1，强酸脱甲基反应
这是最为经典和简单的甲基芳基醚水解去甲基的方法。一般使用过量的浓HI酸回流下、或者大大过量的48% HBr或37% HCl在HOAc或Ac2O中回流，反应完后，浓缩去除过量的酸，加入水，用有机溶剂萃取，然后进一步纯化即可。特点是操作和后处理简单、方便。但要求底物对强酸稳定，对于有些底物，易形成卤代苯副产物。
在48%HBr中加入相转移催化剂是对仅使用强质子酸如48%HBr的改进。加入相转移催化剂后，能提高去甲基化的效率，大大缩短反应的时间。此反应是在一个多相体系（水和有机）中进行，可使用的相转移催化剂有四丁基溴化铵，十六碳烷基三丁基溴化磷,四辛基溴化铵，三辛基甲基溴化铵等。对于甲基芳基醚，一般使用5 mol量的HBr，对于甲基烃基醚，一般使用10 mol量的HBr；值得注意的是，反应的收率和时间不是依赖于使用那一种相转移催化剂，而是依赖于相转移催化剂的浓度和其在有机相的溶解度。
反应实例
Typical Pocedure
The ether (300 mg) was dissolved in 48% HBr (50 mL) and heated for 1 hrunder reflux. The reaction mixture was evaporated to dryness and extracted withether. The ethereal extract was washed with sodium carbonate solution andwater, dried and evaporated. The residue was recrystallized from chloroform togive the product (120 mg, 40%).
【 I. Kawasaki, K. Matsuda, and T. Kaneko, Bull. Chem. Soc. Jpn., 1971, 44, 1986.】
2，三卤化铝脱甲基反应
AlCl3/CH3CN和AlBr3/CH3CN是【Bull. Chem. Soc. Jpn., 1995, 68, 2033】一类常用的去甲基化方法，其操作类似BBr3的使用，只是一般反应温度在0℃到室温。另外加入硫化物，由于硫的亲核性更强，可以增加反应活性。AlBr3/EtSH,AlCl3/EtSH, AlCl3/HSCH2CH2SH体系的活性很高，分子中酯、醛、酮、双键不稳定，但酯在AlCl3/EtSH/CH2Cl2体系相对稳定。
反应机理
加入硫代物
反应实例
Typical Procedure. To dichloromethane (1 mL) or CH3CN (1 mL)wasadded aluminum chloride (3.0 mmol) at 0 ℃. Theresulting solution was warmed to room temperature, and the ether (1.0 mmol) wasadded with stirring. After being stirred for 3-12 h, the reaction mixture was pouredinto water, acidified with dilute HC1, and extracted with dichloromethane. Theorganic layer was treated as usual to give a crude product. Chromatography over a silica gelcolumn gave the desired product.
【Y. Kawamura, H.Takatsuki, F. Torii, and T. Horie, Bull. Chem. Soc. Jpn., 1994,67, 511.】
General Procedure for Demethylation. To a stirredsolution of aluminum halide in ethanethiol cooled in an ice-water bath wasadded the substrate.The reaction was monitored by TLC (aluminum halide was quenched bymethanol in the capillary). The reaction mixture was poured into water,acidified with dilute HC1, and extracted with dichloromethane. The organiclayer was shaken with brine, dried (Na2SO4), filtered,and then evaporated to leave a crude material, which was purified bychromatography over a silica gel column.
AlCl3/EtSH/CH2Cl2体系：To a mixture of dry ethanethiol (1 mL) and dichloromethane (1 mL) was added aluminum chloride (0.40 g, 3.0 mmol) at 0 oC. The resulting solution was warmed to room temperature,and the ether (0.194 g,1.0 mmol) was added with stirring. After being stirred for 9.5 h, the reactionmixture was poured into water, acidified with dilute HCl, and extracted with dichloromethane.The organic layer was treated as usual to give a crude product.Chromatography over a silica gel column gave the desired product (0.157 g, 95.5%) identical with anauthentic sample.
