Synthesis of some novel 3,7-dimethyl-4H-pyrazolo[5,1-c][1,2,4]triazin-4-ones

Article abstract of DOI:10.1002/jhet.5570380328

Some novel 3,7-dimethyl-6H-pyrazolo[5,1-c][1,2,4]triazin-4-ones were prepared (3a-g). Compounds 3a,b were treated with hydrazines to afford various products 7a,b, 8a,b, 9 and 11a,b depending on the type of hydrazine derivative and reaction conditions. The

Full text of DOI:10.1002/jhet.5570380328

May-Jun 2001
Synthesis of Some Novel 3,7-Dimethyl-
711
4H-pyrazolo[5,1-c][1,2,4]triazin-4-ones
*
Ahmed A. El-Barbary , Mahmoud A. El-Badawi and Yasser M. Loksha
Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt
Received August 21, 2000
Some novel 3,7-dimethyl-6H-pyrazolo[5,1-c][1,2,4]triazin-4-ones were prepared (3a-g). Compounds
3a,b were treated with hydrazines to afford various products 7a,b, 8a,b, 9 and 11a,b depending on the type
of hydrazine derivative and reaction conditions. The benzoyloxyimino-pyrazolo[5,1-c][1,2,4]triazines
(13a,b) were synthesized by refluxing of compounds 3a,b with hydroxylamine hydrochloride to afford the
corresponding oxime derivatives followed by treatment with benzoyl chloride.
J. Heterocyclic Chem., 38, 711 (2001).
For few years, we have been occupied with the
between compounds 3a-e and 4a-e. The only differences
capable of differentiating between them were observed in
their mass spectra and elemental analyses. Mass spectra
chemistry of 1,2,4-triazines[1-3] due to their importance
and wide application in biological fields. A number of this
class of compounds were found to act as antimicrobial [4],
antiviral [5], anti-inflammatory [6-8] and antimalarial [9]
agents. 4-Amino-1,2,4-triazin-5(4H)-one derivatives have
attracted considerable interest, because of their herbicidal
activities and important intermediates for the preparation
of the fused 1,2,4-triazinone heterocycles [10].
+
showed the existence of the molecular ion peaks M at m/z
206, 268 and 207 corresponding to 3a, 3b, and 3c
respectively and the elemental microanalysis of these
compounds for S gave zero %. The proof for formation of
elemental sulfur came from its mass spectrum corre-
+
sponding to M = 256 (S ). The above results confirm that
8
In an attempt to synthesize fused 1,2,4-thiadiazine ring
with 1,2,4-triazines, we studied the reaction of 4-amino-6-
methyl-5-oxo-3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazine
(1) with brominated 1,3-dicarbonyl active methylene
compounds. The reaction was carried out by stirring of
1,3-dicarbonyl active methylene compounds (2a-e) with
pyrazolo[5,1-c][1,2,4]triazine structures (3a-e) were
formed, and not the expected [1,2,4]thiadiazino[2,3-c]-
[1,2,4]triazine structures (4a-e).
The mechanism for the formation of compounds 3a-e is
postulated as shown in scheme 2. It proceeds by
nucleophilic attack of the amino group of 1 on the carbonyl
group of 6a to give 6b, followed by elimination of water
from 6b to gave 6c which subsequently undergoes internal
nucleophilic attack accompanied by the elimination of
hydrogen sulfide to give the 8-bromopyrazolo[5,1-c]-
[1,2,4]triazines derivative (6d). Compound 6d undgoes a
redox reaction with the eliminated hydrogen sulfide to
afford the 8-bromo-6,7,8-trihydropyrazolo[5,1-c]-
[1,2,4]triazines (6e) and elemental sulfur. Elimination of
hydrogen bromide from 6e afforded the 6,7-dimethyl-6H-
N-bromosuccinimide (NBS) in the presence of benzoyl
1
peroxide in ethanol at room temperature for / hour
2
followed by addition of compound 1 and refluxing for
2 hours. The products from this reaction were shown to be
3,7-dimethyl-6H-pyrazolo[5,1-c][1,2,4]triazin-4-ones
(3a-e) rather than the expected 3,7-dimethyl-6H-
[1,2,4]thiadiazino[2,3-c][1,2,4]triazin-4-ones (4a-e)
1
13
(cf. Scheme 1). In the ir, H nmr and C nmr spectra no
observable differences are found capable of differentiating

712
Vol. 38
A. A. El-Barbary, M. A. El-Badawi and Y. M. Loksha
pyrazolo[5,1-c][1,2,4]triazin-4-ones (3a-e). The isolation
of elemental sulfur, the observation of a pale red color
resulting from elimination of hydrogen bromide and the
effervescence of the mother liquor upon treatment with
aqueous sodium bicarbonate solution are all consistent
with the proposed mechanism.
