1-Amino-2-hydrazinobenzimidazole and its reactions with some carbonyl compounds

Article abstract of DOI:10.1134/S1070428014050182

1-Amino-2-hydrazinobenzimidazole was obtained for the first time by treating 1-aminobenzimidazole-2-sulfonic acid with hydrazine hydrate. This compound readily condensed with aromatic aldehydes involving both amino groups. The condensation with 2,4-pentanedione affords 1-amino-2-(3,5-dimethylpyrazol-1- yl)benzimidazole, and with α-ketoacids in glacial acetic acid yields mixtures of 10-acetylamino-3-R-1,2,4-triazino[4,3-a]benzimidazol-4(10H)-ones and 4-amino-2-R-1,2,4-triazino[2,3-a]benzimidazol-3(4H)-ones.

Full text of DOI:10.1134/S1070428014050182

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 5, pp. 729–735. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © T.A. Kuz’menko, V.V. Kuz’menko, L.N. Divaeva, A.S. Morkovnik, G.S. Borodkin, 2014, published in Zhurnal Organicheskoi Khimii,
2014, Vol. 50, No. 5, pp. 739–745.
1-Amino-2-hydrazinobenzimidazole and Its Reactions
with Some Carbonyl Compounds
T. A. Kuz’menko, V. V. Kuz’menko†, L. N. Divaeva, A. S. Morkovnik, and G. S. Borodkin
Research Institute of Physical and Organic Chemistry at Southern Federal University,
pr. Stachki 194/2, Rostov-on-Don, 344090 Russia
e-mail: asmork2@ipoc.rsu.ru
Received April 24, 2013
Abstract—1-Amino-2-hydrazinobenzimidazole was obtained for the first time by treating 1-aminoben-
zimidazole-2-sulfonic acid with hydrazine hydrate. This compound readily condensed with aromatic aldehydes
involving both amino groups. The condensation with 2,4-pentanedione affords 1-amino-2-(3,5-
dimethylpyrazol-1-yl)benzimidazole, and with α-ketoacids in glacial acetic acid yields mixtures of 10-
acetylamino-3-R-1,2,4-triazino[4,3-а]benzimidazol-4(10Н)-ones and 4-amino-2-R-1,2,4-triazino[2,3-а]benzi-
midazol-3(4Н)-ones.
DOI: 10.1134/S1070428014050182
The synthetic importance of 2-hydrazinoben-
zimidazoles is well known: they underlie the
preparation of new heterocyclic systems [1–3],
formazans [4], coordination compounds [5]. The
synthetic opportunities of N-amino-benzimidazoles are
no less versatile [6, 7]. We describe in this report 1-
amino-2-hydrazinobenzimidazole I with both function-
nal groups participating in condensations and the fea-
tures of its reactions with aldehydes, 2,4-pentanedione,
and α-ketoacids.
exchange of a chlorine atom or a sulfo group in the
corresponding benzimidazoles [8]. Hydrazine
derivative I we have obtained in a high yield from 1-
aminobenzimidazole-2-sulfonic acid [9] by boiling in
excess of hydrazine hydrate. This compound proved to
be sufficiently stable and gradually turned darker only
at the long storage.
Unlike the 1,2-diaminobenzimidazole which
underwent condensation with aromatic aldehydes only
at the N-amino group [10], hydrazine I reacted at once
with 2 mol of aldehyde forming hydrazones II.
Analogously, e.g., to 4-amino-3-hydrazino-1,2,4-tria-
The main method of the preparation of 2-
hydrazinobenzimidazoles as known is based on the
Scheme 1.
Ar = Ph (а), 2-OHC6H4 (b).
†
Deceased.
729

KUZ’MENKO et al.
730
Scheme 2.
O
O
N
N
Me
Me
HNO2
I
N
N
N
H
N
NH2
V
N
N
RCHO
IV
Me
Me
Me
N
N
N
N
N
Me
CHR
VI, R = 4-NO2C6H4 (a),
VIa, VIb
(b).
S
oline-5-thione the product of this reaction may be
with nitrous acid giving rise to NH-unsubstituted
compound IV whose physicochemical characteristics
coincided with those described in [12]. N-Amine V
readily formed azomethine VIa with 4-nitrobenz-
aldehyde at heating in 2-propanol, but with less
reactive 2-formylthiophene the reaction under these
conditions did not occur, and the corresponding
azomethine VIb was obtained in a moderate yield in
boiling toluene at the azeotropic removal of water.
Initial amine V and azomethines VIa and VIb possess
virtually the same chromatographic mobility.
tetrazinobenzimidazole III [11], yet in this case the
1
results of the elemental analysis and the Н NMR
spectrum of the compound unambiguously prove the
composition and the structure of heterocycle II
(Scheme 1).
