IBN AL- HAITHAM J. FOR PURE & APPL. S CI. VOL. 24 (2) 2011 Synthesis of New Schiff Bases and 2,3-Disubstituted - 1,3-Thiazolidin-4-one Derivatives Containing Benzothiazole Moiety J. H. Tomma Departme nt of Chemistry , College of Education I bn Al- Haitham Unive rsity of Baghdad Received in : 21 January 2008 Accepte d in : 16 June 2011 Abstract Two series of Schiff Bases and 2,3-disubst itut ed-1,3-thiazolidin-4-one derivatives were sy nthesized . Reaction of 2-mercap tobenzot hiazole with α-chloro acetic acid gave comp ound[I]. Esterification of carboxy lic moity of comp ound [I] , using absolute methanol in the presence of conc . H2SO4 y ielded acorresebonding ester [II] , wich was condensation with hy drazine hy drate to give acid hy drazide [III] . The new Schiff bases [V]n were sy nthesized by reaction of acid hydrizide with dialdehy de [IV]n in the p resence of glacial acetic acid . The thiazolidinone derivatives [VI]n have been obtained from the azomethines through the addition of thioglycolic acid . Their chemical st ructures have been confirmed by melting p oints , FT IR and 1 HNM R (of some of them) . Benzot hiazole , thiazolidinone. Introduction Thiazolidin-4-one derivatives have att racted a great deal of interest due to their antibacterial [1-3] , anti-infammatory [4] , fungicidal activity [5], Ant ifeedant activity , Acaricidal activity , Contact toxicity , and Stomach toxicity [6]. Over views of their sy nthesis , p rop erties reactions and app lications have been p ublished [7,8] . Benzot hiazole derivatives have been reported to have broad range of biological activities [9-11] . IBN AL- HAITHAM J. FOR PURE & APPL. S CI. VOL. 24 (2) 2011 These findings focused p articular interest on incorp orating thiazolidinone and 2- mercap tobenzot hiazole in one framework , which could be useful for biological and p harmacological screening. Experime ntal Materials : M ost of chemicals used were sup p lied from Fluka , M erck and BDH Chemicals Co. and used as received . Techni que s: Uncorrected melting p oints were determined by using Hot -Stage, Gallen Kamp melting p oint app aratus. FT IR sp ectra in the range 500-4000cm -1 were obtained by using p otassium bromide discs on FT IR instrument M odel 8000 Shimadzu Sp ectrop hotometer, Jap an . 1 HNM R sp ectra were taken on comp any : Bruker , model: ultra shield 300 M Hz Sp ectrop hotometer using DMSO as a solvent with TM S as an internal standard and element al analysis (C.H.N) were carried out by EA-017. Synthesis of compounds The reaction sequence leading to the formation of new compounds [V]n and [VI]n are outlined in Scheme 1. 2-Mercap t o aceti c acid ben zot h i azol e [I] To a st irred mixture of -chloro acetic acid (0.01mol) and 10% aqueous sodium hy droxide (10 mL), a solution of 2-mercap tobenzot hiazole (0.01mol) in 10% aqueous solution of sodium hy droxide( 10 mL) was added . The mixture was refluxed for three hours. Aft er cooling, the solution was acidified with concentrated hydrochloric acid. The p recipitate was filtered and recry st allized from ethanol [12] to y ield 90%, m.p =155 o C. 2-(methy lthioacetate) benzot hiazole ester[II] : was p repared following the p rocedure described by A. Vogel [13]. 