One pot synthesis and antibacterial activity of (4Z)-4-benzylidene-1-methyl-2-styryl-1H-imidazol-5(4H)-one

Article abstract of DOI:10.14233/ajchem.2016.19763

Green synthesis of (4Z)-4-benzylidene-1-methyl-2-styryl-1H-imidazol-5(4H)-one derivatives have been developed in good yields and tested for their antibacterial activities against Escherichia coli, Providencia aeruginosa, Pseudomonas azotogensis and Baccil

Full text of DOI:10.14233/ajchem.2016.19763

Asian Journal of Chemistry; Vol. 28, No. 7 (2016), 1975-1978
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2016.19763
One Pot Synthesis and Antibacterial Activity of
(4Z)-4-Benzylidene-1-methyl-2-styryl-1H-imidazol-5(4H)-one
1,*
2
V. ANITHA RANI and Y. BHARATHI KUMARI
1
2
Department of Chemistry, Institute of Aeronautical Engineering, Dundigal, Hyderabad-500 043, India
Department of Chemistry, College of Engineering, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad-500 085, India
*
Corresponding author: E-mail: anitha1810@gmail.com
Received: 8 December 2015; Accepted: 16 March 2016;
Published online: 31 March 2016;
AJC-17851
Green synthesis of (4Z)-4-benzylidene-1-methyl-2-styryl-1H-imidazol-5(4H)-one derivatives have been developed in good yields and
tested for their antibacterial activities against Escherichia coli, Providencia aeruginosa, Pseudomonas azotogensis and Baccilus subtillis.
Some of the synthesized compounds possess good activity against Escherichia coli and Baccilus Subtillis compared to standard drug
streptomycin.
Keywords: Green synthesis, Schiff bases, Antibacterial activity.
several transformations such as aldol reactions [14], conjugate
addition [15], additions to imines and nitro-alkenes [16]. This
prompted us to synthesize (4Z)-4-benzylidene-1-methyl-2-
styryl-1H-imidazol-5(4H)-one derivatives of derivatives and
evaluate them for antibacterial activity.
INTRODUCTION
The increasing resistance of human pathogens to current
antimicrobial agents is a serious medical problem. Many of
the drugs currently available have undesirable effects and might
be toxic. Considering the fact that the available antimicrobial
agent originate from a limited number of sources and that most
of them have similar modes of activity. It is very important
to explore additional sources for substances with potential
antimicrobial activity, which could possibly have different
modes of activity or affect different sites in the bacterial and
fungal cells. Imidazole and its derivative are of great signi-
ficance due to their important roles in biological system. The
synthesis of newer class of antibacterial and antifungal agents
is in need of time, especially against drug-resistant bacteria
and fungi, such as Gram-positive and Gram-negative strains,
which are responsible for a number of serious infections in
the acute and chronic care units in hospitals.
Imidazolinone ring system is of biological and chemical
interest since long. The imidazolinone units are found in many
biologically active compounds. The imidazolones compounds
having diverse bioactivities including anticancer [1], anti-HIV
agents [2], anticonvulsant [3,4], monoaminooxidase (MAO)
inhibitory [5], antiparkinsonian [6,7], CNS depression [8],
antimicrobial [9-12], anthelmintics [13], etc.
EXPERIMENTAL
Melting points are uncorrected and taken in open capillary
tubes in sulphuric acid bath. TLC was run on silica gel-G and
visualization was done using UV light. IR spectra were recorded
1
using Perkin-Elmer 1000 instrument in KBr pellets. H NMR
spectra were recorded in CDCl using TMS as internal standard
3
with 400 MHz spectrometer. Mass spectra were recorded on
Agilent-LCMS instrument under CI conditions and given by
Q+1 value only.
Preparation of (Z)-2-acetamido-N-methyl-3-phenyl-
acrylamides: A mixture of 1a-1b (10 mM) and methylamine
(10 mM) was added in ethanol for 5 h at 80 °C. The completion
of the reaction was checked by TLC, then this reaction mixture
was cooled to room temperature and poured into ice-cold water
(50 mL). The solid separated out was collected, washed with
water (10 mL) and dried. The product was recrystallized from
ethanol to obtain 2a-2b.
Preparation of (4Z)-4-benzylidene-1-methyl-2-styryl-
1H-imidazol-5(4H)-one derivatives 6(a-l): Equimolar quan-
tities of 2(a-b) (10 mM) and Schiff bases 3(a-f) (10 mM) were
mixed together in 20 mL of EtOH in the presence of L-tyrosine
(1 mM) as catalyst. The mixture was refluxed for 2 h. The
completion of the reaction was checked by TLC, then this
Schiff bases in heterocyclization can act as hydrogen
acceptors. Proton acceptor-donor catalyst L-tyrosine has been
playing a vital role in synthetic organic chemistry [14].Amino
acids have emerged as an efficient and important catalyst in

