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

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.

Mannich reaction - β-aminoketones - microwave - ultrasound - aqueous media

References

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<A NAME="RU19205ST-10">10</A>

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.

<A NAME="RU19205ST-11">11</A>

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).

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