You are on page 1of 4

Microwave induced synthesis and

characterization of some thiazolidinone
derivatives bearing benzotriazole moeity
Kirti Shrimali, Diwaker Sitha, Jitendra Vardia* and Suresh C. Ameta
Microwave Chemistry Laboratory, Department of Chemistry,
University College of Science, Mohanlal Sukhadia University,
Udaipur - 313 001 (Raj.), INDIA

Síntesis inducida por microondas y caracterización de algunos derivados
de tiazolidinona que contienen el fragmento benzotriazol
Síntesi induïda per microones i caracterització d’alguns derivats de
tiazolidinona que contenen el fragment benzotriazole
*Present Address:-Team Leader, P.I.Industries, Udaipur (Raj)-313001

Resumen

Introduction

Se describe un método extremadamente rápido y eficiente
para la síntesis de algunos derivados de tiazolidinona a
partir de benzotriazol mediante irradiación con microondas. Se caracteriza la estructura de los compuestos sintetizados en base a los análisis elementales y los datos
espectroscópicos.

In recent years, benzotriazole derivatives have gained significant importance because of their wide use in organic
sunthesis1,2 and pharmaceutical chemistry.3 It is known to
exhibit a broad spectrum of biological activities such as
antimicrobial4,5, antifungal6,7, antiinflammatory8, analgesic9,
anticancer10, CNS depressant11, etc. On the other hand,
thiazolidinones and their 5-arylidene derivatives are also
well known for their versatile pharmacological activities12-18
like antileukemic, anti-HIV, anticonvulsant, antimicrobial
and antiviral.

Palabras clave: Benzotriazol, tiazolidinona, irradiación
con microondas.

ABSTRACT
An efficient and extremely fast method for the synthesis of
some thiazolidinone derivatives starting from benzotriazole under microwave irradiation has been described. The
structure of synthesized compounds have been characterized on the basis of their elemental analysis and spectral
data.
Key words: Benzotriazole, thiazolidinone, microwave irradiation.

Resum

With an interest in the synthesis of bioactive heterocycles
and their incorporation into some established pharmacophores like thazolidinone for new drug evolution; ecofriendly synthetic methodologies have been explored under the framework of green chemistry. Microwave induced
organic transformations19-22 stands among the alternative
routes proposed during the last decade or due to various
reasons like higher yields in shortest possible reaction
time. This paper describes the synthesis of 1,3-thiazolidin4-ones bearing benzotriazole moeity under microwave
irradiation, which is an efficient and operationally simple
method of synthesis.

Results and Discussion

Es descriu un mètode extremadament ràpid i eficient per
a la síntesi d’alguns derivats de tiazolidinona a partir de
benzotriazole mitjançant irradiació amb microones. Es caracteritza l’estructura dels compostos sintetitzats en base
als anàlisis elementals i les dades espectroscòpiques.

In the present investigation, 1H-benzotriazole (1) on Nesterification with ethylchloroacetate in presence of K2CO3
as a base affords ethyl ethanoate benzotriazole (2). Compound (2) showed characteristic IR absorption bands in

Mots clau: Benzotriazole, tiazolidinone, irradiació amb microones.

