关键词: 吡啶P, 芳构化, 韩森反应

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 acetoacetate, formalin, ammonium bicarbonate (mol ratio: 2.5:1:1.25) and MeOH was warmed at 50～60℃ until all the NH~4HCO~3 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 hexahydrate is an effective oxidation agent for 1,4-dihydropyridines in acetic acid medium. However, oxidation of 4-isopropyl-1,4-DHP (7) with FeCl~3· 6H~2O afforded the dealkylated pyridine (10). Presumably, a single electron transfer occurred. In comparison with HNO~3, CrO~3, MnO~2 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 Fe^3^+ oxidation make this an important means for the aromatization of 1,4-DHP. After 1,4-DHP (1) was dissolved in acetic acid, FeCl~3·6H~2O (mol ratio: 1:2) was added. The mixture was refluxed for 1 h, before being neutralized with aq. Na~2CO~3. Then the mixture was extracted with CHCl~3. The collected chloroform solution was dried (anhyd. Na~2SO~4) and solvent was removed. The residue was recrystallised from aq ethanol, yielding pale yellow crystals (60%～72%)。

Key words: PYRIDINE P, AROMATIZATION