Synthetic approach to 6-benzoyl-2H-[1,2,4] triazine-3,5-dione and 6-benzyl-5-thioxo-3,4-dihydro-2H-[1,2,4] triazin-3-one and studies on their transformation to fused [1,2,4]triazine systems

Article abstract of DOI:10.1080/10426500307850

Reaction of phenylpyruvic acid with semicarbazide afforded 6-benzyl-2H-[1,2,4]triazine-3,5-dione (1) which upon oxidation with potassium dichromate furnished 6-benzoyl-2H-[1,2,4]triazine-3,5-dione (2) in good yield. Constructing pyrazolo[3,4-e][1,2,4] triazine system (4) was achieved by reacting 2 with arylhydrazines in ethanolic solution. However treatment of 2 with the less reactive heteroarylhydrazines gave only the corresponding hydrazones (3). Attempt for constructing 1,2,4,5,10-pentaaza-dibenzo[a,d]cyclohept-3-one (7) from 2 was failed and (benzoimidazol-2-yl) [1,2,4] triazine derivative (6) was the only product. Reaction of 1 with phosphorus pentasulphide afforded compounds 8 and 9. Compound 8 was transformed to the hydrazino compound 14, which led to the construction of triazolo[4,3-d] [1,2,4]triazine system. Thus compounds 15 and 16 were obtained by reacting 14 with carbon disulfide or acetic anhydride respectively. Attempt to couple 8 with chloroacetic acid failed, while it's known isomer 10 led to the formation of thiazolo [2,3-c] [1,2,4]triazine derivative (13). Simple theoretical calculation using AM1 and PM3 semiempirical Hamitonian provided rational ways to correlate the reactivity with structure proposed.

Full text of DOI:10.1080/10426500307850

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Synthetic Approach to 6-Benzoyl-2H-
[1,2,4]triazine-3,5-dione and 6-Benzyl-5-thioxo-3,4-
dihydro-2H-[1,2,4]triazin-3-one and Studies on Their
Transformation to Fused[1,2,4]triazine Systems
A. M. El Massry a
a Alexandria University, Alexandria, Egypt
Published online: 27 Oct 2010.
To cite this article: A. M. El Massry (2003): Synthetic Approach to 6-Benzoyl-2H-[1,2,4]triazine-3,5-dione and 6-Benzyl-5-
thioxo-3,4-dihydro-2H-[1,2,4]triazin-3-one and Studies on Their Transformation to Fused[1,2,4]triazine Systems, Phosphorus,
Sulfur, and Silicon and the Related Elements, 178:5, 1143-1155
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Phosphorus, Sulfur and Silicon, 2003, Vol. 178:1143–1155
C
Copyright 2003 Taylor & Francis
1042-6507/03 $12.00 + .00
DOI: 10.1080/10426500390208974
SYNTHETIC APPROACH TO 6-BENZOYL-2H-[1,2,4]
TRIAZINE-3,5-DIONE AND
6-BENZYL-5-THIOXO-3,4-DIHYDRO-2H-[1,2,4]
TRIAZIN-3-ONE AND STUDIES ON THEIR
TRANSFORMATION TO FUSED
[1,2,4]TRIAZINE SYSTEMS
A. M. El Massry
Alexandria University, Alexandria, Egypt
(Received May 29, 2002; accepted November 10, 2002)
Reaction of phenylpyruvic acid with semicarbazide afforded 6-benzyl-
2H-[1,2,4]triazine-3,5-dione (1) which upon oxidation with potas-
sium dichromate furnished 6-benzoyl-2H-[1,2,4]triazine-3,5-dione (2)
in good yield. Constructing pyrazolo[3,4-e][1,2,4] triazine system (4)
was achieved by reacting 2 with arylhydrazines in ethanolic solution.
However treatment of 2 with the less reactive heteroarylhydrazines
gave only the corresponding hydrazones (3). Attempt for constructing
1,2,4,5,10-pentaaza-dibenzo[a,d]cyclohept-3-one (7) from 2 was failed
and (benzoimidazol-2-yl) [1,2,4] triazine derivative (6) was the only
product. Reaction of 1 with phosphorus pentasulphide afforded com-
pounds 8 and 9. Compound 8 was transformed to the hydrazino com-
pound 14, which led to the construction of triazolo[4,3-d] [1,2,4]tri-
azine system. Thus compounds 15 and 16 were obtained by reacting
14 with carbon disulfide or acetic anhydride respectively. Attempt to
couple 8 with chloroacetic acid failed, while it’s known isomer 10 led to
the formation of thiazolo [2,3-c] [1,2,4]triazine derivative (13). Simple
theoretical calculation using AM1 and PM3 semiempirical Hamito-
nian provided rational ways to correlate the reactivity with structure
proposed.
Keywords: AM1; (benzoimidazol-2-yl) [1,2,4] triazine; PM3;
pyrazolo[3,4-e][1,2,4]triazine; triazolo [4,3-d] [1,2,4]triazine
The author thanks Dr. H. Perzanowski, Chemistry Department, King Fahd University
of Petroleum and Mineral, for providing the NMR spectra for compounds 3a and 3b.
Address correspondence to A. M. El Massry, Department of Chemistry, Faculty of
Science, Alexandria University, P.O. Box 426 Ibraimia, Alexandria 21321, Egypt. E-mail:
aelmassry@link.net
1143

