Synthetic method of diarylacetylene

Abstract

The invention belongs to the field of organic synthesis, and particularly relates to a synthetic method of diarylacetylene. The preparation method comprises the following steps: mixing a methyl benzoate compound as shown in a formula 1 and a 3, 5-bis (trifluoromethyl) phenyl benzyl maple compound as shown in a formula 2 with an organic solvent (tetrahydrofuran and ethylene glycol dimethyl ether) in the presence of strong base (lithium bis (trimethylsilyl) amide and potassium bis (trimethylsilyl) amide), and reacting to synthesize the diarylacetylene as shown in a formula 3. The adopted raw materials are simple and easy to obtain, the method for synthesizing the diaryl acetylene through the one-pot method is constructed, and the method has the advantages of being simple in synthesis method, economical, environmentally friendly, wide in application range and the like.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and particularly relates to a method for synthesizing diaryl alkynes. Background Art

[0002] The carbon-carbon triple bond of diaryl acetylene has certain rigidity and stability, and plays an important role in the fields of medicine and materials. Alkyne structures exist in various biologically active molecules. For example, acyltryptophan 1,2-diaryl acetylene (Figure 1A) is used as a follicle-stimulating hormone receptor (FSHR) antagonist for birth control and prevention of osteoporosis, diaryl acetylene piperonamide (Figure 1B) can be used as a new type of antianxiety drug with moderate affinity for neurokinin NK-1 and 2 receptors, and halogenated diaryl acetylene (Figure 1C) is an antiproliferative agent that inhibits c-myc expression in cancer cells. Diaryl acetylene is an important precursor for many cyclization reactions, including Larock indole synthesis, benzofuran synthesis, Fagnou's indole synthesis, and the Nobel Prize-winning sodium azide-alkyne cycloaddition reaction.

[0003] Summary of the invention

[0004] The present invention provides a one-pot synthesis reaction of diphenylacetylene from methyl benzoate and 3,5-ditrifluoromethylphenylbenzyl maple, which can obtain a variety of diarylacetylenes with biological activity and medicinal value. The synthesis method is convenient and efficient. The specific scheme is as follows:

[0005]

[0006] A method for synthesizing a diphenylacetylene compound, comprising: using a methyl benzoate compound shown in formula 1 and a 3,5-ditrifluoromethylphenylbenzyl compound shown in formula 2, in the presence of a strong base, and mixing with an organic solvent to react and synthesize a diarylacetylene shown in formula 3;

[0007] Where R 1 R is selected from methoxy, halogen, tert-butyl, quinoline, etc., and R2 is selected from methoxy, tert-butyl, 2-naphthyl, etc.

[0008] The method of the present invention can realize the one-pot synthesis of diphenylacetylene compounds, reduce the reaction steps, and thus improve the product yield; the raw materials used in the synthesis method are convenient and economical; R 1 , R 2 There are many options for wider applicability.

[0009] Preferably, R 1 is selected from methoxy, halogen, tert-butyl, quinoline, etc., R 2 Selected from methoxy, tert-butyl, 2-naphthyl and the like.

[0010] Preferably, the reaction is carried out under the protection of an inert gas, and preferably, the inert gas is nitrogen.

[0011] Preferably, the synthesis occurs in the presence of a strong base and an organic solvent.

[0012] Preferably, the strong base is lithium bis(trimethylsilyl)amide and potassium bis(trimethylsilyl)amide.

[0013] Preferably, the organic solvent is tetrahydrofuran and ethylene glycol dimethyl ether.

[0014] Preferably, in the reaction, the molar ratio of methyl benzoate shown in Formula 1, 3,5-ditrifluoromethylphenylbenzyl benzoate shown in Formula 2 and the strong base is 2.5:1:4:6; and the reaction temperature is 0-80°C.

[0015] Preferably, the method of the present invention can be used to synthesize diphenylacetylene with the following structure:

[0016]

[0017]

[0018] Methyl benzoate and 3,5-ditrifluoromethylphenylbenzyl maple are reacted in the presence of a strong base (lithium bis(trimethylsilyl)amide and potassium bis(trimethylsilyl)amide) and an organic solvent (tetrahydrofuran and ethylene glycol dimethyl ether) to finally synthesize diarylacetylene.

