Synthetic method of trifluoromethyl triazole compound

Abstract

The invention belongs to the technical field of triazole compound synthesis, and discloses a synthesis method of a trifluoromethyl triazole compound. Green and safe trifluoromethylated p-toluenesulfonyl hydrazone is adopted as a safe trifluoromethylated nitrogen source reagent, and the trifluoromethyl triazole compound is obtained through cyclization reaction of the green and safe trifluoromethylated p-toluenesulfonyl hydrazone and an aromatic amine compound under the promotion condition of iodine through a one-pot method. In the synthesis process, expensive metal catalysts or ligands are not required to be used, and toxic or easy-to-explode azide is also not required to be used, so that the problem of toxicity or use safety caused by metal residues or azide in a pharmaceutical process does not exist; in addition, the raw materials used in the process are bulk, cheap and easily available, the reaction system is green and environment-friendly, and the method has the advantages of simple operation steps and post-treatment process and high yield; the obtained trifluoromethyl triazole compound can be applied to synthesis of medical intermediates.

Description

Technical Field

[0001] The present invention belongs to the technical field of synthesis of triazole compounds, and specifically relates to a method for synthesizing trifluoromethyltriazole compounds. Background Art

[0002] The triazole heterocyclic skeleton containing a trifluoromethyl group is widely present in natural products, drugs (examples are shown below) and related bioactive molecular compounds, and has been widely studied. This skeleton plays an extremely important role in many bioactive molecules, so it is extremely important to study its synthesis method.

[0003]

[0004] Many methods for synthesizing trifluoromethyl-containing triazole compounds have been developed. Among them, the most common method is to obtain the target compound by condensing azide compounds with trifluoromethyl-derivatized alkynes. However, the safe use of azide compounds is extremely serious, and the preparation process of trifluoromethyl-derivatized alkynes is also quite complicated (see: J. Fluor. Chem. 2011, 132, 166-174; Tetrahedron 2012, 68, 614-618.). Another method is to synthesize related triazole intermediates using transition metal-catalyzed alkyne coupling reactions as key steps, and then introduce trifluoromethyl groups (see: J. Fluorine Chem. 2013, 156, 170-176; Org. Process. Res. Dev. 2020, 24, 207-215; Molecules 2024, 29, 1191.). Most of these studies further introduced relatively expensive trifluoromethylation reagents in the subsequent process, which has the disadvantages of complicated operation steps and post-processing processes; moreover, due to the use of metal catalysts, the final removal of metal residues from the target product is also very challenging in the pharmaceutical industry.

[0005] Therefore, developing new green synthesis processes and studying methods that have the characteristics of simplifying the operation steps and post-processing processes and improving the yield to prepare trifluoromethyltriazole compounds not only has important academic value, but also shows broad market prospects. Summary of the invention

[0006] The present invention aims to overcome at least one defect in the prior art and provide a method for synthesizing trifluoromethyl triazole compounds, thereby avoiding the use of toxic or explosive azide compounds and expensive metal catalysts or ligands, and obtaining trifluoromethyl-containing triazole compounds in a "one-pot" manner.

[0007] In order to solve the above technical problems, the following technical solutions are adopted:

[0008] Green and safe trifluoromethylated p-toluenesulfonylhydrazone is used as a safe trifluoromethylation nitrogen source reagent, and is reacted with aromatic amine compounds under iodine-promoting conditions to obtain trifluoromethyltriazole compounds in a "one-pot" manner through a cyclization reaction.

[0009] The reaction route of the above synthesis method can be expressed as:

[0010]

[0011] Wherein, Formula 1a is trifluoromethylated p-toluenesulfonylhydrazone, Formula 2 is an aromatic amine compound, and Formula 3 is a trifluoromethyl triazole compound; in Formula 2 or Formula 3, R 1 is methyl, tert-butyl, phenyl, methoxy, phenoxy, amide, halogen, trifluoromethyl, cyano, ethoxy, benzoyl, mesyl or nitro, R 2 is hydrogen, methyl, halogen or methanesulfonyl.

[0012] The above synthesis method can synthesize any one of the following trifluoromethyltriazole compounds:

[0013]

[0014] Accordingly, the aromatic amine compound can be selected from any of the following compounds:

[0015]

[0016] In the above synthesis method, trifluoromethylated p-toluenesulfonylhydrazone can be obtained by reacting 3-bromo-1,1,1-trifluoropropan-2-one with p-toluenesulfonylhydrazone (TsNHNH2), wherein the molar amount of 3-bromo-1,1,1-trifluoropropan-2-one is preferably 1.5±0.2 times the molar amount of p-toluenesulfonylhydrazone; the molar amount of trifluoromethylated p-toluenesulfonylhydrazone is preferably 1.5±0.2 times the molar amount of the aromatic amine compound; and the molar amount of iodine is preferably 0.5±0.2 times the molar amount of the aromatic amine compound.

[0017] The above-mentioned synthesis method preferably comprises the following steps:

[0018] S10. dissolving trifluoromethylated p-toluenesulfonylhydrazone, aromatic amine compounds and iodine in a solvent;

[0019] S20. The mixture obtained in step S10 is placed in a reaction condition of 85 to 120° C. until the reaction is complete;

[0020] S30. Extract, dry and purify the product obtained in step S20.

[0021] In step S10, the solvent used is preferably dimethyl sulfoxide (DMSO). In step S20, the reaction endpoint is preferably monitored by thin layer chromatography (TLC), and the reaction is preferably quenched with a saturated sodium thiosulfate solution. In step S30, the extraction operation is preferably performed by using ethyl acetate as an extractant to extract the product three times; the drying operation is preferably performed by first using anhydrous sodium sulfate as a drying agent to dry the extracted product, and then evaporating the solvent; the purification operation is preferably performed by column chromatography separation to purify the dried product.

[0022] Before performing step S10, the above synthesis method may further include the step of synthesizing trifluoromethylated p-toluenesulfonylhydrazone:

[0023] S01. Slowly add 3-bromo-1,1,1-trifluoropropan-2-one to a solution of p-toluenesulfonyl hydrazide (TsNHNH2) in acetonitrile (MeCN), and react at room temperature (25±5°C) with stirring until the reaction is complete;

[0024] S02. Concentrate, wash and dry the product obtained in step S01.

