Triazole-containing compound as well as synthesis method and application thereof

Abstract

The invention provides a triazole-containing compound as well as a synthesis method and application thereof, and belongs to the field of pesticides. The method comprises the following steps: taking heterocyclic molecules with carboxyl functional groups as raw materials, carrying out amidation reaction on the heterocyclic molecules and aminoacetylene to generate an intermediate as shown in a formula (I), and reacting the intermediate (I) with an azide to obtain the amide-containing triazole compound as shown in a formula (II), substituted benzaldehyde, sodium azide and 2-(benzenesulfonyl) acetonitrile are used as raw materials to react to generate the cyano-containing triazole compound as shown in a formula (III). The method disclosed by the invention is simple to operate, relatively mild in condition and high in functional group tolerance. The prepared intermediate and the final product have certain insecticidal and bactericidal activity, and have potential application prospects.

Description

Technical Field

[0001] The present invention relates to the field of pesticides, and in particular to triazole compounds, synthesis methods and applications thereof. Background Art

[0002] The outbreak of crop diseases and pests poses a serious threat to food security. The global losses caused by diseases and pests account for about 40% of the total crop losses each year, of which the losses caused by diseases and pests account for 14% of the total losses. There are many kinds of pests in agricultural production, and Hemiptera stinging insects have become one of the main threats to my country's crops. With the extensive use of pesticides, some pests have also developed resistance, the dosage has increased, and the impact on the environment has also increased dramatically. The creation of new pesticides is urgent. Heterocyclic compounds are more effective due to their similarity to certain parts of organisms (such as pyrimidines or amino acids). For this reason, fluorine-containing and heterocyclic compounds have become the target of new pesticide creation. According to incomplete statistics. Among the new pesticides developed in the 1990s, about 70% were fluorine-containing or heterocyclic pesticides, and 5% were both fluorine-containing and heterocyclic pesticides. Fluorine-containing and heterocyclic pesticides will still be the main direction of research on chemical pesticides.

[0003] In summary, the present invention adopts the method of bioisostericity and active substructure splicing to develop a new series of triazole compounds and conduct insecticidal and fungicidal activity tests. In the future, with the continuous advancement and innovation of technology, this type of pesticide will provide a more efficient and environmentally friendly solution for agricultural production. Summary of the invention

[0004] In order to solve the above problems, the present invention provides a series of synthesis methods containing triazole compounds, which can be prepared with high yield and high purity, and the method is simple, safe and environmentally friendly.

[0005] In order to achieve the above object, the present invention adopts the following technical solution:

[0006] The triazole compounds include amide triazole compounds of formula (II) and cyano triazole compounds of formula (III), and the structural formula is as follows:

[0007]

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

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

[0010] S1, adding a heterocyclic compound 1 having a carboxyl functional group and aminoacetylene 2 to a solvent, reacting them under the action of a condensing agent, and separating and purifying the fully reacted solution with an eluent to obtain an intermediate of formula (I);

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

[0012]

[0013] S3, adding a substituted benzaldehyde 4 with a cyano functional group, sodium azide 5 and 2-(phenylsulfonyl)acetonitrile 6 into a solvent for sufficient reaction to obtain a triazole compound containing a cyano functional group as shown in formula (III), and the reaction equation is:

[0014]

[0015] Furthermore, the condensing agent in step S1 is one or two of dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI), 4-dimethylaminopyridine (DMAP), 1-hydroxybenzotriazole (HOBT), carbonyldiimidazole (CDI), triethylamine (TEA), diphenylphosphoryl chloride (DPP-Cl), diethyl cyanophosphate (DECP), diphenylphosphoryl azide (DPPA), and thiodimethylphosphoryl azide (MPTA).

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

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

[0018] Furthermore, in step S1, the concentration of compound 1 in the solvent 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 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 reaction temperature of 0-60° C. and reaction time of 0.25-3 h.

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

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

[0025] Furthermore, the solvent 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 sufficient reaction in step S3 are reaction temperature of 0-100° C. and reaction time of 3-24 h.

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

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

[0030] Furthermore, the solvent 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 fully reacted solution is separated and purified, and the volume ratio of the eluent used is petroleum ether and ethyl acetate (1-10):1.

