CN111635375A - Synthetic method of thiazoie - Google Patents
Synthetic method of thiazoie Download PDFInfo
- Publication number
- CN111635375A CN111635375A CN202010640062.4A CN202010640062A CN111635375A CN 111635375 A CN111635375 A CN 111635375A CN 202010640062 A CN202010640062 A CN 202010640062A CN 111635375 A CN111635375 A CN 111635375A
- Authority
- CN
- China
- Prior art keywords
- methyl
- beta
- thiazole
- reaction
- added
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/24—Radicals substituted by oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Abstract
The invention belongs to the field of organic synthesis, and discloses a method for synthesizing thiazoie, which comprises the steps of preparing 4-acetoxyl-2-acetyl-2-chlorobutyric acid methyl ester from methyl acetoacetate and 3-bromo-3-chloropropylacetate under an alkaline condition; a step of hydrolyzing 4-acetoxy-2-acetyl-2-chlorobutyric acid methyl ester under an acidic condition to prepare 3-chloro-3-acetopropanol acetate; a step of preparing 2-mercapto-4-methyl-5- (. beta. -acetoxyethyl) -thiazole from 3-chloro-3-acetylacetonatoacetate and ammonium dithiocarbamate under acidic conditions; adding an oxidant into 2-mercapto-4-methyl-5- (beta-acetoxyethyl) -thiazole under an acidic condition to prepare 4-methyl-5- (beta-acetoxyethyl) -thiazole; a step of preparing 4-methyl-5- (beta-ethoxyl) -thiazole by using 4-methyl-5- (beta-acetoxy ethyl) -thiazole under the alkaline condition. The synthesis method disclosed by the invention is mild in overall reaction conditions, simple in post-treatment and suitable for pilot plant test and industrial production.
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to a synthetic method of thiazothiazole.
Background
Thiazol, which is chemically known as 4-methyl-5- (beta-hydroxyethyl) -thiazole, is a valuable spice, has nut bean flavor, milk flavor, egg fishy smell and meat flavor, and can be used in nuts, milk-flavored meat and flavoring essence.
The prior art has more synthesis methods, which mainly comprise the following steps: firstly, the 4-methyl-5- (beta-hydroxyethyl) -thiazole is obtained by using the alpha-acetyl-gamma-butyrolactone as a raw material through reactions such as chlorination, hydrolysis and carboxyl removal, the steps are longer, side reactions are more, the yield is lower, and the chlorination of the alpha-acetyl-gamma-butyrolactone is easy to generate gamma-position substitution and is difficult to separate. The second is to take 3-halogen-3-acetyl propanol and thioformamide as raw materials, the raw materials can be obtained by the reaction of ethyl acetoacetate and ethylene oxide under the action of oxidant, and the raw materials are hydrolyzed in acid medium and then react with the raw material of thioformamide, the overall reaction process has lower yield and higher cost. Thirdly, 2, 3-dichloro-2-methyl-tetrahydrofuran or a corresponding dibromide compound reacts with thiocarbamide to synthesize the compound, and an acid restraining agent such as organic acid ester is added to facilitate the reaction. Although the method improves the yield, the raw material 2, 3-dichloro-2-methyl-tetrahydrofuran is high in price, and the cost is increased.
Therefore, increasing the overall yield and reducing the cost are important issues for researchers in the synthesis of thiazothiazole.
Disclosure of Invention
The invention aims to provide a method for synthesizing thiazoie, which shortens the reaction process and improves the overall yield.
