Cyclotransformation in the series of fused 5-nitropyridin-2(1H)-ones

Article abstract of DOI:10.1134/s1070428008020152

Reactions with excess hydrazine hydrate of 5-nitropyridin-2(1H)-ones fused with benzene, pyridine, and 1,2,3-triazole rings led to a cyclotransformation of the 5-nitro-2-oxopyridine fragment into the 6-methyl-3-oxopyridazine structure. This cyclotransformation is of general character; a probable mechanism of the process is suggested. Details of the assumed mechanism were experimentally confirmed on model compounds.

Full text of DOI:10.1134/s1070428008020152

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 2, pp. 274−281. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © N.N. Smolyar, Yu.M. Yutilov, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 2, pp. 280−286.
Cyclotransformation in the Series
of Fused 5-Nitropyridin-2(1H)-ones
N. N. Smolyar and Yu. M. Yutilov†
Litvinenko Institute of Physical Organic and Coal Chemistry, National Academy of Sciences of Ukraine,
Donetsk, 83114 Ukraine
e-mail: smolyar@skif.net
Received April 18, 2007
Abstract—Reactions with excess hydrazine hydrate of 5-nitropyridin-2(1H)-ones fused with benzene, pyridine,
and 1,2,3-triazole rings led to a cyclotransformation of the 5-nitro-2-oxopyridine fragment into the 6-methyl-3-
oxopyridazine structure. This cyclotransformation is of general character; a probable mechanism of the process is
suggested. Details of the assumed mechanism were experimentally confirmed on model compounds.
DOI: 10.1134/S1070428008020152
In the course of the study on the chemical properties
of substituted 7-nitro-1,5-dihydro-4H-imidazo[4,5-c]-
pyridin-4-ones we found that these compounds treated
with excess hydrazine hydrate underwent a conversion
into derivatives of 7-methyl-1,5-dihydro-4H-imidazo-
[4,5-d]pyridazin-4-one [1].
[2] was proved by the lack of melting point depression
in a mixed sample of compound III and 4-methyl-
phthalazin-1(2H)-one independently synthesized [3]
from 2-acetylbenzoic acid (IV), and by the coincidence
of their IR and 1H NMR spectra (Scheme 1).
Similarly to the above heterocycles I and II 6-methyl-
8-nitro-1,6-naphthyridin-5(6H)-one (V) also underwent
cyclotransformation giving 8-methylpyrido[2,3-d]pyr-
idazin-5(6H)-one (VI), and the accompanying evolution
of gaseous ammonia and methylamine was proved by
mass spectrometry [4]. The composition and structure
of base VI obtained was proved by its independent
synthesis from 2-acetylnicotinic acid (VII) by procedure
[5], by the data of elemental analysis, IR, and 1H NMR
spectra (Scheme 2).
Therefore an interest was generated whether a similar
transformation would occur also in the series of other
fused heterocycles containing 5-nitro-2-oxopyridine
fragment.
Actually, the heating of 4-nitroisoquinolin-1(2H)-one
(I) and its N-methyl derivative II with hydrazine hydrate
led to the formation of the same compound that based
on the elemental analysis, IR and 1H NMR spectra could
be regarded as 4-methylphthalazin-1(2H)-one (III). Its
1H NMR spectrum contains a singlet from the methyl
group at 2.60 and a multiplet from the protons of the
benzene ring in the region 7.92–8.23 ppm [2]. In the
course of the cyclotransformation of nitroisoquinolines
I and II a liberation of gaseous ammonia and methyl-
amine occurred whose formation was proved by mass
spectrometry. The validity of the assumed structure III
Inasmuch as the 1,2,3-triazolo[4,5-c]pyridine was one
of the closest 2-azaanalogs of imidazo[4,5-c]-pyridine
it was rational to subject to the cyclotransformation 7-
nitro-1,5-dihydro-4H-1,2,3-triazolo-[4,5-c]pyridin-4-one
(VIII) and its N1-alkyl derivatives IX–XIII.
Scheme 1.
NO2
CH3
COCH3
N2H4
N2H4
N
_RNH2
N
NH
R
COOH
O
O
I, II
III
IV
† Deceased.
274

CYCLOTRANSFORMATION IN THE SERIES OF FUSED 5-NITROPYRIDIN-2(1H)-ONES
275
Scheme 2.
NO2
CH3
N
N
N
COCH3
COOH
N2H4
N2H4
N
N
NH
CH3
O
O
V
VI
VII
In the same way as nitro compound VIII its N1-alkyl
It turned out that a short heating of nitro compound
derivatives IX–XIII treated with hydrazine hydrate also
suffered the cyclotransformation into 7-methyl-N1-alkyl-
1,5-dihydro-4H-1,2,3-triazolo-[4,5-d]pyridazin-4-ones
XVI–XX.
