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Industrial production method of 3,3'-difluorobiphenyl

A technology of difluorobiphenyl and fluorophenylmagnesium halide, which is applied in the fields of chemical instruments and methods, preparation of organic compounds, organic chemistry, etc., and can solve the problem of no electron-donating property for meta-fluorine substitution

Inactive Publication Date: 2017-02-22
ZHEJIANG JIUZHOU PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the reaction on the benzene ring, the para-fluorine substitution has a strong electron-donating property, but the meta-position fluorine substitution has no electron-donating property (see, for example, Journal of Chemical Education, 2003, 80, 679-690)
So in practice the 3-fluoro substituted series of compounds cannot be expected to give the same results as the 4-fluoro substituted series

Method used

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  • Industrial production method of 3,3'-difluorobiphenyl
  • Industrial production method of 3,3'-difluorobiphenyl
  • Industrial production method of 3,3'-difluorobiphenyl

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0067] Embodiment 1. Process I: the preparation of 3,3'-difluorobiphenyl

[0068]

[0069] In a 500ml four-neck flask equipped with a dropping funnel, a thermometer, and a magnetic stirrer, add 200ml of anhydrous tetrahydrofuran and 3.75 grams (154 mmol) of magnesium metal. Add 24.5 g (140 mmol) of 3-fluorobromobenzene in the dropping funnel. A small amount of iodine and a small amount of 3-fluorobromobenzene were added to the reaction flask, and then the reaction mixture was heated to about 50° C. to initiate the Grignard reaction. After the Grignard reaction is initiated, the 3-fluorobromobenzene in the dropping funnel is slowly dropped into the reaction solution to control the internal temperature to 45°C-52°C. After dropping, the reaction solution was stirred for 3 hours until the reaction was complete.

[0070] Add 84ml of dry tetrahydrofuran, 8.3g (83.8mmol) of 1,2-dichloroethane, and 0.7g (4.3mmol) of 3mol% FeCl to another four-necked flask equipped with a thermome...

Embodiment 2

[0071] Embodiment 2. technique II: under the effect of tetrabutylammonium chloride, the product gained in technique I is processed with sodium hydroxide aqueous solution.

[0072] The process I product is obtained by standard post-treatment after process I reaction. The standard aftertreatment is acidification with dilute hydrochloric acid, extraction with ethyl acetate, drying over magnesium sulfate, vacuum distillation after concentration, and the purity of the product 3,3'-difluorobiphenyl obtained in the GC analysis process I is 97.0% (NMR analysis purity is 95 %).

[0073] In a 1L bottle, add 200g process I to prepare the resulting product, 196ml contains 2.5N (mol / L) of sodium hydroxide of the phase-transfer catalyst tetrabutylammonium chloride of 5mol% (relative to sodium hydroxide) aqueous solution. Under nitrogen, the mixture was heated to reflux for 3 hours and then allowed to cool to room temperature. The reaction mixture was acidified with dilute hydrochloric ac...

Embodiment 3-5

[0074]Example 3-5. Process II: Under the action of a phase transfer catalyst, the crude product obtained in Process I is treated with an aqueous alkali or acid solution.

[0075] Like embodiment 2, the used raw material of embodiment 3-5 is the product that process 1 obtains. Under the action of a phase transfer catalyst or not under the action of a phase transfer catalyst, the impurity-containing product obtained in process I is treated with an aqueous alkali or acid solution. Table 1 shows the bases, acids and their amounts, reaction conditions and results. High yield and high purity products can be obtained.

[0076] Table I. Process 1 obtained products are treated with alkaline water, aqueous acid solution or pure water

[0077]

[0078]

[0079] ＊ Purity by NMR analysis. >99% means no impurities detected by NMR.

[0080] ＊＊ Purity was analyzed by GC (FID detector).

[0081] + Oil bath temperature is 120°C

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Abstract

The invention relates to a novel, safe, economical and environment-friendly production method of a useful chemical 3,3'-difluorobiphenyl. High-purity 3,3'-difluorobiphenyl can be prepared and obtained in a high-yield manner by making 3-fluorophenyl halogenated magnesium react with 1,2-dihalogenethane under the catalytic action of a trivalent ferric salt, and then treating a product by using an alkali or an acid. In addition, the method comprises a step of using and recycling an ethylene gas released in the reaction to prepare the initial raw material 1,2-dihalogenethane of the reaction, wherein the ethylene gas is a potential air pollutant.

Description

technical field [0001] The present invention relates to a method for the industrial production of high-purity 3,3'-difluorobiphenyl compound, which is used for the preparation of electrophilic trifluoromethylation reagent 2,8-difluoro-S-(trifluoromethyl) Key intermediate of benzothiophene salt and 2,6-difluoro-S-(trifluoromethyl)benzothiophene salt. Background technique [0002] Since the trifluoromethyl functional group is crucial in the development of effective drugs, pesticides and other useful materials, the practical preparation of trifluoromethyl compounds has attracted great attention (see, for example, J. Fluorine Chem. 2006, 127, 1013 -1029; Chem.Soc.Rev., 2008,37,230-330; "Fluorine and the environment", Vol.2, Chapter 4, "Fluorine-Containing Agrochemicals: An Overview of Recent Development", pp 121-175(2006)( ISSN 1872-0358)). Thus new highly active electrophilic trifluoromethylation reagents, 2,8-difluoro-S-(trifluoromethyl)benzothiophene trifluoromethanesulfona...

Claims

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Application Information

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IPC IPC(8): C07C17/263C07C25/18C07D333/76C07C67/343C07C69/757
CPCC07C17/2632C07C67/343C07D333/76C07C25/18C07C69/757Y02A50/20
Inventor 梅本照雄张斌张鹏李原强
Owner ZHEJIANG JIUZHOU PHARM CO LTD
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