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Synlett 2013; 24(1): 24-28
DOI: 10.1055/s-0032-1317858
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© Georg Thieme Verlag Stuttgart · New York

A New Strategy for Calixindole Formation: Synthesis of a Calix[3]indole with 2,2; 7,2; 7,7-Methylene Linkages and a New Calix[4]indole with 2,2; 7,2; 7,7; 2,7-Methylene Linkages

Kittiya Somphol
School of Chemistry, The University of New South Wales, UNSW, Sydney NSW 2052, Australia   Fax: +61(2)93856141   Email: d.black@unsw.edu.au
,
Rui Chen
School of Chemistry, The University of New South Wales, UNSW, Sydney NSW 2052, Australia   Fax: +61(2)93856141   Email: d.black@unsw.edu.au
,
Mohan Bhadbhade
School of Chemistry, The University of New South Wales, UNSW, Sydney NSW 2052, Australia   Fax: +61(2)93856141   Email: d.black@unsw.edu.au
,
Naresh Kumar
School of Chemistry, The University of New South Wales, UNSW, Sydney NSW 2052, Australia   Fax: +61(2)93856141   Email: d.black@unsw.edu.au
,
David StC. Black*
School of Chemistry, The University of New South Wales, UNSW, Sydney NSW 2052, Australia   Fax: +61(2)93856141   Email: d.black@unsw.edu.au
› Author Affiliations
Further Information

Publication History

Received: 05 November 2012

Accepted: 19 November 2012

Publication Date:
10 December 2012 (online)

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Abstract

A new strategy of acid-catalysed reactions of indole methanols with a 3-aryl-4,6-dimethoxyindole-7-aldehyde leads to an efficient synthesis of a calix[3]indole with 2,2; 7,2; 7,7-links. A new calix[4]indole containing four indole units with 2,2; 7,2; 7,7; 2,7-links has also been prepared by this strategy.

Key words

indoles - diindolylmethanes - macrocyclic compounds - acid-catalysed reactions - ipso-substitution reactions - formaldehyde extrusion
 

