A method for preparing trifluoromethyl-substituted 1,2,4-triazole acylhydrazone derivatives

Abstract

A method for preparing trifluoromethyl-substituted 1,2,4-triazole hydrazone derivatives is disclosed, relating to the field of organic synthesis. This invention uses readily available and inexpensive trifluoromethylhydrazone chloride and N-cyano-N-aryl-p-toluenesulfonamide as starting materials. Under alkaline conditions, derivatives containing trifluoromethyl, 1,2,4-triazole rings, and hydrazone structures are constructed in one step via a tandem cyclization and nucleophilic substitution reaction. This process requires no catalysts, metal reagents, or additional oxidants, features mild reaction conditions, simple operation, low equipment requirements, excellent atom economy, high starting material conversion rate, few byproducts, and is easy to scale up and promote. It provides a practical and economical synthetic route for the development of potentially bioactive trifluoromethyltriazole hydrazone compounds.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to a method for preparing trifluoromethyl-substituted 1,2,4-triazole hydrazone derivatives. Background Technology

[0002] 1,2,4-Triazole compounds, due to their unique heterocyclic structures, exhibit a wide range of biological activities and have significant application value in medicinal chemistry, pesticide science, and other fields. Studies have shown that introducing a trifluoromethyl (-CF3) group into the structure of these compounds can significantly improve their lipophilicity, metabolic stability, and pharmacokinetic properties, thereby enhancing their potential as drug lead compounds or active molecules in agrochemicals. Furthermore, modifying the amino groups on the 1,2,4-triazole ring, such as introducing active fragments like acylhydrazones or imines, is an important strategy for constructing novel, highly active molecules and expanding structural diversity. Therefore, developing efficient and convenient methods to synthesize trifluoromethyl-substituted 1,2,4-triazole acylhydrazone derivatives possessing both trifluoromethyl and acylhydrazone pharmacophores is of great significance for the rapid development of related active molecules.

[0003] Currently, there are numerous reported synthetic methods for constructing 1,2,4-triazole rings, such as using amidine / midazinone, trifluoroacetylimine hydrazine, azocarboxylic acid esters, aryl diazonium salts, acylhydrazine / hydrazine, or amines as raw materials to carry out cyclization reactions under specific conditions. However, these existing methods generally have the following drawbacks: (1) the reaction steps are relatively lengthy and require multiple operations; (2) the reaction conditions are harsh, often relying on high temperatures, metal catalysts, or stoichiometric peroxides / oxidants; and (3) the atom economy is low, resulting in numerous byproducts. More importantly, the existing technology lacks a universal synthetic method that can directly construct trifluoromethyl-substituted 1,2,4-triazole hydrazine derivatives in one step with high efficiency. These shortcomings limit the rapid, green, and large-scale preparation of this class of potentially bioactive compounds. Summary of the Invention

[0004] The purpose of this invention is to address the deficiencies in the prior art by providing a method for preparing trifluoromethyl-substituted 1,2,4-triazolylhydrazone derivatives.

[0005] To solve the above-mentioned technical problems, the present invention adopts the following technical solution: a method for preparing trifluoromethyl-substituted 1,2,4-triazole hydrazone derivatives, comprising the following steps:

[0006] Trifluoromethylhydrazone chloride, N-cyano-N-p-toluenesulfonamide (NCTS), a base, and an organic solvent were mixed and subjected to a one-pot cascade reaction of cyclization and nucleophilic substitution in air to obtain the trifluoromethyl-substituted 1,2,4-triazolylhydrazone derivative.

[0007] Preferably, the base is an inorganic base (such as potassium carbonate, cesium carbonate, etc.) or an organic base (such as triethylamine, DBU, etc.). The function of the base is to capture acidic byproducts (such as HCl) generated in the reaction, shift the reaction equilibrium towards the product formation direction, and promote the formation of key intermediates. The type and amount of base can be determined through conventional optimization.

[0008] The reaction can proceed smoothly in an air environment without the need for inert gas (such as nitrogen or argon) protection, which significantly improves the ease of operation and the economic efficiency of equipment requirements.

[0009] The organic solvent is one or more selected from acetonitrile, toluene, tetrahydrofuran, o-xylene, m-xylene, p-xylene, trifluorotoluene, mesitylene, and acetone. The solvent serves to provide a homogeneous medium for the reaction; its polarity and boiling point can affect the reaction rate and conversion rate. The specific solvent can be selected based on the substrate solubility and reaction temperature requirements.

[0010] The molar ratio of trifluoromethylhydrazone chloride to N-cyano-N-p-toluenesulfonamide is 2:1.

[0011] The reaction time is 12 to 48 hours.

[0012] The core reaction process of this invention includes:

[0013] .

[0014] This transformation process involves a tandem reaction of nucleophilic substitution and [3+2] cycloaddition. Specifically, the cyano group (-CN) in NCTS, under base regulation or as a nucleophilic site, interacts with the activated acyl chloride group or hydrazone unit in trifluoromethylhydrazone chloride, undergoing cyclization and ring closure to ultimately construct a 1,2,4-triazole core skeleton, while simultaneously introducing trifluoromethyl and acylhydrazone fragments.

[0015] In addition, the present invention also provides a trifluoromethyl-substituted 1,2,4-triazole hydrazone derivative, which is prepared by the above method.

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0017] (1) It successfully avoids the harsh conditions commonly found in existing technologies, such as multi-step synthesis, use of transition metal catalysts, high temperature (usually >100 °C), stoichiometric oxidants or peroxides, and achieves a great simplification of the steps.

[0018] (2) The designed one-step tandem reaction path allows most atoms in the starting material to enter the target product skeleton, and the by-products are mainly inorganic salts, thereby maximizing the atom economy of the reaction.

[0019] (3) The synthesized trifluoromethyl-substituted 1,2,4-triazole hydrazone derivatives have molecular structures that integrate multiple pharmacophores or active fragments, including a trifluoromethyl group (which imparts high lipophilicity, metabolic stability, and electronic effects), a 1,2,4-triazole ring (which provides coordination ability and various non-covalent interactions), and an hydrazone fragment (which has biological activity and sites for further modification). This structural diversity makes these compounds theoretically possess rich potential for biological and pharmacological activity, and they can be used for screening drug lead compounds or active molecules for agrochemicals.

[0020] (4) This method has the characteristics of simple reaction system (few components), mild conditions (normal pressure, medium and low temperature range), simple operation (one-pot method, no special equipment required), and readily available raw materials (starting materials can be commercially obtained or are easy to prepare). It is convenient for laboratory synthesis scale-up and potential process transformation, laying a good foundation for its application expansion and future market development. Attached Figure Description

[0021] Figure 1 The 3aa compound synthesized in Example 1 of this invention 1 H NMR spectrum;

[0022] Figure 2 The 3aa compound synthesized in Example 2 of this invention 1 H NMR spectrum;

[0023] Figure 3 The 3aa compound synthesized in Example 3 of this invention 1 H NMR spectrum. Detailed Implementation

[0024] To facilitate understanding by those skilled in the art, the present invention will be further described below with reference to embodiments and accompanying drawings. The content mentioned in the embodiments is not intended to limit the present invention.

