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									                               IJPI’s Journal of Medicinal Chemistry



                      Synthesis, characterisation, antimicrobial evaluation of
                                   Thiazolidine-4-one derivatives

                           *S.Ramachandran, P.Shanmugapandiyan
                            Department of Pharmaceutical Chemistry,
       Mohamed Sathak .A.J. College of Pharmacy, Shollinganallur, Chennai 600119, (INDIA)

*Corresponding Author : S.Ramachandran                         E-mail address :

         A new series of 2-phenyl-3-(pyridin-yl)-thiazolidin-4-one derivatives were synthesized by
  the reaction of schiff base(2-aminopyridine and substituted benzaldehyde) with mercaptoacetic acid
  respectively. The chemical structures of the synthesized compounds were confirmed by means of
  IR, 1H-NMR. . The synthesized compounds showed good antibacterial activity against
  Staphylococcus aureus and Escherichia coli.

  Antibacterial, Aromatic aldehyde, Pyridine, Schiff Bases, Thiazolidine-4-one,
Vol 1:1 (2010)                                                             IJPI’s Journal of Medicinal Chemistry

       Azetidinone and Thiazolidinone derivatives were reported to possess antibacterial[1-3], antifungal[1-3],
antitumor[3] antituberculor activity[4], anti-HIV[5], analgesic[6], anti inflammatory[6], and ulcerogenic activity[7].
Pyridine derivatives were reported to possess antimicrobial[8] and analgesic[9] activities. Therefore it was envisaged
that compounds containing both the chemical moieties would result in compounds of interesting biological
activities. In this present study 2-aminopyridines were treated with different substituted aromatic aldehydes to
produceSchiff .s base[10]. The Schiff bases were subjected to addition reactions with thioglycollic acid in the
presence of 1,4dioxane-anhydrous zinc chloride to produce 4-thiazolidinone derivatives respectively[11]. The
chemical structures of the synthesized compounds were confirmed by means of IR, 1H-NMR. The synthesized
compounds were screened for antibacterial(Staphylococcus aureus, Escherichia coli)

      The melting points were taken in open capillary tube and are uncorrected. The IR spectra of the compounds
were recorded on Win-Bommen B-104 IR Spectrophotometer with KBr pellets. 1H-NMR spectra was recorded on
Bruker A VIII 500 MHz NMR Facility using DMSO-d6 as solvent. The chemical shifts are reported as parts per
million downfield from tetramethyl silane(Me4Si). The purity of the compounds was checked by TLC on pre-
coated aluminum sheets(Silica gel 60 F254) using absolute alcohol :ethyl acetate : Glacial Acetic acid as mobile
phase and visualized by iodine vapors

Synthetic scheme for Schiff Bases and Thiazolidine-4 one

                                                  R1                                                              R1
         N         NH2         OHC
                                                          3hrs            N            N    CH
      pyridin-2-amine             benzaldehyde
                                                                                       Schiff base

                 IA- R1= H
                 IIA- R1= Cl                                                  Dioxane                HS
                 IIIA- R1= OH                                                  6 hrs             thioglycolic acid
                 IB- R1= H
                 IIB- R1= Cl
                 IIIB- R1=O H

                                                                      Thiazolidine-4-one              S

Ramachandran .S et al                                                                                                  Page 2
Vol 1:1 (2010)                                                             IJPI’s Journal of Medicinal Chemistry



                        N       N    CH

          (Z)-N-benzylidenepyridin-2-amine (Compound I A)               ( Compound I B)

                                                Cl                                   N

               N        N      CH
        (Z)-N-(4-chlorobenzylidene)pyridin-2-amine 2-(4-chlorophenyl)-3-(pyridin-2-yl)thiazolidin-4-one
                      Compound II a                                 Compound II b

                                                                                     N           O
             N          N    CH
         (Z)-4-((pyridin-2-ylimino)methyl)phenol 2-(4-hydroxyphenyl)-3-(pyridin-2-yl)thiazolidin-4-one
                      Compound IIIa                               Compound IIIb

3.1General Methods of Synthesis of Schiff Bases ( IA,IIA,IIIA)
A mixture of 2-aminopyridine 0.01mol), substituted benzaldehyde[12] (0.01mol) and a drop of acetic acid was
dissolved in ethanol (25ml) and heated on a steam bath for 45-60 min or on a water bath for 2-3 hrs. The reaction
mixture was allowed to stand at room temperature for 24h,The product separated out was filtered, dried under
vacuum and recrystallized by using warm ethanol. The Schiff bases and thiazolidine-4-one derivatives were
prepared by the method of P.Shanmugapandiyan etal, [17] .

