الفهرس 
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Abstract
USE OF SOME CARBONYL COMPOUNDS IN THE SYNTHESIS OF HETEROCYCLES AS ANTIMICROBIAL AND ANTITUMOR AGENTS
* This thesis divided into four chapters, in addition to the references section.
The first chapter containing the literature survey on the coumarin derivatives (synthesis and chemical reactions) through the last years.
** The second chapter containing the results and discussion of the special research work in this thesis focused on study the synthesis of heterocycles via using dicarbonyl compounds, and elucidation of structure of heterocyclic compounds by chemical and spectroscopic methods. This chapter divided into four parts as following.
Part 1:-
Synthesis of 3,5,7- trisubstituted-8-hydroxy(or acetoxy)coumarins.
In this part, we report here the preparation of dibromo and acetoxy of ethyl-8-hydroxycoumarin-3-carboxylate and dibromo, acetoxy of n-phenyl-8-hydroxycoumarin-3-carboxamides, as well as 8-hydroxy(or acetoxy)-3-(N-benzoyl) aminocoumarins.
Ethyl-8-hydroxycoumarine-3-carboxylate (2) was prepared via cyclo condensation of 2,3-dihydroxybenzaldehyde with diethyl malonate in the presence of base.
Bromination and Aminolysis of compound 2 with bromine in acetic acid and aniline in dimethyl formamide to give dibromo and carboxamide derivative (3 and 5).
Halogenation of carboxamide derivatives (5) with bromine in acetic acid gave the dibromo of carboxamide derivatives (7).
Acetylation of compound 3,5 and 7 with acetic anhydride yielded the acetoxy derivatives (4, 6 and 8). The synthetic pathway was outlined in Scheme 1.
Scheme 1
Part 2:-
Syntheses and characterization of substituted coumarin derivatives.
In this part, we reported the using of ethyl-8-hydroxycoumarin-3-carboxylate (2) in the preparation of methyl-8-hydroxycoumarin-3-carboxylate (13) as a key starting material to synthesize of some new substituted coumarin derivatives.
Unexpected methyl-8-hydroxycoumarin-3-carboxylate (2) was obtained via reaction of (13) thiourea in ethanol in the presence of anhydrous potassium carbonate under reflux.
Halogenation and Aminolysis of unexpected structure 13 with bromine and aryl amine (such as P-toludine and O-chloroaniline) lead to the formation of dibromo and carboxamide derivatives (14 and 16). Halogenation of carboxamide derivatives (16) with bromine in acetic acid gave the dibromo of carboxamide derivatives (17). Acetylation of dibromo derivatives of ester carboxamide with acetic anhydride yielded the corresponding acetoxy derivative (15 and 18, Scheme 2).
Scheme 2
Part 3:-
Syntheses of N-substituted coumarin-3-carboxahydrazide derivatives.
This part, we reported the syntheses of some N-substituted coumarin-3-carboxahydrazide derivatives using ethyl 7-hydroxycoumarin-3-carboxylate (19) as a key starting material.
Halogenation of ethyl 7-hydroxycoumarin-3-carboxylate (19) with bromine in acetic acid to give dibromo derivative (20). Treatment of dibromo derivative (20) with acetic anhydride and P-chlorobenzoic acid hydrazide yielded the corresponding acetoxy derivative (21) and N-(P-chlorobenzoyl) 7-hydroxycoumarin-3-carboxahydrazide (23).
Alkylation of carboxahydrazide (22) with methyl iodide gave the corresponding to methoxy derivative (24, Scheme 3).
Scheme 3
Part 4:-
Syntheses of 7-substituted-4-methylcoumarin derivatives
Herein we describe the syntheses of 7-substituted-4-methylcoumarin derivatives from 7-hydroxy-4-methyl coumarin as a key starting material.
Alkylation of 7-hydroxy-4-methyl coumarin (25) with P-chlorophenacyl bromide led to the formation of 7-(P-chlorobenzoyl) methoxy-4-methylcoumarin (26).
Reaction of 7-substituted-4-methylcoumarin (26) with phosphorous oxochloride and aromatic aldehydes to give 7-[(2-P-chlorophenyl-2-chloro)vinyl-1-yloxy]-4-methylcoumarin (27) and 7-{-2-(aryl)-1-(P-chlorobenzoyl)vinyl-1-yloxy}-4-methylcoumarins (28, Scheme 4)
Scheme 4
Also, this chapter containing the characterization of structures of some synthesized heterocycles via means of infrared, proton nuclear magnetic resonance, carbon nuclear magnetic resonance and mass spectral analyses are discussed.
*** The third chapter, containing biological evolution of some prepared heterocyclic compounds against antimicrobial and antitumor activities.
The evaluation results of tested heterocyclic compounds showed a great variable activity against antimicrobial and antitumor compared to reference.
**** In fourth chapter, containing the experimental procedure with details for the preparation of heterocyclic compounds. In addition to the instruments which used in the analysis of some prepared heterocyclic compounds such as IR, 1H-NMR, 13C-NMR and mass spectrum) and elemental analyses.