[0025] A method for preparing trifluoromethyl-substituted 1,2,4-triazole hydrazone derivatives includes the following steps: mixing trifluoromethylhydrazone chloride, N-cyano-N-p-toluenesulfonamide, a base, and an organic solvent, and carrying out a one-pot cascade reaction of cyclization and nucleophilic substitution in air to obtain trifluoromethyl-substituted 1,2,4-triazole hydrazone derivatives. The following examples are all based on this preparation method.

[0026] Example 1

[0027] Using trifluoromethylhydrazone chloride 1a and N-cyano-N-aryl-p-toluenesulfonamide 2a as standard substrates, a trifluoromethyl-substituted 1,2,4-triazolylhydrazone 3aa compound was obtained. The reaction process is as follows:

[0028] ;

[0029] The following table shows the different yields obtained by choosing different base pairs in the reaction:

[0030] Entry Base Yield (%) 1 NaOH 20 2 TMG 40 3 <![CDATA[NaO t This]]> 12 4 18-crown ether-6 n.r. 5 DBU 11 6 <![CDATA[Cs2CO3]]> 10 7 KOH 5 8 CsF 40 9 AgF 14

[0031] In this example, the reaction was carried out at room temperature in 1.0 mL of toluene solvent for 48 hours, using 2.2 equivalents of base; and 1a / 2a = 2.0. TMG represents tetramethylguanidine, 18-crown ether-6 represents 18-crown ether-6, DBU represents 1,8-diazobispirocyclic [5.4.0]undecyl-7-ene; Yield refers to the total yield of 1,2,4-triazoles substituted with trifluoromethyl and imine groups.

[0032] Example 2

[0033] Using trifluoromethylhydrazone chloride 1a and N-cyano-N-aryl-p-toluenesulfonamide 2a as standard substrates, a trifluoromethyl-substituted 1,2,4-triazolylhydrazone 3aa compound was obtained. The reaction process is as follows:

[0034] ;

[0035] The following table shows the different results of choosing different solvents for the reaction yield:

[0036] Entry Solvent yield (%) 1 THF 14 2 1,4-dioxane 13 3 DMF 10 4 EA 11 5 EtOH 9 6 acetone 33 7 toluene 12 8 o-xylene 9

[0037] In this embodiment, the reaction was carried out at room temperature in 1.0 mL of the solvent shown in the table for 48 hours; where equiv represents equivalent volume in the reaction system; Yield refers to the total isolated yield of 1,2,4-triazoles containing trifluoromethyl and imine substituents. 1a / 2a = 2.0. THF refers to tetrahydrofuran, 1,4-dioxane refers to 1,4-dioxane, DMF refers to N,N-dimethylformamide, EA refers to ethyl acetate, EtOH refers to ethanol, acetone refers to acetone, toluene refers to toluene, and o-xylene refers to o-xylene.

[0038] Example 3

[0039] Using trifluoromethylhydrazone chloride 1a and N-cyano-N-aryl-p-toluenesulfonamide 2a as standard substrates, a trifluoromethyl-substituted 1,2,4-triazolylhydrazone 3aa compound was synthesized. The reaction process is as follows:

[0040] ;

[0041] The following table shows the different results of the reaction yield with different molar ratios of base to reactant 1a, molar ratios of 1a to 2a, and different temperatures:

[0042] Entry CsF (X eq.) 1a / 2a <![CDATA[Temp. ( o C)]]> Yield (%) 1 2.2 2.0 5 62 2.2 2.0 0 60 2 3.5 2.0 5 69 3 4.0 2.0 5 76 4 4.0 3.0 5 84 5 4.0 3.5 5 73

[0043] In this embodiment, the reaction was carried out at 5 degrees Celsius in 1.0 mL of acetonitrile solvent for 48 hours; CsF in the reaction system is cesium fluoride; equiv represents equivalent amount; yield refers to the total separation yield of trifluoromethyl-substituted 1,2,4-triazolylhydrazone 3aa.

[0044] Example 4

[0045] In this embodiment, (E)-2,2,2-trifluoro-N,N'-diphenyl-N-[1-phenyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetamide hydrazone 3aa was prepared, and its structural formula is as follows:

[0046] .

[0047] The preparation method includes the following steps:

[0048] Weigh cesium fluoride (121 mg, 0.8 mmol, 4.0 eq.), trifluoromethylhydrazone chloride (133.6 mg, 0.6 mmol, 3.0 eq.), and N-cyano-N-phenyl-p-toluenesulfonamide (54.5 mg, 0.2 mmol, 1.0 eq.) into a 10 mL Schlenk tube equipped with a magnetic strip. Add 2.0 mL of acetonitrile using a pipette, then seal the tube and incubate at 5°C. o The reaction was carried out at C for 12 h. After the reaction was complete, the mixture was filtered through a silica gel funnel. The filter residue was washed with 20 mL of ethyl acetate. The filtrate was concentrated under reduced pressure to obtain the residue, which was then purified and separated by column chromatography to obtain the pyridine product. 200-300 mesh silica gel was used, and the mobile phase was petroleum ether:ethyl acetate.

[0049] The structural characterization data are as follows:

[0050] 84% yield; 1 H NMR (500 MHz, CDCl3) δ 7.99 (s, 1H), 7.34 – 7.33 (m, 2H), 7.26 – 7.14 (m, 8H), 7.01 (t, J = 7.4 Hz, 1H), 6.89 (t, J = 7.3 Hz, 1H), 6.81(d, J = 6.5 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 152.78 (d, J = 40.5 Hz),150.62, 141.68, 139.15, 135.44, 130.33, 129.94, 129.40, 129.28, 125.32,124.19, 122.86, 120.09 (d, J = 273.8 Hz), 119.40 (d, J = 38.3 Hz), 118.75 (q,J = 270.8 Hz), 118.42, 114.05; 19 F NMR (471 MHz, CDCl3) δ -65.82, -65.85.

[0051] Example 5

[0052] In this embodiment, (E)-2,2,2-trifluoro-N'-phenyl-N-(1-phenyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-N-(p-tolyl)acetylhydrazoneamide was prepared, with the following structural formula:

[0053] .

[0054] The structural characterization data are as follows:

[0055] 62% yield; 1 H NMR (500 MHz, CDCl3) δ 8.01 (s, 1H), 7.40 – 7.38 (m, 2H), 7.31 – 7.28 (m, 3H), 7.22 (dd, J = 8.3, 7.6 Hz, 2H), 7.05 (d, J = 8.3 Hz, 2H), 6.94 (t, J = 7.4 Hz, 1H), 6.87 (d, J = 7.7 Hz, 2H), 6.80 (d, J = 8.5 Hz, 2H), 2.24 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 152.69 (q, J = 40.4 Hz), 150.98,141.75, 136.60, 135.49, 135.48, 130.86, 129.87, 129.36, 129.26, 124.27,122.75, 120.11 (q, J = 273.7 Hz), 119.86 (q, J = 38.4 Hz), 118.94, 118.81 (q,J = 270.4 Hz), 114.00, 20.71; 19 F NMR (471 MHz, CDCl3) δ -65.75, -65.80.

[0056] Example 6

[0057] In this embodiment, (E)-2,2,2-trifluoro-N-(4-methoxyphenyl)-N'-phenyl-N-[1-phenyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0058] .

