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

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1222-1231
Number of pages10
JournalACS Omega
Volume2
Issue number3
DOIs
Publication statusPublished - 31 Mar 2017

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Quinazolinones
Alkylation
Sulfonamides
Dimethyl Sulfoxide
o-azidobenzenesulfonamide
Pathway

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title = "N-Alkylation and Aminohydroxylation of 2-Azidobenzenesulfonamide Gives a Pyrrolobenzothiadiazepine Precursor whereas Attempted N-Alkylation of 2-Azidobenzamide Gives Benzotriazinones and Quinazolinones",
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.",
author = "Hamasharif, {Muslih S.} and Smith, {Oliver E.P.} and Curran, {Collette J.} and Karl Hemming",
year = "2017",
month = "3",
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doi = "10.1021/acsomega.7b00211",
language = "English",
volume = "2",
pages = "1222--1231",
journal = "Omega",
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N-Alkylation and Aminohydroxylation of 2-Azidobenzenesulfonamide Gives a Pyrrolobenzothiadiazepine Precursor whereas Attempted N-Alkylation of 2-Azidobenzamide Gives Benzotriazinones and Quinazolinones. / Hamasharif, Muslih S.; Smith, Oliver E.P.; Curran, Collette J.; Hemming, Karl.

In: ACS Omega, Vol. 2, No. 3, 31.03.2017, p. 1222-1231.

Research output: Contribution to journalArticle

TY - JOUR

T1 - N-Alkylation and Aminohydroxylation of 2-Azidobenzenesulfonamide Gives a Pyrrolobenzothiadiazepine Precursor whereas Attempted N-Alkylation of 2-Azidobenzamide Gives Benzotriazinones and Quinazolinones

AU - Hamasharif, Muslih S.

AU - Smith, Oliver E.P.

AU - Curran, Collette J.

AU - Hemming, Karl

PY - 2017/3/31

Y1 - 2017/3/31

N2 - 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.

AB - 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.

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