One-Pot Multicomponent Synthesis of β-Acetamido Ketones Based on BiCl₃ Generated in situ from the Procatalyst BiOCl and Acetyl Chloride

Abstract

Aromatic aldehydes react in one pot at room temperature with enolizable ketones and acetonitrile in the presence of acetyl chloride and catalytic amount of BiOCl producing the corresponding β-acetamido ketones in very high to excellent yields. BiCl₃ ­generated in situ from BiOCl and acetyl chloride catalyzes the ­multicomponent reaction.

Key words

multicomponent reaction - BiOCl - procatalyst - BiCl₃ - β-acetamido ketone

References

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General Experimental Procedure: To a solution of aldehyde (1 mmol), enolizable ketone (1 mmol) and BiOCl (20 mol%) in dry MeCN (4 mL) MeCOCl (2 mmol) was added and the reaction mixture was stirred at r.t. After completion of the reaction (checked by TLC, Table [1] ) the mixture was diluted with CH₂Cl₂ and washed with brine solution (10 mL). The aqueous layer was extracted with CH₂Cl₂ (3 × 5 mL), the pooled organic layer was then washed subsequently with H₂O (1 × 6 mL), NaHCO₃ (1 × 6 mL) and finally with H₂O (1 × 6 mL). The organic layer was dried over Na₂SO₄, concentrated and the residue was purified by column filtration on silica gel.

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All products were characterized by NMR, IR spectroscopy and/or elemental analysis and by comparing the physical data with those in the literature. [4] The following spectral data are representative:
Compound 21: White crystals [EtOAc-petroleum ether (60-80 °C)]; mp 130 °C. IR (KBr): 3270, 1675, 1640, 1598, 1570, 1525, 1420, 1365, 1250, 1205, 1170, 1020, 990, 830, 800, 700 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 2.00 (s, 3 H), 3.31-3.39 (dd, 1 H, J = 5.95, 16.59 Hz), 3.64-3.71 (dd, 1 H, J = 5.28, 16.57 Hz), 3.84 (s, 3 H), 5.53 (m, 1 H), 6.86 (br s, 1 H), 6.89 (br d, 2 H, J = 8.82 Hz), 7.18-7.34 (m, 5 H), 7.88 (br d, 2 H, J = 8.81 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 23.37, 42.76, 50.02, 55.46, 113.80, 126.41, 127.30, 128.55, 129.66, 130.45, 141.07, 163.77, 169.49, 197.08. Anal. Calcd for C₁₈H₁₉O₃N: C, 72.71; H, 6.44; N, 4.71. Found: C, 72.65; H, 6.82; N, 4.67.
Compound 22: White crystals [EtOAc-petroleum ether (60-80 °C)]; mp 194-195 °C. IR (KBr): 3285, 1685, 1635, 1545, 1525, 1400, 1350, 1310, 1290, 1225, 1200, 755, 735, 700, 690 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 3.57-3.64 (dd, 1 H, J = 5.38 Hz, 17.45 Hz), 3.87-3.95 (dd, 1 H, J = 4.94, 17.45 Hz), 5.85 (m, 1 H), 7.44-7.62 (m, 7 H), 7.78 (br d, 1 H, J = 7.8 Hz), 7.84-7.93 (m, 5 H), 8.10 (br d, 1 H, J = 8.11 Hz), 8.28 (s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 42.55, 49.63, 121.39, 122.48, 127.11, 128.16, 128.74, 128.89, 129.64, 131.98, 132.89, 133.67, 134.09, 136.21, 143.47, 166.89, 198.63. Anal. Calcd for C₂₂H₁₈N₂O₄: C, 70.57; H, 4.84; N, 7.48. Found: C, 70.16; H, 4.96; N, 7.23.