AlCl3/EtSH 体系：To a solutionof aluminum chloride (47 mg, 0.35 mmol) in dry ethanethiol (1 mL) was added the ether (11 mg, 0.03mmol) at 0 oC. After being stirred for 2.5 h at 0 oC, the reactionmixture was poured into water and extracted with dichloromethane. The usualworkup of theorganic layer gave the product: 7.5 mg (81.5%).
【 M. node, K.Nishide, K. Fuji and E. Fujita, J. Org. Chem. 1980, 45,4275. 】
3，苯甲醚利用LiCl脱甲基
当邻位和对位有吸电子基团存在时，此体系去甲基化容易进行。此条件下，乙基和异丙基也可以脱去。底物中有醛和酯时，去甲基需要更长的时间，但产率还是很好的。底物中有甲酯会去甲基形成酸。
Cleavage of 2,3-Dimethoxybenzaldehyde. 2,3-Dimethoxybenzaldehyde (1.0 g,6 mmol) and LiCl (0.76 g,18 mmol) are heated in boiling DMF (10 mL), the reaction being monitored by GLC. When the starting material disappears, 10% aqueous NaOH (30 mL) is added;the solution is washed with ether (2×25 mL), then acidified with 10%aqueous HCl (50 mL), and extracted with ether (2×25 mL). The organic phase is washedwith brine (30 mL), dried (sodium sulfate) and concentrated in a rotaryevaporator to afford 2-hydroxy-3-methoxybenzaldehyde (0.88 g, 98%).
【A.M. Bernard, M. R. Ghiani, P. P. Piras and A. Rivoldini,Synthesis,1989, 287】
4，三甲基碘硅烷脱甲基反应
三甲基碘硅烷脱甲基是通过芳基甲醚与三甲基碘硅烷生成芳基硅醚，水解得到脱甲基产物。一种常用的去甲基试剂，在此体系中，双键、三键、酮羰基、氨基和卤代物稳定，但苄醚、三苯甲基醚、叔丁基醚不稳定。三甲基碘硅烷能裂解酯但比醚慢。
反应实例
【J. Chem. Res., 2009 , 4 , 229- 230.】
General Procedure forDealkylation of Ether. To a 2 M solution of ether (1 equiv.) in a suitable solvent (Table 10) is added neattrimethylsilyl iodide (1.3 equiv.) through a dry syringe. The reaction is maintained at temperature indicated in Table 10 and monitored by NMR forcompletion. Yields are calculated by NMR integration of pertinent peaks. Forisolation of the alcohols, at the completion of the reaction, the excesstrimethylsilyl iodide is destroyed and the intermediate trimethylsilyl etherformed during the reaction is hydrolyzed to alcohol by pouring the reactionmixture into methanol (4 equiv.). The volatile components are removed atreduced pressure and the residue is taken up in ether, washed with aqueoussodium bisulfite, aqueous sodium bicarbonate and brine and dried. The residueleft after evaporation of solvent is further purified (if necessary) by columnchromatography on silica gel.
【M. E. Jung and M. A.Lyster, J. Org. Chem., 1977, 42, 3761】
Typical Procedure.Dealkylation of m-Methoxytoluene. Ethanethiol (1.25 g, 11.8 mmol) dissolved in dry DMF (20 mL) is added to asuspension of sodium hydride (1.0 gof a 50% oil dispersion) in dry DMF (10 mL) under an atmosphere of nitrogen.The mixture is stirred for 5 min before solution of m-methoxytoluene (1.09 g) in dry DMF is added. The solutionis then refluxed for 3 hrs. The cooled mixture is acidified with 10% aqueoushydrochloric acid and extracted with ether. The ether layer is washed withwater and extracted with 5% sodium hydroxide. The alkaline extracts are thenacidified and reextracted with ether. The ethereal solution is washed withwater, dried and evaporated to give m-cresol as a light brown oil; yield: 0.85 g (78%).
【G. I. Feutrill and R.N. Mirrington, Tetrahedron Lett., 1970, 11, 1327. 】
6，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.】
6、氟化学手册（Handbook of Fluorous Chemistry）
7、GPC（ 凝胶渗透色谱）的原理与应用（PPT/136页）