[0019] The technical solution of the present invention can achieve at least one of the following beneficial effects:

[0020] The raw materials used in the synthesis method of the present invention are cheap and readily available;

[0021] The synthesis method of the present invention does not use transition metal catalysts and is green and environmentally friendly;

[0022] The present invention adopts a one-pot synthesis method, which reduces the loss of raw materials and improves the yield of the product due to fewer reaction steps;

[0023] The operation steps required by the present invention are relatively simple, and no extreme heating or cooling is required. The reaction can be performed at normal pressure, which is safe and convenient.

[0024] In the present invention, R 1 , R 2 There are many options, so the method of the present invention has wider applicability and can synthesize a variety of diphenylacetylenes. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The accompanying drawings are hydrogen and carbon nuclear magnetic resonance spectra of the products of each embodiment. The serial numbers of the accompanying drawings correspond to the serial numbers of the embodiments. Figure A is a hydrogen nuclear magnetic resonance spectrum, and Figure B is a carbon nuclear magnetic resonance spectrum. Figure 1A is the hydrogen nuclear magnetic resonance spectrum of the product obtained in Example 1, Figure 1B The carbon nuclear magnetic resonance spectrum of the product obtained in Example 1; Figure 2A is the hydrogen nuclear magnetic resonance spectrum of the product obtained in Example 2, Figure 2B is the carbon nuclear magnetic resonance spectrum of the product obtained in Example 2; Figure 3A is the hydrogen nuclear magnetic resonance spectrum of the product obtained in Example 3, Figure 3B The carbon nuclear magnetic resonance spectrum of the product obtained in Example 3; Figure 4A is the hydrogen nuclear magnetic resonance spectrum of the product obtained in Example 4, Figure 4B The carbon nuclear magnetic resonance spectrum of the product obtained in Example 4; Figure 5A is the hydrogen nuclear magnetic resonance spectrum of the product obtained in Example 5, Figure 5B is the carbon nuclear magnetic resonance spectrum of the product obtained in Example 5; Fig. 6A is the hydrogen nuclear magnetic resonance spectrum of the product obtained in Example 6, Figure 6B is the carbon nuclear magnetic resonance spectrum of the product obtained in Example 6; Fig. 7A is the hydrogen nuclear magnetic resonance spectrum of the product obtained in Example 7, Figure 7B is the carbon nuclear magnetic resonance spectrum of the product obtained in Example 7; Fig. 8A is the hydrogen nuclear magnetic resonance spectrum of the product obtained in Example 8, Figure 8B is the carbon nuclear magnetic resonance spectrum of the product obtained in Example 8; Fig.9A is the hydrogen nuclear magnetic resonance spectrum of the product obtained in Example 9, Fig. 9B is the carbon nuclear magnetic resonance spectrum of the product obtained in Example 9; Fig. 10A is the hydrogen nuclear magnetic resonance spectrum of the product obtained in Example 10, Fig. 10B The carbon nuclear magnetic resonance spectrum of the product obtained in Example 10 is shown in FIG. Specific embodiments

[0026] In order to facilitate the understanding of those skilled in the art, the concept of the present invention is further described below in conjunction with the embodiments. The specific description of the following embodiments is not a limitation of the present invention, but is only for the convenience of those skilled in the art to understand the technical solution. Various raw materials involved in the specification are purchased from the market, or through simple synthesis, other medicines are purchased from Anaiji, Bi De, Sigma-Aldrich, Acros, Alfa Aesar, Adamas-beta or J&K., and the nuclear magnetic resonance spectrometer model is Bruker 400M.

