A method for synthesizing diphenylacetylene

Abstract

The application belongs to the field of organic synthesis, and particularly relates to a synthesis method of diaryl acetylene. Methyl benzoate compounds shown in formula 1 and 3, 5-di-trifluoromethyl phenyl benzyl maple compounds shown in formula 2 are mixed with organic solvents (tetrahydrofuran and ethylene glycol dimethyl ether) in the presence of strong base (lithium bis (trimethylsilyl) amine and potassium bis (trimethylsilyl) amine), and are reacted to synthesize diaryl acetylene shown in formula 3. The raw material used in the application is simple and easy to obtain, a one-pot synthesis method of diaryl acetylene is constructed, and the application has the advantages of simple synthesis method, economy, environmental protection and wide application range.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of organic synthesis, and particularly relates to a synthesis method of diaryl acetylene. BACKGROUND

[0002] The carbon-carbon triple bond of diaryl acetylene has certain rigidity and stability, and plays an important role in the fields of medicine, materials and the like. The acetylene structure exists in various bioactive molecules. For example, acyl tryptophan 1,2-diaryl acetylene (Figure 1A) is used for controlling fertility and preventing osteoporosis as a follicle stimulating hormone receptor (FSHR) antagonist, diaryl acetylene piperamide (Figure 1B) can be used as a novel anxiolytic drug with moderate affinity to neurokinin NK-1 and 2 receptors, and halogenated diaryl acetylene (Figure 1C) is an anti-proliferative agent having the effect of inhibiting the expression of c-myc in cancer cells. Diaryl acetylene is an important precursor of many cyclization reactions, including Larock indole synthesis, benzofuran synthesis, Fagnou indole synthesis, and the Nobel Prize-winning sodium azide-acetylene cycloaddition reaction.

[0003] SUMMARY

[0004] The present application provides a one-pot synthesis reaction of diphenyl acetylene from methyl benzoate and 3,5-bistrifluoromethylphenyl benzyl maple, and can obtain various diphenyl acetylenes having biological activity and medicinal value. The synthesis method is convenient and efficient. The specific scheme is as follows:

[0005]

[0006] A synthesis method of a diphenyl acetylene compound, which adopts a methyl benzoate compound shown in formula 1 and a 3,5-bistrifluoromethylphenyl benzyl maple compound shown in formula 2 to react and synthesize diphenyl acetylene shown in formula 3 in the presence of a strong base and mixed with an organic solvent;

[0007] wherein R 1 is selected from methoxy, halogen, t-butyl, quinoline and the like, R 2 is selected from methoxy, t-butyl, 2-naphthyl and the like.

[0008] The method can realize one-pot synthesis of the diphenyl acetylene compound, reduces the reaction steps, and thus can improve the yield of the product; the raw materials used in the synthesis method are convenient and economical; R 1 , R 2 in the present application can be various options, and have wider applicability.

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

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

[0011] Preferably, the synthesis is carried out in the presence of strong base and 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, the molar ratio of methyl benzoate represented by formula 1, 3, 5-ditrifluoromethylphenyl benzyl maple represented by formula 2 and strong base in the reaction is: 2.5:1:4:6; the reaction temperature is 0-80℃.

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

[0016]

[0017]

[0018] Methyl benzoate and 3, 5-ditrifluoromethylphenyl benzyl maple are reacted in the presence of strong base (lithium bis(trimethylsilyl)amide and potassium bis(trimethylsilyl)amide) and mixed with organic solvent (tetrahydrofuran and ethylene glycol dimethyl ether), and finally diphenylacetylene is synthesized.

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

[0020] The raw materials used in the synthesis method of the present application are cheap and easy to obtain;

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

[0022] The synthesis method of the present application uses one-pot method, which has fewer reaction steps, reduces the loss of raw materials, and improves the yield of products;

[0023] The operation steps required by the present application are relatively simple, do not need extreme heating or cooling, and only need to react at normal pressure, which is safe and convenient;

[0024] R 1 , R 2 in the present application can be selected in many ways, so the method of the present application is more widely applicable and can synthesize a variety of diphenylacetylenes.

