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The preparation method of 4-trifluoromethyl nicotinic acid

A technology of trifluoromethyl nicotinic acid and trifluoroacetyl chloride, which is applied in the field of chemical drug intermediate preparation, can solve the problems of difficulty in industrialized production, long process routes, increased steps, etc., and achieves high product yield and easy operation of the method. , the effect of fewer steps

Active Publication Date: 2020-09-01
浙江工业大学上虞研究院有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The preparation of 4-trifluoromethyl nicotinic acid disclosed at home and abroad mainly contains the following three kinds: it is prepared by reacting with CO2 containing trifluoromethyl pyridine compounds in the presence of a strong base such as LDA and then acidifying, but the raw materials of this method are expensive, The yield is low and strict anhydrous conditions are required, so it is difficult to realize industrial production; react with vinyl ethyl ether with trifluoroacetyl chloride or trifluoroacetic anhydride, then ammonify, then react with 3-methoxymethyl acrylate, and finally form The target product is obtained by ring hydrolysis. This method has a long process route and low overall yield; using ethyl trifluoroacetoacetate and cyanoacetamide as raw materials, it undergoes four steps of cyclization, chlorination, cyanohydrolysis, and catalytic hydrogenolysis. Preparation of 4-trifluoromethyl nicotinic acid, the current route is not yet mature, the yield is low during chlorination, the cyano group is easily reduced during catalytic hydrogenolysis, and the pyridine ring is easily partially reduced. Li Wei et al. improved this method, Using ethyl trifluoroacetoacetate and cyanoacetamide as raw materials, through cyclization and chlorination, then hydrolyzed to amide, then catalytic hydrogenolysis, and finally hydrolyzed to obtain 4-trifluoromethylnicotinic acid, although this route can avoid cyanide The group is reduced, but the number of steps increases, and the yield is low when chlorinated

Method used

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  • The preparation method of 4-trifluoromethyl nicotinic acid

Examples

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Effect test

Embodiment 1

[0020] Example 1: Preparation of 4-ethoxy-1,1,1-trifluoro-3-en-2-one.

[0021] In a 1000mL airtight four-necked reaction flask, add 72.1g of vinyl ether, 87.0g of pyridine and 500mL of toluene, stir evenly, control the temperature at 10-15°C, slowly add 145.8g of trifluoroacetyl chloride dropwise, and the dropping time lasts for 1 hour , after the dropwise addition was completed, the stirring was continued for 3 hours, the reaction was completed, and 300 mL of ice water was added to the reaction system to quench, the organic phase was washed twice with saline, and the solvent toluene was distilled off under reduced pressure to obtain a light yellow liquid 4-ethoxy-1 , 1,1-trifluoro-3-en-2-one 115.2 g, yield 68.5%.

Embodiment 2

[0022] Example 2: Preparation of 4-ethoxy-1,1,1-trifluoro-3-en-2-one.

[0023] In a 1000mL airtight four-necked reaction flask, add 72.1g of vinyl ether, 87.0g of pyridine and 500mL of toluene, stir evenly, control the temperature at 0-5°C, slowly add 145.8g of trifluoroacetyl chloride dropwise, and the dropping time lasts for 1 hour , after the dropwise addition was completed, the stirring was continued for 3 hours, the reaction was completed, and 300 mL of ice water was added to the reaction system to quench, the organic phase was washed twice with saline, and the solvent toluene was distilled off under reduced pressure to obtain a light yellow liquid 4-ethoxy-1 , 1,1-trifluoro-3-en-2-one 145.7 g, yield 86.7%.

Embodiment 3

[0024] Example 3: Preparation of 4-ethoxy-1,1,1-trifluoro-3-en-2-one.

[0025] In a 1000mL airtight four-necked reaction flask, add 72.1g of vinyl ether, 87.0g of pyridine and 500mL of toluene, stir evenly, control the temperature at 0-5°C, and slowly add 159.0g of trifluoroacetyl chloride dropwise for 1 hour , after the dropwise addition was completed, the stirring was continued for 3 hours, the reaction was completed, and 300 mL of ice water was added to the reaction system to quench, the organic phase was washed twice with saline, and the solvent toluene was distilled off under reduced pressure to obtain a light yellow liquid 4-ethoxy-1 , 1,1-trifluoro-3-en-2-one 155.2 g, yield 92.3%.

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Abstract

The invention discloses a method for preparing 4-(trifluoromethyl)nicotinic acid, and belongs to the technical field of methods for preparing chemical pharmaceutical intermediates. The method comprises steps of using trifluoroacetyl chloride, vinyl ethyl ether and 3-aminoacrylonitrile as raw materials to prepare the 4-(trifluoromethyl)nicotinic acid through acylation, cyclization and hydrolysis reactions. The method provided by the invention is relatively cheap and easily available in adopted raw material, simple and convenient to operate, easy in separation and purification of products in each step, high in yield, and more suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of preparation methods of chemical drug intermediates, and in particular relates to a preparation method of 4-trifluoromethyl nicotinic acid. Background technique [0002] 4-trifluoromethyl nicotinic acid, the structure is as shown in formula (I), is a kind of important chemical pesticide intermediate, is used for synthesizing a kind of novel low-toxicity pyridine amide class insect growth regulator class insecticide sulfoxinil Amide, obtained the temporary registration certificate of pesticide products in my country in 2007, and the preparation is 10% water dispersible granules. [0003] In addition to its contact and stomach poisoning effects, flonicamid also has a good nerve agent and rapid antifeedant effect. Aphids and other piercing-sucking mouthparts will be quickly prevented from sucking the juice after inhaling the plant juice with flonicamid. There will be no excrement at all within 1 hour, and eve...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D213/80C07D213/803
CPCC07D213/80C07D213/803
Inventor 方标柯军梁许萌
Owner 浙江工业大学上虞研究院有限公司
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