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

Abstract

Dipolar aprotic and ethereal solvents comprise just over 40% of all organic solvents utilized in synthetic organic, medicinal, and process chemistry. Unfortunately, many of the common “go-to” solvents are considered to be “less-preferable” for a number of environmental, health, and safety (EHS) reasons such as toxicity, mutagenicity, carcinogenicity, or for practical handling reasons such as flammability and volatility. Recent legislative changes have initiated the implementation of restrictions on the use of many of the commonly employed dipolar aprotic solvents such as dimethylformamide (DMF) and N -methyl-2-pyrrolidinone (NMP), and for ethers such as 1,4-dioxane. Thus, with growing legislative, EHS, and societal pressures, the need to identify and implement the use of alternative solvents that are greener, safer, and more sustainable has never been greater. Within this review, the ubiquitous nature of dipolar aprotic and ethereal solvents is discussed with respect to the physicochemical properties that have made them so appealing to synthetic chemists. An overview of the current legislative restrictions being imposed on the use of dipolar aprotic and ethereal solvents is discussed. A variety of alternative, safer, and more sustainable solvents that have garnered attention over the past decade are then examined, and case studies and examples where less-preferable solvents have been successfully replaced with a safer and more sustainable alternative are highlighted. Finally, a general overview and guidance for solvent selection and replacement are included in the Supporting Information of this review.

Recyclable and Convenient-to-Handle Pt/Ethylene Glycol Catalytic System – an Approach to Sustainable Hydrosilylation

“…10 EG is an inexpensive, commercially available, low-toxic and nonvolatile solvent. 11 Like other alcohols, it can reduce metal ions, including those of platinum. An important feature of EG, like other polyols, is that it can act as a ligand and stabilizer of M 0 -particles.…”

“…Furthermore, we studied the prospects of the Pt/EG-catalytic system in the synthesis of linear ( 8) and cross-linked (11) organosiloxane polymers (Figure 2). Note: (a) 6 (0.225 mmol, 0.042 g, 1 eq), 7 (0.225 mmol, 0.…”

Regioselective Magnesiations of Fluorinated Arenes and Heteroarenes Using Magnesium‐bis‐Diisopropylamide (MBDA) in Hydrocarbons

“…Also, Lessène and Bordeau reported the regio‐ and stereo‐selective generation of silyl enol ethers with magnesium‐ bis ‐diisopropylamide (MBDA) 4 [12b] . The use of an apolar, industrially friendly [13] solvent compared to THF should suppress any aryne formation and allow magnesiations at non‐cryogenic temperatures. Thus, treating i Pr 2 NH (DA) with commercially available Bu 2 Mg [14] in hexanes (25 °C, 4 h) produced a light‐yellow ca.…”

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

“…The pharmaceutical industry and other institutions such as the ACS Green Chemistry Institute (ACS GCI), the University of York and several others have edited a number of solvent guides that are very useful for synthetic chemists. [13][14][15][16][17][18][19][20][21][22][23][24][25][26] The ACS GCI also made an online tool available to select solvents based on many properties, which the user can easily filter on. 30 These guides are excellent documents which classify solvents based on holistic sustainability assessments, 31 i.e.…”