ORGANIC LETTERS
Ammonium Ion Binding with Pyridine-Containing Crown Ethers
2000 Vol. 2, No. 19 2947-2950
Theresa Chang,† Aaron M. Heiss,† Stuart J. Cantrill,† Matthew C. T. Fyfe,† Anthony R. Pease,† Stuart J. Rowan,† J. Fraser Stoddart,*,† Andrew J. P. White,‡ and David J. Williams‡ Department of Chemistry and Biochemistry, UniVersity of California, Los Angeles, 405 Hilgard AVenue, Los Angeles, California 90095-1569, and Chemical Crystallography Laboratory, Department of Chemistry, Imperial College, South Kensington, London SW7 2AY, U.K.
[email protected] Received June 9, 2000
ABSTRACT
Dipyrido[24]crown-8 (DP24C8) has been synthesized and shown to form [2]pseudorotaxanes spontaneously with dibenzylammonium ions. These complexes, which have been demonstrated by 1H NMR spectroscopy to form faster in solution than when the macrocyclic polyether is dibenzo[24]crown-8 (DB24C8), are also stronger than their DB24C8 counterparts. One of the [2]pseudorotaxanes has been used to construct a [2]rotaxane (see above) comprising a dumbbell-shaped component based on a dibenzylammonium ion which is encircled by a DP24C8 macrocycle and terminated by (triphenylphosphonium)methyl stoppers.
Dibenzo[24]crown-8 (DB24C8) is a versatile host1 to a variety of dialkylammonium guests, such as the dibenzylammonium ion 1-H+. However, for the construction of more intricate interlocked molecules using the DB24C8/1-H+ recognition motif, it becomes desirable to functionalize DB24C8. The use of mono- and bifunctionalized DB24C8 hosts leads inevitably to complications2 as a result of the formation of stereoisomeric complexes when two or more hosts participate. Solutions to the problemswhich is a symmetry-based oneshave been sought in the past by replacing one3a,b or both3b,c of the catechol rings in DB24C8 †
University of California, Los Angeles. ‡ Imperial College, London. (1) Fyfe, M. C. T.; Stoddart, J. F. AdV. Supramol. Chem. 1999, 5, 1-53. (2) Ashton, P. R.; Baxter, I.; Cantrill, S. J.; Fyfe, M. C. T.; Glink, P. T.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. Angew. Chem., Int. Ed. 1998, 37, 1294-1297. 10.1021/ol0061889 CCC: $19.00 Published on Web 08/19/2000
© 2000 American Chemical Society
with resorcinol rings to give benzo-m-phenylene[25]crown8 (BMP25C8) and bis-m-phenylene-[26]crown-8 (BMP26C8), respectively. Although they provide a solution to the symmetry problem, these particular crown ethers afford3 much poorer binding of R2NH2+ ions because both BMP25C8 and BMP26C8 have forfeited some of the O-C-C-O repeating units from their constitutions. Here, we report the preparation and crystal structure of dipyrido[24]crown-8 (DP24C8), which not only has the [24]crown-8 constitution but can also be functionalized on one or both pyrido rings symmetrically (3) (a) Ashton, P. R.; Bartsch, R. A.; Cantrill, S. J.; Hanes, R. E., Jr.; Hickingbottom, S. K.; Lowe, J. N.; Preece, J. A.; Stoddart, J. F.; Talanov, V. S.; Wang, Z.-H. Tetrahedron Lett. 1999, 40, 3661-3664. (b) Cantrill, S. J.; Fulton, D. A.; Heiss, A. M.; Pease, A. R.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. Chem. Eur. J. 2000, 6, 2274-2287. (c) Bryant, W. S.; Guzei, I. A.; Reingold, A. L.; Merola, J. S.; Gibson, H. W. J. Org. Chem. 1998, 63, 7634-7639.
