CN111825553A

CN111825553A - Preparation method of methyl acetoacetate

Info

Publication number: CN111825553A
Application number: CN201910308703.3A
Authority: CN
Inventors: 陈安源; 马在河; 王蒙; 夏洪坤; 张晓军; 盛东杨
Original assignee: Qingdao Haiwan Group Co ltd; Qingdao Haiwan Specialty Chemicals Co ltd
Current assignee: Qingdao Haiwan Group Co ltd; Qingdao Haiwan Specialty Chemicals Co ltd
Priority date: 2019-04-17
Filing date: 2019-04-17
Publication date: 2020-10-27

Abstract

The invention belongs to the technical field of production of chemical raw materials, and particularly relates to a preparation method of methyl acetoacetate. The preparation method comprises the following steps: 1) fully mixing methanol and a catalyst to obtain a methanol solution containing the catalyst; 2) respectively and simultaneously conveying the methanol solution containing the catalyst and the crude diketene obtained in the step 1) into a microreactor through an infusion pump for esterification reaction to obtain crude methyl acetoacetate; 3) inputting the crude methyl acetoacetate obtained in the step 2) into a methyl acetoacetate rectifying tower through a pipeline, and rectifying to obtain methyl acetoacetate. The method overcomes the defects of the prior art, has less side reaction in the reaction process, high product purity, high yield, safety, reliability and less equipment investment, and realizes the continuous production esterification reaction process.

Description

Preparation method of methyl acetoacetate

Technical Field

The invention belongs to the technical field of production of chemical raw materials, and particularly relates to a preparation method of methyl acetoacetate.

Background

Methyl acetoacetate is an important organic synthesis intermediate, the application of the methyl acetoacetate is wide, most of derivatives of the methyl acetoacetate are varieties with larger tonnage, and currently, pesticide intermediates and medical intermediates are intensively developed to meet the market demand.

The methyl acetoacetate is widely used, and in the pesticide industry, the methyl acetoacetate is mainly used for synthesizing pesticides diazinon and propyzamide, herbicides pyrazolate, pyroxene and pyraclonil, bactericide hymexazol and the like in the pesticide industry. The chemical auxiliary agent, methyl acetoacetate can be used as a solvent for synthesizing antimalarial drugs, essence and paint besides being used as a cellulose ester solvent; in addition, the aluminum alkoxide and the chelating agent are synthesized as a solvent and are used for modifying resin, thickening printing ink, improving adhesive force and the like; can also be used as a polymerization catalyst for preparing metal coordination compounds with aluminum, chromium and the like; in the pharmaceutical industry, methyl acetoacetate is mainly used for synthesizing important intermediates of cephalosporin antibiotics, namely p-hydroxy glycine dane salt, and can also be used for synthesizing vasodilator dipyridamole, antiepileptic intermediate valproic acid, calcium antagonist and the like, namely 3-amino methyl crotonate; the most potential application field of vitamin and methyl acetoacetate is used for synthesizing series of vitamins, and the most used raw materials at present are linalool and isophytol for synthesizing vitamin E; methyl acetoacetate can synthesize beta-ionone, which is an important raw material for preparing vitamin A and carotene; the methyl acetoacetate can also be used for synthesizing orotic acid, also called vitamin B₁₃The orotic acid is used as a medicine for treating liver diseases, can participate in the synthesis of nucleic acid, and has development potential as a health-care product and the like; the methyl acetoacetate can synthesize vitamin B₁The raw material alpha acetyl-gamma-butyrolactone; organic synthesis, and fine chemical engineering of synthesizing several Chinese medicines with methyl acetoacetateIntermediates, most notably acetylacetone and 2, 6-methylpyridine; in the dye industry, methyl acetoacetate serving as a raw material can synthesize various novel important aniline series dye intermediates and pyrazolone intermediates, and the products are novel dye and pigment intermediates with development prospects.

The traditional method for producing methyl acetoacetate in China is a kettle type batch method, methanol and a catalyst are added into an esterification reaction kettle to be fully mixed, diketene is added in a flowing mode, crude methyl acetoacetate is obtained after heat preservation after the feeding is finished, and fine products are obtained after rectification. Due to the method structure, the problems of poor operation stability, low device production capacity, low conversion rate and the like exist, and the market demand is difficult to meet.

