Arenesulfonic acids, sulfonylation with

The iso)tazole ring is rather resistant to sulfonation. However, on prolonged heating with chlorosulfonic acid, 5-methyl-, 3-methyl- and 3,5-diraethyl-isoxazoles are converted into a mixture of the sulfonic acid and the corresponding sulfonyl chloride. The sulfonic acid group enters the 4-position even when other positions are available for substitution. The sulfonation of the parent isoxazole occurs only under more drastic conditions (20% oleum) than that of alkyl isoxazoles isoxazole-4-sulfonic acid is obtained in 17% yield. In the case of 5-phenylisoxazole (64), only the phenyl nucleus is sulfonated to yield a mixture of m-and p-arenesulfonic acid chlorides (65) and (66) in a 2 1 ratio (63AHC(2)365). 

Friedel-Crafts-type intermolecular sulfonylation of aromatics can also be conveniently carried out over Nafion-H by reacting aromatics with arenesulfonic acids at reflux temperature with azeotropic water removal465 [Eq. (5.168)]. Methanesulfonic acid also reacts with para-xylene to yield 2-methanesulfonyl-1,4-dimethylbenzene in much lower yield (30%). 

---