Hydrazones II do not undergo cyclization either in the
melt at a temperature exceeding the melting point by 20°С
or at prolonged boiling in glacial acetic acid whereas their
N-unsubstituted analogs under these conditions transform
into 3-aryl-1,2,4-triazolo[4,3-а]benzimidazoles [3].
In the mass spectrum of compound V the molecular
ion peak is the most abundant. Its fragmentation occurs
analogously to the other N-aminoazoles.
Klyuev et al. [12] studied the reaction of 2-
hydrazinobenzimidazole with 2,4-pentanedione and
found that in this case not a seven-membered ring was
closed involving the hydrazino group and the endocyclic
nitrogen atom, but a pyrazole ring with the formation of
2-(pyrazol-1-yl)benzimidazole (IV). This compound is
characterized by a relatively low melting point and a
high chromatographic mobility (Rf 0.75), uncommon as
a rule for N-unsubstituted benzimidazoles. The structure
of pyrazolyl derivative IV was sufficiently compellingly
We believe that the unusual physical properties of
2-pyrazolylbenzimidazoles IV and V are due to the
location in the same plane of both heterocyclic
scaffolds in these bihetaryls. This configuration proved
for pyrazolylbenzimidazole IV by XRD analysis [12]
is stabilized mainly by the attractive electrostatic
interaction of the sp2-nitrogen atom of the pyrazole
ring with the hydrogen atoms of the NH or NNH2
moieties of the benzimidazole thus sterically impeding
the intermolecular association through hydrogen
bonds.
1
proved by Н spectra and X-ray diffraction (XRD)
analysis. Later in publications [3, 13] without
reference to [12] melting points were indicated
differing for each other by nearly 130°С.
We established that 1-amino-2-hydrazinoben-
zimidazole I also underwent cyclization with 2,4-
pentanedione involving only the hydrazino group
giving 1-amino-2-pyrazolylbenzimidazole V, which
also was significantly distinguished from the known N-
aminobenzimidazoles by the high chromatographic
mobility, relatively low melting point, and a good
solubility in nonpolar solvents (Scheme 2).
2-Hydrazinobenzimidazole and its 1-alkyl
derivatives are known to undergo cyclization with α-
ketoacids through the intermediate formation of
relatively stable hydrazones giving finally 1,2,4-tria-
zino[4,3-а]-benzimidazol-4-ones [2] capable of effi-
cient blocking adenosine receptors [14]. 1,2-
Diaminobenzimidazole and its 2-alkylamino
derivatives also easily underwent cyclization with α-
ketoacids furnishing isomeric 1,2,4-triazino-[2,3-а]-
benzimidazol-3-ones [15, 16]. Therefore both these
Yet like the most N-aminoazoles [6], N-amino
derivative V easily suffered deamination when treated
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 5 2014

1-AMINO-2-HYDRAZINOBENZIMIDAZOLE
731
Scheme 3.
O
1
9
6
10
R
CH3COCOOEt,
PhCOCOOH
4
N
3
2
R
5N
8
N
7
8
+
I
3
N 2
7
10
N
N
N
N
1
O
6
4
9
5
NH2
NHCOMe
H+
VIIIa, VIIIb
VIIa, VIIb
O
N
O
O
CH3COCOOEt,
PhCOCOOH
R
R
N
R
HNO2
N
N
CHO
O2N
N
N
N
N
N
N
NHNH2
N
N
N
H
N
H
N
NH2
NO2
O
R
Xa, Xb
IXa, IXb
XIIb
N
N
CH3COCOOEt,
PhCOCOOH
NH2
NH2
N
N
R
HNO2
4-NO2C6H4CHO
NO2
N
N
N
N
O
VIIIa, VIIIb
N
N
H
O
N
XIIIa, XIIIb
XIa, XIb
R = Me (а), Ph (b).
cyclization versions are theoretically probable for 1-
amino-2-hydrazinobenzimidazole I.
СО group is very weak the proton signals of Н6 and Н9
are observed at 7.8 and 7.7 ppm providing a possibility
to reliably identify the structures VIII and IX. The
chemical shifts of the protons of the N-amino group in
compounds VIII and IX are virtually identical (6.21
and 6.20 ppm).
We established that the heating of compound I with
ethyl pyruvate or phenylglyoxalic acid in glacial acetic
acid afforded a mixture of 10-acetylamino-1,2,4-tria-
zino[4,3-а]benzimidazol-4-ones VIIа and VIIb and 4-
amino-1,2,4-triazino[2,3-а]benzimidazol-3-ones VIIIа
and VIIIb in a nearly quantitative overall yield.
