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Abstract Summary The thesis includes three Parts : Part I & II: The Reactivity and uses of 6-iodo-2-(phenylamino)- 4H-benzo[d][1,3]oxazin-4-one in the synthesis of quinazolinones 1) 6-Iodo-2-(phenylamino)-4H-benzo[d][1,3]oxazin-4-one 4 was synthesized via the reaction of 5-iodo anthranilic acid 1 with phenyl isocyanate 2 followed by refluxing with acetic anhydride. I COOH NH2 + PhN=C=O Dioxane I COOH NHCONHPh N O I NHPh O Ac2O 1 3 4 2 Scheme 1 2) The benzoxazinone derivative 4 reacted with sodium azide , ethyl acetoacetate, ethyl cyanoacetate , malonitrile, hydrazine hydrate, hydrazine hydrate in presence of carbon disulphide and potassium hydroxide in boiling ethanol to give N-(6-Iodo-4-oxo-2-(phenylamino) quinazolin-3(4H)-yl)ben-zamide 5, N’-(6-Iodo-4-oxo-2 (phenylamino)- 2,4-dihydro-1H-benzo[d][1,3]-oxazin-2yl)benzohydra-zide 6, 1-(2-acetyl-4-iodophen-yl)-3-phenylurea 7, 3-Amino-6-iodo-2- (phenylamino)quinazolin-4(3-H)-one 8, 1-(4-iodo-2-(5-thioxo-4,5- dihydro-1,3,4-oxadiazol-2-yl)phenyl)-3-phenylurea 9 respectively. N O I NHPh O N N I NHPh O NH2 N2H4.H2O 4 8 I CO2H N N N N PhHN I N NH CONHPh O NaN3 AcOH/ 5 6 + I 7 RCH2COOEt R = COOEt, CN, CH3CO N HNH Ph O H3C O I NHCONHPh O N NH 9 NH2NH2.H2O CS2/alc.KOH S Scheme 2 Part III novel quinazolin-4(3H)-one derivatives were synthesized by the reaction of hydrazonoyl chlorides with each of 6-iodo-2- phenylamino-3H-quinazolin-4-one and 3-amino-6-iodo-2- phenylamino-3H-quinazolin-4-one: 3) Amino quinazolinone reacted with phenyl isothiocyanate, benzaldhyde and β-aroyl acrylic acid, acetic anhydride, carbon disulphide, cycloheptanone, sodium nitrite in presence of hydrochloric acid and hydrozonoyl chloride to afford 1-(6-iodo-4- oxo-2-(phenylamino) quinazolin-3(4H)-yl)-3-phenylthiourea 10, 3- (benzylideneamino)-6-iodo-2-(phenylamino)quinazolin-4(3H)-one 11, 2-(2-(4-chloro-3-methylphenyl)-2-oxoethylidene)-8-iodo-4-phenyl- 1H-[1,2,4]triaz-ino(3,2-b)quinazoline-3,10(2H,4H)-dione 13, N- (6-iodo-4-oxo-2-(phenylamino)quinazolin-3(4H)-yl)acetamide 14, 7- iodo-3-phenyl-2-thioxo-2,3-dihydro-[1,2,4]triazolo[5,1-b]quinazolin9( 1H)one 15 , 3,4-cycloheptanopyrazole derivative 16, 3-((2- hydroxynaphthalen-1-yl)diazenyl)-6-iodo-2-(phenylamino)- quinazolin-4(3H)-one 17 and quinazolin-4(3H)-one derivatives 19 respectively. N N O NHPh I NH2 8 N N O NHPh I N=CHPh N N O I 11 10 H NC NHPh S PhNCS NHPh PhCHO Ar-COCH=CH-COOH 12 13 N N O I N N H Ph O CH3 Cl O Ar Ar = N N O I NHPh N N O I 14 15 NHCOCH3 NH N S Ph AC2O CS2 / KOH dioxane O N H N O I 16b N NH Ph