[0027] Example 1

[0028] In a glove box filled with nitrogen, LiN(SiMe3)2 (66.9 mg, 0.4 mmol), methyl benzoate (31.2 μL, 0.25 mmol), 3,5-ditrifluoromethylphenylbenzyl maple (36.8 mg, 0.1 mmol) and THF (1.0 mL) were added to a dry microwave tube with a magnetron in sequence, the microwave tube was sealed with a lid, and it was taken out of the glove box, and the reaction mixture was reacted in an ice-water bath at 0°C for 6 hours. The flask was removed from the ice-water bath, brought into the glove box, and KN(SiMe3)2 (119.7 mg, 0.6 mmol) and DME (0.6 mL) were added, the microwave tube was sealed with a lid, and it was taken out of the glove box. The reaction mixture was heated in an oil bath at 80°C for 24 hours. The flask was removed from the oil bath, cooled to room temperature, exposed to air, and then three drops of water were slowly added to quench the reaction. The reaction mixture was passed through a short pad of silica and washed with an additional 3 mL of ethyl acetate (3 x 1 mL), and the combined solution was concentrated under reduced pressure. The crude product was purified by flash chromatography on a silica gel column (eluted with petroleum ether) to give the product (12.2 mg, 69% yield) as a white solid. The H NMR and C NMR spectra of the product were Figure 1A and Figure 1B , the spectrum data is: 1 H NMR (401MHz, CHCl3) δ7.54-7.52(m, 4H), 7.34-7.32(m, 6H)ppm. 13 C NMR (101MHz, CDCl3) δ131.6, 128.3, 128.2, 123.2, 89.3ppm.

[0029] The raw materials in Example 1 were changed, and the following 10 groups of experimental examples were designed, wherein the first group of experiments was Example 1, and the corresponding nuclear magnetic resonance spectrum of the product was shown in Figure 1. The serial numbers of the nuclear magnetic resonance spectra of the remaining groups 2-10 of products correspond to the serial numbers of the corresponding examples.

[0030] The table lists the structural formulas of the products in Examples 1-10, the last column lists the yields of the products in each Example, and indicates the specific implementation conditions of each Example. The specific meanings of the implementation conditions of each Example are shown below the table.

[0031]

[0032]

[0033] Example 2

[0034] In a glove box filled with nitrogen, LiN(SiMe3)2(66.9mg, 0.4mmol), methyl 4-phenylbenzoate(53.1mg, 0.25mmol), 3,5-ditrifluoromethylphenylbenzyl maple(36.8mg, 0.1mmol) and THF(1.0mL) were added to a dry microwave tube with a magnetron in sequence, the microwave tube was sealed with a lid, and it was taken out of the glove box, and the reaction mixture was reacted in an ice-water bath at 0°C for 6 hours. The flask was removed from the ice-water bath, brought into the glove box, and KN(SiMe3)2(119.7mg, 0.6mmol) and DME(0.6mL) were added continuously, the microwave tube was sealed with a lid, and it was taken out of the glove box. The reaction mixture was heated in an oil bath at 80°C for 24 hours. The flask was removed from the oil bath, cooled to room temperature, exposed to air, and then three drops of water were slowly added to quench the reaction. The reaction mixture was passed through a short pad of silica and washed with an additional 3 mL of ethyl acetate (3 x 1 mL), and the combined solution was concentrated under reduced pressure. The crude product was purified by flash chromatography on a silica column (eluted with petroleum ether) to give the product (13.2 mg, 52% yield) as a white solid. The H NMR and C NMR spectra of the product were Figure 2A and Figure 2B , the spectrum data is: 1 H NMR (401MHz, CHCl3) δ7.62-7.54 (m, 8H), 7.45 (t, J=7.5Hz, 2H), 7.40-7.34 (m, 4H)ppm. 13 C NMR (101MHz, CDCl3) δ140.9, 140.3, 132.0, 131.6, 128.8, 128.4, 128.3, 127.6, 127.0, 123.2, 122.1, 90.0, 89.3ppm.

