Continuous synthesis method of diethyl methylmalonate

Abstract

The invention belongs to the technical field of organic synthesis, and specifically relates to a continuous synthesis method of diethyl methylmalonate. 2-chloropropionic acid is continuously cyanidedto obtain 2-cyanopropionic acid; 2-cyanopropionic acid and ethanol carry out esterification reactions under the action of sulfuric acid to obtain a crude product of diethyl methylmalonate directly inone step; and the finished product is obtained after steps of washing and distillation. The reaction process is simple, and the yields of hydrolysis and esterification are high.

Description

technical field

[0001] The invention belongs to the technical field of organic synthesis, in particular to a method for continuously synthesizing diethyl methylmalonate. Background technique

[0002] Diethyl methylmalonate is an important intermediate in organic synthesis and is widely used in the production of medicines, dyes, spices, pesticides and herbicides. In medicine, diethyl methylmalonate is mainly used in the production of muscone. At present, the synthesis of diethyl methylmalonate mainly includes heating diethyl oxalylpropionate to violently release carbon monoxide at a temperature of 130-150°C. After the released gas is reduced, gradually increase the temperature to make the liquid reflux until the gas escapes. Diethyl methylmalonate was obtained by distillation with a yield of 97%.

[0003] In the synthesis process, the price of raw materials is higher and difficult to obtain, resulting in the high price of diethyl methylmalonate. Contents of the invention...

Examples

Embodiment 1

[0012] A method for continuously synthesizing diethyl methylmalonate, the steps are as follows:

[0013] Add 2-cyanopropionic acid to ethanol to dissolve, control the molar ratio of 2-cyanopropionic acid to ethanol to be 1:4, transfer to the reaction kettle after dissolving. Stirring, under room temperature conditions, slowly add 98% concentrated sulfuric acid to the reactor from the dropping funnel, control the mass ratio of 2-cyanopropionic acid to sulfuric acid to 1:1.3, control the temperature at 60°C, and raise the system after the addition is completed The temperature is controlled at 80°C, and the reaction ends after 4 hours of reaction; at 85°C, the ethanol component in the reaction system is distilled off, and 12% ammonia water is added dropwise to the system for neutralization, the temperature is controlled at 85°C, and the pH of the feed solution is adjusted to 7- 8. Separate the crude diethyl methylmalonate in the organic phase. The diethyl methylmalonate crude p...

Embodiment 2

[0015] A method for continuously synthesizing diethyl methylmalonate, the steps are as follows:

[0016] Add 2-cyanopropionic acid to ethanol to dissolve, control the molar ratio of 2-cyanopropionic acid to ethanol to be 1:6, transfer it to the reaction kettle after dissolving; Slowly add 98wt.% concentrated sulfuric acid to the mixture, control the mass ratio of 2-cyanopropionic acid to sulfuric acid to 1:2.8, control the temperature at 65°C, increase the temperature of the system after the dropwise addition and control it at 95°C, and the reaction ends after 5 hours of reaction; At 60°C, distill out the ethanol component in the reaction system, add dropwise 12wt.% ammonia water to the reaction system for neutralization, control the temperature at 90°C, adjust the pH of the feed solution to 7, and separate diethyl methylmalonate Crude product: drop the diethyl methylmalonate crude product into rectification under reduced pressure in the rectifying tower, obtain diethyl methyl...

Embodiment 3

[0018] A method for continuously synthesizing diethyl methylmalonate, the steps are as follows:

[0019] Add 2-cyanopropionic acid to ethanol to dissolve, control the molar ratio of 2-cyanopropionic acid to ethanol to be 1:2.5, transfer it to the reaction kettle after dissolving; Slowly add 98wt.% concentrated sulfuric acid to the mixture, control the mass ratio of 2-cyanopropionic acid to sulfuric acid to 1:0.5, control the temperature at 55°C, increase the temperature of the system after the dropwise addition and control it at 70°C, and the reaction ends after 2 hours of reaction; At 45°C, distill out the ethanol component in the reaction system, add 12wt.% ammonia water dropwise to the reaction system for neutralization, control the temperature at 70°C, adjust the pH of the feed solution to 8, and separate diethyl methylmalonate Crude product: drop the diethyl methylmalonate crude product into rectification under reduced pressure in the rectifying tower, obtain diethyl meth...

