Pyrophosphoryl Chloride: A Green, Reductive Chlorination Reagent Utilized in the One-Pot Synthesis of Quetiapine

GRAPHICAL ABSTRACT

Abstract

A one-pot synthesis of quetiapine from dibenzo[b,f][1,4]thiazepin-11(10H)-one and 4-hydroxyethoxy ethyl piperazine (HEEP) in toluene using N,N-dimethylaniline (DMA) and pyrophosphoryl chloride (P₂O₃Cl₄) as a green reductive chlorination agent is described. A significant shortening of reaction times, a nearly quantitative yield, and high atom economy in the product were observed. The simplicity of the reaction, ease of execution, simple workup, and good yields, together with the use of easily accessible starting materials and an environmentally friendly procedure, are hallmarks of this process.

Keywords:

• One-pot synthesis
• quetiapine, pyrophosphoryl chloride
• antipsychotic
• 4-hydroxyethoxy ethyl piperazine (HEEP)

ACKNOWLEDGMENT

The partial support of this research by the Research Committee of the University of Guilan is gratefully acknowledged. We also acknowledge the useful suggestions made by Douglas Fry of SAFC, USA.