Synthesis and antibacterial activity of some novel 6-(1H-benz[d] imidazol-2-yl)-8-(5-nitro-2-furyl)-3-(4-pyridyl)-7,8-dihydro[1,2,4] triazolo[3,4-b][1,3,4]thiadiazepines

Article abstract of DOI:10.1248/cpb.58.1081

A new series of novel 6-(1H-benz[d]imidazol-2-yl)-8-(5-nitro-2-furyl)-3-(4- pyridyl)-7,8-dihydro[1,2,4]triazolo[ 3,4-b][1,3,4]thiadiazepines 8a - d has been synthesized. These compounds were evaluated for their efficiency as antibacterial agents against two Gram-positive and Gram-negative strains of bacteria along with anti-fungal activity against two fungal organisms. The antibacterial and antifungal activities of the present compounds were not comparable with those of the standard drugs employed. But, however, all the test compounds could exhibit notable activities only at higher concentrations (250, 500 μg/ml). The chemical structures of these compounds were confirmed on the basis of spectral data.

Full text of DOI:10.1248/cpb.58.1081

August 2010
Note
Chem. Pharm. Bull. 58(8) 1081—1084 (2010)
1081
Synthesis and Antibacterial Activity of Some Novel 6-(1H-Benz[d]
imidazol-2-yl)-8-(5-nitro-2-furyl)-3-(4-pyridyl)-7,8-dihydro[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazepines
Vanga MALLA REDDY* and Kunduru RAVINDER REDDY
Dr. Ch. Ravishanker Memorial Medicinal Chemistry Research Laboratory, University College of Pharmaceutical Sciences,
Kakatiya University; Warangal–506009, India. Received December 26, 2009; accepted April 30, 2010
A new series of novel 6-(1H-benz[d]imidazol-2-yl)-8-(5-nitro-2-furyl)-3-(4-pyridyl)-7,8-dihydro[1,2,4]tri-
azolo[3,4-b][1,3,4]thiadiazepines 8a—d has been synthesized. These compounds were evaluated for their effi-
ciency as antibacterial agents against two Gram-positive and Gram-negative strains of bacteria along with anti-
fungal activity against two fungal organisms. The antibacterial and antifungal activities of the present com-
pounds were not comparable with those of the standard drugs employed. But, however, all the test compounds
could exhibit notable activities only at higher concentrations (250, 500 mg/ml). The chemical structures of these
compounds were confirmed on the basis of spectral data.
Key words benzimidazole; triazole; thiadiazepine; antimicrobial activity
Benzimidazoles show significant activity against several 6-(1H-benz[d]imidazol-2-yl)-8-(5-nitro-2-furyl)-3-(4-pyri-
viruses such as human cytomegalovirus (HCMV),1) human dyl)-7,8-dihydro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepines
immunodeficiency virus (HIV),2) herpes (HSV-1),3) RNA4) 8a—d skeleton system represented in Chart 1.
and influenza.5) In view of the tremendous activities of ben-
The key intermediate 4-amino-5-(4-pyridyl)-4H-1,2,4-tri-
zimidazoles, their preparation has gained considerable atten- azol-3-ylhydrosulfide 7, required for the synthesis of the title
tion. While many strategies are available for benzimidazole compounds was prepared by the cyclocondensation of
synthesis.6—9) Almost all benzimidazoles with their two ring 4-pyridinecarbohydrazide with hydrazine hydrate and CS2
systems bear different functional substituents and this leads in presence of potassium hydroxide and ethanol.39) 2-(a-
to essential modification of the physico-chemical, metabolic Hydroxy)ethyl-benzimidazoles 3a—d was prepared by the
and pharmacokinetic properties of drugs.