* E-mail: ameta_sc@yahoo.com

Afinidad LXVI, 540, Marzo-Abril 2009

173

which may be attributed to the chalcone moeity (C=CH-absorption). Synthesis of ethyl-1. 2-[(1.18) 7.3-thiazolidin-4-one (5a): General Procedure All the reactions were carried out in a domestic microwave oven (Kenstar. 1H NMR spectra (DMSO-d6) were taken a Bruker DRX spectrometer (300 MHz FTNMR) using TMS as internal standard and chemical shift are expressed in δ (ppm). Reactions were monitored by thin layer chromatography using silica gel-G as adsorbent using ethyl acetate : n-hexane (7 : 3) as eluent.thiazolidin-4-ones (5ad).38 (20. To this chlorobenzaldehyde (0. The separated solid was filtered washed with water and crystallized from glacial acetic acid.01 mole) and anhydrous sodium acetate (0.00 (3. Synthesis of 2-[(1. 1597 (C-N str. which showed the presence of a thiazolidinone ring.68) 20. Mass spectra were tak- Compound (4) (0.01 mole) and thiosemicarbazide (0. The solid thus separated was filtered. The physical and analytical data are presented in Table 1 and spectral data are given in Table 2.06 (51.51 (45. Formation of (3) was confirmed by the presence of N-H stretching peaks at 3378 and 3237 cm-1 in IR and a multiplet at δ 8.) and 3. IR spectra (KBr pellets) were recorded on Perkin-Elmer 1800 (FTIR) spectrometer.8 (12.4 (s).20 (43.3-benzotriazol) acetohydrazido]1.56) 8.98) 5a Cl C18H13N6O2SCl 412 282 82 52. 3-benzotriazol-1-yl-acetate) hydrazine carbothioamide (3) was prepared by condensation of (2) with thiosemicarbazide. other compounds (5b-d) were also synthesized.53 (58.2.84 (7.42 (52. dried and recrystallized from ethanol.01 mole) in ethanol was kept under microwave irradiation for 8:00-8:30 minutes with a time interval of 10 seconds.02 mol) and glacial acetic acid (10 ml) were added and irradiated for 3:00-5:00 minutes under microwave irradiation.3.2.the region 1743 (C=O str).W. 4-one (4).3-benzotriazol-1-yl acetate (2): To the solution of benzotriazole (1) (0. NH.03 (10.3.01 mole) in ethanol. anhydrous sodium acetate (0.2.3-benzotriazolyl) acetohydrazido]5-(4-chlorobenzylidene)-1. Synthesis of 2-[(1.01 mole) and catalytic amount of K2CO3 was added as a base. Marzo-Abril 2009 .70 (3. The reaction mixture was then allowed to cool and the obtained yellow solid was recrystallized from absolute alcohol. chloroacetic acid (0.54 (3.88 (55. In the IR spectrum.) and 1029 cm-1 (C-O str. The IR spectrum of compound (5a) showed the absence of carbonyl absorption of thiazolidinone at 1712 cm-1 and the presence of a chalcone carbonyl band (C=C-C=O) at 1685 cm-1.72) 5b OCH3 C19H16N6O3S 408 257 67 55. X Molecular formula (M.83) 3. 1H NMR signals were found at δ 5.40) 3. Power-1200W).56 (7.708 δ for –NCH2 group in 1H NMR spectrum.16 (23.12) 20.6 (s) and 4. Synthesis of 2-[1. washed with water.54) 12. The reaction mixture was cooled and poured into ice-cold water.2.01 mole).3-benzotiazol-1-yl-acetate hydrazine carbothioamide (3): An equimolar mixture of (2) (0.60 (33.) Molecular weight Melting point (°C) Yield (%) C H N S 2 – C10H11N3O2 205 74 86 58.96 (28.89) 11.11) 3. Similarly. Recrystallization was carried out from absolute alcohol. band at 1712 cm-1 were obtained due to carbonyl stretching. 2-(1. 540.50) 3.5) 4 – C11H10N6O2S 290 154 75 45. Reaction of compound (4) with aromatic aldehydes led to the formation of final product i.51) 5d H C18H14N6O2S 378 248 76 57.02) 3.14 (57. Compound 1 was prepared according to literature reported23.76 (7.36 (5. ethyl chloroacetate (0.58 (20.27) 7. Compounds (5a-d) were characterized by IR and 1H NMR spectral data.10) 7.42) Table 1 : Characterization data of synthesized compounds 174 Afinidad LXVI. The reaction mixture was cooled at room temperature and then poured into icecold water. Model No.16) 4.2.89) 22.42) – 3 – C9H10N6OS 250 145 92 43.01 mole).33) 20.79) 5c NO2 C18H15N7O4S 423 278 72 51.22 (22.3-thiazolidin-4-one (4): A mixture of carbothioamide (3) (0.50) 5.3-benzotriazolyl) acetohydrazido]1. Its 1H NMR spectrum displayed a new singlet at δ 6. The mass spectrum also supported the proposed structure by the presence of molecular ion peak at m/z 412. Compound (3) underwent ready heterocyclisation upon its reaction with chloroacetic acid in presence of sodium acetate to afford 2-[(1.2.42) 28.C C=S. NH2 group in 1H NMR spectra. Melting points were determined in open capillaries. Solvent was allowed to evaporate to yield the product as white shining crystals. OM-26 EGO. 2.01 mole) as a base in absolute alcohol was irradiated under microwave irradiation for 4:00-4:30 minutes using funnel as a loose top.01 mole) was suspended in minimum quantity of ethanol. The reaction mixture was irradiated under microwave for 8:00 – 9:00 minutes and then it was filtered hot.3 for NH.15 (3.3-benzotriazolyl) acetohydrazido]5-(4-substituted benzylidene)-1.49) 23.48 (20.44 (3.3-thiazolidin.46 (8.92 (3.e. Calculated / Found (%) Compound No. Experimental Section en on Jeol SX-102/PA-6000 (EI) spectrometer.97) 33.