VIII with hydrazine hydrate provided compound XIV
in nearly quantitative yield. The H NMR spectrum of
1
the compound contained an only singlet signal at 2.90
ppm characteristic of the protons of the methyl group.
These results indicate that the cyclotransformation occurs
also in this case resulting in 7-methyl-1,5-dihydro-4H-
1,2,3-triazolo[4,5-d]pyridazin-4-one (XIV). The identity
of compound XIV obtained to an authentic sample
synthesized from 4,5-diamino-6-methylpyridazin-3(2H)-
one (XV) by procedure [6] confirmed the validity of the
above conclusion (Scheme 3).
In the IR spectra of obtained compounds XVI–XX
characteristic absorption bands νC=O were observed in
1
the region 1685–1700 cm–1. In the H NMR spectra
of compounds XVI–XX signals were present from the
C-methyl groups in the pyridazine ring with the chemical
shifts 2.74–2.85 ppm, and also the signals of the N1-alkyl
groups.
Scheme 3.
We showed by examples of fused heterocycles I, II,
V, and VIII–XIII containing a fragment of 5-nitro-
pyridin-2(1H)-one that the described type of cyclotrans-
formation into pyridazinone derivatives was of a general
character, and we suggested a mechanism of the process.
NO2
CH3
H
N
H
N
N2H4
_NH3
N
N
N
HN
HN
N
N
The details of the assumed mechanism were
confirmed experimentally on model compounds. The fact
that the cyclotransformation of fused nitropyridones I,
II, V, and VIII–XIII cannot start by reduction of the
nitro group is proved by the lack of reaction between the
hydrazine hydrate and 4-aminoisoquinolin-1(2H)-one
(XXVI) or 7-amino-1,5-dihydro-4H-1,2,3-triazolo-
[4,5-c]pyridin-4-one (XXVII).
O
O
XIV
VIII
CH3
NH2
NH2
HNO2
N
HN
The opportunity of the cyclotransformation originates
from the electron-withdrawing effect of the nitro group
on the carbonyl carbon of the pyridine fragment in the
initial compounds thus permitting the nucleophilic attack
of the hydrazine on this carbon atom resulting in the
opening of the pyridine ring. The necessity of the nitro
group presence in structures I, II, V, and VIII–XIII is
proved by the lack of cyclotransformation in reaction
with hydrazine hydrate of 1-methyl-1,5-dihydro-4H-
1,2,3-triazolo[4,5-c]pyridin-4-one (XXVIII) or its
7-bromo derivative XXIX (Scheme 5). The opening of
the pyridine ring in compounds I, II, V, and VIII–XIII
led to the formation of structure XXI containing a carbo-
hydrazide group and aminoethylene moiety; the
O
XV
Scheme 4.
NO2
CH3
R
N
R
N
N
N
N
N2H4
N
N
HN
HN
O
O
XVI_XX
IX_XIII
R = Me (IX, XVI), Et (X, XVII), Bu (XI, XVIII),
(CH2)3NMe2 (XII, XIX), cyclo-C6H11 (XIII, XX).
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SMOLYAR, YUTILOV
276
Scheme 5.
NO2
NO2
NO2
N
N2H4
_RNH2
N2H4
H2N
R
NH
N
N
N
R
H2N
H2N
O
H
O
H
O
I, II, V, VIII_XIII
XXI
XXII
NH2
CH3
H
CH3
H3C
HN
HN
N
N2H4
_NH3
_H2
HN
N
H2N
O
H
O
O
XXIV
XXV
XXIII
confirmed that among the gaseous products of hydrazine
reaction with 1-methyl-7-nitro(15N)-1,5-dihydro-4H-
1,2,3-triazolo-[4,5-c]pyridin-4-one (XXXI) ammonia
15NH3 was present. This result demonstrates that in
formation of the pyridazine ring both its nitrogens
originate from the hydrazine. The actual formation and
conversion of structures of the type XXIII, XXIV into
the final methylpyridazinone XXV was supported by
heating the hydrazine hydrate with 2-α-aminoethyl-
benzoic acid (XXXII) to obtain in nearly quantitative
yield phthalazone III [7] through the stages of formation
of hydrazide XXXIII and dihydrophthalazone XXXIV
(Scheme 6).
transformation of the latter govern further process
according to the assumed scheme. We showed first of
all that the methyl group in structure XXIII formed from
hydrazone XXII. To this end initial compound IX was
subjected to the cyclotransformation in excess of
hydrazine-D4 to obtain 7-dideuteromethyl-1-methyl-1,5-
dihydro-4H-1,2,3-triazolo[4,5-d]pyridazin-4-one (XXX).
