Synthesis method of 4-methyl-5-thiazoleethanol
By using a micro-nano bubble generator to react ethyl acetate-dissolved 2-mercapto-4-methyl-5-thiazolethanol with hydrogen peroxide at low temperature in the presence of a catalyst, followed by extraction and distillation, the problems of low yield and high temperature in existing technologies have been solved, achieving high yield and high purity of 4-methyl-5-thiazolethanol production.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- NINGXIA CHANGSHENG PHARMACEUTICAL CO LTD
- Filing Date
- 2024-10-31
- Publication Date
- 2026-05-01
AI Technical Summary
In existing methods for synthesizing 4-methyl-5-thiazolidineethanol, the yield using hydrogen peroxide oxidation is low and the production conditions are quite harsh. There is a need to develop a production method that can improve the yield and reduce the temperature.
A micro-nano bubble machine was used to react 2-mercapto-4-methyl-5-thiazolylethanol with hydrogen peroxide in the presence of a catalyst by dissolving it in ethyl acetate, controlling the temperature at 10-15℃, and then performing extraction and distillation.
It significantly improved the yield and purity of 4-methyl-5-thiazolethanol, reduced the production temperature requirements, and achieved milder production conditions.
Abstract
Description
A method for synthesizing 4-methyl-5-thiazolylethanol Technical Field
[0001] This invention belongs to the field of chemical synthesis technology, specifically relating to a method for synthesizing 4-methyl-5-thiazolylethanol. Background Technology
[0002] 4-Methyl-5-thiazolylethanol, also known as 4-methyl-5-(2-hydroxyethyl)thiazolyl, is a meat flavoring agent, mainly used for flavoring food, meat, condiments, and seafood. It is also an important intermediate in the synthesis of 4-methyl-5-(2-hydroxyethyl)thiazolyl acetate, vitamin B1, and pharmaceuticals. This review summarizes the synthetic methods for this flavoring product. There are two main synthetic routes: the first is the direct reaction of 3-chloro-5-hydroxy-2-pentanone and thioformamide. However, due to the difficulty in preparing and the instability of thioformamide, this method faces certain challenges for industrialization. The second route involves the reaction of 3-chloro-5-hydroxy-2-pentanone (chloroketone) and ammonium dithiocarbamate (ammonium salt) to generate 2-mercapto-4-methyl-5-thiazolylethanol, which is then oxidized with dilute nitric acid or hydrogen peroxide.
[0003] The second synthesis method uses hydrogen peroxide, which is more environmentally friendly. However, the current oxidation method using hydrogen peroxide has a low product yield and requires temperatures above 40°C. Therefore, there is an urgent need for a production method that can increase the yield, lower the temperature, and provide gentler production conditions. Summary of the Invention
[0004] To address the aforementioned technical problems, this invention provides a method for synthesizing 4-methyl-5-thiazolylethanol with high production yield and mild production conditions.
[0005] In order to solve the above technical problems, the technical solution adopted by the present invention is as follows: a method for synthesizing 4-methyl-5-thiazolethanol, the method comprising the following steps: (1) mixing water, ethyl acetate and 2-mercapto-4-methyl-5-thiazolethanol in a reactor, setting the temperature to 10-15°C, adding a catalyst, and purging by a micro-nano bubble machine at the bottom of the reactor; (2) after purging, adding hydrogen peroxide, reacting, allowing to stand and separate into layers, taking the water layer, extracting the water layer at 20-30°C with dichloromethane, concentrating, and distilling to obtain 4-methyl-5-thiazolethanol.
[0006] Preferably, in step (1), the volume ratio of water to ethyl acetate is 4:1, and the solid-liquid ratio of 2-mercapto-4-methyl-5-thiazolylethanol to water is 1 to 3:8.
[0007] Preferably, in step (1), the mass ratio of 2-mercapto-4-methyl-5-thiazolylethanol to catalyst is 20:1.
[0008] Preferably, the catalyst is a Pd / SiO2-NH2 catalyst with a loading of 1.0%.
[0009] Preferably, the flow rate of the micro / nano bubble machine is 10 mL / min.