1029 (C-O str. 2H.5 (S. Authors also pay their thanks to the Director. 4H.11 (S.Comp. 1H.9 (S.). L. 2H. 3.).).). 2H.26 (t. CONH). Department of Chemistry. 1712. -CH2).). 3. NCH2) 5a IR (cm-1): 1 HNMR (δ): 3436 (N-H str. 1685 (C=O str. COOCH2 CH3) 3 IR (cm-1): 1 H NMR (δ): 3378. NCH2) 5c IR (cm-1): 3416 (N-H str. 7. CH2). 1H. Ar-H).)..1 (S.6 (S.) 8. COOCH2 CH3).24 (q. Udaipur (Raj. 1H. NH. CONH). 695 (C-S-C str. NH of thiazolidinone ring).. 4H.. RSIC. 159s4 (C=N str. 6.7 (m.9 (m.5 (S.68 (S. 691 (C-S-C str. 7. 1556 & 1340 C-NO2 asymmetric and symmetric stretching 1 H NMR (δ): 8.1 (S.). CH2). C= CH-Ar).NHC=S.) 1597 (C=N str. NH of thiazolidinone ring).2 (S. CH2) 1695.3 (S. 1686 (C=O str. 4.). 2934 (C-H str. 1702. 1105 (C=S str. -CONH).).7-7. Ar-H). 1705. 7.).68 (S. 2967. Ar-4). 2940 (C-H str. C=CH-Ar). 4H.6 (S. 1. 5. 3H. CONH).. 3. 6.) 8. 2967 (C-H str.) 1 H NMR (δ): 8. No. 1685 IR (cm-1): (C=O str. NCH2) 5b 3413 (N-H str. 5. 2810 (C-H str. 1694 (C=O str. 2H.) 7.). Ar-H). Lucknow for analytical and spectral studies.9 (m.. 1H. 1H. 1H.). 1040 (C-O str. 1745 (C=O str. Sukhadia University. 2H.4 (3. 4. 2290 (C-H str.7 (m.6 (m. NCH2). Ar-H).7-7. 9H. 5. 1H. 1H. NH of thiazolidinone ring). 5. 7. CH3)...). 6.0 (S. CDRI.) 8. 1H. 2957 (C-H str.0 (S.). C=CH-Ar). 742 (C-Cl str. 1594 (C=N str. 8H. M.) for providing laboratory facilities.NH2). 1H.9 (m.7-7.) 7. 2H. 1H. 3237 (N-H str. 8H. 5. -CH2). Ar-H) 3. 1597 (C=N str. Spectral Data 2 IR (cm-1): 1 H NMR (δ): 2987 (C-H str.6-7.9 (m. 1712 (C=O str. 2H. Ar-H).70 (S. 7. 2940 (C-H str. CH2). 3.).6-7. 6. 1H. C=CH-Ar). 8H.3 (m.5 (S. 4H. CH2). Afinidad LXVI. 1H. 1H.. CH2). NH of thiazole) 5d IR (cm-1): 1 H NMR (δ): 3413 (N-H str. NH of thiazolidinone ring) Table 2 : Spectral data of synthesized compounds Acknowledgements The authors are thankful to Head.2 (S. Marzo-Abril 2009 175 .). 7. NCH2) 4 IR (cm-1): 1 H NMR (δ): 3431 (N-H str. 540. CONH). 1743 (C=O str.9 (S.6-7.6 (S.

