Sulfolane: A Versatile Dipolar Aprotic Solvent

Sulfolane is a highly stable and attractive alternative to other more common dipolar aprotic solvents such as DMSO, DMF, DMAC, and NMP. Sulfolane is more toxic than the other solvents but has a very low skin penetration in comparison to that of the others. A high skin penetration is not beneficial for organic solvents as dissolved toxic compounds might be transferred through the skin. Sulfolane has a high dipole moment (μ = 4.7 debye), elevated relative permittivity (ευ = 43.4), and a high Hildebrand solubility parameter (δ = 27.2 [MPa]1/2). This means a high solvency power for reactions containing polarizable intermediates. Sulfolane is capable of strong solvation of cations by the oxygens in the sulfone group which increases the nucleophilicity of the corresponding less solvated anions. With its high stability against strong acids and bases as well as its thermal stability sulfolane is a solvent that can be operated within a wide range of reaction conditions. This makes it the solvent of choice for different acid-catalyzed reactions at elevated temperatures. Sulfolane has also found use in halo exchange reactions for the formation of various fluoroaromatic compounds. It has also been used as solvent for oxidations, nitrations, rearrangements, phosphonylations, and condensation reactions.