Abstract
A new compound, 4,6-diamino-5-(3,4-dichlorobenzylidene)pyrimidin-2(5H)-one, was synthesized and its IR, 1H NMR,13C NMR, MS spectroscopic data and elemental analysis are presented.
There is continuous interest in the synthesis of pyrimidine derivatives because of the diverse biological properties associated with these systems. For instance, compounds with annulated uracils have antitumor [1], antibacterial [2], leishmanicidal [3] anticonvulsant [4], antirubella [5], anti-HIV [6], calcium channel modulation [7], and selective hepatitis B virus inhibition [8] activity.
The Biginelli reaction is a well-known multicomponent reaction which involves a one-pot cyclocondensation of an aldehyde, a methylene-active compound and urea/thiourea, has been used in the synthesis of pyrimidine derivatives [9,10,11,12,13]. Nevertheless, little attention has been given thus far to the synthesis and biological activity of the pyrimidine nucleus with the benzylidene group in position 5, next to two amino groups in positions 4 and 6. In continuation of our work [11,12], in this communication, the synthesis, characterization and antibacterial activity of 4,6-diamino-5-(3,4- dichlorobenzylidene)-2(5H)-pyrimidinone 2 are presented. Compound 2 was obtained from the reaction between (3,4-dichlorobenzylidene)propanedinitrile 1 and urea. The title compound thus synthesized is original to this study. The reaction of 1 and urea have not been previously studied.
A mixture of (3,4-dichloroenzylidene)propanedinitrile 1 [14] (0.2 g, 1.19 mmol), urea (0.14 g, 2.33 mmol), and K2CO3 (0.20 g, 1.17 mmol) in methanol was refluxed for 24 h. The solid obtained was filtered and washed with water. After recrystallization from water-DMF, 2 was obtained as a yellowish solid (0.18 g, 80%). Synthesis of other pyrimidine derivatives and studies of their biological activities are in progress, including tests of antibacterial and anticonvulsive activity as a part of a research program directed to the synthesis of novel heterocyclic compounds of pharmacological interest.
Melting point: 133–135 °C
IR (KBr, cm−1): 3270 (NH), 1780 (C=O), 1651 (C=N)
1H NMR (DMSO-d6, 270 MHz): δ: 8.04 (1H, s, olefinic-H); 7.97 (1H, d, J = 8.4 Hz, Ar-H); 7.76 (1H, d, J = 2.2 Hz, Ar-H); 7.56 (1H, dd, J = 10.8 and 2.0 Hz, Ar-H); 5.22 (4H, s, NH2).
13C NMR (DMSO-d6, 69 MHz): 166.27, 164.89, 135.20, 131.56, 131.47, 131.03, 124.00, 116.46, 116.24, 115.94.
EI-MS m/z (rel. int. %): 285 (5) [M+2]+; 284 (9) [M+1]+; 283 (27) [M]+; 255 (100) [M -CO]+; 184 (63), 77 (27).
Anal. Calcd for C11H8Cl2N4O: C: 46.67%; H: 2.85%; Cl: 25.05%; N: 19.79%; O: 5.65%. Found: C: 46.31%; H: 2.69%; N: 19.74%.
Antibacterial Activity
Compound 2 showed antibacterial activity against Bacillus cereus (ATCC 14579) (Gram positive bacteria) and Staphylococcus aureus (ATCC 25922) (Gram positive bacteria), as reference drugs were used: Ampicillin, Sulbactam, Norfloxacin and Nystatin.
Supplementary materials
Supplementary File 1Supplementary File 2Supplementary File 3Supplementary File 4Acknowledgements
We are grateful to “Consejo de Desarrollo Científico y Humanístico de la Universidad Central de Venezuela /CDCH-UCV)” for financing the Project: PI 06-00-6759-2007.