reaction of substituted o-phenylenediamines 1 with a-
The benzodiazepine nucleus is a pharmacophoric scaffold hydroxy propionic acid 2 in presence of hydrochloric acid
and represents a class of heterocycles with a wide range of under reflux, followed by oxidation of compounds 3a—d in
biological applications.10) Many of them are widely used as presence of potassium dichromate and sulfuric acid at room
anticonvulsant, antianxiety, sedative, antidepressive, hypnotic temperature yields 2-acetyl benzimidazoles 4 which on con-
and neuroleptic agents.11—14) Some heterocycles containing densation reaction with 5-nitro furfural 5 at room tempera-
benzodiazepines moiety were reported to possess anti inflam- ture in presence of concentrated sulfuric acid and glacial
matory,15) antiviral,16) anti-HIV-1,17) antimicrobial18) and anti- acetic acid provides the formation of (E)-1-(1H-benzo[d]
tumor19) activities. It has been noticed that introduction of an imidazol-2-yl)-3-(5-nitro-2-furyl)-2-propen-1-ones 6a—d.
extra ring to the benzodiazepine core tends to exert profound These compounds 6a—d on cyclocondensation reaction with
influence in conferring novel biological activities in these 4-amino-5-(4-pyridyl)-4H-1,2,4-triazol-3-ylhydrosulfide 7 in
molecules.20—24) Although many methods for synthesizing presence of polyphosphoric acid afforded the compounds 6-
benzodiazepine ring systems have been reported, they con- (1H-benz[d]imidazol-2-yl)-8-(5-nitro-2-furyl)-3-(4-pyridyl)-
tinue to receive a great deal attention.25—27)
7,8-dihydro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepines 8a—
Another class of heterocycles used as scaffolds in medici- d. The synthetic route leading to the title compounds is sum-
nal chemistry is devoted to benzotriazole derivatives. They marized in Chart 1. The chemical structures of all the newly
exhibit useful pharmacological properties and clinical appli- synthesized compounds were confirmed by their IR, 1H-
cations.28—31) In addition to these considerable biological NMR, and MS analysis and further the compounds were
applications, benzotriazoles are important intermediates, screened for their antibacterial and antifungal activities.
protecting groups and final products in organic synthesis.32)
Antibacterial Activity The antibacterial activity of the
Inspired with biological profile of benzimidazoles, synthesized compounds was evaluated against two Gram-
traizoles and diazepines and their increasing importance in positive bacteria viz., Bacillus subtilus and Staphylococcus
pharmaceutical and biological fields, and in connection with aureus, and two Gram-negative bacteria viz., Escherichia coli
our research on the design and synthesis of biologically ac- and Klebsiella pneumoniae using streptomycin and benzyl
tive and pharmacologically important new heterocycles,33—38) penicillin as standard drugs, respectively by the ‘cup-plate
it was thought worthwhile to synthesize the title compounds method’40) using dimethyl sulfoxide (DMSO) as the solvent
with a view to obtain certain new chemical entities with three and the results are given in Table 1. The results of the test
active pharmacophores in a single molecular frame work in compounds could not be directly compared with those of the
order to prepare molecules having with potentially enhanced standard drugs, employed for a very simple reason that they
biological activities and to have them evaluated for their vary greatly in their test concentrations, that is, 250 mg/ml
antimicrobial activity. On the other hand, to the best of our and 500 mg/ml of test compounds against 40 mg/ml only of
knowledge, previously there is no report, on the synthesis of reference drugs. Hence, this data was used to compare the
∗ To whom correspondence should be addressed. e-mail: vanga_mreddy@rediffmail.com
© 2010 Pharmaceutical Society of Japan

1082
Vol. 58, No. 8
Chart 1
Table 1. Antibacterial and Antifungal Activity of 6-(1H-Benz[d]imidazol-2-yl)-8-(5-nitro-2-furyl)-3-(4-pyridyl)-7,8-dihydro[1,2,4]triazolo[3,4-b]
[1,3,4]thiadiazepines 8a—d
Antibacterial activitya,b)
Antifungal activitya,b)
Compound
B. subtilus
S. aureus
E. coli
K. pneumoniae
F. oxysporum
A. niger
8a
8b
8c
08/06
13/12
14/13
15/14
—
08/07
14/13
13/12
13/12
—
05/04
14/12
13/12
14/13
16
06/05
12/11
14/13
13/12
16
03/02
04/03
05/04
05/04
—
03/02
03/02
04/03
05/04
—
8d
Streptomycinc)
Benzyl penicillinc)
Fluconazolec)
16
—
16
—
—
—
—
—
—
06
—
06
a) Zone of inhibition in mm at 500 mg/ml concentration. b) Zone of inhibition in mm at 250 mg/ml concentration. c) Zone of inhibition in mm at 40 mg/ml concentration.