In order to improve the yield and the yield of methyl acetoacetate, the following patent documents exist in China at present:

the patent application with the application number of 200810020812.7 and the name of invention being a method for producing methyl acetoacetate by using a novel composite catalyst provides that triethylene diamine is used as a catalyst before the esterification reaction of ketene dimer and methanol, and concentrated sulfuric acid is added after the esterification reaction is finished to prevent the decomposition of the ketene dimer in the subsequent rectification process, thereby ensuring the more complete esterification reaction of the methyl acetoacetate. However, this method is still not free from the use of concentrated sulfuric acid.

The patent application with the application number of 99114312.4 and the name of invention of methyl acetoacetate discloses a production method of methyl acetoacetate, and specifically comprises the steps of purifying crude diketene by negative pressure membrane evaporation and rectification before esterification reaction to obtain refined diketene with the content of more than 97%, carrying out esterification reaction with methanol under the action of a catalyst, and carrying out continuous negative pressure rectification on a product of the esterification reaction by two towers to obtain the methyl acetoacetate with the purity of 99%. Wherein, the crude diketene is diketene which is generated by polymerization of ketene, is not purified and has purity of 90-95%.

However, this production method also has the following disadvantages: firstly, the crude diketene is very unstable when being heated, safety accidents are easy to happen in the rectification process of the crude diketene, the generated residues are unstable, and the problem of how to treat the residues is also difficult, and the safety accidents happen in the process basically by diketene production enterprises; secondly, the diketene is polymerized when the crude diketene is rectified, the yield of the diketene is only 80-90%, and the energy consumption is high.

Moreover, because the esterification reaction is a violent exothermic process, the solution can be violently subjected to bumping (the temperature can reach more than 120 ℃) in the process of feeding diketene, so that part of diketene is oxidized and polymerized under the high-temperature condition, side reactions are increased, the product purity is reduced, the yield is reduced, and the cost is increased. Meanwhile, methanol, methyl acetoacetate and diketene all belong to flammable liquids, and the danger of safety accidents is increased under the condition of severe bumping.

If the crude diketene can be directly reacted with methanol to generate methyl acetoacetate, the method is safe, saves energy, reduces consumption and simultaneously can reduce investment. However, the crude diketene contains acetic anhydride, has strong acidity, weakens the catalytic activity of a weak base catalyst, has low reaction speed, has low content of the crude diketene, and generates a plurality of crude ester impurities by direct reaction, so the high-quality methyl acetoacetate cannot be obtained by simple rectification.

The invention discloses a production method of methyl acetoacetate with application number of 201110267363.8, and the production method comprises the following steps: (1) carrying out esterification reaction on crude diketene and methanol at the temperature of 20-150 ℃, wherein one of tertiary amine, a compound containing ethylene amine or an alkaline compound is used as a catalyst in the esterification reaction; (2) and (2) carrying out four-tower negative pressure continuous rectification on the product generated in the esterification reaction in the step (1) to prepare methyl acetoacetate. The method adopts the esterification reaction of the crude diketene, does not need the rectification and purification of the diketene, has low energy consumption, high yield, easy obtainment of a catalyst, mild reaction conditions, safe process, high product content and high yield, and is suitable for industrial mass production. However, the method adopts a kettle type reaction, and the reaction product needs to be subjected to continuous negative pressure rectification by four towers of a low-boiling-point removal tower, a medium-boiling-point removal tower, a finished product tower and a high-boiling-point removal tower, so that the process is complex.

The invention discloses a methyl acetoacetate esterification reaction process, which has the application number of 201810394783.4 and the invention name of the methyl acetoacetate esterification production process, and comprises the following specific steps: pumping methanol and triethylamine into a melting material kettle, and pumping the mixture into a high liquid level tank; then dripping a catalyst, fully mixing and pumping into a mixer; pumping diketene into a mixer for fully mixing, introducing the mixture into a spiral wound tube microchannel reactor for esterification, pumping into a cooling kettle for cooling after reaction, and pumping into a rectifying tower; rectifying to obtain methyl acetoacetate. The process realizes the continuity of production operation, has high reaction stability, prevents the temperature runaway problem caused by the inaccurate temperature control of a common reactor, and eliminates the potential explosion possibility of the reactor operation; high flux, high heat transfer capacity, high synthesis rate and low processing cost of the esterification reaction are realized, and the economic benefit of enterprises is obviously increased. Because methyl ester is easy to decompose in the rectification process, the yield is reduced, the purity is reduced, and in order to prevent the methyl ester from decomposing in the rectification process, a catalyst p-toluenesulfonic acid is added in the method as a stabilizer, and the function of the catalyst p-toluenesulfonic acid is to prevent the methyl ester from decomposing in the rectification process; meanwhile, before being pumped into a rectifying tower for rectification, the waste water needs to be pumped into a cooling kettle for cooling. Therefore, the method increases the investment of reaction materials and reaction equipment and increases the production cost.