[0010] Preferably, the hydrogen peroxide is 28% by mass, and the mass ratio of hydrogen peroxide to 2-mercapto-4-methyl-5-thiazolylethanol is 1.4–1.6:1. Beneficial effects
[0011] This invention uses 2-mercapto-4-methyl-5-thiazolylethanol as a base material to effectively dissolve ethyl acetate. By utilizing the action of a catalyst in a microbubble system, the reaction time is shortened, the oxidation effect is greatly improved, and the yield and quality of the product are enhanced. Detailed Implementation
[0012] Unless otherwise specified, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. In case of any discrepancy, the definitions in this specification shall prevail.
[0013] Unless otherwise stated, all percentages, portions, proportions, etc. are by weight.
[0014] The terms “comprising,” “including,” “having,” “containing,” “or any other variation thereof” as used herein are intended to cover a non-exclusive inclusion. For example, a composition, process, method, article, or apparatus that comprises a list of elements is not necessarily limited to those elements, but may also include elements not expressly listed or other elements inherent to such composition, process, method, article, or apparatus.
[0015] When quantities, parts by weight, or other numerical values or parameters are given as ranges, preferred ranges, or a series of upper and lower preferred values, it should be understood that they specifically disclose all ranges formed by any pair of values of any larger or preferred range limit and any smaller or preferred range limit, regardless of whether the ranges are disclosed separately. For example, when describing a range of "1 to 5", the described range should be understood to include ranges such as "1 to 4", "1 to 3", "1 to 2", "1 to 2 and 4 to 5", "1 to 3 and 5", etc. Unless otherwise stated, where numerical ranges are described herein, the range is intended to include the range endpoints as well as all integers, fractions, decimals, etc., within that range.
[0016] Furthermore, the indefinite articles “a” and “an” preceding the elements or components of this disclosure are intended to indicate that there is no limitation on the number of times the said element or component appears (i.e., occurs). Therefore, “a” or “an” should be understood to include one or at least one, and unless the quantity is explicitly stated to be singular, the singular form of the said element or component also includes the plural case.
[0017] Unless otherwise specified, the materials, methods, and examples described herein are exemplary and not limiting. While similar or equivalent methods and materials may be used in implementing or testing this disclosure, suitable methods and materials are also described herein.
[0018] This disclosure is described in detail below.
[0019] Yield calculation formula: (Product mass: Product molecular weight) / (Raw material mass: Raw material molecular weight). Example 1
[0020] A method for synthesizing 4-methyl-5-thiazolylethanol, comprising the following steps: (1) mixing 40 mL of water, 10 mL of ethyl acetate, and 5 g of 2-mercapto-4-methyl-5-thiazolylethanol in a reactor, setting the temperature to 10 °C, adding 0.25 g of Pd / SiO2-NH2 catalyst with a loading of 1.0%, and bubbling the mixture for 10 min at a flow rate of 10 mL / min using a micro-nano bubble machine at the bottom of the reactor; (2) after bubbling, adding 7 g of 28% hydrogen peroxide, reacting for 1.2 h, allowing the mixture to stand and separate into layers, taking the aqueous layer, extracting the aqueous layer at 25 °C with dichloromethane, concentrating, and distilling to obtain 3.6 g of 4-methyl-5-thiazolylethanol, with a yield of 88.1% and a purity of 98.9%. Example 2
