IBN AL- HAITHAM J. FOR PURE & APPL. SCI. 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 Department of Chemistry , College of Education Ibn Al- Haitham University of Baghdad Received in : 21 January 2008 Accepted in : 16 June 2011 Abstract Two series of Schiff Bases and 2,3-disubstituted-1,3-thiazolidin-4-one derivatives were synthesized . Reaction of 2-mercaptobenzothiazole with α-chloro acetic acid gave compound[I]. Esterification of carboxylic moity of compound [I] , using absolute methanol in the presence of conc . H2SO4 yielded acorresebonding ester [II] , wich was condensation with hydrazine hydrate to give acid hydrazide [III] . The new Schiff bases [V]n were synthesized by reaction of acid hydrizide with dialdehyde [IV]n in the presence of glacial acetic acid . The thiazolidinone derivatives [VI]n have been obtained from the azomethines through the addition of thioglycolic acid . Their chemical structures have been confirmed by melting points , FTIR and 1 HNMR (of some of them) . Benzothiazole , thiazolidinone. Introduction Thiazolidin-4-one derivatives have attracted a great deal of interest due to their antibacterial [1-3] , anti-infammatory[4] , fungicidal activity [5], Antifeedant activity, Acaricidal activity, Contact toxicity , and Stomach toxicity [6]. Over views of their synthesis , properties reactions and applications have been published [7,8] . Benzothiazole derivatives have been reported to have broad range of biological activities [9-11] . IBN AL- HAITHAM J. FOR PURE & APPL. SCI. VOL.24 (2) 2011 These findings focused particular interest on incorporating thiazolidinone and 2- mercaptobenzothiazole in one framework , which could be useful for biological and pharmacological screening. Experimental Materials : Most of chemicals used were supplied from Fluka , Merck and BDH Chemicals Co. and used as received . Techniques: Uncorrected melting points were determined by using Hot-Stage, Gallen Kamp melting point apparatus. FTIR spectra in the range 500-4000cm -1 were obtained by using potassium bromide discs on FTIR instrument Model 8000 Shimadzu Spectrophotometer, Japan . 1HNMR spectra were taken on company : Bruker , model: ultra shield 300 MHz Spectrophotometer using DMSO as a solvent with TMS as an internal standard and elemental 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-Mercapto acetic acid benzothiazole [I] To a stirred mixture of -chloro acetic acid (0.01mol) and 10% aqueous sodium hydroxide (10 mL), a solution of 2-mercaptobenzothiazole (0.01mol) in 10% aqueous solution of sodium hydroxide( 10 mL) was added . The mixture was refluxed for three hours. After cooling, the solution was acidified with concentrated hydrochloric acid. The precipitate was filtered and recrystallized from ethanol [12] to y ield 90%, m.p=155 o C. 2-(methylthioacetate) benzothiazole ester[II] : was prepared following the procedure described by A. Vogel [13]. 2-(thioacetyl hydrazide) benzothiazole [III] This compound was prepared according to references [14 ] . Polymethylene-α,ω-bis-4-oxybenzaldehyde [IV]n In a 100 mL flask ,4-Hydroxybenzaldehyde (2.44gm , 0.02 mol) was dissolved in 15mL of DM F. Anhydrous sodium carbonate ( 0.025mol) and (0.01mol) of the appropriate α,ω –dibromo or dichloro alkane were added to the reaction flask . The stirred mixture was refluxed for 4hrs , allowed to cool , and then poured into 400 mL of cold water , cooled at 5 o C overnight , and then filtered , washed well with water , dried in air , recrystalized from ethanol(15), yield 88-98% . IBN AL- HAITHAM J. FOR PURE & APPL. SCI. VOL.24 (2) 2011 N SH S ClCH2COOH [I] N S SCH2COOH N S SCH2CONHNH2 [III] [V]n N S SCH2CONHN HC N S [II] N S SCH2COOMe [VI] n N S SCH2CONH N S N S N S O HNCOCH2S O HC O