Synthesis of new trifluoromethyl substituted 11H-isonindolo[2,1-a]benzimidazol-11-one derivatives

Article abstract of DOI:10.3987/COM-05-10453

A convenient method has been developed for the synthesis of new trifluoromethyl-substituted 11H-isoindolo[2,1-a]benzimidazol-11-one derivatives from 3-nitro-5-trifluoromethyl-o-phenylenediamine and aromatic anhydrides on the surface of silica gel impregnated with ZnCl₂ under solvent free microwave irradiation conditions.{A figure is presented}.

Full text of DOI:10.3987/COM-05-10453

HETEROCYCLES, Vol. 65, No. 10, 2005
2329
HETEROCYCLES, Vol. 65, No. 10, 2005, pp. 2329 - 2337
Received, 19th May, 2005, Accepted, 8th August, 2005, Published online, 12th August, 2005
SYNTHESIS OF NEW TRIFLUOROMETHYL SUBSTITUTED 11H-
ISOINDOLO[2,1-a]BENZIMIDAZOL-11-ONE DERIVATIVES
Boddupally P V Lingaiah, Tallapally Yakaiah, Pamulaparthy S Rao,* and
Banda Narsaiah
Fluoroorganic Division, Indian Institute of Chemical Technology, Hyderabad 500007,
India. E-mail: shanthanpp@yahoo.co.in
Abstract - A convenient method has been developed for the synthesis of new
trifluoromethyl-substituted 11H-isoindolo[2,1-a]benzimidazol-11-one derivatives from
3-nitro-5-trifluoromethyl-o-phenylenediamine and aromatic anhydrides on the surface of
silica gel impregnated with ZnCl2 under solvent free microwave irradiation conditions.
INTRODUCTION
Although a large number of benzimidazole analogs have been synthesized, there still exists much scope for
the synthesis of new benzimidazolea derivatives possessing different pharmacophores.1-3 Tricyclic4 and
tetracyclic5,6 heterofused benzimidazoles are known to possess bronchodilator activity and also considered as
potential candidates as plant growth regulators. Some of them are thoroughly evaluated as antitumor agents
due to their structural resemblance with batracyclin 8-aminoisoindolo[1,2-b]quinazolin-12(10H)-one which
exhibits antineoplastic activity5 in vivo against marine leukemia P-388. Preeti and coworkers7 used
tetracyclic heterofused benzimidazoles as active synthons for 2-aryl–5-[2,1-(benzimidazol-2'-yl)phenyl]-
1,3,4-oxadiazoles possessing antitubercular activity and antibacterial activity. The preparation of
nonfluorinated isoindolo[2,1-a]benzimidazoles was reported from o-diamines and phthalic anhydride in
refluxing ethanol,4 n-amyl alcohol,5 and acetic anhydride.6
In view of our interest in the synthesis of fluorinated benzimidazoles8,9 we have developed the most concise,
effluent free and an efficient method for the synthesis of new trifluoromethyl substituted tetracyclic
heterofused benzimidazoles using microwave irradiation in presence of catalytic amount of zinc chloride
without the aid of any reagent or solvent. Incorporating trifluoromethyl group into a molecule can often lead
to an enhancement in the biological activity and change in physiological properties.10 These modifications
are associated with increased stability and lipophilicity, while the steric distortion, compared to the parent
compound is relatively small.

2330
HETEROCYCLES, Vol. 65, No. 10, 2005
RESULTS AND DISCUSSION
The reaction of 3-nitro-5-trifluoromethyl-o-phenylenediamine (1)9 with phthalic anhydride (2) in presence of
anhydrous zinc chloride on silica gel support under controlled microwave irradiation by maintaining 450 W
current resulted 2-arylbenzimidazoles (3). It is interesting to note that, the basicity of two amino functions
present in the diamine (1) is not equal due to their position with reference to electron withdrawing groups in
the ring. It is presumed that the reaction is initiated by the attack of the more basic amino group (meta to CF3
and NO2) onto the carbonyl function of phthalic anhydride resulting in an open-chain amide by cleavage of
anhydride. Cyclization of this amide by reacting with the other amino function present at ortho position,
followed by dehydration furnished 2-arylbenzimidazole. The 2-arylbenzimidazoles (3) can exist in two
possible positional isomers depending on the presence of hydrogen on either of the nitrogens of imidazole
moiety. It is very difficult to differentiate these isomers based on spectral data. The possibility of assigning
structure is based on forming H-bonding with the NO2 group makes the H-atom to be present on the N-atom
ortho to NO2 group in the 2-arylbenzimidazole (3). The structure of 3 is further confirmed by converting it to
ethylated derivative and synthesizing it by an unambiguous method to further confirm the structure of 3.