[0025] In step S01, the reaction endpoint is preferably monitored by thin layer chromatography (TLC). In step S02, the concentration operation is preferably performed by using a rotary evaporator to concentrate the product; the washing operation is preferably performed by using petroleum ether to wash the concentrated product; and the drying operation is preferably performed by drying the washed product under vacuum conditions.

[0026] Compared with the prior art, this solution has the following beneficial effects:

[0027] (1) No expensive metal catalysts or ligands are required, so there is no toxicity problem caused by heavy metal residues in the pharmaceutical process;

[0028] (2) The process does not require the use of toxic or explosive azide as a nitrogen source reagent, so there is no toxicity or safety issue caused by azide in the pharmaceutical process;

[0029] (3) The raw materials used in the synthesis process are large, cheap, and easily available. The reaction system is green and environmentally friendly, and has the advantages of simple operation steps and post-treatment processes and high yields.

[0030] (4) The synthesized trifluoromethyltriazole compounds can be used in the synthesis of pharmaceutical intermediates. DETAILED DESCRIPTION

[0031] This scheme proposes a new method for synthesizing trifluoromethyltriazole compounds: using green and safe trifluoromethylated p-toluenesulfonylhydrazone as a safe trifluoromethylation nitrogen source reagent, and aromatic amine compounds under the promotion of iodine (I2) through a cyclization reaction, a "one-pot method" to obtain trifluoromethyltriazole compounds.

[0032] The reaction scheme of the above-mentioned synthesis method is as follows:

[0033]

[0034] Wherein, Formula 1a is trifluoromethylated p-toluenesulfonylhydrazone, Formula 2 is an aromatic amine compound, and Formula 3 is a trifluoromethyl triazole compound; in Formula 2 or Formula 3, R 1 is methyl, tert-butyl, phenyl, methoxy, phenoxy, amide, halogen, trifluoromethyl, cyano, ethoxy, benzoyl, mesyl or nitro, R 2 is hydrogen, methyl, halogen or methanesulfonyl.

[0035] In order to allow those skilled in the art to better understand this solution, the solution is further described in detail below in conjunction with specific examples. The process methods used in the examples are all conventional methods unless otherwise specified; the materials used are all commercially available unless otherwise specified.

[0036] Among them, trifluoromethylated p-toluenesulfonylhydrazone 1a was synthesized in the laboratory, and its reaction route is as follows:

[0037]

[0038] In an air atmosphere, in a 500mL dry reaction bottle, 3-bromo-1,1,1-trifluoropropane-2-one (cas: 431-35-6, 1.5 times equivalent, 150mmol, 15.60mL) was slowly added to a solution of p-toluenesulfonylhydrazine (TsNHNH2, 1.0 times equivalent, 100mmol, 18.62g) in acetonitrile (MeCN, 200mL), and then stirred at room temperature for 24 hours (monitored by TLC). After the reaction was completed, the resulting solution was concentrated on a rotary evaporator to obtain a pale yellow solid crude product. The crude product was washed with petroleum ether (300mL) and dried under vacuum to obtain trifluoromethylated p-toluenesulfonylhydrazone 1a (white solid, 100mmol, 30.53g, yield 85%).

[0039] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) confirmed the structure of the trifluoromethylated p-toluenesulfonylhydrazone 1a obtained above, and the results were as follows:

[0040] 1H NMR (400MHz, CDCl3): δ8.76(br,s,1H),7.86-7.84(m,2H),7.36-7.34(m,2H),3.90(s,2H),2.45(s,3H);

[0041] 19 F NMR(376MHz, CDCl3):-69.89(s,3F);

[0042] 13 C{ 1 H}NMR (100MHz, CDCl3): 145.4, 136.9 (q, J = 35.5Hz), 134.0, 130.0, 128.0, 119.6 (q, J = 273.2Hz), 21.7, 14.8. Example 1

[0043] This example synthesizes trifluoromethyltriazole compound 3a, and the reaction scheme is as follows:

[0044]

[0045] In a 35mL reaction tube, add a magnetic stirrer and solvent DMSO (2.0mL), weigh trifluoromethylated p-toluenesulfonylhydrazone 1a (1.5 times, 0.45mmol, 162.0mg), p-toluidine 2a (1.0 times, 0.3mmol, 32.0mg) and iodine (0.5 times, 0.15mmol, 38.0mg). Cover the reaction tube and transfer it to an 85℃ oil bath pot to react for 15 hours (monitored by TLC). After the reaction of raw material 2a is complete, the reaction tube is cooled to room temperature, and then saturated sodium thiosulfate solution (10mL) is added, and ethyl acetate (10mL×3) is extracted, the organic layer solution is taken, dried over anhydrous sodium sulfate, and the solvent is evaporated, and then the crude product is separated by column chromatography (eluent: petroleum ether and ethyl acetate) to obtain trifluoromethyl triazole compound 3a (white solid, 58.7mg, yield 86%).

[0046] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) confirmed the structure of the trifluoromethyltriazole compound 3a obtained above, and the results are as follows:

[0047] 1H NMR (400MHz, CDCl3): δ8.24 (d, J = 0.6Hz, 1H), 7.62-7.60 (m, 2H), 7.37-7.35 (m, 2H), 2.44 (s, 3H);

[0048] 19 F NMR(376MHz, CDCl3):-61.15(s,3F);

[0049] 13 C{ 1 H}NMR (100MHz, CDCl3): 140.1, 139.4 (q, J = 39.1Hz), 133.8, 130.5, 121.4 (q, J = 2.5Hz), 120.8, 120.4 (q, J = 266.2Hz), 21.1. Example 2

[0050] This example synthesizes trifluoromethyltriazole compound 3b, and the reaction scheme is as follows:

[0051]

[0052] In a 35mL reaction tube, add a magnetic stirrer and solvent DMSO (2.0mL), weigh trifluoromethylated p-toluenesulfonylhydrazone 1a (1.5 times, 0.45mmol, 162.0mg), 3,4-dimethylaniline 2b (1.0 times, 0.3mmol, 36.4mg) and iodine (0.5 times, 0.15mmol, 38.0mg). Cover the reaction tube and transfer it to an 85℃ oil bath for 15 hours (monitored by TLC). After the reaction of raw material 2b is complete, the reaction tube is cooled to room temperature, and then saturated sodium thiosulfate solution (10mL) is added, and ethyl acetate (10mL×3) is extracted. The organic layer solution is taken, dried over anhydrous sodium sulfate, and the solvent is evaporated. Then the crude product is separated by column chromatography (eluent: petroleum ether and ethyl acetate) to obtain trifluoromethyl triazole compound 3b (white solid, 51.5mg, yield 71%).