1
In the H NMR spectrum of compound XXX obtained
the area under the peak of the C-methyl group is equal to
1/3 of the area under the signal of the N1-methyl group
proving the formation of the dideuteromethyl group
CHD2. The formation of hydrazone XXII should involve
evolution of, for instance, methylamine at treatment with
hydrazine of nitro compounds II and V, or ammonia in
reaction of compounds I and VIII–XIII. Thus the NH–
R group at the nitroethylene fragment (structure XXI)
gets replaced by hydrazino group (structure XXII). It
was shown that the amino group of structure XXIII was
liberated as NH3 involving the terminal hydrogen of the
hydrazide group, and this led to the formation of bicycle
XXIV. The data of mass-spectroscopic measurements
In this connection it was presumable that 2-α-
aminoethylbenzoic acid hydrazide XXXIII is the
reduction product of α-nitroethylbenzoic acid hydrazide
XXXV formed in reaction with hydrazine of 4-nitro-
quinolin-1(2H)-one (I). It is quite possible that these
transformations occurring in the side chain of the α-nitro-
ethyl fragment are related to the reduction by the
hydrazine of the nitro group to nitroso group (XXXVI),
Scheme 6.
CH3
NH2
CH3
CH3
NH2
CONHNH2
XXXIII
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 2 2008
CH3
NH
NH
H
N2H4
N2H4
N
N2H4
NH
COOH
XXXII
O
O
XXXIV
III

CYCLOTRANSFORMATION IN THE SERIES OF FUSED 5-NITROPYRIDIN-2(1H)-ONES
277
Scheme 7.
O
NO2
CH3
N
NOH
CH3
NH2
CH3
N2H4
N2H4
N2H4
CH3
CONHNH2
XXXV
CONHNH2
XXXVI
CONHNH2
XXXVII
CONHNH2
XXXIII
and the isomerization of the latter may result in 2-acetyl-
benzoic acid oxime (XXXVII) followed by its further
reduction into amino derivative XXXIII.
ethanol, detection in iodine vapor and under UV
irradiation). Synthesis of compounds I and II is described
in [9], compound XI was prepared by procedure [10].
To prove this assumption we brought into the reaction
with hydrazine a model compound, 2-acetylbenzoic acid
oxime (XXXVII). It turned out that in conditions ana-
logous to used with amino compound XXXII oxime
XXXVII reacted with hydrazine giving in nearly
quantitative yield also 4-methylphthalazin-1(2H)-one
(III).
4-Methylphthalazin-1(2H)-one (III). a. A solution
of 0.6 g (3.15 mmol) of 4-nitroisoquinolin-1(2H)-one (I)
in 3.0 ml (64.2 mmol) of hydrazine hydrate was heated
for 3–5 h at 130–140°C. On dissolution of compound I
in the hydrazine hydrate the solution got dark red. In the
course of the reaction ammonia liberated that was passed
through an ethanol solution of hydrogen chloride and
then identified as ammonium chloride (mp 334–336°C).
To the end of the reaction the solution decolorized. Then
the hydrazine hydrate was distilled off in a vacuum of
a water-jet pump. To the residue 5.0 ml of 2-propanol
was added, and the reaction product was filtered off.Yield
0.4 g (80%), mp 220–222°C (ethanol) (221–222°C [3]).
IR spectrum, ν, cm–1: 1670 (C=O). 1H NMR spectrum
(CF3COOH), δ, ppm: 7.92–8.23 m (4H, C6H4). Found,
%: C 67.36; H 4.96; N 17.37. C9H8N2O. Calculated, %:
C 67.49; H 5.03; N 17.49.
The described cyclotransformation of fused 5-nitro-
pyridin-2(1H)-ones I, II, V, and VIII–XIII results from
a series of successive transformations whose specificity
and consistency is evidenced by the high purity and yields
(up to 99%) of fused pyridazinones. Asignificant feature
of this reaction consists in the driving from the pyridine
ring of the initial nitro compound in the course of
pyridazine ring formation of one methine group (6-CH)
and its reduction to methyl. A necessary condition for
the cyclotransformation reaction to occur is the presence
of an α-carbonyl group and a nitro group in the position
5 of the pyridine ring fused to an aromatic ring [8].
b. The synthesis was carried out similarly from 1.3 g
(6.4 mmol) of 2-methyl-4-nitroisoquinolin-1(2H)-one
(II) and 6.5 ml (130 mmol) of hydrazine hydrate. In the
course of the reaction ammonia and methylamine
liberated that were passed through an ethanol solution
of hydrogen chloride and then identified as the cor-
responding hydrochlorides. Along with ammonium
chloride {mp 332°C (336°C [11])} equimolar amount of
methylamine hydrochloride was isolated with mp 224°C
(226°C [11]). Hydrochlorides of ammonia and
methylamine were separated due to their different
solubility in anhydrous ethanol [12]. Methylamine was
identified in the gas phase by mass spectrometry by its
molecular ion peak (M+ 31). Yield 0.61 g (60%), mp 219–
221°C (ethanol) (221–222°C [3]). IR spectrum, ν, cm–1:
EXPERIMENTAL
1H NMR spectra were registered on a spectrometer
Tesla BS-467 at operating frequency 80 MHz from
solution in CF3COOH, and also on a spectrometer Varian
Gemini-200 at operating frequency 200 MHz from
solutions in CD3OD, DMSO-d6, and DMF-d7, internal
reference HMDS.