Compounds 3a,f,g were prepared directly in good yields
by the reaction of 1 with 3-chloro-2,4-pentandione 5a
and/or methyl(ethyl)-2-chloroacetoacetate 5f,g in
refluxing ethanol (cf. Scheme 1).
Treatment of 3a,b with hydrazine hydrate in 2-propanol
at room temperature afforded the hydrazinium salts 7a,b
which by refluxing in 2-propanol in the presence of few
drops of acetic acid furnished N,N'-bis[(3,7-dimethyl-4-
oxo-4,6-dihydro-pyrazolo[5,1-c][1,2,4]triazin-8-yl)-ethyl-
idene(and/or benzylidene)]-hydrazine (8a,b). Compounds
8a,b were prepared directly by the reaction of 3a,b with
hydrazine hydrate in refluxing 2-propanol in the presence
1
of few drops of acetic acid (cf. Scheme 3). The H nmr
spectrum of compounds 7a showed the presence of a broad
singlet signal (five protons) at 6.8 ppm corresponding to
+
13
the hydrazinium ion (N H ). The C nmr spectrum of
2
5
∆/2-PrOH
∆/2-PrOH
∆/2-PrOH

713
May-Jun 2001
Synthesis of Some Novel 3,7-Dimethyl-4H-pyrazolo[5,1-c][1,2,4]triazin-4-ones
General Procedure for the Preparation of 3,7-Dimethyl-6H-pyra-
zolo[5,1-c][1,2,4]triazin-4-one (3a-e).
compound 7a showed a resonance at 191.6 ppm corre-
sponding to the 8-CO carbon. A signal corresponding to
this carbon was not observed in the spectra of 8a,b . In the
mass spectrum of compound 7a, the base peak is observed
at m/z 206 (M -32) corresponding to loss of hydrazine,
which is additional evidence for the postulated structure.
Method A
To a solution of active methylene diketones (2,4-pentandione,
1-phenylbutane-1,3-dione, 3-oxobutyramide, 3-oxo-N-phenyl-
butyramide and/or N-(4-chlorophenyl)-3-oxobut-yramide) (2a-e)
(0.0064 mol) in ethanol (50 ml.), N-bromosuccinimide (1.36 g.,
0.0076 mol) and benzoyl peroxide (0.05 g.) were added and the
reaction mixture was stirred for 30 minutes at room temperature.
Compound 1 (1 g., 0.0064 mol) was then added and the reaction
mixture was refluxed for 2 hours until the starting material was
consumed (tlc). On cooling, the solid that formed was ioslated by
filtration, dried and recrystallized from methanol to give 3a-e.
+
In the mass spectra of compounds 8a,b, molecular ion
+
peaks M were observed at m/z 408 and 532, respectively.
The reaction of crude 3b, contaminated with elemental
sulfur, with phenyl hydrazine in refluxing 2-propanol
furnished
bis(3,7-dimethyl-4-oxo-4,6-dihydro-
pyrazolo[5,1-c][1,2,4]- triazin-8-yl)-disulfide (9) which
was also prepared by refluxing pure 3b with elemental
sulfur and phenyl hydrazine. While, the reaction of 3a,b
with methyl and/or phenyl hydrazine (10a,b) in the
presence of a few drops of acetic acid in refluxing
2-propanol yielded the corresponding hydrazono
8-Acetyl-3,7-dimethyl-6H-pyrazolo[5,1-c][1,2,4]triazin-4-
one (3a).
1
Compound 3a was obtained in 90% yield, mp 300-02 ˚C; H
nmr (DMSO-d ): δ 2.3 (s, 3H, 7-CH ), 2.4 (s, 3H, 3-CH ), 2.6
6
3
3
1
13
13
derivatives (11a-d) (cf. Scheme 3). In the H nmr and
C
(s, 3H, COCH ), 13.2 (s, 1H, NH); C nmr (DMSO-d ): δ 15.2
3
6
nmr spectra of compound 9, aromatic protons or carbons
(CH of C-7), 16.3 (CH of C-3), 29.5 (CH CO), 103.6 (C-8),
3
3
3
141.5 (C-7), 145.1 (C-3), 148.5 (C-4), 153.5 (C-9), 191.4
were not observed, showing that the phenyl group is not
present. The H nmr spectrum of compound 11b showed
-1
1
(COCH ); ir (potassium bromide): 3412, 1713, 1644, 1594 cm ;
3
hrms Calcd. for C H N O : 206.0800. Found: 206.0450.