[0035] Example 3

[0036] In a glove box filled with nitrogen, LiN(SiMe3)2 (66.9 mg, 0.4 mmol), methyl 4-tert-butylbenzoate (48.1 mg, 0.25 mmol), 3,5-ditrifluoromethylphenylbenzyl maple (36.8 mg, 0.1 mmol) and THF (1.0 mL) were added to a dry microwave tube with a magnetron in sequence, the microwave tube was sealed with a lid, and it was taken out of the glove box, and the reaction mixture was reacted in an ice-water bath at 0°C for 6 hours. The flask was removed from the ice-water bath, brought into the glove box, and KN(SiMe3)2 (119.7 mg, 0.6 mmol) and DME (0.6 mL) were added continuously, the microwave tube was sealed with a lid, and it was taken out of the glove box. The reaction mixture was heated in an oil bath at 80°C for 24 hours. The flask was removed from the oil bath, cooled to room temperature, exposed to air, and then three drops of water were slowly added to quench the reaction. The reaction mixture was passed through a short pad of silica and washed with an additional 3 mL of ethyl acetate (3 x 1 mL), and the combined solution was concentrated under reduced pressure. The crude product was purified by flash chromatography on a silica column (eluted with petroleum ether) to give the product (9.6 mg, 41% yield) as a white solid. The H NMR and C NMR spectra of the product were Figure 3A and Figure 3B , the spectrum data is; 1 H NMR (401MHz, CHCl3) δ7.54-7.51(m, 2H), 7.48-7.45(m, 2H), 7.38-7.32(m, 5H), 1.32(s, 9H)ppm. 13 C NMR (101MHz, CDCl3) δ151.5, 131.6, 131.3, 128.3, 128.1, 125.3, 123.5, 120.2, 89.5, 88.7, 34.8, 31.2ppm.

[0037] Example 4

[0038] In a glove box filled with nitrogen, LiN(SiMe3)2(66.9mg, 0.4mmol), methyl 4-phenoxybenzoate(57.1mg, 0.25mmol), 3,5-ditrifluoromethylphenylbenzyl maple(36.8mg, 0.1mmol) and THF(1.0mL) were added to a dry microwave tube with a magnetron in sequence, the microwave tube was sealed with a lid, and it was taken out of the glove box, and the reaction mixture was reacted in an ice-water bath at 0°C for 6 hours. The flask was removed from the ice-water bath, brought into the glove box, and KN(SiMe3)2(119.7mg, 0.6mmol) and DME(0.6mL) were added continuously, the microwave tube was sealed with a lid, and it was taken out of the glove box. The reaction mixture was heated in an oil bath at 80°C for 24 hours. The flask was removed from the oil bath, cooled to room temperature, exposed to air, and then three drops of water were slowly added to quench the reaction. The reaction mixture was passed through a short pad of silica and washed with an additional 3 mL of ethyl acetate (3 x 1 mL), and the combined solution was concentrated under reduced pressure. The crude product was purified by flash chromatography on a silica column (eluted with petroleum ether) to give the product (16.2 mg, 60% yield) as a white solid. The H NMR and C NMR spectra of the product were Figure 4A and Figure 4B , the spectrum data is: 1 H NMR (401MHz, CHCl3) δ 7.53-7.47 (m, 4H), 7.39-7.32 (m, 5H), 7.14 (t, J = 7.4Hz, 1H), 7.04 (d, J = 8.1Hz, 2H), 6.96 (d, J = 8.7Hz, 2H) ppm. 13 C NMR (101MHz, CDCl3) δ157.5, 156.3, 133.2, 131.5, 129.9, 128.3, 128.1, 123.8, 123.2, 119.4, 118.3, 117.7, 88.9, 88.7ppm.

