Synthesis of some new 1,2,4-Triazine and 1,2,5-Oxadiazine derivatives with antimicrobial activity

Article abstract of DOI:10.1155/2019/2326514

1,2,4-Triazine and 1,2,5-oxadiazine derivatives 2-12 were obtained from treated 1,3-oxazolone (1) with phenyl hydrazine or hydroxylamine hydrochloride. Chlorotriazine derivative 3 undergoing condensation reactions with different reagents produced new fused tetrazolo-triazine and triazino-quinazolinone derivatives. 1,2,5-Oxadiazine has been used as a synthon for the fused pyrazolo-oxadiazine derivative. The constitution of the prepared compounds was built up based on microanalytical and spectral data. Some of the new compounds were assessed for their antimicrobial activity.

Full text of DOI:10.1155/2019/2326514

Hindawi
Heteroatom Chemistry
Volume 2019, Article ID 2326514, 7 pages
https://doi.org/10.1155/2019/2326514
Research Article
Synthesis of Some New 1,2,4-Triazine and 1,2,5-Oxadiazine
Derivatives with Antimicrobial Activity
Heba E. Hashem 1 and Ahmed M. Abo-Bakr2
1Department of Chemistry, Faculty of Women, Ain Shams University, Heliopolis, Cairo 11457, Egypt
2Department of Chemistry, Faculty of Science, South Valley University, 83523 Qena, Egypt
Correspondence should be addressed to Heba E. Hashem; hebahashem89@yahoo.com
Received 19 June 2019; Accepted 21 August 2019; Published 25 September 2019
Academic Editor: Xing-Hai Liu
Copyright © 2019 Heba E. Hashem and Ahmed M. Abo-Bakr. -is is an open access article distributed under the Creative
Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the
original work is properly cited.
1,2,4-Triazine and 1,2,5-oxadiazine derivatives 2–12 were obtained from treated 1,3-oxazolone (1) with phenyl hydrazine or
hydroxylamine hydrochloride. Chlorotriazine derivative 3 undergoing condensation reactions with diŽerent reagents produced
new fused tetrazolo-triazine and triazino-quinazolinone derivatives. 1,2,5-Oxadiazine has been used as a synthon for the fused
pyrazolo-oxadiazine derivative. -e constitution of the prepared compounds was built up based on microanalytical and spectral
data. Some of the new compounds were assessed for their antimicrobial activity.
1. Introduction
2. Results and Discussion
-e importance of studying the azlactones’ chemistry re-
mains unabated because of their uses as intermediates for
synthesis of new heterocyclic and fused heterocyclic com-
pounds. 1,2,4-Triazine derivatives exhibit antifungal [1, 2],
anti-HIV [3], anticancer [4], anti-in™ammatory [5], anal-
gesic [6], and antihypertensive [7] activities, besides their
uses as herbicides, pesticides, and dyes [8, 9]. -e phar-
macological eœcacy of oxadiazine is also known; derivatives
of 1,3,4-oxadiazine exhibit antibacterial, cardiovascular
plant growth-regulating, miticidal, nematocidal, insecticidal,
and anticonvulsive activities [10, 11]. In addition, oxadia-
zines are valuable intermediates in the synthesis of tenidap
prodrugs or lactam anti-infection agents, specižcally in the
synthesis of carbapenems and penems [12–14]. On the
contrary, 1,2,5-oxadiazines are not very common hetero-
cyclic systems.
“(Z)-4-(4-Methoxybenzylidene)-2-phenyloxazol-5(4H)-one”
(1) is synthesized via reaction of hippuric acid with p-ani-
saldehyde under Perkin–Erlenmeyer reaction conditions as
reported in the literature [16].
