الفهرس 
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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.