3-氨基-7,8-二甲氧基-2(1H)-喹诺酮的合成

为了改进和优化3-氨基-2(1H)-喹诺酮环的合成工艺,从芳草醛出发,依次经过乙酰化、硝化、甲基化、还原,制备出2-氨基-3,4-二甲氧基苯甲醛(Ⅴ),Ⅴ与硝基乙酸甲酯环合得3-硝基-7,8-二甲氧基-2(1H)喹诺酮(Ⅵ),还原Ⅵ,得到3-氨基-7,8-二甲氧基-2(1H)-喹诺酮。优化后的环合条件为:以体积比7∶3的甲苯和环己烷为混合溶剂,哌啶为催化剂;Ⅵ最佳还原条件为:乙醇为溶剂,5%钯碳和甲酸铵为还原剂。在该条件下,3-氨基-7,8-二甲氧基-2(1H)-喹诺酮合成总收率从邻氨基苯甲醛(Ⅴ)计可达70%以上。

The Synthesis of the 3-amino-7,8-dimethyl-2(H)-quinolone

To improve and optimize the synthetic process of 3-amino-2(1H)-quinolone ring, 3-amino-7,8-dimethoxyl-2(1H)-quinolone (VII) was synthesized by the reduction of 3-nitro-7,8-dimethoxyl-2(1H)-quinolone (IV), which was prepared by the cyclization of 2-amino-3,4-dimethoxylbenzaldehyde (V) with methyl nitroacetate. The compound V was successively prepared from vanillin via actylation, nitrolation, methylation and reduction. The results showed that preferred synthetic conditions were as following: the piperidine catalyzed the cyclization reaction in the mixed solvent of toluene and cyclohexane in volume ratio 7: 3, the 5% Pd/C and ammonium formate were used as the reduced system to reduce the compound VI. The synthetic yield of the 3-amino-7,8-dimethoxyl-2(1H)-quinolone could reach higher than 70%, calculated from the O-aminobenzaldehyde V.