Reaction of oxazolone 1 with phenyl hydrazine in acetic
acid (glacial) and fused sodium acetate aŽorded the 1,2,4-
triazine-6(5H)-one derivative (2). Compound 2 could be
present in lactam-lactim tautomers (2A and 2B), but the
lactam form is thermodynamically more stable because the
oxo form is more stabilized by 54.4 kJ mol− 1 than the enol
form [17]. -e structure of 2 can be deduced from its
spectroscopic properties. -e IR spectrum showed a band
correlated with CꢀO lactam at 1690 cm− 1. Furthermore,
1HNMR spectrum showed one broad singlet signal in the
downželd region correlated with the NH proton.
Re™uxing of compound 2 with phosphorus oxychloride
and phosphorus pentachloride produces the chlorotriazine
derivative 3 which is used as a synthon for new triazine
derivatives (Scheme 1). Reaction of chlorotriazine 3 with
hydrazine hydrate gave the hydrazine derivative 4. Spectral
data of compound 4 established its suggested structure. Its
IR spectrum exhibited absorption bands belonging to NH,
A comprehensive review of the synthesis and reactivity
of these systems has been reported by Smalley [15]. In view
of these observations, the present work tends to utilize “(Z)-
4-(4-methoxybenzylidene)-2-phenyloxazol-5(4H)-one” [16]
for the synthesis of new 1,2,5-oxadiazine and 1,2,4-triazine
derivatives.

2
Heteroatom Chemistry
O
OH
N
O
NH
N
N
N
N
O
O
Ph
O
PhNHNH2
Ph
O
N
Ph
AcOH/ AcOHa
Ph
Ph
(1)
(2A)
(2B)
Scheme 1: Synthesis of the triazine derivative from azlactone (1).
1
NH2, and C�N groups. *e HNMR spectrum exhibited
exchangeable broad singlet signals corresponding to the two
protons of NH2 and other in the downfield region for the
NH proton.
*e structure of oxadiazine Z-8 gets further support by
its acetylation with acetic anhydride, giving the N-acetyl
derivative 10 (Scheme 5).
*e infrared spectrum of compound 10 does not show
any absorption bands corresponding to the NH proton;
instead, it exhibits broad bands at 1775 cm− 1 for the two
C�O groups. 1HNMR of compound 10 shows a good
agreement with the proposed structure (shown in Experi-
mental). Further support for the suggested structure gained
from its mass spectra revealed the correct molecular ion peak
as well as some of the important peaks (base peak).
Alkylation of compound 8 via treatment of a solution of
compound 8 in acetone with ethyl chloroacetate in the
presence of potassium carbonate yielded the carboxylic acid
derivative 11. IR of compound 11 showed absorption bands
at 3432 cm− 1 for υ OH as well as the strong absorption band
*e structure of compound 4 established chemically by
refluxing in acetic anhydride yielded the N,N′-diacetyl de-
rivative 5 (Scheme 2). *e structure of compound 5, also
deduced from the IR spectrum, showed two strong absorption
bands at 1726, 1701 cm− 1 for the C=O group (due to symmetric
and antisymmetric stretching of the N-diacetyl group).
1HNMR spectra exhibited a strong singlet signal (δ
2.28 ppm) for the two magnetically equivalent CH3 protons,
besides one broad singlet signal for the NH proton. *e mass
spectrum confirmed the assigned structure of 5 (shown in
Experimental).
Also, treatment of chlorotriazine 3 with sodium azide in
acetic acid gave 8-(4-methoxybenzylidene)-5,8-dihydro-5,6-
diphenyltetrazolo[1,5-f][1,2,4]triazine (6) (Scheme 3).
It is interesting to note that refluxing chlorotriazine (3)
with anthranilic acid in “acetic acid” gave the triazino-
quinazolinone derivative 7. *e structure of compound 7 is
elucidated from the spectral data. Infrared spectrum
showed absorption bands characteristic of υ C�O at
1678 cm− 1.
1
at 1696 cm− 1 for the C�O group. Moreover, the HNMR
spectrum displayed a singlet signal of the two methylene
protons at 3.83 ppm and a broad singlet signal correlated
with the COOH proton.
