Synthesis method of 4-trifluoromethylthiophene compound

Abstract

The invention belongs to the technical field of organic synthesis, and discloses a synthesis method of a 4-trifluoromethylthiophene compound, which comprises the following steps: in a gas atmosphere, sequentially adding a metal catalyst, an alkyne compound as shown in a formula I, a disulfide compound as shown in a formula II and an organic solvent into a reactor, and reacting at 25-100 DEG C for 2-12 hours to obtain the 4-trifluoromethylthiophene compound. And after the alkyne compound is completely converted, extracting, combining organic phases, drying, concentrating, and carrying out column chromatography to obtain the 4-trifluoromethylthiophene compound as shown in a formula III. The trifluoromethyl-containing phenyl alkyne compound is used as a raw material, a series of target products are synthesized, the synthesis method of the 4-trifluoromethyl-containing thiophene compound is widened, the raw material is easy to obtain, the cost is low, and the requirement of industrial production is met.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis and relates to a method for synthesizing 4-trifluoromethylthiophene compounds. Background Art

[0002] High refractive index (n) has the characteristics of low birefringence and high transparency, which is the basis for the continuous research and development of advanced integrated optoelectronic devices. In recent years, the technology of realizing polymer materials with high refractive index and optical transparency has attracted strong attention. The advantages of organic polymers as candidates for optoelectronic applications are that they allow lightweight sustainable flat display technology with a larger coverage and enable low-cost low-temperature manufacturing.

[0003] Polymers with a refractive index greater than 1.5 (n>1.5) are high-refractive-index polymers. The preparation of high-refractive-index poly(arylether)s, poly(arylether sulfide)s, polyimides, poly(phenylene sulfide)s, etc. for optical devices is a current research hotspot. Thiophene has become a commonly used monomer in conjugated polymer electrochromic materials due to its good electrochemical properties. However, the potential of thiophene during electrochemical polymerization is high, which has a certain impact on the quality of the polymer film formed by it. Therefore, how to reduce the polymerization potential of the monomer through structural modification has become an effective way to improve the quality of its polymer film.

[0004] Currently, phenylthiophene can be synthesized by the following methods:

[0005] 1) Reaction of 1-bromo-2-(3-(trifluoromethyl)but-3-ene-1-yn-1-yl)benzene with sulfur: 1-bromo-2-(3-(trifluoromethyl)but-3-ene-1-yn-1-yl)benzene (1 equivalent), sulfur (1.2 equivalents) and DMF are stirred at 90°C for 10 hours and then post-treated to obtain a dimer of phenylthiophene (reference; Shengnan Jin, Shi-Jun Li, Xingxing Ma, JiankeSu, Haohua Chen, Yu Lan,* and Qiuling Song*, Angew. Chem. Int. Ed. 2021, 60, 881-888).

[0006] 2) Reaction of 4-fluoro-3-trifluoromethylphenylboronic acid with 2,5-dibromothiophene: In this reaction, 4-fluoro-3-trifluoromethylphenylboronic acid (1 equivalent) and 2,5-dibromothiophene (2.4 equivalents), tetrakis(triphenylphosphine)palladium (3% mmol), sodium carbonate aqueous solution (1M) and toluene were vigorously stirred and refluxed for 5 days. The palladium catalyst used in this reaction is difficult to remove and the reaction conditions are harsh (Reference: Susanta Banerjee, Gerhard Maier,* and Martin Burger, Macromolecules, 1999, 32, 4279-4289).

[0007] In summary, although phenylthiophene is an important organic synthesis intermediate, there are few existing synthesis methods so far, and the conditions are high and the operation is complicated, which is not conducive to industrial production. Therefore, it is of great significance to develop a new synthesis method of phenylthiophene. Summary of the invention

[0008] In view of the above technical problems, the present invention provides a method for synthesizing 4-trifluoromethylthiophene compounds, using phenylacetylene compounds containing trifluoromethyl as raw materials to synthesize a series of target products, thereby broadening the synthesis method of thiophene compounds containing 4-trifluoromethyl, and the raw materials are easily available, the cost is low, and the requirements of industrial production are met.