  • References and Notes

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  • 18 Compound 4 was prepared from the indole-7-aldehyde 3 (0.900 g, 2.50 mmol), diindolyl dimethanol 1 (0.490 g, 1.25 mmol), p-toluenesulfonic acid monohydrate and isopropanol (100 mL). After stirring for 1 h, filtration and drying, the compound 7 (1.21 g, 90%) was obtained as a yellow solid; mp 256–257 °C (CH2Cl2–light petroleum). 1H NMR (300 MHz, CDCl3): δ = 3.66, 3.70, 3.82, 3.95, 3.99, 4.07 (6 × s, 18 H, OMe), 3.82 (s, 2 H, CH2, 2,2′-link), 4.18 (s, 2 H, CH2, 2,7′-link), 6.05, 6.15, 6.30 (3 × s, 3 H, indolyl H5), 6.91 (s, 1 H, NH), 6.96–7.32 (m, 12 H, ArH), 9.98, 10.59 (2 × s, 2 H, NH), 10.28, 10.32 (2 × s, 2 H, CHO). 13C NMR (75 MHz, CDCl3): δ = 20.9, 23.7 (CH2), 55.1, 55.2, 55.3, 56.3, 56.4, 56.7 (OMe), 86.6, 86.8, 89.1 (indolyl C5), 130.0, 130.3, 130.7, 132.1, 132.2, 132.4 (ArCH), 101.3, 104.2, 104.3, 110.9, 111.2, 111.9, 113.5, 114.6, 119.7, 119.9, 120.1, 129.1, 130.5, 130.7, 132.1 (2×), 133.6, 134.0, 134.3, 134.4, 136.3, 153.0, 153.3, 160.2, 160.5, 162.3, 162.4 (ArC), 187.8, 188.0 (CHO). IR (KBr): 3409, 3342, 2934, 2843, 1643, 1593, 1562, 1511, 1487, 1464, 1434, 1393, 1367, 1353, 1247, 1214, 1120, 994, 817, 794 cm–1. UV–Vis (CH2Cl2): λmax = 234 (ε = 83,900 cm–1M–1), 257 (72,400), 317 (35,200) nm. MS (ESI): m/z (%) = 1074 [M, 79/79/79Br] (10), 862 (15), 796 (20), 663 (80), 647 (30), 429 (60), 135 (100), 108 (70). Anal. Calcd for C52H42Br3N3O8: C, 58.0; H, 3.9; N, 3.9. Found: C, 57.9; H, 4.0; N, 3.7.
  • 19 Compound 6 was prepared by treatment of the triindolyl dimethanol 8 (0.300 g, 0.280 mmol) in anhyd dimethylsulfoxide (5 mL) with a catalytic amount of p-toluenesulfonic acid monohydrate and stirred at r.t. After 5 min, H2O was added and the resulting green precipitate was filtered off, washed with H2O, dried and recrystallised from EtOAc–hexane to yield the calixindole 9 (0.26 g, 89%) as a yellow-green solid; mp >300 °C. 1H NMR [300 MHz, (CD3)2SO]: δ = 3.61, 3.62, 3.63, 3.64, 3.73, 3.76 (6 × s, 18 H, OMe), 3.93, 4.15, 4.20 (3 × s, 6 H, CH2), 6.33, 6.34 (2 × s, 3 H, indolyl H5), 7.10–7.15 (m, 4 H, ArH), 7.31–7.36 (m, 4 H, ArH), 7.45 (d, J = 8.3 Hz, 2 H, ArH), 7.54 (d, J = 8.3 Hz, 2 H, ArH), 9.49, 9.62, 9.95 (3 × s, 3 H, NH). 13C NMR [75 MHz, (CD3)2SO]: δ = 19.2, 21.6, 23.3 (CH2), 55.3, 55.4, 55.5, 56.8, 57.4, 57.7 (OMe), 89.7, 90.5, 90.8 (C5), 125.9, 128.4, 130.1, 132.9, 133.2, 133.5 (ArCH), 102.0, 104.3, 105.0, 111.4, 111.8 (2 ×), 114.0, 119.1, 131.4, 132.1, 132.3, 132.9, 134.8, 135.2, 135.4, 135.6, 136.1, 136.7, 137.0, 138.0, 152.0 (2 ×), 152.3, 152.5, 153.3, 154.1, 154.3 (ArC). IR (KBr): 3419, 2933, 2835, 1619, 1595, 1520, 1488, 1463, 1434, 1393, 1341, 1295, 1207, 1141, 1112, 1073, 997, 819 cm–1. UV–Vis (CH2Cl2): λmax = 233 (ε = 111,200 cm–1M–), 289 (41,800) nm. MS (ESI): m/z (%) = 1036 [M + 1, 81/81/81Br] (24), 1034 [M + 1, 79/81/81Br] (43), 1032 [M + 1, 79/79/81Br] (20), 1030 [M + 1, 79/79/79Br] (20). Anal. Calcd for C51H42Br3N3O6·1.5 H2O: C, 57.8; H, 4.3; N, 4.0. Found: C, 57.8; H, 4.2; N, 3.9.
