الفهرس 
IntroductionOnly 14 pages are availabe for public view
Abstract
The present work aimed to utilize 4-Arylidene-2-phenyl-oxazol-5(4H)-one 29a,b in the synthesis of some new heterocycles of potent biological activity.
In the present investigation we aimed to study the action of hydrazine hydrate on 4-Arylidene-2-phenyl-oxazol-5(4H)-one 29a,b under different conditions.
The treatment of 29a,b with hydrazine hydrate in refluxing ethanol afforded the E-configurated isomers hydrazide derivative 165a,b. While, on carrying out the same reaction by stirring at room temperature on 29a in methanol with hydrazine hydrate we obtained the Z-configurated isomer of hydrazide derivative 166. However, refluxing 29b in methanol with hydrazine hydrate for 1h afforded the cyclic pyrazolidinone derivative 167.
The authors aimed to utilize the hydrazide derivative Z-166 to synthesis some heterocycles of anticipated biological activity.
Ring closure of hydrazide Z-166 using 1:1 mixture of hydrochloric and acetic acid afforded the Z-configurated isomer of 5-benzylidene-3-phenyl-1,2-dihydro-1,2,4-triazin-6(5H)-one 168, while refluxing Z-166 in 10% aqueous sodium hydroxide gave the 5-benzyl-3-phenyl-1,2,4-triazine-6(5H)-one 170 as a major product.
Heating of hydrazide (Z)-166 with benzoyl chloride in dry benzene gave the E-configurated isomer of dibenzoyl hydrazide derivative N(2-benzoylhydrazinyl)-3-oxo-1-phenylprop-1-en-2-yl) benzamide (E)-171. The latter compound underwent cyclization with phosphorus oxychloride to give the five membered imidazolone derivative 173, while, when heated with 1:1 mixture of hydrochloric and acetic acid gave the six membered triazinone derivative 174.Refluxing of the hydrazide (Z)-166 with carbon disulphide in alkaline medium (10% alcoholic sodium hydroxide) yielded the oxadiazole thione derivative 5-(1-amino-2-phenylethenyl)-1,3,4-oxadiazol-2(3H)-thione 175.
While, on carrying out the same reaction in acidic medium (conc. Sulfuric acid) it gives the six membered triazinone derivative 176.
Action of potassium thiocyanate or potassium isocyanate on hydrazide Z-166 in acetic acid afforded the thiosemicarbazide derivative 178 and semicarbazide derivative 179.
Ring closure of 178 and 179 by heating with 2N sodium hydroxide afforded the six membered triazinone 170.
Treatment of an alcoholic solution of oxazolone 29a with semicarbazide hydrochloride in the presence of fused sodium acetate as a base furnished the E-configurated isomer adduct of five membered imidazolone derivative 180
Similar, treatment of oxazolone 29a with thiosemicarbazide afforded the imidazolone derivative 182.
Part (2)
Authors aimed to study the action of carbon and nitrogen nucleophiles on oxazolone 29a under different conditions.
Refluxing 29a with malononitrile in dry benzene and in the presence of ammonium acetate as a base afforded the unexpected 4-benzylidene-2-phenyl-1H-imidazole-5(4H)-one (184). Acetylation of 184 with acetic anhydride gave the N-acetyl derivative 185.
Refluxing of oxazolone 29a with malononitrile in ethanol and in the presence of piperidine as a base gave a mixture of 2-(2-amino-4,4-dicyano-3-phenylbut-2-enoyl) malonamide (186) (minor) andN-((4,4-dicyano-1-oxo-3-phenyl-1-(piperidin-1-yl)-but-2-en-2-yl) benzamide (187) (major).
Acetylation of 186 with acetic anhydride in pyridine afforded N-acetyl derivative 2-(2-acetamido-4,4-dicyano-3-phenyl-2-enoyl)-N1,N3-diacetylmalonamide (188).
Heating of the benzamide derivative 187 with formic acid yielded 2-benzamido-3-phenyl acrylic acid 189.
Refluxing of the benzamide derivative 187 with acetic anhydride gave the starting material oxazolone 29a.
Fusion of oxazolone 29a with p-anisidine gave the open chain adduct N-(3-(4-methoxyphenylamino)-3-oxo-1-phenylprop-1-en-2-yl)-benzamide (190) which undergoes cyclization by refluxing with a mixture of equimolar amounts of concentrated HCl and acetic acid to give 4-benzylidene-1-(4-
methoxyphenyl)-2-phenyl-1H-imidazol-5(4H)-one (191).
Fusion of imidazolone 191 with malononitrile and in the presence of ammonium acetate as a base gave (2Z, 6Z)-7-amino-4-benzylidene-1-(4-methoxyphenyl)-5-oxo-2-phenyl-4,5-dihydro-1H-1,3-diazepine-6-carbonitrile (192).
Part (3)
We aimed to synthesize the Schiff base of isatin with hydrazide 165b. Then studying its behavior towards some carbon nucleophiles, on the hope of getting some heterocyclic compounds of anticipated biological activity.
Refluxing an equimolar amounts of the hydrazide 165b with isatin in ethanol and trace amounts of acetic acid furnished N-(3-oxo-3-(2-(oxindolin-3-ylidene)hydrazinyl)-1-(thiophen-2-yl)prop-1-en-2-yl)benzamide (193).Cyclization of 193 by heating with a redistilled acetic anhydride afforded 1-acetyl-3-((Z)-5-oxo-2-phenyl-4-(thiophen-2-yl-methylene)-4,5-dihydro-1H-imidazol-1-ylimino)indolin-2one (194).
Refluxing benzamide derivative 193 with ethyl cyanoacetate in n-butanol and in the presence of piperidine as a base yielded N-(3-(2,5’-dioxo-4’-piperidine-1-carbonyl)spiro[indoline-3,3’-pyrazolidine]-1’-yl)-3-oxo-1-(thiophen-2-yl)prop-1-en-2-yl)benzamide (195). However, on carrying out the same reaction with malononitrile afforded N-(3-(2-(3-(1-cyano-2-oxo-2-(piperidin-1-yl)ethyl)-2-oxindolin-3-yl)hydrazinyl-3-oxo-1-(thiophen-2-yl)prop-1-en-2-yl)benzamide (197). Similar treatment with acetyl acetone furnished N-(1-(4’-acetyl-5’-methyl-2-oxo-5’-(piperidin-1-yl)spiro[indoline-3,3’-pyrazolidine]-1’-yl)-2-(thiophen-2-yl)vinyl)benzamide (196) and with ethyl acetoacetate afforded N-(3-(2-(3-(1,3-dioxo-1-(piperidin-1-yl)butan-2-yl)-2-oxindolin-3-yl)hydrazinyl)-3-oxo-1-(thiophen-2-yl)prop-1-en-2-yl)benzamide (198).
Structural assignment of the newly synthesized compounds was based on their infrared, mass and nuclear magnetic resonance spectra.
Also, the biological activity of the newly synthesized compounds was screened, which revealed that the synthesized compounds showed high and / or very high antimicrobial activity against the examined bacteria and fungi, respectively. It could be concluded from the results that the biologically active synthesized compounds are nearly active against the tested Gram positive bacteria (Bacillus subtilis ATCC 6633, Micrococcus luteus ATCC 25922), Gram negative bacteria (Escherichia coli ATCC 23282 and Bordetella pertussis ATCC 9340), Yeast (Candida albicans IMRU 3669) and Filamentous Fungus (Aspergillus niger ATCC 16404).