Abstract
α,β-Unsaturated nitroalkenes are readily reduced to alkylamines by in situ generated BH3·THF in refluxing THF.
Table I
Reduction of α,β-Unsaturated Nitroalkenes to Alkylamines
| Nitroalkene | Producta | Yieldb |
 | 74% | |
75% | ||
85% | ||
79% | ||
78% | ||
Notes:
- Products exhibited physical and spectral properties
in accord with the assigned structures. - Isolated and unoptimized yields.
Alkylamines are generally accessible via the reduction of nitroalkenes with lithium aluminum hydride1-4. However, the process often produces mixture of products in modest yields. In our search for a rapid synthetic methodology applicable to the synthesis of radiolabelled amphetamine derivatives5, we recently developed synthetic routes to N-substituted hydroxylamines6 and alkylamines from nitroalkenes. The essential feature of the syntheses is the sodium borohydride catalyzed reduction of nitroalkenes by borane.
The procedure utilizes BH3·THF, which is not readily available in all laboratories. In addition, the amine syntheses require six days to reach completion. Consequently, we sought to develop a more practical synthetic route to alkylamines.
We now wish to report that the reduction of α,β-unsaturated nitroalkenes to alkylamines8 can be achieved utilizing in situ generated BH3·THF. The reaction yields are comparable to those reported earlier and the reaction can be carried out in one pot in approximately five hours. Our results are summarized in Table I.
Experimental
The glassware was thoroughly dried in an oven and cooled under dry nitrogen before use THF was dried over CaH2, distilled from LiAlH4 and stored under dry nitrogen. Commercial reagents, BF3·Et2O, 1-nitro-1-cyclohexene and β-nitrostyrene (Aldrich) were used as received. Other nitroalkenes were prepared via published procedures4,9.
Synthesis of Alkylamines - General Procedure
The synthesis of β-phenylethylamine is representative of the procedure employed.
A flame-dried, nitrogen-flushed, 100 mL flask equipped with a septum inlet, magnetic stirring bar and reflux condenser was cooled to 0°C. Sodium borohydride (9.5 mmol, 0.36g) was placed in the flask followed by sequential addition of THF (13-15 mL) and BF3·Et2O (12 mmol, 1.5 mL) at 0°C. After the addition, the ice bath was removed and the contents were stirred at room temperature for 15 min. The solution of β-nitrostyrene in THF (2 mmol, 0.3g in 5 mL THF) was then injected dropwise into the reaction flask via a syringe and the reaction mixture refluxed on an oil bath for 5.5 h. After cooling to room temperature, the reaction was quenched by careful addition of ice water (25 mL), the mixture acidified (1N HCl, 25 mL), and then heated at 80-85°C (oil bath) for 2 h. After cooling to room temperature, the acidic layer was washed with ether (2x15 mL) and the amine liberated via the addition of aqueous sodium hydroxide. Solid NaCl was added and the product extracted into ether (3x25 mL). The combined ethereal extracts were dried over anhydrous MgSO4 and the solvent removed under reduced pressure to yield 0.181g (75%) of β-phenylethylamine. The product exhibited physical properties and spectral characteristics in accord with the assigned structure.