69.81 (43.58-82.26), 186.3 (160.1-215.2), 91.91 (81.52-102.5), and 112.4 (106.5-129.1), respectively; 50 They reached 5.308 (2.597-8.024), 5.428 (2.997-8.575), and 4.674 (3.505-5.973), respectively.

[0037] 4. The fungicidal activity of the cyanotriazole compounds (III) prepared in this invention was determined. The cyanotriazole compounds exhibited certain fungicidal activity against four fungi: *Phytophthora infestans*, *Fusarium oxysporum*, *Fusarium graminearum*, and *Botrytis cinerea*. Compound III-3 showed fungicidal activity of 91.43% and 70.00% against *Phytophthora infestans* and *Fusarium graminearum*, respectively; Compound III-1 showed fungicidal activity of 98.19% and 100.00% against *Fusarium graminearum* and *Botrytis cinerea*, respectively; and at a concentration of 100 mg / L, Compound III-7 achieved 100.00% fungicidal activity against *Fusarium graminearum*. Detailed Implementation

[0038] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0039] Unless otherwise specified, all reagents and instruments used are standard products that can be purchased through legitimate channels. Unless otherwise stated, all raw materials used are commercially available products.

[0040] Example 1

[0041] (1) Synthesis of N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide (compound number I-1): Under air atmosphere, 4-trifluoromethylnicotinic acid (1.2 mmol, 0.23 g), EDCI (2.4 mmol, 0.46 g), and DMAP (2.4 mmol, 0.29 g) were added to a 50 mL round-bottom flask, followed by 10 mL of dichloromethane. The mixture was stirred in an ice bath for 15-30 minutes, and then aminoacetylene (1 mmol, 0.068 mL) was added. After stirring at room temperature for 12 h, the reaction was monitored by TLC. After the reaction was complete, the product was extracted and purified by column chromatography. The developing solvent ratio was DCM:MeOH = 50:1, yielding I-1 (yield: 89%).

[0042] (2) Synthesis of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-4-(trifluoromethyl)nicotinamide (chemical designation II-1): Under air atmosphere, intermediate I-1 (1.1 mmol, 0.25 g), benzyl azide (1 mmol, 0.125 mL), CuSO4 (5 mmol, 2.5 mL) and sodium ascorbate (0.5 mmol, 0.5 mL) were dissolved in t-BuOH:water = 1:1 (3 mL), reacted at room temperature for 0.5 h, extracted with dichloromethane, and purified by column chromatography with a developing solvent ratio of DCM:MeOH of 30:1 to obtain II-1 (yield: 98%).

[0043] (3) The synthesis steps of ethyl-2-(4-((4-(trifluoromethyl)nicotinamide)methyl)-1H-1,2,3-triazol-1-yl)acetate (compound number II-2) are the same as in Example 1, except that the benzyl azide in step (2) is replaced with an equimolar amount of ethyl azide. (Yield: 93%)

[0044] (4) The synthesis steps of N-((1-p-toluenesulfonyl-1H-1,2,3-triazol-4-yl)methyl)-4-(trifluoromethyl)nicotinamide (compound number II-3) are the same as in Example 1, except that the benzyl azide in step (2) is replaced with an equimolar amount of p-toluenesulfonyl azide. (Yield: 34%)

[0045] Example 2

[0046] (1) The synthesis steps of N-(prop-2-yn-1-yl)-5-(trifluoromethyl)nicotinamide (compound number I-2) are the same as in Example 1, except that 4-trifluoromethylnicotinic acid in step (1) is replaced with an equimolar amount of 5-trifluoromethylnicotinic acid. (Yield: 85%)

[0047] (2) The synthesis steps of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-5-(trifluoromethyl)nicotinamide (compound number II-4) are the same as in Example 1, except that N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (2) is replaced with an equimolar amount of N-(prop-2-yn-1-yl)-5-(trifluoromethyl)nicotinamide. (Yield: 94%)

[0048] (3) The synthesis steps of ethyl-2-(4-((4-(trifluoromethyl)nicotinamide)methyl)-1H-1,2,3-triazol-1-yl)acetate (compound number II-5) are the same as in Example 1, except that N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (3) is replaced with an equimolar amount of N-(prop-2-yn-1-yl)-5-(trifluoromethyl)nicotinamide.