Also, refluxing 11 with N2H4·H2O in ethanol furnished
the unexpected fused pyrazolo-oxadiazine derivative 12. *e
structure of compound 12 can be deduced from spectral
data. *e infrared spectrum was devoid of any absorption
In addition, the 1HNMR spectrum of compound 7
showed the different protons from low- to high-field signals
for aromatic and aliphatic protons in harmony with the
proposed structure. *e mass spectrum of compound 7 gave
us a good indication about stability of that structure, where
the molecular ion peak together with some important peaks
was displayed (base peak).
corresponding to NH and CO groups, while the HNMR
1
spectrum proposed the structure of compound 12 (shown in
Experimental).
*e proposed pathway for the formation of compound
12 is illustrated in Scheme 6.
3. Biological Activity
Treatment of oxazolone 1 with NH2OH·HCl in pyridine
afforded the Z-configurated isomer adduct which could have
one of the two possible structures, oxadiazone Z-8 or
imidazolone Z-9 (Scheme 4). *e infrared spectrum
exhibited two bands at 3240 cm− 1 for NH and 1700 cm− 1 for
the CO group. *e lower frequency of the carbonyl group
supported the six-membered oxadiazine structure Z-8. *e
1HNMR spectrum of compound Z-8 showed a mixture of
lactam-lactim tautomers Z-8a and Z-8b in a 1 : 4 ratio such
that two absorption singlet signals for the two methoxy
protons are given besides extra exchangeable broad signals
due to the OH proton for Z-8b.
*e antimicrobial screening of some synthesized com-
pounds was done using the Kirby–Bauer disc diffusion
method. *e possible antimicrobial activities of compounds
2, 3, 6, and 7 were investigated on four standard organisms
including the Gram-positive bacteria, Staphylococcus aureus
and Bacillus subtilis, and the Gram-negative bacteria,
Escherichia coli, in addition to the fungus Aspergillus niger.
*e obtained results are presented in Table 1. Standard
solutions of ciprofloxacin (Cip) and erythromycin (CN) as
the antibacterial agent and amphotericin (Am) as the an-
tifungal agent served as positive controls.
*e configuration assignment as the Z-isomer may be
due to the downfield value of vinyl proton at δ 7.17 ppm that
is more deshielded by the anisotropic effect of the carbonyl
group.
*e obtained results emphasized the fact that “chemical
agent symbolized” 2 exhibited medium activity only against
“Aspergillus niger (fungus)” and that compound 7 revealed
low activity only against Staphylococcus aureus (Gram-

Heteroatom Chemistry
3
Cl
O
N
N
NH
N
POCl3/PCl5
N
N
Ph
Ph
O
O
Ph
Ph
(2)
(3)
N2H4·H2O
NHN(COCH3)2
N
NHNH2
N
Ac2O
N
N
N
N
Ph
Ph
O
O
Ph
Ph
(5)
(4)
Scheme 2: Synthesis of new 1,2,4-triazine derivatives.
N
N3
N
N
N
NaN3
AcOH
N
N
N
N
N
Ph
O
O
Ph
Cl
Ph
Ph
(6)
N
N
N
Ph
O
Ph
N
(3)
NH2
O
N
N
COOH
N
O
AcOH
Ph
Ph
(7)
Scheme 3: Reaction of chlorotriazine 3 with a different nucleophile.
positive bacterium). *e compounds 6 and 3 showed me-
dium activity against both “Staphylococcus aureus” and
“Bacillus subtilis” (Gram-positive bacterium).
300 BB NMR spectrometer using tetramethylsilane
(TMS) as the internal standard in deuterated dime-
thylsulphoxide (DMSO-d6) at the main defense chemical
laboratory. *e mass spectra were recorded on a Shi-
madzu GCMS-QP-1000EX mass spectrometer operating
at 70 eV at the Regional Center for Mycology and Bio-
technology of Al-Azhar University. *e elemental ana-
lyses were performed on a PerkinElmer 2400 CHN
elemental analyzer at the Micro Analytical Center of
Cairo University. *e reactions were monitored by the
thin layer chromatography on Merck Kiesel gel 60 F254
aluminum backed plates. *e spots were detected by UV
irradiation at 254–365 nm [18].
