Cyclization of 3-ethoxycarbonylmethyl-, 3-cyanomethyl-, and 3-acetylmethyl-1-amino-2-methylbenzimidazolium salts effected by acetic anhydride in the presence of a base

Article abstract of DOI:10.1023/B:RUJO.0000034945.99852.58

3-Ethoxycarbonylmethyl- and 3-cyanomethyl-1-amino-2-methylbenzimidazolium chlorides cyclized at treatment with acetic anhydride in the presence of potassium carbonate to afford a mixture of derivatives of pyrazolo[1,5-a] benzimidazole and 4-aminopyrrolo[1,2-a]benzimidazole. Therewith in the first case prevails the process of pyrazole ring fusion, and in the latter pyrrole ring is fused. 3-Aroyl(thenoyl)methyl-1-amino-2-methylbenzimidazolium bromides under the same conditions are converted into 1-aroyl(thenoyl)-2-methyl- and 2-4-acetamido-3-acetylpyrrolo[1,2-a]benzimidazoles.

Full text of DOI:10.1023/B:RUJO.0000034945.99852.58

Russian Journal of Organic Chemistry, Vol. 40, No. 2, 2004, pp. 221-227. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 2, 2004,
pp. 249-255.
Original Russian Text Copyright Ó 2004 by T. Kuz’menko, V. Kuz’menko, Anisimova.
.
Cyclization of 3-Ethoxycarbonylmethyl-, 3-Cyanomethyl-,
and 3-Acetylmethyl-1-amino-2-methylbenzimidazolium Salts
Effected by Acetic Anhydride in the Presence of a Base
†
T.A. Kuz’menko, V. V. Kuz’menko , and V.A.Anisimova
Research Institute of Physical and Organic Chemistry at Rostov State University Rostov-on-Don, 344090 Russia
e-mail: anis@ ipoc.rsu.ru
Received April 10, 2002
Abstract—3-Ethoxycarbonylmethyl- and 3-cyanomethyl-1-amino-2-methylbenzimidazolium chlorides cyclized at
treatment with acetic anhydride in the presence of potassium carbonate to afford a mixture of derivatives of
pyrazolo[1,5-a]benzimidazole and 4-aminopyrrolo[1,2-a]benzimidazole. Therewith in the first case prevails the
process of pyrazole ring fusion, and in the latter pyrrole ring is fused. 3-Aroyl(thenoyl)methyl-1-amino-2-
methylbenzimidazolium bromides under the same conditions are converted into 1-aroyl(thenoyl)-2-methyl- and 2-
4-acetamido-3-acetylpyrrolo[1,2-a]benzimidazoles
.
3-Alkoxycarbonylmethyl- and 3-cyanomethyl-1-alkyl-
2-methylbenzimidazolium salts were reported [1] to
cyclize under treatment with carboxylic acids anhydrides
in the presence of bases furnishing functionally-substituted
2,4-dialkylpyrrolo[1,2-a]benzimidazoles. The pyrrole ring
closure occurred here involving an activated methyl group
in substituents in the position 3 of benzimidazole ring.
The cations of 1-amino-3-alkyl-2-methylbenzimidazolium
transformed under these conditions involving N-amino-
and 2-methyl groups into 2,4-dialkyl-pyrazolo[1,5-a]-
benzimidazoles [2].
The double recrystallization of the mixture from
ethanol afforded in the pure state pyrazolobenzimidazole
IV whose structure is confirmed by the presence in the
1H NMR spectrum of the signal from the protons of
methylene group at d 5.7 ppm. In the IR spectrum of
compound IV appear two strong bands at 1630 and 1733
cm assigned to the absorption of acetyl and ester
carbonyls respectively. At short boiling in concn. HCl
ether IV readily yielded acid VII.
–1
We failed to isolate 4-diacetylaminopyrrolo[1,2-a]-
benzimidazole V from the reaction mixture by chromato-
graphy due to very close values of Rf of compounds IV
and V. Therefore by treatment with concn. NH4OH com-
pound V (Rf 0.6) was converted into monoacetylamino
derivative VI (Rf 0.3). In the IR spectrum of compound
VI alongside the three absorption band of carbonyl groups
In the present study we investigated the features of
reaction of acetic anhydride and potassium carbonate with
3-ethoxycarbonylmethyl- I, 3-cyanomethyl- II, and 3-
acylmethyl-1-amino-2-methylbenzimidazolium IIIa–c
salts which presumably might undergo cyclization both
into derivatives of 4-aminopyrrolo[1,2-a]benzimidazole
and pyrazolo[1,5-a]benzimidazole.