[0032] The insecticidal application of intermediate formula (I) and triazole compound formula (II) to whitefly, peach aphid and spider mite; the fungicidal application of compound formula (III) to Phytophthora, red star pathogen, fusarium and gray mold

[0033] Beneficial effects of the present invention:

[0034] 1. The present invention adopts the method of bioisostericity and active substructure splicing, uses aminoacetylene compounds as raw materials, and carries out amide reaction with heterocyclic molecules with carboxyl groups to obtain the structure shown in the intermediate formula (I), and then uses the intermediate (I) as a raw material to carry out click reaction with azide compounds to generate amide compounds with triazole structure (II). The reaction is simple to operate, the conditions are relatively mild, the functional group tolerance is strong, and the reaction only needs to add a certain amount of raw materials, catalysts and solvents. It has high step economy, and the atomic utilization rate reaches 80-100%, which is a typical example of green synthesis. At the same time, the prepared nitrogen-containing heterocyclic amide compound formula (II) enriches the molecular library of such compounds.

[0035] 2. The present invention adopts the method of bioisostericity and active substructure splicing, uses sodium azide and 2-(phenylsulfonyl)acetonitrile as raw materials, and reacts with substituted benzaldehyde to obtain the structure shown in formula (III). The reaction is simple to operate, the conditions are relatively mild, the functional group tolerance is strong, no catalyst is required, and distilled water is used as solvent, and only a certain amount of raw materials need to be added. The reaction has high step economy, and the atomic utilization rate reaches 40-98%, which is a typical example of green synthesis. At the same time, the prepared cyano triazole compound formula (III) enriches the molecular library of such compounds.

[0036] 3. The intermediate (I) and the amide-containing triazole compound (II) prepared by the present invention were tested for insecticidal activity. The intermediate (I) and the amide-containing triazole compound (II) both showed certain insecticidal activity against the pest Bemisia tabaci. Among them, the LC of intermediates I-5, I-6, I-7 and the amide-containing triazole compound II-7 against Bemisia tabaci was 50 The LC values ​​of compounds I-1, II-16 and II-14 against green peach aphid were 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 cyanotriazole compounds shown in the compound formula (III) prepared by the present invention were tested for fungicidal activity. The cyanotriazole compounds showed certain fungicidal activity against four fungi, namely, Phytophthora, Alternaria alternata, Gibberella fusiformis and Botrytis cinerea. The fungicidal activity of compound III-3 against Phytophthora and Gibberella fusiformis reached 91.43% and 70.00%, respectively; compound III-1 showed fungicidal activity of 98.19% and 100.00% against Alternaria alternata and Botrytis cinerea, respectively; at a concentration of 100 mg / L, the fungicidal activity of compound III-7 against Alternaria alternata reached 100.00%. DETAILED DESCRIPTION

[0038] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments 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 creative work are within the scope of protection of the present invention.

[0039] The reagents or instruments used without indicating the manufacturer are all conventional products that can be purchased through regular channels. Unless otherwise specified, the 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, 10 mL of dichloromethane was added, and the mixture was stirred for 15-30 minutes under an ice bath, 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 completed, the product was extracted and purified by column chromatography. The ratio of the developing solvent was DCM:MeOH=50:1, and I-1 was obtained (yield: 89%).

[0042] (2) Synthesis of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-4-(trifluoromethyl)nicotinamide (chemical number II-1): Under air atmosphere, the 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. The developing solvent ratio DCM:MeOH was 30:1 to obtain II-1 (yield: 98%).

[0043] (3) The synthesis steps of ethyl-2-(4-((4-(trifluoromethyl)nicotinamido)methyl)-1H-1,2,3-triazol-1-yl)acetate (compound number II-2) are the same as those in Example 1, except that the benzyl azide in step (2) is replaced by an equimolar amount of ethyl azidoacetate. (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 those in Example 1, except that the benzyl azide in step (2) is replaced by 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 those of Example 1, except that 4-trifluoromethylnicotinic acid in step (1) is replaced by an equal molar 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 those in Example 1, except that the N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (2) is replaced by 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)nicotinamido)methyl)-1H-1,2,3-triazol-1-yl)acetate (compound number II-5) are the same as those in Example 1, except that N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (3) is replaced by 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 those of Example 1, except that 4-trifluoromethylnicotinic acid in step (1) is replaced by 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 those in Example 1, except that the N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (2) is replaced by 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 those in Example 1, except that N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (3) is replaced by an equimolar amount of N-(prop-2-ynyl)-2-(trifluoromethyl)benzamide.

