酚羥基結(jié)構(gòu)廣泛存在于天然產(chǎn)物和合成藥物中，但其易氧化，形成氧負離子參與親核反應(yīng)，所以利用甲基醚保護酚羥基是一種重要的保護方法。常見的脫甲基試劑主要分為：1、酸（氫鹵酸和路易斯酸）；2、堿（醇鈉和氨基鈉）；3、三甲基碘硅烷，鹽酸吡啶，離子液體等其他方法。
下面介紹一下氨基鈉的脫甲基方法：對于氨基鈉（NaNH2）脫芳甲醚的反應(yīng)，要求苯環(huán)上沒有給電子基團，否則很容易發(fā)生Birth還原反應(yīng)（Birch還原反應(yīng)）。對于苯環(huán)上有給電子取代基的底物可以用N-甲基苯胺基鈉進行脫甲基。
反應(yīng)實例：
在HMPT中芳基甲基醚利用N-甲基苯胺基鈉脫甲基示例
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.】