Ramachandran .S et al                                                                                        Page 3
Vol 1:1 (2010)                                                             IJPI’s Journal of Medicinal Chemistry

(Z)-N-Benzylidenepyridin-2-amine ( Compound IA)
Yield=74.7%, m.p. 110oC, Rf=0.21. IR (KBr) cm-1:1681(C=N), 1320(C-N), 872( CH-Ph)

(Z)-N-(4-chlorobenzlidene)pyridine-2-amine ( Compound IIA)
.Yield=85.2.7%, m.p. 124 oC, Rf=0.8. IR (KBr) cm-1:1683(C=N), 1321(C-N), 871( CH-Ph)

(Z)-4-((pyridine-2-ylimino)methyl phenol ( Compound IIIA).
Yield=84.2.7%, m.p. 100 oC, Rf=0.78. IR (KBr) cm-1:1671(C=N), 1325(C-N), 893(CH-Ph), 1388(OH)

General Methods of Synthesis of Thiazolidine-4-one ( IB,IIB,IIIB)
To a mixture of schiff base(0.01mol) and thioglycolic acid (0.01mol) dissolved in 1,4 dioxane (20ml),
anhydrous zinc chloride (0.004 mol) was added and refluxed for 8h. The reaction mixture was cooled,
filtered, washed with water, vacuum dried and recrystallised using absolute ethanol.

2-phenyl-3-(pyridin-yl)-thiazolidin-4-one ( Compound IB)
Yield=54.1%, m.p. 125 oC, Rf=0.76
(DMSO-d6) : 7.4-7.9(m, 2H; CH Pyridine ), 6.6-6.7(m, 2H; benzene ) 5.5(s, 1H; CH), 3.6,3.7(s, 2H;
 IR (KBr) cm-1:1688(C=O), 1488( CH2 Bending) , 1329(C-N), 896( CH=Ph)

2-(4-chlorophenyl)-3-(pyridin-2-yl)-thiazolidin-4-one ( Compound IIB)
Yield=58.3%, m.p. 140 oC, Rf=0.4
(DMSO-d6) : 7.4-7.8(m, 2H; CH Pyridine ), 6.5-6.6(m, 2H; benzene ) 5.5(s, 1H; CH), 3.5,3.6(s, 2H;
IR (KBr) cm-1:1688 (C=O), 1488( CH2 Bending), 1330(C-N), 897( CH-Ph)

2-(4-hydroxyphenyl)-3-(pyridine-2-yl)-thiazolidin-4-one ( Compound IIIB)
Yield=64.6%, m.p. 105 oC, Rf=0.84
(DMSO-d6) : 7.2-8.0(m, 2H; CH Pyridine ), 6.6-6.7(m, 2H; benzene ) 6.42(s, 1H; CH), 3.28,3.35(s,
2H; 5-CH2),5.13 ( aromatic OH)
IR (KBr) cm-1:1669(C=O), 1479( CH2 Bending) , 1223(C-N), 898( CH=Ph), 1381 (OH)

3.3Antimicrobial activity
The antibacterial activity[13] of the synthesised compounds was tested against gram(+) bacteria (Staphylococcus
aureus ATCC5144 Bacillus cereus and gram(-) bacteria (Escherichia coli ATCC 25922 using Nutrient agar
medium [13] .

3.4Paper disc diffusion method
The sterilized(autoclaved at 1200C for 30min), liquefied medium (40-500C) was inoculated (1ml/ 100ml of
medium) with the suspension of the micro organism and poured into the petri dish to give a depth of 3-4mm
            . The paper discs impregnated with the test compounds100, 200µl/disc for antibacterial and using dimethyl
sulphoxide as solvent) were placed on the solidified medium. The plates were refrigerated (pre-incubated) for two
hours at 40oC and then incubated at 370C for 24h for antibacterial respectively at the end of which the zone of
inhibition was observed (TABLE 1). Ciprofloxacin (5 µl/disc) was used as standards. The data are presented in
Table 1.

