New cyclophane hosts: polyether-bridged hexaoxacyclophanes

摘要

J. CHEM. SOC. PERKIN TRANS. I 1989 New Cyclophane Hosts: Polyether-Bridged Hexaoxacyclophanes Gary R. Bower, Alexandra M. Z. Slawin, and David J. Williams Department of Chemistry, Imperial College, London SW7 2AY George R. Brown Chemistry Department, lCl Pharmaceuticals, Mereside, Alderle y Park, Macclesfield, Cheshire SK I0 4TG Surinder S. Chana and J. Fraser Stoddart Department of Chemistry, The University, Sheffield S3 7HF The polyether- bridged hexaoxacyclophane (3)has been shown by X-ray crystallography to include a CH,CI, molecule within its molecular cavity. The conformational properties of the free hexaoxacyclophane (1) displayed' in the solid state encouraged us to progress to the incorporation of pol yether ribbons between the two rn-xylylene rings in (1) in order to increase the rigidity of the cyclophane unit and introduce a potential alkali-metal cation binding site.In this communication, we (i) report on the synthesis of the pol yether-bridged hexaoxacyclophanes (2) and (3), and (ii) illustrate by X-ray crystallography how (3) includes a CH2Cl, molecule within its molecular cavity in the solid state. As a result of separate reactions Cs,CO,/MeCN/reflux/ 24-28 h of bis(4-hydroxyphenyl) ether2 with 1,8-bis2,6-bis(bromomethy1)phenoxy I-3,6-dioxaoctane, and 1,l l-bis(2,6-bis(bromomethy1)phenoxy)-3,6,9-trio~aundecane~respectively (2) 3, m.p. 239-242 "C, M,754 (f.a.b.m.s.); G(CD,Cl,) 3.28-3.30 (8 H, s and m), 3.78-383 (4 H, m), 5.05 (8 H, s), 6.78-7.01 (16 H, A,B,), 7.22 (2 H, t, J7.5 Hz), 7.50 (4 H, d, J7.5 Hz) was isolated after preparative t.1.c.SiO,/CHCl,-EtOAc (20 :1, v/v) and (3) 7, m.p. 257-260°C, M, 798 (f.a.b.m.s.), G(CD,Cl,) 3.50-3.57 (8 H, m), 3.63-3.66 (4 H, m), 3.82-3.87 (4 H, m), 5.14 (8 H, s), 6.74-7.03 (16 H, A,B,), 7.21 (2 H, t, J7.5 Hz), and 7.52 (4 H, d, J 7.5 Hz) was isolated after column chromatography SiO,/CH,CI,-Et20 (20: 1, v/v). Single crystals of (3) suitable for X-ray crystallography were grown from CH,Cl,-hexane. New Cyclophane Hosts: A Hexaoxacyclophane Figure 1. Diagrammatic representation of a potential bireceptor molecule for alkali metal phenoxides To face p. 212 Figure 2. Space-filling representation of the solid state structure of (1): the oxygen atoms are shown in red Figure 3.The solid-state structure of (1) giving the atomic numbering scheme and selected torsional angles: the carbon and oxygen atoms are shown in grey and red, respectively. Note that there is a non-linearity of 9" between the 0(7)-C(8) and C(11)-O(12) bonds emanating from ring E (and from ring B) Figure 4. The packing of adjacent molecules (red and black) of (1) in the crystal. Aromatic ring centroid-centroid distances (A), angles (") between their mean planes: AA', 4.77,20; BB', 3.83,6; FF', 4.70,'19 Figure 5. The solid-state structure of (l)-C,H, giving the aromatic numbering scheme and selected torsional angles: the carbon and oxygen atoms are shown in grey and red, respectively Figure 6. Space-filling representation of the solid-state structure of (l)*C,H, corresponding to the view of the framework representation illustrated in Figure 5: the oxygen atoms are shown in red and the encapsulated benzene molecule is highlighted in grey Figure 7.The packing of adjacent supermolecules (red and black) of (l).C6H, in the crystal New Cyclophane Hosts: Polyether- Bridged Hexaoxacyclophanes