relative antibacterial potencies of the test compounds only. series.
Though all of the test compounds could cause inhibition of
Experimental
both Gram (ϩ)ve and Gram (Ϫ)ve bacteria employed, effec-
tively at a concentration of 500 mg/ml, the compound 8d with
two nitro groups was found to be relatively more potent
among the test compounds.
General All reagents and solvents were used as purchased without
further purification. Melting points were determined on a Fisher–Johns melt-
ing point apparatus and are uncorrected. Crude products were purified by
column chromatography on silica gel of 60—120 mesh. IR spectra were
obtained on a Perkin Elmer BX serried FTIR 5000 spectrometer using KBr
pellet. NMR spectra were recorded on a Varian 300 MHz spectrometer for
1H-NMR. The chemical shifts were reported as ppm down field using
tetramethylsilane (TMS) as an internal standard. Mass spectra were recorded
on a VG-Micromass 7070H spectrometer operating at 70 eV.
Typical Procedure 2-(a-Hydroxy)ethyl Benzimidazoles (3) o-Phenyl-
enediamine (0.01 mol) was mixed with lactic acid (0.01 mol) in presence
of 4 N hydrochloric acid (5 ml) and refluxed for 24 h. After completion of the
reaction, (monitored by TLC) the reaction mixture was cooled and neutral-
ized with NH3 solution. The solid was separated through filter and recrystal-
lized from ethanol.
Antifungal Activity The newly prepared compounds
were also screened for their antifungal activity against two
fungi, viz., Fusarium oxysporum and Aspergillus niger by the
‘cup-plate method’40) using Fluconazole as a standard drug
and DMSO as the solvent and the results are summarized in
Table 1. Similar to antibacterial activity the antifungal activ-
ity of the present compounds was also not comparable to that
of the standard drug Fluconazole because of the concentra-
tion variation. But, however, the test compounds could also
exhibit antifungal activity against both the fungi employed.
Table 1 indicates once again the compound 8d with two nitro
groups as the superior, relatively among the present new
2-Acetyl Benzimidazoles (4) To a solution of 2-(a-hydroxy)ethyl benz-
imidazoles 3 (0.01 mol) in dil. H2SO4 (5%, 40 ml) was drop wise added the
solution of K2Cr2O7 (0.15 mol) and aqueous H2SO4 (25%, 80 ml) with con-
stant stirring at room temperature over a period of 20 min. Further the reac-

August 2010
1083
Jϭ7.6 Hz), 2.43 (3H, s). MS m/z: 298 (Mϩϩ1).
tion mixture was stirred at room temperature for 2 h. After completion of the
reaction, (monitored by TLC), the reaction mixture neutralized with NH3
solution (1 : 1) and formed orange solid was filtered, washed with water and
dried, recrystallized from ethyl acetate.
(E)-1-(1H-benzo[d]imidazol-2-yl)-3-(5-nitro-2-furyl)-2-propen-1-ones
(6) To a solution of 2-acetyl benzimidazoles 4 (0.01 mol) and 5-nitrofur-
fural (0.01 mol) in glacial acetic acid (20 ml) was added con. sulfuric acid
(2 ml). Then the reaction mixture stirred at 40 °C for 24 h. The solid formed
was filtered and recrystallized form ethylacetate.