technical field

[0001] The invention belongs to the technical field of organic synthesis, in particular to a method for continuously synthesizing diethyl methylmalonate. Background technique

[0002] Diethyl methylmalonate is an important intermediate in organic synthesis and is widely used in the production of medicines, dyes, spices, pesticides and herbicides. In medicine, diethyl methylmalonate is mainly used in the production of muscone. At present, the synthesis of diethyl methylmalonate mainly includes heating diethyl oxalylpropionate to violently release carbon monoxide at a temperature of 130-150°C. After the released gas is reduced, gradually increase the temperature to make the liquid reflux until the gas escapes. Diethyl methylmalonate was obtained by distillation with a yield of 97%.

[0003] In the synthesis process, the price of raw materials is higher and difficult to obtain, resulting in the high price of diethyl methylmalonate. Contents of the invention...

Examples

Embodiment 1

[0012] A method for continuously synthesizing diethyl methylmalonate, the steps are as follows:

[0013] Add 2-cyanopropionic acid to ethanol to dissolve, control the molar ratio of 2-cyanopropionic acid to ethanol to be 1:4, transfer to the reaction kettle after dissolving. Stirring, under room temperature conditions, slowly add 98% concentrated sulfuric acid to the reactor from the dropping funnel, control the mass ratio of 2-cyanopropionic acid to sulfuric acid to 1:1.3, control the temperature at 60°C, and raise the system after the addition is completed The temperature is controlled at 80°C, and the reaction ends after 4 hours of reaction; at 85°C, the ethanol component in the reaction system is distilled off, and 12% ammonia water is added dropwise to the system for neutralization, the temperature is controlled at 85°C, and the pH of the feed solution is adjusted to 7- 8. Separate the crude diethyl methylmalonate in the organic phase. The diethyl methylmalonate crude p...

Embodiment 2

[0015] A method for continuously synthesizing diethyl methylmalonate, the steps are as follows:

[0016] Add 2-cyanopropionic acid to ethanol to dissolve, control the molar ratio of 2-cyanopropionic acid to ethanol to be 1:6, transfer it to the reaction kettle after dissolving; Slowly add 98wt.% concentrated sulfuric acid to the mixture, control the mass ratio of 2-cyanopropionic acid to sulfuric acid to 1:2.8, control the temperature at 65°C, increase the temperature of the system after the dropwise addition and control it at 95°C, and the reaction ends after 5 hours of reaction; At 60°C, distill out the ethanol component in the reaction system, add dropwise 12wt.% ammonia water to the reaction system for neutralization, control the temperature at 90°C, adjust the pH of the feed solution to 7, and separate diethyl methylmalonate Crude product: drop the diethyl methylmalonate crude product into rectification under reduced pressure in the rectifying tower, obtain diethyl methyl...

Embodiment 3

[0018] A method for continuously synthesizing diethyl methylmalonate, the steps are as follows:

[0019] Add 2-cyanopropionic acid to ethanol to dissolve, control the molar ratio of 2-cyanopropionic acid to ethanol to be 1:2.5, transfer it to the reaction kettle after dissolving; Slowly add 98wt.% concentrated sulfuric acid to the mixture, control the mass ratio of 2-cyanopropionic acid to sulfuric acid to 1:0.5, control the temperature at 55°C, increase the temperature of the system after the dropwise addition and control it at 70°C, and the reaction ends after 2 hours of reaction; At 45°C, distill out the ethanol component in the reaction system, add 12wt.% ammonia water dropwise to the reaction system for neutralization, control the temperature at 70°C, adjust the pH of the feed solution to 8, and separate diethyl methylmalonate Crude product: drop the diethyl methylmalonate crude product into rectification under reduced pressure in the rectifying tower, obtain diethyl meth...