Allyl acetoacetate (Acros Organics)

5-bromovanillin (Aldrich)

urea (Merck)

nickel chloride hexahydrate (Merck)

37% HCl (Merck)

A solution of allyl acetoacetate (2.5 mmol), 5-bromovanillin (2.5 mmol), urea (3.75 mmol), nickel chloride hexahydrate (0.62 mmol) and conc. HCl (2 drops) in EtOH (5 mL) were heated under reflux for 6h. After cooling to room temperature the reaction mixture was poured onto crushed ice (20 g) and stirred for 10 min. The crude product was filtered, washed with cold water (2x10 mL) and then recrystallized from ethanol afford white solid.  Yield (0.74 g, 75%).

This reaction was carried out with allyl acetoacetate and thiourea to give the corresponding Biginelli product in good yield. The author thanks Çanakkale Onsekiz Mart University (BAP 2008/28) for financial support.

White solid, R_f= 0.11 (50% ethyl acetate/hexane), m.p. 212-214 ºC.
IR-ATR: 3566, 3221, 3103, 2939, 1701, 1680, 1630, 1579 cm^-1. ¹H NMR (400 MHz, DMSO-d₆): ppm = 7.04 (1H, d, J= 1.69 Hz, H_ar), 6.76 (1H, d, J= 1.66 Hz, H_ar), 5.92 (1H, br s, NH), 5.81-5.88 (2H, m, CH₂=CH), 5.5 (1H, br s, NH or OH), 5.46 (1H, br s, NH or OH), 5.35 (1H, d, J=2.55 Hz, CH₂=CH ), 5.23 (1H, d, J=7.55 Hz, CH₂=CH), 5.19 (1H, s, CHNH), 4.57-4.54 (1H, m, CH₂O), 3.87 (3H, s, CH₃O), 2.37 (3H, s, CH₃). ¹³C NMR (100 MHz, DMSO-d₆): ppm = 165.08, 152.58, 147.26, 146.57, 142.89, 136.31, 132.17, 122.81, 118.30, 108.50, 108.29, 100.96, 64.97, 56.37, 55.33, 19.00.

J. Lu, Y.Bai, Synthesis 2002, 466-470 doi:10.1055/s-2002-20956

J. Lu, H. Ma, Synlett 2000, 63-64 doi:10.1055/s-2000-6469