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Synlett 2012; 23(13): 1950-1954
DOI: 10.1055/s-0032-1316583
DOI: 10.1055/s-0032-1316583
letter
A Facile Method for the Synthesis of 3-(Aminomethylene)oxindoles from Isatylidene Malononitriles and α-Azido Ketones
Further Information
Publication History
Received: 23 April 2012
Accepted after revision: 05 June 2012
Publication Date:
23 July 2012 (online)
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Abstract
A simple one-pot synthesis of 3-(aminomethylene)oxindoles was achieved by the reaction of α-azido ketones and isatylidene malononitriles via Michael addition followed by the conversion of azides to amines. All the synthesized 3-(aminomethylene)oxindoles exhibited good diastereoselectivity.
Key words
isatylidene malononitriles - azido ketones - oxindoles - 3-(aminomethylene)oxindoles - one-pot synthesisSupporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
- Supporting Information
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References and Notes
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- 11 Crystallographic data for compound 5c in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplemental publication number CCDC 840032. Copies of the data can be obtained, free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44(1223)336033 or email: deposit@ccdc.cam.ac.uk]
- 12 General Procedure for the Synthesis of Oxyindolyl Enaminone: To a stirred solution of isatylidene malononitrile 1 (1.0 mmol) and α-azido ketone 2 (1.25 mmol) in EtOH (5 mL), was added piperidine (1.0 mmol). Stirring was continued at r.t. for appropriate times as mentioned in Table 2. After the reaction was complete as indicated by TLC, solvent was removed under vacuum and the crude product was purified by column chromatography on silica gel (Merck, 100–200 mesh, EtOAc–PE, 25:75). (Z)-3-(1-Amino-2-oxo-2-phenylethylidene)indolin-2-one (5a): brown solid; mp 246–248 °C. IR (KBr): 3413, 3260, 2925, 1665, 1616, 1461, 1324, 1210, 1005, 783, 724, 669, 581, 513 cm–1. 1H NMR (500 MHz, DMSO-d 6 + CDCl3): δ = 6.45 (d, J = 7.65 Hz, 1 H, ArH), 6.52 (t, J = 7.65 Hz, 1 H, ArH), 6.75–6.78 (m, 2 H, ArH), 7.42 (d, J = 7.65 Hz, 2 H, ArH), 7.65 (t, J = 7.65 Hz, 1 H, ArH), 7.72 (br s, 1 H, D2O exchangeable, NH), 7.99 (d, J = 7.65 Hz, 2 H, ArH), 9.01 (br s, 1 H, D2O exchangeable, NH), 9.81 (s, 1 H, D2O exchangeable, NH). 13C NMR (125 MHz, DMSO-d 6): δ = 94.2, 109.4, 117.9, 120.4, 122.9, 123.6, 129.3, 130.1, 134.0, 135.1, 136.8, 154.5, 171.1, 192.0. Anal. Calcd for C16H12N2O2: C, 72.72; H, 4.58; N, 10.60. Found: C, 72.82; H, 4.56; N, 10.62. HRMS (ESI): m/z calcd for C16H12N2O2: 265.0972 [M + H]+; found: 265.0977. (Z)-3-(1-Amino-2-oxo-2-phenylethylidene)-1-(prop-2-ynyl)indolin-2-one (5c): orange solid; mp 220–222 °C. IR (KBr): 3407, 3285, 2931, 1665, 1616, 1464, 1352, 724, 679, 583 cm. 1H NMR (500 MHz, DMSO-d 6): δ = 3.18 (s, 1 H, ≡CH), 4.62 (s, 2 H, CH2), 6.46 (d, J = 7.65 Hz, 1 H, ArH), 6.68 (t, J = 7.65 Hz, 1 H, ArH), 6.96 (t, J = 7.65 Hz, 1 H, ArH), 7.00 (d, J = 7.65 Hz, 1 H, ArH), 7.59 (t, J = 7.65 Hz, 2 H, ArH), 7.73 (t, J = 7.65 Hz, 1 H, ArH), 8.00 (d, J = 7.65 Hz, 2 H, ArH), 8.64 (br s, 1 H, D2O exchangeable, NH), 8.99 (br s, 1 H, D2O exchangeable, NH). 