–1
at 1630, 1685, and 1710 cm appears a band nNH at 3250
–1
cm . The proton signal of the NH group in the 1H NMR
Initial chlorides I and II were obtained by fusion of 1-
amino-2-methylbenzimidazole with the corresponding
monochloroacetic acid derivatives. The synthesys of
ketones III is described in [3].
spectrum is observed at 9.4 ppm (Scheme 1).
The cyclization of 1-amino-2-methyl-3-cyano-methyl-
benzimidazolium chloride II under the same conditions
also afforded a mixture of the corresponding compounds
from the pyrrolo- and pyrazolobenzimidazole series.
However here the main reaction product was 1-cyano-
pyrrolobenzimidazole VIII, and the yield of 4-cyano-
methylpyrazolo[1,5-a]benzimidazole IX did not exceed
14–15% (Scheme 2).
It was established that at boiling of ether I with acetic
anhydride and potassium carbonate formed a mixture of
3-acetyl-2-methyl-4-ethoxycarbonylmethylpyrazolo[1,5-
a]benzimidazole IV and 3-acetyl-4-di-acetylamino-1-
ethoxycarbonylpyrrolo[1,2-a]benzimidazole V in a ratio
~ 4:1 (according to 1H NMR spectrum).
Diacetylamino derivative VIII partially loses one of
its N-acetyl groups even in the process of chromato-
†
Deceased.
1070-4280/04/4002-0221Ó2004 MAIK “Nauka/Interperiodica”

222
KUZ’MENKO et al.
Scheme 1.
&+ &22(W
0H
&22(W
0H
$F 2ꢀꢁ. &2
1
1
1
1
1
ꢀ
1
0H
1
$F
$F
1+ &O
(W22&+ &
$F 1
B
,
9ꢀꢁꢂꢃꢁꢁꢁꢂꢄꢅ
,9ꢀꢁꢄꢆꢅ
+
1+ 2+
&22(W
0H
1
1
1
1
0H
1
$F
$F
+22&+ &
9,,
$F+1
9,
Scheme 2.
&+ &1
0H
&1
1
1
$F 2ꢀꢁ. &2
1
1
1
ꢀ
1
0H
1
0H
$F
$F
&O
1+
$F 1
1&+ &
B
B
,,
,;ꢀꢁꢂꢃꢁꢁꢁꢂꢄꢅ
9,,,ꢀꢁꢆꢇꢁꢁꢁꢇꢈꢅ
1+ 2+
&1
+
1+ 2+
&1
0H
&1
1
1
+
1
1
1
0H
1
0H
$F
$F
$F
+ 1
$F+1
Qꢉ2 1& + +& 1
;,,
;
;,
graphic separation on alumina giving compound X. The
latter was obtained in a quantitative yield at treating
diacetylamine VIII with the concn NH4OH. Therewith
in the IR spectrum of compound X were retained two
3 [3], amine XI cleanly formed Schiff bases of XII type
at heating with aromatic aldehydes in acetic acid.
In the IR spectra of 1-cyanopyrrolobenzimidazoles
VIII, X–XII a strong absorption band of the cyano group
–1
absorption band of C=O groups at 1632 and 1650 cm
–1
is observed in the region 2200 cm , whereas in the
present in the spectrum of the initial compound VIII and
spectra of initial salt II and 4-cyanomethylpyr-
azolobenzimidazole IX where this group is not conjugated
with the heterocycle this band does not appear.
–1
the band in the 1736 cm region disappeared.
The boiling of acetamides VIII and X in concn
HCl for 20–25 min resulted in pyrrolobenzimidazole
XI unsubstituted at the N-amino group. Interestingly,
the 3-actyl group wasnot affected although as a rule
1- and 3—acylpyrrolobenzimidazoles were easily
hydrolysable in acid media [1, 4]. In contrast to 4-amino-
pyrrolo-benzimidazoles with unoccupied positions 1 and
We believe that the considerably different ratio of
derivatives of pyrrolo[1,2-a]- and pyrazolo[1,5-a]benz-
imidazoles arising at cyclization of chlorides I and II
originates from unlike CH-acidity of 3-methylene groups
in these salts. In keeping with the generally accepted
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 2 2004

223
CYCLIZATION OF 3-ETHOXYCARBONYLMETHYL-...
Scheme 3.
