Synthesis and Characterization of Novel 1,3-Thiazole and 2-Amino-1,3,4-Thiadiazole Derivatives

Authors

  • Mustafa Er Department of Chemistry, Karabuk University, 78050 Karabuk, Turkey
  • Ayşe Şahin Department of Chemistry, Karabuk University, 78050 Karabuk, Turkey
  • Hakan Tahtacı Department of Chemistry, Karabuk University, 78050 Karabuk, Turkey

DOI:

https://doi.org/10.20450/mjcce.2014.522

Keywords:

Thiosemicarbazone, 1, 3-thiazole, 2-amino-1, 3, 4-thiadiazole, Hantzsch reaction

Abstract

Thiosemicarbazone derivatives 3a–e were synthesized by the reaction of various aldehydes 1a–e with 4-methyl thiosemicarbazide 2 in 78% to 90% yield. Then, the thiazole moieties of the target materials 5a–e were obtained in high yields (71–93%) using the Hantzsch reaction utilizing thiosemicarbazone derivatives 3a–e with ethyl-2-chloroacetoacetic ester. The substituted nitrile derivatives 7a–e were obtained in moderate to high yield (58–84%) from the reaction of compounds 5a–e with chloroacetonitrile by the nucleophilic aliphatic substitution reaction in the presence of anhydrous potassium carbonate. Finally, substituted 2-amino-1,3,4-thiadiazole compounds 9a–e were obtained in moderate to good yields (51–62%) from the reaction of thiosemicarbazide with substituted nitrile derivatives 7a–e. As a result, compounds that all share a high disposition for biological activities were obtained. The structures of the newly synthesized compounds were confirmed by IR, 1H NMR, 13C NMR, elemental analysis, and mass spectrometric techniques.

Author Biographies

Mustafa Er, Department of Chemistry, Karabuk University, 78050 Karabuk, Turkey

Department of Chemistry, Karabuk University, 78050 Karabuk, Turkey

Ayşe Şahin, Department of Chemistry, Karabuk University, 78050 Karabuk, Turkey

Department of Chemistry, Karabuk University, 78050 Karabuk, Turkey

Hakan Tahtacı, Department of Chemistry, Karabuk University, 78050 Karabuk, Turkey

Department of Chemistry, Karabuk University, 78050 Karabuk, Turkey

References

A. K. Jain, S. Sharma, A. Vaidya, V. Ravichandran, R. K. Agrawal, 1,3,4-Thiadiazole and its derivatives: A review on recent progress in biological activities, Chem. Biol. Drug. Des., 81, 557–576 (2013).

G. Kolavi, V. Hedge, I. A. Khazi, Intramolecular amidation: Synthesis of novel imidazo[2,1-b][1,3,4]thiadiazole and imidazo[2,1-b][1,3]thiazole fused diazepinones, Tetrahedron Lett., 47, 2811–2814 (2006).

J. M. Guernon, Y. J. Wu, 3-Bromocyclohexane-1,2-dione as a useful reagent for Hantzsch synthesis of thiazoles and the synthesis of related heterocycles, Tetrahedron Lett., 52, 3633–3635 (2011).

K. D. Hargrave, F. K. Hess, J. T. Oliver, N-(4-substituted-thiazolyl)oxamic acid derivatives, a new series of potent, orally active antiallergy agents, J. Med. Chem., 26, 1158–1163 (1983).

S. Bondock, H. El-Azab, E. E. M. Kandeel, M. A. Metwally, Efficient synthesis of new functionalized 2-(hetaryl)thiazoles, Synth. Commun., 43, 59–71 (2013).

A. A. Kadi, E. S. Al-Abdullah, I. A. Shehata, E. E. Habib, T. M. Ibrahim, A. A. El-Emam, Synthesis, anti-microbial and anti-inflammatory activities of novel 5-(1-adamantyl)-1,3,4-thiadiazole derivatives, Eur. J. Med. Chem., 45, 5006–5011 (2010).