9
10 4 2
the presence of a singlet corresponding to the NH-hydra-
zono at 9.2 ppm and a singlet corresponding to the pyra-
zolo NH at 13.0 ppm. In addition, a signal corresponding
8-Benzoyl-3,7-dimethyl-6H-pyrazolo[5,1-c][1,2,4]triazin-4-
one (3b).
13
to the 8-CO carbon was not observed in C nmr spectrum
1
Compound 3b was obtained in 56% yield, mp 240-42 °C; H nmr
of 11. The mass spectrum of compound 9 showed a
(DMSO-d ): δ 2.0 (s, 3H, 7-CH ), 2.2 (s, 3H, 3-CH ), 7.2-7.6
6
3
3
+
13
molecular ion peak M at m/z 390 and the base peak
(m. 5H, Ar), 13.3 (s, 1H, NH); C nmr (DMSO-d ): δ 15.3 (CH of
C-7), 16.7 (CH of C-3), 102.9 (C-8), 128.4, 128.9 132.3, 139.6
6
3
1
+
( / M ) at m/z at 195, which is a strong evidence for the
3
2
(C
), 141.7 (C-7), 145.9 (C-3), 148.9 (C-4), 153.8 (C-9), 189.5
disulfide structure of 9.
arom
-1
(COPh); ir (potassium bromide): 3439, 1712, 1619, 1551 cm ; hrms
Calcd. for C H N O : 268.0960. Found: 268.0620.
Condensation of 3a,b with hydroxylamine hydro-
chloride in refluxing 2-propanol in the presence of
triethylamine afforded the corresponding oxime
derivatives (12a,b) which were reacted with benzoyl
chloride in anhydrous pyridine at 0 ˚C to give the corre-
sponding benzoyloxyimino derivatives (13a,b) through
protection of the hydroxyl group (cf. Scheme 3). A
singlet corresponding to the OH protons at 10.8 and 11.7
14 12
4 2
3,7-Dimethyl-4-oxo-4,6-dihydropyrazolo[5,1-c][1,2,4]triazine-
8-carboxamide (3c).
1
Compound 3c was obtained in 46% yield, mp >350 °C;
H
nmr (DMSO-d ): δ 2.2 (s, 3H, 7-CH ), 2.5 (s, 3H, 3-CH ), 7.2
6
3
3
13
(s, 2H, NH ), 13.3 (s, 1H, NH); C nmr (DMSO-d ): δ 14.3
(CH of C-7), 16.1 (CH of C-3), 97.9 (C-8), 139.8 (C-7), 145.6
2
6
3
3
(C-3), 149.7 (C-4), 153.0 (C-9), 164.7 (CO of C-8); ir (potassium
1
ppm, respectively, was observed in the H nmr spectra of
-1
bromide): 3443, 3340, 3246, 1701, 1654, 1599 cm ; hrms Calcd.
13
compounds 12a,b. The C nmr spectrum of compound
for C H N O : 206.0756. Found: 206.0588.
8
9 5 2
12b showed that the 8-CO carbon is no longer present.
1
N-Phenyl3,7-dimethyl-4-oxo-4,6-dihydropyrazolo[5,1-c]-
[1,2,4]triazine-8-carboamide (3d).
The H nmr spectra of compounds 13a,b showes that the
OH groups are no longer present, and the singlets at 13.0
and 13.6 ppm show that the NH groups are present,
which confirmed that protection occurred on the OH
groups not the NH groups.
1
Compound 3d was obtained in 35% yield, mp 295-97 °C; H
nmr (DMSO-d ): δ 2.3 (s, 3H, 7-CH ), 2.6 (s, 3H, 3-CH ),
6
3
3
13
7.1-7.7 (m, 5H, Ar), 9.56 (s, 1H, NHCO) 13.7 (s, NH); C nmr
(DMSO-d ): δ 14.3 (CH of C-7), 16.5 (CH of C-3), 97.8 (C-8),
6
3
3
120.5, 123.8, 128.8, 139.1 (C
), 139.2 (C-7), 144.2 (C-3),
arom
EXPERIMENTAL
149.1 (C-4), 153.0 (C-9), 160.7 (CONH) ppm.; ir (potassium
-1
bromide): 3417, 3268, 1717, 1635, 1597 cm .
Melting points were measured in open capillary tubes and are
uncorrected. The nmr spectra were recorded on a Bruker 250 FT
nmr spectrometer, with tetramethylsilane as internal standard.