[0059] The structural characterization data are as follows:

[0060] 65% yield; 1 H NMR (500 MHz, CDCl3) δ 7.97 (s, 1H), 7.37 – 7.34 (m, 2H), 7.30 (dd, J = 7.0, 3.6 Hz, 3H), 7.24 – 7.20 (m, 2H), 6.95 (t, J = 7.4 Hz, 1H), 6.92 – 6.86 (m, 4H), 6.78 – 6.76 (m, 2H), 3.72 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 157.52, 152.58 (q, J = 40.3 Hz), 151.35, 141.78, 135.46, 131.86,129.89, 129.31, 129.26, 124.47, 122.71, 121.49, 120.34 (q, J = 38.1 Hz), 120.07 (q, J = 273.9 Hz), 118.81 (q, J = 270.3 Hz), 115.47, 113.96, 55.52; 19FNMR (471 MHz, CDCl3) δ -65.49, -65.81.

[0061] Example 7

[0062] In this embodiment, (E)-N-(4-butoxyphenyl)-2,2,2-trifluoro-N'-phenyl-N-[1-phenyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0063] .

[0064] The structural characterization data are as follows:

[0065] 40% yield; 1 H NMR (500 MHz, CDCl3) δ 7.96 (s, 1H), 7.37 – 7.34 (m, 2H), 7.30 – 7.29 (m, 3H), 7.23 (dd, J = 14.3, 6.6 Hz, 2H), 6.95 (t, J = 7.4 Hz, 1H), 6.90 – 6.85 (m, 4H), 6.79 – 6.74 (m, 2H), 3.86 (t, J = 6.5 Hz, 2H), 1.74 – 1.68 (m, 2H), 1.48 – 1.41 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H); 13 C NMR (126MHz, CDCl3) δ 157.12, 152.59 (q, J = 40.3 Hz), 151.36, 141.80, 135.48,131.67, 129.85, 129.29, 129.25, 124.48, 122.68, 121.47, 120.40 (q, J = 37.9Hz), 120.05 (q, J = 274.0 Hz), 118.80 (q, J = 270.5 Hz), 116.05, 113.95,68.06, 31.15, 19.17, 13.81; 19 F NMR (471 MHz, CDCl3) δ -65.52, -65.84.

[0066] Example 8

[0067] In this embodiment, (E)-N-[4-(tert-butyl)phenyl]-2,2,2-trifluoro-N'-phenyl-N-[1-phenyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0068] .

[0069] The structural characterization data are as follows:

[0070] 57% yield; 1 H NMR (500 MHz, CDCl3) δ 8.05 (s, 1H), 7.37 – 7.35 (m, 2H), 7.30 – 7.21 (m, 7H), 6.95 (t, J = 7.4 Hz, 1H), 6.87 (d, J = 7.8 Hz, 2H), 6.83(dd, J = 9.2, 2.3 Hz, 2H), 1.23 (s, 9H); 13 C NMR (126 MHz, CDCl3) δ 152.66 (q,J = 40.4 Hz), 151.07, 148.69, 141.k79, 136.32, 135.49, 129.83, 129.29,129.26, 127.14, 124.48, 122.73, 120.09 (q, J = 273.9 Hz), 119.73 (q, J = 38.7Hz), 118.81 (q, J = 270.2 Hz), 118.64, 114.01, 34.41, 31.18; 19 F NMR (471 MHz, CDCl3) δ -65.64, -65.80.

[0071] Example 9

[0072] In this embodiment, (E)-N-[1,1'-biphenyl]-4-yl-2,2,2-trifluoro-N'-phenyl-N-[1-phenyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0073] .

[0074] The structural characterization data are as follows:

[0075] 75% yield; 1H NMR (500 MHz, CDCl3) δ 8.06 (s, 1H), 7.41 – 7.38 (m, 4H), 7.35 – 7.31 (m, 4H), 7.26 – 7.20 (m, 4H), 7.16 – 7.13 (m, 2H), 6.89 – 6.86(m, 3H), 6.82 (d, J = 7.8 Hz, 2H); 13 C NMR (126 MHz, CDCl3) δ 152.81 (q, J =40.5 Hz), 150.67, 141.67, 139.54, 138.37, 138.30, 135.42, 130.06, 129.47,129.32, 128.94, 128.86, 127.65, 126.82, 124.30, 122.95, 120.11 (q, J = 273.7Hz), 119.30 (q, J = 38.5 Hz), 118.78 (q, J = 270.6 Hz), 118.77, 114.12; 19 FNMR (471 MHz, CDCl3) δ -65.70, -65.75.

[0076] Example 10

[0077] In this embodiment, methyl (E)-4-[2,2,2-trifluoro-N'-phenyl-N-(1-phenyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)acetylhydrazone]benzoate was prepared, with the following structural formula:

[0078] .

[0079] The structural characterization data are as follows:

[0080] 67% yield; 1 H NMR (500 MHz, CDCl3) δ 8.30 (s, 1H), 7.95 – 7.92 (m, 2H), 7.45 – 7.43 (m, 2H), 7.36 – 7.31 (m, 3H), 7.26 – 7.23 (m, 2H), 6.98 (t, J =7.4 Hz, 1H), 6.94 (d, J = 7.7 Hz, 2H), 6.87 (d, J = 8.9 Hz, 2H), 3.86 (s,3H); 13C NMR (126 MHz, CDCl3) δ 165.93, 152.91 (q, J = 40.8 Hz), 149.69,143.30, 141.44, 135.20, 131.91, 130.28, 129.62, 129.33, 126.34, 123.99,123.24, 120.00 (q, J = 273.5 Hz), 118.63 (q, J = 270.6 Hz), 118.00 (q, J =38.9 Hz); 116.64, 114.21, 52.24, 26.93; 19 F NMR (471 MHz, CDCl3) δ -65.80, -66.01.

[0081] Example 11

[0082] In this embodiment, (E)-N-[4-(trifluoromethyl)phenyl]-2,2,2-trifluoro-N'-phenyl-N-[1-phenyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0083] .

[0084] The structural characterization data are as follows:

[0085] 74% yield; 1 H NMR (500 MHz, CDCl3) δ 8.34 (s, 1H), 7.56 (d, J = 8.7 Hz,2H), 7.43 (dd, J = 7.8, 1.8 Hz, 2H), 7.39 – 7.35 (m, 3H), 7.28 – 7.24 (m,2H), 7.00 (t, J = 7.4 Hz, 1H), 6.94 (dd, J = 7.8, 6.6 Hz, 4H); 13C NMR (126MHz, CDCl3) δ 152.95 (q, J = 40.8 Hz), 149.75, 142.69, 141.37, 135.09,130.45, 129.70, 129.38, 127.58 (q, J = 3.6 Hz), 126.75 (q, J = 33.3 Hz), 123.67 (q, J = 271.7 Hz), 124.10, 123.37, 116.95, 119.93 (q, J = 273.5 Hz), 118.60 (q, J = 270.7 Hz), 117.90 (q, J = 39.0 Hz), 114.24; 19 F NMR (471 MHz, CDCl3) δ -62.32, -65.82, -65.99.

