A kind of chiral synthesis method of gamma-nitrophenol compound

A synthesis method and technology for ketone compounds, which are applied in the preparation of organic compounds, organic chemistry methods, chemical instruments and methods, etc., can solve the problems of few application reports, and achieve the effects of improving reaction yield, simple operation and reducing use.

CN107188771BActive Publication Date: 2021-08-24ZHEJIANG UNIV OF TECH
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Publication Date
2021-08-24

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Abstract

The invention provides a method for chiral synthesis of γ-nitrophenol compounds. The method is carried out as follows: a chiral catalyst, a cocatalyst, and an organic solvent A are mixed, and the compound shown in formula (iii) is added under stirring conditions. The ketone compound and the nitroalkene compound shown in formula (iv) are stirred and reacted at 10-40°C for 6-18h to obtain the compound shown in formula (v); to the compound shown in formula (v) Add organic brominating reagent, benzoic acid, tryptophan, and copper bromide, and stir the reaction at 90-120°C for 1h-15h in an organic solvent B. After the reaction, the obtained reaction solution B is post-processed to obtain the formula (i ) shown in the gamma-nitrophenol compounds. The present invention has the advantages that: the chiral nitroalkane-substituted phenol compound has wide application space; the synthesis method of the present invention has simple operation, mild reaction conditions, good reaction characteristics, high reaction yield and selectivity Good sex.
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Description

[0001] (1) Technical field

[0002] The invention relates to a chiral synthesis method of gamma-nitrophenol compounds.

[0003] (2) Background technology

[0004] The α-bromination reaction of carbonyl compounds is a very important reaction in organic synthesis, because the brominated products of α-carbonyl compounds are highly reactive and are commonly used as synthetic intermediates for the preparation of various biologically active compounds . The brominating reagents commonly used in the α-bromination reaction of carbonyl compounds are bromine, bromosuccinimide (NBS) and copper bromide. In recent years, hexamethylenetetramine / bromine compound salt (HMTAB), alkyl bromide / sodium hydride / DMSO combination, H 2 o 2 / HBr oxidation bromination system, Cu(II) / lithium bromide / O 2 Oxidative bromination system, (CH 3 ) 3 SiBr–KNO 3 , ammonium bromide / potassium hydrogen peroxosulfate, LiBr / Cu(NO 3 ) 2 ·3H 2 Different new bromination reagents and bromination systems such as O ...

Examples

Embodiment 1

[0066] Embodiment 1: the preparation of (S)-4-methyl-2-(2-nitro-1-phenethyl)phenol

[0067]

[0068] Take a clean 10mL small test tube, add 2-nitrovinylbenzene (0.6mmol, 0.0894g), 4-methylcyclohexanone (1.2mmol, 0.1344g), chiral catalyst L-proline (0.12mmol, 12.1mg ), benzoic acid (0.12mmol, 14.6mg) was dissolved in 1.0mL of dichloromethane, stirred at 25°C, after 12h, 2mL of water was added, washed with water, extracted with ether (1mL*3), added anhydrous sodium sulfate to dry, Filter and remove the solvent under reduced pressure. The crude product was separated by chromatography (petroleum ether:ethyl acetate=80:20). Michael addition product (0.5mmol), organic brominating reagent (1.0mmol, 0.2891g), copper bromide (0.075mmol, 16.8mg), benzoic acid (0.25mmol, 30.5mg), tryptophan (0.25mmol, 51.0mg), dissolved in 1mL redistilled acetonitrile solution, stirred at 100°C, detected by TLC, reacted for 12h, after the reaction, added 2mL water, washed with water, extracted with ...

Embodiment 2

[0069] Embodiment 2: Preparation of (S)-4-methyl-2-(2-nitro-1-phenethyl)phenol

[0070]

[0071] Take a clean 10mL small test tube, add 2-nitrovinylbenzene (0.6mmol, 0.0894g), 4-methylcyclohexanone (1.2mmol, 0.1344g), chiral catalyst 1,3-dimethyl-2-imidazole Linone (0.12mmol, 13.7mg), benzoic acid (0.12mmol, 14.6mg) were dissolved in 1.0mL chloroform, stirred at 10°C, after 12h, 2mL water was added, washed with water, extracted with diethyl ether (1mL*3), added Dry over anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure. The crude product was separated by chromatography (petroleum ether:ethyl acetate=80:20). Michael addition product (0.5mmol), organic brominating reagent (1.0mmol, 0.2891g), copper bromide (0.075mmol, 16.8mg), benzoic acid (0.25mmol, 30.5mg), tryptophan (0.25mmol, 51.0mg), dissolved in 1mL redistilled acetonitrile solution, stirred and reacted at 100°C for 12h, after the reaction, added 2mL water, washed with water, extracted w...

Embodiment 3

[0072] Embodiment 3: Preparation of (S)-4-methyl-2-(2-nitro-1-phenethyl)phenol

[0073]

[0074] Take a clean 10mL small test tube, add 2-nitrovinylbenzene (0.6mmol, 0.0894g), 4-methylcyclohexanone (1.2mmol, 0.1344g), chiral catalyst dimercaptopyridine (0.12mmol, 13.3mg), Benzoic acid (0.12mmol, 14.6mg) was dissolved in 1.0mL ether, stirred at 40°C, after 12h, 2mL water was added, washed with water, extracted with ether (1mL*3), dried by adding anhydrous sodium sulfate, filtered, and reduced pressure Remove the solvent. The crude product was separated by chromatography (petroleum ether:ethyl acetate=80:20). Michael addition product (0.5mmol), organic brominating reagent (1.0mmol, 0.2891g), copper bromide (0.075mmol, 16.8mg), benzoic acid (0.25mmol, 30.5mg), tryptophan (0.25mmol, 51.0mg), dissolved in 1mL redistilled acetonitrile solution, stirred and reacted at 100°C for 12h, after the reaction, added 2mL water, washed with water, extracted with dichloromethane (1mL*3), a...