Mass spectra were recorded using electron ionization (EI) on a
varian Mat 311A spectrometer. The ir spectra were recorded on a
Perkin-Elmer 1720 spectrometer. The microanalysis were
measured at the microanalysis unit, Faculty of Science, Tanta
University.
Anal. Calcd. for C
Found: C, 59.13; H, 4.52; N, 24.34.
H N O : C, 59.36; H, 4.63; N, 24.72.
14 13 5 2
N-(4-chloro-phenyl)-3,7-dimethyl-4-oxo-4,6-dihydropyra-
zolo[5,1-c][1,2,4]triazine-8-carboxamide (3e).
1
Compound 3e was obtained in 32% yield, mp >350 °C;
H
nmr (DMSO-d ): δ 2.4 (s, 3H, 7-CH ), 2.6 (s, 3H, 3-CH ),
6
3
3
13
7.4-7.7 (m, 5H, Ar), 9.7 (s, 1H, NHCO); C nmr (DMSO-d ): δ
6

714
Vol. 38
A. A. El-Barbary, M. A. El-Badawi and Y. M. Loksha
14.8 (CH of C-7), 17.10 (CH of C-3), 98.4 (C-8), 122.6, 127.9,
(DMSO-d ): δ 16.4 (CH of C-7), 17.5 (CH of C-3), 30.8
3
3
6
3
3
129.3, 138.8 (C
), 139.8 (C-7), 144.9 (C-3), 149.7 (C-4),
(CH CO), 104.6 (C-8), 139.5 (C-7), 149.8 (C-3), 153.1 (C-4),
arom
3
155.7 (C-9), 191.6 (CO of C-8); ir (potassium bromide): 3332,
3247, 1711, 1631, 1541, 1461 cm .
153.8 (C-9), 161.4 (CONH); ir (potassium bromide): 3420, 3325,
1706, 1650, 1609 cm .
-1
-1
Anal. Calcd. for C H N O : C, 45.37; H,5.92; N, 35.27 .
Found: C, 45.12; H, 5.83; N, 35.11.
Anal. Calcd. for C
Found: C, 52.51; H, 3.75; N, 21.95.
H ClN O : C, 52.92; H, 3.81; N, 22.04.
9
14 6 2
14 12 5 2
Hydrazinium 8-Benzoyl-3,7-dimethyl-6H-pyrazolo[5,1-c]-
[1,2,4]triazin-4-on-6-ide (7b).
Method B.
To a solution of 1 (3.16 g., 0.02 mol) in ethanol (80 ml),
3-chloro-2,4-pentandione (2.4 ml, 0.02 mol) was added in one
portion and refluxed for 1 / hour at which time the starting
material was consumed (tlc). On cooling, the solid that separated
out was isolated by filtration, dried and recrystallized from
methanol to give 8-acetyl-3,7-dimethyl-6H-pyrazolo[5,1-c]-
[1,2,4]triazin-4-one (3a); yield 3.9 g. (95%); mp 300-02 °C.
Melting point depression was not observed in a mixed melting
point experiment with an authentic sample of 3a.
Compound 7b was obtained in 93% yield, mp 110-112°C, ir
-1
(potassium bromide): 3425, 3247, 1699, 1612, 1513, 1425 cm .
1
2
Anal. Calcd. for C
H N O : C, 55.99; H, 5.37; N, 27.98.
14 16 6 2
Found: C, 55.38; H, 5.21; N, 27.71.
N,N'-Bis[(3,7-dimethyl-4-oxo-4,6-dihydropyrazolo[5,1-c]-
[1,2,4]triazin-8-yl)-alkylidene]-hydrazine (8a,b).
Method A.
Compound 7a,b (0.005 mol) and glacial acetic acid (0.5 ml)
were refluxed in 2-propanol for 2 hours until the starting material
was consumed (tlc). The solid product that formed was separated
out and recrystallized from dimethylformamid/water
Methyl and/or ethyl 3,7-dimethyl-4-oxo-4,6-dihydropyra-
zolo[5,1-I][1,2,4]triazine-8-carboxylate (3f,g).
To a solution of (1a) (3.16 g., 0.02 mol) in ethanol (70 ml), methyl
and/or ethyl 2-chloroacetoacetate (5f,g) (0.02 mol) was added in one
(DMF/H O) to give (8a,b).
2
portion and refluxed for 11/ hour at which time the starting material
was consumed (tlc). On cooling, the solid that separated out was
2
Method B.