O CH HSCH2CO2H [IV] n O(CH2)nO CH NHNCOCH2S O(CH2)nO NH2NH2.H2 O MeOH H2SO4 10%N aOH 2 glacial acetic acid O(C H2)nO n=2-4 , 10, 12 Scheme 1 α,ω-bis-[(2-thioacetylhydrazidebenzothiazole-2-yl)benzylidene-4-oxy]alkane [V]n A mixture of compound[III] (0.02mmol) , dialdehyde [VI]n=2 (0.01mmol) , three drops of glacial acetic acid and absolute ethanol (10mL) was refluxed for 4 hours. The reaction mixture was concentrated , cooled and the formed precipitate was filtered off , dried and then recrystallized using chloroform to give pale yellow [16], Yield (80%) , m.p=210 oC. Likewise other compounds [V] with n=3,4,10,12 (were prepared in a same way using dialdehyde [IV]n with different n=3,4,10,12) .Characterization data are presented in table 1. Polymethylene-α,ω-bis-[N-(2-thioacetylhydrazinebenzothiazole) -4-oxo-1,3-thiazolidin-2-(p- oxybenzene)] [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. SCI. VOL.24 (2) 2011 neutralized with cold dilute sodium bicarbonate solution , the formed product was filtered off and recrystallized from acetone to yield 70% , m.p=188-190 o C. Likewise other compounds [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-mercaptobenzothiazole and -chloroacetic acid in alkali media was used to prepare the compound [I]. The -halogroup in -chloroacetic acid is good leaving group and sulfur compounds are a good nucleophile. Thus, the reaction is a typical of the nucleophilic substitution reaction of the thiol group , where the -halo group could be replaced easily in this reaction to get good yield[17]. The mechanism of this reaction may be outlined as follows, Scheme (2). N SH S Cl CH 2CO OH NaOH NaClSCH2COOH N S N S + S Na + + + Schem 2 H2O The structure of this compound [I] was studied by its melting point 155 oC and FTIR spectrum , which showed broad band at 2750-3390cm-1 due to νO-H group , sharp peak at 1690 cm-1 assigned to carbonyl group of carboxylic moity and the aliphatic C-H stretching at 2950 cm-1 . also showed significant bands in the region (3060 , 1575 , 1454 and 750) cm-1 that indicated the presence of benzothiazole moiety . 2-(Methylthioacetate) benzothiazole[II] was obtained by esterification of the carboxylic acid moity of compound [I] using absolute methanol with conc. H2SO4 was identified by FTIR spectrum . FTIR spectrum showed disappearance of two peaks of νOH and νC=O of carboxylic moiety of compound [I] together with the appearance of good peak at 1705 cm -1 which could be attributed to νC=O of ester group. Condensation of ester [II] with hydrazine hydrate yielded the 2-(thioacetyl hydrazide)benzothiazole [III] which is characterized by its melting points 120oC . FTIR spectra , showed the following absorption bands: νC=O of amide group at 1645 cm-1, bands in the regions (3460, 3282, 3197) cm-1 due to asymmetric and symmetric stretching vibration of NH , NH2 groups , respectively. The spectra showed band at 2928 cm-1 assignable to the stretching of aliphatic (C-H). IBN AL- HAITHAM J. FOR PURE & APPL. SCI. VOL.24 (2) 2011 The Schiff bases of series [V]n were prepared by refluxing of compound [III]n with dialdehyde [IV]n (which are obtained from the reaction of 4-hydroxybenzaldehyde with α,ω- dibromo or dichloro alkane using DM F as the solvent in Na2CO3 medium) in glacial acetic acid as a catalyst. These compounds series [V]n are characterized by FTIR and 1 HNMR spectroscopy . FTIR spectra showed the disappearance of two absorption bands due to NH2 stretching of compound [III] together with the appearance of a band at (1614-1616) cm-1 assignable to imine group (CH=N) . The spectra also shows the bands at (2840-2954) cm-1 is due to aliphatic C-H stretching . Table 2 exhibited the characteristic FTIR absorption bands of these compounds 1HNMR