[0053] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) confirmed the structure of the trifluoromethyltriazole compound 3b obtained above, and the results are as follows:

[0054] 1H NMR (400MHz, CDCl3): δ8.23(s,1H),7.52-7.51(m,1H),7.43-7.41(m,1H),7.30-7.28(m,1H),2.36(s,3H),2.34(s,3H);

[0055] 19 F NMR(376MHz, CDCl3):-61.13(s,3F);

[0056] 13 C{ 1 H} NMR (100MHz, CDCl3): 139.3 (q, J = 39.3Hz), 138.8, 138.7, 134.0, 130.8, 121.4 (q, J = 2.4Hz), 122.0, 120.4 (q, J = 266.2Hz), 118.1, 19.9, 19.5. Example 3

[0057] In this example, trifluoromethyltriazole compound 3c is synthesized, and the reaction scheme is as follows:

[0058]

[0059] In a 35mL reaction tube, add a magnetic stirrer and solvent DMSO (2.0mL), weigh trifluoromethylated p-toluenesulfonylhydrazone 1a (1.5 times, 0.45mmol, 162.0mg), p-tert-butylaniline 2c (1.0 times, 0.3mmol, 44.8mg) and iodine (0.5 times, 0.15mmol, 38.0mg). Cover the reaction tube and transfer it to an 85℃ oil bath pot to react for 15 hours (monitored by TLC). After the reaction of raw material 2c is complete, the reaction tube is cooled to room temperature, and then saturated sodium thiosulfate solution (10mL) is added, and ethyl acetate (10mL×3) is extracted. The organic layer solution is taken, dried over anhydrous sodium sulfate, and the solvent is evaporated. Then the crude product is separated by column chromatography (eluent: petroleum ether and ethyl acetate) to obtain trifluoromethyl triazole compound 3c (white solid, 73.0mg, yield 90%).

[0060] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) confirmed the structure of the trifluoromethyl triazole compound 3c obtained above, and the results are as follows:

[0061] 1H NMR (400MHz, CDCl3): δ8.26(s,1H),7.66-7.64(m,2H),7.58-7.56(m,2H),1.37(s,9H);

[0062] 19 F NMR(376MHz, CDCl3):-61.12(s,3F);

[0063] 13 C{ 1 H} NMR (100MHz, CDCl3): 153.3, 139.3 (q, J = 39.3Hz), 133.7, 126.9, 121.4 (q, J = 2.4Hz), 120.6, 120.4 (q, J = 266.2Hz), 34.9, 31.2. Example 4

[0064] This example synthesizes trifluoromethyltriazole compound 3d, and the reaction scheme is as follows:

[0065]

[0066] In a 35mL reaction tube, add a magnetic stirrer and solvent DMSO (2.0mL), weigh trifluoromethylated p-toluenesulfonylhydrazone 1a (1.5 times, 0.45mmol, 162.0mg), p-phenylaniline 2d (1.0 times, 0.3mmol, 50.8mg) and iodine (0.5 times, 0.15mmol, 38.0mg). Cover the reaction tube and transfer it to an 85℃ oil bath pot to react for 15 hours (monitored by TLC). After the reaction of raw material 2d is complete, the reaction tube is cooled to room temperature, and then saturated sodium thiosulfate solution (10mL) is added, and ethyl acetate (10mL×3) is used for extraction. The organic layer solution is taken, dried over anhydrous sodium sulfate, and the solvent is evaporated. Then the crude product is separated by column chromatography (eluent: petroleum ether and ethyl acetate) to obtain trifluoromethyl triazole compound 3d (white solid, 61.0mg, yield 70%).

[0067] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) confirmed the structure of the trifluoromethyl triazole compound 3d obtained above, and the results were as follows:

[0068] 1H NMR (400MHz, CDCl3): δ8.33 (d, J = 0.6Hz, 1H), 7.83-7.77 (m, 4H), 7.64-7.62 (m, 2H), 7.52-7.48 (m, 2H), 7.45-7.41 (m, 1H);

[0069] 19 F NMR(376MHz, CDCl3):-61.12(s,3F);

[0070] 13 C{ 1 H} NMR (100MHz, CDCl3): 142.8, 139.6 (q, J = 39.2Hz), 139.2, 135.1, 129.1, 128.6, 128.2, 127.1, 121.4 (q, J = 2.4Hz), 121.2, 120.3 (q, J = 266.3Hz). Example 5

[0071] In this example, trifluoromethyltriazole compound 3e is synthesized, and the reaction scheme is as follows:

[0072]

[0073] In a 35mL reaction tube, add a magnetic stirrer and solvent DMSO (2.0mL), weigh trifluoromethylated p-toluenesulfonylhydrazone 1a (1.5 times, 0.45mmol, 162.0mg), p-methoxyaniline 2e (1.0 times, 0.3mmol, 37.0mg) and iodine (0.5 times, 0.15mmol, 38.0mg). Cover the reaction tube and transfer it to an 85℃ oil bath pot to react for 15 hours (monitored by TLC). After the reaction of raw material 2e is complete, the reaction tube is cooled to room temperature, and then saturated sodium thiosulfate solution (10mL) is added, and ethyl acetate (10mL×3) is extracted. The organic layer solution is taken, dried over anhydrous sodium sulfate, and the solvent is evaporated. Then the crude product is separated by column chromatography (eluent: petroleum ether and ethyl acetate) to obtain trifluoromethyl triazole compound 3e (white solid, 64.0mg, yield 88%).

