Method for preparing quinoline compounds by catalysis of zirconocene dichloride

Abstract

The invention discloses a method for preparing quinoline compounds by catalyzing zirconocene dichloride. The method uses 3-butyne-2-ketone compounds and anthranilobenzenethiol compounds as raw materials, As a catalyst, L-phenylalanine, tyrosine, etc. are used as catalyst ligands, N,N-dimethylformamide is used as a solvent, and elemental iodine, hydrogen peroxide, tert-butanol peroxide, etc. are used as oxidants, The quinoline compounds can be prepared efficiently and in high yield. The catalyst used in the present invention is low in cost, stable to air, mild in reaction conditions, and simple in operation. After the reaction is completed, the product is extracted and washed and separated by simple column chromatography to obtain quinoline compounds, which are quinoline compounds The preparation of opens a low-cost and high-efficiency way, and has broad application prospects.

Description

technical field

[0001] The invention belongs to the technical field of synthesis of quinoline compounds, in particular to a method for efficiently preparing quinoline compounds by catalyzing the reaction of zirconocene 3-butyn-2-one compounds and o-aminobenzenethiol compounds with dichlorozirconocene . Background technique

[0002] Quinolines are a class of alkaloids that exist widely, and are often used in medicine, pesticides, dyes, etc., and have attracted people's attention because of their extensive biological and pharmacological effects. The quinoline pharmacophore has important functions, and it has been reported to have a variety of pharmacological activities, such as: anti-cancer, anti-malarial, anti-tuberculosis, anti-bacterial, anti-inflammatory, antioxidant, anti-hypertensive, anti-AIDS, treatment of lupus erythematosus And neurodegenerative diseases, etc., it is of great significance in medicine and organic synthesis.

[0003] At present, there are various met...

Examples

Embodiment 1

[0017] Preparation of 2,4-diphenylquinoline with the following structural formula

[0018]

[0019] Add 0.103g (0.5mmol) 1,4-diphenyl-3-butyne-2-one, 0.0073g (0.025mmol) zirconocene dichloride, 0.0082g (0.05mmol) L-phenylpropane to the reaction flask Amino acid, 64μL (0.6mmol) o-aminobenzenethiol, 1mL DMF, stirred and reacted at 30°C for 5 hours, then added 0.1518g (0.6mmol) iodine, continued to stir and reacted at 30°C for 2 hours, stopped the reaction, added Add 10 mL of saturated sodium thiosulfate aqueous solution, add 10 mL of ethyl acetate and extract 3 times, remove the ethyl acetate by rotary evaporation of the organic phase, and separate with a silica gel column (the eluent is petroleum ether and dichloromethane in a volume ratio of 2:1) Mixed liquor), obtains 2,4-diphenylquinoline, and its productive rate is 93%, and the spectral data of product is: 1 H NMR (400MHz, CDCl 3 )δ8.16(d, J=8.4Hz, 1H), 8.10(d, J=7.4Hz, 2H), 7.81(d, J=8.3Hz, 1H), 7.72(s, 1H), 7.63(t, ...

Embodiment 2

[0025] Preparation of 2-(4-chlorophenyl)-4-phenylquinoline with the following structural formula

[0026]

[0027] In this example, the 1,4-diphenyl-3-butane used in Example 1 was replaced with equimolar 1-(4-chlorophenyl)-4-phenyl-3-butyn-2-one Alkyn-2-ketone, other steps are identical with embodiment 1, obtain 2-(4-chlorophenyl)-4-phenylquinoline, and its productive rate is 84%, and the spectral data of product is: 1 H NMR (400MHz, CDCl 3 )δ8.12(d, J=8.4Hz, 1H), 8.05(d, J=8.4Hz, 2H), 7.80(d, J=8.3Hz, 1H), 7.68-7.60(m, 2H), 7.44( s,5H),7.38(d,J=8.2Hz,3H); 13 C NMR (101MHz, CDCl 3 )δ155.51, 149.41, 148.78, 138.27, 138.03, 135.58, 130.11, 129.70, 129.55, 129.01, 128.84, 128.65, 128.51, 126.55, 125.84, 125.69, 118.89.

