Barber R B, Rapoport H
J Med Chem. 1976 Oct;19(10):1175-80. doi: 10.1021/jm00232a002.
An improved conversion of thebaine to codeine has been developed. Oxymercuration of thebaine with mercuric acetate in refluxing methanol, followed by hydrolysis of the intermediate 7-acetomercurineopinone dimethyl ketal with 3 N acetic acid, or, alternatively, reduction of the organomercury compound with sodium borohydride and mild acid hydrolysis of the resulting neopinone dimethyl ketal, gives neopinone in 95-100% yields. Either acid- or alkali-catalyzed isomerization to codeinone leads to the equilibrium mixture consisting of codeinone-neopinone, 3:1. Complete conversion to codeinone in 85-90% yield results from treatment of neopinone with anhydrous hydrogen chloride or hydrogen bromide in ether-methylene chloride, followed by elimination of hydrogen halide from the intermediate 8-halodihydrocodeinone. The known borohydride reduction of codeinone then gives codeine in 85% overall yield from thebaine.
已开发出一种改进的将蒂巴因转化为可待因的方法。在回流的甲醇中用醋酸汞对蒂巴因进行氧汞化反应，然后用3N醋酸水解中间体7-乙酰汞新皮诺酮二甲基缩酮，或者，用硼氢化钠还原有机汞化合物并对所得新皮诺酮二甲基缩酮进行温和的酸水解，可得到产率为95 - 100%的新皮诺酮。酸催化或碱催化异构化为可待因酮会得到由可待因酮 - 新皮诺酮组成的平衡混合物，比例为3:1。用无水氯化氢或溴化氢在乙醚 - 二氯甲烷中处理新皮诺酮，然后从中间体8 - 卤代二氢可待因酮中消除卤化氢，可得到产率为85 - 90%的完全转化为可待因酮的产物。然后，已知的可待因酮的硼氢化钠还原反应可从蒂巴因得到总产率为85%的可待因。