2-(thi oacetyl hydrazide) benz othi azole [III] This comp ound was p repared according to references [14 ] . Polyme thyl ene -α,ω-bis-4-oxybenzaldehyde [IV]n In a 100 mL flask ,4-Hy droxy benzaldehy de (2.44gm , 0.02 mol) was dissolved in 15mL of DM F. Anhy drous sodium carbonate ( 0.025mol) and (0.01mol) of the app rop riate α,ω –dibromo or dichloro alkane were added to the reaction flask . The st irred mixture was refluxed for 4hrs , allowed to cool , and then p oured into 400 mL of cold water , cooled at 5 o C overnight , and then filtered , washed well with water , dried in air , recry st alized from ethanol(15), yield 88-98% . IBN AL- HAITHAM J. FOR PURE & APPL. S CI. VOL. 24 (2) 2011 N SH S ClCH 2COO H [I] N S SCH2COO H N S SCH2CON HN H2 [III] [V] n N S SCH2 CON HN HC N S [II] N S SCH2 COO Me [VI] n N S SCH2 CON H N S N S N S O HN COCH 2 S O HC O O CH HSCH2 CO2H [IV] n O(CH 2)n O C H NHNCO CH2 S O(CH 2 ) n O NH2NH2.H2 O MeO H H2SO4 10%N aOH 2 glacial acetic acid O(C H2)nO n= 2-4 , 10, 12 Scheme 1 α,ω-bis-[(2-thioacetyl hydrazidebenz othi azole-2-yl)benz ylidene -4-oxy]alkane [V]n A mixture of comp ound[III] (0.02mmol) , dialdehy de [VI]n=2 (0.01mmol) , three drop s of glacial acetic acid and absolute ethanol (10mL) was refluxed for 4 hours. The reaction mixture was concentrated , cooled and the formed p recipitate was filtered off , dried and then recry st allized using chloroform to give p ale yellow [16], Yield (80%) , m.p=210 o C. Likewise other comp ounds [V] with n=3,4,10,12 (were p repared in a same way using dialdehy de [IV]n with different n=3,4,10,12) .Characterization data are p resented in table 1. Poly methy lene-α,ω-bis-[N-(2-t hioacety lhydrazinebenzothiazole) -4-oxo-1,3-thiazolidin-2-(p- oxy benzene)] [VI]n A mixture of Schiff base [v]n( 0.01mmol), thioglycolic acid (0.022mmol) was refluxed in dry benzene 6mL for 6 hours . The solvent was evaporated and the reaction mixture was IBN AL- HAITHAM J. FOR PURE & APPL. S CI. VOL. 24 (2) 2011 neutralized with cold dilute sodium bicarbonate solution , the formed p roduct was filtered off and recryst allized from acetone to y ield 70% , m.p =188-190 o C. Likewise other comp ounds [VI] with n=3,4,10,12 (were prepared in a same way using Schiff bases [V]n with different n=3,4,10,12) .Characterization data are presented in table 3. Results and Discussion The reaction between 2-mercap tobenzot hiazole and -chloroacetic acid in alkali media was used to p repare the comp ound [I]. The -halogroup in -chloroacetic acid is good leaving group and sulfur comp ounds are a good nucleophile. Thus, the reaction is a ty p ical of the nucleophilic substitut ion reaction of the thiol group , where the -halo group could be replaced easily in this reaction to get good y ield[17]. The mechanism of this reaction may be outlined as follows, Scheme (2). N SH S Cl CH 2CO OHNaOH Na ClSC H2COO H N S N S + S Na + + + S chem 2 H2O The structure of this comp ound [I] was studied by its melting p oint 155 o C and FTIR sp ectrum , which showed broad band at 2750-3390cm -1 due to νO-H group , sharp p eak at 1690 cm -1 assigned to carbony l group of carboxy lic moity and the aliphatic C-H st retching at 2950 cm -1 . also showed significant bands in the region (3060 , 1575 , 1454 and 750) cm -1 that indicated the p resence of benzot hiazole moiety . 