Synlett 2005(14): 2245-2247  
DOI: 10.1055/s-2005-872246
LETTER
© Georg Thieme Verlag Stuttgart · New York

Dramatically Accelerated Synthesis of β-Aminoketones via Aqueous Mannich Reaction under Combined Microwave and Ultrasound Irradiation

Yanqing Peng, Ruiling Dou, Gonghua Song*, Jun Jiang
Shanghai Key Laboratory of Chemical Biology, Institute of Pesticides & Pharmaceuticals, East China University of Science and Technology, Shanghai 200237, P. R. China
Fax: +86(21)64252603; e-Mail: ghsong@ecust.edu.cn;
Further Information

Publication History

Received 22 June 2005
Publication Date:
03 August 2005 (online)

Abstract

An efficient green chemistry approach to the synthesis of β-aminoketones was developed under combined microwave and ultrasound irradiation. With this technique, the title compounds were rapidly synthesized in aqueous media with good yields.

10

Typical experimental procedure under CMUI condition: The apparatus employed in the experiments has been described in detail in the literature.7 To a mixture of aromatic 4-nitroacetophenone (3.30 g, 20 mmol), trioxymethylene (0.72 g, 8 mmol), and dimethylamine hydrochloride (1.96 g, 24 mmol) in a 25 mL two-necked flask was added water (3 mL). The mixture was then subjected to CMUI (microwave 200 W/2450 MHz; ultrasound: 50 W/20 KHz) for 45 s (monitored by TLC). The resulting solution was then poured into acetone (15 mL) and cooled in a refrigerator for several hours. The crude product thus precipitated was collect by filtration and recrystallized from 95% aqueous EtOH (95%) gave pure product (4.14 g, 80% yield) as yellowish crystals.

11

Characteristic data of selected β-aminoketones: 3-Dimethylamino-1-(4-nitrophenyl)propan-1-one hydrochloride (2): mp 190-191 °C (lit.4d 187.5-188.5 °C); FTIR (KBr): 3110, 3066, 2965, 2910, 2680, 2580, 2475, 1700, 1525, 1335, 1214, 964, 855, 740 cm-1; 1H NMR (500 MHz, CD3OD): δ = 2.96 (s, 6 H, 2 × CH3), 3.57 (t, 2 H, J = 6.4 Hz, NCH2), 3.68 (t, 2 H, J = 6.4 Hz, COCH2), 8.23 (d, 2 H, J = 8.8 Hz, C6H4NO2), 8.39 (d, 2 H, J = 8.8 Hz, C6H4NO2). 3-Morpholino-1-(4-nitrophenyl)propan-1-one hydrochloride (8): mp 207-209 °C (lit.4d 207-209 °C); FTIR (KBr): 3100, 3060, 3035, 3000, 2960, 2895, 2640, 2560, 2460, 1695, 1598, 1520, 1445, 1380, 1340, 1265, 1215, 1125, 1090, 970, 745 cm-1; 1H NMR (500 MHz, CD3OD): δ = 3.21 (br s, 2 H, CH2), 3.58 (br s, 2 H, CH2), 3.63 (t, 2 H, J = 6.4 Hz, NCH2), 3.71 (t, 2 H, J = 6.4 Hz, COCH2), 3.82 (br s, 2 H, CH2), 4.17 (br s, 2 H, CH2), 8.27 (d, 2 H, J = 8.5 Hz, C6H4NO2), 8.39 (d, 2 H, J = 8.6 Hz, C6H4NO2). 3-Pyrrolidino-1-(4-nitrophenyl)propan-1-one hydrochloride (10): mp 181-183 °C (lit.4d 182.5-185 °C); FTIR (KBr): 3095, 3025, 2985, 2925, 2905, 2654, 2545, 2365, 1685, 1598, 1521, 1450, 1345, 1225, 980, 745 cm-1; 1H NMR (500 MHz, CD3OD): δ = 1.85 (br s, 2 H, CH2), 2.01 (br s, 2 H, CH2), 3.02 (br s, 2 H, CH2), 3.47 (t, 2 H, J = 6.4 Hz, NCH2), 3.57 (br s, 2 H, CH2), 3.70 (t, 2 H, J = 6.3 Hz, COCH2), 8.22 (d, 2 H, J = 8.7 Hz, C6H4NO2), 8.38 (d, 2 H, J = 8.8 Hz, C6H4NO2).