【摘要】 改进了Hantzsch合成法,通过一锅煮合成1,4-二氢吡啶衍生物,大大缩短了反应时间,操作简便,发现氯化铁是一个较好的1,4-二氢吡啶衍生物芳构化的氧化剂。更多还原

【Abstract】 4 - Substituted - 2,6 - dimethyl - 3,5 - bis(alkoxycarbonyl) - 1,4 - dihydropyridines are important calcium channel blockers. A practical and general procedure for the Hantzsch cyclocondensation reaction using ammonium bicarbonate in stead of ammonia is described. This is a novel, one - pot operationthat not only preserves the simplicity of Hantzsch synthesis but also gives high yields (70% - 86% ) of the 1,4- dihydropyridines. Thus a solution of ethyl ace-toacetate, formalin, ammonium bicarbonate (mol ratio: 2.5:1:1.25 ) and MeOH was warmed at 50 - 60 ℃ until all the NH4HCO3 was decomposed. After refluxing for 0.5 h, the solution was cooled and the resulting suspension was filtered, washed with methanol and dried. The product was obtained as yellow crystals was products. Iron(III) chloride hexahy-drate is an effective oxidation agent for 1,4 - dihydropyridines in acetic acid medium. However, oxidation of 4 - iso-propyl - 1,4 - DHP (7) with FeCl3·6H2O afforded the dealkylated pyridine (10) . Presumably, a single electron transfer occurred. In comparison with HNOs3, CrO3, MnO2 et al. , Iron (III) chloride hexahydrate is an effective oxidation agent in the aromatization of 1,4- dihydropyridines. Moreover, excellent yields with environment friendly nature of Fe3+ oxidation make this an important means for the aromatization of 1,4 - DHP. After 1,4- DHP (1) was dissolved in acetic acid, FeCl3·6H2O (mol ratio: 1-2) was added. The mixture was refluxed for 1 h, before being neutralized with aq. Na2CO3. Then the mixture was extracted with CHCl3. The collected chloroform solution was dried (anhyd. Na2SO4) and solvent was removed. The residue was recrystallised from aq ethanol, yielding pale yellow crystals (60% -72%).更多还原