[0025] Drawings of the specification

[0026] The figures are hydrogen spectrum and carbon spectrum nuclear magnetic resonance spectra of products of various embodiments, the serial numbers of the figures correspond to the serial numbers of the embodiments, Figure A is a hydrogen spectrum nuclear magnetic resonance spectrum, and Figure B is a carbon spectrum nuclear magnetic resonance spectrum, as follows: Figure 1A Figure A is a hydrogen spectrum nuclear magnetic resonance spectrum of the product obtained in Example 1, Figure 1B Figure B is a carbon spectrum nuclear magnetic resonance spectrum of the product obtained in Example 1; Figure 2A Figure A is a hydrogen spectrum nuclear magnetic resonance spectrum of the product obtained in Example 2, Figure 2B Figure B is a carbon spectrum nuclear magnetic resonance spectrum of the product obtained in Example 2; Figure 3A Figure A is a hydrogen spectrum nuclear magnetic resonance spectrum of the product obtained in Example 3, Figure 3B Figure B is a carbon spectrum nuclear magnetic resonance spectrum of the product obtained in Example 3; Figure 4A Figure A is a hydrogen spectrum nuclear magnetic resonance spectrum of the product obtained in Example 4, Figure 4B Figure B is a carbon spectrum nuclear magnetic resonance spectrum of the product obtained in Example 4; Figure 5A Figure A is a hydrogen spectrum nuclear magnetic resonance spectrum of the product obtained in Example 5, Figure 5B Figure B is a carbon spectrum nuclear magnetic resonance spectrum of the product obtained in Example 5; Figure 6A Figure A is a hydrogen spectrum nuclear magnetic resonance spectrum of the product obtained in Example 6, Figure 6B Figure B is a carbon spectrum nuclear magnetic resonance spectrum of the product obtained in Example 6; Figure 7A Figure A is a hydrogen spectrum nuclear magnetic resonance spectrum of the product obtained in Example 7, Figure 7B Figure B is a carbon spectrum nuclear magnetic resonance spectrum of the product obtained in Example 7; Figure 8A Figure A is a hydrogen spectrum nuclear magnetic resonance spectrum of the product obtained in Example 8, Figure 8B Figure B is a carbon spectrum nuclear magnetic resonance spectrum of the product obtained in Example 8; Figure 9A Figure A is a hydrogen spectrum nuclear magnetic resonance spectrum of the product obtained in Example 9, Figure 9B Figure B is a carbon spectrum nuclear magnetic resonance spectrum of the product obtained in Example 9; Figure 10A Figure A is a hydrogen spectrum nuclear magnetic resonance spectrum of the product obtained in Example 10, Figure 10B Figure B is a carbon spectrum nuclear magnetic resonance spectrum of the product obtained in Example 10. Specific embodiments

[0027] In order to facilitate the understanding of those skilled in the art, the concept of the present application is further described below in conjunction with the embodiments. The specific description of the following embodiments is not a limitation of the present application, but is only for the convenience of those skilled in the art to understand the technical solution. The various raw materials involved in the specification are purchased from the market or synthesized simply, and other drugs are purchased from Anjie, Bide, Sigma-Aldrich, Acros, Alfa Aesar, Adamas-beta or J&K. The nuclear magnetic resonance spectrometer is Bruker 400M.

[0028] Example 1

[0029] In a nitrogen filled glove box, a dry microwave tube with a magnetic stir bar was charged with LiN(SiMe3)2(66.9 mg, 0.4 mmol), methyl benzoate (31.2 μL, 0.25 mmol), 3,5-bistrifluoromethylphenyl benzyl boronic acid (36.8 mg, 0.1 mmol) and THF (1.0 mL), the microwave tube was sealed with a cap and removed from the glove box, the reaction mixture was allowed to react in an ice water bath at 0 °C for 6 h. The flask was removed from the ice water bath and taken into the glove box to continue with the addition of KN(SiMe3)2(119.7 mg, 0.6 mmol) and DME (0.6 mL), the microwave tube was sealed with a cap and removed from the glove box. The reaction mixture was heated in an oil bath at 80 °C for 24 h. The flask was removed from the oil bath, allowed to cool to room temperature, exposed to air and then quenched by the slow addition of three drops of water. 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 silica gel (eluted with petroleum ether) to give the product (12.2 mg, 69% yield) as a white solid. 1 H NMR (401 MHz, CHCI3) δ 7.54-7.52 (m, 4H), 7.34-7.32 (m, 6H) ppm. 13 C NMR (101 MHz, CDCI3) δ 131.6, 128.3, 128.2, 123.2, 89.3 ppm.

