Efficient and selective synthesis of quinoline derivatives

Sahin A., Cakmak O., Demirtas İ., Okten S., Tutar A.

Tetrahedron, vol.64, no.43, pp.10068-10074, 2008 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 64 Issue: 43
  • Publication Date: 2008
  • Doi Number: 10.1016/j.tet.2008.08.018
  • Journal Name: Tetrahedron
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.10068-10074
  • Keywords: 1,2,3,4-Tetrahydroquinoline, 4,6,8-Tribromoquinoline, Bromination, Lithiation
  • Ondokuz Mayıs University Affiliated: No


The bromination reaction of 1,2,3,4-tetrahydroquinoline (7) was investigated by NBS and molecular bromine. One-pot synthesis is described for synthetically valuable 4,6,8-tribromoquinoline (3) and 6,8-dibromo-1,2,3,4-tetrahydroquinoline (6) on bromination of 1,2,3,4-tetrahydroquinoline (7) in efficient yields (75 and 90%, respectively). 6-Bromo- (4) and 6,8-dibromo-1,2,3,4-tetrahydroquinolines (6) were converted to 6-bromo- (1) and 6,8-dibromo quinolines (2), respectively, by aromatization with DDQ in 83 and 77% yields, respectively. Several novel trisubstituted quinoline derivatives were efficiently prepared via lithium-halogen exchange reactions of tribromide 3. Treatment of 4,6,8-tribromoquinoline with BuLi followed by quenching with electrophiles [Si(CH3)3Cl, S2(CH3)2, I2] regioselectively proceeded at C-4 and C-8 sites and afforded corresponding 4,8-disubstituted-6-bromoquinolines. Similarly, lithiation of tribromide 3 followed by addition of water to the intermediate produced 6-bromoquinoline in 65% yield. Copper-induced nucleophilic substitution of tribromide 3 with NaOMe afforded 4,6,8-trimethoxyquinoline (17) in 60% yield. © 2008 Elsevier Ltd. All rights reserved.