IR spectra of compounds synthesized were recorded
on spectrophotometers UR-20 and Specord 75IR from
samples pelletized with KBr or in mulls with mineral
oil.
1
1670 (C=O). H NMR spectrum (CF3COOH), δ, ppm:
Molecular mass of compounds was measured by mass
spectrometry on Varian MAT-112 instrument with direct
admission of a sample into the ion source at the energy
of ionizing electrons 70 eV.
2.60 s (3H, 4-CH3), 7.92–8.23 m (4H, C6H4). Found, %:
C 67.33; H 4.97; N 17.35. C9H8N2O. Calculated, %:
C 67.49; H 5.03; N 17.49.
c. To a solution of 1.64 g (10.0 mmol) of o-acetyl-
benzoic acid (IV) in 10.0 ml of 1-PrOH was added
The purity and homogeneity of compounds obtained
was checked by TLC on Silufol UV-254 plates (eluent
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 2 2008

SMOLYAR, YUTILOV
278
0.6 ml (12.8 mmol) of hydrazine hydrate, and the mixture
was heated on a boiling water bath for 2 h. On cooling
the separated white precipitate was filtered off and dried.
Yield 1.3 g (87%), mp 220–222°C (ethanol). IR spectrum,
ν, cm–1: 1670 (C=O). 1H NMR spectrum (CF3COOH),
δ, ppm: 2.60 s (3H, 4-CH3), 7.91–8.23 m (4H, C6H4).
d. A mixture of 0.8 g (5 mmol) of 2-α-aminoethyl-
benzoic acid (XXXII) prepared by procedure [13], and
5 ml (100 mmol) of hydrazine hydrate was heated at 130–
140°C for 4–5 h, then excess hydrazine hydrate was
distilled off in a vacuum to dryness, the residue was
ground with 3 ml of 2-propanol, and the precipitate was
filtered off. Yield 0.78 g (quantitative), mp 222–224°C.
IR spectrum, ν, cm–1: 1670 (C=O). 1H NMR spectrum
(CF3COOH), δ, ppm: 2.60 s (3H, 4-CH3), 7.90–8.21 m
(4H, C6H4). Found, %: C 67.35; H 4.99; N 17.38.
C9H8N2O. Calculated, %: C 67.49; H 5.03; N 17.49.
an alcoholic solution of picric acid and then identified
as picrate {mp 214–216°C (215°C [16])}, and also by
its molecular ion peak in the mass spectrum of the gas
phase (M+ 31). Yield 0.74 g (94%), mp 249–250°C
(ethanol) (249–250°C [5]). IR spectrum, ν, cm–1: 1700
(C=O). 1H NMR spectrum (CF3COOH), δ, ppm: 2.83 s
(3H, 8-CH3), 8.33–9.65 m (3H, H2, H3, H4). Found, %:
C 59.44; H 4.30; N 25.92. C8H7N3O. Calculated, %:
C 59.62; H 4.38; N 26.07.
7-Nitro-1,5-dihydro-4H-1,2,3-triazolo[4,5-c]-
pyridin-4-one (VIII). In 35 ml of concn. H2SO4 was
dissolved 4.0 g (30.5 mmol) of 1,5-dihydro-4H-1,2,3-
triazolo[4,5-c]pyridin-4-one [17] at stirring and cooling,
then at 0–5°C was added dropwise 6 ml (144.7 mmol) of
fuming nitric acid (d 1.5 g/cm3), and the reaction mixture
was maintained at this temperature for 0.5–1.0 h. The
reaction mixture was gradually warmed to room
temperature, heated for 2–3 h at 60°C, cooled, poured
on ice, and neutralized with ammonium hydrogen
carbonate. The separated light-yellow precipitate was
filtered off, washed with ethanol, with ether, and
crystallized from water. Yield 3.0 g (54%), mp > 280°C
e. A mixture of 0.9 g (5 mmol) of 2-acetylbenzoic
acid oxime (XXXVII) [14] and 5 ml (100 mmol) of
hydrazine hydrate was heated at 135–140°C for 3–4 h,
then excess hydrazine hydrate was distilled off in
a vacuum to dryness, the residue was ground with 3 ml
of 2-propanol, and the precipitate was filtered off. Yield
0.8 g (quantitative), mp 222–224°C (ethanol). IR
spectrum, ν, cm–1: 1670 (C=O). 1H (CF3COOH), δ, ppm:
2.59 s (3H, 4-CH3), 7.93–8.22 m (4H, C6H4). Found, %:
C 67.39; H 4.98; N 17.37. C9H8N2O. Calculated, %:
C 67.49; H 5.03; N 17.49.