[0021] A method for synthesizing 4-methyl-5-thiazolylethanol, comprising the following steps: (1) mixing 40 mL of water, 10 mL of ethyl acetate, and 8 g of 2-mercapto-4-methyl-5-thiazolylethanol in a reactor, setting the temperature to 10 °C, adding 0.25 g of Pd / SiO2-NH2 catalyst with a loading of 1.0%, and bubbling the mixture for 10 min at a flow rate of 10 mL / min using a micro-nano bubble machine at the bottom of the reactor; (2) after bubbling, adding 11.2 g of hydrogen peroxide with a mass fraction of 28%, reacting for 1.2 h, allowing the mixture to stand and separate into layers, taking the aqueous layer, extracting the aqueous layer at 25 °C with dichloromethane, concentrating, and distilling to obtain 6 g of 4-methyl-5-thiazolylethanol, with a yield of 91.8% and a purity of 99.3%. Example 3
[0022] A method for synthesizing 4-methyl-5-thiazolylethanol, comprising the following steps: (1) mixing 40 mL of water, 10 mL of ethyl acetate, and 11 g of 2-mercapto-4-methyl-5-thiazolylethanol in a reactor, setting the temperature to 10 °C, adding 0.25 g of Pd / SiO2-NH2 catalyst with a loading of 1.0%, and bubbling the mixture for 10 min at a flow rate of 10 mL / min using a micro-nano bubble machine at the bottom of the reactor; (2) after bubbling, adding 15.4 g of hydrogen peroxide with a mass fraction of 28%, reacting for 1.2 h, allowing the mixture to stand and separate into layers, taking the aqueous layer, extracting the aqueous layer at 25 °C with dichloromethane, concentrating, and distilling to obtain 8.3 g of 4-methyl-5-thiazolylethanol, with a yield of 92.3% and a purity of 99.7%. Example 4
[0023] A method for synthesizing 4-methyl-5-thiazolylethanol, comprising the following steps: (1) mixing 40 mL of water, 10 mL of ethyl acetate, and 15 g of 2-mercapto-4-methyl-5-thiazolylethanol in a reactor, setting the temperature to 10 °C, adding 0.25 g of Pd / SiO2-NH2 catalyst with a loading of 1.0%, and bubbling the mixture for 10 min at a flow rate of 10 mL / min using a micro-nano bubble machine at the bottom of the reactor; (2) after bubbling, adding 21 g of hydrogen peroxide with a mass fraction of 28%, reacting for 1.2 h, allowing the mixture to stand and separate into layers, taking the aqueous layer, extracting the aqueous layer at 25 °C with dichloromethane, concentrating, and distilling to obtain 11.1 g of 4-methyl-5-thiazolylethanol, with a yield of 90.6% and a purity of 99.5%. Example 5
[0024] A method for synthesizing 4-methyl-5-thiazolylethanol, comprising the following steps: (1) mixing 40 mL of water, 10 mL of ethyl acetate, and 11 g of 2-mercapto-4-methyl-5-thiazolylethanol in a reactor, setting the temperature to 10 °C, adding 0.25 g of Pd / SiO2-NH2 catalyst with a loading of 1.0%, and bubbling the mixture for 10 min at a flow rate of 10 mL / min using a micro-nano bubble machine at the bottom of the reactor; (2) after bubbling, adding 16.5 g of hydrogen peroxide with a mass fraction of 28%, reacting for 1.2 h, allowing the mixture to stand and separate into layers, taking the aqueous layer, extracting the aqueous layer at 25 °C with dichloromethane, concentrating, and distilling to obtain 8.6 g of 4-methyl-5-thiazolylethanol, with a yield of 95.7% and a purity of 99.4%. Example 6
[0025] A method for synthesizing 4-methyl-5-thiazolethanol, comprising the following steps: (1) mixing 40 mL of water, 10 mL of ethyl acetate, and 11 g of 2-mercapto-4-methyl-5-thiazolethanol in a reactor, setting the temperature to 10 °C, adding 0.25 g of Pd / SiO2-NH2 catalyst with a loading of 1.0%, and bubbling the mixture for 10 min at a flow rate of 10 mL / min using a micro-nano bubble machine at the bottom of the reactor; (2) after bubbling, adding 17.6 g of hydrogen peroxide with a mass fraction of 28%, reacting for 1.2 h, allowing the mixture to stand and separate into layers, taking the water layer, extracting the water layer at 25 °C with dichloromethane, concentrating, and distilling to obtain 8.2 g of 4-methyl-5-thiazolethanol, with a yield of 9.2% and a purity of 99.1%.
