Non-stereospecific Ring Expansion Reactions of Benzothiazoline Sulfoxides

Abstract

The stereochemistry of novel ring expansions of benzothiazoline sulfoxides to benzothiazines by reaction with acetic anhydride was examined. Reaction of trans-3-acetyl-2-ethyl-2-methyl-benzothiazoline 1-oxide with acetic anhydride afforded 4-acetyl-3-ethylidene-2, 3-dihydro-4H-1, 4-benzothiazine and 4-acetyl-3-ethyl-4H-1, 4-benzothiazine, which are the products expanded in the direction of the substituent cis to the sulfoxide moiety, and 4-acetyl-2-methyl-3-methylene-2, 3-dihydro-4H-1, 4-benzothiazine and 4-acetyl-2, 3-dimethyl-4H-1, 4-benzothiazine, which are the products expanded in the opposite direction (trans). Similar results were also obtained from the reaction of the sulfoxides, trans-4-acetyl-2-benzyl-2-methylbenzothiazoline 1-oxide, and cis-and trans-3-acetyl-2-ethoxycarbonylmethyl-2-methylbenzothiazoline 1-oxides, with acetic anhydride. Thus, it was confirmed that this ring expansion is non-stereospecific and quite different from the similar ring transformation of penicillin sulfoxides to cephalosporins. The major factor in this non-stereospecificity was found to be an easy cleavage of the C₂-S bond of the benzothiazoline ring due to electronic effects of the nitrogen atom at the β-position to the sulfur atom in comparison with the ring expansions of related six-membered benzothiazine sulfoxides and thiochroman sulfoxides.