4. Experimental
All the melting points are uncorrected and were mea-
sured on a Gallenkamp electric melting point apparatus.
*e infrared spectra were recorded using potassium
bromide disks on a *ermo Fisher Scientific Nicolet FTIR
7600 (USA) infrared spectrometer at the Central Labo-
ratory of Faculty of Science, Ain Shams University.
1HNMR spectra were recorded at 300 MHz on a Gemini

4
Heteroatom Chemistry
O
OH
N
NH
O
N
O
N
O
O
O
Ph
NH2OH·HCl
Pyridine
(Z-8a)
(Z-8b)
Ph
O
O
N
Ph
(1)
O
N
OH
O
N
Ph
(Z-9)
Scheme 4: Preparation of 1,2,5-oxadiazine from azlactone (1).
O
OCH2COOH
O
O
ArHC
ArHC
Ar
Ac2O
NH
O
CH3
N
O
N
O
ClCH2COOEt
N
N
N
Acetone/K2CO3
Ph
(10)
Ph
Ph
(11)
(Z-8)
N2H4·H2O
N
N
Ar = H3CO
Ar
N
O
N
Ph
(12)
Scheme 5: Reaction of 1,2,5-oxadiazine (8) with a carbon electrophile.
4.1. (Z)-4-(4-Methoxybenzylidene)-2-phenyloxazol-5(4H)-one
(1). *is compound is synthesized according to the method
described in [16].
224–226°C (EtOH); IR (KBr) (υ, cm− 1): 3248 (NH), 3066
(CHarom), 2955 (CHalkyl), 1708 (C�O), and 1638 (C�N);
1HNMR (DMSO-d6) δ: 3.98 (s, 3H, OCH3), 6.61 (s, 1H, �CH),
6.76–7.56 (m, 10H, Ar-H), 8.06 (t, 2H, Ar-H), 8.27 (d, 2H, Ar-
H, J � 6.6 Hz), and 8.96 (br.s, H, NH, exchangeable); MS
(70 eV) m/z (%): 369 (M+, 34), 327 (4), 262 (5), 103 (18), 91 (88),
77 (37), 65 (100), 52 (5), and 44 (10). Anal. calcd for
C23H19O2N3 (396.42): C (74.78); H (5.18); and N (11.37).
Found: C (74.65); H (5.07); and N (11.12).
4.2. 5-(4-Methoxybenzylidene)-1,2-dihydro-2,3-diphenyl-1,2,4-
triazin-6(5H)-one(2). To a solution of oxazolone 1 (0.01 mol)
in acetic acid (30 ml), phenyl hydrazine (0.01 mol) and fused
anhydrous sodium acetate (0.2 gm) were added. *e reaction
mixture refluxed for 3 hrs. *e solvent was distilled under
reduced pressure, and the residue was poured onto crushed ice.
*e solid obtained was filtered off and recrystallized from
ethanol to give compound 2. Yield 60%; yellow crystals; m.p.
4.3. 5-(4-Methoxybenzylidene)-6-chloro-2,5-dihydro-2,3-
diphenyl-1,2,4-triazine (3). *e mixture of 2 (0.01 mol)

Heteroatom Chemistry
5
H2N
HN
NH
OCH2COOH
NH
Ar
Ar
N
O
Ar
NH
O
N
O
N2H4·H2O
Intramolecular
Nucleophilic addition
N
N
N
Ph
Ph
(Not isolated)
Ph
(11)
-H2
Oxidation
N
N
Ar
N
O
N
Ph
(12)
Scheme 6: Route of formation for compound 12.
Table 1: Antimicrobial activity of selected compounds.
Inhibition zone diameter (cm/gm sample)
Sample no.