1144
A. M. El Massry
The chemistry of fused 1,2,4-triazines were surveyed in two recent
reviews,1,2 various members of these compounds were reported to
posses anti-HIV, anticancer,3 6, antihypertensive, anesthetic, antide-
pressant, tranquilizer, sedative, muscle relaxant,1,2 herbicidal as well
as selective weed control in wheat, antibacterial, antiviral, antifungal,
anti-inflammatory, anticonvulsant activities, and carragreen-induced
edema inhibitor.1,2
Such activities and applications furnished the impetus to continue
12
our earlier work7
on the utilization of keto acids and their func-
tionalized analogues as precursors for the preparation of new series of
1,2,4-triazines and condensed derivatives.
DISCUSSION
Our initial plan is summarized in Scheme 1. Thus the starting 6-benzyl-
2H-[1,2,4] triazine-3,5-dione (1) was prepared in good yield by two dif-
ferent methods; the first is slightly modified earlier reported condition13
through the condensation of phenylpyruvic acid with semicarbazide hy-
drochloride in aqueous potassium hydroxide solution, the second by the
reaction of phenylpyruvic acid thiosemicarbazone with methyl iodide.14
The oxidation of 1 with potassium dichromate in acetic acid afforded 6-
benzoyl-2H-[1,2,4]triazine-3,5-dione (2), which revealed IR absorption
for the carbonyl group at 1690 cm 1. Its 13C-NMR showed the absence
of benzylic carbon signal of the starting material 1 at 35 ppm and
the appearance of the carbonyl carbon signal at 187.6 ppm. Heating
2 with aryl hydrazines (Ar = C6H5, p-MeC6H4, p-ClC6H4) smoothly
produced orange precipitates, where the elemental analyses as well
as the mass spectrum of 4a as a prototype showed the elimination
of two molecules of water from the sum of the molecular formula of
their corresponding starting materials. Their assigned structures 5-
aryl-7-phenyl-2,5-dihydro-pyrazolo [3,4-e][1,2,4]triazin-3-ones (4 a–c)
1
were confirmed by spectral data analysis. Thus, their H-NMR spec-
tra showed only one exchangeable signal at about 13.6 ppm due to
the remaining NH group. However, reaction of 2 with heteroarylhy-
drazines afforded the corresponding hydrazones (3). Attempts to cyclize
the later compounds under acidic conditions met with no success. This
could be explained by the delocalization of the electron density of the
N atom over the heterocyclic ring which decreases their nucleophilic-
ity. Also the reaction of 2 with hydrazinecarbodithioic acid methyl
ester gave the corresponding hydrazone derivative (5). On the other
hand, reaction of 2 with phenylene-1,2-diamine led to the formation

Fused [1,2,4]triazine Systems
1145
i) NH2-NH-CO-NH2.HCl/KOH, ii) K2Cr2O7/HOAc , iii) NH2-NH-CS-SCH3,
iv) Ar-NH-NH2, v) Phenylene-1,2-diamine
SCHEME 1
of 6-(2-Phenyl-2,3-dihydro-1H-benzoimidazol-2-yl)-2H-[1,2,4]triazine-
3,5-dione (6) rather than 11-phenyl-2,5-dihydro-1,2,4,5,10-pentaaza-
dibenzo[a,d]cyclohepten-3-one (7), where the binucleophilic sites of
the diamine attack the side chain carbonyl carbon. The structure

