Base Catalyzed Rearrangement of Penicillin S-Oxide -Selective Formation of Isothiazolone-

Abstract

Isothiazolone [5] has been obtained in good yields by the reactions of penicillin S-oxide with pyridinealcohols. The reaction with 3-pyridinol also gave [5] in a good yield, but the reactions with pyridine, .2- and 4-pyridinol resulted in very low yields, of [5]. These results seem to be attributed to the pyridone structures of pyridinols and imply that hydroxyl g roup may be playing an important role in the formation of isothiazolone. The isothiazolone has also been prepared in good yields in the presence of 1-morpholineethanol, 1-piperidineethanol and triethanolamine. In the presence of primary a n d secondary amines containing hydroxyl group, the isothiazolone can not be isolated. Since thes e amines have a relatively active NH₂- or NH- group, many side reactions are considered to take p lace. A concerted mechanism through the cyclic intermediate can be proposea. The initial path of the reactions seems to be the abstraction, of a proton base followed by the formation of t he cyclic intermediate through the interaction of the hydroxyl group with the sulfenic acid derived from penicillin S-oxide. The reactions o f penicillin S-oxide with pyridinealcohols-phosphoric acid salts are also discussed.