&+ 5
&+ 5
&$F
1
1
1
0H
&O
1
1+
1+
,ꢀꢁ,,
$
B
&+ 5
&+5
1
1
$F
$F
$F
1
&
1
&
$F
1+
1+
5
1
1
1
1
0H
1
0H
$F
$F
5+ &
$F 1
9ꢀꢁ9,,,
,9ꢀꢁ,;
R = COOEt (I, IV, V), CN (II, VIII, IX).
views both pyrazolo[1,5-a]benzimidazoles and pyrrolo-
[1,2-a]benzimidazoles should form under these conditions
through the same intermediate compound, acetyl-
substituted methylene anhydrobase A (Scheme 3) [5].
1-Amino-3-acylmethyl-2-methylbenzimidazolium
bromides IIIa–IIIc like cyanomethyl salt II in reaction
with acetic anhydride and potassium carbonate more
favored conversion into pyrrolo[1,2-a]benzimidazoles. We
failed to detect in this case formation of pyrazolo[1,5-a]-
benzimidazole derivatives. The cyclization of 3-phenacyl-
and 3-thenoylmethyl derivatives IIIa, IIIc afforded
several products but here it was due to the possibility to
build up the pyrrole ring both involving the activated
methylene group and ketone carbonyl of the 3-acylmethyl
moiety in the initial salt. 1-Amino-2-methyl-3-(4-
nitrophenacyl)benzimidazolium bromide IIIb is an
exception for it selectively reacts involving the keto group
to afford light-yellow 3-acetyl-4-diacetylamino-2-(4-
nitrophenyl)pyrrolobenzimidazole XIII (yield 75%) that
easily loses one of its N-acetyl groups similarly to
compound VIII.
It is clear that the cyclization of diacetylmethineAoccurs
rather involving the arising in the reaction mixture more
nucleophilic carbanion than the neutral N-amino group
(as shown in [6], formation of an N-anion under these
conditions is hardly possible). The values of s constants
of groups COOEt (0.398) and CN (0.678) [7] show that
the C-anion would be easier generated from the
cyanomethyl salt II resulting in the prevailing formation
of pyrrolobenzimidazole VIII. Inasmuch as the CH-
acidity of the 3-methylene group in ester I is lower,
dominates the cyclization process involving the N-amino
group of pyrazolobenzimidazole IV.
The problem whether the precursors of compounds
IV, V, VIII and IX are mono- or diacetylmethines of A
type is open to discussion. However our experiments with
ketones III has unambiguously demonstrated as we
discuss below that the presence of the C-acetyl sub-
stituents in the final reaction products XIII, XIVa, XIVc
originates just from acetylation of the methylene
anhydrobases and not of tricyclic systems.
The structure of compound XIII as 2-(4-nitrophenyl)
derivative was proved by formation at its acid hydrolysis
of orange 4-amino-2-(4-nitrophenyl)pyrrolobenzimidazole
XIV. It should be noted that the attempt to obtain this
pyrrolobenzimidazole from salt IIIb under Chichibabin
reaction conditions failed [3]. In the 1H NMR spectrum
of compound XIV the signals of protons H3 and H1 appear
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 2 2004

224
KUZ’MENKO et al.
Scheme 4.
&+ &2 2
&+ 2
12
12
&
1
1
1
0H
%U
1
&+$F
1+
1+
,,,E
$F
1
1
1
$F 2
+
1
12
1
12
1
12
1$F $F
1+$F
1+
;,,,
;9
;,9
Scheme 5.
&25
0H
&+ &25
&+ &25
0H
1
1
$F 2ꢀꢁ. &2
1
&20H
1
1
&
1
&20H
$F
%U
1+
1+
1+$F
,,, ꢀꢁ,,,F
;9, ꢀꢁ;9,F
III, XVI, R = Ph (a), 2-thienyl (c).
as doublets (J 1.46 Hz) due to coupling with each other,
and they are observed at d 6.01 and 8.0 ppm respectively
(cf. [4, 8]). On the contrary, in the spectrum of acetyl
derivative XIII the signal of H3 proton is lacking, and the
peak of the H1 proton turns out as a singlet thus indicating
that the C-acetyl group is attached to position 3 of the
heterosystem. A direct acetylation of 4-aminopyrrolo-
benzimidazole XIV gives 1-acetyl isomer XV in a good
yield. Therefore it may be assumed that the formation of
a 3-acetyl substituents in compound XIII is due to the
reaction proceeding through B intermediate.
high solubility in the majority of organic solvents. However
it proved that a colorless low-melting precipitate obtained
after separation of compound XVIa on boiling for a short
time in the hydrochloric acid converted into a known 4-
amino-2-phenylpyrrolo[1,2-a]benzimidazole [3]. 1-Acetyl-
4-diacetylamino-2-phenylpyrrolo[1,2-a]-benzimidazole
XVII obtained by acetylation of the latter was not similar
to the cyclization product of ketone IIIa and thus
presumably the unidentified compound was an analog of
3-acetylpyrrolobenzimidazole XIII.