1
576 Rani et al.
Asian J. Chem.
reaction mixture was cooled to room temperature and poured
into ice-cold water (50 mL). Solid separated out which was
collected, washed with water (10 mL) and dried. The product
was recrystallized from ethanol to obtain products 6(a-l).
Compound 6i: m.f.: C19
H
16
N
2
OFCl; m.p.: 218-220 °C; yield:
-1
65 %; IR (KBr, νmax, cm ): 1673 (-C=O), 1200 (C-N), 725
1
(-C=Cl); H NMR (400 MHz, DMSO-d
-CH ), 7.4-8.4 (m, 8H, Ar-H and s, 3H, =CH-Ar), C NMR
(100 MHz, DMSO-d /TMS): 111.3 (-C=C), 118.8 (-C=C),
6
/TMS): δ 3.3 (s, 3H,
13
3
Compound 6a: m.f.: C19
H
16
N
2
O; m.p.: 182-184 °C; yield:
5 %; IR (KBr, νmax, cm ): 303 (Ar), 2958 (-CH ), 1661(-C=O)
625 (-C=C) 1199 (-C=N); H NMR (400 MHz, DMSO-d
), 7.4-8.0 (m, 10H, Ar-H) δ8.O, 8.4,
6
-1
7
1
3
122.2 (-C=C) Ar, 138.6 (C-N), 150.7 (-C=N), 162.8 (>C=O)
M+H = 345.
1
6
/
TMS): δ 3.3 (s, 3H, -CH
D (2H (-CH=CH) and s, 3H, =CH-Ar), C NMR (100 MHz,
DMSO-d /TMS): 110 (-C=C), 119 (-C=C), 122 (-C=C) Ar,
38.2 (C-N), 150.9 (-C=N), 162.8 (>C=O). M+H = 291.
Compound 6b: m.f.: C20 ; m.p.: 195-197 °C; yield:
3
Compound 6j: m.f.: C19
H
16
N
3 3
O C1; m.p.: > 230 °C; yield:
13
-1
65 %; IR (KBr, νmax, cm ): 1661 (-C=O)1200 (C-N), 725
1
6
(-C=Cl); H NMR (400 MHz, DMSO-d
-CH ), 7.4-8.3 (m, 10H, Ar-H and s, 3H, =CH-Ar), C NMR
(100 MHz, DMSO-d /TMS): 112.2 (-C=C), 118.6 (-C=C),
6
/TMS): δ 3.3 (s, 3H,
13
1
7
3
H
19
N
2
O
2
6
-1
1
0 %; IR (KBr, νmax, cm ): 1665(-C=O); 1199 (C-N); H NMR
/TMS): δ 3.3 (s, 3H, -CH ), 4.5 (s, 3H,
), 7.4-8.3 (m, 9H, Ar-H and s, 3H, =CH-Ar), C NMR
100 MHz, DMSO-d /TMS): 111.1 (-C=C), 118.8 (-C=C),
22.7 (-C=C) Ar, 138.4 (C-N), 145.9 (-C=N), 164.3 (>C=O).
M+H = 321.
Compound 6c: m.f.: C19
122.1 (-C=C) Ar, 138.2 (C-N), 150.9 (-C=N), 162.8 (>C=O)
M+H = 372.
(
-
(
400 MHz, DMSO-d
6
3
13
CH
3
Compound 6k: m.f.: C19
H
16
N
2 2
OCl ; m.p.: 222-224 °C; yield:
-1
6
55 %; IR (KBr, νmax, cm ): 1690 (-C=O), 1199 (C-N), 725
1
1
(-C=Cl); H NMR (400 MHz, DMSO-d
-CH ), 7.4-8.5 (m, 8H, Ar-H and s, 3H, =CH-Ar), C NMR
(100 MHz, DMSO-d /TMS): 111.2 (-C=C), 119 (-C=C), 123.3
6
/TMS): δ 3.3 (s, 3H,
13
3
H
16
2
N OF; m.p.: 180-182 °C; yield:
6
-1
6
5 %; IR (KBr, νmax, cm ): 1670 (-C=O), 1199 (C-N), 1050
(-C=C) Ar, 138.5 (C-N), 144.6 (-C=N), 162.5 (>C=O) M+H
= 362.
1
(
-
(
-C=F); H NMR (400 MHz, DMSO-d
CH ), 7.4-8.4 (m, 9H, Ar-H and s, 3H, =CH-Ar), C NMR
100 MHz, DMSO-d /TMS): 110.4 (-C=C), 118.2 (-C=C),
22.3 (-C=C) Ar, 138.5 (C-N), 152.8 (-C=N), 160.7 (>C=O)
M+H = 310.
Compound 6d: m.f.: C19
6
/TMS): δ 3.4 (s, 3H,
13
3
Compound 6l: m.f.: C19
H
16
N
2
OCl
2
; m.p.: > 230 °C; yield:
-1
6
60 %; IR (KBr, νmax, cm ): 1685 (-C=O), 1199 (C-N), 725
1
1
(-C=Cl); H NMR (400 MHz, DMSO-d
-CH ), 7.4-8.5 (m, 8H, Ar-H and s, 3H, =CH-Ar), C NMR
(100 MHz, DMSO-d /TMS): 110.2 (-C=C), 118.6 (-C=C),
6
/TMS): δ 3.2 (s, 3H,
13
3
H
16
N
3
O
3
; m.p.: 210-212 °C; yield:
6
-1
1
6
0 %; IR (KBr, νmax, cm ): 1661(-C=O), 1199 (C-N), H NMR
400 MHz, DMSO-d /TMS): δ 3.3 (s, 3H, -CH ), 7.4-8.3 (m,
H, Ar-H and s, 3H, =CH-Ar), C NMR (100 MHz, DMSO-
/TMS): 110 (-C=C), 119 (-C=C), 122 (-C=C) Ar, 138.2
125.7 (-C=C) Ar, 138.9 (C-N), 143.9 (-C=N), 165.7 (>C=O)
M+H = 362.
(
9
d
6
3
13
6
RESULTS AND DISCUSSION
(
C-N), 150.9 (-C=N), 162.8 (>C=O) M+H = 337.
Compound 6e: m.f.: C19 OCl; m.p.: 189-191 °C; yield:
H N
16 2
Title compounds (4Z)-4-benzylidene-1-methyl-2-styryl-
1H-imidazol-5(4H)-one derivatives 6(a-l) have been synthe-
sized by green approach through synthetic sequence shown in
Scheme-I. Initially, the azalactone (Z)-4-benzylidene-2-methyl-
oxazol-5(4H)-one (1) was treated with methylamine and refluxed
for 5 h in ethanol to produce (Z)-2-acetamido-N-methyl-3-
phenylacrylamides 2(a,b) (Scheme-I). Compounds 2(a,b)
were reacted with the Schiff bases benzylidine/substituted
benzylidine anilines (3a-f) in the presence of L-tyrosine as a
catalyst in the presence of ethanol under reflux condition for
2 h to produce in situ (4Z)-4-benzylidene-1-methyl-2-styryl-
1H-imidazole-5(4H)-ones 6(a-l).A reasonable mechanism has
been formulated for the formation of these imidazoline 5-ones.
The mass spectrum of the compound 6a showed the molecular
ion peak at m/z 291 corresponding to molecular formula. The
IR spectrum of the compound showed the absence of absorp-
-1
1
5
5 %; IR (KBr, νmax, cm ): 1680(-C=O); 725 (-C=Cl); H NMR
/TMS): δ 3.0 (s, 3H, -CH ), 7.4-8.5 (m,
H, Ar-H and s, 3H, =CH-Ar), C NMR (100 MHz, DMSO-
/TMS): 112.2 (-C=C), 119.3 (-C=C), 122.3 (-C=C)Ar, 138.5
(400 MHz, DMSO-d
6
3
13
9
d
(
6
C-N), 143.9 (-C=N), 160.3 (>C=O), M+H = 326.
Compound 6f: m.f.: C19 OCl; m.p.: 220-222 °C; yield:
0 %; IR (KBr, νmax, cm ): 1690 (-C=O), 1200 (C-N), 725
H N
16 2
-1
5
1
(
-
(
-C=Cl); H NMR (400 MHz, DMSO-d
CH ), 7.4-8.3 (m, 9H, Ar-H and s, 3H, =CH-Ar), C NMR
100 MHz, DMSO-d /TMS): 110.3 (-C=C), 118.6 (-C=C),
23.4 (-C=C) Ar, 138.3 (C-N), 145.6 (-C=N), 160.6 (>C=O)
M+H = 325.2.
Compound 6g: m.f.: C19
6
/TMS): δ 3.2 (s, 3H,
13
3
6
1
H
16
N
2
OCl; m.p.:195-197 °C; yield:
-1
7
0 %; IR (KBr, νmax, cm ): 1694 (-C=O); 1199 (C-N), 725
1
(
-
(
-C=Cl); H NMR (400 MHz, DMSO-d
CH ), 7.4-8.3 (m, 9H, Ar-H and s, 3H, =CH-Ar), C NMR
100 MHz, DMSO-d /TMS): 112.5 (-C=C), 118.9 (-C=C),
22.3 (-C=C) Ar, 138.4 (C-N), 150.4 (-C=N), 161.4 (>C=O)
M+H = 326.
Compound 6h: m.f.: C20
6
/TMS): δ 3.3 (s, 3H,
13
-1
1
tion for –NH group at 1662 cm and the H NMR (DMSO-d )
6
3
lacked signals for methyl protons of acetamido group, instead
two trans olefinic protons were observed at δ 8.0 and δ 8.4
along with additional signals for aromatic compounds. This
data conforms the structure of 6a and in the similar way the
structures of 6(b-l) were confirmed.
The mechanism of the reaction is rationalized as the
styrilation of acetamido group of 2 followed by dehydration.
The mechanism can be explained as Michael type addition of
the active methyl group 2 across the carbon-nitrogen double
bond of the Schiff base 3 leading to the generation of styryl
6
1
H
19
N
2
O
2
Cl; m.p.: 182-185 °C; yield:
-1
7
0 %; IR (KBr, νmax, cm ): 1660 (-C=O) 1199 (C-N), 725
1
(
-
=
-C=Cl); H NMR (400 MHz, DMSO-d
CH ), 4.4 (s, 3H, -CH ), 7.4-8.3 (m, 8H, Ar-H and s, 3H,
CH-Ar), C NMR (100 MHz, DMSO-d /TMS): 110.2
6
/TMS): δ 3.2 (s, 3H,
3
3
1
3
6
(
(
-C=C), 118.5 (-C=C), 122.2 (-C=C) Ar, 138.3 (C-N), 146.3
-C=N), 164.2 (>C=O) M+H = 357.

Vol. 28, No. 7 (2016)
Synthesis and Antibacterial Activity of (4Z)-4-Benzylidene-1-methyl-2-styryl-1H-imidazol-5(4H)-one 1577
O
O
O
CH
3
Ar1 C N Ar
2
H
H
Ar
H
N
NH
2 3
-CH
H
- Ar -NH2
2
O
H
N
H
CH3
3
Ar
NH
C
N
Ethanol
Ar
H C
NH
CO
CH3
O
EtOH/L-Tyrosine
H
1
C
CH
2
1
3
Ar HN
2
Ar2
O
CH3
O
H
CH3
H
N
O
H
N
H
H
Ar
CH3
NH
C
CH
Ar
N
C
Ar
N
-
H O
O
2
H
OH
N
C
CH CH Ar1
C
CH
Ar1
6
4
Ar1
5
Cl
,
Ar2=
Ar=
Ar1=
,
,
,
,
,
Cl
2b
Cl
3f
OMe F
3b 3c
NO2
3d 3e
2a
3a
Scheme-I
O
O
O
H
H
H
NH -CH3
2
N
H
CH3 L-Tyrosine
O
O
N
H
CH3
L-Tyrosine
Ar
Ar
N
Ar
H C
NH
CO
NH
CO
CH3
Ar1 C N Ar2
H
1
H
C
H
2
3
3
2
H
O
O
CH3
CH
3
N
H
CH3
H
H
Ar
N
NH
CO
C H
N
H
H
Ar
NH
C
Ar
H
N
C
CH
H N Ar2
2
H
O
H
OH
H
C
CH
C
Ar1 C N Ar
2
Ar1
Ar1
H
4
5
O
H
CH3
Ar
N
-
H O
2
N
CH CH Ar1
6
Scheme-II
group by the loss of aniline. The resulting unstable inter-
mediates 4 and 5 readily undergoes dehydrative cyclization to
form stable imidazolin-5-one derivative 6(a-l) (Scheme-II).
in vitro Antibacterial activity: The synthesized com-
pounds [6(a-l)] were screened for their in vitro antibacterial
activity aganist Escherichia coli (NCIM 2065), Providencia
aeruginosa (NCIM 2200), Pseudomonas azotogensis (NCIM
and allowed to solidify. Different bacterial species were
inoculated on to the medium by streak plate method. The plates
were incubated at 30 °C temperature and zone of inhibition
was measured after 24 h. The standard used for determining
the antibacterial activity is streptomycin. The compounds were
dissolved in DMF and activity described at 100 µg/mL level.
From the data presented in Table-1, it is clear that compounds
6c, 6e, 6f, 6i, 6k and 6l possess good activity against
Escherichia coli and Baccilus Subtillis. Other compounds
exhibited moderate antibacterial activity against E. coli. However,
all compounds showed moderate activity against, Providencia
aeruginosa and Pseudomonas azotogensis (Table-1).
2
075) and Baccilus subtillis (NCIM 2063). Antibacterial
activity of compounds was evaluated using agar-well diffusion
method [17]. The petri plates were sterilized using an autoclave
at 120 °C for 30 min. A petri-dish of 100 mm diameter was
filled with 50 mL of freshly prepared Nutrient Agar media

1
578 Rani et al.
Asian J. Chem.
TABLE-1
ANTIBACTERIAL ACTIVITY OF COMPOUNDS 6(a-l)
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