References
- Grivsky, E.M.; Lee, S.; Siyal, C.W.; Duch, D.S.; Nichol, C.A. Synthesis and antitumor activity of 2,4-diamino-6-(2,5-dimetoxibencil)-5-methylpyrido [2,3-d]Pyrimidine. J. Med. Chem. 1980, 23, 237–329. [Google Scholar] [CrossRef]
- Gossnitzer, E.; Feierl, G.; Wagner, U. Synthesis, structure investigations, and antimicrobial activity of selected s-tran-6-aril-4-isopropyl-2-2[2-[(E)-1-phenylalkylidene]-(E)-hydrazino]-1,4-dihydropyrimidine hydrochlorides. Eur. J. Pharm. Sci. 2002, 15, 49–61. [Google Scholar] [CrossRef]
- Ram, V.J.; Haque, N. Synthesis of functionalized pyrazolo[3,4-d]pyrimidine as potential leishmanicides. Indian J. Chem. 1995, 34B, 521–524. [Google Scholar]
- Calis, U.; Koksal, M. Synthesis and evaluation of anticonvulsant activities of some new aryl-hexahydropyrimidine-2,4-dione. Arzneim.-Forsch/Drug Res. 2001, 51, 523–528. [Google Scholar]
- Saladino, R.; Ciambecchini, U.; Maga, G.; Mastromarino, P.; Conti, C.; Botta, M. A new and efficient synthesis of substituted 6-[(2’-dialkylamino)ethyl]pyrimidine and 4-N,N-dialkyl-6-vinylcytosine derivatives and evaluation of their anti-Rubella activity. Bioorg. Med. Chem. 2002, 10, 2143–2153. [Google Scholar] [CrossRef]
- San-Felix, A.; Velazquez, S.; Perez-Perez, M.J.; Balzarini, J.; De Clercq, E.; Canarasa, M.J. Novel series of TSAO-T derivatives. Synthesis and anti-HIV-1 activity of 4-, 5-. and 6- substituted pyrimidine analogues. J. Med. Chem. 1994, 37, 453–460. [Google Scholar] [CrossRef] [PubMed]
- Vanden Eynde, J.J.; Audiart, N.; Canonne, V.; Michel, S.; van Haverbeke, Y.; Kappe, C.O. Synthesis and Aromatization of Dihydropyrimidines Structurally Related to Calcium Channel Modulators of the Nifedipine-Type. Heterocycles 1997, 45, 1967–1978. [Google Scholar]
- Kumar, R.; Nath, M.; Tyrrell, D.L. Design and synthesis of novel 5-substituted acyclic pyrimidine nucleosides as potent and selective inhibitor of hepatitis B virus. J. Med. Chem. 2002, 45, 2032–2040. [Google Scholar] [CrossRef] [PubMed]
- Lu, J.; Bai, Y. Catalysis of the Biginelli Reaction by Ferric and Nickel Chloride Hexahydrates. One-Pot Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones. Synthesis 2002, 466–470. [Google Scholar] [CrossRef]
- Hazarkhani, H.; Karimi, B. N-Bromosuccinimide as an Almost Neutral Catalyst for Efficient Synthesis of Dihydropyrimidinones Under Microwave Irradiation. Synthesis 2004, 1239–1242. [Google Scholar]
- Lobo, G.; Charris, J.; Valderrama, M.; Taddei, A. 4,6-Diamino-5-[4-(dimethylamino)benzylidene]pyrimidin-2(5H)-one. Molbank 2009, 2009, M615. [Google Scholar] [CrossRef]
- Lobo, G.; Charris, J.; Valderrama, M.; Romero, J.; Castelli, C.; Taddei, A. 4,6-Diamino-5-(4-methylbenzylidene]pyrimidin-2(5H)-one. Molbank 2010, 2010, M653. [Google Scholar] [CrossRef]
- Aydin, F. Synthesis of 4-[4-(dimethylamino)phenyl)]-5-acethyl-6-phenyl-3,4-dihydropyrimidin-2-(1H)thione. Molbank 2006, 2006, M468. [Google Scholar] [CrossRef]
- Tietze, L.F.; Beifus, U.; Trost, B.M.; Fleming, I.; Heathcock, C.H. Comprehensive Organic Synthesis; Pergamon Press: Oxford, UK, 1991; Volume 2, Chapter 1.11; p. 341. [Google Scholar]
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