硝基的还原是一种常用的合成伯胺的方法特别是芳香伯胺，一般而言，干净和简便的还原方法就是通过Pd/C或Raney Ni加氢，但是当分子内存在对加氢敏感的官能团如：卤素（Cl, Br and I; F 对加氢不敏感），双键，三键时，我们不得不采用化学还原的方法， 为经典的要数铁粉的还原，SnCl2还原， 另外Abderahman曾报道（Synthesis 1988, 2, 154-155）应用保险粉在乙醇中加热的方法还原硝基， 虽然在文献中他们使用了碱，但在实践中我们发现，只要用保险粉在乙醇中回流几小时即可。这一方法也是一个较为简便，易于处理的反应。
芳香硝基 Pd/C 加氢还原示例
To a solution of the starting material (10 g) in 200 ml of ethanol was added 1.03 g of 10 percent Pd/C and the mixture was stirred for two hours at room temperature in a hydrogen atmosphere under atmospheric pressure. Insoluble matters were removed using Celite, and the filtrate was concentrated in vacuo to give 9.54 g of the product。
脂肪硝基 Pd/C 加氢还原示例
To a solution of the starting material (3 g, 16 mmol) in ethanol (100 mL) was added 10 percent Pd/C (1 g) and the resulting mixture shaken under a hydrogen atmosphere (4 bar) for 3 days. The catalyst was removed by filtration and the solvent evaporated. To the resulting oil was added a saturated solution of ethanolic hydrochloric acid (5 mL) and the solvent was evaporated. Addition of ether gave a white solid which was collected and washed with ether to provide 3-amino-1,1,1-trifluoro-2-pentanol hydrochloride (1.3 g) as a white solid; TLC: Rf =0.1, methanol:dichloromethane (10:90).
芳香硝基 Raney Ni 加氢还原示例
To a suspension of the above product (6.1 g, 29.6 mmol) in ethanol (170 mL) was added Raney nickel (0.5 g) and the resultant mixture was hydrogenated at ambient pressure until the hydrogen uptake had ceased. Filtration through celite and evaporation of the solvent from the filtrate left the desired product, quantitatively.
脂肪硝基 Raney Ni 加氢还原示例
To the starting material (1.00 g, 5.88 mmol) and NaOH (0.235 g (5.88 mmol) in 5 mL of ethanol, 0.40 g of Raney nickel were added to stir the mixture under hydrogen atmosphere at 20.deg. C. for 12 hours. The catalyst was filtered off, and then the filtrate was poured into 33percent HCl/isopropanol (5.0 mL) below 20.deg. C. The reaction mixture was evaporated to dryness to give crude crystal. The crude crystal was suspended in toluene (5.0 mL) and to the suspension was introduced NH3 gas to stir at 20.deg. C. for 12 hours. The precipitate was filtered off and the filtrate was evaporated to afford 716 mg of the desired compound (Yield: 86.9%).
To the starting material (3.1 g) was added acetic acid (24.4 mL) and then, reduced iron powder (9.15 g), and the mixture was stirred for 16 hours at room temperature. The mixture was filtered with Celite, and washed with ethyl acetate. The solvent was removed under reduced pressure, and water was added to the obtained residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was removed under reduced pressure, and the obtained residue was purified by silica gel column chromatography, to give 1.4 g of the desired product.
To 80 percent ethanol (5.0 mL), the starting material (300 mg, 1.76 mmol) and concentrated hydrochloric acid (0.45 ml, 5.28 mmol) were added to stir for 10 minutes at 20°C. Then, iron powder (500 mg, 8.95 mmol) was added to the mixture to further stirring for 1 hour at 20°C. Insoluble matters were filtered off and the filtrate was concentrated, adding 0.5N NaOH (10 mL) to the residue, filtering the solution to further remove insoluble matters, extracting the filtrate with chloroform, drying the extract over anhydrous sodium sulfate, concentrating the extract, and distilling the resulting crude product to afford 224 mg of the desired compound (91% yield).
3 、硝基 SnCl2 还原示例
芳香硝基 SnCl2 还原示例
A stirred solution of stannous chloride dihydrate (38 g, 0.183 mol) in concentrated hydrochloric acid (100 ml, 1.2 mol) was treated portionwise with the starting material (10 g). Ethanol (10 mL) was added to clarify the solution and the mixture is stirred at 60 °C for 3
hours. The solution was evaporated to near dryness and three 100 mL. portions of ethanol are added sequentially and evaporated from the residue. The residual syrup was stirred with 800 mL. of ether and the resulting solid is collected by filtration, washed with ether and dried at reduced pressure. This solid (a tin complex) is dissolved in 150 mL of water and the tin is precipitated as the sulfide by bubbling hydrogen sulfide gas into the solution. The mixture is filtered and the filter cake washed with water. The filtrate and washings are combined and evaporated at reduced pressure. The residue is repeatedly evaporated with 100 mL portions of ethanol. The final residual gum is triturated with 30 mL of ethanol to give as a crystalline solid product dihydrochloride, which is collected by filtration, washed with ethanol and dried at reduced pressure; m.p. 155 °C
脂肪硝基 SnCl2 还原还原示例
A mixture of 106.6 g (0.41 mol) of the above material, 350 g (1.5 mol) of SnCl2.H2O, 1 L of MeOH, and 350 ml of AcOH was stirred and refluxed for 3 hr. The reaction mixture was then partly concentrated (500 ml collected), cooled, and treated portionwise with a cold solution 700 g of K2CO3 in 1 L of H2O. Ether (600 mL) and CHCl3 (200 mL) were added and the mixture was shaken. The layers were separated and the aqueous phase was extracted twice with the same Et2O-CHCl3 mixture. The organic phase were combined and dried over MgSO4 and the solvents were removed under reduced pressure to give 90 g of residue.
