Synthetic method of 5-(2-hydroxyethyl)-4-methylthiazole

A synthesis method and thiothiazole technology, applied in the direction of organic chemistry and the like, can solve the problems of long steps, many side reactions, low yields, etc., and achieve the effects of mild reaction conditions, saving reaction time, and simple post-processing.

Pending Publication Date: 2020-09-08
KUNSHAN YAXIANG SPICEL CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] There are many synthetic methods in the prior art, mainly at present: the first is to use α-acetyl-γ-butyrolactone as a raw material to obtain 4-methyl-5-(β-hydroxyethyl Base)-thiazole, longer steps, more side reactions, resulting in lower yield, α-acetyl-γ-butyrolactone chlorination is prone to γ-position substitution and difficult to separate
The second is prepared from 3-halo-3-acetylpropanol and thioformamide. The raw...

Method used

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  • Synthetic method of 5-(2-hydroxyethyl)-4-methylthiazole
  • Synthetic method of 5-(2-hydroxyethyl)-4-methylthiazole

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Dissolve 11.6g (0.1mol) of methyl acetoacetate in 300ml of anhydrous tetrahydrofuran, at 0°C, under the protection of nitrogen, add 4.8g (0.12mol) of 60% sodium hydrogen in batches, and then drop in 21.5g (0.1mol) ) 50ml tetrahydrofuran solution of 3-bromo-3-chloropropyl acetate, after putting in, continue to react for 2 hours, then heat up to reflux for 0.5-1 hour. After the reaction was detected by GC-MS, the temperature was lowered to 0°C, and a sufficient amount of 5% dilute hydrochloric acid was slowly added dropwise to adjust the pH to neutral, extracted with ether, and then the ether was distilled off to obtain 24 g of 4-acetoxy- The crude product of methyl 2-acetyl-2-chlorobutyrate was 95% of methyl 4-acetoxy-2-acetyl-2-chlorobutyrate by GC-MS, and 2.8% of 4- Acetoxy-2-acetyl-2-bromobutyric acid methyl ester, the content of disubstituted impurities is less than 1%, and the content of non-halogenated impurities is less than 1%. No further purification is needed, ...

Embodiment 2

[0032] Dissolve 200g (1.72mol) of methyl acetoacetate in 1.5L of anhydrous tetrahydrofuran, and at -5°C, under nitrogen protection, add 72g (1.80mol) of 60% sodium hydrogen in batches, and then drop 369.8g (1.72mol) ) 3-bromo-3-chloropropyl acetate, input is completed, continue to react for 2 hours, then heat up to reflux for 1 hour. After the reaction was detected by GC-MS, the temperature was lowered to 0°C, and a sufficient amount of 5% dilute hydrochloric acid was slowly added dropwise to adjust the pH to neutral, extracted with ether, and then the ether was distilled off to obtain 240 g of 4-acetoxy- 2-acetyl-2-chlorobutyric acid methyl ester crude product, 408g of 4-acetoxy-2-acetyl-2-chlorobutyric acid methyl ester crude product with 96% content detected by GC-MS, no further purification needed, directly into the next reaction.

[0033] Add 408 g of the crude product 4-acetoxy-2-acetyl-2-chlorobutyric acid methyl ester prepared above into a 2L reaction flask, add 1.2L ...

Embodiment 3

[0038]Put 5kg of methyl acetoacetate into a 50L reaction kettle, add 20L of anhydrous tetrahydrofuran to dissolve it, and put 1.81kg of 60% sodium hydrogen in batches at -10~-5°C under the protection of nitrogen, and then drop in 8.62kg of 3- Bromo-3-chloropropyl acetate, the input was completed, and the reaction was continued for 8 hours, and then the temperature was raised to room temperature for 2 hours. After the reaction was detected by GC-MS, lower the temperature to -5°C, slowly drop in a sufficient amount of 10% dilute hydrochloric acid, adjust the pH to neutral, extract with ether, and then distill off the ether to obtain 9.98kg of 4-acetoxy The crude product of methyl-2-acetyl-2-chlorobutyrate was 97% 4-acetoxy-2-acetyl-2-chlorobutyric acid methyl ester by GC-MS, without purification, directly Enter the next reaction.

[0039] Add 9.98kg of the crude product 4-acetoxy-2-acetyl-2-chlorobutyrate methyl ester prepared above in a 100L reactor, add 50L of 20% sulfuric ac...

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Abstract

The invention belongs to the field of organic synthesis, and discloses a 5-(2-hydroxyethyl)-4-methylthiazole synthesis method, which comprises: preparing 4-acetoxy-2-acetyl-2-methyl chlorobutyrate from methyl acetoacetate and 3-bromo-3-chloropropyl acetate under an alkaline condition; hydrolyzing the 4-acetoxy-2-acetyl-2-methyl chlorobutyrate under an acidic condition to prepare 3-chloro-3-acetylpropanol acetate; preparing 2-mercapto-4-methyl-5-(beta-acetoxyethyl)-thiazole from the 3-chloro-3-acetyl propanol acetate and ammonium dithiocarbamate under an acidic condition; adding an oxidizing agent into the 2-mercapto-4-methyl-5-(beta-acetoxyethyl)-thiazole under an acidic condition to prepare 4-methyl-5-(beta-acetoxyethyl)-thiazole; and preparing 4-methyl-5-(beta-acetoxyethyl)-thiazole from the 4-methyl-5-(beta-acetoxyethyl)-thiazole under an alkaline condition. The synthesis method is mild in overall reaction condition, simple in post-treatment and suitable for pilot scale test and industrial production.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to a synthesis method of thiothiazole. Background technique [0002] Thiazole, the full name of which is 4-methyl-5-(β-hydroxyethyl)-thiazole, is a precious spice, which has a nutty, bean, milky, eggy and meaty smell, and can be used in nuts, milk Fragrant meat and seasoning essence. [0003] There are many synthetic methods in the prior art, mainly at present: the first is to use α-acetyl-γ-butyrolactone as a raw material to obtain 4-methyl-5-(β-hydroxyethyl Base)-thiazole, longer steps, more side reactions, resulting in lower yield, α-acetyl-γ-butyrolactone chlorination is prone to γ-position substitution and difficult to separate. The second is prepared from 3-halo-3-acetylpropanol and thioformamide. The raw material can be obtained by reacting ethyl acetoacetate with ethylene oxide under the action of an oxidant, and then hydrolyzed in an acidic medium and then thiolated with ...

Claims

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Application Information

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IPC IPC(8): C07D277/24
CPCC07D277/24
Inventor 陈清周军学强剑康汤建刚黎信业汤化雪刘天进
Owner KUNSHAN YAXIANG SPICEL CO LTD
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