D. Sharma et al. / European Journal of Medicinal Chemistry 44 (2009) 1119e1127
1121
Table 1
Physicochemical characteristics of 2-(substituted phenyl)-1H-benzimidazoles
and [2-(substituted phenyl)-benzimidazol-1-yl]-pyridin-3-yl-methanones
8e9 ppm. Further, it is important to note that the appearance
of a singlet at d 11.07 ppm indicated the presence of COOH
group in compound 18. The absence of a singlet at
d 11 ppm in the NMR spectra of compounds 11e17 and 19
indicated the absence of the free COOH group. This confirms
that compounds 11e19 are tertiary amides and not the physi-
cal mixture of nicotinic acid and compounds 1e10. Therefore,
this assures the reaction of nicotinyl chloride with the second-
ary nitrogen of benzimidazole nucleus.
Compound Mol. formula Mol. wt. M.p. (ꢁC)
Rf valuea Yield (%)
Above 250 0.09
179e181 0.18
Above 250 0.29
79e81 0.80
1
C13H9N2Cl
C13H9N2Cl
C13H9N2Cl
C13H10N2
228.71
228.71
228.71
194.22
228.28
228.28
228.28
238.29
225.27
210.25
36.71
17.55
48.02
14.42
49.30
15.12
25.53
15.76
16.12
30.02
39.13
47.82
73.91
11.20
48.59
70.09
14.95
45.08
14.20
2
3
4
5
C13H9N3O2
C13H9N3O2
C13H9N3O2
C14H10N2O2
C14H10N2O
C13H10N2O
Above 250 0.40
Above 250 0.16
6
7
239e241
133e135
119e121
224e226
84e86
0.81
0.16
0.36
0.48
0.95
0.48
0.59
0.15
0.22
0.31
0.90
0.13
0.90
8
3. Results and discussion
9
10
11
12
13
14
15
16
17
18
19
a
3.1. Antimicrobial activity
C19H12N3OCl 333.83
C19H12N3OCl 333.83
C19H12N3OCl 333.83
224e226
149e151
64e66
The synthesized compounds were screened for their in vitro
antimicrobial activities against two Gram-positive bacteria e
Staphylococcus aureus, Bacillus subtilis, Gram-negative bacte-
rium e Escherichia coli and fungal strains e Aspergillus niger
and Candida albicans by tube dilution method [34] using
ciprofloxacin and fluconazole as control drugs for antibacterial
and antifungal activities, respectively. The results of
antimicrobial studies are presented in Table 3. In general the
compounds showed improved antibacterial activity when
compared to their antifungal activity. The deduced patterns
of antimicrobial activity of substituted benzimidazoles are in
the following order.
C19H13N3O2
C19H12N4O3
C19H12N4O3
C19H12N4O3
C20H13N3O3
C20H15N3O2
315.37
344.30
344.30
344.30
343.41
329.39
244e246
239e241
49e51
139e141
99e101
TLC mobile phase: toluene/chloroform (7:3).
amide linkage between the 3-substituted pyridine and the
benzimidazole nucleus.
Compound 5 showed a doublet at d 8.11e8.14 ppm and
7.85e7.89 ppm corresponding to a proton of the C3, C5 and
C2, C6 of NO2 substituted benzene ring. Further, the appear-
ance of NMR signals at d 7.52e7.56 ppm and 6.54e
6.56 ppm demonstrated the presence of C4, C7 and C5, C6
protons of benzimidazole nucleus.