Therewith in the reaction with ethyl pyruvate as shows
the 1Н NMR spectrum of the reaction mixture the ratio
of triazinones VIIIа and VIIа equals 1.2 : 1, and with
phenylglyoxalic acid, on the contrary, acetylamino
derivative VIIb is the main reaction product (yield
70%) (Scheme 3).
N-Amines VIII and IX were deaminated in the
presence of nitrous acid giving NH-unsubstituted
compounds X and XI identical to the known
cyclization products of 2-hydrazino- and 1,2-
diaminobenzimidazole with the corresponding α-
ketoacids; this fact proved the structure of products
obtained.
At heating with aldehydes in glacial acetic acid
amines VIII and IX provided azomethines XII and
XIII.
Acetylamino derivatives VII are readily hydrolyzed
with conc. HCl into amines IX; therewith in their IR
spectra the absorption bands in the region ν 1700 cm–1
belonging to the vibration of the С=О bond of the
acetyl group disappear.
In the course of the cyclocondensation of hydrazine
I with α-ketoacids the primary nucleophilic addition to
the keto group may occur involving two competing
centers, hydrazine and N-amino groups. According to
the quantum-chemical calculations by the DFT
method (B3LYP/6-31G**) in the absence of solvation
and of the effect of the proton catalysis the reaction
involving the hydrazino group through the transition state
1
In the Н NMR spectra of triazinones VII and IX
the proton signals of Н6 under the effect of the СО
group shift downfield and appear as a doublet in the
region 8.4–8.5 ppm. In the spectra of isomeric
triazinones VIII where this interaction with the remote
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 5 2014

KUZ’MENKO et al.
vity of the reaction at the decrease in the substrate
732
C
C
C
C
N
reactivity (http://goldbook.iupac.org/R05186.html).
N
C
EXPERIMENTAL
C
N
N
C
IR spectra were recorded on a spectrophotometer
Varian Excalibur 3100 FT-IR from samples in solid
phase. 1H NMR spectra were registered on a
spectrometer Varian Unity-300 (300 MHz), solvent
DMSO-d6, CDCl3 for compounds II, V, and VI.
Chemical shifts of protons are given with respect to the
residual protons of deuterated solvents. Mass spectrum
of electron impact (70 eV) was obtained on an
instrument Finnigan MAT INCOS 50 with the direct
admission of the sample into the ion source.
C
N
1.225
C
C
C
1.619
1.344
O
1.373
C
C
C
C
O
O
TS1
The reaction progress was monitored and the
homogeneity of compounds was checked by TLC on
plates with Al2O3 of III activity grade, eluent CHCl3,
development in iodine vapor. Eluent for compounds
VII–IX was a mixture CHCl3–EtOH, 20 : 1.
C
C
C
N
C
N
The optimization of geometry of hydrazine I, phe-
nylglyoxalic acid, and transition states TS1 and TS2
was carried out using the program Firefly 8.0 [17],
partially based on the code of the program GAMESS
[18]. The calculation of the energy of the found
structures was performed with accounting for the
correction for the oscillation energy of the zero level
applying the scaling factor 0.961 [19].
C
C
O
C
C
N
1.623
N
C
N
1.368
1.370
C
1.208
C
O
O
C
1-Aminobenzimidazole-2-sulfonic acid was synt-
hesized by procedure [9], hydrazine hydrate,
aldehydes, 2,4-pentanedione, phenylglyoxalic acid,
and ethyl pyruvate were purchased from Aldriсh.
C
C
C
TS2
1-Amino-2-hydrazinobenzimidazole (I).
A
Transition states at the phenylglyoxalic acid addition
to hydrazine I [hydrogen atoms of the phenyl group
and benzimidazole fragment are not shown; the
figures correspond to bond lengths (Å) in four-
membered reaction nodes of transition states].
solution of 2.13 g (0.01 mol) of 1-aminobenzimidazole-
2-sulfonic acid in 15 mL of hydrazine hydrate was
boiled for 2.5 h. The precipitate separated on cooling was
filtered off, washed with 30 mL of cold water. Yield
1.50 g (93%), colorless crystals, mp 216–218°С (Н2О),
1
gradually darkening when exposed to air. Н NMR
TS1 (see the figure) is by 6–7 kcal mol−1 more
favorable than with the participation of the N-amino
group through TS2. However since TS2 is far more
polar than TS1 (μcalc. 7.0 and 2.5 D respectively), in the
solution the preference of the first reaction route
becomes less considerable.
spectrum, δ, ppm: 4.23 s (2Н, NHNH2), 5.49 s (2Н,
NNH2), 6.92–6.96 m (2Н, Н5,6), 7.10–7.13 m (1Н, Н7),
7.17–7.21 m (1Н, Н4), 7.33 br.s (1Н, NH). Found, %: С
51.32; Н 5.67; N 42.70. С7Н9N5. Calculated, %: С
51.52; Н 5.56; N 42.92.
