A facile synthesis of 6-chloro-2-methylene-2,3-dihydro-1,4-oxazepines from N-propargylic β-enaminones

Ozge Ibis, Metin Zora*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

A new and efficient method for the synthesis of 6-chloro-substituted 2-methylene-2,3-dihydro-1,4-oxazepines has been demonstrated. Upon treatment with N-chlorosuccinimide in acetonitrile, N-propargylic β-enaminones underwent chlorination to afford α-chlorinated N-propargylic β-enaminones, which was then subjected to electrophilic cyclization with zinc chloride in refluxing chloroform to yield 6-chloro-2-methylene-2,3-dihydro-1,4-oxazepines. It was shown for the first time that on N-propargylic β-enaminone systems, α-chlorination exclusively preponderates over the formation of chloronium ion. The method was found to be general for a diversity of N-propargylic β-enaminones and tolerated the presence of a wide range of aryl, heteroaryl and alkyl groups with electron-donating and electron-withdrawing substituents. The method was also applicable as the one-pot two-step process without isolating the intermediate α-chlorinated N-propargylic β-enaminones. This operationally easy method may provide a rapid entry to a library of highly functionalized 6-chloro-2-methylene-2,3-dihydro-1,4-oxazepines with potential medicinal applications for human health.

Original languageEnglish
Article number131650
JournalTetrahedron
Volume76
Issue number48
DOIs
Publication statusPublished - 27 Nov 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Ltd

Keywords

  • 1,4-Oxazepine
  • Alkynes
  • Cyclization
  • N-chlorosuccinimide
  • N-Propargylic β-enaminone
  • Zinc chloride

Fingerprint

Dive into the research topics of 'A facile synthesis of 6-chloro-2-methylene-2,3-dihydro-1,4-oxazepines from N-propargylic β-enaminones'. Together they form a unique fingerprint.

Cite this