CN111018704A - Preparation method of diethyl methylmalonate by taking heteropoly acid as catalyst - Google Patents
Preparation method of diethyl methylmalonate by taking heteropoly acid as catalyst Download PDFInfo
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- CN111018704A CN111018704A CN201911165397.9A CN201911165397A CN111018704A CN 111018704 A CN111018704 A CN 111018704A CN 201911165397 A CN201911165397 A CN 201911165397A CN 111018704 A CN111018704 A CN 111018704A
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- acid
- cyanopropionic
- diethyl methylmalonate
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- ethanol
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/18—Preparation of carboxylic acid esters by conversion of a group containing nitrogen into an ester group
- C07C67/22—Preparation of carboxylic acid esters by conversion of a group containing nitrogen into an ester group from nitriles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/14—Preparation of carboxylic acid nitriles by reaction of cyanides with halogen-containing compounds with replacement of halogen atoms by cyano groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
- C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
Abstract
The invention relates to a preparation method of diethyl methylmalonate with heteropoly acid as a catalyst, which comprises the steps of adding 2-cyanopropionic acid into ethanol for dissolving, controlling the molar ratio of the 2-cyanopropionic acid to the ethanol to be 1: 3-4, and transferring the dissolved 2-cyanopropionic acid to a reaction kettle; stirring at room temperature, adding a heteropoly acid catalyst, controlling the mass ratio of 2-cyanopropionic acid to the heteropoly acid catalyst to be 2: 1-2, controlling the temperature to be 65-80 ℃, reacting for 3-4h, and finishing the reaction; distilling and separating ethanol, adding ammonia water for neutralization, adjusting the pH value to be neutral, and fractionating a crude product of the diethyl methylmalonate; and (3) putting the crude product of the diethyl methylmalonate into a rectifying tower for vacuum rectification to obtain the diethyl methylmalonate. The method uses the heteropolyacid catalyst to replace sulfuric acid for esterification reaction, and has the advantages of good selectivity, high catalytic activity, high regeneration speed and low corrosion to equipment.
Description
Technical Field
The invention relates to the technical field of pharmacy, in particular to a preparation method of diethyl methylmalonate by taking heteropoly acid as a catalyst.
Background
Diethyl methylmalonate is a colorless liquid, insoluble in water, and used as an organic intermediate; can be used for synthesizing dipropylmalonic acid, and further synthesizing antiepileptic medicine antiepileptic. There are two main routes for the synthesis of diethyl methylmalonate: 1) reacting diethyl malonate as raw material with methylating agent (such as: methyl iodide, methyl bromide, dimethyl sulfate, etc.) to undergo a methylation substitution reaction. 2) 2-chloropropionic acid is used as a raw material, and the diethyl methylmalonate is prepared by neutralization, cyanidation, alkaline hydrolysis, acidification and esterification. At present, concentrated sulfuric acid and hydrochloric acid are mostly used as catalysts for acidification and esterification. Due to the dehydration, esterification and oxidation of concentrated sulfuric acid and hydrochloric acid, the esterification mixture is easy to contain by-products such as ether, sulfate, unsaturated compounds, carbonyl compounds and the like, so that the production process has more side reactions, the product post-treatment is complex, and the used concentrated sulfuric acid and hydrochloric acid corrode equipment and pollute the environment.
The heteropoly acid catalyst is a novel high-efficiency catalyst, can be used as an acid-base, oxidation-reduction or bifunctional catalyst with excellent performance no matter in homogeneous and heterogeneous systems, and has the advantages of good selectivity, high catalytic activity, high regeneration speed, small corrosion to equipment, no environmental pollution, easy recovery of the catalyst, repeated use and the like.
Disclosure of Invention
The invention aims to provide a preparation method of diethyl methylmalonate by taking heteropoly acid as a catalyst, which has the advantages of good selectivity, high catalytic activity, high regeneration speed, small corrosion to equipment, no environmental pollution, easy recovery of the catalyst, repeated use and the like by using the heteropoly acid catalyst to replace sulfuric acid for esterification.
The technical scheme of the invention is as follows: a method for preparing diethyl methylmalonate by taking heteropoly acid as a catalyst comprises the following steps:
the method comprises the following steps: neutralizing with 2-chloropropionic acid and potassium carbonate to generate potassium 2-chloropropionate, continuously cyaniding with potassium cyanide, and acidifying with hydrochloric acid to obtain 2-cyanopropionic acid;
step two: adding 2-cyanopropionic acid into ethanol for dissolving, controlling the molar ratio of the 2-cyanopropionic acid to the ethanol to be 1: 3-4, and transferring the dissolved 2-cyanopropionic acid to a reaction kettle; stirring at room temperature, adding a heteropoly acid catalyst, controlling the mass ratio of 2-cyanopropionic acid to the heteropoly acid catalyst to be 2: 1-2, controlling the temperature to be 65-80 ℃, reacting for 3-4h, and finishing the reaction; distilling and separating ethanol, adding ammonia water for neutralization, adjusting the pH value to be neutral, and fractionating a crude product of the diethyl methylmalonate; and (3) putting the crude product of the diethyl methylmalonate into a rectifying tower for vacuum rectification to obtain the diethyl methylmalonate.