In order to achieve the purpose, the invention adopts the following technical scheme:
a method for synthesizing thiazoie is characterized by comprising the following reaction processes,
the method comprises the following steps:
a. a step of preparing methyl 4-acetoxy-2-acetyl-2-chlorobutyrate from methyl acetoacetate and 3-bromo-3-chloropropylacetate under alkaline conditions;
a step of hydrolyzing 4-acetoxy-2-acetyl-2-chlorobutyric acid methyl ester under an acidic condition to prepare 3-chloro-3-acetopropanol acetate;
c. a step of preparing 2-mercapto-4-methyl-5- (. beta. -acetoxyethyl) -thiazole from 3-chloro-3-acetylacetonatoacetate and ammonium dithiocarbamate under acidic conditions;
d. adding an oxidant into 2-mercapto-4-methyl-5- (beta-acetoxyethyl) -thiazole under an acidic condition to prepare 4-methyl-5- (beta-acetoxyethyl) -thiazole;
e. a step of preparing 4-methyl-5- (beta-ethoxyl) -thiazole by using 4-methyl-5- (beta-acetoxy ethyl) -thiazole under the alkaline condition.
Further, in the step a, methyl acetoacetate is dissolved in anhydrous tetrahydrofuran or anhydrous ether, 1.1-1.2 molar equivalents of 60% sodium hydrogen or 1-1.2 molar equivalents of n-butyllithium solution are added in batches under the protection of inert gas at-5-10 ℃, after the adding or the dropping is finished, a tetrahydrofuran solution of 3-bromo-3-chloropropylacetate is dropped, the reaction is carried out for 2-4 hours, then the temperature is raised to reflux, and the reaction is continued for 0.5-1 hour.
Further, in the step b, 4-acetoxyl-2-acetyl-2-chlorobutyric acid methyl ester is added into a reaction vessel, 10-30% sulfuric acid is added, and after the reaction is finished, alkali is used for neutralization, and dichloromethane is used for extraction.
Further, in the step c, at normal temperature, 3-chloro-3-acetyl propanol acetate is added into a reaction container, 3-10% of diluted hydrochloric acid is added, then ammonium dithiocarbamate aqueous solution is added, stirring is started, the temperature is increased to 45-60 ℃, reaction is carried out for 3-8 hours, after the reaction is finished, the temperature is cooled to 0-5 ℃, white solid is filtered out, and drying is carried out to obtain the 2-mercapto-4-methyl-5- (beta-acetoxyethyl) -thiazole.
Further, in the step d, at normal temperature, dissolving 2-mercapto-4-methyl-5- (beta-acetoxyethyl) -thiazole in water, adding a certain amount of 36% concentrated hydrochloric acid, heating to 40-60 ℃, dropping hydrogen peroxide, cooling after the detection reaction is finished, adjusting the pH value to be neutral, extracting with dichloromethane, and evaporating to dryness to obtain 4-methyl-5- (beta-acetoxyethyl) -thiazole.
Further, in the step e, at normal temperature, adding 4-methyl-5- (beta-acetoxyethyl) -thiazole into a reaction bottle, adding toluene, adding 5-15% sodium hydroxide solution, and stirring until the reaction is completed to obtain the 4-methyl-5- (beta-hydroxyethyl) -thiazole.
The invention has the beneficial effects that:
1. compared with the prior reaction which takes the alpha-acetyl-gamma-butyrolactone as the raw material, the preparation method of the invention saves one step and saves the reaction time.
2. The invention has the advantages of overall yield of over 50 percent, lower cost and avoidance of more side reactions.
3. The invention has mild overall reaction conditions and simple post-treatment, and is suitable for pilot plant test and industrial production.
Detailed Description
The technical solution of the present invention is further explained by the following embodiments.
Example 1
Dissolving 11.6g (0.1mol) of methyl acetoacetate in 300ml of anhydrous tetrahydrofuran, adding 4.8g (0.12mol) of 60% sodium hydrogen in batches at 0 ℃ under the protection of nitrogen, then dropping 21.5g (0.1mol) of 50ml of tetrahydrofuran solution of 3-bromo-3-chloropropylacetate, continuing the reaction for 2 hours after the addition is finished, and then heating to reflux for 0.5-1 hour. After the reaction is finished through GC-MS detection, the temperature is reduced to 0 ℃, sufficient 5% dilute hydrochloric acid is slowly dropped, the PH is adjusted to be neutral, ether is used for extraction, then ether is evaporated to obtain 24g of crude 4-acetoxy-2-acetyl-2-chlorobutyric acid methyl ester, the content of the crude 4-acetoxy-2-acetyl-2-chlorobutyric acid methyl ester detected through GC-MS is 95%, 4-acetoxy-2-acetyl-2-bromobutyric acid methyl ester is additionally contained, the content of disubstituted impurities is less than 1%, the content of halogen-free impurities is less than 1%, further purification is not needed, and the crude 4-acetoxy-2-acetyl-2-chlorobutyric acid methyl ester is directly put into the next reaction.