[0026] Comparative Example 1: A method for synthesizing 4-methyl-5-thiazolethanol, comprising the following steps: (1) 40 mL of water, 10 mL of ethyl acetate, and 11 g of 2-mercapto-4-methyl-5-thiazolethanol are mixed evenly in a reactor, the temperature is set at 10 °C, and aeration is carried out for 10 min by a micro-nano bubble machine at the bottom of the reactor at a flow rate of 10 mL / min; (2) After the aeration is completed, 15.4 g of hydrogen peroxide with a mass fraction of 28% is added, the reaction is carried out for 1.2 h, the mixture is allowed to stand and separate into layers, the water layer is taken, and the water layer is extracted with dichloromethane at 25 °C, concentrated, and distilled to obtain 7.4 g of 4-methyl-5-thiazolethanol, with a yield of 82.3% and a purity of 99.1%.
[0027] Comparative Example 2: A method for synthesizing 4-methyl-5-thiazolethanol, comprising the following steps: (1) 40 mL of water, 10 mL of ethyl acetate, and 11 g of 2-mercapto-4-methyl-5-thiazolethanol are mixed evenly in a reactor, the temperature is set to 10 °C, and 0.25 g of Pd / SiO2-NH2 catalyst with a loading of 1.0% is added and mixed evenly; (2) 15.4 g of hydrogen peroxide with a mass fraction of 28% is added, the reaction is carried out for 1.2 h, the mixture is allowed to stand and separate into layers, the aqueous layer is taken, and the aqueous layer is extracted with dichloromethane at 25 °C, concentrated, and distilled to obtain 7.6 g of 4-methyl-5-thiazolethanol, with a yield of 84.6% and a purity of 98.9%.
[0028] Comparative Example 3: A method for synthesizing 4-methyl-5-thiazolethanol, comprising the following steps: (1) mixing 40 mL of water, 10 mL of ethyl acetate, and 11 g of 2-mercapto-4-methyl-5-thiazolethanol in a reactor and setting the temperature to 10 °C; (2) adding 15.4 g of hydrogen peroxide with a mass fraction of 28%, reacting for 1.2 h, allowing the mixture to stand and separate into layers, taking the aqueous layer, extracting the aqueous layer at 25 °C with dichloromethane, concentrating, and distilling to obtain 6.5 g of 4-methyl-5-thiazolethanol, with a yield of 72.3% and a purity of 99.0%.
[0029] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.
Claims
1. A method for synthesizing 4-methyl-5-thiazolylethanol, characterized in that, The synthesis method includes the following steps: (1) Water, ethyl acetate and 2-mercapto-4-methyl-5-thiazolethanol are mixed evenly in a reactor, the temperature is set to 10-15℃, a catalyst is added, and gas is blown by a micro-nano bubble machine at the bottom of the reactor; (2) After the gas blowing is completed, hydrogen peroxide is added, the reaction is carried out, the layers are allowed to stand and separate, the water layer is taken, the water layer is extracted with dichloromethane at 20-30℃, concentrated, and distilled to obtain 4-methyl-5-thiazolethanol.
2. The method for synthesizing 4-methyl-5-thiazolylethanol according to claim 1, characterized in that, In step (1), the volume ratio of water to ethyl acetate is 4:1, and the solid-liquid ratio of 2-mercapto-4-methyl-5-thiazolylethanol to water is 1 to 3:
8.
3. The method for synthesizing 4-methyl-5-thiazolylethanol according to claim 2, characterized in that, In step (1), the mass ratio of 2-mercapto-4-methyl-5-thiazolylethanol to the catalyst is 20:
1.
4. The method for synthesizing 4-methyl-5-thiazolylethanol according to claim 3, characterized in that, The catalyst is a Pd / SiO2-NH2 catalyst with a loading of 1.0%.
5. The method for synthesizing 4-methyl-5-thiazolylethanol according to claim 4, characterized in that, The flow rate of the micro-nano bubble machine is 10 mL / min.
6. The method for synthesizing 4-methyl-5-thiazolylethanol according to claim 1, characterized in that, The hydrogen peroxide is 28% by mass, and the mass ratio of hydrogen peroxide to 2-mercapto-4-methyl-5-thiazolylethanol is 1.4 to 1.6:1.