Staphylococcus aureus G+
Bacillus subtilis G+
Escherichia coli G−
Aspergillus niger (fungus)
2
00
13
12
11
15
16
—
00
15
14
00
20
22
—
00
00
00
00
16
20
—
15
00
00
00
—
—
17
3
6
7
Cip
CN
Am
Cip � ciprofloxacin (antibacterial agent); CN � erythromycin (antibacterial agent); Am � amphotericin (antifungal agent). *e concentration of all syn-
thesized compounds and the reference was 5 mg/1 ml of DMSO. Zone of inhibition: 0–16 mm � low; 14–16 mm � moderate; <16 mm � high; 0 � no inhibition.
and phosphorus pentachloride (0.01 mol) in phosphorus
oxychloride (30 ml) refluxed on the water bath for 6 hrs. *e
reaction mixture was then poured gradually onto crashed ice.
*e solid obtained was filtered off and recrystallized from
benzene to give compound 3. Yield 90%; pale brown crystals;
m.p.160–162°C (benzene); IR (KBr) (υ, cm− 1): 3068 (CHarom),
2935 (CHalkyl), and 1600 (C�N); 1HNMR (DMSO-d6) δ: 3.72
(s, OCH3), 6.86 (s, 1H, �CH), and 7.20–7.93 (m, 14H, Ar-H);
MS (70 eV) m/z (%): 387.75 (M+, 7), 356 (14), 328 (5), 235 (3),
194 (8), 104 (5), 93 (13), 77 (100), and 62 (30). Anal. calcd for
C23H18ON3Cl (387.86): C (71.22); H (4.68); and N (10.83).
Found: C (70.94); H (4.77); and N (10.51).
and hydrazine hydrate (0.01 mol) refluxed in ethyl alcohol
(20 ml) for 12 hrs. A solid product obtained after cooling to
room temperature was filtered off and recrystallized from
ethanol to give compound 4. Yield 88%; colorless crystals;
m.p.170–172°C (EtOH); IR (KBr) (υ, cm− 1): 3300, 3220 (NH,
NH2), 3065 (CHarom), 2957 (CHalkyl), and 1604 (C�N);
1HNMR (DMSO-d6) δ: 3.72 (s, OCH3), 4.00 (br.s, 2H, NH2),
6.43 (s, 1H, �CH), 7.85–7.95 (m, 14H, ArH), and 8.97 (br.s,
1H, NH, exchangeable); MS (70 eV) m/z (%): 383 (M+, 2),
352 (1), 277 (5), 189 (8), 107 (8), 70 (100), 58 (2), and 44 (17).
Anal. calcd for C23H21N5O (383.45): C (72.04); H (5.52); and
N (18.26). Found: C (71.66); H (5.21); and N (17.95).
4.4. 1-(5-(4-Methoxybenzylidene)-2,5-dihydro-2,3-diphenyl-
1,2,4-triazin-6-yl)hydrazine (4). Compound 3 (0.01 mol)
4.5. N′-(5-(4-Methoxybenzylidene)-2,5-dihydro-2,3-diphenyl-
1,2,4-triazin-6-yl)-N-acetylacetohydrazide (5). Solution of 4

6
Heteroatom Chemistry
(0.5 gm) in acetic anhydride (15 ml) was heated under reflux
for 6 hrs. *e solvent was distilled off under reduced
pressure, and the residue was poured onto crushed ice. *e
solid obtained was filtered off and recrystallized to give
compound 5. Yield 90%; white crystals; m.p. 108–110°C
(EtOH); IR (KBr) (υ, cm− 1): 3445 (NH), 3066 (CHarom),
2956, 2923, 2852 (CHalkyl), 1726, 1701 (C�O), and 1640
Z-8b: 3.75 (s, OCH3), and 11.23 (br.s, 1H, OH, exchange-
able); MS (70 eV) m/z (%): 294 (M+, 37), 278 (40), 267 (1.5),
263 (1), 91 (88), 234 (1.1), 186 (6), 146 (12), 119 (16), 107
(1.3), 77 (97), 59 (15), and 40 (100). Anal. calcd for
C17H14O3N2 (294.31): C (69.38); H (4.79); and N (9.52).
Found: C (68.98); H (4.52); and N (9.36).
