Improved Preparation of α,N-Diphenylnitrones and N-Benzyl-N-Phenylhydroxylamines by direct Oxidation of Secondary Anilines
✍ Scribed by John W. Gorrod; Nigel J. Gooderham
- Publisher
- John Wiley and Sons
- Year
- 1986
- Tongue
- English
- Weight
- 346 KB
- Volume
- 319
- Category
- Article
- ISSN
- 0365-6233
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✦ Synopsis
A simple and rapid method for the oxidation of secondary anilines to a,N-diphenylnitrones and the subsequent reduction to secondary N-benzyl-N-phenylhydroxylamines is described.
Verbesserte Synthese von a,N.Diphenylnitronen und N-Benzyi-N-phenylhydroxylaminen durch direkte Oxidation von sekundären Anüien Es wird Über eine einfache und schnelle Methode der Oxidation von sekundären Anilinen zu a,N-Diphenylnitronen und deren nachfolgende Reduktionen zu sekundären N-Benzyl-N-phenylhydroxylaminen berichtet.
To facilitate our studies of the metabolism of N-alkylanilines, authentic samples of N-oxidised derivatives were required to help identify and quantitate metabolites. However, examples of such compounds are few and the literature on their chemica1 properties differ. Renner" reviewed the synthesis of N-methyl-N-phenylhydroxylamine in an attempt to resolve the conflicting reports concerning this compound. Attempted preparations included the reactions of methyl halides and dimethyl sulphate with phenylhydroxylamine'), of nitro compounds with Grignard reagents') and hydrolysis and deamination of N-methyl-N-acetoxy-4-aminoaniline4). More recently, the preparation of N-methyl-N-phenylhydroxylamine has been reported in which a modified Cope elimination procedure was employed with N-methyl-N-ethylaniline-N-oxide5.6'. No isolation or identification data were reported as the product was very unstable. The preparation of N-ethyl-N-phenylhydroxylamine and the 4-tolyl derivative were first described by Utzinger and Regenass7), and repeated by Renner'). The products, obtained by the action of alkylhalide on the appropiate phenylhydroxylamine, were very unstable. The Same authors als0 reported the synthesis of N-n-butylphenylhydroxylamines and N-benzyl-N-phenylhydroxylamine using similar te~hniques'.~). An alternative approach to preparing N-substituted phenylhydroxylamines was adopted by Calder and Forrestep), who reacted Crignard reagents with 2-methyl-2-nitrosopropane to yieid a series of N-t-butyl derivatives. Methods commonly used for the synthesis of N, N-disubstituted hydroxylamines generally require rigorous conditions'). However, when one of the nitrogen substituents is a phenyl group, the required molecule is often unstable, and considerable difficulty has been experienced in the preparation of such simple N-alkyl-N-phenylhydroxylamines. In the majority of successful methods, preparation of the desired product was achieved using phenylhydroxylamine derivatives and alkylhalide. In nearly every case the resulting reaction was lengthy and subsequent isolation and purification of the product difficult.