N-Alkylation and Aminohydroxylation of 2-Azidobenzenesulfonamide Gives a Pyrrolobenzothiadiazepine Precursor whereas Attempted N-Alkylation of 2-Azidobenzamide Gives Benzotriazinones and Quinazolinones

Muslih S. Hamasharif, Oliver E.P. Smith, Collette J. Curran, Karl Hemming

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N-Alkylation of 2-azidobenzenesulfonamide with 5-bromopent-1-ene gave an N-pentenyl sulfonamide, which underwent intramolecular aminohydroxylation to give an N-(2-azidoaryl)sulfonyl prolinol, a precursor for the synthesis of a pyrrolobenzothiadiazepine. The attempted N-alkylation of 2-azidobenzamide gave a separable mixture (∼1:1) of a benzotriazinone and a quinazolinone in a 72% combined yield. Other primary alkyl halides (3 examples) gave similar mixtures of benzotriazinones and quinazolinones. Benzylic, allylic, and secondary and tertiary alkyl halides (5 examples) gave only benzotriazinones in moderate yields. The results of mechanistic studies show the likely involvement of nitrene intermediates in the quinazolinone pathway and a second pathway involving a dimethylsulfoxide or dimethylsulfide-mediated conversion of 2-azidobenzamide into benzotriazinones.

Original languageEnglish
Pages (from-to)1222-1231
Number of pages10
JournalACS Omega
Issue number3
Publication statusPublished - 31 Mar 2017


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