抗癌药1,4-二[2-(二甲胺基)乙胺基]-5,8-二羟基蒽醌的合成研究

Study on the synthesis of anti-tumor agent 1,4-Bis {(dimethylamino) ethyl]amino}-5,8-dihydroxyanthraquinone

以2，3-二氢-1，4，5，8-四羟基蒽醌和N，N-二甲基乙二胺为原料，合成了抗癌药物1，4-二[2-（二甲胺基）乙胺基]-5，8-二羟基蒽醌（下称：AQ4），考察了温度、溶剂、催化剂、氧化方式等对其产品收率的影响．确定的较佳工艺方法为：以2，3-二氢-1，4，5，8-四羟基蒽醌和N，N-二甲基乙二胺为起始原料进行缩合反应，用N，N-二甲基乙二胺兼做溶剂，首先制得1，4-二[2-（二甲胺基）乙胺基]-5，8-二羟基蒽醌隐色体（AQ4隐色体），进而用硝基苯进行氧化反应制得AQ4，产品总收率达到67．5％，产品结构利用红外（IR）、核磁（。HNMR）进行了表征．较佳的缩合反应条件为：反应温度50～55℃、反应时间2h；较佳的氧化反应条件为：反应温度140～145℃、回流反应时间15min．

The synthesis of 1,4-Bis { [ 2- （dimethylamino） ethyl ] amino 1-5,8-dihydroxyanthraquinone （ AQ4 ） was studied as antitumor agent in this paper with 2,3-dihydro-1,4,5,8-tetrahydroxyanthraquinone and N, N-dimethylaminoethylamine as raw materials. The reaction conditions, such as the reaction temperature, the solvents, the catalysts and the oxidizing agents were optimized. The optimized reactive conditions was that condensation of 2,3-dihydro-1,4,5,8-tetrahydroxyanthraquinone with a large excess amount of N, N-dimethylaminoethylamine as solvent at 50 - 55 ℃ for 2 h, followed by nitrobenzene oxidation of the dihydro intermediate at 140 - 145 ℃ for 15min get AQ4 with the yield of 67.5%. The product has been charactered by IR and ^1H NMR.