腈还是较为容易还原为相应的伯胺，催化加氢或化学试剂还原都可以用于这类还 原，催化加氢的方法最为常用的催化剂为Ranney Ni, 在使用Ranney Ni 做催化剂加氢还原成胺时，若用乙醇作溶剂时，一般需要加入氨水，主要由于在此条件下，有时有微量的乙醇会氧化为乙醛，其与产品发生还原胺化得到乙基化的产物，加入氨水或液氨可抑制该副反应(www.qiesu.com.cn)。化学还原方法则以LAH 和硼烷较为多用。LAH还原不稳定的底物可以考虑利用NaBH4/CoCl2条件还原。
1、Reney Ni 催化加氢还原腈基示例
A mixture of the material (413 mg, 1.51 mmol), Raney nickel (413 mg) and ammonia (0.9 g) in methanol (20 mL) was hydrogenated under 340 KPa (50 psi) hydrogen overnight at room temperature. The mixture was filtered and the filtrate was concentrat- ed in vacuo. The residue was partitioned between ethyl acetate (50 mL) and water (40 mL) and the ethyl acetate extract was washed with brine (30 mL), dried (sodium sulfate) and concentrated in vacuo. The residue (400 mg) was purified by column chromatography on silica gel (100 g), eluting with 85: 15 ethyl acetate/methanol to yield the title compound as an oil (321 mg, 77% yield).
2 、Reney Ni-NH2-NH2 催化加氢还原腈基示例
The starting material (1.39 g, 3.1 mmol) was dissolved in ethanol and warmed to 55 °C before it was treated with Raney-nickel (1 mL slurry in water) followed by addition of hydrazine monohydrate (1.5 mL). The resulting mixture was allowed to stir at 55°C for 30 min or until the evolution of gas had stopped. The cooled reaction mixture was filtered through diatomaceous earth, rinsed with methanol and dichloro- methane. The filtrate was diluted with saturated sodium bicarbonate (50 ML) and extracted with dichloromethane (50 mL×3). The combined organic layers were dried with sodium sulfate and concentrated. Chromatography with NH4OH: MeOH: EtOAc (5:10:85) afforded the product (1.30 g, 93% yield).
3、 PtO2 催化加氢还原腈基示例
The material (3 g, 13 mmol) was dissolved in methanol (35 mL) and concentrated HCl (4.4 mL). This solution was combined with 10 percent PtO2 (0.1 g) and hydrogenated under 50 psi for 2 hours. The methanol was removed under reduced pressure and the residue was diluted with 35 mL of ice cold water and 2.5 mL of 50 percent NaOH. The product was extracted with CH2Cl2, dried with MgSO4 and evaporated to an oil. This oil was purified by Prep 500 chromatography (10 percent MeOH/DCM) to yield 2.5 g of an oil. The salicylate was precipitated from an ether solution to give 3.3 g of product. m.p. 160°C.
4、 LAH 还原腈基示例
2-bromophenylacetonitrile (10.0 g, 51.0 mmol) were dissolved in ether (80 mL) and the solution was added dropwise to lithium aluminium hydride (5.81 g, 153 mol) in ether (230mL). The mixture was heated under reflux for three hours, while stirring, and, after cooling, 80 mL of potassium hydroxide solution (10 wt. percent) were slowly added dropwise, with vigorous stirring. After stirring overnight, the supernatant was decanted off, the residue was rinsed twice with 100 mL of ether each time, the combined organic phases were dried over anhydrous magnesium sulfate and filtered and the filtrate was concentrated on a rotary evaporator (500~10 mbar). 9.48 g of 2-(2-bromo-phenyl)-ethylamine (93% yield) were obtained in this manner.
5 、BH3 还原腈基示例
The material (1.0 g, 3.7 mmol) was dissolved in anhydrous THF (10 mL). BH3.THF (10 mL, 1.0 M solution in THF, 10 mmol) is added. The reaction mixture is maintained under reflux for 3 hours before being cooled to room temperature. An aqueous solution (12 mL) trifluoroacetic acid (50 percent) was added dropwise. The mixture was heated under reflux for 1 hour. The solvents and the trifluoroacetic acid are eva- porated. The residue is redissolved in 20 ml of THF and evaporated to dryness. A crude solid product is obtained which contains essentially the desired product and is used directly in the following acetylation step.
6 、NaBH4 还原腈基示例
Sodium borohydride (2.2 g, 58.2 mmol) are suspended in dry THF (50 mL) and cooled to ca. 0°C under moisture exclusion. The material (6.7 g, 23.1 mmol) are added and the mixture is subsequently cooled to -5°C to -10°C and added dropwise to (1.5 mL, 26.7 mmol) 95% sulfuric acid (vigorous foaming). The suspension is left to stand for two days at RT without further cooling. Under renewed cooling to ca. 0°C, 40 mL of 2 M sodium hydroxide solution is added dropwise. The aqueous phase is extracted with 30 mL of THF and thereafter the combined organic phases are washed twice, each with 30 mL of saturated NaCl solution, dried over sodium sulfate and the solution is removed under vacuum. The residue is chromatographically purified over silica gel with CHCl3/CH3OH/NH4OH (90/10/1). Yield: 3.9 g (57% yield).