4-Amino-5-(4-pyridyl)-4H-1,2,4-triazol-3-ylhydrosulfide (7) 4-Pyri-
dine carbohydrazide (0.01 mol) was dissolved in 10% alcoholic potassium
hydroxide (25 ml) and stirred with an equimolar quantity of CS2, slowly
while cooling in an ice both. The resultant bulk potassium dithiacarbazate
was filtered and subjected to a reaction with excess of hydrazine hydrate.
The product was filtered and recrystallized from alcohol to get a colorless
crystalline solid. mp 250—254 °C.
(E)-1-(5-Chloro-1H-benz[d]imidazol-2-yl)-3-(5-nitro-2-furyl)-2-propen-
1-one (6c): Yellow solid, yield 40%, mp 208—210 °C. IR (KBr) cmϪ1: 3278,
3026, 2919, 1687, 1526, 1032, 1014, 875. 1H-NMR (CDCl3) d: 8.77 (1H, s),
7.78 (1H, s), 7.79 (1H, d, Jϭ7.8 Hz), 7.64 (1H, d, Jϭ7.6 Hz), 7.58 (1H, d,
Jϭ7.4 Hz), 7.43 (1H, d, Jϭ7.2 Hz), 7.08 (1H, d, Jϭ8.0 Hz), 6.87 (1H, d,
Jϭ7.8 Hz). MS m/z: 318 (Mϩϩ1).
(E)-1-(5-Nitro-1H-benz[d]imidazol-2-yl)-3-(5-nitro-2-furyl)-2-propen-1-
one (6d): Yellow solid, yield 30%, mp 193—195 C. IR (KBr) cmϪ1: 3279,
3012, 2921, 1669, 1512, 1018, 1012, 879. 1H-NMR (CDCl3) d: 9.09 (1H, s),
8.77 (1H, s), 8.30 (1H, d, Jϭ7.8 Hz), 8.19 (1H, d, Jϭ7.6 Hz), 7.64 (1H, d,
Jϭ7.4 Hz), 7.43 (1H, d, Jϭ7.6 Hz), 7.08 (1H, d, Jϭ7.8 Hz), 6.87 (1H, d,
Jϭ7.4 Hz). MS m/z: 329 (Mϩϩ1).
6-(1H-Benz[d]imidazol-2-yl)-8-(5-nitro-2-furyl)-3-(4-pyridyl)-7,8-dihy-
dro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine (8a): Yellow solid, yield 90%,
mp 192—194 °C. IR (KBr) cmϪ1: 3420, 3025, 2925, 1560, 1410, 1124,
1214. 1H-NMR (CDCl3) d: 10.17 (1H, s), 9.17 (2H, d, Jϭ8.0 Hz), 8.62 (2H,
d, Jϭ7.8 Hz), 7.50 (2H, d, Jϭ7.6 Hz), 7.41 (2H, d, Jϭ7.4 Hz), 7.21 (1H, d,
Jϭ7.6 Hz), 5.91 (1H, d, Jϭ7.8 Hz), 4.99 (1H, t, Jϭ7.6 Hz), 2.15 (2H, d,
Jϭ8.2 Hz). MS m/z: 459 (Mϩϩ1).
6-(1H-benz[d]imidazol-2-yl)-8-(5-nitro-2-furyl)-3-(4-pyridyl)-7,8-
dihydro[1,2,4]triazolo[3,4-b] [1,3,4]thiadiazepines (8) The com-
pounds (E)-1-(1H-benz[d]imidazol-2-yl)-3-(5-nitro-2-furyl)-2-propen-1-ones
(0.01 mol) and 4-amino-5-(4-pyridyl)-4H-1,2,4-triazol-3-ylhydrosulfide
6
7
(0.01 mol) were rapidly mixed with help of mortar and converted into paste
form. The resulting mixture was then refluxed in presence of polyphosphoric
acid for 7 h. After completion of the reaction (monitored by TLC), the reac-
tion mixture was cooled to room temperature poured into ice cold water. The
formed pale brown precipitate was separated by using ether, dried and
recrystallized from ethylacetate.