1-Benzylideneamino-2-benzylidenehydrazino-
benzimidazole (IIа). A solution of 0.33 g (2 mmol) of
hydrazine I and 0.4 mL (4 mmol) of benzaldehyde in
5 mL of 2-propanol was boiled for 1.5 h. The light-
yellow precipitate separated on cooling was filtered off
and washed with ether. Yield 0.50 g (73%), mp 82–83°С
Therewith the higher regioselectivity of the
cyclization with phenylglyoxalic acid as compared
with ethyl pyruvate is obviously due to the lower elect-
rophilicity of the carbon atom in its keto group in
agreement with the general trend of increased selecti-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 5 2014

1-AMINO-2-HYDRAZINOBENZIMIDAZOLE
733
(i-PrOH), Rf 0.9. IR spectrum, ν, cm–1: 3300–3100
(NH), 1615 (С=N), 1584. 1Н NMR spectrum, δ, ppm:*
7.04–7.12 m (3Н, Н3'–5'), 7.33–7.52 m (7Н, Н4–7,3''–5''),
7.77 d (2Н, Н2',6', J 7.2 Hz), 7.87 d (2Н, Н2'',6'', J 7.2 Hz),
8.47 s (1Н, NH), 8.86 s (1Н, =СН'), 10.12 s (1Н, =СН'').
Found, %: С 74.52; Н 5.20; N 20.81. С21Н17N5. Calcu-
lated, %: С 74.32; Н 5.05; N 20.63.
(1 mmol) of amine V and 0.15 g (1 mmol) of 4-nitro-
benzaldehyde in 3 mL of 2-propanol was boiled for 1 h
in the presence of catalytic amount of piperidine. On
cooling the formed yellow precipitate was filtered off
and washed with ether. Yield 0.26 g (71%), mp 216–
217°С (i-PrOH), Rf 0.8. IR spectrum, ν, cm–1: 1598,
1
1575, 1541, 1518. Н NMR spectrum, δ, ppm: 2.32 s
(3Н, СН3), 2.36 s (3Н, СН3), 6.11 s (1Н, Н4'), 7.41–
7.46 m (2Н, Н5,6), 7.75 d (2Н, Н2'',6'', J 7.8 Hz), 7.83–7.91
m (2Н, Н4,7), 8.30–8.33 m (3Н, Н3'',5'', =CH). Found,
%: С 63.52; Н 4.28; N 23.18. С19Н16N6О2. Calculated,
%: С 63.33; Н 4.48; N 23.32.
1-(2-Hydroxybenzylidene)amino-2-(2-hydroxy-
benzylidene)hydrazinobenzimidazole (IIb) was
obtained similarly to compound IIа. Yield 70%, light-
yellow needle crystals, mp 111–112°С (i-PrOH),
1
Rf 0.75. Н NMR spectrum, δ, ppm: 6.93–7.42 m
(12Нarom), 8.44 s (1Н, NH), 8.53 s (1Н, =СН'), 10.15 s
(1Н, =СН''), 10.95 s (1Н, OH), 11.55 s (1Н, ОН).
Found, %: С 68.12; Н 4.47; N 19.04. С21Н17N5О2. Cal-
culated, %: С 67.91; Н 4.61; N 18.86.
2-(3,5-Dimethylpyrazol-1-yl)-1-(thenylidene-2)-
aminobenzimidazole (VIb). A solution of 0.23 g
(1 mmol) of amine V and 0.1 mL (1 mmol) of 2-
formylthiophene in 5 mL of toluene was boiled for 3 h
with azeotropic distilling off water, the solution was
evaporated to dryness, the residue was recrystallized
from 2-propanol. Yield 0.19 g (58%), colorless
crystals, mp 131–132°С. IR spectrum, ν, cm–1: 1612,
1-Amino-2-(3,5-dimethylpyrazol-1-yl)benzim-
idazole V. A slurry of 0.50 g (3 mmol) of hydrazine I
and 0.3 mL (3 mmol) of 2,4-pentanedione in 7 mL of
2-propanol was boiled for 1 h till complete dissolution
of the precipitate, and then for 2 h more. The solution
was evaporated to dryness, the residue was
chromatographed on a column packed with Al2O3
(60 × 20 mm), eluent chloroform. The fraction with Rf
0.8 was separated. Yield 0.52 g (76%), mp 124–125°С
(isooctane). IR spectrum, ν, cm–1: 3310, 3169 (NH2),
1
1557, 1521, 1448. Н NMR spectrum, δ, ppm: 2.22 s
(3Н, СН3), 2.48 s (3Н, СН3), 6.09 s (1Н, Н4'), 7.17 t
(1Н, Н4'', J 5.0, 3.7 Hz), 7.31–7.41 m (2Н, Н5,6), 7.59–
7.61 d.d (1Н, Н5'', J 3.7, 1.1 Hz), 7.69–7.72 m (2Н,
Н3'',7), 7.77–7.80 m (1Н, H4), 8.80 s (1Н, =СН). Found,
%: С 63.40; Н 4.52; N 21.74; S 9.83. С17Н15N5S.
