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Synlett 2013; 24(12): 1497-1500
DOI: 10.1055/s-0033-1338868
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Semi-Calix[4]indoles Containing Combinations of Direct Links and Methylene Linkages

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
,
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
,
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: 19 April 2013

Accepted after revision: 02 May 2013

Publication Date:
17 June 2013 (online)

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Abstract

Macrocyclic compounds containing four 3-substituted-4,6-dimethoxyindole units joined through the C2 and C7 positions, by a combination of direct links or methylene bridges, can be prepared by acid-catalyzed reactions of indole methanols and 2,7′-bi­indolyldimethanols with indoles and 2,7′-biindolyls.

Key words

indoles - 2,7′-biindolyls - diindolylmethanes - macrocyclic compounds - acid-catalyzed reaction - ipso-substitution reaction - formaldehyde extrusion
 

  • References and Notes

  • 1 Black DStC, Bowyer MC, Kumar N, Mitchell PS. R. J. Chem. Soc., Chem. Commun. 1993; 819
  • 2 Black DStC, Craig DC, Kumar N. Tetrahedron Lett. 1995; 36: 8075
  • 3 Black DStC, Craig DC, Kumar N, McConnell DB. Tetrahedron Lett. 1996; 37: 241
    Crossref
  • 4 Black DStC, Kumar N, McConnell DB. Tetrahedron 2000; 56: 8513
    Crossref
  • 5 Somphol K, Chen R, Bhadbhade M, Kumar N, Black DStC. Tetrahedron Lett. 2013; 54: 24
  • 6 Chen R, Bhadbhade M, Kumar N, Black DStC. Tetrahedron Lett. 2012; 53: 3337
    Crossref
  • 7 Black DStC, Bowyer MC, Bowyer PK, Ivory AJ, Kim M, Kumar N, McConnell DB, Popiolek M. Aust. J. Chem. 1994; 47: 1741
    Crossref
  • 8 To an ice cold solution of phosphoryl chloride (0.37 mL, 4.00 mmol) in anhyd N,N-dimethylformamide (5 mL) was added a cold solution of biindolyl 3 (1.0 g, 1.5 mmol) in anhyd N,N-dimethylformamide (1 mL). The mixture was stirred at r.t. for 30 min, and then at 50–60 °C for an additional 8 h. After cooling to r.t., the mixture was diluted with ice-water, basified with 20% aq NaOH and stirred for 1 h. The crude solid was filtered, washed with H2O, dried and purified by flash chromatography (CH2Cl2–n-hexane, 9:1) to yield compound 6 (0.86 g, 80%) as a yellow solid; mp 175 °C. 1H NMR (300 MHz, CDCl3): δ = 3.79 (s, 3 H, OMe), 3.80 (s, 3 H, OMe), 3.91 (s, 3 H, OMe), 3.99 (s, 3 H, OMe), 6.18 (s, 1 H, H5), 6.27 (s, 1 H, H5), 7.25 (d, J = 9.5 Hz, 2 H, ArH), 7.30 (d, J = 9.5 Hz, 4 H, ArH), 7.49 (d, J = 8.5 Hz, 2 H, ArH), 8.75 (s, 1 H, NH), 9.26 (s, 1 H, CHO), 10.24 (s, 1 H, CHO), 10.74 (s, 1 H, NH). 