Compound 3a,b (0.01 mol), and hydrazine hydrate 80%
filtered off and recrystallized from methanol to give 3f,g.
(0.25 ml, 0.0052 mol) in 2-propanol (50 ml) in the presence of
Methyl 3,7-Dimethyl-4-oxo-4,6-dihydro-pyrazolo[5,1-c]-
[1,2,4]triazine-8-carboxylate (3f).
1
acetic acid (1 ml) were refluxed for 2 / hours until the starting
2
material was consumed (tlc). The solid product that formed was
1
Compound 3f was obtained in 76% yield, mp 250-52 °C; H
separated out and recrystallized from DMF/H O to give 8a,b.
2
nmr (DMSO-d ): δ 2.3 (s, 3H, 7-CH ), 2.4 (s, 3H, 3-CH ), 3.8
6
3
3
N,N'-Bis[(3,7-dimethyl-4-oxo-4,6-dihydropyrazolo[5,1-c]-
[1,2,4]triazin-8-yl)-ethylidene]hydrazine (8a).
13
(s, 3H, OCH ), 13.4 (s, 1H, NH); C nmr (DMSO-d ): δ 13.8
3
6
(CH of C-7), 16.3 (CH of C-3), 51.0 (OCH ), 92.5 (C-8), 140.5
3
3
3
(C-7), 144.9 (C-3), 148.6 (C-4), 154.8 (C-9), 161.9 (COO of
C-8); ir (potassium bromide): 3288, 1719, 1681, 1621 cm .
Compund 8a was obtained in 38% yield (method A), 56%
-1
1
(method B), mp >300 °C, H nmr (DMSO-d ): δ 2.1 (s, 3H,
6
Anal. Calcd. for C H N O : C, 48.65; H, 4.54; N, 25.21.
9
10 4 3
7-CH ), 2.3 (s, 3H, 3-CH ), 2.5 (s, 3H, hydrazono-CH ) ppm; ir
3
3
3
Found: C, 48.32; H, 4.47; N, 25.11.
-1
(potassium bromide): 3278, 1703, 1602, 1546 cm .
Anal. Calcd. for C O : C, 52.93; H, 4.94; N, 34.29.
H
N
Ethyl 3,7-Dimethyl-4-oxo-4,6-dihydro-pyrazolo[5,1-c][1,2,4]-
triazine-8-carboxyate (3g).
18 20 10
2
Found: C, 52.73; H, 4.81; N, 34.13.
1
N,N'-Bis[(3,7-dimethyl-4-oxo-4,6-dihydropyrazolo[5,1-c]-
[1,2,4]triazin-8-yl)-benzylidene]hydrazine (8b).
Compound 3g was obtained in 71% yield, mp 200-02 °C; H
nmr (DMSO-d ): δ 1.3 (t, 3H, CH CH ), 2.3 (s, 3H, CH ), 2.4
6
3
2
3
13
(s, 3H, CH ),4.3 (9, 2H, OCH CH ),13.4 (s,1H, NH); C nmr
3
2
3
Compound 8b was obtained in 36% yield (method A), 52%
(DMSO-d ): δ 14.0 (CH -CH ), 14.4 (CH of C-7), 16.3 (CH of
6
3
2
3
3
1
(method B); mp >300 °C, H nmr (DMSO-d ): δ 2.1 (s, 3H,
6
C-3), 60.6 (OCH ), 93.6 (C-8), 141.4 (C-3), 145.9 (C-4 ), 155.6
2
7-CH ), 2.4 (s, 3H, 3-CH ), 7.2-7.7 (m, 5H, Ar), 8.98 (br s, 1H,
3
3
(C-9), 162.5 (COO of C-8); ir (potassium bromide): 3252, 1712,
13
NH); C nmr (DMSO-d ): δ 14.1 (CH of C-7), 17.0 (CH of
-1
6
3
3
1673, 1624 cm ; hrms Calcd. for C
Found: 236.0325.
H N O : 236.0909.
10 12 4 3
C-3), 92.2 (C-8), 125.8, 127.8, 129.1, 133.9 (Ar), 137.5 (C-7),
139.3 (C-3), 142.6 (C=N of C-8) 150.5 (C-4), 154.1 (C-9) ppm; ir
Hydrazinium 8-Acyl-3,7-dimethyl-6H-pyrazolo[5,1-c][1,2,4]-
triazin-on-6-ides (7a,b).
-1
(potassium bromide): 3426, 1694, 1624, 1546 cm .
Anal. Calcd. for C
H N O : C, 63.15; H, 4.54; N, 26.30.
