Meth-Cohn喹啉合成反应

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on style="text-indent: 2em;">1978年，Meth-Cohn课题组报道了乙酰基芳胺和Vilsmeier-Haack试剂反应得到2-氯-3-喹啉甲醛（68%产率）。酰基芳胺和Vilsmeier试剂在加热条件下反应关环得到2-氯-3-取代喹啉的反应被称为Meth-Cohn喹啉合成反应。

【Tetrahedron 1995, 51, 12869】

反应操作：酰基苯胺（1 mol. equiv.）和Vilsmeier试剂{由POC13 (7 mol. equiv.) 和N,N-dimethylformamide (DMF, 2.5 mol. equiv.) 制备得到}在75℃反应4-20小时就可得到喹啉产物。反应完毕倒入冰水中，过滤即可得到产物，个别产物需要碱化后过滤。活化的芳胺底物 [e.g. R = 4-Me (70%), 4-OMe (56%)] 反应较快产率相对较高，钝化的芳胺产率较低[e.g. R = 4-Br (23%), 4-C1 (2%), 4-NO2 (O%)] 。

反应机理

反应实例

2-chloro-3-quinolinearboxaldehyde (34) To an ice-cooled solution of N,N-dimethylformamide (10.95 g, 11.6 mL, 0.15 mol) was added dropwise with stirring phosphoryl chloride (53.7 g, 32.3 mL, 0.35 mol). Acetanilide 33 (6.75 g, 0.05 mol) was then added and the reaction raised to 75 ℃ and stirred for a further 16.5 h. The reaction mixture was poured into ice-water (300 mL) and stirred for 0.5 h at < 10 ℃. The precipitated solid was collected by filtration and washed well with water (100 mL), air dned and recrystallised from ethyl acetate to afford the product 34 (6.5 g, 68%) as a white solid, mp 148 - 149 ℃; 'H NMR (a-DMSO) 6 7.60 - 8.30 (m, 4H), 8.83 (s, lH), 10.35 (s, 1H).

【.J. Chem. Soc., Perkin Trans. 1 1981, 1520】