Antibacterial and antifungal screening of newly synthesized benzimidazole-clubbed chalcone derivatives

Article abstract of DOI:10.1007/s00044-012-0369-3

Different derivatives of chalcone-possessing benzimidazole as a prime motif were synthesized by the authors by acid catalyzed aldol condensation reaction. The synthesis of the desired compounds was initiated by undertaking two parallel reactions: (i) synthesis of 2-mercaptobenzimidazole and (ii) synthesis of N-(4-acetylphenyl)-2-chloroacetamide from 4-aminoacetophenone. The two intermediates so prepared were condensed to yield 2-(1H-benzo[d]imidazol-2- ylthio)-N-(4-acetylphenyl)acetamide (II) using acetone as solvent and K ₂CO₃ as a scavenger. The resultant product was further reacted with differently substituted aldehydes to produce the titled compounds using thionyl chloride (SOCl₂) in catalytic amount. The synthesized compounds were confirmed for their structure by means of various spectrometric techniques like IR, ¹H NMR, ¹³C NMR, Mass spectra, and Elemental analysis. Thus-obtained chalcone derivatives were tested for their antibacterial and antifungal activities and were reported in form of minimum inhibitory concentration values.

Full text of DOI:10.1007/s00044-012-0369-3

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2013) 22:3688–3697
DOI 10.1007/s00044-012-0369-3
ORIGINAL RESEARCH
Antibacterial and antifungal screening of newly synthesized
benzimidazole-clubbed chalcone derivatives
•
Kalpesh Parikh Deepkumar Joshi
Received: 20 July 2012 / Accepted: 14 November 2012 / Published online: 30 November 2012
Ó Springer Science+Business Media New York 2012
Abstract Different derivatives of chalcone-possessing
benzimidazole as a prime motif were synthesized by the
authors by acid catalyzed aldol condensation reaction. The
synthesis of the desired compounds was initiated by
undertaking two parallel reactions: (i) synthesis of 2-mer-
captobenzimidazole and (ii) synthesis of N-(4-acetylphe-
nyl)-2-chloroacetamide from 4-aminoacetophenone. The
two intermediates so prepared were condensed to yield
2-(1H-benzo[d]imidazol-2-ylthio)-N-(4-acetylphenyl)acet-
amide (II) using acetone as solvent and K2CO3 as a
scavenger. The resultant product was further reacted with
differently substituted aldehydes to produce the titled
compounds using thionyl chloride (SOCl2) in catalytic
amount. The synthesized compounds were confirmed for
their structure by means of various spectrometric techniques
Chalcones are found to be potent analgesics, antioxidants,
and anti-inflammatory agents (Iwalewa et al., 2008). The
multiple pharmacological actions of chalcones prove it to
be highly efficacious as they can be used extensively as
antifungal (Sarma et al., 2007), antiplasmodial (Mei-Lin
Go et al., 2004), antiprotozoal (Azam et al., 2011), and
antibacterial (Bandgar et al., 2010). Some of the substituted
vinyl chalcones have proved to be TNF-a and IL-6 inhib-
itors (Bandgar et al., 2010). Chalcones are potent hydro-
phobic modulators of P-glycoprotein-mediated multidrug
resistance (Boumendjel et al., 1999). Chalcones derived
from the condensation between different acetophenones
and aldehydes make them a potent motif as they exhibit a
wide variety of biological activities including antimitotic
(Ducki et al., 1998), anticancer (Barnard et al., 1993, De
Meyer et al., 1991), Cardiovascular (Furman et al., 2001),
and anti-tubercular (Linn et al., 2002). Similarly derived
chalcones have also proved to be hyperglycemic agents
(Satyanarayana et al., 2004).
1
like IR, H NMR, 13C NMR, Mass spectra, and Elemental
analysis. Thus-obtained chalcone derivatives were tested for
their antibacterial and antifungal activities and were reported
in form of minimum inhibitory concentration values.
Chalcones on incorporation with different biologically
active scaffolds have always shown comparative more
potent activities; like benzfuran chalcones have exhibited
both antioxidant and antibacterial activity (Patil et al.,
2010). Benzimidazole–‘‘a heterocyclic scaffold’’ is a
widely used medicinal component due to its broad spec-
trum of biological activities. Benzimidazoles are the class
of compounds exhibiting excellent antiparasitic activity
(Castilloa et al., 2002), anticancer activity (Reffat, 2011),
antidiabetic, and anticonvulsant activity (Hosamani et al.,
2010). Benzimidazole derivatives have proved to be potent
analgesics (Dixit et al., 2012) and chemotherapeutic agents
(Youssef et al., 2012). Benzimidazole derivatives on
combining with chalcones have resulted in formation of
compounds possessing antiviral properties (Tebbe and
Spiyzer, 1997). Benzimidazole chalcones have proved to
Keywords Chalcones ꢀ Benzimidazole ꢀ
Antimicrobial activity ꢀ MIC
Introduction
Chalcones demonstrate extensive applicability in medicinal
science due to their wide range of biologic activities.
Deepkumar Joshi DST-JRF (INSPIRE Fellow)
K. Parikh (&) ꢀ D. Joshi
Chemistry Division, Chemistry Research Laboratory,
Sheth M. N. Science College, Patan 384265, INDIA
e-mail: deepjoshi359@yahoo.co.in
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Med Chem Res (2013) 22:3688–3697
3689
Fig. 1 Carbon numbering of
the synthesized compounds
(III)1–16
e
k
l
f
O
N
d
c
j
m
NH
i
S
p
g
a
q
N
H
h
n
o
b
r
O
t
s
x
u
R
Chalcones (III)1-16
w
v
Fig. 2 Anionic delocalization
of aldehydic component in
presence of base
be good antimicrobials in recent times (Baviskar et al.,
2009). 2-mercaptobenzimidazole a very good antioxidant,
inhibitor, and antiseptic; is used as a precursor for the
synthesis of titled compounds (Goodman, 1975; Saxena
et al., 1982; Scherhag et al., 1974). Esomeprazole and
lansoprazole possessing benzimidazole skeletal are widely
used for treatment of gastric problems (Gatta et al., 2003).
Authors have tried to demonstrate the synthesis of
chalcones via acid catalyzed aldol condensation method
using acetophenone-bearing benzimidazole and various
substituted aldehydes. There are several methods reported
for the synthesis of chalcones viz. Base catalyzed con-
densation of chalcones is a very popular and the widely
used method (Solankee et al., 2010), Catalyst like BF3-
Etherate (Narender and Reddy, 2007), natural phosphate
modified with sodium nitrate (Sebti et al., 2003), Zinc
(L-proline)2 and water in combination are also used for the
synthesis of chalcones (Siddiqui and Musthafa, 2011). The
prominent method of acid catalyzed aldol condensation
resulting chalcones in the shortest time and maximum yield
reported by utilizing thionyl chloride and ethanol in com-
bination was adapted by the researchers for the synthesis of
the titled compounds as shown in Fig. 1 (Petrov et al.,
2008, Jayapal and Sreedhar, 2010). The use of SOCl2 as an
acid catalyst in aldol condensation helps to overcome the
error of decrease in the activity of aldehydes due to use of
basic catalysts resulting in delocalization of anion formed.