[0074] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) confirmed the structure of the trifluoromethyl triazole compound 3e obtained above, and the results are as follows:

[0075] 1H NMR (400MHz, CDCl3): δ8.20 (d, J = 0.6Hz, 1H), 7.64-7.60 (m, 2H), 7.06-7.02 (m, 2H), 3.88 (s, 3H);

[0076] 19 F NMR(376MHz, CDCl3):-61.14(s,3F);

[0077] 13 C{ 1 H} NMR (100MHz, CDCl3): 160.5, 139.3 (q, J = 39.3Hz), 129.4, 122.6, 121.6 (q, J = 2.5Hz), 120.4 (q, J = 266.2Hz), 115.0, 55.6. Example 6

[0078] This example synthesizes trifluoromethyltriazole compound 3f, and the reaction scheme is as follows:

[0079]

[0080] In a 35mL reaction tube, add a magnetic stirrer and solvent DMSO (2.0mL), weigh trifluoromethylated p-toluenesulfonylhydrazone 1a (1.5 times, 0.45mmol, 162.0mg), p-phenoxyaniline 2f (1.0 times, 0.3mmol, 55.6mg) and iodine (0.5 times, 0.15mmol, 38.0mg). Cover the reaction tube and transfer it to an 85℃ oil bath pot to react for 15 hours (monitored by TLC). After the reaction of raw material 2f is complete, the reaction tube is cooled to room temperature, and then saturated sodium thiosulfate solution (10mL) is added, and ethyl acetate (10mL×3) is extracted. The organic layer solution is taken, dried over anhydrous sodium sulfate, and the solvent is evaporated. Then the crude product is separated by column chromatography (eluent: petroleum ether and ethyl acetate) to obtain trifluoromethyl triazole compound 3f (white solid, 78.0mg, yield 85%).

[0081] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) confirmed the structure of the trifluoromethyl triazole compound 3f obtained above, and the results are as follows:

[0082] 1H NMR (400MHz, CDCl3): δ8.25 (d, J = 0.6Hz, 1H), 7.69-7.65 (m, 2H), 7.43-7.38 (m, 2H), 7.22-7.18 (m, 1H), 7.16-7.12 (m, 2H), 7.09-7.06 (m, 2H);

[0083] 19 F NMR(376MHz, CDCl3):-61.12(s,3F);

[0084] 13 C{ 1 H} NMR (100MHz, CDCl3): 158.8, 155.8, 139.4 (q, J = 39.3Hz), 131.0, 130.1, 124.5, 122.7, 121.6, 120.3 (q, J = 266.3Hz), 119.7, 119.1. Example 7

[0085] In this example, 3 g of trifluoromethyl triazole compound was synthesized, and the reaction route is as follows:

[0086]

[0087] In a 35mL reaction tube, add a magnetic stirrer and solvent DMSO (2.0mL), weigh trifluoromethylated p-toluenesulfonylhydrazone 1a (1.5 times, 0.45mmol, 162.0mg), p-amidoaniline 2g (1.0 times, 0.3mmol, 40.8mg) and iodine (0.5 times, 0.15mmol, 38.0mg). Cover the reaction tube and transfer it to a 120℃ oil bath pot to react for 15 hours (monitored by TLC). After the reaction of 2g of the raw material is complete, the reaction tube is cooled to room temperature, and then a saturated sodium thiosulfate solution (10mL) is added, and ethyl acetate (10mL×3) is extracted. The organic layer solution is taken, dried over anhydrous sodium sulfate, and the solvent is evaporated. Then the crude product is separated by column chromatography (eluent: petroleum ether and ethyl acetate) to obtain 3g of trifluoromethyl triazole compound (white solid, 31.5mg, yield 41%).

[0088] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) confirmed the structure of the trifluoromethyl triazole compound 3g obtained above, and the results were as follows:

[0089] 1H NMR (400MHz, DMSO-d6): δ9.68(d,J=0.8Hz,1H),8.17(br,s,1H),8.13-8.11(m,2H),8.08-8.05(m,2H),7.58(br,s,1H);

[0090] 19 F NMR(376MHz,DMSO-d6):-59.89(s,3F);

[0091] 13 C{ 1 H}NMR (100MHz, DMSO-d6): 166.6, 137.8 (q, J = 38.2Hz), 137.7, 135.0, 129.2, 124.5 (q, J = 2.7Hz), 120.7 (q, J = 265.6Hz), 120.3. Example 8

[0092] This example synthesizes trifluoromethyltriazole compound 3h, and the reaction scheme is as follows:

[0093]

[0094] In a 35mL reaction tube, add a magnetic stirrer and solvent DMSO (2.0mL), weigh trifluoromethylated p-toluenesulfonylhydrazone 1a (1.5 times, 0.45mmol, 162.0mg), p-fluoroaniline 2h (1.0 times, 0.3mmol, 33.3mg) and iodine (0.5 times, 0.15mmol, 38.0mg). Cover the reaction tube and transfer it to a 100℃ oil bath pot to react for 15 hours (monitored by TLC). After the raw material 2h reacts completely, the reaction tube is cooled to room temperature, and then a saturated sodium thiosulfate solution (10mL) is added, and ethyl acetate (10mL×3) is extracted. The organic layer solution is taken, dried over anhydrous sodium sulfate, and the solvent is evaporated. Then the crude product is separated by column chromatography (eluent: petroleum ether and ethyl acetate) to obtain trifluoromethyl triazole compound 3h (white solid, 55.6mg, yield 80%).

[0095] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) confirmed the structure of the trifluoromethyl triazole compound 3h obtained above, and the results are as follows:

[0096] 1H NMR (400MHz, CDCl3): δ8.30 (d, J = 0.6Hz, 1H), 7.78-7.73 (m, 2H), 7.32-7.26 (m, 2H);

[0097] 19 F NMR(376MHz, CDCl3):-61.23(s,3F),-110.31(s,1F);

[0098] 13 C{ 1 H}NMR (100MHz, CDCl3): 162.9 (d, J = 249.4Hz), 139.6 (q, J = 39.4Hz), 132.3 (d, J = 2.9Hz ), 123.0 (d, J = 8.8Hz), 121.7 (q, J = 2.5Hz), 120.2 (q, J = 266.4Hz), 117.1 (d, J = 23.2Hz). Example 9

[0099] This example synthesizes trifluoromethyltriazole compound 3i, and the reaction scheme is as follows:

[0100]

[0101] In a 35mL reaction tube, add a magnetic stirrer and solvent DMSO (2.0mL), weigh trifluoromethylated p-toluenesulfonylhydrazone 1a (1.5 times, 0.45mmol, 162.0mg), p-chloroaniline 2i (1.0 times, 0.3mmol, 38.3mg) and iodine (0.5 times, 0.15mmol, 38.0mg). Cover the reaction tube and transfer it to a 100℃ oil bath to react for 15 hours (monitored by TLC). After the reaction of raw material 2i is complete, the reaction tube is cooled to room temperature, and then saturated sodium thiosulfate solution (10mL) is added, and ethyl acetate (10mL×3) is extracted. The organic layer solution is taken, dried over anhydrous sodium sulfate, and the solvent is evaporated. Then the crude product is separated by column chromatography (eluent: petroleum ether and ethyl acetate) to obtain trifluoromethyl triazole compound 3i (white solid, 62.5mg, yield 84%).