The 2-arylbenzimidazole (3) is reacted with ethyl iodide using potassium carbonate as base to obtain the
corresponding ethylated derivative (8). The authentic synthesis is designed starting from 3,5-dinitro-4-
chlorobenzotrifluoride, reacted with ethylamine to furnish 3,5-dinitro-4-ethylaminobenzotrifluoride (9).
Partial reduction of 9 gave 3-amino-4-ethylamino-5-nitrobenzotrifluoride (10). The condensation of N- ethyl
diamine (10) with phthalic anhydride under specified microwave irradiation conditions (450 W) resulted in
1-ethyl-2-aryl-5-trifluoromethyl-7-nitrobenzimidazole (8). The mp of 8 and ethylated compound of 3 are
exactly matching and the mixed mp is not depressed. The IR spectra of both ethylated 3 and 8 are
superimposable. By confirming the structure of the compound (8), compound (3) is characterized as 2-aryl-5-
trifluoromethyl-7-nitrobenzimidazole (Scheme-1).
The presence of NH and carboxylic functions in 2-arylbenzimidazoles (3) can be conveniently utilized in
making tetracyclic systems. 2-Arylbenzimidazole (3) on microwave irradiation in presence of catalytic
amount of anhydrous zinc chloride at 800 W furnished a new compound. The NMR spectrum showed
absence of NH and carboxylic acid proton, indicating the formation of cyclised product, characterized as
isoindolobenzimidazole (4). The tetracyclic ring system (4) is also obtained directly by reacting the diamine
(1) and phthalic anhydride (2) under microwave irradiation at 800 W in presence of zinc chloride. However
non-fluorinated isoindolobenzimidazoles are also prepared from diamine and phthalic anhydride in refluxing
ethanol4 (yield 60%), in n-amyl alcohol5 (yield 39%), and in acetic anhydride6 (yield 29%). The condensation
of diamine (1) with tricyclic anhydride (5) by MW irradiation at 450 W resulted in the corresponding 2-
arylbenzimidazole, which on further exposure to 800 W microwave power gave pentacyclic derivative (7)
(Scheme-1).

HETEROCYCLES, Vol. 65, No. 10, 2005
2331
R'''
R
F3C
N
N
F3C
N
R''
R'
F3C
N
N
MW
N
H
HO2C
NO2
NO2
800 W
O
NO2
6
O
4
O
O
O
7
MW
ZnCl2
800 W
MW
2
MW
ZnCl2
800 W
ZnCl2
450 W
5
R
O
R'''
R'
R''
R
F3C
N
O
F3C
NH2
R'
R''
F3C
NO2
Cl
N
H
O
2
R'''
NH2
HO2C
NO2
NO2
3
MW
450 W
ZnCl2
NO2
1
base
EtI
EtNH2
R
O
R'
O
R'''
R''
F3C
NO2
R''
F3C
NH2
F3C
Reduction
N
N
2a
O
R'''
R'
NHEt
NHEt
MW
450 W
ZnCl2
NO2
HO2C
R
Et
NO2
NO2
9
10
8
R'' R'''
R'
Compound No
R
3a/4a
H
H
Cl
H
H
H
Cl
3b/4b
3c/4c
Cl
Cl
NO2
H
H
H
H
NO2
H
F
H
H
3d/4d
3e/4e
H
Scheme-1
The methodology has been extended to aliphatic anhydrides to make it a general applicability for the
synthesis of trifluoromethylated tetracyclic isoindolobenzimidazoles. The diamine is utilized with succinic
anhydride admixed with zinc chloride under microwave irradiation furnished 2-alkylbenzimidazoles (11).
