Synthesis of new oxadiazole, triazole and oxazepine derivatives of quinazoline moiety

Article abstract of DOI:10.14233/ajchem.2018.21277

New 2-(4-oxo-2-phenylquinazolin-3(4H)-yl)-3-phenyl propanoic acid derivatives have been prepared by reaction of 2-phenyl-4H-1,3-benzoxazin-4-one with phenylalanine. The reaction of compound 1 with thionyl chloride produced 2-[4-oxo-2-phenylquinazolin-3(4H)-yl]-3-phenylpropanoyl chloride (2). Condensation of compound 2 with hydrazine hydrate afforded 2-[4-oxo-2-phenylquinazolin-3(4H)-yl]-3-phenyl propane hydrazide (3). The reaction of compound 3 with carbon disulfide and potassium hydroxide yielded 3-[1-(5-mercapto-1,3,4-oxadiazol-2-yl)-2-phenylethyl]-2-phenylquinazolin-4(3H)-one (4). Teratment of compound 4 with hydrazine hydrate gave 3-[1-(5-mercapto-4H-1,2,4-triazol-3-yl)-2-phenylethyl]-2-phenylquinazolin- 4(3H)-one (5). The reaction of compound 3 with phenyl isothiocyanate resulted in formation of 2-[2-(2-phenyl-4-oxoquinazolin-3(4H)-yl)-3-phenylpropanoyl] hydrazine carbothioamide (6). Treatment of compound 6 with aqueous sodium hydroxide solution produced 3-[1-(5-mercapto-4-phenyl-4H-1,2,4-triazol-3-yl)-2-phenylethyl]2-phenylquinazolin-4(3H)-one (7). The azomethines 8a-d were synthesized from the reaction between the corresponding aldehydes and acid hydrazide 3. Moreover, N-(3-methyl-1,5-dioxobenzo[e][1,3]oxazepin-4(1H,3H,5H)-yl-2-(4-oxo-2-phenyl quinazoline-3(4H)-yl)acetamide 9a-d were synthesized from the cyclic condensation of imines with phthalic anhydride. The structure of novel synthesized compounds were suggested from IR,¹H NMR and and¹³C NMR spectral studies.

Full text of DOI:10.14233/ajchem.2018.21277

Asian Journal of Chemistry; Vol. 30, No. 8 (2018), 1706-1710
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2018.21277
Synthesis of New Oxadiazole, Triazole and Oxazepine Derivatives of Quinazoline Moiety
*
FADHEL OMRAN ESSA and KADHUM J.K. AL-HAMDANI
Department of Chemistry, College of Basic Education, University of Babylon, Hilla, Iraq
*Corresponding author: E-mail: fathel_omran61@yahoo.com
Received: 9 February 2018;
Accepted: 3 April 2018;
Published online: 30 June 2018;
AJC-18960
New 2-(4-oxo-2-phenylquinazolin-3(4H)-yl)-3-phenyl propanoic acid derivatives have been prepared by reaction of 2-phenyl-4H-1,3-
benzoxazin-4-one with phenylalanine. The reaction of compound 1 with thionyl chloride produced 2-[4-oxo-2-phenylquinazolin-3(4H)-
yl]-3-phenylpropanoyl chloride (2). Condensation of compound 2 with hydrazine hydrate afforded 2-[4-oxo-2-phenylquinazolin-3(4H)-
yl]-3-phenyl propane hydrazide (3). The reaction of compound 3 with carbon disulfide and potassium hydroxide yielded 3-[1-(5-mercapto-
1,3,4-oxadiazol-2-yl)-2-phenylethyl]-2-phenylquinazolin-4(3H)-one (4). Teratment of compound 4 with hydrazine hydrate gave 3-[1-(5-
mercapto-4H-1,2,4-triazol-3-yl)-2-phenylethyl]-2-phenylquinazolin- 4(3H)-one (5). The reaction of compound 3 with phenyl isothiocyanate
resulted in formation of 2-[2-(2-phenyl-4-oxoquinazolin-3(4H)-yl)-3-phenylpropanoyl] hydrazine carbothioamide (6). Treatment of
compound 6 with aqueous sodium hydroxide solution produced 3-[1-(5-mercapto-4-phenyl-4H-1,2,4-triazol-3-yl)-2-phenylethyl]2-
phenylquinazolin-4(3H)-one (7). The azomethines 8a-d were synthesized from the reaction between the corresponding aldehydes and
acid hydrazide 3. Moreover, N-(3-methyl-1,5-dioxobenzo[e][1,3]oxazepin-4(1H,3H,5H)-yl-2-(4-oxo-2-phenyl quinazoline-3(4H)-
yl)acetamide 9a-d were synthesized from the cyclic condensation of imines with phthalic anhydride. The structure of novel synthesized
compounds were suggested from IR, 1H NMR and and 13C NMR spectral studies.