[0039] Example 5

[0040] In a glove box filled with nitrogen, LiN(SiMe3)2 (66.9 mg, 0.4 mmol), 4-fluorobenzoic acid methyl ester (32.9 μL, 0.25 mmol), 3,5-ditrifluoromethylphenylbenzyl maple (36.8 mg, 0.1 mmol) and THF (1.0 mL) were added to a dry microwave tube with a magnetron in sequence, the microwave tube was sealed with a lid, and it was taken out of the glove box, and the reaction mixture was reacted in an ice-water bath at 0°C for 6 hours. The flask was taken out of the ice-water bath, brought into the glove box, and KN(SiMe3)2 (119.7 mg, 0.6 mmol) and DME (0.6 mL) were added continuously, the microwave tube was sealed with a lid, and it was taken out of the glove box. The reaction mixture was heated in an oil bath at 80°C for 24 hours. The flask was removed from the oil bath, cooled to room temperature, exposed to air, and then three drops of water were slowly added to quench the reaction. The reaction mixture was passed through a short pad of silica and washed with an additional 3 mL of ethyl acetate (3x1 mL), and the combined solution was concentrated under reduced pressure. The crude product was purified by flash chromatography on a silica column (eluted with petroleum ether) to give the product (9.2 mg, 47% yield) as a white solid. The H NMR and C NMR spectra of the product were: Figure 5A and Figure 5B , the spectrum data is: 1 H NMR (401MHz, CHCl3) δ7.54-7.49 (m, 4H), 7.35-7.34 (m, 3H), 7.03 (t, J=8.7Hz, 2H)ppm. 13 C NMR (101MHz, CDCl3) δ162.4 (d, J 1 C-F =249.5Hz), 133.4(d, J 3 C-F =8.4Hz), 131.5, 128.4, 128.3, 123.0, 119.3 (d, J 4 C-F =3.5Hz), 115.6(d, f 2 C-F =22.0Hz), 89.0, 88.2ppm.

[0041] Example 6

[0042] In a glove box filled with nitrogen, LiN(SiMe3)2 (66.9 mg, 0.4 mmol), methyl 3-phenoxybenzoate (57.1 mg, 0.25 mmol), 3,5-ditrifluoromethylphenylbenzyl maple (36.8 mg, 0.1 mmol) and THF (1.0 mL) were added to a dry microwave tube with a magnetron in sequence, the microwave tube was sealed with a lid, and it was taken out of the glove box, and the reaction mixture was reacted in an ice-water bath at 0°C for 6 hours. The flask was removed from the ice-water bath, brought into the glove box, and KN(SiMe3)2 (119.7 mg, 0.6 mmol) and DME (0.6 mL) were added continuously, the microwave tube was sealed with a lid, and it was taken out of the glove box. The reaction mixture was heated in an oil bath at 80°C for 24 hours. The flask was removed from the oil bath, cooled to room temperature, exposed to air, and then three drops of water were slowly added to quench the reaction. The reaction mixture was passed through a short pad of silica and washed with an additional 3 mL of ethyl acetate (3 x 1 mL), and the combined solution was concentrated under reduced pressure. The crude product was purified by flash chromatography on a silica column (eluted with petroleum ether) to give the product (13.0 mg, 48% yield) as a white solid. The H NMR and C NMR spectra of the product were Fig. 6A and Figure 6B , the spectrum data is: 1 H NMR (401MHz, CHCl3) δ7.51-7.49(m,2H), 7.36-7.27(m,7H), 7.16-7.10(m,2H), 7.04-6.97(m,3H)ppm. 13 C NMR (101MHz, CDCl3) δ157.3, 156.7, 131.6, 129.8, 129.7, 128.4, 128.3, 126.5, 124.7, 123.6, 123.0, 121.4, 119.1, 119.0, 89.8, 88.7ppm.

[0043] Example 7

[0044] In a glove box filled with nitrogen, LiN(SiMe3)2(66.9mg, 0.4mmol), methyl 6-quinolinecarboxylate(46.8mg, 0.25mmol), 3,5-di(trifluoromethyl)phenyl-4-tert-butylbenzylsulfone(36.8mg, 0.1mmol) and THF(1.0mL) were added to a dry microwave tube with a magnetron in sequence, the microwave tube was sealed with a lid, and it was taken out of the glove box, and the reaction mixture was reacted in an ice-water bath at 0°C for 6 hours. The flask was removed from the ice-water bath, brought into the glove box, and KN(SiMe3)2(119.7mg, 0.6mmol) and DME(0.6mL) were added continuously, the microwave tube was sealed with a lid, and it was taken out of the glove box. The reaction mixture was heated in an oil bath at 80°C for 24 hours. The flask was removed from the oil bath, cooled to room temperature, exposed to air, and then three drops of water were slowly added to quench the reaction. The reaction mixture was passed through a short pad of silica and washed with another 3 mL of ethyl acetate (3 x 1 mL), and the combined solution was concentrated under reduced pressure. The crude product was purified by flash chromatography on a silica gel column (eluted with petroleum ether: ethyl acetate = 10:1) to give the product (19.1 mg, 67% yield) as a white solid. The H NMR and C NMR spectra of the product were Fig. 7A and Figure 7B , the spectrum data is: 1 H NMR (401MHz, CHCl3) δ8.91-8.90 (m, 1H), 8.13-8.11 (m, 1H), 8.07 (d, J=8.7Hz, 1H), 8.01 (d, J=1. 8Hz, 1H), 7.82 (dd, J=8.7, 1.9Hz, 1H), 7.52 (d, J=8.4Hz, 2H), 7.43-7.39 (m, 3H), 1.34 (s, 9H)ppm. 13 C NMR (101MHz, CDCl3) δ151.9, 150.8, 147.6, 135.7, 132.2, 131.4, 130.9, 129.5, 128.0, 125.4, 121.8, 121.7, 119.8, 90.8, 88.3, ​​34.8, 31.1ppm.

