The synthesis of valproic acid from diethyl malonate
diethyl malonate, which is a common raw material for organic synthesis. With it as the starting point, valproic acid can be prepared. The method is as follows:

First, diethyl malonate reacts with appropriate halogenated hydrocarbons under alkaline conditions. Alkalis, such as sodium ethyl alcohol, can cause the methylene hydrogen of diethyl malonate to leave and generate carbonegative ions. This carbonegative ion has strong nucleophilic properties and can undergo nucleophilic substitution reactions with halogenated hydrocarbons. When selecting halogenated hydrocarbons,

should be selected according to the structure of valproic acid. After this reaction, a specific alkyl group is introduced into the methylene of diethyl malonate.

Then, the obtained product is hydrolyzed. Acid or base is used as catalyst to hydrolyze the ester group to carboxylic group. If alkali is used to catalyze hydrolysis, it needs to be acidified later to obtain a product containing carboxyl groups.

Furthermore, the product after hydrolysis is decarboxylated. Under appropriate conditions, the carbon-carbon bond between the carboxyl group and the adjacent methylene group is broken, and carbon dioxide is removed to obtain valproic acid.

The whole process of synthesis, the reaction conditions of each step are very important. The amount of base, the reaction temperature and time length all affect the reaction yield and purity. After fine operation and optimization of conditions, high-purity valproic acid can be obtained.