Calculated, %: С 63.53; Н 4.70; N 21.79; S 9.98.
1
1592, 1573, 1548, 1479. Н NMR spectrum, δ, ppm:
2.32 s (3Н, СН3), 2.62 s (3Н, СН3), 5.51 s (2Н, NH2),
6.06 s (1Н, Н4'), 7.24–7.36 m (2Н, Н5,6), 7,56 d (1Н,
Н7, J 7.5 Hz), 7.68 d (1Н, Н4, J 8.1 Hz). Mass
spectrum, m/z (Irel, %): 227 (100) [M]+, 212 (10), 198
(42.9), 118 (17.1), 96 (17.1), 81 (21.4), 75 (17.1), 43
(32.1). Found, %: С 63.52; Н 5.60; N 30.94. С12Н13N5.
Calculated, %: С 63.42; Н 5.77; N 30.81.
Reaction of hydrazine I with ethyl pyruvate. A
solution of 0.50 g (3 mmol) of hydrazine I and 0.33 mL
(3 mmol) of ethyl pyruvate in 5 mL of glacial acetic
acid was boiled for 2 h. The precipitate formed on
cooling (0.34 g) was separated and recrystallized from
MeCOOH. We obtained 0.22 g of colorless crystals of
4-amino-2-methyl-1,2,4-triazino[2,3-а]benzimida-
zol-3(4Н)-one (VIIIа), mp 262–264°С, Rf 0.2. IR
spectrum, ν, cm–1: 3287, 3178 (NH2), 1682 (С=О),
2-(3,5-Dimethylpyrazol-1-yl)benzimidazole (IV).
To a solution of 0.23 g (1 mmol) of amino derivative V
in 2 mL of glacial acetic acid cooled with an ice bath
was added a solution of 0.07 g (1 mmol) of NaNО2 in
1 mL of water, 0.5 h later the mixture was doubly
diluted with water, a precipitate separated and was
filtered off and washed with water. Yield 0.18 g
(85%), mp 134–135°С (134–136 [12], 175 [3], >300°С
1
1638, 1604, 1554. Н NMR spectrum, δ, ppm: 2.45 s
(3Н, СН3), 6.10 s (2Н, NH2), 7.28–7.38 m (2Н, Н7,8),
7.64 d (1Н, Н6, J 8.7 Hz), 7.74 d (1Н, Н9, J 8.4 Hz).
Found, %: С 55.60; Н 4.16; N 32.35. С10Н9N5О.
Calculated, %: С 55.81; Н 4.22; N 32.54.
The combined filtrates were evaporated to dryness,
the residue (0.44 g) was treated with 10 mL of boiling
chloroform. The insoluble 0.1 g of compound VIIIа
was separated. The overall yield of amine VIIIа 0.32 g
(50%). The residue after evaporation of the chloroform
extract was twice recrystallized from CH3CN to obtain
0.23 g (29%) of 10-acetylamino-3-methyl-1,2,4-tria-
zino[4,3-а]benzimidazol-4(10Н)-one (VIIа), color-
less crystals, mp 235–237°С, Rf 0.05. The spots of
1
[13]). Н NMR spectrum, δ, ppm: 2.29 s (3Н, СН3),
2.74 s (3Н, СН3), 6.05 s (1Н, Н4'), 7.07–7.12 m (2Н,
Н5,6), 7.45 d.d (2Н, Н4,7, J 2.7 Hz), 12.51 s (1Н, NН).
2-(3,5-Dimethylpyrazol-1-yl)-1-(4-nitrobenzyli-
dene)aminobenzimidazole (VIа). A solution of 0.23 g
* Here and hereinafter one stroke designates the position of
substituents at the hydrazino group, two strokes, at the N-amino
group.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 5 2014

KUZ’MENKO et al.
734
compound VIIа were not visualized on
chromatograms in iodine vapor, but were seen under
UV irradiation. IR spectrum, ν, cm–1: 3360–3170
(NH), 1716 (С=О), 1697 (С=О), 1582. 1Н NMR
spectrum, δ, ppm: 2.20 s (3Н, СН3), 2.45 s (3Н, СН3),
7.37–7.42 m (2Н, Н7,8), 7.54 d (1Н, Н9, J 8.1 Hz), 8.43
d (1Н, Н6, J 8.1 Hz), 11.45 s (1Н, NH). Found, %: С
56.17; Н 4.35; N 27.09. С12Н11N5О2. Calculated, %: С
56.03; Н 4.31; N 27.22.
