Efforts to Replace Methylene Chloride in Pharmaceutical Process Chemistry

Abstract

Methylene chloride (MC) or dichloromethane is a halogenated organic solvent of choice used in many chemical industries such as pharmaceutical, insecticide, paint, and polymer industries. Several health hazards associated with the use of MC are known to us through available literature. MC is reported to be a potential neurotoxic, cardiotoxic, cancer-causing, and tissue-damaging agent. Inhalation and direct skin contact are the major routes of exposure to MC in occupational environments. Most government agencies and environment, health and safety forums throughout the world have recognized MC as a hazardous solvent and have kept strict regulatory control on the usage of MC. MC is a Class 2 solvent as per ICH guidelines. This review article presents some case studies where MC has been replaced in commercial synthetic processes and column chromatography by other solvents and solvent mixtures, demonstrating that it is possible to either reduce the usage or replace MC in process chemistry. Many industrial and academic efforts have brought in place several solvent selection guides helpful for effectively replacing MC from existing or planned synthetic processes. Sustainable and environment-friendly synthetic processes can be developed by implementing the concept of green chemistry, such as replacing the use of MC in the existing chemical processes and avoiding the use of MC in future chemical processes. Successful introduction of MC-free chemical processes in the pharmaceutical industry can surely be achieved with continuous efforts in this direction.