ABSTRACT Condensation of β-Oxoanilide 1 with active methylene derivatives 2a,bafforded the pyridine derivative 5, and with crotononitrile afforded the pyridine 8. Compounds 9 and 11a-c were obtained by reaction of 1 with malononitrile dimer and arylidinemalononitrile 10a-10c. In contrast, when compound 1 reacted with ethoxymethylen malononitrile afforded the pyridine derivative 13. On the other hand, treatment of 1 with anthranilic acid gave the quinoline derivative 14. Also, reactions of 1 with isothiocyanate derivatives afforded compounds 16-18. The reaction of 1 with chalcone derivative afforded the pyridine derivative 22. Treatment of compound 1 with thiourea produced pyrimidine derivative 23. Furthermore, compound 1 converted into pyrimidinethione 24a and pyrimidinone 24b on treatment with a mixture of aromatic aldehydes and thiourea or urea respectively. Reaction of 24a with hydrazonyl halide, thiosemicarbazide and arylidinecyanothioacetamide afforded compounds 26, 28 and 29. Compound 29 was treated with chloroacetonitrile to afford compound 30. Six compounds from the newly synthesized were screened for antibacterial and antifungal activity against bacteria staphylococcus aureus, bacillus cereus and klebsiella pneumonia and fungi aspergillus flavus and aspergillus ochraceous, respectively. Some of the tested compounds showed significant antimicrobial activity. IR, 1H NMR, mass spectral data, and elemental analysis elucidated the structures of all the newly synthesized compounds.
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A. Hussein, M. Gad-Elkareem, A. El-Adasy, A. Khames and I. Othman, "β-Oxoanilides in Heterocyclic Synthesis: Synthesis and Antimicrobial Activity of Pyridines, Pyrans, Pyrimidines and Azolo, Azinopyrimidines Incorporating Antipyrine Moiety," International Journal of Organic Chemistry, Vol. 2 No. 4, 2012, pp. 341-351. doi: 10.4236/ijoc.2012.24047.
 E. Rajanarendar, P. Ramesh, M. Srinivas, K. Ramu and G. Mohan, “Solid-Supported Synthesis of Isoxazole-Substituted 1,4-Dihydropyridines by Modified Hantzsch Method and Their Aromatization,” Synthetic Communications, Vol. 36, No. 5, 2006, pp. 665-671.
 A. T. Manvar, R. R. Pissurlenkar, V. R.Virsodia, K. D. Upadhyay, D. R. Manvar, A. K. Mishra, H. D. Acharya, A. R. Parecha, C. D. Dholakia, A. K. Shah and E. C. Coutinho, “Synthesis, in Vitro Antitubercular Activity and 3D-QSAR Study of 1,4-Dihydropyridines,” Molecular Diversity, Vol. 14, No. 2, 2010 pp. 285-305.
 W. W. Wardakhan, G. A. Elmegeed and F. M. Manhi, “Utility of 2-Aminothiophene-3-carboxamide in the Synthesis of Biologically Active, Fused Heterocyclic Derivatives” Phosphorus, Sulfur, Silicon, and Related Elements, Vol. 180, No. 1, 2005, pp. 125-140.
 A. M. Hussein, A. A. Harb, and I. A. Mousa, “β-Oxoanilides in Heterocyclic Synthesis: An Expeditious Synthesis of New Polyfunctionally Substituted Pyridine and Pyrazole Derivatives,” Journal of Heterocyclic Chemistry., Vol. 45, No. 6, 2008, pp. 1819-1823.
 T. M. Abu Elmaati, “Alkyl Heterocycles in Heterocyclic Synthesis (II): Novel Synthesis of Isoquinoline, Thiazolopyridine, and Thieno[2,3-b]pyridine Derivatives,” Journal of Heterocyclic Chemistry, Vol. 41, No. 6, 2004, pp. 947-950. doi:10.1002/jhet.5570410614
 A. A. Harb, A. M. Hussein and I. A. Mousa, “Acetoacetanilides in Heterocyclic Synthesis, Part 1: An Expeditious Synthesis of Thienopyridines and Other Fused Derivatives,” Phosphours, Sulfur and Silicon, and Related Elements, Vol. 181, No. 10, 2006, pp. 2247-2261.
 A. M. Hussein, A. A. M. El-Adasy, M. A. M. Gad-Elkareem and I, M. Othman, “β-Oxoanilides in Heterocyclic Synthesis: A Convenient Synthetic Route to Polyfunctionally Substituted Pyridazines and Pyridines,” Organic Chemistry an Indian Journal, Vol. 4, No. 3, 2008, pp. 178-186.
 A. M. Hussein, M. S. El-Gaby, F. A. Abu-Shanab and M. A. M. Abdel-Raheim, “β-Oxoanilides in Heterocyclic Synthesis: Synthesis of Tri-and Tetracyclic Heteroaromatic Containing a Bridgehead Nitrogen Atom,” Organic Communications, Vol. 2, No. 3, 2009, pp. 66-71.