10-Amino-3-phenyl-1,2,4-triazino[4,3-а]benzimi-
dazol-4(10Н)-one (IXb) was obtained similarly. Yield
83%, light-yellow crystals, mp 219–221°С (BuOH), Rf
0.1. IR spectrum, ν, cm–1: 3316, 3216 (NH2), 1671,
1
1633, 1602, 1557, 1454. Н NMR spectrum, δ, ppm:
6.20 s (2Н, NH2), 7.34–7.56 m (5Н, Н7,8,3'–5'), 7.63–
7.68 m (1Н, Н9), 8.18–8.20 m (2Н, Н2',6'), 8.48 d (1Н,
Н6, J 8.1 Hz). Found, %: С 64.78; Н 3.85; N 25.12.
С15Н11N5О. Calculated, %: С 64.97; Н 4.00; N 25.26.
Reaction of hydrazine I with phenylglyoxalic
acid. A solution of 0.50 g (3 mmol) of hydrazine I and
0.45 g (3 mmol) of phenylglyoxalic acid in 5 mL of
glacial acetic acid was boiled for 2 h. The light-yellow
precipitate formed on cooling of 10-acetylamino-3-
phenyl-1,2,4-triazino[4,3-а]-benzimidazol-4(10Н)-
one (VIIb) was filtered off and washed with ether.
Yield 0.67 g (70%), mp 254–255°С (MeCOOH). IR
spectrum, ν, cm–1: 3300–3100 (NH), 1722 (С=О),
3-Methyl-1,2,4-triazino[4,3-а]benzimidazol-4
(10Н)-one (Xа). At cooling with an ice bath to a
solution of 0.11 g (0.5 mmol) of amine IXа in 2 mL of
glacial acetic acid was added a solution of 0.04 g
(0.6 mmol) of NaNO2 in 1 mL of water. After 0.5 h
the formed precipitate was filtered off and washed with
water. Yield 0.1 g (100%), mp 317–318°С (DMF),
(320°С [2]). IR spectrum, ν, cm–1: 3160–2432, 1698,
1639, 1604, 1557, 1451, 1285, 1174, 897, 843, 808. IR
spectrum was identical to the spectrum of an authentic
sample obtained by the cyclization of 2-hydra-
zinobenzimidazole with ethyl pyruvate by procedure
[2].
1
1698 (С=О), 1578, 1466. Н NMR spectrum, δ, ppm:
2.48 s (3Н, СН3), 7.39–7.48 m (5Н, Н7,8,3'–5'), 7.59–
7.68 m (1Н, Н9), 8.11–8.21 m (2Н, Н2',6'), 8.55 d (1Н,
Н6, J 7.8 Hz), 11.63 s (1Н, NН). Found, %: С 64.10; Н
4.22; N 22.03. С17Н13N5О2. Calculated, %: С 63.94; Н
4.10; N 21.93.
Compounds Xb, XIа and XIb were similarly
obtained.
The filtrates was evaporated to dryness, the residue
(0.27 g) was chromatographed on a column (15 × 20 mm)
packed with Al2O3, eluent a mixture СHCl3−EtOH,
20 : 1, collecting the fraction with Rf 0.2 of 4-amino-2-
phenyl-1,2,4-triazino[2,3-а]benzi-midazol-3(4Н)-
one (VIIIb). Yield 0.18 g (21%), light-yellow crystals,
mp 236–237°С (BuOH). IR spectrum, ν, cm–1: 3310,
3-Phenyl-1,2,4-triazino[4,3-а]benzimidazol-4-
(10Н)-one (Xb) was obtained from amine VIIb. Yield
98%, mp >320°С (DMФА), (322–323°С [2]). IR
spectrum, ν, cm–1: 3148–2400 (NН), 1697, 1640, 1605,
1526, 1444, 1288, 1256, 1196, 891, 796, 757, 688,
664. IR spectrum was identical to the spectrum of an
authentic sample obtained by the cyclization of 2-
hydrazinobenzimidazole with phenylglyoxalic acid by
procedure [2].
1
3192 (NH2), 1678, 1654, 1638, 1610, 1436. Н NMR
spectrum, δ, ppm: 6.21 s (2Н, NH2), 7.34–7.39 m (2Н,
Н7,8), 7.54–7.56 m (3Н, Н3'–5'), 7.68 d (1Н, Н6, J 7.5 Hz),
7.84 d (1Н, Н9, J 7.0 Hz), 8.05–8.08 m (2Н, Н2',6').