[0049] (Yield: 95%)

[0050] Example 3

[0051] (1) The synthesis steps of N-(prop-2-ynyl)-2-(trifluoromethyl)benzamide (compound number I-3) are the same as in Example 1, except that 4-trifluoromethylnicotinic acid in step (1) is replaced with an equimolar amount of o-trifluoromethylbenzoic acid. (Yield: 59%)

[0052] (2) The synthesis steps of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-2-(trifluoromethyl)benzamide (compound number II-6) are the same as in Example 1, except that N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (2) is replaced with an equimolar amount of N-(prop-2-yn-yl)-2-(trifluoromethyl)benzamide. (Yield: 100%)

[0053] (3) The synthesis steps of ethyl 2-(4-((2-(trifluoromethyl)benzamido)methyl)-1H-1,2,3-triazol-1-yl)acetate (chemical number II-7) are the same as in Example 1, except that N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (3) is replaced with an equimolar amount of N-(prop-2-yn-yl)-2-(trifluoromethyl)benzamide.

[0054] (Yield: 100%)

[0055] (4) The synthesis steps of N-((1-p-toluenesulfonyl-1H-1,2,3-triazol-4-yl)methyl)-2-(trifluoromethyl)benzamide (chemical number II-8) are the same as in Example 1, except that N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (4) is replaced with an equimolar amount of N-(prop-2-yn-yl)-2-(trifluoromethyl)benzamide.

[0056] (Yield: 41%)

[0057] Example 4

[0058] (1) The synthesis steps of 6-methyl-N-(prop-2-yn-1-yl)pyrazin-2-carboxamide (compound number I-4) are the same as in Example 1, except that 4-trifluoromethylnicotinic acid in step (1) is replaced with an equimolar amount of 6-methylpyrazin-2-carboxylic acid. (Yield: 79%)

[0059] (2) The synthesis steps of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-6-methylpyrazine-2-carboxamide (compound number II-9) are the same as in Example 1, except that N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (2) is replaced with an equimolar amount of 6-methyl-N-(prop-2-yn-1-yl)pyrazine-2-carboxamide. (Yield: 98%)

[0060] (3) The synthesis steps of ethyl 2-(4-((6-methylpyrazin-2-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)acetate (chemical number II-10) are the same as in Example 1, except that N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (3) is replaced with an equimolar amount of 6-methyl-N-(prop-2-yn-1-yl)pyrazin-2-carboxamide. (Yield: 100%)

[0061] (4) The synthesis steps of 6-methyl-N-((1-p-toluenesulfonyl-1H-1,2,3-triazol-4-yl)methyl)pyrazine-2-carboxamide (chemical number II-11) are the same as in Example 1, except that N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (4) is replaced with an equimolar amount of 6-methyl-N-(prop-2-yn-1-yl)pyrazine-2-carboxamide. (Yield: 18%)

[0062] Example 5

[0063] (1) The synthesis steps of 3-bromo-N-(prop-2-yn-1-yl)-5-(trifluoromethyl)benzamide (compound number I-5) are the same as in Example 1, except that 4-trifluoromethylnicotinic acid in step (1) is replaced with an equimolar amount of 3-bromo-5-trifluoromethylbenzoic acid. (Yield: 65%)

[0064] (2) The synthesis steps of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-3-bromo-5-(trifluoromethyl)benzamide (compound number II-12) are the same as in Example 1, except that N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (2) is replaced with an equimolar amount of 3-bromo-N-(prop-2-yn-1-yl)-5-(trifluoromethyl)benzamide. (Yield: 98%)

[0065] Example 6

[0066] (1) The synthesis steps of 2-methyl-N-(prop-2-yn-1-yl)-4-(trifluoromethyl)thiazol-5-carboxamide (compound number I-6) are the same as in Example 1, except that 4-trifluoromethylnicotinic acid in step (1) is replaced with an equimolar amount of 2-methyl-4-trifluoromethylthiazol-5-carboxylic acid. (Yield: 68%)

[0067] (2) The synthesis steps of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-2-methyl-4-(trifluoromethyl)thiazol-5-carboxamide (compound number II-13) are the same as in Example 1, except that N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (2) is replaced with an equimolar amount of 2-methyl-N-(prop-2-yn-1-yl)-4-(trifluoromethyl)thiazol-5-carboxamide. (Yield: 98%)