In contrast to ketones IIIa and IIIb the cyclization of
1-amino-2-methyl-3-(2-thenoylmethyl)benzimidazolium
bromide IIIc occurred predominantly with participation
of the methylene and not the carbonyl group of the
thenoylmethyl fragment affording yellow 3-acetyl-2-
methyl-1-(2-thenoyl)pyrrolobenzimidazole XVIc in 57–
60% yield.
As already mentioned, from 1-amino-2-methyl-3-
phenacylbenzimidazolium bromide IIIa by treating with
acetic anhydride and potassium carbonate a mixture of
two compounds was obtained to one of which was
assigned the structure of 1-benzoyl-2-methylpyrrolo-
benzimidazole XVIa (yield 22%). Actually, only the
presence of a C-benzoyl substituent can be responsible
both for the bright yellow color of compound XVIa and
for the isolation of benzoic acid from its hydrolysis
Apparently the reactivity of the keto group here is
due to the conjugation with the p-rich thiophene ring.
Taking into account the existing data on lack of further
acetylation of 1-acylpyrrolobenzimidazoles even under
very severe conditions [9] the presence of 3-acetyl
substituents in compounds XVIa, c can be rationalized
1
products. The IR and H NMR spectra are also
completely consistent with structure XVIa.
We failed to isolate in the individual state the main
product of salt IIIa cyclization because of its lability and
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 2 2004

225
CYCLIZATION OF 3-ETHOXYCARBONYLMETHYL-...
only by assuming intermediate formation of diacetylated
methylene anhydrobases of A type.
The combined mother liquors containing compounds
IV and V were evaporated to dryness, the residue was
dissolved in 10 ml of chloroform, and the solution was
shaken for 4 h at 20–25°C with 1 ml of concn. NH4OH.
Then the chloroform solution was separated, evaporated
till the volume of 5 ml, and subjected to chromatography
EXPERIMENTAL
IR spectra were recorded on spectrophotometer
Specord 75IR from mulls in mineral oil. 1H NMR spectra
were registered on spectrometer Unity-300 (300 MHz).
The reaction progress was monitored and the homogeneity
of the compounds synthesized was checked by TLC on
plates with Al2O3 of the III activity grade, eluent
chloroform, development in iodine vapor in a humid
chamber.
on a column (20´200 mm) packed with Al2O3, eluent
chloroformAs first fraction with Rf 0.6 was additionally
obtained 0.24 g of pyrazolobenzimidazole IV. Yield
1.16 g (64%), mp 171–172°C (from EtOH). IR spectrum,
–1
cm : 1630 (COMe), 1733 (COOEt). 1H NMR spectrum,
d, ppm: 1.20 t (3H, CH2CH3, J7.2 Hz), 2.43 s (3H, CH3),
2.63 s (3H, COCH3), 4.18 q (2H, CH2CH3, J 7.2 Hz),
5.57 s (2H, CH2), 7.28 m (3H, H5–7), 7.79 m (1H, H8).
Found, %: C 64.27; H 5.85; N 14.18. C16H17N3O3.
Calculated, %: C 64.20; H 5.72; N 14.04.
1-Amino-2-methyl-3-ethoxycarbonylmethyl-
benzimidazolium chloride (I). A mixture of 1.47 g
(0.01 mol) of 1-amino-2-methylbenzimidazole [2] and
2.1 ml (0.02 mol) of ethyl monochloroacetate was fused
for 5 min at 100°C. On cooling the melt was ground with
20 ml of acetone, and the precipitate was filtered off.
Yield 2.60 g (97%), colorless crystals, mp 278–279°C
From the second fraction with Rf 0.3 pyrrolo[1,2-a]-
benzimidazole VI was isolated in amount of 0.26 g (yield
13%), mp 186–187°C (from EtOH). IR spectrum, n,
–1
cm : 1630 (COMe), 1685 (NHCOMe), 1710 (COOEt),
1
3250 (NH). H NMR spectrum, d, ppm: 1.46 t (3H,
–1
(EtOH). IR spectrum, cm : 1651 (C=N), 1736 (C=O),
CH2CH3, J 7.1 Hz), 2.21 s (3H, NHCOCH3), 2.48 s (3H,
CH3), 2.69 s (3H, C-COCH3), 4.46 q (2H, CH2CH3,
J 7.1 Hz), 7.21–7.35 m (3H, H5-7), 8.56 d (1H, H8,
J 8.06 Hz), 9.40 s (1H, NH). Found, %: C 63.44; H 5.47;
N 12.42. C18H19N3O4. Calculated, %: C 63.33; H 5.61;
N 12.31.