Found, %: С 65.13; Н 4.08; N 25.41. С15Н11N5О.
Calculated, %: С 64.97; Н 4.00; N 25.26.
2-Methyl-1,2,4-triazino[2,3-а]benzimidazol-3-
(4Н)-one (XIа) was obtained from 4-amino derivative
VIIIа. Yield 100%. Colorless crystals, mp 350–352°С
(DMF) (350–355°С [15]). IR spectrum, ν, cm–1: 3074–
2557 (NH), 1618, 1596, 1579, 1552, 1513, 1498, 1400,
1187. IR spectrum was identical to the spectrum of an
authentic sample obtained from 1,2-diamino-
benzimidazole and ethyl pyruvate by procedure [15].
10-Amino-3-methyl-1,2,4-triazino[4,3-а]benzimi-
dazol-4(10Н)-one (IXа). A solution of 0.26 g (1 mmol)
of 10-acetylamine VIIа in 3 mL of conc. HCl was
boiled for 10 min, neutralized with 22% NH4OH and
on cooling the separated precipitate was filtered off.
Yield 0.17 g (81%), colorless crystals, mp 225–226°С
(BuOH), Rf 0.1. IR spectrum, ν, cm–1: 3333–3280
(NH2), 1688, 1676, 1605, 1570, 1467. 1Н NMR
spectrum, δ, ppm: 2.48 s (3Н, СН3), 6.05 s (2Н, NH2),
7.36–7.42 m (1Н, Н8), 7.62–7.63 m (2Н, Н7,9), 8.37 d
(1Н, Н6, J 8.1 Hz). Found, %: С 56.03; Н 4.32; N
32.47. С15Н11N5О. Calculated, %: С 55.81; Н 4.22; N
32.54.
2-Phenyl-1,2,4-triazino[2,3-а]benzimidazol-3-
(4Н)-one (XIb) was obtained from 4-amino derivative
VIIIb. Yield 100%, mp 352–355°С (DMF–Н2О)
(355–358°С [15]). IR spectrum, ν, cm–1: 3054–2640
(NН), 1629, 1611, 1528, 1441, 1214, 1014, 779, 747.
IR spectrum was identical to the spectrum of an
authentic sample obtained by the cyclization of 1,2-
diaminobenzimidazole with phenylglyoxalic acid [15].
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1-AMINO-2-HYDRAZINOBENZIMIDAZOLE
735
1990, vol. 16, p. 1500; Lukov, V.V., Bogatureva, E.V.,
Kogan, V.A., Starikov, A.G., and Lokshin, V.A., Zh.
Neorg. Khim., 1991, vol. 36, p. 2310.
10-(5-Nitrofurfurylidene)amino-3-phenyl-1,2,4-
triazino[4,3-а]benzimidazol-4(10Н)-one (XIIb). A
solution of 0.14 g (0.5 mmol) of amine IXb and 0.07 g
(0.5 mmol) of 5-nitrofurfural in 2 mL of glacial acetic
acid was boiled for 15 min. The formed yellow
precipitate was separated after cooling. Yield 0.2 g
6. Kuz’menko, V.V., and Pozharskii, A.F., Adv. Hetero-
cyclic Chem., 1992, vol. 53, p. 89.
7. Vasil’chenko, I.S., Kuz’menko, T.A., Shestakova, T.E.,
Borisenko, R.N., Divaeva, L.N., Burlov, A.S.,
Borisenko, N.I., Uflyand, I.E., and Garnovskii, A.D.,
Russ. J. Coord. Chem., 2005, vol. 31, p. 747;
Kuz’menko, T.A., Divaeva, L.N., and Morkovnik, A.S.,
Russ. Chem. Bull., 2011, vol. 60, p. 548.
8. Bednyagina, N.P., and Postovskii, I.Ya., Zh. Obshc.
Khim., 1960, vol. 30, p. 1431; Mokrushina, G.A., and
Bednyagina, N.P., Chem. Heterocycl. Comp., 1970,
vol. 6, p. 1304.
9. Kuz’menko, T.A., Kuz’menko, V.V., Pozharskii, A.F.,
and Simonov, A.M., Chem. Heterocycl. Comp., 1988,
vol. 24, p. 880.
10. Zeiger, A.V., and Joullie, M.M., J. Org. Chem., 1977,
vol. 42, p. 542; Kumar, A., Parshad, M., Gupta, R.K.,
and Kumar, D., Synthesis, 2009, p. 1663.
