الفهرس 
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Abstract
Part 1: Mannich reactions with acyclic secondary enaminones.
Transamination reaction between the tertiary enaminone 1 and the appropriate primary aromatic amines gave a series of 1-phenyl-3-(arylamino)propenones (2a-e). Mannich reaction of secondary enaminones 2 a-e with formaldehyde and some primary aromatic amines afforded 5-benzoyl-1, 3-diaryl-1, 2, 3, 4-tetrahydropyrimidines derivatives 3a-e, respectively. A similar reaction of 2b with ammonium acetate gave 5-benzoyl-1-p-tolyl-1, 2, 3, 4-tetrahydropyrimidine )3f( . In addition, Mannich reaction of 2b and 2c with p-phenylene diamine and formaldehyde yielded 1, 4-bis (5-benzoyl-1-(p-tolyl)-1, 2, 3, 4-tetrahydropyrimidin-3-yl)-benzene) 4a( and the 1-p-anisyl analogue 4b, respectively. As well as, the reaction of 2a with ethylenediamine by the same procedure take place yielding bis-(1, 2, 3, 4-tetrahydropyrimidine) 5. On the other hand, reaction of 2c with formaldehyde in molar ratio (1: 2) led to the formation of 5-Benzoyl-3-(p-anisyl)-3,6-dihydro-2H-1,3-oxazine )6(. The interest in the pharmacological activity of phenolic Mannich bases and related compounds, promoted us to prepare 5-benzoyl-1-(4-hydroxyphenyl)-3-(p-tolyl)-1, 2, 3, 4-tetrahydropyrimidine )7(, which was used as precursor for the synthesis of tetrahydropyrimidines incorporating a phenolic Mannich base as a structural unit. This has been achieved by treating 7 with dimethylamine, piperidine or morpholine and formaldehyde to give the phenolic Mannich bases 8 a-c or the phenolic bis-(Mannich bases) 9 a-c, respectively, this depend on the molar ratio of the reactants. In addition, Mannich reaction of 2d with formaldehyde and p-aminophenol furnished 5-benzoyl-1,3-di(4-hydroxyphenyl)-1, 2, 3, 4-tetrahydropyrimidine )10(, which was treated with formaldehyde and piperidine or morpholine in a molar ratio (1: 4: 4) to give the tetra (Mannich bases ) 11 a and 11 b, respectively.
Transamination reaction between 1 and p-phenylenediamine lead to the formation of N, N`-(bis-(1-phenyl prop-2-en-1-one-3-yl))- p-phenylenediamine) 12(. Mannich reaction of bis (secondary enaminone) 12 is particular interest, because it provides access to bis (1, 2, 3, 4- tetrahydropyrimidines). Also, treatment of 12 with the some primary aromatic amines and formaldehyde gave a series of 1, 4-bis (5-benzoyl-3-aryl-1, 2, 3, 4-tetrahydropyrimidin-1-yl)-benzenes (13 a-f). In addition, the synthesis of 1, 4-bis (5-benzoyl-3, 6-dihydro-2H-1, 3-oxazine-3-yl)-benzene )14( was achieved by treating 12 with formaldehyde in a molar ratio (1: 4). In a similar approach, Mannich reaction of the bis (secondary enaminone) 15 with different primary aromatic amines or ammonium acetate and formaldehyde afforded bis (1, 2, 3, 4-tetrahydropyrimidines) 16 a-d, respectively. Also, compound 15 reacted with formaldehyde to give 1, 2-bis (5-benzoyl-3, 6-dihydro-2H-1, 3-oxazine-3yl) ethane (17).
In the course of this study, the synthesis of bis (tetrahydropyrimidines) 20 a, b were realized via reaction sequence which involves transamination between the bis (enaminone) 18 and p-toluidine or 4-aminopyridine to give the bis (secondary enaminones) 19 a, b, which were subjected to Mannich reaction with formaldehyde and p-toluidine or 4-aminopyridine to give the target compounds 20 a, b. A similar reaction of 19 a and 19 b with formaldehyde and ammonium acetate lead to the formation of 1, 4-Phenylenebis ((1-(p-tolyl)-1,2,3,4-tetrahydropyrimidin-5-yl) methanone) )21 a( and the 1-(pyridine-4-yl) analogue) 21 b(, respectively. On the other hand, 1, 4-phenylene bis (3-p-tolyl)-3, 6-dihydro-2H-1, 3-oxazin-5-yl) methanone) )22 ( was obtained by the reaction of 19 a with formaldehyde in a molar ratio (1 : 4). Treatment of 2b and 2e with hydrazine hydrate and subsequently with formaldehyde gave 7- phenyl-4-(p-tolyl)-3, 4-dihydro-2H-1, 2, 4-triazepine )23 a( and the 4-(pyridine-2-yl) analogue 23b, respectively. A similar reaction was carried out by treating 2c with phenyl hydrazine and glutaric dialdhyde yielded bis-(1, 2, 4-triazepine) )24(. Compound 15 was treated with hydrazine hydrate and subsequently with formaldehyde to afford 1, 2-bis (7-phenyl-2, 3-dihydro-4H, 1, 2, 4-triazepin-4-yl) ethane ) 25(.