3130, 3200 (NH2). Found, %: C 53.25; H 6.07; Cl 13.32;
N 15.71. C12H16ClN3O2. Calculated, %: C 53.44; H 5.98;
Cl 13.14; N 15.58.
1-Amino-2-methyl-3-cyanomethylbenzimid-
azolium hydrate chloride (II). A mixture of 1.47 g
(0.01 mol) of 1-amino-2-methylbenzimidazole and 1.3 ml
(0.02 mol) of chloroacetonitrile was fused for 10 min at
110–115°C. On cooling the melt was ground with 20 ml
of acetone, and the precipitate was separated and dried
at 100°C. Yield 1.98 g (82%), colorless crystals that
started to melt at 167–168°C, then again crystallized and
melted for another time at 183–184°C (from EtOH). IR
3-Acetyl-2-methyl-4-carboxymethylpyrazolo-
[1,5-a]benzimidazole (VII). Asolution of 0.6 g (2 mmol)
of ester IV in 10 ml of conc. HCl was boiled for 30 min.
On cooling the separated precipitate was filtered off and
washed with water. Yield 0.50 g(92%), mp 273– 274°C
–1
(from BuOH). IR spectrum, cm : 1629 (COMe), 1727
1
(CO), 3340–3560 (OH). H NMR spectrum, d, ppm:
–1
spectrum, cm : 1640 (C=N), 3121, 3211 (NH2), 3388,
2.40 s (3H, CH3), 2.58 s (3H, COCH3), 5.58 s (2H, CH2),
7.32 t (1H, H7, J 7.54 Hz), 7.37 t (1H, H6, J 7.39 Hz),
7.69 d (1H, H5, J 7.40 Hz), 7.80 d (1H, H8, J 7.54 Hz),
13.04 br.s (1H, OH). Found, %: C 61.82; H 4.91; N 15.32.
C14H13N3O3. Calculated, %: C 61.99; H 4.83; N 15.49.
3464 (H2O). Found, %: C 50.10; H 5.41; Cl 14.58;
N 23.12. C10H11ClN4×H2O. Calculated, %: C 49.90;
H 5.44; Cl 14.73; N 23.28.
3-Acetyl-2-methyl-4-ethoxycarbonylmethyl-
pyrazolo[1,5-a]benzimidazole (IV) and 4-acetamido-
3-acetyl-2-methyl-1-ethoxycarbonylpyrrolo[1,2-
a]benzimidazole (VI). Adispersion of 1.62 g (6 mmol)
of chloride I and 0.83 g (6 mmol) of anhydrous potassium
carbonate in 30 ml of acetic anhydride was heated at
reflux for 3 h. On cooling 60 ml of water was added, and
the precipitate separated after decomposition of excess
acetic anhydride (1.76 g) was filtered off and washed
with water. After two-fold recrystallization from ethanol
0.92 g of pyrazolo[1,5-a]benzimidazole IV was obtained.
Reaction on chloride II with acetic anhydride. A
dispersion of 1.22 g (5 mmol) of salt II and 0.69 g (5
mmol) of potassium carbonate was boiled in 15 ml of
acetic anhydride for 3 h. On cooling the excess acetic
anhydride was decomposed by adding 30 g of ice. The
separated crystals were filtered off, washed with water,
and dried in a vacuum desiccator over P2O5. From this
precipitate (1.25 g) by means of two-fold recrystallization
from butanol was separated 3-acetyl-4-diacetylamino-
2-methyl-1-cyanopyrrolo[1,2-a]benzimidazole (VIII)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 2 2004

226
KUZ’MENKO et al.
in 0.63 g (38%) yield, mp 220–221°C (from BuOH). IR
spectrum, cm : 1632 (COMe), 1650 (NCOMe), 1736
spectrum, d, ppm: 2.59 s (3H, CH3), 2.68 s (3H, COCH3),
7.41 t (1H, H6, J 7.62 Hz), 7.48 t (1H, H7, J 7.47 Hz),
7.83 d (1H, H5, J 7.63 Hz), 7.85 s (1H, N=CH), 7.99 d
(1H, H8, J 7.47 Hz), 8.02 d (2H, H2',6', J 8.73 Hz), 8.33 d
(2H, H3', 5', J 8.72 Hz). Found, %: C 65.34; H 3.83;
N 18.35. C21 H15N5O3. Calculated, %: C 65.45; H 3.92;
N 18.17.