1
(100%), mp 248–250°С (BuOH), Rf 0.7. Н NMR
spectrum, δ, ppm: 7.52–759 m (4Н, Н8 or 7,3'–5'), 7.70–
7.75 m (2Н, H7 or 8,3''), 7.86–7.91 m (2Н, Н9,4''), 8.22–
8.25 m (2Н, Н2',6'), 8.51 d (1Н, Н6, J 7.8 Hz), 10.34 s
(1Н, =СН). Found, %: С 59.83; Н 3.17; N 21.15.
С20Н12N6О4. Calculated, %: С 60.00; Н 3.02; N 20.99.
2-Methyl-4-(4-nitrobenzylidene)amino-1,2,4-tri-
azino[2,3-а]benzimidazol-3(4Н)-one (XIIIа). A solution
of 0.11 g (0.5 mmol) of amine VIIIа and 0.08 g
(0.5 mmol) of 4-nitrobenzaldehyde in 2 mL of glacial
acetic acid was boiled for 1 h. The formed after
cooling yellow precipitate was filtered off and washed
with ether. Yield 0.15 g (85%), mp 273–275°С
(MeCOOH), Rf 0.8. 1Н NMR spectrum, δ, ppm: 2.43 s
(3Н, СН3), 7.35–7.38 m (2Н, Н7,8), 7.67–7.70 m (1Н,
Н6), 7.78–7.80 m (1Н, Н9), 8.27 d (2Н, Н2'',6'', J 8.7 Hz),
8.43 d (2Н, Н3'',5'', J 8.4 Hz), 9.67 s (1Н, =СН). Found,
%: С 58.40; Н 3.26; N 23.89. С17Н12N6О3. Calculated,
%: С 58.62; Н 3.47; N 24.13.
11. Dickinson, H.G., and Jacobson, N.W., J. Chem. Soc.,
Chem. Commun., 1970, p. 1719.
12. Klyuev, N.A., Povstyanoi, N.V., Aleksandrov, G.G., and
Gumennyi, V.P., Chem. Heterocycl. Comp., 1983,
vol. 19, p. 79.
13. Joshi, K.C., Jain, R., Dandia, A., and Sharma, K.,
J. Heterocyclic. Chem., 1988, vol. 25, p. 1641.
14. Da Settimo, F., Primofiore, G., Taliani, S., Marini, A.M.,
La Motta, C., Novellino, E., Greco, G., Lavecchia, A.,
Trincavelli, L., and Martini, C., J. Med. Chem., 2001,
vol. 44, p. 316; Scatena, A., Fornai, F., Trincavelli, M.L.,
Taliani, S., Daniele, S., Pugliesi, I., Cosconati, S.,
Martini, C., and Da Settimo, F., ACS Chem. Neurosci.,
2011, vol. 2, p. 526; Taliani, S., Pugliesi, I., Barresi, E.,
Simorini, F., Salerno, S., La Motta, C., Marini, A.M.,
Cosimelli, B., Cosconati, S., Di Maro, S., Marinelli, L.,
Daniele, S., Trincavelli, M.L., Greco, G., Novellino, E.,
Martini, C., and Da Settimo, F., J. Med. Chem., 2012,
vol. 55, p. 1490.
4-(4-Nitrobenzylideneamino)-2-phenyl-1,2,4-tri-
azino[2,3-а]benzimidazol-3(4Н)-one (XIIIb) was
similarly obtained from amine VIIIb. Yield 89%.
Yellow crystals, mp 241–242°С (MeCOOH), Rf 0.8.
1Н NMR spectrum, δ, ppm: 7.36–7.39 m (2Н, Н7,8),
7.51–7.55 m (3Н, Н3'–5'), 7.64–7.66 m (1Н, Н6), 7.81–
7.84 m (1Н, Н9), 8.07–8.10 m (2Н, Н2',6'), 8.33 d (2Н,
Н2'',6'', J 9.0 Hz), 8.41 d (2Н, Н3'',5'', J 8.7 Hz), 9.73 s
(1Н, =СН). Found, %: С 64.32; Н 3.57; N 20.30.
С22Н14N6О3. Calculated, %: С 64.39; Н 3.44; N 20.48.
The study was carried out using the equipment of
the Center of joint use “Molecular Spectroscopy” of
the Research Institute of Physical and Organic
Chemistry at Southern Federal University.
15. I-fu, Ho R., and Day, A.R., J. Org. Chem., 1973,
vol. 38, p. 3084.
16. Kuz’menko, T.A., Kuz’menko, V.V., Pozharskii, A.F.,
and Simonov, A.M., Chem. Heterocycl. Comp., 1988,
vol. 24, p. 880; Kuz’menko, T.A., Kuz’menko, V.V.,
Morkovnik, A.S., and Divaeva, L.N., Chem. Heterocycl.
Comp., 2006, vol. 42, p. 648.
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