28 24 10 2
Found: C, 62.89; H, 4.38; N, 26.21.
Compounds 3a,b (0.01mol) and hydrazine hydrate 80% (0.45 ml.,
0.015 mol) in 2-propanol (50 ml) were stirred at room temperature
for 6 hours at which time the starting material has been consumed
(tlc). The solid product that formed was separated out and recrystal-
lized from ethanol to give 7a,b.
Bis(3,7-dimethyl-4-oxo-4,6-dihydropyrazolo[5,1-c][1,2,4]-
triazin-8-yl)-disulfide (9).
Compound 3b (1.34 g., 0.005 mol) contaminated with
elemental sulfur (as a crude material) and phenyl hydrazine
(0.55 ml, 0.005 mol) in 2-propanol (25 ml) were refluxed for
2 hours until the starting material was consumed (tlc). The solid
product that formed was filtered off and recrystallized from
Hydrazinium 8-Acetyl-3,7-dimethyl-6H-pyrazolo[5,1-c]-
[1,2,4]triazin-4-on-6-ide (7a).
1
Comound 7a was obtained in 85% yield, mp 150-152 °C, H
1
nmr (DMSO-d ): δ 2.4 (s, 3H, 7-CH ), 2.5 (s, 3H, 3-CH ), 2.6
methanol to give 1.1 g of 9. Yield 56%, mp >300 °C; H nmr
6
3
3
13
(s, 3H, COCH ), 6.9 ( br s, 5H, hydrazinum-H's); C nmr
(DMSO-d ): δ 2.1 (s, 3H, 7-CH ), 2.3 (s, 3H, 3-CH ), 13.8
3
6
3
3

715
May-Jun 2001
Synthesis of Some Novel 3,7-Dimethyl-4H-pyrazolo[5,1-c][1,2,4]triazin-4-ones
13
Anal. Calcd. for C H N O: C, 67.03; H, 5.06; N, 23.45.
20 18 6
Found: C, 66.96; H, 5.02; N, 23.23.
(s, 1H, NH); C nmr (DMSO-d ): δ 11.5 (CH of C-7), 16.1
6
3
(CH of C-3), 90.3 (C-8), 138.9 (C-7), 145.6 (C-3), 148.8 (C-4),
156.9 (C-9); ir (potassium bromide): 3431, 1685, 1599 cm .
Anal. Calcd. for C
Found: C, 42.88; H, 3.51; N, 28.56.
3
-1
8-(1-Hydroxyiminoalkyl)-3,7-dimethyl-6H-pyrazolo[5,1-c]-
[1,2,4]triazin-4-ones (12a,b).
H N O S : C, 43.07; H, 3.61; N, 28.70.
14 14 8 2 2
Compound 3a,b (0.01 mol) and hydroxylamine hydrochloride
(0.94 g. 0015 mol) in 2-propanol (60 ml) in the presence of
triethyl amine (0.2 ml) were heated gradually to 90 °C followed
by refluxing for 3 hours until the starting material was consumed
(tlc). The solid product that formed was separated out and
recrystallized from methanol.
For more confirmation of the above reaction, the pure
compound 3b (1.34 g, 0.005 mol), elemental sulfur (0.32 g,
0.01 mol), and phenylhydrazine (0.55 ml, 0.005 mol) in
2-propanol (25 ml) were refluxed for 2 hours until the starting
material was consumed (tlc). The solid product that formed was
filtered off and recrystallized from methanol to give 1.5 g of 9
(Yield 77%, mp >300 °C).
8-(1-Hydroxyiminoethyl)-3,7-dimethyl-6H-pyrazolo[5,1-c]-
[1,2,4]triazin-4-one (12a).
3,7-Dimethyl-8-[1-(methylhydrazono)-alkyl and/or aryl]-6H-
pyrazolo[5,1-c] [1,2,4]triazin-4-ones (11a-d).
1
Compound 12a was obtained in 94% yield, mp 225-227 °C, H
Compound 3a,b (0.01mol) and methyl (and/or phenyl)
hydrazine (11a,b) (0.01 mol) in 2-propanol (50 ml) in the
presence of acetic acid (1 ml) were ref luxed for 1 hour until the
starting material was consumed (tlc). The solid product that
nmr (DMSO-d ): δ 2.0 (s, 3H, 7-CH ), 2.2 (s, 3H, CH -C=NOH),
6
3
3
2.3 (s, 3H, 3-CH ), 10.9 (s, 1H, OH) ppm; ir (potassium
3
-1
bromide): 3227, 3042, 1691, 1631, 1600 cm .