The delocalization phenomena discussed here is shown in
Fig. 2.
Result and discussion
Chemistry
The synthetic methods adapted for the formation of the
benzimidazole-based chalcone synthesis are depicted in
Scheme 1. Two parallel reactions were undertaken
simultaneously, of which the formation of heterocyclic
structure benzimidazole was made possible by a reported
procedure reacting o-phenylenediamine with carbon
disulfide and KOH (Wang and Liu, 2007). On the other
hand 4-aminoacetophenone was reacted with chloroace-
tyl chloride to form an intermediate N-(4-acetylphenyl)-
2-chloroacetamide, which on reaction with 2-mercapto
benzimidazole resulted in the formation of 2-(1H-
benzo[d]imidazol-2-ylthio)-N-(4-acetylphenyl)acetamide (II).
This product (II) on reaction with different aldehydes via
acid-catalyzed aldol condensation resulted in the formation
of titled compounds (III)1–16 in a good yield. The minimum
inhibitory concentration (MIC) values of the synthesized
compounds are indicated in Table 1. The retardation
factor (Rf) value of compounds (III)1–16 is indicated in
Table 2.
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Med Chem Res (2013) 22:3688–3697
NH
NH2
Cl
CAC / TEA
Toluene
O
O
O
Reflux 4 hrs
4-aminoacetophenone
CH3
N-(4-acetylphenyl)-2-chloroacetamide I
CH3
N
K2CO3 / Acetone
Synthesis of
Stirring at RT for
2-mercaptobenzimidazole
SH
4 hrs
NH2
N
H
2-mercaptobenimidzole
NH2
N
NH
S
CS2 / KOH
Ethanol / HCl
N
H
O
O
N
2-(1H-benzo[d]imidazol-2-ylthio)-N-(4-
acetylphenyl)acetamide II
SH
CH3
N
H
CHO
Ethanol / SOCl2
Stirr at RT for 4 hrs
R
CAC : Chloroacetylchloride
TEA : Triethylamine
Substituted Aldehydes
RT : Room temperature
N
R
NH
S
N
H
O
Chalcones III (1-16)
O
Synthesis of benzimidazole endowed chalcone derivatives
Scheme 1 Synthesis of Compounds (III)1–16
Characterization
1H NMR data
IR data
1H NMR spectrum observed for the compound under
investigation exhibited several absorption peaks corre-
sponding to desired protons. Proton of secondary amine
appearing at d = 9.97 confirmed its presence on nitrogen
attached to aromatic ring by single bond, whereas the
absorption peak at d = 11.17 indicated the presence of
proton attached to the secondary nitrogen of the benz-
imidazole nucleus. A peak appearing particularly at
d = 4.65 confirmed the protons of methylene group in the
final structure. The protons of aromatic rings corresponded
to the d values between d = 6.62–8.10. The protons
appearing in the chalcone formation confirmed its position
at d = 7.67 and d = 7.82. The geometry of each proton
Considering a particular compound from the series of deriv-
atives synthesized, let us try to focus on the interpretation of
spectral data. IR spectra obtained at 3236 and 3359 cm-1
indicated the presence of secondary amine in vicinity to car-
bonyl group and in the benzimidazole nucleus, respectively.
A weak absorption stretching vibration band observed at
2750 cm-1 confirmed the presence of methylene group in the
final motif. A sharp intensified band at 1640 cm-1 proved the
presence of carbonyl group in the structure. The presence of
C=C double bond in the aromatic ring was proved by the
absorption band observed at 1413 cm-1
.
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Med Chem Res (2013) 22:3688–3697
3691
Table 1 Results for
-R (Derivatives)
Minimum inhibitory concentration (MIC) in lg/ml
antibacterial and antifungal
screening of compounds
(III)1–16
Gram-positive bacteria Gram-negative bacteria Fungi
S. aureus E. faecalis E. coli P. aeruginosa C. albicans A. niger
-H
250
250
250
250
125
125
125
125
250
250
250
125
250
250
125
250
125
–
125
250
125
125
125
125
125
125
125
125
250
125
250
62.5
31.25
250
250
–
250
250
125
125
125
250
250
250
125
250
250
62.5
125
62.5
125
125
125
–
125
125
62.5
62.5
125
125
125
250
250
250
125
125
62.5
125
125
125
62.5
–
-4-Cl
125
62.5
31.25
62.5
31.25
31.25
62.5
62.5
31.25
31.25
31.25
62.5
62.5
31.25
62.5
62.5
–
-3,4-dimethoxy
-4-NO2
62.5
62.5
125
-N,N-dimethyl
-4-Br
125
-3-Cl
31.25
31.25
31.25
31.25
31.25
15.62
-3-Br
-3,4,5-trimethoxy
-2-NO2
-2,5-dimethoxy
Vanillin
-2-Hydroxy-1-napthaldehyde 62.5
-2-OH
62.5
31.25
31.25
–
-4-OCH3
-4-OH
MIC minimum inhibitory
concentration, Std :standard
drug Fluconazole for antifungal
and Ciprofloxacin for
Fluconazole
Ciprofloxacin
62.5
125
125
125
antibacterial tests
13C NMR data
Table 2 Retardation factor (Rf) value of compounds (III)1–16
Compounds
Substitutions
Rf value
The 13C NMR spectral data helped to confirm the formation
of desired structure. The d values for the spectral study was
seen to vary between d = 39.2 to d = 191. The carbon
atoms ‘‘i’’ and ‘‘p’’ in contact to the electronegative element
oxygen in the carbonyl group appeared downfield, nearly at
161.0 and 191.0, respectively, of which the carbon in the
environment of secondary amine and methylene was seen to
appear a bit up field (i.e. 161.0) than the one near to a,
b-unsaturation. The carbon indicated as ‘‘g’’ present in
benzimidazole nucleus between to nitrogen atoms and
attached to sulfur was observed at d = 148. The two carbons
of chalcone linkage, i.e., carbon-q appeared at d = 121.0and
carbon-r appeared at d = 146.0. When the spectra of final
product possessing nitro at ortho position to ‘‘s’’ carbon was
observed, the d value was seen to be shifting at d = 127.3.
Similar shift was seen in the spectra of 2, 5-dimethoxy sub-
stitution as the d value shifted to 117.3. The carbon num-
bering to the structure is given in Fig. 1.
