Specific Solvent Issues with the SNAr Reaction
In assessing the greenness of an SNAr reaction, solvent issues tend to predominate and the reprotoxic solvents like NMP, MEP, DMF, DMAC, TMU, DMI, DMPU and sulfolane should be avoided or replaced where possible.
DMF
The combination of NaH/DMF is still commonly seen in experimental procedures for SNAr and SN2 reactions. While many small scale experiments proceed without incident, this combination can decompose very exothermically leading to loss of thermal control and potential explosion.
While less serious than safety concerns listed above, the use of NaH-DMF mixture can lead to by-products resulting from the decomposition of DMF – notably Me2NH.
The use of strong bases, especially Na/K hydrides with any dipolar aprotic solvent should really be avoided
Org. Proc. Res. Dev., 2003, 7, 1029–1033 Safety Notables: Information from the Literature
Sulfolane
Sulfolane has recently been listed with H360- may damage fertility or the unborn child.
National Institute of Environmental Health Sciences report on sulfolane
DMSO
DMSO has very little adverse data around human and environmental toxicity but can decompose violently at high temperatures. The presence of certain bases/electrophiles can considerably lower the temperature at which this decomposition occurs. These safety issues have been well documented.
Org. Process Res. Dev. 2012, 16, 1994–2000 Safety Concerns in a Pharmaceutical Manufacturing