1146
A. M. El Massry
SCHEME 2
assignment of 6 was based on the spectroscopic data as well as the
elemental analysis, which indicated the loss of one molecule of water
during the condensation process. Heating compound 1 with phospho-
rus pentasulphide in pyridine under reflux for 3 h afforded a mixture
of the hitherto unknown product 8 and the known compound 915 as
indicated by TLC. They were separated easily by heating in benzene.
The structure of 8 as 6-benzyl-5-thioxo-4,5-dihydro-2H-[1,2,4]triazin-
3-one was based on spectroscopic data and secured by comparative
study with the known 3-thioxo isomer (10) which was prepared by
an independent experimental procedure reported earlier by Khamaev
et al.16
Moreover, attempted coupling of 8 with chloroacetic acid by heat-
ing in dry acetone and anhydrous potassium carbonate for 3 h led
only to the recovery of the starting materials, while the reaction of
its isomer 10 took place and afforded most likely 3-benzyl-thiazolo[2,3-
c][1,2,4]triazine-4,6-dione (13) as a single product via regiospecific reac-
tion. To better understand why 10 rather than 8 reacts with chloroacetic
acid why the former most likely gave 13 rather than its isomeric one
12, we decided to study the theoretical electron distribution to deter-
mine whether the reactivity as well as the regiospecifity are charge
controlled. We used a semiempirical approachs, namely PM3 and AM1

Fused [1,2,4]triazine Systems
1147
SCHEME 3
(MOPAC). The main electronic characteristics of 8 and 10 are shown
in Figure 1, which agree with high nucleophilicity of the sulfur atom of
10 over 8. Next the optimized geometry of the expected reaction inter-
mediate 11 in its two tautomeric forms 11a and 11b is represented in
Figure 2 using PM3 approach followed by charge density calculations
by AM1.17 The results show that the negative charge density located
upon N-4 of 11a is higher than N-2 of 11b which prompted us to propose
structure 13 over 12.
In continuation of our goal, compound 8 was allowed to react with
hydrazine to afford 6-benzyl-5-hydrazino-2H-[1,2,4]triazin-3-one (14).
Annelation of five-membered to 1,2,4-triazine ring was achieved upon
FIGURE 1 Calculated charge densities and optimized geometries of com-
pounds 8 and 10.

1148
A. M. El Massry
FIGURE 2 Calculated charge densities and optimized geometries of the tau-
tometric forms 11a and 11b.
reacting 14 with carbon disulphide or acetic anhydride to give 8-benzyl-
3-thioxo-2,6-dihydro-3H-[1,2,4] triazolo[4,3-d][1,2,4]triazin-5-one (15)
or 8-benzyl-3-methyl-6H-[1,2,4]triazolo [4,3-d] [1,2,4]triazin-5-one (16)
respectively.
Attempt to annelate six-membered ring to 1,2,4-triazine ring,
namely,1,2,4-triazino-1,2,4-triazine, met with no success. Thus, heat-
ing 14 with pyruvic acid, ethyl pyruvate, or phenylpyruvic acid in boil-
ing ethanol gave the corresponding hydrazones (17a–c) respectively.
Treating compounds 17a and17c with polyphosphoric acid or heating
compound 17b over its melting point led only to the recovery of the
starting materials.
EXPERIMENTAL
Melting points were determined with a Mel-Temp apparatus and are
uncorrected. 1H-NMR and 13C-NMR spectra were recorded on a Bruker
AC-250 and/or Varian EM-390 spectrometers. Chemical shifts are ex-
pressed in scale in part per million relative to tetramethylsilane as
internal standard. TLC was performed using the ascending technique
with EM silica gel 60 F254 precoated on plastic sheets. The IR spectra
were obtained with Unicam SP 1025 spectrometer. A Hewlett-Packard
5995 Gas chromatograph/Mass spectrometer was used to record Mass
spectral data at 70ev. Geometry optimizations were performed initially
by PM3/MOPAC in Alchemy 2000 and subsequently the electron den-
sity were calculated using the AM1 in Gaussian/98W. The compounds
were named using Chem. Draw Ultra version 6, Cambridgesoft Corpo-
ration. Elemental analyses were performed in the Chemistry Depart-
ment, Faculty of Science, Cairo and Beirut Universities.
6-Benzoyl-2H-[1,2,4]triazine-3,5-dione (2)
A mixture of 6-benzyl-2H-[1,2,4]triazine-3,5-dione (2.03 g, 10 mmol)
and potassium dichromate (4.42 g, 15 mmol) in glacial acetic acid (40 ml)
was heated under reflux for 11 h. The mixture was poured onto crushed

