详细机理见：常用还原剂----氢化铝锂

反应机理

反应实例
1、 LAH 还原酰胺示例

LAH 还原酰胺一般是在加热回流下进行，但也可不回流在室温下进行；反应的条件在某种程度上决定于原料的位阻。以下为一反应示例。

200 mL of anhydrous ether and 10.7 g (0.282 mol) of lithium aluminium hydride were placed in a 500 mL three-necked flask with stirrer, two-neck attachment, dropper funnel and reflux condenser with a calcium chloride tube, and a solution of 43.0 g (0.189 mol) of the starting material in 60 mL of absolute ether was added dropwise with constant stirring so that the ether was maintained at a steady boil. After the end of the dropwise addition the mixture was stirred for a further 6 hours whilst simultaneously being refluxed, then the excess lithium aluminium hydride was decomposed by the dropwise addition of 11 mL of water, 11 mL of 15% aqueous sodium hydroxide solution and 33 mL of water, one after the other, and the aluminium oxide hydrate precipitated was filtered off. The filtrate was dried over sodium sulphate, the solvent was removed and the residue was distilled in a fine vacuum. 12.7 g of a colourless oil were obtained.

2、 硼烷-二甲硫醚还原酰胺示例

Under argon the starting material (48.46 g, 0.108 mol) was suspended in dry tetrahy- drofuran(270 mL). This mixture was then heated to reflux. Borane-methyl sulfide complex (41.3 g,0.543 mol) was then slowly added to the reaction mixture. All of the starting amide dissolved during the addition of the borane-methyl sulfide complex. This solution was then stirred overnight in an 83°C oil bath. After cooling a 1:1 mixture of tetrahydrofuran: water (75 mL total) was then added to the solution. Sodium hydroxide (5N, 230 mL) was then added to the mixture, which was then heated to reflux for about 30 minutes. After partitioning the aqueous and organic layers, the organic layer was collected. The aqueous layer was then extracted with tetrahydrofuran. The organic layers were combined and the solvents were then removed by evaporation. The resulting liquid was then partitioned between ethyl acetate and brine and was washed a second time with brine. The solution was

then dried over sodium sulfate and the solvents were removed in vacuo to yield 46.68 g of the desired product.

3 、NaBH4-Lewis acid 体系还原酰胺

3.1 、NaBH4-BF3 体系还原酰胺

To a solution of 8.8 g (39.8 mmol) of the starting material in 100 mL of dry THF, 4.52 g (119 mmol) of sodium borohydride was slowly added with cooling by ice under nitrogen atmosphere. To the obtained suspension, a solution of 16.1 mL of BF3-ether complex in 50ml of THF was slowly added with cooling by ice and then stirred for 4 hours with cooling by ice and for 4 hours at room temperature. Then, the reaction solution was poured into water, acidified by the addition of dilute hydrochloric acid and stirred for two hours. The solution was alkalized by the addition of an aqueous potassium hydroxide solution and extracted with ethyl acetate. The extract was dried on magnesium sulfate and filtered. The filtrate was concentrated and subjected to purification by silica gel column chromatography to give 2.2 g of the desired product.

3.2、 NaBH4-AlCl3 体系还原酰胺

To a solution of the starting material (21.6 g, 58.6 mmol) and dimethoxyethane (175 mL) one adds portionwise at 15°C~20°C anhydrous aluminium chloride (31.3 g, 0.234 mol) and allows to stir further for 30min. One then adds NaBH4 (8.85 g, 0.234 mol) portionwise at15°C~20°C within 1/2 hr. After 3 hrs, stirring while cooling, ice-water (130mL) are carefully added dropwise, whereby the internal temperature is not to exceed 25°C. While cooling withice, one brings the PH value to 8.5 by addition of conc. NaOH, adds 75 mL ethyl acetate and filters. The precipitate is after-washed with ethyl acetate. After separation of the phases, the aqueous phase is also extracted with ethyl acetate, the organic extracts is dried, evaporated and combined with precipitate to afford the desired product.

4 、DIBAL 还原酰胺【常用还原剂----DIBAL】

A solution of the material (250 mg, 0.80 mmol) in dichloromethane (10 mL) was cooled to 0°C, then DIBAL-H (7.4 mL, 7.4 mmol of 1M in toluene) was added dropwise into the solution over 45 min. The mixture was stirred for 1 hour, then warmed to room temperature and stirred for 14 h. The reaction was quenched with potassium sodium tartrate aqueous solution. The mixture was extracted with dichloromethane (3×10 mL). The combined extracts were washed with water and brine, dried over sodium sulfate and concentrated under vacuum to afford an oil. Purification by column chromatography (silica; 90: 10, v/v, dichloromethane/methan- ol followed by 89: 10: 1 dichloromethane/methanol/ammonium hydroxide) produced the desired product (54 mg, 23% un-optimized yield) as a clear colorless oil.

5、 伯胺经碳酰胺还原后单甲基化示例【常用还原剂----氢化铝锂】

600 mg (1.96 mmol) of the material in THF is slowly added dropwise to a suspension of 250 mg (6.59 mmol) of lithium aluminium hydride in 10 mL tetrahydrofuran. The reaction is stirred overnight and heated to 50.deg. C. for a further hour. Working up is carried out by the successive addition of 0.25 mL water, 0.25 mL 15percent NaOH solution and 0.75 mL water. After filtration the organic phase is dried over magnesium sulphate and the solvent is eliminated using the rotary evaporator. 350 mg of the product was obtained (81.1% yield).

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