1
(decomp.). H NMR spectrum (DMSO-d6), δ, ppm:
8.43 s (1H, H6). Found, %: C 33.25; H 1.74; N 38.70.
C5H3N5O3. Calculated, %: C 33.16; H 1.67; N 38.67.
1-Methyl-7-nitro-1,5-dihydro-4H-1,2,3-triazolo-
[4,5-c]pyridin-4-one (IX). In 20 ml of concn. H2SO4
was dissolved 2.4 g (16.0 mmol) of 1-methyl-1,5-
dihydro-4H-1,2,3-triazolo[4,5-c]pyridin-4-one at stirring
and cooling, then at 5–10°C was added by portions 2.4 g
(22.0 mmol) of potassium nitrate, and the mixture was
kept at this temperature for 0.5 h. The reaction mixture
was gradually warmed to room temperature, heated for
2 h at 60°C, cooled, poured on ice, and neutralized with
aqueous ammonia. The separated precipitate was filtered
off, washed with ice water, and dried. Yield 2.0 g (75%),
mp 278–281°C. 1H NMR spectrum (CF3COOH), δ, ppm:
4.60 s (3H, N1CH3), 8.83 s (1H, H6). Found, %: C 36.85;
H 2.61; N 35.94. C6H5N5O3. Calculated, %: C 36.93;
H 2.58; N 35.89.
6-Methyl-8-nitro-1,6-naphthyridin-5(6H)-one (V).
To a solution of 0.8 g (5.0 mmol) of 6-methyl-5,6-
dihydro-1,6-naphthyridin-5-one [15] in 12 ml of concn.
H2SO4 was added within 0.5 h at 0–5°C a solution of
2.4 ml (57.4 mmol) of fuming nitric acid (d 1.5 g/cm3) in
4 ml of concn. H2SO4. The reaction mixture was gradual-
ly warmed to 10°C and kept at that temperature for
0.5 h. Then the mixture was warmed to room temperature
and in 1 h it was poured into ice water and neutralized
with sodium carbonate. The solution was evaporated to
dryness, and the reaction product was extracted from the
residue into ethanol. Yield 0.88 g (86%), mp 200–201°C
(benzene–heptane, 2:1). 1H NMR spectrum (CF3COOH),
δ, ppm: 3.81 s (3H, N6CH3), 8.22 s (1H, H7), 9.20–9.63 m
(3H, H2–4). Found, %: C 52.73; H 3.42; N 20.41.
C9H7N3O3. Calculated, %: C 52.69; H 3.44; N 20.48.
1-Methyl-1,5-dihydro-4H-1,2,3-triazolo[4,5-c]-
pyridin-4-one was obtained by procedure [17] from 4-
chloro-1-methyl-1,5-dihydro-4H-1,2,3-triazolo[4,5-
C]pyridine [18]. Yield 96%, mp 326–329°C (ethanol).
1
IR spectrum, ν, cm–1: 1670–1690 (C=O). H NMR
8-Methylpyrido[2,3-d]pyridazin-5(6H)-one (VI)
was obtained from 1.2 g (5.84 mmol) of reagent V and
6.0 ml (128.4 mmol) of hydrazine hydrate in the same
way as compound III (method b). In the course of the
reaction evolved methylamine, that was passed through
spectrum (CF3COOH), δ, ppm: 4.52 s (3H, N1CH3),
7.20 d (1H, H7, J 7.0 Hz), 7.82 d (1H, H6, J 7.0 Hz).
Found, %: C 47.79; H 3.94; N 37.14. C6H6N4O.
Calculated, %: C 48.00; H 4.00; N 37.3.
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CYCLOTRANSFORMATION IN THE SERIES OF FUSED 5-NITROPYRIDIN-2(1H)-ONES
279
1
1-Ethyl-7-nitro-1,5-dihydro-4H-1,2,3-triazolo-
[4,5-c]pyridin-4-one (X) was obtained similarly to com-
pound IX from 1.08 g (6.6 mmol) 1-ethyl-1,5-dihydro-4H-
1,2,3-triazolo[4,5-c]pyridin-4-one and 1.6 ml (38 mmol)
of concn. HNO3 (d 1.5 g/cm3). Yield 1.0 g (73%), mp 212–
214°C. 1H NMR spectrum (CF3COOH), δ, ppm: 1.21 t
(3H, CH2CH3), 4.71 q (2H, CH2CH3), 8.45 s (1H, H6).
Found, %: C 40.05; H 3.30; N 33.32. C7H7N5O3.
Calculated, %: C 40.20; H 3.37; N 33.48.
