The synthesis method of Piracetam

Introduction

2-Pyrrolidone acetamide, also known as piracetam, pirroxil, pyracetam, pyramem and 2-pyrrolidinone acetamide, is a derivative of 2-pyrrolidone. Molecular formula: C6H10N2O2, molecular weight: 142.1558. It is a white crystalline powder with a melting point of 151.5 to 152.5 °C. It is odorless and tastes slightly bitter. 2-Pyrrolidone acetamide is soluble in water, slightly soluble in ethanol, and almost insoluble in ether.

Piracetam was used as an anti-vertigo and antiemetic drug in the early stage. It is currently used as a nervous system nutrition medicine to promote and enhance the brain's memory function. It is effective for senile memory loss and for the intelligence improvement of some low-skill children. It also has a certain effect on memory and thinking disorders caused by Alzheimer's disease and brain trauma.

Synthesis method

The process of manufacturing 2-pyrrolidone acetamide includes three steps. Firstly, 2-pyrrolidone reacts with sodium methoxide to yield the sodium salt of 2-pyrrolidone. Secondly, the sodium salt of 2-pyrrolidone reacts with ethyl chloroacetate to form ethyl 2-pyrrolidoneacetate by condensation reaction. Thirdly, ethyl 2-pyrrolidoneacetate reacts with ammonia to produce 2-pyrrolidone acetamide by amination:

About 850 kg of 2-pyrrolidone was dissolved in sodium methoxide solution to form sodium salt of 2-pyrrolidone, which was soluble in water. After the crystals were dissolved in a solvent, a condensation reaction added about 128 kg of ethyl chloroacetate to form ethyl 2-pyrrolidoneacetate. Ammonia gas was introduced, stirring the reaction mixture for 2 h. Then, the reaction mixture was allowed to stand, crystallized, and dried to obtain 2-pyrrolidone acetamide. The yield was 76%.

References

[1] Andrei G Malykh, M Reza Sadaie. “Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders.” Drugs 70 3 (2010): 287–312.

[2] Li, Sifang. “Manufacture of Fine Chemicals from Acetylene.” 2021. 0.