1
(C�N); HNMR (DMSO-d6) δ: 2.28 (s, 6H, 2CH3), 3.83 (s,
4.10. 4-(4-Methoxybenzylidene)-2-acetyl-6-phenyl-2H-1,2,5-
oxadiazin-3(4H)-one (10). A solution of 8 (0.5 gm) in acetic
anhydride (20 ml) was heated under reflux for 3 hrs. *e
solvent was distilled off under reduced pressure, and the
residue was poured onto crushed ice. *e solid obtained was
filtered off and recrystallized from ethanol to give compound
10. Yield 87%; yellow crystals; m.p. 124–126°C (EtOH); IR
(KBr) (υ, cm− 1): 3087 (CHarom), 2940, 2840 (CHalkyl), 1775,
3H, OCH3), 7.00 (s, 1H, �CH), 7.07–7.92 (m, 14H, ArH),
and 8.32 (br.s, 1H, NH, exchangeable); MS (70 eV) m/z (%):
467 (M+, 8), 424 (1), 368 (13), 360 (7), 352 (24), 327 (25), 273
(8), 235 (7), 194 (2), 141 (3), 91 (66), and 42 (100). Anal. calcd
for C27H25N5O3 (467.52): C (69.36); H (5.39); and N (14.98).
Found: C (69.12); H (5.50); and N (15.18).
4.6. Reaction of Chlorotriazine Derivative (3) with Some
1
1700 (C�O), and 1651 (C�N); HNMR (DMSO-d6) δ: 3.82
Nucleophilic Reagents
(s, 3H, CH3), 3.84 (s, 3H, OCH3), 7.32 (s, 1H, �CH), and
7.04–8.30 (m, 9H, ArH); MS (70 eV) m/z (%): 336 (M+, 25),
294 (1.5), 251 (21), 234 (17), 186 (47), 159 (6), 143 (100), 107
(12), and 77 (29). Anal. calcd for C19H16N2O4 (336.34): C
(67.85); H (4.79); and N (8.33). Found: C (67.74); H (4.67);
and N (7.95).
4.6.1. General Procedure. Compound 3 (0.01 mol) and so-
dium azide or anthranilic acid (0.01 mol) refluxed in acetic
acid “glacial” (20 ml) for about 10–12 hrs. *e solid product
formed was filtered off and then recrystallized from ethanol
to give compounds 6 and 7, respectively.
4.7. 8-(4-Methoxybenzylidene)-5,8-dihydro-5,6-diphenylte-
trazolo[1,5-f][1,2,4]triazine(6). Yield 75%; red crystals; m.p.
150–152°C; IR (KBr) (υ, cm− 1): 3065 (CHarom), 2976, 2837
4.11. 2-(4-(4-Methoxybenzylidene)-6-phenyl-4H-1,2,5-oxa-
diazin-3-yloxy)acetic Acid (11). A mixture of compound 8
(0.01 mol) and ethyl chloroacetate (0.01 mol) refluxed in
acetone (25 ml) and potassium carbonate (0.9 gm) for
10 hrs. *e solvent was distilled off under reduced pressure,
and the residue was poured onto ice water. *e solid
product was filtered off and recrystallized from diluted
ethanol to give compound 11. Yield 40%; orange crystals;
m.p. 280–282°C (dil. EtOH); IR (KBr) (υ, cm− 1): 3432 (OH),
3073 (CHarom), 2981, 2846 (CHalkyl), 1696 (C�O), and 1597
(C�N); 1HNMR (DMSO-d6) δ: 3.78 (s, OCH3), 3.83 (s, 2H,
CH2), 6.96–8.24 (m, 9H, ArH + �CH), and 11.99 (br.s, 1H,
OH, exchangeable); MS (70 eV) m/z (%): 352 (M+, 12), 334
(4.7), 294 (14), 235 (1.6), 117 (15), 77 (12), 69 (100), and 41
(34). Anal. calcd for C19H16N2O5 (352.34): C (64.77); H
(4.58); and N (7.95). Found: C (64.39); H (4.32); and N
(7.68).
