Benzimidazole annulated new heterocyclic compounds: Synthesis of new polycyclic Pyrazole Derivatives

Article abstract of DOI:10.1002/jhet.867

Several (3) new benzimidazole based polycyclic compounds of potential pharmaceutical interest have been prepared starting from 2-benzimidazolelyl (1,3-dioxo-2-indenylidene) acetonitrile. Unhypothesized, the C=N function of the plausible intermediates was released as HCN rather than a classical nucleophilic addition when treated with bidentate reagents such as hydrazines, 5-amino-1H-1,2,4-triazole, 5-amino-4-cyano-1H-pyrazole and 2-aminobenzimidazole. When compound 3 reacted with active acetonitrile derivatives it afforded new polyfunctional pyridines via elimination of HCN in addition to, new pyrimidine, pyrazine and azepine derivatives.

Full text of DOI:10.1002/jhet.867

806
Benzimidazole Annulated New Heterocyclic Compounds: Synthesis of
New Polycyclic Pyrazole Derivatives
Vol 49
*
Mohamed Ali A. Khalil
Department of Chemistry, Faculty of Science, South Valley University, Aswan 81528, Egypt
*
E-mail: khalil_asw@yahoo.com
Received October 16, 2010
DOI 10.1002/jhet.867
View this article online at wileyonlinelibrary.com.
Several (3) new benzimidazole based polycyclic compounds of potential pharmaceutical interest have
been prepared starting from 2-benzimidazolelyl (1,3-dioxo-2-indenylidene) acetonitrile. Unhypothesized,
the CꢀN function of the plausible intermediates was released as HCN rather than a classical nucleophilic
addition when treated with bidentate reagents such as hydrazines, 5-amino-1H-1,2,4-triazole, 5-amino-4-cy-
ano-1H-pyrazole and 2-aminobenzimidazole. When compound 3 reacted with active acetonitrile derivatives
it afforded new polyfunctional pyridines via elimination of HCN in addition to, new pyrimidine, pyrazine
and azepine derivatives.
J. Heterocyclic Chem., 49, 806 (2012).
INTRODUCTION
contributions in the synthesis of new azole and azine deri-
vatives [28–32], it was thought worthwhile to prepare
some new azole derivatives annulated benzimidazole core,
which might have pharmaceutical action.
Benzimidazole derivatives are some of the most effec-
tive heteroaryl compounds, which are used in the synthesis
of many important drugs such as omeprazole and meben-
dazole [1,2]. Many benzimidazole derivatives have shown
evidence of potential anti-inflammatory and analgesic
activity [3,4]. Some derivatives also have been found to
possess antimicrobial [5], antiviral [6], antifungal [7], anti-
parasitic [8], pesticidal [9], and herbicidal properties [10].
Furthermore, they also play an important role in anticancer
applications [11,12], and cardiovascular diseases treatment
[13]. Recently pyridines and pyrimidines synthesis have
become the focus in numerous publications [14–17].
