Replacement strategies for non-green dipolar aprotic solvents

Abstract

Dipolar aprotic solvents (DMSO, DMF, DMAc, NMP, etc.) have been widely used in organic synthesis and pharmaceutical research because of their remarkable polarities and solubilities, while most of them are not green because of their detrimental effects on human health and hazards to the natural environment caused by their inescapable toxicity as well as large wastewater streams and high-energy-input requirements. This dangerous situation is further complicated by the surging demand of dipolar aprotic solvents in the research and development in the pharmaceutical industry and other chemical processes. Therefore, minimizing and avoiding the use of such solvents has become one of the most important facets of green chemistry. So far, substantial efforts have been devoted in response to this problem that has entailed the development of green and novel reaction systems that fulfill numerous requirements, which are also met by traditional dipolar aprotic solvents. In this context, this review summarizes the methods and strategies for replacing non-green polar aprotic solvents, which mainly include direct replacement with new green alternatives and utilization of polarized catalysts in common green solvents for avoiding the use of conventional polar aprotic solvents. Besides, the strengths and weaknesses of these two strategies are analyzed. Compared with the direct replacement strategy, the rational design of polarized catalysts not only expands the choice of green solvents, but also provides new possibilities for the design and preparation of multifunctional catalysts, suggesting a promising prospect in substitution strategies for non-green polar aprotic solvents. Certainly, other methods are being explored to realize the green and sustainable replacement of conventional dipolar aprotic solvents in an economical and handy tactic.