The compound 3-((2, 3-diphenyl-1H-indol-6-yl) amino)-1-phenylprop-2-en-1-one )27( was performed through transamination reaction between 6-amino-2, 3-diphenylindole )26 (and enaminone 1. Mannich reaction of enaminone 27 with formaldehyde in a molar ratio (1: 2) yielded 5-benzoyl-3-(2, 3-diphenyl-1H-indol-6-yl)-3,6-dihydro-2H, 1, 3-oxazine (28). Mannich reaction of 27 with p-toluidine, p-anisidine, 4-aminopyridine, aniline or ammonium acetate and formaldehyde gave series of 5-benzoyl-1-heteroaryl-3-aryl-1, 2, 3, 4- tetrahydropyrimidines 29 ( a-d) and 5-benzoyl-1-(2, 3-diphenyl-1H- indol-6-yl)-1, 2, 3, 4-tetrahydriopyrimidine (29 e), respectively.
The enaminone 30 was achieved via transamination reaction between enaminone 1 and 2-aminobenzothiazole. The latter enaminone 30 reacted with formaldehyde (1: 2) as well as with some primary aromatic amines, ammonium acetate and formaldehyde afforded 5-benzoyl-3-(benzo[d]thiazol-2-yl)-3,6-dihydro-2H-1,3-oxazine (31) and 5-benzoyl-N-benzothiazolyl pyrimidine derivatives 32 a-d.
Part 2: Chemical Reactivity of Diazoenaminone Towards N and C Nucleophiles
The key precursor 3-((4-hydroxyphenyl) diazenyl) acetophenone 34 or 4((4-hydroxyphenyl) diazenyl acetophenone 35 was readily prepared via diazonium salts of 3-amino-acetophenone or 4- aminoacetophenone with phenol. The compounds 34 and 35 were reacted with dimethylformamide dimethylacetal (DMF DMA) to give the diazoenaminones 36 and 37, respectively. Reaction of the diazoenaminone 36 with some N-nucleophiles such as thiourea, hydroxylamine hydrochloride, hydrazine hydrate and Guanidine hydrochloride gave the compounds (38-41), respectively. Analogously, the behavior of the diazoenaminone 36 towards some N-nucleophiles related to aminoheterocycles has been also studied. Reaction of 36 with 2-aminobenzoimidazole, 6-amino-2-thioxo-2, 3-dihydropyrimidin-4(1H) -one, 5-amino-3-(methylthio)-1H-pyrazole-4-carbonitrile or 3-amino-4, 6-dimethyl-1H-pyrazolo [3, 4 -b] pyridine gave in quantities yields the condensed pyrimidine derivatives (42-45) respectively. In connection with this work, the reactivity of diazoenaminone towards diverse C-nucleophiles was studied, thus, treatment of diazoenaminone 37 with malononitrile or ethylcyanoacetate via refluxing in glacial AcOH afforded 46a and 46 b, respectively. Treatment of diazoenaminone 37 with each of acetylacetone and ethylacetoacetate in presence of ammonium acetate gave the compounds 47a and 47b, respectively. On the other hand, refluxing of diazoenaminone 37 with dimedone or 1, 4-benzoquinone in glacial acetic acid yielded the compounds 48 and 49, respectively. Finally, self-condensation (2.2.2 Cycloaddition) reaction of diazoenaminone 37 by refluxing in glacial acetic acid led to triaroyl benzene derivative 51.
Part 3: Biological Evaluation of Some The Newly Synthesized Compounds.
In this study we had selected a series of the new synthesized compounds to evaluate their antibacterial activities against Staphylococcus aureus, Bacillus Subtilis and Methicillin-Resistant Staphylococcus aureus Clinical isolate (gram positive bacteria) and Escherichia coli and Pseudomonas aeruginosa (gram negative bacteria), as well as against Aspergillus fumigates and Candida albicans to evaluate their antifungal activities. Using Gentamycin and Ketoconazole as reference drugs. It showed from data, some of the newly compounds having higher activity comparable with reference and the others having moderately or no activities.