Fused [1,2,4]triazine Systems
1149
ice and left overnight. The product that precipitated out was filtered
off, washed with water, and dried, then crystallized from ethanol to
give colorless needles (yield 1.45 g, 66.8%) m.p. 225–227 C; IR (KBr):
3186 (NH), 1757 (CON), 1690 (CO), and 1640 (C N) cm 1; MS (m/z, %):
217 (83), 105 (100), 77 (95), 61 (14). 1H NMR (DMSO-d6): (ppm) 6.93,
7.07, 7.33 (3m, 5H, ArH), 11.76 (s, 1H, NH, D2O exchangeable), 12.16
(s, 1H, NH, D2O exchangeable). 13C-NMR (DMSO-d6): 128.8, 129.6,
133.6, 135.1, 140.0, 148.8, 155.2, 187.6. Found: C, 55.1; H, 3.1; N, 19.6%.
C10H7N3O3 required: C, 55.3; H, 3.2; N, 19.3%.
6-[Phenyl-(pyridin-2-yl)-hydrazono)-methyl]-2H-
[1,2,4]triazine-3,5-dione (3a)
To a solution of 6-benzoyl-2H-[1,2,4]triazine-3,5-dione (0.22 g, 1 mmol)
in ethanol (30 ml), 2-hydrazinopyridine (0.11 g, 1 mmol) was added.
The reaction mixture was heated under reflux for 10 h, concentrated,
and allowed to cool. The formed yellow precipitate was filtered off, dried,
and crystallized from ethanol to give yellow needles (yield 0.15 g, 48.7%)
m.p. 303–304 C; IR (KBr): 3328, 3215 (NH), 1699, 1651 (CO), and 1603
cm 1 (C N). 1H NMR (DMSO-d6): (ppm) 6.89, 7.42, 7.73, 8.19 (t, m, m,
d, 9H, ArH), 10.86, 12.13, 12.67 (s, bs, bs, 3H, 3NH, D2O exchangeable).
13C-NMR (DMSO-d6): 106.9, 115.7, 125.5, 128.2, 128.5, 135.8, 136.7,
138.1, 139.0, 147.6, 149.8, 156.5, 157.1. Found: C, 58.7; H, 4.0; N, 27.0%.
C15H12N6O2 required: C, 58.4; H, 3.9; N, 27.3%.
6-[Phenyl-(phthalazin-1-yl-hydrazono)-methyl]-2H-
[1,2,4]triazine-3,5-dione (3b)
To a solution of 6-benzoyl-2H-[1,2,4]triazine-3,5-dione (0.22 g, 1 mmol)
in ethanol (30 ml), hydralazine (0.16 g, 1 mmol) was added. The re-
action mixture was refluxed for 10 h and allowed to cool. The formed
yellow precipitate was filtered off and crystallized from ethanol to give
yellow crystals (yield 0.23 g, 64.1%) m.p. 247–249 C; IR (KBr): 3361,
1
3220, 3129 (NH), 1710, 1685 (CON), and 1612 cm 1, (C N). H NMR
(DMSO-d6): (ppm) 7.48, 7.81, 8.14, 8.24 (3m, s, 10H, ArH), 11.78,
12.20, 12.49 (3s, 3H, 3NH, D2O exchangeable). 13C-NMR (DMSO-d6):
123.7, 126.0, 126.5, 127.1, 127.5, 128.2, 129.5, 132.0, 132.6, 135.8,
138.3, 144.0, 147.8, 149.6, 151.3, 155.9. Found: C, 60.0; H, 3.8; N, 27.1%.
C18H13N7O2required: C, 60.2; H, 3.6; N, 27.3%.
5,7-Diphenyl-2,5-dihydro-pyrazolo[3,4-e]-
[1,2,4]triazin-3-one (4a)
To a solution of 6-benzoyl-2H-[1,2,4]triazine-3,5-dione (0.44 g, 2 mmol)
in ethanol (18 ml), phenylhydrazine (0.22 g, 2 mmol) was added. The

