The displacement of aromatic halides by secondary amines in DMSO has been studied rather extensively. The fluoro-compounds undergo substitution by various nucleophiles, such as secondary aliphatic and alicyclic amines, at rates 100 to 1000 times faster than their chloro- analogs. The rate of displacement of fluorine is further enhanced by the order of 103 to 105 in dipolar aprotic solvents, such as DMSO, as compared with reactions in aprotic solvents [Miller, J.; Parker, A. J., J. Am. Chem. Soc. 83, 117-123 (1961)]. Thus, 4-fluoroacetophenone undergoes a very rapid displacement of the halogen by amines, such as morpholine, in DMSO and affords in high yields the corresponding 4-amino derivatives, which are otherwise difficult to prepare [Bader, H.; Hansen, A. R.; McCarty, F. J., J. Org. Chem. 31, 2319-2321 (1966)].
X = F, Cl, Br
The yields of products obtained in DMSO are higher than those obtained with DMF under comparable conditions.
See the work on Comparative Reaction Solvents.
