Synlett, Inhaltsverzeichnis Synlett 2013; 24(12): 1573-1577DOI: 10.1055/s-0033-1339195 letter © Georg Thieme Verlag Stuttgart · New YorkMicrowave-Assisted Molybdenum-Catalyzed Reductive Cyclization of o-Nitrobenzylidene Amines to 2-Aryl-2H-indazoles Authors Institutsangaben Ahmed H. Moustafa a Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, Egypt b Bioorganische Chemie, Institut für Chemie, Universität Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany Fax: +49(711)45922951 eMail: ubeifuss@uni-hohenheim.de Chandi C. Malakar b Bioorganische Chemie, Institut für Chemie, Universität Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany Fax: +49(711)45922951 eMail: ubeifuss@uni-hohenheim.de Nayyef Aljaar b Bioorganische Chemie, Institut für Chemie, Universität Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany Fax: +49(711)45922951 eMail: ubeifuss@uni-hohenheim.de Elena Merisor b Bioorganische Chemie, Institut für Chemie, Universität Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany Fax: +49(711)45922951 eMail: ubeifuss@uni-hohenheim.de Jürgen Conrad b Bioorganische Chemie, Institut für Chemie, Universität Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany Fax: +49(711)45922951 eMail: ubeifuss@uni-hohenheim.de Uwe Beifuss* b Bioorganische Chemie, Institut für Chemie, Universität Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany Fax: +49(711)45922951 eMail: ubeifuss@uni-hohenheim.de Artikel empfehlen Abstract Artikel einzeln kaufen(opens in new window) Alle Artikel dieser Rubrik(opens in new window) Abstract The reductive cyclization of o-nitrobenzylidene amines under microwave conditions employing MoO2Cl2(dmf)2 as catalyst and Ph3P as reducing agent delivers 2-aryl-2H-indazoles with yields ranging from 61–92%. Key words Key wordscatalysis - cyclization - indazoles - molybdenum - Schiff bases Volltext Referenzen References and Notes 1a Cerecetto H, Gerpe A, González M, Arán VJ, de Ocáriz CO. Mini-Rev. Med. Chem. 2005; 5: 869 2a Schmidt A, Beutler A, Snovydovych B. Eur. J. Org. Chem. 2008; 4073 2b Stadlbauer W. Sci. Synth. 2002; 12: 227 3a Fedorov AY, Finet J.-P. Tetrahedron Lett. 1999; 40: 2747 3b Lam PY. S, Clark CG, Saubern S, Adams J, Winters MP, Chan DM. T, Combs A. Tetrahedron Lett. 1998; 39: 2941 3c Cerrada ML, Elguero J, de la Fuente J, Pardo C, Ramos M. Synth. Commun. 1993; 23: 1947 3d Seela F, Bourgeois W. Helv. Chim. Acta 1991; 74: 315 4a Sun F, Feng X, Zhao X, Huang Z.-B, Shi D.-Q. Tetrahedron 2012; 68: 3851 4b Shi D.-Q, Dou G.-L, Ni S.-N, Shi J.-W, Li X.-Y, Wang X.-S, Wu H, Ji S.-J. Synlett 2007; 2509 4c Campi EM, Habsuda J, Jackson WR, Jonasson CA. M, Mccubbin QJ. Aust. J. Chem. 1995; 48: 2023 4d Busch V, Hartman P. J. Prakt. Chem. 1895; 2: 404 4e Paal C. Ber. Dtsch. Chem. Ges. 1891; 24: 959 4f Paal C, Krecke F. Ber. Dtsch. Chem. Ges. 1890; 23: 2640 5 Frontana-Uribe BA, Moinet C. Tetrahedron 1998; 54: 3197 6a Cadogan JI. G, Cameron-Wood M, Mackie RK, Searle RJ. G. J. Chem. Soc. 1965; 4831 6b Varughese DJ, Manhas MS, Bose AK. Tetrahedron Lett. 2006; 47: 6795 7 Halland N, Nazaré M, R’kyek O, Alonso J, Urmann M, Lindenschmidt A. Angew. Chem. Int. Ed. 2009; 48: 6879 8 Song JJ, Yee NK. Org. Lett. 2000; 2: 519 9 Stokes BJ, Vogel CV, Urnezis LK, Pan M, Driver TG. Org. Lett. 2010; 12: 2884 10 Kumar MR, Park A, Park N, Lee S. Org. Lett. 2011; 13: 3542 11 Hu J, Cheng Y, Yang Y, Rao Y. Chem. Commun. 