[0009] To achieve the above object, the present invention adopts the following technical solutions:

[0010] The present invention provides a method for synthesizing 4-trifluoromethylthiophene compounds, comprising the following steps: in a gas atmosphere, sequentially adding a metal catalyst, an acetylene compound represented by formula I, a disulfide compound represented by formula II and an organic solvent into a reactor, reacting at 25 to 100° C. for 2 to 12 hours, extracting after the acetylene compound is completely converted, combining the organic phases, drying, concentrating, and obtaining the 4-trifluoromethylthiophene compound represented by formula III through column chromatography;

[0011] The structural formula of the acetylene compound shown in Formula I is as follows:

[0012]

[0013] The structural formula of the disulfide compound shown in Formula II is as follows:

[0014]

[0015] The structural formula of the 4-trifluoromethylthiophene compound shown in Formula III is as follows:

[0016]

[0017] Where: R 1 is selected from one or two of hydrogen, halogen, alkyl, phenyl, methoxy or nitrile, R 2 One selected from methyl or ethyl.

[0018] The metal catalyst in the technical solution of the present invention is selected from one of ferric chloride, ferric bromide, ferrous iodide and ferrous acetylacetonate.

[0019] The organic solvent in the technical solution of the present invention is selected from one of toluene, ethanol, tetrahydrofuran, dimethyl sulfoxide, acetonitrile, dichloromethane, N,N-dimethylformamide or acetone.

[0020] The molar ratio of the acetylene compound represented by formula I to the disulfide compound represented by formula II in the technical solution of the present invention is 1:2-9.

[0021] The amount of the metal catalyst used in the technical solution of the present invention is 0.2 to 2.5 of the molar amount of the acetylene compound shown in formula I.

[0022] The gas atmosphere described in the technical solution of the present invention refers to a nitrogen atmosphere.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] 1. The raw materials in the method of the present invention are cheap and readily available, and the cost is low, which meets the requirements of industrial production.

[0025] 2. The reaction in the method of the present invention has no complicated intermediate links and has low requirements on the experimental operation level.

[0026] 3. The method of the present invention uses phenylacetylene compounds containing trifluoromethyl as raw materials to synthesize a series of target products, thereby broadening the synthesis method of thiophene compounds containing 4-trifluoromethyl. DETAILED DESCRIPTION

[0027] The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention. Unless otherwise specified, the technical means used in the examples are conventional means known to those skilled in the art. The test methods in the following examples are conventional methods unless otherwise specified.

[0028] Example 1 Synthesis of 3-(methylthio)-2-phenyl-4-(trifluoromethyl)thiophene

[0029] Under nitrogen atmosphere, ferric chloride (162.2 mg, 1.0 mmol), (3-(trifluoromethyl)but-3-ene-1-yn-1-yl)benzene (78.5 mg, 0.4 mmol), dimethyl disulfide (339 mg, 3.6 mmol), and solvent DCM (4 mL) were added in sequence to a dry 25 mL schlenk reaction tube. The reaction was carried out at room temperature for 2 h and then heated to 80 ° C for 12 h. The reaction of the raw materials was complete as detected by TLC, and the reaction was stopped. The reaction mixture was concentrated and separated by column chromatography with (petroleum ether) as the eluent to obtain 79 mg of a light yellow liquid product, 3-(methylthio)-2-phenyl-4-(trifluoromethyl)thiophene, with a yield of 72%.

[0030] The reaction equation for the above reaction is as follows:

[0031]

[0032] The H NMR data of 3-(methylthio)-2-phenyl-4-(trifluoromethyl)thiophene are as follows: 1 H NMR (400MHz, CDCl3) δ7.74(s,1H),7.68-7.63(m,2H),7.50-7.40(m,3H),2.15(s,3H).

[0033] The NMR fluorine spectrum data of 3-(methylthio)-2-phenyl-4-(trifluoromethyl)thiophene are as follows: 19 F NMR (376MHz, CDCl3) δ-59.97.

