A General Protocol for the Solvent- and Catalyst-Free Synthesis of 2-Styrylquinolines under Focused Microwave Irradiation

Abstract

Focused microwave irradiation promoted the very efficient synthesis of 2-styrylquinolines by reaction between quinaldines and benzaldehydes or cinnamaldehydes in the presence of acetic anhydride.

Key words

aldol condensations - heterocycles - quinolines - microwave-assisted synthesis

References and Notes

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12

General Experimental Procedure
The suitable quinaldine derivative (1 mmol) and the corresponding aromatic aldehyde (1 equiv) were suspended in Ac₂O (0.5 mL) in a pressure-tight microwave tube containing a stirring bar. The reaction mixture was heated under microwave irradiation for 1 h at 130-180 ˚C, with an irradiation power of 200 W, using a CEM Discover SP microwave reactor. The solvent was removed under reduced pressure to give a black residue that was purified by chroma-tography through a silica column using PE-EtOAc (90:10, v/v) as the mobile phase. Characterization data for three representative compounds are given below. For further characterization data, see the Supporting Information.
( E )-2-(4-Fluorostyryl)-6-methoxyquinoline (3h) Pale yellow solid; mp 138-141 ˚C. IR (neat): ν_max = 1592.4, 1509.8, 1231.9, 1164.1, 1030.8, 965.4, 856.2, 837.0 cm^-¹. ^¹H NMR (250 MHz, CDCl₃): δ = 3.96 (s, 3 H), 7.08-7.14 (m, 3 H), 7.33 (d, J = 16.6 Hz, 1 H), 7.39 (dd, J = 9.3, 2.8 Hz, 1 H), 7.58-7.65 (m, 4 H), 8.02 (d, J = 8.9 Hz, 1 H), 8.05 (d, J = 8.4 Hz, 1 H). ^¹³C NMR (62.9 MHz, CDCl₃): δ = 56.0 (CH₃), 105.6 (CH), 116.2 (d, J = 21.7 Hz, 2 CH), 119.2 (CH), 122.9 (CH), 128.7 (C), 129.1 (d, J = 8.1 Hz, 2 CH), 130.9 (CH), 132.5 (CH), 133.2 (C), 133.3 (C), 135.7 (CH), 144.6 (C), 153.9 (C), 158.1 (C), 163.21 (d, J = 248.4 Hz, C). Anal. Calcd for C₁₈H₁₄FNO: C, 77.40; H, 5.05; N, 5.01. Found: C, 77.15; H, 5.01; N, 4.77.
( E )-7-Chloro-2-(4-methoxystyryl)quinolone (3j) White solid; mp 149-151 ˚C. IR (neat): ν_max = 1604.2, 1511.3, 1408.0, 1250.8, 1177.9, 1032.8, 970.1, 831.8 cm^-¹. ^¹H NMR (250 MHz, CDCl₃): δ = 3.89 (s, 3 H), 6.98 (d, J = 8.7 Hz, 2 H), 7.23 (d, J = 16.1 Hz, 1 H), 7.46 (dd, J = 8.6, 2.1 Hz, 1 H), 7.61-7.75 (m, 5 H), 8.09-8.13 (m, 2 H). ^¹³C NMR (62.9 MHz, CDCl₃): δ = 55.8 (CH₃), 114.7 (2 CH), 120.0 (CH), 125.9 (C), 126.7 (CH), 127.3 (CH), 128.5 (CH), 129.1 (CH), 129.2 (2 CH), 129.5 (C), 135.2 (CH), 135.9 (C), 136.4 (CH), 149.1 (C), 157.7 (C), 160.7 (C). Anal. Calcd for C₁₈H₁₄ClNO: C, 73.10; H, 4.77; N, 4.74. Found: C, 73.19; H, 4.81; N, 4.86.
6-Chloro-2-[(1 E ,3 E )-4-phenylbuta-1,3-dienyl]quinoline (3m) Yellow solid; mp 105-108 ˚C. IR (neat): ν_max = 1590.2, 1485.5, 1070.0, 1001.7, 892.3, 825.7, 751.7 cm^-¹. ^¹H NMR (250 MHz, CDCl₃): δ = 6.87-7.15 (m, 3 H), 7.31-7.43 (m, 3 H), 7.52-7.62 (m, 4 H), 7.65 (dd, J = 9.0, 2.3 Hz, 1 H) 7.78 (d, J = 2.3 Hz, 1 H), 8.01 (d, J = 8.9 Hz, 1 H), 8.04 (d, J = 8.5 Hz, 1 H). ^¹³C NMR (62.9 MHz, CDCl₃): δ = 120.8 (CH), 126.6 (CH), 127.2 (2 CH), 128.2 (C), 128.7 (CH), 128.8 (CH), 129.2 (2 CH), 131.0 (CH), 131.2 (CH), 132.1 (CH), 132.7 (CH), 135.7 (CH), 135.8 (CH), 136.8 (CH), 137.3 (C), 147.1 (C), 156.6 (C). Anal. Calcd for C₁₉H₁₄ClN: C, 78.21; H, 4.84; N, 4.80. Found: C, 78.45; H, 5.01; N, 5.03.