[0054] (Yield: 100%).

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

[0056] (Yield: 41%).

[0057] Example 4

[0058] (1) The synthesis steps of 6-methyl-N-(prop-2-yn-1-yl)pyrazine-2-carboxamide (compound number I-4) are the same as those in Example 1, except that 4-trifluoromethylnicotinic acid in step (1) is replaced by an equal molar amount of 6-methylpyrazine-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 those in Example 1, except that the N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (2) is replaced by an equal molar 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-methylpyrazine-2-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)acetate (chemical number II-10) are the same as those in Example 1, except that N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (3) is replaced by an equal molar amount of 6-methyl-N-(prop-2-yn-1-yl)pyrazine-2-carboxamide. (Yield: 100%).

[0061] (4) The synthesis steps of 6-methyl-N-((1-toluenesulfonyl-1H-1,2,3-triazol-4-yl)methyl)pyrazine-2-carboxamide (chemical number II-11) are the same as those in Example 1, except that N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (4) is replaced by an equal molar 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 those in Example 1, except that 4-trifluoromethylnicotinic acid in step (1) is replaced by an equal molar 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 those in Example 1, except that the N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (2) is replaced by an equal molar 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)thiazole-5-carboxamide (compound number I-6) are the same as those in Example 1, except that 4-trifluoromethylnicotinic acid in step (1) is replaced by an equal molar amount of 2-methyl-4-trifluoromethylthiazole-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)thiazole-5-carboxamide (compound number II-13) are the same as those in Example 1, except that the N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (2) is replaced by an equal molar amount of 2-methyl-N-(prop-2-yn-1-yl)-4-(trifluoromethyl)thiazole-5-carboxamide. (Yield: 98%).

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

[0069] (4) The synthesis steps of 2-methyl-N-((1-toluenesulfonyl-1H-1,2,3-triazol-4-yl)methyl)-4-(trifluoromethyl)thiazole-5-carboxamide (chemical number II-15) are the same as those in Example 1, except that N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (4) is replaced by an equal molar amount of 2-methyl-N-(prop-2-yn-1-yl)-4-(trifluoromethyl)thiazole-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 those in Example 1, except that 4-trifluoromethylnicotinic acid in step (1) is replaced by an equal molar 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)propanamide (compound number II-16) are the same as those in Example 1, except that the N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (2) is replaced by an equimolar amount of N-(propyn-2-yl-1-yl)-3-[4-(trifluoromethyl)phenyl]propanamide. (Yield: 92%).

[0073] (3) The synthesis steps of ethyl 2-(4-((3-(4-(trifluoromethyl)phenyl)propionamido)methyl)-1H-1,2,3-triazol-1-yl)acetate (chemical number II-17) are the same as those in Example 1, except that the N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (3) is replaced by an equimolar amount of N-(propyn-2-yl-1-yl)-3-[4-(trifluoromethyl)phenyl]propionamide. (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 those of Example 1, except that 4-trifluoromethylnicotinic acid in step (1) is replaced by an equal molar amount of 3-(trifluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid. (Yield: 98%).

[0076] (2) The synthesis steps of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide (compound number II-18) are the same as those in Example 1, except that the N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (2) is replaced by an equal molar amount of 1-methyl-N-(propyn-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-pyrazole-4-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)acetate (chemical number II-19) are the same as those in Example 1, except that N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (3) is replaced by an equal molar amount of 1-methyl-N-(propyn-2-yl-1-yl)-5-(trifluoromethyl)-1H-pyrazole-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 those in Example 1, except that 4-trifluoromethylnicotinic acid in step (1) is replaced by an equal molar 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)picolinamide (compound number II-20) are the same as those in Example 1, except that the N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (2) is replaced by an equal molar amount of 3-chloro-N-(propyn-2-yl-1-yl)-5-(trifluoromethyl)nicotinamide. (Yield: 89%).