Syn. Sci. Bajaj M. 540. De S. and Singh J. Chem. Org. Vol. 106 (1955). Pharm.T.. and Misra P. Indian Chem.P. 64. Synth.L. Vazquez-Tafo M... 77. 1039 (2006).. Chem.. Sarala B. Novellino E. 20. 992 (1978).. Comb.. Monforte M. Bosco A. El-Feky S. 14. Negi N.W .. and Parekh H.. 51. and Peterson W. Synth.H. Al-Soud Y. Bapodra A. 9.. Commun.G.4. Chem.W . Thiery V... Etman H. 55. Med. 49... French G. and Besson T. Pharmazie.. The Chemistry of Heterocycles. 16. 57(12).C. Chem.K.K.C. Heterocycl. Rawal R. 11(8). and Rogoroy B.. and Srivastava S.D. Coll.S.(4. Marakos P. 39(5). Sci. Swamy S. Capasso R.. Bertamino. Mahmood M. (2003). High throughput Screen.N N + N E thanol / K 2 C O 3 C lC H 2 C OOC 2 H 5 N M. 1701 (2003).. and Krarchenko D.R.G. 19. and Forestieri A.R. Frere S. Commun. 2215 (2000). Chem. 5... Leung H.. Singh P. 54(1).W .. Kidwai M. 2587 (2005). Pouli N. 22. and Fekry A.30) min NH H 2N N O N H N N NH N S E thanol O N C lC H 2 C OOH C H 3 C OONa N NH 2 O N NH M. and Rangappa K.. Agric.A. Zappaala C.. Med. Papakonstantinou-Garoufalias S. Indian Chem... 17. 53672W (1983). and De-Clercq E.00 .M. Demsctiroder R.(8. Biol.. Sulfur and Silicon and the Related Elements.. 10.30) min (4) (3) NH S H 2N E thanol M. and Marting M. 432 (2006).. Afinidad LXVI. Mazzoni O.. Siddiqui I.8. Chem. Borrelli F. 999 (2006) 8.P. Gaonkar S..S.A. and Diurrw M.(8. and Chand V.. Prabhakar Y. Prasad J. and Chtyroglou-Ladas A. 41.. Weinheim. 11.00) min N N C H 3 C OONa / gl.. Eicher T.. 894 (1993). 8.C.K. Soc.00) min N H N (2) (1) C H 2 C OOC 2 H 5 E thanol S M. Eur.G. 439 (2005)..V. Vigorita M.(3. Biorg.. Metwally M.S....d) c = -NO 2 d = -H O R eaction S cheme BIBLIOGRAPHY 1. 830 (1990). 46 (2000).. 2. Chain Ho L. 501 (2002). Chem. 3 (1994).M. 25 (1992).W .K. J..G. Hauptmann S.. 29B. 21..A. and El-khair A. Marzo-Abril 2009 ... Al-Masoudi N..R. Indian J. Wiley-VCH.00 . 3.. 7062 (2005). 4.R.00 . Sengupta A.. Seyas J.H. and Ferwanah Ael-R.V.. Pershin D. J. 18.A.. Mahareb R. 3789 (2003).. Al-Qmran F.00 . 4586 (2003)... 6.. 877 (2002).S. Pharm. 181. 176 12. 99. Katritzky A. 38B.R.. Srivastava S. Previtera T. and Hung K..5. 48. Griew P. 623 (1999).A.. Purohit M... Drugs Des. 23.D. Indian J. Chem.M. 13.. Chem Abst. Krasavin M. Katti S. 15.. Keshk E. Farmaco.. Farmaco.N.. 67. Indian J. 33. J... 973 (2002).B.A. Bharmal F... Indian J. J. Priya B. III.. Tetrahedron Lett. and Rawat T. C H 3 C OOH X O N NH N X S a = -C l b = -OC H 3 HN 5 (a . J.. 35.K. Food Chem. 7. 9.. Larkin D. Phosphorus. Solomon V.. 16. Giordano A.. Soc.9. Biorg.