Figure 1. The solid-state structure of (3).CH,CI, giving the atomic numbering scheme and selected torsima1 angles: the carbon, oxygen, and chlorine atoms are shown in grey, red and green, respectively. The angles between the O(I)-C(Z) and C(5)-0(4) and 0(25)-C(25)and C(22)-O(21) bonds are 8 and 2",respectively Figure 2. Space-filling representation of the solid state structure of (3)*CH2C1,corresponding to the view of the framework representation illustrate( in Figure 1: the oxygen and chlorine atoms are shown in red and green, respectively Figure 3.Space-filling representation of the solid state structure of (3)-CH2C1, looking into the molecular cave of (1): the oxygen and chlorine atom! are shown in red and green, respectively To face p. 2 131 3. CHEM. SOC. PERKIN TRANS. I 1989 The X-ray crystal structure* of (3) reveals (Figures 1 and 2) that the conformation of its hexaoxacyclophane unit changes from that adopted' in (1). The aromatic rings A and D are no longer parallel but they are folded in towards each other and so partially fill the macrocyclic ring aperture that was present' in (1).However, the bridging polyether ribbon, together with the aromatic rings F, A, and B form (Figure 3) the boundary to a sizable molecular cave in which a CH,CI, molecule4 resides.? The closest contacts to this encapsulated substrate are between one of the CH, protons on C(49) of CH,CI, and the two oxygen atoms, O(44) and 0(40), of the bridging polyether ribbon in (3), namely 2.51 and 2.55 A, respectively.$ In common with (l),aromatic rings A and B, and D and E, of the two diphenyl ether units are approximately orthogonal to each other. Again, in both cases, these geometries are produced by two non-zero torsional components about the 0(4)-C(5), 0(4)-C(8), and 0(25)-C(25), 0(25)-C(28) bonds, respectively (Figure 1). Approximate coplanarity5 of the methyleneoxy units with the aromatic rings A, B and D is retained; however, the C(21)-O(21) bond is rotated by 58" out-of-the-plane of aromatic ring E.The conformation of the polyether ribbon linking C(40) with C(20) has the torsional angle sequence g-g+g-a for the four contiguous 0-C-C-0 units. The solubility properties of (2) and (3) are very different: whilst (2) is virtually insoluble in most organic solvents, (3) is readily soluble in, for example, CHCl, and CH,CI,. As in the case of (l),' when 1 molar equivalent of potassium p-nitrophenolate was added to a CD,CI, solution (ca. 6 mM) of (3), insignificantly small displacements (ca. 0.03 p.p.m.) in the * Crystal data for compound (3). C,,H,,O,,~CH,Cl,, M = 883.8, triclinic, a = 9.524(3), b = 14.953(5), c = 17.278(7) A, a = 112.40(3),0 = 89.83(3), y = 98.53(3)", U = 2 246 A3, space group PT, Z = 2, D,= 1.31 g cm-,, ~(CU-K,) = 18 cm-'.The structure was solved by direct methods and refined anisotropically to give R = 0.066, R, = 0.066 for 3 985 independent observed reflections IFo 3 3u(IF,I), 8 < 55'1. Data were measured on a Nicolet R3m diffractometer with Cu-K, radiation (graphite monochromator) using o-scans. Atomic co- ordinates, bond lengths and angles, and thermal parameters have been deposited, at the Cambridge Crystallographic Data Centre. See 'Instructions for Authors (1989),' J. Chem. Soc., Perkin Trans. 