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

SyntheticPage 501
DOI: 10.1039/SP501
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="" />

Chemicals Used

3-Oxo-N-[4-[4-(-3oxobutanoylamino) phenoxy]phenyl]butanamide Gulten,  Gulten, S, SyntheticPages, 2011, 499
Benzaldehyde (Acros Organics)
Thiourea (Acros Organics)
37% HCl (Merck)

Procedure

A mixture of 3-oxo-N-[4-[4-(-3oxobutanoylamino) phenoxy]phenyl]butanamide (300 mg, 0.814 mmol), thiourea (185 mg, 2.44 mmol), benzaldehyde (0.25 mL, 2.44 mmol) and catalytic amoun 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-(-3oxobutanoylamino) phenoxy]phenyl]butanamide and dried. The title compound was obtained as a light yellow solid (486 mg, 94% 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 Nilüfer Hamarat in the  final year research project under my supervision.

Data

IR-ATR:  3380, 3190,  2973, 2873, 1669, 1646, 1602, 1495, 1178, 828 cm-1.
1H NMR (400 MHz, DMSO-d6): ppm = 2.07 (s, 6H, CH3), 5.40 (s, 2H, CH) 6.90 (d, 4H, J= 8.9 Hz,  CHAr), 7.25-7.38 (m, 10H, CHAr), 7.5 (d, 4H, J= 8.9 Hz, CHAr), 9.42 (s, 2H, NH), 9.73 (s, 2H, NH), 9.98 (s, 2H, NH).
13C NMR (100 MHz, DMSO-d6): ppm = 174.63, 165.22, 153.10, 143.53, 135.81, 134.91, 129.09, 128.16, 126.83, 121.79, 119.01, 107.70,  55.57, 16.96.


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, European Journal of Medicinal Chemistry, 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, European Journal of Medicinal Chemistry, 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, ketones, nucleophilic, thermal

Post new comment
  • Guest Alex ClarkAug 30 2014 3:12PMStructure incorrect?

    One of the substituents has moved from para to meta, while the other one has stayed in the same place: is this real?

    • Registered user Peter ScottSep 1 2014 9:38AM

      Well spotted. Will be corrected

    • Registered user Peter ScottSep 1 2014 10:39AM

      corrected. thanks again.

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