2-(M ethy lthioacetate) benzot hiazole[II] was obtained by esterification of the carboxy lic acid moity of comp ound [I] using absolute methanol with conc. H2SO4 was identified by FT IR sp ectrum . FT IR sp ectrum showed disapp earance of two p eaks of ν OH and νC=O of carboxy lic moiety of comp ound [I] together with the app earance of good p eak at 1705 cm -1 which could be att ributed to νC=O of ester group . Condensation of ester [II] with hy drazine hy drate y ielded the 2-(thioacety l hy drazide)benzothiazole [III] which is characterized by its melting p oints 120 o C . FT IR sp ectra , showed the following absorp tion bands: νC=O of amide group at 1645 cm -1 , bands in the regions (3460, 3282, 3197) cm -1 due to asy mmetric and sy mmetric stretching vibration of NH , NH2 group s , resp ectively. The sp ectra showed band at 2928 cm -1 assignable to the st retching of aliphatic (C-H). IBN AL- HAITHAM J. FOR PURE & APPL. S CI. VOL. 24 (2) 2011 The Schiff bases of series [V]n were p repared by refluxing of comp ound [III]n with dialdehy de [IV]n (which are obtained from the reaction of 4-hy droxy benzaldehy de with α,ω- dibromo or dichloro alkane using DM F as the solvent in Na2CO3 medium) in glacial acetic acid as a cataly st . These compounds series [V]n are characterized by FT IR and 1 HNM R sp ectroscop y . FT IR sp ectra showed the disapp earance of two absorp tion bands due to NH2 st retching of comp ound [III] together with the app earance of a band at (1614-1616) cm -1 assignable to imine group (CH=N) . The sp ectra also shows the bands at (2840-2954) cm -1 is due to aliphatic C-H st retching . Table 2 exhibited the characterist ic FT IR absorp tion bands of these comp ounds 1 HNM R sp ectrum of compound [V]n=2 (DM SO as a solvent) showed single broad peak at  9.15 p p m that could be att ributed to the two p rotons of NH , a multip let signal at  7.0- 7.55 p p m for eight aromatic p rotons of the p henyl rings of benzot hiazole moiety and a doublet of doublets at  7.8-8.25 p p m for eight aromatic protons of two benzene rings . The imine p rotons ap p eared at  4.92 p p m . The 1 HNM R sp ectrum also showed the a singlet at  4.65 p p m assigned for four p rotons of the mercap to methy lene group s to (SCH2) and triplet signal between  3.80-3.92 p p m that could be assigned to t he four protons of methy lene group (O-CH2) 2,3-Disubstitut ed-1,3-thiazolidin-4-ones[VI]n were obtained by reacting the Schiff bases [V]n with thioglycolic acid acid in dry benzene and reflux for 6hrs. The mechanism of this reaction may be outlined as follows, Schem (3). IBN AL- HAITHAM J. FOR PURE & APPL. S CI. VOL. 24 (2) 2011 N S SCH2CONHN HC N S N S SCH 2CONH N S N S N S HNC OCH 2S O Ar = O O N S SCH2CONHN HC N S SH CH 2 HS OHHO O OCH 2 C C N S SCH2CONHN HC N S S CH 2 S OH 2H 2O O OCH2 C C HO C CH 2S H HSCH 2 C OH C H N HN C OCH 2 S -2H 2O CH N HN COC H 2S CH NHN CO CH2S O Ar Ar Ar Ar [V ]n O( C H2)nO [ V I]n Sche me 3 The structural assignments of t hese compounds [VI]n was based on sp ectral data FT IR and 1 HNM R sp ectroscop y . The FTIR exhibited significant bands at 3210 cm -1 and 1730 cm -1 which could be att ributed to NH st retching and C=O st retching of thiazolidinone ring , resp ectively . Besides this , a band about 1660 cm -1 is due to C=O (amide) st retching and disapp earance of absorp tion st retching band due to imine group . Table 4 exhibited the characterist ic FT IR absorp tion bands of t hese compounds. 