Author name:
احمد ماهر فهيم
Supervisor name:
نبيل عبد عبد الرضا
Abstract:
The present work involved synthesis of new indole derivatives containing other heterocyclic ring. These derivatives could be divided into the following parts : 1. The first part involved synthesis and characterization of novel 1,3 - diazidine[XIII]a - d and [XIV]a - d by the following steps : Scheme(1).a. Synthesis of 3 - [(5 - hydrazinyl - 4 - phenyl - 1,2,4 - triazol - 3 - yl)methyl] - 1H - indole [VI], this compound is synthesized by neucleophilic substitution reaction of 1,2,4 - triazole - 5 - thiol compound [V]a with excess of hydrazine hydrate in absolute ethanol as a solvent.b. Synthesis of 2 - {5 - [(1H - indol - 3 - yl) - propyl] - 4 - phenyl - 1,2,4 - triazol - 3 - yl} - thio - acetohydrazide[VIII]b, by the reaction of ester compounds[VII]b with excess of 80% hydrazine hydrate in ethanol under reflux.c. Synthesis of new Schiff bases[IX]a - d and [X]a - d by condensation reaction of primary amino compounds[VI] or [VIII]b with different aromatic aldehyde in absolute ethanol as a solvent.d. Synthesis of new N - acyl derivatives[XI]a - d and [XII]a - d by reaction of acetyl chloride with the synthesized Schiff bases[IX]a - d, [X] a - d in dry benzene.e. Synthesis of 1, 3 - diazetine derivatives[XIII]a - d and [XIV]a - d by addition reaction of compound[XI]a - d or [XII]a - d with sodium azide in dimethylformamid as a solvent at (55 - 60)0C temperature.2 - While the second part involved synthesis and characterization of novel thiazolidine - 4 - one compounds[XXI]a - d and [XXII]a - d by the following steps : Scheme(2).a. Synthesis of 2 - [5 - (2 - methyl - 1H - indol - 3 - yl) - 4H - 1,2,4 - triazol - yl] - thio - ethyl hydrazide[XVIII] by the reaction of ester compound[XVII] with excess of 80% hydrazine hydrate in ethanol under reflux.b. Synthesis of 2 - {5 - [(1H - indol - 3 - yl) - methylene] - 4 - phenyl - 1,2,4 - triazol - 3 - yl} - IXthio - ethylhydrazide[XVIII], by the reaction of ester compounds[XVII] with excess of hydrazine hydrate in ethanol under reflux. Also synthesize new Schiff bases [XIX]a - d and [XX]a - d by condensation reaction of acid hydrazide compounds [VIII]a or [XVIII] with different aromatic aldehyde in absolute ethanol as a solvent.c. Synthesis of new thiazolidine - 4 - one derivatives, [XXI]a - d and [XXII]a - d by refluxing equimolar amounts from Schiff bases[XIX]a - d and [XX]a - d with excess of thioglycolic acid in dry benzene.3. The third part involved synthesis and characterization of new series of thiazolidine - 4 - one [XXVII]a - c and [XXVIII]a - c by many steps reaction as follows : Scheme(3).a. Synthesis of new Schiff [XXIII]a,b, [XXIV]a,b by condensation reaction of acid hydrazide [III]a,b with two types of aromatic aldehyde in absolute ethanol.b. Synthesis of another type from thiazolidine - 4 - one derivatives [XXV]a, b and [XXVI]a, b from the reaction of Schiff bases [XXIII]a,b, [XXIV] a,b with excess of thioglycolic acid in dry benzene. The alkoxy derivatives of compounds [XXVII] and [XXVIII]; 2 - (4 - N - alkoxyphenyl) - 3 - (2 - methyl - 1H - indol - 3 - yl)amido - 1,3 - thiazolidine - 4 - one[XXVII]a - c and 2 - (4 - N - alkoxyphenyl) - 3 - (1H - indol - 3 - yl) acetamido - 1,3 - thiazolidine - 4 - one [XXVIII]a - c were synthesized by the reaction of terminal OH group of compound[XXV]a or [XXVI]a with different n - alkyl bromide in alkaline media.4 - The fourth part involved synthesis and characterization of amide derivatives of 1,3,4 - thiadiazole[XXXI]a - d, [XXXII]a - d and [XXXIII]a - d by the following steps : Scheme(4)a. Preparation of 2 - amino - 5 - (2 - methyl - 1H - indol - 3 - yl) - 1,3,4 - thiadiazole[XXIX] by cyclization reaction of 2 - (2 - methyl - 1H - indole - 3 - carbonyl) hydrazine carbo - thio amide [XV] in conc. H2SO4 under reflux followed by neutralized with liquid ammonia. While 2 - amino - 5 - [(1H - indol - 3 - yl)methyl] - 1,3,4 - thiadiazole[XXX]aand 2 - amino - 5 - [(1H - indol - 3 - yl)propyl] - 1,3,4 - thiadiazole[XXX]b synthesized by cyclization reaction under reflux of indole - 3 - acetic acid or indole - 3 - butric acid with thiosemicarbazide in the presence of phosphorous oxychloride.b. Synthesis of new amide derived from 2 - amino - 1,3,4 - thiadiazole [XXXI]a - d, [XXXII]a - d and [XXXIII]a - d from the reaction equimolar of suitable 2 - amino - 1,3,4 - thiadiazoles[XXIX] and [XXX]a,b with different acid chlorides in DMF and pyridine as accepter.5. The fifth part involved synthesis and characterization of new hydrazones [XXXVII]a - d and [XXXVIII]a - d. These compounds were synthesized according to the follows steps : Scheme(5)a. Synthesis and characterization of 1 - (2 - methyl - 1H - indole - 3 - yl) carbonyl - 3 - methyl - pyrazol - 5(4H) - one[XXXIV] and 1 - [(1H - indol - 3 - yl) ethanoyl or butanoyl] - 3 - methyl - pyrazol - 5(4H) - one [XXXV]a, b by heating under reflux a solution of equimolar from acid hydrazides[III]a - c with ethylacetoacetate in absolute ethanol.b. Synthesis and characterization of 1 - [4 - acetyl - (1H - indol - 3 - yl)ethanoyl or butanoyl] - 3 - methyl - pyrazol - 5 - one [XXXVI]a, b through reaction of pyrazolone derivatives[XXXV]a,b with acetyl chloride in 1,4 - dioxane in presence of calcium hydroxide.c. Synthesis and characterization of novel hydrazones [XXXVII]a - d and [XXXVIII]a - d by the reaction of 4 - acetyl - pyrazolone compounds[XXXVI]a, b with phenyl hydrazine or substituted phenyl hydrazine in ethanol.The synthesized compounds have been characterized by their melting points, elemental analysis (C.H.N) and by their spectral data, FTIR, 1HNMR and Mass spectroscopy (of some of theme).Study of the biological activity of some of the synthesized compounds against Gram - positive bacteria (Staphylococcus aureus) and Gram - negative bacteria (Escherichia coli). The results showed that most of the tested
