Base-Induced Fragmentation of β-Hydroxy Nitrosamines

Article abstract of DOI:10.1021/jo00146a003

β-Hydroxy nitrosamines have been found to undergo a base-induced fragmentation reaction.The reaction cleaves the C_α-C_β bond of the substrate to produce an aldehyde or ketone and a smaller alkylnitrosamine.Rate contants for the fragmentation induced by potassium tert-butoxide in THF or tert-butyl alcohol have been measured for nine substrates at temperatures between 35 and 70 deg C.The rate constants are a function of base concentration and range between 0.15x10^-6 and 308x10^-6 s^-1.Rate constants have been determined for (2-hydroxyethyl)methylnitrosamine,N-nitrosodiethanolamine, (2-hydroxy-2-methylpropyl)methylnitrosamine, (2-hydroxy-2-phenylethyl)methylnitrosamine, N-nitrosoephedrine, (2-hydroxy-2,2-diphenylethyl)methylnitrosamine, and (2-hydroxy-2-phenylpropyl)methylnitrosamine.The nitrosamino alcohol fragmentation rates are in the order tertiary > secondary > primary, and the rate appears to be a function of product stability and steric strain in the substrate.A mechanism which accounts for these observations is proposed.