contain a stoichiometric amount of included water which, because of its hydrogen-bonding interactions, probably influences the conformation adopted by the DP24C8 macrocycle. The molecule has a distinctly folded geometry (Figure 1) with the two pyrido rings inclined by ca. 97° to
as shown above. Moreover, DP24C8 is demonstrated to bind dibenzylammonium ions (1-H+ and derivatives) stronger than DB24C8 in solution and can be employed in the templatedirected synthesis of a [2]rotaxane. DP24C8, which, to the best of our knowledge, has not been reported in the literature to date, retains a [24]crown-8 constitution in which two -CH2OCH2- units have been replaced by 2,6-disubstituted pyridine rings. Pyridinecontaining crown ethers with [18]crown-6 constitutions have been investigated at length as hosts for various charged guests such as primary alkylammonium ions,4 zwitterionic amino acids,5 guanidinium ions,6 and a variety of metal ions.7 Often, in such systems,8 there is an appreciable increasesrelative to the analogous all-oxygen atom-containing crown etherss in the strength of binding of hydrogen-bonded guests since an aromatic nitrogen atom is a better hydrogen bond acceptor9 than either aliphatic or phenolic ether oxygen atoms. DP24C8 was obtained10 in 12% yield by reaction of 2,6bis(p-toluenesulfonyloxymethyl)pyridine with diethylene glycol in THF in the presence of NaH as base. X-ray quality single crystals11 were grown from an Et2O solution of DP24C8 upon slow evaporation. The crystals (4) Newcomb, M.; Timko, J. M.; Walba, D. M.; Cram, D. J. J. Am. Chem. Soc. 1977, 99, 6392-6398. (5) Czekalla, M.; Stephan, H.; Habermann, B.; Trepte, J.; Gloe, K.; Schmidtchen, F. P. Thermochim. Acta 1998, 137-144. (6) Uiterwijk, J. W. H. M.; van Staveren, C. J.; Reinhoudt, D. N.; den Hertog, H. J., Jr.; Kruise, L.; Harkema, S. J. Org. Chem. 1986, 51, 15751587. (7) Bradshaw, J. S.; Izatt, R. M. Acc. Chem. Res. 1997, 30, 338-345. (8) For example, the binding of various crown ethers of [18]crown-6 constitution to glycine has been investigated. At 25 °C in MeOH, the binding of glycine to pyrido[18]crown-6 was found to be five times larger than that of [18]crown-6. See ref 5. (9) Kamlet, M. J.; Abbout, J. L. Abraham, M. H.; Taft, R. W. J. Org. Chem. 1983, 48, 2877-2887. (10) Synthetic details and characterization data relating to DP24C8 and 4-H‚3PF6 can be found in the Supporting Information. 2948
Figure 1. Solid-state structure of DP24C8‚H2O showing the linking, via hydrogen bonding, of a centrosymmetrically related pair of DP24C8 molecules. The hydrogen bonding geometries are O-H‚‚‚X, H‚‚‚X distances (Å) and O-H‚‚‚X angles (deg): (a) 2.97, 2.08, 167 and (b) 2.87, 1.98, 174. The H‚‚‚π distance and C-H‚‚‚π angle (c) are 2.81 Å, 148°. The interdimer B‚‚‚B′ centroid‚‚‚centroid and mean interplanar separations are 3.63 and 3.50 Å, respectively.
each other and the polyether arms both having all gauche geometries for their OCH2CH2O linkages. Ci related pairs of molecules are linked by O-H‚‚‚O, O-H‚‚‚N, and C-H‚‚‚π hydrgen-bonding interactions (Figure 1), and these “dimers” are then B-B′ π-stacked with their neighbors to form continuous chains. The ability of DP24C8 to form a [2]pseudorotaxane12 with 1-H‚PF6 has been investigated by 1H NMR spectroscopy in CD CN solutions. The rate of 3 exchange of this 1:1 complex with its free components was of the same order13 as the 1H NMR time scale (400 MHz), resulting in broad, time-averaged signals (Figure 2b) at 300 K compared with the well-resolved 1H NMR spectrum (Figure 2a) of DP24C8 at the same temperature. For example, resonances for R-OCH2 and CH2N+ protons that are in complexed and uncomplexed species overlap and are ob(11) Crystal data for DP24C8‚H2O: C22H30N2O6‚H2O, M ) 436.5, triclinic P1h (No. 2), a ) 8.291(1), b ) 11.375(1), c ) 13.973(1) Å, R ) 101.58(1)°, β ) 106.28(1)°, γ ) 107.04(1)°, V ) 1150.50(9) Å3, Z ) 2, Dc ) 1.260 g cm-3, µ(Cu KR) ) 7.78 cm-1, F(000) ) 468, T ) 293 K; clear prisms, 0.50 × 0.33 × 0.32 mm, refined based on F2 to give R1 ) 0.051, wR2 ) 0.136 for 2737 independent observed reflections [|Fo| > 4σ(|Fo|), 2θ e 120°] and 289 parameters. (12) The 1:1 complex [DP24C8‚1]+ (m/z 616) and the free crown ether [DP24C8 + H]+ (m/z 419) were observed by FABMS. (13) The exchange rate of the 1-H‚PF6/DB24C8 complex is slow with respect to the 1H NMR time scale under identical conditions. Org. Lett., Vol. 2, No. 19, 2000
signals for the OCH2 protons in the 1H NMR spectrum (Figure 2c) at 235 K suggest that such processes might, indeed, be occurring. However, the important point is that the 1:1 complex formed between 1-H‚PF6 and DP24C8 is much stronger than that17 involving DB24C8. In contrast to 1-H‚PF6, when the bis(4-methoxycarbonylbenzyl)ammonium salt 2-H‚PF6 was added to a CD3CN solution of DP24C8, complexation-decomplexation was found to be slow on the 1H NMR time scale at 400 MHz. A Ka value for this [2]pseudorotaxane18 of 1700 M-1 was obtained for a 10 mM solution at 298 Ksa value that is somewhat larger than the 1100 M-1 reported3a,b for the 1:1 complex formed between DB24C8 and 2-H‚PF6 under exactly the same conditions. Similarly, a Ka value of 1100 M-1 was obtained for DP24C8 and 3-H‚PF6 at 5 mM in CD3CN (400 MHz, 298 K) while a weaker complexation (Ka ) 352 M-1) has been observed19 when DB24C8 replaces DP24C8 under otherwise identical conditions. To access the potential of DP24C8 in (supra)molecular synthesis, a DP24C8-containing [2]rotaxane has been prepared (Scheme 1) using a threading-followed-by-stoppering
Scheme 1a
Figure 2. Partial 1H NMR spectra (400 MHz, CD3CN) of (a) DP24C8 (10 mM) at 300 K, (b) 1-H‚PF6 and DP24C8 (2 mM) at 300 K, (c) 1-H‚PF6 and DP24C8 (2 mM) at 235 K. Complexed and uncomplexed species are denoted by “c” and “uc”, respectively.
served as one broad resonance centered at 4.43. However, upon cooling the solution down to 235 K, these resonances sharpen (Figure 2c), indicating that the rate of exchange has become slow on the 1H NMR time scale (400 MHz) and signals are observed for both complexed and uncomplexed species at δ ) 4.21 and 4.65 ppm, respectively, for R-OCH2 protons and at δ ) 4.60 and 4.19, respectively, for the CH2N+ protons.14 From integrations of these signals, binding constants (Ka) can be calculated using the single-point method.15 The Ka values were, however, found to be dependent on concentration16 and vary between 23000 and 48000 M-1 in CD3CN over the concentration range of 1-5 mM. This concentration dependence suggests that there are other dynamic processes, e.g., aggregation, taking place in addition to pseudorotaxane formation, and that the singlepoint method does not allow for them. The relatively broad (14) It is known from previous studies that the 1H NMR spectra of 1-H‚ PF6/DB24C8 complexes display the peak corresponding to the resonance of the methylene protons next to the ammonium center (in both pseudorotaxanes and rotaxanes) as a singlet when unbound and a multiplet when encircled by DB24C8. The same phenomenon is observed when DP24C8 is used as the macrocyclic component. (15) Connors, K. A. Binding Constants; Wiley: New York, 1987. (16) The concentration dependence of this system has led us to reinvestigate the validity of the single-point method. The binding of DB24C8 and 1-H‚PF6 exhibits a similar, but much less dramatic, concentration dependence. Org. Lett., Vol. 2, No. 19, 2000
a Reagents and conditions: i, DP24C8, PPh , MeNO , rt; ii, 3 2 NH4PF6, H2O. Note that the free dumbbell compound 5-H‚3PF6 was also isolated in 45% yield from this reaction.