[0081] (3) The synthesis steps of ethyl 2-(4-((3-chloro-5-(trifluoromethyl)pyridinylamido)methyl)-1H-1,2,3-triazol-1-yl)acetate (chemical number II-21) are the same as those in Example 1, except that the N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (3) is replaced by an equal molar amount of 3-chloro-N-(propyn-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]thiazole-6-carboxamide (compound number I-10) are the same as those in Example 1, except that 4-trifluoromethylnicotinic acid in step (1) is replaced by an equal molar amount of imidazo[2,1-b]thiazole-6-carboxylic acid. (Yield: 64%).

[0084] (2) The synthesis steps of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)imidazo[2,1-b]thiazole-6-carboxamide (compound number II-22) are the same as those in Example 1, except that the N-(prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide in step (2) is replaced by an equimolar amount of N-(propyn-2-yl-1-yl)imidazo[2,1-b]thiazole-6-carboxamide. (Yield: 95%).

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

[0086] Embodiment 11

[0087] Synthesis of 5-(2,4-dichlorophenyl)-2H-1,2,3-triazole-4-carbonitrile (compound number III-1): In a 50mL round-bottom flask, add 2,4-dichlorobenzaldehyde (5mmol, 0.875g), sodium azide (7.5mmol, 0.488g), benzenesulfonyl acetonitrile (6mmol, 1g), add 15mL distilled water, reflux for 3-5h, and monitor the reaction progress by TLC. After the reaction is completed, cool to room temperature, transfer the reaction solution into 60mL of ice water, solid precipitates, filter, wash the filter cake with 5-10mL of water to obtain a crude product, dry and recrystallize with a methanol-water mixed solvent or a petroleum ether-ethyl acetate (PE:EA=3:1) mixed solvent as the eluent, and obtain the product III-1 by silica gel column chromatography. (Yield: 48%).

[0088] Example 12

[0089] The synthesis steps of 5-(4-methoxyphenyl)-2H-1,2,3-triazole-4-carbonitrile (compound number III-2) are the same as those in Example 11, except that 2,4-dichlorobenzaldehyde is replaced with an equal molar amount of 4-methoxybenzaldehyde.

[0090] (Yield: 46%).

[0091] Example 13

[0092] The synthesis steps of 5-(4-phenoxyphenyl)-2H-1,2,3-triazole-4-carbonitrile (compound number III-3) are the same as those of Example 11, except that 2,4-dichlorobenzaldehyde is replaced with an equal molar amount of 4-phenoxybenzaldehyde.

[0093] (Yield: 42%).

[0094] Embodiment 14

[0095] The synthesis steps of 5-(4-hydroxyphenyl)-2H-1,2,3-triazole-4-carbonitrile (compound number III-4) are the same as those of Example 11, except that 2,4-dichlorobenzaldehyde is replaced with an equal molar amount of p-hydroxybenzaldehyde. (Yield: 74%).

[0096] Embodiment 15

[0097] The synthesis steps of 5-(p-tolyl)-2H-1,2,3-triazole-4-carbonitrile (compound number III-5) are the same as those of Example 11, except that 2,4-dichlorobenzaldehyde is replaced with an equal molar amount of p-tolualdehyde (yield: 48%).

[0098] Example 16

[0099] The synthesis steps of 5-(4-(dimethylamino)phenyl)-2H-1,2,3-triazole-4-carbonitrile (compound number III-6) are the same as those of Example 11, except that 2,4-dichlorobenzaldehyde is replaced with an equal molar amount of 4-dimethylaminobenzaldehyde. (Yield: 92%).

[0100] Embodiment 17

[0101] The synthesis steps of 5-(4-bromophenyl)-2H-1,2,3-triazole-4-carbonitrile (compound number III-7) are the same as those of Example 11, except that 2,4-dichlorobenzaldehyde is replaced with an equal molar amount of 4-bromobenzaldehyde. (Yield: 73%).

