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Method for directly preparing alpha-fluoro acetophenone by acetophenone one-pot method

A technology for substituting acetophenone and acetophenone, which is applied in the field of preparation of fine chemical products, can solve the problems of difficulty in controlling electrophilic fluorination reagents, low yield, expensive use, etc., and achieves reduction of synthesis cost, simple method, Efficiently obtained results

Inactive Publication Date: 2010-03-10
EAST CHINA NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0017] Tetrabutyl fluoride salts such as tetrabutyl ammonium fluoride and a hydrogen fluoride conjugate TBAF-HF are also commonly used nucleophilic fluorinating agents, but the yield is not high: 20-51%
[0019] In summary, the direct conversion of acetophenone to α-fluoroacetophenone using electrophilic fluorinating reagents requires the use of expensive or toxic electrophilic fluorinating reagents that are difficult to control

Method used

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  • Method for directly preparing alpha-fluoro acetophenone by acetophenone one-pot method
  • Method for directly preparing alpha-fluoro acetophenone by acetophenone one-pot method
  • Method for directly preparing alpha-fluoro acetophenone by acetophenone one-pot method

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Embodiment 1

[0036] Preparation of α-fluoro-p-methylacetophenone from p-methylacetophenone

[0037]Take 1mmol choline chloride and 1mmol TsOH in a round bottom flask, heat to form a eutectic, and slowly cool to room temperature. Add 3ml of acetonitrile, add 2mmol of p-methylacetophenone, slowly add 1.1mmol of DCDMH, react for 3 hours, and continue to stir for 1 hour. After adding 5 mmol of zinc fluoride, 6 mmol of tetramethylammonium fluoride was added in batches, and the reaction was continued for 8 hours at 50° C. After filtering, the filtrate was rotary evaporated to remove the solvent, then added 20ml of 5% dilute hydrochloric acid, extracted with 20ml of dichloromethane, and washed twice with 20ml of water until neutral. MgSO 4 After drying and rotary evaporation to remove the solvent, a crude product was obtained, which was separated and purified by column chromatography to obtain the product α-fluoro-p-methylacetophenone. yield and product 1 The H NMR data are shown in Table 1. ...

Embodiment 2

[0039] Preparation of α-fluoroacetophenone dimethyl ketal from acetophenone

[0040] Take 1mmol of choline chloride and 1mmol of zinc chloride in a round bottom flask, heat to form a eutectic, and slowly cool to room temperature. Add 2 mmol of acetophenone, slowly add 2.0 mmol of NCS, react for 3 hours, and continue stirring for 1 hour. After adding 3 mmol of potassium fluoride, 6 mmol of tetrabutylammonium fluoride was added in batches, and the reaction was continued at 80° C. for 5 hours. After filtering, the filtrate was rotary evaporated to remove the solvent, then added 20ml of 5% dilute hydrochloric acid, extracted with 20ml of dichloromethane, and washed twice with 20ml of water until neutral. MgSO 4 After drying and rotary evaporation to remove the solvent, a crude product was obtained, which was separated and purified by column chromatography to obtain the product α-fluoroacetophenone. yield and product 1 The H NMR data are shown in Table 1.

Embodiment 3

[0042] Preparation of α-fluoro-p-bromoacetophenone from p-bromoethanone

[0043] Take 1mmol of tetrabutylammonium bromide and 1mmol of p-toluenesulfonic acid in a round-bottomed flask, heat to form a eutectic, and slowly cool to room temperature. Add 3 ml of DMF, add 2 mmol of p-bromoacetophenone, slowly add 1.2 mmol of DBDMH, react for 3 hours, and continue stirring for 1 hour. After adding 2 mmol of CsF first, 6 mmol of tetramethylammonium fluoride was added in batches, and the reaction was continued for 4 hours at 100° C. After filtering, the filtrate was rotary evaporated to remove the solvent, then added 20ml of 5% dilute hydrochloric acid, extracted with 20ml of dichloromethane, and washed twice with 20ml of water until neutral. MgSO 4 After drying and rotary evaporation to remove the solvent, a crude product was obtained, which was separated and purified by column chromatography to obtain the product α-fluoro-p-bromoacetophenone. yield and product 1 The H NMR data a...

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Abstract

The invention discloses a method for directly preparing alpha-fluoro acetophenone by an acetophenone one-pot method, comprising the following steps: firstly preparing eutectic mixture, and sequentially adding acetophenone compound and alpha-halogenated reagent to react for 3-5h under the condition of 10-100 DEG C; and then, adding nucleophilic fluorinating agent to react for 5-10h under the condition of 50-150 DEG C, wherein the using quantity of the alpha-halogenated reagent is 0.5-2.0 times molar weight of the acetophenones compound, the using quantity of the nucleophilic fluorinating agentis 1-10 times molar weight of the the acetophenones compound, and the molar weight ratio between the eutectic mixture and the acetophenones compound is 5:1-1:1. The method directly utilizes various easily obtained acetophenones compounds as raw material, and the alpha-halogenation reaction is combined with nucleophilic fluorination reaction to realize the one-pot method for effectively obtaining the alpha-fluoro acetophenones compound; furthermore, the method has mild reaction condition and simple method, reduces the cost for synthesizing the alpha-fluoro acetophenones compound and has betterindustrialization prospect.

Description

technical field [0001] The invention belongs to the technical field of preparation of fine chemical products, and relates to a method for preparing α-fluoroacetophenone compounds. Background technique [0002] The importance of fluorine-containing compounds in the development of new medicines, pesticides and functional materials has been fully recognized by the scientific and industrial circles (R.N.Perutz, Science, 2008, 321, 1168-1169). α-fluoroacetophenone is an important class of fluorine-containing intermediates because it can be introduced into various important compounds as a fluorine-containing building block through various reactions on its α-position, carbonyl and benzene ring , the research and development of its synthetic method has received great attention (eg: E.Fuglseth, T.H.K.Thvedt, M.F.Moll and B.H.Hoff, Tetrahedron, 2008, 64, 7318-7323). [0003] As shown in the figure below: starting from acetophenone compounds, there are two main ways to prepare α-fluor...

Claims

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Application Information

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IPC IPC(8): C07B39/00C07C45/63C07C49/80C07C205/45C07C201/12C07C49/84C07C255/56C07C253/30
Inventor 邹新琢陈梓湛朱伟
Owner EAST CHINA NORMAL UNIV
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