Joshi, Dharti

Oza, Haresh

Parekh, Hansa

NOPR

Indian Journal of ChemistryVol. 37B,August 1998 , pp.822-824Synthesis and antitubercular activity ofnovel thiazolidinone derivativesHaresh Oza, Dharti Joshi & Hansa Parekh*Department of Chemistry, Saurashtra University,Rajkot 360 005, India.Received 16 October 1997; accepted (revised) 10 March 19984-111iazolidinones 48-0, 58-0 have been synthesised by thecyclocondensation of different schiff's bases 3a-o withthioglycolic acid and thiolactic acid respectively. All thecompounds were screened for their antitubercular activityagainst Mycobacterium tuberculosis H37 Rv.4- Thiazolidinones are endowed a variety ofbiological activities 1-5 Further, paracetamol deri-vatives have been found to exhibit the therapeuticactivity'". In order to explore the activitiesassociated with this nucleus, we report herein thesynthesis and antitubercular activity of thederivatives of thiazolidinone.The reaction of p-hydroxy acetanilide with ethylchloro acetate in the presence of dry acetone andanhyd. K2C03 gave the desired ethyl p-acetamido-phenoxy- acetate" 1 which was converted to p-acetamidophenoxy acetyl hydrazide" 2 by treatmentwith a slight excess of hydrazine hydrate in absoluteethanol under reflux. The hydrazide 2 was.condensed with different araldehydes to obtaincorresponding NI -substituted benzal, N2 -p-aceta-midophenoxy acyl hydrazines 3a-o (schiffs bases).These different schiffs bases were cyclocondensedwith thioglycolic acid and thiolactic acid to affordrespective 2-aryl-3-p-acetamidophenoxy acetamido-5-H-4-thiazolidinones 4a-o and 2-aryl-3-p-aceta-midophenoxy acetan1ido-5-methyl-4-thiazolidinones5a-o (Scheme I).The structure of the compounds synthesised wereassigned on the basis of elemental analyses, JR, lHNMR and mass spectral data. The compounds wereevaluated for antitubercular activity towards astrain of Mycobacterium tuberculosis H37 Rv.Note0-0-\I r;H3C - C . HN ~ OH + CICH COOC H2 2 5o -0- 0\I IIH3C - C - HN r; ~ OCt I c· a .CH - CH2 2 3. -(1)1 NH? Nil:> 11,,0H3C . g -HN-{ ')- OCH2g· NH - NH2(2)1 R-CHOo -0- 0II IIH3C - C - HN r;_ ~ OCH2C . NH . N = CH . R(3a-o)1 SH.?H-COOHXx = C113. n ~ AlylScheme IAntitubercular activityThe antitubercular evaluation of the compoundswas carried out at Tuberculosis AntimicrobialAcquisition Co-ordinating Facility (T AACF) USA.Primary screening of the compounds for antituber-cular activity have been conducted at 12.5 ug/mlagainst Mycobacterium tuberculosis H37 Rv inBACTEC 12B medium using the BACTEC 460radiometric system.All the compounds are reported in Table J fortheir antitubercular activity data. It can be con-cluded from Table-I that compounds 3a-o and 5a-o exhibited various degree of activity (0 to 35%)whereas compounds 4a-o were inactive.NOTES 823Table 1-Physical constants and antitubercular activity data of compounds 3a-o, 4a-o and 5a-o.N(%) %ofCompd R Mol. formula m.p.