[0086] Example 12

[0087] In this embodiment, (E)-N-(4-fluorophenyl)-2,2,2-trifluoro-N'-phenyl-N-[1-phenyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0088] .

[0089] The structural characterization data are as follows:

[0090] 80% yield; 1 H NMR (500 MHz, CDCl3) δ 8.02 (s, 1H), 7.39 – 7.36 (m, 2H), 7.34 – 7.31 (m, 3H), 7.24 (dd, J = 8.4, 7.6 Hz, 2H), 6.99 – 6.95 (m, 3H), 6.92 – 6.89 (m, 4H); 13C NMR (126 MHz, CDCl3) δ 159.94 (d, J = 246.5 Hz), 152.75 (q, J = 40.5 Hz), 150.81, 141.55, 135.29, 135.21 (d, J = 2.9 Hz), 130.16, 129.49, 129.34, 124.35, 123.04, 120.68 (d, J = 8.3 Hz), 120.00 (q, J= 273.9 Hz), 119.54 (q, J = 38.5 Hz), 118.71 (q, J = 270.6 Hz), 117.20 (d, J= 23.3 Hz), 114.07; 19 F NMR (471 MHz, CDCl3) δ -65.63, -65.84, -115.96.

[0091] Example 13

[0092] In this embodiment, (E)-N-(4-chlorophenyl)-2,2,2-trifluoro-N'-phenyl-N-[1-phenyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0093] .

[0094] The structural characterization data are as follows:

[0095] 77% yield; 1 H NMR (500 MHz, CDCl3) δ 8.11 (s, 1H), 7.41 – 7.38 (m, 2H), 7.37 – 7.33 (m, 3H), 7.26 – 7.23 (m, 4H), 6.98 (t, J = 7.4 Hz, 1H), 6.91 (d,J = 7.8 Hz, 2H), 6.85 – 6.82 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 152.83 (q, J= 40.6 Hz), 150.33, 141.48, 137.96, 135.22, 130.57, 130.34, 130.26, 129.58,129.35, 124.20, 123.15, 119.40, 119.97 (q, J = 273.7 Hz), 118.88 (q, J = 38.6Hz), 118.67 (q, J = 270.6 Hz), 114.14; 19 F NMR (471 MHz, CDCl3) δ -65.80, -65.81.

[0096] Example 14

[0097] In this embodiment, (E)-N-(4-bromophenyl)-2,2,2-trifluoro-N'-phenyl-N-[1-phenyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0098] .

[0099] The structural characterization data are as follows:

[0100] 58% yield; 1 H NMR (500 MHz, CDCl3) δ 8.14 (s, 1H), 7.41 – 7.34 (m, 7H), 7.25 (dd, J = 9.6, 6.2 Hz, 2H), 6.99 (t, J = 7.4 Hz, 1H), 6.92 (d, J = 7.8Hz, 2H), 6.77 (d, J = 8.9 Hz, 2H); 13 C NMR (126 MHz, CDCl3) δ 152.83 (q, J =40.6 Hz), 150.22, 141.46, 138.55, 135.20, 133.27, 130.28, 129.60, 129.35,124.18, 123.17, 119.58, 119.96 (q, J = 273.6 Hz), 118.74 (q, J = 38.7 Hz), 118.66 (q, J = 270.6 Hz), 118.03, 114.15; 19 F NMR (471 MHz, CDCl3) δ -65.80, -65.82.

[0101] Example 15

[0102] In this embodiment, (E)-N-(4-iodophenyl)-2,2,2-trifluoro-N'-phenyl-N-[1-phenyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0103] .

[0104] The structural characterization data are as follows:

[0105] 63% yield; 1 H NMR (500 MHz, CDCl3) δ 8.17 (s, 1H), 7.58 (d, J = 8.9 Hz,2H), 7.40 (dd, J = 6.9, 3.0 Hz, 2H), 7.37 – 7.35 (m, 3H), 7.27 – 7.24 (m,2H), 6.99 (t, J = 7.4 Hz, 1H), 6.92 (d, J = 7.8 Hz, 2H), 6.64 (d, J = 8.9 Hz, 2H); 13 C NMR (126 MHz, CDCl3) δ 152.83 (q, J = 40.6 Hz), 150.12, 141.46,139.36, 139.16, 135.19, 130.28, 129.60, 129.35, 124.16, 123.17, 119.94 (q, J = 273.6 Hz), 119.71, 118.64 (q, J = 269.8 Hz), 118.58 (q, J = 38.7 Hz), 114.16, 88.43.

[0106] Example 16

[0107] In this embodiment, (E)-N-(3-bromo-4-methylphenyl)-2,2,2-trifluoro-N'-phenyl-N-[1-phenyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0108] .

[0109] The structural characterization data are as follows:

[0110] 70% yield; 1H NMR (500 MHz, CDCl3) δ 8.14 (s, 1H), 7.40 – 7.39 (m, 3H), 7.34 – 7.33 (m, 3H), 7.24 (t, J = 6.9 Hz, 2H), 6.98 (t, J = 7.3 Hz, 1H), 6.92(d, J = 7.4 Hz, 2H), 6.73 (s, 1H), 6.59 (d, J = 8.6 Hz, 1H), 2.29 (d, J = 1.6Hz, 3H); 13 C NMR (126 MHz, CDCl3) δ 152.80 (q, J = 40.6 Hz), 150.37, 141.55,140.27, 138.54, 135.33, 133.90, 130.18, 129.52, 129.33, 124.17, 123.09,120.70, 120.26, 119.99 (q, J = 273.8 Hz), 118.99 (q, J = 38.6 Hz), 118.70 (q,J = 270.6 Hz), 117.16, 114.16, 23.18; 19 F NMR (471 MHz, CDCl3) δ -65.71, -65.78.

[0111] Example 17

[0112] In this embodiment, (E)-N-(o-tolyl)-2,2,2-trifluoro-N'-phenyl-N-[1-phenyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0113] .

[0114] The structural characterization data are as follows:

[0115] 20% yield; 1 H NMR (500 MHz, CDCl3) δ 7.61 (s, 1H), 7.36 – 7.29 (m, 3H), 7.25 – 7.22 (m, 4H), 7.16 – 7.13 (m, 3H), 7.06 – 7.04 (m, 1H), 6.95 (t, J =7.4 Hz, 1H), 6.82 (d, J = 7.8 Hz, 2H), 2.12 (s, 3H); 13C NMR (126 MHz, CDCl3)δ 152.62 (q, J = 40.2 Hz), 151.97, 141.99, 137.22, 135.27, 132.60, 132.42,130.13, 129.35, 129.26, 128.06, 128.03, 125.04, 124.45, 122.63, 121.29 (q, J= 37.7 Hz), 119.66 (q, J = 274.9 Hz), 118.78 (q, J = 270.4 Hz), 18.08; 19 F NMR (471 MHz, CDCl3) δ -63.54, -65.90.

[0116] Example 18

[0117] In this embodiment, (E)-N-(2-cyanophenyl)-2,2,2-trifluoro-N'-phenyl-N-[1-phenyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0118] .

