Unconventional Ethereal Solvents in Organic Chemistry: A Perspective on Applications of 2-Methyltetrahydrofuran, Cyclopentyl Methyl Ether, and 4-Methyltetrahydropyran

Abstract

Solvents are crucial platforms in organic synthesis. Thereby, the choice of a solvent is critical in order to develop sustainable eco-friendly synthetic methodologies. Hence, the present consensus is to employ environmentally friendly solvents which have broad applications in fine chemical syntheses, especially from the context of large-scale industrial preparations. In this review, we provide several examples for the utilization of 2-MeTHF, CPME, and 4-MeTHP in several organic reactions pertaining to organometallic-, organo-, and biocatalysis and highlight their potential use as benign alternatives to conventional ether solvents. These solvents have favorable physical and chemical characteristics, such as low toxicity and high chemical and thermal stabilities, which make them promising media for a large breadth of synthetic chemistry and triggers development of reactions with green chemistry protocols.

A case study in green chemistry: the reduction of hazardous solvents in an industrial R&D environment

“…Similarly, we observed the increased usage of greener MeTHF 64–68 as a solvent from year to year (Fig. 17).…”

“…16. 63 Similarly, we observed the increased usage of greener MeTHF [64][65][66][67][68] as a solvent from year to year (Fig. 17 This was particularly noticeable in the preparation of Grignard reagents.…”

Replacement of Less-Preferred Dipolar Aprotic and Ethereal Solvents in Synthetic Organic Chemistry with More Sustainable Alternatives

“…For further reviews of 2-MeTHF use, see Pace et al 2012, 153 Monticelli et al 2017, 160 and most recently Bijoy et al 2021. 162 …”

“…Applications where it has been successfully employed include organometallic chemistry, transition metal catalysis, acid catalysis, amidation reactions, oxidations, radical reactions, and as an organic phase in biphasic chemistry. 168 For specific examples, see reviews by Azzena et al, 168 Watanabe et al., 165 and most recently Bijoy et al 162 …”

“…Depending on the details of the reaction concerned, it is therefore easily conceivable that the increased cost of purchase could be offset by other reduced costs (e.g., less aqueous waste for incineration). For further reviews of 2-MeTHF use, see Pace et al 2012, Monticelli et al 2017, and most recently Bijoy et al 2021 …”