Author name:
اسراء شكيب عبد الرزاق القاضي
Supervisor name:
زكريا هادي ايوب | علي حمادي سمير
Abstract:
Many researches in pyrimidine have interesting future in antimicrobial and pharmaceutical studies. For this purpose wedesign to synthesize compounds containing pyrimidines unitcontaining some effective biological active groups at positions - 2,4and 6, in order to increase the extension of its antimicrobial effect,like p - benzenesulphonamidophenyl, p - ureidophenyl, p(Nmethylamino) phenylazophenyl p,N - phthalimidophenyl and p(Nphthalimido)benzamido - N' - phenyl groups at position - 4, pchlorophenyl and p - nitrophenyl groups at position - 6, and oxo,imino, thioxo groups at position - 2.In order to build up such pyrimidines derivatives, thefollowing steps are involved : I. Synthesis of : A - p - acetylphenylbenzenesulphonamide [1a], by condensation ofbenzenesulphonylchloride with p - aminoacetophenone in thepresence of pyridine.B - p - acetylphenylurea [10a], by reaction of potassium cyanate withp - aminoacetophenone, in water solution containg acetic acid.H2N COCH3 phSO2Cl phSO2NHpyridineCOCH3[1a]H2N COCH3 KOCN CH3COOKGlacial CH3COOHCOCH3H2OH2NCONH[10a]AbstractIIglacialacetic acidH2N COOHCOCOOCNCOOCOOHC - p - acetyl - p'(N - methylamino)azobenzene [19a], by diazotization ofp - aminoacetophenone with sodium nitrite in presence ofhydrochloric acid, to give p - acetylphenyl diazonium salt, whichwas coupled with p(N - methylamino) aniline to give the titledcompound.D - N - (4 - acetyl)phenylphthalimide [28a], by reaction ofp - aminoacetophenone with phthalic anhydride in the presenceof glacial acetic acid.E - N(4 - acetylphenyl)p - (N - phthalimido)benzamide [37a]This compound was synthesized in three steps : Step I. Synthesis of 4 - N - phthalimidobenzoic acid, by reactionof phthalic anhydride with p - aminobenzoic acid in the presence ofglacial acetic acid.Step II. Synthesis of 4 - N - phthalimidobenzoyl chloride, byreaction of 4 - N - phthalimidobenzoic acid with thionyl chloride in drybenzene.dry BenzeneCNCOOCOOH SOCl2CNCOOC ClO[A] [28a]COCH2N C CH3OOglacialacetic acidOCNCOOC CH3O[19a]H2N COCH3H2OHClNaNO2Cl N2 COCH3MeNH NH2MeNH N N COCH3AbstractIIIStep III. Synthesis of 4(4' - acetylphenylamido)phenylphthalimide [37a], by reaction of 4 - N - phthalimidobenzoyl chloridewith p - aminoacetophenone in dry benzene.II. Chalconization processes, involve condensation of equimolarratio of compounds [1a], [10a], [19a], [28a] and [37a] withp - chlorobenzaldehyde and p - nitrobenzaldehyde in the presenceof sodium hydroxide to give p - substituted - 1,3 - diaryl - propene - 2 - 1 - one [2a], [3a], [11a], [12a], [20a], [21a], [29a], [30a] [38a] and[39a] as following scheme : III. Synthesis of 2,4,6 - substiuted pyrimidines : A - Condensation of equimolar ratio of following chalcones [2a],[3a], [11a], [12a], [20a], [21a], [29a], [30a], [38a] and [39a] withurea in the presence of sodium hydroxide, gave 4(p - subsituted) - phenyl - 6(p - subsituted) - phenyl - 2 - oxo(1H) pyrimidines [4a], [5a],[13a], [14a], [22a], [23a], [31a], [32a], [40a] and [41a].