[0119] The structural characterization data are as follows:

[0120] 60% yield; 1 H NMR (500 MHz, Acetone) δ 9.18 (s, 1H), 8.18 (d, J = 7.9Hz, 1H), 7.69 (t, J = 7.6 Hz, 1H), 7.60 (d, J = 7.9 Hz, 1H), 7.55 (d, J = 6.8Hz, 3H), 7.11 – 6.94 (m, 5H), 6.88 (t, J = 7.5 Hz, 2H), 6.79 (t, J = 7.3 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 159.60, 158.10, 156.13 (d, J = 39.2 Hz), 148.10 (d, J = 36.0 Hz), 145.82, 145.29, 142.66, 139.10, 135.01, 134.59,133.90, 133.63, 133.55, 130.78, 130.63, 130.35, 127.29, 125.70, 124.56 (d, J= 269.4 Hz), 122.99 (d, J = 276.8 Hz); 19 F NMR (471 MHz, CDCl3) δ -61.23, -62.01.

[0121] Example 19

[0122] In this embodiment, (E)-N-(m-tolyl)-2,2,2-trifluoro-N'-phenyl-N-[1-phenyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0123] .

[0124] The structural characterization data are as follows:

[0125] 77% yield; 1 H NMR (500 MHz, CDCl3) δ 8.07 (s, 1H), 7.40 – 7.39 (m, 2H), 7.33 – 7.29 (m, 3H), 7.25 – 7.21 (m, 2H), 7.13 (t, J = 7.8 Hz, 1H), 6.96 (t,J = 7.4 Hz, 1H), 6.88 (t, J = 6.8 Hz, 3H), 6.74 – 6.64 (m, 2H), 2.24 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 152.73 (d, J = 40.4 Hz), 150.68, 141.73, 140.54,139.01, 135.54, 130.11, 129.85, 129.31, 129.25, 126.24, 124.13, 122.77,120.09 (q, J = 273.8 Hz), 119.58 (d, J = 38.4 Hz), 119.11, 118.76 (q, J =270.4 Hz), 115.70, 114.04, 21.43; 19 F NMR (471 MHz, CDCl3) δ -65.73, -65.77.

[0126] Example 20

[0127] In this embodiment, (E)-N-(naphth-2-yl)-2,2,2-trifluoro-N'-phenyl-N-[1-phenyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0128] .

[0129] The structural characterization data are as follows:

[0130] 89% yield; 1 H NMR (500 MHz, CDCl3) δ 8.17 (s, 1H), 7.74 (t, J = 9.3 Hz,2H), 7.65 (d, J = 8.1 Hz, 1H), 7.45 – 7.40 (m, 4H), 7.25 – 7.18 (m, 6H), 7.07(dd, J = 8.9, 2.5 Hz, 1H), 6.92 (t, J = 7.4 Hz, 1H), 6.86 – 6.85 (m, 2H); 13CNMR (126 MHz, CDCl3) δ 152.86 (q, J = 40.5 Hz), 150.76, 141.65, 136.75,135.43, 133.74, 130.84, 130.83k, 129.99, 129.40, 129.26, 127.78, 127.48,127.30, 126.01, 124.18, 122.91, 120.18 (q, J = 273.8 Hz), 119.47 (q, J = 38.3Hz), 118.83 (q, J = 270.5 Hz), 117.72, 115.54, 114.11; 19 F NMR (471 MHz, CDCl3) δ -65.62, -65.70.

[0131] Example 21

[0132] In this embodiment, (E)-N-[4-(diphenylamino)phenyl]-2,2,2-trifluoro-N'-phenyl-N-[1-phenyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0133] .

[0134] The structural characterization data are as follows:

[0135] 50% yield; 1 H NMR (500 MHz, CDCl3) δ 8.34 (d, J = 0.7 Hz, 1H), 7.92 (d,J = 7.6 Hz, 4H), 7.79 – 7.76 (m, 4H), 7.50 – 7.45 (m, 9H), 7.37 – 7.34 (m,5H), 6.99 (d, J = 13.1 Hz, 2H); 13C NMR (126 MHz, CDCl3) δ 152.65 (d, J = 40.4Hz), 151.02, 147.12, 145.76, 141.85, 135.71, 132.76, 129.68, 129.38, 129.34,129.32, 124.96, 124.57, 124.26, 123.36, 122.79, 120.91, 120.11 (q, J = 273.9Hz), 120.10 (q, J = 38.2 Hz), 118.79 (q, J = 270.4 Hz), 113.99; 19 F NMR (471MHz, CDCl3) δ -65.42, -65.82.

[0136] Example 22

[0137] In this embodiment, (E)-N-[4-(1,2,2-tristyryl)phenyl]-2,2,2-trifluoro-N'-phenyl-N-[1-phenyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0138] .

[0139] The structural characterization data are as follows:

[0140] 40% yield; R f = 0.4 (PE : EA = 4 : 1). 1 H NMR (500 MHz, CDCl3) δ 7.87 (s,1H), 7.37 – 7.28 (m, 7H), 7.09 – 7.07 (m, 6H), 7.01 (t, J = 7.1 Hz, 2H), 6.96– 6.68 (m, 10H), 6.82 (d, J = 7.2 Hz, 2H), 6.63 (d, J = 8.1 Hz, 2H); 13C NMR(126 MHz, CDCl3) δ 152.71 (d, J = 40.4 Hz), 150.44, 143.31, 143.13, 142.97,141.69, 141.68, 141.54, 139.16, 136.63, 135.67, 133.35, 131.26, 131.18,131.12, 129.52, 129.33, 129.26, 127.82, 127.73, 126.77, 126.72, 126.70,124.19, 122.85, 120.16 (q, J = 273.7 Hz), 119.56 (q, J = 38.1 Hz), 118.76 (q, J = 270.2 Hz), 118.57, 114.02; 19 F NMR (471 MHz, CDCl3) δ -65.80, -65.82.

[0141] Example 23

[0142] In this embodiment, (E)-N-phenyl-2,2,2-trifluoro-N'-(p-tolyl)-N-[1-(p-tolyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0143] .

[0144] The structural characterization data are as follows:

[0145] 80% yield; 1 H NMR (500 MHz, CDCl3) δ 7.78 (s, 1H), 7.20 – 7.15 (m, 4H), 7.01 – 6.99 (m, 3H), 6.93 (d, J = 8.3 Hz, 2H), 6.79 (d, J = 7.9 Hz, 2H), 6.65(d, J = 8.4 Hz, 2H), 2.17 (s, 3H), 2.09 (s, 3H); 13C NMR (126 MHz, CDCl3) δ151.60 (q, J = 40.4 Hz), 149.81, 139.53, 138.33, 138.22, 131.71, 131.27,129.19, 128.93, 128.63, 123.99, 123.23, 119.11 (q, J = 273.6 Hz), 117.76 (q, J = 270.5 Hz), 117.64 (q, J = 38.3 Hz), 117.04, 112.95, 19.95, 19.57; 19 F NMR (471 MHz, CDCl3) δ -65.71, -65.75.

[0146] Example 24

[0147] In this embodiment, (E)-N'-(4-ethylphenyl)-2,2,2-trifluoro-N-phenyl-N-[1-(4-ethylphenyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0148] .