[0034] The C NMR data of 3-(methylthio)-2-phenyl-4-(trifluoromethyl)thiophene are as follows: 13 C NMR (101MHz, CDCl3) δ 149.3, 134.5 (q, J = 33.3Hz), 132.8, 129.5, 128.9, 128.6, 126.1 (q, J = 5.4Hz), 121.9 (q, J = 271.7Hz), 20.0.

[0035] Example 2 Synthesis of 2-(4-ethylphenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene

[0036] Under nitrogen atmosphere, ferric chloride (162.2 mg, 1.0 mmol), 1-ethyl-4-(3-(trifluoromethyl)but-3-en-1-ynyl)benzene (89.7 mg, 0.4 mmol), dimethyl disulfide (440.1 mg, 3.6 mmol), and solvent DCM (4 mL) were added in sequence to a dry 25 mL schlenk reaction tube. The reaction was carried out at room temperature for 2 h and then heated to 80°C for 12 h. The reaction of the raw materials was complete as determined by TLC. The reaction was stopped and the reaction mixture was concentrated and separated by column chromatography with petroleum ether as the eluent to obtain 65.3 mg of a light yellow liquid product, 2-(4-ethylphenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene, with a yield of 54%.

[0037] The reaction equation for the above reaction is as follows:

[0038]

[0039] The H NMR data of 2-(4-ethylphenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene are as follows: 1H NMR (400MHz, CDCl3) δ7.71 (s, 1H), 7.58 (d, J = 7.9Hz, 2H), 7.29 (d, J = 7.9Hz, 2H), 2.72 (q, J = 7.6Hz, 2H), 2.16 (s, 3H), 1.29 (t, J = 7.6Hz, 3H).

[0040] The NMR fluorine spectrum data of 2-(4-ethylphenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene are as follows: 19 F NMR (376MHz, CDCl3) δ-59.96.

[0041] The C NMR data of 2-(4-ethylphenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene are as follows: 13 C NMR (101MHz, CDCl3) δ 149.6, 145.2, 134.4 (q, J = 33.3Hz), 130.1, 129.4, 128.1, 125.9 (q, J = 5.4Hz), 125.6, 123.3 (q, J = 271.7Hz), 28.7, 20.1, 15.4.

[0042] Example 3 Synthesis of 2-([1,1'-biphenyl]-4-yl)-3-(methylthio)-4-(trifluoromethyl)thiophene

[0043] Under nitrogen atmosphere, ferric chloride (162.2 mg, 1.0 mmol), 4-(3-(trifluoromethyl)but-3-ene-1-yn-1-yl)-1,1'-biphenyl (108.9 mg, 0.4 mmol), dimethyl disulfide (339 mg, 3.6 mmol), and solvent DCM (4 mL) were added in sequence to a dry 25 mL schlenk reaction tube. The reaction was carried out at room temperature for 2 h and then heated to 80 °C for 12 h. The reaction of the raw materials was complete as detected by TLC, and the reaction was stopped. The reaction mixture was concentrated and separated by column chromatography with (petroleum ether) as the eluent to obtain 98.1 mg of a white solid product, 2-([1,1'-biphenyl]-4-yl)-3-(methylthio)-4-(trifluoromethyl)thiophene, with a yield of 70%.

[0044] The reaction equation for the above reaction is as follows:

[0045]

[0046] The H NMR data of 2-([1,1'-biphenyl]-4-yl)-3-(methylthio)-4-(trifluoromethyl)thiophene are as follows: 1HNMR (400MHz, CDCl3) δ7.78-7.73(m,3H),7.71-7.63(m,4H),7.48(t,J=7.6Hz,2H),7.41-7.36(m,1H),2.20(s,3H).

[0047] The NMR fluorine spectrum data of 2-([1,1'-biphenyl]-4-yl)-3-(methylthio)-4-(trifluoromethyl)thiophene are as follows: 19 FNMR (376MHz, CDCl3) δ-59.96.