The compound (11) did not cyclize further even or prolonged microwave irradiation at 800 W, remained
unchanged. In order to get the cyclised compound, the carboxylic function of 11 is esterified to 12. The ester
underwent cyclization in presence of a base to furnish a tricyclic compound (13) in good yield. The NMR
spectra of 13 showed the characteristic signal for methylenes as triplets and absence of ester methyl group.
Based on spectral data it has been charectarised as 8-nitro-6-trifluoromethyl-2, 3-dihydro-1H-benzo[d]
pyrrolo[1,2-a]imidazolyl-1-one (13). The reaction of diamine (1) with maleic anhydride resulted a
regioselective ring open product 2-alkylbenzimidazole (14). The amino function of diamine attacked on the
more reactive electron deficient carbonyl to yield the product (14) by ring opening regioselectively, such a
selective reaction is known with an analogous molecule (S)-acetoxysuccinic anhydride.11 The open chain

2332
HETEROCYCLES, Vol. 65, No. 10, 2005
acid (14) is esterified to 15 and further cyclised to result the corresponding tricyclic system (16) in good yield
(Scheme-2).
O
O
F3C
NH2
NH2
F3C
F3C
N
N
F3C
3 drops
N
N
DMF
MeOH
H2SO4
O
CH2CH2CO2Me
CH2CH2CO2H
K2CO3
N
H
N
H
MW
450 W
ZnCl2
NO2
NO2
13
NO2
11
NO2
O
1
12
O
O
O
R
MW
450 W
ZnCl2
F3C
N
CR=CHCO2H
F3C
N
N
F3C
N
DMF
K2CO3
MeOH
H2SO4
N
H
CR=CHCO2Me
3 drops
NO2
N
H
R
NO2
NO2
14a, R = H
O
14b, R = Me
15a, R = H
16a, R = H
16b, R= Me
15b, R= Me
Scheme-2
In conclusion, the synthesis of polycyclic trifluoromethylbenzimidazoles by a fast, cleaner, efficient and
solventless method using microwave irradiation technique is described. The behavior of aliphatic anhydrides
is also same but the latter cyclization part is by a chemical method. It involves easy workup and negligible
effluent formation during the course of reaction.
ACKNOWLEDGEMENTS
The authors are thankful to Dr. J. S. Yadav, Director, IICT and Shri. S. Narayan Reddy, Head, Fluoroorganic
division, IICT, Hyderabad for their constant encouragement and financial support from industry-sponsored
project.
EXPERIMENTAL
General methods: 1H NMR spectra were recorded in CDCl3 on Gemini 200 spectrometer, chemical shifts are
reported in ppm relative to internal TMS (δ = 0.00 ppm). Melting points were recorded on VMP-AM melting
point apparatus and are uncorrected. Elemental analyses were carried out on Elemental Vario EL (Germany)
apparatus. IR spectra were recorded on FT-IR Schimadzu Perkin-Elmer 1310 infrared spectrophotometer.
Electron Impact (EI) MS spectra were recorded on VG 7070 H ev instrument at 70 ev.
General procedure for the synthesis of substituted 2-aryl-5-trifluoromethyl-7-nitrobenzimidazoles (3).
A mixture of 3-nitro-5-trifluoromethyl-o-phenylenediamine (1) (0.3 g, 1.3 mmol), aromatic anhydride (2)
(1.3 mmol) and zinc chloride (17 mg, 0.13 mmol) was adsorbed uniformly on the surface of silica gel (2 g,

HETEROCYCLES, Vol. 65, No. 10, 2005
2333
100-200 mesh) and irradiated in domestic microwave oven at 450 W in an open tube for 2-4 min. The solid
was allowed to cool to rt and confined a silica gel column using n-hexane: chloroform (1:1) as eluent to
furnish the title compound, in sufficiently pure form.