 A. M. Hussein, M. A. M. Gad-Elkareem, A. A. M. El-Adasy and I. M. Othman, “N-1-naphthyl-3-oxo-butanamide in Heterocyclic Synthesis: A Facile Synthesis of Nicotinamide, Thieno[2,3-b]pyridine, and Bior Tricyclic Annulated Pyridine Derivatives Containing Naphthyl Moiety,” Phosphorus, Sulfur, Silicon, and Related Elements, Vol. 184, No. 9, 2009, pp. 2263-2280.
 A. Riahi, M. Wurster, M. Lalk, U. Lindequist and P. Langer, “Synthesis and Antimicrobial Activity of 4-Hydroxy-4-(pyridyl)alk-3-en-2-ones,” Bioorganic & Medicinal Chemistry, Vol. 17, 2009, pp. 4323-4326.
 X. Zhu and D. Shi, “Convenient Synthesis and Biological Activities of Pyridine Derivatives of 3,4-Dihydropyrimidin-2(1H)-ones,” Journal of Heterocyclic Chemistry, Vol. 48, No. 3, 2011, pp. 572-576.
 B. Ramesh and C. M. Bhalgat,” Novel dihydropyrimidines and its pyrazole derivatives: Synthesis and pharmacological screening” Eur. J. Med. Chem., Vol. 46, 2011, pp. 1882-1891. doi:10.1016/j.ejmech.2011.02.052
 H. Behbehani, H. M. Ibrahim, S. Makhseed and H. Mahmoud, “Applications of 2-Arylhydrazononitriles in Synthesis: Preparation of New Indole Containing 1,2,3-Triazole, Pyrazole and Pyrazolo[1,5-a]pyrimidine Derivatives and Evaluation of Their Antimicrobial Activities,” European Journal of Medicinal Chemistry, Vol. 46, 2011, pp. 1813-1820. doi:10.1016/j.ejmech.2011.02.040
 H. Bayrak, A. Demirbas, N. Demirbas and S. A. Karaoglu, “Cyclization of Some Carbothioamide Derivatives Containing Antipyrine and Triazole Moieties and Investigation of Their Antimicrobial Activities,” European Journal of Medicinal Chemistry, Vol. 45, 2010, pp. 4726-4732.
 A. A. H. Abdel Rahman, A. H. A. Ahmed and M. M. M. Ramiz, “Synthesis and Anti-Hbv Activity of 4-Aminoantipyrine Derivatives,” Chemistry of Heterocyclic Compounds, Vol. 46, No. 1, 2010, pp. 72-78.
 S. Krivokolysko, V. Dyachenko and V. Litvinov, “A Convenient Method for the Synthesis of Substituted 2-Alkylthio-3-cyano-4,6-dimethyl-5-phenylcarbamoyl-1,4-dihydropyridines” Chemistry of Heterocyclic Compounds, Vol. 36, No. 3, 2000, pp. 284-286.
 V. L. Gein, E. V. Levandovskaya, N. V. Nosova, N. V. Antonova, E. V. Voronina, M. I. Vakhrin and A. P. Krivenko, “Synthesis and Antibacterial Activity of N,N′-diaryl-2-aryl-6-hydroxy-6-methyl-4-oxocyclohexane-1,3-dicarboxamides,” Pharmaceutical Chemistry Journal, Vol. 41, No. 12, 2007, pp. 21-23.
 M. A. M. Gad-Elkareem, M. A. A. Elneairy and A. M. Taha, “Reactions with 3,6-Diaminothieno[2,3-b]-pyridines: Synthesis and Characterization of Several New Fused Pyridine Heterocycles，” Heteroatom Chemistry, Vol. 18, No. 4, 2007, pp. 405-413. doi:10.1002/hc.20313
 H. M. Madkour, M. R. Mahmoud, M. H. Nassar and M. M. Habashy, “Behaviour of Some Activated Nitriles toward Barbituric Acid, Thiobarbituric Acid and 3-Methyl-1-phenylpyrazol-5-one,” Molecules, Vol. 5, No. 5, 2000, pp. 746-755. doi:10.3390/50500746
 S. A. Ahmed, A. M. Hussein, W. G. Hozayen, A. H. H. El-Ghandour and A. O. Abdelhamid, “Synthesis of Some Pyrazolopyrimidines as Purine Analogues,” Journal of Heterocyclic Chemistry, Vol. 44, No. 4, 2007, pp. 803- 810. doi:10.1002/jhet.5570440408
 A. B. A. El-Gazzar, H. N. Hafez and E. M. A. Yakout, “One-Pot Synthesis of Pyrido[2,3-d]pyrimidine-2-thiones and a Study of Their Reactivity towards Some Reagents,” Journal of the Chinese Chemical Society, Vol. 54, No. 5, 2007, p. 1303.
 National Committee for Clinical Laboratory Standards, “Performance Standards for Antimicrobial Disk Suscepti bility Tests,” Approved Standard NCCLS. M2-A5, 13, 24, NCCLS, Villanova, 1993.