(III)1
(III)2
(III)3
(III)4
(III)5
(III)6
(III)7
(III)8
(III)9
(III)10
(III)11
(III)12
(III)13
(III)14
(III)15
(III)16
-H
0.57
0.48
0.62
0.43
0.43
0.49
0.47
0.47
0.41
0.40
0.38
0.36
0.37
0.50
0.35
0.34
-4-Cl
-3,4-dimethoxy
-4-NO2
-N,N-dimethyl
-4-Br
-3-Cl
-3-Br
-3,4,5-trimethoxy
-2-NO2
-2,5-dimethoxy
-Vanillin
-2-Hydroxy-1-napthaldehyde
-2-OH
-4-OCH3
-4-OH
Retardation Factor= Distance travelled by analyte/Distance travelled
by solvent
Antimicrobial activity
Mobile phase: Toluene/Acetone = 7/3
The compounds (III)1–16 were tested for their antimicrobial
activities against gram-positive bacteria, gram-negative
bacterial, and fungal strains. The resulting MIC (lg/ml)
values are indicated in the Table 1. It was observed that more
than half of the compounds exhibited excellent activity in
attached with C = C double bond of chalcone indicated to
be Trans (E) as the coupling constant values for the two
were 15.5 and 15.6 Hz, respectively.
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Med Chem Res (2013) 22:3688–3697
comparison to the standards used, while the remaining were
good and one or two of them were poor in comparison to the
standards. The standards used for antifungal activity
screening was Fluconazole and Ciprofloxacin was used as
standard for anti bacterial assay. The MIC value for Fluco-
nazole (standard) against Candida albicans was recorded to
be 125 lg/ml where as against Aspergillus niger was 62.5
lg/ml. Similarly, the MIC values for Ciprofloxacin used as
a standard against gram-positive bacteria S. aureus and
E. faecalis were 62.5 lg/ml and 125 lg/ml, respectively.
When the same standard drug Ciprofloxacin was used against
gram-negative bacterial strains E. coli and P. aeruginosa;
MIC value was observed to be 125 lg/ml. Some of the
compounds showing excellent activity against particular
bacteria and fungi are represented separately and in detail in
the discussion of antibacterial and antifungal section below.
substitutions p-Cl (III)2, p-NO2 (III)4, m-Cl (III)7, m-Br
(III)6, 3-OCH34-OH (III)12, 2-OH-1-napthaldehyde (III)13,
and p-OH (III)16 too exhibited good activity in comparison
to the standard but were less than the one exhibiting
31.25 lg/ml. Only one compound from the series showed
equivalent activity to the standard. The compounds when
tested against another gram-negative bacteria P. aeruginosa
did show few excellent results, especially compound (III)13
2-OH-1-napthaldehyde substituent and compound (III)14
o-OH substituent showed excellent activity. All other sub-
stituents were equivalent in activity with the standard.
Overall, most of the derivatives were more effective on
E. coli than the other bacterial strains.
Antifungal activity
The same synthesized motifs were tested for their anti-
fungal activity against two different fungal strains. The
method implemented for the MIC tests was same as in
antibacterial activity test. Only the strains used were
C. albicans and A. niger. The standard drug used here for
comparison was Fluconazole. The MIC values for the
standard against both the strains appeared to be 125 lg/ml.
Compounds (III)12 and (III)14 with 3-OCH3-4-OH and
2-OH substituent, respectively, showed excellent activity
against C. albicans. When tested on C. albicans, Com-
pounds (III)3, (III)4, (III)5, (III)9, (III)13, (III)15, and (III)16
exhibited equivalent activity to that of standard drug
Fluconazole. Compounds (III)1, (III)2, (III)6, (III)7, (III)8,
(III)10, and (III)11 exhibited poor activity as compared to
standard when tested against C. albicans (ATCC No.
10231). The same compounds were tested against A. niger
(ATCC 1015), where few compounds, viz., (III)3, (III)4,
and (III)13 resulted in equivalent MIC values with refer-
ence. Other compounds exhibited poor activity against
A. niger in comparison to the standard drug used.
Antibacterial activity
The newly synthesized compounds (III)1–16 were screened
for their antibacterial activity against gram-positive bacteria
S. aureus (ATCC No. 25923) and E. faecalis (ATCC No.
29212) and the gram-negative bacterial strain E. coli
(ATCC No. 25922) and P. aeruginosa (ATCC No. 27853).
The samples were tested by standard protocols like Micro
dilution/Broth titer method. The screening for antibacterial
activity was carried out by diluting the solution and pre-
paring the sets consecutively from 1000, 500, 250, 125,
62.5, 31.25, 15.62 up to 7.8 lg/ml. Among all the synthe-
sized derivatives, compound (III)12 exhibited the best MIC
value up to 15.62 lg/ml against gram-positive bacteria
S. aureus. Other compounds showing higher activity than
standard but less than compound (III)12 against the bacterial
strain S. aureus included compounds (III)7, (III)8, (III)9,
(III)10, (III)11, (III)15, and (III)16. Also, derivatives (III)3,
(III)4, and (III)13 possessed MIC value equivalent to that of
the reference. When E. faecalis strain was used for con-
ducting the MIC tests with the same standard Ciprofloxacin,
compounds (III)4, (III)5, (III)6, (III)7, (III)11, (III)14, and
(III)16 exhibited MIC value similar to the standard used. In
general, the derivatives with substitutions like p-NO2 (III)4,
m-Cl (III)7, 2,5-diOCH3 (III)11, o-OH (III)14, and p-OH
(III)16 exhibited good activity against gram-positive bacte-
ria when tested and compared with standard drug. The rest
of the derivatives were showing moderate or lower activity
than reference drug. Compound (III)1 showed poor MIC
value among all screened compounds against gram-positive
bacterial strains. The same synthesized compounds when
tested against gram-negative bacterial strains E. coli,
Compounds with substitutions 3,4-diOCH3 (III)3, N,N-
diCH3 (III)5, p-Br (III)6, 3,4,5-triOCH3 (III)9, o-NO2 (III)10,
2,5-diOCH3 (III)11, and o-OH (III)14 showed excellent
activity near to MIC value 31.25 lg/ml. Compounds with
SAR study
The use of SAR study helped in concluding that the dif-
ferent substitutions on the aromatic ring exerted varied
biological activity. The substitutions were so selected as to
confer different electronic environments of the molecules.
Both electron-withdrawing and electron-donating groups
were chosen as substituents on the chemical structure of the
targeted compound. In major, compounds with electron
donating groups such as methoxy and hydroxy exhibited
lower MIC value than the reference drug used. Compounds
(III)12 and (III)14 with substitutions 3-OCH3-4OH and 2-OH
showed lower MIC value against S. aureus, E. coli, and
C. albicans as compared to the standards used for antimicro-
bial screening. Compounds with substituent from electron-
donating groups like 3,4,5-trimethoxy (III)9, 2,5-dimethoxy
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Med Chem Res (2013) 22:3688–3697
3693
(III)11, 4-methoxy (III)15, and 4-hydroxy (III)16 also showed
lower MIC value than the reference drug used, as described
in Table 1. On the other hand, the derivatives with electron
withdrawing group like chloro, bromo, and nitro did not
execute lower MIC values as compared to the reference
when treated with the fungal strains. From the above results,
it can be concluded that the derivatives with electron-
donating substitutions like hydroxy and methoxy are the
most efficient compounds as antimicrobial agents. The
results in Table 1 strongly support the report that the elec-
tron-donating group having the capacity to increase the
electron density makes the compound more effective
toward the microorganisms. Thus, It is inevitable for a
compound to possess an optimum electron density to
achieve a significant antimicrobial activity.
