Synthesis of 4-Arylidene-2-Alkylthio-4H-Thiazol-5-Ones from Aminoacid Based Dithiocarbamates and Aldehydes

Document Type : Research Article


1 Department of Chemistry, Kharazmi University, Tehran, I.R. IRAN

2 Chemistry Department, Gilan University, Rasht, I.R. IRAN


Heterocyclic compounds containing two heteroatoms in the structure are well known molecules with diverse biologically activities. Among them, thiazoles, thiazolidines, thiazolidinones and thiazolones are the most important scaffolds associated in the structure of many naturally occurring biological active compounds. A simple and efficient procedure for the synthesis of 4-arylidene-2-alkylthio-4H-thiazol-5-ones, the thia analogue of azlactones, via the condensation reaction of an aldehyde with an amino acid based dithiocarbamate is described. Also the bis [2-(alkylthio)-thioazlactone] was prepared using terephthaldehyde. High to excellent yields of products, simple reaction procedure and synthesis of complex molecules with simple starting materials are the most advantages of this protocol.


Main Subjects

[1] Kalkhambkar R.G., Kulkarni G.M., Shivkumar H.,Rao R.N., Synthesis of Novel Triheterocyclic Thiazoles as Anti-Inflammatory and Analgesic Agents, Eur. J. Med. Chem., 42: 1272-1276 (2007).
[2] Yang B.V., Weinstein D.S., Doweyko L.M., Gong H., Vaccaro W., Huynh T., Xiao H.-Y., Doweyko A. M., McKay L., Holloway D. A., Somerville J. E., Habte S., Cunningham M., McMahon M., Townsend R., Shuster D., Dodd J. H., Nadler S. G., Barrish J. C., Dimethyl-Diphenyl-Propanamide Derivatives as Nonsteroidal Dissociated Glucocorticoid Receptor Agonists, J. Med. Chem., 53: 8241-8251 (2010).
[3] Andreani A., Burnelli S., Granaiola M., Leoni A., Locatelli A., Morigi R., Rambaldi M., Varoli L., Calonghi N., Cappadone C., Farruggia G., Zini M., Stefanelli C., Masotti L., Radin N. S., Shoemaker R. H., New Antitumor Imidazo[2,1-b]Thiazole Guanylhydrazones and Analogues, J. Med. Chem.,51: 809-816 (2008).
[4] Andreani A., Granaiola M., Leoni A., Locatelli A., Morigi R., Rambaldi M., Garaliene V., Welsh W., Arora S., Farruggia G., Masotti L., Antitumor Activity of New Substituted 3-(5-Imidazo[2,1-b]Thiazolylmethylene)-2-Indolinones and Sstudy of their Effect on the Cell Cycle, J. Med. Chem., 48: 5604-5607 (2005).
[5] Liu X., Deng L., Song H., Jia H., Wang R., Asymmetric aza-Mannich Addition: Synthesis of Modified Chiral 2-(Ethylthio)-Thiazolone Derivatives with Anticancer Potency, Org. Lett.,13: 1494-1497 (2011).
[6] Crute J. J., Grygon C. A., Hargrave K. D., Simoneau B., Faucher A.-M., Bolger G., Kibler P., Liuzzi M., Cordingley M. G., Herpes Simplex Virus Helicase-Primase Inhibitors are Active in Animal Models of Human Disease, Nat. Med., 8: 386-391 (2002).
[7] Borelli C., Schaller M., Niewerth M., Nocker K., Baasner B., Berg D., Tiemann R., Tietjen K., Fugmann B., Lang-Fugmann S., Korting H. C., Modes of Action of the New Arylguanidine Abafungin Beyond Interference with Ergosterol Biosynthesis and in Vitro Activity Against Medically Important Fungi, Chemotherapy, 54: 245-259 (2008).
