Method for compounding tri-substituted pyridine derivatives

Abstract

The invention provides a method for compounding tri-substituted pyridine derivatives, which belongs to the compound technical field of pyridine derivatives. The method for compounding the tri-substituted pyridine derivatives use amine compounds and troponoid compounds to react and compound pyridine derivatives when having trifluoromethanesulfonic acids, wherein a response equation is (img file='878185 dest_path_image001.TIF' wi='250' he='66' / ). The method for compounding the tri-substituted pyridine derivatives is suitable for a large number of functional groups, and is simple in operation and high in yield, single in product structure, convenient to separate and purify, safe, low in price and small in pollution.

Description

technical field

[0001] The invention belongs to the technical field of synthesis of pyridine derivatives, in particular to a method for synthesizing trisubstituted pyridine derivatives. Background technique

[0002] Pyridine derivatives are important fine chemical intermediates, which are widely used in pesticides, pharmaceutical rubber additives, surfactants, binders and daily chemicals. With the continuous progress of human society and the deepening of application research, Demand for pyridine derivatives has also increased dramatically. Therefore, it is also very necessary to study its new, simple and industrialized synthesis method, which will also produce better economic benefits.

[0003] Although there are many synthesis methods of pyridine derivatives at present, these methods mainly include gas-phase method and liquid-phase method, but there are great limitations. For example, the gas phase method uses acetic acid to acidify acetaldehyde to polymerize acetaldehyde...

Examples

Embodiment 1

[0023] The preparation of 2,6-diphenyl-4-p-picoline: add acetophenone 1mmol (120mg), p-methylbenzylamine 0.75mmol (91.6mg), catalyst HOTf0.05mmol (7.5mg) in the reaction vessel . React in an oil bath at 120°C for 24 hours, cool to room temperature, add water to quench the reaction, wash three times with ethyl acetate, separate the layers, combine the organic layers, decolorize with activated carbon, filter, dry over anhydrous sodium sulfate, concentrate under reduced pressure, and the product passes through Purified by column chromatography, the eluent was petroleum ether:ethyl acetate=50:1 (v / v), and a white solid product was obtained with a yield of 92% and a purity of 99.9%. 1 HNMR (400MHz, DMSO- d 6 ) δ ppm: δ8.33(d, J =7.2Hz, 4H), 8.18(s, 2H), 7.96(d, J =8.4Hz, 2H), 7.49-7.58(m, 6H), 7.38(d, J =8.0Hz, 2H); 13 CNMR (100MHz, DMSO- d 6 ) δ ppm: δ156.4, 149.9, 139.5, 139.3, 135.2, 130.2, 129.7, 129.2, 127.6, 127.4, 116.7, 21.3; HRMS (EI) Calcd.forC 24 h 19 N:[M +...

Embodiment 2

[0025] The preparation of 4-(4-fluorophenyl)-2,6-diphenylpyridine: add acetophenone 1mmol (120mg), p-fluorobenzylamine 0.75mmol (93.8mg), catalyst HOTf0.05mmol ( 7.5mg). React in an oil bath at 120°C for 24 hours, cool to room temperature, add water to quench the reaction, wash three times with ethyl acetate, separate the layers, combine the organic layers, decolorize with activated carbon, filter, dry over anhydrous sodium sulfate, concentrate under reduced pressure, and the product passes through Purified by column chromatography, the eluent is petroleum ether:ethyl acetate=50:1 (v / v), to obtain a white solid product with a yield of 78% and a purity of 99.8% 1 HNMR (400MHz, DMSO- d 6 ) δ ppm: δ8.36(d, J =7.6Hz, 4H), 8.21(s, 2H), 8.15(q, 2H), 7.49-7.60(m, 6H), 7.43(t, 2H); 13 CNMR (100MHz, DMSO- d 6 ) δ ppm: δ164.7, 162.2, 157.0, 148.9, 139.2, 134.6, 130.1, 129.7, 129.2, 127.4, 116.5; HRMS (EI) Calcd.forC 23 h 16 NF: [M + ], 325.1267. Found: m / z 325.1268.

Embodiment 3

[0027]The preparation of 2,6-diphenyl-4-m-picoline: add acetophenone 1mmol (120mg), m-methylbenzylamine 0.75mmol (91.6mg), catalyst HOTf0.05mmol (7.5mg) in the reaction vessel . React in an oil bath at 120°C for 24 hours, cool to room temperature, add water to quench the reaction, wash three times with ethyl acetate, separate the layers, combine the organic layers, decolorize with activated carbon, filter, dry over anhydrous sodium sulfate, concentrate under reduced pressure, and the product passes through Purified by column chromatography, the eluent was petroleum ether: ethyl acetate = 50:1 (v / v), to obtain a white solid product with a yield of 91% and a purity of 99.9%. 1 HNMR (400MHz, CDCl 3 ) δ ppm: δ8.22(d, J =7.6Hz, 4H), 7.87(q, 2H), 7.41-7.55(m, 9H), 7.29(s, 1H); 13 CNMR (100MHz, CDCl 3 ) δ ppm: δ157.5, 150.4, 139.7, 139.1, 138.9, 129.8, 129.1, 128.8, 128.0, 127.2, 127.2, 124.4, 117.2, 21.6; HRMS (EI) Calcd.forC 24 h 19 N:[M + ], 321.1517. Found: m / z 321.1519....