1150
A. M. El Massry
reaction mixture was refluxed for 6 h and allowed to cool. The formed
dark red precipitate was filtered off and recrystallized from acetic acid
to give yellow crystals (yield 0.30 g, 51.9%) m.p. 314–316 C (dec.);
IR (KBr): 3153 (NH), 1665 (CON), and 1601, 1581 cm 1(C N); MS
(m/z, %): 289 (85), 261 (43), 232 (13), 103 (20), 77 (100). 1H NMR
(DMSO-d6): (ppm) 6.71, 6.90, 7.67 (t, m, m, 10 H, ArH), 13.63 (s, 1H,
NH, D2O exchangeable). 13C-NMR (DMSO-d6): 119.6, 126.1, 126.7,
128.3, 128.5, 128.7, 130.3, 132.2, 137.2, 145.1, 149.7, 153.8. Found:
C, 66.7; H, 3.5; N, 24.0%. C16H11N5O required: C, 66.4; H, 3.8; N,
24.2%.
7-Phenyl-5-(p-tolyl)-2,5-dihydro-pyrazolo[3,4-e]
[1,2,4]triazin-3-one (4b)
To a solution of 6-benzoyl-2H-[1,2,4]triazine-3,5-dione (0.22 g, 1 mmol)
in ethanol (40 ml), p-tolylhydrazine (0.122 g, 1 mmol) was added.
The reaction mixture was heated under reflux for 9 h. The sol-
vent was evaporated under reduced pressure to give a dark precip-
itate, which upon crystallization from acetic acid gave orange crys-
tals (yield 0.18 g, 59.4%) m.p. 293–295 C; IR (KBr): 3154 (NH),
1672 (CON), and 1592 cm 1(C N). 1H NMR (DMSO-d6):
(ppm)
2.28 (s, 3H, CH3), 7.39 (d, 2H, ArH), 7.42, 7.62 (m, 3H, ArH),
8.00 (m, 2H, ArH), 8.23 (m, 2H, ArH), 13.90 (s, 1H, NH, D2O ex-
changeable). 13C-NMR (DMSO-d6): 21.0, 120.1, 127.1, 129.1, 129.5,
130.0, 131.0, 133.0, 135.5, 136.2, 145.2, 150.5, 154.3. Found: C,
67.0; H, 4.4; N, 22.7%. C17H13N5O required: C, 67.3; H, 4.3; N,
23.1%.
5-(p-Chlorophenyl)-7-phenyl-2,5-dihydro-
pyrazolo[3,4-e][1,2,4]triazin-3-one (4c)
To a solution of 6-benzoyl-2H-[1,2,4]triazine-3,5-dione (0.22 g, 1 mmol)
in ethanol (40 ml), p-chlorophenylhydrazine (0.16 g, 1 mmol) was added.
The reaction mixture was heated under reflux for 21 h. The solvent was
evaporated under reduced pressure to give a dark precipitate, which
upon crystallization from acetic acid gave orange crystals (yield 0.11 g,
34.0%) m.p. 303–304 C; IR (KBr): 3153 (NH), 1665 (CON), and 1582
1
cm (C N). 1H NMR (DMSO-d6): (ppm) 7.68 (m, 5 H, ArH), 8.33 (m,
4H, ArH), 14.69 (s, 1H, NH, D2O exchangeable). 13C-NMR (DMSO-d6):
121.3, 127.2, 128.8, 129.3, 129.5, 130.8, 131.1, 132.9, 136.7, 145.6,
150.7, 153.9. Found: C, 59.7; H, 3.3; N, 21.4%. C16H10N5OCl required:
C, 59.4; H, 3.1; N, 21.6%.