[0149] The structural characterization data are as follows:

[0150] 70% yield; 1 H NMR (500 MHz, CDCl3) δ 7.79 (s, 1H), 7.21 – 7.16 (m, 4H), 7.04 – 6.95 (m, 5H), 6.81 (d, J = 7.6 Hz, 2H), 6.68 (d, J = 8.3 Hz, 2H), 2.47(q, J = 7.5 Hz, 2H), 2.40 (q, J = 7.6 Hz, 2H), 1.09 (t, J = 7.6 Hz, 3H), 0.96(t, J = 7.6 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 151.61 (q, J = 40.3 Hz),149.88, 145.78, 138.49, 138.18, 137.88, 131.81, 129.18, 127.75, 127.51,124.01, 123.41, 119.09 (q, J = 273.8 Hz), 117.76 (q, J = 270.5 Hz), 117.68 (d, J = 38.2 Hz), 117.17, 112.97, 27.30, 27.11, 14.81, 13.95; 19 F NMR (471MHz, CDCl3) δ -65.68, -65.78.

[0151] Example 25

[0152] In this embodiment, (E)-2,2,2-trifluoro-N'-(4-isopropylphenyl)-N-phenyl-N-[1-(4-isopropylphenyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0153] .

[0154] The structural characterization data are as follows:

[0155] 72% yield; 1 H NMR (500 MHz, CDCl3) δ 7.83 (s, 1H), 7.30 – 7.24 (m, 4H), 7.14 (d, J = 8.4 Hz, 2H), 7.09 – 7.06 (m, 3H), 6.90 (d, J = 7.8 Hz, 2H), 6.76(d, J = 8.5 Hz, 2H), 2.84 – 2.78 (m, 1H), 2.76 – 2.71 (m, 1H), 1.18 (d, J =6.9 Hz, 6H), 1.04 (d, J = 6.9 Hz, 6H); 13C NMR (126 MHz, CDCl3) δ 152.68 (d, J= 40.3 Hz), 151.50, 151.02, 143.61, 139.56, 139.16, 132.86, 130.22, 127.44,127.14, 125.08, 124.58, 120.13 (q, J = 273.8 Hz), 118.83 (q, J = 270.5 Hz), 118.71 (d, J = 38.2 Hz), 118.31, 113.94, 33.76, 33.48, 24.08, 23.50; 19 F NMR (471 MHz, CDCl3) δ -65.65, -65.78.

[0156] Example 26

[0157] In this embodiment, (E)-N'-[4-(tert-butyl)phenyl]-2,2,2-trifluoro-N-phenyl-N-[1-(4-(tert-butyl)phenyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0158] .

[0159] The structural characterization data are as follows:

[0160] 69% yield; 1 H NMR (500 MHz, CDCl3) δ 7.78 (s, 1H), 7.30 (s, 4H), 7.28 –7.22 (m, 4H), 7.08 (t, J = 7.4 Hz, 1H), 6.91 (d, J = 7.8 Hz, 2H), 6.76 (d, J= 8.7 Hz, 2H), 1.25 (s, 9H), 1.10 (s, 9H); 13C NMR (126 MHz, CDCl3) δ 153.89,152.73 (d, J = 40.3 Hz), 151.11, 145.85, 139.13, 139.10, 132.49, 130.22,126.41, 126.09, 125.05, 124.33, 120.09 (q, J = 273.9 Hz), 118.82 (q, J =270.5 Hz), 118.65 (d, J = 38.2 Hz), 118.25, 113.58, 34.71, 34.23, 31.38,30.89; 19 F NMR (471 MHz, CDCl3) δ -65.69, -65.78.

[0161] Example 27

[0162] In this embodiment, (E)-2,2,2-trifluoro-N-phenyl-N'-[4-(trifluoromethoxy)phenyl]-N-{1-[4-(trifluoromethoxy)phenyl]-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl}acetylhydrazoneamide was prepared, with the following structural formula:

[0163] .

[0164] The structural characterization data are as follows:

[0165] 61% yield; 1 H NMR (500 MHz, CDCl3) δ 8.05 (s, 1H), 7.37 – 7.34 (m, 2H), 7.27 – 7.24 (m, 2H), 7.21 – 7.17 (m, 4H), 7.03 (t, J = 7.4 Hz, 1H), 6.77 (d,J = 7.9 Hz, 2H), 6.71 (d, J = 8.8 Hz, 2H); 13C NMR (126 MHz, Acetone) δ151.80, 151.74 (q, J = 39.8 Hz), 149.35 (d, J = 1.5 Hz), 149.16 (d, J = 1.7Hz), 143.94 (d, J = 1.6 Hz), 141.65, 137.98, 134.67, 129.53, 127.41, 125.96,122.26, 121.62, 121.46, 120.20 (d, J = 257.2 Hz), 120.07 (q, J = 37.4 Hz), 119.19 (q, J = 269.4 Hz), 118.40, 115.33; 19 F NMR (471 MHz, CDCl3) δ -58.20, -58.43, -65.97, -66.09.

[0166] Example 28

[0167] In this embodiment, (E)-2,2,2-trifluoro-N'-(4-fluorophenyl)-N-phenyl-N-[1-(4-fluorophenyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0168] .

[0169] The structural characterization data are as follows:

[0170] 65% yield; 1 H NMR (500 MHz, CDCl3) δ 8.12 (s, 1H), 7.39 (dd, J = 8.9,4.5 Hz, 2H), 7.27 (dd, J = 14.7, 7.0 Hz, 2H), 7.11 (t, J = 7.4 Hz, 1H), 7.00(t, J = 8.4 Hz, 2H), 6.94 (t, J = 8.6 Hz, 2H), 6.88 – 6.85 (m, 4H); 13C NMR(126 MHz, CDCl3) δ 162.86 (d, J = 251.8 Hz), 158.78 (d, J = 241.6 Hz), 152.78(q, J = 40.7 Hz), 150.56, 138.99, 137.94 (d, J = 2.3 Hz), 131.52 (d, J = 3.4Hz), 130.44, 126.22 (d, J = 9.0 Hz), 125.53, 120.06 (q, J = 273.7 Hz), 119.32(q, J = 38.5 Hz), 118.63 (q, J = 270.4 Hz), 118.34, 116.47 (d, J = 23.2 Hz), 116.01 (d, J = 23.0 Hz), 115.33 (d, J = 8.0 Hz); 19 F NMR (471 MHz, CDCl3) δ -65.89, -65.96, -109.49, -120.63.

[0171] Example 29

[0172] In this embodiment, (E)-N'-(4-chlorophenyl)-2,2,2-trifluoro-N-phenyl-N-[1-(4-chlorophenyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0173] .

[0174] The structural characterization data are as follows:

[0175] 56% yield; 1 H NMR (500 MHz, CDCl3) δ 8.14 (s, 1H), 7.36 (d, J = 8.8 Hz, 2H), 7.30 – 7.27 (m, 4H), 7.20 (d, J = 8.8 Hz, 2H), 7.12 (t, J = 7.4 Hz, 1H), 6.88 – 6.83 (m, 4H); 13C NMR (126 MHz, CDCl3) δ 152.91 (q, J = 40.7 Hz),150.32, 140.26, 138.90, 135.95, 133.90, 130.54, 129.61, 129.32, 127.92,125.62, 125.16, 119.98 (q, J = 273.7 Hz), 119.80 (q, J = 38.7 Hz), 118.58 (q, J = 270.8 Hz), 118.20, 115.28; 19 F NMR (471 MHz, CDCl3) δ -65.89, -66.08.

