Synthesis of 2-aryl-1-hydroxy-1H-naphtho[2,3-d]imidazole-4,9-diones by reaction of 2-benzylamino-1,4-naphthoquinones with nitric acid

Article abstract of DOI:10.1134/S1070428013090194

2-Aryl-1-hydroxy-1H-naphtho[2,3-d]imidazole-4,9-diones were synthesized by treatment of 2-benzylamino-1,4-naphthoquinones with a mixture of nitric and sulfuric acids in acetic acid.

Full text of DOI:10.1134/S1070428013090194

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 9, pp. 1354–1357. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © L.M. Gornostaev, M.V. Vigant, O.I. Kargina, A.S. Kuznetsova, Yu.G. Khalyavina, T.I. Lavrikova, 2013, published in Zhurnal
Organicheskoi Khimii, 2013, Vol. 49, No. 9, pp. 1369–1372.
Synthesis of 2-Aryl-1-hydroxy-1H-naphtho[2,3-d]imidazole-
4,9-diones by Reaction of 2-Benzylamino-1,4-naphthoquinones
with Nitric Acid
L. M. Gornostaev, M. V. Vigant, O. I. Kargina, A. S. Kuznetsova,
Yu. G. Khalyavina, and T. I. Lavrikova
Astaf’ev Krasnoyarsk State Pedagogical University, ul. A. Lebedevoi 89, Krasnoyarsk, 660049 Russia
e-mail: gornostaev@kspu.ru
Received March 4, 2013
Abstract—2-Aryl-1-hydroxy-1H-naphtho[2,3-d]imidazole-4,9-diones were synthesized by treatment of 2-ben-
zylamino-1,4-naphthoquinones with a mixture of nitric and sulfuric acids in acetic acid.
DOI: 10.1134/S1070428013090194
Heterocyclic quinoid compounds containing a fused
imidazole ring exhibit various kinds of biological ac-
tivity. For example, benzimidazoledione derivatives
showed anticancer activity [1]. Naphtho[2,3-d]imid-
azole-4,9-diones attract interest as bacteriostatic agents
[2]. Nowadays, increased interest is observed in fused
N-hydroxyimidazoles since they also display diverse
biological activity. N-Hydroxybenzimidazole deriva-
tives were reported to control the activity of some
common microbial species via inhibition of their
growth and resistance to antibiotics and oxidants [3].
acetic acid gives 2-aryl-1-hydroxy-1H-naphtho[2,3-d]-
imidazole-4,9-diones (hydroxyimidazoles) IIIa–IIIc
(Scheme 3).
Presumably, the transformation II→III involves
nitration of initial compounds IIa–IIc and fast cycliza-
tion of intermediate 2-benzylamino-3-nitro-1,4-naph-
thoquinones IVa–IVc to N-hydroxyimidazoles IIIa–
IIIc, though nitroquinones IVa–IVc were not detected
in the reaction mixture by chromatography. Com-
pounds IIIa–IIIc are the first representatives of fused
quinoid hydroxyimidazoles. Accessibility of these
compounds opens a simple route to 2-aryl-1H-
naphtho[2,3-d]imidazole-4,9-diones I (Scheme 4).
2-Aryl-1H-naphtho[2,3-d]imidazole-4,9-diones I
are generally synthesized by reactions of 2,3-diamino-
1,4-naphthoquinone with aromatic aldehydes [1] or
acid chlorides [2] (Scheme 1). N-Hydroxyimidazole
ring is formed in reactions of vicinal nitroso amines
with aldehydes [4], as well as in base-catalyzed cy-
clization of 2-benzylaminonitroarenes [3] (Scheme 2).
We have found that treatment of 2-benzylamino-1,4-
naphthoquinones IIa–IIc with a nitrating mixture in
The structure of hydroxyimidazoles IIIa–IIIc was
1
confirmed by spectral data. The H NMR spectra of
IIIa–IIIc were identical to those of 2-aryl-1H-
naphtho[2,3-d]imidazole-4,9-diones I; proton in the
hydroxy group of IIIa–IIIc resonated as a broadened
singlet at δ 13.10–13.30 ppm. In the IR spectrum of
IIIa, absorption bands due to stretching vibrations of
Scheme 1.
ArCHO
O
O
O
O
O
O
H
N
H
N
NH2
NH2
Ar
OH–
ArC(O)Cl
Ar
O
N
NH2
I
1354