Fused [1,2,4]triazine Systems
1151
N-[(3,5-Dioxo-2,3,4,5-tetrahydro-[1,2,4]triazin-6-yl)-
phenyl-methylene]-hydrazinecarbodithioc Acid Methyl
Ester (5)
A mixture of 6-benzoyl-2H-[1,2,4]triazine-3,5-dione (0.22 g, 1 mmol) and
hydrazinecarbodithioic acid methyl ester (0.12 g, 1 mmol) in isopropyl
alcohol was heated under reflux for 18 h. The solvent was evaporated
under reduced pressure to give yellow precipitate. It was recrystallized
from ethyl acetate to give yellow crystals (yield 0.14 g, 43.6%) m.p.
193–195 C (dec.); IR (KBr): 3112, 3047 (NH), 1728, 1699 (CON), 1647
cm 1(C N). 1H NMR (DMSO-d6): (ppm) 2.49 (s, 3H, CH3S), 7.39, 7.69
(2m, 5H, ArH), 12.18 (s, 1H, NH, D2O exchangeable), 12.75 (s, 1H, NH,
D2O exchangeable), 13.00 (s, 1H, NH, D2O exchangeable). 13C-NMR
(DMSO-d6): 17.1, 127.0, 128.8, 130.5, 135.1, 138.0, 142.7, 149.8, 156.5,
201.0. Found: C, 44.7; H, 3.7; N, 21.5%. C12H11N5O2S2 required: C, 44.8;
H, 3.5; N, 21.8%.
6-(2-Phenyl-2,3-dihydro-1H-benzoimidazol-2-yl)-2H-
[1,2,4]triazine-3,5-dione (6)
A mixture of 6-benzoyl-2H-[1,2,4]triazine-3,5-dione (0.22 g, 1 mmol)
and o-phenylenediamine (0.11 g, 1 mmol) in ethanol (12 ml) was heated
under reflux for 7 h. The reaction mixture was left to cool and the sepa-
rated red precipitate was filtered off, washed with small amount of cold
methanol, and dried (yield 0.12 g , 39.0%) m.p. 185–186 C; IR (KBr):
3398, 3333, 3216, 3138 (NH), 1698 (CON), and 1598 cm 1(C N); MS
(m/z, %): 307 (24), 230 (44), 195 (100), 159 (19), 92 (26), 83 (38), 77
(6).1H NMR (DMSO-d6): (ppm) 6.41 (m, 4H, ArH), 6.51 (s, 2H, 2NH,
D2O exchangeable), 7.28, 7.44 (2m, 5H, ArH), 12.05 (s, 1H, NH, D2O
exchangeable), 12.40 (s, 1H, NH, D2O exchangeable). 13C-NMR (DMSO-
d6): 84.0, 107.0, 118.1, 125.5, 127.4, 128.0, 138.7, 143.6, 144.6, 149.6,
156.1. Found: C, 62.2; H, 4.4; N, 22.6%. C16H13N5O2 required: C, 62.5;
H, 4.3; N, 22.8%.
6-Benzyl-5-thioxo-4,5-dihydro-2H-[1,2,4]triazin-3-one (8)
& 6-Benzyl-2H-[1,2,4]triazine-3,5-dithione (9)
A mixture of 6-benzyl-2H-[1,2,4]triazine-3,5-dione (7.22 g, 35.5 mmol)
and phosphorus pentasulphide (23.8 g, 53.6 mmol) in dry pyridine
(130 ml) was heated under reflux for 3 h. The reaction mixture was
cooled and poured onto crushed ice. The precipitate was left overnight,
filtered off, washed with water, and dried. The dry crude was boiled
with about 200 ml of benzene and filtered off. The filtrate was concen-
trated and left to cool to give dark orange crystals of 6-benzyl-2H-[1,

1152
A. M. El Massry
2,4]triazin-3,5-dithione (yield 2.4 g, 28.8%) m.p. 184–185 C [Lit15 m.p.
175–176 C].
The precipitate was recrystallized from ethanol to give orange
needles of 6-benzyl-5-thioxo-4,5-dihydro-2H-[1,2,4]triazin-3-one (yield
2.9 g, 37.3%) m.p. 218–220 C (dec.); IR (KBr): 3212 (NH), 1728 (CON),
and 1662 cm 1(C N); MS (m/z, %): 219 (100), 186 (10), 143 (12), 117 (13),
91 (14), 77 (6). 1H NMR (DMSO-d6): (ppm) 4.03 (s, 2H, CH2Ph), 7.22
(m, 5H, ArH), 12.60 (s, 1H, NH, D2O exchangeable), 13.45 (s, 1H, NH,
D2O exchangeable). 13C-NMR (DMSO-d6): 37.6, 126.3, 128.2, 129.0,
137.4, 146.0, 147.5, 184.2. Found: C, 54.7; H, 4.3; N, 19.5%. C10H9N3OS
required: C, 54.8; H, 4.1; N, 19.2%.
3-Benzyl-thiazolo[2,3-c][1,2,4]triazine-4,6-dione (13)
To a mixture of 6-benzyl-3-thioxo-3,4-dihydro-2H-[1,2,4]triazin-5-one
(1.10 g, 5 mmol) and anhydrous potassium carbonate (1.38 g, 10 mmol)
in dry acetone (10 ml), a solution of chloroacetic acid (0.47 g, 5 mmol)
in dry acetone was added. The mixture was refluxed for 7 h, then
poured onto cold dilute hydrochloric acid and left to stand overnight.
The formed precipitate was filtered off, washed with water, and dried.
It was recrystallized from ethyl acetate to give colorless needles (yield
0.90 g, 69.5%) m.p. 144–146 C; IR (KBr): 1726, 1698 (CON), and 1587
cm 1(C N); MS (m/z, %): 259 (100), 143 (15), 117 (79), 91 (56), 77 (40).
1H NMR (DMSO-d6): (ppm) 3.82 (s, 2H, CH2Ph), 3.94 (s, 2H, CH2S),
7.24 (m, 5H, ArH). 13C-NMR (DMSO-d6): 31.8, 35.8, 126.5, 127.8,
128.4, 129.4, 136.8, 151.0, 163.0, 169.1. Found: C, 55.9; H, 3.7; N, 15.9%.
C12H9N3O2S required: C, 55.6; H, 3.5; N, 16.2%.
6-Benzyl-5-hydrazino-2H-[1,2,4]triazin-3-one (14)
To a solution of 6-benzyl-5-thioxo-4,5-dihydro-2H-[1,2,4]triazin-3-one
(0.22 g, 1 mmol) in ethanol (5 ml) was added hydrazine hydrate 99%
(2 ml) in ethanol (25 ml). The mixture was refluxed for 4 h, concentrated,
and then allowed to cool to room temperature. The product was filtered
off and dried. It was recrystallized from methylene chloride to give color-
less needles (yield 0.14 g, 64.5%) m.p. 337–338 C (dec.); IR (KBr): 3355,
3216, 3094 (NH), 1727 (CON), and 1662 cm 1(C N); MS (m/z, %): 217
(100), 143 (37), 128 (63), 106 (73), 91 (99), 77 (90).1H NMR (DMSO-d6):
(ppm) 3.65 (s, 2H, CH2Ph), 5.97 (bs, 2H, NH2, D2O exchangeable), 7.19
(m, 5H, ArH), 9.68 (bs, 1H, NH, D2O exchangeable), 10.74 (s, 1H, NH,
D2O exchangeable). 13C-NMR (DMSO-d6): 35.6, 126.2, 128.1, 128.9,
130.5, 138.0, 144.3, 149.0. Found: C, 55.5; H, 4.9; N, 32.0%. C10H11N5O
required: C, 55.3; H, 5.1; N, 32.2%.