[0068] (3) The synthesis steps of ethyl 2-(4-((2-methyl-4-(trifluoromethyl)thiazolyl-5-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)acetate (chemical number II-14) are the same as in Example 1, except that N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (3) is replaced with an equimolar amount of 2-methyl-N-(prop-2-yn-1-yl)-4-(trifluoromethyl)thiazolyl-5-carboxamide. (Yield: 98%)

[0069] (4) The synthesis steps of 2-methyl-N-((1-p-toluenesulfonyl-1H-1,2,3-triazol-4-yl)methyl)-4-(trifluoromethyl)thiazol-5-carboxamide (chemical number II-15) are the same as in Example 1, except that N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (4) is replaced with an equimolar amount of 2-methyl-N-(prop-2-yn-1-yl)-4-(trifluoromethyl)thiazol-5-carboxamide. (Yield: 43%)

[0070] Example 7

[0071] (1) The synthesis steps of N-(propyn-2-yl-1-yl)-3-[4-(trifluoromethyl)phenyl]propionamide (compound number I-7) are the same as in Example 1, except that 4-trifluoromethylnicotinic acid in step (1) is replaced with an equimolar amount of 3-(4-trifluoromethylphenyl)propionic acid. (Yield: 84%)

[0072] (2) The synthesis steps of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-3-(4-(trifluoromethyl)phenyl)propionamide (compound number II-16) are the same as in Example 1, except that N-(propynyl-1-yl)-4-(trifluoromethyl)nicotinamide in step (2) is replaced with an equimolar amount of N-(propynyl-2-yl-1-yl)-3-[4-(trifluoromethyl)phenyl]propionamide. (Yield: 92%)

[0073] (3) The synthesis steps of ethyl 2-(4-((3-(4-(trifluoromethyl)phenyl)propamido)methyl)-1H-1,2,3-triazol-1-yl)acetate (chemical number II-17) are the same as in Example 1, except that N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (3) is replaced with an equimolar amount of N-(propyn-2-yl-1-yl)-3-[4-(trifluoromethyl)phenyl]propamido. (Yield: 93%)

[0074] Example 8

[0075] (1) The synthesis steps of 1-methyl-N-(propyn-2-yl-1-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide (compound number I-8) are the same as in Example 1, except that 4-trifluoromethylnicotinic acid in step (1) is replaced with an equimolar amount of 3-(trifluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid. (Yield: 98%)

[0076] (2) The synthesis of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide (compound number II-18) was performed in the same manner as in Example 1, except that N-(propynyl-1-yl)-4-(trifluoromethyl)nicotinamide in step (2) was replaced with an equimolar amount of 1-methyl-N-(propynyl-2-yl-1-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide. (Yield: 95%)

[0077] (3) The synthesis steps of ethyl 2-(4-((1-methyl-5-(trifluoromethyl)-1H-pyrazol-4-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)acetate (chemical number II-19) are the same as in Example 1, except that N-(propynyl-1-yl)-4-(trifluoromethyl)nicotinamide in step (3) is replaced with an equimolar amount of 1-methyl-N-(propynyl-2-yl-1-yl)-5-(trifluoromethyl)-1H-pyrazol-4-carboxamide. (Yield: 91%)

[0078] Example 9

[0079] (1) The synthesis steps of 3-chloro-N-(propyn-2-yl-1-yl)-5-(trifluoromethyl)nicotinamide (compound number I-9) are the same as in Example 1, except that 4-trifluoromethylnicotinic acid in step (1) is replaced with an equimolar amount of 3-chloro-5-trifluoromethylpyridine-2-carboxylic acid. (Yield: 77%)

[0080] (2) The synthesis steps of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-3-chloro-5-(trifluoromethyl)pyridineamide (compound number II-20) are the same as in Example 1, except that N-(propynyl-1-yl)-4-(trifluoromethyl)nicotinamide in step (2) is replaced with an equimolar amount of 3-chloro-N-(propynyl-2-yl-1-yl)-5-(trifluoromethyl)nicotinamide. (Yield: 89%)

[0081] (3) The synthesis steps of ethyl 2-(4-((3-chloro-5-(trifluoromethyl)pyridinamido)methyl)-1H-1,2,3-triazol-1-yl)acetate (chemical number II-21) are the same as in Example 1, except that N-(propynyl-1-yl)-4-(trifluoromethyl)nicotinamide in step (3) is replaced with an equimolar amount of 3-chloro-N-(propynyl-2-yl-1-yl)-5-(trifluoromethyl)nicotinamide. (Yield: 85%)