[0048] The C NMR data of 2-([1,1'-biphenyl]-4-yl)-3-(methylthio)-4-(trifluoromethyl)thiophene are as follows: 13 CNMR(101MHz, CDCl3)δ149.0,141.7,140.2,134.6(q,J=33.0Hz),131.7,129.8 ,129.0,127.8,127.3,127.1,126.2(q,J=5.4Hz),121.9(q,J=271.7Hz),20.1.

[0049] Example 4 Synthesis of 2-(3-chlorophenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene

[0050] Under nitrogen atmosphere, ferric chloride (162.2 mg, 1.0 mmol), 1-chloro-3-(3-(trifluoromethyl)but-3-ene-1-yn-1-yl)benzene (92.2 mg, 0.4 mmol), dimethyl disulfide (339 mg, 3.6 mmol), and solvent DCM (4 mL) were added in sequence to a dry 25 mL schlenk reaction tube. The reaction was carried out at room temperature for 2 h and then heated to 80 °C for 12 h. The reaction of the raw materials was complete as determined by TLC. The reaction was stopped and the reaction mixture was concentrated and separated by column chromatography with petroleum ether as the eluent to obtain 91.4 mg of a light yellow liquid product, 2-(3-chlorophenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene, with a yield of 74%.

[0051] The reaction equation for the above reaction is as follows:

[0052]

[0053] The H NMR data of 2-(3-chlorophenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene are as follows: 1H NMR (400MHz, CDCl3) δ7.77 (s, 1H), 7.66 (s, 1H), 7.55 (ddd, J = 5.7, 2.8, 1.6Hz, 1H), 7.40 (m, J = 4.9, 1.8Hz, 2H), 2.16 (s, 3H).

[0054] The NMR fluorine spectrum data of 2-(3-chlorophenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene are as follows: 19 F NMR (376MHz, CDCl3) δ-60.01.

[0055] The C NMR data of 2-(3-chlorophenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene are as follows: 13 C NMR (101MHz, CDCl3) δ 147.53, 134.7 (q, J = 33.3Hz), 134.5, 134.4, 129.9, 129.5, 129.0, 127.7, 126.9, 126.6 (q, J = 5.4Hz), 121.8 (q, J = 272.4Hz), 20.1.

[0056] Example 5 Synthesis of 2-(4-chlorophenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene

[0057] Into a 5mL schlenk reaction tube dried under nitrogen atmosphere, ferric chloride (162.2mg, 1.0mmol), 1-chloro-4-(3-(trifluoromethyl)but-3-ene-1-yn-1-yl)benzene (92.2mg, 0.4mmol), dimethyl disulfide (339mg, 3.6mmol), and solvent DCM (4mL) were added in sequence. The reaction was carried out at room temperature for 2h and then heated to 80°C for 12h. The reaction of the raw materials was complete as detected by TLC, and the reaction was stopped. The reaction mixture was concentrated and separated by column chromatography with (petroleum ether) as the eluent to obtain 97.6mg of a light yellow liquid product, 2-(4-chlorophenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene, with a yield of 79%.

[0058] The reaction equation for the above reaction is as follows:

[0059]

[0060] The H NMR data of 2-(4-chlorophenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene are as follows: 1 H NMR (400MHz, CDCl3) δ7.75(s,1H),7.63-7.58(m,2H),7.46-7.41(m,2H),2.15(s,3H).

[0061] The NMR fluorine spectrum data of 2-(4-chlorophenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene are as follows: 19 F NMR (376MHz, CDCl3) δ-60.04.

[0062] The C NMR data of 2-(4-chlorophenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene are as follows: 13 C NMR (101MHz, CDCl3) δ 147.9, 135.1, 134.7 (q, J = 33.3Hz), 131.2, 130.7, 128.9, 126.6, 126.4 (q, J = 5.7Hz), 121.8 (q, J = 271.7Hz), 20.0.