(ethanol). H NMR spectrum (CF3COOH), δ, ppm:
2.73 t (2H, γ-CH2), 3.08 s [6H, N(CH3)2], 3.56 t (2H,
β-CH2), 4.90 t (2H, N1CH2), 7.18 d (1H, H7, J 7.0 Hz),
7.78 d (1H, H6, J 7.0 Hz). Found, %: C 46.41; H 6.20;
N 26.98. C10H15N5·HCl. Calculated, %: C 46.60; H 6.26;
N 27.17.
7-Nitro-1-cyclohexyl-1,5-dihydro-4H-1,2,3-tri-
azolo[4,5-c]pyridin-4-one (XIII) was obtained similarly
to compound XI from 0.45 g (2.1 mmol) of 1-cyclohexyl-
1,5-dihydro-4H-1,2,3-triazolo[4,5-c]-pyridin-4-one and
1.0 ml (24 mmol) of concn. HNO3 (d 1.5 g/cm3). Yield
1-Ethyl-1,5-dihydro-4H-1,2,3-triazolo[4,5-c]-
pyridin-4-one was obtained by procedure [17] from
4-chloro-1-ethyl-1,5-dihydro-4H-1,2,3-triazolo[4,5-c]-
pyridine [18]. Yield 93%, mp 220–222°C. IR spectrum,
ν, cm–1:1680–1690(C=O). 1HNMRspectrum (CF3COOH),
δ, ppm: 1.31 t (3H, CH2CH3), 4.43 q (2H, CH2CH3),
6.70 d (1H, H7, J 7.0 Hz), 7.40 d (1H, H6, J 7.0 Hz).
Found, %: C 51.07; H 4.83; N 34.15. C7H8N4O.
Calculated, %: C 51.21; H 4.91; N 34.27.
1
0.52 g (98%), mp 228–231°C. H NMR spectrum
(DMSO-d6), δ, ppm: 1.27–2.25 m (10H, 5-CH2), 4.93–
5.15 m (1H, CH), 8.64 (1H, H6). Found, %: C 50.02;
H 4.94; N 26.46. C11H13N5O3. Calculated, %: C 50.19;
H 4.98; N 26.60.
1-Cyclohexyl-1,5-dihydro-4H-1,2,3-triazolo-
[4,5-c]pyridin-4-one was obtained by procedure [17]
from 4-chloro-1-cyclohexyl-1,5-dihydro-4H-1,2,3-tri-
azolo[4,5-c]pyridine [18]. Yield 90%, mp 273–275°C.
1H NMR spectrum (DMSO-d6), δ, ppm: 1.33–2.08 m
(10H, 5-CH2), 4.62–4.78 m (1H, CH), 6.82 d (1H, H7,
J 6.0 Hz), 7.37 d (1H, H6, J 6.0 Hz). Found, %: C 60.41;
H 6.39; N 25.52. C11H14N4O. Calculated, %: C 60.53;
H 6.46; N 25.67.
1-Butyl-7-nitro-1,5-dihydro-4H-1,2,3-triazolo-
[4,5-c]pyridin-4-one (XI).To a solution of 0.8 g (4.2 mmol)
of 1-butyl-1,5-dihydro-4H-1,2,3-triazolo-[4,5-c]pyridin-
4-one [10] in 8.0 ml of concn. H2SO4 was added by
portions at 0°C a solution of 2.0 ml (48.0 mmol) of concn.
HNO3 (d 1.5 g/cm3) in 2 ml of concn. H2SO4. After 0.5 h
the mixture was warmed to 10°C and was kept at this
temperature for 15 min. Then the reaction mixture was
poured on 40 g of crushed ice, the separated precipitate
was filtered off, washed with ice water, and dried. Yield
7-Methyl-1,5-dihydro-4H-1,2,3-triazolo[4,5-d]-
pyridazin-4-one (XIV). A mixture of 0.8 g (4.4 mmol)
of reagent VIII and 4.5 ml (90 mmol)of hydrazine
hydrate was heated for 3–5 h at 135–140°C. In the course
of the reaction ammonia liberated. On completion of the
reaction excess hydrazine hydrate was distilled off in
a vacuum till dryness, the residue was ground with 3 ml
of 2-propanol, and the precipitate was filtered off. Yield
0.57 g (86%), mp 283–285°C (ethanol) [6]. IR spectrum,
ν, cm–1: 1680 (C=O). 1H NMR spectrum (DMSO-d6), δ,
ppm: 2.90 s (3H, 7-CH3). Found, %: C 39.65; H 3.36;
N 46.42. C5H5N5O. Calculated, %: C 39.74; H 3.33;
N 46.34.
1
1.0 g (99%), mp 198–200°C. H NMR spectrum
(CF3COOH), δ, ppm: 1.00 s (3H, δ-CH3), 1.42 q (2H,
γ-CH2), 1.88 q (2H, β-CH2), 5.10 t (2H, N1CH2), 8.88 s
(1H, H6). Found, %: C 45.39; H 4.61; N 29.38.