Biological applications for pyrazol derivates have been
shown considerable interest for their use as muscimol ana-
logs and bacterial metabolites of antipyrine [18–20]. In the
pharmaceutical field, pyrazole derivatives serve as anti-
pyretics, analgesics, anti-inflammatories, antireheumatics,
antiphlogistics, diuretics, ulcer inhibitors, and cardiovascu-
lar agents among others [21–26]. Despite the indan
receiving little attention, new indenothiophene derivative
has been reported [27]. In conjunction with our previous
RESULTS AND DISCUSSION
2-Cyanomethylbenzimidazole 1 effortlessly reacted
with equimolar amount of 1,2,3-indantrione monohy-
drate 2 in ethanol at reflux temperature for 20 min
affording 2-cyano-2-(1,3-dioxo-2-indenylidene) benz-
imidazole 3 (Scheme 1). Formation of 3 proceeded via
an initial condensation reaction of the methylene group
of 2-Cyanomethylbenzimidazole and two hydroxyl
groups of compound 2. The IR spectrum (KBr) of 3
illustrated the presence of absorption bands at v 1680,
1724, and 2220 cmꢁ1 due to CO and CN functions,
1
respectively. Accordingly, the H NMR spectrum of 3
illustrated signals as multiplet at d 7.1–7.9 ppm due to
aromatic and NH protons. In addition, its 13C NMR
exhibited characteristics signals at d 95.3 and 115.2
ppm for the methylene, and the carbonitrile carbons,
© 2012 HeteroCorporation

July 2012
Benzimidazole Annulated New Heterocyclic Compounds: Synthesis of
New Polycyclic Pyrazole Derivatives
807
Scheme 1
while expected signals of carbonyl carbons at 165.1 and
167.5 ppm have been shown. The MS of compound 3
displayed [M]+ at m/z (299, 100%). However, the reactiv-
ity of 3 was explored since it contains an active carbonitrile
and carbonyl functions, which are easily converted to a variety
of other functional groups making it a convenient reactant for
the synthesis of various heterocyclic compounds. Thus, benz-
imidazole 3 reacted easily with hydrazine hydrate in ethanol
solution in the presence of few drops of triethylamine at a re-
flux temperature for 1 h yielding a yellow solid formed during
the reflux. The IR spectrum of the product revealed the
absence of the absorption band due to CN function, and the
presence of bands at 1690, and 3135 cmꢁ1. However, its
1H NMR spectrum illustrated two singlet signals at d 9.2
and 9.3 ppm, and a multiplet at 7.1–7.9 ppm integrated for
eight protons only. Meanwhile, its MS measurement dis-
played M+ at m/z 286 (100) and M+1 at 287 (25%). Based
on these data, it is concluded that, one of the hydrazine hydrate
amine group condensed with the carbonyl oxygen of 3, while
the second amine group of the hydrazine was added to the
activated double bond of 3 forming the intermediate 5, which
subsequently released hydrogen cyanide to furnish the unex-
pected pyrazole compound 6 rather than the pyridazine 4,
which would have been produced as a result of a classical
addition of the amine function to the carbonitrile group.
(Scheme 1).
to the corresponding polycyclic compound 9 when it
reacted with ethyl chloroformate 8 via elimination of
HCl, and ethanol (Scheme 2). Both compounds 7 and 9
illustrated no absorption bands due to NH functions. Nev-
ertheless, absorption bands were recorded at v 1693–1695
and 1710–1725 cmꢁ1 due to CO functions alone. Although
1
the corresponding H NMR spectrum of 7 illustrated one
singlet signal assigned for six protons of two methyl
groups at 2.1 ppm, the spectrum of compound 9 displayed
multiplet due to aromatic protons only. The MS of 7
revealed M+ at m/z at 370 (35%), while of compound 9
m/z at 312 (M+, 100%).
The two hydrogen atoms of pyrazole and imidazole
rings of 6 were released when reacted with each of α-
bromoacetone 10a, α-bromo-acetophenone 10b, and/or 3-
(α-bromoacetyl)-coumarin 10c, respectively yielding pyra-
zine derivatives 11a, 11b, and 11c, respectively, (Scheme
2). The IR spectra of 11 illustrated absorption bands at
1692–1712 cmꢁ1 assigned for CO functions only, with a
complete lack of any absorption bands due to NH
functions. The 1H NMR spectra of 11a illustrated multiplet
at d 7.1–7.9 ppm due to aromatic protons with an addi-
tional two singlet signals at 2.2 and 7.2 ppm for methyl
and pyrazine protons; however, the signal of methyl was
absent in the spectra of 11b and 11c.
As expected, 5-amino-1H-1,2,4-triazole 12, 2-minoben-
zimidazole 14 and 5-amino-1H-3-methylsulfanylpyrazole-
4-carbonitrile 16 derivatives reacted under the same
The pyrazole 6 directly transformed to the diacetyl com-
pound 7 via acylation with acetic anhydride, and cyclized
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M. A. A. Khalil
Vol 49
Scheme 2
hypothesis with compound 3. Annulation of the pyrimidine
ring afforded pyrazole derivatives indenopyrimidotriazole
13, indenopyrimidobenzimidazole 15, and indenopyrimi-
dopyrazole 17, respectively. However, the new pyrazole
derivative 17 was simply converted to the corresponding
new polycyclic pyrazole derivative 18, when refluxed with
hydrazine hydrate in DMF, in the presence of triethylamine
for 2 h via cycloaddition–elimination reaction, (Scheme 3).