1 HNM R sp ectrum of comp ound [VI]n=2 , figure (1) showed the following characterist ics chemical shifts (DM SO as a solvent) singlet at  11.5 p p m could be att ributed to the two p rotons of NH group s , a multiplet signal at  7.05-7.5 p p m for eight aromatic p rotons of t he phenyl rings of benzothiazole moiety and a doublet of doublets at  7.65-8.2 p p m for eight aromatic p rotons of two benzene rings . A sharp singlet was abserved at  4.80 p p m that could be assingned to the four p rotons of the mercap to methy lene group s (SCH2) . A singlet signal app eared at  4.65 p p m for four p rotons of H-5 thiazolidinone . The triplet signal observed between  4.2-4.49 p p m was assinged to four p rotons of methy lene group (O-CH2) showed singlet signal at  6.66 p p m that could be attributed to the two p rotons of H-2 thiazolidinone (2). IBN AL- HAITHAM J. FOR PURE & APPL. S CI. VOL. 24 (2) 2011 References 1- El-M as ry ,A. H.; F ahmy ,H. H. and Ali A bdal wah ed, S. H. (2000) “ Sy nthesis and Ant imicrobial Activity of Some New Benzimidazole Derivatives ” , Molecu les 5:1429- 1438 . 2- Ko hli ,P.; Srivastav a ,S. D. and Srivastav a ,S. K. (2007) “ Sy nthesis and Biological Activity of M ercaptobenzimidazole Based Thiazolidinons and their Acry lidenes” J . of the C hinese Chemical Soci ety , 54 :10 03-1010. 3- Ab od Elhafez ,O. M.; El Kh arsy ,E. A.; B adria ,F. and Fat hy, A. E. (2003) “ Sy nthesis and Biological Investigation of New T hiazolidinone and Oxadiazoline Coumarin Deriv atives” ,A rch Pham Res . , 26(8):686-696. 4- Va zzan a , I.E. ;Terrano va , F.; M attioli and F. Sp ar atore (2004) “ Aromatic Schiff Bases and 2,3-Disubst ituted 1,3-Thiazolidin-4-one Derivatives as Ant i-inflammatory agents” ,ARKIVO C , V , 364-374. 5- Ling Liu ,H.; Li ,Z. and Anth onsen ,T . (2000) “ Sy nthesis and Fungicidal Activity 2- Imino-3(4-Ary lthiazole-2-yl) Thiazoliden-4-ones and their Acry lidene Derivatives” ,Molecules, 5 :1055-1061. 6- Pareek,D. ; Chaudhary , M .; Pareek , P. K. ; Kant, R.; Ojha , K. G. ; Pareeka, R. and Pareeka, A. (2011) “ Sy nthesis and biological evaluation of 4-thiazolidinone d erivatives incorp orating benzot hiazole moiety ”, Der Pharmacia Sinica , 2 (1): 170-181 . 7- Br own ,F. C. (1 961) “ Th iaz olidin-4-ones” . Chem. Revs. 61 :46 3-521. 8- N ew co me, G. R. and N ayak, A. (1961), “Th iazo lidin-4-ones ”. adv . Het erocycl. Chem. 25 : 8 3-112. 9- Al i , E. ; Tomma , J. and M ubbrik, S . (2008) “ Sy nthesis of Study The Biological Activity of Some Schiff-Bases Deriv ed from 2-Aminobenzot hiazole and Vanillin Derivatives ” , Ibn Al-Haitham Journal for Pure and App lied Sciences , 21(1):73-80. 10- Argy rop oulou , I. ; Geronikaki, A.; Vicini,b. P. and Zanib, F. (2009) “Sy nthesis and biolo gical ev aluation of sulfonamide thiazole and benzothiazole derivatives as antimicrobial agents ” , ARKIVOC , (vi) :89-102. 11- Kaur, H.; Kumar, S. I. ; Singh, K.K. ;Saxena, A. and Kum ar ,(2010), “Synthesis, Characterization and Biolo gical Activity of Various Substitut ed Benzothiazole Derivatives” Di gest Journal of Nanomaterials and Biostructures , 5(1): 67 - 76 12- Tomma, J. H.; Rouil, I. H. and AL-Dujaili ,A. H. (2009) “ ٍ◌Sy nthesis and M esomorphic Behavior of Some Nove l Comp ounds Cont aining 1,3,4-Thiadiazole and 1,2,4-triazole Rings ” , M ol. Cryst. Liq. Cry st. , 501 :3-19. IBN AL- HAITHAM J. FOR PURE & APPL. S CI. VOL. 24 (2) 2011 13- Vogel , I. (1974) “A text Book Of Pract ical Organ ic Chemistry ” , Longman Group Lt d., London 3 rd Ed.m , 781. 14- Smith , P. A. (1946) “ Organ ic Reactions” 3(9) : 3 66. 15- Griffin , A. and Havens, S. (1981) “ M esogenic Polymers . III . T hermal Prop erties and Sy nthesis of Three Homologus Series of T hermotrop ic Liquid Crystalline “Backbone”Poly esters” , J. of Poly m. Sci. Poly mer Phy sics Edition , 19: 951-969. 