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Synlett 2008(19): 3001-3005  
DOI: 10.1055/s-0028-1087340
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Ionic Liquid - an Efficient Recyclable System for the Synthesis of 2,4-Disubstituted Quinolines via Meyer-Schuster Rearrangement

Rupam Sarma, Dipak Prajapati*
Department of Medicinal Chemistry, North East Institute of Science and Technology, Jorhat 785 006, Assam, India
Fax: +91(376)2370011; e-Mail: dr_dprajapati2003@yahoo.co.uk;
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Publication History

Received 4 June 2008
Publication Date:
12 November 2008 (online)

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Abstract

An improved and eco-friendly method for the synthesis of 2,4-disubstituted quinolines via Meyer-Schuster rearrangement of 2-aminoaryl ketones and phenylacetylenes in the presence of zinc trifluoromethanesulfonate in [hmim]PF6 has been developed.

Key words

ionic liquid - Meyer-Schuster rearrangement - green solvents - quinolines

30

General Procedure for the Synthesis of 2,4-Disubstituted Quinoline Derivatives under Thermolytic Conditions Using Ionic Liquids A mixture of 2-amino-5-chloro-2′-fluoro-benzophenone (1a, 0.25 g, 1 mmol), and phenylacetylene (0.18 g, 1.8 mmol) in 1-hexyl-3-methylimidazolium hexafluoro-phosphate (1 g) was placed in a round-bottom flask (50 mL) in the presence of Zn(OTf)2 (15 mg). Two phases were formed at r.t. The flask was then dipped in a pre-heated oil bath at 80-90 ˚C (bath temperature), the mixture becomes homogeneous, and was stirred for about 2.5 h. After completion (monitored by TLC), the reaction mixture was cooled to r.t. and extracted with Et2O (2 × 15 mL). The ether layer was dried over anhyd Na2SO4 for 10 h and concentrated in a rotary evaporator to half the volume and left overnight. The yellow crystals of the products so obtained was filtered, dried, and recrystallized from CHCl3-MeOH (1:1) mixture to get the pure product; mp 125 ˚C in 98% yield. The filtrate containing the Et2O is evaporated to expel the Et2O completely and ionic liquid is reused directly for the second run. Similarly other 2-aminoaryl ketones and phenylacetylene were reacted in the presence of Zn(OTf)2 under thermal heating at 80-90 ˚C to produce the corresponding quinoline derivatives in excellent yields. The results are summarized in the Table  [¹] .
2-Phenyl-4-(2′-fluorophenyl)-6-chloroquinoline (3a) Mp 125 ˚C. IR (KBr): 1615, 1370, 1280, 1165, 1125 cm-¹. ¹H NMR (90 MHz, CDCl3): δ = 7.15-7.28 (m, 7 H), 7.72 (m, 1 H), 8.02 (m, 1 H), 8.10-8.30 (m, 4 H). Anal. Calcd for C21H13ClFN: C, 75.68; H, 3.90; N, 4.20. Found: C, 75.70; H, 4.02; N, 4.11. MS: m/z = 333 [M+].
2,4-Diphenylquinoline (3b)
Mp 107 ˚C. IR (KBr): 1610, 1370, 1270, 1160, 1125 cm-¹. ¹H NMR (90 MHz, CDCl3): δ = 7.10-7.23 (m, 9 H), 7.65 (m, 1 H), 7.95 (m, 1 H), 8.10-8.25 (m, 4 H). Anal. Calcd for C21H15N: C, 89.69; H, 5.34; N, 4.98. Found: C, 89.75; H, 5.42; N, 4.88. MS: m/z = 281 [M+].
6-Chloro-2,4-diphenylquinoline (3c)
Mp 98 ˚C. IR (KBr): 1610, 1375, 1270, 1165, 1125 cm-¹. ¹H NMR (90 MHz, CDCl3): δ = 7.12-7.25 (m, 8 H), 7.65 (m,
1 H), 8.05 (m, 1 H), 8.13-8.28 (m, 4 H). Anal. Calcd for C21H14ClN: C, 80.00; H, 4.44; N, 4.44. Found: C, 80.09; H, 4.50; N, 4.35. MS: m/z = 315 [M+].
2,4-Diphenyl-6-nitroquinoline (3d) Mp 264 ˚C. IR (KBr): 1630, 1375, 1240, 1150, 1040 cm-¹. ¹H NMR (90 MHz, CDCl3): δ = 7.25-7.65 (m, 8 H), 7.83 (m, 1 H), 8.05-8.15 (m, 5 H). Anal. Calcd for C21H14N2O2: C, 77.30; H, 4.29; N, 8.59. Found: C, 77.37; H, 4.20; N, 8.68. MS: m/z = 326 [M+].
2,4-Diphenyl-8-nitroquinoline (3e) Mp 264 ˚C. IR (KBr): 1635, 1375, 1240, 1150, 1035 cm-¹. ¹H NMR (90 MHz, CDCl3): δ = 7.25-7.60 (m, 8 H), 7.75 (m, 1 H), 8.12-8.20 (m, 5 H). Anal. Calcd for C21H14N2O2: C, 77.30; H, 4.29; N, 8.59. Found: C, 77.41; H, 4.35; N, 8.49. MS: m/z = 326 [M+].
2-Phenyl-4-(2′-chlorophenyl)-6-chloroquinoline (3f) Mp 112 ˚C. IR (KBr): 1615, 1375, 1275, 1165, 1130 cm-¹. ¹H NMR (90 MHz, CDCl3): δ = 7.30 (s, 1 H), 7.42-7.88 (m, 7 H), 8.15 (s, 1 H), 8.16-8.25 (m, 4 H). Anal. Calcd for C21H13Cl2N: C, 72.21; H, 3.72, N, 4.01. Found: C, 72.14; H, 3.80; N, 4.10. MS: m/z = 349 [M+].
2-Phenyl-4-(2′-fluorophenyl)quinoline (3g) Mp 90 ˚C. IR (KBr): 1615, 1375, 1275, 1160, 1130 cm-¹. ¹H NMR (90 MHz, CDCl3): δ = 7.10-7.23 (m, 7 H), 7.65 (m, 1 H), 8.02 (m, 1 H), 8.15-8.30 (m, 4 H). Anal. Calcd for C21H14FN: C, 84.28; H, 4.68; N, 4.68. Found: C, 84.38; H, 4.58; N, 4.76. MS: m/z = 299 [M+].