1
(CHalkyl), 1600 (C�N), and 1573 (N�N); HNMR (DMSO-
d6) δ: 3.78 (s, 3H, OCH3) and 6.76–7.94 (m, 15H,
ArH + CH�); MS (70 eV) m/z (%): 394 (M+, 4.5), 354 (37),
325 (2), 250 (11), 133 (5), 107 (18), 67 (4), and 48 (100). Anal.
calcd for C23H18N6O (394.43): C (70.04); H (4.60); and N
(21.31). Found: C (70.31); H (4.73); and N (20.90).
4.8. 4-(4-Methoxybenzylidene)-1,2-diphenyl-1H-[1,2,4]triazino
[6,1-b]quinazolin-10(4H)-one (7). Yield− 1 80%; off-white
crystals; m.p. 128–130°C; IR (KBr) (υ, cm ): 3049 (CHarom),
2944, 2844 (CHalkyl), 1678 (C�O), and 1597 (C�N); 1HNMR
(DMSO-d6) δ: 3.70 (s, OCH3), 6.42 (s, 1H, �CH), and
6.87–8.44 (m, 18H, ArH); MS (70 eV) m/z (%): 470 (M+, 7),
443 (3), 369 (6), 352 (6), 294 (15), 194 (1), 185 (3), 162 (4),
134 (3), 107 (7), 91 (64), and 43 (100). Anal. calcd for
C30H22N4O2 (470.52): C (76.58); H (4.71); and N (11.91).
Found: C (76.17); H (4.33); and N (11.54).
4.12. 5-(4-Methoxyphenyl)-3-phenylpyrazolo[3,4-c][1,2,5]oxa-
diazine (12). To a solution of compound 11 (0.01 mol) in
ethyl alcohol (20 ml), hydrazine hydrate (0.015 mol) was
added. *e reaction mixture refluxed for 6 hrs. *e solvent
was distilled under reduced pressure, and the residue was
poured onto crushed ice. *e solid obtained was filtered off
and recrystallized from ethanol to give compound 12. Yield:
58%; pink needles; m.p. 155–157°C (EtOH); IR (KBr) (υ,
cm− 1): 3015 (CHarom), 2937, 2844 (CHalkyl), and 1606 (C�N);
1HNMR (DMSO-d6) δ: 3.81 (s, OCH3) and 7.02–8.61 (m,
10H, ArH + �CH); MS (70 eV) m/z (%): 304 (M+, 8), 276 (6),
227 (1), 195 (1.4), 185 (3), 119 (9), 107 (8), 91 (10), 77 (79), 70
(23), 57 (100), and 54 (12). Anal. calcd for C17H12N4O2
(304.30): C (67.10); H (3.97); and N (18.41). Found: C
(66.72); H (4.25); and N (18.12).
4.9. (4Z)-4-(4-Methoxybenzylidene)-6-phenyl-2H-1,2,5-oxa-
diazin-3(4H)-one (8). To a solution of oxazolone 1
(0.01 mol) in pyridine (30 ml), hydroxylamine hydrochloride
(0.01 mol) was added. *e reaction mixture refluxed for
3 hrs. *e solvent was distilled under reduced pressure, and
the residue was poured onto crushed ice. *e solid obtained
was filtered off and recrystallized to give compound 8. Yield
53%; yellowish brown needles; m.p. 195–197°C (EtOH); IR
(KBr) (υ, cm− 1): 3202 (NH), 3068 (CHarom), 2962 (CHalkyl),
1
1700 (C�O), and 1675 (C�N); HNMR (DMSO-d6) δ: 7.17
(s, 1H, �CH), 6.92–8.31 (m, 18H, ArH + �CH), for Z-8a:
3.82 (s, 3H, OCH3), 9.81 (br.s, 1H, NH, exchangeable), for

Heteroatom Chemistry
7
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Data Availability
*e instrumental data including IR, mass, HNMR, and el-
emental analysis data used to support the findings of this
study are included within the article.
Conflicts of Interest
*e authors declare that they have no conflicts of interest.
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