13C NMR (75 MHz, CDCl3): δ = 55.1, 55.3, 56.2, 56.3 (OMe), 86.6, 89.0 (C5), 96.3 (C7), 104.2, 111.2, 111.6, 115.1, 119.9, 121.8, 126.7, 128.2 (ArC), 130.3, 130.5(ArCH), 131.0, 131.1 (ArC), 131.6, 132.7 (ArCH), 134.3, 137.0, 137.9, 157.4, 158.7, 161.0, 162.8 (ArC), 180.4, 187.9 (CH=O). IR (KBr): 3418, 2936, 2842, 1639, 1583, 1342, 1214, 1136, 1120, 987, 784, 714 cm–1. UV/Vis (THF): λmax = 226 nm (ε 49,300 cm–1M–1), 267 (43,800), 328 (26,700). HRMS (+ESI): m/z [M + H]+ calcd for C34H27Br2N2O6: 717.0230; found: 717.0233. Single crystals were obtained from CDCl3. Crystal data for compound 6: 2(C34H26Br2N2O6)/5(CDCl3), M = 1906.73, triclinic, a = 14.7856(11) Å, b = 16.0855(12) Å, c = 19.0647(14) Å, α = 76.490(4)°, β = 78.004(3)°, γ = 68.849(3)°, V = 4073.4(5) Å3, T = 150(2) K, space group P–1, Z = 2, μ(MoKα) = 2.428 mm–1, 42158 reflections measured, 11460 independent reflections (Rint = 0.1944). The final R1 values were 0.1769 [I > 2σ(I)]. The final wR(F 2) values were 0.4235 [I > 2σ(I)]. The final R1 values were 0.3679 (all data). The final wR(F 2) values were 0.5123 (all data). The goodness of fit on F 2 was 1.362 (all data). Crystallographic data for compound 6 has been deposited with the Cambridge Crystallographic Data Centre as supplementary publication No. CCDC 895310. 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].
  • 9 Black DStC, Bowyer MC, Catalano MM, Ivory AJ, Keller PA, Kumar N, Nugent SJ. Tetrahedron 1994; 50: 10497
    Crossref
  • 10 To a solution of tetraindolyl dimethanol 15 (1.00 g, 0.80 mmol) in anhyd dimethyl sulfoxide (100 mL), trifluoroacetic acid (3 drops) was added. The mixture was allowed to stir at r.t. for 10 min before the addition of H2O (100 mL). The mixture was then extracted with CH2Cl2 (3 × 100 mL). The organic phases were combined, washed with brine and dried over Na2SO4. The solvent was removed under reduced pressure and the crude product was purified by flash chromatography (CH2Cl2–n-hexane, 1:1) to yield 18 (0.23 g, 24%) as a white solid; mp 243 °C. 1H NMR (300 MHz, acetone-d 6): δ = 3.34 (s, 3 H, OMe), 3.72 (s, 6 H, OMe), 3.72 (s, 2 H, CH2), 3.73 (s, 3 H, OMe), 3.78 (s, 3 H, OMe), 3.83 (s, 3 H, OMe), 3.89 (s, 3 H, OMe), 3.90 (s, 3 H, OMe), 4.10 (d, J = 16.8 Hz, 1 H, CH2), 4.30 (d, J = 16.8 Hz, 1 H, CH2), 4.38 (br s, 2 H, CH2), 6.35 (s, 1 H, H5), 6.44 (s, 1 H, H5), 6.45 (s, 1 H, H5), 6.51 (s, 1 H, H5), 7.09–7.41 (m, 16 H, ArH), 8.31 (s, 1 H, NH), 8.92 (s, 1 H, NH), 9.08 (s, 1 H, NH), 9.18 (s, 1 H, NH). 13C NMR (75 MHz, acetone-d 6): δ = 20.9, 21.7, 23.6 (CH2), 132.8, 133.5, 134.5, 134.9, 135.2, 135.8, 136.6, 136.8, 137.1, 54.5, 54.6, 54.7, 55.4, 55.6, 56.3, 56.5, 56.7 (OMe), 88.9, 89.3, 89.8 (C5), 97.6, 100.1, 102.6, 103.5, 111.5, 111.9, 112.2, 112.2, 112.4, 112.5, 113.4, 114.7 (ArC), 126.5, 126.9, 127.0, 127.1 (ArCH), 127.3, 127.5, 129.6, 129.9, 130.0, 130.6, 130.7, 130.9, 131.0, 131.4 (ArC), 131.5, 131.9, 132.0, 132.4, 132.5 (ArCH), 137.5, 138.3, 152.4, 152.6, 153.3, 153.7, 153.9, 154.0, 154.1, 154.5 (ArC). IR: 3401, 3369, 3323, 2932, 2836, 1595, 1549, 1490, 1334, 1196, 1117, 1088, 997, 817, 788, 740 cm–1. UV/Vis (THF): λmax = 224 nm (ε 203400 cm–1M–1), 287 (77600). HRMS (+ESI): m/z [M]+ calcd for C67H54Cl4N4O8: 1184.2666; found: 1184.2689.
