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

• Published in: Journal of physical organic chemistry Vol. 12; no. 5; pp. 357 - 363
• Main Authors: Polyakov, Vladimir A., Nelen, Marina I., Nazarpack-Kandlousy, Noureddin, Ryabov, Alexander D., Eliseev, Alexey V.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.05.1999
• Subjects: aqueous 'dynamic' combinatorial libraries; imine exchange; kinetics; oximes; thermodynamics
• ISSN: 0894-3230; 1099-1395
• DOI: 10.1002/(SICI)1099-1395(199905)12:5<357::AID-POC129>3.0.CO;2-Y

Kinetics and mechanisms of the imine exchange reactions of O‐alkyl and O‐aryl oximes with O‐alkyl‐ and O‐aryloxyamines, respectively, were studied by 1H NMR spectroscopy in aqueous solutions. The reaction between benzaldehyde O‐methyloxime and O‐ethylhydroxylamine at 60 °C is first order in both oxime and the alkoxylamine (the second‐order rate constant k2 = 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‐diaminooxypropane with bifunctional oximes. Testing of various additives as potential catalysts for the reaction revealed imidazole as a moderately effective 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 rate‐limiting hydration of the oxime molecule. Mechanisms of the exchange reactions are discussed in relation to their possible use to generate diverse pools of compounds for the recently proposed ‘dynamic’ combinatorial chemistry approach. Copyright © 1999 John Wiley & Sons, Ltd.