F. Diederich, K. Dick, D. Griebel
Apr 1, 1986
Citations
0
Influential Citations
47
Citations
Journal
Journal of the American Chemical Society
Abstract
As spherical hosts for neutral arenes, the macrobicyclic compounds 2 and 3 were synthesized. 1 -Acetyl-4,4-bis[4-succinimidyloxycarbonylmethoxy-3,5-dimethylphenyl]piperidine (8) and l-ethyl-4,4-bis[4-(2-aminoethoxy)-3,5-dimethylphenyllpiperidine (10) were cyclized to the tetraoxadiaza[7.1.7.1 Iparacyclophane 4. Cyclization component 8 was obtained by starting from 1 -acetyl-4,4-bis(4-hydroxy-3,5-dimethylphenyl)piperidine and following the reaction sequence 6 7 8. Compound 10 was obtained with use of the reaction sequence 8 9 10. Reduction of 4 afforded l’,l”-diethyl9,13,17,19,29,33,37,39-octamethyldispiro[ 1,7,21,27-tetraoxa-4,24-diaza[7.1.7.l]paracyclophane-14,4’:34,4”-bispiperidine] (5). 5 was cyclized with 1 -benzyloxycarbonyl-4,4-bis[chloroformylmethoxy-3,5-dimethylphenyl]piperidine (12), obtained by the reaction sequence 6 11 12, to yield the macrobicyclic compound 13. The advantages of amide macrocyclizations with N-hydroxysuccinimide esters as activated carboxylic acid derivatives are discussed. 13 was transformed into the target host 2 by following the sequence 13 14 2. Host 3 was obtained by using the sequence 14 15 3 or by reduction of host 2. Host 3, l’,l”,l”’-triethyl-6,12,22,28,37,43,48,51,52,55,56,59-dodecamethyltrispiro[4,14,2O,3O,35,45-hexaoxa-1,17-diazaoctacyclo[ 15.15.1 5.25~8.21o~13.221~24.226~2g.236~39.241.44]nonapentaconta-5,7,l 0,12,21,23 26,28,36,38,41,43,48,50,52,54,56,58octadecaene-9,4’:25,4’’:40,4’’-trispiperidine], has D3,, symmetry. In host 3, three diphenylmethane units bearing N-ethylpiperidine rings are attached each by two -O-CH2-CH2chains to two cryptand-nitrogen atoms, through which the D3,, symmetry axis passes. In host 2, one of the three diphenylmethane units is attached to the two nitrogens by two O-CH,-C(0) bridges. The complexation between hosts 2 and 3 and neutral arenes in weakly acidic aqueous solution is studied. Association constants of the complexes were determined from solid-liquid and liquid-liquid extractions. The geometry of complexes in aqueous solution was elucidated by IH NMR spectroscopy. The considerable difference in binding, which was observed with the two very similar hosts 2 and 3, is discussed. The first extensive study of the binding between neutral arenes and artificial macrocyclic hosts in various organic solvents of different polarity is presented. The complexation between arenes and hosts 2, 3, and 16 in organic solvents was monitored by electronic absorption and emission spectroscopy and ‘H NMR spectroscopy. Host 3 is a better binder for arena in organic solvents than hosts 2 and 16. Complexation between 3 and perylene, pyrene, or fluoranthene was even observed in benzene. The geometry of the complex of a specific host and a guest was found to be very similar in all solvents. The association constants of the complexes in organic solvents are discussed in terms of the contribution of attractive van der Waals interactions between host and guest in the complex and in terms of contributions of solvation4esolvation processes. Artificial host-guest complexation in aqueous solution is closely related to complexation in biological systems and has attracted considerable interest during the past years.4 In order to investigate the interaction between apolar hosts and guests in aqueous solution, we have designed and synthesized water-soluble macromonocyclic hosts such as l.5-’0 These compounds possess cavities of very ( I ) This paper is dedicated to Prof. H. A. Staab on the occasion of his 60th (2) University of California, Los Angeles. (3) Max-Planck-Institut fur medizinische Forschung, Heidelberg. (4) For a recent review on host-guest complexation in aqueous solution, see: Diederich, F. Nachr. Chem., Tech. Lab. 1984, 32, 787-795. ( 5 ) Diederich, F.; Dick, K. Tetrahedron Lett. 1982, 23, 3167-3171. (6) Diederich, F.; Dick, K. Angew. Chem., Int. Ed. Engl. 1983, 22, 715(7) Diederich, F.; Dick, K. J . Am. Chem. SOC. 1984, 106, 8024-8036. (8) Diederich, F.; Griebel, D. J . Am. Chem. SOC. 1984, 106, 8037-8046. birthday. 717; Angew. Chem. Suppl. 1983, 957-972. pronounced hydrophobic character as binding sites for apolar guests in aqueous solution. Extensive studies of binding by cyclodextrins” and by synthetic macrocycles in 0ur5-10 and in other have definitely established that apolar hosts and (9) Diederich, F.; Dick, K.; Griebel, D. Chem. Ber. 1985, 118, 3588-3619. ( I O ) Diederich, F.; Dick, K. Chem. Ber. 1985, 118, 3817-3829. (1 1) Bender, M. L.; Komiyama, M. ‘Cyclodextrin Chemistry”: Springer: Berlin, 1978. (12) Murakami, Y. Top. Curr. Chem. 1983, 115, 107-159. (13) Tabushi, 1.; Yamamura, K. TOU. Curr. Chem. 1983, 113, 145-182. (14) Odashima, K.; Koga, K. In “Cy’clophanes”; Keehn, P. M.; Rosenfeld, St. M., Eds.; Academic Press: New York, 1983; Vol. 2, pp 629-678. (15) (a) Jarvi, E. T.; Whitlock, H. W. J . Am. Chem. SOC. 1982, 104, 7196-7204. (b) Miller, S. P.; Whitlock, H. W., Jr . J . Am. Chem. SOC. 1984, (16) Winkler, J.; Coutouli-Argyropoulou, E.; Leppkes, R.; Breslow, R. J . 106, 1492-1494. Am. Chem. SOC. 1983, 105, 7198-7199. 0002-7863/86/ 1508-2273$01.50/0