3-Oxo-N-[4-[4-(3-oxobutanoylamino)phenyl]ethylphenyl]butanamide, Gulten, S, SyntheticPages, 2011, 498

5-Bromovanillin (Aldrich)

Thiourea (Acros Organics)

37% HCl (Merck)

A mixture of 3-oxo-N-[4-[4-(3-oxobutanoylamino)phenyl]ethylphenyl]butanamide (300 mg, 0.789 mmol), thiourea (180 mg, 2.37 mmol), 5-bromovanilin (460 mg, 1.97 mmol) and catalytic amount of conc. HCl (4 drops) in EtOH (10 mL) was heated at reflux for 3 days. After the completion of reaction, the mixture was allowed to cool. The solid product formed was filtered, washed with water (5 mL) and cold ether (3x5 mL) and dried. The title compound was obtained as a mustard yellow coloured solid (650 mg, 89% yield).

This reaction was carried out with catalytic amount of pTSA to give the corresponding bis Biginelli product in 43% yield.

The authors thank the Çanakkale Onsekiz Mart University Scientific Research Projects Coordination Department (BAP, FYL-2014-178) for financial support.

IR-ATR: 3249, 3195, 3119, 2970, 2934, 1674, 1633, 1575, 1495, 1280, 1180, 1042, 680 cm-1. ¹H NMR (300 MHz, DMSO-d6): ppm = 10.02 (s, 2H, NH), 9.73 (s, 2H, NH), 9.52 (br s, 2H, OH), 9.40 (s, 2H, NH), 7.48 (d, 4H, J = 10.17 Hz, CH_Ar), 7.15 (d, 4H, J = 8.45 Hz, CH_Ar), 6.99 (s, 2H, CH_Ar), 6.87 (s, 2H, CH_Ar), 5.36 (s, 2H, CH), 3.77 (s, 6H, OCH₃), 2.81 (s, 4H, CH₂CH₂), 2.10 (s, 6H, CH₃).
¹³C NMR (75 MHz, DMSO-d6): ppm = 175.13, 165.26, 148.76, 143.77, 137.15, 137.07, 135.71, 135.24, 128.92, 122.40, 120.20, 110.41, 110.07, 107.44, 56.52, 54.91, 37.02, 16.97.

Vijay Virsodia, Raghuvir R.S. Pissurlenkar, Dinesh Manvar, Chintan Dholakia, Priti Adlakha, Anamik Shah, Evans C. Coutinho, Synthesis, screening for antitubercular activity and 3D-QSAR studies of substituted N-phenyl-6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxamides, Eur. J. Med. Chem., 43, 2008, 2103-2115. doi:10.1016/j.ejmech.2007.08.004

B.R. Prashantha Kumar, Gopu Sankar, R.B. Nasir Baig, Srinivasan Chandrashekaran, Novel Biginelli dihydropyrimidines with potential anticancer activity: A parallel synthesis and CoMSIA study, Eur. J. Med. Chem., 44, 2009, 4192-4198. doi:10.1016/j.ejmech.2009.05.014