卤代烃水解制备醇

该类反应属于典型的亲核取代反应，按照反应历程分两种类型：单分子的亲核取代反应(S_N1)和双分子的亲核取代反应(S_N2)。

一、单分子的亲核取代反应(S_N1)

单分子的亲核取代反应(S_N1)历程中反应速度只与反应底物卤代物的浓度有关，与碱的浓度无关。因此，从动力学上讲它是一个一级反应。例如溴代叔丁烷的水解：

此反应是分两步进行,第一步是反应物在溶剂中首先离解成叔丁基正离子和溴负离子：

    第二步则是生成的叔丁基碳正离子再与HO^-作用,生成叔丁醇：

二、双分子的亲核取代反应(SN2)

另一类为双分子的亲核取代反应(S_N2)，它的水解速度与卤代烃的浓度和碱的浓度成正比，因此该类反应是一个二级反应。例如溴甲烷的水解：

反应过程中C-Br键的断裂与C-O键的形成是同时进行的。当进攻试剂HO^-从离去基团Br的背后进攻中心碳原子时(这是比较有利的进攻方式)。此时，HO^- 、Br和中心碳原子几乎处于同一直线上，形成一个“过渡态”。而中间碳上的三个H原子则处于垂直于这个直线的平面上，当HO^-与中心碳原子进一步接近，最终形成一个稳定的C-O键时，C-Br也彻底断裂，生成Br^-离子，同时中心碳上的三个H原子也向后翻转，使碳原子恢复成原来的sp³杂化状态。从立体化学上来看，在反应过程中发生了构型的转化，使得产物与原来的反应物构型正好相反，这也正是在1893年发现的瓦尔登(Walden)转化。另外许多反应，卤代物直接水解并不是太好，因此一般先用AcO－取代，而后再水解得到相应的醇。

反应实例

一、卤代烃的水解反应制备醇示例

Combined the material with 75%DMF, 1.2 equiv of NaOH were stirred for 30 min at room temperature. Andrecrystallized from MeOH to give the colourless needles (95% yield).

【J.Org.Chem.1982, 47, 4024-4029】

二、卤代烃的水解反应制备醇示例

Water (100mL) and CaCO₃(18g, 180mmol) were added into a solution of 10.5g (35mmol) of1-bromo-2-(bromomethyl)naphthalene in 100mL of p-dioxane ,and the mixture wasrefluxed for 10hrs. The solution was cooled and the dioxane removed underreduced pressure. Methylene chloride (200mL) was added followed by treatmentwith dilute HCl until all solid had dissolved .The organic phase was separated,washed with NaHCO₃ solution, dried over MgSO4, and filtered. Removalof the solvent left a white solid, which was recrystallized from hexane to give7.9g of (1-bromonaphthalen-2-yl)methanol (95% yield).

【J.Org.Chem.1986, 51, 3762-3768】

三、卤代烃的乙酰氧基取代示例

A 150 g portion of thethus obtained 1-chloro-(E,Z)-7,9-dodecadiene was admixed with 150 g ofanhydrous potassium ace-tate and 100 g of acetic acid and the mixture washeated at 160 .deg.C for 6 hours under agitation in an atmosphere of nitrogento convert the chloride into acetate.. After completion of thereaction, the reaction mixture was poured into a large volume of water and theorganic phase taken by phase separation was distilled under reduced pressure togive 80 g of 7,9-dodecadienyl acetate of which the purity of the E,Z-isomer wasat least 75percent.

【Patent; Shin-Etsu Chemical Co., Ltd.; Publ.: EP241335 A1 (1987/10/14),Appl.: EP1987-400592 (1987/03/17)】

四、酯水解得到相应的醇示例

2N sodium hydroxide (40 ml) was added to a solution of 5-(2-acetoxyethyl)-2-methyl-4-phenyloxazole (16.6 g) in methanol (40 ml) and the mixture was stirred for 30 minutes, diluted with water and extracted withethyl acetate..The ethyl acetate layer was washed with water and dried overanhydrous magnesium sulfate.

The solvent was thendistilled off and the residue wwas purified by silica gel chromatography(silica gel: 190 g, eluent: isopropyl ether) to give an oil of5-(2-hydroxyethyl)-2-methyl-4-phenyloxazole, yield 11.7 g (84.8percent).NMR(CDCl3) : 2.40 (3H, s), 3.07 (2H, t), 3.20 (1H, broad), 3.97 (2H, broad),7.23-7.80 (5H, m).

【Patent;Takeda Chemical Industries, Ltd.; Publ.: US4596816 A1 (1986/06/24), Appl.:US198】

用户“哈喽小壮”留言：

对于卤代烃水解，特别是分子量很高的卤代烃，直接水解往往发生的是消除反应，经过研究发现，使用甜菜碱，80℃的乙腈溶液中回流24h，可以制备对应的酯，碳酸氢钠60℃水解，即可获得对应醇亲测有效（药明康德）