1, 1989, Issue 1. t When a tetrahydrofuran (THF) solution of (3) was allowed to evaporate, single crystals containing THF and suitable for X-ray crystallography were isolated.The results of this investigation will be reported at a later date. $ Note, however, that there are no significant intermolecular short contacts between symmetry related (3).CH,Cl, molecular complexes. §Interestingly, when attempts were made to record the negative-ion f.a.b.m.s. of (3):potassium p-nitrophenolate in m-nitrobenzyl alcohol (mNBA) as the matrix, a peak was observed at m/z 951 for M + mNBA -. This observation suggests that (3) is complexing with mNBA under the conditions of the f.a.b. experiment, i.e. mNBA is present in large excess. chemical shifts of the protons on the anion relative to those for the same protons in the free potassium p-nitrophenolate in CD,CI, were observed.$ Dynamic H n.m.r.spectroscopy (CD,CI,) indicates that (3) undergoes a conformational inversion process as a result of passage of the polyether ribbon through the middle of the cyclophane (cJ: ref. 6). The singlet for the benzylic methylene protons in (3) at room temperature separates out into an AB system below -83 "C. The barrier to conformational inversion was increased by only 2.7 kJ mob1 from 36.7 to 39.4 kJ mol-' on addition of 1 molar equivalent of potassium p-nitrophenolate to (3).And so we conclude that any complexation is very small and that it is going to be necessary to add a second polyether ribbon (i.e. form a macrocyclic polyether) across the floor of the cyclophane. Acknowledgements We thank A.F.R.C.(A. M. Z.) and S.E.R.C. and I.C.I. Pharmaceuticals (S. S. C.) for their support of this research and the Leverhulme Trust for the award of a Research Fellowship to J. F. S. References 1 G. R. Brown, S. S. Chana, A. M. Z. Slawin, J. F. Stoddart, and D. J. Williams, J. Chem. SOC.,Perkin Trans. I, preceding communication. 2 G. Koga, M. Yasaka, and Y. Nakano, Org. Prep. Proced., 1969, 1(3), 205. 3 D. R. Alston, A. M. Z. Slawin, J. F. Stoddart, D. J. Williams, and R. Zarzycki, Angew. Chem., Int. Ed. Engl., 1987, 26, 692. 4 For other examples of CH,Cl, (and CHCl,) molecules included within the cavities of synthetic neutral host molecules, see F. Vogtle, H. Puff, E. Friedrichs, and W. M. Muller, J. Chem. SOC.,Chem.Commun., 1983, 1398; F. Vogtle and W. M. Muller, J. Incl. Phenom., 1984, 1, 369; I. Tabushi, K. Yamamura, H. Nonoguchi, K. Hirotsu, and T. Higuchi, J. Am. Chem. SOC.,1984, 106, 2621; J. Canceill, M. Cesario, A. Collet, J. Guilhem, and C. Pascard, J. Chern. Soc., Chem. Commun., 1985,361; J. Canceill, M. Cesario, A. Collet, J. Guilhem, and C. Pascard, ibid., p. 361; J. Canceill, M. Cesario, A. Collet, J. Guilhem, C. Riche, and C. Pascard, ibid., 1986,339; J. Canceill, L. Lacombe, and A. Collet, J. Am. Chem. Soc., 1986, 104,4230; A. W. Coleman, S. G. Bott, and J. L. Atwood, J. Incl. Phenom., 1986,4,247; I. Goldberg and K. M. Doxsee, ibid., p. 303; J. Jazwinski, J.-M. Lehn, R. Mkric, J.-P. Vigneron, M. Cesario, J. Guilhem, and C. Pascard, Tetrahedron Lett., 1987,28,3489.5 cf. A. Makriyannis and S. Fesik, J. Am. Chem. Soc., 1982, 104, 6462; L. I. Kruse and J. K. Cha, J. Chen?.Soc., Chem. Conzmun., 1982, 1329; J. D. Mersh, J. K. M. Sanders, and S. A. Maitlin, ibid., 1983, 306. 6 D. R. Alston, A. M. Z. Slawin, J. F. Stoddart, and D. J. Williams, Angew. Chem., Int. Ed. Engl., 1984, 23, 821; H. M. Colquhoun, J. F. Stoddart, and D. J. Williams, ibid., 1986, 25,487. Received 19th September 1988;Paper 8/03552K 0Copyright 1989 by The Royal Society of Chemistry