American-Eurasian Journal of Scientific Research 2 (2): 161-169, 2007 ISSN 1818-6785 © IDOSI Publications, 2007 Corresponding Author: Dr. M.A.I. Salem, Synthetic Organic Chemistry Laboratory, Department of Chemistry, Faculty of Science, Ain Shams University, Abbassiya, Cairo, Egypt 161 Utility of Cyanothioacetamide in the Synthesis of Pyrazolo [4, 3-c], Isoxazolo [4, 5-c], Thieno [2, 3-b] and Furo [2, 3-c] of Thioxopyridine Derivatives and their Antibacterial Activities H.M.F. Madkour, M.A.I. Salem, M.I. Marzouk, M.E. Azab and N.F.H. Mahmoud Synthetic Organic Chemistry Laboratory, Department of Chemistry, Faculty of Science, Ain Shams University, Abbassiya, Cairo, Egypt Abstract: The 4-oxo-2-thioxopyridines 2 and 6-oxo-2-thioxopyridines 3 have been synthesized via the reaction of cyanothioacetamide and arylidenecyanoacetic ester. Thioxopyridines 2 was reacted with acetic anhydride, hydrazine hydrate, chloroacetonitrile and sodium hypochlorite/ammonia to yield N, N- diacetylpyridin-6-thione 4, pyrazolopyridin-6-thione 5, furopyridin-6-thione 6 and isoxazolpyridin-6-thione 7, respectively. Treatment of 6 with sodium ethoxide gave 8, while, reaction of 2 with ethyl chloroacetate yielded 9 and 10 according to the reaction conditions. When 2 was allowed to react with POCl3/PCl5, it afforded 13. Treatment of 9 with hydrazine hydrate furnished 11 which reacted with p-chlorobenzaldehyde to yield 12. Reaction of 2 and 3 with methyl iodide produced 14 and 15 respectively. When hydrazine hydrate was allowed to react with 15 it gave 16. Finally, boiling of 2 and 3 in cumene in the presence of copper bronze yielded the disulfide derivatives 17 and 18 respectively. Biological screening of some new synthesized compounds were determined in vitro using gram-positive and gram-negative bacterial strains. Key words: Cyanothioacetamide · thioxopyridine · pyrazolopyridine · isoxazolopyridine · furopyridine · thienopyridine · gram-positive and gram-negative bacterial strains INTRODUCTION A number of pyridone and thioxopyridine derivatives have a widely medicinal and pharmaceutical activities as anti-inflammation in rheumatism, osteoposis, collagen diseases, bursitis, gout, anti- parasitic, analgesic and muscular rheumatism [1-5], fungicidal [6, 7] (specially in shampoos), insecticidal [8], mammalian toxicity [9], neuromuscular stimulant [10], antidepressant [11, 12], anticancer [13], antimobic [14], antimalarial [15], antiviral [16], antihistaminic agents [17, 18]. Also, these compounds are used as irreversible Human Rhinovirus 3C protease inhibitor [19], DNA-ligand bending [20], antituberculosis [21], antitumor [22], antibacterial [23, 24] and antipyretic agents [25]. On the other hand, some pyridine derivatives are used to reduce lipids and cholestrol levels in the blood [26], as treatment of unstable angina [27], hair dyes [28], as X-ray contrast media [1, 29], elastomer and ion exchange resins [30], in floation process for recovery of metal concentrates from metal bearing ores [31], as nitrogen stabilizer in soil [32] and gyrase inhibitor [33]. RESULTS AND DISCUSSION Within this respect, the aim of the present work is to synthesise a wide derivatives of thioxopyridine and study both the chemical behaviour towards some chemical reagents and biological activity towards some gram-positive and gram-negative bacteria [34-36]. It has been reported that cyanothioacetamide reacted with the arylidene cyanoacetic ester in the presence of triethylamine to give 3, 5-dicyano-6-oxo-4-phenyl-2- thioxo-1, 2, 3, 4-tetrahydropyridine [37, 38] 1 as a sole product while in our investigation we isolated two products which are identified to be (5E)-6-amino-5-arylidene-3-cyano-4-oxo-2-thioxo -2, 3, 4, 5-tetrahydropyridine 2 and (5E) 4-amino-5- arylidine-3-cyano-6-oxo-2-thioxo -1, 2, 5, 6- tetrahydropyridine 3.