1-(1H-Benz[d]imidazol-2-yl)-1-ethanol (3a): Yellow solid, yield 90%, mp
180—182 °C. IR (KBr) cmϪ1: 2971, 1623, 1458, 1215, 1103. 1H-NMR
(CDCl3) d: 10.30 (1H, br s), 7.52 (2H, m, Jϭ7.8 Hz), 7.12 (2H, m, Jϭ7.6
Hz), 4.8 (1H, s), 3.05 (1H, q, Jϭ7.4 Hz), 1.62 (3H, d, Jϭ7.2 Hz). MS m/z:
163 (Mϩϩ1).
1-(5-Methyl-1H-benz[d]imidazol-2-yl)-1-ethanol (3b): Dark yellow solid,
yield 90%, mp 160—162 °C. IR (KBr) cmϪ1: 3038, 2701, 1629, 1449, 1316,
1101. 1H-NMR (CDCl3) d: 9.61 (1H, br s), 7.32 (3H, m, Jϭ8.0 Hz), 4.85
(1H, s), 3.05 (1H, q, Jϭ7.8 Hz), 1.62 (3H, d, Jϭ7.4 Hz). MS m/z: 177
(Mϩϩ1).
6-(6-Methyl-1H-benz[d]imidazol-2-yl)-8-(5-nitro-2-furyl)-3-(4-pyridyl)-
7,8-dihydro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine (8b): Yellow solid,
yield 75%, mp 195—197 °C. IR (KBr) cmϪ1: 3437, 3032, 2932, 1542, 1436,
1132, 1236. 1H-NMR (CDCl3) d: 10.17 (1H, s), 9.17 (2H, d, Jϭ7.8 Hz),
8.62 (2H, d, Jϭ7.6 Hz), 7.24 (1H, d, Jϭ7.4 Hz), 7.21 (1H, d, Jϭ7.6 Hz),
7.12 (1H, d, Jϭ7.8 Hz), 7.09 (1H, s), 5.91 (1H, d, Jϭ7.4 Hz), 4.99 (1H, t,
Jϭ8.0 Hz), 2.43 (3H, s), 2.15 (2H, d, Jϭ7.8 Hz). MS m/z: 473 (Mϩϩ1).
6-(6-Chloro-1H-benz[d]imidazol-2-yl)-8-(5-nitro-2-furyl)-3-(4-pyridyl)-
7,8-dihydro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine (8c): Yellow solid,
yield 65%, mp 201—203 °C. IR (KBr) cmϪ1: 3456, 3015, 2939, 1525, 1436,
1142, 1246, 746. 1H-NMR (CDCl3) d: 10.17 (1H, s), 9.17 (2H, d, Jϭ
7.8 Hz), 8.62 (2H, d, Jϭ7.6 Hz), 7.38 (1H, s), 7.36 (1H, d, Jϭ8.0 Hz), 7.28
(1H, d, Jϭ7.6 Hz), 7.21 (1H, d, Jϭ7.8 Hz), 5.91 (1H, d, Jϭ7.6 Hz), 4.99
(1H, t, Jϭ8.0 Hz), 2.15 (2H, d, Jϭ7.8 Hz). MS m/z: 493 (Mϩϩ1).
6-(6-Nitro-1H-benz[d]imidazol-2-yl)-8-(5-nitro-2-furyl)-3-(4-pyridyl)-
7,8-dihydro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine (8d): Yellow solid,
yield 45%, mp 189—191 °C. IR (KBr) cmϪ1: 3412, 3014, 2945, 1542, 1425,
1136, 1224. 1H-NMR (CDCl3) d: 10.17 (1H, s), 9.17 (2H, d, Jϭ7.8 Hz),
8.62 (2H, d, Jϭ7.6 Hz), 8.39 (1H, d, Jϭ7.8 Hz), 8.13 (1H, d, Jϭ8.0 Hz),
7.79 (1H, d, Jϭ7.6 Hz), 7.21 (1H, d, Jϭ7.8 Hz), 5.91 (1H, d, Jϭ7.6 Hz),
4.99 (1H, t, Jϭ8.0 Hz), 2.15 (2H, d, Jϭ7.8 Hz). MS m/z: 504 (Mϩϩ1).