–1
(NCOMe), 2200 (CN). 1H NMR spectrum, d, ppm: 2.44
s (3H, CH3), 2.46 s [6H, N(COCH3)2], 2.62 s (3H, C–
COCH3), 7.26 m (1H, H8), 7.42 m (2H, H6,7), 7.98 m
(1H, H5). Found, %: C 64.40; H 4.63; N 16.58.
C18H16N4O3. Calculated, %: C 64.28; H 4.79; N 16.66.
The butanol mother liquors were treated as described
above for isolation of compounds IV and VI to obtain
0.15 g of 3-acetyl-2-methyl-4-cyanomethylpyr-
azolo[1,5-a]benzimidazole (IX) (yield 12%, Rf 0.6) and
0.28 g of 4-acetamido-3-acetyl-2-methyl-1-cyano-
pyrrolo[1,2-a]benzimidazole (X) (yield 19%, Rf 0,3).
Compound IX has mp 239–240°C (from BuOH). IR
spectrum, cm : 1627 (COMe). H NMR spectrum, d,
ppm: 2.52 s (3H, CH3), 2.70 s (3H, COCH3), 6.19 s (2H,
CH2), 7.50 m (3H, H5–7), 7.87 m (1H, H8). Found, %:
C 66.73; H 4.82; N 22.38. C14H12N4O. Calculated, %:
C 66.65; H 4.79; N 22.21.
3-Acetyl-4-diacetylamino-2-(4-nitrophenyl)pyr-
rolo[1,2-a]benzimidazole (XIII). A solution of 0.82 g
(2 mmol) of salt IIIb and 0.28 g (2 mmol) of potassium
carbonate in 10 ml of acetic anhydride was boiled for
25 min. On cooling the light-yellow precipitate was
filtered off and washed with ether on the filter. Yield
0.63 g (75%), mp 233–234°C (from BuOH). IR spectrum,
–1
1
–1
cm : 1613 (COMe), 1653 (NCOMe), 1760 (NCOMe).
1H NMR spectrum, d, ppm: 1.94 s (3H, COCH3), 2.52 s
[6H, N(COCH3)2], 7.06 s (1H, H1), 7.25 d (1H, H8,
J 7.04 Hz), 7.35 t (1H, H7, J 7.04 Hz), 7.40 t (1H, H6,
J 7.33 Hz), 7.61 d (1H, H5, J 7.33 Hz), 7.63 d (2H, H2', 6'
,
J 8.78 Hz), 8.30 d (2H, H3', 5', J 8.79 Hz). Found, %:
C 63.30; H 4.47; N 13.50. C22H18N4O5. Calculated,
%: C 63.15; H 4.34; N 13.39.
For compound X mp 231–232°C (EtOH). IR spectrum,
–1
n, cm : 1633 (COMe), 1652 (NHCOMe), 2197 (CN),
3198 (NH). 1H NMR spectrum, d, ppm: 2.12 s (3H, CH3),
2.32 s (3H, COCH3), 2.40 s (3H, NHCOCH3), 7.25 m
(3H, H6–8), 7.72 m (1H, H5), 9.20 s (1H, NH). Found, %:
C 65.48; H 4.65; N 19.17. C16H14N4O2. Calculated, %:
C 65.30; H 4.79; N 19.04.
4-Amino-2-(4-nitrophenyl)pyrrolo[1,2-a]-benz-
imidazole (XIV). A solution of 0.84 g (2 mmol) of
compound XIII in 10 ml of conc. HCl was boiled for 15
min. On cooling the precipitate was filtered off, treated
on the filter with 2 ml of concn. NH4OH, and washed
with water to obtain 0.32 g of orange solid.Alkalizing of
the mother liquor provided additional 0.16 g of compound
4-Amino-3-acetyl-2-methyl-1-cyanopyrrolo-[1,2-
a]benzimidazole (XI). A solution of 0.34 g (1 mmol) of
diacetylamino derivative VIII in 10 ml of concn. HCl
was boiled for 20 min. On cooling the precipitate was
filtered off and washed with water. Yield 0.22 g (88%),
XIV. Yield 0.48 g (83%), mp 219–221°C (BuOH). IR
–1
spectrum, cm : 3349, 3440 (NH2). 1H NMR spectrum
,
–1
mp 213–214°C (from 1-BuOH). IR spectrum, n, cm :
d, ppm: 5.75 s (2H, NH2), 6.01 d (1H, H3, 4J 1.76 Hz),
7.10 t (1H, H7, J 7.03 Hz), 7.28 t (1H, H6, J 7.54 Hz),
7.35 d (1H, H8, J 7.03 Hz), 7.71 d (1H, H5, J 7.51 Hz),
7.90 d (2H, H2' 6', J 9.08 Hz), 8.01 d (1H, H1, J 1.47
Hz), 8.20 d (2H, H3',5', J 9.08 Hz). Found, %: C 65.81;
H 4.27; N 19.28. C16H12N4O2. Calculated, %: C 65.75;
H 4.14; N 19.17.
