Cyclopentyl methyl ether (CPME) and 4-methyltetrahydropyran (4-MeTHP): Basic chemical properties and applications as next generation reaction solvents

The solvent of a reaction is an important element in the synthetic preparation of chemical and pharmaceutical products. The uses of green solvents that balance safety, health and environmental aspects are increasingly desirable these days, especially in pilot-scale syntheses. Due to ease of handling, good solubility and low reactivity with reactants, low-molecular-weight ethers such as diethyl ether (Et2O), tetrahydrofuran (THF), and tert-butyl methyl ether (TBME) are often used in laboratory-scale syntheses. These solvents, however, are less than ideal for large-scale synthesis due to their high inflammability, non-recyclabilty, and aptitude to form peroxides as well as volatile organic compound (VOC) emissions. Herein, I showcase the applicability of two recently developed, recyclable ethereal solvents, cyclopentyl methyl ether (CPME) and 4-methyltetrahydropyran (4-MeTHP), in organic synthesis, and their potential as alternatives to not only conventional ethers but also harmful aromatic hydrocarbon and halogenated solvents. In addition, the basic chemical properties involving stability and reactivity against free-radical, organometallic, oxidation, and other conditions, as well as possible degradation pathways are reported. These comprehensive studies are expected to inform a broad range of synthetic chemists, from beginners to professional process chemists, who require green chemistry perspectives to be met in the advanced organic synthesis of the 21st century.