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Biginelli reaction with benzaldehyde; N,N'-(4,4'-(ethane-1,2-diyl)bis(4,1-phenylene))bis(6-methyl-4-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide)

SyntheticPage 500
DOI: 10.1039/SP500
Submitted Aug 01, 2011, published Aug 01, 2011
Sirin Gülten (siringulten@hotmail.com)
A contribution from Gülten Group, Çanakkale


			Reaction Scheme: <img src="/images/empty.gif" alt="" />Biginelli reaction<img src="/images/empty.gif" alt="" />&nbsp;with benzaldehyde

Chemicals Used

3-Oxo-N-[4-[4-(3-oxobutanoylamino)phenyl]ethylphenyl]butanamide Gulten, S, SyntheticPages, 2011, 498
Benzaldehyde (Acros Organics)
Thiourea (Acros Organics)
37% HCl (Merck)

Procedure

A mixture of 3-oxo-N-[4-[4-(3-oxobutanoylamino)phenyl]ethylphenyl]butanamide (300 mg, 0.789 mmol), thiourea (183 mg, 2.41 mmol), benzaldehyde (0.24 mL, 2.41 mmol) and catalytic amount of conc. HCl (4 drops) in EtOH (10 mL) was refluxed overnight. After the completion of reaction, the reaction mixture was allowed to cool. The solid product formed was filtered, washed with water (5 mL) and cold ether (3x5 mL) to remove the unreacted thiourea or benzaldehyde or 3-oxo-N-[4-[4-(3-oxobutanoylamino)phenyl]ethylphenyl]butanamide and dried. The title compound was obtained as a cream coloured solid (450 mg, 88% yield).

 

Author's Comments

This reaction was carried out with catalytic amount of pTSA to give the corresponding bis Biginelli product in good yield.
This reaction was carried out by Elif Özdemir in the  final year research project under my supervision.

Data

IR-ATR:  3377, 3188,  3031, 2969, 2922, 2858, 1672, 1632, 1593, 1515, 1180, 824 cm-1.
1H NMR (400 MHz, DMSO-d6): ppm = 2.06 (s, 6H, CH3), 2.76 (s, 4H, CH2), 5.39 (s, 2H, CH) 7.08 (d, 4H, J= 7.8 Hz,  CHAr), 7.25-7.40 (m, 10H, CHAr), 7.43 (d, 4H, J= 7.8 Hz, CHAr), 9.41 (s, 2H, NH), 9.65 (s, 2H, NH), 9.97 (s, 2H, NH).
13C NMR (100 MHz, DMSO-d6): ppm = 174.10, 164.74, 143.04, 136.75, 136.48, 135.23, 128.58, 128.38, 127.63, 126.33, 119.62, 107.29,  55.06, 36.47, 16.45.


Lead Reference

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

 

Other References

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

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Get structure file (.cdx, .sk2, .mol)

Keywords: addition, amides, aromatics/arenes, Biginelli dihydropyrimidine, heterocyclic compounds, nucleophilic, thermal

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