In each reaction, the cyano function was released as
HCN and a condensative step led to the stylization product.
The chemical structure of the product was established
based on the elemental and spectral analysis (Scheme 3).
The IR spectra of 13, 15, and 18 illustrated no absorption
band of CN function whereas, an absorption is recorded
as a sharp band in case of compound 17.
by elimination of HCN resulted in the pyridine annulated
products 20a,b, 23 and 25, respectively (Scheme 4).
Furthermore, the pyridines 20 easily reacted with ethyl
chloroformate 8 in DMF in the presence of triethylamine
yielding new imidazolone derivatives 21a,b. The IR spec-
tra of 20a,b demonstrated absorption bands at v 1320,
1692, 1695, and 2220 and 3154–3127 cmꢁ1 assigned for
CS, CO, CN, and NH functions, respectively. Furthermore,
the IR spectra of the 21a,b revealed intense absorption
bands at v 1315, 1682, 1694 and 2221 cmꢁ1 due to CS,
CO, and CN functions, respectively, while the bands of
NH was absent. Meanwhile, an intense absorption bands
appeared at v 3345–3355 cmꢁ1 for the generated amino
group of compounds 24a,b with the lack of cyano absorp-
tion bands at v 2222–2225 cmꢁ1 in the IR spectrum of 23.
The 1H NMR spectra of the products demonstrated gen-
eral features for aromatic protons as multiplet at d 7.1–7.9
ppm. The MS of 20a,b illustrated m/z at 338 (100) and at
354 (87%), as for compounds 21a,b M+ was displayed at
m/z 468 (85) and 380 (100).
New pyridine derivatives were prepared when compound 3
reacted with cyanoacetamide 19a, cyanothioacetamide 19b,
cyanoacetanilides 22a,b, and 2-cyanomethylbenzimidazole 1.
An initial condensation step of the active methylene center
and the carbonyl oxygen at position 3 of compound 3 followed
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Benzimidazole Annulated New Heterocyclic Compounds: Synthesis of
New Polycyclic Pyrazole Derivatives
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Scheme 3
EXPERIMENTAL
Seven-membered benzimidazole based compounds
28a–c were prepared via boiling compound 3 with an equi-
molar amounts of 2-aminophenol derivatives 26a–c for
about 3 h, plausibly via formation of the condensative
intermediate 27, which subsequently afforded 28a–c after
losing HCN (Scheme 5).
The compound 28a isolated during reflux was found insolu-
ble in most organic solvents. The IR spectra of 28a–c revealed
absorption bands at v 1672–1685 and 3219–3215 cmꢁ1
assigned for CO and NH functions. 1H NMR spectra of 28b,
c illustrated multiplet signals at d 7.1–7.8 ppm due to the
aromatic and NH protons. The MS of 28a–c was displayed at
m/z 363 (78), 379 (100), and 362 (100%), respectively.
Nevertheless, the new benzimidazole annulated polycy-
clic azoles and azines have been prepared using inexpen-
sive laboratory chemicals through facile and convenient
reactions.
All melting points are measured using Galenkamp melting
point apparatus and are uncorrected. Elemental analyses were
carried out at the Micro analytical Center of Cairo University.
IR (KBr pellets υ = cmꢁ1) spectra were determined in 1650 FTIR
1
instrument (Cairo University). H NMR and 13C NMR spectra
(d = ppm) (DMSO-d) were accomplished using 300 MHz NMR
spectrometer and mass spectroscopy were recorded on GCMS-
QP-1000 EX spectrometer (Cairo University).