Anal. Calcd. for C H N O : C, 48.87; H, 5.01; N, 31.66.
9
11 5 2
formed was separated out and recrystallized from DMF/H O to
Found: C, 48.76; H, 4.98; N, 31.25.
2
give 11a-d.
8-(1-Hydroxyimino-1-phenylmethyl)-3,7-dimethyl-6H-pyra-
zolo[5,1-c][1,2,4]triazin-4-one (12b).
3,7-Dimethyl-8-[1-(methylhydrazono)-ethyl]-6H-pyrazolo-
[5,1-c][1,2,4]triazin-4-one (11a).
Compound 12b was obtained in 63% yield, mp 2258-260 °C,
Compound 11a was obtained in 65% yield, mp >300 °C; ir
(potassium bromide): 3402, 3232, 1702, 1583, 1540 cm ; hrms
Calcd. for C
1
H nmr (DMSO-d ): δ 2.0 (s, 3H, CH ), 2.3 (s, 3H, triazine-CH ),
6
3
3
-1
13
7.4-7.5 (m. 5H, Ar), 11.8 (s, 1H, OH); C nmr (DMSO-d ): δ
14.6 (CH of C-7), 17.0 (CH of C-3), 93.7 (C-8), 127.7, 129.4,
6
H N O: 234.1229. Found: 234.1955.
10 14 6
3
3
129.9, 136.5 (C
(C-3), 150.1 (C-4), 153.7 (C-9) ppm; ir (potassium romide): 3294,
3034, 1713, 1636, 1558 cm .
Anal. Calcd. for C
), 137.8 (C-7), 142.6 (Ph-C=NOH), 147.4
arom
3,7-Dimethyl-8-[1-(phenylhydrazono)-ethyl]-6H-pyrazolo-
[5,1-c][1,2,4]triazin-4-one (11b).
-1
1
Compound 11b was obtained in 72% yield, mp 280-282 °C, H
H N O : C, 59.36; H, 4.63; N, 24.72.
14 13 5 2
nmr (DMSO-d ): δ 2.3 (s, 3H, 7-CH ), 2.4 (s, 3H, 3-CH ), 2.5
6
3
3
Found: C, 59.11; H, 4.53; N, 24.33.
(s, 3H, CH ), 6.7-7.3 (m. 5H, Ar), 9.17 (s, 1H, hydrazono-NH),
3
13
8-(1-Benzoyloxyiminoalkyl)-3,7-dimethyl-6H-pyrazolo[5,1-c]-
[1,2,4]triazin-4-ones (13a,b).
13.0 (s, 1H, pyrazolo-NH); C nmr (DMSO-d ): δ 14.7 (CH of
C-7), 16.0 (CH of C-3), 16.1 (hydrazono-CH ), 101.5 (C-8),
6
3
3
3
113.9, 119.9, 130.1, 137.4, (C
(C=N-NH), 147.9 (C-3), 150.4 (C-4), 153.4 (C-9); ir (potassium
bromide): 3437, 3318, 1682, 1599, 1502 cm ; hrms Calcd. for
), 138.4 (C-7), 141.9
arom
A mixture of (12a,b) (0.005 mol) and benzoyl chloride (0.9 ml
0.0075 mol) was stirred in anhydrous pyridine (25 ml) at 0 °C for
6 hours until the starting material was consumed (tlc). The
reaction mixture was poured on ice cold water. The solid product
obtained was isolated by filtration, dried and stirred with carbon
tetrachloride (20 ml) at 30 °C to remove the residual benzoic
acid. The solid was again isolated by filtration and recrystallized
from methanol to give 13a,b.
-1
C
H N O: 296.1385. Found: 296.2814.
15 16 5
3,7-Dimethyl-8-[1-(methylhydrazono)-1-phenyl-methyl]-6H-
pyrazolo[5,1-c][1,2,4]triazin-4-one (11c).
1
Compound 11c was obtained in 74% yield, mp >300 °C, H
nmr (DMSO-d ): δ 2.1 (s, 3H, 7-CH ), 2.4 (s, 3H, 3-CH ), 3.0
6
3
3
(s, 3H, hydrazono-CH ) 7.3-7.5 (m. 5H, Ar), 10.0 (br s, 1H, NH);
8-(1-Benzoyloxyiminoethyl)-3,7-dimethyl-6H-pyrazolo[5,1-c]-
[1,2,4]triazin-4-one (13a).
