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Current Organic Chemistry

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ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

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Research Article

A Novel Cu(II)-Iodine Catalyzed Hantzsch Type Synthesis of 2-Aminothiazole Derivatives

Author(s): Sankaran Radhika, Purushothaman Yamuna and Gopinathan Anilkumar*

Volume 26, Issue 19, 2022

Published on: 29 December, 2022

Page: [1779 - 1788] Pages: 10

DOI: 10.2174/1385272827666221221103955

Price: $65

Abstract

Heterocycles having nitrogen and sulphur atoms attract chief attention due to their importance in diverse fields, especially in medicinal chemistry and pharmaceutical industry. Among those, 2-aminothiazole, one of the most flexible and pervasive heterocyclic scaffolds found in many natural and synthetic products, exhibits a wide variety of biological activities. A one-pot method for the synthesis of 2-aminothiazoles through Cu(II)-iodine-catalyzed Hantzsch condensation has been achieved for the first time. This novel green methodology facilitates the formation of a broad range of 2-aminothiazole derivatives utilizing catalytic quantities of Cu(II) salts and iodine, incorporating various methyl aryl ketones and thiourea as substrates. This novel strategy involves a Hantzsch-type condensation between thiourea and in situ generated α-iodoketones, formed from the reaction of methyl aryl ketones and iodine. The present protocol reveals PEG-400 as the best solvent, which furnishes moderate to good yields of the desired 2- aminothiazole derivatives. The addition of a catalytic quantity of copper acetate ensures the continuous availability of iodine for several catalytic cycles, as copper(II) allows the oxidation of iodide to iodine. The feasibility of this novel route is studied with electron-withdrawing, electron-donating and halo-substituted derivatives of methyl aryl ketones with thiourea to confirm the functional group compatibility of the reaction. Moreover, this efficient strategy evades the direct use of noxious and lachrymatory α–halocarbonyls as reaction substrates and strong oxidants. Using a catalytic quantity of iodine in the reaction makes the separation of the desired products much easier by reducing the amount of unwanted side-products than utilizing a stoichiometric amount of iodine.