The present invention has been made in view of this situation.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provide a preparation method of methyl acetoacetate.

In order to solve the technical problems, the invention adopts the following technical scheme:

a preparation method of methyl acetoacetate, which comprises the following steps:

1) fully mixing methanol and triethylamine to obtain methanol solution containing triethylamine;

2) respectively and simultaneously conveying the methanol solution containing triethylamine and the crude diketene obtained in the step 1) into a microreactor through an infusion pump for esterification reaction to obtain crude methyl acetoacetate;

3) inputting the crude methyl acetoacetate obtained in the step 2) into a methyl acetoacetate rectifying tower through a pipeline, and rectifying to obtain methyl acetoacetate.

The methanol solution containing the catalyst and the crude diketene are simultaneously conveyed into the microchannel of the microreactor by two liquid conveying pumps to react in the microchannel. The material flowing out through the micro-channel directly enters a rectifying device for rectification and purification. The synthesis process has the advantages of less side reaction, high product purity, high yield, safety, reliability and less equipment investment in the reaction process, and realizes the continuous production esterification reaction process. Meanwhile, in the method, the materials are directly input into the methyl ester rectifying tower for rectification through a pipeline after the reaction in the microreactor is finished, and the materials do not need to be pumped into a cooling kettle for cooling and then rectified, so that the investment of equipment is saved. In addition, the invention adopts simple rectification and can obtain high-quality methyl acetoacetate without four continuous negative pressure rectification of a low-boiling tower, a medium-boiling tower, a finished product tower and a high-boiling tower.

Further, in the step 1), the mass ratio of methanol to triethylamine is 500-1500: 1, preferably 800 to 1200: 1, more preferably 1000: 1.

further, in the step 2), the molar ratio of the methanol solution containing triethylamine to the crude diketene calculated by methanol is 0.08-1.08: 1, preferably 1.00 to 1.05: 1, more preferably 1.02: 1.

further, in the step 2), the reaction temperature in the microreactor is controlled to be 110-115 ℃, and preferably 115 ℃.

Further, in the step 2), the reaction pressure in the microreactor is controlled to be 2.5-4 MPa, and preferably 3.5 MPa.

In the method, the reaction in the microreactor is carried out at 110-115 ℃, and the preferable temperature is 115 ℃; the method is carried out under the condition of 2.5-4 MPa, preferably 3.5MPa, and meanwhile, the materials are directly input into a methyl ester rectifying tower for rectification through a pipeline without being cooled by a cooling kettle after the reaction in the microreactor is finished, the materials are gasified instantly under negative pressure in the rectifying tower, so that the decomposition of the methyl ester in the temperature rising process is prevented, the yield is improved, the product purity is improved, and the purpose of preventing the decomposition of the methyl ester in the temperature rising process can be achieved without additionally adding a catalyst to the methylbenzenesulfonic acid as a stabilizer.

Further, in the step 2), the feeding speed of the methanol solution containing triethylamine is 30-40 g/min, preferably 35 g/min.

Further, in the step 2), the feeding speed of the crude diketene is 90-100 g/min, preferably 94.3 g/min.

Further, in the step 2), the residence time of the methanol solution containing triethylamine and the crude diketene in the microreactor is 55-65 s, preferably 60 s.

Further, the purity of the crude diketene is 90-92%.

The original process uses the refined diketene, and the product loss is large in the rectification process. The invention adopts crude diketene, thereby avoiding the loss of products in the rectification process.

In the invention, the rectification is vacuum rectification, and specifically comprises the following steps: carrying out reduced pressure rectification under the vacuum degree of 100-900 kPa, collecting fractions with the temperature higher than 58 ℃, cooling to 40-45 ℃ when the liquid temperature reaches 140 ℃, breaking the air, and stopping rectification.