13C NMR (125 MHz, DMSO-d 6): δ = 28.0, 73.9, 78.9, 91.4, 108.6, 117.0, 121.1, 121.9, 123.4, 129.6, 129.7, 130.1, 133.5, 135.5, 155.5, 167.2, 191.5. Anal. Calcd for C19H14N2O2: C, 75.48; H, 4.67; N, 9.27. Found: C, 75.44; H, 4.63; N, 9.23. HRMS (ESI): m/z calcd for C19H14N2O2: 303.1128 [M + H]+; found: 303.1142. (Z)-Ethyl 2-[3-(1-Amino-2-oxo-2-phenylethylidene)-2-oxoindolin-1-yl]acetate (5d): pale orange solid; mp 230–232 °C. IR (KBr): 3404, 3294, 2924, 1714, 1668, 1624, 1496, 1365, 728, 588 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 1.18 (t, J = 6.05 Hz, 3 H, Me), 4.12 (q, J = 7.65 Hz, 2 H, CH2), 4.63 (s, 2 H, CH2), 6.46 (d, J = 7.65 Hz, 1 H, ArH), 6.66 (t, J = 5.35 Hz, 1 H, ArH), 6.91 (t, J = 6.10 Hz, 2 H, ArH), 7.60 (t, J = 7.65 Hz, 2 H, ArH), 7.74 (t, J = 7.65 Hz, 1 H, ArH), 8.00 (d, J = 2 H, ArH), 8.61 (br s, 1 H, D2O exchangeable, NH), 8.90 (br s, 1 H, D2O exchangeable, NH). 13C NMR (125 MHz, DMSO-d 6): δ = 14.6, 41.0, 61.5, 92.0, 108.7, 117.4, 121.3, 122.3, 123.8, 130.1, 134.0, 135.9, 137.4, 155.7, 168.5, 169.0, 192.0. Anal. Calcd for C20H18N2O4: C, 68.56; H, 5.18; N, 8.00. Found: C, 68.52; H, 5.16; N, 8.06. HRMS (ESI): m/z calcd for C20H18N2O4: 351.1339 [M + H]+; found: 351.1345. (Z)-3-(1-Amino-2-oxo-2-phenylethylidene)-1-benzyl-indolin-2-one (5e): brown solid; mp 233–235 °C. IR (KBr): 3410, 3281, 3057, 1663, 1619, 1464, 741, 700, 600 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 5.00 (s, 2 H, CH2), 6.46 (d, J = 8.4 Hz, 1 H, ArH), 6.62 (t, J = 3.85 Hz, 1 H, ArH), 6.84 (d, J = 7.65 Hz, 2 H, ArH), 7.27–7.37 (m, 5 H, ArH), 7.59 (t, J = 7.65 Hz, 2 H, ArH), 7.73 (t, J = 7.65 Hz, 1 H, ArH), 8.02 (d, J = 7.65 Hz, 2 H, ArH), 8.61 (br s, 1 H, D2O exchangeable, NH), 9.00 (br s, 1 H, D2O exchangeable, NH). 13C NMR (125 MHz, DMSO-d 6): δ = 42.6, 92.1, 109.0, 117.4, 121.2, 122.4, 123.8, 127.5, 127.7, 129.1, 130.1, 130.2, 134.0, 135.9, 137.9, 137.9, 155.7, 168.6, 192.1. Anal. Calcd for C23H18N2O2: C, 77.95; H, 5.12; N, 7.90. Found: C, 77.89; H, 5.18; N, 7.92. HRMS (ESI): m/z calcd for C23H18N2O2: 355.1441 [M + H]+; found: 355.1457. (Z)-3-(1-Amino-2-oxo-2-phenylethylidene)-5-methyl-indolin-2-one (5g): orange solid; mp 210–212 °C. IR (KBr): 3423, 3154, 1665, 1618, 1481, 1326, 791, 718, 671, 587 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 1.94 (s, 3 H, Me), 6.20 (s, 1 H, ArH), 6.65–6.68 (m, 2 H, ArH), 7.58 (t, J = 7.65 Hz, 2 H, ArH), 7.72 (t, J = 7.65 Hz, 1 H, ArH), 7.98 (d, J = 7.65 Hz, 2 H, ArH), 8.33 (br s, 1 H, D2O exchangeable, NH), 9.01 (br s, 1 H, D2O exchangeable, NH), 10.32 (s, 1 H, D2O exchangeable, NH). 