The Toxicological Assessment of Cyclopentyl Methyl Ether (CPME) as a Green Solvent

Kiyoshi Watanabe

doi:10.3390/molecules18033183

Abstract

Cyclopentyl methyl ether (CPME) has been used in chemical synthesis as an alternative to hazardous solvents. According to some earlier investigation by others, CPME has low acute or subchronic toxicity with moderate irritation and negative mutagenicity and negative skin sensitization (Local Lymph Node Assay). Calculated Permitted Daily Exposure (PDE) value of CPME obtained by our 28-day oral toxicity test is 1.5 mg/day, and CPME is thus assumed to be a class 2 equivalent solvent in the ICH (International Conference on Harmonization) Harmonized Tripartite Guideline Q3C (R5). Wide synthetic utility and a detailed toxicity study suggest CPME as a green and sustainable solvent of choice for modern chemical transformations.

Highlights

Ethereal solvents are widely used in chemical synthesis, albeit with some well-known drawbacks for large scale operation [1,2]
To complement our previous reports [2,3,4] as well as those of others [5], we report here the notable utility of cyclopentyl methyl ether (CPME) in organic synthesis, especially in process chemistry research
Many synthetic applications with CPME have been published.Some notable and practical examples of catalytic reactions using CPME as a solvent are summarized in Schemes 1–3

Summary

Introduction

Ethereal solvents are widely used in chemical synthesis, albeit with some well-known drawbacks for large scale operation [1,2]. Under these circumstances, cyclopentyl methyl ether (CPME) has been developed by us as a low toxic alternative solvent with wide synthetic applicability [3]. We disclose some important toxicological evaluations, including acute toxicity and mammalian subchronic toxicity studies and mutagenicity. As it has already been emphasized in our previous review [3], CPME has seven notable physical properties that can be summarized as follows: (1) low peroxide formation; (2) high hydrophobicity;. Many synthetic applications with CPME have been published.Some notable and practical examples of catalytic reactions using CPME as a solvent are summarized in Schemes 1–3

Objectives

Results

Conclusion