ÚÓ‘Ój�n€a@Î@Úœäñ€a@‚Ï‹»‹€@·rÓ:a@Âig@Ú‹©@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@Ü‹1a26@@ÖÜ»€a@I2@‚b«@H2013 Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 26 (2) 2013 Synthesis And Characterization Of Some 1,3,4 - Thiadiazole Derivatives Ismaeel Y. Majeed Iman F. Mustafa Muhand J. Mahmoud Dept. of Chemistry/College of Education For pure Science (Ibn Al-Haitham)/ University of Baghdad Received in :19 February 2013 , Accepted in : 19 May 2013 Abstract A series of N- benzoyl - 2 – alkyl -1- ( 2- thio – 1,3,4- thiadiazole -5- yl ) , have been synthesized from DL- α– amino acids , The methyl and sulfon thio ethers of these compounds were also prepared , representative samples of the prepared compounds were characterized from their IR- spectrum and elemental analysis . Key Words :1,3,4 – thiadiazole derivatives , thio – ethers , sulfon compounds . 220 | Chemistry ÚÓ‘Ój�n€a@Î@Úœäñ€a@‚Ï‹»‹€@·rÓ:a@Âig@Ú‹©@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@Ü‹1a26@@ÖÜ»€a@I2@‚b«@H2013 Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 26 (2) 2013 Introduction Thiadiazoles and in particular 1,3,4- thiadiazole derivatives were among the various heterocycles that received more attention during the last two decades as antimicrobial agents.[1,2] Most of the substitutions have been carried out at the 2- and 5- positions of the thiadiazole ring , these inclued , the introduction of a double bond on the thiadiazole ring is reported to have a strong antibacterial activity [ 3, 4 ] antifungal[5,6] , antimitotic [7] widely used formedicinal [8] and antihistaminic [9] , substituted thiadiazoles have been reported to display nematocidal [10] and antiinflammatory [11]. Keeping these facts in mind it was thought worth while to synthesize some new [5-(N- benzoyl - alkyl amino ) - (1,3,4- thiadiazole -2- thione] derived from N- benzoyl α – amino acids derivatives see (scheme1). Scheme – 1 – 221 | Chemistry ÚÓ‘Ój�n€a@Î@Úœäñ€a@‚Ï‹»‹€@·rÓ:a@Âig@Ú‹©@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@Ü‹1a26@@ÖÜ»€a@I2@‚b«@H2013 Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 26 (2) 2013 Experimental Melting points were determined by using " Electro thermal " melting point apparatus mettler . I.R. spectra were recorded using FTIR – 8300 fourier transforn infared spectrophototmeter schimadzu , for KBr disc . Microanalytical samples were analysed at the Ministry of Oil Laboratories , Baghdad . • N- Benzoyl α – amino acid [ I a,b,c ] This was carried out following the procedure of vogel [12] . • N- Benzoyl methylester of α – amino acid [ II a, b ,c ] A solution of sodium carbonate ( 0.01 mole ) in water was added gradually with continous stirring to N- benzoyl α – amino acid [I a,b,c ] ( 0.01 mole ) which was dissolved in dry acetone , to a stirred solution dimethyl sulfate ( 0.0l mole ) was added . The mixture was refluxed for 3hr . Evaporated under reduced pressure and extracted with ethyl acetate . A syrup was obtaind which showed one spot on T.L.C. ( ethyl acetate as a solvent system ) . • N – Benzoyl α – amino acid hydrazide [ III a,b,c ] To a stirred solution of ( 0.01 mole ) of N – benzoyl α – amino methyl ester [ II a,b,c ] in ethanol ( 10 ml ) hydrazine hydrate (0.02 mole ) was added . The mixture was refluxed for 3hr . After cooling a white crystalline solid was formed , the crude product was filtered and recrystallized from ethanol . m.p. of [III a] = 175 – 177 co ,[ III b] = 243-244 co ,[ III c]= 230-232 co yield % of [III a] 73% , [III b] 82% , [ III c] 86% • N- benzoyl α – amino acid xanthate salt : [13] [ IV a,b,c] N- benzoyl α – amino acid hydrazide [ III a,b,c ] (0.0l mole) was mixed with ( 10 ml ) ethanolic KOH solution , a clear solution was thus obtained , carbon disulphide (0.01 mole ) (5ml) was now added to it and the resulting solution was stirred for overnight at room temperature , the yellow precipitate is separated and washed with ether . m.p. of [IV a]= 140-141 co , [IV b] = 220-222 co decom . [IV c]= 190-192 decom yield %of [ IV a] 74% ,[ IV b] 67% , [IV c] 62%. • [ 5 – ( N- benzoyl - alkyl amino ) - 1,3,4 – thiadiazole -2-thione)[13] [ V a,b,c ] Xanthate salt ( 0.01 mole) was dissolved in ice cold conc . Sulphuric acid ( 10 ml ) , the resulting solution was kept at room temperature for 2hr. Stirred at intervals and then poured over crushed ice . It was stirred , diluted with water and flitered , the residue obtained was washed and recrystallized from ethanol – water . Physical properties of compounds [Va,b,c] are shown in (Table -1- ) . • [ 5- ( N – benzoyl – methyl amino) - 1,3,4 – thiadiazole –2 –thio ether ] [14] [ VI a,b,c ] . The compounds [V a,b,c ] ( 0.01 mole ) , were dissolved in dioxane ( 10 ml ) , which contained ( 0.01 mole ) potassium hydroxide , alkyl iodide ( 0.01 mole ) was added drop wise with stirring , the reactans were refluxed 1hr . and monitored by (T.L.C) . After evaporating the solvent under reduced pressure , water was added , and the crude product was extracted with ethyl acetate and dried over anhydrous sodium sulphate . Evaporation of the organic solvent gave a solid that was crystallized from ( benzene – petroleum ether 40 – 60 ) physical properties are shown in ( Table – 1 - ) . • [ 5- ( N – benzoyl –alkyl amino ) – 2- methyl sulphonyl – 1,3,4 – thiadiazole )] [ 15] [ VII a,b,c ] . The alkyl thioether [ VI a,b,c ] ( 0.01 mole ) was dissolved in 80% aqueous acetic acid ( 3 ml ) , to this solution of potassium permanganate ( 0.03 mole ) in water ( 5 ml ) , was added during a period of 0.5hr . 30% hydrogen peroxide was added in a quantity sufficient to 222 | Chemistry ÚÓ‘Ój�n€a@Î@Úœäñ€a@‚Ï‹»‹€@·rÓ:a@Âig@Ú‹©@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@Ü‹1a26@@ÖÜ»€a@I2@‚b«@H2013 Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 26 (2) 2013 discharge the colour . Work – up neutralization with sodium hydrogen carbonate soluation , extracting with ethyl acetate and evaporation of the organic solvent . Results and Discussion In the present work a series of 1,3,4 – thiadiazole derivatives were synthesized from glycine , DL – 3-5- diiodo tyrosine and DL- trptophan as outlined in ( scheme 1 ) . The key intermediates. N- benzoyl ( α- amino acid hydrazide ) [ III a,b,c ] were prepared by the reaction of methyl ester of ( N- benzoyl - α- amino acid ) [ I a,b,c ] with hydrazine . The IR spectra showed the normal secondary amide stretching of the acid hydrazide which appeared at ( 1640 – 1600 cm-1 ) as compared to stretching of the carbonyl group in the corresponding esters , which appeared at ( 1740 – 1660 cm-1 ) . Scheme – 2 – Treating the acid hydrazides [ III a,b,c ] with carbon disulphide in alkalin medium gave yellow solids ,which are characterized as N- benzoyl-α-amino acid Xanthate salt [IVa,b,c ],The IR spectra showed to stretching bands