SYNTHESIS OF 2-ARYL-1-HYDROXY-1H-NAPHTHO[2,3-d]IMIDAZOLE-4,9-DIONES
1355
Scheme 2.
O
O
OH
DMSO
145–150°C
NO
CHO
N
HN
HN
+
X
N
O
N
H
NH2
X
O
N
H
X = H, OMe, Cl.
R1
NO2
OH
NaOH, MeOH, 25–60°C
or NaH, THF, 40–60°C
R1
R2
N
N
R2
N
H
R1 = NO2, H, F, CN; R2 = H, 4-Br, 4-OH, 4-OMe, 2-NH2, 4-NH2, 3-NH2, 4-OPh, 4-NMe2, 3-NMe2, 2-NHAc,
4-NHAc, 3-NHAc, 4-NHC(O)Ph.
Scheme 3.
O
O
O
O
O
OH
H
N
H
HNO3, H2SO4
AcOH
N
N
CH2C6H4R-4
CH2C6H4R-4
C6H4R-4
–H2O
N
NO2
O
IIa–IIc
IVa–IVc
IIIa–IIIc
R= H (a), Me (b), Cl (c).
Scheme 4.
O
O
O
OH
H
N
N
Zn, AcOH, HCl
Ph
Ph
N
N
O
IIIa
Ia
the carbonyl groups appeared at 1680 and 1662 cm–1.
It is known that intramolecular hydrogen bonding in
1-hydroxy- and 1-amino-9,10-anthraquinones leads to
low-frequency shift of the carbonyl absorption bands
[5]. Presumably, intramolecular hydrogen bonds are
also formed in compounds IIIa–IIIc.
had low intensity; the most abundant fragment ions
were acylium ions which are likely to be formed with
participation of the hydroxy group (Scheme 5). Unlike
compounds IIIa–IIIc, the molecular ion peak in the
mass spectrum of Ia was the most intense, while the
intensity of the benzoyl cation peak [PhCO]+ was low
(8.10%), which indicated a different fragmentation
pattern.
The UV spectra of N-hydroxyimidazoles IIIa–IIIc
and naphthoimidazole Ia were almost identical. The
molecular ion peaks in the mass spectra of IIIa–IIIc
Thus we have found a convenient synthetic ap-
proach to 2-aryl-1-hydroxy-1H-naphtho[2,3-d]imid-
azole-4,9-diones IIIa–IIIc.
Scheme 5.
+
+·
O
CO
OH
EXPERIMENTAL
N
R
1
The H NMR spectra were recorded on a Bruker
N
DRX spectrometer at 500 MHz from solutions in
DMSO-d6, The chemical shifts were measured relative
O
R
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 9 2013