[0102] Embodiment 18

[0103] The synthesis steps of 5-(2-bromo-4-fluorophenyl)-2H-1,2,3-triazole-4-carbonitrile (compound number III-8) are the same as those of Example 11, except that 2,4-dichlorobenzaldehyde is replaced with an equal molar amount of 2-bromo-4-fluorobenzaldehyde. (Yield: 64%).

[0104] Embodiment 19

[0105] The synthesis steps of 5-(3,4,5-trifluorophenyl)-2H-1,2,3-triazole-4-carbonitrile (compound number III-9) are the same as those of Example 11, except that 2,4-dichlorobenzaldehyde is replaced with an equal molar amount of 3,4,5-trifluorobenzaldehyde. (Yield: 93%).

[0106] Embodiment 20

[0107] The synthesis steps of 5-(3-methoxy-4-hydroxyphenyl)-2H-1,2,3-triazole-4-carbonitrile (compound number III-10) are the same as those of Example 11, except that 2,4-dichlorobenzaldehyde is replaced with an equal molar amount of 3-methoxy-4-hydroxybenzaldehyde. (Yield: 90%).

[0108] Embodiment 21

[0109] The synthesis steps of 5-(2-bromophenyl)-2H-1,2,3-triazole-4-carbonitrile (compound number III-11) are the same as those of Example 11, except that 2,4-dichlorobenzaldehyde is replaced with an equal molar amount of 2-bromobenzaldehyde. (Yield: 98%).

[0110] Embodiment 22

[0111] The synthesis steps of 5-(4-chlorophenyl)-2H-1,2,3-triazole-4-carbonitrile (compound number III-12) are the same as those of Example 11, except that 2,4-dichlorobenzaldehyde is replaced with an equal molar amount of 4-chlorobenzaldehyde. (Yield: 96%).

[0112] Embodiment 23

[0113] The synthesis steps of 5-(2-chloro-4-fluorophenyl)-2H-1,2,3-triazole-4-carbonitrile (compound number III-13) are the same as those in Example 11, except that 2,4-dichlorobenzaldehyde is replaced with an equal molar amount of 2-chloro-4-fluorobenzaldehyde.

[0114] (Yield: 90%).

[0115] Embodiment 24

[0116] The synthesis steps of 5-(2-chlorophenyl)-2H-1,2,3-triazole-4-carbonitrile (compound number III-14) are the same as those of Example 11, except that 2,4-dichlorobenzaldehyde is replaced with an equal molar amount of 2-chlorobenzaldehyde. (Yield: 92%).

[0117] Embodiment 25

[0118] The synthesis steps of 5-phenyl-2H-1,2,3-triazole-4-carbonitrile (compound number III-15) are the same as those of Example 11, except that 2,4-dichlorobenzaldehyde is replaced with an equal molar amount of benzaldehyde (yield: 87%).

[0119] Embodiment 26

[0120] The synthesis steps of 5-(2-nitrophenyl)-2H-1,2,3-triazole-4-carbonitrile (compound number III-16) are the same as those of Example 11, except that 2,4-dichlorobenzaldehyde is replaced with an equal molar amount of m-nitrobenzaldehyde. (Yield: 76%).

[0121] Embodiment 27

[0122] The synthesis steps of 5-furan-2H-1,2,3-triazole-4-carbonitrile (compound number III-17) are the same as those of Example 11, except that 2,4-dichlorobenzaldehyde is replaced with an equal molar amount of furanaldehyde (yield: 71%).

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

[0124] Table 1 Physicochemical properties of target compounds and their mass spectrometry analysis data

[0125]

[0126]

[0127]

[0128]

[0129]

[0130]

[0131]

[0132] Test Example 1

[0133] Insecticidal activity of some compounds of formula (I) against Bemisia tabaci:

[0134] The formulated insecticide was diluted with distilled water to produce 5-7 serial dilutions. Cotton leaf discs (3.5 cm in diameter) were cut 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 soaked in distilled water were used as controls. 25 female adult whiteflies were placed on each treated cotton leaf disc. For each dilution, 75 adult females were treated. All tests were maintained at 25°C and mortality was recorded after 24h, 48h and 72h.