technical field

[0001] The invention belongs to the technical field of synthesis of pyridine derivatives, in particular to a method for synthesizing trisubstituted pyridine derivatives. Background technique

[0002] Pyridine derivatives are important fine chemical intermediates, which are widely used in pesticides, pharmaceutical rubber additives, surfactants, binders and daily chemicals. With the continuous progress of human society and the deepening of application research, Demand for pyridine derivatives has also increased dramatically. Therefore, it is also very necessary to study its new, simple and industrialized synthesis method, which will also produce better economic benefits.

[0003] Although there are many synthesis methods of pyridine derivatives at present, these methods mainly include gas-phase method and liquid-phase method, but there are great limitations. For example, the gas phase method uses acetic acid to acidify acetaldehyde to polymerize acetaldehyde...

Examples

Embodiment 1

[0023] The preparation of 2,6-diphenyl-4-p-picoline: add acetophenone 1mmol (120mg), p-methylbenzylamine 0.75mmol (91.6mg), catalyst HOTf0.05mmol (7.5mg) in the reaction vessel . React in an oil bath at 120°C for 24 hours, cool to room temperature, add water to quench the reaction, wash three times with ethyl acetate, separate the layers, combine the organic layers, decolorize with activated carbon, filter, dry over anhydrous sodium sulfate, concentrate under reduced pressure, and the product passes through Purified by column chromatography, the eluent was petroleum ether:ethyl acetate=50:1 (v / v), and a white solid product was obtained with a yield of 92% and a purity of 99.9%. 1 HNMR (400MHz, DMSO- d 6 ) δ ppm: δ8.33(d, J =7.2Hz, 4H), 8.18(s, 2H), 7.96(d, J =8.4Hz, 2H), 7.49-7.58(m, 6H), 7.38(d, J =8.0Hz, 2H); 13 CNMR (100MHz, DMSO- d 6 ) δ ppm: δ156.4, 149.9, 139.5, 139.3, 135.2, 130.2, 129.7, 129.2, 127.6, 127.4, 116.7, 21.3; HRMS (EI) Calcd.forC 24 h 19 N:[M +...

Embodiment 2

[0025] The preparation of 4-(4-fluorophenyl)-2,6-diphenylpyridine: add acetophenone 1mmol (120mg), p-fluorobenzylamine 0.75mmol (93.8mg), catalyst HOTf0.05mmol ( 7.5mg). React in an oil bath at 120°C for 24 hours, cool to room temperature, add water to quench the reaction, wash three times with ethyl acetate, separate the layers, combine the organic layers, decolorize with activated carbon, filter, dry over anhydrous sodium sulfate, concentrate under reduced pressure, and the product passes through Purified by column chromatography, the eluent is petroleum ether:ethyl acetate=50:1 (v / v), to obtain a white solid product with a yield of 78% and a purity of 99.8% 1 HNMR (400MHz, DMSO- d 6 ) δ ppm: δ8.36(d, J =7.6Hz, 4H), 8.21(s, 2H), 8.15(q, 2H), 7.49-7.60(m, 6H), 7.43(t, 2H); 13 CNMR (100MHz, DMSO- d 6 ) δ ppm: δ164.7, 162.2, 157.0, 148.9, 139.2, 134.6, 130.1, 129.7, 129.2, 127.4, 116.5; HRMS (EI) Calcd.forC 23 h 16 NF: [M + ], 325.1267. Found: m / z 325.1268.

Embodiment 3

[0027]The preparation of 2,6-diphenyl-4-m-picoline: add acetophenone 1mmol (120mg), m-methylbenzylamine 0.75mmol (91.6mg), catalyst HOTf0.05mmol (7.5mg) in the reaction vessel . React in an oil bath at 120°C for 24 hours, cool to room temperature, add water to quench the reaction, wash three times with ethyl acetate, separate the layers, combine the organic layers, decolorize with activated carbon, filter, dry over anhydrous sodium sulfate, concentrate under reduced pressure, and the product passes through Purified by column chromatography, the eluent was petroleum ether: ethyl acetate = 50:1 (v / v), to obtain a white solid product with a yield of 91% and a purity of 99.9%. 1 HNMR (400MHz, CDCl 3 ) δ ppm: δ8.22(d, J =7.6Hz, 4H), 7.87(q, 2H), 7.41-7.55(m, 9H), 7.29(s, 1H); 13 CNMR (100MHz, CDCl 3 ) δ ppm: δ157.5, 150.4, 139.7, 139.1, 138.9, 129.8, 129.1, 128.8, 128.0, 127.2, 127.2, 124.4, 117.2, 21.6; HRMS (EI) Calcd.forC 24 h 19 N:[M + ], 321.1517. Found: m / z 321.1519....

Images