[0176] Example 30

[0177] In this embodiment, (E)-N'-(4-bromophenyl)-2,2,2-trifluoro-N-phenyl-N-[1-(4-bromophenyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0178] .

[0179] The structural characterization data are as follows:

[0180] 70% yield; 1 H NMR (500 MHz, CDCl3) δ 8.19 (s, 1H), 7.46 – 7.43 (m, 2H), 7.27 (dd, J = 8.4, 7.7 Hz, 2H), 7.16 (d, J = 8.6 Hz, 2H), 7.12 – 7.09 (m,3H), 6.94 – 6.91 (m, 2H), 6.87 (d, J = 7.9 Hz, 2H); 13 C NMR (126 MHz, CDCl3) δ151.87 (q, J = 40.7 Hz), 149.24, 139.69, 137.80, 133.34, 131.55, 131.17,129.50, 124.61, 124.31, 122.94, 118.93 (q, J = 273.8 Hz), 118.86 (q, J = 38.5Hz), 117.53 (q, J = 270.7 Hz), 117.16, 114.63, 114.31, 114.27; 19F NMR (471MHz, CDCl3) δ -65.87, -66.07.

[0181] Example 31

[0182] In this embodiment, (E)-2,2,2-trifluoro-N'-(4-iodophenyl)-N-phenyl-N-[1-(4-iodophenyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0183] .

[0184] The structural characterization data are as follows:

[0185] 58% yield; 1 H NMR (500 MHz, CDCl3) δ 8.08 (s, 1H), 7.65 – 7.63 (m, 2H), 7.53 – 7.52 (m, 2H), 7.30 – 7.25 (m, 2H), 7.16 – 7.11 (m, 3H), 6.84 (d, J =7.8 Hz, 2H), 6.69 – 6.66 (m, 2H); 13 C NMR (126 MHz, CDCl3) δ 152.96 (q, J =40.6 Hz), 150.25, 141.40, 138.87, 138.60, 138.15, 135.06, 130.57, 125.62,125.44, 120.00 (q, J = 38.5 Hz), 119.96 (q, J = 274.0 Hz), 118.57 (q, J =270.8 Hz), 118.12, 116.10, 95.58, 85.49.

[0186] Example 32

[0187] In this embodiment, (E)-2,2,2-trifluoro-N'-(naphth-2-yl)-N-phenyl-N-[1-(naphth-2-yl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0188] .

[0189] The structural characterization data are as follows:

[0190] 50% yield; 1H NMR (500 MHz, CDCl3) δ 8.14 (s, 1H), 7.90 (d, J = 1.9 Hz,1H), 7.77 (d, J = 8.8 Hz, 1H), 7.70 – 7.62 (m, 4H), 7.58 (d, J = 8.2 Hz, 1H), 7.51 (dd, J = 8.8, 2.1 Hz, 1H), 7.41 – 7.35 (m, 3H), 7.33 – 7.30 (m, 1H), 7.27 – 7.24 (m, 2H), 7.06 – 6.96 (m, 5H); 13 C NMR (126 MHz, CDCl3) δ 152.90(q, J = 40.6 Hz), 150.93, 139.26, 139.14, 133.83, 133.13, 132.62, 132.50,130.39, 130.06, 129.78, 129.35, 128.18, 127.75, 127.65, 127.33, 126.92,126.78, 125.39, 124.35, 123.44, 121.32, 120.17 (d, J = 274.0 Hz), 119.76 (d,J = 38.1 Hz), 118.82 (q, J = 270.9 Hz), 118.37, 115.02, 109.53; 19 F NMR (471MHz, CDCl3) δ -65.59, -65.71.

[0191] Example 33

[0192] In this embodiment, (E)-2,2,2-trifluoro-N-phenyl-N'-(o-tolyl)-N-[1-(o-tolyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0193] .

[0194] The structural characterization data are as follows:

[0195] 31% yield; 1H NMR (500 MHz, CDCl3) δ 7.97 (s, 1H), 7.28 – 7.24 (m, 2H), 7.19 – 7.16 (m, 3H), 7.09 (q, J = 7.3 Hz, 3H), 6.90 (d, J = 8.2 Hz, 2H), 6.77(d, J = 7.5 Hz, 1H), 6.70 (s, 1H), 6.65 (d, J = 8.0 Hz, 1H), 2.28 (s, 3H), 2.21 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 152.65 (q, J = 40.5 Hz), 150.69,141.67, 139.75, 139.35, 139.18, 135.29, 130.66, 130.25, 129.16, 129.10,125.33, 124.80, 123.69, 121.25, 120.13 (q, J = 273.8 Hz), 119.33 (q, J = 38.4Hz), 118.79 (q, J = 270.5 Hz), 118.59, 114.59, 111.22, 21.43, 21.08; 19 F NMR (471 MHz, CDCl3) δ -65.65, -65.79.

[0196] Example 34

[0197] In this embodiment, (E)-2,2,2-trifluoro-N-phenyl-N'-(m-tolyl)-N-[1-(m-tolyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0198] .

[0199] The structural characterization data are as follows:

[0200] 40% yield; 1H NMR (500 MHz, CDCl3) δ 7.96 (s, 1H), 7.28 – 7.24 (m, 2H), 7.19 – 7.18 (m, 3H), 7.11 – 7.07 (m, 3H), 6.90 (d, J = 7.9 Hz, 2H), 6.77 (d,J = 7.5 Hz, 1H), 6.70 – 6.66 (m, 2H), 2.28 (s, 3H), 2.21 (s, 3H); 13 C NMR (126MHz, CDCl3) δ 152.67 (q, J = 40.3 Hz), 150.73, 141.70, 139.78, 139.38,139.20, 135.32, 130.69, 130.28, 129.19, 129.13, 125.37, 124.83, 123.72,120.15 (q, J = 273.7 Hz), 119.34 (q, J = 38.3 Hz), 118.81 (q, J = 270.5 Hz),114.61, 111.24, 21.43, 21.08; 19 F NMR (471 MHz, CDCl3) δ -65.64, -65.78.

[0201] Example 35

[0202] In this embodiment, (E)-N'-(3-chlorophenyl)-2,2,2-trifluoro-N-phenyl-N-[1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0203] .

[0204] The structural characterization data are as follows:

[0205] 47% yield; 1 H NMR (500 MHz, CDCl3) δ 8.07 (s, 1H), 7.43 (s, 1H), 7.32 –7.23 (m, 5H), 7.16 – 7.11 (m, 2H), 6.96 – 6.93 (m, 2H), 6.88 (d, J = 8.3 Hz,2H), 6.75 (d, J = 8.2 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 152.97 (q, J = 40.6Hz), 150.41, 142.77, 138.56, 136.27, 135.21, 135.15, 130.57, 130.37, 130.33,129.95, 125.93, 124.29, 122.92, 121.94, 120.38 (q, J = 38.7 Hz), 119.91 (q, J= 274.1 Hz), 118.56 (q, J = 270.4 Hz), 118.69, 114.27, 112.28; 19 F NMR (471MHz, CDCl3) δ -65.92, -66.04.