Preparation of 2-cyano-2-(1,3-dioxo-2-indenylidene)
benzimidazole (3). A mixture of 1,2,3-indan-trione monohydrate
2 (0.18 g, 0.001 mol) and 2-cyanomethylbenzimidazole 1 (0.16 g,
0.001 mol) in 40 mL of ethanol was refluxed for 20 min. A red
crystalline product that was formed, filtered, washed with ethanol,
and recrystallized from dimethylformamide.
Yield: 0.25 g (83%). mp 295–97ꢂC. IR: υ 1680 (CO), 1724
1
(CO), 2220 (CN). H NMR: d 7.1–7.9 (m, 8H, Ar-H+NH). 13C
NMR: 95.3 (C—CN), 115.2 (CN), 121.1, 124.4, 125.8, 130.1
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M. A. A. Khalil
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Scheme 4
(Ph), 122.5, 126.9, 128.7, 132.6 (Ph), 140.1 (C-2-inden), 142.2
(C-2-benzimid.), 165.1 (CO), 167.5 (CO). Ms: m/z 299 (M+,
100%). Anal. Calcd for C18H9N3O2 (299.29): C 72.24, H 3.03,
N 14.04. Found: C 72.35, H 3.11, N 14.17.
Preparation of 3-(1H-benzimidazol-2-yl)-2H-indeno[3,2-c]
pyrazole-4-one (6). A mixture of 1 (0.8 g, 0.003 mol) and 40
mL of ethanol was warmed for 5 min, then 0.1 mL (excess) of
hydrazine hydrate was added whereupon the suspension was
Scheme 5
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Benzimidazole Annulated New Heterocyclic Compounds: Synthesis of
New Polycyclic Pyrazole Derivatives
811
turned to a clear yellow solution and was refluxed for 1 h. A
yellow crystalline product that precipitated during the reflux was
filtered, washed with ethanol, and recrystallized from dioxane.
The pyridine solution was evaporated under vacuum, and the
residue was washed with methanol producing a brownish
powder, which was isolated by filtration, washed, and
crystallized from DMF furnishing compound 13. Accordingly,
equimolar amounts of compound 6 reacted with 0.22 g of
Yield: 0.6 g (78%). mp 320–22ꢂC. IR: υ 1690 (CO), 3135
1
(NH). H NMR: d 7.1–7.9 (m, 8H, Ar-H), 9.2 (s, 1H, NH), 9.3
(s, 1H, NH). 13C NMR: 121.1, 124.4, 125.8, 130.1 (Ph), 121.5,
124.9, 126.7, 131.6 (Ph), 167.5 (CO). MS: m/z 286 (M+,
100%). Anal. Calcd for C17H10N4O (286.28): C 71.32, H 3.52,
N 19.57. Found: C 71.46, H 3.67, N 19.79.
2-aminobenzimidazole 14 and 0.26
g
of 5-amino-3-
methylsulfanyl-1H-pyrazole-4-carbonitrile 16 under the same
reaction conditions affording 15 and 17, respectively.
10-(1H-Benzimdazole-2-yl)indeno[1,2:4,5]pyrimido[1,2-b]
[1,2,4] triazole-9-one (13). Yield: 0.3 g (65%), mp 265–67ꢂC.
IR: υ 1698 (CO), 3214 (NH). 1H NMR: d 7.1–7.9 (m, 8H,
Ar-H), 8.1 (s, 1H, triazole-H), 9.6 (s, 1H, NH). MS: m/z 337
(M+, 55%). Anal. Calcd for C19H9N6O (337.32): C 67.65, H
2.69, N 24.9. Found: C 67.78, H 2.80, N 25.1.
12-(1H-Benzimidazole-2-yl)indeno[1,2:4,5]pyrimido[1,2-a]
benz-imidazole-11-one (15). Yield: 0.16 g (62%), mp 285–
87ꢂC, pale yellow (DMF). IR: υ 1695 (CO), 3222 (NH). 1H
NMR: d 7.1–7.9 (m, 12H, Ar-H), 9.2 (s, 1H, NH). MS: m/z
387 (M+, 75%). Anal. Calcd for C24H13N5O (387.40): C
74.41, H 3.38, N 18.08. Found: C 74.56, H 3.49, N 18.15.