[0082] Example 10

[0083] (1) The synthesis steps of N-(propyn-2-yl-1-yl)imidazo[2,1-b]thiazol-6-carboxamide (compound number I-10) are the same as in Example 1, except that 4-trifluoromethylnicotinic acid in step (1) is replaced with an equimolar amount of imidazo[2,1-b]thiazol-6-carboxylic acid. (Yield: 64%)

[0084] (2) The synthesis of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)imidazo[2,1-b]thiazol-6-carboxamide (compound number II-22) was performed in the same manner as in Example 1, except that N-(propynyl-1-yl)-4-(trifluoromethyl)nicotinamide in step (2) was replaced with an equimolar amount of N-(propynyl-2-yl-1-yl)imidazo[2,1-b]thiazol-6-carboxamide. (Yield: 95%)

[0085] (3) The synthesis steps of ethyl 2-(4-((imidazo[2,1-b]thiazo-6-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)acetate (chemical number II-23) are the same as in Example 1, except that N-(propynyl-1-yl)-4-(trifluoromethyl)nicotinamide in step (3) is replaced with an equimolar amount of N-(propynyl-2-yl-1-yl)imidazo[2,1-b]thiazo-6-carboxamide. (Yield: 86%)

[0086] Example 11

[0087] Synthesis of 5-(2,4-dichlorophenyl)-2H-1,2,3-triazol-4-carboxynitrile (compound number III-1): In a 50 mL round-bottom flask, 2,4-dichlorobenzaldehyde (5 mmol, 0.875 g), sodium azide (7.5 mmol, 0.488 g), and benzenesulfonylacetonitrile (6 mmol, 1 g) were added, followed by 15 mL of distilled water. The mixture was refluxed for 3-5 h, and the reaction progress was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature and transferred to 60 mL of ice water. A solid precipitated out. The solid was filtered, and the filter cake was washed with 5-10 mL of water to obtain the crude product. After drying, the crude product was recrystallized from the methanol-water mixture or by silica gel column chromatography using a petroleum ether-ethyl acetate mixture (PE:EA = 3:1) as the eluent to obtain product III-1 (yield: 48%).

[0088] Example 12

[0089] The synthesis steps for 5-(4-methoxyphenyl)-2H-1,2,3-triazole-4-carboxynitrile (compound number III-2) were the same as in Example 11, except that 2,4-dichlorobenzaldehyde was replaced with an equimolar amount of 4-methoxybenzaldehyde.

[0090] (Yield: 46%)

[0091] Example 13

[0092] The synthesis steps for 5-(4-phenoxyphenyl)-2H-1,2,3-triazole-4-carboxynitrile (compound number III-3) were the same as in Example 11, except that 2,4-dichlorobenzaldehyde was replaced with an equimolar amount of 4-phenoxybenzaldehyde.

[0093] (Yield: 42%)

[0094] Example 14

[0095] The synthesis of 5-(4-hydroxyphenyl)-2H-1,2,3-triazol-4-carboxynitrile (compound number III-4) was performed in the same manner as in Example 11, except that 2,4-dichlorobenzaldehyde was replaced with an equimolar amount of p-hydroxybenzaldehyde. (Yield: 74%)

[0096] Example 15

[0097] The synthesis of 5-(p-tolyl)-2H-1,2,3-triazol-4-carboxynitrile (compound number III-5) was performed in the same manner as in Example 11, except that 2,4-dichlorobenzaldehyde was replaced with an equimolar amount of p-methylbenzaldehyde. (Yield: 48%)

[0098] Example 16

[0099] The synthesis of 5-(4-(dimethylamino)phenyl)-2H-1,2,3-triazol-4-carboxynitrile (compound number III-6) was performed in the same manner as in Example 11, except that 2,4-dichlorobenzaldehyde was replaced with an equimolar amount of 4-dimethylaminobenzaldehyde. (Yield: 92%)

[0100] Example 17

[0101] The synthesis of 5-(4-bromophenyl)-2H-1,2,3-triazol-4-carboxynitrile (compound number III-7) was performed in the same manner as in Example 11, except that 2,4-dichlorobenzaldehyde was replaced with an equimolar amount of 4-bromobenzaldehyde. (Yield: 73%)