[0206] Example 36

[0207] In this embodiment, (E)-N'-(3-bromophenyl)-2,2,2-trifluoro-N-phenyl-N-[1-(3-bromophenyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0208] .

[0209] 50% yield; 1 H NMR (500 MHz, CDCl3) δ 8.04 (s, 1H), 7.57 (s, 1H), 7.43 (d,J = 8.1 Hz, 1H), 7.36 (dd, J = 8.0, 1.1 Hz, 1H), 7.29 (t, J = 8.0 Hz, 2H),7.18 (t, J = 8.1 Hz, 1H), 7.14 – 7.07 (m, 4H), 6.89 (d, J = 8.0 Hz, 2H), 6.81– 6.79 (m, 1H); 13C NMR (126 MHz, CDCl3) δ152.98 (q, J = 40.5 Hz), 150.45,142.87, 138.53, 136.33, 132.88, 130.58, 127.15, 125.99, 125.85, 123.16,122.75, 122.44, 120.48 (q, J = 38.4 Hz), 119.92 (q, J = 274.1 Hz), 118.58 (q,J = 270.7 Hz), 118.78, 117.14, 112.78; 19 F NMR (471 MHz, CDCl3) δ -65.89, -65.98.

[0210] Example 37

[0211] In this embodiment, (E)-N'-(3,4-dimethylphenyl)-2,2,2-trifluoro-N-phenyl-N-[1-(3,4-dimethylphenyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0212] .

[0213] The structural characterization data are as follows:

[0214] 41% yield; 1 H NMR (500 MHz, CDCl3) δ 7.74 (s, 1H), 7.28 (t, J = 7.5 Hz, 2H), 7.13 – 7.03 (m, 4H), 6.96 (d, J = 8.1 Hz, 1H), 6.89 (d, J = 7.8 Hz, 2H), 6.59 – 6.53 (m, 2H), 2.18 (d, J = 9.5 Hz, 6H), 2.07 (d, J = 6.7 Hz, 6H); 13CNMR (126 MHz, CDCl3) δ 152.58 (q, J = 40.4 Hz), 150.93, 139.68, 139.38,139.26, 138.24, 137.56, 132.85, 131.01, 130.37, 130.19, 130.16, 125.48,124.99, 121.84, 120.17 (q, J = 274.0 Hz), 118.83 (q, J = 270.4 Hz), 118.65(d, J = 38.2 Hz), 118.14, 115.27, 111.39, 19.88, 19.59, 19.34, 18.99; 19 F NMR (471 MHz, CDCl3) δ -65.56 (d, J = 1.9 Hz), -65.76 (d, J = 1.7 Hz).

[0215] Example 38

[0216] In this embodiment, (E)-N'-(2,4-dichlorophenyl)-2,2,2-trifluoro-N-phenyl-N-[1-(2,4-dichlorophenyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0217] .

[0218] The structural characterization data are as follows:

[0219] 43% yield; 1 H NMR (500 MHz, CDCl3) δ 8.15 (s, 1H), 7.36 – 7.33 (m, 3H), 7.29 (dd, J = 8.5, 2.1 Hz, 1H), 7.23 – 7.18 (m, 5H), 7.13 (d, J = 7.9 Hz, 2H); 13C NMR (126 MHz, CDCl3) δ 153.49 (q, J = 40.8 Hz), 152.86, 137.83,137.61, 136.33, 132.35, 131.30, 130.36, 130.17, 130.08, 128.95, 128.39,128.31, 127.71, 126.81, 122.22 (q, J = 38.3 Hz), 120.74, 119.59 (q, J = 275.0Hz), 119.13, 118.56 (q, J = 270.7 Hz), 115.78; 19 F NMR (471 MHz, CDCl3) δ -65.54, -66.02.

[0220] Example 39

[0221] In this embodiment, (E)-N'-(3-chloro-4-methylphenyl)-2,2,2-trifluoro-N-phenyl-N-[1-(3-chloro-4-methylphenyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]acetylhydrazoneamide was prepared, with the following structural formula:

[0222] .

[0223] The structural characterization data are as follows:

[0224] 59% yield; 1 H NMR (500 MHz, CDCl3) δ 7.91 (s, 1H), 7.41 (d, J = 1.1 Hz,1H), 7.30 (t, J = 7.8 Hz, 2H), 7.21 – 7.19 (m, 1H), 7.16 – 7.10 (m, 2H), 7.05(d, J = 8.3 Hz, 1H), 6.91 – 6.88 (m, 3H), 6.69 – 6.64 (m, 1H), 2.27 (s, 3H), 2.24 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 152.85 (q, J = 40.6 Hz), 150.65,140.63, 138.78, 138.58, 135.00, 134.97, 133.78, 131.42, 131.30, 130.47,130.26, 125.64, 124.84, 122.27, 120.01 (q, J = 273.9 Hz), 119.75 (q, J = 38.4Hz), 118.67 (q, J = 270.7 Hz), 118.44, 114.70, 112.45, 19.71, 19.23; 19 F NMR (471 MHz, CDCl3) δ -65.86, -65.91.

[0225] To facilitate understanding by those skilled in the art of the improvements of this invention over the prior art, some of the accompanying drawings and descriptions have been simplified. The above embodiments are preferred implementations of this invention. In addition, this invention can be implemented in other ways. Any obvious substitutions without departing from the concept of this technical solution are within the protection scope of this invention.

Claims

1. A method for preparing a trifluoromethyl-substituted 1,2,4-triazole hydrazone derivative, characterized in that: Trifluoromethylhydrazone chloride, N-cyano-N-p-toluenesulfonamide, a base, and an organic solvent are mixed and reacted in an air atmosphere to obtain the trifluoromethyl-substituted 1,2,4-triazolylhydrazone derivative.

2. The method for preparing trifluoromethyl-substituted 1,2,4-triazole hydrazone derivatives according to claim 1, characterized in that: The alkali is an inorganic alkali or an organic alkali.

3. The method for preparing trifluoromethyl-substituted 1,2,4-triazole hydrazone derivatives according to claim 2, characterized in that: The base is one or more of triethylamine, DBU, potassium carbonate, and cesium carbonate.

4. The method for preparing trifluoromethyl-substituted 1,2,4-triazole hydrazone derivatives according to claim 1, characterized in that: The organic solvent is one or more of acetonitrile, toluene, tetrahydrofuran, o-xylene, m-xylene, p-xylene, trifluorotoluene, mesitylene, and acetone.

5. The method for preparing trifluoromethyl-substituted 1,2,4-triazole hydrazone derivatives according to claim 1, characterized in that: The molar ratio of trifluoromethylhydrazone chloride to N-cyano-N-p-toluenesulfonamide is 2:

1.

6. The method for preparing trifluoromethyl-substituted 1,2,4-triazole hydrazone derivatives according to claim 1, characterized in that: The reaction time is 12 to 48 hours.

7. The method for preparing trifluoromethyl-substituted 1,2,4-triazole hydrazone derivatives according to claim 1, characterized in that, The reaction process includes: 。 8. A trifluoromethyl-substituted 1,2,4-triazolylhydrazone derivative, characterized in that: It is prepared by the method described in any one of claims 1-7.

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