4-(1H-Benzimdazole-2-yl)-1-methylsulfanyl-5-oxo-indeno
Preparation of 2-acetyl-3-(1-acetyl-benzimidazole-2-yl)
indeno[1,2-c]pyrazol-4(2H)-one (7). A mixture of 6 (0.8 g,
0.003 mol) and 20 mL of acetic anhydride was refluxed for 1 h,
the acetic anhydride was evaporated under vacuum. The residue
was washed thoroughly with cold water several times (25 mL
each), and was extracted with hot 10 mL methanol three times.
The combination of the methanol was concentrated whereupon
a colorless product was isolated, filtered, washed with ethanol,
and recrystallized from dioxane.
Yield: 0.5 g (50%). mp 283–84ꢂC. IR: υ 1693, 1715 (CO). 1H
NMR: d 2.1 (s, 6H, 2 CH3), 7.1–7.9 (m, 8H, Ar-H). MS: m/z 370
(M+, 35%). Anal. Calcd for C21H14N4O3 (370.37): C 68.81, H
3.81, N 15.13. Found: C 68.98, H 3.90, N 15.40.
Preparation of benzimidazo[100,200:50,10]imidazo[40,30:1,5]
pyrazolo[4,3-b]- indene-3,12-dione (9). A mixture of 6 (0.8 g,
0.003 mol) and ethyl chloroformate 8 (0.33 g, 0.003 mol) was
refluxed for 3 h in 20 mL of dioxane in the presence of 0.1 mL
of triethylamine. The mixture was evaporated under vacuum,
and the residue was triturated with 15 mL cold methanol,
forming a colorless product, which was filtered, washed with
methanol, and crystallized from ethanol.
Yield: 0.72 g (82%). m.p. 265–67ꢂC. IR: υ 1693, 1695, (CO).
1H NMR: d 7.1–7.9 (m, 8H, Ar-H). MS: m/z 312 (M+, 100%).
Anal. Calcd for C18H8N4O2 (312.29): C 69.23, H 2.58, N
17.94. Found: C 69.35, H 2.73, N 18.11.
[1,2:4,5] pyrimido-[1,2-b]pyrazole-11-carbonitrile (17).
Yield:
0.16 g (62%), mp 280ꢂC, pale yellow (DMF). IR: υ 1692 (CO),
2225 (CN), 3222 (NH). 1H NMR: d 3.4 (s, 3H, SCH3), 7.1–7.9 (m,
8H, Ar-H), 9.6 (s, 1H, NH). MS: m/z 408 (M+, 100%). Anal. Calcd
for C22H12N6OS (408.44): C 64.69, H 2.96, N 20.57, S 7.85. Found:
C 64.81, H 3.11, N 20.69, S 7.94.
3-Amino-10-(1H-benzimdazole-2-yl)indeno[1,2:4,5]pyrimido
[1,2: 5,1]- pyrazolo[3,4-c]pyrazol-11-one (18).. A mixture of
10 (0.5 g, 0.0013 mol) and hydrazine hydrate 0.1 g, (excess)
was refluxed for 2 h in 10 mL of DMF in the presence of few
drops of triethylamine. The solution was evaporated under
vacuum, and the residue was washed with methanol resulting in
a pale yellow powder that was isolated by filtration, washed,
and crystallized from DMF.
General procedure for preparation of 4-methylbenzimidazo
[100,200:10,20]-pyrazino[30,40:1,5]pyrazolo[4,3-b]indene-12-one
(11a) and its derivatives (11b,c). A mixture of 6 (0.8 g,
0.003 mol) and bromoacetone 10a (0.41 g ,0.003 mol) was
refluxed for 4 h. in 20 mL of dioxane in the presence of
triethylamine (0.1 mL). A colorless crystalline product was
isolated during reflux, filtered, washed with dioxane, and
recrystallized from DMF. In analogy, equimolar amounts of
compound 6 and 2-bromo-acetophenone 10b (0.59 g), and 3-
(bromoacetyl)coumarin 10c (0.8 g) reacted under the same
reaction conditions affording 11b and 11c, respectively.
