Mono-aryl thioether compound as well as preparation method and application thereof

Abstract

The invention discloses a mono-aryl thioether compound: 2-((substituted thiophenyl) benzyl)-3-hydroxy-5,5-dimethylcyclohexyl-2-ketene. According to the compound, a benzyl side chain of the compound has 3-hydroxy-5,5-dimethylcyclohexyl-2-ketene, so that the compound has antifungal activity and can be used for preparing antifungal pharmaceutical preparations. The invention also discloses a preparation method of the mono-aryl thioether compound, and the preparation method comprises the following steps of taking aromatic aldehyde, thiophenol or substituted thiophenol and 5,5-dimethyl-1,3-cyclohexanedione, and performing heating reaction under the catalysis of catalysts including silica gel sulfuric acid and the like to generate a target product. The catalysts used in the preparation method disclosed by the invention are low in cost, the reaction conditions are mild, the operation is simple, and the problems of the existing thioether preparation method are solved, so that the mono-aryl thioether compound is suitable for large-scale application.

Description

technical field

[0001] The present invention relates to compound, specifically a kind of monoaryl sulfide compound and its preparation method and application. Background technique

[0002] Thioether is an important class of basic organic compounds, including alkenyl sulfide, alkynyl sulfide, propargyl sulfide, monoaryl sulfide and diaryl sulfide. Among the many different thioether compounds, monoaryl sulfide is the most widely used and most researched. Monoaryl sulfides, as intermediates in organic synthesis and drug synthesis, are widely used in the fields of medicine, polymer materials, pesticides, and fragrances.

[0003] In the past ten years, the synthesis method and research of monoaryl sulfide have also made relatively great progress (Authors: Shi Shaohui, Tu Xingzhao, Zhang Xiaoping, Dai Chuan, Zeng Qingle, Research progress in sulfide synthesis, "Guangzhou Chemical Industry", 2012 March, Volume 40, Issue 6, Pages 1-4). At present, the main method of synthesizing ...

Examples

Embodiment 1

[0064] Compound A: Its chemical structural formula is shown in (I), where R 1 is 4-fluoro, R 2 is hydrogen; its chemical formula is: C 21 h 21 FO 2 S; chemical name: 2-((4-fluorophenylthio)(phenyl)methyl)-3-hydroxy-5,5-dimethylcyclohex-2-ene.

[0065] a) Mix 1 mmol of benzaldehyde, 145 mg of 4-fluorothiophenol, 140 mg of 5,5-dimethyl-1,3-cyclohexanedione and 38 mg of catalyst silica gel sulfuric acid, put them into a reaction vessel, and then Heating and stirring in an oil bath, using a TLC plate to follow the reaction process until the aromatic aldehyde is completely reacted to obtain a solution containing compound A precipitate;

[0066] b) Add dichloromethane to the above solution, stir to dissolve compound A precipitate, and then filter to obtain silica gel sulfuric acid filter cake and filtrate;

[0067] c) The filtrate was concentrated under reduced pressure, separated and purified through a 200-300 mesh silica gel column, and then rinsed with petroleum ether, and t...

Embodiment 2

[0078] Compound B: Its chemical structural formula is shown in (I), where R 1 is 2-fluoro, R 2 is hydrogen; its chemical formula is: C 21 h 21 FO 2 S; chemical name: 2-((2-fluorophenylthio)(phenyl)methyl)-3-hydroxy-5,5-dimethylcyclohex-2-ene.

[0079] a) Mix 1 mmol of benzaldehyde, 110 mg of 2-fluorothiophenol, 130 mg of 5,5-dimethyl-1,3-cyclohexanedione and 30 mg of catalyst dodecylbenzenesulfonic acid, and put them into a reaction vessel , and then heated and stirred in an oil bath at 85° C., using a TLC plate to track the reaction process until the aromatic aldehyde was completely reacted to obtain a solution containing compound B precipitate;

[0080] b) Add dichloromethane to the above solution, stir to dissolve compound B precipitate, and then filter to obtain dodecylbenzenesulfonic acid filter cake and filtrate;

[0081] c) Concentrate the filtrate under reduced pressure, pass through a 200-300 mesh silica gel column for separation and purification, and then use a ...

Embodiment 3

[0092] Compound C: Its chemical structural formula is shown in (I), where R 1 is 4-methoxy, R 2 is hydrogen; its chemical formula is: C 22 h 24 o 3 S; chemical name: 2-((4-methoxyphenylthio)(phenyl)methyl)-3-hydroxy-5,5-dimethylcyclohex-2-ene.