spectrum of compound [V]n=2 (DM SO as a solvent) showed single broad peak at  9.15 ppm that could be attributed to the two protons of NH , a multiplet signal at  7.0- 7.55 ppm for eight aromatic protons of the phenyl rings of benzothiazole moiety and a doublet of doublets at  7.8-8.25 ppm for eight aromatic protons of two benzene rings . The imine protons appeared at  4.92 ppm . The 1HNMR spectrum also showed the a singlet at  4.65 ppm assigned for four protons of the mercapto methylene groups to (SCH2) and triplet signal between  3.80-3.92 ppm that could be assigned to the four protons of methylene group (O-CH2) 2,3-Disubstituted-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. SCI. VOL.24 (2) 2011 N S SCH2CONHN HC N S N S SCH2CONH N S N S N S HNC OCH 2S O Ar = O O N S SCH2CONHN HC N S SH CH2 HS OHHO O O CH2 C C N S SCH2CONHN HC N S S CH2 S OH2H2O O OCH2 C C HO C CH2SH HSCH2 C OH CH NHNCOCH2S -2H2O CH NHN COCH 2S CH NHN COCH2S O Ar Ar Ar Ar [V]n O(CH2)nO [VI]n Scheme 3 The structural assignments of these compounds [VI]n was based on spectral data FTIR and 1HNMR spectroscopy . The FTIR exhibited significant bands at 3210 cm-1 and 1730 cm-1 which could be attributed to NH stretching and C=O stretching of thiazolidinone ring , respectively . Besides this , a band about 1660 cm-1 is due to C=O (amide) stretching and disappearance of absorption stretching band due to imine group . Table 4 exhibited the characteristic FTIR absorption bands of these compounds. 1 HNMR spectrum of compound [VI]n=2 , figure (1) showed the following characteristics chemical shifts (DM SO as a solvent) singlet at  11.5 ppm could be attributed to the two protons of NH groups , a multiplet signal at  7.05-7.5 ppm for eight aromatic protons of the phenyl rings of benzothiazole moiety and a doublet of doublets at  7.65-8.2 ppm for eight aromatic protons of two benzene rings . A sharp singlet was abserved at  4.80 ppm that could be assingned to the four protons of the mercapto methylene groups (SCH2) . A singlet signal appeared at  4.65 ppm for four protons of H-5 thiazolidinone . The triplet signal observed between  4.2-4.49 ppm was assinged to four protons of methylene group (O-CH2) showed singlet signal at  6.66 ppm that could be attributed to the two protons of H-2 thiazolidinone (2). IBN AL- HAITHAM J. FOR PURE & APPL. SCI. VOL.24 (2) 2011 References 1- El-M asry ,A. H.; Fahmy ,H. H. and Ali Abdalwahed, S. H. (2000) “ Synthesis and Antimicrobial Activity of Some New Benzimidazole Derivatives ” , Molecules 5:1429- 1438 . 2- Kohli ,P.; Srivastava ,S. D. and Srivastava ,S. K. (2007) “ Synthesis and Biological Activity of Mercaptobenzimidazole Based Thiazolidinons and their Acrylidenes” J . of the Chinese Chemical Society , 54 :1003-1010. 3- Abod Elhafez ,O. M.; El Kharsy ,E. A.; Badria ,F. and Fathy, A. E. (2003) “ Synthesis and Biological Investigation of New Thiazolidinone and Oxadiazoline Coumarin Derivatives” ,Arch Pham Res. , 26(8):686-696. 4- Vazzana , I.E. ;Terranova , F.; M attioli and F. Sp aratore (2004) “ Aromatic Schiff Bases and 2,3-Disubstituted 1,3-Thiazolidin-4-one Derivatives as Anti-inflammatory agents” ,ARKIVOC , V , 364-374. 5- Ling Liu ,H.; Li ,Z. and Anthonsen ,T . (2000) “ Synthesis and Fungicidal Activity 2- Imino-3(4-Ary lthiazole-2-yl) Thiazoliden-4-ones and their Acrylidene Derivatives” ,Molecules, 5 :1055-1061. 6- Pareek,D. ; Chaudhary , M.; Pareek , P. K. ; Kant, R.; Ojha , K. G. ; Pareeka, R. and Pareeka, A. (2011) “ Synthesis and biological evaluation of 4-thiazolidinone derivatives incorporating benzothiazole moiety”, Der Pharmacia Sinica , 2 (1): 170-181 . 7- Brown ,F. C. (1961) “ Thiazolidin-4-ones” . Chem. Revs. 61 :463-521. 