Convenient and Clean Synthesis of Isatins by Metal-Free Oxidation of Oxindoles

Abstract

A metal-free synthesis of isatins was achieved through the oxidative reactions of oxindoles with molecular oxygen in the presence of tert-butyl nitrite as an additive. This strategy provides a convenient and simple synthetic route to the construction of C=O bonds without the need for any catalyst or base. The attractive features of this reaction include its convenient procedure and mild reaction conditions.

Key words

oxidation - oxindoles - butyl nitrite - isatins - metal-free synthesis

• References

• 1a Popp PD. Adv. Heterocycl. Chem. 1975; 18: 1
• 1b da Silva JF. M. Garden SJ. Pinto AC. J. Braz. Chem. Soc. 2001; 12: 273
• 2a Yoshikawa M. Murakami T. Kishi A. Sakurama T. Matsuda H. Nomura M. Matsuda H. Kubo M. Chem. Pharm. Bull. 1998; 46: 886
• 2b Gil-Turners MS. Hay ME. Fenical W. Science 1989; 246: 116
• 2c Itoh J. Han SB. Krische MJ. Angew. Chem. Int. Ed. 2009; 48: 6313
• 2d Franz AK. Dreyfuss PD. Schreiber SL. J. Am. Chem. Soc. 2007; 129: 1020
• 3a Pinto AC. Moreira Lapis AA. Vasconcellos da Silva B. Bastos RS. Dupont J. Neto BA. D. Tetrahedron Lett. 2008; 49: 5639
• 3b Rewcastle GW. Sutherland HS. Weir CA. Blackburn AG. Denny WA. Tetrahedron Lett. 2005; 46: 8719
• 3c Zhao P.-B. Zhao B.-B. Li Y. Gao W.-T. Youji Huaxue 2014; 34: 126
• 4a Stollé R. J. Prakt. Chem. 1922; 105: 137
• 4b Bryant III WM. Huhn GF. Jensen JH. Pierce ME. Stammbach C. Synth. Commun. 1993; 23: 1617
• 5a Martinet J. C. R. Hebd. Seances Acad. Sci. 1918; 166: 851
• 5b Hewawasam P. Meanwell NA. Tetrahedron Lett. 1994; 35: 7303
• 6a Lyons TW. Sanford MS. Chem. Rev. 2010; 110: 1147
• 6b Li C.-J. Acc. Chem. Res. 2009; 42: 335
• 6c Zhang C. Tang C. Jiao N. Chem. Soc. Rev. 2012; 41: 3464
• 6d Shi Z. Zhang C. Tang C. Jiao N. Chem. Soc. Rev. 2012; 41: 3381
• 7 Yu J.-W. Mao S. Wang Y.-Q. Tetrahedron Lett. 2015; 56: 1575
• 8 Prathima PS. Bikshapathi R. Rao VJ. Tetrahedron Lett. 2015; 56: 6385
• 9a Ma J. Hu Z. Li M. Zhao W. Hu X. Mo W. Hu B. Sun N. Shen Z. Tetrahedron 2015; 71: 6733
• 9b Itoh I. Matsusaki Y. Fujiya A. Tada N. Miura T. Itoh A. Tetrahedron Lett. 2014; 55: 3160
• 9c Naidu S. Reddy SR. J. Mol. Liq. 2016; 222: 441
• 9d Zi Y. Cai Z.-J. Wang S.-Y. Ji S.-J. Org. Lett. 2014; 16: 3094
• 9e Wei W.-T. Song R.-J. Ouyang X.-H. Li Y. Li H.-B. Li J.-H. Org. Chem. Front. 2014; 1: 484
• 9f Yang X.-H. Ouyang X.-H. Wei W.-T. Song R.-J. Li J.-H. Adv. Synth. Catal. 2015; 357: 1161
• 9g Yang X.-H. Song R.-J. Li J.-H. Adv. Synth. Catal. 2015; 357: 3849
• 9h Hu M. Liu B. Ouyang X.-H. Song R.-J. Li J.-H. Adv. Synth. Catal. 2015; 357: 3332
• 10 Wei W.-T. Zhu W.-M. Wu Y. Huang Y.-L. Liang HZ. Youji Huaxue 2017;
• 11 Isatins 2a–n; General Procedure A Schlenk tube was charged with the appropriate oxindole 1 (0.3 mmol), t-BuONO (0.6 mmol), and THF (2 mL), and the mixture was stirred at 50 °C under O₂ (1 atm) until the starting material was completely consumed (TLC). The mixture was then washed with brine, and the aqueous phase was extracted with EtOAc (3 × 10 mL). The organic extracts were combined, dried (Na₂SO₄), and concentrated under a vacuum to give a crude product that was purified by column chromatography [silica gel, hexane–EtOAc (10:1)]. The products were characterized by means of ¹H and ¹³C NMR spectroscopy and mass spectrometry (see Supporting Information). Isatin (1H-Indole-2,3-dione; 2a) Yellow solid; yield: 0.0379 g (86%); mp 122.8–123.4 °C; ¹H NMR (400 MHz, DMSO-d ₆): δ = 11.07 (s, 1 H), 7.59 (t, J = 8.0 Hz, 1 H), 7.50 (d, J = 7.6 Hz, 1 H), 7.07 (t, J = 7.6 Hz, 1 H), 6.92 (d, J = 8.0 Hz, 1 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 184.8, 159.8, 151.2, 138.8, 125.1, 123.2, 118.2, 112.7. LRMS (EI, 70 eV): m/z (%) = 147 (M⁺, 61), 119 (100), 92 (74).
• 12 Peng X.-X. Deng Y.-J. Yang X.-L. Zhang L. Yu W. Han B. Org. Lett. 2014; 16: 4650
• 13a Deng G.-B. Zhang J.-L. Liu Y.-Y. Liu B. Yang X.-H. Li J.-H. Chem. Commun. (Cambridge) 2015; 51: 1886
• 13b Maity S. Naveen T. Sharma U. Maiti D. Org. Lett. 2013; 15: 3384
• 14 Kirchner F. Mayer-Figge A. Zabel F. Becker KH. Int. J. Chem. Kinet. 1999; 31: 127