C9H11N5O3. Calculated, %: C 45.57; H 4.67; N 29.52.
7-Nitro-1-(γ-N,N-dimethylaminopropyl)-1,5-di-
hydro-4H-1,2,3-triazolo[4,5-c]pyridin-4-one (XII) was
obtained similarly to compound XI from 1.5 g (5.8 mmol)
of 1-(γ-N,N-dimethylaminopropyl)-1,5-dihydro-4H-
1,2,3-triazolo[4,5-c]pyridin-4-one hydrochloride and
1.4 ml (33.8 mmol) of concn. HNO3 (d 1.5 g/cm3). Yield
0.8 g (52%), mp 99–101°C (2-propanol). 1H NMR spec-
trum (CF3COOH), δ, ppm: 2.73 t (2H, γ-CH2), 3.10 d
[6H, N(CH3)2], 3.55 q (2H, β-CH2), 5.22 t (2H, N1CH2),
8.93 s (1H, H6). Found, %: C 45.00; H 5.25; N 31.40.
C10H14N6O3. Calculated, %: C 45.11; H 5.30; N 31.56.
1,7-Dimethyl-1,5-dihydro-4H-1,2,3-triazolo-
[4,5-d]pyridazin-4-one (XVI). a. In 8.2 ml (175.5 mmol)
of hydrazine hydrate was dissolved 1.7 g (8.7 mmol) of
reagent IX, and the reaction was carried out similarly to
the preparation of compound XIV. Yield 1.3 g (90%),
mp 269–271°C (ethanol). IR spectrum, ν, cm–1: 1690
(C=O). 1H NMR spectrum (DMSO-d6), δ, ppm: 2.86 s
(3H, 7-CH3), 4.56 s (3H, N1CH3). Found, %: C 43.45;
H 4.22; N 42.28. C6H7N5O. Calculated, %: C 43.64;
H 4.27; N 42.40.
1-(γ-N,N-Dimethylaminopropyl)-1,5-dihydro-4H-
1,2,3-triazolo[4,5-c]pyridin-4-one hydrochloride was
obtained by procedure [17] from 4-chloro-1-(γ-N,N-di-
methylaminopropyl)-1,5-dihydro-4H-1,2,3-triazolo-
[4,5-c]pyridine [18]. Yield 93%, mp 246–249°C
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 2 2008

SMOLYAR, YUTILOV
280
b. In 7.2 ml (154.1 mmol) of hydrazine hydrate was
similarly to compound XVI. Yield 0.91 g (93%). The
reaction product was an oily base that was identified as
hydrochloride. The alcoholic solution of the base was
mixed with an ethanol solution of hydrogen chloride,
and the separated precipitate was filtered off. mp >250°C
(ethanol). IR spectrum, ν, cm–1: 1685 (C=O). 1H NMR
spectrum (DMF-d7), δ, ppm: 1.25 t (2H, γ-CH2), 2.83 s
(3H, 7-CH3), 3.10 s [6H, N(CH3)2], 3.55 t (2H, β-CH2),
3.95 t (2H, α-CH2). Found, %: C 43.89; H 6.22; N 30.64.
C10H16N6O·HCl. Calculated, %: C 44.04; H 6.28; N 30.81.
dissolved 1.5 g (7.6 mmol) of 1-methyl-7-nitro-(15N)-
1,5-dihydro-4H-1,2,3-triazolo[4,5-c]pyridin-4-one
(XXXI), and the reaction was carried out similarly to
the preparation of compound XIV. In the course of the
reaction gas evolution was observed. In order to identify
the gas it was passed with an argon flow through a trap
with concn. HCl. The hydrochloric solution was
evaporated to dryness, the residue was ground with
2-propanol, and the product was filtered off like colorless
crystals of mp 334°C. The mass of the product was
measured by mass spectrometry to find molecular ion
peaks M+ 53 and M+ 54 corresponding to ammonium
chloride containing isotopes (14N) and (15N). The other
part of the evolved gas under the pressure of the argon
flow was placed into the trap for gas sampling. When
the trap was completely filled with the gas it was
introduced through an adapter into the mass spectrometer
in order to measure the mass of the gaseous substance.
The masses of the corresponding molecular ions were
M+ 17 and M+ 18. Therefore the gas evolved was a
mixture of 14NH3 and 15NH3. Yield of compound XVI
1.2 g (95%), mp 268–270°C (ethanol). IR spectrum, ν,
7-Methyl-1-cyclohexyl-1,5-dihydro-4H-1,2,3-
triazolo[4,5-d]pyridazin-4-one (XX) was obtained from
1.0 g (4.0 mmol) of reagent XIII and 9 ml (180 mmol)
of hydrazine hydrate similarly to compound XVI. Yield
0.85 g (96%), mp 187–189°C (H2O). 1H NMR spectrum
(DMF-d7), δ, ppm: 1.28–2.38 m (10H, 5CH2), 2.74 s (3H,
7-CH3), 4.85–5.15 m (1H, CH). IR spectrum, ν, cm–1:
1700 (C=O). Found, %: C 56.47; H 6.41; N 29.86.