1633 (COMe), 2202 (CN), 3221, 3312 (NH2). 1
H NMR
spectrum, d, ppm: 2.52 s (3H, CH3), 2.58 s (3H, COCH3),
3
4
6.42 s (2H, NH2), 7.34 t (1H, H6, J 8.13, J 1.17 Hz),
7.47 t (1H, H7, 3J 7.47, 4J 1.09 Hz), 7.62 d (1H, H5,
3J 8.13 Hz), 7.76 d (1H, H8, 3J 7.47 Hz). Found, %:
C 66.72; H 4.85; N 22.12. C14H12N4O. Calculated, %:
C 66.65; H 4.79; N 22.21.
4-Acetamido-1-acetyl-2-(4-nitrophenyl)pyrrolo-
[1,2-a]benzimidazole (XV). A solution of 0.29 g
(1 mmol) of 4-aminopyrrolobenzimidazole XIV in 3 ml of
acetic anhydride was boiled for 1 h. On cooling the excess
acetic anhydride was decomposed with 10 ml of water,
Amine XI was obtained in the same way from
reagent X.
3-Acetyl-2-methyl-4-(4-nitrobenzylideneamino)-
1-cyanopyrrolo[1,2-a]benzimidazole (XII). Asolution
of 0.25 g (1 mmol) of 4-aminopyrrolobenzimidazole XI
and 0.15 g (1 mmol) of 4-nitro-benzaldehyde in 3 ml of
acetic acid was boiled for 20 min. On cooling the
separated yellow precipitate was filtered off and washed
with water. Yield 0.31 g (79%), mp 203–204°C ( from
the separated light-yellow precipitate was filtered off
.
Yield 0.30 g (79%), mp 275–276°C (from BuOH). IR
–1
1
spectrum, cm : 1630 (COMe), 1710 (NHCOMe). H
NMR spectrum, d, ppm: 1.45 s (3H, COCH3), 2.13 s
(3H, NHCOCH3), 6.00 s (1H, H3), 7.28 t (1H, H7,
DMF). IR spectrum, cm : 1635 (COMe). H NMR
J 8.40 Hz), 7.37 m (2H, H6, 8), 7.78 d (2H, H2', 6'
,
–1
1
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227
CYCLIZATION OF 3-ETHOXYCARBONYLMETHYL-...
J 8.49 Hz), 8.30 d (2H, H3', 5', J 8.45 Hz), 8.83 d (1H, H5,
J 8.20 Hz), 11.38 s (1H, NH). Found, %: C 63.92;
H 4.38; N 14.75. C20H16N4O4. Calculated, %: C 63.83;
H 4.28; N 14.89.
4-Acetamido-3-acetyl-2-methyl-1-(2-thenoyl)-
pyrrolo[1,2-a]benzimidazole (XVIc) was prepared by
the same procedure as 1-benzoylpyrrolobenzimidazole
XVIa from 0.7 g (2 mmol) of bromide IIIc, 0.28 g
(2 mmol) of potassium carbonate, and 10 ml of acetic
anhydride.After crystallization of the isolated precipitate
from alcohol was obtained 0.44 g (yield 58%) of bright
yellow crystals, mp 254–255°C (from BuOH). IR
4- Acetamido-3-acetyl-1-benzoyl-2-methylpyr-
rolo[1,2-a]benzimidazole (XVIa). A dispersion of
1.38 g (4 mmol) of salt IIIa and 0.55 g (4 mmol) of
potassium carbonate in 15 ml of acetic anhydride was
boiled for 30 min. On cooling 40 ml of water was added,
and after decomposition of excess acetic anhydride the
reaction mixture was alkalized with concn. NH4OH. The
separated precipitate (1.23 g) was filtered off and washed
with water.After crystallization from ethanol was isolated
0.35 g (yield 22%) of lemon-yellow crystals of mp 239–
–1
spectrum, cm : 1600 (2-thenoyl), 1620 (COMe), 1721
1
(NHCOMe), 3270 (NH). H NMR spectrum, d, ppm:
2.14 s (3H, CH3), 2.39 s (3H, COCH3), 2.46 s (3H,
NHCOCH3), 7.29 m (2H, H7,8), 7.40 t (1H, H4', J 8.20 Hz),
7.43 t (1H, H6, J 8.20 Hz), 7.78–7.80 m (2H, H5, 5'),
8.12 d (1H, H3', J 7.69 Hz), 11.47 s (1H, NH). Found, %:
C 63.45; H 4.48; N 11.19; S 8.60. C20H17N3O3S.