Keywords: Oxazines, Oxazepines, Oxadiazoles, Triazoles, Phenylquinazolines.
N
N
INTRODUCTION
H
H3CO
N
C
OCH3
Heterocyclic compounds that have a ring structure con-
taining more than one type of atoms. Such as nitrogen, oxygen
and sulfur in addition to the carbon atom . Due to the fact that
these compounds are widespread in nature, they have received
a great deal of attention from the researchers to their importance
of life, they are included in the composition of chlorophyll in
the plant and the hemoglobin contains four rings of pyrroles
[1,2].These compounds are also involved in the structures of
sugars and their derivatives and in the synthesis of most
vitamins, such as vitamin C, which is in the form of five- or-six-
iron (pyran) rings containing one atom of oxygen [3,4]. Most
members of vitamin B group have heterogeneous nitrogen-
containing rings, including pyridoxine (B6), a pyridine deriv-
ative, essential for the metabolism of amino acids [4]. There
are several types of life molecules that contain heterocyclic
compounds systems, including nitrogenous bases such as purine
and pyrimidine, which are incorporated into the synthesis of
DNA and RNA and interfere with the structures of amino acids
such as proline, histidine, tryptophan [3].The compound A
was found to have a biological effect against anticancer and
compound B has antiretroviral [5].
S
A
O
N
N
H2N
N
S
B
Structure of compound A and B
2-Substituted benzoxazinones have been the object of
interest for past three decades, due to increased importance in
pharmaceutical and biological field [6-12]. Oxazine deri-
vatives are an important class of heterocyclic, which has attracted
much synthetic interest due to their wide range of biological
activities like sedative [13], analgesic [14], anticancer [15],
antitubercular [16], antimicrobial [17], antimalarial activity
[18]. Oxadiazole and triazole have a variety of potential biolo-
gical activities [19-21] and utilities as technologically useful
[22-24].

Vol. 30, No. 8 (2018)
Synthesis of New Oxadiazole, Triazole and Oxazepine Derivatives of Quinazoline Moiety 1707
Oxazepine derivatives introduced in 1965 for use in relief
of the psychoneuroses’ characterized by anxiety and tension
[25].
was filtered and recrystallized from ethanol. IR (KBr, νmax,
cm–1): 3332 NH oxadaizole, 3059 C-H benzene, 2931 CH2,
2781 CH, 2532 SH, 1681 C=O ester, 1616 C=N 1598-1494
C=C benzene, 1228 C=S. 1H NMR (DMSO-d6) δ (ppm) 9.7
(s, SH), 8.2 (s, NH), 6.6-7.9 (ArH), 3.6 (t, CH), 3.1 (d, CH2).
2-[2-(2-Phenyl-4-oxoquinazolin-3(4H)-yl)-3-phenyl
propanoyl]hydrazine carbothioamide (6): To a solution of
compound 3 (1 mmol) in absolute ethanol (25 mL), phenyl
isothiocyanate (1 mmol) was added with continuous stirring
and the mixture was refluxed for 5 h, then the reaction mixture
was cooled and the resulting solid 6 was recrystallized from
ethanol. IR (KBr, νmax, cm–1): 3203, 3188 and 3169 due to NH
groups, 3063 C-H benzene, 2948 CH2, 2845 CH, 1660 C=O
ester, 1639 C=O amide and C=N, respectivaly 1597-1446 C=C
benzene, 2489 SH, 1317 C=S. 1H NMR (DMSO-d6) δ (ppm)
8.9 (s, NH amide), 5.2 (s, NH), 2.7 (s, NH), 6.39-7.9 (ArH),
3.8 (t, CH), 3.4 (d, CH2).