Compound 11a. Yield: 0.65 g (72%). mp 310–12ꢂC. IR: υ 1693
(CO). 1H NMR: d 2.2 (s, 3H, CH3),7.2 (s, 1H, pyrazine-H), 7.1–7.9
(m, 8H, Ar-H). MS: m/z 324 (M+, 75%). Anal. Calcd for
C20H12N4O (324.34): C 74.06, H 3.73, N 17.27. Found: C 74.21, H
3.89, N 17.41.
Yield: 0.3 g (64%), mp 188–90ꢂC. IR: υ 1699 (CO), 3222 (NH), 3326
(NH2). 1H NMR: d 6.4 (s, 2H, NH2), 7.1–7.9 (m, 9H, Ar-H + NH),
8.6 (s, 1H, NH). MS: m/z 390 (M+, 80%). Anal. Calcd for
C21H12N8O (392.38): C 64.28, H 3.08, N 28.56. Found: C 64.43,
H 3.25, N 28.72.
Reaction of compound 3 with the active methylene compounds:
Preparation of 9-(1H-benzimd-azole-2-yl)-1,2(H)-oxo-pyrido
[2,1-c]indene-3-carbonitrile (20a) and its 2-thioxo derivative
(20b). A mixture of 3 (0.5 g, 0.002 mol) and cyanoacetamide 19a
(0.14 g, 0.002 mol) was refluxed for 3 h in 10 mL of pyridine. The
solution was evaporated under vacuum, and the residue was washed
with acidified cold water several times, and triturated with methanol
producing a pale brown powder that was isolated by filtration,
washed, and crystallized from DMF. Similarly, compound 3 reacted
with 0.17 g of cyanothioacetamide 19b (0.002 mol) under the same
reaction conditions affording thioxopyridine 20b.
Compound 11b. Yield: 0.8 g (74%). mp 280–81ꢂC. IR: υ 1695
(CO). 1H NMR: d 7.1–7.9 (m, 14H, Ar-H). MS: m/z 386 (M+, 85%).
Anal. Calcd for C25H14N4O (386.41): C 77.71, H 3.65, N 14.50.
Found: C 77.84, H 3.78, N 14.65.
Compound 20a. Yield: 0.35 g (61%), mp 280–81ꢂC. IR: υ
1685, 1692 (CO), 2220 (CN), 3223, 3225 (NH). 1H NMR: d
7.1–7.9 (m, 9H, Ar-H + NH), 9.3 (s, 1H, NH). MS: m/z 338
(M+, 100%). Anal. Calcd for C20H10N4O2 (338.33): C 71.00, H
2.98, N 16.56. Found: C 71.14, H 3.13, N 16.69.
Compound 11c. Yield: 0.65 g (50%). mp 340–42ꢂC. IR: υ 1698,
1705 (CO). 1H NMR: d 7.1–7.9 (m, 14H, Ar-H). MS: m/z 454
(M+, 77%). Anal. Calcd for C28H14N4O3 (454.43): C 74.01, H 3.10,
N 12.33. Found: C 74.12, H 3.26, N 12.48.
Compound 20b. Yield: 0.45 g (75%), mp 292ꢂC, brownish
yellow (DMF). IR: υ 1320 (CS), 1695 (CO), 2220 (CN), 3154,
3227 (NH). 1H NMR: d 7.1–7.9 (m, 9H, Ar-H + NH), 8.7 (s, 1H,
NH). MS: m/z 354 (M+, 87%). Anal. Calcd for C20H10N4OS
(354.39): C 67.78, H 2.84, N 15.81, S 9.05. Found: C 67.91, H
3.1, N 15.96, S 9.16.
General procedure for the reaction with amino compounds.
A mixture of 6 (0.4 g, 0.004 mol) and 5-amino-1,2,4–1H-triazole
12 (0.28 g, 0.004 mol) was refluxed for 3 h in 10 mL of pyridine.