N N O NHPh I N (CH2)n (CH2)n O X 16a N N O NHPh I N=N 17 HO NaNO2/HCl -naphthol dioxane / Et3N RCO(Cl)=N-NH-Ar N N O I NHPh R N H N 19(a-h) X Scheme 3 4) benzoxazinone react with p- toluidine, o-Phenylene diamine, benzylamine and benzoyl hydrazide in boiling ethanol to afford 6- Iodo-2-(phenylamino)-3-p-tolylquinazolin-4(3H)-one 21a, 3-(2-aminophenyl)- 6-iodo-2-(phenylamino)quinazolin-4(3H)-one 21b,1-(2- (benzylcarbamoyl)-4-iodophenyl)-3-phenylurea 22, N-(6-Iodo-4- oxo-2-(phenylamino)-quinazolin-3(4H)-yl)benzamide 23 and N’-(6- Iodo-4-oxo-2-(phenylamino)-2,4-dihydro-1H-benzo[d]-[1,3]oxazin- 2yl)benzohydrazide 24 PhCONHNH2 I N N O NHPh I NHCOPh N H O O NHPh NHNHCOPh stirring rt /3h 23 24 EtOH/ EtOH N N I NHPh O Me p-toluidine 21a CH2NH2 N H O O HN NH Ph Ph I 22 NH2 NH2 N N I O NHPh H2N 21b N O I NHPh O 4 Scheme 4 5) benzoxazinone react with furan derivative 25 and hydroxyl amine hydrochloride to afford N-(6-iodo-4-oxo-2 (phenylamino)- quinaz-olin-3(4H)-yl)-2-methyl-5-(1,2,3,4-tetrahy-droxybutyl)furan- 3-carb-oxamide 26 and 3-Hydroxy-6-iodo-2-(phenylamino)- quinazolin-4(3H)-one 27 which reacted with acetic anhydride and ethyl chloroacetate to afford 6-Iodo-4-oxo-2-(phenylamino)- quinazolin-3(4H)-yl acetate 28 and Ethyl 2-(6-iodo-4-oxo-2- (phenylamino)-quinazolin-3(4H)-yloxy)acetate 29, respectively O H3C N N I NHPh O NH O 26 2-methyl-5-(1,2,3,4- tetrahydroxybutyl)furan- 3-carbohydrazide 25 HO H H OH H OH CH2OH N O I NHPh O N N I NHPh O OH NH2OH.HCl pyridine N N I NHPh O OCOMe Ac2O 4 27 29 ethyl chloroacetate N N I NHPh O OCH2CO2Et 28 Scheme 5 6) benzoxazinone react with formamide to afford 6-Iodo-2-(Phenyl amino)quinazolin-4(3H)-one 30 which react with benzoyl chloride, acetyl chloride to afford N-(3-Benzoyl-6-iodo-4-oxo-3,4-dihydroquinazolin- 2-yl)-N-phenylbenzamide 31 and 3-Acetyl-6-iodo-2- (phenylamino) quinazolin-4(3H)-one 32, respectively N NH I NHPh O 4 N N I N O 31 N N I NHPh O 32 COPh Ph COPh COCH3 PhCOCl Ac2O N O I NHPh O 30 HCONH2 Scheme 6 7) 6-Iodo-2-(Phenyl amino)quinazolin-4(3H)-one react with β- glucose penta acetate, epichlorohydrin, hydrozonoyl halide, ethyl chloro acetate to afford 3(3,4,5-triacetoxy-6-acetoxymethyl)- tetrahydro-pyran-2-yl 33, 6-iodo-3-(oxiran-2-yl)methyl)-2-(phenylamino) quinazolin-4(3H)-one 34, quinazolin-4(3H)-one derivatives 35, Ethyl 2-(6-iodo-4-oxo-2-(phenylamino)quinazolin-3(4H)- yl)acetate 36, the latter compound react with hydrazine hydrate to afford 2-(6-Iodo-4-oxo-2-(Phenylamino)quinazolin-3(4H)-yl)acetohydrazide 37 respectively. N N I O NHPh H 33 N N I O NHPh O 30 34 O H AcO H AcO H