  • 11 To a solution of biindolyl 1 (0.9 g, 1.57 mmol) and dihydroxymethyl biindolyl 7 (1.00 g, 1.57 mmol) in a mixture of isopropanol (100 mL) and CH2Cl2 (100 mL), concentrated hydrochloric acid (3 drops) was added. The mixture was stirred at r.t. for 5 min before the addition of H2O (200 mL). The mixture was then extracted with CH2Cl2 (3 × 100 mL) and the organic phases were combined, washed with brine and dried over Na2SO4. The solvent was removed under reduced pressure. The crude product was purified by flash chromatography (CH2Cl2–n-hexane, 1:1) to yield 20 (0.60 g, 30%) as a white solid; mp 262 ºC. 1H NMR (300 MHz, acetone-d 6): δ = 3.71 (s, 3 H, OMe), 3.73 (s, 3 H, OMe), 3.75 (s, 3 H, OMe), 3.76 (s, 3 H, OMe), 3.84 (s, 3 H, OMe), 3.85 (s, 3 H, OMe), 3.89 (s, 3 H, OMe), 3.94 (s, 3 H, OMe), 4.36 (s, 4 H, CH2), 6.49 (s, 2 H, H5), 6.54 (s, 1 H, H5), 6.57 (s, 1 H, H5), 7.09–7.63 (m, 16 H, ArH), 9.63 (s, 1 H, NH), 9.81 (s, 1 H, NH), 10.05 (s, 2 H, NH). 13C NMR (75 MHz, acetone-d 6): δ = 18.1, 21.5 (CH2), 54.5, 54.6, 54.7, 54.9, 56.0, 56.1, 56.8, 57.0 (OMe), 89.1, 89.2 (C5), 97.6, 98.1 (C7), 103.6, 103.7, 110.3, 111.2, 112.4, 114.4, 114.5, 114.7, 116.8, 122.2, 126.5 (ArC), 126.6, 126.8, 127.4, 128.9 (ArCH), 127.5, 127.6, 130.3, 130.5, 130.7 (ArC), 130.8 (ArCH), 130.9 (ArC), 131.9 (ArCH), 132.4, 134.5, 135.3, 135.8, 136.3, 137.5, 137.6, 137.9, 151.3, 151.4, 153.2, 153.3, 154.9, 155.0, 155.1 (ArC). IR: 3440, 3330, 2932, 2837, 1595, 1487, 1327, 1207, 1088, 995, 832, 792, 740 cm–1. UV–vis (THF): λmax = 240 nm (ε 113900 cm–1M–1), 291 (55200). HRMS (+ESI): m/z [M + H]+ calcd for C66H52Cl4N4O8: 1169.2539; found: 1169.2538. Single crystals were obtained from (CD3)2CO. Crystal data for compound 20: C40.50H41Cl2N2O6.50, M = 730.65, monoclinic, a = 21.490(4) Å, b = 10.494(2) Å, c = 33.299(7) Å, α = 90.00°, β = 95.71(3)°, γ = 90.00°, V = 7472(3) Å3, T = 100(2) K, space group C2/c, Z = 8, μ(Synchrotron) = 0.225 mm–1, 45914 reflections measured, 6568 independent reflections (Rint = 0.0377). The final R1 values were 0.0736 [I > 2σ(I)]. The final wR(F 2) values were 0.1951 [I > 2σ(I)]. The final R1 values were 0.0809 (all data). The final wR(F 2) values were 0.2015 (all data). The goodness of fit on F 2 was 1.037 (all data). Crystallographic data for compound 20 has been deposited with the Cambridge Crystallographic Data Centre as supplementary publication No. CCDC 895299. 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].