2-[7-Nitro-5-trifluoromethyl-1H-benzo[d]imidazol-2-yl]benzoic acid (3a)
Yield 82%; mp 287.9 oC (chloroform); νmax/cm-1 3485, 3329, 1645, 1524, 1338, 1290; δH (CDCl3) 8.00-8.18
(4H, m), 8.36 (1H, s), 8.50 (1H, s), 13.18 (1H, br s); MS m/z 351(M+), 333, 307, 261; Anal. Calcd for
C15H8N3O4F3: C, 51.29; H, 2.29; N, 11.96. Found: C, 51.24; H, 2.36; N, 12.02.
2,3,4,5-Tetrachloro-6-[7-nitro-5-trifluoromethyl-1H-benzo[d]imidazol-2-yl]benzoic acid (3b)
Yield 79%; mp 256.7 oC (chloroform); νmax/cm-1 3480, 3375, 3083, 1724, 1540, 1292, 1119; δH (CDCl3) 8.38
(1H, s), 8.64 (1H, s), 13.21(1H, br s); MS m/z 489(M+), 445, 399; Anal. Calcd for C15H4N3O4Cl4F3: C,
36.84; H, 0.89; N, 8.77. Found: C, 36.89; H, 0.71; N, 8.58.
2-Nitro-6-[7-nitro-5-trifluoromethyl-1H-benzo[d]imidazol-2-yl]benzoic acid (3c)
Yield 74%; mp 284.7 oC (chloroform); νmax/cm-1 3443, 2922, 1539, 1272; δH (CDCl3) 8.06-8.15 (3H, m),
8.37 (1H, s), 8.60 (1H, s), 13.20 (1H, br s); MS m/z 396 (M+), 378, 306; Anal. Calcd for C15H7N4O6F3: C,
45.47; H, 1.78; N, 14.14. Found: C, 45.38; H, 1.72; N, 14.09.
5-Nitro-2-[7-nitro-5-trifluoromethyl-1H-benzo[d]imidazol-2-yl]benzoic acid (3d)
Yield 77%; mp 282.7 oC (chloroform); νmax/cm-1 3455, 2922, 1539, 1272; δH (CDCl3) 8.22-8.34 (3H, m),
8.42(1H, s), 8.66(1H, s), 13.00 (1H, br s); MS m/z 396 (M+), 378, 306, 260; Anal. Calcd for C15H7N4O6F3: C,
45.47; H, 1.78; N, 14.14. Found: C, 45.36; H, 1.70; N, 14.10.
2-Fluoro-6-[7-nitro-5-trifluoromethyl-1H-benzo[d]imidazol-2-yl]benzoic acid (3e)
Yield 72%; mp 291.9 oC (chloroform); νmax/cm-1 3454, 2934, 1602, 1211; δH (CDCl3) 8.15-8.25 (3H, m) 8.38
(1H, s), 8.60 (1H, s), 13.12 (1H, br s); MS m/z = 369 (M+), 351,325; Anal. Calcd for C15H7N3O4F4: C,
48.79; H, 1.91; N, 11.38. Found: C, 48.72; H, 1.89; N, 11.33.
8-[7-Nitro-5-trifluoromethyl-1H-benzo[d]imidazol-2-yl]-1-naphthoic acid (6)
Yield 78%; mp 274.8 oC (chloroform); νmax/cm-1 3384, 1600, 1338, 1290; δH (CDCl3) 7.80-7.90 (3H, m),
8.00-8.12 (3H, m), 8.38 (1H, s), 8.44 (1H, s), 13.22 (1H, br s); MS m/z = 401(M+), 383, 357, 312; Anal.
Calcd for C19H10N3O4F3: C, 56.86; H, 2.51; N, 10.47. Found: C, 56.83; H, 2.48; N, 10.40.