GORNOSTAEV et al.
1356
to tetramethylsilane as internal reference. The mass
spectra were obtained on a Finnigan MAT 8200 instru-
ment. The electronic absorption spectra were recorded
on an Evolution 300 spectrophotometer from solutions
in ethanol (cell path length 1 cm, c = 2×10–4 M). The
IR spectra were obtained on a Tensor 27 instrument
from samples pelleted with KBr. The progress of reac-
tions and the purity of the isolated compounds were
monitored by TLC on Silufol plates using acetone–
toluene (1:4) as eluent. The melting points were deter-
mined on a Boetius micro hot stage. 1,4-Naphtho-
quinone used in the synthesis of IIa–IIc was com-
mercial product (from Acros Organics). Compound IIa
was synthesized as described in [6].
C17H12ClNO2. Calculated, %: C 68.57; H 4.03;
Cl 11.93; N 4.71. M 297.74.
1-Hydroxy-2-phenyl-1H-naphtho[2,3-d]imid-
azole-4,9-dione (IIIa). A mixture of 1.5 ml of 60%
nitric acid and 2.5 ml of 94% sulfuric acid was added
dropwise to 1.32 g (5.02 mmol) of compound IIa in
30 ml of acetic acid, and the mixture was stirred for
3 h at 20°C. The mixture was then poured onto 250 g
of ice. The yellow–orange precipitate was filtered off,
washed with water, and dried. A 1.14-g portion of the
dry product was heated for 5 min in 20 ml of boiling
chloroform, the mixture was cooled, and the yellow
precipitate was filtered off. Yield 0.98 g (67%),
mp 248–250°C. UV spectrum, λmax, nm (logε): 332
(3.47), 392 (3.19). IR spectrum, ν, cm–1: 3425 br
2-[(4-Methylbenzyl)amino]-1,4-dihydronaphtha-
lene-1,4-dione (IIb). 4-Methylbenzylamine, 4.84 g
(40.00 mmol), was added to 4.80 g (30.38 mmol) of
1,4-naphthoquinone in 40 ml of isopropyl alcohol, and
the mixture was stirred for 3 h at 20°C. The mixture
was then kept for 15 h at –10°C, and the orange pre-
cipitate was filtered off, washed with aqueous alcohol
and water, and recrystallized from alcohol. Yield 4.80 g
(53%), mp 168–170°C. UV spectrum: λmax 454 nm
1
(NOH), 1680–1662 s (C=O). H NMR spectrum, δ,
ppm: 7.55–7.63 m (3H, 3′-H, 4′-H, 5′-H), 7.86 d and
7.88 t (1H each, 5-H, 8-H, J = 5.5 Hz), 8.12 t (2H,
6-H, 7-H, J = 5.5 Hz), 8.19 d (2H, 2′-H, 6′-H, J =
7.5 Hz), 13.20 br.s (1H, OH). Mass spectrum, m/z
(Irel, %): 290 (2.50) [M]+, 114 (19.12), 105 (100), 77
(28.63), 39 (6.71). Found, %: C 70.81; H 3.48; N 9.60.
C17H10N2O3. Calculated, %: C 70.34; H 3.44; N 9.65.
M 290.30.
1
(logε 3.55). H NMR spectrum, δ, ppm: 2.25 s (3H,
Me), 4.40 d (2H, CH2, J = 7.0 Hz), 5.50 s (1H, 3-H),
7.14 d (2H, 3′-H, 5′-H, J = 8.0 Hz), 7.24 d (2H, 2′-H,
6′-H, J = 8.0 Hz), 7.72 t and 7.81 t (1H each, 6-H, 7-H,
J = 7.0 Hz), 7.90 d and 8.99 d (1H each, 5-H, 8-H, J =
7.0 Hz), 8.10 br.s (1H, NH). Mass spectrum, m/z
(Irel, %): 277 (39.84) [M]+, 260 (25.93), 105 (100), 89
(10.11), 32 (76.68). Found, %: C 78.00; H 5.22;
N 5.14. C18H15NO2. Calculated, %: C 77.98; H 5.41;
N 5.05. M 272.32.