[0102] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) confirmed the structure of the trifluoromethyl triazole compound 3i obtained above, and the results are as follows:

[0103] 1H NMR (400MHz, CDCl3): δ8.30 (d, J = 0.6Hz, 1H), 7.73-7.69 (m, 2H), 7.56-7.53 (m, 2H);

[0104] 19 F NMR(376MHz, CDCl3):-61.24(s,3F);

[0105] 13 C{ 1 H} NMR (100MHz, CDCl3): 139.7 (q, J = 39.4Hz), 135.7, 134.5, 130.2, 122.1, 121.5 (q, J = 2.8Hz), 120.1 (q, J = 266.2Hz). Example 10

[0106] This example synthesizes trifluoromethyltriazole compound 3j, and the reaction scheme is as follows:

[0107]

[0108] In a 35mL reaction tube, add a magnetic stirrer and solvent DMSO (2.0mL), weigh trifluoromethylated p-toluenesulfonylhydrazone 1a (1.5 times, 0.45mmol, 162.0mg), p-bromoaniline 2j (1.0 times, 0.3mmol, 51.6mg) and iodine (0.5 times, 0.15mmol, 38.0mg). Cover the reaction tube and transfer it to a 100℃ oil bath to react for 15 hours (monitored by TLC). After the reaction of raw material 2j is complete, the reaction tube is cooled to room temperature, and then saturated sodium thiosulfate solution (10mL) is added, and ethyl acetate (10mL×3) is extracted. The organic layer solution is taken, dried over anhydrous sodium sulfate, and the solvent is evaporated. Then the crude product is separated by column chromatography (eluent: petroleum ether and ethyl acetate) to obtain trifluoromethyl triazole compound 3j (white solid, 73.0mg, yield 83%).

[0109] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) confirmed the structure of the trifluoromethyl triazole compound 3j obtained above, and the results are as follows:

[0110] 1 H NMR (400MHz, CDCl3): δ8.31 (d, J = 0.6Hz, 1H), 7.72-7.69 (m, 2H), 7.66-7.62 (m, 2H);

[0111] 19 F NMR(376MHz, CDCl3):-61.23(s,3F);

[0112] 13 C{ 1 H} NMR (100MHz, CDCl3): 139.7 (q, J = 39.6Hz), 135.0, 133.2, 123.6, 123.2, 121.4 (q, J = 2.4Hz), 120.1 (q, J = 266.1Hz). Embodiment 11

[0113] In this example, trifluoromethyl triazole compound 3k is synthesized, and the reaction scheme is as follows:

[0114]

[0115] In a 35mL reaction tube, add a magnetic stirrer and solvent DMSO (2.0mL), weigh trifluoromethylated p-toluenesulfonylhydrazone 1a (1.5 times, 0.45mmol, 162.0mg), 2,4-dimethylaniline 2k (1.0 times, 0.3mmol, 36.4mg) and iodine (0.5 times, 0.15mmol, 38.0mg). Cover the reaction tube and transfer it to a 100℃ oil bath for 15 hours (monitored by TLC). After the reaction of the raw material 2k is complete, the reaction tube is cooled to room temperature, and then a saturated sodium thiosulfate solution (10mL) is added, and ethyl acetate (10mL×3) is used for extraction. The organic layer solution is taken, dried over anhydrous sodium sulfate, and the solvent is evaporated. Then the crude product is separated by column chromatography (eluent: petroleum ether and ethyl acetate) to obtain trifluoromethyl triazole compound 3k (light yellow liquid, 45.0mg, yield 62%).

[0116] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) confirmed the structure of the trifluoromethyl triazole compound 3k obtained above, and the results are as follows:

[0117] 1 H NMR (400MHz, CDCl3): δ8.03(s,1H),7.21-7.19(m,2H),7.16-7.14(m,1H),2.41(s,3H),2.17(s,3H);

[0118] 19F NMR(376MHz, CDCl3):-60.95(s,3F);

[0119] 13 C{ 1 H} NMR (100MHz, CDCl3): 140.9, 138.6 (q, J = 39.3Hz), 133.3, 133.0, 132.2, 127.6, 125.7, 124.7 (q, J = 2.5Hz), 120.4 (q, J = 266.2Hz), 21.1, 17.6. Example 12

[0120] This example synthesizes trifluoromethyltriazole compound 31, and the reaction scheme is as follows:

[0121]

[0122] In a 35 mL reaction tube, add a magnetic stirrer and solvent DMSO (2.0 mL), weigh trifluoromethylated p-toluenesulfonylhydrazone 1a (1.5 times, 0.45 mmol, 162.0 mg), 3-chloro-4-fluoroaniline 2l (1.0 times, 0.3 mmol, 43.7 mg) and iodine (0.5 times, 0.15 mmol, 38.0 mg). Cover the reaction tube and transfer it to a 100 ° C oil bath pot to react for 15 hours (monitored by TLC). After the reaction of raw material 2l is complete, the reaction tube is cooled to room temperature, and then saturated sodium thiosulfate solution (10 mL) is added, and ethyl acetate (10 mL × 3) is extracted, the organic layer solution is taken, dried over anhydrous sodium sulfate, and the solvent is evaporated, and then the crude product is separated by column chromatography (eluent: petroleum ether and ethyl acetate) to obtain trifluoromethyl triazole compound 3l (white solid, 57.4 mg, yield 72%).