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[1]
(a) Radhakrishnan, R.; Sreejalekshmi, K.G. Computational design, synthesis and structure property evaluation of 1,3-thiazole-based color-tunable multi-heterocyclic small organic fluorophores as multifunctional molecular materials. J. Org. Chem., 2018, 83(7), 3453-3466.
[http://dx.doi.org/10.1021/acs.joc.7b02978] [PMID: 29334220];
(b) Feng, M.; Tang, B.; Liang, S.H.; Jiang, X. Sulfur containing scaffolds in drugs: Synthesis and application in medicinal chemistry. Curr. Top. Med. Chem., 2016, 16(11), 1200-1216.
[http://dx.doi.org/10.2174/1568026615666150915111741] [PMID: 26369815]
[2]
Khalil, A.; Edwards, J.A.; Rappleye, C.A.; Tjarks, W. Design, synthesis and biological evaluation of aminothiazole derivatives against the fungal pathogens Histoplasma capsulatum and Cryptococcus neoformans. Bioorg. Med. Chem., 2015, 23(3), 532-547.
[http://dx.doi.org/10.1016/j.bmc.2014.12.006] [PMID: 25543205]
[3]
Das, D.; Sikdar, P.; Bairagi, M. Recent developments of 2-aminothiazoles in medicinal chemistry. Eur. J. Med. Chem., 2016, 109, 89-98.
[http://dx.doi.org/10.1016/j.ejmech.2015.12.022] [PMID: 26771245]
[4]
Yurttas, L.; Ciftci, G.A.; Temel, H.E.; Saglik, B.N.; Demir, B.; Levent, S. Biological activity evaluation of novel 1,2,4-triazine derivatives containing thiazole/benzothiazole rings. Anticancer. Agents Med. Chem., 2017, 17(13), 1846-1853.
[PMID: 28356019]
[5]
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, 2008, 54(4), 245-259.
[http://dx.doi.org/10.1159/000142334] [PMID: 18587237]
[6]
Guay, D.R.P. Cefdinir: An advanced-generation, broad-spectrum oral cephalosporin. Clin. Ther., 2002, 24(4), 473-489.
[http://dx.doi.org/10.1016/S0149-2918(02)85125-6] [PMID: 12017394]
[7]
Obach, R.S.; Kalgutkar, A.S.; Ryder, T.F.; Walker, G.S. In vitro metabolism and covalent binding of enol-carboxamide derivatives and anti-inflammatory agents sudoxicam and meloxicam: Insights into the hepatotoxicity of sudoxicam. Chem. Res. Toxicol., 2008, 21(9), 1890-1899.
[http://dx.doi.org/10.1021/tx800185b] [PMID: 18707140]
[8]
Engelhardt, G.; Homma, D.; Schlegel, K.; Utzmann, R.; Schnitzler, C. Anti-inflammatory, analgesic, antipyretic and related properties of meloxicam, a new non-steroidal anti-inflammatory agent with favourable gastrointestinal tolerance. Inflamm. Res., 1995, 44(10), 423-433.
[http://dx.doi.org/10.1007/BF01757699] [PMID: 8564518]
[9]
Hantzsch, A.; Weber, J.H. Ueber verbindungen des thiazols (pyridins der thiophenreihe). Ber. Dtsch. Chem. Ges., 1887, 20(2), 3118-3132.
[http://dx.doi.org/10.1002/cber.188702002200]
[10]
Sultanova, R.M.; Lobov, A.N.; Shumadalova, A.V.; Meshcheryakova, S.A.; Zileeva, Z.R.; Khusnutdinova, N.S.; Vakhitov, V.A.; Vakhitova, Y.V. Synthesis of new 1,3-thiazol derivatives of maleopimaric acid as anticancer, antibacterial and antifungal agents. Nat. Prod. Res., 2021, 35(8), 1340-1348.
[http://dx.doi.org/10.1080/14786419.2019.1648459] [PMID: 31429302]
[11]
Abdelmoniem, A.M.; Abdelrahman, M.G.M.; Ghozlan, S.A.S.; Elwahy, A.H.M.; Abdelhamid, I.A. Hantzsch reaction with bis -indole-2,3-diones: Synthesis of novel bis -spirocyclic oxindole incorporating acridine, dipyrazolo[3,4- b:4′,3′- e]pyridine and pyrido[2,3- d:6,5- d’]dipyrimidine. Synth. Commun., 2021, 51(12), 1814-1824.