[0102] Example 18

[0103] The synthesis of 5-(2-bromo-4-fluorophenyl)-2H-1,2,3-triazol-4-carboxynitrile (compound number III-8) was performed in the same manner as in Example 11, except that 2,4-dichlorobenzaldehyde was replaced with an equimolar amount of 2-bromo-4-fluorobenzaldehyde. (Yield: 64%)

[0104] Example 19

[0105] The synthesis of 5-(3,4,5-trifluorophenyl)-2H-1,2,3-triazol-4-carboxynitrile (compound number III-9) was performed in the same manner as in Example 11, except that 2,4-dichlorobenzaldehyde was replaced with an equimolar amount of 3,4,5-trifluorobenzaldehyde. (Yield: 93%)

[0106] Example 20

[0107] The synthesis of 5-(3-methoxy-4-hydroxyphenyl)-2H-1,2,3-triazol-4-carboxynitrile (compound number III-10) was performed in the same manner as in Example 11, except that 2,4-dichlorobenzaldehyde was replaced with an equimolar amount of 3-methoxy-4-hydroxybenzaldehyde. (Yield: 90%)

[0108] Example 21

[0109] The synthesis of 5-(2-bromophenyl)-2H-1,2,3-triazol-4-carboxynitrile (compound number III-11) was performed in the same manner as in Example 11, except that 2,4-dichlorobenzaldehyde was replaced with an equimolar amount of 2-bromobenzaldehyde. (Yield: 98%)

[0110] Example 22

[0111] The synthesis of 5-(4-chlorophenyl)-2H-1,2,3-triazol-4-carboxynitrile (compound number III-12) was performed in the same manner as in Example 11, except that 2,4-dichlorobenzaldehyde was replaced with an equimolar amount of 4-chlorobenzaldehyde. (Yield: 96%)

[0112] Example 23

[0113] The synthesis steps for 5-(2-chloro-4-fluorophenyl)-2H-1,2,3-triazol-4-carboxynitrile (compound number III-13) were the same as in Example 11, except that 2,4-dichlorobenzaldehyde was replaced with an equimolar amount of 2-chloro-4-fluorobenzaldehyde.

[0114] (Yield: 90%)

[0115] Example 24

[0116] The synthesis of 5-(2-chlorophenyl)-2H-1,2,3-triazol-4-carboxynitrile (compound number III-14) was performed in the same manner as in Example 11, except that 2,4-dichlorobenzaldehyde was replaced with an equimolar amount of 2-chlorobenzaldehyde. (Yield: 92%)

[0117] Example 25

[0118] The synthesis of 5-phenyl-2H-1,2,3-triazol-4-carboxynitrile (compound number III-15) was performed in the same manner as in Example 11, except that 2,4-dichlorobenzaldehyde was replaced with an equimolar amount of benzaldehyde. (Yield: 87%)

[0119] Example 26

[0120] The synthesis of 5-(2-nitrophenyl)-2H-1,2,3-triazol-4-carboxynitrile (compound number III-16) was performed in the same manner as in Example 11, except that 2,4-dichlorobenzaldehyde was replaced with an equimolar amount of m-nitrobenzaldehyde. (Yield: 76%)

[0121] Example 27

[0122] The synthesis of 5-furan-2H-1,2,3-triazol-4-carboxynitrile (compound number III-17) was performed in the same manner as in Example 11, except that 2,4-dichlorobenzaldehyde was replaced with an equimolar amount of furanaldehyde. (Yield: 71%)

[0123] The physicochemical properties and mass spectrometry data of the compounds synthesized in Examples 1–27 are shown in Table 1.

[0124] Table 1 Physicochemical properties and mass spectrometry analysis data of the target compound

[0125]

[0126]

[0127]

[0128]

[0129]

[0130]

[0131]

[0132] Experimental Example 1

[0133] The insecticidal activity of some compounds of formula (I) against whiteflies:

[0134] The prepared insecticide was diluted with distilled water to produce 5-7 consecutive dilutions. Cotton leaf discs (3.5 cm in diameter) were cut open and immersed in these insecticide dilutions for 10 seconds. After drying, the discs were placed individually on 1% agar in plastic petri dishes (3.5 cm in diameter). Discs immersed in distilled water were used as controls. Twenty-five adult female whiteflies were placed on each treated cotton leaf disc. For each dilution, 75 adult females were treated. All tests were conducted at 25°C, and mortality rates were recorded after 24 h, 48 h, and 72 h.

