Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Preparation method for 2-methyl-4-(trifluoromethyl)thiazole-5-formyl acid

A technology of trifluoromethyl, bromotrifluoroethyl acetoacetate is applied in the field of preparation of 2-methyl-4-thiazole-5-carboxylic acid, and can solve the problem of low utilization rate of ethyl trifluoroacetoacetate and lower reaction temperature , low reaction yield and other problems, to achieve the effects of convenient and easy-to-obtain raw materials, simple process and mild reaction conditions

Active Publication Date: 2013-06-12
SINOCHEM LANTIAN +1
View PDF10 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The reaction yield of this method is low, being 38%, and diethyl ether needs to be used as the extractant in the post-treatment stage;
[0008] (2) U.S. Patent No. 4,837,242 has reported the method for the synthesis of 2-methyl-4-(trifluoromethyl)thiazole-5-formic acid with thioacetamide in acetic acid with ethyl 2-chlorotrifluoroacetoacetate as raw material, This method has a low reaction yield of 56%, and the product is complex and difficult to purify;
[0009] (3) Chinese patent CN1102410 has reported the method for the synthesis of 2-methyl-4-(trifluoromethyl)thiazole-5-formic acid with acetonitrile as solvent, ethyl 2-chlorotrifluoroacetoacetate and thioacetamide reaction, This method controls the exothermic speed of reaction by the method for adding 2-chlorotrifluoroethyl acetate dropwise, and has reduced reaction temperature, and reaction yield is brought up to 90.6%, but in aftertreatment stage, still need to use diethyl ether as Extracting agent
Ethyl 2,2-dichlorotrifluoroacetoacetate cannot be cyclized with thioacetamide to generate ethyl 2-methyl-4-(trifluoromethyl)thiazole-5-carboxylate, resulting in the raw material trifluoroacetoacetate The utilization rate of ethyl ester is low

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method for 2-methyl-4-(trifluoromethyl)thiazole-5-formyl acid
  • Preparation method for 2-methyl-4-(trifluoromethyl)thiazole-5-formyl acid
  • Preparation method for 2-methyl-4-(trifluoromethyl)thiazole-5-formyl acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Embodiment 1: Preparation of ethyl 2-bromotrifluoroacetoacetate and ethyl 2,2-dibromotrifluoroacetoacetate

[0032] The reactor is a 1000ml three-necked flask equipped with a stirring device, a thermometer and a dropping funnel. After adding 192 g of liquid bromine (1.2 mol), 184 g of ethyl trifluoroacetoacetate (1.0 mol) and 300 ml of dichloromethane were added to the reactor at room temperature. After stirring and reacting at room temperature for 10 hours, the reaction solution was washed with saturated sodium bicarbonate solution and saturated salt until neutral, and 260 g of ethyl 2-bromotrifluoroacetoacetate and 2,2-dibromotrifluoroacetoacetate were obtained after precipitation. A mixture of ethyl esters containing 95.3% ethyl 2-bromotrifluoroacetoacetate and 4.3% ethyl 2,2-dibromotrifluoroacetoacetate. The yield of the bromination reaction was 97.48%. This mixture is directly used as starting material for the cyclization reaction.

Embodiment 2

[0033] Embodiment 2: Preparation of ethyl 2-methyl-4-(trifluoromethyl)thiazole-5-carboxylate

[0034]Add 30 g (0.11 mol) of a mixture of ethyl 2-bromotrifluoroacetoacetate and ethyl 2,2-dibromotrifluoroacetoacetate into a reactor with a stirring device, and start adding sulfur dropwise after cooling to 0°C Acetonitrile solution of thioacetamide, which contains 11.3 g (0.15 mol) of thioacetamide and 50 ml of acetonitrile. During the dropwise addition of the acetonitrile solution of thioacetamide, the exothermic heat of the system increases the reaction temperature, and the rate of addition is controlled so that the temperature in the system does not exceed 5°C. Yellow solids are continuously precipitated during the stirring reaction. The dropping time is 150min. After the acetonitrile solution of thioacetamide has been added dropwise, it is warmed up to room temperature, and at room temperature, 30.3 g (0.3 mol) of triethylamine is started to be added dropwise, and the time fo...

Embodiment 3

[0035] Embodiment 3: Preparation of 2-methyl-4-(trifluoromethyl)thiazole-5-carboxylic acid

[0036] Get the ethyl acetate solution of the 2-methyl-4-(trifluoromethyl)thiazole-5-formic acid ethyl ester (0.102mol) of 115g, add dropwise in the reactor 50g content and be 40% Hydroxide Sodium solution, control the rate of addition so that the internal temperature of the system is lower than 40 ° C, after the sodium hydroxide solution is added dropwise, keep the reaction for 60 minutes. After the heat preservation is over, separate the liquid, take the organic phase, slowly add 10% hydrochloric acid to it, and adjust the pH of the system to ≤ 2. At this time, there is a large amount of precipitation, filter the product, and wash the filter cake twice with 10% hydrochloric acid Then put it in a vacuum oven for drying. Obtain light yellow 2-methyl-4-(trifluoromethyl)thiazole-5-formic acid powdery solid 21.5g, wherein the content of 2-methyl-4-(trifluoromethyl)thiazole-5-formic acid i...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a method for preparing 2-methyl-4-(trifluoromethyl)thiazole-5-formyl acid. The method comprises the steps of synthesizing 2-bromo-trifluoro-ethyl acetoacetate and 2,2-dibromo-trifluoro-ethyl acetoacetate by reacting trifluoro ethyl acetoacetate with liquid bromine by using trifluoro ethyl acetoacetate as a raw material; then preparing ethyl acetoacetate of 2-methyl-4-(trifluoromethyl)thiazol-5-ethyl formate by reacting with an inert organic solvent solution of thioacetamide; and finally obtaining 2-methyl-4-(trifluoromethyl)thiazole-5-formyl acid by a hydrolysis reaction. The method has the advantages of novel raw materials and route, mild reaction conditions, simple operations, relatively high raw material conversion rate and product selectivity, convenient separation of target products, etc. The prepared 2-methyl-4-(trifluoromethyl)thiazole-5-formyl acid can be used for synthesizing a key intermediate of thiazole amide fungicides (thifluzamide).

Description

technical field [0001] The invention relates to a preparation method of 2-methyl-4-(trifluoromethyl)thiazole-5-carboxylic acid. Background technique [0002] 2-methyl-4-(trifluoromethyl)thiazole-5-carboxylic acid, the English name is 2-methyl-4-trifluoromethyl-thiazole-5-carboxylic acid, and the CAS number is 117724-63-7. Molecular formula is C 6 h 4 f 3 NO 2 S, molecular weight 211.16, off-white crystal. Its structural formula is as follows: [0003] [0004] 2-Methyl-4-(trifluoromethyl)thiazole-5-carboxylic acid is the key intermediate of thifluzamide, a thiazole amide fungicide, and its synthesis method mainly uses ethyl trifluoroacetoacetate as raw material Chlorination reaction to prepare 2-chlorotrifluoroacetoacetate ethyl ester and thioacetamide for cyclization and hydrolysis reaction in the system. In the process of preparing ethyl 2-chlorotrifluoroacetoacetate, the by-product of ethyl 2,2-dichlorotrifluoroacetoacetate will inevitably be generated simultane...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D277/56
Inventor 李华徐卫国蒋强蒋芬芳
Owner SINOCHEM LANTIAN
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com