  • 20 Compound 7 was prepared from the indole-7-aldehyde 3 (49.0 mg, 0.136 mmol), diindolyl dimethanol 2 (50.0 mg, 0.068 mmol), p-toluenesulfonic acid monohydrate and isopropanol (30 mL). After stirring for 1 h, the yellowish precipitate was filtered off to yield compound 7 (66.0 mg, 68%); mp 292 °C (dec.; CH2Cl2–light petroleum). 1H NMR (300 MHz, CDCl3): δ = 3.57 (s, 2 H, CH2, 2,2′-link), 3.63, 3.70, 3.94, 4.08 (4 × s, 24 H, OMe), 4.07 (s, 4 H, CH2, 2,7′-link), 5.99, 6.36 (2 × s, 4 H, indolyl H5), 6.82 (s, 2 H, NH), 6.85–6.89 (m, 6 H, ArH), 6.98–7.01 (m, 6 H, ArH), 7.17 (d, J = 8.3 Hz, 4 H, ArH), 10.26 (s, 2 H, CHO), 10.53 (s, 2 H, NH). 13C NMR (75 MHz, CDCl3): δ = 21.0, 23.9 (CH2), 55.0, 55.2, 56.2, 56.9 (OMe), 86.7, 89.3 (indolyl C5), 129.9, 130.4, 132.1, 132.3 (ArCH), 101.3, 104.1, 110.8, 112.1, 112.5, 114.5, 119.4, 120.0, 129.2, 132.2, 133.8 (2×), 134.0, 136.2, 152.8, 153.3, 160.3, 162.3 (ArC), 188.0 (CHO). IR (KBr): 3414, 2934, 2839, 1722, 1644, 1591, 1561, 1517, 1487, 1464, 1434, 1393, 1367, 1352, 1327, 1291, 1250, 1213, 1119, 1071, 993, 817, 794 cm–1. UV–Vis (CH2Cl2): λmax = 239 (ε = 147,800 cm–1M–1), 312 (55,800) nm. MS (MALDI): m/z (%) = 1137 (100), 1059 (25). Anal. Calcd for C69H56Br4N4O10·H2O: C, 57.6; H, 4.1; N, 3.9. Found: C, 57.5; H, 4.3; N, 3.6.
  • 21 Compound 9 was prepared by treatment of the tetraindolyl dimethanol 8 (100 mg, 0.070 mmol) in anhyd dimethylsulfoxide (5 mL) with a catalytic amount of p-toluenesulfonic acid monohydrate and stirred at r.t. After 5 min, H2O was added and the resulting yellow-green precipitate was filtered off, washed with H2O, dried and recrystallised from EtOAc–hexane to yield the calixindole 9 (67.0 mg, 69%) as a pale yellow solid; mp >300 °C. 1H NMR (300 MHz, CDCl3): δ = 3.44, 3.53, 3.75, 3.80 (2 ×), 3.95, 3.99, 4.01 (8 × s, 24 H, OMe), 3.98 (d, J = 12.7 Hz, 2 H, CH2), 3.99 (d, J = 16.0 Hz, 2 H, CH2), 4.16 (d, J = 13.7 Hz, 4 H, CH2), 5.91, 6.26, 6.33, 6.48 (4 × s, 4 H, indolyl H5), 6.95 (d, J = 8.3 Hz, 4 H, ArH), 7.03 (d, J = 8.3 Hz, 4 H, ArH), 7.24 (d, J = 8.3 Hz, 4 H, ArH), 7.40 (d, J = 8.3 Hz, 4 H, ArH), 8.31, 8.81 (2 × s, 4 H, NH). 13C NMR (75 MHz, CDCl3): δ = 21.3, 21.5, 29.6 (CH2), 55.2, 55.5, 57.4, 57.5 (OMe), 88.8, 89.8 (C5), 130.3, 130.7, 132.1, 132.7 (ArCH), 102.3, 111.8, 112.0, 112.3, 119.3, 119.7, 119.9, 130.5, 132.5, 136.2, 136.6, 136.9, 137.0, 152.2 (2 ×), 152.3, 152.5, 152.6 (ArC). IR (KBr): 3415, 2933, 2837, 1620, 1596, 1489, 1463, 1434, 1342, 1296, 1257, 1213, 1147, 1114, 996 cm–1. UV–Vis (CH2Cl2): λmax = 279 nm (ε = 111,100 cm–1M–). MS (MALDI): m/z (%) = 1379 [M – 1, 81/81/81/81Br] (27), 1377 [M – 1, 79/81/81/81Br] (70), 1375 [M – 1, 79/79/81/81Br] (100), 1373 [M – 1, 79/79/79/81Br] (72), 1371 [M – 1, 79/79/79/79Br] (35). Anal. Calcd for C68H56Br4N4O8: C, 59.3; H, 4.1; N, 4.1. Found: C, 59.6; H, 4.3; N, 4.0. Single crystals were obtained from a solvent mixture of CH2Cl2 and EtOAc: C68H56Br4N4O8·CCl3, M = 1495.17, monoclinic, a = 25.00(3) Å, b = 19.47(2) Å, c = 12.594(10) Å, α = 90.00°, β = 102.39(3)°, γ = 90.00°, V = 5986(10) Å3, T = 150(2) K, space group C2/c, Z = 4, μ(MoKα) = 2.887 mm–1, 19259 reflections measured, 5245 independent reflections (R int = 0.2689). The final R 1 values were 0.0824 [I >2σ(I)]. The final wR(F2) values were 0.0864 [I > 2σ(I)]. The final R 1 values were 0.3272 (all data). The final wR(F2) values were 0.1306 (all data). The goodness of fit on F2 was 0.988 (all data). Crystallographic data for compound 9 has been deposited with the Cambridge Crystallographic Data Centre as supplementary publication No. CCDC 894925. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB21EZ, UK [fax: +44(1223)336033; email: deposit@ccdc.cam.ac.uk].