在有机合成中，羧酸和酯可以很方便地相互转换，因此酯化反应是保护羧基的一种常用方法，酯水解也成为水解法制羧酸的重要方法。

酯的碱水解

       水解反应是酯化反应的逆反应，酯化反应要在酸性条件下进行的，因此多数情况下酯的水解在碱性条件下进行是有利的。一般来说非位阻酯的水解主要通过LiOH-MeOH-H 2 O 体系于室温下进行反应，正常条件是氢氧化锂的当量为 2-5 当量，甲醇与水的比例为 5:1~3:1。如果反应仍不能水解，可适当加热直至回流。对于有些位阻大、惰性的酯，需要用更强的反应条件，一般可使用 NaOH、KOH 的水溶液或水甲醇的混合溶液进行水解，其中最强烈的条件是用 KOH 的水甲醇的混合溶液回流水解，KOH的浓度越大、溶剂甲醇的比例越高，水解条件越强，很少有在这种条件下水解不了的酯。对于该类水解反应的后处理一般先浓缩去处醇类溶剂，然后用有机溶剂提取可能未反应完的非酸类副产物，再酸化，许多酸在此时可以析出沉淀，过滤即可得到，若为油则用有机溶剂提取。

      有时当一个分子同时存在甲酯和叔丁酯时，用以上条件很难较好的选择性的水解甲酯，有时需要控制碱的当量数和反应温度。

LiOH-MeOH-H 2 O 水解体系的标准操作

      To a solution of ester (10 mmol) in MeOH-H 2 O (30 mL, MeOH:H 2 O=3:1~5:1, 甲醇浓度越高，水解能力越强) at 0°C was slowly added LiOH.H 2 O (800 mg ~ 2 g, 20-50 mmol).The reaction mixture was allowed to warm to room temperature overnight (若水解不完全就加热至反应完全). Methanol was removed in vacuo and the residual aqueous solution was partitioned with Et 2 O or AcOEt (~20 mL), then the organic phase was extracted with H 2 O (5-10 mL, two times). The combined aqueous extracts was acidified to pH 2 with 1N HCl. The aqueous phase was extracted with CHCl 3 (three times) (注意若有固体析出则过滤得到相应的酸). The combined organic extract was dried over MgSO 4 and concentrated to afford the desired acid (normal yield >95%).

LiOH-MeOH-H 2 O 体系的选择性水解甲酯和叔丁酯示例

      To a solution of compound 1 (14.15 g, 48.1mmol) in MeOH (250 ml) at 0°C was slowly added aqueous LiOH (1M, 48 ml, 48mmol) over 15 min. The reaction mixture was allowed to warm to room temperature overnight with stirring.

    The organic solvent was removed in vacuo and the residual aqueous solution was partitioned with Et 2 O, then the organic phase was extracted with H 2 O (two times). The combined aqueous extract was acidified to pH 2 with 1N HCl. The aqueous phase was extracted with CHCl 3 (three times). The combined organic extract was dried over MgSO 4 and concentrated to afford the desired acid (11.4 g, 85%).

KOH-H 2 O 体系的水解示例

    A mixture of ethyl 3-methylcoumarilate (70 g, 0.34mol) and 10% aqueous potassium hydroxide solution (500 mL) was refluxed for 1 hour. The clear yellowish solution was acidified while hot with a slight excess of concentrated hydrochloric acid to precipitate 3-methylcoumarilic acid. The suspension was cooled to room temperature, and the colorless solid was filtered with suction. The filter cake was resuspended in 500 mL of cold water, stirred vigorously for several minutes, and filtered again with suction. The colorless powder The filter cake was dried in a desiccator under reduced pressure to give a colorless powder (54~57 g, 90~95%) which melts at 192~193°C.