The invention has the beneficial effects that: in the esterification reaction of the prepared diethyl methyl malonate, the sulfuric acid is replaced by the heteropoly acid catalyst, and the 2-cyanopropionic acid and the ethanol are esterified under the action of the heteropoly acid catalyst to directly obtain the diethyl methyl malonate in one step.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to the following embodiments, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments.
A method for preparing diethyl methylmalonate by taking heteropoly acid as a catalyst comprises the following steps:
the method comprises the following steps: neutralizing with 2-chloropropionic acid and potassium carbonate to generate potassium 2-chloropropionate, continuously cyaniding with potassium cyanide, and acidifying with hydrochloric acid to obtain 2-cyanopropionic acid;
step two: adding 2-cyanopropionic acid into ethanol for dissolving, controlling the molar ratio of the 2-cyanopropionic acid to the ethanol to be 1: 3-4, and transferring the dissolved 2-cyanopropionic acid to a reaction kettle; stirring at room temperature, adding a heteropoly acid catalyst, controlling the mass ratio of 2-cyanopropionic acid to the heteropoly acid catalyst to be 2: 1-2, controlling the temperature to be 65-80 ℃, reacting for 3-4h, and finishing the reaction; distilling and separating ethanol, adding ammonia water for neutralization, adjusting the pH value to be neutral, and fractionating a crude product of the diethyl methylmalonate; and (3) putting the crude product of the diethyl methylmalonate into a rectifying tower for vacuum rectification to obtain the diethyl methylmalonate.
Example 1:
adding 108kg of 2-chloropropionic acid and 138kg of potassium carbonate into a reaction kettle to neutralize to generate potassium 2-chloropropionate, gradually dropwise adding potassium cyanide to carry out cyanidation until complete cyanidation, and acidifying with hydrochloric acid to obtain 2-cyanopropionic acid;
adding 2-cyanopropionic acid into ethanol for dissolving, controlling the molar ratio of the 2-cyanopropionic acid to the ethanol to be 1:4, and transferring the dissolved 2-cyanopropionic acid to a reaction kettle; stirring at room temperature, adding a heteropoly acid catalyst, controlling the mass ratio of 2-cyanopropionic acid to the heteropoly acid catalyst to be 2:1, controlling the temperature to be 65 ℃, reacting for 3 hours, and finishing the post-reaction; distilling and separating ethanol, adding ammonia water for neutralization, adjusting the pH value to be neutral, and fractionating a crude product of the diethyl methylmalonate; and (3) putting the crude product of the diethyl methylmalonate into a rectifying tower for vacuum rectification to obtain the diethyl methylmalonate.
Example 2:
adding 108kg of 2-chloropropionic acid and 138kg of potassium carbonate into a reaction kettle to neutralize to generate potassium 2-chloropropionate, gradually dropwise adding potassium cyanide to carry out cyanidation until complete cyanidation, and acidifying with hydrochloric acid to obtain 2-cyanopropionic acid;
adding 2-cyanopropionic acid into ethanol for dissolving, controlling the molar ratio of the 2-cyanopropionic acid to the ethanol to be 1:3, and transferring the dissolved 2-cyanopropionic acid to a reaction kettle; stirring at room temperature, adding a heteropoly acid catalyst, controlling the mass ratio of 2-cyanopropionic acid to the heteropoly acid catalyst to be 2:2, controlling the temperature to be 70 ℃, reacting for 4 hours, and finishing the post-reaction; distilling and separating ethanol, adding ammonia water for neutralization, adjusting the pH value to be neutral, and fractionating a crude product of the diethyl methylmalonate; and (3) putting the crude product of the diethyl methylmalonate into a rectifying tower for vacuum rectification to obtain the diethyl methylmalonate.
