Novel Reaction of Indoles and Pyrrole with Pyrillium Catalyzed by Ceric Ammonium Nitrate (CAN)

Abstract

The reaction of xanthene derivatives with indoles and pyrrole catalyzed by CAN in methanol through S_N1 reaction of ­pyrillium with a nucleophilic reagent afforded the corresponding ­indole- and pyrrole-substituted xanthene derivatives in high yields, respectively.

Key words

CAN - indole - pyrrole - xanthen - pyrillium

References and Notes

• 1a Menchen SM, Benson SC, Lam JYL, Zhen W, Sun D, Rosenblum BB, Khan SH, and Taing M. inventors; US  6583168. 
• 1b Banerjee A. Mukherjee AK. Stain Technol.  1981,  56:  83 
• 1c Reynolds GA, Tuccio SA, Peterson OG, and Specht DP. inventors; DE  2109040. 
• 2a Arnone A. Merlini L. Nasini G. Tetrahedron Lett.  1972,  13:  3503 
• 2b Ravindranath B. Seshadri TR. Phytochemistry  1973,  12:  2781 
• 2c Gurudutt KN. Seshadri TR. Phytochemistry  1974,  13:  2845 
• 2d Kumar N. Seshadri TR. Curr. Sci.  1974,  43:  611 
• 2e Arnone A. Camarda L. Merlini L. Nasini G. Taylor DAH. J. Chem. Soc., Perkin Trans. 1  1977,  2116 
• 3 Hideo T. inventors; Jpn. Tokkyo Koho JP  56005480. 
• 4a Carreon JR. Roberts MA. Wittenhagen LM. Kelley SO. Org. Lett.  2005,  7:  99 
• 4b Ion R.-M. Albulescu C. Sirkecioglu O. Talinli N. http://www.photobiology.com/photobiology2000/rodica2/index.htm, The Third Internet Photochemistry and Photobiology Conference, 2000, 
• 5 Poupelin JP. Saint-Ruf G. Foussard-Blanpin O. Narcisse G. Uchida-Ernouf G. Lacroix R. Eur. J. Med. Chem.  1978,  13:  67 
• 6 Lambert RW, Martin JA, Merrett JH, Parkes KEB, and Thomas GJ. inventors; WO  9706178. 
• 7 Buu-Hoi NP. Saint-Ruf G. De A. Hieu HT. Bull. Chim. Ther.  1972,  7:  83 
• 8a Rieche A. Kirschke K. Schule M. Justus Liebigs Ann. Chem.  1968,  711:  103 
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• 9 Ji S.-J. Wang S.-Y. Synlett  2003,  2074 
• In the last 20 years, reactions of xanthen-9-ol with indole, promoted by AcOH and BF₃·OEt₂, have been reported. See:
• 13a Deschner R. Pindur U. J. Heterocycl. Chem.  1984,  21:  1485 
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Compound 1a with 3.0 equiv morpholine proceeded smoothly under sonic waves to give the 3′ after 3 h under neat conditions.

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General Procedure for the Reaction of Indoles with 1-Oxo-13c-alkyloxy-1,13c-dihydro-dibenzo[ a , kl ]-xanthene
A mixture of 1-oxo-13c-methoxy-1,13c-dihydro-dibenzo[a,kl]-xanthene (1a, 0.157 g, 0.5 mmol), indole 2a (0.059 g, 0.5 mmol), CAN (0.014 g, 5 mol%), and anhyd MeOH (2 mL) was irradiated with ultrasound in an open vessel at r.t. until the indole was completely consumed (3 h, monitored by TLC). Then the reaction mixture was washed with cold H₂O (3 × 15 mL) and cold EtOH (3 × 0.5 mL), respectively. The crude mixture was purified by flash chromatography to afford the pure product 4a (0.190 g, yield: 95%).

1-Oxo-13c-3-indoly-1,13c-dihydro-dibenzo[ a , kl ]-xanthene ( 4a)
Kelly needles (chartreuse, acicular crystals) mp 192-194 °C. IR (KBr): ν = 3465, 3056, 1697 (C=O), 1458, 1227, 1026, 810, 740 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 6.43 (d, 1 H, J = 9.6 Hz), 6.84-6.88 (m, 2 H), 6.97-7.21 (m, 4 H), 7.78-7.81 (m, 7 H), 7.35-7.40 (m, 3 H), 7.65 (d, 1 H, J = 8.0 Hz), 7.75 (d, 1 H, J = 8.8 Hz), 7.89 (d, 1 H, J = 8.0 Hz), 8.08 (br, s, 1 H, NH). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 50.1, 111.8, 112.8, 115.8, 117.3, 117.4, 117.9, 118.8, 120.8, 122.2, 123.2, 123.6, 124.4, 124.5, 125.5, 127.4, 127.7, 128.0, 129.0, 130.6, 130.9, 132.3, 132.4, 135.3, 138.3, 147.6, 148.6, 201.0. HRMS: m/z calcd for C₂₈H₁₇NO₂: 399.1259; found: 399.1240 [M⁺].

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Crystallographic data for the structural analysis have been deposited with the Cambridge Crystallographic Data Centre, CCDC No. 268046 for compound 4e. Copies of this information may be obtained free of charge from The Director, CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK [e-mail: [e-mail] or [e-mail]; fax: [phone]]. Crystal data for 4e·C₃H₆O: C₂₉H₁₉NO₂·C₃H₆O, Mr = 471.53, triclinic, space group P-1, a = 9.7116(16) Å, b = 10.9061(18) Å, c = 11.572(2) Å, α = 95.996(5)°, β = 101.305(5)°, γ = 96.887(5)°, V = 1182.8(4) ų, Z = 2, Dcalc = 1.324 g cm^-3, (MoKα) = 0.085 mm^-1; 11701 reflections collected, 4286 unique reflections, R = 0.0196.

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General Experimental Procedure
A mixture of indole 2a (0.059 g, 0.5 mmol), 7 (0.099 g, 0.5 mmol), CAN (0.014 g, 0.025 mmol), and anhyd MeOH (2 mL) was stirred in flask at r.t. until 2a was completely consumed (1 h, checked by TLC). After standing 0.5 h, the reaction mixture was washed with cold H₂O (3 × 15 mL). The crude mixture was purified by flash chromatography to afford the pure product 3a (0.134 g, yield: 90%).
3-(9 H -Xanthen-9-yl)-1 H -indole ( 8a)
Mp 143-145 °C (lit. [13a] 145 °C). IR (KBr): ν = 3429 (NH), 3051, 2920, 2850, 1254, 749 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 5.55 (s, 1 H, CH), 6.90-7.36 (m, 13 H), 8.02 (br, s, 1 H, NH). ¹³C NMR (100 MHz, CDCl₃): δ = 59.8, 111.2, 116.3, 119.6, 119.6, 120.3, 122.1, 122.8, 123.1, 124.4, 125.8, 127.7, 129.4, 136.7, 151.3. HRMS: m/z calcd for C₂₁H₁₅NO: 297.1154; found: 297.1157 [M+].