Sulfonamide bond cleavage in benzenesulfonamides and rearrangement of the resulting p‐aminophenylsulfonyl cations: application to a 2‐pyrimidinyloxybenzylaminobenzenesulfonamide herbicide

Abstract

AbstractThe gas‐phase fragmentation/rearrangement reactions of compound 1, [2‐(4,6‐dimethoxypyrimidin‐2‐yloxy)‐benzyl]‐[4‐(piperidine‐1‐sulfonyl)phenyl]amine, have been examined by Fourier transform ion cyclotron resonance mass spectrometry (FTICR‐MS). The analyses reveal that under sustained off‐resonance irradiation collision‐induced dissociation (SORI‐CID) conditions in the FTICR cell, protonated 1 undergoes two competitive pathways initiated by different protonation positions. The first pathway is initiated by protonation on the amino group and yields only one fragment ion due to loss of the entire benzenesulfonamide moiety. In the second pathway, protonation of the sulfonamide group leads to cleavage of a sulfonamide bond with loss of the neutral piperidine, followed by loss of SO via a sulfonyl cation rearrangement. An intramolecular SNAr mechanism is proposed to rationalize the rearrangement of the p‐aminophenylsulfonyl cation and the resulting SO loss. To test the generality of this process, SORI‐CID spectra of protonated sulfamethoxazole and of the p‐aminophenylsulfonyl cation (SBN) were obtained. For the SBN ion, SORI‐CID experiments as well as density functional theory (B3LYP) calculations show that rearrangement, assigned as a SNAr reaction of the sulfonyl cation group, can account for the observed SO loss process. Candidate transition state structures were optimized at the B3LYP/6‐31+G (d, p) level of theory using the Gaussian98 molecular modeling package. The computational results show that the barrier for SO loss from SBN is much lower than that for SO2 loss, which satisfactorily rationalizes the SORI‐CID experimental results for SBN. Moreover, it is proposed that a fragment ion at m/z 196 in the MS/MS spectrum of protonated 1 is formed via the ion resulting from SO loss via a second intramolecular SNAr mechanism. Copyright © 2005 John Wiley & Sons, Ltd.