[8] Gallardo-Godoy A., Gever J., Fife K. L., Silber B. M., Prusiner S. B., Renslo A. R. 
2-Aminothiazoles as Therapeutic Leads for Prion Dseases, J. Med. Chem., 54: 1010-1021 (2011).
[9] Andreani A., Rambaldi M., Leoni A., Locatelli A., Andreani F., Gehret J. C., Synthesis of Imidazo[2,1-b]Thiazoles as Herbicides, Pharm. Acta Helv., 71:247-252 (1996).
[10] Troutman H. D., Long L. M., The Synthesis of 2,3-Disubstituted-4-Thiazolidones, J. Am. Chem. Soc., 70:3436-3439 (1948).
[13] قاسمی، محمدهادی؛ مفتاح، سکینه؛ سنتز سولفاتیازول در شرایط ملایم، نشریه شیمی و مهندسی شیمی ایران، (4)30: 97 تا 103 (1390).
[14] Diosdado S., Etxabe J., Izquierdo J., Landa A., Mielgo A., Olaizola I., Lópezm R., Palomo C., Catalytic Enantioselective Synthesis of Tertiary Thiols from 5H-Thiazol-4-Ones and Nitroolefins: Bifunctional Ureidopeptide-Based Brønsted Base Catalysis, Angew. Chem. Int. Ed., 52:11846-11851 (2013).
[16] Arenal I., Bernabe M., Cuevas O., Fernandez-Alvarez E., Reaction of 5(4h)-Thiazolones with Diazomethane, Tetrahedron, 39: 1387-1393 (1983).
[17] Mosey R. A., Fisk J. S., Tepe J. J., Stereoselective Syntheses of Quaternary Substituted α-Amino Acids Using Oxazol-5-(4H)-Ones, Tetrahedron: Asymmetry, 19: 2755-2762 (2008).
[18] Alba A. N. R., Rios R., Oxazolones in Organocatalysis, New Tricks for an Old Reagent, Chem. Asian J., 6: 720-734 (2011).
[20] Sun W., Zhu G., Wu C., Li G., Hong L., Wang R., Organocatalytic Diastereo- and Enantioselective 1,3-Dipolar Cycloaddition of Azlactones and Methyleneindolinones, Angew. Chem. Int. Ed., 52: 8633-8637 (2013).
[22] Paponov B. V., Lvov S. V., Ichetovkina E. V., Panasenko I. A., Stepanian S. J., Ultrasound-Assisted Synthesis of Azlactone and Its Reactions with Nucleophiles, Mendeleev Commun., 22: 273-274 (2012).
[23] Fisk J. S., Mosey R. A., Tepe J. J., The Diverse Chemistry of Oxazol-5-(4H)-Ones, Chem. Soc. Rev., 36: 1432-1440 (2007).
[24] Salami-Ranjbaran E., Khosropour A. R., Mohammadpoor-Baltork I., A Domino Approach for the Synthesis of Naphtho[2,1-b]Furan-2(1H)-Ones from Azlactones, Tetrahedron, 70: 9268-9273 (2014).
[25] Badshah A., Khan N. H., Kidwai A. R., Catalytic Reduction of Azlactones in Alkaline Media. Synthesis of Amino Acids, J. Org. Chem., 37: 2916-2918 (1972).
[26] Ghabraei E., Moghimi M., Balalaie S., Bararjanian M., Rominger F., Bijanzadeh H. R., Efficient Synthesis of Functionalaized Dithiocarbamate Derivatives Through One-Pot Three-component Reaction and Evaluation of Their Antimicrobial Activities, J. Iran. Chem. Soc., 10: 725-732 (2013).
[27] Greene T.W., Wuts P.G.M., "Protecting Groups in Organic synthesis", 3rd ed., Wiley Interscience, New York (1999) [484].
[28] Ziyaei-Halimehjani A., Porshojaei Y., Saidi M. R., Highly Efficient and Catalyst-Free Synthesis of Unsymmetrical Thioureas Under Solvent-Free Conditions, Tetrahedron Lett., 50: 32-34 (2009).
[29] Maddani M., Prabhu K. R., A Convenient Method for the Synthesis of Substituted Thioureas, Tetrahedron Lett., 48: 7151-7154 (2007).