[0030] The starting materials in Example 1 were changed and designed 10 groups of experimental examples as follows, wherein the first group of experiments is Example 1, and the nuclear magnetic resonance spectrum of the corresponding product is Figure 1. The nuclear magnetic resonance spectrum of the product of each of the remaining 2-10 groups corresponds to the serial number of the corresponding example.

[0031] The structure of the product in each of Examples 1-10 is listed in the table, the last column lists the yield of the product of each example, and the specific implementation conditions of each example are indicated. The specific meanings of the implementation conditions of each example are shown below the table.

[0032]

[0033]

[0034] Example 2

[0035] In a nitrogen filled glove box, a dry microwave tube with a magnetic stir bar was charged with LiN(SiMe3)2(66.9 mg, 0.4 mmol), 4-phenylbenzoic acid methyl ester (53.1 mg, 0.25 mmol), 3,5-bistrifluoromethylphenyl benzyl boronic acid (36.8 mg, 0.1 mmol) and THF (1.0 mL), the microwave tube was sealed with a cap and removed from the glove box, the reaction mixture was allowed to react in an ice water bath at 0 °C for 6 h. The flask was removed from the ice water bath and taken into the glove box to continue with the addition of KN(SiMe3)2(119.7 mg, 0.6 mmol) and DME (0.6 mL), the microwave tube was sealed with a cap and removed from the glove box. The reaction mixture was heated in an oil bath at 80 °C for 24 h. The flask was removed from the oil bath, cooled to room temperature, exposed to air and then the reaction was quenched by the slow addition of three drops of water. 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 silica gel (eluted with petroleum ether) to give the product (13.2 mg, 52% yield) as a white solid. 1 H NMR (401 MHz, CHCI3) δ 7.62 - 7.54 (m, 8H), 7.45 (t, J = 7.5 Hz, 2H), 7.40 - 7.34 (m, 4H) ppm. 13 C NMR (101 MHz, CDCI3) δ 140.9, 140.3, 132.0, 131.6, 128.8, 128.4, 128.3, 127.6, 127.0, 123.2, 122.1, 90.0, 89.3 ppm.

[0036] Example 3

[0037] In a nitrogen filled glove box, a dry microwave tube with a magnetic stir bar was charged with LiN(SiMe3)2(66.9 mg, 0.4 mmol), methyl 4-tert-butylbenzoate (48.1 mg, 0.25 mmol), 3,5-bistrifluoromethylphenyl benzyl boronic acid (36.8 mg, 0.1 mmol), and THF (1.0 mL), the microwave tube was sealed with a cap and removed from the glove box, the reaction mixture was allowed to react in an ice water bath at 0 °C for 6 h. The flask was removed from the ice water bath and taken into the glove box to continue the addition of KN(SiMe3)2(119.7 mg, 0.6 mmol) and DME (0.6 mL), the microwave tube was sealed with a cap and removed from the glove box. The reaction mixture was heated in an oil bath at 80 °C for 24 h. The flask was removed from the oil bath, cooled to room temperature, exposed to air, and then the reaction was quenched by the slow addition of three drops of water. 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 silica gel (eluted with petroleum ether) to give the product (9.6 mg, 41% yield) as a white solid. 1 H NMR (401 MHz, CHCI3) δ 7.54-7.51 (m, 2H), 7.48-7.45 (m, 2H), 7.38-7.32 (m, 5H), 1.32 (s, 9H) ppm. 13 C NMR (101 MHz, CDC13) δ 151.5, 131.6, 131.3, 128.3, 128.1, 125.3, 123.5, 120.2, 89.5, 88.7, 34.8, 31.2 ppm.

