Isobornylamine
1.67g (10 mmol) camphor oxime and 5.7g (20 mmol) NiCl2·6H2O was dissolved in 100ml methanol and cooled to -30°C, and during 30 minutes 3.8g (10 mmol) NaBH4 was added in portions. The mixture was stirred for another 30 minutes and then the cooling bath was removed and the reaction mixture worked up as usual. Yield after sublimation at 100°C/14 mmHg 1.40g (92%).
4-tert-Butyl-Cyclohexylamine
1.69g (10 mmol) 4-tert-butylcyclohexanone oxime and 2.0g (13.8 mmol) MoO3 was dissolved in 100ml methanol with cooling in an ice-bath, and 3.8g (0.1 mol) NaBH4 was added in portions. After the exothermic reaction had subsided (1h) the reaction mixture was worked up the usual way. After kugelrohr distillation, the yield was 1.35g (87%), the product having a 3:1 cis/trans ratio.
To a solution of the oxime (24.6 mg, 0.521 mmol) in 10% H2O-THF (30ml) were added aluminum amalgam, which was prepared from 0.25g of granular aluminum and 2% HgCl2 (0.1ml) in 10% H2O-THF (0.5ml). The reaction mixture was stirred for 3h at room temperature. 3ml conc NaHCO3 was added, and the reaction mixture was filtered and the filter cake washed with ethyl acetate. The filtrate was diluted with water and extracted with ethyl acetate. The extracts was washed with brine, dried over MgSO4 and concentrated in vacuo to give 20.34 mg (85%) of the desired amine as an oil.
(Rhodium's Voice)
Use only 4 equivs of NaBH4 and 2 equivs of TiCl4 if your molecule only has one oxime group to be reduced. The yields will also be higher with only one oxime.
A solution of the oxime (11g, 19 mmol) in 250ml dry THF was treated with aluminum foil (5g, 190 mmol) that had been cut into small pieces and immersed successively in 2% aqueous HgCl2, distilled H2O and THF. The dark gray suspension was stirred for 12h at room temperature, at which time TLC revealed the absence of starting material. The suspension was filtrered and concentrated to yield 7.8g (75%) of the product amine as a light yellow oil.
(Rhodium's Voice)
The oxime reduced here is a large indole derivative. Use less solvent with smaller molecules at a larger scale.
NaBH4 (0.112 mol, 4.1g, 8 eqv.) and titanium(IV) tetrachloride (0.056 mol, 6ml, 4 equiv) were combined in a 1000ml RB flask (fitted with a rubber septum and purged with nitrogen) and the flask was cooled in an ice-bath. Freshly distilled dimethoxyethane (100ml) was added slowly while the flask was vented with a large bore needle. The dioxime (0.014 mol, 4g) was added as a powder over 5 minutes. The reaction mixture changed color over half an hour, from bright green to green-brown. The solution was allowed to return to room temperature and was stirred for 24 hours. The mixture waas cooled on ice, and water (200ml) was added slowly to quench the reaction. The solution was basified with concentrated aqueous ammonia to pH 13, at which point it became gelatinous and turned dark blue. The aqueos layer was extracted several times with methylene chloride (total 1000ml). The organic layer was dried over sodium sulfate, filtered and the solvent evaporated under vacuum to give 1.7g (60%) of diamine.
(Rhodium's Voice)
Use only 4 equivs of NaBH4 and 2 equivs of TiCl4 if your molecule only has one oxime group to be reduced. The yields will also be higher with only one oxime.
At room temperature with stirring, Zinc dust (74 mg) was added to a solution of the oxime (44mg, 0.185 mmol) in 2 ml glacial acetic acid. Stirring was continued for another 15 minutes. The reaction mixture was then filtered through a sintered glass funnel with suction. The filtrate was concentrated under vacuum to afford the amine as an oil (37mg, 0.166 mmol, 90% yield).
3-Amino-5-pentanol-2-one Hydrochloride
In a flask surrounded by a bath at -15°C was placed 75g of stannous chloride, 100 mL of concentrated hydrochloric acid and 150g of mossy tin. To this was added 14 g of 3-Oximino-5-pentanol-2-one at such a rate that the reaction temperature did not rise above 0°C (about ten minutes). The resulting mixture was allowed to stand at room temperature for one-half hour and then heated to boiling for several minutes. The liquid was decanted, the tin was washed with water and the combined aqueous solutions, after diluting to about 1300 mL, treated with hydrogen sulfide until precipitation of tin sulfide was complete. After filtration, the filtrate was evaporated in vacuo to yield a yellow syrup which was used directly for the next step in the synthesis [a cyclization with SCN- to a thiazole. The overall isolated yield of the purified thiazole from the oxime was 56%, placing the yield for the oxime reduction significantly above that]. In another similar preparation, the sirup was treated with absolute alcohol and anhydrous ether and allowed to crystallize in an icebox. The small amount of crystalline material separating was recrystallized from n-butanol/ether to give needles, mp 134°C (dec.). Yield 60-70%.
Cf. Künne, Ber. 48, 2036 (1895); Gabriel & Pinkus, Ber. 26, 2199 (1893)
Indium powder (~100 mesh, 0.92 g, 8.0 mmol) was added to a solution of the oxime (2.0 mmol), acetic anhydride (0.51 g, ~0.47 mL, 5.0 mmol) and acetic acid (0.48 g, ~0.46 mL, 8.0 mmol) in THF (10 mL) and the mixture heated at reflux for 18 h. Saturated aqueous sodium bicarbonate solution (10 mL) was carefully added to the cooled reaction mixture, and stirring continued for 1 h. The resulting mixture was diluted with water (30 mL) and extracted with ethyl acetate (3x15 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. If necessary, the crude material was purified by flash column chromatography (silica eluting with ~20% ethyl acetate in dichloromethane) to give the N-acetyl amine.
The appropriate oxime (0.02 mole) and 6 mL 64% N2H4·H2O in 50 mL EtOH treated with Raney-Ni W-4 sludge in portions to maintain a steady reaction, refluxed about 4 hrs., filtered, and treated with gaseous HCl gave the amine-HCl salt, or the reaction mixt. dild. with H2O gave the free (H2O-insol.) amine. Mesityl oxide oxime (11.81g), 30 mL 64% N2H4, and 100 mL EtOH yielded 3,5,5-trimethylpyrazoline (I), b45 80-84°C.
By the general procedure were reduced the oximes of the following compds. (% corresponding amine given): Me2CO, 36; EtCOMe, 76; AcPr, 42; AcC9H19 9; cyclopentanone, 27; cyclohexanone, 65; cycloheptanone, 29; menthone, 90; carvomenthone, 36; dihydrocarvone, 8; fenchone, 6; camphor, 0; BzPh, 45; BzEt, 24; BzCH2Ph, 74; fluorenone, 94; 3-hydroxy-1,2-benzofluorenone, 97; (AcCH2)2, 31; C6H13CHO, 0; BzH, 0. Isophorone and carvone gave similarly I. AcC(=NOH)Me and [MeC(=NOH)]2CH2 gave Ni complexes.