("C) YieJd(%) Found Caled. inhibition"38 -CJIs- CI7HI7N)03 212 52 13.58 13.50 173b 2-CI-CJ-L- C17HloN303CI 205 54 12.24 12.15 353c 4-CI-CJ-L- CI7H1oN3O)CI 200 58 12.21 12.15 293d 2,4-CI2-CJI3- CJ7H1sN303C12 230 60 11.10 11.053e 3,4-( OCH3 )2-CJI3- CI9H21N30S 205 57 11.25 11.323f 4-N,N-(CH3)2-C6H4- CI9HnN403 220 62 18.75 18.81 203g CJ·hO- CisHIsN304 195 63 13.90 13.95 153h 2-0H-CJ-L- CJ7HJ7N304 228 65 12.80 12.843i 4-0H-CJ-L- CJ7HJ7N304 155 61 12.78 12.843j 4-OCH3-CJI4- C1sHI9N304 208 58 12.25 12.31 253k 3-(OCH3)-4-(OH)-CoH3- CIsHI9N30S 225 62 11.70 11.7631 2-N02-CJ14- CI7HloN40S 255 58 15.79 15.73 093m 3-N02-C6H4- CI7HloN40S 232 60 15.79 15.733n -CH=CH-C6Hs CI9HI9N303 234 55 12AO 12.46 0430 3,4,5-(OCH3)J-CoH2- C2oH2)N306 200 57 10Al 10.47 0143 CJIs- CI9HI9N304S 218 50 10.80 10.90 004b 2-CI-C6H4- C 19H1sN304SCI 210 48 10.10 1001 004c 4-CI-C6H4- CI9H1sN304SCI 250 45 10.11 10.01 004d 2,4-Ch-CoH3- C 19HI7N304SCh 205 47 9.20 9.25 004e 3,4-(OCH3)2-C6H3- C21H2)N30oS 290 41 9.38 9.43 004f 4-N,N(CH3)2-C6H4- C2IH2~40.IS 320 44 13.12 13.08 004g CM3O- CJ7HI7N30SS 265 47 11.28 11.20 004h 2-0H-CoH4- CI9HI9N)OsS 241 46 9.68 9.74 004i 4-0H-CoH4- CI9HI9N30SS 245 49 10Al 10.47 004j 4-0CH3-CoH4- C2oH2IN30SS 175 49 10.19 10.12 004k 3-(OCH3)-4-(OH)-C6H3- C2oH2IN306S 212 49 9.70 9.74 0041 2-N02-CoH4- CI9H1sN406S 205 40 13.10 13.02 004m 3-N02-C6H4- CI9H1sN4OoS 207 41 13.12 1302 004n -CH=CI-I-C6I-1S Cl11-I11N304S 270 40 10.15 10.21 0040 3,4,5-(OCI-I3h-C61-11- C211-12sN307S 210 42 8.80 8.84 005a C61-1s- C2ol-bN304S 215 45 10A5 10.52 005b 2-CI-C61-14- Clol-lzoN304SCI 105 42 9.61 9.68 005c 4-CI-C61-14- C lol-hoN304SCI 207 44 9.59 9.68 005d 2,4-CIz-C61-13- C201-119N304SCIz 198 47 8.91 8.97 005e 3,4-(OCI-I3)2-CoI-l3- C121-12sN)OoS 102 49 9.19 9.15 005f 4-N,N(CI-I3)z-CoI-l4- CdbN404S 225 45 12.70 12.66 005g CM3O- C ISl-l19N30SS 265 46 10.83 10.79 005h 2-01-l-CoI-l4- C1Ol-l21N30SS 201 43 10.06 10.12 005i 4-01-l-C61-14- C1OI-I1IN3OsS 207 42 1008 10.12 005j 4-0CI-I3-C6H4- Clll-l2)N3OSS 300 48 9.72 9.79 285k 3-(OCI-I3)-4-(OH)-C,,/b- C2IH23N)OoS 168 45 9A7 9.43 2451 2-N02-C61-14- C2ol-hoN40oS 178 47 12.54 12.61 275m 3-NOrC6H4- C1o/-izoN40"S 108 45 12.56 12.61 275n -CI-I=CI-I-Col-Is Clll-l2)N30.IS 218 42 9.80 9.88 1850 3,4,5-(OCI-I3»)-CoI-l2- C2)/--\z7N307S 162 43 8.52 8.57 27* Mycobacterium Tuberculosis J/37 Rv824 INDIAN J CHEM, SEC.B, AUGUST 1998Experimental SectionAll the melting points are uncorrected. Infraredspectra were recorded on Shimadzu 435-IRspectrophotometer, IH NMR spectra on Brucker-300F MHz spectrophotometer using TMS as aninternal standard and mass spectra on Jeol Jms 0-300 spectrophotometer.NI-4-Methoxy benzal, N2 -p-acetamidophenoxy-acyl hydrazine 3j. A mixture of 2 (0.01 mole) and4-methoxy benzaldehyde (0.015 mole) was refluxedin absolute ethanol for 5-6 h. The contents werecooled and poured onto crushed ice and trituratedwith sodium bisulphite solution. The product wasisolated and crystallised from dioxane to give 3j,yield 58%, m.p. 208° (Found : C, 63.39; H, 5.50,N, 12.25. CI8HI9N304 requires C, 63.34; H, 5.57,N, 12.31%); IR (KBr) ; 3300 (N-H), 1680 (C=O),1660 (C=O of ~NHCOCH3), 1585 (C=N), 1245 (C-O-C sym.) 1030 cm-I(C-O-C