13C NMR (400 MHz, DMSO-d6, d, ppm): 27.2 (q), 43.2 (h),
121.0 (k), 121.0 (o), 129.2 (l), 129.2 (n), 137.2 (m), 142.2 (j),
166.0 (i), 198.2 (p); (MS (m/z): 212 (M?).
Synthesis of 2-(1H-benzo[d]imidazol-2-ylthio)-N-(4-
acetylphenyl)acetamide II
N-(4-acetylphenyl)-2-chloroacetamide I (0.01 mol, 211.5gm/
mol, 2.11gm) obtained was further reacted with 2-mer-
catobenzimidazole (0.01 mol, 150.2gm/mol, 1.50gm). The
reaction was stirred for 4 h at room temperature in the pres-
ence of K2CO3 (0.02 mol, 138gm/mol, 2.76gm) and acetone
(20 ml) was used as reaction medium. After the completion of
reaction monitored on TLC using Toluene: Acetone (8:2) as
mobile phase, product was poured into water and stirred
vigorously for 1 h. The separated precipitates were collected
and dried. The product was recrystallized from methanol.
Compound II: Solid white; Yield: 85 %; M.P.: 210 °C;
IR (ATR, cm-1): 1413 (C=C str. aromatic ring), 1640
(C=O str.), 2750 (CH2 str. methylene), 3049 (CH str. aromatic
Experimental
Methods, materials and physical measurements
1
ring), 3232 (NH str.), 3359 (NH str. benzimidazole); H
All the chemicals and solvents required for the synthesis
were purchased from Merck ltd., sdfine chemicals, LOBA
Chemie, and HIMEDIA. Melting points reported here are
obtained by open end capillary method and are uncor-
rected. TLC plates used for monitoring the completion of
reaction were purchased from Merck (TLC Silica gel 60
NMR (400 MHz, DMSO-d6, d, ppm): 2.56 (3H, s, -CH3),
4.65 (2H, s, -CH2), 7.30–8.10 (8H, d, Ar–H), 9.97 (1H, s,
-NH), 11.17 (1H, s, benzimidazole-NH); 13C NMR (400 MHz,
DMSO-d6, d, ppm): 27.2 (q), 39.2 (h), 116.2 (b), 116.2 (e),
121.0 (k), 121.0 (o), 124.0 (c), 124.0 (d), 129.2 (l), 129.2 (n),
137.2 (m), 140.0 (a), 140.0 (f), 142.2 (j), 148.0 (g), 166.0
(i), 198.2 (p); MS (m/z): 326 (M?).
F
254). The IR spectral data were measured using Bruker
FT-IR alpha-t (ATR). The H NMR and 13C NMR were
obtained using Bruker Spectrophotometer-400 MHz where
DMSO-d6 was used as solvent and TMS as Reference. The
mass spectral analysis was conducted on Shimadzu mass
spectrophotometer. The elemental analysis was carried out
on Perkin-Elmer 2400 CHN Analyzer.
1
Synthesis of 2-mercaptobenzimidazole
2-mercaptobenzimidazole required for the formation of
compound II was prepared by literature procedure (Castilloa
et al., 2002). Yield: 70 %; M.P. : 286 °C; IR (ATR, cm-1):
1413 (C=C str. aromatic ring), 1640 (C=O str.), 2750 (CH2
str. methylene), 3049 (CH str. aromatic ring), 3232 (NH str.),
3359 (NH str. benzimidazole); 1H NMR (400 MHz, DMSO-
d6, d, ppm): 7.30–8.10 (4H, d, Ar–H), 11.17 (1H, s, benz-
imidazole-NH), 11.69 (1H, s, -SH); 13C NMR (400 MHz,
DMSO-d6, d, ppm): 116.2 (b), 116.2 (e), 124.0 (c), 124.0 (d),
140.0 (a), 140.0 (f), 158.0 (g); MS (m/z): 151 (M?).
Synthesis and physical data
Synthesis of N-(4-acetylphenyl)-2-chloroacetamide I
The titled compound I was obtained by reacting 4-amino-
acetophenone (0.01 mol, 135gm/mol, 1.35gm) with chlo-
roacetylchloride (0.015 mol, 113gm/mol, 1.19 ml) and
Triethylamine (3–4drops) using toluene (25 ml) as solvent.
The reaction mixture was refluxed for 4 h. The completion of
reaction was monitored by TLC with mobile phase Toluene:
Acetone (7:3). The obtained intermediate was buff in color
and solid by state. Crystallization was carried in toluene.
Compound I: Solid light brown crystals; Yield: 87 %;
M.P.: 154 °C; IR (ATR, cm-1): 740 (C–Cl str.), 1413 (C=C
str. aromatic ring), 1640 (C=O str.), 2750 (CH2 str. methy-
lene), 3049 (CH str. aromatic ring), 3232 (NH str.); 1H NMR
(400 MHz, DMSOd6, d, ppm): 2.56 (3H, s, -CH3), 4.89
(2H, s, -CH2), 7.77–8.10 (4H, d, Ar–H), 9.97 (1H, s, -NH);
General procedure for the synthesis of chalcones III
1-16
Acid-catalyzed aldol condensation (Jayapal and Sreedhar,
2010) was implemented for the synthesis of final deriva-
tives (III)1–16 of benzimidazole-clubbed chalcones. 2-(1H-
benzo[d]imidazol-2-ylthio)-N-(4-acetylphenyl)acetamide II
(0.01 mol, 325gm/mol, 3.25gm) was further treated with
different substituted aldehydes (0.01 mol) in the presence
of ethanol and SOCl2 (in catalytic amount). This reaction
was carried out at room temperature for 4 h with constant
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Med Chem Res (2013) 22:3688–3697
stirring and then poured onto crushed ice. The product
obtained is filtered and washed with water periodically and
dried. The final products thus obtained were crystallized
from alcohol and melting points of each synthesized het-
erocyclic chalcones were measured.
7.01–8.19 (11H, d, Ar–H), 7.73(1H, d, HC = CH,
J = 15.4 Hz), 7.83 (1H, d, HC = CH, J = 15.5 Hz), 9.93
(1H, s, -NH), 11.18 (1H, s, benzimidazole-NH); 13C NMR
(400 MHz, DMSO-d6, d, ppm): 39.2 (h), 112.8(w), 112.8
(t), 116.2 (b), 116.2 (e), 121.0 (k), 121.0 (o), 121.9 (q),
123.7 (x), 124.0 (c), 124.0 (d), 127.4 (s), 129.2 (n), 129.2
(l), 137.2 (m), 140.0 (f), 140.0 (a), 142.2 (j), 146.0 (r),
148.0 (g), 150.7 (u), 150.7(v), 166.0 (i), 191.1 (p); MS (m/z):
474(M?). For C26H23N3O4S: C, 65.94; H, 4.90 N, 8.87; S,
6.77 %. Found: C, 65.90; H, 4.93; N, 8.91; S, 6.82 %.