Compounds IIIb and IIIc were synthesized in
a similar way.
1-Hydroxy-2-(4-methylphenyl)-1H-naphtho-
[2,3-d]imidazole-4,9-dione (IIIb) was synthesized
from 1.39 g (5.02 mmol) of compound IIb. The reac-
tion mixture was stirred for 1.5 h at 20°C, and the
product was recrystallized from 2-ethoxyethanol. Yield
0.98 g (64%), mp 268–270°C. UV spectrum, λmax, nm
1
(logε): 335 (3.45), 400 (3.14). H NMR spectrum, δ,
2-[(4-Chlorobenzyl)amino]-1,4-dihydronaphtha-
lene-1,4-dione (IIc). A solution of 6.00 ml
(49.35 mmol) of 4-chlorobenzylamine in 10 ml of
ethanol was added to 4.80 g (30.38 mmol) of 1,4-naph-
thoquinone in 30 ml of ethanol, and the mixture was
stirred for 2 h at 20°C. The mixture was then kept for
12 h at –10°C, and the red–brown precipitate was
filtered off and washed with aqueous alcohol and
water. Yield 4.40 g (49%), mp 215–217°C. UV spec-
ppm: 2.36 s (3H, Me), 7.39 d (2H, 3′-H, 5′-H, J =
8.0 Hz), 7.86 d and 7.87 d (1H each, 5-H, 8-H, J =
3.3 Hz), 8.09 d (2H, 2′-H, 6′-H, J = 8.0 Hz), 8.10–
8.13 m (2H, 6-H, 7-H), 13.10 br.s (1H, OH). Mass
spectrum, m/z (Irel, %): 304 (3.70) [M]+, 288 (7.31),
119 (100), 91 (17.92), 32 (11.01). Found, %: C 70.97;
H 3.86; N 9.12. C18H12N2O3. Calculated, %: C 71.05;
H 3.95; N 9.21. M 304.30.
1
trum: λmax 452 nm (logε 3.49). H NMR spectrum, δ,
2-(4-Chlorophenyl)-1-hydroxy-1H-naphtho-
[2,3-d]imidazole-4,9-dione (IIIc) was synthesized
from 1.50 g (5.04 mmol) of compound IIc. The reac-
tion mixture was stirred for 3 h at 20°C. The product
was recrystallized from toluene–DMF (1:1). Yield
1.19 g (73%), mp 295– 297°C. UV spectrum, λmax, nm
ppm: 4.44 d (2H, CH2, J = 6.5 Hz), 5.56 s (1H, 3-H),
7.37– 7.42 m (4H, 2′-H, 3′-H, 5′-H, 6′-H), 7.73 t and
7.81 t (1H each, 6-H, 7-H, J = 7.0 Hz), 7.90 d and
8.00 d (1H each, 5-H, 8-H, J = 7.0 Hz), 8.19 t (1H,
NH, J = 6.5 Hz). Mass spectrum, m/z (Irel, %): 297
(34.53) [M]+, 280 (27.53), 125 (100), 89 (38.74), 32
(23.52). Found, %: C 68.60; H 4.02; Cl 11.33; N 4.37.
1
(logε): 331 (3.55), 392 (3.15). H NMR spectrum, δ,
ppm: 7.66 d (2H, 3′-H, 5′-H, J = 8.5 Hz), 7.86 d and
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 9 2013

SYNTHESIS OF 2-ARYL-1-HYDROXY-1H-NAPHTHO[2,3-d]IMIDAZOLE-4,9-DIONES
1357
7.88 d (1H each, 5-H, 8-H, J = 3.3 Hz), 8.09–8.14 m
(2H, 6-H, 7-H), 8.22 d (2H, 2′-H, 6′-H, J = 8.5 Hz),
13.30 br.s (1H, OH). Mass spectrum, m/z (Irel, %): 324
(4.80) [M]+, 139 (100), 101 (19.82), 76 (24.22), 32
(21.82). Found, %: C 62.85; H 2.69; Cl 10.36; N 8.36.
C17H9ClN2O3. Calculated, %: C 62.87; H 2.77;
Cl 10.94; N 8.63. M 324.72.
J = 7.8 Hz), 14.40 s (1H, NH). Mass spectrum, m/z
(Irel, %): 274 (100) [M]+, 171 (39.84), 130 (34.23), 104
(45.75), 76 (37.64), 32 (98.90). M 274.28.
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1
trum, λmax, nm (logε): 339 (3.43), 402 (3.26). H NMR
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 9 2013