EXPERIMENTAL
All the chemicals used in this research were of analytical
grades. Melting points were measured using electro thermal
melting point apparatus. Infrared spectra were recorded as KBr
1
disc on SHIMADZU-FT-IR-8400 spectrometer. H and 13C
NMR spectra were recorded on Burker 300 MHz instrument
using DMSO-d6 as a solvent and TMS as internal reference at
Al-Albayt University, Jordan. The progress of the reaction was
monitored by TLC using aluminum silica gel plates.
2-[4-Oxo-2-phenylquinazolin-3(4H)-yl]-3-phenyl
propanoic acid (1): A mixture of equimolar amounts (1 mmol)
of 2-phenyl-4H-benzo[d][1,3]oxazin-8-one and of phenyl-
alanine (1mmol) with glacial acetic acid (15 mL) was refluxed
for 5 h. The mixture was allowed to cool down to room tempe-
rature. Ice cold distilled water (25 mL) was added to the reac-
3-[1-(5-Mercapto-4-phenyl-4H-1,2,4-triazol-3-yl)-2-
phenylethyl]2-phenylquinazolin-4(3H)-one (7): Compound
6 (1 mmol) was refluxed with (10 %) aqueous sodium hydro-
xide solution (20 mL) for 5 h. The reaction mixture was cooled,
filtered and neutralized by gradual addition with stirring of
(15 %) acetic acid solution. The resulting solid was filtered
and recrystallized from ethanol to give brown crystal. IR (KBr,
tion mixture was recrystallized from ethanol. IR (KBr, νmax
,
cm–1): 3420 OH, 1700 C=O acid, 1685 C=O ester, 1643 C=N,
3049 C-H benzene, 2952 CH2, 2854 CH, 1587-1450 C=C
benzene.
2-[4-Oxo-2-phenylquinazolin-3(4H)-yl]-3-phenylpro-
panoylchloride (2):A mixture of compound 1 (27 mmol) and
thionyl chloride (5 mL) in dry benzene (15 mL) was refluxed
for 3 h. The solution was cooled then the excess of thionyl
chloride and benzene evaporated under vacuum, the product
was recrystallized from ethanol. IR (KBr, νmax, cm–1): 3066 C-
H benzene, 2944 CH2, 2832 CH, 1726 C=O acetyl chloride,
1655 C=O ester, 1612 C=N, 1598-1473 C=C benzene.
2-[4-Oxo-2-phenylquinazolin-3(4H)-yl]-3-phenyl
propane hydrazide (3): (26 mmol) of compound 2 and (80
%) hydrazine hydrate (50 mmol) in dry benzene (15 mL) was
refluxed for 4 h with stirring. After cooling, the benzene and
excess hydrazine hydrate were removed under reduced
pressure, the residue was washed well with diethyl ether, then
recrystallized from ethanol to provide solid product. IR (KBr,
ν
max, cm–1): 3184 NH, 3061 C-H benzene, 2968 CH2, 2924
CH, 2537 SH, 1674 C=O ester, 1600 C=N, 1570-1450 C=C
benzene, 1209 C=S. 1H NMR (DMSO-d6) δ (ppm) 11.0 (s, S-
H), 8.2 (s, NH), 6.6-7.9 (ArH), 4.0 (t, CH), 3.2 (d, CH2).
Synthesis of imines (8a-d): A mixture of equimolar
amounts (13 mmol) of corresponding aldehydes and compound
3 in (30 mL) of absolute ethanol. Glacial acetic acid (2 drops)
was added to the mixture which was refluxed on a water bath
for 7 h, then the mixture was cooled to room temperature. The
products were filtered and purified from ethanol.