(E)-2-(1H-benzo[d]imidazol-2-ylthio)-N-(4-cinnamoylphe-
nyl)acetamide (III)1 Solid brown; Yield: 68 %; M.P.:
180 °C; IR (ATR, cm-1): 1359 (C–N str. sec. amine), 1413
(C=C str. aromatic ring), 1596 (C=C str. conjugated to car-
bonyl group), 1660 (C=O str. a,b-unsaturation), 2750 (CH2
str. methylene), 3049 (CH str. aromatic ring), 3236 (NH str.
sec. amine); 1H NMR (400 MHz, DMSO-d6, d, ppm): 4.65
(2H, s, -CH2), 6.62–8.10 (13H, d, Ar–H), 7.67(1H, d,
HC = CH, J = 15.7 Hz), 7.82 (1H, d, HC = CH,
J = 15.5 Hz), 9.97 (1H, s, -NH), 11.17 (1H, s, benzimid-
azole-NH); 13C NMR (400 MHz, DMSO-d6, d, ppm): 39.2
(h), 116.2 (b), 116.2 (e), 121.0 (k), 121.0 (o), 121.9 (q), 124.0
(c), 124.0 (d), 127.6 (v), 128.8 (t), 128.8 (x)128.9 (u), 128.9
(w), 129.2 (n), 129.2 (l), 136.0 (s), 137.2 (m), 140.0 (a),,
140.0 (f), 142.2 (j), 146.0 (r), 148.0 (g), 166.0 (i), 191.1 (p);
MS (m/z): 414 (M?). For C24H19N3O2S: C, 69.71 %; H,
4.63 %; N, 10.16 %; S, 7.75 %. Found: C, 69.75 %; H,
4.59 %; N, 10.21 %; S, 7.71 %.
(E)-2-(1H-benzo[d]imidazol-2-ylthio)-N-(4-(3-(4-nitro-
phenyl)acryloyl)phenyl)acetamide (III)4 Solid cream
yellow; Yield: 60 %; M.P.:148 °C; IR (ATR, cm-1): 1360
(C–N str. sec. amine), 1411 (C=C str. aromatic ring), 1599
(C=C str. conjugated to carbonyl group), 1656 (C=O str.
a,b-unsaturation), 2753 (CH2 str. methylene), 3053 (CH str.
aromatic ring), 3247 (NH str. sec. amine); 1H NMR
(400 MHz, Dmso-d6, d, ppm): 4.69 (2H, s, -CH2), 6.82–8.03
(12H, d, Ar–H), 7.59(1H, d, HC=CH, J=15.5 Hz), 7.81 (1H,
d, HC=CH, J = 15.5 Hz), 10.01 (1H, s, -NH), 11.21 (1H, s,
benzimidazole-NH); 13C NMR (400 MHz, DMSO-d6, d,
ppm): 39.2 (h), 116.2 (b), 116.2 (e), 121.0 (k), 121.0 (o),
121.9 (q), 123.9 (u), 123.9 (w), 124.0 (c), 124.0 (d), 128.8 (t),
128.8 (x), 129.2 (n), 129.2 (l), 137.2 (m), 140.0 (f), 140.0 (a),
140.9 (s), 142.2 (j), 146.0 (r), 147.6 (v), 148.0 (g), 166.0 (i),
191.1 (p); MS (m/z): 459(M?). For C24H18N4O4S: C, 62.87;
H, 3.96; N, 12.22; S, 6.99 %. Found: C, 62.90; H, 4.01; N,
12.30; S, 7.03 %.
(E)-2-(1H-benzo[d]imidazol-2-ylthio)-N-(4-(3-(4-chloro-
phenyl)acryloyl)phenyl)acetamide (III)2 Solid dark
brown; Yield: 71 %; M.P.:184 °C(D); IR (ATR, cm-1):
1352 (C–N str. sec. amine), 1421 (C=C str. aromatic ring),
1591 (C=C str. conjugated to carbonyl group), 1662 (C=O
str. a,b-unsaturation), 2763 (CH2 str. methylene), 3032 (CH
(E)-2-(1H-benzo[d]imidazol-2-ylthio)-N-(4-(3-(4-(dimeth-
ylamino)phenyl)acryloyl)phenyl)acetamide (III)5 Solid
light orange; Yield: 65 %; M.P.:188 °C; IR (ATR, cm-1):
1369 (C–N str. sec. amine), 1423 (C=C str. aromatic ring),
1600 (C=C str. conjugated to carbonyl group), 1671 (C = O
str. a,b-unsaturation), 3053 (CH str. aromatic ring), 2759
1
str. aromatic ring), 3234 (NH str. sec. amine); H NMR
(400 MHz, DMSO-d6, d, ppm): 4.63 (2H, s, -CH2),
6.92–8.10 (12H, d, Ar–H), 7.69(1H, d, HC = CH,
J = 15.6 Hz), 7.83 (1H, d, HC = CH, J = 15.4 Hz), 9.97
(1H, s, -NH), 11.20 (1H, s, benzimidazole-NH); 13C NMR
(400 MHz, DMSO-d6, d, ppm): 39.2 (h), 116.2 (b), 116.2 (e),
121.0 (k), 121.0 (o), 121.9 (q), 124.0 (c), 124.0 (d), 128.5 (u),
128.5(w), 129.2 (n), 129.2 (l), 129.8 (t), 129.8 (x), 133.6 (v),
134.4 (s), 137.2 (m), 140.0 (f), 140.0 (a), 142.2 (j), 146.0 (r),
148.0 (g), 166.0 (i), 191.1 (p); MS (m/z): 448(M?). For
C24H18N3O2SCl: C, 64.35 %; H, 4.05 %; N, 9.38 %; S,
7.16 %. Found: C, 64.39; H, 4.03; N, 9.43; S, 7.19 %.
1
(CH2 str. methylene), 3247 (NH str. sec. amine); H NMR
(400 MHz, Dmso-d6, d, ppm): 3.16 (6H, s, -CH3 N,N-
dimethyl group), 4.59 (2H, s, -CH2), 6.69–8.10 (12H, d,
Ar–H), 7.71(1H, d, HC=CH, J = 15.5 Hz), 7.79 (1H, d,
HC=CH, J = 15.8 Hz), 10.07 (1H, s, -NH), 11.13 (1H, s,
benzimidazole-NH); 13C NMR (400 MHz, DMSO-d6, d,
ppm): 39.2 (h), 116.2 (b), 112.9 (u), 112.9 (w), 116.2 (e),
121.0 (o), 121.0 (k), 121.9 (q), 124.0 (c), 124.0 (d), 124.9 (s),
129.2 (l), 129.2 (n), 129.8 (x), 129.8 (t), 137.2 (m), 140.0 (a),
140.0 (f), 142.2 (j), 146.0 (r), 148.0 (g), 166.0 (i), 150.6 (v),
191.1 (p); MS (m/z): 460(M?). For C26H24N4O2S: C, 68.40;
H, 5.30; N, 12.27; S, 7.02 %. Found: C, 68.36; H, 5.34;
N, 12.30; S, 7.16 %.
