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Synlett 2014; 25(5): 708-712
DOI: 10.1055/s-0033-1340666
letter
© Georg Thieme Verlag Stuttgart · New York

Indium Trichloride Catalysed Domino Reactions of Isatin: A Facile Access to the Synthesis of Spiro(indoline-3,4′-pyrano[2,3-c]pyrazol)-2-one Derivatives

Nataraj Poomathi
Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 6000 20, India   Fax: +91(44)24911589   Email: ptperumal@gmail.com
,
Jayabal Kamalraja
Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 6000 20, India   Fax: +91(44)24911589   Email: ptperumal@gmail.com
,
Sivakalai Mayakrishnan
Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 6000 20, India   Fax: +91(44)24911589   Email: ptperumal@gmail.com
,
D. Muralidharan
Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 6000 20, India   Fax: +91(44)24911589   Email: ptperumal@gmail.com
,
Paramasivan T. Perumal*
Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 6000 20, India   Fax: +91(44)24911589   Email: ptperumal@gmail.com
› Author Affiliations
Further Information

Publication History

Received: 21 November 2013

Accepted: 31 December 2013

Publication Date:
31 January 2014 (online)

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Abstract

A versatile high-yielding indium trichloride mediated one-pot regioselective synthesis of spiroxindoles via domino one-pot, three-component reaction of isatins, pyrazoles, and (E-)-N-methyl-1-(methylthio)-2-nitroethenamine is described. This reaction presumably occurs via domino Knoevenagel condensation–­Michael addition–intramolecular O-cyclization sequence. The salient features of the methodology are its clean reaction conditions, the eco-friendly medium, low cost, easy isolation, and excellent yields without column chromatographic purification.

Key words

domino reaction - spiroxindole - indium trichloride - ­Michael addition - regioselective synthesis
 

  • References and Notes

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  • 15 General Procedure for the Preparation of Spiro(indoline-3,4′-pyrano[2,3-c]pyrazol)-2-one Derivatives by a One-Pot, Three-Component Reaction of Isatin, Pyrazole, and NMSM A mixture of isatin 1 (1 mmol), pyrazole 2 (1 mmol), NMSM (3, 1 mmol), and InCl3 (0.20 mmol) in EtOH (3 mL) were charged in a 25 mL round-bottomed flask, and the mixture was heated at reflux. The resulting solution was stirred for 5–7 h. The consumption of the starting material was monitored by TLC. The precipitated solid was filtered, washed with EtOH (5–7 mL), and dried under vacuum to obtain pure 4a–z in good yields (80–94%). The identities of products 4a–z were confirmed by FTIR, NMR, and ESI-Mass, giving good agreement with the assigned structures. Compound 4a: white solid, 94%; mp 275–278 °C. IR (KBr): ν = 3356, 2344, 1725, 1652, 1130, 1068, 924.91, 753.0 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 10.78 (br S, 1 H, NH), 10.75–10.76 (d, 1 H, J = 4.96 Hz, NH), 7.75–7.77 (d, 2 H, J = 8.04 Hz, ArH), 7.53–7.57 (t, 2 H, J = 7.78 Hz, ArH), 7.36–7.40 (t, 1 H, J = 7.38 Hz, ArH), 720–7.24(t, 1 H, J = 7.64 Hz, ArH), 7.13–7.15 (d, 1 H, J = 7.28 Hz, ArH), 6.91–6.95 (t, 2 H, J = 7.62 Hz, ArH), 3.20–3.21 (d, 3 H, J = 4.72 Hz, NHCH3), 1.63 (s, 3 H, CH3) ppm. 13C NMR (100 MHz, DMSO-d 6): δ = 176.5, 159.5, 144.6, 142.9, 142.9, 137.2, 132.1, 130.0, 128.8, 127.5, 123.6, 122.4, 121.1, 109.7, 107.5, 98.3, 50.0, 36, 29, 15, 12.0 ppm. ESI-MS: m/z = 404.07 [M + 1]+. Compound 4q: white solid, 90%; mp >350 °C. IR (KBr): ν = 3275, 1708, 1647, 1467, 1355, 1171, 1054, 1020, 921, 738 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 12.5 (br s, 1 H, NH), 10.7 (br s, 1 H, NH), 10.6 (s, 1 H, NH), 7.15–7.19 (t, 1 H, J = 7.52 Hz, ArH), 6.90–7.00 (d, 1 H, J = 7.36 Hz, ArH), 6.87–6.90 (t, 2 H, J = 6.72 Hz, ArH), 3.17 (br s, 3 H, NHCH3), 1.61 (s, 3 H, CH3) ppm. 13C NMR (100 MHz, DMSO-d 6): δ = 176.8, 160.5, 153.7, 142.7, 136.0, 132.7, 128.5, 123.6, 122.36, 109.60, 107.35, 96.70, 49.54, 28.90, 9.36 ppm. ESI-MS: m/z = 328.50 [M + 1]+
  • 16 Crystallographic data for compound 4b has been deposited with the Cambridge Crystallographic Data Center as supplementary publication number CCDC-964326. Copy of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44(1223)762911 or e-mail: deposit@ccdc.cam.ac.uk].