(4-(3-Nitrophenyl)piperazin-1-yl)(phenyl)methanone → (4-(3-Aminophenyl)piperazin-1-yl)(phenyl)methanone

Participants

Reaction Steps

A solution of 3-iodo-nitrobenzene (3.0 g, 12.0 mmol), piperazine (1.6 g, 18.1 mmol), copper (I) iodide (0.23 ml, 1.2 mmol) and potassium carbonate (3.3 g, 24.1 mmol) in 40 ml DMSO was stirred at 45° C. for 16 hours. The run was quenched with 10 ml water and extracted with ethyl acetate (3×30 ml). The extraction was washed with water (2×30 ml) and dried over anhydrous sodium sulfate. 1-(3-Nitrophenyl)piperazine hydrochloride (2.0 g, 80%) was obtained when bubbling the HCl gas in ether solution. A solution of 1-(3-nitrophenyl)piperazine (1.50 g, 7.2 mmol), benzoyl chloride, and triethylamine (5.0 ml, 36.1 mmol) was stirred at 0° C. for 2 hours. The mixture was washed with water (2×30 ml) and dried over anhydrous sodium sulfate. (4-(3-Nitrophenyl)piperazin-1-yl)(phenyl)methanone (1.2 g, 73%) was obtained by flash column chromatograph (50% ethyl acetate in hexanes). The obtained (4-(3-nitrophenyl)piperazin-1-yl)(phenyl)methanone (1.2 g, 3.8 mmol) was dissolved in 30 ml ethanol and 10 ml THF, followed by the addition of platinum oxide (0.12 mg, 10%) and stirred under hydrogen gas for 16 hours. The reaction was filtered with the aid of celite. (4-(3-aminophenyl)piperazin-1-yl)(phenyl)methanone (0.81 g, 80%) was obtained by flash column chromatograph (90% ethyl acetate in hexanes), and its hydrochloride was made by bubbling HCl gas in ether solution. 1H NMR (500 MHz, DMSO-d6) δ (ppm) 3.25 (s, br, 4H), 3.53 (d, br, 4H), 6.83 (dd, J=1.2, 7.7 Hz, 1H), 6.99 (s, 1H), 7.04 (d, J=8.4 Hz, 1H), 7.34 (t, J=8.2 Hz, 1H), 7.44-7.48 (m, 5H), 10.35 (s, br, 2H). 13C NMR (125 MHz, DMSO-d6): δ (ppm) 42.4, 48.1, 110.0, 112.8, 115.1, 120.2, 127.1, 127.2, 128.4, 129.6, 129.9, 130.2, 135.7, 151.0, 169.1.

Provenance & Evidence