C11H15N5O. Calculated, %: C 56.64; H 6.48; N 30.02.
7-Dideuteromethyl-1-methyl-1,5-dihydro-4H-
triazolo[4,5-d]pyridazin-4-one (XXX) was obtained
similarly to compound XVI from 1.0 g (5.1 mmol) of
reagent IX and 5.7 ml (102 mmol) of deuterohydrazine
1
cm–1: 1690 (C=O). H NMR spectrum (DMSO-d6), δ,
ppm: 2.85 s (3H, 7-CH3), 4.56 s (3H, N1CH3). Found,
%: C 43.47; H 4.23; N 42.25. C6H7N5O. Calculated, %:
C 43.64; H 4.27; N 42.40.
.
hydrate (N2D4 D2O). On completion of the reaction the
deuterohydrazine hydrate was distilled off in an argon
flow till dryness, the residue was ground with 1.0 ml of
deuterium oxide, and the white precipitate was distilled
off, dried, and recrystallized from dioxane to obtain
colorless crystals. Yield 0.75 g (87%), mp 260–263°C.
IR spectrum, ν, cm–1: 1685 (C=O). 1H NMR spectrum
(DMSO-d-6), δ, ppm: 2.03 s (1H, 7-CHD2), 3.38 s (3H,
N1CH3-). Found, %: C 42.69; H (D) 5.91; N 41.50.
C6H4N5O. Calculated, %: C 42.85; H (D) 5.99; N 41.64.
7-Methyl-1-ethyl-1,5-dihydro-4H-1,2,3-triazolo-
[4,5-d]pyridazin-4-one (XVII) was obtained from
0.9 g (4.2 mmol) of reagent X and 9 ml (180 mmol) of
hydrazine hydrate similarly to compound XVI. Yield
0.75 g (97%), mp 181–183°C (2-propanol). IR spectrum,
1
ν, cm–1: 1700 (C=O). H NMR spectrum (CD3OD), δ,
ppm: 1.70 t (3H, CH2CH3), 2.76 s (3H, 7-CH3), 4.86 q
(2H, CH2CH3). Found, %: C 46.79; H 5.01; N 38.93.
C7H9N5O. Calculated, %: C 46.92; H 5.06; N 39.09.
1-Methyl-7-nitro(15N)-1,5-dihydro-4H-1,2,3-
triazolo[4,5-c]pyridin-4-one (XXXI). To a solution of
3.1 g (20.6 mmol) of 1-methyl-1,5-dihydro-4H-1,2,3-
triazolo[4,5-c]pyridin-4-one in 25 ml of concn. H2SO4
at 0–5°C was added by portions 2.4 g (23.5 mmol) of
dry K15NO3, and the reaction mixture was maintained at
0–5°C for 0.5–1.0 h. Then the reaction mixture was
treated and worked up as described for compound IX.
1-Butyl-7-methyl-1,5-dihydro-4H-1,2,3-triazolo-
[4,5-d]pyridazin-4-one (XVIII) was obtained from
0.9 g (3.8 mmol) of reagent XI and 4.0 ml (80 mmol) of
hydrazine hydrate similarly to compound XVI. Yield
0.72 g (92%), mp 151–153°C (ethanol). IR spectrum, ν,
cm–1: 1700 (C=O). 1H NMR spectrum (CF3COOH), δ,
ppm: 0.97 t (2H, δ-CH3), 1.49 q (2H, γ-CH2), 2.85 s (2H,
7-CH3), 4.90 q (2H, β-CH2), 5.30 t (2H, α-CH2). Found,
%: C 52.05; H 6.30; N 33.71. C9H13N5O. Calculated, %:
C 52.16; H 6.32; N 33.80.
1
Yield 2.8 g (70%), mp 291–294°C (DMF). H NMR
spectrum (CF3COOH), δ, ppm: 4.66 s (3H, N1CH3), 8.90
s (1H, H6). Found, %: C 36.60; H 2.54; N 36.33. M+
196. C6H5N5O3. Calculated, %: C 36.74; H 2.57; N 36.22.
1-(γ-N,N-Dimethylaminopropyl)-7-methyl-1,5-
dihydro-4H-1,2,3-triazolo[4,5-d]pyridazin-4-one hy-
drochloride (XIX) was obtained from 1.1 g (4.1 mmol)
of reagent XII and 4.5 ml (90 mmol) of hydrazine hydrate
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