24g of the crude product of 4-acetoxyl-2-acetyl-2-chlorobutyric acid methyl ester prepared in the previous step is added into a 500ml reaction bottle, 20 percent sulfuric acid is added, reflux is carried out, after the reaction is finished, sodium carbonate is used for neutralization, dichloromethane is used for extraction, reduced pressure distillation is carried out to obtain 18g of crude product of 3-chloro-3-acetyl propanol acetic ester, and the crude product is put into the next step without purification.
At normal temperature, 18g of 3-chloro-3-acetyl propanol acetate and 200ml of water are added into a 500ml reaction bottle, 20 drops of 10% diluted hydrochloric acid are dropped by a dropper, then 11g of 50ml of ammonium dithiocarbamate aqueous solution is dropped, stirring is started, the temperature is raised to 55 ℃ for reaction for 3 hours, after the reaction is finished, the reaction is cooled to 0 ℃, white solid is filtered out, and 20g of 98.8% pure 2-mercapto-4-methyl-5- (beta-acetoxyethyl) -thiazole is obtained after drying.
At normal temperature, 20g of 2-mercapto-4-methyl-5- (beta-acetoxyethyl) -thiazole is dissolved in water, 20ml of 36% concentrated hydrochloric acid is added, then the temperature is raised to 48 ℃, 30ml of 35% hydrogen peroxide is dropped, after the detection reaction is finished, the solution is cooled, the PH is adjusted to be neutral, dichloromethane is used for extraction, and reduced pressure evaporation is carried out to dryness, so as to obtain 16g of 4-methyl-5- (beta-acetoxyethyl) -thiazole with the content of 96.8%.
At normal temperature, 16g of 4-methyl-5- (beta-acetoxyethyl) -thiazole is put into a 250ml reaction bottle, added with toluene for dissolution, added with 100ml of 10 percent sodium hydroxide solution, stirred until the reaction is finished, adjusted to slightly acidic pH, extracted by dichloromethane, decompressed and distilled to obtain 13g of crude 4-methyl-5- (beta-hydroxyethyl) -thiazole, and rectified and purified to obtain 11g of 100 percent pure product.
Example 2
200g (1.72mol) of methyl acetoacetate are dissolved in 1.5L of anhydrous tetrahydrofuran, 72g (1.80mol) of 60 percent sodium hydrogen is added in batches at the temperature of minus 5 ℃ under the protection of nitrogen, 369.8g (1.72mol) of 3-bromo-3-chloropropylacetate is then added dropwise, the reaction is continued for 2 hours after the addition is finished, and then the temperature is raised to reflux reaction for 1 hour. After the reaction is finished through GC-MS detection, the temperature is reduced to 0 ℃, sufficient 5% dilute hydrochloric acid is slowly dropped, the PH is adjusted to be neutral, ether is used for extraction, then ether is evaporated to obtain 240g of crude 4-acetoxy-2-acetyl-2-chlorobutyric acid methyl ester, 408g of crude 4-acetoxy-2-acetyl-2-chlorobutyric acid methyl ester with the content of 96% is obtained through GC-MS detection, further purification is not needed, and the mixture is directly put into the next reaction.
