Is sulfolane a green solvent?

Introduction

Sulfolane is an organosulfur compound, formally a cyclic sulfone, with the formula (CH2)4SO2. It is a high-boiling (285 °C) dipolar aprotic solvent developed by Shell, and it has been used in industrial applications in gas and oil refining, for example, the Sulfinol Process. Sulfolane can be produced industrially via the reaction of SO2 with butadiene, followed by hydrogenation of the intermediate sulfolene to give sulfolane.

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 compared to the others. High skin penetration is not beneficial for organic solvents as dissolved toxic compounds might be transferred through the skin[1].

Chemical properties and uses

HSP values for sulfolane suggest it has very high solubilizing power for polar compounds, similar to DMSO. However, Sulfolane's hydrogen bond basicity β is much lower at 0.39 compared to DMSO 0.76 and is closer to propylene carbonate in this parameter (π* = 0.90, β = 0.38). Sulfolane is immiscible with alkanes and MTBE, which can allow for facile workups and product extraction of MTBE-soluble products.

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 ofstrongsolvation of cations by the oxygens in the sulfone group, which increases the nucleophilicity of the corresponding less solvated anions. With its high stability againststrongacids and bases and its thermal stability,sulfolaneis a solvent that canbe operatedwithin a wide range of reaction conditions.Thismakes it the solvent for different acid-catalyzed reactions at elevated temperatures. Sulfolane has alsobeen foundto be helpful in halo exchange reactions for the formation of various fluoroaromatic compounds. It has also been used as a solvent for oxidations, nitrations, rearrangements, phosphonylations, and condensation reactions.

Safety

Sulfolane has previously been considered a safer dipolar aprotic solvent, as sulfolane has much lower skin permeability than DMSO, DMF, DMAc, and NMP. Sulfolane, however, has been identified as potentially more hazardous than originally thought. A study on the reproductive toxicity effects of sulfolane in rats has suggested that the solvent could harm the unborn child. Some SDS now carry a H360 warning to reflect this evidence. Furthermore, sulfolane has been recategorized according to the Chem21 solvent selection guide from “recommended” to “hazardous .”Sulfolane contamination of groundwater and drinking water was reported near the oil refinery in Fairbanks, Alaska. Hence, sulfolane is not considered a suitable green solvent[2].

References

[1] Tilstam*, Ulf. “Sulfolane: A Versatile Dipolar Aprotic Solvent.” Organic Process Research & Development 16 7 (2012): 1273–1278.

[2] Andrew Jordan*. “Replacement of Less-Preferred Dipolar Aprotic and Ethereal Solvents in Synthetic Organic Chemistry with More Sustainable Alternatives.” Chemical Reviews 122 6 (2022): 6749–6794.