Base-Promoted Ring-Opening and Elimination of 4-Chloro- and 4-(Methylthio)azetidinones

Article abstract of DOI:10.1021/jo00297a048

In a search for elimination within the β-lactam ring, reactions of N-phenyl- and N-benzyl-, 4-chloro-, and 4-(methylthio)azetidinones with sodium methoxide in methanol have been investigated.The products formed are enamine esters, consistent with the occurrence of both an elimination reaction and opening of the β-lactam ring.Substituent and leaving-group effects indicate, however, that ring-opening is the first and rate-controlling reaction and that elimination occurs from an initially formed ring-opened intermediate.Thus a small leaving-group rate ratio (k_Cl/k_SMe) and insensitivity of the rate to the stereochemistry of cis- and trans-3-(tosyloxy)-4-chloro substituents rule out elimination by a concerted mechanism (E2), while similar substituent effects at the 3- and 4-positions, and reaction at the predicted rate for β-lactam methanolysis, exclude a carbanion mechanism (E1cB).Also, for the thiomethyl leaving group, 1,2-rearrangement, a reaction almost certainly occurring after ring-opening, competes with elimination.For β-lactams with a 4-chloro substituent and a relatively basic nitrogen atom, solvolysis accompanies ring-opening, but substitution and not elimination products are formed.It is concluded that more effective carbanion and double bond stabilizing substituents than used in this investigation will be required to observe the sought for elimination.