Competing acyl transfer and intramolecular O ? N acyl group migration from an isolable O-acylisourea

Abstract

The O-acylisourea (16a), which is a model for the proposed intermediate in carbodi-imide condensations, and is formed on reaction of the chloride (15) with benzoate ion, was shown using X-ray crystallography to have the Z-configuration. Crystals are monoclinic, space group P21/c with four molecules in a cell of dimensions a= 15.732(3), b= 16.246(5), c= 7.628(1)Å, β= 108.94(1)°. The structure was solved by direct methods and refined by full-matrix least-squares calculations to an R value of 0.044 for 1 281 observed reflexions. The benzoyl group is trans to the lone pair of the imine nitrogen and the CN bond length is 1.286(6)Å. The isourea undergoes uncatalysed (at 25° in 1 : 4 dioxan–water, µ= 1.0) O → N acyl transfer to give the N-acylamide (17) at pH > 7; the slow step is a Z→E isomerisation. At lower pH (3–6), Z→E isomerisation of the isourea (and thus O → N acyl transfer) is acid catalysed, but at pH < than the pKa of (16a), intramolecular acyl transfer is inhibited by protonation of the substrate. Competing intermolecular reaction of (16a) with the solvent [to give the urea (18)] occurs at all pH. In acid, reaction is between the protonated (16a) and water and in base between the free isourea (16a) and hydroxide ion. The O-acylisourea also undergoes rapid intermolecular acyl transfer to a variety of amines, although reaction between the free amine and protonated isourea was too slow to be observed. The implications of these results for the design of conditions to optimise inter-(rather than intra-) molecular reactions in carbodi-imide-mediated condensations are discussed.