Overview[1]
Aminoacetaldehyde dimethanol, also known as 2,2-dimethoxyethylamine, is a valuable primary amine compound. The amino functional group is a very active reactive group that can undergo salt and amidation reactions. It is It is an important intermediate for the synthesis of ivabradine hydrochloride, proline analogues, phosphoramidates and other drugs, and is widely used in chemistry, chemical industry, medicine and other fields.
Synthesis method[1]
There are three main methods for synthesizing aminoacetal dimethyl acetate:
(1 Using chloroacetaldehyde dimethylacetal as raw material, solvent methanol, and high temperature and high pressure in 28% ammonia water, aminoacetaldehyde dimethylacetal can be obtained;
(2>Using allyl 2,2-dimethoxyethylcarbamic acid as raw material, aminoacetaldehyde dimethyl acetal is obtained through Ni (II) catalyzed hydrolysis;
(3>Using 2-(2,2-dimethoxyethyl)-1H-isoceran-1,3(2H)-dione as raw material, in sodium bisulfite and sodium hydroxide aqueous solution Hydrolyze to obtain aminoacetal dimethyl acetate;
The first two synthesis methods are not suitable for industrial production due to low reaction yield and high cost. The third method is a hydrolysis reaction with low yield and the reaction time is too long, so it is not suitable for industrial production.
Preparation method[2]
Directly mix chloroacetal dimethyl acetal and ammonia solution containing carbon dioxide in proportion to react. After the reaction is completed, the ammonia is removed. Then, after cooling the system, add liquid caustic soda to the system to adjust the pH to alkaline, and continue to raise the temperature. All the product and water are evaporated, and highly polar alcohols are added to the evaporated solution, followed by distillation under reduced pressure to obtain high-purity aminoacetaldehyde dimethyl acetal.
Further, the molar ratio of chloroacetal dimethyl acetal: ammonia: water: carbon dioxide is controlled at 1:25-35:70-90:3-5.
Further, control the reaction pressure between 1.0-1.5MPa and the reaction temperature between 120-150°C.
Further, the reaction solution after deamination is boiled and refluxed in the kettle for 4-8 hours to obtain the hydrochloride of aminoacetaldehyde dimethyl acetal while recovering carbon dioxide, and then the system temperature is lowered to below 30°C, and then added to Add liquid caustic soda to the system.
Further, add liquid caustic soda to adjust the pH to 10-12.
Further, the highly polar alcohol is glycerol, ethylene glycol or polyethylene glycol.
Further, continue to raise the temperature to 130-150°C to steam out all the product and water.
Furthermore, the preferred molar ratio of chloroacetal dimethyl acetal:ammonia:water:carbon dioxide is 1:30-35:75-85:3.5-4.5.
In practice, this process can reduce the consumption of ammonia and water, achieve the same yield as the traditional process under higher concentration conditions, and reduce the demand for energy. Under the same ratio, The yield is about 10-20% higher than that of traditional processes, which can save energy, reduce consumption, and increase quality.
Reference materials
[1] Huang Zhen. Synthesis of a Series of Aminoacetal Acetal Compounds[D]. 2015.
[2] Bai Shenke, Yang Fengle, Ma Hua. A production process of aminoacetal dimethyl acetal:, 2019.
