Basic Informations

C.V

phoebe Farag Allah Lamie

Master Title

Synthesis of New Quinoxaline Derivatives of

Master Abstract

This study involves a survey covering the synthesis, reactions and biological values of some quinoxaline derivatives. Introducing the quinoxaline nucleus in different types of reactions to give a novel target compounds, was the aim of this thesis to study their expected antimicrobial activity. This was accomplished during the course of this thesis via four schemes. Scheme I includes the reaction of o- phenylenediamine wth a mixture of diethyl oxalate and ethyl acetate to obtain 3-ethoxycarbonylmethyl quinoxalin-2(1H)-one (I), from which we obtain 3-methyl quinoxaline II. Bromination of the later with Br2/AcOH led us to prepare 3-bromomethyl quinoxaline III. Reaction of compound III with different primary and secondary amines gave compounds IVa-e. Also, reacting III with hydrazine afforded 3-hydrazinomethyl quinoxalin-2 (1H)-one (V), this compound was entered in two reactions, the first was condensation with different aromatic aldehydes to give compounds VIa-c, while the second one was cyclization of the hydrazino compound V with some aromatic aldehydes to give VIId&e. Also, compounds VIa-c were cyclized to give VIIa-c. Scheme II consists of hydrazinolysis of the ester I resulted in the hydrazide VIII. Condensation of the later with some aromatic aldehydes afforded the arylidene derivatives IXa-g. Cyclization of IXa-e with acetic anhydride yielded substituted 1,3,5-oxadiazolines Xa-e. Also, reaction of the hydrazide VIII with certain acid anhydrides led to imide derivatives XIa-c. Moreover, 3-hydrazinocarbonylmethyl quinoxalin-2(1H)-one (VII) was reacted with isocyanate and isothiocyanate derivatives to yield semi and thiosemicarbazides XIIa-d. Also, we obtain 5-oxo-1,2,4-triazole derivatives XIIIa&b from the reaction of VIII with isocyanate derivatives. Scheme III includes the reaction of substituted thiosemicarbazides XIIc&d either maleic anhydride or chloroacetic acid to afford thiazolidinone derivatives XIVa&b and XVa&b, respectively. One the other hand, ethyl or phenyl thiosemicarbazide XIIc&d was then cyclized either in acid medium to give 2,5-disubstituted 1,3,4-thiadiazole derivatives XVIa&b or in basic medium to yield 5-thioxo-1,2,4-triazoles XVIIa&b. Upon alkylation of the later with different alkyl or aryl halides, gave XVIIIa-f. In scheme IV, 5-substituted-1,3,4-oxadiazol-2-thione XIX was prepared by heating the hydrazide VIII with CS2 in the presence of alcoholic KOH. When XIX was subjected to Mannich reaction conditions, by reacting it with formaldehyde and different secondary amines in ethanol, it gave the corresponding 3-substituted aminomethyl-5-substituted 1,3,4-oxadiazol-2-thiones XXa-d. Also, reaction of XIX with chloroacetic acid resulted in the formation of XXI, the later was oxidized with H2O2 to yield 5-substituted-1,3,4-oxadiazol-2-one XXII. Alkylation of XIX with different alkyl or aryl halides gave XXIIIa-c. The structural elucidation of the new compounds was supported by elemental analysis, IR, 1H-NMR as well as mass spectral data. The antimicrobial activity of seventeen selected novel compounds was performed at the department of Microbiology and Immunology, Faculty of pharmacy, Beni-Suef University. Some of the selected compounds showed antimicrobial activity.

PHD Title

Synthesis of The New Pyrazolo[3,4-d]Pyrimidine Derivatives of Expected Antitumor Activity

PHD Abstract