[0038] Example 4

[0039] In a nitrogen filled glove box, a dry microwave tube with a magnetic stir bar was charged with LiN(SiMe3)2(66.9 mg, 0.4 mmol), methyl 4-phenoxybenzoate (57.1 mg, 0.25 mmol), 3,5-bistrifluoromethylphenyl benzyl boronic acid (36.8 mg, 0.1 mmol) and THF (1.0 mL), the microwave tube was sealed with a cap and removed from the glove box, the reaction mixture was allowed to react in an ice water bath at 0 °C for 6 h. The flask was removed from the ice water bath and taken into the glove box to continue with the addition of KN(SiMe3)2(119.7 mg, 0.6 mmol) and DME (0.6 mL), the microwave tube was sealed with a cap and removed from the glove box. The reaction mixture was heated in an oil bath at 80 °C for 24 h. The flask was removed from the oil bath, cooled to room temperature, exposed to air and then the reaction was quenched by the slow addition of three drops of water. 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 silica gel (eluted with petroleum ether) to give the product (16.2 mg, 60% yield) as a white solid. 1 H NMR (401 MHz, CHCI3) δ 7.53-7.47 (m, 4H), 7.39-7.32 (m, 5H), 7.14 (t, J = 7.4 Hz, 1H), 7.04 (d, J = 8.1 Hz, 2H), 6.96 (d, J = 8.7 Hz, 2H) ppm. 13 CNMR (101 MHz, CDCI3) δ 157.5, 156.3, 133.2, 131.5, 129.9, 128.3, 128.1, 123.8, 123.2, 119.4, 118.3, 117.7, 88.9, 88.7 ppm.

[0040] Example 5

[0041] In a nitrogen filled glove box, a dry microwave tube with a magnetic stir bar was charged with LiN(SiMe3)2(66.9 mg, 0.4 mmol), methyl 4-fluorobenzoate (32.9 μL, 0.25 mmol), 3,5-bistrifluoromethylphenyl benzyl boronic acid (36.8 mg, 0.1 mmol) and THF (1.0 mL), the microwave tube was sealed with a cap and removed from the glove box, the reaction mixture was allowed to react in an ice water bath at 0 °C for 6 h. The flask was removed from the ice water bath and taken into the glove box to continue the addition of KN(SiMe3)2(119.7 mg, 0.6 mmol) and DME (0.6 mL), the microwave tube was sealed with a cap and removed from the glove box. The reaction mixture was heated in an oil bath at 80 °C for 24 h. The flask was removed from the oil bath, cooled to room temperature, exposed to air and then the reaction was quenched by the slow addition of three drops of water. 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 silica gel (eluted with petroleum ether) to give the product (9.2 mg, 47% yield) as a white solid. 1 H NMR (401 MHz, CHCI3) δ 7.54 - 7.49 (m, 4H), 7.35 - 7.34 (m, 3H), 7.03 (t, J = 8.7 Hz, 2H) ppm. 13 C NMR (101 MHz, CDCI3) δ 162.4 (d, J = 249.5 Hz), 133.4 (d, J = 8.4 Hz), 131.5, 128.4, 128.3, 123.0, 119.3 (d, J = 22.0 Hz), 89.0, 88.2 ppm. 1 C-F = 249.5 Hz), 133.4 (d, J = 8.4 Hz), 131.5, 128.4, 128.3, 123.0, 119.3 (d, J = 22.0 Hz), 89.0, 88.2 ppm. 3 C-F = 249.5 Hz), 133.4 (d, J = 8.4 Hz), 131.5, 128.4, 128.3, 123.0, 119.3 (d, J = 22.0 Hz), 89.0, 88.2 ppm. 4 C-F = 249.5 Hz), 133.4 (d, J = 8.4 Hz), 131.5, 128.4, 128.3, 123.0, 119.3 (d, J = 22.0 Hz), 89.0, 88.2 ppm. 2 C-F = 249.5 Hz), 133.4 (d, J = 8.4 Hz), 131.5, 128.4, 128.3, 123.0, 119.3 (d, J = 22.0 Hz), 89.0, 88.2 ppm.