2-(4-Oxo-2-phenyl-4H-quinazolin-3-yl)-3-phenyl-
propionic acid benzylidene-hydrazide (8a): IR (KBr, νmax
,
cm–1): 3224 NH, 3066 C-H benzene, 2899 CH2, CH, respec-
tively, 1660 C=O ester, 1647 C=O hydrazide 1600 C=N, 1575-
max, cm–1): 3307 and 3215 H2, 3062 C-H benzene, 2932 CH2,
1
ν
1494 C=C benzene). H NMR (DMSO-d6) δ (ppm) 9.3 (s,
2848 CH, 1660 C=O ester, 1651 C=O hydrazide, 1604 C=N
and NH2 bending, 1595-1448 C=C benzene.
N=CH), 8.1 (s, NH), 7.3-7.8 (ArH), 3.9 (t, CH), 3.4 (d, CH2).
13C NMR (DMSO-d6) 34.96 CH, 50.21 CH2, (124.21-134.60)
δ ppm due to aromatic carbon, (162.71) for (C=N), 154.54
C=N Schiff base, 168.25 N-C=O, 170.17 HN-C=O.
3-[1-(5-Mercapto-1,3,4-oxadiazol-2-yl)-2-phenylethyl]-
2-phenyl quinazolin-4(3H)-one (4): To a solution of com-
pound 3 (26 mmol) in ethanol (40 mL) and KOH (26 mmol)
was added, after that (5 mL) of CS2 was added. The mixture
was refluxed for 8 h. The solvent was evaporated under
vacuums, then the product was acidified with diluted HCl.
The precipitate was collected, washed with distilled water and
recrystallized from ethanol. IR (KBr, νmax, cm–1): 3332 NH
oxadaizole, 3059 C-H benzene, 2931 CH2, 2781 CH, 2532
SH, 1681 C=O ester, 1616 C=N, 1598-1494 C=C benzene,
1228 C=S. 1H NMR (DMSO-d6) δ (ppm) 10 (s, SH), 8.3 (s,
NH), 7.2-7.9 (ArH), 3.8 (t, CH), 3.3 (d, CH2).
3-[1-(5-Mercapto-4H-1,2,4-triazol-3-yl)-2-phenylethyl]-
2-phenyl quinazolin- 4(3H)-one (5): A mixture of substituted
oxadiazole 4 (10 mmol) with hydrazine hydrate (4 mL) in
ethanol (15 mL) was refluxed to 7 h, then the solvent was
evaporated under reduced pressure to form precipitate which
2-(4-Oxo-2-phenyl-4H-quinazolin-3-yl)-3-phenyl-
propionic acid (4-dimethylamino-benzylidene)-hydrazide
(8b): IR (KBr, νmax, cm–1): 3203 NH, 3062 C-H benzene, 2970
CH3, 2934 CH2, 2890 CH, 1676 C=O ester, 1635 C=O
hydrazide 1607 C=N, 1589-1519 C=C benzene. 1575-1494
C=C benzene. 1H NMR (DMSO-d6) δ (ppm) 9.1 (s, N=CH),
8.0 (s, NH), 7.3-7.9 (ArH), 3.9 (t, CH), 3.1 (d, CH2), 1.8 (s,
N(CH3)2. 13C NMR (DMSO-d6) N(CH3)2 36.92, 34.27 CH,
49.86 CH2, (124.25-135.33) ppm due to aromatic carbon,
(162.13) for (C=N), 153.84 C=N Schiff base, 168.08 N- C=O,
171.80 HN-C=O.
2-(4-Oxo-2-phenyl-4H-quinazolin-3-yl)-3-phenyl-pro-
pionic acid (4-hydroxy-3-methoxy-benzylidene)hydrazide
(8c): IR (KBr, νmax, cm–1): 3375 OH, 3192 NH, 3062 C-H
benzene, 2924 CH3, 2843 CH2 and CH, 1676 C=O ester, 1670

1708 Essa et al.
Asian J. Chem.
C=O hydrazide 1600 C=N, 1568-1450 C=C benzene. 1575-
1494 C=C benzene). H NMR (DMSO-d6) δ (ppm) 9.5 (s,
CH), 2.9 (d, CH2), 2.2 (s, N(CH3)2). 13C NMR (DMSO-d6)
N(CH3)2 36.90, 34.31 CH, 50.07 CH2, (124.41-135,15) ppm
due to aromatic carbon, (162.13) for (C=N), 168.13 N-C=O,
172.49 HN-C=O, 165.51 N-C=O oxazepine, 167.52 O-C=O
oxazepine.
