الفهرس 
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Abstract
PART(I) A) NOVEL 2-THIOXOHYDANTOIN KETENE PITHIOACETALS: VERSATILE INTERMEDIATES FOR SYNTHESIS OF METHYL-SULFAWYLIMIDAZO[5.4-c[PYRAZOLES AND METHYL-SULFANYLPYRKOLO [ 1,2-c] IMIDAZOLES; The reaction of 2-thioxohydantoin derivatives la,b with carbon disulfide in the presence of sodium ethoxide gives the corresponding sodium dithiolate derivatives 2a,b in high yields. The latters on treatment with methyl iodide give the novel 2-thioxohydantoin ketene dithioacetals 3a,b. The structures of 3 have been established on the basis of their elemental analysis and spectral data (MS, IR, 1HNMR, and l3C NMR). Also, salts 2 reacted with benzoyl chloride and phenacyl bromide to yield the corresponding alkylating products 4 and 5, respectively. The structures of 4 and 5 were established and confirmed on the basis of their elemental analysis and spectral data. The 2-thioxohydantoin ketene dithioacetals 3 bearing latent functional substituents were found useful for the synthesis of fused methylsulfanylimidazole derivatives. Thus, it has been found that the reaction of ketene dithioacetals 3 with substituted hydrazines refluxing in ethanol containing a catalytic amount of piperidine gives the corresponding 4-methylsulfanylirnidazo[5,4-c]pyrazoles 6a-d in good yields The structures of 6 were established and confirmed for the reaction products on the basis of their elemental analysis and spectral data (MS, IR and 1H NMR). When compounds 3 were subjected to the reaction with cyanothioacetamide in refluxing ethanol containing a catalytic amount of piperidine, the corresponding 2-mercapto-3-cyano-4-methylsulfanyl-7-thioxopyrrolo[l,2-c]imidazole-5-ones 7 were obtained, the structures of which were established on the basis of spectral evidence. The formation of 7 from the reaction of 3 and cyanothioacetamide is assumed to proceed via initial Michael addition of the active methylene group of cyanothioacetamide to the exocyclic double bond of 3. The Michael adducts cyclized smoothly via CH3SH and NH3 elimination. Similarly, compounds 3 reacted with malononitrile in refluxing ethanol containing a catalytic amount of piperidine to give the corresponding 2-amino-3-cyano-4-methylsulfanyl-7-thioxopyrrolo[l,2-c]imidazole-5-ones 8. The structures of 8 were established and confirmed on the basis of their elemental analysis and spectral data (MS, IR, 1H NMR, and 13C NMR). The formation of 8 from the reaction of 3 and malononitrile is assumed to proceed via the intermediacy of acyclic Michael adducts, which cyclize via CH3SH elimination and addition to the cyano group to yield the final stable diazapentalene analogues 8. The course of the reaction between 3 and malononitrile prompted us to investigate this reaction between 2-thioxohydantoin 1 and bis[(methylthio)methylene]-malononitrile 9 under the same conditions. The products obtained were shown to be the same as those obtained from the reaction of 3 with malononitrile by their melting points and spectral data to give the pyrrolo[l,2-c]imidazoles 8. B) THE FIRST SYNTHESIS OF HETEROCYCLIC KETENE DITHIOACETAL NUCLEOSIDES USING 2-THIOXO¬HYDANTOIN KETENE SS-ACETALS: Compounds 3 can be coupled with different classes of sugar halides to give a novel ring system of glycosides. Thus, it has been found that compounds 3a,b reacted with 2,3,4,6-tetra-O-acetyl-α-D-gluco- and galacto-pyranosyl bromides 11a,b in the presence of aqueous potassium hydroxide to give the corresponding S-glycosides 12a-d. The structures of the reaction products 12a-d were established and confirmed for the reaction products on the basis of their elemental analysis and spectral data (MS, IR, UV, 1H NMR, and I3C NMR). The formation of the S-glycosides 12 and not the corresponding N-glycosides 13 was proven by using I3C NMR and UV analysis. The corresponding S-methyl derivative 10 was prepared by the reaction