General procedure for the synthesis of substituted 11H-Isoindolo[2,1-a]benzimidazol-11-one (4)
Procedure-A: A mixture of diamine (1) (0.3 g, 1.3 mmol), aromatic anhydride (2) (1.3 mmol) and zinc
chloride (17 mg, 0.13 mmol) was adsorbed on silica gel (2 g, 100-200 mesh) and subjected to microwave
irradiation in an open tube at 800 W for 2-4 min. Passing through a silica gel column using n-hexane:
chloroform (3:1) as eluent furnished the title compound (4).
Procedure-B: The compound (3) (0.5 mmol), zinc chloride (40 mg, 0.3 mmol) and catalytic amount of
acetic acid (2 drops) was adsorbed on silica gel (2 g, 100-200 mesh) and subjected to microwave irradiation

2334
HETEROCYCLES, Vol. 65, No. 10, 2005
at 800 W for 1-2 min. The solid was passed through a silica gel column using n-hexane: chloroform (3:1) as
eluent to afford the title compound (4).
9-Nitro-7-trifluoromethyl-11H-benzo[4,5]imidazo[2,1-a]isoindol-11-one (4a)
Yield 80%; mp 184.5 oC (chloroform); νmax/cm-1 1645, 1600, 1524, 1338; δH (CDCl3) 7.95-8.10 (3H, m), 8.42
(1H, s), 8.58 (1H, s); MS m/z 333(M+), 307; Anal. Calcd for C15H6N3O3F3: C, 54.06; H, 1.81; N, 12.61.
Found: C, 54.00; H, 1.78; N, 12.58.
1,2,3,4-Tetrachloro- 9-nitro-7-trifluoromethyl-11H-benzo[4,5]imidazo[2,1-a]isoindol-11-one (4b)
Yield 68%; mp 234.6 oC (chloroform); νmax/cm-1 1648, 1602, 1555, 1291; δH (CDCl3) 8.53 (1H, s), 8.66 (1H,
s); MS m/z = 471(M+), 425; Anal. Calcd for C15H2N3O3Cl4F3: C, 38.25; H, 0.42; N, 8.92. Found: C, 38.16;
H, 0.47; N, 8.98.
1,9-Dinitro-7-trifluoromethyl-11H-benzo[4,5]imidazo[2,1-a]isoindol-11-one (4c)
Yield 75%; mp 269.5 oC (chloroform); νmax/cm-1 1654, 1600, 1553, 1299; δH (CDCl3) 8.10-8.18 (3H, m), 8.38
(1H, s), 8.42 (1H, s); MS: m/z 378(M+), 332, 286; Anal. Calcd for C15H5N4O5F3: C, 47.63; H, 1.33; N, 14.81.
Found: C, 47.58; H, 1.38; N, 14.72.
2,9-Dinitro-7-trifluoromethyl-11H-benzo[4,5]imidazo[2,1-a]isoindol-11-one (4d)
Yield 76%; mp 268.0 oC (chloroform); νmax/cm-1 1655, 1600, 1555, 1291; δH (CDCl3) 8.35-8.50 (3H, m),
8.58 (1H, s), 8.66 (1H, s); MS m/z = 378(M+), 332, 286; Anal. Calcd for C15H5N4O5F3: C, 47.63; H, 1.33; N,
14.81. Found: C, 47.59; H, 1.34; N, 14.76.
1-Fluoro9-nitro-7-trifluoromethyl-11H-benzo[4,5]imidazo[2,1-a]isoindol-11-one (4e)
Yield 71%; mp 252.4 oC (chloroform); νmax/cm-1 1678, 1599, 1299; δH (CDCl3) 7.98-8.20 (3H, m), 8.44 (1H,
s), 8.58 (1H, s); MS m/z = 351(M+), 305, 282; Anal. Calcd for C15H5N3O3F4: C, 51.29; H, 1.43; N, 11.96.
Found: C, 51.28; H, 1.52; N, 11.89.