[0063] Example 6 Synthesis of 2-(3-bromophenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene

[0064] Under nitrogen atmosphere, ferric chloride (162.2 mg, 1.0 mmol), 1-bromo-3-(3-(trifluoromethyl)but-3-en-1-yl)benzene (110 mg, 0.4 mmol), dimethyl disulfide (339 mg, 3.6 mmol), and solvent DCM (4 mL) were added in sequence to a dry 25 mL schlenk reaction tube. The reaction was carried out at room temperature for 2 h and then heated to 80 °C for 12 h. The reaction of the raw materials was complete as determined by TLC. The reaction was stopped and the reaction mixture was concentrated and separated by column chromatography with petroleum ether as the eluent to obtain 97.5 mg of a transparent liquid product, 2-(3-bromophenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene, in a yield of 69%.

[0065] The reaction equation for the above reaction is as follows:

[0066]

[0067] The H NMR data of 2-(3-bromophenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene are as follows: 1 H NMR (400MHz, CDCl3) δ7.81 (t, J = 1.9 Hz, 1H), 7.76 (d, J = 1.0 Hz, 1H), 7.58 (m, 2H), 7.33 (t, J = 7.9 Hz, 1H), 2.16 (s, 3H).

[0068] The NMR fluorine spectrum data of 2-(3-bromophenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene are as follows: 19 F NMR (376MHz, CDCl3) δ-60.01.

[0069] The C NMR data of 2-(3-bromophenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene are as follows: 13 C NMR (101MHz, CDCl3) δ 147.4, 134.7, 134.3 (q, J = 33.3Hz), 132.3, 131.9, 130.1, 128.2, 127.0, 126.7 (q, J = 5.4Hz), 122.5, 121.8 (q, J = 271.7Hz), 20.1.

[0070] Example 7 Synthesis of 2-(4-fluorophenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene

[0071] Under nitrogen atmosphere, ferric chloride (162.2 mg, 1.0 mmol), 1-fluoro-4-(3-(trifluoromethyl)but-3-en-1-yl)benzene (85.7 mg, 0.4 mmol), dimethyl disulfide (339 mg, 3.6 mmol), and solvent DCM (4 mL) were added in sequence to a dry 25 mL schlenk reaction tube. The reaction was carried out at room temperature for 2 h and then heated to 80°C for 12 h. The reaction of the raw materials was complete as determined by TLC. The reaction was stopped and the reaction mixture was concentrated and separated by column chromatography with petroleum ether as the eluent to obtain 77.2 mg of a transparent liquid product, 2-(4-fluorophenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene, in a yield of 66%.

[0072] The reaction equation for the above reaction is as follows:

[0073]

[0074] The H NMR data of 2-(4-fluorophenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene are as follows: 1H NMR (400 MHz, CDCl3) δ7.73 (s, 1H), 7.68-7.59 (m, 2H), 7.2 (t, J=8.6 Hz, 2H), 2.1 (s, 3H).

[0075] The nuclear magnetic fluorine spectrum data of 2-(4-fluorophenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene are as follows: 19F NMR (376MHz, CDCl3) δ -60.04, -112.10.

[0076] The C NMR data of 2-(4-fluorophenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene are as follows: 13C NMR (101MHz, CDCl3) δ163.1 (d, J = 250.5Hz), 148.2, 134.5 (q, J = 33.3Hz), 131.4 (d, J = 8.1Hz), 12 8.8 (d, J = 4.0Hz), 126.3, 126.1 (q, J = 5.7Hz), 121.8 (q, J = 271.7Hz), 115.7 (d, J = 22.2Hz), 20.0.