[0135]

[0136] Wherein, 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 group is >20%, the experiment should be repeated. The insecticidal activity data of some compounds of formula I against Bemisia tabaci are shown in Table 2.

[0137] Table 2 Insecticidal activity of some compounds of formula (I) against Bemisia tabaci (100 mg / L, 10 mg / L, 1 mg / L)

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

[0139]

[0140]

[0141] As can be seen from Table 2, some of the compounds of formula (I) provided by the present invention have moderate to good insecticidal activity against the tested whiteflies. At a concentration of 100 mg / L, 72 hours after the compound treatment, the growth and development of whiteflies were significantly hindered, showing symptoms of atrophy of the insect body, wrinkled cuticle, and abnormal molting with deformed insect body. Compound I-7 has an insecticidal activity of more than 70% against whiteflies, and has a prospect of being used as an insecticide to control agricultural pests whiteflies.

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

[0143]

[0144]

[0145] As can be seen from Table 3, some of the compounds of formula (II) provided by the present invention have moderate to good insecticidal activity against the tested whiteflies. At a concentration of 100 mg / L, 72 hours after the compound treatment, the growth and development of whiteflies were significantly hindered, and the whiteflies also showed symptoms of atrophy, wrinkled cuticle, and abnormal molting with deformed body. Three compounds II-5, II-7 and II-23 had an insecticidal activity of more than 50% against whiteflies, and had the prospect of being used as insecticides to control agricultural pests whiteflies.

[0146] Table 4: LC of some compounds against Bemisia tabaci 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, the LC 50 The test results show that compound I-5 has insecticidal activity close to that of the commercial pesticide control flubendiamide.

[0149] Test Example 2

[0150] Insecticidal activity of some compounds of formula (I) against green peach aphid:

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

[0152]

[0153] As can be seen from Table 5, some of the compounds of formula (I) provided by the present invention have certain insecticidal activity against the tested peach aphid. At a concentration of 10 mg / L, the growth and development of peach aphid was significantly hindered 72 hours after the compound treatment. Compound I-1 has an insecticidal activity of more than 50% against peach aphid, and has a prospect of being used as an insecticide to control the agricultural pest peach aphid.

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

[0155]

[0156]

[0157] As can be seen from Table 6, some of the compounds of formula (II) provided by the present invention have certain insecticidal activity against the tested peach aphid. At a concentration of 10 mg / L, the growth and development of peach aphid was hindered to a certain extent 72 hours after the compound treatment. Compounds II-16 and II-14 have an insecticidal activity of more than 50% against peach aphid, and have the prospect of being used as insecticides to control the agricultural pest peach aphid.

[0158] Table 7: LC of some compounds against green 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, the 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, flubendiamide, and the activity of compound II-14 is even better than that of the control.

[0161] Test Example 3

[0162] Insecticidal activity of some compounds of 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) Table 8: Insecticidal activity of some compounds of formula (I) against spider mites

[0164]

[0165] As shown in Table 8, some of the compounds of formula (I) provided by the present invention have certain insecticidal activity against the tested spider mites at a concentration of 10 mg / L 72 hours after the compound treatment, and have the prospect of being used as insecticides to control the agricultural pest green peach aphid.

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

[0167]

[0168]

[0169] As shown in Table 9, some of the compounds of formula (II) provided by the present invention have certain insecticidal activity against the tested spider mites at a concentration of 10 mg / L 72 hours after the compound treatment, and have the prospect of being used as insecticides to control agricultural pests spider mites.

[0170] Test Example 4

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

[0172] 4 types of fungi: Phytophthora, Alternaria alternata, Gibberellic acid and Botrytis cinerea.

[0173] Specific operation: Take the synthesized drug (compound) and dissolve it in 1% DMSO, then add an aqueous solution containing 1% Tween 80 to make a 100mg / L original drug. Pipette an appropriate amount of the prepared original drug into a conical bottle under sterile conditions, shake it thoroughly, and then pour it into three culture dishes with a diameter of 9cm in equal amounts. The above experiment sets the treatment without drug as a blank control, and each treatment is repeated three times. Cut the bacterial cake along the edge of the colony with a 6.5mm diameter puncher on the clean bench, inoculate the bacterial cake in the center of the drug-containing plate with an inoculator, with the mycelium facing up, cover the dish cover, and seal it with a sealing film to avoid miscellaneous bacteria. Place the culture dish in a 25℃ constant temperature incubator for culture. When the diameter of the control colony expands to more than 6cm, measure the colony diameter using the cross method, take the average value, and calculate the antibacterial rate.