1-(5-Chloro-1H-benz[d]imidazol-2-yl)-1-ethanol (3c): Brown solid, yield
1
65%, mp 171—173 °C. IR (KBr) cmϪ1: 2981, 1623, 1444, 1210, 1082. H-
NMR (CDCl3) d: 12.50 (1H, s), 7.55 (2H, d, Jϭ7.2 Hz), 7.20 (1H, d, Jϭ7.4
Hz), 4.91 (1H, m, Jϭ6.8 Hz), 1.52 (3H, d, Jϭ7.0 Hz). MS m/z: 197 (Mϩϩ1).
1-(5-Nitro-1H-benz[d]imidazol-2-yl)-1-ethanol (3d): Brown solid, yield
75%, mp 148—150 °C. IR (KBr) cmϪ1: 3342, 3215, 3024, 2865, 2240,
1
1420, 1248. H-NMR (CDCl3) d: 8.63 (1H, s), 7.91 (1H, d, Jϭ7.0 Hz), 76
References
(1H, d, Jϭ7.2 Hz), 6.64 (1H, s), 6.59 (1H, d, Jϭ7.4 Hz), 5.16 (1H, m, Jϭ
1) Porcari A. R., Devivar R. V., Kucera L. S., Drach J. C., Townsend L.
B., J. Med. Chem., 41, 1252—1262 (1998).
7.6 Hz), 1.77 (1H, d, Jϭ7.8 Hz). MS m/z: 208 (Mϩϩ1).
1-(1H-Benz[d]imidazol-2-yl)-1-ethanone (4a): Yellow solid, yield 78%,
mp 189—191 °C. IR (KBr) cmϪ1: 3289, 3059, 3015, 1674, 1580, 1445,
1235, 1147. 1H-NMR (CDCl3) d: 13.02 (1H, s), 7.85 (1H, d, Jϭ7.8 Hz),
7.52 (1H, d, Jϭ7.6 Hz), 7.32 (2H, t, Jϭ7.4 Hz), 2.74 (3H, s). MS m/z: 161
(Mϩϩ1).
2) Roth Y., Morningstar M. L., Boyer P. L., Hughes S. H., Buckheitjr R.
W., Michejda C. J., J. Med. Chem., 40, 4199—4207 (1997).
3) Migawa M. T., Girardet J. L., Walker J. A., Koszalka G. W., Chamber-
lain S. D., Drach J. C., Townsend L. B., J. Med. Chem., 41, 1242—
1251 (1998).
1-(5-Methyl-1H-benz[d]imidazol-2-yl)-1-ethanone (4b): Yellow solid,
4) Tamm I., Sehgal P. B., Adv. Virus Res., 22, 187—258 (1978).
5) Tamm I., Science, 126, 1235—1236 (1957).
1
yield 80%, mp 170—172 °C. IR (KBr) cmϪ1: 3365, 2919, 2852, 1693. H-
NMR (CDCl3) d: 11.23 (1H, s), 7.65 (1H, d, Jϭ8.0 Hz), 7.48 (1H, d, Jϭ7.8
Hz), 7.24 (1H, s), 3.42 (3H, s), 2.45 (3H, s). MS m/z: 174 (Mϩϩ1).