4、不饱和硝基氢化锂铝(LAH)或 NaBH4-Lewis 酸还原示例
To a slurry of LiAlH4 (15.0 g, 0.395 mole) and anhydrous ether (500 mL) in a 5 liter, 3-necked flask fitted with a condenser, mechanical stirrer and dropping funnel was added the starting material (20.0 g, 0.084 mol) dissolved in 2 liters of ether. The addition was made
over a period of about 4 hours while refluxing the ether slurry. When the addition was completed, refluxing was continued for an additional 1 to 2 hours. After the addition of diatomaceous earth (20 g) and then water (70 mL) slowly, dropwise, with cooling in an ice bath, the supernatant ether was decanted, the salts were washed with fresh ether several times followed by decantation and finally filtration. The solvent was removed by distillation and more thoroughly on a rotary evaporator. Cooling in an ice bath gave 15.91 g (90% yield) of the desired product as a slightly yellow solid, m.p., 45°C. High vacuum distillation gave an analytical sample.
不饱和硝基 NaBH4-Lewis 酸还原示例
Boron trifluoride etherate (17.7 g) was added under nitrogen with ice-cooling to sodium borohydride (3.94 g, 0.104 mol) suspended in tetrahydrofuran (150 mL). After stirring at room temperature for fifteen minutes, the starting material (5.78 g, 0.208 mol), dissolved in tetrahydrofuran (80 mL) was added dropwise. The mixture was refluxed overnight, quenched by the addition of ice-water, acidified with 5M hydrochloric acid and refluxed for a further two hours. The aqueous layer was washed with ether and the amine liberated by the
addition of ammonia solution which was extracted into dichloromethane. The extracts were washed with water, dried and evaporated to give pure product as an oil.
To a suspension of 3-(p-nitrobenzyl)-7-benzyladenine bromaide (2.5 mmol) and sodium dithionite (1.74 g, 10 mmol) in EtOH (100 mL) is added 0.2 N aq. NaOH (100 mL, 20 mmol). The mixture is stirred at 40°C for 24 h. After cooling to room temperature, the solution is concentrated under reduced pressure to a volume of 70 mL. The precipitate obtained is filtered with suction, washed water (2×25 mL) and then dried in vacuo at 100°C in 65% yield. Analytical samples of 7-benzyladenine are obtained by recrystallization in water/EtOH.
硝基 Raney-Ni 还原示例
Hydrogenation of the material (7 g, 20.2 mmols) in tetrahydrofuran (300 mL) and methanol (150 mL) in the presence of Raney nickel (1.5 g) for 1 hour yielded crude product. The mixture was hydrogenated for 5 hours at atmospheric pressure. The catalyst was removed by filtration and the filtrate was evaporated to give the crude product, then it was purified by silica gel chromatography.
水合肼-Raney Ni 还原硝基示例
To a refluxing mixture of 19.2 g (0.058 mol) of the above material and 2 teaspoonsful of raney nickel in 200 mL ethanol is added over a 15-minute period a solution of 9.6 g of 99% hydrazine hydrate in 30 mL ethanol. The reaction is refluxed 1 hour, cooled, and evaporated to a residue which is dissolved in ether. The ether solution is treated with decolorizing carbon and evaporated to give 3-amino-4-benzyloxyphenyl 2-pyridyl ketone as an oil, 14.2 g (yield 86%).
The material (2.9 g, 7.4 mmols) was dissolved in acetone (60 mL) and the solution stirred at 5°C in an ice bath. 30 percent titanium trichloride solution (40 mL) in hydrochloric acid was added dropwise over 30 minutes and the reaction mixture stirred at 5°C for a further 45 minutes before warming to room temperature overnight. The reaction mixture was poured into water and extracted with diethyl ether. The combined ethereal extracts were washed with water, dried (MgSO4), filtered and the filtrate evaporated under reduced pressure to give a pale yellow solid (1.7 g). This was triturated with a 1:1 petroleum/ether mixture and filtered to yield the desired product (1.2 g) as a cream solid.