Imine exchange in O-aryl and O-alkyl oximes as a base reaction for aqueous'dynamic' combinatorial libraries. A kinetic and thermodynamic study

Kinetics and mechanisms of the imine exchange reactions of O-alkyl and O-ar yl oximes with O-alkyl and O-aryloxyamines, respectively, were studied by H -1 NMR spectroscopy in aqueous solutions,The reaction between benzaldehyde O-methyloxime and O-ethylhydroxylamine at 60 degrees C is first order in bo th oxime and the alkoxylamine (the second-order rate constant k(2) = 0.86 /- 0.08 l mol(-1) min(-1) at pD 2.9), the reaction being subject to acidic catalysis. A similar imine transfer was studied in the reaction of 1,3-diam inooxypropane with bifunctional oximes. Testing of various additives as pot ential catalysts for the reaction revealed imidazole as a moderately effect ive catalyst. The exchange in O-aryl oximes was studied in the interaction between 3-pyridinealdehyde O-phenyloxime and O-(p-nitrophenyl)hydroxylamine . The reaction is first order in the oxime, but its rate is independent on the aryloxyamine concentration and pD. The proposed mechanism involves a ra te-limiting hydration of the oxime molecule. Mechanisms of the exchange rea ctions are discussed in relation to their possible use to generate diverse pools of compounds for the recently proposed 'dynamic' combinatorial chemis try approach. Copyright (C) 1999 John Wiley & Sons, Ltd.