2011; 47: 10133 12 Akazome M, Kondo T, Watanabe Y. J. Org. Chem. 1994; 59: 3375 13 For a review on high-valent oxomolybdenum complexes in synthesis, see: de Noronha RG, Fernandes AC. Curr. Org. Chem. 2012; 16: 33 14 General Procedure for the Synthesis of o-Nitrobenzylidene Amines 3 o-Nitrobenzaldehyde 1 (10 mmol) and aniline 2 (10 mmol) in i-PrOH (3 mL) were placed in a round-bottomed flask and heated under reflux with magnetic stirring for 10 min. The reaction mixture was cooled to r.t., and the crystalline o-nitrobenzylidene amine 3 was isolated by filtration. The crude product was purified by crystallization from i-PrOH–EtOH = 1:1. 15a Merişor E, Conrad J, Klaiber I, Mika S, Beifuss U. Angew. Chem. Int. Ed. 2007; 46: 3353 15b Merişor E, Conrad J, Mika S, Beifuss U. Synlett 2007; 2033 15c Merişor E, Beifuss U. Tetrahedron Lett. 2007; 48: 8383 16 Malakar CC, Merişor E, Conrad J, Beifuss U. Synlett 2010; 1766 17 General Procedure for the MoO2Cl2(dmf)2-Catalyzed Reductive Cyclization of o-Nitrobenzylidene Amines 3 to 2-Aryl-2H-indazoles 4 A mixture of 3 (1 mmol), Ph3P (2.4 mmol), MoO2Cl2(dmf)2 (0.05 mmol), and toluene (3 mL) was sealed in a 10 mL septum reaction vial and irradiated with microwaves (DiscoverTM by CEM, 2450 MHz, 300 W, 150 °C, 20 bar) for 10 min. After filtration and removal of the solvent the reaction mixture was poured into H2O (50 mL) and extracted with EtOAc (3 × 30 mL). The combined organic extracts were washed with brine (30 mL). After drying over anhyd MgSO4 and concentration in vacuo the resulting residue was purified by flash chromatography on silica gel (cyclohexane–EtOAc = 20:1). Alternatively, the reaction mixture can also be purified by flash column chromatography without any workup procedure. 18 Selected Data for 2-(2,4,6-Trimethylphenyl)-2H-indazole (4d) Rf = 0.36 (cyclohexane–EtOAc = 3:1). IR (ATR): 1627, 1518, 1490, 1377, 1349, 1267, 1195, 1144, 1044, 964, 939, 851, 782, 755, 733, 671 cm–1. UV (MeCN): λmax (log ε) = 276 nm (4.08). 1H NMR (300 MHz, CDCl3): δ = 7.96 (d, 5 Ј = 1.1 Hz, 1 H, 3-H), 7.81 [dq, 4 Ј and 5 Ј ~ 1.0 Hz, 3 Ј (6-H, 7-H) = 8.7 Hz, 1 H, 7-H], 7.75 [dt, 4 Ј and 5 Ј ~ 1.0 Hz, 3 Ј (4-H, 5-H) = 8.4 Hz, 1 H, 4-H], 7.34 [ddd, 4 Ј (4-H, 6-H) = 1.2 Hz, 3 Ј (5-H, 6-H) = 6.7 Hz, 3 Ј (6-H, 7-H) = 8.8 Hz, 1 H, 6-H], 7.15 [ddd, 4 Ј (5-H, 7-H) = 0.9 Hz, 3 Ј (5-H, 6-H) = 6.6 Hz, 3 Ј (4-H, 5-H) = 8.5 Hz, 1 H, 5-H], 6.99 (br s, 2 H, 3′-H and 5′-H), 2.37 (br s, 3 H, 4′′-H), 1.95 (br s, 6 H, 2′′-H and 6′′-H). 13C NMR (75 MHz, CDCl3): δ = 149.1 (C-7a), 139.2 (C-4′), 137.3 (C-1′), 135.1 (C-2′ and C-6′), 128.7 (C-3′ and C-5′), 126.0 (C-6), 124.6 (C-3), 121.9 (C-5), 121.8 (C-3a), 120.3 (C-4), 118.0 (C-7), 21.1 (C-4′′), 17.1 (C-2′′ and C-6′′). MS (EI, 70 eV): m/z (%) = 336 (100) [M+], 221 (21), 220 (14), 28 (23). HRMS (EI): m/z calcd for C16H16N2 [M+]: 236.1314; found: 236.1334. Zusatzmaterial Zusatzmaterial Supporting Information (PDF)