After adopting the technical scheme, compared with the prior art, the invention has the following beneficial effects:

1) the method overcomes the defects of the prior art, has less side reaction in the reaction process, high product purity, high yield, safety, reliability and less equipment investment, and realizes the continuous production esterification reaction process;

2) compared with the prior art, the method has the advantages that the feeding is carried out at room temperature, the esterification process does not need heat preservation, the energy consumption is reduced, and the micro structure in the microchannel reactor ensures that the micro reactor equipment has extremely large specific surface area which can be hundreds of times or even thousands of times of the specific surface area of the stirring kettle. The micro-reactor has excellent heat transfer and mass transfer capacity, can realize the instant uniform mixing of materials and high-efficiency heat transfer, eliminates the potential safety hazard of accumulation of a large amount of reactants in the amplification production of the traditional reactor due to the very low reactant liquid holdup of the reaction module, realizes the continuous production, and has high product purity and high yield;

3) according to the method, after the reaction in the microreactor is finished, the material is not required to be cooled by a cooling kettle, and is directly input into a methyl ester rectifying tower through a pipeline for rectification, the pressure in the rectifying tower is negative, the material is instantly gasified, the decomposition of the methyl ester in the temperature rising process is prevented, the yield is improved, the product purity is improved, the purpose of preventing the decomposition of the methyl ester in the temperature rising process can be achieved without additionally adding a catalyst, namely p-toluenesulfonic acid, as a stabilizer, and the investment of the material and equipment is saved. In addition, the invention adopts simple rectification and can obtain high-quality methyl acetoacetate without four continuous negative pressure rectification of a low-boiling removal tower, a medium-boiling removal tower, a finished product tower and a high-boiling removal tower.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments will be clearly and completely described below with reference to the embodiments of the present invention, and the following embodiments are used for illustrating the present invention and are not intended to limit the scope of the present invention.

Example 1

1) Methanol and a catalyst triethylamine are mixed according to a mass ratio of 1000: 1, fully mixing to obtain a methanol solution containing a catalyst;

2) the molar ratio of the methanol solution containing the catalyst and the diketene obtained in the step 1) to the methanol solution containing the catalyst in terms of methanol to the diketene is 1.02: 1, respectively conveying the mixture into a microreactor simultaneously through an infusion pump, controlling the reaction temperature in the microreactor to be 115 ℃, controlling the pressure to be 3.5Mpa, controlling the feeding speed of a methanol solution containing a catalyst to be 35g/min, controlling the feeding speed of diketene to be 94.3g/min, keeping the residence time to be 60s, and obtaining crude methyl acetoacetate after the esterification reaction is stabilized for 10 min; the crude methyl acetoacetate is sent to a sample for gas phase detection, the purity of the crude methyl acetoacetate product reaches 98 percent, and the yield is more than 98 percent;

3) pumping the crude methyl acetoacetate obtained in the step 2) into a cooling kettle for cooling, pumping into a rectifying tower for rectifying to obtain colorless transparent liquid of methyl acetoacetate, wherein the purity is more than or equal to 99.5%, the yield is 95.8%, the acidity is less than or equal to 0.07%, and the water content is less than or equal to 0.07%.

Example 2

1) Methanol and a catalyst triethylamine are mixed according to a mass ratio of 800: 1, fully mixing to obtain a methanol solution containing a catalyst;

2) the molar ratio of the methanol solution containing the catalyst and the diketene obtained in the step 1) to the methanol solution containing the catalyst in terms of methanol to the diketene is 1.00: 1, respectively conveying the raw materials into a microreactor simultaneously through an infusion pump, controlling the reaction temperature in the microreactor at 110 ℃, controlling the pressure in the microreactor at 2.5Mpa, controlling the feeding speed of a methanol solution containing a catalyst at 30g/min, controlling the feeding speed of diketene at 90g/min, keeping the residence time at 55s, and obtaining crude methyl acetoacetate after the esterification reaction is stabilized for 10 min; the crude methyl acetoacetate is sent to a sample for gas phase detection, the purity of the crude methyl acetoacetate product reaches 97.8 percent, and the yield is 96.1 percent;

3) pumping the crude methyl acetoacetate obtained in the step 2) into a cooling kettle for cooling, pumping into a rectifying tower for rectifying to obtain colorless transparent liquid of methyl acetoacetate, wherein the purity is more than or equal to 99.5%, the yield is 95.4%, the acidity is less than or equal to 0.07%, and the water content is less than or equal to 0.07%.