1
N=CH), 8.0 (s, NH), 6.7-7.6 (ArH), 4.0 (t, CH), 3.4 (s, OCH3),
3.2 (d, CH2). 13C NMR (DMSO-d6), 33.61 CH, 49.29 CH2,
55.27 O-CH3, (123.35-136.10) ppm due to aromatic carbon,
143.73 C-OH, (162.64) for (C=N), 153.70 C=N Schiff base,
167.90 N-C=O, 171.62 HN-C=O.
2-(4-Oxo-2-phenyl-4H-quinazolin-3-yl)-3-phenyl-
propionic acid (4-hydroxy-benzylidene)-hydrazide (8d): IR
(KBr, νmax, cm–1): 3380 OH, 3206 NH, 3071 C-H benzene,
2843 CH2 and CH, 1668 C=O ester, 1642 C=O hydrazide 1616
C=N, 1568-1450 C=C benzene. 1575-1494 C=C benzene).
1H NMR (DMSO-d6) δ (ppm) 9.0 (s, N=CH), 8.1 (s, NH), 6.5-
7.9 (ArH), 6.0 (s, OH), 3.9 (t, CH), 3.1 (d, CH2). 13C NMR
(DMSO-d6), 34.61 CH, 48.77 CH2, (121.19-138.05) ppm due
to aromatic carbon, 147.03 C-OH, 164.01 for C=N, 154.06
C=N Schiff base, 167.75 N-C=O, 170.99 HN-C=O.
N-[7-(3-Hydroxy-4-methoxy-phenyl)-5,9-dioxo-5,9-
dihydro-6-oxa-8-aza-benzo cyclo hepten-8-yl]-2-(4-oxo-2-
phenyl-4H-quinazolin-3-yl)-3-phenyl-propionamide (9c):
IR (KBr, νmax, cm–1): 3407 OH, 3338 N-H, 3007 C-H, benzene,
2900 CH3, 2814 (CH2, CH and C-H, oxazepine), 1743 C=O
lactone, 1653 (C=O lactam and C=O amid), 1595 and 1444
1
C=C, benzene. H NMR (DMSO-d6) δ (ppm) 10 (s, CH-
oxazepnne), 8.1 (s, NH,) 6.3-7.8 (ArH), 5.3 (t, CH), 4.2 (d,
CH2), 3.4 (s, OCH3). 13C NMR (DMSO-d6), 33.60 CH, 49.50
CH2, 54.99 O-CH3, (122.79-136.42) ppm due to aromatic
carbon, 143.59 C-OH, (163.04) for (C=N), 167.31 N-C=O,
172.02 HN-C=O, 164.94N-C=O oxazepine,167.81 O-C=O
oxazepine.
Synthesis of oxazepines (9a-d):A mixture of compounds
8a-d (2 mmol) and phthalic anhydride (2 mmol) was dissolved
in of dry benzene (15 mL) and refluxed on a water bath for 14
h. The remaining solution was treated with sodium bicarbonate
to produce compounds 9a-d as a solid precipitate and recrysta-
llized from ethanol.
N-[7-(4-Hydroxy-phenyl)-5,9-dioxo-5,9-dihydro-6-
oxa-8-aza-benzocyclohepten-8-yl]-2-(4-oxo-2-phenyl-4H-
quinazolin-3-yl)-3-phenyl-propionamide (9d): IR (KBr, νmax
,
cm–1): 3309 OH, 3241 N-H, 3050 C-H, benzene, 2970 CH2,
2850 CH, C-H, oxazepine), 1728 C=O lactone, 1678 C=O
lactam,1637 C=O amid, 1600 C=N), 1585 and 1440 (C=C,
benzene). 1H NMR (DMSO-d6) δ(ppm) 9.8 (s, CH-oxazepnne),
8.0 (s, NH), 6.7-7.8 (ArH), 6.3 (s, OH), 5.1 (t, CH), 4.0 (d,
CH2). 13C NMR (DMSO-d6), 34.61 CH, 48.77 CH2, (122.09-
138.61) ppm due to aromatic carbon, 148.00 C-OH, 164.51
for (C=N), 167.09 N-C=O, 171.70 HN-C=O, 164.51 N-C=O
oxazepine, 167.49 O-C=O.
