Synthesis and antifungal activity of 2-Ketophenyl-3 substituted aryl-1-thiazolidin-4-ones

Article abstract of DOI:10.1155/2010/979353

A new series of 2-ketophenyl-3-substituted aryl-1- thiazolidin-4- ones were synthesized by cyclocondensation of ketoazomethines and thioglycolic acid. Ketoazomethines were synthesized by condensation of phenyl glyoxal (prepared by partial oxidation of ace

Full text of DOI:10.1155/2010/979353

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
2010, 7(3), 1040-1044
http://www.e-journals.net
Synthesis and Antifungal Activity of
2-Ketophenyl-3-substituted aryl-1-thiazolidin-4-ones
VISHNU VATS*, R. K. UPADHYAY and PRATHIBHA SHARMA§
Department of Chemistry,
N.R.E.C.College, Chaudhary Charan Singh University, Meerut, India.
§Department of Plant Pathology,
Indian Agricultural Research Institute, New Delhi, India.
vatsvish_2006@yahoo.co.in
Received 5 September 2009; Revised 11 November 2009; Accepted 5 January 2010
Abstract: A new series of 2-ketophenyl-3-substituted aryl-1- thiazolidin-4-
ones were synthesized by cyclocondensation of ketoazomethines and
thioglycolic acid. Ketoazomethines were synthesized by condensation of
phenyl glyoxal (prepared by partial oxidation of acetophenone) and various
para-substituted anilines. Their structures were elucidated by elemental
analysis, IR and H1 NMR; they were screened for their antifungal activity
against hazardous fungi namely Fusarium Oxysporum, Pythium, Sclerotium
and Alternaria brassicola.
Keywords: Synthesis, 2-Ketophenyl-3-substituted aryl-1-thiazolidin-4-ones, Antifungal activity.
Introduction
4-Thiazolidinones are most popular, probably owing to their high versatility in exhibiting
diverse potent biological properties viz., antiprotozoa1, analgesic2-5, anti-inflammatory6-9 anti-
HIV10, CFTR-inhibitor11, anticonvulsant12-13
,
SHP-inhibitor14, antimicrobial15,16 and
fungicidal17 etc. Although plenty of thiazolidinones and their derivatives have been synthesized
by condensation of Schiff bases18-20, halo acetanilide21, thiosemicarbazone22, thiamide23, with
thiocyanates, halo fatty acid and aldehydes etc. This project includes synthesis of these
compounds and their elemental, spectral studies and screening for antifungal activity against
hazardous fungi i.e. Fusarium Oxysporum, Alternaria Brasssicola, Sclerotium and Pythium
which cause harm to crops like tomato, onion and cauliflower.
Experimental
All the chemicals used were either E-Merck or Qualigens. Melting points of all the
compounds determined in open glass capillaries were uncorrected. Elemental analysis of

Synthesis and Antifungal Activity
1041
samples was carried out on Euro EA Elemental Analyzer. Infrared spectra were recorded in KBr
medium on Thermo Nicolet Nexus FT-IR spectrophotometer and 300 MHz NMR spectra were
recorded in dimethylsulphoxide medium on Varian C-13 NMR spectrometer using TMS as
internal standard. Column chromatography was carried out using silica gel (finer than
200#).Characterization data is presented in Table 1 and spectral data in Table 2.
Table 1. Characterization data of compounds (6a-f).
Compds
Yield m.p. Elemental analysis, % Cald.(found)
oC
M.F.
Colour
Pink
%
S
7.6
C
60.37
H
3.77
N
4.40
C16H12NO2SCl
C16H12NO2SBr
C20H22N2O2S
C17H15NO2S
C16H12N2O4S
67.4 223
6a
6b
6c
6d
6e
(7.8) (60.44) (3.18)
9.2 53.35 3.31
(9.1) (53.39) (3.35)
8.0 67.79 6.21
(7.8) (67.83) (6.35)
8.9 68.68 5.75
(9.1) (68.65) (5.86)
8.6 58.53 3.65
(8.5) (58.74) (3.46)
8.3 67.84 4.59
(8.4) (67.73) (4.13)
(4.76)
3.86
Yellow 78.5 245
(3.15)
7.90
Light
63.6 235
brown
(7.65)
4.71
(4.23)
Brown 71.5 218
Light
8.53
(8.32)
65.6 228
green
4.96
(4.12)
C16H13NO2S
Orange 69.5 210
6d
Table 2. IR, H1 NMR Spectral data of the compounds (6a-f).
Compds.
IR, cm-1 (KBr)
560, 700, 750,818,
1241,1324,1486,
H 1 NMR (δ ppm)
7.48-7.50(6H,m),6.89(4H,m),
5.11(1H,s),3.98(2H,s)
6a
1542, 1605,1651,3061
660, 752 , 822, 1326,
1489,1549, 1609, 1648,3066
7.51-7.72(6H,m), 6.78(4H,m),
5.15(1H,s),3.82(2H,s)
6b
6c
6d
6e
6f
692,778,1407,1594,1680,1684, 7.56-7.73(6H,m),7.11(2H,d) 6.92(2H,d),
2970,3032 3.89(2H,s), 2.75(3H,m),5.21(1H,s)
694,756,1238,1316,1496,1543, 7.48-7.51(6H,m),4.02(2H,s),4.31(2H,s),
1595,1670,3052 2.75(3H,s,Ar-CH3),5.43(1H,s)
683,771,888,1286, 1569,1652, 7.33-7.36(6H,m),
1713, 3045
648,700,748,813,1257,1458,
1515,1682,1726,3056
4.05(2H,S),4.28(2H,s),5.34(1H,s)
7.35-7.54(5H,m),7.51-
7.64(4H,m),4.25(2H,s),5.32(1H,s)
Preparation of phenyl glyoxal
Phenyl glyoxal was prepared by the partial oxidation of acetophenone with selenium
dioxide. Reaction mixture containing acetophenone (1,0.2 mol) and selenium dioxide (0.4 mol)
was taken in a round bottom flask containing 300 mL of 95% ethyl alcohol and refluxed for
4-6 h. Orange yellow reaction mixture was decanted and concentrated over water bath and
dissolved in ether to remove selenium from the product.
General procedure for preparation of 4- thiazolidinones
Preparation of ketoazomethines (4a-f)
Phenyl glyoxal (2, 0.2 mol) and aniline (3a-f, 0.2 mol ) were taken in a round bottom flask
containing 100 mL of ethanol and refluxed on water bath for 8 h. Excess of ethanol was