408g of the crude product of the 4-acetoxyl-2-acetyl-2-chlorobutyric acid methyl ester prepared in the previous step is added into a 2L reaction bottle, 1.2L of 10% sulfuric acid is added for reflux, after the reaction is finished, 10% sodium hydroxide solution is used for neutralizing until the pH value is 7, dichloromethane is used for extraction, reduced pressure distillation is carried out, and purification is carried out, so that 295g of 3-chloro-3-acetyl propanol acetate with the content of 99.8% is obtained.
At normal temperature, 295g of 3-chloro-3-acetyl propanol acetate and 800ml of water are added into a 2L reaction bottle, 100ml of 10% diluted hydrochloric acid is dripped into a dropper, then 181.7g of 200ml of ammonium dithiocarbamate aqueous solution is dripped into the reaction bottle, stirring is started, the reaction bottle is heated to 50 ℃ for reaction for 8 hours, after the reaction is finished, the reaction bottle is put into ice brine, the mixture is cooled to 0 ℃, white solid is filtered out, and 350g of 99% pure 2-mercapto-4-methyl-5- (beta-acetoxyethyl) -thiazole is obtained after drying.
At normal temperature, 350g of 2-mercapto-4-methyl-5- (beta-acetoxyethyl) -thiazole is dissolved in water, 200ml of 36% concentrated hydrochloric acid is added, then the temperature is raised to 45 ℃, 165ml of 35% hydrogen peroxide is dropped, after the detection reaction is finished, the solution is cooled, the PH is adjusted to be neutral, dichloromethane is used for extraction, anhydrous sodium sulfate is used for drying, and reduced pressure evaporation is carried out to dryness, thus obtaining 278g of 4-methyl-5- (beta-acetoxyethyl) -thiazole with the content of 98%.
At normal temperature, 278g of 4-methyl-5- (beta-acetoxyethyl) -thiazole is put into a 2L reaction bottle, 600ml of toluene is added for dissolution, 500ml of 15 percent sodium hydroxide solution is added, the mixture is stirred until the reaction is completed, the pH value is adjusted to be slightly acidic, the mixture is extracted by dichloromethane, reduced pressure distillation is carried out to obtain 214 g of crude product of the 4-methyl-5- (beta-hydroxyethyl) -thiazole, and the crude product is rectified and purified to obtain 210 g of pure product with the content of 100 percent.
Example 3
Putting 5kg of methyl acetoacetate into a 50L reaction kettle, adding 20L of anhydrous tetrahydrofuran for dissolving, adding 1.81kg of 60% sodium hydrogen in batches at-10 to-5 ℃ under the protection of nitrogen, then dripping 8.62kg of 3-bromo-3-chloropropylacetate, continuing to react for 8 hours after the addition is finished, and then heating to room temperature for reacting for 2 hours. After the reaction is finished through GC-MS detection, the temperature is reduced to-5 ℃, sufficient 10% diluted hydrochloric acid is slowly dropped, the PH is adjusted to be neutral, ether is used for extraction, then ether is evaporated to obtain 9.98kg of crude 4-acetoxy-2-acetyl-2-chlorobutyric acid methyl ester, the content of the crude 4-acetoxy-2-acetyl-2-chlorobutyric acid methyl ester is 97% through GC-MS detection, and the crude 4-acetoxy-2-acetyl-2-chlorobutyric acid methyl ester is directly put into the next reaction without purification.
9.98kg of the crude product of 4-acetoxyl-2-acetyl-2-chlorobutyric acid methyl ester prepared in the above way is added into a 100L reaction kettle, 50L of 20% sulfuric acid is added for reflux, after the reaction is finished, sodium hydroxide is used for neutralization until the PH value is 7, dichloromethane is used for extraction, and the crude product of 7.4kg of 3-chloro-3-acetyl propanol acetate with the content of 98% is obtained by reduced pressure distillation and is put into the next step without purification.
