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


Ibis O., ZORA M.

TETRAHEDRON, vol.76, no.48, 2020 (Peer-Reviewed Journal) identifier identifier

  • Publication Type: Article / Article
  • Volume: 76 Issue: 48
  • Publication Date: 2020
  • Doi Number: 10.1016/j.tet.2020.131650
  • Journal Name: TETRAHEDRON
  • Journal Indexes: Science Citation Index Expanded, Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chimica, EMBASE, Veterinary Science Database
  • Keywords: 1,4-Oxazepine, N-Propargylic beta-enaminone, N-chlorosuccinimide, Zinc chloride, Alkynes, Cyclization, ONE-POT SYNTHESIS, HIV-1 REVERSE-TRANSCRIPTASE, CHLORIDE MEDIATED SYNTHESIS, MEDICINAL CHEMISTRY, INTRAMOLECULAR CYCLIZATION, PGE(2) ANTAGONIST, CASCADE SYNTHESIS, INHIBITORS, AMOXAPINE, DIACYLHYDRAZINE

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 beta-enaminones underwent chlorination to afford alpha-chlorinated N-propargylic beta-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 beta-enaminone systems, alpha-chlorination exclusively preponderates over the formation of chloronium ion. The method was found to be general for a diversity of N-propargylic beta-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 alpha-chlorinated N-propargylic beta-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. (C) 2020 Elsevier Ltd. All rights reserved.