[0045] Example 8

[0046] In a glove box filled with nitrogen, LiN(SiMe3)2(66.9mg, 0.4mmol), methyl 6-quinolinecarboxylate(46.8mg, 0.25mmol), 3,5-bis(trifluoromethyl)phenyl-4-methoxybenzyl sulfone(46.8mg, 0.1mmol) and THF(1.0mL) were added to a dry microwave tube with a magnetron in sequence, the microwave tube was sealed with a lid, and it was taken out of the glove box, and the reaction mixture was reacted in an ice-water bath at 0°C for 6 hours. The flask was removed from the ice-water bath, brought into the glove box, and KN(SiMe3)2(119.7mg, 0.6mmol) and DME(0.6mL) were added continuously, the microwave tube was sealed with a lid, and it was taken out of the glove box. The reaction mixture was heated in an oil bath at 80°C for 24 hours. The flask was removed from the oil bath, cooled to room temperature, exposed to air, and then three drops of water were slowly added to quench the reaction. The reaction mixture was passed through a short pad of silica and washed with another 3 mL of ethyl acetate (3 x 1 mL), and the combined solution was concentrated under reduced pressure. The crude product was purified by flash chromatography on a silica gel column (eluted with petroleum ether: ethyl acetate = 10:1) to give the product (18.0 mg, 70% yield) as a white solid. The H NMR and C NMR spectra of the product were Fig. 8A and Figure 8B , the spectrum data is: 1 H NMR (401MHz, CHCl3) δ8.91-8.90 (m, 1H), 8.13-8.11 (m, 1H), 8.06 (d, J=8.7Hz, 1H), 7.99 (d, J =1.8Hz, 1H), 7.80 (dd, J = 8.7, 1.9Hz, 1H), 7.53-7.51 (m, 2H), 7.43-7.41 (m, 1H), 6.92-6.90 (m 2H), 3.84(s, 3H)ppm. 13 C NMR (101MHz, CDCl3) δ159.8, 150.7, 147.5, 135.7, 133.2, 132.2, 130.7, 129.5, 128.1, 121.9, 121.7, 114.9, 114.1, 90.7, 87.7, 55.3ppm.

[0047] Example 9

[0048] In a glove box filled with nitrogen, LiN(SiMe3)2 (66.9 mg, 0.4 mmol), methyl benzoate (31.2 μL, 0.25 mmol), 3,5-di(trifluoromethyl)phenyl-3-methoxybenzyl sulfone (39.8 mg, 0.1 mmol) and THF (1.0 mL) were added to a dry microwave tube with a magnetron in sequence, the microwave tube was sealed with a lid, and it was taken out of the glove box, and the reaction mixture was reacted in an ice-water bath at 0°C for 6 hours. The flask was removed from the ice-water bath, brought into the glove box, and KN(SiMe3)2 (119.7 mg, 0.6 mmol) and DME (0.6 mL) were added continuously, the microwave tube was sealed with a lid, and it was taken out of the glove box. The reaction mixture was heated in an oil bath at 80°C for 24 hours. The flask was removed from the oil bath, cooled to room temperature, exposed to air, and then three drops of water were slowly added to quench the reaction. The reaction mixture was passed through a short pad of silica and washed with an additional 3 mL of ethyl acetate (3 x 1 mL), and the combined solution was concentrated under reduced pressure. The crude product was purified by flash chromatography on a silica column (eluted with petroleum ether) to give the product (10.0 mg, 48% yield) as a white solid. The H NMR and C NMR spectra of the product were Fig.9A and Fig. 9B , the spectrum data is: 1 H NMR (401MHz, CHCl3) δ7.55-7.53(m, 2H), 7.36-7.34(m3H), 7.28-7.26(m,1H), 7.15-7.13(m, 1H), 7.07-7.06(m, 1H), 6.91-6.88(m 1H), 3.83(s, 3H)ppm. 13 C NMR (101MHz, CDCl3) δ159.3, 131.6, 129.4, 128.3, 128.3, 124.2, 124.1, 123.1, 116.2, 114.9, 89.2, 89.1, 55.3ppm.