[0123] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) was used to confirm the structure of the trifluoromethyltriazole compound 31 obtained above, and the results were as follows:

[0124] 1 H NMR (400MHz, CDCl3): δ8.33(s,1H),7.88-7.86(m,1H),7.68-7.64(m,1H),7.38-7.34(m,1H);

[0125] 19F NMR(376MHz, CDCl3):-61.28(s,3F),-112.29(s,1F);

[0126] 13 C{ 1 H} NMR (100MHz, CDCl3): 158.5 (d, J = 252.0Hz), 139.8 (q, J = 39.5Hz), 132.6 (d, J = 3.6Hz), 123.6, 122. 9(d,J=19.2Hz), 121.8(q,J=2.4Hz), 120.8(d,J=2.4Hz), 120.1(q,J=266.3Hz), 117.9(d,J=22.9Hz). Embodiment 13

[0127] In this example, trifluoromethyl triazole compound 3m is synthesized, and the reaction scheme is as follows:

[0128]

[0129] In a 35mL reaction tube, add a magnetic stirrer and solvent DMSO (2.0mL), weigh trifluoromethylated p-toluenesulfonylhydrazone 1a (1.5 times, 0.45mmol, 162.0mg), 3,4-dichloroaniline 2m (1.0 times, 0.3mmol, 48.6mg) and iodine (0.5 times, 0.15mmol, 38.0mg). Cover the reaction tube and transfer it to a 100℃ oil bath for 15 hours (monitored by TLC). After the reaction of the raw material 2m is complete, the reaction tube is cooled to room temperature, and then a saturated sodium thiosulfate solution (10mL) is added, and ethyl acetate (10mL×3) is used for extraction. The organic layer solution is taken, dried over anhydrous sodium sulfate, and the solvent is evaporated. Then the crude product is separated by column chromatography (eluent: petroleum ether and ethyl acetate) to obtain trifluoromethyl triazole compound 3m (white solid, 60.0mg, yield 71%).

[0130] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) confirmed the structure of the trifluoromethyl triazole compound 3m obtained above, and the results were as follows:

[0131] 1 H NMR (400MHz, CDCl3): δ8.35 (s 1H), 7.92-7.91 (m, 1H), 7.67-7.62 (m, 2H);

[0132] 19 F NMR(376MHz, CDCl3):-61.36(s,3F);

[0133] 13 C{ 1 H} NMR (100MHz, CDCl3): 139.8 (q, J = 39.5Hz), 135.0, 134.3, 134.1, 131.7, 122.7, 121.5 (q, J = 2.5Hz), 120.1 (q, J = 266.6Hz), 119.8. Embodiment 14

[0134] This example synthesizes trifluoromethyl triazole compound 3n, and the reaction scheme is as follows:

[0135]

[0136] In a 35mL reaction tube, add a magnetic stirrer and solvent DMSO (2.0mL), weigh trifluoromethylated p-toluenesulfonylhydrazone 1a (1.5 times, 0.45mmol, 162.0mg), 5-amino-2-methoxybenzoic acid methyl ester 2n (1.0 times, 0.3mmol, 54.3mg) and iodine (0.5 times, 0.15mmol, 38.0mg). Cover the reaction tube and transfer it to a 100℃ oil bath pot to react for 15 hours (monitored by TLC). After the reaction of raw material 2n is complete, the reaction tube is cooled to room temperature, and then saturated sodium thiosulfate solution (10mL) is added, and ethyl acetate (10mL×3) is extracted, the organic layer solution is taken, dried over anhydrous sodium sulfate, and the solvent is evaporated, and then the crude product is separated by column chromatography (eluent: petroleum ether and ethyl acetate) to obtain trifluoromethyl triazole compound 3n (white solid, 63.5mg, yield 70%).

[0137] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) confirmed the structure of the trifluoromethyl triazole compound 3n obtained above, and the results are as follows:

[0138] 1 H NMR (400MHz, CDCl3): δ8.30 (d, J = 0.6Hz, 1H), 8.11-8.10 (m, 1H), 7.89-7.86 (m, 1H), 7.15-7.13 (m, 1H), 3.96 (s, 3H), 3.90 (s, 3H);

[0139] 19F NMR(376MHz, CDCl3):-61.20(s,3F);

[0140] 13 C{ 1 H} NMR (100MHz, CDCl3): 164.9, 159.8, 139.4 (q, J = 39.4Hz), 128.7, 126.1, 124.3, 121.6 (q, J = 2.5Hz), 120.8, 120.2 (q, J = 266.2Hz), 113.2, 56.4, 52.4. Embodiment 15

[0141] In this example, trifluoromethyltriazole compound 3o is synthesized, and the reaction scheme is as follows:

[0142]

[0143] In a 35mL reaction tube, add a magnetic stirrer and solvent DMSO (2.0mL), weigh trifluoromethylated p-toluenesulfonylhydrazone 1a (1.5 times, 0.45mmol, 162.0mg), p-trifluoromethylaniline 2o (1.0 times, 0.3mmol, 48.3mg) and iodine (0.5 times, 0.15mmol, 38.0mg). Cover the reaction tube and transfer it to a 100℃ oil bath pot to react for 15 hours (monitored by TLC). After the reaction of raw material 2o is complete, the reaction tube is cooled to room temperature, and then saturated sodium thiosulfate solution (10mL) is added, and ethyl acetate (10mL×3) is extracted. The organic layer solution is taken, dried over anhydrous sodium sulfate, and the solvent is evaporated. Then the crude product is separated by column chromatography (eluent: petroleum ether and ethyl acetate) to obtain trifluoromethyl triazole compound 3o (white solid, 50.6mg, yield 60%).

[0144] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) confirmed the structure of the trifluoromethyl triazole compound 3o obtained above, and the results are as follows:

[0145] 1 H NMR (400MHz, CDCl3): δ8.38 (d, J = 0.6Hz, 1H), 7.94-7.92 (m, 2H), 7.87-7.85 (m, 2H);

[0146] 19F NMR(376MHz, CDCl3):-61.31(s,3F),-62.76(s,3F);

[0147] 13 C{ 1 H} NMR (100 MHz, CDCl3): 140.0 (q, J = 39.5 Hz), 138.5, 131.8 (q, J = 33.0 Hz), 127.4 (q, J = 3.7 Hz), 123.3 (q, J = 270.1 Hz), 120.1 (q, J = 266.3 Hz), 121.4 (q, J = 2.5 Hz), 121.0. Example 16

[0148] This example synthesizes trifluoromethyltriazole compound 3p, and the reaction scheme is as follows:

[0149]

[0150] In a 35mL reaction tube, add a magnetic stirrer and solvent DMSO (2.0mL), weigh trifluoromethylated p-toluenesulfonylhydrazone 1a (1.5 times, 0.45mmol, 162.0mg), p-nitriloaniline 2p (1.0 times, 0.3mmol, 35.4mg) and iodine (0.5 times, 0.15mmol, 38.0mg). Cover the reaction tube and transfer it to a 100℃ oil bath to react for 15 hours (monitored by TLC). After the reaction of the raw material 2p is complete, the reaction tube is cooled to room temperature, and then a saturated sodium thiosulfate solution (10mL) is added, and ethyl acetate (10mL×3) is used for extraction. The organic layer solution is taken, dried over anhydrous sodium sulfate, and the solvent is evaporated. Then the crude product is separated by column chromatography (eluent: petroleum ether and ethyl acetate) to obtain trifluoromethyl triazole compound 3p (white solid, 31.5mg, yield 44%).