9-Nitro-11-trifluoromethyl-7H-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one (7)
Yield 72%; mp 298 oC (chloroform); νmax/cm-1 1689, 1602, 1599, 1542, 1299; δH (CDCl3) 8.15-8.35 (6H, m),
8.42 (1H, s), 8.66 (1H, s); MS: m/z 383(M+), 338, 259; Anal. Calcd for C19H8N3O3F3: C, 59.53; 2.10;N,
10.96. Found: C, 59.48; H, 2.01; N, 10.89.
1-Ethyl -2-substituted phenyl-5-trifluoromethyl-7-nitrobenzimidazole (8)
Procedure-A: The compound (10) (0.35 g, 1.43 mmol), phthalic anhydride (2a) (207 mg, 1.4 mmol) and
zinc chloride (19 mg, 0.14 mmol) were adsorbed on silica gel (2 g, 100-200 mesh) and exposed to microwave
irradiation at 450 W for 2 min. The solid was purified by passing through a silica gel column using n-hexane:
chloroform (1:1) as eluent afforded the title compound. (362 mg, Yield = 68%).
Procedure-B: To a solution of compound (3a) (0.5 g, 1.4 mmol) in dry dimethylformamide(4 mL),
potassium carbonate (0.58 g, 4.2 mmol) and ethyl iodide (1.1 g, 7.1 mmol) were added and the mixture was
heated at 75-800C for 15 h. The progress of the reaction monitered by TLC. The solvent was recovered under
reduced pressure and the residue was treated with crushed ice. The separated solid was filtered, dried and

HETEROCYCLES, Vol. 65, No. 10, 2005
2335
purified by silica gel column chromatography using n-hexane: chloroform (1:1) as eluent gave the title
compound. (329 mg, Yield = 61%)
2-[1-Ethyl-7-nitro-5-trifluoromethyl-1H-benzo[d]imidazol-2-yl]benzoic acid (8)
mp 244.9 oC (chloroform); νmax/cm-1 3489, 3000, 1594, 1548, 1334, 1299 ; δH (CDCl3) 1.44-1.48 (3H, t, J= 9
Hz), 4.14-4.16 (2H, q, J= 9 Hz), 7.82-7.95 (4H, m), 8.28 (1H, s), 8.32 (1H, s); MS m/z 379 (M+), 350, 333;
Anal. Calcd for C17H12N3O4F3: C, 53.83; H, 3.18; N, 11.07. Found: C, 53.73; H, 3.10; N, 11.17.
General procedure for the preparation of 1H-benzo[d]pyrrolo[1,2-a]imidazolyl-1-ones.
Preparation of 3-[7-Nitro-5-trifluoromethyl-1H-benzo[d]imidazol-2-yl]propanoic acid (11) and (14).
A mixture of diamine (1) (1.3 mmol), aliphatic anhydride (1.3 mmol) and zinc chloride (17 mg, 0.13 mmol)
adsorbed on silica gel (2 g, 100-200 mesh) and subjected to microwave irradiation in an open tube at 450 W
for 1-2 min. The reaction mixture was purified by passing through a silica gel column using n-
hexane:chloroform (1:1) as eluent to afford the title compounds (11) and (14).
3-[7-Nitro-5-trifluoromethyl-1H-benzo[d]imidazol-2-yl]propanoic acid (11)
Yield 84%; mp 202.9 oC (chloroform); νmax/cm-1 3485, 3373, 3095, 1713, 1540, 1300; δH (CDCl3) 2.72-2.78
(2H, t, J = 9 Hz), 2.82-2.88 (2H, t, J= 9 Hz), 8.09 (1H, s), 8.29 (1H, s), 13.24 (1H, s); MS m/z 303 (M+),
258,74; Anal. Calcd for C11H8N3O4F3: C, 43.58; H, 2.66; N, 13.86. Found: C, 42.73; H, 2.10; N, 12.17.
3-[7-Nnitro-5-trifluoromethyl-1H-benzo[d]imidazol-2-yl]propenoic acid (14a)
Yield 82%; mp 229.4 oC (chloroform); νmax/cm-1 3482, 3371, 3103, 2924, 1717, 1539, 1345; δH (CDCl3) 5.96
(1H, d, J = 7 Hz), 7.27 (1H, d, J = 7 Hz), 8.34 (1H, s), 8.39 (1H, s), 13.22 (1H, s); MS m/z 301 (M+),
257,211; Anal. Calcd for C11H6N3O4F3: C, 43.87; H, 2.01; N, 13.95. Found: C, 42.73; H, 2.10; N, 13.17.