[0077] Example 8 Synthesis of 2-(4-(tert-butyl)phenyl)-3-(thiomethyl)-4-(trifluoromethyl)thiophene

[0078] Under nitrogen atmosphere, ferric chloride (162.2 mg, 1.0 mmol), 1-(tert-butyl)-4-(3-(trifluoromethyl)-3-ene-1-yn-1-yl)benzene (100.9 mg, 0.4 mmol), dimethyl disulfide (339 mg, 3.6 mmol), and solvent DCM (4 mL) were added in sequence to a dry 25 mL schlenk reaction tube. The reaction was carried out at room temperature for 2 h and then heated to 80° C. for 12 h. The reaction of the raw materials was complete as determined by TLC. The reaction was stopped and the reaction mixture was concentrated and separated by column chromatography with petroleum ether as the eluent to obtain 92.5 mg of a white solid product, 2-(4-(tert-butyl)phenyl)-3-(thiomethyl)-4-(trifluoromethyl)thiophene, with a yield of 70%.

[0079] The reaction equation for the above reaction is as follows:

[0080]

[0081] The H NMR data of 2-(4-(tert-butyl)phenyl)-3-(thiomethyl)-4-(trifluoromethyl)thiophene are as follows: 1 HNMR (400MHz, CDCl3) δ7.7 (s, 1H), 7.6 (d, J = 8.5Hz, 2H), 7.5 (d, J = 8.5Hz, 2H), 2.2 (s, 3H), 1.4 (s, 9H).

[0082] The NMR fluorine spectrum data of 2-(4-(tert-butyl)phenyl)-3-(thiomethyl)-4-(trifluoromethyl)thiophene are as follows: 19 FNMR (376MHz,CDCl3)δ-59.94.

[0083] The C NMR data of 2-(4-(tert-butyl)phenyl)-3-(thiomethyl)-4-(trifluoromethyl)thiophene are as follows: 13CNMR (101MHz, CDCl3) δ152.0, 149.6, 134.5 (q, J = 33.0Hz), 129.9, 129.1, 125.9 (q, J = 5.7Hz), 125.6, 121.9 (q, J = 271.7Hz), 34.8, 31.3, 20.2.

[0084] Example 9 Synthesis of 2-(4-methoxyphenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene

[0085] Under nitrogen atmosphere, ferric chloride (162.2 mg, 1.0 mmol), 1-methoxy-4-(3-(trifluoromethyl)but-3-en-1-yl)benzene (90.5 mg, 0.4 mmol), dimethyl disulfide (339 mg, 3.6 mmol), and solvent DCM (4 mL) were added in sequence to a dry 25 mL schlenk reaction tube. The reaction was carried out at room temperature for 2 h and then heated to 80°C for 12 h. The reaction of the raw materials was complete as detected by TLC, and the reaction was stopped. The reaction mixture was concentrated and separated by column chromatography with an eluent of (petroleum ether / ethyl acetate=100 / 1) to give 96.2 mg of a yellow liquid product, 2-(4-methoxyphenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene, in a yield of 79%.

[0086] The reaction equation for the above reaction is as follows:

[0087]

[0088] H NMR spectrum of 2-(4-methoxyphenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene: 1 H NMR (400MHz, CDCl3) δ7.7 (d, J = 1.0 Hz, 1H), 7.62-7.56 (m, 2H), 7.03-6.95 (m, 2H), 3.9 (s, 3H), 2.2 (s, 3H).

[0089] NMR fluorine spectrum of 2-(4-methoxyphenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene: 19 F NMR (376MHz, CDCl3) δ-60.01.

[0090] 2-(4-methoxyphenyl)-3-(methylthio)-4-(trifluoromethyl)thiophene's C NMR spectrum: 13 C NMR (101MHz, CDCl3) δ160.1, 149.3, 134.4 (q, J = 33.0Hz), 130.7, 125.5 (q, J = 5.7Hz), 125.3, 125.2, 121.9 (q, J = 271.7Hz), 114.0, 55.4, 19.9.