S. K. Bhati, A. Kumar, Synthesis of new substituted azetidinoyl and thiazolidinoyl-1,3,4-thiadiazino (6,5-b) indoles as promising anti-inflammatory agents, Eur. J. Med. Chem., 43, 2323–2330 (2008).

J. C. Jaen, L. D. Wise, B. W. Caprathe, H. Tecle, S. Bergmeier, C. C. Humblet, T. G. Heffner, L. T. Meltzner, T. A. Pugsley, 4-(1,2,5,6-Tetrahydro-1-alkyl-3-pyridinyl)-2-thiazolamines: A novel class of compounds with central dopamine agonist properties, J. Med. Chem., 33, 311–317 (1990).

J. Matysiak, Z. Malinski, 2-(2,4-Dihydroxyphenyl)-1,3,4-thiadiazole analogues: Antifungal activity in vitro against candida species, Russ. J. Bioorg. Chem., 33, 594–601 (2007).

A. A. Kadi, N. R. El-Brollosy, O. A. Al-Deeb, E. E. Habib, T. M. Ibrahim, A. A. El-Emam, Synthesis, anti-microbial and anti-inflammatory activities of novel 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles and 2-(1-adamantylamino)-5-substituted-1,3,4-thiadiazoles, Eur. J. Med. Chem., 42, 235–242 (2007).

S. N. Pandeya, D. Sriram, G. Nath, E. DeClerq, Synthesis, antibacterial, antifungal and anti-HIV activities of Schiff and Mannich bases derived from isatin derivatives and N-[4-(4′-chlorophenyl)thiazol-2-yl] thiosemicarbazide, Eur. J. Pharm. Sci., 9, 25–31 (1999).

N. U. Güzeldemirci, Ö. Küçükbasmacı, Synthesis and antimicrobial activity evaluation of new 1,2,4-triazoles and 1,3,4-thiadiazoles bearing imidazo[2,1-b]thiazole moiety, Eur. J. Med. Chem., 45, 63–68 (2010).

G. V. S. Kumar, Y. R. Prasad, B. P. Mallikarjuna, S. M. Chandrashekar, Synthesis and pharmacological evaluation of clubbed isopropylthiazole derived triazolothiadiazoles, triazolothiadiazines and mannich bases as potential antimicrobial and antitubercular agents, Eur. J. Med. Chem., 45, 5120–5129 (2010).

S. A. F. Rostom, I. M. El-Ashmawy, H. A. B. El Razik, M. H. Badr, H. M. A. Ashour, Design and synthesis of some thiazolyl and thiadiazolyl derivatives of antipyrine as potential non-acidic anti-inflammatory, analgesic and antimicrobial agents, Bioorg. Med. Chem., 17, 882–895 (2009).

P. Zhan, X. Liu, Z. Li, Z. Fang, Z. Li, D. Wang, C. Pannecouque, E. De Clercq, Novel 1,2,3-thiadiazole derivatives as HIV-1 NNRTIs with improved potency: Synthesis and preliminary SAR studies, Bioorg. Med. Chem., 17, 5920–5927 (2009).

N. Siddiqui, W. Ahsan, Synthesis, anticonvulsant and toxicity screening of thiazolyl-thiadiazole derivatives, Med. Chem. Res., 20, 261–268 (2011).

M. Yusuf, R. A. Khan, B. Ahmed, Syntheses and anti-depressant activity of 5-amino-1, 3, 4-thiadiazole-2-thiol imines and thiobenzyl derivatives, Bioorg. Med. Chem., 16, 8029–8034 (2008).

M. Juszczak, J. Matysiak, M. Szeliga, P. Pozarowski, A. Niewiadomy, J. Albrecht, W. Rzeski, 2-Amino-1,3,4-thiadiazole derivative (FABT) inhibits the extracellular signal-regulated kinase pathway and induces cell cycle arrest in human non-small lung carcinoma cells, Bioorg. Med. Chem. Lett., 22, 5466–5469 (2012).

K. M. Dawood, T. M. A. Eldebss, H. S. A. El-Zahabi, M. H. Yousef, P. Metz, Synthesis of some new pyrazole-based 1,3-thiazoles and 1,3,4-thiadiazoles as anticancer agents, Eur. J. Med. Chem., 70, 740–749 (2013).