Example 3:
adding 108kg of 2-chloropropionic acid and 138kg of potassium carbonate into a reaction kettle to neutralize to generate potassium 2-chloropropionate, gradually dropwise adding potassium cyanide to carry out cyanidation until complete cyanidation, and acidifying with hydrochloric acid to obtain 2-cyanopropionic acid;
adding 2-cyanopropionic acid into ethanol for dissolving, controlling the molar ratio of the 2-cyanopropionic acid to the ethanol to be 1:4, and transferring the dissolved 2-cyanopropionic acid to a reaction kettle; stirring at room temperature, adding a heteropoly acid catalyst, controlling the mass ratio of 2-cyanopropionic acid to the heteropoly acid catalyst to be 2:1, controlling the temperature to be 80 ℃, reacting for 3 hours, and finishing the post-reaction; distilling and separating ethanol, adding ammonia water for neutralization, adjusting the pH value to be neutral, and fractionating a crude product of the diethyl methylmalonate; and (3) putting the crude product of the diethyl methylmalonate into a rectifying tower for vacuum rectification to obtain the diethyl methylmalonate.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.
Claims (3)
1. A method for preparing diethyl methylmalonate by taking heteropoly acid as a catalyst is characterized by comprising the following steps: the method comprises the following steps:
the method comprises the following steps: neutralizing with 2-chloropropionic acid and potassium carbonate to generate potassium 2-chloropropionate, continuously cyaniding with potassium cyanide, and acidifying with hydrochloric acid to obtain 2-cyanopropionic acid;
step two: adding 2-cyanopropionic acid into ethanol for dissolving, controlling the molar ratio of the 2-cyanopropionic acid to the ethanol to be 1: 3-4, and transferring the dissolved 2-cyanopropionic acid to a reaction kettle; stirring at room temperature, adding a heteropoly acid catalyst, controlling the mass ratio of 2-cyanopropionic acid to the heteropoly acid catalyst to be 2: 1-2, controlling the temperature to be 65-80 ℃, reacting for 3-4h, and finishing the reaction; distilling and separating ethanol, adding ammonia water for neutralization, adjusting the pH value to be neutral, and fractionating a crude product of the diethyl methylmalonate; and (3) putting the crude product of the diethyl methylmalonate into a rectifying tower for vacuum rectification to obtain the diethyl methylmalonate.
2. The process according to claim 1, wherein the diethyl methylmalonate is prepared by reacting: adding 108kg of 2-chloropropionic acid and 138kg of potassium carbonate into a reaction kettle to neutralize to generate potassium 2-chloropropionate, gradually dropwise adding potassium cyanide to carry out cyanidation until complete cyanidation, and acidifying with hydrochloric acid to obtain 2-cyanopropionic acid; adding 2-cyanopropionic acid into ethanol for dissolving, controlling the molar ratio of the 2-cyanopropionic acid to the ethanol to be 1:4, and transferring the dissolved 2-cyanopropionic acid to a reaction kettle; stirring at room temperature, adding a heteropoly acid catalyst, controlling the mass ratio of 2-cyanopropionic acid to the heteropoly acid catalyst to be 2:1, controlling the temperature to be 65 ℃, reacting for 3 hours, and finishing the post-reaction; distilling and separating ethanol, adding ammonia water for neutralization, adjusting the pH value to be neutral, and fractionating a crude product of the diethyl methylmalonate; and (3) putting the crude product of the diethyl methylmalonate into a rectifying tower for vacuum rectification to obtain the diethyl methylmalonate.
3. The process according to claim 1, wherein the diethyl methylmalonate is prepared by reacting: adding 108kg of 2-chloropropionic acid and 138kg of potassium carbonate into a reaction kettle to neutralize to generate potassium 2-chloropropionate, gradually dropwise adding potassium cyanide to carry out cyanidation until complete cyanidation, and acidifying with hydrochloric acid to obtain 2-cyanopropionic acid; adding 2-cyanopropionic acid into ethanol for dissolving, controlling the molar ratio of the 2-cyanopropionic acid to the ethanol to be 1:3, and transferring the dissolved 2-cyanopropionic acid to a reaction kettle; stirring at room temperature, adding a heteropoly acid catalyst, controlling the mass ratio of 2-cyanopropionic acid to the heteropoly acid catalyst to be 2:2, controlling the temperature to be 70 ℃, reacting for 4 hours, and finishing the post-reaction; distilling and separating ethanol, adding ammonia water for neutralization, adjusting the pH value to be neutral, and fractionating a crude product of the diethyl methylmalonate; and (3) putting the crude product of the diethyl methylmalonate into a rectifying tower for vacuum rectification to obtain the diethyl methylmalonate.
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| CN201911165397.9A CN111018704A (en) | 2019-11-25 | 2019-11-25 | Preparation method of diethyl methylmalonate by taking heteropoly acid as catalyst |
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| CN201911165397.9A CN111018704A (en) | 2019-11-25 | 2019-11-25 | Preparation method of diethyl methylmalonate by taking heteropoly acid as catalyst |
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