(E)-2-(1H-benzo[d]imidazol-2-ylthio)-N-(4-(3-(3,4-dime-
thoxyphenyl)acryloyl)phenyl)acetamide
(III)3 Solid
chrome yellow; Yield: 64 %; M.P.:136 °C; IR (ATR,
cm-1): 1347 (C–N str. sec. amine), 1403 (C=C str. aro-
matic ring), 1589 (C=C str. conjugated to carbonyl group),
1661 (C=O str. a,b-unsaturation),), 2756 (CH2 str. meth-
ylene), 3041 (CH str. aromatic ring, 3242 (NH str. sec.
amine); 1H NMR (400 MHz, DMSO-d6, d, ppm): 3.75
(3H, s, OCH3), 3.81 (3H, s, OCH3),4.61 (2H, s, -CH2),
(E)-2-(1H-benzo[d]imidazol-2-ylthio)-N-(4-(3-(4-bromo-
phenyl)acryloyl)phenyl)acetamide (III)6 Solid dark
brown; Yield: 57 %; M.P.:190 °C; IR (ATR, cm-1): 1361
123

Med Chem Res (2013) 22:3688–3697
3695
(E)-2-(1H-benzo[d]imidazol-2-ylthio)-N-(4-(3-(3,4,5-trime-
thoxyphenyl)acryloyl)phenyl)acetamide (III)9 Solid light
yellow; Yield: 78 %; M.P.:148 °C; IR (ATR, cm-1): 1352
(C–N str. sec. amine), 1423 (C=C str. aromatic ring), 1593
(C=C str. conjugated to carbonyl group), 1667 (C=O str.
a,b-unsaturation), 2759 (CH2 str. methylene), 3059 (CH
(C–N str. sec. amine), 1409 (C=C str. aromatic ring), 1586
(C=C str. conjugated to carbonyl group), 1656 (C=O str.
a,b-unsaturation), 2747 (CH2 str. methylene), 3059 (CH str.
aromatic ring), 3242 (NH str. sec. amine); 1H NMR
(400 MHz, Dmso-d6, d, ppm): 4.60 (2H, s, -CH2), 6.72–8.00
(12H, d, Ar–H), 7.72(1H, d, HC=CH, J = 15.7 Hz), 7.85
(1H, d, HC=CH, J = 15.5 Hz), 9.92 (1H, s, -NH), 11.12 (1H,
s, benzimidazole-NH); 13C NMR (400 MHz, DMSO-d6, d,
ppm): 39.2 (h), 116.2 (b), 116.2 (e), 120.6 (v), 121.0 (k),
121.0 (o), 121.9 (q), 124.0 (c), 124.0 (d), 128.3 (x), 128.3 (t),
129.2 (n), 129.2 (l), 131.9 (u), 131.9 (w), 133.9 (s), 137.2 (m),
140.0 (a), 140.0 (f), 142.2 (j), 146.0 (r), 148.0 (g), 166.0 (i),
191.1 (p); MS (m/z): 492(M?). For C24H18N3O2SBr: C,
58.54 H, 3.68; N, 8.53; S, 6.51 %. Found: C, 58.58; H, 3.71;
N, 8.57; S, 6.54 %.
1
str. aromatic ring), 3249 (NH str. sec. amine); H NMR
(400 MHz, DMSO-d6, d, ppm): 4.59 (2H, s, -CH2),
6.69–7.99 (10H, d, Ar–H), 7.70(1H, d, HC = CH,
J = 15.7 Hz), 7.80 (1H, d, HC=CH, J = 15.5 Hz), 9.91
(1H, s, -NH), 11.21(1H, s, benzimidazole-NH); 13C NMR
(400 MHz, DMSO-d6, d, ppm): 39.2 (h), 103.7 (t), 103.7
(x), 116.2 (b), 116.2 (e), 121.0 (k), 121.0 (o), 121.9 (q),
124.0 (c), 124.0 (d), 127.9 (s), 129.2 (l), 129.2 (n), 137.2
(m), 138.7 (v), 140.0 (a), 140.0 (f), 142.2 (j), 146.0 (r),
148.0 (g), 153.9 (u), 153.9 (w), 166.0 (i), 191.1 (p); MS (m/z):
504(M?). For C27H25N3O5S: C, 64.40; H, 5.00; N, 8.34; S,
6.37 %. Found: C, 64.35; H, 5.03; N, 8.39; S, 6.69 %.
(E)-2-(1H-benzo[d]imidazol-2-ylthio)-N-(4-(3-(3-chloro-
phenyl)acryloyl)phenyl)acetamide (III)7 Solid light
yellow; Yield: 77 %; M.P.: 126 °C; IR (ATR, cm-1): 1361
(C–N str. sec. amine), 1411 (C=C str. aromatic ring), 1591
(C=C str. conjugated to carbonyl group), 1661 (C=O str.
a,b-unsaturation), 2747 (CH2 str. methylene), 3053 (CH
(E)-2-(1H-benzo[d]imidazol-2-ylthio)-N-(4-(3-(2-nitro-
phenyl)acryloyl)phenyl)acetamide (III)10 Solid off white;
Yield: 78 %; M.P.:202 °C; IR (ATR, cm-1): 1352 (C–N str.
sec. amine), 1410 (C=C str. aromatic ring), 1586 (C=C str.
conjugated to carbonyl group), 1652 (C=O str. a,b-unsatu-
ration), 2747 (CH2 str. methylene), 3062 (CH str. aromatic
ring), 3249 (NH str. sec. amine); 1H NMR (400 MHz,
DMSO-d6, d, ppm): 4.59 (2H, s, -CH2), 6.53–7.89 (12H, d,
Ar–H), 7.73(1H, d, HC=CH, J = 15.7 Hz), 7.80 (1H, d,
HC=CH, J = 15.7 Hz), 9.97 (1H, s, -NH), 11.19 (1H, s,
benzimidazole-NH); 13C NMR (400 MHz, DMSO-d6, d,
ppm): 39.2 (h), 116.2 (b), 116.2 (e), 121.0 (o), 121.0 (k),
121.9 (q), 123.9 (u), 124.0 (c), 124.0 (d), 127.3 (s), 127.3 (x),
128.7 (v), 129.2 (l), 129.2 (n), 134.9 (w), 137.2 (m), 140.0
(a), 140.0 (f), 142.2 (j), 146.0 (r), 148.7 (t), 148.0 (g), 166.0
(i), 191.1 (p); MS (m/z): 459(M?). Anal. calc. For
C24H18N4O4S: C, 62.87; H, 3.96; N, 12.22; S, 6.99 %.
Found: C, 62.93; H, 3.87; N, 12.18; S, 6.94 %.