At normal temperature, 7.4kg of 3-chloro-3-acetyl propanol acetate and 50L of water are added into a 100L reaction bottle, 2L of 10% diluted hydrochloric acid is added, then 4.557kg of ammonium dithiocarbamate aqueous solution is dripped in, stirring is started, the temperature is increased to 50 ℃ for reaction for 2 hours, after the reaction is finished, the reaction is cooled to 0 ℃, white solid is filtered out, and 8.110kg of 99% pure 2-mercapto-4-methyl-5- (beta-acetoxyethyl) -thiazole is obtained after drying.
At normal temperature, 8.11Kg of 2-mercapto-4-methyl-5- (beta-acetoxyethyl) -thiazole is put into a 100L reaction kettle, 30L and 5L of 36 percent concentrated hydrochloric acid are added, 36L of 35 percent hydrogen peroxide is sucked in by a vacuum pump in five batches, the temperature is raised to 50 ℃, after the reaction is detected, the reaction is cooled, sodium hydroxide is added to adjust the pH to be neutral, sufficient sodium sulfite is added to remove the excessive hydrogen peroxide, dichloromethane is used for extraction, and the pressure is reduced and the evaporation is carried out to obtain 5.948Kg of 4-methyl-5- (beta-acetoxyethyl) -thiazole with the content of 99 percent.
At normal temperature, 5.948kg of 4-methyl-5- (beta-acetoxyethyl) -thiazole is put into a 100L reaction kettle, 50L of toluene is added for dissolution, 1.54kg of sodium hydroxide and 10L of water are added, the mixture is stirred until the reaction is finished, the pH value is adjusted to be slightly acidic, dichloromethane is used for extraction, reduced pressure distillation is carried out to obtain a crude product of the 4-methyl-5- (beta-hydroxyethyl) -thiazole, and the crude product is rectified and purified to obtain 4.3kg of 100 percent pure product.
The technical principle of the present invention is described above in connection with specific embodiments. The description is made for the purpose of illustrating the principles of the invention and should not be construed in any way as limiting the scope of the invention. Based on the explanations herein, those skilled in the art will be able to conceive of other embodiments of the present invention without inventive effort, which would fall within the scope of the present invention.
Claims (6)
1. A method for synthesizing thiazoie is characterized by comprising the following reaction processes,
the method comprises the following steps:
a step of preparing methyl 4-acetoxy-2-acetyl-2-chlorobutyrate from methyl acetoacetate and 3-bromo-3-chloropropylacetate under alkaline conditions;
a step of hydrolyzing 4-acetoxy-2-acetyl-2-chlorobutyric acid methyl ester under an acidic condition to prepare 3-chloro-3-acetopropanol acetate;
a step of preparing 2-mercapto-4-methyl-5- (. beta. -acetoxyethyl) -thiazole from 3-chloro-3-acetylacetonatoacetate and ammonium dithiocarbamate under acidic conditions;
adding an oxidant into 2-mercapto-4-methyl-5- (beta-acetoxyethyl) -thiazole under an acidic condition to prepare 4-methyl-5- (beta-acetoxyethyl) -thiazole;
a step of preparing 4-methyl-5- (beta-ethoxyl) -thiazole by using 4-methyl-5- (beta-acetoxy ethyl) -thiazole under the alkaline condition.
2. The method according to claim 1, wherein in step a, the methyl acetoacetate is dissolved in anhydrous tetrahydrofuran or anhydrous ether, 1.1-1.2 molar equivalents of 60% sodium hydrogen or 1-1.2 molar equivalents of n-butyllithium solution are added in batches under the protection of inert gas at-5-10 ℃, after the addition or the addition of n-butyllithium solution is completed, a tetrahydrofuran solution of 3-bromo-3-chloropropylacetate is added dropwise, the reaction is carried out for 2-4 hours, and then the reaction is continued for 0.5-1 hour after the temperature is raised to reflux.
3. The method for synthesizing thiazothiazole, according to claim 2, wherein in the step b, 4-acetoxyl-2-acetyl-2-chlorobutyric acid methyl ester is added into a reaction vessel, 10-30% sulfuric acid is added, after the reaction is finished, alkali is used for neutralization, and dichloromethane is used for extraction.