8- Newcome, G. R. and Nayak, A. (1961), “Thiazolidin-4-ones ”. adv. Heterocycl. Chem. 25 : 83-112. 9- Ali , E. ; Tomma , J. and Mubbrik, S . (2008) “ Synthesis of Study The Biological Activity of Some Schiff-Bases Derived from 2-Aminobenzothiazole and Vanillin Derivatives ” , Ibn Al-Haitham Journal for Pure and Applied Sciences , 21(1):73-80. 10- Argyropoulou , I. ; Geronikaki, A.; Vicini,b. P. and Zanib, F. (2009) “Synthesis and biological evaluation 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 Kumar ,(2010), “Synthesis, Characterization and Biological Activity of Various Substituted Benzothiazole Derivatives” Digest Journal of Nanomaterials and Biostructures , 5(1): 67 - 76 12- Tomma, J. H.; Rouil, I. H. and AL-Dujaili ,A. H. (2009) “ ٍ◌Synthesis and Mesomorphic Behavior of Some Novel Compounds Containing 1,3,4-Thiadiazole and 1,2,4-triazole Rings ” , Mol. Cryst. Liq. Cryst. , 501 :3-19. IBN AL- HAITHAM J. FOR PURE & APPL. SCI. VOL.24 (2) 2011 13- Vogel , I. (1974) “A text Book Of Pract ical Organic Chemistry ” , Longman Group Ltd., London 3rd Ed.m , 781. 14- Smith, P. A. (1946) “ Organic Reactions” 3(9) : 366. 15- Griffin , A. and Havens, S. (1981) “ Mesogenic Polymers . III . Thermal Properties and Synthesis of Three Homologus Series of Thermotropic Liquid Crystalline “Backbone”Polyesters” , J. of Polym. Sci. Polymer Physics Edition , 19: 951-969. 16- Tomma , J. H. (2010) “ Synthesis , Characterization and Study The Liquid Crystalline Properties of N-Acyl , Thiourea and Imidazole Derivatrives” , Ibn Al-Haitham J. for Pure and Appl. Sci., 23(3):134-151. 17- March, J. (1992) “Advanced Organic Chemistry Reaction Mechanism and Structure” , 4th. Ed., Wiley and Sons. Inc. New-York . Table (1):Physi cal an d C.H.N da ta of S chiff bases [V]n. Com p No. Mol ecul ar Formul a Yiel ds % Color M.P 0 C Theoriti cal Calc. C% H% N% C% H% N% [V]2 C34H28N6S4O4 80 Pal e yallow 210 [V]3 C35H30N6S4O4 82 yallow 175 57.8 5 4.13 2 11.5 7 57.8 2 4.05 11.8 2 [V]4 C36H32N6S4O4 85 yallow 202 [V]10 C42H44N6S4O4 80 Pal e yallow 198 61.1 6 5.33 10.1 9 61.2 5 5.68 10.4 9 [V]12 C44H48N6S4O4 84 Pal e yallow 184- 186 61.9 7 5.63 9.85 61.8 8 5.85 9.96 IBN AL- HAITHAM J. FOR PURE & APPL. SCI. VOL.24 (2) 2011 Table (2): FTIR data of S chiff bases [V]n Co mp No. Ch a ract eri st ic ban ds FT I R sp ect ra ( cm-1) νN-H νC- H al iph. νC= O amide νC= N imine νC-O e the r [ V]2 3211 2883-2932 1662 1614 1244 [ V]3 3210 2885-2930 1660 1614 1242 [ V]4 3210 2882-2932 1662 1614 1242 [ V]10 3208 2885-2932 1662 1616 1242 [ V]12 3208 2885-2930 1660 1616 1244 Table (3): physical and C.H.N data of series [VI]n Com p. No. Mol ecul ar Formul a Yie ld % Color M.P 0C Theoriti cal Calc. C% H% N% C% H % N% [VI]2 C38H32N6S6O 6 70 Yallow- orange 188-190 53.0 2 3.72 9.76 53.2 4 3.6 6 9.8 2 [VI]3 C39H32N6S6O 6 75 yallow 165 [VI]4 C40H36N6S6O 6 82 orange 176 54.0 5 4.05 9.45 54.1 4 4.4 5 9.8 9 [VI]10 C46H48N6S6O 6 85 yallow 154-156 [VI]12 C48H52N6S6O 6 86 Yallow- orange 149 57.6 5.2 8.4 57.8 4 5.4 5 8.6 9 Table( 4): FTIR data of series [VI]n Com p No. Ch aracteristi c bands FT IR spectra (cm -1 ) νN-H νC-H aliph. νC=O ketone νC=O amide νC-O ether [VI]2 3140 2885-2962 1730 1664 1236 [VI]3 3138 2890-2964 1730 1662 1236 [VI]4 3145 2888-2964 1730 1664 1236 [VI]10 3142 2885-2960 1730 1662 1232 [VI]12 3140 2886-2966 1730 1662 1232 IBN AL- HAITHAM J. FOR PURE & APPL. SCI. 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 ـة حـامض الهیدرازیـد النـاتج مـع االلدیهیـدات الثنائیـة n[IV]تكثیـف االسـتر المحضـر مـع الهیـدرازین المـائي ومـن ثـم مفاعلـ - 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 ،FTIRواالشعة تحت الحمراء ،د رجات االنصهار المعاثبت التركیب الكیمیائي لهذه المركبات المحضرة باست .بعض منها ل 1HNMRلمغناطیسي وطیف الرنین النووي ا ثایازولدینون ,بنزوثایازول : الكلمات المفتاحیة