[A]C CH3OH2N CCNCOOC ClODry BenzeneCNCOOCCH3ONO H[37a][2a], [3a], [11a], [12a], [20a], [21a],[29a], [30a], [38a], [39a]Y COCH3 X CHO Y COCHMeNH NCH XEtOHNaOHH2OY= phSO2NH - , H2NCONH - ,X = Cl, NO2NCNCOOCNCOOCHNOand,AbstractIVB - But condensation of equimolar ratio of following chalcones [2a],[3a], [11a], [12a], [20a], [21a], [29a], [30a], [38a] and [39a] withquanidine hydrochloride in the presence of double molar ratio ofsodium hydroxide gave 4(p - subsituted)phenyl - 6 - (p - subsituted) - phenyl - 2 - imino (1H) pyrimidines [6a], [7a], [15a], [16a], [24a],[25a], [33a], [34a], [42a] and [43a].C - Upon condensation of equimolar ratio of following chalcones[2a], [3a], [11a], [12a], [20a], [21a], [29a], [30a], [38a] and[39a] with thiourea in the presence of sodium hydroxide, gave4(p - subsituted)phenyl - 6 - (p - subtituted)phenyl - 2 - thioxo(1H) - pyrimidines [8a], [9a], [17a], [18a], [26a], [27a], [35a], [36a],[44a] and [45a].[4a], [5a], [13a], [14a], [22a],[23a], [31a], [32a], [40a], [41a]Y COCH X YMeNH NNNHEtOHNaOHH2NY= phSO2NH - , H2NCONH - ,X = Cl, NO2N - ,CH C NH2OXOCNCOOCNCOOCHNOand[6a], [7a], [15a], [16a], [24a], [25a],[33a], [34a], [42a], [43a]Y COCH X YMeNH NNNHEtOHNaOHH2NY= phSO2NH - , H2NCONH - ,X = Cl, NO2N - ,CH C NH2.HClNHXNH2H2OCNCOOCNCOOCHNOandAbstractVAll new synthesized compounds [1a - 45a], are characterizedusing various spectral analysis FTIR, 1HNMR, 13C NMR and Massmeasurements.Antimicrobial activities of all types of synthesized compounds[1a - 45a] and p - aminoacetophenone[A] were examined againstGram - Ve (Serratia marcescens, pseudomonas aeroginosa),Gram+Ve bacteria (Staphylococcus aureus and streptococcuspyogenes) and (candida albicans) fungi, in comparison withantimicrobial effect of known pharmaceutical antibiotics likeCephalexin, Amoxicillin, Tetracycline, Lincomycin and antifungalNystatine and Flucanazole, results show : First : Syntheized p - substituted acetophenone [1a], [10a],[19a], [28a], [37a] and p - aminoacetophenone[A], showed goodantimicrobial effect on (G - Ve) bacteria (Serratia marcescens andpseudomonas aeroginosa), better than used antibiotics and rank was[10a] > [1a] > [19a] > [A] > [28a], [37a].Second : Synthesized chalcones also have much better effectthan used antibiotics, but with small increasing effect that psubstitutedacetophenones on (G - Ve) bacteria (Serratia marcescensY COCH X YMeNH NNNHEtOHNaOHH2NY= phSO2NH - , H2NCONH - ,X = Cl, NO2N - ,CH C NH2SXS2H2OCNCOOCNCOOCHNOand[8a], [9a], [17a], [18a], [26a],[27a], [35a], [36a], [44a], [45a]AbstractVIand pseudomonas aeroginosa), in the fallowing rank [11a], [29a], [38a] > [2a], [20a], but in case of chalcone [21a] containing NO2 - group showed much better effect than others.Third : All Synthesized pyrimidines [4a], [5a], [6a], [7a], [8a], [9a], [13a], [14a], [15a], [16a], [17a], [18], [22a], [23a], [24a], [25a], [26a], [27a], [31a], [32a], [33a], [34a], [35a], [36a], [40a], [41a], [42a], [43a], [44a] and [45a] showed good antimicrobial effect, but much better than antibiotics used in these studies, specially that containing, thioxo and imino groups at position - 2.Fourth : All Synthesized compounds, p - substituted acetophenones, chalcones and pyrimidines [1a - 45a], showed very good inhibition effect on candida albicance fungi, specially, that chalcones [21a] and pyrimidine [22a] which contain azo group