asym.); IH NMR(TF A + DMSO-d6); 0 2.52 (s, 3H, -COCH3), 4.07(s, 3H, -OCH3), 4.94 (s, 2H, -OCH2), 7.12-7.29 (m,8H, Ar-H), 7.7 (s,IH, CH=N), 8.1 (s, IH, -NH-N);MS : mJz 342 (~), 279, 237, 233, 223, 208, 203,197, 191, 175, 165, 119, 108,91 and 77.Compounds 3a-o were prepared similarly andthe physical data are given in Table I.2-(4' -Methoxy phenyl)-3-p-acetamidophenoxyacetamido-5-H/methyl-4-thiazolidinones 4j, 5j. A 2mixture of 3j (0.01 mole) and thioglycolic acid! 3thiolactic acid (0.01 mole) was heated on an oil-bathat 120-25°C for 12 h. The reaction mixture was 4cooled and treated with 10% sodium bicar-bonatesolution. The product was isolated and crystallisedfrom ethanol.4j : Yield 49%, m.p. 175° (Found: C, 57.60; H,5.01, N, 10.19. C2oH21N30SSrequires C, 57.83; H,5.06, N, 10.12%); IR (KBr) : For 4a, 3300 (N-H),1700 (C=O thiazolidinone moiety),1670 (C=O),1660 (C=O of -NHCOCH3), 1275 (C-O-C sym.)605 cm-I(C-S-C); IH NMR (CDCh + DMSO-d6); 02.56 (s, 3H, -COCH3), 3.82 (s, 2H, -CHz-CO), 4.95(s, 2H, -OCH2), 5.96 (m, IH, -S-CH-Ar), 6.9-7.6(m, 9H, Ar-H), 8.1 (s,IH, -NHCO), 8.31 (s, lH, -NH-N) MS : For 4e : mJz 446 (~), 308, 247, 233,191, 174, 165, 159, 134, 121 and 77.5j : Yield 48%, m.p. 300° (Found : C, 58.62; H,5.39, N, 9.74. C21H23N30SSrequires C, 58.74; H,5.36, N, 9.79%); IR (KBr) : 3300 (N-H), 1715(C=O thiazolidinone moiety),1680 (C=O), 1660(C=O of -NHCOCH3), 1225 (C-O-C sym.) 1055(C-O-C asym.) 700 cm-I(C-S-C); IH NMR (CDCh+TFA); 0 1.70-1.72 (d, 3H, -CH-CH3), 2.35 (s, 3H,-COCH3), 3.88 (s, 3H, -OCH3), 4.20 (q, IH, -CH-CH3), 4.81 (S, 2H, -OCH2); 5.96 (s, lH, -S-CH-Ar)6.93-7.68 (m, 8H, Ar-H), 8,32 (s, lH, -NH-N).Compounds 4a-o and 5a-o were preparedsimilarly and the physical data are given in Table I.AcknowledgementThe authors are thankful to Dr. A R Parikh, Prof.and Head. Dept of Chemistry, SaurashtraUniversity for providing facilities and valuableguidance and Dr Cecil 0 Kwong, ResearchChemist, Tuberculosis Antimicrobial AcquisitionCo-ordinating Facility (TAACF) for antitubercularfacility.ReferencesLadva K, Dave V & Parekh H, J Indian Chem Soc, 68,1991, 379.Vashi B S, Mehta D S & Shah V H, Indian J Chem, 34B,1995,802.Hogale M B, Uthale A C & Nikam B P, Indian J Chem,30B, 1991, 717.Viltaria D M, Orazio M, Eugenio P, Anlonia C, FedericoG & Adde B, J Med Chem, 35, 1992,2910; Chem Abstr,117, 1992, 62288t.5 Pandya D & Nair K B, Pharemazie, 48, 1993,414; ChemAbstr, 120, 1994, 106843p.6 Bjune K, Stubhaug A, Dodgson M S & Breirik H, ActaAnaestheriol Scnad, 40(4), 1996, 399; Chem Abstr, 125,1996,491.7 Claris D A, S. African Z A 92, 01, 1991, 849; ChemAbstr, 119, 1993, 34322x.8 Bianchi M & Paneri A E, BrJ Pharmacol, 117(1), 1996,13.0;Chem Abstr, 124, 1996, 135088j.9 Nargund L V G , Reddy G R N & Hariprasad V, Indian JChem, 35B, 1996,499.

Synthesis and antitubercular activity of novel thiazolidinone derivatives

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Synthesis and antitubercular activity of novel thiazolidinone derivatives

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