Calculated, %: C 63.31; H 4.52; N 11.07; S 8.45.
–1
240°C. IR spectrum, cm : 1602 (COPh), 1640 (COMe),
1
1723 (NHCOMe), 3272 (NH). H NMR spectrum, d,
ppm: 2.05 s (3H, CH3), 2.10 s (3H, COCH3), 2.40 s (3H,
NHCOCH3), 7.20–8.13 m (9H, H arom), 11.38 s (1H,
NH). Found, %: C 70.91; H 4.98; N 11.18. C22H19N3O3.
Calculated, %: C 70.76; H 5.13; N 11.25.
REFERENCES
1. Kovtunenko, V.A. and Babichev, F.S., Ukr.Kkhim. Zh., 1972,
vol. 38, p. 1244. ,
Acid hydrolysis of compound (XVIa). A solution
of 0.37 g (1mmol) of 1-benzoylpyrrolobenzimidazole
XVIa in 5 ml of concn. HCl was boiled for 15 min. The
separated precipitate of benzoic acid was filtered off on
cooling and washed with cold water. Yield 0.09 g (74%),
mp 121–122°C (from water).
2. Kuz’menko, V.V., Komissarov, V.N., and Simonov,A.M., Khim
Geterotsikl. Soed., 1980, p. 814.
3. Kuz’menko, T.A., Kuz’menko, V.V., andAnisimova, V.A., Zh.
Org. Khim., 1996, vol. 32, p. 114.
4. Babichev, F.S., Kutrov, G.P., and Kornilov, M.Yu., Ukr.
Khim.Zh., 1968, vol. 34, p. 1020. ,
At alkalizing the dark-green mother liquor with concn.
NH4OH separated an intractable resinous substance.
5. Kuz’menko, V.V., Pozharskii, A.F. Adv. Heterocycl. Chem.,
1992, vol. 53, p. 190; Prostakov, N.S. and Baktibaev, O.B.,
Usp. Khim., 1975, vol. 44, p. 1661.
1-Acetyl-4-diacetylamino-2-phenylpyrrolo[1,2-a]-
benzimidazole (XVII) was prepared similarly to
compound XV by boiling 0.25 g (1 mmol) of 4-amino-2-
phenylpyrrolo[1,2-a]benzimidazole [3] in 3 ml of acetic
anhydride for 1 h. Yield 0.27 g (74%), mp 174–175°C
6. Kuz’menko, T.A., Kuz’menko, V.V., Pozharskii, A.F.,
Kryshtalyuk, O.V., andAleksandrov, G.G., Khim. Geterotsikl.
Soed., 1992, p. 205.
7. Zhdanov, Yu.A. and Minkin, V.I., Korrelyatsionnyi analiz v
organicheskoi khimii (CorrelationAnalysis in Organic Chem-
istry), Rostov na Donu: Rostov. Gos. Univ., 1966, p. 86.
–1
(from EtOH). IR spectrum, cm : 1620 (COMe), 1740
1
(NCOMe). H NMR spectrum, d, ppm: 2.03 s (3H,
COCH3), 2.49 s [6H, N(COCH3)2], 5.72 s (1H, H3),
7.05 m (1H, H8), 7.33 m (2H, H6, 7), 7.42 m (5H, C6H5),
8. Pozharskii,A.F., Kuz’menko, T.A., Kuz’menko, V.V., Bum-
ber,A.A., Klyuev, N.A., Suslov,A.N., and Chernyshev,A.I.,
Khim. Geterotsikl. Soed., 1984, p. 188.
8.95 m (1H, H5). Found, %:
C
70.64; H 5.27; N 11.37.
9. Kutrov, G.P., Cand. Sci. (Chem.) Dissertation, Kiev, 1971.
C22H19N3O3. Calculated, %: C 70.76; H 5.13; N 11.25.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 2 2004