芳基甲基醚利用N-甲基苯胺基钠脱甲基

酚羟基结构广泛存在于天然产物和合成药物中，但其易氧化，形成氧负离子参与亲核反应，所以利用甲基醚保护酚羟基是一种重要的保护方法。常见的脱甲基试剂主要分为：1、酸（氢卤酸和路易斯酸）；2、碱（醇钠和氨基钠）；3、三甲基碘硅烷，盐酸吡啶，离子液体等其他方法。

下面介绍一下氨基钠的脱甲基方法：对于氨基钠（NaNH2）脱芳甲醚的反应，要求苯环上没有给电子基团，否则很容易发生Birth还原反应（Birch还原反应）。对于苯环上有给电子取代基的底物可以用N-甲基苯胺基钠进行脱甲基。

反应实例：

在HMPT中芳基甲基醚利用N-甲基苯胺基钠脱甲基示例

TypicalProcedure. Cleavage of 1,2,4-Trimethoxybenzene.  N-Methylaniline (2.68 g, 25 mmol) is added dropwise at 65°C to a stirred suspension of sodiumhydride (0.6 g, 25 mmol) insodium-dried xylene (5 mL) and HMPT (4.26 g, 25 mmol, distilled over calcium hydride and stored in darkover molecular sieves, 8A°).After 15 min, the ether (12.5 mmol in the minimum amount of xylene) is addedand the mixture is heated at 85°C.The reaction is monitored by GLC (3 mSE 30 column) and by TLC. When the starting material disappears (6 hrs) themixture is poured into water, acidified with dilute hydrochloric acid, and theproduct is extracted with ether. The ether phase is washed with dilutehydrochloric acid (2×90 mL) to remove HMPT and the amines and then the product isextracted with 10% sodium hydroxide solution (2×90 mL). The aqueous phaseis acidified with dilute hydrochloric acid and extracted with ether (3×90 mL). The organic phaseis dried over calcium chloride and concentrated on a rotary evaporator to givepure 2,5-dimethoxyphenol; yield: 1.9 g(90%). The product may be further purified by column chromatography on silicagel.

【B. Loubinoux, G.Coufert and G. Guillaumet, Synthesis, 1980, 638.】