[0049] Example 10

[0050] In a glove box filled with nitrogen, LiN(SiMe3)2(66.9mg, 0.4mmol), methyl benzoate (31.2μL, 0.25mmol), 3,5-di(trifluoromethyl)phenyl-2-naphthylmethylsulfone (41.8mg, 0.1mmol) and THF (1.0mL) were added to a dry microwave tube with a magnetron in sequence, the microwave tube was sealed with a lid, and it was taken out of the glove box, and the reaction mixture was reacted in an ice-water bath at 0°C for 6 hours. The flask was removed from the ice-water bath, brought into the glove box, and KN(SiMe3)2(119.7mg, 0.6mmol) and DME(0.6mL) were added continuously, the microwave tube was sealed with a lid, and it was taken out of the glove box. The reaction mixture was heated in an oil bath at 80°C for 24 hours. The flask was removed from the oil bath, cooled to room temperature, exposed to air, and then three drops of water were slowly added to quench the reaction. The reaction mixture was passed through a short pad of silica and washed with an additional 3 mL of ethyl acetate (3 x 1 mL), and the combined solution was concentrated under reduced pressure. The crude product was purified by flash chromatography on a silica column (eluted with petroleum ether) to give the product (12.2 mg, 53% yield) as a white solid. The H NMR and C NMR spectra of the product were Fig. 10A and Fig. 10B , the spectrum data is: 1 H NMR (401MHz, CHCl3) δ8.06 (s, 1H), 7.84-7.80 (m, 3H), 7.60-7.57 (m, 3H), 7.51-7.48 (m, 2H), 7.39-7.35 (m, 3H)ppm. 13 C NMR (101MHz, CDCl3) δ133.0, 132.7, 131.6, 131.4, 128.4, 128.3, 128.0, 127.8, 126.7, 126.5, 123.2, 120.5, 89.7, 89.6ppm.

Claims

1. A method for synthesizing diarylacetylene, characterized in that: A method for synthesizing a diarylacetylene compound comprises: using a methyl benzoate compound shown in formula 1 and a 3,5-ditrifluoromethylphenylbenzyl compound shown in formula 2 to mix with an organic solvent in the presence of a strong base to react and synthesize a diarylacetylene shown in formula 3; Where R 1 is selected from methoxy, halogen, tert-butyl, quinoline, etc., R 2 Selected from methoxy, tert-butyl, 2-naphthyl and the like.

2. The synthesis method according to claim 1, characterized in that The strong base is lithium bis(trimethylsilyl)amide and potassium bis(trimethylsilyl)amide.

3. The synthesis method according to claim 1, characterized in that The reaction is carried out under the protection of an inert gas, wherein the inert gas is nitrogen.

4. The synthesis method according to claim 1, characterized in that The organic solvent is tetrahydrofuran and methyl tert-butyl ether.

5. The synthesis method according to claim 1, characterized in that In the reaction, the molar ratio of methyl benzoate shown in formula 1, 3,5-ditrifluoromethylphenylbenzyl benzoate shown in formula 2 and the strong base is: 2.5; 1:4:6; and the reaction temperature is 0-80°C.

6. The synthesis method according to claim 1, characterized in that The methyl benzoate compounds, 3,5-ditrifluoromethylphenylbenzyl compounds and the product diarylacetylene are as shown in the following table:

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