[0135]

[0136] Where T represents the mortality rate of the tested compound group, and C represents the mortality rate of the blank control group (T and C are expressed as percentages). If the mortality rate of the blank control is >20%, the experiment should be repeated. The insecticidal activity data of some compounds in Formula I against whiteflies are shown in Table 2.

[0137] Table 2 shows the insecticidal activity of some compounds of formula (I) against whiteflies (100 mg / L, 10 mg / L, 1 mg / L).

[0138] Table 2: Insecticidal activity of some compounds in intermediate (I) against whiteflies

[0139]

[0140]

[0141] Table 2 shows that the compound of formula (I) provided by this invention has moderate to good insecticidal activity against the tested whiteflies. At a concentration of 100 mg / L, after 72 hours of treatment with the compound, the growth and development of whiteflies were significantly hindered, exhibiting symptoms such as body shrinkage, cuticle wrinkling, and abnormal molting. Compound I-7 has an insecticidal activity of over 70% against whiteflies and shows promise as an insecticide for controlling the agricultural pest whitefly.

[0142] Table 3. Insecticidal activity of some compounds of formula (II) against whiteflies (100 mg / L, 10 mg / L, 1 mg / L)

[0143]

[0144]

[0145] Table 3 shows that the compounds of formula (II) provided in this invention have moderate to good insecticidal activity against the tested whiteflies. At a concentration of 100 mg / L, after 72 hours of treatment with the compounds, the growth and development of whiteflies were significantly hindered, exhibiting symptoms such as body shrinkage, cuticle wrinkling, and abnormal molting. The three compounds, II-5, II-7, and II-23, showed insecticidal activity exceeding 50% against whiteflies, demonstrating promise as insecticides for controlling the agricultural pest, the whitefly.

[0146] Table 4: LC50 of some compounds against whiteflies 50 test

[0147] compound <![CDATA[LC 50 (95%CL)]]> Slope±SE <![CDATA[χ 2 (df)]]> Flonicamid 57.25(38.28-73.25) 1.044±0.142 36.66(21) I-5 69.81(43.58-82.26) 0.689±0.111 27.47(21) I-6 186.3(160.1-215.2) 0.866±0.131 29.50(21) I-7 91.91(81.52-102.5) 0.628±0.114 33.51(21) II-7 112.4(106.5-129.1) 0.568±0.094 30.86(21)

[0148] From Table 4 LC 50 The test results show that compound I-5 has insecticidal activity similar to that of the commercial pesticide control flupyradifurone.

[0149] Experimental Example 2

[0150] The insecticidal activity of some compounds in formula (I) against peach aphids:

[0151] Table 5. Insecticidal activity of some compounds of formula (I) against peach aphids (10 mg / L, 1 mg / L)

[0152]

[0153] Table 5 shows that the partial formula (I) compound provided by this invention has certain insecticidal activity against the tested peach aphid. At a concentration of 10 mg / L, the growth and development of peach aphids were significantly inhibited after 72 hours of treatment with the compound. Compound I-1 has an insecticidal activity of over 50% against peach aphids and shows promise as an insecticide for controlling the agricultural pest peach aphid.

[0154] Table 6. Insecticidal activity of some compounds of formula (II) against peach aphids (10 mg / L, 1 mg / L)

[0155]

[0156]

[0157] Table 6 shows that some of the compounds of formula (II) provided in this invention have certain insecticidal activity against the tested peach aphids. At a concentration of 10 mg / L, the growth and development of peach aphids were somewhat hindered 72 hours after treatment with the compounds. Compounds II-16 and II-14 have insecticidal activity exceeding 50% against peach aphids, showing promise as insecticides for controlling the agricultural pest, peach aphid.

[0158] Table 7: LC50 of some compounds against peach aphid 50 test

[0159] compound <![CDATA[LC 50 (95%CL)]]> Slope±SE <![CDATA[χ 2 (df)]]> Flonicamid 5.079(3.566-6.803) 1.895±0.228 2.988(4) I-1 5.308(2.597-8.024) 1.119±0.235 1.705(3) II-16 5.428(2.997-8.575) 1.494±0.204 5.245(4) II-14 4.674(3.505-5.973) 1.822±0.226 1.048(4)

[0160] From Table 7 LC 50 The test results show that compounds I-1, II-16, and II-14 have insecticidal activity comparable to that of the commercial pesticide control flupyradifurone, with compound II-14 even showing better activity than the control.