1-(5-Chloro-1H-benz[d]imidazol-2-yl)-1-ethanone (4c): Yellow solid,
yield 65%, mp 185—187 °C. IR (KBr) cmϪ1: 3294, 3066, 3021, 1677, 1574,
1335, 1219, 1060. 1H-NMR (CDCl3) d: 10.70 (1H, s), 7.82 (1H, t, Jϭ7.6
Hz), 7.51 (1H, m, Jϭ7.4 Hz), 7.30 (1H, m, Jϭ7.2 Hz), 2.81 (3H, s). MS m/z:
195 (Mϩϩ1).
6) Czarny A., Wilson W. D., Boykin D. W., J. Heterocycl. Chem., 33,
1393—1397 (1996).
7) Reddy G. V., Rao V. V. V. N. S. R., Narsaiah B., Rao B. P. S., Synth.
Commun., 32, 2467—2476 (2002).
8) Chakrabarty M., Karmakar S., Mukherji A., Arima S., Harigaya Y.,
Heterocycles, 68, 967—974 (2006).
9) Gogoi P., Konwar D., Tetrahedron Lett., 47, 79—82 (2006).
10) Randall L. O., “Psychopharmacological Agents,” ed. by Gordon M.,
Academic Press, New York, 1974, pp. 175—281.
11) Fryer R. I., “Comprehensive Heterocyclic Chemistry,” ed. by Taylor E.
C., Wiley, New York, 1991, p. 50.
12) Devi T. K., Achaiah G., Reddy V. M., J. Ind. Chem. Soc., 65, 567—
570 (1988).
13) Narayana B., Vijaya Raj K. K., Ashalatha B. V., Suchetha Kumari N.,
Eur. J. Med. Chem., 41, 417—422 (2006).
14) Hussenether T., Hubner H., Gmeiner P., Troschutz, Bioorg. Med.
Chem., 12, 2625—2637 (2004).
1-(5-Nitro-1H-benz[d]imidazol-2-yl)-1-ethanone (4d): Pale yellow solid,
yield 70%, mp 155—157 °C. IR (KBr) cmϪ1: 3360, 3040, 2865, 2160, 1720,
1356, 1240. 1H-NMR (CDCl3) d: 8.91 (1H, s), 8.77 (1H, s), 8.13 (1H, d, Jϭ
7.2 Hz), 8.09 (1H, d, Jϭ7.4 Hz), 2.79 (3H, s). MS m/z: 206 (Mϩϩ1).
(E)-1-(1H-Benz[d]imidazol-2-yl)-3-(5-nitro-2-furyl)-2-propen-1-one
(6a): Yellow solid, yield 40%, mp 205—207 °C. IR (KBr) cmϪ1: 3289, 3014,
1
2917, 1674, 1508, 1021, 1005, 871. H-NMR (CDCl3) d: 8.77 (1H, s), 8.11
(2H, d, Jϭ7.8 Hz), 7.76 (2H, dd, Jϭ7.4 Hz) 7.64 (1H, d, Jϭ7.2 Hz), 7.43
(1H, d, Jϭ7.6 Hz), 7.08 (1H, d, Jϭ8.0 Hz), 6.87 (1H, d, Jϭ8.2 Hz). MS m/z:
284 (Mϩϩ1).
(E)-1-(5-Methyl-1H-benz[d]imidazol-2-yl)-3-(5-nitro-2-furyl)-2-propen-
1-one (6b): Yellow solid, yield 50%, mp 195—197 °C. IR (KBr) cmϪ1: 3276,
3021, 2915, 1682, 1524, 1025, 1011, 875. 1H-NMR (CDCl3) d: 8.77 (1H, s),
7.71 (1H, d, Jϭ8.0 Hz), 7.66 (1H, s), 7.64 (1H, d, Jϭ7.2 Hz), 7.43 (1H, d,
Jϭ7.6 Hz), 7.39 (1H, d, Jϭ7.2 Hz), 7.08 (1H, d, Jϭ7.8 Hz), 6.87 (1H, d,
15) Roma G., Grossi G. C., Di Braccio M., Ghia., Mattioli F., Eur. J. Med.