at ( 3300 – 3330 cm-1 ) which could be attributed to – NH group , and the disappearance of – NH2 bands at ( 3290 – 3275 cm-1 ) which could be due to obtain the reaction . Another characteristic bands were observed at ( 1074 – 1050 cm- 1 ) which could be due to C = S , then the bands at (1630 – 1635 cm-1 ) were obtained which could be attributed to a secondary amide ( V C=O amide I ) and abroad band was obtained at (1670 – 1640 cm-1 ) which could be attributed to the ( amide II ) . Then treated the xanthate salt [ IV a,b,c ] with Conc. sulphuric acid , to obtain 1,3,4 – thiadiazole [ V a,b,c ] . IR spectra showed stretching bands at ( 1065 – 1060 cm-1 ) , (2233-2490cm-1) which could be attributed ( C = S ) [16] , -SH stretching and the disappearance of the C=O 223 | Chemistry ÚÓ‘Ój�n€a@Î@Úœäñ€a@‚Ï‹»‹€@·rÓ:a@Âig@Ú‹©@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@Ü‹1a26@@ÖÜ»€a@I2@‚b«@H2013 Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 26 (2) 2013 hydrazide ( amid I ) indicated the reaction is obtained , and a strong stretching band appeared at ( 1485 – 1488 cm-1) which could be due to ( N – C=S )[17] stretching band in thiadiazole ring . See ( figure -1- ) Alkylation of compounds [ V a,b,c ] with alkyl iodide in basic medium see ( scheme -2- ) afforded [ 5- ( N- benzoyl alkyl amino - 1,3,4 – thiadiazole -2- thio ether ] [ VI a,b,c ] in 80% yield . NN S SH R NH O Ph + KOH Dioxane NN S SK R NH O Ph NN S S R NH O Ph + R-X SN2 NN S SR R NH O Ph Scheme (3) The mechanism f ormation of thio ether The IR spectra of these compounds showed the disappearance of the C=S and the SH stretching's at ( 1065-1060cm-1) ( 2233-2490cm-1) respectively . New bands at (1423 cm-1) and at (1303 cm -1) appeared which could be attributed to the new -S-CH3 stretching band in compound [ VI a] , then another characteristic band was observed at ( 1410 cm-1) which could be due to ( -SCH2 )(18) in compound [ VIb ] . See (figure -2-) . The sulphones [ VII a,b,c ] were prepared by oxidation of [ VI a,b,c ] with potassium permanganate and hydrogen peroxide see ( scheme -2-) . The IR spectra are characterized by the sulphone 0=S=0 absorption[18] bands at ( 1319 – 1325 cm-1) and (1155 – 1159cm-1) see ( figure -3-) . 224 | Chemistry ÚÓ‘Ój�n€a@Î@Úœäñ€a@‚Ï‹»‹€@·rÓ:a@Âig@Ú‹©@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@Ü‹1a26@@ÖÜ»€a@I2@‚b«@H2013 Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 26 (2) 2013 NN S SR R NH O Ph Scheme (4) The mechanism f ormation of sulf one KMnO4 NN S S-R R NH O Ph O O Mn O O NN S S-R R NH O Ph O O +MnO2 References 1. Asif ,M. and Asthana, Ch. ( 2010 ) Synthesized of some new subsituted – 2,4- diphenyl -5- amino 1,3,4 – thiadiazole derivatives ,Acta pharmaceutica sciencia 52 :443-451 2. Kokila ,P.; Sarju ,P. ; Rinku ,P. and Rekha, P. (2011 ) Synthesized some new and biologically [ 1,2,4] triazolo [3,4- b ] [ 1,3,4 ] thiadiazole -2- aryl thiazolidinone -4- ones ,Research Journal of chemical Sciences 1 (1) :18 – 24 3. Sharma ,V. and Sharma, K.V. ( 2006 ) Synthesis and Biological some 3,5- Diaryl -1- benzothiazolopyrazoline Derivatires , Reaction of chalcones with 2- Hydrazino benzothiazoles " , E – Journal of chemistry , 6 (2): 356 – 384 4. Lamani ,R. S.; Shelty, N.S.; Kamble ,R.R.; Khazi, I.A . ( 2009 ) Synthesized novel methylene bridged benzisoxazolylimidazo [ 2,1 b ] [ 1,3,4 ] thiadiazoles, Eur. J. Med . Chem . 