4. The method for synthesizing thiazothiazole, according to claim 3, characterized in that in the step c, 3-chloro-3-acetyl propanol acetate is added into a reaction vessel at normal temperature, 3-10% diluted hydrochloric acid is added, then ammonium dithiocarbamate aqueous solution is added, stirring is started, the temperature is raised to 45-60 ℃ for reaction for 3-8 hours, after the reaction is finished, the reaction is cooled to 0-5 ℃, white solid is filtered out, and the 2-mercapto-4-methyl-5- (beta-acetoxyethyl) -thiazole is obtained by drying.
5. The method for synthesizing thiazothiazole, according to claim 4, wherein in the step d, 2-mercapto-4-methyl-5- (beta-acetoxyethyl) -thiazole is dissolved in water at normal temperature, a certain amount of 36% concentrated hydrochloric acid is added, then the temperature is raised to 40-60 ℃, hydrogen peroxide is added dropwise, after the detection reaction is finished, cooling is carried out, the pH is adjusted to be neutral, dichloromethane is used for extraction, and evaporation to dryness is carried out, thus obtaining 4-methyl-5- (beta-acetoxyethyl) -thiazole.
6. The method for synthesizing thiazothiazole, according to claim 5, wherein in the step e, 4-methyl-5- (beta-acetoxyethyl) -thiazole is put into a reaction flask at normal temperature, toluene is added, 5-15% sodium hydroxide solution is added, and the mixture is stirred until the reaction is completed, so that 4-methyl-5- (beta-hydroxyethyl) -thiazole is obtained.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010640062.4A CN111635375B (en) | 2020-07-06 | 2020-07-06 | Method for synthesizing thiothiazole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010640062.4A CN111635375B (en) | 2020-07-06 | 2020-07-06 | Method for synthesizing thiothiazole |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111635375A true CN111635375A (en) | 2020-09-08 |
| CN111635375B CN111635375B (en) | 2024-06-04 |
Family
ID=72326243
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010640062.4A Active CN111635375B (en) | 2020-07-06 | 2020-07-06 | Method for synthesizing thiothiazole |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111635375B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112979461A (en) * | 2021-02-26 | 2021-06-18 | 复旦大学 | Full continuous flow preparation method of 3-chloro-4-oxoacetic acid amyl ester |
| CN113105410A (en) * | 2021-03-12 | 2021-07-13 | 山东吉田香料股份有限公司 | Preparation method of 4-methyl-5- (2-acetoxyethyl) thiazole |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB456751A (en) * | 1935-05-13 | 1936-11-13 | Ig Farbenindustrie Ag | Process for the manufacture of 4-alkyl-5-hydroxy-alkylthiazoles |
| WO2005095344A1 (en) * | 2004-03-24 | 2005-10-13 | Array Biopharma Inc. | Thioalkeneamides as transketolase inhibitors |
| CN103772313A (en) * | 2014-01-02 | 2014-05-07 | 郑桂富 | Method for synthesizing 4-methyl-5-(2- ethoxy) thiazole |
-
2020
- 2020-07-06 CN CN202010640062.4A patent/CN111635375B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB456751A (en) * | 1935-05-13 | 1936-11-13 | Ig Farbenindustrie Ag | Process for the manufacture of 4-alkyl-5-hydroxy-alkylthiazoles |
| WO2005095344A1 (en) * | 2004-03-24 | 2005-10-13 | Array Biopharma Inc. | Thioalkeneamides as transketolase inhibitors |
| US20070293501A1 (en) * | 2004-03-24 | 2007-12-20 | Array Biopharma Inc. | Thioalkeneamides as Transketolase Inhibitors |
