Regioselective bromination: Synthesis of brominated methoxyquinolines

Cakmak O. , Okten S.

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

  • Publication Type: Article / Article
  • Volume: 73 Issue: 36
  • Publication Date: 2017
  • Doi Number: 10.1016/j.tet.2017.07.044
  • Title of Journal : TETRAHEDRON
  • 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


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.