3
13
C nmr (DMSO-d ): δ 14.1 (CH of C-7), 16.9 (CH of C-3),
38.2 (s, 3H, CH -NH), 92.8 (C-8), 125.7, 127.7, 129.1,131.2
6
3
3
3
1
Compound 13a was obtained in 72% yield, mp 176-178 °C, H
(C
), 137.5 (C-7), 139.0 (C=N-NH), 142.7 (C-3), 150.5 (C-4),
arom
nmr (DMSO-d ): δ 2.3 (s, 3H, 7-CH ), 2.6 (s, 6H, 7-CH and
6
3
3
154.1 (C-9) ppm; ir (potassium bromide): 3431, 3244, 1694,
CH -C=N-OCOPh), 7.6-8.13 (m. 5H, Ar), 13.0 (s, 1H, NH); ir
-1
3
1620 cm .
-1
(potassium bromide): 3461, 1713, 1609, 1543, 1498 cm .
Anal. Calcd. for C
H N O: C, 60.80; H, 5.44; N, 28.36.
15 16 6
Anal. Calcd. for C
H N O : C, 59.07; H, 4.65; N, 21.53.
16 15 5 3
Found: C, 60.54; H, 5.31; N, 28.06.
Found: C, 59.01; H, 4.62; N, 21.45.
3,7-Dimethyl-8-[1-phenyl-1-(phenylhydrazono)methyl]-6H-
pyrazolo[5,1-c][1,2,4]triazin-4-one (11d).
8-(1-Benzoyloxyimino-1-phenylmethyl)-3,7-dimethyl-6H-
pyrazolo[5,1-c][1,2,4]triazin-4-one (13b).
1
Compound 11d was obtained in 67% yield, mp 260-262°C, H
1
Compound 13b was obtained in 68% yield, mp 209-211°C, H
nmr (DMSO-d ): δ 2.1 (s, 3H, 7-CH ), 2.4 (s, 3H, 3-CH ), 6.8-7.6
6
3
3
nmr (DMSO-d ): δ 1.9 (s, 3H, 7-CH ), 2.4 (s, 6H, 3-CH ), 7.4-7.8
(m. 10 H, Ar), 9.4 (s, 1H, hydrazono-NH), 13.5 (br s, 1H, pyra-
6
3
3
(m. 10H, Ar), 13.6 (s, 1H, NH); ir (potassium bromide): 3129, 1743,
zolo-NH); (DMSO-d ): δ 11.6 (CH of C-7), 16.2 (CH of C-3),
6
3
3
-1
1624, 1590, 1533 cm . Ms, peak matching for C H N O : Calcd.,
90.3 (C-8), 138.9 (C-7), 145.6 (C-3), 148.8 (C-4), 156.9 (C-9); ir
10 12
4 3
-1
387.1331. Found, 387.2130.
(potassium bromide): 3248, 3140, 1693, 1609, 1549 cm .

716
Vol. 38
A. A. El-Barbary, M. A. El-Badawi and Y. M. Loksha
Acknowledgement.
[4] A. K. Mansour, S. B. Awad and S. Antown, Z. Naturforsch.,
B29, 792 (1974).
[5] W. M. Davidson and W. D. Boykin, J. Pharm. Sci., 65, 737
(1978).
The authors are thankful to the Danish International
Development Agency (DANIDA) for their support.
[6] P. W. Hielman, R. D. gielman, A. J. Scozzie, R. J. Wayner, M.
J. Gollo and S. Z. Ariyan, J. Pharm. Sci, 69, 282 (1980).
[7] M. J. Gollo, P. W. Iteillman, R. J. Wayner and E. G. Robert,
German Offen, 2, 84, 381; Chem. Abstr., 90, 121664m (1979).
[8] W. B. Lacefield, French Demande, 2, 243, 479; Chem. Abstr.,
89, 24372m (1979).
REFERENCES AND NOTES
[*] Author to whom corresponding should be addressed: Fax 20
40 3350804; e-mail: aaelbarbary@hotmail.com
[1] M. A. Sakaran, A. A. El-Barbary, and M. A. El-Madani, Delta
J. Sci., 22,30 (1998).
[2] A. A. El-Barbary, M. A. Sakaran and M. A. El-Madani, Polish
J. Chem., Accepted.
[9] L. C. March, G. S. Bajwa, J. Lee, K. Wasti and M. M. Joullie,
J. Med. Chem., 19, 845 (1976).
[10] M. Mizutani and Y. Sanemitsu, J. Heterocyclic Chem., 19,
1577 (1982).
[3] A. A. El-Barbary, F. I. Abdel-Hay and A. M. Zohdi, Synthetic
Comm., Submitted.