[0161] Experimental Example 3

[0162] The insecticidal activity of some compounds in formula (I) against spider mites:

[0163] Table 8: Insecticidal activity of some compounds of formula (I) against spider mites (10 mg / L, 1 mg / L)

[0164]

[0165] Table 8 shows that the compound of formula (I) provided by this invention, at a concentration of 10 mg / L, exhibits certain insecticidal activity against the tested spider mites after 72 hours of treatment. It shows promise as an insecticide for controlling the agricultural pest, the peach aphid.

[0166] Table 9. Insecticidal activity of some compounds of formula (II) against spider mites (10 mg / L, 1 mg / L)

[0167]

[0168]

[0169] Table 9 shows that the compound of formula (II) provided by this invention, at a concentration of 10 mg / L, exhibits certain insecticidal activity against the tested spider mites after 72 hours of treatment. It shows promise as an insecticide for controlling the agricultural pest spider mite.

[0170] Test Example 4

[0171] In vitro activity assays of the compound represented by formula (III) against four fungi:

[0172] Four types of fungi: Phytophthora, Aureobasidium, Fusarium, and Botrytis.

[0173] Specific procedures: Dissolve the synthesized drug (compound) in 1% DMSO, then add an aqueous solution containing 1% Tween 80 to prepare a 100 mg / L solution of the original drug. Under aseptic conditions, take an appropriate amount of the prepared original drug into each conical flask, shake thoroughly, and then pour equal amounts into three 9 cm diameter petri dishes. A blank control (treatment without the drug) is included in the above experiment, and each treatment is repeated three times. Using a 6.5 mm diameter punch, cut a mycelial cake along the edge of the cultured pathogen on a clean bench. Inoculate the mycelial cake onto the center of the drug-containing plate with the mycelial side facing up. Cover the plate and seal it with sealing film to prevent contamination. Place the petri dish in a 25°C incubator. When the diameter of the control colony exceeds 6 cm, measure the colony diameter using the cross-sectional method, take the average value, and calculate the inhibition rate.

[0174] The calculation formula is: Antibacterial rate I = (D0 - D) t ) / D0×100%

[0175] D0 is the average diameter of hyphae in the control plate, and Dt is the average diameter of hyphae in the sample plate.

[0176] The activity data of the compound shown in formula (III) against four fungi are shown in Table 10.

[0177] Table 10: Fungicidal activity of compound (III) against four fungi (100 mg / L)

[0178]

[0179] As shown in Table 10, the compounds of formula (III) provided by this invention exhibit moderate to excellent fungicidal activity against four fungi—Phytophthora, Acorus graminearum, Fusarium graminearum, and Botrytis cinerea—at a concentration of 100 mg / L. Compound III-3 showed fungicidal activity of 91.43% and 70.00% against Phytophthora and Fusarium graminearum, respectively; Compound III-1 showed fungicidal activity of 98.19% and 100.00% against Acorus graminearum and Botrytis cinerea, respectively; and at a concentration of 100 mg / L, Compound III-7 achieved 100.00% fungicidal activity against Acorus graminearum. These compounds all show promise as fungicides for controlling agricultural fungal diseases.