of 3a with methyl iodide in the presence of aqueous potassium hydroxide. The prepared nucleosides 12a-d can be utilized as an excellent starting material for the synthesis of other carbohydrate derivatives and for biological evaluation studies . PART (II) A CONVENIENT SYNTHESIS OF PYRAZOLO[3,4-cl-PYRAZOLES USING SOME NOVEL cr-CYANOKETENE DITHIOACETALS: The reaction of N-cyanoacetylarylhydrazones 1 with carbon disulfide in the presence of sodium ethoxide gives the corresponding sodium dithiolate derivatives 2 in moderate yields. On treatment the dithiolate derivatives with methyl iodide, the novel ketene dithioacetals 3 were produced. The structures of 3 have been established on the basis of their elemental analysis and spectral data (IR, 1H NMR, 13C NMR and MS). Reaction of compounds 3 with hydrazine derivatives 4 in a molar ratio 1:2 in refluxing ethanol containing catalytic amounts of piperidine or by fusion at 175-185 °C gave the corresponding pyrazolo[3,4-c]pyrazoles 5. The structures of 5 were established on the basis of their elemental analysis and spectral data (IR, 1H NMR, 13C NMR and MS). The formation of 5 from the reaction of 3 with 4 is assumed to proceed via intermediacy of acyclic Michael adducts, which cyclized via addtion to the cyano group and elimination of two molecules of CH3SH and one molecule of H2o. PART (III) HIPPURIC ACID IN HETEROCYCLIC SYNTHESIS; NOVEL SYNTHESIS OF PYRANOf2,3-c)PYRAZOLES, PYRAZOLO-^ll’VUIDIMS AND PYRIDO|l,2-«l BENZIMIDAZOLES; It has been found that 3-methylpyrazolin-5-one la and 3-aminopyrazolin-5-one lb react with triethyl orthoformate and hippuric acid derivatives 3 in refluxing acetic anhydride in a one-pot reaction to yield the novel l-acetylpyrano[2,3-c]pyrazoles 4a-h. The structures of 4 have been established on the basis of their elemental analysis and spectral data (IR 1H NMR and MS). The formation of 4 is assumed to take place via the intermediate 2, which cyclizes via Michael addition of the methylene moiety in 3 to the double bond in 2, followed by ethanol elimination and acetylation of the ring nitrogen. When 4 were refluxed with ethanol in the presence of ammonium acetate, their pyran ring undergo acid catalysed ring opening to afford the acyclic structures 5a-h. The structures of 5 have been established on the basis of their elemental analysis and spectral data (IR1H NMR and MS). Refluxing of the acyclic compounds 5 in acetic anhydride produced the corresponding pyrazolo[3,4-6]pyridines 6. The structures of 6 have been established on the basis of their elemental analysis and spectral data (IR 1H NMR and MS). Compounds 6 can also be prepared when compounds 4 were heated with ammonium acetate at 160-170 °C (bath temp.). The formation of 6 from fusion of 4 with ammonium acetate is assumed to proceed via pyran ring opening in 4 followed by recyclization. Similarly, l-phenyl-3-methylpyrazolin-5-one lc reacts With triethyl orthoformate and hippuric acid derivatives 3 under the same condition to yield the novel l-phenylpyrano[2,3-c]-pyrazoles 4i-I following the same mechanism. In order to investigate the scope of this reaction further and in order to prove that this type of reactions can be extended to constitute a general approach for the synthesis of pyrano- and pyidodiazoles, we studied the reaction of 2-benzimidazole acetonitrile 7 with triethyl orthoformate and hippuric acid derivatives under the same conditions. Thus, it has been found that 7 reacts with triethyl orthoformate and hippuric acid derivatives 3 in refluxing acetic anhydride to afford the novel pyrido[l,2-a]benzimidazole derivatives 10. The structures of 10 have been established on the basis of their elemental analysis and spectral data (MS, IR and 1H NMR). The formation of 10 is assumed to take place via the intermediates 8 then 9. The latter cyclizes via water elimination to yield finally the pyrido[l,2-a]benzimidazole derivatives 10 .