[31] Ziyaei-Halimehjani A., Maleki H., Saidi M. R., Regiospecific Iodocyclization of S-Allyl Dithiocarbamates: Synthesis of 2-Imino-1,3-Dithiolane and 2-Iminium-1,3-Dithiolane Derivatives, Tetrahedron Lett., 50: 2747-2749 (2009).
[32] Jamir L., Sinha U. B., Nath J., Patel B. K., Environmentally Benign One-Pot Synthesis of Cyanamides from Dithiocarbamates Using I2 and H2O2, Synth. Commun., 42: 951-958 (2012).
[34] Zhang D., Chen J., Liang Y., Zhou H., Facile Synthesis of Novel Ionic Liquids Containing Dithiocarbamate, Synth. Commun., 35: 521-526 (2005).
[35] Kumar K. N., Sreeramamurthy K., Palle S., Mukkanti K., Das P., Dithiocarbamate and DBU-Promoted Amide Bond Formation Under Microwave Condition, Tetrahedron Lett., 51: 899-902 (2010).
[36] Saha A., Baig R. B. N., Leazer J., Varma R. S., A Modular Synthesis of Dithiocarbamate Pendant Unnatural α-Amino Acids, Chem. Commun., 48: 8889-8891 (2012).
[37] Chen W., Shao J., Hu M., Yu W., Giulianotti M. A., Houghten R. A., Yu Y., A Traceless Approach to Amide and Peptide Construction from Thioacids and Dithiocarbamate-Terminal Amines, Chem. Sci., 4: 970-976 (2013).
[38] Ziyaei Halimehjani A., Ranjbari M. A., Pasha Zanussi H., Synthesis of a New Series of Dithiocarbamate-Linked Peptidomimetics and Their Application in Ugi Reactions, RSC Adv., 3: 22904-22908 (2013).
[39] Kiran Kumar S.T.V.S., Kumar L., Sharma V.L., Jain A., Jain R.K., Maikhuri J.P., Kumar M., Shukla P.K., Gupta G., Carbodithioic Acid Esters of Fluoxetine, a Novel Class of Dual-Function Spermicides, Eur. J. Med. Chem.,43: 2247-2256 (2008).
[40] Kumar L., Lal N., Kumar V., Sarswat A., Jangir S., Bala V., Kumar L., Kushwaha B., Pandey A.K., Siddiqi M. I., Shukla P. K., Maikhuri J. P., Gupta G., Sharma V. L., Azole–Carbodithioate Hybrids as Vaginal Anti-Candida Contraceptive Agents: Design, Synthesis and Docking Studies, Eur. J. Med. Chem.,70: 68-77 (2013).
[41] Ates O., Kocabalkanli A., Cesur N., Otuk G., Synthesis and Antimicrobial Activity of some
5-Aryl-2-[(N,N-Disubstituted Thiocarbamoylthio)Acylamino]-1,3,4-Oxadiazoles
, Il Farmaco, 53: 541-544 (1998).
[43] Ziyaei Halimehjani A., Hajiloo Shayegan M., Hashemi M. M., Notash B., Investigation of the Reaction of Dithiocarbamic Acid Salts with Aromatic Aldehydes, Org. Lett., 14: 3838-3841 (2012).
[44] Ziyaei Halimehjani A., Marjani K., Ashouri A., Synthesis of Dithiocarbamate by Markovnikov Addition Reaction in Aqueous Medium, Green Chem., 12: 1306-1310 (2010).
[45] Aryanasab F., Ziyaei Halimehjani A., Saidi M. R., Dithiocarbamate as an Efficient Intermediate for the Synthesis of 2-Amino-1,3,4-Thiadiazoles in Water, Tetrahedron Lett., 51: 790-792 (2010).
[46] Ziyaei Halimehjani A., Marjani K., Ashouri A., A One-Pot, Three-Component Synthesis of Thiazolidine-2-Thiones, Tetrahedron Lett., 53: 3490-3492 (2012).
[47] Ziyaei Halimehjani A., Pasha Zanussi H., Ranjbari M. A., Regiospecific Synthesis of Dithiocarbamates via Markovnikov Addition Reaction Under Solvent-Free Conditions, Synthesis, 45: 1483-1488 (2013).