16- Tomma , J. H. (2010) “ Sy nthesis , Characterization and Study The Liquid Cry stalline Prop erties of N-Acy l , Thiourea and Imidazole Der ivatrives” , Ibn Al-Haitham J. for Pure and App l. Sci., 23(3):134-151. 17- M arch, J. (1992) “ Advanced Organic Chemistry Reaction M echanism and Structure” , 4 th . Ed., Wiley and Sons. Inc. New-York . Ta ble ( 1): Physi cal an d C. H .N da ta o f S chi f f base s [ V] n. Com p No. Mol ecul ar For mul a Yi el ds % Colo r M.P 0 C T heoriti cal Cal c. C% H % N % C% H % N % [V]2 C34H28N6S4O4 80 Pal e yall o w 210 [V]3 C35H30N6S4O4 82 yall o w 175 57.8 5 4.13 2 11.5 7 57.8 2 4.05 11.8 2 [V]4 C36H32N6S4O4 85 yall o w 202 [V]10 C42H44N6S4O4 80 Pal e yall o w 198 61.1 6 5.33 10.1 9 61.2 5 5.68 10.4 9 [V]12 C44H48N6S4O4 84 Pal e yall o w 184 - 186 61.9 7 5.63 9.85 61.8 8 5.85 9.96 IBN AL- HAITHAM J. FOR PURE & APPL. S CI. VOL. 24 (2) 2011 Table (2): FTIR data of S chi ff bases [V]n Co m p N o . Ch a ract eri st ic b an ds FT I R sp ect ra ( c m -1 ) ν N -H ν C- H al ip h . ν C= O a m ide ν C= N im ine ν C-O e the r [ V]2 3 2 1 1 2 8 8 3 -2 9 3 2 1 6 6 2 1 6 1 4 1 2 4 4 [ V]3 3 2 1 0 2 8 8 5 -2 9 3 0 1 6 6 0 1 6 1 4 1 2 4 2 [ V]4 3 2 1 0 2 8 8 2 -2 9 3 2 1 6 6 2 1 6 1 4 1 2 4 2 [ V]10 3 2 0 8 2 8 8 5 -2 9 3 2 1 6 6 2 1 6 1 6 1 2 4 2 [ V]12 3 2 0 8 2 8 8 5 -2 9 3 0 1 6 6 0 1 6 1 6 1 2 4 4 Table (3): physi cal and C.H.N data of se ries [VI] n Com p. No. Mol ecul ar For mul a Yi e ld % Colo r M.P 0 C T heoriti cal Cal c. C% H % N % C% H % N % [VI]2 C38H32N6S6O 6 70 Y allo w - orang e 188 -19 0 53.0 2 3.72 9.76 53.2 4 3.6 6 9.8 2 [VI]3 C39H32N6S6O 6 75 yall o w 165 [VI]4 C40H36N6S6O 6 82 orang e 176 54.0 5 4.05 9.45 54.1 4 4.4 5 9.8 9 [VI]10 C46H48N6S6O 6 85 yall o w 154 -15 6 [VI]12 C48H52N6S6O 6 86 Y allo w - orang e 149 57.6 5.2 8.4 57.8 4 5.4 5 8.6 9 Table( 4): FTIR data of se ries [VI]n Com p No. Ch ara ct eristi c b ands FT IR sp ect ra (c m -1 ) νN- H νC- H alip h. νC =O ketone νC =O ami d e νC -O ethe r [VI]2 314 0 288 5 -2 96 2 173 0 166 4 123 6 [VI]3 313 8 289 0 -2 96 4 173 0 166 2 123 6 [VI]4 314 5 288 8 -2 96 4 173 0 166 4 123 6 [VI]10 314 2 288 5 -2 96 0 173 0 166 2 123 2 [VI]12 314 0 288 6 -2 96 6 173 0 166 2 123 2 IBN AL- HAITHAM J. FOR PURE & APPL. S CI. VOL. 24 (2) 2011 Fig.(1): 1 HNMR spectrum of compound [VI]2 2011) 2( 24المجلد مجلة ابن الھیثم للعلوم الصرفة والتطبیقیة - 4-ثایازولدین -3,1 -ثنائیة التعویض- 3 , 2تحضیر قواعد شف ومشتقات ون جدیدة تحتوي على وحدة البنزوثایازول جمبد هرمز توما جامعة بغداد ، ابن الهیثم –كلیة التربیة ،قسم الكیمیاء 2008كانون الثاني 21:استلم البحث في 2011 حزیران 16 :قبل البحث في الخالصة -ثایازولـدین-1,3-ثنائیـة التعـویض -3, 2تم في هذا البحث تحضیر سلسلتین جدیـدة مـن قواعـد شـف ومشـتقات الـذي تـم تحویلـه الـى [I]كلورو حـامض الخلیـك یعطـي المركـب -مركبتوبنزوثایازول مع الفا -2ان تفاعل المركب .ون -4 مـن [III]حضـر حـامض الهیدرازیـد. باسـتعمال المیثـانول المطلـق وبوجـود حـامض الكبریتیـك المركـز [II]االسـتر المقابـل n[IV]تكثیـف االسـتر المحضـر مـع الهیـدرازین المـائي ومـن ثـم مفاعلــة حـامض الهیدرازیـد النـاتج مـع االلدیهیـدات الثنائیـة - 3 , 1امــا مشــتقات . n[V] دیــدةة مــن حــامض الخلیــك الثلجــي لنحصــل علــى قواعــد شــف جیــدبوجـود قطــرات عد .مركبتو حامض الخلیك الى مجموعة االزومیثین -2نحصل علیها من اضافة ف n[VI]ون -4-ثایازولدین FTواالشعة تحت الحمراء ،د رجات االنصهار المعاثبت التركیب الكیمیائي لهذه المركبات المحضرة باست IR، لمغناطیسي وطیف الرنین النووي ا 1 HNM R بعض منها ل. ثایازولدینون ,بنزوثایازول : الكلمات المفتاحیة