Fused [1,2,4]triazine Systems
1153
8-Benzyl-3-thioxo-2,6-dihydro-3H-[1,2,4]triazolo-
[4,3-d][1,2,4]triazin-5-one (15)
A mixture of 6-benzyl-5-hydrazino-2H-[1,2,4]triazin-3-one (0.22 g, 1
mmol), carbon disulphide (3 ml) in pyridine was refluxed for 18 h. The
solvent was evaporated under reduced pressure to give colorless precip-
itate. It was filtered off and recrystallized from ethyl acetate/n-hexane
as colorless crystals (yield 0.20 g, 77.2%) m.p. 202–204 C; IR (KBr):
3114, 3029 (broad NH), 1720 (CON), and 1628 cm 1(C N); MS (m/z, %):
259 (100), 217 (42), 143 (20), 117 (20), 91 (96), 77 (40).1H NMR (DMSO-
d6): (ppm) 4.15 (s, 2H, CH2Ph), 7.25 (m, 5H, ArH), 12.29, 14.43 (s,
bs, 2H, 2NH, D2O exchangeable). 13C-NMR (DMSO-d6): 35.9, 127.0,
128.7, 129.4, 136.3, 139.6, 142.7, 143.9, 164.6. Found: C, 51.3; H, 3.3;
N, 27.1%. C11H9N5OS required: C, 51.0; H, 3.5; N, 27.0%.
8-Benzyl-3-methyl-6H-[1,2,4]triazolo-
[4,3-d][1,2,4]triazin-5-one (16)
A solution of 6-benzyl-5-hydrazino-2H-[1,2,4]triazin-3-one (0.55 g, 2.5
mmol) in acetic anhydride (7 ml) was refluxed for 1.5 h. The reac-
tion mixture was cooled and poured onto crushed ice to give color-
less precipitate. It was filtered off, washed with water, dried, and
recrystallized from benzene/n-hexane to give colorless needles (yield
0.46 g, 76.3%) m.p. 165–167 C; IR (KBr): 3156 (NH), 1724 (CON), and
1590 cm 1(C N).1H NMR (CDCl3): (ppm) 2.64 (s, 3H, CH3), 4.28 (s,
2H, CH2Ph), 7.23, 8.05 (2m, 5H, ArH), 11.23 (s, 1H, NH, D2O exchange-
able). 13C-NMR (CDCl3): 14.8, 37.4, 128.7, 129.3, 129.7, 135.7, 141.7,
144.7, 148.8, 166.3. Found: C, 60.0; H, 4.7; N, 28.7%. C12H11N5O re-
quired: C, 59.7; H, 4.6; N, 29.0%.
2-[(6-Benzyl-3-oxo-2,3-dihydro-[1,2,4]triazin-5-
yl)hydrazono]-propionic Acid (17a)
To a solution of 6-benzyl-5-hydrazino-2H-[1,2,4]triazin-3-one (0.44 g, 2
mmol) in ethanol (80 ml), pyruvic acid (0.18 g, 2 mmol) was added; the
reaction mixture was heated under reflux for 0.5 h and then was allowed
to cool to room temperature. The faint yellow product was filtered off,
washed with ethanol, and dried (yield 0.4 g, 69.6%) m.p. 227–229 C;
IR (KBr): 3240 (OH + NH), 1727 (acid carbonyl + CON), and 1621
1
cm 1(C N). H NMR (DMSO-d6): (ppm) 2.10 (s, 3H, CH3), 3.88 (s,
2H, CH2Ph), 7.25 (m, 5H, ArH), 11.96, 12.23 (s, bs, 3H, 2NH, COOH,
D2O exchangeable). 13C-NMR (DMSO-d6): 10.7, 33.9, 124.3, 126.1,
126.9, 135.1, 140.9, 144.8, 145.5, 154.1, 163.0. Found: C, 54.1; H, 4.8;
N, 24.1%. C13H13N5O3 required: C, 54.4; H, 4.6; N, 24.4%.

