Isothiazole chemistry. V. Acylation and acyl migration in 3-hydroxyisothiazole

Abstract

In aprotic solvents acylation of 3-hydroxyisothiazole is subject to kinetic control, leading almost exclusively to the 3-acyloxyisothiazoles. On heating or standing a reversible O → N migration occurs, the final composition of the mixture depending on the nature of the acyl group. Where aliphatic acyl groups are involved (RCO: R = CH₃, C₂H₅, C₃H₇, ClCH₂, CH₃O, C₂H₅O) the tendency towards migration to nitrogen is inversely related to the size of the group, whereas with aromatic groups (R = C₆H₅, 4-MeC₆H₄, 4-NO₂C₆H₅, 3,5-(NO₂)₂C₆H₃, C₆H₅CH₂), little or no N-acyl derivative results. Sulphonyl halides lead only to 0-sulphonyl derivatives, which presumably do not rearrange. The migration of the acyl group is shown to be intermolecular, involving both O + O and O → N migration, by the usual mixed migration experiments, and is catalysed by 3-hydroxyisothiazole and other nucleophiles. The greater thermodynamic stability of the O- or ,N-acyl derivatives, as revealed by equilibrium measurements, is seen to be a function of the steric requirements of the acyl group, the larger groups being more stable on oxygen. Examination of the infrared spectra reveals that this is probably due to out-of-plane twisting in the N-acyl-3- isothiazolones, which prevents N-CO overlap in all derivatives except the formyl which exists as 100% N-formyl at equilibrium.