N-(5,9-Dioxo-7-phenyl-5,9-dihydro-6-oxa-8-aza-
benzocyclohepten-8-yl)-2-(4-oxo-2-phenyl-4H-quinazolin-
3-yl)-3-phenyl-propionamide (9a): IR (KBr, νmax, cm–1): 3315
N-H, 3047 C-H, benzene, 2941 CH2, 2887 (CH and C-H,
oxazepine), 1726 C=O lactone, 1683 C=O lactam, 1643 C=O
1
amid, 1610 C=N, 1583 and 1450 (C=C, benzene), H NMR
(DMSO-d6) δ (ppm) 8.9 (s, CH-oxazepnne), 8.3 (s, NH), 7.4-
7.9 (ArH), 5.1 (t, CH), 3.09 (d, CH2). 13C NMR (DMSO-d6)
34.50 CH, 50.71 CH2, (123.90-135.09) ppm due to aromatic
carbon, (163.08) for (C=N), 167.25 N-C=O, 171.21 HN-C=O,
165.02 N-C=O oxazepine,167.83 O-C=O oxazepine.
RESULTS AND DISCUSSION
Scheme-I summarized the performed reactions in this
work. Compound 1 reacted with SOCl2 in dry benzene to
give acid chloride derivative 2, the reaction was followed by
changing the absorption of carbonyl group of acid from1685
to 1760 cm-1 for a carbonyl of acyl chloride and disappearance
of stretching absorption band at 3427 cm-1 for OH of acid.
Reaction between compound 2 and hydrazine hydrate
afforded the acid hydrazide derivative 3.The FT-IR spectrum
showed the NH2, NH stretching absorption near 3303 and 3215
cm-1, the carbonyl stretching band appeared at 1661 cm-1.
N-[7-(4-Dimethylamino-phenyl)-5,9-dioxo-5,9-dihydro-
6-oxa-8-aza-benzocyclohepten-8-yl]-2-(4-oxo-2-phenyl-
4H-quinazolin-3-yl)-3-phenyl-propionamide (9b): IR (KBr,
ν
max, cm–1): 3212 N-H, 3084 and 3027 (C-H, benzene), 2967
CH3, 2861 and 2754 (CH2, CH and C-H, oxazepine), 1693
C=O lactone, 1649 C=O lactam, 1627 C=O amid, 1682 C=O,
1582 and 1450 (C=C, benzene). 1H NMR (DMSO-d6) δ (ppm)
10.8 (s, CH-oxazepnne), 10 (s, NH), 6.4-8.2 (ArH), 3.5 (t,
TABLE-1
PHYSICAL PROPERTIES AND SPECTRAL DATA FOR SYNTHESIZED COMPOUNDS (1-9d)
Compd. No.
m.f.
m.w. (g/mol)
Colour
Yellow
Dark yellow
Pale yellow
Brown
Dark brown
Orange
Pale orange
Orange
Orange
Brown
Brown
Pale orange
Red
m.p. (°C)
Yield (%)
Purification solvent
1
2
3
4
5
C23H18N2O3
C23H17N2O2
C23H20N4O2
C24H18N4O2S
C24H19N5OS
C30H25N5O2S
C30H23N5OS
C30H24N4O2
C32H29N5O4
C31H26N4O4
C30H24N4O3
C38H28N4O5
C40H33N5O5
C39H30N4O7
C38H28N4O6
370
388
384
426
425
519
501
472
515
518
488
620
663
666
636
168-171
120-122
178-180
218-220
200-202
Decomp.