13C NMR (125 MHz, DMSO-d 6): δ = 21.5, 93.3, 109.4, 118.2, 123.2, 124.4, 128.9, 130.0, 130.1, 134.1, 134.9, 135.8, 154.9, 170.8, 192.2. Anal. Calcd for C17H14N2O2: C, 73.37; H, 5.07; N, 10.07. Found: C, 73.41; H, 5.11; N, 10.03. HRMS (ESI): m/z calcd for C17H14N2O2: 279.1128 [M + H]+; found: 279.1133. (Z)-3-[1-Amino-2-(naphthalen-2-yl)-2-oxoethylidene]-1-(prop-2-ynyl)indolin-2-one (5i): bright orange solid; mp 246–248 °C. IR (KBr): 3410, 3297, 3054, 2931, 1669, 1619, 1468, 1357, 1278, 1183, 669, 582 cm–1. 1H NMR (500 MHz, CDCl3): δ = 2.23 (t, J = 2.3 Hz, 1 H, ≡CH), 4.63 (d, J = 2.3 Hz, 2 H, CH2), 5.61 (br s, 1 H, D2O exchangeable, NH), 6.69–6.74 (m, 2 H, ArH), 7.00–7.05 (m, 2 H, ArH), 7.53 (t, J = 8.05 Hz, 1 H, ArH), 7.63 (t, J = 8.05 Hz, 1 H, ArH), 7.86–7.94 (m, 3 H, ArH), 8.14 (d, J = 8.55 Hz, 1 H, ArH), 8.57 (s, 1 H, ArH), 9.1 (br s, 1 H, D2O exchangeable, NH). 13C NMR (125 MHz, CDCl3-d 6): δ = 28.7, 71.9, 77.7, 95.6, 108.6, 119.0, 121.8, 121.9, 123.8, 124.5, 127.4, 128.0, 129.6, 129.9, 130.2, 132.5, 134.0, 136.6, 137.1, 153.4, 168.5, 191.7. Anal. Calcd for C23H16N2O2: C, 78.39; H, 4.58; N, 7.95. Found: C, 78.43; H, 4.63; N, 7.91. HRMS (ESI): m/z calcd for C23H16N2O2: 353.1285 [M + H]+; found: 353.1290. (Z)-3-[1-Amino-2-(4-chlorophenyl)-2-oxoethylidene]-indolin-2-one (5k): orange solid; mp 236–238 °C. IR (KBr): 3317, 3158, 2925, 2854, 1664, 1614, 1469, 1359, 1279, 1182, 785, 749, 477 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 6.38 (d, J = 7.65 Hz, 1 H, ArH), 6.59 (t, J = 7.65 Hz, 1 H, ArH), 6.79 (d, J = 7.65 Hz, 1 H, ArH), 6.85 (t, J = 7.65 Hz, 1 H, ArH), 7.65 (d, J = 8.45 Hz, 2 H, ArH), 7.99 (d, J = 8.45 Hz, 2 H, ArH), 8.38 (br s, 1 H, D2O exchangeable, NH), 9.02 (br s, 1 H, D2O exchangeable, NH), 10.47 (s, 1 H, D2O exchangeable, NH). 13C NMR (125 MHz, DMSO-d 6): δ = 79.6, 93.4, 109.7, 117.5, 120.6, 123.9, 130.3, 131.9, 132.8, 137.1, 140.8, 154.4, 170.6, 191.1. Anal. Calcd for C16H11ClN2O2: C, 64.33; H, 3.71; N, 9.38. Found: C, 64.39; H, 3.67; N, 9.32. (Z)-Ethyl 2-{3-[1-Amino-2-(4-chlorophenyl)-2-oxoethylidene]-2-oxoindolin-1-yl}acetate (5l): bright orange solid; mp 221–223 °C. IR (KBr): 3347, 3194, 2925, 1743, 1663, 1613, 1469, 1368, 1275, 1174, 1092, 1016, 754, 593, 539 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 1.18 (t, J = 7.3 Hz, 3 H, Me), 4.12 (q, J = 6.85 Hz, 2 H, CH2), 4.63 (s, 2 H, CH2), 6.45 (d, J = 7.65 Hz, 1 H, ArH), 6.68 (t, J = 7.65 Hz, 1 H, ArH), 6.89–6.93 (m, 2 H, ArH), 7.67 (d, J = 8.4 Hz, 2 H, ArH), 8.0 (d, J = 7.6 Hz, 2 H, ArH), 8.59 (br s, 1 H, D2O exchangeable, NH), 8.94 (br s, 1 H, D2O exchangeable, NH). 13C NMR (125 MHz, DMSO-d 6): 14.6, 41.0, 61.5, 92.0, 108.7, 117.4, 121.4, 122.1, 123.9, 130.3, 131.9, 132.7, 137.5, 140.9, 155.0, 169.0, 191.0. Anal. Calcd for C20H17ClN2O4: C, 62.42; H, 4.45; N, 7.28. Found: C, 62.48; H, 4.51; N, 7.21. HRMS (ESI): m/z calcd for C20H17ClN2O4: 385.0950 [M + H]+; found: 385.0955
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