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General method for the reaction of 20a,b with ethyl
12-(1-H-Benzimidazole-2-yl)-11-oxo-benzimidazo[10,20:1,2]pyrido
[4,5-b]-indene-6-carbonitrile (25). An equivalent amounts of 3 (0.5 g,
0.002 mol) and 2-cyanomethylbenz-imidazole (1) (0.26 g, 0.002 mol)
were refluxed for 3 h in 15 mL of pyridine. The solution was
evaporated under vacuum, the residue was washed several time with
acidified cold water, and triturated with 20 mL hot methanol
producing a brown powder ultimately isolated by filtration, washed,
and crystallized from DMF.
chloroformate. An equivalent amounts of 20a (0.5 g, 0.0015
mol) and ethyl chloroformate (8) (0.16 g, 0.0015 mol) were
refluxed for 2 h in 10 mL of DMF in the presence of few drops
of triethylamine. The solution was evaporated under vacuum,
and the residue was triturated with methanol resulting in a
yellowish powder (21a). The yellowish powder was isolated by
filtration, washed, and crystallized from DMF. Similarly, of
compound 20b (0.5 g) reacted with ethyl chloroformate (8)
(0.15 g, 0.0015 mol) under the same reaction conditions
affording the thioxo derivative 21b.
Yield: 0.4 g (58%), m.p. 320–22ꢂC. IR: υ 1690 (CO), 2223
1
(CN), 3115 (NH). H NMR : d 7.1–7.9 (m, 13H, Ar-H + NH).
MS: m/z 411 (M+, 72%). Anal. Calcd for C26H13N5O (411.42):
C 75.90, H 3.18, N 17.20. Found: C 76.07, H 3.37, N 17.37.
General procedure for preparation of 6-(1H-benzimidazole-
2-yl)indeno-[1,2-b][1,5]-benzoxazepine-7-one (28a) and its
derivatives (28b and 28c). An equivalent amounts of 3 (0.5 g,
0.002 mol) and of 2-aminophenol 26a (0.18 g, 0.002 mol) were
refluxed for 3 h in 15 mL of pyridine. The solution was
evaporated under vacuum, and the residue was washed several
times with acidified cold water, and triturated with methanol
producing a brown powder (28a). In due course, the brown
powder was isolated by filtration from the hot solution and found
insoluble in most organic solvents.
2,4,12-Trioxo-benzimidazo[100,200:50,10]imidazo[40,30:1,2]pyrido
[3,4-b]-indene-1-carbonitrile (21a). Yield: 0.45 g (83%), mp
1
223–25ꢂC. IR: υ 1682, 1685, 1692 (CO), 2221(CN). H NMR: d
7.1–7.9 (m, 8H, Ar-H). MS: m/z 470 (M+2, 100), 468 (M+, 65%).
Anal. Calcd for C21H8N4O3 (364.32): C 69.23, H 2.21, N 15.38.
Found: C 69.41, H 2.36, N 15.55.
Compound 21b. Yield: 0.48 g (86%), mp 275–77ꢂC. IR: υ
1315 (CS), 1688, 1694 (CO), 2221(CN). 1H NMR: d 7.1–7.9
(m, 8H, Ar-H). MS: m/z 380 (M+, 100%). Anal. Calcd for
C21H8N4O2S (380.38): C 66.31, H 2.12, N 14.73, S 8.43.
Found: C 66.48, H 2.38, N 14.90, S 8.59.
General procedure for preparation of 9-(1H-benzimdazole-2-yl)-
1,2(H)-2-oxo-indeno[2,1-c]-1-phenyl-pyridine-3-carbonitrile
(23a) and its 1-thiazolyle derivative (23b). An equivalent
amounts of 3 (0.6 g, 0.002 mol) and of cyanoacetanilide 22a
(0.32 g, 0.002 mol) were refluxed for 3 h in 10 mL of pyridine
solution. The solution was evaporated under vacuum, the
residue was washed thoroughly with acidified cold water, and
triturated with methanol, producing a brownish powder. The
brownish powder was isolated by filtration, washed, and
crystallized from DMF. Under same reaction conditions, the
thiazolyl derivative 22b was prepared.