44(7) :2828 – 2833 5. Elsayed Rashed, A.; Shamroukh ,A.H .; Hegab, M.I. and Awad , H.M. (2005)Synthesis of some biologically Active pyrazoles and C- Nucleosides , Acta chim , Solv. 52:429-434 . 6. Mehta ,D.S. ; Vashi , B.S.; Shah ,V.S. (1997 ) Synthesized a series of 2-Arylsulfonamido - 5- ( Benzthiazol – 2yl –thiamethyl )-1,3,4 – thiadiazoles , Asian Journal of chemistry , 9 (3) :333-335 . 7. Ghiram, D. ; Schwartz and Simiti , I. ;Faramacia , 22 (141) , ( 1974 ) chem . Abs . 82 (43274 c) ( 1975 ). 8. Siddiqui ,N.; Alam, M.S. and Ahsan, W. (2008 ) Synthesis , anticonvulsant and toxicity evalution of 2-(1H- lndol -3- yl) acetyl – N- ( substituted phenyl ) hydrazine – carbothioamides and their related heterocyclic derivatives , Acta pharm , 58 :445-454. 9. Alagarsmy , V.; Gividhar, R. and Yadar, M.R. ( 2005 ) Synthesis and HI – Antihistaminic Activity of some Novel 1- Substituted -4- ( 3 – methyl phenyl ) – 1,2,4 – triazolo [4-3-a] quinazolin -5 ( 4H) – ones " Boil , pharm , Bull 28 (8):1531-1534 10. Maver , W.; Boehner, B. and Dawes, D. Ger. Offen , (1974) , 2,418 , 363 ; 225hem.. Abs . (1975) , 82 , 31328 K . 11. Unangst , P.C.; Shrum , G. –P.; Connor , D.- T .; Dyer , R-D.; Schrier R-J. (1992) J.Med . chem , 35 :369i 225 | Chemistry ÚÓ‘Ój�n€a@Î@Úœäñ€a@‚Ï‹»‹€@·rÓ:a@Âig@Ú‹©@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@Ü‹1a26@@ÖÜ»€a@I2@‚b«@H2013 Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 26 (2) 2013 12. Vogel , I.A. (1974) Atext book of practical organic chemistry " 3rd Edit , Longman , London 439 - 584 , 13. Badger , G.M. (1961) “ The chemistry of Heterocyclic compounds “ Academic press , 1 nc , London , LTD, 183b-187c – 188. 14.Mustafa,I.F. (1997)Synthesis and characterization of some oxadiazole and triazole derivatives , Mu'tah Journal for Research and studies , 12(3) :153-165 15. House ,H.O. (1972) " Modern Synthetic reaction " , 2nd Ed . , 276 , 16. Mahmoud ,M.J.; Mustafa ,I.F. ; Ali , M.A. (1997) Synthesis of 1,3,4- oxadiazole sulphones , College of Science 1:191-196 .. 17. Copper , J.W. (1980) Spectroscopic techniques for organic chemistry, Wiley new yourk 18. Koji ,N. (1962) Infrared Absorption spectorscop , Nankodo company limited , Tokyo , 54 Fig.(1): ( compound V c) Fig. (2) :( compound VI a) 226 | Chemistry ÚÓ‘Ój�n€a@Î@Úœäñ€a@‚Ï‹»‹€@·rÓ:a@Âig@Ú‹©@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@Ü‹1a26@@ÖÜ»€a@I2@‚b«@H2013 Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 26 (2) 2013 Fig.(3): ( compound VII b) Table (1) :Physical properties of compounds [ V – VII ] a,b,c 227 | Chemistry ÚÓ‘Ój�n€a@Î@Úœäñ€a@‚Ï‹»‹€@·rÓ:a@Âig@Ú‹©@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@Ü‹1a26@@ÖÜ»€a@I2@‚b«@H2013 Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 26 (2) 2013 ) ثایودایزول وتشخیصھا 4,3,1تحضیر وتشخیص بعض مشتقات ( إسماعیل یاسین مجید إیمان فیصل مصطفى مھند جمیل محمود / جامعة بغداد )ابن الھیثم(قسم الكیمیاء / كلیة التربیة للعلوم الصرفة 2013آیار 19، قبل البحث : 2013شباط 19استلم البحث في : الخالصة یل ) -5-ثایودایزول – 4,3,1 –ثایو -2( -1-الكیل -2-بنزویل -Nتم في ھذا البحث تحضیر سلسلة من المركبات الفا حمض امیني ) وقد اجریت لھذه المركبات عملیة االلكلة بھالیدات االلكیل وتحویلھا الى مركبات الثایو اثیر ، من ( وكذلك اجریت عملیة االكسدة لمركب الثایو اثیر وتحویلھ الى مركب السلفون . وقد شخصت ھذه المركبات باستخدام مطیافیھ األشعة تحت الحمراء ، وتحلیل العناصر . .ثایو ایثرات ،مركبات السلفون ثایادایازول ،-4و3و 1مشتقات :لكلمات المفتاحیة ا 228 | Chemistry