1042
VISHNU VATS et al.
removed from reaction mixture and cooled at room temperature. Then it was poured in ice
cold water and filtered. Solid obtained were collected and recrystallized with ethanol.
Similarly, other ketoazomethines of p-chloro, p-bromo, p-nitro, p-methyl and p-diethylaminoaniline
were prepared.
Preparation of 2-ketophenyl-3-substituted aryl-1-thiazolidin-4-one (6a-f)
Ketoazomethines (0.2 mol, 4a-f) and thioglycolic acid (0.3 mol,5) were refluxed in dry
benzene for ~ 15 h. The reaction mixture was concentrated to half of its volume over water
bath and then neutralized with sodium bicarbonate solution. The contents were cooled and
poured in ice cold water and filtered. The solid obtained was collected and purified by
recrystallization (Scheme l).
3a: p-Chloroaniline
3b: p-Bromoaniline
3c: p-Diethylaminoaniline
3d: p-Methylaniline
3e: p-Nitroaniline
3f: Aniline
Scheme l
Antifungal activities
Preparation of medium and sample solutions
For the preparation of PDA (Potato Dextrose Agar) medium 250 g potato pieces boiled in
water were filtered and filtrate was made up to 1 litre. To this solution 20 g dextrose powder
was added followed by heating to a syrupy viscous consistency. Standard solutions of all the
samples were prepared by dissolving known quantity of compounds in known volume of
DMSO (dimethylsulphoxide).
The synthesized thiazolidinones were screened for their antifungal activity against
hazardous fungi namely Fusarium Oxysporum, Pythium, Alternaria brassicola and
Sclerotium by paper disc method24 using Diethane-M45 as reference fungicide and DMSO
0
as control showing no inhibition, incubation periods of 72 h at 25-30 C for the growth of
fungi were measured in triplicates and the results of inhibition were noted in Table 3.

Synthesis and Antifungal Activity
1043
Table 3. Antifungal activity of 2-ketophenyl-3-substituted aryl-1-thiazolidin-4-one.
Incb. Time,
M.F.
days
Compound
S.
P.
F.O. A.B.
C16H12NO2SCl
C16H12NO2SBr
C20H22N2O2S
C17H15NO2S
C16H22N2O4S
C16H13NO2S
Diethane-M45
3
3
3
3
3
3
3
++
++
-
++
++
+
+
++
-
++
++
-
6a
6b
6c
-
+
-
+
6d
6e
++
++
+
-
-
+
-
-
++
++
6f
++
-
Ref.
Sample 10 mg/mL, S.-Sclerotium, P.-Pythium, F.O.-Fusarium Oxysporum, A.B - Alternaria
Brasssicola -ve=1-7 mm, +ve= 10-15 mm and ++ve=15-18 mm.
Results and Discussion
The antifungal studies of the compounds were tested by paper bit method against hazardous
fungi namely Fusarium Oxysporum, Alternaria Brassicola, Pythium and Sclerotium and
were compared with reference fungicidal Diethane-M45, 2-ketophenyl-3-(4-bromoaryl)-1-
thiazoldin-4-one (6b) and 2-ketophenyl-3-(4-chloroaryl)-1-thiazolidin-4-one (6a) showed
highest inhibition against Fusarium Oxysporum, Alternaria Brassicola, Sclerotium and
Pythium. 2-ketophenyl-3-(4-nitroaryl)-1-thiazolidin-4-one (6e) showed highest inhibition
against Sclerotium, 2-ketophenyl-3-aryl-1-thiazolidin-4-one (6f) was effective against
Alternaria brassicola and Sclerotium. Therefore, from the results it is evident that
compounds having electronegative groups are responsible for antifungal activity.
Acknowledgment
We are grateful to Mrs. Prathibha Sharma (Principal Scientist) and the staff of Plant
Pathology department of Indian Agricultural Research Institute, New Delhi and staff of IIT
Roorkee for their immense support.
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