Chem., 26, 489—496 (1991).
16) Kavali J. R., Badami B. V., Il Farmaco, 55, 406—409 (2000).
17) Di Braccio M., Grossi G. C., Roma G., Vargiu L., Mura M., Marongiu
M. E., Eur. J. Med. Chem., 36, 935—949 (2001).

1084
Vol. 58, No. 8
18) Kumar R., Joshi Y. C., Arkivoc, 2007, 142—149 (2007).
30) Boido A., Vazzana I., Mattioli F., Sparatore F., Il Farmaco, 58, 33—44
19) Kamal A., Shankaraiah N., Prabhakar S., Reddy C. R., Markandeya
(2003).
N., Laxma K., Devaiah X., Bioorg. Med. Chem. Lett., 18, 2434—2439 31) Biagi B., Calderone V., Giorgi I., Livi O., Scartoni V., Baragatti B.,
(2008). Martinotti E., Il Farmaco, 56, 841—849 (2001).
20) Kosychova L., Stumbreviciute Z., Pleckaitiene L., Janciene R., Puodzi- 32) Katritzky A. R., Lan X., Yang J. Z., Denisko O. V., Chem. Rev., 98,
unaite B. D., Chem. Heterocycl. Comp., 40, 811—815 (2004). 409—548 (1998).
21) Janciene R., Vektariene A., Stumbreviciute Z., Kochychova L., Kli- 33) Reddy A. M., Reddy R. R., Reddy V. V., Reddy A. M., Reddy R. R.,
mavicius A. A., Heteroatom. Chem., 15, 363—368 (2004). Reddy V. M., Ind. J. Pharm. Sci., 53, 229—232 (1991).
22) Kosychova L., Pleckaitiene L., Staniulyte Z., Janciene R., Palaima A., 34) Achaiah G., Reddy V. M., Reddy V. M., Ind. J. Pharm. Sci., 53, 253—
Puodziunaite B. D., Arkivoc, 2006, 158—164 (2006). 255 (1991).
23) Che X., Zheng L., Dang Q., Bai X., Tetrahedron, 62, 2563—2568 35) Suresh T., Patnaik S., Chakravarthy A. K., Reddy V. M., J. Pharm.
(2006). Res., 5, 116—121 (2006).
24) Terret N. K., Bojanic D., Merson J. R., Stephenson P. T., Bioorg. Med. 36) Suresh T., Swamy S. K., Reddy V. M., Ind. J. Chem., 46B, 115—125
Chem. Lett., 2, 1745—1750 (1992). (2007).
25) Sanghetti J. N., Kokare N. D., Shinde D. B., Chinese Chem. Lett., 18, 37) Suresh T., Srinivas Naik A., Reddy V. M., Ind. J. Heterocycl. Chem.,
1305—1308 (2007).
17, 97—101 (2007).
26) Kusanur Raviraj A., Ghate M., Kulkarni M. V., J. Chem. Sci., 116,
265—127 (2004).
38) Gajbhiya A., Reddy V. M., Achaiah G., Ind. J. Pharm. Sci., 70, 118—
120 (2008).
27) Kidwai M., Ruby M. K., Venkataramanan R., Chem. Heterocycl. 39) Laddi U. V., Talwar M. B., Desai S. R., Bennur R. S., Bennur S. C.,
Comp., 40, 631—634 (2004).
Ind. J. Chem., 40B, 828—832 (2001).
28) Sanna P., Carta A., Nikookar M. E., Eur. J. Med. Chem., 35, 535—543
(2000).
29) Kopanska K., Najda A., Zebrowska J., Chomicz L., Piekarczyk J.,
Myjak P., Bretner M., Bioorg. Med. Chem., 12, 2617—2624 (2004).
40) Barry A. L., “The Anti-microbial Susceptibility Test,” Principle and
Practice, ed. by Illus-lea and Febiger, Philadelphia, PA, U.S.A., 1976,
p. 180.