[http://dx.doi.org/10.1080/00397911.2021.1908564]
[12]
Kakati, P.; Singh, P.; Yadav, P.; Awasthi, S.K. Aiding the versatility of simple ammonium ionic liquids by the synthesis of bioactive 1,2,3,4-tetrahydropyrimidine, 2-aminothiazole and quinazolinone derivatives. New J. Chem., 2021, 45(15), 6724-6738.
[http://dx.doi.org/10.1039/D1NJ00280E]
[13]
Liu, G.; Pan, R.; Wei, Y.; Tao, L. The hantzsch reaction in polymer chemistry: From synthetic methods to applications. Macromol. Rapid Commun., 2021, 42(6), 2000459.
[http://dx.doi.org/10.1002/marc.202000459] [PMID: 33006198]
[14]
Wu, H.; Wang, Z.; Tao, L. The Hantzsch reaction in polymer chemistry: Synthesis and tentative application. Polym. Chem., 2017, 8(47), 7290-7296.
[http://dx.doi.org/10.1039/C7PY01718A]
[15]
Costanzo, P.; Nardi, M.; Oliverio, M. Similarity and competition between biginelli and hantzsch reactions: An opportunity for modern medicinal chemistry. Eur. J. Org. Chem., 2020, 2020(26), 3954-3964.
[http://dx.doi.org/10.1002/ejoc.201901923]
[16]
Hou, R.S.; Wanga, H-M.; Tsai, H.H.; Chen, L.C. Synthesis of 2-phenylthiazoles from α-tosyloxyketones and thiobenzamide in [Bmim][PF6] ionic liquid at ambient temperature. J. Chin. Chem. Soc. (Taipei), 2006, 53(4), 863-866.
[http://dx.doi.org/10.1002/jccs.200600114]
[17]
King, L.C.; Miller, F.M. The reaction of diazoketones with thioamide derivatives. J. Am. Chem. Soc., 1949, 71(1), 367-368.
[http://dx.doi.org/10.1021/ja01169a509] [PMID: 18108952]
[18]
Madhav, B.; Narayana Murthy, S.; Anil Kumar, B.S.P.; Ramesh, K.; Nageswar, Y.V.D. A tandem one-pot aqueous phase synthesis of thiazoles/selenazoles. Tetrahedron Lett., 2012, 53(30), 3835-3838.
[http://dx.doi.org/10.1016/j.tetlet.2012.04.097]
[19]
Donohoe, T.J.; Kabeshov, M.A.; Rathi, A.H.; Smith, I.E.D. Direct preparation of thiazoles, imidazoles, imidazopyridines and thiazolidines from alkenes. Org. Biomol. Chem., 2012, 10(5), 1093-1101.
[http://dx.doi.org/10.1039/C1OB06587D] [PMID: 22159268]
[20]
Sadashiva, M.; Rangappa, K.; Lingaraju, G.; Swaroop, T.; Vinayaka, A.; Sharath Kumar, K. An easy access to 4,5-disubstituted thiazoles via base-induced click reaction of active methylene isocyanides with methyl dithiocarboxylates. Synthesis, 2012, 44(9), 1373-1379.
[http://dx.doi.org/10.1055/s-0031-1290762]
[21]
Dodson, R.M.; King, L.C. The reaction of acetophenone with thiourea and oxidizing agents. J. Am. Chem. Soc., 1946, 68(5), 871.
[http://dx.doi.org/10.1021/ja01209a049] [PMID: 21024895]
[22]
Dodson, R.M.; King, L.C. The reaction of ketones with halogens and thiourea. J. Am. Chem. Soc., 1945, 67(12), 2242-2243.
[http://dx.doi.org/10.1021/ja01228a059] [PMID: 21005695]
[23]
(a) Safari, J.; Abedi-Jazini, Z.; Zarnegar, Z.; Sadeghi, M. Nanochitosan: A biopolymer catalytic system for the synthesis of 2-aminothiazoles. Catal. Commun., 2016, 77, 108-112.
[http://dx.doi.org/10.1016/j.catcom.2016.01.007];
(b) Safari, J.; Sadeghi, M. Nanostarch: A novel and green catalyst for synthesis of 2-aminothiazoles. Monatsh. Chem., 2017, 148(4), 745-749.
[http://dx.doi.org/10.1007/s00706-016-1805-8];
(c) Zarnegar, Z.; Shokrani, Z.; Safari, J. Asparagine functionalized Al2O3 nanoparticle as a superior heterogeneous organocatalyst in the synthesis of 2-aminothiazoles. J. Mol. Struct., 2019, 1185, 143-152.
