Wolff–Kishner-黄鸣龙还原反应

醛酮在碱性条件下与肼作用生腙，加热分解，将羰基还原为亚甲基的反应。原来Wolff-Kishner的方法是将醛或酮与肼和金属钠或钾在高温(约200 °C)下加热反应，需要在封管或高压釜中进行，操作不方便。黄鸣龙改进了此反应，不用封管而在高沸点溶剂如一缩二乙二醇(二甘醇，b.p.245 °C)中反应，用氢氧化钠或氢氧化钾代替金属钠作碱。 黄鸣龙改进法只需将酮类和醛类与氢氧化钾和氢氧化钠(代替金属钠)，85%(有时可用50%)水合肼(代替无水肼)及双缩乙二醇或三缩乙二醇(代替封管或高压釜)，同置于圆底烧瓶内，回流1 小时生成腙，移去冷凝管，继续加热，除去水和过量的肼，直到溶液温度上升至190-200 oC 时，再插上冷凝管，保持此温度23小时，然后按常规方法处理即得。 若被还原的物质还原后的生成物沸点低于190-200 oC，则在蒸去水分时，物质亦随之逸去，故必须在冷凝管与烧瓶间装一分液管，借以除去水分。

后来发展出了利用TsNH2NH2和酮反应生成Ts腙，再还原为亚甲基的条件更加温和，而且不用加碱。

反应机理

反应实例

黄鸣龙改进法，此反应会消除一分子乙烯。

【Tetrahedron Lett. 1989, 30, 1353-1356】

【Synlett1999, 1573-1592】

【J. Org. Chem., 1999, 64, 3398】

【Steroids2002, 67, 31-38】

【J. Am. Chem. Soc., 2004, 126, 5436】

【Synth. Commun. 2006, 36, 2183-2187】

【Org. Process Res. Dev.2009, 13, 576–580】

【Green Chem., 2014, 16, 176-180】

A mixture of 18.2 g of benzophenone, 7 g of sodium hydroxide, 100 mL of triethylene glycol and 10 mL of 85% hydrazine hydrate was refluxed for 1 h. Then the condenser was removed until the temperature of the solution was had reached 195~200 oC, when refluxing was continued for about three hours. The mixture was cooled and extracted with ether. The ether residue on distillation over sodium gave 14.0 g (83.3%) of pure hydrocarbon, b. p. 149 oC at 29 mmg.

A reaction with 14.2 g (0.1 mol) of the ketone, 9 mL (0.18 mol) of hydrazine hydrate, 20 g of sodium and 400 mL of dithethlene glycol was carried out at 170-190 o for sixty-eight hours. After dilution with water, extraction with ether. The organic layer was washed in turn with water, dilute hydrochloric acid, and again with water. The extract was dried over anhydrous magnesium sulfate. Removal of solvent left the crude hydrocarbon, which was redistilled over sodium to give 8.95 g (70 %) of 2,6-dimethylheptane, bp 131-133 oC。

相关文献

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参考资料：

一、J.J. Li, Name Reactions: A Collection of Detailed Mechanisms and Synthetic Applications, Wolff–Kishner reduction，page 644-645.

二、CHEMINFOGRAPHIC：Wolff-Kishner Reduction 1911（机理图片）