Method for preparing 4 - bromine 2,6 - difluoro benzoic acid

A technology of difluorobenzoic acid and difluorobromobenzene, which is applied in the field of organic chemical synthesis, and can solve the problems of large environmental pollution, difficulty in industrialization, and difficulty in synthesizing final products.

Active Publication Date: 2007-10-10
SHANGHAI CHEMSPEC CORP
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  • Abstract
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Problems solved by technology

[0008] The weak point of above-mentioned each reaction is: oxidation method is limited to must have hydrocarbon group on the side chain of aromatic ring, and strong oxidant such as potassium dichromate pollutes environment very much, once destroyed, it is difficult to restore; Grignard reaction generates The intermediate is unstable, easily destroyed, and it is difficult to obtain the desired compound; the hydrolysis of the nitrile group will produce a series of by-products, so it is difficult to industrialize
[0012] The weak point of the above-mentioned Grignard reagent synthesis method is: if use the above-mentioned Grignard reagent synthesis method to synthesize 4-bromo-2,6-difluorobenzoic acid, there are two Br on the benzene ring, when finally synthesizing the Grignard reagent, It is possible to synthesize on both Br groups, and the probability is equal, it is difficult to synthesize the final product, and the selectivity is poor

Method used

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  • Method for preparing 4 - bromine 2,6 - difluoro benzoic acid
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  • Method for preparing 4 - bromine 2,6 - difluoro benzoic acid

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preparation example Construction

[0058] The preparation method of the present invention is described in detail below:

[0059] The steps of the preparation method of 4-bromo-2,6-difluorobenzoic acid

[0060] The preparation method of 4-bromo-2,6-difluorobenzoic acid of the present invention comprises the following steps:

[0061] (a) 3,5-difluorobromobenzene reacts with organolithium reagent in the presence of organic solvent to obtain the 4-position substituted lithium salt of 3,5-difluorobromobenzene;

[0062] (b) The 4-position substituted lithium salt of 3,5-difluorobromobenzene obtained in step (a) is subjected to hydrolysis to obtain 4-bromo-2,6-difluorobenzoic acid.

[0063] In a preferred embodiment of the present invention, the preparation method of 4-bromo-2,6-difluorobenzoic acid of the present invention comprises the following steps:

[0064] (a) 3,5-difluorobromobenzene reacts with an organolithium reagent in the presence of an organic solvent to obtain a 4-position substituted lithium salt of ...

Embodiment 1

[0098] Add 300ml THF (molecular weight 72.11, density 0.8892, 3.7mol), 10% butyllithium solution 0.39mol (250g) and 2,2,6,6-tetramethylpiperidine (0.39mol 56g) into a 1L bottle, Add 0.3 mol (58 g) of 3,5-difluorobromobenzene (99.8%) dropwise at -10°C (the molar ratio of solvent to 3,5-difluorobromobenzene is 12.3:1), stir for about 30 min, and cool to - 90℃ through CO 2 gas, to saturation. CO 2 After saturation, the temperature rises naturally. When rising to the internal temperature of -10°C, add 400ml of dilute hydrochloric acid, to PH<1, separate the upper organic layer, the aqueous layer is extracted with ether, the organic layer is washed with water, dried, and evaporated to remove the solvent to obtain 71 grams of the product, the product is cream color. After recrystallization, 59 grams of white product was obtained, the HPLC content was 99.4%, and the molar yield of raw material to product=88.9%.

Embodiment 2

[0100] Add 400ml of ether (molecular weight 74.12, density 0.7135, 3.85mol), 10% butyllithium solution 0.15mol (96g) and 0.15mol (18g) tetramethylethylenediamine to a 1L bottle, add 3 dropwise at 50°C, 0.3mol (58g) of 5-difluorobromobenzene (molar ratio of solvent to 3,5-difluorobromobenzene is 12.8:1), stirred for about 30min, cooled to 10°C and passed through CO 2 gas, to saturation. CO 2 After saturation, the temperature rises naturally. When the internal temperature was raised to 30°C, 400ml of dilute hydrochloric acid was added, to pH<1, the upper organic layer was separated, the aqueous layer was extracted with ether, the organic layer was washed with water, dried, and the solvent was evaporated to obtain 58 grams of the product, which was beige color. After recrystallization, 49 grams of white product were obtained, and the HPLC content was 99.0%. Molar yield of feedstock to product = 67.8%

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Abstract

This invention provides a method for preparing 4-bromo-2, 6-difluorobenzoic acid. The method comprises: reacting 3, 5-difluoro bromobenzene and organic lithium reagent in organic solvent to obtain 4-substituted lithium salt of 3, 5-difluoro bromobenzene, and hydrolyzing to obtain 4-bromo-2, 6-difluorobenzoic acid. The method has such advantages as abundant raw materials, simple process, easy post treatment, mild reaction conditions, little pollution, and high yield.

Description

technical field [0001] The invention relates to the field of organic chemical synthesis, in particular to a preparation method of 4-bromo-2,6-difluorobenzoic acid. Background technique [0002] Fluorinated aromatic compounds are mainly used as intermediates of physiologically active compounds such as pesticides and medicines, and have good thermal stability and high fat solubility. For example, it is used as herbicides, fungicides, anti-tumor drugs, anti-senile dementia drugs, functional dyes and so on. Because fluorine itself is highly reactive and difficult to control in reactions, especially when introducing molecules at specific positions, the preparation of fluorine-containing organics remains a challenging research area. [0003] The compound 4-bromo-2,6-difluorobenzoic acid of the present invention is an intermediate with increasingly wide application, and is a commonly used intermediate for synthesizing liquid crystal compounds, medicinal compounds and pesticide com...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C63/70C07C51/15
Inventor 袁云龙金叠汤秋莲
Owner SHANGHAI CHEMSPEC CORP
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