反应详情

A mixture of N-methylbis (2-chloroethyl)amine hydrochloride (9.8 g) and 3-nitroaniline (7.0 g) in 1-butanol (100 ml) was heated at reflux for 60 h then cooled to room temperature. Sodium carbonate (2.8 g) was then added and the mixture heated at reflux for a further 18 h, then cooled to 0° C. and filtered. The solid was collected, washed with anhydrous ether then partitioned between dichloromethane (200 ml) and sodium hydroxide solution (1M, 150 ml). The organic layer was separated and the aqueous phase washed once more with dichloromethane (200 ml). The combined organic layers were dried (K2CO3) and evaporated in vacuo. The resultant residue was chromatographed on silica gel, using dichloromethane:methanol (96:4) as the eluant, to afford an orange oil. The oil crystallised on standing and the resultant solid was triturated with petrol (60/80) to give the desired piperazine (5.64 g). 1H NMR (360 MHz, CDCl3) δ2.37 (3H, s), 2.58 (4H, t, J=5 Hz), 3.30 (4H, t, J=5 Hz), 7.18 (1H, dd, J=9 and 3 Hz), 7.35 (1H, t, J=8 Hz), 7.64 (1H, dd, J=9 and 2 Hz), 7.71 (1H, d, J=2 Hz). MS (CI, NH3) 222 (M+1).

1. temperaturewas heated
2. temperatureat reflux for 60 h
3. temperaturethe mixture heated
4. temperatureat reflux for a further 18 h
5. temperaturecooled to 0° C.
6. filtrationfiltered
7. customThe solid was collected
8. washwashed with anhydrous ether
9. customthen partitioned between dichloromethane (200 ml) and sodium hydroxide solution (1M, 150 ml)
10. customThe organic layer was separated
11. washthe aqueous phase washed once more with dichloromethane (200 ml)
12. dry with materialThe combined organic layers were dried (K2CO3)
13. customevaporated in vacuo
14. customThe resultant residue was chromatographed on silica gel
15. customto afford an orange oil
16. customThe oil crystallised
17. customthe resultant solid was triturated with petrol (60/80)