271-273
215-217
204-206
198-200
240-242
166-168
173-175
168-170
177-179
73
80
88
86
81
56
50
65
80
78
54
53
63
46
55
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
6
7
8a
8b
8c
8d
9a
9b
9c
9d
Yellow
Yellow

Vol. 30, No. 8 (2018)
Synthesis of New Oxadiazole, Triazole and Oxazepine Derivatives of Quinazoline Moiety 1709
O
O
O
N
O
O
Phenyalanine
O
N
OH
N
Cl
SOCl2
N
N
1
2
Hydrazine hydrate
O
N
O
NH2
N
N
H
O
O
N
KOH
CS2
N
N
N
NH
N
N
O
SH
O
S
3
N
R
4
O
Hydrazine hydrate
Ethanol
Ethanol
H
O
N
N
N
N
O
R
O
N
H
SH
N
N
N
H
R1
NH
O
N
N
O
H
5
N
N
N
H
(8a-d)
S
Benzene
Phthalic anhydride
O
N
6
N
NH
N
N
H
S
O
N
R
10 % aqueous NaOH
O
N
N
N
H
O
O
O
O
N
O
N
N
NH
N
N
N
(9a-d)
SH
S
N
N
N
7
R = Phenyl, 4-dimethylaminophyenyl, 4-hydroxy-3-methoxy phenyl, 4-hydroxy phenyl; R1 = Phenyl
Scheme-I
The treatment of compound 3 with CS2 in KOH solution
resulted 3-[(5-mercapto-1,3,4-oxadiazol-2-yl)methyl]-2-phenyl-
quinazolin-4(3H)-one (4). The FT-IR spectrum of compound
4 showed a peak at 1616 cm-1 belong to C=N of imine. The
carbonyl absorption band was seen at 1660 cm-1. Also absence
of peaks in the region 3303 and 3215 cm-1 for NH2 group. In

1710 Essa et al.
Asian J. Chem.
1H NMR spectrum of this compound appeared two signals
related to CH2 protons, CH protons, S-H proton and NH proton
of thione form were observed between 3.3, 3.8, 10.0 and 8.3
ppm, respectively. The 13C NMR spectrum of compound 4,
C=S group signal at 164.30 ppm, while new signal was seen
at 38.76 ppm due to C-S group.
The resulting substituted 1,3,4-oxadiazole 4 was treated
with hydrazine hydrate to give 1,3,4-triazole derivative 5. The
IR spectral data showed absorptions at 3250, 1631,1622 cm-1
assigned to NH, C=N, NH bending respectively. The band at
1228 cm-1 due to (C=S) in thione form. In 1H NMR spectrum
of this compound appeared signals related to NH traizole proton
at 4.7 ppm.
The synthesis of compound 6 was carried out by reaction
of compound 4 with phenylisothiocyanate. The FT-IR spectrum
of compound 6 showed three peaks at 3203, 3180 and 3145
cm-1 due to NH groups. The formation of this compound 6 was
indicated by the presence of the azomethine (C=N), (C=S) and
(C=O) stretching band at 1639,1128 and 1658 cm-1, respec-
tively. The 1H NMR spectrum provided a perfect confirmation
to the structure formation in which the compound 6 showed
new singlet signals 7.21-7.52 ppm for aromatic protons, while
signals resonating at 8.9 ppm, 5.2 ppm and 2.7 ppm related to
NH groups proton. Moreover, signal resonating at 3.4 ppm
due to –CH2 group.
13C NMR spectrum of compound 9a-d, appeared the carbonyl
groups of lactone resonated at 167.83-167.49 ppm, while 165.54-
164.51 ppm due to carbon of carbonyl of amide.
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Refluxing of compound 6 with NaOH and acidified the
product afforded compound 7 containing triazole-2-yl moiety
which disappearance of two bands at 1658 and 1128 cm-1 for
(C=O) group of amide and (C=S) group, respectively. In
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1
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techniques. The FT-IR spectrum of compounds 9a-d showed
a peak at region 1743-1683 cm-1 belong to carbonyl of lactone.
The carbonyl absorption band of lactom was observed at 1678-
1643 cm-1. The 1H NMR spectrum for these compounds show
the new signals observed at 10.8-9.8 ppm integrating for (CH
oxazepine), disappearance the signals at 9.5-9.0 ppm integrating
for (CH=N) showing the characteristics chemical shifts. The