Regioselective bromination: Synthesis of brominated methoxyquinolines

Cakmak O., Okten S.

TETRAHEDRON, vol.73, no.36, pp.5389-5396, 2017 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 73 Issue: 36
  • Publication Date: 2017
  • Doi Number: 10.1016/j.tet.2017.07.044
  • Journal Name: TETRAHEDRON
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.5389-5396
  • Keywords: Quinoline, 1,2,3,4-Tetrahydroquinoline, Bromo quinoline, Methoxy quinoline, Bromination of methoxy quinoline, Multifunctionalization of quinoline, Regioselective bromination, Molecular bromine, QUINOLINE DERIVATIVES, CATALYZED SYNTHESIS, SUBSTITUTION, CYCLIZATION, EFFICIENT, WATER
  • Yıldız Technical University Affiliated: No

Abstract

Simple synthetic methods are described for the synthesis of valuable polyfunctional brominated methoxyquinolines 10-13, 20-21, and 24-25. Three regioselective routes are described for convenient preparation of brominated methoxyquinolines at the C-2, C-3, and C-5 positions with consecutive reaction steps under mild reaction conditions using molecular bromine. While bromination of 6-bromo-8methoxy-1,2,3,4-tetrahydroquinoline (8) selectively gave 3,6-dibromo-8-methoxyquinoline (10) and 3,5,6-tribromo-8-methoxyquinoline (11), the reaction of 6,8-dimethoxy-1,2,3,4-tetrahydroquinoline (9) resulted in the formation of 3-bromo-6,8-dimethoxyqinoline (12) and tribromide 13. On the other hand, direct bromination of 6-methoxy- 17 and 6,8-dimethoxyquinoline (19) gave 5-bromo derivatives 20 and 21. However, the reaction 3,6-dimethoxyquinoline (8) resulted in dibromination to form 2,5dibromoquinoline (24). This process selectively led to functionalization of the quinoline ring at both the C-2 and C-5 positions. (C)2017 Elsevier Ltd. All rights reserved.