Each of 2-aminothiophenol 26b (0.2 g) and 2-phenylenedia-
mine 26c (0.18 g) reacted similarly with compound 3 to yield
the corresponding 1,5-benzothiazepine 28b and 1,5-benzodiaze-
pine 28c, respectively.
Compound 28a. Yield: 0.4 g (67%), mp 340–42ꢂC. IR: υ 1672
(CO), 3215 (NH). MS: m/z 363 (M+, 78%). Anal. Calcd for
C23H13N3O2 (363.37): C 76.02, H 3.60, N 11.56. Found: C
76.18, H 3.76, N 11.73.
Compound 28b. Yield: 0.5 g (83%), mp 352–45ꢂC. IR: υ 1680
(CO), 3222 (NH). 1H NMR: d 7.1–7.9 (m, 13H, Ar-H + NH). MS:
m/z 379 (M+, 100%). Anal. Calcd for C23H13N3OS (379.44): C
72.80, H 3.45, N 11.07, S 8.45. Found: C 72.97, H 3.67, N
11.23, S 8. 63.
Compound 23a. Yield 0.54g (77%), mp 320–22ꢂC. IR: υ 1690,
1
1694 (CO), 2225 (CN), 3134 (NH). H NMR: d 7.1–7.9 (m, 14H,
Compound 28c. Yield: 0.38 g (63%), mp 330–32ꢂC. IR: υ
Ar-H+NH). MS: m/z 414 (M+, 100%). Anal. Calcd for C26H14N4O2
(414.42): C 75.35, H 3.40, N 13.52. Found: C 75.52, H 3.56, N 13.69.
Compound 23b. Yield 0.5g (71%), mp 340–42ꢂC, green (DMF).
1
1685 (CO), 3215, 3213 (NH). H NMR: d 7.1–7.9 (m, 14H, Ar-
H + NH). MS: m/z 362 (M+, 100%). Anal. Calcd for
C23H14N4O (362.39): C 76.28, H 3.89, N 15.46. Found:
C76.42, H 4.08, N 15.63.
1
IR: υ 1320 (CS), 1695, 1715 (CO), 2222 (CN), 3134 (NH). H
NMR: d 7.1–7.9 (m, 14H, Ar-H+NH). MS: m/z 421 (M+, 94%).
Anal. Calcd for C23H11N5O2S (421.44): C 65.55, H 2.63, N 16.62, S
7.61. Found: C 65.72, H 2.80, N 16.80, S 7.77.
Reaction of 23a,b with hydrazine hydrate: Preparation of
1-amino-5(1H-benzimidazole-2-yl)-4(N)-phenyl-indeno
[2,3:3,4] pyrido[6,5-c]pyrazole-6-one 24a and its 2-thiazolyl
derivative 24b. An equivalent amounts of 23a and hydrazine
hydrate 0.1 g (excess) were refluxed for 2 h in 15 mL of DMF.
The solution was evaporated under vacuum, the residue was
triturated with methanol producing a yellow powder of 24a,
which was isolated by filtration, washed, and crystallized from
DMF. Similarly, compound 23b reacted with hydrazine hydrate
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Compound 24a. Yield: 0.4 g (75%), mp. 215–17 0C. IR: v 1693
1
(CO), 3115 (NH), 3355 (NH2). H NMR: d 6.3 (s, 2H, NH2), 7.1–
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Compound 24b. Yield: 0.35 g (66%), mp. 246–66 0C. IR: v 1696
1
(CO), 3117 (NH), 3345 (NH2). H NMR: d 6.4 (s, 2H, NH2), 6.8
(d, 2H, thiazole), 7.1–7.9 (m, 14 H, Ar-H + NH). MS: m/z 435 (M+,
75%). Anal. Calcd. for C23H13N7OS (435.47): C 63.43, H 3.01, N
22.52, S 7.37. Found: C 63.62, H 3.15, N 22.67, S 7.52.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2012
Benzimidazole Annulated New Heterocyclic Compounds: Synthesis of
New Polycyclic Pyrazole Derivatives
813
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