1
str. aromatic ring), 3239 (NH str. sec. amine); H NMR
(400 MHz, DMSO-d6, d, ppm): 4.61 (2H, s, -CH2), 6.79–
8.17 (12H, d, Ar–H), 7.77(1H, d, HC=CH, J = 15.7 Hz),
7.89 (1H, d, HC=CH, J = 15.8 Hz), 9.89 (1H, s, -NH),
11.15 (1H, s, benzimidazole-NH); 13C NMR (400 MHz,
DMSO-d6, d, ppm): 39.2 (h), 116.2 (b), 116.2 (e), 121.0
(o), 121.0 (k), 121.9 (q), 124.0 (c), 124.0 (d), 126.3 (x),
126.3 (t), 128.6 (v), 129.2 (n), 129.2 (l), 130.9 (w), 134.9
(u), 136.9 (s), 137.2 (m), 140.0 (a), 140.0 (f), 142.2 (j),
146.0 (r), 148.0 (g), 166.0 (i), 191.1 (p); MS (m/z):
448(M?). For C24H18N3O2SCl: C, 64.35; H, 4.05; N, 9.38;
S, 7.16 %. Found: C, 64.39; H, 4.09; N, 9.34; S, 7.22 %.
(E)-2-(1H-benzo[d]imidazol-2-ylthio)-N-(4-(3-(3-bromo-
phenyl)acryloyl)phenyl)acetamide (III)8 Solid light
brown; Yield: 80 %; M.P.:110 °C; IR (ATR, cm-1): 1352
(C–N str. sec. amine), 1416 (C=C str. aromatic ring), 1582
(C=C str. conjugated to carbonyl group), 1653 (C=O str.
a,b-unsaturation), 2759 (CH2 str. methylene), 3056 (CH str.
aromatic ring), 3239 (NH str. sec. amine); 1H NMR
(400 MHz, DMSO-d6, d, ppm): 4.57 (2H, s, -CH2),
6.62–8.10 (12H, d, Ar–H), 7.72(1H, d, HC=CH, J =
15.5 Hz), 7.82 (1H, d, HC=CH, J = 15.5 Hz), 9.91 (1H, s,
-NH), 11.23 (1H, s, benzimidazole-NH); 13C NMR
(400 MHz, DMSO-d6, d, ppm): 39.2 (h), 116.2 (b), 116.2
(e), 121.0 (k), 121.0 (o), 121.9 (q), 123.9 (u), 124.0 (c),
124.0 (d), 127.3 (x), 129.2 (n), 129.2 (l), 129.5 (w), 130.6
(v), 133.7 (t), 137.2 (m), 137.9 (s), 140.0 (f), 140.0 (a),
142.2 (j), 146.0 (r), 148.0 (g), 166.0 (i), 191.1 (p); MS (m/z):
492(M?). For C24H18N3O2SBr: C, 58.54; H, 3.68; N, 8.53 ;
S, 6.51 %. Found: C, 58.59; H, 3.72; N, 8.55; S, 6.56 %.
(E)-2-(1H-benzo[d]imidazol-2-ylthio)-N-(4-(3-(2,5-dime-
thoxyphenyl)acryloyl)phenyl)acetamide
(III)11 Solid
lemon yellow; Yield: 82 %; M.P.:168 °C; IR (ATR,
cm-1): 1361 (C–N str. sec. amine), 1421 (C=C str. aro-
matic ring), 1589 (C=C str. conjugated to carbonyl group),
1659 (C=O str. a,b-unsaturation), 2756 (CH2 str. methy-
lene), 3051 (CH str. aromatic ring), 3231 (NH str. sec.
amine); 1H NMR (400 MHz, DMSO-d6, d, ppm): 3.56 (6H,
s, -OCH3), 4.69 (2H, s, -CH2), 6.62–8.10 (11H, d, Ar–H),
7.62(1H, d, HC=CH, J = 15.7 Hz), 7.79 (1H, d, HC=CH,
J = 15.7 Hz), 9.91 (1H, s, -NH), 11.21 (1H, s, benzimid-
azole-NH); 13C NMR (400 MHz, DMSO-d6, d, ppm): 39.2
(h), 112.3 (x), 116.2 (b), 116.2 (e), 116.7 (v), 117.3 (s),
117.9 (u), 121.0 (k), 121.0 (o), 121.9 (q), 124.0 (c), 124.0
(d), 129.2 (l), 129.2 (n), 137.2 (m), 140.0 (a), 140.0 (f),
123

3696
Med Chem Res (2013) 22:3688–3697
142.2 (j), 143.0 (r), 148.0 (g), 152.7 (t), 152.9 (w), 166.0
(i), 191.1 (p); MS (m/z): 474(M?). Anal. calc. For
C26H23N3O4S: C, 65.94 %; H, 4.90; N, 8.87; S, 6.77 %.
Found: C, 65.91; H, 4.87; N, 9.78; S, 6.80 %.
C = C, J = 15.7 Hz), 10.02 (1H, s, -NH), 11.24 (1H, s,
benzimidazole-NH); 13C NMR (400 MHz, dmso, d,ppm):21.0
(k), 39.2 (h), 116.2 (b), 116.2 (e), 117.9 (u), 121.0 (o), 121.9 (w),
121.9 (q), 123.3 (s), 124.0 (c), 124.0 (d), 128.3 (x), 129.2 (l),
129.2 (n), 129.7 (v), 137.2 (m), 140.0 (a),140.0 (f), 142.0 (r),
142.2 (j), 148.0 (g), 158.7 (t), 166.0 (i), 191.1 (p); MS (m/z):
430(M?). Anal. calc. For C24H19N3O3S: C, 67.12; H, 4.46; N,
9.78; S, 7.47 %. Found: C, 67.14; H, 4.43; N, 9.74; S, 7.46 %.
(E)-2-(1H-benzo[d]imidazol-2-ylthio)-N-(4-(3-(4-hydroxy-
3-methoxyphenyl)acryloyl)phenyl)acetamide (III)12 Solid
lemon yellow; Yield: 76 %; M.P.:158 °C; IR (ATR,
cm-1): 1356 (C–N str. sec. amine), 1421 (C=C str. aro-
matic ring), 1599 (C=C str. conjugated to carbonyl group),
1662 (C = O str. a,b-unsaturation), 2752 (CH2 str. meth-
ylene), 3056 (CH str. aromatic ring), 3241 (NH str. sec.
amine); 1H NMR (400 MHz, DMSO-d6, d, ppm): 3.78 (3H,
s, -OCH3), 3.19 (1H, s, -OH), 4.59 (2H, s, -CH2), 6.89–8.00
(11H, d, Ar–H), 7.70(1H, d, HC=CH, J = 15.7 Hz), 7.83
(1H, d, HC=CH, J = 15.5 Hz), 9.89 (1H, s, -NH), 11.14
(1H, s, benzimidazole-NH),; 13C NMR (400 MHz, DMSO-
d6, d, ppm): 39.2 (h), 112.7 (t), 116.2 (b), 116.2 (e), 116.9
(w), 121.0 (k), 121.0 (o), 121.9 (q), 122.3 (x), 124.0 (c),
124.0 (d), 127.3 (s), 129.2 (n), 129.2 (l), 137.2 (m), 140.0
(a), 140.0 (f), 142.2 (j), 146.0 (r), 146.7 (v), 147.9 (u),
148.0 (g), 166.0 (i), 191.1 (p); MS (m/z): 460(M?). Anal.
calc. For C25H21N3O4S: C, 65.34; H, 4.61; N, 9.14; S,
6.98 %. Found: C, 65.39; H, 4.63; N, 9.18; S, 6.94 %.