Embodiment 3

[0029] Preparation of 2-(4-fluorophenyl)-4-phenylquinoline of the following structural formula

[0030]

[0031] In this example, the 1,4-diphenyl-3-butane used in Example 1 was replaced with equimolar 1-(4-fluorophenyl)-4-phenyl-3-butyn-2-one Alkyn-2-one, other steps are the same as in Example 1, obtain 2-(4-fluorophenyl)-4-phenylquinoline, its productive rate is 90%, and the spectral data of product is: 1 H NMR (400MHz, CDCl 3 )δ8.16-8.06 (m, 3H), 7.83-7.77 (m, 1H), 7.69-7.60 (m, 2H), 7.49-7.40 (m, 5H), 7.38 (ddd, J = 8.2, 6.8, 1.3 Hz,1H),7.11(t,J=8.7Hz,2H); 13 C NMR (101MHz, CDCl 3 )δ165.07,162.59,155.76,149.35,148.77,138.32,135.81,135.77,130.04,129.66,129.55,129.48,129.39,128.63,128.48,126.40,125.70,125.68,118.98,115.88,115.67.

technical field

[0001] The invention belongs to the technical field of synthesis of quinoline compounds, in particular to a method for efficiently preparing quinoline compounds by catalyzing the reaction of zirconocene 3-butyn-2-one compounds and o-aminobenzenethiol compounds with dichlorozirconocene . Background technique

[0002] Quinolines are a class of alkaloids that exist widely, and are often used in medicine, pesticides, dyes, etc., and have attracted people's attention because of their extensive biological and pharmacological effects. The quinoline pharmacophore has important functions, and it has been reported to have a variety of pharmacological activities, such as: anti-cancer, anti-malarial, anti-tuberculosis, anti-bacterial, anti-inflammatory, antioxidant, anti-hypertensive, anti-AIDS, treatment of lupus erythematosus And neurodegenerative diseases, etc., it is of great significance in medicine and organic synthesis.

[0003] At present, there are various met...

Examples

Embodiment 1

[0017] Preparation of 2,4-diphenylquinoline with the following structural formula

[0018]

[0019] Add 0.103g (0.5mmol) 1,4-diphenyl-3-butyne-2-one, 0.0073g (0.025mmol) zirconocene dichloride, 0.0082g (0.05mmol) L-phenylpropane to the reaction flask Amino acid, 64μL (0.6mmol) o-aminobenzenethiol, 1mL DMF, stirred and reacted at 30°C for 5 hours, then added 0.1518g (0.6mmol) iodine, continued to stir and reacted at 30°C for 2 hours, stopped the reaction, added Add 10 mL of saturated sodium thiosulfate aqueous solution, add 10 mL of ethyl acetate and extract 3 times, remove the ethyl acetate by rotary evaporation of the organic phase, and separate with a silica gel column (the eluent is petroleum ether and dichloromethane in a volume ratio of 2:1) Mixed liquor), obtains 2,4-diphenylquinoline, and its productive rate is 93%, and the spectral data of product is: 1 H NMR (400MHz, CDCl 3 )δ8.16(d, J=8.4Hz, 1H), 8.10(d, J=7.4Hz, 2H), 7.81(d, J=8.3Hz, 1H), 7.72(s, 1H), 7.63(t, ...

Embodiment 2

[0025] Preparation of 2-(4-chlorophenyl)-4-phenylquinoline with the following structural formula

[0026]

[0027] In this example, the 1,4-diphenyl-3-butane used in Example 1 was replaced with equimolar 1-(4-chlorophenyl)-4-phenyl-3-butyn-2-one Alkyn-2-ketone, other steps are identical with embodiment 1, obtain 2-(4-chlorophenyl)-4-phenylquinoline, and its productive rate is 84%, and the spectral data of product is: 1 H NMR (400MHz, CDCl 3 )δ8.12(d, J=8.4Hz, 1H), 8.05(d, J=8.4Hz, 2H), 7.80(d, J=8.3Hz, 1H), 7.68-7.60(m, 2H), 7.44( s,5H),7.38(d,J=8.2Hz,3H); 13 C NMR (101MHz, CDCl 3 )δ155.51, 149.41, 148.78, 138.27, 138.03, 135.58, 130.11, 129.70, 129.55, 129.01, 128.84, 128.65, 128.51, 126.55, 125.84, 125.69, 118.89.

Embodiment 3

[0029] Preparation of 2-(4-fluorophenyl)-4-phenylquinoline of the following structural formula

[0030]

[0031] In this example, the 1,4-diphenyl-3-butane used in Example 1 was replaced with equimolar 1-(4-fluorophenyl)-4-phenyl-3-butyn-2-one Alkyn-2-one, other steps are the same as in Example 1, obtain 2-(4-fluorophenyl)-4-phenylquinoline, its productive rate is 90%, and the spectral data of product is: 1 H NMR (400MHz, CDCl 3 )δ8.16-8.06 (m, 3H), 7.83-7.77 (m, 1H), 7.69-7.60 (m, 2H), 7.49-7.40 (m, 5H), 7.38 (ddd, J = 8.2, 6.8, 1.3 Hz,1H),7.11(t,J=8.7Hz,2H); 13 C NMR (101MHz, CDCl 3 )δ165.07,162.59,155.76,149.35,148.77,138.32,135.81,135.77,130.04,129.66,129.55,129.48,129.39,128.63,128.48,126.40,125.70,125.68,118.98,115.88,115.67.

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