1154
A. M. El Massry
2-[(6-Benzyl-3-oxo-2,3-dihydro-[1,2,4]triazin-5-yl)-
hydrazono]propionic Acid Ethyl Ester (17b)
A mixture of 6-benzyl-5-hydrazino-2H-[1,2,4]triazin-3-one (0.44 g, 2
mmol) and ethyl pyruvate (0.24 g, 2 mmol) in ethanol (100 ml) was
heated under reflux for 3 h. The reaction mixture was concentrated,
left to cool, and the yellow precipitate was filtered off and dried. It was
recrystallized from benzene to give yellow needles (yield 0.6 g, 95.2%)
m.p. 137–138 C; IR (KBr): 3333, 3234 (NH), 1727 (ester carbonyl), 1711
(CON), and 1628 cm 1(C N).1H NMR (CDCl3): (ppm) 1.35 (t, 3H,
CH3), 2.25 (s, 3H, CH3), 3.91 (s, 2H, CH2Ph), 4.34 (q, 2H, CH2), 7.29
(m, 5H, ArH), 9.27, 9.45 (s, bs, 2H, 2NH, D2O exchangeable). 13C-NMR
(CDCl3): 14.6, 15.0, 36.8, 62.4, 127.3, 128.8, 129.6, 136.8, 145.1, 145.2,
147.7, 159.0, 165.1. Found: C, 57.4; H, 5.6; N, 21.9%. C15H17N5O3 re-
quired: C, 57.1; H, 5.4; N, 22.2%.
2-[(6-Benzyl-3-oxo-2,3-dihydro-[1,2,4]triazin-5-yl)-
hydrazono]-3-phenyl-propionic Acid (17c)
A mixture of 6-benzyl-5-hydrazino-2H-[1,2,4]triazin-3-one (0.22 g, 1
mmol) and phenylpyruvic acid (0.16 g, 1 mmol) in ethanol (30 ml) was
heated under reflux for 1 h. The reaction mixture was left to cool and
the yellow precipitate was filtered off and dried. It was recrystallized
from ethanol to give yellow crystals (yield 0.3 g, 82.6%) m.p. 223–224 C;
IR (KBr): 3239 (OH + NH), 1739 (acid carbonyl), 1695 (CON), and
1
1
1621 cm (C N). H NMR (DMSO-d6): (ppm) 3.93 (s, 2H, CH2Ph),
3.99 (s, 2H, CH2Ph), 7.18 (m, 10H, ArH), 11.78, 12.07, 12.37 (3s, 1H
each, 2NH, COOH, D2O exchangeable). 13C-NMR (DMSO-d6): 31.8,
36.0, 126.3, 126.4, 128.3, 128.4, 128.7, 128.9, 136.3, 137.3, 142.7, 147.6,
148.0, 156.7, 164.6. Found: C, 62.6; H, 4.8; N, 19.6%. C19H17N5O3 re-
quired: C, 62.8; H, 4.7; N, 19.3%.
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Fused [1,2,4]triazine Systems
1155
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