[0151] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) confirmed the structure of the trifluoromethyl triazole compound 3p obtained above, and the results are as follows:

[0152] 1 H NMR (400MHz, CDCl3): δ8.40 (d, J = 0.6Hz, 1H), 7.97-7.95 (m, 2H), 7.91-7.89 (m, 2H);

[0153] 19F NMR(376MHz, CDCl3):-61.34(s,3F);

[0154] 13 C{ 1 H} NMR (100MHz, CDCl3): 140.2 (q, J = 39.7Hz), 138.9, 134.1, 121.4 (q, J = 2.6Hz), 121.1, 120.0 (q, J = 266.8Hz), 117.3, 113.6. Embodiment 17

[0155] In this example, trifluoromethyl triazole compound 3q is synthesized, and the reaction scheme is as follows:

[0156]

[0157] In a 35 mL reaction tube, add a magnetic stirrer and solvent DMSO (2.0 mL), weigh trifluoromethylated p-toluenesulfonylhydrazone 1a (1.5 times, 0.45 mmol, 162.0 mg), ethyl 4-aminobenzoate 2q (1.0 times, 0.3 mmol, 49.6 mg) and iodine (0.5 times, 0.15 mmol, 38.0 mg). Cover the reaction tube and transfer it to a 100 ° C oil bath to react for 15 hours (monitored by TLC). After the reaction of the raw material 2q is complete, the reaction tube is cooled to room temperature, and then a saturated sodium thiosulfate solution (10 mL) is added, and ethyl acetate (10 mL × 3) is extracted, the organic layer solution is taken, dried over anhydrous sodium sulfate, and the solvent is evaporated, and then the crude product is separated by column chromatography (eluent: petroleum ether and ethyl acetate) to obtain trifluoromethyl triazole compound 3q (white solid, 54.0 mg, yield 63%).

[0158] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) confirmed the structure of the trifluoromethyl triazole compound 3q obtained above, and the results were as follows:

[0159] 1 H NMR (400MHz, CDCl3): δ8.41 (d, J = 0.6Hz, 1H), 8.25-8.23 (m, 2H), 7.87-7.85 (m, 2H), 4.42 (q, J = 7.1Hz, 2H), 1.42 (t, J = 7.1Hz, 3H);

[0160] 19F NMR(376MHz, CDCl3):-61.28(s,3F);

[0161] 13 C{ 1 H} NMR (100MHz, CDCl3): 165.1, 139.8 (q, J = 39.5Hz), 139.0, 131.6, 131.4, 121.5 (q, J = 2.6Hz), 120.3, 120.1 (q, J = 266.4Hz), 61.6, 14.2. Embodiment 18

[0162] In this example, trifluoromethyl triazole compound 3r is synthesized, and the reaction scheme is as follows:

[0163]

[0164] In a 35mL reaction tube, add a magnetic stirrer and solvent DMSO (2.0mL), weigh trifluoromethylated p-toluenesulfonylhydrazone 1a (1.5 times, 0.45mmol, 162.0mg), (4-aminophenyl)(phenyl)methanone 2r (1.0 times, 0.3mmol, 59.2mg) and iodine (0.5 times, 0.15mmol, 38.0mg). Cover the reaction tube and transfer it to a 100℃ oil bath to react for 15 hours (monitored by TLC). After the reaction of the raw material 2r is complete, the reaction tube is cooled to room temperature, and then a saturated sodium thiosulfate solution (10mL) is added, and ethyl acetate (10mL×3) is used for extraction. The organic layer solution is taken, dried over anhydrous sodium sulfate, and the solvent is evaporated. Then the crude product is separated by column chromatography (eluent: petroleum ether and ethyl acetate) to obtain trifluoromethyl triazole compound 3r (white solid, 61.0mg, yield 64%).

[0165] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) confirmed the structure of the trifluoromethyl triazole compound 3r obtained above, and the results are as follows:

[0166] 1 H NMR (400MHz, CDCl3): δ8.42 (d, J = 0.6Hz, 1H), 8.03-8.00 (m, 2H), 7.93-7.90 (m, 2H), 7.83-7.81 (m, 2H), 7.67-7.63 (m, 1H), 7.55-7.51 (m, 2H);

[0167] 19F NMR(376MHz, CDCl3):-61.24(s,3F);

[0168] 13 C{ 1 H}NMR (100MHz, CDCl3): 195.0, 139.9 (q, J = 39.6Hz), 138.6, 138.5, 136.7, 13 3.1,131.8,130.0,128.6,121.5(q,J=2.4Hz),120.4,120.1(q,J=266.6Hz). Embodiment 19

[0169] This example synthesizes trifluoromethyltriazole compound 3s, and the reaction scheme is as follows:

[0170]

[0171] In a 35mL reaction tube, add a magnetic stirrer and solvent DMSO (2.0mL), weigh trifluoromethylated p-toluenesulfonylhydrazone 1a (1.5 times, 0.45mmol, 162.0mg), 4-methylsulfonylaniline 2r (1.0 times, 0.3mmol, 51.4mg) and iodine (0.5 times, 0.15mmol, 38.0mg). Cover the reaction tube and transfer it to a 120℃ oil bath pot to react for 15 hours (monitored by TLC). After the reaction of raw material 2r is complete, the reaction tube is cooled to room temperature, and then saturated sodium thiosulfate solution (10mL) is added, and ethyl acetate (10mL×3) is extracted. The organic layer solution is taken, dried over anhydrous sodium sulfate, and the solvent is evaporated. Then the crude product is separated by column chromatography (eluent: petroleum ether and ethyl acetate) to obtain trifluoromethyl triazole compound 3r (white solid, 31.5mg, yield 36%).