[0180] Finally, it should be reiterated that the above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. Use of a triazole compound, characterized in that Specifically, the application relates to the insecticidal application of an amide triazole compound to a whitefly, wherein the compound is selected from II-1, II-2, II-4, II-16, II-7, II-10, II-14, II-5, II-8, II-11, II-15, II-17, II-19, II-20, II-21, II-22 and II-23. II-1 is N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-4-(trifluoromethyl)nicotinamide, II-2 is ethyl-2-(4-((4-(trifluoromethyl)nicotinamido)methyl)-1H-1,2,3-triazol-1-yl)acetate, II-4 is N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-5-(trifluoromethyl)nicotinamide, II-5 is ethyl-2-(4-((5-(trifluoromethyl)nicotinamido)methyl)-1H-1,2,3-triazol-1-yl)acetate, II-7 is ethyl 2-(4-((2-(trifluoromethyl)benzamido)methyl)-1H-1,2,3-triazol-1-yl)acetate, II-8 is N-((1-p-toluenesulfonyl-1H-1,2,3-triazol-4-yl)methyl)-2-(trifluoromethyl)benzamide, II-10 is ethyl 2-(4-((6-methylpyrazine-2-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)acetate, II-11 is 6-methyl-N-((1-p-toluenesulfonyl-1H-1,2,3-triazol-4-yl)methyl)pyrazine-2-carboxamide, II-13 is N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-2-methyl-4-(trifluoromethyl)thiazole-5-carboxamide, II-14 is ethyl 2-(4-((2-methyl-4-(trifluoromethyl)thiazole-5-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)acetate, II-15 is 2-methyl-N-((1-p-toluenesulfonyl-1H-1,2,3-triazol-4-yl)methyl)-4-(trifluoromethyl)thiazole-5-carboxamide, II-16 is N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-3-(4-(trifluoromethyl)phenyl)propanamide, II-17 is ethyl 2-(4-((3-(4-(trifluoromethyl)phenyl)propanamido)methyl)-1H-1,2,3-triazol-1-yl)acetate, II-19 is ethyl 2-(4-((1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)acetate, II-20 is N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-3-chloro-5-(trifluoromethyl)picolinamide, II-21 is ethyl 2-(4-((3-chloro-5-(trifluoromethyl)picolinamido)methyl)-1H-1,2,3-triazol-1-yl)acetate, II-22 is N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)imidazo[2,1-b]thiazole-6-carboxamide, II-23 is ethyl 2-(4-((imidazo[2,1-b]thiazole-6-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)acetate.

2. Use of a triazole compound, characterized in that Specifically, the application relates to the application of an amide triazole compound to peach aphids, wherein the compound is selected from II-16, II-14, II-11, II-15, II-17 and II-19, and the specific compound names are as shown in claim 1.

3. Use of a triazole compound, characterized in that Specifically, the application relates to the application of an amide triazole compound to spider mites, wherein the compound is selected from II-1, II-2, II-4, II-16, II-5, II-10, II-14, II-8, II-11, II-15, II-17, II-19, II-20, II-21, II-22 and II-23, and the specific compound names are as shown in claim 1.

4. Use of a triazole compound, characterized in that Specifically, the application relates to the application of a cyano triazole compound to phytophthora, alternaria, sclerotinia and botrytis, wherein the compound is selected from III-1, III-2, III-3, III-4, III-5, III-6, III-7, III-8, III-9, III-10, III-11, III-12, III-13, III-14, III-15, III-16 and III-17, III-1 is 5-(2,4-dichlorophenyl)-2H-1,2,3-triazole-4-carbonitrile, III-2 is 5-(4-methoxyphenyl)-2H-1,2,3-triazole-4-carbonitrile, III-3 is 5-(4-phenoxyphenyl)-2H-1,2,3-triazole-4-carbonitrile, III-4 is 5-(4-hydroxyphenyl)-2H-1,2,3-triazole-4-carbonitrile, III-5 is 5-(p-tolyl)-2H-1,2,3-triazole-4-carbonitrile, III-6 is 5-(4-(dimethylamino)phenyl)-2H-1,2,3-triazole-4-carbonitrile, III-7 is 5-(4-bromophenyl)-2H-1,2,3-triazole-4-carbonitrile, III-8 is 5-(2-bromo-4-fluorophenyl)-2H-1,2,3-triazole-4-carbonitrile, III-9 is 5-(3,4,5-trifluorophenyl)-2H-1,2,3-triazole-4-carbonitrile, III-10 is 5-(3-methoxy-4-hydroxyphenyl)-2H-1,2,3-triazole-4-carbonitrile, III-11 is 5-(2-bromophenyl)-2H-1,2,3-triazole-4-carbonitrile, III-12 is 5-(4-chlorophenyl)-2H-1,2,3-triazole-4-carbonitrile, III-13 is 5-(2-chloro-4-fluorophenyl)-2H-1,2,3-triazole-4-carbonitrile, III-14 is 5-(2-chlorophenyl)-2H-1,2,3-triazole-4-carbonitrile, III-15 is 5-phenyl-2H-1,2,3-triazole-4-carbonitrile, III-16 is 5-(2-nitrophenyl)-2H-1,2,3-triazole-4-carbonitrile and III-17 is 5-furan-2H-1,2,3-triazole-4-carbonitrile.

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