| CN103772313A (en) * | 2014-01-02 | 2014-05-07 | 郑桂富 | Method for synthesizing 4-methyl-5-(2- ethoxy) thiazole |
Non-Patent Citations (3)
| Title |
|---|
| 张小林;李海峰;欧阳红霞;朱礼良;: "4-甲基-5-(2-羟乙基)噻唑的合成新工艺", 南昌大学学报(理科版), vol. 35, no. 03, 25 June 2011 (2011-06-25), pages 256 - 257 * |
| 张广军;孙斌;郭鸽;李新;王立志;陈祥;卫洁;: "4-甲基-5-(β-羟乙基)噻唑合成工艺的研究进展", 山东化工, vol. 42, no. 11, 15 November 2013 (2013-11-15), pages 62 - 63 * |
| 舒宏福;卫洁;臧传近;张华;: "4-甲基-5-羟乙基噻唑的合成与香气特征及杂质分析", 香料香精化妆品, no. 06, 31 December 2019 (2019-12-31), pages 71 - 76 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112979461A (en) * | 2021-02-26 | 2021-06-18 | 复旦大学 | Full continuous flow preparation method of 3-chloro-4-oxoacetic acid amyl ester |
| CN112979461B (en) * | 2021-02-26 | 2022-03-18 | 复旦大学 | A kind of fully continuous flow preparation method of 3-chloro-4-oxoacetate amyl |
| US11618727B2 (en) | 2021-02-26 | 2023-04-04 | Fudan University | Method for preparing 3-chloro-4-oxopentyl acetate using fully continuous-flow micro-reaction system |
| CN113105410A (en) * | 2021-03-12 | 2021-07-13 | 山东吉田香料股份有限公司 | Preparation method of 4-methyl-5- (2-acetoxyethyl) thiazole |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111635375B (en) | 2024-06-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111635375A (en) | Synthetic method of thiazoie | |
| AU2011317371A1 (en) | Process for producing a lactic acid-amine complex | |
| CN109553550B (en) | Method for synthesizing dihydrooat alkaloid | |
| CN112479938B (en) | Preparation method of N-cyclohexyl-2-aminoethanesulfonic acid | |
| CN113173844B (en) | Preparation method of 2-methyl-4-chlorophenoxyacetic acid | |
| CN111153821A (en) | Preparation method of D-p-hydroxyphenylglycine methyl ester | |
| CN112608243A (en) | Synthesis method of trans-3-aminobutanol | |
| CN112295608A (en) | Recycling method for regenerating ferric trichloride for aromatizing triazole compounds | |
| CN1035814C (en) | Process for production of dichloroacetic acid | |
| CN108752217B (en) | Synthesis method of dolutegravir key intermediate 2, 4-difluorobenzylamine | |
| CN115784875A (en) | Preparation process of bis (2-acetoxybenzoic acid) calcium urea | |
| CN112479853B (en) | Preparation method of D-2-chloropropionyl chloride and D-2-chloropropionyl chloride | |
| CN115819382A (en) | Method for synthesizing 2, 5-dimethyl-4-hydroxy-3 (2H) -furanone perfume by one-pot method | |
| CN113861136A (en) | Vitamin B5Recovery method of production residual liquid | |
| CN111187146A (en) | Method for producing 2-methyl-3-buten-2-ol | |
| CN115215802A (en) | Method for purifying vitamin H intermediate cyclic acid | |
| CN108947831A (en) | A kind of purification process of salbutamol intermediate III | |
| CN118702571A (en) | A resource disposal method for 2-methyl-4-chlorophenoxyacetic acid wastewater | |
| CN110938020A (en) | Preparation process of lauroyl arginine ethyl ester hydrochloride | |
| CN114044783B (en) | Preparation method of idosiban and intermediate thereof | |
| CN115181033B (en) | Catalytic synthesis method of propanil | |
| CN114478271B (en) | Preparation method of desmethylvenlafaxine succinate | |
| CN109776448B (en) | Preparation method of febuxostat crystal form A | |
| CN109796395B (en) | Preparation method of N, N-dimethylpiperidine chloride salt | |
| CN101914008A (en) | Catalyst recovery method in the process of preparing dichloropropanol by glycerin method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |