Efficient synthesis of 5(4H)-imidazolones and IN VITRO antifungal activity studies against selected phytopathogens

Article abstract of DOI:10.14233/ajchem.2014.15893

A series of five new 1-(substituted phenyl)-2-phenyl-4-(substituted benzylidine)imidazole-5-one derivatives (or) 5(4H)-imidazolones I have been synthesized adopting SiO₂, Al₂O₃-90 and Y-faujasite (Y-H type) zeolite as cata

Full text of DOI:10.14233/ajchem.2014.15893

Asian Journal of Chemistry; Vol. 26, No. 10 (2014), 2873-2876
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.15893
Efficient Synthesis of 5(4H)-Imidazolones and in vitro Antifungal
Activity Studies Against Selected Phytopathogens
*
CHRISTOPHER VOOSALA , LAKSHMI NARASIMHA MURTHY YELLAJYOSULA, VIPLAVA PRASAD UPPULETI and PADMA SUHASINI KILARU
Department of Organic Chemistry & FDW, Andhra University, Visakhapatnam-530 003, India
*Corresponding author: E-mail: chrissvoosala@yahoo.co.in
Received: 11 June 2013;
Accepted: 14 October 2013;
Published online: 10 May 2014;
AJC-15138
A series of five new 1-(substituted phenyl)-2-phenyl-4-(substituted benzylidine)imidazole-5-one derivatives (or) 5(4H)-imidazolones
have been synthesized adopting SiO2, Al2O3-90 and Y-faujasite (Y-H type) zeolite as catalysts. These compounds were assayed for their
antifungal activity on three different selected phytopathogens which disparately affects the Jowar crop (Sorghum vulgare) of poaceae
family. Among the screened target molecules, compound 18 exhibited potent inhibitory activity compared to the standard drug bavistine,
which is worth for further investigation.
Keywords: Y-faujasite zeolite, Imidazolone, Phytopathogens, Antifungal activity.
INTRODUCTION
EXPERIMENTAL
Imidazolones have been associated with several pharma-
cological activities1-4 such as antimicrobial (antifungal, antibac-
terial and antiviral), anticancer activity, CNS depressant activity
etc. Benzylidene derivatives have been reported to possess
anticonvulsant and MAO inhibitory activity. Shaw et al.5 have
reported that certain 5-imidazolones act as cardiotonic agents.
Thus construction of these heterocyclic systems using various
synthetic methodologies is of great importance is combinatorial
organic synthesis6 and medicinal chemistry.
All the melting points were recorded on VEB Analytica
Dreader, HMK hot plate and are uncorrected. IR spectra (KBr)
were recorded on Perkin Elmer IR 841 spectrophotometer. 1H
NMR and 13C NMR spectra were recorded on JEOL JNM
FTNMR (90 MHz) spectrometer using CDCl3 or DMSO (d6)
and TMS as internal reference. GCMS were recorded on QP
5050A, Schimazu spectrometer. All the compounds showed
satisfactory elemental analyses.
General procedure for the synthesis of oxazolones
(7-11) by conventional and microwave assisted methods13:
A mixture of different substituted benzaldehydes (2-6) (2.3
mmol), hippuric acid (2.6 mmol), acetic anhydride (7.2 mmol),
sodium acetate (2.4 mmol) were refluxed at 110 °C with constant
stirring for 4 h. The crude product was separated, filtered and
washed with ice cold ethanol, followed by boiling water and
recrystallized from chloroform. All the five oxazolones (7-11)
were characterized using advanced spectroscopic data.
In microwave assisted synthesis of oxazolones (7-11)
(450 W, 15 min), all the reactants were taken in the same mole
ratios as that were taken in the usual conventional method. It
was made sure that acetic anhydride was not evaporated from
the mixture. The product obtained by this method was identical
with that of the conventional method.
Attempts have been reported to synthesize these compounds
by several methods7,8 such as condensing glycine ester of aceti-
midic or phenylacetimidic acid in the presence of benzene,
dioxane or acetone.
Though some of the imidazolones have been reported
using microwave irradiation, a suitable support or sensitizer
is invariable in many of these reactions9. Therefore a method-
ology in synthesizing these potent compounds is still a necessary
requirement. To the best of our knowledge, the synthesis of
imidazolones adopting zeolites10 (crystalline aluminosilicates
of various metals) and its constituents i.e., SiO2 and Al2O3 as
catalysts11,12 were not comparatively studied. Motivated by this
fact, herein we report the yields of imidazolones adopting these
catalysts and exposit their antifungal properties against
specified pathogens viz., Fusarium oxysporum, Rhizoctonia
solani and Curvularia lunata which destroyed the Jowar plants.
The target molecules (17-21) were synthesized following the
procedure described in Scheme-I.
General procedure for the synthesis of 5(4H)-
imidazolones (17-21) using SiO2,Al2O3-90 andY-H zeolite14:
Oxazolones (7-11) (0.01 mol) were heated to reflux with
substituted anilines (12-16) (0.01 mol) in a solution of slight

2874 Voosala et al.
Asian J. Chem.
R1
CHO
HN
O
CH3COONa/CH3COOK
(CH3CO)2O, 110 oC
COOH
R2
+
N
or
MW, 450W, 15 min
R1
O
O
R2
2-6
7-11
1
NH2
Pyridine, 150 oC,
SiO2 (or) Al2O3-90 or
Y-H zeolite
R3
R4
R1
2,7,17, R1=H, R2=NMe2
3,8,18, R1=H, R2=Cl
12-16
R2
4,9,19, R1=H, R2=OCH3
5,10,20, R1=OCH3, R2=OH
6,11,21, R1=R2=OCH3
12,17, R3=H, R4=Br
N
N
O
13,18, R3=H, R4=CH3
14,19, R3=NO2, R4=H
15,20, R3=H, R4=NO2
16,21, naphthylamine
R3
R4
17-21
Scheme-I
excess of pyridine (0.01 mol) in an oil bath at 150-170 °C
with SiO2, Al2O3-90 or Y-H zeolite as catalyst (2.5 g). The
excess of pyridine was distilled off in a Rotavapor, cooled and
poured into crushed ice in 10 % HCl. The crude imidazolone
precipitated was filtered, dried over MgSO4 and chromato-
graphed over Silica gel using hexane and ethyl acetate as
eluants.
164.0, 132.1, 128.0, 54.2; mass: m/z (399); Anal. calcd. for
C23H17N3O4 : C 69.17, H 4.26, N 10.52. Found: C 69.15, H
4.27, N 10.49.
1-(4-Nitrophenyl)-2-phenyl-4-(3'-methoxy, 4'-hydroxy
benzylidene)-imidazol-5-one (20): Yellow solid; m.p. 118 °C;
IR (KBr, νmax, cm-1): 3420, 3059, 2928, 1720, 1637, 1590,
1452, 1380, 1267, 1134, 813; 1H NMR (90 MHz, DMSO, δ):
9.3 (s, 1H), 8.32 (d, J = 8.1Hz, 2H), 7.01-7.92 (m, 11H), 3.98
(s, 3H); 13C NMR (22.5 MHz, DMSO, δ): δ 168.9, 163.8, 131.6,
127.2, 54.1; mass: m/z (415); Anal. calcd. for C23H17N3O5: C
66.50, H 4.09, N 10.12. Found: C 66.48, H 4.10, N 10.12.
1-(Naphthyl)-2-phenyl-4-(4',5'-dimethoxy benzylidene)-
imidazol-5-one (21): Pale yellow solid; m.p. 211 °C; IR (KBr,
1-(4-Bromophenyl)-2-phenyl-4-(4'-N,N-dimethyl
benzylidene)-imidazol-5-one (17): Light reddish solid, m.p.
152 °C, IR (KBr, νmax, cm-1): 2924, 2854, 2373, 2339, 1710,
1
1649, 1598, 1525, 1381, 1162, 761; H NMR (90 MHz,
DMSO, δ): 6.61-8.19 (m, 14 H), 2.96 (s, 6 H); 13C NMR (22.5
MHz, DMSO, δ): 166.8, 164.6, 132.2, 128.3, 36.7; Mass: m/z
(446);Anal. calcd. for C24H20N3OBr: C 64.57, H 4.48, N 9.41.
Found: C 64.55, H 4.49, N 9.39.
ν
max, cm-1): 3017, 2960, 2814, 2760, 2318, 1716, 1660, 1615,
1490, 1316, 1211; 1H NMR (90 MHz, DMSO, δ): 6.82-8.20
13
(m, 16H), 3.85 (s, 3H), 3.82 (s, 3H); C NMR (22.5 MHz,
1-(4-Methylphenyl)-2-anisyl-4-(4'-chloro benzylidene)-
imidazol-5-one (18): Pale yellow solid; m.p. 174 °C; IR (KBr,
DMSO, δ): 166.5, 160.9, 131.1, 126.5, 54.1, 54.3; mass: m/z
(434); Anal. calcd. for C28H22N2O3: C 77.41, H 5.06, N 6.45.
Found: C 77.39, H 5.06, N 6.43.
ν
max,cm-1): 2960, 2813, 2319, 2390, 1700, 1656, 1620, 1603,
813; 1H NMR (90 MHz, DMSO, δ): 6.68-8.37 (m, 14 H), 2.4 (s,
3 H); 13C NMR (22.5 MHz, DMSO, δ): δ 167.1, 164.8, 134.6,
131.5, 26.5; mass m/z (372); Anal. calcd. for C23H17N2OCl: C
74.09, H 4.56, N 7.51. Found: C 74.01, H 4.56, N 7.49.
1-(3-Nitrophenyl)-2-phenyl-4-(4'-methoxy benzylidene)-
imidazol-5-one (19): Lemon yellow solid; m.p. 121 °C; IR
(KBr, νmax, cm-1): 3015, 2930, 2882, 2320, 1710, 1635, 1600,
1580, 1215; 1H NMR (90 MHz, DMSO, δ): 7.03-8.35 (m, 14
RESULTS AND DISCUSSION
The key intermediates i.e., 5(4H)-oxazolones (7-11) were
synthesized13 in both conventional and microwave assisted
methods in good yields. Subsequently the target compounds
(17-21) were synthesized using SiO2,Al2O3-90 orY-H zeolite14,15
as catalysts. 5(4H)-oxazolones (7-11) were heated to reflux
with various substituted aromatic amines (12-16) consisting
13
H), 3.86 (s, 3 H); C NMR (22.5 MHz, DMSO, δ): 167.9,

Vol. 26, No. 10 (2014)
Efficient Synthesis of 5(4H)-Imidazolones 2875
of various electron donating and withdrawing groups in a
solution of slight excess of pyridine with these catalysts. Further
work up and chromatography over silica gel using hexane and
ethyl acetate resulted in the final products. Interestingly the
reaction times were drastically less and high yields of the
products were obtained adopting large poredY-faujasite (Y-H
zeolite)16 as catalyst over SiO2 andAl2O3-90 as visualized from
Table-1.
compounds were tested at a concentration of 5, 25, 50 and
100 µg/mL, each of 50 µL against the above said fungal strains.
Bavistine was taken as the standard drug for comparison of
the results and DMSO as the control. Nutrient agar and Sabourds
medium are used as culture media for these fungal phyto-
pathogens.
In vitro antifungal activity of the target molecules (17-
21) was evaluated by cup-plate method17,18, starting with low
concentrations viz., 5, 25, 50 and 100 µg/mL for their MIC
(minimum inhibitory concentration) values. 50 µL of each
concentration was tested against the fungal phytopathogens
i.e., F. oxysporum, R. solani and C. lunata. The MIC values and
zones of inhibition were compared with Bavistine, a standard
antifungal drug. Solvent employed was DMSO which showed
no effect on the tested fungal strains. The results are presented
in Table-2.
The structures of the target molecules were characterized
by IR, NMR, mass and elemental analysis. A possible mecha-
nism is shown in Scheme-II, refers to that, the large pore size of
Y-faujasite type zeolite i.e.,Y-H zeolite affected the dehydration
effectively, thus paving way for increase in the yield of the
products i.e., imidazolones (17-21) (Table-1) in less reaction
times.
Evaluation of antifungal activity: Antifungal activity
of the synthesized imidazolones (17-21) were tested against
three fungal phytopathogens viz., Fusarium oxysporum,
Rhizoctonia solani and Curvularia lunata which effect Jowar
plant (local name: Zonnalu) (Sorghum vulgare) of the family
Poaceae. The method adopted was cup-plate method. The
All the compounds (17-21) in general showed antifungal
activity against the specified pathogens. Compound 18 showed
a comparable activity to that of standard drug used (bavistine)
against R. solani and compound 20 showed MIC value at 5
µg/mL against F. oxysphorum which proved to be better than
N
N
N
OH
O
OH
Ph
Ph
O
Ph
O
O
N
N
+NH2
Ph
H
Ph
Ph
HN
N
HN
HO
O
O
H
Ph
Ph
H
O
Ph
O
HN
O
N
N
Ph
Ph
Ph
-H2O
N
Ph
O
N
Ph
Scheme-II: A possible mechanism showing the formation of 5(4H)-imidazolone
TABLE 1
PERCENTAGE YIELDS OF IMIDAZOLONES (17-21) WITH VARIOUS CATALYSTS
Compound
Catalyst
17
18
19
20
21
Conventional heating
SiO2
22 (14.30 h)a
25 (14 h)a
45 (12 h)a
78 (4.30 h)a
26 (15 h)a
30 (13 h)a
43 (11.30 h)a
75 (4.30 h)a
20 (15 h)a
28 (13 h)a
33 (13 h)a
23 (13 h)a
28 (13 h)a
30 (13 h)a
66 (6.30 h)a
25 (13.30 h)a
32 (13 h)a
36 (11 h)a
68 (5.30 h)a
Al2O3-90
Y-H Zeolite
a Values inside the brackets indicate the reaction times for the formation of the products

2876 Voosala et al.
Asian J. Chem.
TABLE 2
ANTIFUNGAL EVALUATION OF IMIDAZOLONES (17-21)
Diameter of zone of inhibition (mm)
Fusarium oxysporum
Rhizoctonia solani
Curvularia lunata
Conc. (µg/mL)
Compd.
5
–
–
–
7
–
–
25
13
16
–
50
14
19
–
100
15
19
5
5
15
19
9
25
18
20
11
11
7
50
19
22
13
13
8
100
19
24
14
15
8
5
13
9
25
14
10
9
50
16
18
9
100
19
20
10
11
9
17
18
19
20
7
9
10
7
10
7
10
6
9
10
8
10
8
21
Bavistine
6
17
7
–
–
18
20
22
–
–
15
16
20
(– indicates no activity); (Solvent DMSO did not have inhibition zone against all the three organisms)
2. H.K. Urman, O. Bulay, D.B. Clayson and P. Shubik, Cancer Lett., 1,
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the standard drug. The MIC values were better for compounds
17-20 against C. lunata compared to the standard drug. Strong
electron withdrawing groups on phenyl ring in compounds 18
and 20 (-Cl & -NO2) could obviously effect on pharmacological
activity and antifungal spectrum.
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Conclusion
In conclusion we have developed a new synthetic method-
ology for a facile synthesis of 5(4H)-imidazolones usingY-H
zeolite, SiO2 andAl2O3-90. These compounds exhibited potent
antimicrobial activity against the specified phytopathogens.
The conclusions made were just preliminary, further studies
on their synthesis and other pharmacological properties are in
progress.
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ACKNOWLEDGEMENTS
The authors thank DRDO, New Delhi, India for their
financial assistance and also to Department of Microbiology,
Andhra University, India for conducting antifungal studies.
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