The absence of an additional d at 7.02e7.06 ppm in com-
pound 5 (in contrast to compound 4) indicated the absence
of proton at C4 of aromatic ring which has been occupied by
the NO2 group. The appearance of d at 6.5e7.8 ppm
corresponds to the aromatic protons of benzene and benzimid-
azole nucleus whereas the nicotinic acid nucleus showed d at
E. coli > B. subtilis > S. aureus > C. albicans > A. niger
Compounds 11e13 are the most effective compounds
against S. aureus with pMICsa value of 1.73, 1.73 and 1.79
(Table 3), respectively. For activity against B. subtilis
compounds 5 and 10 yielded better activity (Table 3) in com-
parison to other compounds synthesized. The antimicrobial
spectrum of substituted benzimidazoles against E. coli demon-
strated that compounds 12e14 were the most active ones with
Table 2
Spectral characterization of selected compounds of 2-(substituted phenyl)-1H-benzimidazoles and [2-(substituted phenyl)-benzimidazol-1-yl]-pyridin-3-yl-
methanones
Compound
IR (KBr pellets) cmꢀ1
1H NMR (CDCl3) d ppm
4
1557.41, 1411.80 (skeletal bands), 1649.99
(CeH str., Ar), 1518.84 (CeC str., Ar)
7.02e7.06 (t, 1H, CH of C4 of Ar-H), 7.25e7.29 (t, 2H, CH of C5 and C6 of
benzimidazole), 7.36e7.39 (d, 2H, CH of C3 and C5 of ArH), 7.47e7.48 (d, 2H,
CH of C2 and C6 of ArH), 7.81e7.82 (d, 2H, CH of C4 and C7 of benzimidazole)
6.54e6.56 (t, 2H, CH of C5 and C6 of benzimidazole), 7.52e7.56 (d, 2H, CH of
C4 and C7 of benzimidazole), 7.85e7.89 (d, 2H, CH of C2 and C6 of Ar-H), 8.11e
8.14 (d, 2H, CH of C3 and C5 of ArH)
5
1558.38, 1416.62 (skeletal bands), 1653.52 (CeH str., Ar),
1520.77 (CeC str., Ar), 1344.29 (NO2 sym str., Ar)
15
16
17
18
1527, 1466 (skeletal bands), 1633.9 (C]O, ter. amide),
799.8 (CeH, 3-sub. pyridine), 1333 (NO2 sym str., Ar)
9.39 (s, 1H, CH of C2 of nicotinic acid), 9.00 (d, 1H, CH of C4 of nicotinic acid),
8.71 (d, 1H, CH of C6 of nicotinic acid), 8.06e8.43 (m, 4H, CH of Ar-NO2), 6.9e
7.5 (m, 4H, CH of C4eC7 of benzimidazole)
9.36 (s, 1H, CH of C4 of nicotinic acid), 8.82e8.86 (d, 1H, CH of C6 of nicotinic
acid), 9.10 (d, 1H, CH of C6 of Ar-NO2), 7.48e8.02 (m, 4H, CH of C4eC7 of
benzimidazole)
1523.9, 1467.8 (skeletal bands), 1637.2 (C]O, ter. amide),
832 (CeH, 3-sub. pyridine), 1349.7 (NO2 sym str., Ar)
1574.0, 1463.2 (skeletal bands), 1637.2 (C]O, ter. amide),
842.2 (CeH, 3-sub. pyridine), 1347.6 (NO2 sym str., Ar)
8.81 (s, 1H, CH of C2 of nicotinic acid), 8.11e8.13 (d, 1H, CH of C6 of nicotinic
acid), 7.94e7.96 (m, 4H, CH of C4eC7 of Ar-NO2), 7.77e7.80 (m, 4H, CH of
C4eC7 of benzimidazole)
1527.3, 1438.7 (skeletal bands), 669.2 (ring bend,
3-substituted pyridine), 3411.0 (OH str., COOH)
11.07 (s, 1H, COOH), 9.20 (s, 1H, CH of C2 of nicotinic acid), 8.91 (d, 1H, CH of
C4 of nicotinic acid), 8.80 (d, 1H, CH of C6 of nicotinic acid), 7.84e7.86 (d, 1H,
CH of C3 of AreCOOH), 6.85e6.95 (m, 4H, CH of C4eC7 of benzimidazole)