2-Methyl-3-[7-nitro-5-trifluoromethyl-1H-benzo[d]imidazol-2-yl]propenoic acid (14b)
Yield 79%; mp 279.4 oC (chloroform); νmax/cm-1 3471, 3359, 3104, 1716, 1639, 1344, 1118; δH (CDCl3) 1.95
(3H, s), 7.70 (1H, s), 8.37 (1H, s), 8.40 (1H, s), 13.20 (1H, s); MS m/z 315 (M+), 270,224; Anal. Calcd for
C12H8N3O4F3 : C, 45.73; H, 2.56; N, 13.33. Found: C, 44.73; H, 2.39; N, 13.17.
Preparation of Methyl 3-[7-nitro-5-trifluoromethyl-1H-benzo[d]imidazol-2-yl]propanoate (12) and
(15). The acid compound (11) (484 mg, 1.6 mmol) was dissolved in methanol (5 mL) and 3, 4 drops of
sulfuric acid was added. Then mixture was refluxed for 6 h. After completion of reaction, the solvent was
removed under reduced pressure and the residue was treated with crushed ice. The separated solid was
filtered, dried and purified by silica gel column chromatography using n-hexane: chloroform (1:1) as eluent
gave the title compounds (12) and (15).
Methyl 3-[7-nitro-5-trifluoromethyl-1H-benzo[d]imidazol-2-yl]propanoate (12)
Yield 68%; mp 245.7 oC (chloroform); νmax/cm-1: 3385, 1695, 1684, 1600, 1540, 1345; δH (CDCl3) 2.62-2.68
(2H, t, J= 10 Hz), 3.00-3.10 (2H, t, J= 10 Hz), 3.58 (3H, s), 8.28(1H, s), 8.31(1H, s) 13.2 (1H, br s); MS m/z
303 (M+), 258,74; Anal. Calcd for C12H10N3O4F3: C, 43.58; H, 2.66; N, 13.86. Found: C, 42.79; H, 2.11; N,
12.19.

2336
HETEROCYCLES, Vol. 65, No. 10, 2005
Methyl-3-[7-nitro-5-trifluoromethyl-1H-benzo[d]imidazol-2-yl]propenoate (15a)
Yield 65%; mp 279.7 oC (chloroform); νmax/cm-1: 3371, 3103, 2924, 1690, 1639, 1539; δH (CDCl3) 3.63 (3H,
s), 5.98 (1H, d, J= 7 Hz), 7.17(1H, d, J= 7 Hz), 8.37(1H, s), 8.58(1H, s) 10.09 (1H, br s); MS m/z 315 (M+),
300, 271, 269; Anal. Calcd for C12H8N3O4F3: C, 45.73; H, 2.56; N, 13.33. Found: C, 44.79; H, 2.41; N,
12.19.
Methyl 2-methyl-3-[7-nitro-5-trifluoromethyl-1H-benzo[d]imidazol-2-yl]propenoate (15b)
Yield 68%; mp 289.7 oC (chloroform); νmax/cm-1 3359, 1689, 1540, 1344, 1244; δH (CDCl3) 1.89 (3H, s), 3.73
(3H, s), 7.49 (1H, s), 8.37(1H, s), 8.59(1H, s) 10.9 (1H, br s); MS m/z 329 (M+), 297,283; Anal. Calcd for
C13H10N3O4F3: C, 47.43; H, 3.06; N, 12.76. Found: C, 48.79; H, 3.21; N, 12.19.
Preparation of 8-nitro-6-trifluoromethyl-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazolyl-1-one (13)
and (16). The ester compound (12) (317 mg, 1.0 mmol) was dissolved in DMF (5 mL) and potassium
carbonate (414 mg, 3.0 mmol) was added. The mixture was heated at 1000C for 4-5 h. After completion of
reaction, the solvent was removed under reduced pressure and the residue was treated with water. The
separated solid was filtered, dried and purified by silica gel column chromatography using n-
hexane:chloroform (3:1) as eluent furnished the title compounds (13) and (16).