S. S. Karki, K. Panjamurthy, S. Kumar, M. Nambiar, S. A. Ramareddy, K. K. Chiruvella, S. C. Raghavan, Syn-thesis and biological evaluation of novel 2-aralkyl-5-substituted-6-(4′-fluorophenyl)-imidazo[2,1-b][1,3,4]thi¬adiazole derivatives as potent anticancer agents, Eur. J. Med. Chem., 46, 2109–2116 (2011).

I. Kayagil, S. Demirayak, Synthesis and anticancer activities of some thiazole derivatives, Phosphorus, Sulfur Silicon Relat. Elem., 184, 2197–2207 (2009).

F. Karipcin, B. Dede, S. Percin-Ozkorucuklu, E. Kabalcilar, Mn(II), Co(II) and Ni(II) complexes of 4-(2-thiazolylazo)resorcinol: Syntheses, characterization, catalase-like activity, thermal and electrochemical behavior, Dyes and Pigments, 84, 14–18 (2010).

F. Clemence, O. L. Martert, F. Delevallee, J. Benzoni, A. Jouanen, S. Jouquey, M. Mouren, R. Deraedt, 4-Hydroxy-3-quinolinecarboxamides with antiarthritic and analgesic activities, J. Med. Chem., 31, 1453–1462 (1998).

J. V. Metzger, Comprehensive Heterocyclic Chemistry 1; Pergamon Press, Vol. 6, 1984, p 328.

B. B. Shingate, B. G. Hazra, D. B. Salunke, V. S. Pore, F. Shirazi, M. V. Deshpande, Stereoselective synthesis and antimicrobial activity of steroidal C-20 tertiary al-cohols with thiazole/pyridine side, J. Med. Chem., 46, 3681–3689 (2011).

G. Dede, R. Bayrak, M. Er. A. R. Özkaya, İ. Değirmen¬cioğlu, DBU-catalyzed condensation of metal free and metallophthalocyanines containing thiazole and azine moieties-synthesis, characterization and electrochemical properties, J. Organomet. Chem., 740, 70–77 (2013).

İ. Değirmencioğlu, E. Atalay, M. Er, Y. Köysal, Ş. Işık, K. Serbest, Novel phthalocyanines containing substituted salicyclic hydrazone-1,3-thiazole moieties: Microwave-assisted synthesis, spectroscopic characterization, X-ray structure and thermal characterization, Dyes and Pigments, 84, 69–78 (2009).

M. Er, Y. Ünver, K. Sancak, E. Dügdü, Synthesis and characterizations of some new tetrathiosemicarbazones and their cyclization reactions; tetra-4-methyl-5-eto¬xycarbonyl-2,3-dihydro-1,3-thiazole and tetra-2-acetyl¬amino-4-acetyl-4,5-dihydro-1,3,4-thiodiazole derivatives, Arkivoc, (xv), 99–120 (2008).

M. D. Mullican, M. W. Wilson, D. T. Connor, C. R. Konstlan, D. J. Schrier, R. D. Dyer, Design of 5-(3,5-di-tert-butyl-4-hydroxyphenyl)-l,3,4-thiadiazoles, -1,3,4-oxa¬diazoles, and -1,2,4-triazoles as orally-active, nonulcerogenic antiinflammatory agents, J. Med. Chem., 36, 1090–1099 (1993).

R. Ustabaş, U. Çoruh, K. Sancak, M. Er, Y. Ünver, M. Yavuz, 2-[2-(Cyanomethoxy) phenoxy]acetonitrile, Acta Crytallographica, Sect. E, 60, 968–970 (2004).

Downloads

Published

2014-11-24

How to Cite

Er, M., Şahin, A., & Tahtacı, H. (2014). Synthesis and Characterization of Novel 1,3-Thiazole and 2-Amino-1,3,4-Thiadiazole Derivatives. Macedonian Journal of Chemistry and Chemical Engineering, 33(2), 189–198. https://doi.org/10.20450/mjcce.2014.522

Issue

Section

Organic Chemistry