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

doi:10.1021/acsomega.7b00211

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

ACS Omega. 2017 Mar 31;2(3):1222-1231. doi: 10.1021/acsomega.7b00211.

Authors

Muslih S Hamasharif¹, Oliver E P Smith¹, Collette J Curran¹, Karl Hemming¹

Affiliation

¹ Department of Chemistry, University of Huddersfield, Queensgate, Huddersfield, West Yorkshire HD1 3DH, United Kingdom.

Abstract

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.