H H OAc N N I O NHPh glucose pentaacetate epichlorohydrin Ha’ Hb’ Ha Hb OAc R Hc N N Ar Cl H dioxane / Et3N N N O I NHPh R N H N 35(a-f) X N N I NHPh O 36 CH2COOCH2CH3 ClCH2COOEt N N I NHPh O 37 CH2CONHNH2 N2H4.H2O acetone/K2CO3 EtOH Scheme 7 R X R X 35a COMe 4-OMe 35g COOEt 4-OMe 35b COMe 4-Me 35h COOEt 4- Me 35c COMe H 35i COOEt 4-Cl 35d COMe 3Cl 35j COOEt 4-NO2 35e COMe 4Cl 35k COOEt 4-COMe 8) Reaction of 2-(6-iodo-4-oxo-2-(phenylamino)quinazolin-3(4H)-yl)acetohydrazide with acetyl acetone, ethyl aceto acetate and benzaldhyde in boiling butanol afforded 3-(2-(3,5-Dimethyl-1H-pyrazol-1-yl)-2-oxoethyl)-6-iodo-2-(phenylamino)quinazolin-4(3H)-one 38 , 6-iodo-3-(2-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)-2-oxoethyl)-2(phenylamino)quinazolin-4(3H)-one 39 and N’-Benzylidene-2-(6-iodo-4-oxo-2-(phenylamino)quinazolin-3(4H)-yl)acetohydrazide 40, respectively.the latter compound which react with thioglycolic acid afforded 2-(6-Iodo-4-oxo-2-(phenylamino)quinazolin-3(4H)-yl)-N-(4-oxo-2-phenylthiazo-lidin-3-yl)acetamide 41, heating aceto hydrazide with Phthalic anhydride in ethanol afforded N-(1,3-Dioxoisoindolin-2-yl)-2-(6-iodo-4-oxo-2-(phenylamino)quinazolin-3(4H)-yl)acetamide 42 N N I NHPh O 37 CH2CONHNH2 N N I NHPh O 39 N N O CH3 EAA O n-butanol CH3COCH2COCH3 N N I NHPh O 38 N N O CH3 CH3 PhCHO n-butanol N N I NHPh O 40 CH2CONHN=CHPh N N I NHPh O 41 O NH N S O Ph thioglycolic acid/ n-butanol N N I NHPh O 42 H NO N O O Phthalic anhydride Scheme 8 9) Reaction of acetohydrazide 37 with glucose, benzoic acid, carbon disulfide , afforded 2-(6-Iodo-4-oxo-2-(phenylamino)quinazolin- 3(4H)-yl)-N’-(2,3,4,5,6-pentahydroxy-hexylidene)acetohydrazide 43, 6-iodo-3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)-2-(phenylamino)- quinazolin-4(3H)-one 44, 6-iodo-3-((5-mercapto-1,3,4-oxadiazol-2- yl)methyl)-2-(phenylamino)quinaz-olin-4(3H)-one 45, the latter compound reacted with ethyl iodide to afford 3-((5-(ethylthio) 1,3,4- oxadiazol-2-yl)meth-yl)-6-iodo-2-(phenylamino)-quinazolin-4(3H)- one 46, which reacted with hydrazine hydrate to afford 3-((5- (hydrazinyl)-1,3,4-oxadiazol-2-yl)methyl)-6-iodo-2-(phenylamino)- quinazolin-4(3H)-one 47. N N I O NHPh N N I O NHPh O N N Ph CS2/KOH N N I O NHPh N N O N N I O NHPh O N N SC2H5 N N I O NHPh O N N NHNH2 NH2NH2.H2O 44 45 47 46 36 benzoic acid POCl3 EtOH EtI HN NH2 O HS N N I NHPh O 43 CH2CONHN=CH H OH HO H H OH H OH CH2OH butanol glucose Scheme 9 Some of the synthesized compounds were screened for antimicrobial activity. Almost all of the tested compounds showed statifactory activity. |