Example 3

1) Methanol and a catalyst triethylamine are mixed according to a mass ratio of 1200: 1, fully mixing to obtain a methanol solution containing a catalyst;

2) the molar ratio of the methanol solution containing the catalyst and the diketene obtained in the step 1) to the methanol solution containing the catalyst in terms of methanol to the diketene is 1.05: 1, respectively conveying the raw materials into a microreactor simultaneously through an infusion pump, controlling the reaction temperature in the microreactor to be 112 ℃, controlling the pressure to be 4Mpa, controlling the feeding speed of a methanol solution containing a catalyst to be 40g/min, controlling the feeding speed of diketene to be 100g/min, keeping the residence time to be 65s, and obtaining crude methyl acetoacetate after the esterification reaction is stabilized for 10 min; the crude methyl acetoacetate is sent to a sample for gas phase detection, the purity of the crude methyl acetoacetate product reaches 97.6 percent, and the yield is 95.4 percent;

3) pumping the crude methyl acetoacetate obtained in the step 2) into a cooling kettle for cooling, pumping into a rectifying tower for rectifying to obtain colorless transparent liquid of methyl acetoacetate, wherein the purity is more than or equal to 99.5%, the yield is 95.6%, the acidity is less than or equal to 0.07%, and the water content is less than or equal to 0.07%.

Example 4

1) Methanol and a catalyst triethylamine are mixed according to a mass ratio of 500: 1, fully mixing to obtain a methanol solution containing a catalyst;

2) the molar ratio of the methanol solution containing the catalyst and the diketene obtained in the step 1) to the methanol solution containing the catalyst in terms of methanol to the diketene is 0.08: 1, respectively conveying the mixture into a microreactor simultaneously through an infusion pump, controlling the reaction temperature in the microreactor at 113 ℃, controlling the pressure in the microreactor at 3.0Mpa, controlling the feeding speed of a methanol solution containing a catalyst at 38g/min, controlling the feeding speed of diketene at 92g/min, controlling the retention time at 58s, and obtaining crude methyl acetoacetate after the esterification reaction is stabilized for 10 min; the crude methyl acetoacetate is sent to a sample for gas phase detection, the purity of the crude methyl acetoacetate product reaches 97.7 percent, and the yield is 95.8 percent;

3) pumping the crude methyl acetoacetate obtained in the step 2) into a cooling kettle for cooling, pumping into a rectifying tower for rectifying to obtain colorless transparent liquid of methyl acetoacetate, wherein the purity is more than or equal to 99.5%, the yield is 95.3%, the acidity is less than or equal to 0.07%, and the water content is less than or equal to 0.07%.

Example 5

1) Methanol and a catalyst triethylamine are mixed according to a mass ratio of 1500: 1, fully mixing to obtain a methanol solution containing a catalyst;

2) the molar ratio of the methanol solution containing the catalyst and the diketene obtained in the step 1) to the methanol solution containing the catalyst in terms of methanol to the diketene is 1.08: 1 are respectively and simultaneously conveyed into the microreactors by an infusion pump, the reaction temperature in the microreactors is controlled at 114 ℃, the pressure is controlled at 3.6Mpa, the feeding speed of a methanol solution containing a catalyst is 38g/min, the feeding speed of diketene is 95.2g/min, the residence time is 62s, and the crude methyl acetoacetate is obtained after the esterification reaction is stabilized for 10 min; the crude methyl acetoacetate is sent to a sample for gas phase detection, the purity of the crude methyl acetoacetate product reaches 97.9 percent, and the yield is 95.6 percent;

Although the present invention has been described with reference to the preferred embodiments, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims.

Claims

1. A preparation method of methyl acetoacetate is characterized by comprising the following steps:

2. The preparation method according to claim 1, wherein in the step 1), the mass ratio of methanol to triethylamine is 500-1500: 1, preferably 800 to 1200: 1, more preferably 1000: 1.

3. the preparation method according to claim 1, wherein in the step 2), the molar ratio of the methanol solution containing triethylamine to the crude diketene is 0.08-1.08 in terms of methanol: 1, preferably 1.00 to 1.05: 1, more preferably 1.02: 1.

4. the preparation method according to claim 1, wherein in the step 2), the reaction temperature in the microreactor is controlled to be 110-115 ℃, preferably 115 ℃.

5. The preparation method according to claim 2, wherein in the step 2), the reaction pressure in the microreactor is controlled to be 2.5 to 4MPa, preferably 3.5 MPa.

6. The method according to claim 1, wherein the feeding rate of the methanol solution containing triethylamine in the step 2) is 30 to 40g/min, preferably 35 g/min.

7. The process according to claim 1, wherein the crude diketene is fed at a rate of 90 to 100g/min, preferably 94.3g/min in step 2).

8. The preparation method according to claim 1, wherein in step 2), the residence time of the methanol solution containing triethylamine and the crude diketene in the microreactor is 55-65 s, preferably 60 s.

9. The process according to any one of claims 1 to 8, wherein the crude diketene has a purity of 90% to 92%.