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

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

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

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

[0178]

[0179] As can be seen from Table 10, the compounds of formula (III) provided by the present invention show moderate to excellent fungicidal activity against four fungi, namely, Phytophthora, Red Star Pathogen, Fusarium Scab and Botrytis Cinerea, at a concentration of 100 mg / L. The fungicidal activity of compound III-3 against Phytophthora and Fusarium Scab reached 91.43% and 70.00%, respectively; compound III-1 showed fungicidal activity of 98.19% and 100.00% against Red Star Pathogen and Botrytis Cinerea, respectively; under the condition of a concentration of 100 mg / L, the fungicidal activity of compound III-7 against Red Star Pathogen reached 100.00%. These compounds have the prospect of being used as fungicides to prevent and control 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, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A triazole compound, characterized in that: It includes amide-containing triazole compounds of formula (II) and cyano-containing triazole compounds of formula (III), and the structural formula is as follows: In the formula, R 1 is any one of methyl, methoxy, trifluoromethyl, hydroxyl, nitro or halogen; Ar is a benzene ring, a furan ring, a pyridine ring, a thiazole ring, a pyrazole ring, a pyrazine ring or an imidazothiazole ring; R 2 is hydrogen, methyl or dimethyl; R 3 It is benzylbenzene, ethyl acetate or p-toluenesulfonyl.

2. A method for synthesizing a triazole compound, characterized in that: The method comprises the following steps: S1, adding a heterocyclic compound 1 having a carboxyl functional group and an aminoacetylene compound 2 to a solvent, reacting them under the action of a condensing agent, and separating and purifying the fully reacted solution with an eluent to obtain an intermediate of formula (I); S2, the intermediate (I) reacts with the azide compound 3 under the action of a catalyst to obtain an amide compound containing a triazole structure as shown in formula (II), and the reaction equation is: S3, adding a substituted benzaldehyde 4 with a cyano functional group, sodium azide 5 and 2-(phenylsulfonyl)acetonitrile 6 into a solvent for sufficient reaction to obtain a triazole compound containing a cyano functional group as shown in formula (III), and the reaction equation is:

3. The method for synthesizing a triazole compound according to claim 2, characterized in that: The conditions for the full reaction in step S1 are a reaction temperature of 0-60° C., a reaction time of 8-24 h, a molar ratio of the reaction of compound 1 and compound 2 of (1-2):1, a concentration of compound 1 in the solvent of 0.05-0.2 mol / L, and an eluent volume ratio of dichloromethane and methanol of (20-100):

1.

4. The method for synthesizing a triazole compound according to claim 2, characterized in that: The reaction conditions in step S2 are as follows: reaction temperature 0-60° C., reaction time 0.25-3 h, the molar ratio of the intermediate (I) to the azide compound 3 is (1-2):1, the concentration of the intermediate (I) in the solvent is 0.05-0.2 mol / L, and 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.

5. The method for synthesizing a triazole compound according to claim 2, characterized in that: The conditions for the sufficient reaction in step S3 are a reaction temperature of 0-100° C., a reaction time of 3-24 h, a molar ratio of the reaction of compound 4, compound 5 and compound 6 of 1:(1-2):(1:2), a concentration of compound 4 in the solvent of 0.05-0.2 mol / L, and separation and purification of the solution after the sufficient reaction, using an eluent having a volume ratio of (1-10):1 of petroleum ether and ethyl acetate.

6. The use of triazole compounds, characterized in that: The intermediate (I) and the amide-containing triazole compound of formula (II) are used for insecticidal use against whitefly, peach aphid and spider mite.

7. The use of triazole compounds, characterized in that: The cyanotriazole compound of formula (III) is used for sterilizing Phytophthora, Alternaria alternata, Gibberella and Botrytis cinerea.

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