[0093] a) Mix 1 mmol of benzaldehyde, 125 mg of 4-methoxythiophenol, 135 mg of 5,5-dimethyl-1,3-cyclohexanedione and 40 mg of catalyst p-toluenesulfonic acid, and put them into a reaction vessel. Then heat and stir in an oil bath at 90°C, and use a TLC plate to track the reaction process until the aromatic aldehyde is completely reacted to obtain a solution containing compound C precipitate;

[0094] b) Add dichloromethane to the above solution, stir to dissolve the compound C precipitate, and then filter to obtain p-toluenesulfonic acid filter cake and filtrate;

[0095]c) Concentrate the filtrate under reduced pressure, pass through a 200-300 mesh silica gel column for separation and purification, and then use a mixture of petro...

technical field

[0001] The present invention relates to compound, specifically a kind of monoaryl sulfide compound and its preparation method and application. Background technique

[0002] Thioether is an important class of basic organic compounds, including alkenyl sulfide, alkynyl sulfide, propargyl sulfide, monoaryl sulfide and diaryl sulfide. Among the many different thioether compounds, monoaryl sulfide is the most widely used and most researched. Monoaryl sulfides, as intermediates in organic synthesis and drug synthesis, are widely used in the fields of medicine, polymer materials, pesticides, and fragrances.

[0003] In the past ten years, the synthesis method and research of monoaryl sulfide have also made relatively great progress (Authors: Shi Shaohui, Tu Xingzhao, Zhang Xiaoping, Dai Chuan, Zeng Qingle, Research progress in sulfide synthesis, "Guangzhou Chemical Industry", 2012 March, Volume 40, Issue 6, Pages 1-4). At present, the main method of synthesizing ...

Examples

Embodiment 1

[0064] Compound A: Its chemical structural formula is shown in (I), where R 1 is 4-fluoro, R 2 is hydrogen; its chemical formula is: C 21 h 21 FO 2 S; chemical name: 2-((4-fluorophenylthio)(phenyl)methyl)-3-hydroxy-5,5-dimethylcyclohex-2-ene.

[0065] a) Mix 1 mmol of benzaldehyde, 145 mg of 4-fluorothiophenol, 140 mg of 5,5-dimethyl-1,3-cyclohexanedione and 38 mg of catalyst silica gel sulfuric acid, put them into a reaction vessel, and then Heating and stirring in an oil bath, using a TLC plate to follow the reaction process until the aromatic aldehyde is completely reacted to obtain a solution containing compound A precipitate;

[0066] b) Add dichloromethane to the above solution, stir to dissolve compound A precipitate, and then filter to obtain silica gel sulfuric acid filter cake and filtrate;

[0067] c) The filtrate was concentrated under reduced pressure, separated and purified through a 200-300 mesh silica gel column, and then rinsed with petroleum ether, and t...

Embodiment 2

[0078] Compound B: Its chemical structural formula is shown in (I), where R 1 is 2-fluoro, R 2 is hydrogen; its chemical formula is: C 21 h 21 FO 2 S; chemical name: 2-((2-fluorophenylthio)(phenyl)methyl)-3-hydroxy-5,5-dimethylcyclohex-2-ene.

[0079] a) Mix 1 mmol of benzaldehyde, 110 mg of 2-fluorothiophenol, 130 mg of 5,5-dimethyl-1,3-cyclohexanedione and 30 mg of catalyst dodecylbenzenesulfonic acid, and put them into a reaction vessel , and then heated and stirred in an oil bath at 85° C., using a TLC plate to track the reaction process until the aromatic aldehyde was completely reacted to obtain a solution containing compound B precipitate;

[0080] b) Add dichloromethane to the above solution, stir to dissolve compound B precipitate, and then filter to obtain dodecylbenzenesulfonic acid filter cake and filtrate;

[0081] c) Concentrate the filtrate under reduced pressure, pass through a 200-300 mesh silica gel column for separation and purification, and then use a ...

Embodiment 3

[0092] Compound C: Its chemical structural formula is shown in (I), where R 1 is 4-methoxy, R 2 is hydrogen; its chemical formula is: C 22 h 24 o 3 S; chemical name: 2-((4-methoxyphenylthio)(phenyl)methyl)-3-hydroxy-5,5-dimethylcyclohex-2-ene.

[0093] a) Mix 1 mmol of benzaldehyde, 125 mg of 4-methoxythiophenol, 135 mg of 5,5-dimethyl-1,3-cyclohexanedione and 40 mg of catalyst p-toluenesulfonic acid, and put them into a reaction vessel. Then heat and stir in an oil bath at 90°C, and use a TLC plate to track the reaction process until the aromatic aldehyde is completely reacted to obtain a solution containing compound C precipitate;

[0094] b) Add dichloromethane to the above solution, stir to dissolve the compound C precipitate, and then filter to obtain p-toluenesulfonic acid filter cake and filtrate;

[0095]c) Concentrate the filtrate under reduced pressure, pass through a 200-300 mesh silica gel column for separation and purification, and then use a mixture of petro...

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