(E)-2-(1H-benzo[d]imidazol-2-ylthio)-N-(4-(3-(4-methoxy-
phenyl)acryloyl)phenyl)acetamide (III)15 Solid light yel-
low; Yield: 86 %; M.P.:164 °C; IR (ATR, cm-1): 1351 (C–N
str. sec. amine), 1429 (C=C str. aromatic ring), 1599 (C=C str.
conjugated to carbonyl group), 1653 (C=O str. a,b-unsaturation),
2759 (CH2 str. methylene), 3051 (CH str. aromatic ring), 3249
(NH str. sec. amine); 1H NMR (400 MHz, DMSO-d6, d, ppm):
3.79 (3H, s, -OCH3), 4.61 (2H, s, -CH2), 6.79–8.06 (12H, d, Ar–
H), 7.77(1H, d, HC=CH, J = 15.6 Hz), 7.83 (1H, d, HC=CH,
J = 15.5 Hz), 9.99 (1H, s, -NH), 11.23 (1H, s, benzimidazole-
NH); 13C NMR (400 MHz, DMSO-d6, d, ppm): 39.2 (h), 114.9
(w), 114.9 (u), 116.2 (b), 116.2 (e), 121.0 (o), 121.0 (k), 121.9 (q),
124.0 (c), 124.0 (d), 128.3 (s), 129.2 (l), 129.2 (n), 130.3 (x),
130.7 (t), 137.2 (m), 140.0 (a),140.0 (f), 142.2 (j), 146.0 (r), 146.0
(r), 148.0 (g), 166.0 (i), 191.1 (p); MS (m/z): 444(M?). Anal.
calc. For C25H21N3O3S: C, 67.70; H, 4.77; N, 9.47; S, 7.23 %.
Found: C, 67.74; H, 4.73; N, 9.42; S, 7.26 %.
(E)-2-(1H-benzo[d]imidazol-2-ylthio)-N-(4-(3-(2-hydrox-
ynaphthalen-1-yl)acryloyl)phenyl)acetamide (III)13 Solid
purple; Yield: 76 %; M.P.:186 °C; IR (ATR, cm-1): 1359
(C–N str. sec. amine), 1413 (C = C str. aromatic ring),
1596 (C = C str. conjugated to carbonyl group), 1660
(C = O str. a,b-unsaturation), 2750 (CH2 str. methylene),
3049 (CH str. aromatic ring), 3236 (NH str. sec. amine); 1H
NMR (400 MHz, DMSO-d6, d, ppm): 3.09 (1H, s, -OH),
4.65 (2H, s, -CH2), 6.63–8.10 (14H, d, Ar–H), 7.67(1H, d,
HC=CH), 7.82 (1H, d, HC=CH), 9.97 (1H, s, -NH), 11.17
(1H, s, benzimidazole-NH); 13C NMR (400 MHz, DMSO-
d6, d, ppm): 21.0 (k), 39.2 (h), 116.2 (b), 116.2 (e), 117.9
(u), 121.0 (o), 121.9 (w), 121.9 (q), 123.3 (s), 124.0 (c),
124.0 (d), 128.3 (x), 129.2 (l), 129.2 (n), 129.7 (v), 137.2
(m), 140.0 (a),140.0 (f), 142.0 (r), 142.2 (j), 148.0 (g),
158.7 (t), 166.0 (i), 191.1 (p); MS (m/z): 430(M?). Anal.
calc. For C28H21N3O3S: C, 70.13; H, 4.41; N, 8.76; S,
6.69 %. Found: C, 70.16; H, 4.47; N, 8.80; S, 6.74 %.
(E)-2-(1H-benzo[d]imidazol-2-ylthio)-N-(4-(3-(4-hydroxy-
phenyl)acryloyl)phenyl)acetamide (III)16 Solid chrome
yellow; Yield: 63 %; M.P.:168 °C; IR (ATR, cm-1): 1351
(C–N str. sec. amine), 1419 (C=C str. aromatic ring), 1591
(C=C str. conjugated to carbonyl group), 1658 (C=O str. a,b-
unsaturation), 2763 (CH2 str. methylene), 3055 (CH str.
aromatic ring), 3249 (NH str. sec. amine); 1H NMR
(400 MHz, DMSO-d6, d, ppm): 3.16 (1H, s, -OH), 4.67 (2H,
s, -CH2), 6.82–8.17 (12H, d, Ar–H), 7.62(1H, d, CH=CH,
J = 15.6 Hz), 7.79 (1H, d, HC=CH, J = 15.7 Hz), 9.92 (1H,
s, -NH), 11.25 (1H, s, benzimidazole-NH); 13C NMR
(400 MHz, DMSO-d6, d, ppm): 39.2 (h), 115.9 (u), 115.9
(w), 116.2 (b), 116.2 (e), 121.0 (k), 121.0 (o), 121.9 (q), 124.0
(c), 124.0 (d), 127.3 (s), 129.2 (l), 129.2 (n), 130.7 (x), 130.7
(t), 137.2 (m), 140.0 (a), 140.0 (f), 142.2 (j), 146.0 (r), 148.0
(g), 156.7 (v), 166.0 (i), 191.1 (p); MS (m/z): 430(M?). Anal.
calc. For C24H19N3O3S: C, 67.12; H, 4.46; N, 9.78; S,
7.47 %. Found: C, 66.09; H, 4.43; N, 9.82; S, 7.46 %.
(E)-2-(1H-benzo[d]imidazol-2-ylthio)-N-(4-(3-(2-hydroxy-
phenyl)acryloyl)phenyl)acetamide (III)14 Solid light
brown; Yield: 56 %; M.P.:186 °C; IR (ATR, cm-1): 1352
(C–N str. sec. amine), 1429 (C=C str. aromatic ring), 1589
(C=C str. conjugated to carbonyl group), 1663 (C=O str. a,b-
unsaturation), 2751 (CH2 str. methylene), 3053 (CH str. aro-
Conclusion
In the present research work, we have synthesized benz-
imidazole-clubbed chalcone derivatives as microorganism
growth inhibitors. The antifungal and antibacterial data
displayed significant activity of the synthesized compounds.
1
matic ring), 3239 (NH str. sec. amine); H NMR (400 MHz,
dmso, d, ppm): 3.06 (1H, s, -OH), 4.59 (2H, s, -CH2), 6.59–8.03
(11H, d, Ar), 7.72(1H, d, C=C, J = 15.5 Hz), 7.88 (1H, d,
123

Med Chem Res (2013) 22:3688–3697
3697
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Acknowledgments The authors are thankful to Sheth M. N. Science
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digarh, for providing analytical and instrumentation facilities. We are
also thankful to the Department of Science and Technology-INDIA for
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