8-Nitro-6-trifluoromethyl-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazolyl-1-one (13)
Yield 72%; mp 210.7 oC (chloroform); νmax/cm-1 3091, 1692, 1548, 1332, 1099; δH (CDCl3) 2.83-2.91 (2H, t,
J= 10 Hz), 3.02-3.10 (2H, t, J= 10 Hz), 8.39(1H, s), 8.57(1H, s); MS m/z 285 (M+), 239; Anal. Calcd for
C11H6N3O3F3: C, 46.33; H, 2.12; N, 14.73. Found: C, 45.79; H, 2.11; N, 13.19.
8-Nitro-6-trifluoromethyl-1H-benzo[d]pyrrolo[1,2-a]imidazolyl-1-one (16a)
Yield 68%; mp 194.7 oC (chloroform); νmax/cm-1 1690, 1539, 1345, 1126; δH (CDCl3) 6.83 (1H, d, J= 7 Hz),
8.59(1H, s), 8.62 (1H, s), 8.98(1H, d, J= 7Hz); MS m/z 283 (M+), 237; Anal. Calcd for C11H4N3O3F3:C,
46.66; H, 1.42; N, 14.84. Found: C, 45.79; H, 1.21; N, 13.19.
2-Methyl-8-nitro-6-trifluoromethyl-1H-benzo[d]pyrrolo[1,2-a]imidazolyl-1-one (16b)
Yield 68%; mp 194.7 oC (chloroform); νmax/cm-1 1692, 1639, 1539, 1345,1298, 1167, 1118; δH (CDCl3) 2.21
(3H, s), 8.60(1H, s), 8.63 (1H, s), 8.74(1H, s); MS m/z 297 (M+), 282,251; Anal. Calcd for C12H6N3O3F3: C,
48.50; H, 2.03; N, 14.14. Found: C, 47.79; H, 2.21; N, 13.29.
REFERENCES
1. K. Taniguchi, S. Shigenaga, T. Ogahara, T. Fujitsu, and M. Matsuo, Chem. Pharm. Bull., 1993, 41,
301.
2. W. G. Schulz, E. Islam, and E. B. Skibo, J. Med. Chem., 1995, 38, 109.
3. D. M. Downing, S. A. Glase, S. J. Johnson, L. D. Wise, and J. L. Wright, PCT Inst. Appl. 1995, Wo
95 30,659, (Chem. Abstr., 1996, 124, 202263c).
4. R. L. Sharma, M. Kumari, N. Kumar, and B. K.Sharma, Indian J. Heterocycl. Chem., 1998, 8, 155.

HETEROCYCLES, Vol. 65, No. 10, 2005
2337
5. S. K. Meegalla, G. J. Stenvens, C. A. McQueen, A. Y. Chen, C. Yu, L. F. Liu, L. R. Barrows, and E.
J. LaVoie, J. Med. Chem., 1994, 37, 3435.
6. Baum, S. Jonathan, Chen, M. Tsong, USP, 1986, 4,623,379, (Chem. Abstr., 1986, 106, 45729t).
7. R. K. Preeti, S. S. Neeraj, K. D. Rajeev, and H. H. Parekh, Indian J. Chem., 1999, 38B, 572.
8. G. V. Reddy, V. V. V. N. S. Rama Rao, B. Narsaiah, and P. S. Rao, Synth. Commun., 2002, 32, 2467.
9. G. V. Reddy, V. V. V. N. S. RamaRao, D. Maitraie, S. Ravikanth, R. Yadla, S. N. Reddy, B.
Narsaiah, and P. S. Rao, J. Fluorine Chem., 2003, 124, 203.
10. R. Filler, Y. Kobayashi, and L. M. Yagupolskii, Organo Fluorine Compounds in Medicinal
Chemistry and Biomedicinal Applications, 1993, pp.1-23.
11. S. B. Mhaske and N. P. Argade, J. Org. Chem., 2001, 66, 9038.