[0042] Example 6

[0043] In a nitrogen filled glove box, a dry microwave tube with a magnetic stir bar was charged with LiN(SiMe3)2(66.9 mg, 0.4 mmol), methyl 3-phenoxybenzoate (57.1 mg, 0.25 mmol), 3,5-bistrifluoromethylphenyl benzyl boronic acid (36.8 mg, 0.1 mmol) and THF (1.0 mL), the microwave tube was sealed with a cap and removed from the glove box, the reaction mixture was allowed to react in an ice water bath at 0 °C for 6 h. The flask was removed from the ice water bath and taken into the glove box to continue with the addition of KN(SiMe3)2(119.7 mg, 0.6 mmol) and DME (0.6 mL), the microwave tube was sealed with a cap and removed from the glove box. The reaction mixture was heated in an oil bath at 80 °C for 24 h. The flask was removed from the oil bath, allowed to cool to room temperature, exposed to air and then the reaction was quenched by the slow addition of three drops of water. 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 silica gel (eluted with petroleum ether) to give the product (13.0 mg, 48% yield) as a white solid. 1 H NMR (401 MHz, CHCI3) δ 7.51 - 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 (101 MHz, CDCI3) δ 157.3, 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, 88.7 ppm.

[0044] Example 7

[0045] In a nitrogen filled glove box, a dry microwave tube with a magnetic stir bar was charged with LiN(SiMe3)2(66.9 mg, 0.4 mmol), methyl 6-quinolinecarboxylate (46.8 mg, 0.25 mmol), 3,5-di(trifluoromethyl)phenyl-4-tert- butylbenzylsulfone (36.8 mg, 0.1 mmol) and THF (1.0 mL), the microwave tube was sealed with a cap and removed from the glove box, the reaction mixture was allowed to react in an ice water bath at 0 °C for 6 h. The flask was removed from the ice water bath and taken into the glove box to continue with the addition of KN(SiMe3)2(119.7 mg, 0.6 mmol) and DME (0.6 mL), the microwave tube was sealed with a cap and removed from the glove box. The reaction mixture was heated in an oil bath at 80 °C for 24 h. The flask was removed from the oil bath, cooled to room temperature, exposed to air and then the reaction was quenched by the slow addition of three drops of water. 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 silica gel (eluted with petroleum ether: ethyl acetate = 10: 1) to give the product (19.1 mg, 67% yield) as a white solid. 1 H NMR (401 MHz, CHCI3) δ 8.91-8.90 (m, 1H), 8.13-8.11 (m, 1H), 8.07 (d, J = 8.7 Hz, 1H), 8.01 (d, J = 1.8 Hz, 1H), 7.82 (dd, J = 8.7, 1.9 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.43-7.39 (m, 3H), 1.34 (s, 9H) ppm. 13 C NMR (101 MHz, CDCI3) δ 151.9, 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, 31.1 ppm.

[0046] Example 8

[0047] In a nitrogen filled glove box, a dry microwave tube with a magnetic stir bar was charged with LiN(SiMe3)2(66.9 mg, 0.4 mmol), methyl 6-quinolinecarboxylate (46.8 mg, 0.25 mmol), 3,5-di(trifluoromethyl)phenyl-4-methoxybenzyl sulfone (46.8 mg, 0.1 mmol) and THF (1.0 mL), the microwave tube was sealed with a cap and removed from the glove box, the reaction mixture was allowed to react in an ice water bath at 0 °C for 6 h. The flask was removed from the ice water bath and taken into the glove box to continue with the addition of KN(SiMe3)2(119.7 mg, 0.6 mmol) and DME (0.6 mL), the microwave tube was sealed with a cap and removed from the glove box. The reaction mixture was heated in an oil bath at 80 °C for 24 h. The flask was removed from the oil bath, cooled to room temperature, exposed to air and then the reaction was quenched by the slow addition of three drops of water. 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 silica gel (eluted with petroleum ether: ethyl acetate = 10: 1) to give the product (18.0 mg, 70% yield) as a white solid. 1 H NMR (401 MHz, CHCI3) δ 8.91-8.90 (m, 1H), 8.13-8.11 (m, 1H), 8.06 (d, J = 8.7 Hz, 1H), 7.99 (d, J = 1.8 Hz, 1H), 7.80 (dd, J = 8.7, 1.9 Hz, 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 (101 MHz, CDC13) δ 159.8, 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, 55.3 ppm.