technique.19 Triphenylphosphine was reacted10 with a mixture of DP24C8 and 3-H‚PF618 in MeNO2 to yield the [2]rotaxane 4-H‚3PF6 in 39% yield.20 X-ray quality single crystals of the [2]rotaxane were grown by layer diffusion of hexane into a MeOH solution of 4-H‚ (17) By comparison, the association constant of 1-H‚PF6 with DB24C8 is dramatically lower (3700 M-1, CD3CN, 1 mM, 235 K). Ashton, P. R.; Chrystal, E. J. T.; Glink, P. T.; Menzer, S.; Schiavo, C.; Spencer, N.; Stoddart, J. F.; Tasker, P. A.; White, A. J. P.; Williams, D. J. Chem. Eur. J. 1996, 2, 709-728. (18) The pseudorotaxane complex is also observed by FABMS as [DP24C8‚2]+ (m/z 732) in addition to the protonated free crown ether (m/z 419). (19) Rowan, S. J.; Cantrill, S. J.; Stoddart, J. F. Org. Lett. 1999, 1, 129132. (20) In the FABMS spectrum of 4-H‚3PF6, three signals corresponding to molecular ions having lost one, two, or three of their PF6- counterions at m/z 1456.5, 1310.5, and 1164.5, respectively, are observed. This pattern is similar to those observed in other, similar, triphenylphosphoniumstoppered [2]rotaxanes. A small peak corresponding to [5-H‚PF6]+ (m/z 892) was also observed, probably arising as a consequence of fragmentation and decomplexation of the crown ether from around the dumbbell. 2949
Figure 3. Solid-state structure of the [2]rotaxane 4-H3+. The hydrogen-bonding geometries are X-H‚‚‚Y, H‚‚‚Y distances (Å) and X-H‚‚‚Y angles (deg): (a) 2.99, 2.09, 176; (b) 2.93, 2.04, 169; (c) 3.24, 2.36, 153; (d) 3.32, 2.43, 155 and (e) 3.22, 2.40, 142.
3PF6. The solid-state structure21 reveals (Figure 3) the anticipated threading of the cationic component through the center of the DP24C8 macrocycle. Binding is via a combination of N+-H‚‚‚N, N+-H‚‚‚O, C-H‚‚‚N, and C-H‚‚‚O hydrogen bonding. The DP24C8 macrocycle adopts a very different conformation from that observed for the “free” crown: it has an open, but distinctly twisted, conformation (the vectors linking the ortho-methylene carbon atoms of each pyrido ring are inclined by ca. 84°), while still retaining all-gauche geometries for the OCH2CH2O linkages. There are no inter[2]rotaxane interactions of note. The partial 1H NMR spectrum of the [2]rotaxane 4-H‚ 3PF6 is compared with that of the dumbbell-shaped compound 5-H‚3PF6 in Figure 4. A significant downfield shift (∆δ ) +0.35 ppm) was observed for the signal of the N+CH2 protons in 4-H‚3PF6 compared with that present in the spectrum of 5-H‚3PF6. The deshielding of these protons is presumably a direct result of their being involved in hydrogen bonding to the DP24C8 macrocycle. Dramatic shifts (∆δ ) -0.42 and -0.15 ppm) were also observed for the resonance of the p-xylyl ring protons (Ha and Hb) in (21) For 4-H‚3PF6‚3MeOH: [C74H78N3O6P2][PF6]3‚3MeOH, M ) 1698.4, monoclinic, P21/c (No. 14), a ) 28.253(3), b ) 19.535(2), c ) 15.658(2) Å, β ) 104.10(1)°, V ) 8382(2) Å3, Z ) 4, Dc ) 1.346 g cm-3, µ(Cu KR) ) 18.4 cm-1, F(000) ) 3528, T ) 183 K; clear needles, 1.00 × 0.23 × 0.10 mm, refined based on F2 to give R1 ) 0.106, wR2 ) 0.283 for 6401 independent observed reflections [|Fo| > 4σ(|Fo|), 2θ e 120°] and 984 parameters.
2950
Figure 4. Partial 1H NMR (400 MHz, 5 mM in CD3CN, 298 K) spectra of (a) the DP24C8-containing [2]rotaxane 4-H‚3PF6 and (b) the dumbbell-shaped compound 5-H‚3PF6.
4-H‚3PF6 relative to the corresponding resonances arising from 5-H‚3PF6, suggesting that the p-xylyl units are in close contact with the pyrido rings in the [2]rotaxane. In this Letter, we have demonstrated that DP24C8 is an efficient receptor for dialkylammonium cationsssuch as 1-H+, 2-H+, and 3-H+sand displays strengths of binding in excess of those observed with DB24C8. DP24C8 can also be incorporated into rotaxanes and pseudorotaxanes, making it an attractive alternative for DB24C8. Since the pyrido rings can be substituted at their C-4 positions, resulting in a symmetric structure, DP24C8 promises to be a versatile component in supramolecular synthesis. Acknowledgment. We thank the National Science Foundation for their support of this research. Supporting Information Available: Synthetic procedures, characterization, and crystal data for DP24C8 and 4-H‚ 3PF6. This material is available free of charge via the Internet at http://pubs.acs.org. OL0061889
Org. Lett., Vol. 2, No. 19, 2000