[0172] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) confirmed the structure of the trifluoromethyltriazole compound 3s obtained above, and the results are as follows:

[0173] 1 H NMR (400MHz, DMSO-d6): δ9.78(s,1H),8.28-8.26(m,2H),8.21-8.19(m,2H),3.33(s,3H);

[0174] 19F NMR(376MHz,DMSO-d6):-59.97(s,3F);

[0175] 13 C{ 1 H}NMR (100MHz, DMSO-d6): 141.3, 139.3, 137.9 (q, J = 38.5Hz), 129.1, 121.4, 125.0 (q, J = 2.8Hz), 120.6 (q, J = 265.6Hz), 43.3. Embodiment 20

[0176] This example synthesizes trifluoromethyl triazole compound 3t, and the reaction scheme is as follows:

[0177]

[0178] In a 35mL reaction tube, add a magnetic stirrer and solvent DMSO (2.0mL), weigh trifluoromethylated p-toluenesulfonylhydrazone 1a (1.5 times, 0.45mmol, 162.0mg), p-nitroaniline 2t (1.0 times, 0.3mmol, 41.1mg) and iodine (0.5 times, 0.15mmol, 38.0mg). Cover the reaction tube and transfer it to a 120℃ oil bath pot to react for 15 hours (monitored by TLC). After the reaction of the raw material 2t is complete, the reaction tube is cooled to room temperature, and then a saturated sodium thiosulfate solution (10mL) is added, and ethyl acetate (10mL×3) is used for extraction. The organic layer solution is taken, dried over anhydrous sodium sulfate, and the solvent is evaporated. Then the crude product is separated by column chromatography (eluent: petroleum ether and ethyl acetate) to obtain trifluoromethyl triazole compound 3t (light yellow solid, 31.0mg, yield 40%).

[0179] H 1 -NMR (Bruker FT-NMR), F 19 -NMR (Bruker FT-NMR) and C 13 -NMR (Bruker FT-NMR) confirmed the structure of the trifluoromethyl triazole compound 3t obtained above, and the results were as follows:

[0180] 1 H NMR (400MHz, CDCl3): δ8.50-8.46(m,2H),8.44(s,1H),8.04-8.01(m,2H);

[0181] 19 F NMR(376MHz, CDCl3):-61.35(s,3F);

[0182] 13 C{ 1 H} NMR (100MHz, CDCl3): 147.9, 140.3 (q, J = 39.8Hz), 140.2, 125.8, 121.5 (q, J = 2.7Hz), 121.1, 119.9 (q, J = 266.7Hz).

[0183] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation methods of the present invention. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all implementation methods here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention shall be included in the protection scope of the claims of the present invention.

Claims

1. A method for synthesizing trifluoromethyltriazole compounds, characterized in that: Trifluoromethyl triazole compounds are obtained by cyclization of trifluoromethylated p-toluenesulfonylhydrazone with aromatic amine compounds under iodine-promoting conditions.

2. The method for synthesizing trifluoromethyltriazole compounds according to claim 1, characterized in that: The reaction route is: Wherein, Formula 1a is the trifluoromethylated p-toluenesulfonylhydrazone, Formula 2 is the aromatic amine compound, and Formula 3 is the trifluoromethyl triazole compound; in Formula 2 or Formula 3, R 1 is methyl, tert-butyl, phenyl, methoxy, phenoxy, amide, halogen, trifluoromethyl, cyano, ethoxy, benzoyl, mesyl or nitro, R 2 is hydrogen, methyl, halogen or methanesulfonyl.

3. The method for synthesizing trifluoromethyltriazole compounds according to claim 1, characterized in that: The trifluoromethyl triazole compound is selected from any one of the following compounds: The aromatic amine compound is selected from any one of the following compounds:

4. The method for synthesizing trifluoromethyltriazole compounds according to claim 1, characterized in that: The structural formula of the trifluoromethylated toluenesulfonylhydrazone is:

5. The method for synthesizing trifluoromethyltriazole compounds according to claim 4, characterized in that: The trifluoromethylated p-toluenesulfonylhydrazone is obtained by reacting 3-bromo-1,1,1-trifluoropropan-2-one with p-toluenesulfonylhydrazone, and the molar amount of the 3-bromo-1,1,1-trifluoropropan-2-one is 1.5±0.2 times the molar amount of the p-toluenesulfonylhydrazone.

6. The method for synthesizing trifluoromethyltriazole compounds according to any one of claims 1 to 5, characterized in that: The molar amount of the trifluoromethylated p-toluenesulfonylhydrazone is 1.5±0.2 times the molar amount of the aromatic amine compound; and / or the molar amount of the iodine is 0.5±0.2 times the molar amount of the aromatic amine compound.

7. The method for synthesizing trifluoromethyltriazole compounds according to any one of claims 1 to 5, characterized in that: The synthesis method comprises the following steps: S10. dissolving trifluoromethylated p-toluenesulfonylhydrazone, aromatic amine compounds and iodine in a solvent; S20. The mixture obtained in step S10 is placed in a reaction condition of 85 to 120° C. until the reaction is complete; S30. Extract, dry and purify the product obtained in step S20.

8. The method for synthesizing trifluoromethyltriazole compounds according to claim 7, characterized in that: The solvent in step S10 is dimethyl sulfoxide; and / or step S20 monitors the reaction endpoint by thin layer chromatography; and / or step S20 uses a saturated sodium thiosulfate solution to quench the reaction; and / or step S30 uses ethyl acetate to extract the product; and / or step S30 first dries the extracted product with anhydrous sodium sulfate and then evaporates the solvent; and / or step S30 purifies the dried product by column chromatography separation.

9. The method for synthesizing trifluoromethyltriazole compounds according to claim 7, characterized in that: Before performing step S10, the synthesis method further comprises the step of synthesizing trifluoromethylated p-toluenesulfonylhydrazone: S01. Slowly add 3-bromo-1,1,1-trifluoropropane-2-one to the acetonitrile solution of p-toluenesulfonylhydrazide, and react at 25±5°C with stirring until the reaction is complete; S02. Concentrate, wash and dry the product obtained in step S01.

10. The method for synthesizing trifluoromethyltriazole compounds according to claim 9, characterized in that: Step S02 uses a rotary evaporator to concentrate the product; and / or step S02 uses petroleum ether to wash the concentrated product; and / or step S02 dries the washed product under vacuum conditions.

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