Synlett, Inhaltsverzeichnis Synlett 2014; 25(07): 965-968DOI: 10.1055/s-0033-1340959 letter © Georg Thieme Verlag Stuttgart · New York Synthesis of Thieno[2,3-d]imidazoles by Copper-Catalyzed Amidine Cyclization Kostiantyn Liubchak* a Institute of Organic Chemistry of NAS of Ukraine, Murmanska Street 5, Kyiv 02094, Ukraine c Enamine Ltd., Aleksandra Matrosova Street 23, Kyiv 01103, Ukraine Fax: +380(50)445373253 eMail: kliubchak@gmail.com , Andrey Tolmachev b Kyiv National Taras Shevchenko University, Volodymyrska Street 64, Kyiv 01601, Ukraine , Kostiantyn Nazarenko a Institute of Organic Chemistry of NAS of Ukraine, Murmanska Street 5, Kyiv 02094, Ukraine › Institutsangaben Artikel empfehlen Abstract Artikel einzeln kaufen Alle Artikel dieser Rubrik Abstract A new synthetic approach to thieno[2,3-d]imidazoles is presented on the basis of the N′-(3-halothiophen-2-yl)amidine cyclization under copper-catalyzed cross-coupling. Using commercially available starting materials such as 2-aminothiophenes or their Boc-protected derivatives and copper catalysts, this method offers a convenient route to a wide range of thieno[2,3-d]imidazole derivatives, especially the 5-alkyl-subtituted thieno[2,3-d]imidazoles. Key words Key wordsamidines - cyclization - copper - thiophenes - imidazoles Volltext Referenzen References and Notes 1a Luca LD. Curr. Med. Chem. 2006; 1: 1 1b Forte B, Malgesini B, Piutti C, Quartieri F, Scolaro A, Papeo G. Marine Drugs 2009; 7: 705 2a Toque HA. F, Priviero FB. M, Teixeira CE, Perissutti E, Fiorino F, Severino B, Frecentese F, Lorenzetti R, Baracat JS, Santagada V, Caliendo G, Antunes E, Nucci GD. J. Med. Chem. 2008; 51: 2807 2b Vernekar SK. V, Hallaq HY, Clarkson G, Lochner M, Thompson AJ, Silvestr L, Lummis SC. R. J. Med. 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Ethyl 1,6-Dimethyl-2-phenyl-1H-thieno[2,3-d]imidazole-5-carboxylate (4a): yield: 91%; mp 118–120 °C; Rf 0.38 (25% EtOAc–hexane). 1H NMR (500 MHz, CDCl3): δ = 1.37 (t, J = 9.0 Hz, 3 H, Et), 2.82 (s, 3 H, Me), 3.95 (s, 3 H, Me), 4.33 (q, J = 9.0 Hz, 2 H, Et), 7.45–7.55 (m, 3 H, 3 × CH), 7.55–7.75 (m, 2 H, 2 × CH). 13C NMR (125 MHz, CDCl3): δ = 163.4, 147.2, 137.8, 129.8, 129.3, 129.2, 128.8, 123.3, 60.7, 33.4, 14.3, 13.0. Anal. Calcd for C16H16N2O2S: C, 63.98; H, 5.37; N, 9.33. Found: C, 64.03; H, 5.15; N, 9.22. Ethyl 2-(3-Chlorophenyl)-1,6-dimethyl-1H-thieno[2,3-d]imidazole-5-carboxylate (4b): yield: 93%; mp 167–168 °C; Rf 0.40 (25% EtOAc–hexane). 1H NMR (500 MHz, CDCl3): δ = 1.38 (t, J = 7.1 Hz, 3 H, Et), 2.82 (s, 3 H, Me), 3.97 (s, 3 H, Me), 4.33 (q, J = 7.1 Hz, 2 H, Et), 7.40–7.49 (m, 2 H, 2 × CH), 7.49–7.60 (m, 1 H, CH), 7.63–7.71 (m, 1 H, CH). 13C NMR (125 MHz, CDCl3): δ = 12.3, 14.4, 30.5, 60.4, 123.9, 127.3, 129.0, 129.4, 129.8, 130.0, 131.5, 134.6, 137.8, 147.1, 154.3, 163.8. Anal. Calcd for C16H15ClN2O2S: C, 57.40; H, 4.52; N, 8.37. Found: C, 57.02; H, 4.75; N, 8.50. 1,5-Dimethyl-2-phenyl-1H-thieno[2,3-d]imidazole (13): yield: 92%; mp 110–115 °C; Rf 0.20 (25% EtOAc–hexane). 1H NMR (500 MHz, CDCl3): δ = 2.56 (s, 3 H, Me), 3.82 (s, 3 H, NMe), 6.62 (s, 1 H, CH), 7.34–7.45 (m, 1 H, CH), 7.48 (t, J = 7.8 Hz, 2 H, 2 × CH), 7.67 (d, J = 7.1 Hz, 2 H, 2 × CH). 13C NMR (125 MHz, CDCl3): δ = 17.0, 33.7, 106.8, 128.6, 128.7, 130.7, 137.9, 138.2, 141.8, 150.7. Anal. Calcd for C13H12N2S: C, 68.38; H, 5.30; N, 12.27. Found: C, 68.12; H, 5.50; N, 12.45. Zusatzmaterial Zusatzmaterial Supporting Information
