1-Methyl-4-(4-nitrobenzyl)piperazine

Synthesis

GENERAL PROCEDURE: Acetic acid (AcOH, 100%, 140 mL, 2.44 mol) was added slowly and dropwise over a period of 1 hour to a flask containing sodium hydride (NaBH4, 20.0 g, 0.53 mol) and chloroform (CHCl3, 220 mL) stirred at 0-5° C. The mixture was then stirred for 1.5 hours. The resulting mixture was continued to be stirred at 0-5°C for 1.5 hours. Subsequently, a solution of N-methylpiperazine (28.0 mL, 0.25 mol) and p-nitrobenzaldehyde (43.4 g, 0.26 mol) dissolved in chloroform (60 mL) was added to the above mixture. The reaction mixture was stirred at 0-5°C for 1 hour and then at room temperature for 12 hours. After completion of the reaction, the mixture was treated with distilled water (150 mL) and sodium carbonate (Na2CO3) and the pH was adjusted to 8.0-9.0. The aqueous phase was extracted with ethyl acetate (EtOAc, 2 x 100 mL), the organic layers were combined, washed with distilled water (1 x 100 mL) and dried over anhydrous sodium sulfate (Na2SO4). Filtration and evaporation of the solvent gave 1-methyl-4-(4-nitrophenyl)piperazine (4a) as a pale yellow oil; yield: 61.6 g, 99% yield.

References

[1] Tetrahedron Letters, 2012, vol. 53, # 38, p. 5056 - 5058
[2] Russian Journal of Organic Chemistry, 2013, vol. 49, # 4, p. 563 - 567
[3] Zh. Org. Khim., 2013, vol. 49, # 4, p. 580 - 584
[4] Journal of Medicinal Chemistry, 2017, vol. 60, # 21, p. 8801 - 8815
[5] Russian Journal of Organic Chemistry, 2011, vol. 47, # 10, p. 1556 - 1563