[0091] Example 10 Synthesis of 3-(methylthio)-4-trifluoromethyl-2-(3-(trifluoromethyl)phenyl)thiophene

[0092] Under nitrogen atmosphere, ferric chloride (162.2 mg, 1.0 mmol), 1-(trifluoromethyl)-3-(3-(trifluoromethane)but-3-en-1-yl)benzene (105.7 mg, 0.4 mmol), dimethyl disulfide (339 mg, 3.6 mmol), and solvent DCM (4 mL) were added in sequence to a dry 25 mL schlenk reaction tube. The reaction was carried out at room temperature for 2 h and then heated to 80°C for 12 h. The reaction of the raw materials was complete as determined by TLC. The reaction was stopped and the reaction mixture was concentrated. The mixture was separated by column chromatography using petroleum ether as the eluent to obtain 104.1 mg of a light yellow liquid product, 3-(methylthio)-4-trifluoromethyl-2-(3-(trifluoromethyl)phenyl)thiophene, with a yield of 76%.

[0093] The reaction equation for the above reaction is as follows:

[0094]

[0095] The H NMR spectrum data of 3-(methylthio)-4-trifluoromethyl-2-(3-(trifluoromethyl)phenyl)thiophene are as follows: 1HNMR (400 MHz, CDCl3) δ7.92 (s, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.8 (s, 1H), 7.7 (d, J = 7.9 Hz, 1H), 7.6 (t, J = 7.8 Hz, 1H), 2.2 (s, 3H).

[0096] The NMR fluorine spectrum data of 3-(methylthio)-4-trifluoromethyl-2-(3-(trifluoromethyl)phenyl)thiophene are as follows: 19 FNMR (376MHz, CDCl3) δ-60.05,-62.72.

[0097] The C NMR data of 3-(methylthio)-4-trifluoromethyl-2-(3-(trifluoromethyl)phenyl)thiophene are as follows: 13 CNMR(101MHz, CDCl3)δ147.5,134.8(q,J=33.3Hz),133.6,132.8,131.1(q,J=33.0Hz), 129.2,127.3,126.8(q,J=5.7Hz),126.3(q,J=4.0Hz),125.5(q,J=3.7Hz),123.8(q,J=

[0098] 273.7Hz), 121.7 (q, J=271.7Hz), 20.1.

[0099] The embodiments described above are only preferred embodiments of the present invention and are only used to explain the present invention, not to limit the scope of implementation of the present invention. For those skilled in the art, other implementation methods can certainly be easily made by replacement or modification based on the technical contents disclosed in this specification. Therefore, all changes and improvements made on the principles of the present invention should be included in the scope of the patent application of the present invention.

Claims

1. A method for synthesizing 4-trifluoromethylthiophene compounds, characterized in that: The following steps are involved: In a gas atmosphere, a metal catalyst, an acetylene compound represented by formula I, a disulfide compound represented by formula II and an organic solvent are sequentially added to a reactor, and the reaction is carried out at 25 to 100° C. for 2 to 12 hours. After the acetylene compound is completely converted, extraction is performed, the organic phases are combined, dried, concentrated, and column chromatography is performed to obtain a 4-trifluoromethylthiophene compound represented by formula III; The structural formula of the acetylene compound shown in Formula I is as follows: The structural formula of the disulfide compound shown in Formula II is as follows: The structural formula of the 4-trifluoromethylthiophene compound shown in Formula III is as follows: Wherein: R1 is selected from one or two of hydrogen, halogen, alkyl, phenyl, methoxy or nitrile, R 2 One selected from methyl or ethyl.

2. The synthesis method according to claim 1, characterized in that The metal catalyst is selected from one of ferric chloride, ferric bromide, ferrous iodide and ferrous acetylacetonate.

3. The synthesis method according to claim 1, characterized in that The organic solvent is selected from one of toluene, ethanol, tetrahydrofuran, dimethyl sulfoxide, acetonitrile, dichloromethane, N,N-dimethylformamide or acetone.

4. The synthesis method according to claim 1, characterized in that The molar ratio of the acetylene compound represented by formula I to the disulfide compound represented by formula II is 1:2-9.

5. The synthesis method according to claim 1, characterized in that The amount of the metal catalyst used is 0.2 to 2.5 of the molar amount of the acetylene compound shown in Formula I.

6. The synthesis method according to claim 1, characterized in that The gas atmosphere refers to nitrogen.

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