Ramachandran .S et al                                                                                         Page 4
Vol 1:1 (2010)                                                              IJPI’s Journal of Medicinal Chemistry

Table 1: Zone of Inhibition in mm

                                                Standard                             Sample
                                                5µl/disc                100µl/disc            200µl/disc

Compound synthesised                    IB         IIB     IIIB    IB     IIB   IIIB    IB      IIB   IIIB

Staphylococcus aure( Gram +ve )         38         38      38      18     10    18      22      16    25

Escherichia coli ( Gram -ve )           40         38      39      16     12    20      24      19    26

4.Summary and conclusion

 The present work describes the synthesis of Schiff bases and their thiazolidinone derivatives along with their
antibacterial activities. The Schiff bases and thiazolidine-4-one derivatives were prepared by the method of
P.Shanmugapandiyan etal,. The reaction completion was confirmed by TLC and the synthesised compounds were
purified by recrystallisation. The structures of the synthesised compounds were assigned on the basis of the spectral
data. The infra red , nuclear magnetic resonanace spectra of these Schiff bases and thiazolidinone compounds
showed the expected frequencies and signals. The antimicrobial activity of the thiazolidinone derivatives was
screened by the paper disc diffusion method for the standard drug, control and the sample. It showed that the
compound had mild activity both towards gram +ve and gram –ve organism. The standard used was ciprofloxacin.


1.    G.S.Singh, B.J.Molotsi; Il Farmaco., 60, 727-730 (2005).

2.    V. P. M.Rahman, S.Mukhtar, W. H.Ansari, G.Lemiere; Eur.J.Med.Chem., 40, 173-184 (2005).

3.    D.S.Mehta, V.H.Shah; Indian.J.Heterocyc.Chem., 11, 139144(2001).

4.    S.G.Kucukguzel, E.E.Orul, S.Rollas, F.Salin, A.Ozbek;\ Eur.J.Med.Chem., 37, 197-206 (2002).

5.    R.K.Rawal, Y.S.Prabhakar, S.B.Katti, E.DeClercq; Bioorg.Med.Chem., 13, 6771-6776 (2005).

6.    M.G.Vigorita, R.Ottana, F.Monforte, R.Maccari, A. Trovato, M.T.Monforte, M.F.Taviano; Bioorg.Med.
      Chem.Lett., 11, 2791-2794 (2001).

7.     B.Goel, T.Ram, R.Tyagi, E.Bansal, A.Kumar, D.Mukherjee, J.N.Sinha; Eur.J.Med.Chem., 34, 265-269

8.    M.A.Mahran, S.M.El-Nassry, S.R.Allam, L.A.El- Zawawy; Pharmazie., 58, 527-530 (2003).

9.    R.Paramashivappa, P.P.Kumar, S.P.V.Rao, S.A.Rao; Bioorg.Med.Chem.Lett., 13, 657-660 (2003)

10.   M.Conli, R.Gulielmetli, J.Metzger; Bull.Soc.Chim.Fr, 8, 2834-2841 (1967).

11.   S.V.More, D.V.Dongarkhadekar, R.N.Chavan, W.N. Jadhav, S.R.Bhusare, R.P.Pawar;
      J.Indian.Chem.Soc.,79, 768-769 (2002).

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Vol 1:1 (2010)                                                          IJPI’s Journal of Medicinal Chemistry

12.   P. Shanmugapandiyan , A.Ramesh Organic chemistry – an Indian Journal, 1-8,(2008)

13.   S.H.Gillespie; .Medical Microbiology-Illustrated., Butterworth Heinemann Ltd., United Kingdom, 234- 247,

14.   Bentley’s textbook of Pharmaceutics, Eighth edition, ,596-597,(1996).

15.   Indian Pharmacopoeia, A-100,105, (1996)

16.    S.H.Gillespie; .Medical Microbiology-Illustrated., Butterworth Heinemann Ltd., United Kingdom, 234-247,

17.   P. Shanmugapandiyan , K.S. Denshing, R. Ilavarasan, N. Anbalagan, R. Nirmal International Journal of
      Pharmaceutical Sciences and Drug Research 2(2), 115-119.( 2010)

Ramachandran .S et al                                                                                   Page 6

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