[http://dx.doi.org/10.1016/j.molstruc.2019.02.080]
[24]
(a) Zhu, Y.P.; Yuan, J.J.; Zhao, Q.; Lian, M.; Gao, Q.H.; Liu, M.C.; Yang, Y.; Wu, A.X. I2/CuO-catalyzed tandem cyclization strategy for one-pot synthesis of substituted 2-aminothiozole from easily available aromatic ketones/α,β-unsaturated ketones and thiourea. Tetrahedron, 2012, 68(1), 173-178.
[http://dx.doi.org/10.1016/j.tet.2011.10.074];
(b) Narender, M.; Reddy, M.S.; Kumar, V.P.; Reddy, V.P.; Nageswar, Y.V.D.; Rao, K.R. Supramolecular synthesis of selenazoles using selenourea in water in the presence of β-cyclodextrin under atmospheric pressure. J. Org. Chem., 2007, 72(5), 1849-1851.
[http://dx.doi.org/10.1021/jo062421q] [PMID: 17266376]
[25]
Amal Joseph, P.J.; Priyadarshini, S. Copper-mediated C–X functionalization of aryl halides. Org. Process Res. Dev., 2017, 21(12), 1889-1924.
[http://dx.doi.org/10.1021/acs.oprd.7b00285]
[26]
(a) Thomas, A.M.; Asha, S.; Sindhu, K.S.; Anilkumar, G. A general and inexpensive protocol for the Cu-catalyzed C–S cross-coupling reaction between aryl halides and thiols. Tetrahedron Lett., 2015, 56(47), 6560-6564.
[http://dx.doi.org/10.1016/j.tetlet.2015.10.014];
(b) Saranya, S.; Radhika, S.; Anilkumar, G. Ligand- and base-free Cu-catalyzed C−N coupling of aminoquinolines with boronic acids. ChemistrySelect, 2021, 6(27), 6847-6850.
[http://dx.doi.org/10.1002/slct.202101932]
[27]
(a) Thapa, S.; Shrestha, B.; Gurung, S.K.; Giri, R. Copper-catalysed cross-coupling: An untapped potential. Org. Biomol. Chem., 2015, 13(17), 4816-4827.
[http://dx.doi.org/10.1039/C5OB00200A] [PMID: 25829351];
(b) Surry, D.S.; Buchwald, S.L. Diamine ligands in copper-catalyzed reactions. Chem. Sci., 2010, 1(1), 13-31.
[http://dx.doi.org/10.1039/c0sc00107d] [PMID: 22384310]
[28]
Ujwaldev, S.M.; Harry, N.A.; Neetha, M.; Anilkumar, G. Novel synthesis of 2‐aminothiazoles via Fe(III)‐Iodine‐catalyzed Hantzsch‐type condensation. J. Heterocycl. Chem., 2021, 58(2), 646-653.
[http://dx.doi.org/10.1002/jhet.4166]
[29]
Ma, C.; Miao, Y.; Zhao, M.; Wu, P.; Zhou, J.; Li, Z.; Xie, X.; Zhang, W. Synthesis of 2-aminothiazoles from styrene derivatives mediated by 1,3-dibromo-5,5-dimethylhydrantoin (DBH). Tetrahedron, 2018, 74(27), 3602-3607.
[http://dx.doi.org/10.1016/j.tet.2018.05.021]
[30]
Zhu, D.; Chen, J.; Xiao, H.; Liu, M.; Ding, J.; Wu, H. Efficient and expeditious synthesis of di- and trisubstituted thiazoles in PEG under catalyst-free conditions. Synth. Commun., 2009, 39(16), 2895-2906.
[http://dx.doi.org/10.1080/00397910802691874]
[31]
Potewar, T.M.; Ingale, S.A.; Srinivasan, K.V. Catalyst-free efficient synthesis of 2-aminothiazoles in water at ambient temperature. Tetrahedron, 2008, 64(22), 5019-5022.
[http://dx.doi.org/10.1016/j.tet.2008.03.082]
[32]
Gallardo-Godoy, A.; Gever, J.; Fife, K.L.; Silber, B.M.; Prusiner, S.B.; Renslo, A.R. 2-Aminothiazoles as therapeutic leads for prion diseases. J. Med. Chem., 2011, 54(4), 1010-1021.
[http://dx.doi.org/10.1021/jm101250y] [PMID: 21247166]
[33]
Singh, S.P.; Naithani, R.; Aggarwal, R.; Prakash, O. A convenient synthesis of 4-(2-furyl)-2-substituted thiazoles utilising [hydroxy(tosyloxy)iodo]] benzene. Synth. Commun., 1998, 28(13), 2371-2378.
[http://dx.doi.org/10.1080/00397919808004289]

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