[0048] Example 9

[0049] In a nitrogen filled glove box, a dry microwave tube with a magnetic stir bar was charged with LiN(SiMe3)2(66.9 mg, 0.4 mmol), methyl benzoate (31.2 μL, 0.25 mmol), 3,5- bis(trifluoromethyl)phenyl-3-methoxybenzyl sulfone (39.8 mg, 0.1 mmol) and THF (1.0 mL), the microwave tube was sealed with a cap and removed from the glove box, the reaction mixture was allowed to react in an ice water bath at 0 °C for 6 h. The flask was removed from the ice water bath and taken into the glove box to continue with the addition of KN(SiMe3)2(119.7 mg, 0.6 mmol) and DME (0.6 mL), the microwave tube was sealed with a cap and removed from the glove box. The reaction mixture was heated in an oil bath at 80 °C for 24 h. The flask was removed from the oil bath, cooled to room temperature, exposed to air and then the reaction was quenched by the slow addition of three drops of water. 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 silica gel (eluted with petroleum ether) to give the product (10.0 mg, 48% yield) as a white solid. 1 H NMR (401 MHz, CHCI3) δ 7.55-7.53 (m, 2H), 7.36-7.34 (m 3H), 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 (101 MHz, CDCI3) δ 159.3, 131.6, 129.4, 128.3, 128.3, 124.2, 124.1, 123.1, 116.2, 114.9, 89.2, 89.1, 55.3 ppm.

[0050] Example 10

[0051] In a nitrogen filled glove box, a dry microwave tube with a magnetic stir bar was charged with LiN(SiMe3)2(66.9 mg, 0.4 mmol), methyl benzoate (31.2 μL, 0.25 mmol), 3,5- bis(trifluoromethyl)phenyl-2-naphthylsulfone (41.8 mg, 0.1 mmol) and THF (1.0 mL), the microwave tube was sealed with a cap and removed from the glove box, the reaction mixture was allowed to react in an ice water bath at 0 °C for 6 h. The flask was removed from the ice water bath and taken into the glove box to continue the addition of KN(SiMe3)2(119.7 mg, 0.6 mmol) and DME (0.6 mL), the microwave tube was sealed with a cap and removed from the glove box. The reaction mixture was heated in an oil bath at 80 °C for 24 h. The flask was removed from the oil bath, cooled to room temperature, exposed to air and then the reaction was quenched by the slow addition of three drops of water. 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 silica gel (eluted with petroleum ether) to give the product (12.2 mg, 53% yield) as a white solid. 1 H NMR (401 MHz, CHCI3) δ 8.06 (s, 1 H), 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 (101 MHz, CDCI3) δ 133.0, 132.7, 131.6, 131.4, 128.4, 128.3, 128.0, 127.8, 126.7, 126.5, 123.2, 120.5, 89.7, 89.6 ppm.

Claims

1. A method of synthesizing a diphenylacetylene compound, characterized by: The methyl benzoate compound shown in formula 1 and the 3,5-bistrifluoromethylphenyl benzyl maple compound shown in formula 2 are mixed with an organic solvent in the presence of a strong base to react and synthesize the diphenylacetylene shown in formula 3; wherein R 1 is selected from halogen, tert-butyl, quinoline, R2is selected from methoxy, tert-butyl, 2-naphthyl.

2. A method of synthesizing a diaryl acetylene, characterized by: The methyl benzoate compound and the 3,5-bistrifluoromethylphenyl benzyl maple compound are mixed with an organic solvent in the presence of a strong base to react and synthesize the product diaryl acetylene compound and the product diphenylacetylene as shown in one of the following tables:

3. The method of synthesis according to claim 1 or 2, wherein, The strong base is lithium bis(trimethylsilyl)amide and potassium bis(trimethylsilyl)amide.

4. The method of synthesis according to claim 1 or 2, wherein, The reaction is carried out under the protection of an inert gas, and the inert gas is nitrogen.

5. The method of synthesis of claim 1 or 2, wherein, The organic solvent is methyl tert-butyl ether.

6. The method of synthesis of claim 1 or 2, wherein, The molar ratio of the methyl benzoate shown in formula 1, the 3,5-bistrifluoromethylphenyl benzyl maple shown in formula 2 and the strong base in the reaction is 2.5:1:4:6, and the reaction temperature is 0-80℃.

7. The method of synthesis of claim 1, wherein, The methyl benzoate compound, the 3,5-bistrifluoromethylphenyl benzyl maple compound and the product diphenylacetylene are as shown in one of the following tables:

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