High-yielding, regiospecific synthesis of cis(4,4′)- di(carbomethoxybenzo)-30-crown-10, its conversion to a pyridyl cryptand and strong complexation of 2,2′- and 4,4′-bipyridinium derivatives

Article abstract of DOI:10.1021/jo801886x

(Chemical Equation Presented) A high yielding (93%), regiospecific synthesis of cis(4,4′)-di(carbomethoxybenzo)-30-crown-10 (1c) is reported. The derived crown ether diol 1d was converted to pyridyl cryptand 12 in 44% yield by reaction with pyridine-2,6-dicarbonyl chloride. Binding of two different 4,4′-bipyridinium (paraquat) species (3) and 2,2′-bipyridinium (diquat) 4 by 12 was explored via ¹H NMR spectroscopy, NOE experiments, mass spectrometry, X-ray crystallographic analyses, and isothermal titration calorimetry. Cryptand 12 exhibits the highest association constant for diquat ever reported (K_a = 1.9 × 10⁶ M^-1) and very high association constants for paraquats (K_a > 10⁵ M^-1) in acetone at 22°C. The binding constant of diquat 4 by cryptand 12 is nearly 6-times higher than any other reported host.

Full text of DOI:10.1021/jo801886x

High-Yielding, Regiospecific Synthesis of
cis(4,4′)-Di(carbomethoxybenzo)-30-crown-10, Its Conversion to a
Pyridyl Cryptand and Strong Complexation of 2,2′- and
4,4′-Bipyridinium Derivatives
Adam M.-P. Pederson, Elizabeth M. Ward, Daniel V. Schoonover, Carla Slebodnick, and
Harry W. Gibson*
Department of Chemistry, Virginia Polytechnic Institute and State UniVersity,
Blacksburg, Virginia 24061-0212
hwgibson@Vt.edu
ReceiVed August 25, 2008
A high yielding (93%), regiospecific synthesis of cis(4,4′)-di(carbomethoxybenzo)-30-crown-10 (1c) is
reported. The derived crown ether diol 1d was converted to pyridyl cryptand 12 in 44% yield by reaction
with pyridine-2,6-dicarbonyl chloride. Binding of two different 4,4′-bipyridinium (paraquat) species (3)
and 2,2′-bipyridinium (diquat) 4 by 12 was explored via 1H NMR spectroscopy, NOE experiments, mass
spectrometry, X-ray crystallographic analyses, and isothermal titration calorimetry. Cryptand 12 exhibits
the highest association constant for diquat ever reported (Ka ) 1.9 × 106 M-1) and very high association
constants for paraquats (Ka > 105 M-1) in acetone at 22 °C. The binding constant of diquat 4 by cryptand
12 is nearly 6-times higher than any other reported host.
Introduction
respectively), but the synthesis of diol 1d via 1b was low
yielding.3 From 1d, Stoddart et al. synthesized a cryptand, 6,
which significantly improved binding of 4 due to the addition
of binding sites and preorganization of the host.4 Likely due to
synthetic challenges of making cryptands and functional diquats,
little work has been done with these systems since the 1980s.
The Gibson group has spent the past 10 years working on
creating synthetically accessible crown ethers5 and cryptands6
that have specific and strong interactions with guests 3 and 4
and monopyridinium guests. Our overall goal is then to use these
binding interactions to build supramolecular polymers.7 We
previously reported a pyridyl cryptand, 8, made via bis(meta-
Crown ether-based molecular recognition1 has been a goal
since Pedersen′s first report of crown ether binding of alkali
metal ions.2 In the mid-1980s, Stoddart and co-workers reported
that cis(4,4′)-disubstituted dibenzo-30-crown-10 crown ethers
(1) are good hosts for dimethyl paraquat and diquat (3b and 4,
(1) Reviews: (a) Vo¨gtle, F. Supramolecular Chemistry; John Wiley and Sons:
New York, 1991. (b) Cram, D. J.; Cram, J. M. Container Molecules and Their
Guests; Royal Society of Chemistry: Cambridge, UK, 1994. (c) Lehn, J.-M.
Supramolecular Chemistry; VCH Publishers: New York, 1995. (d) Comprehen-
siVe Supramolecular Chemistry; Atwood, J. L., Davies, J. E. D., MacNicol, D. D.,
Vo¨gtle, F., Exec. Eds.; Pergamon Press: New York, 1996. (e) Monographs in
Supramolecular Chemistry: Self-Assembly in Supramolecular Systems; Lindoy,
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(f) Supramolecular Chemistry; Steed, J. W., Atwood, J. L., Eds.; J. Wiley and
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558–571. Individual papers of note: (h) Lehn, J.-M. Science 2002, 295, 2400–
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1142. (b) Kohnke, F. H.; Stoddart, J. F.; Allwood, B. L.; Williams, D. J.
Tetrahedron Lett. 1985, 26, 1681–1684. (c) Kohnke, F. H.; Stoddart, J. F.
Tetrahedron Lett. 1985, 26, 1685–1658. (d) Colquhoun, H. M.; Goodings, E. P.;
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F. H.; Stoddart, J. F. J. Chem. Soc., Chem. Commun. 1985, 314–317. (c) Allwood,
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(2) (a) Pedersen, C. J. J. Am. Chem. Soc. 1967, 89, 2495–2496. (b) Pedersen,
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9094 J. Org. Chem. 2008, 73, 9094–9101
10.1021/jo801886x CCC: $40.75 2008 American Chemical Society
Published on Web 10/24/2008

cis-Dicarbomethoxy-dibenzo-30-crown-10
phenylene)-32-crown-10 derivatives 5a and 5b, that complexed
paraquat 3b with an association constant, Ka ) 5 × 106 M-1
(in acetone, 22 °C).6b However, the synthesis of precursor 5a
is tedious and low-yielding.5a We began to seek alternative hosts
that were more readily synthesized and complexed guests 3 and/
or 4 equally strongly. We previously reported a high-yielding
regiospecific synthesis of cis(4,4′)-di(carbomethoxybenzo)-24-
crown-8 (2a);5e however, disappointingly the cryptand 7 made
from 2a was less able to bind paraquat (1.0 × 104 M-1 in
acetone at 22 °C) than the larger host 8 and does not appear to
bind diquat at all due to steric effects.6d
polymers. To date, diquats have not been employed as widely
as paraquats in such self-assembly process, but recently Pd
catalyzed coupling to form functional 2,2′-bipyridines has been
vastly improved,10 allowing for synthesis of functional diquats
for use in the production of supramolecular polymers.
Having an excellent methodology for regiospecific syntheses
of symmetrical “cis(4,4′)”-disubstituted dibenzocrown ethers5e
and the knowledge that the 32-membered bis(m-phenylene)-
based cryptand afforded very high association constants with
paraquats, we naturally were drawn to consider the analogous
30-membered dibenzocrown ether-based cryptand 12 as poten-
tially possessing the best of both worlds: facile synthetic
accessiblity and powerful binding of paraquats and diquats. CPK
models indicated that cryptand 12 would be a good host for
paraquats. In this paper we show that the same synthetic method
used to synthesize dibenzo-24-crown-8 derivative 2a does, in
fact, work extremely well for the larger dibenzo-30-crown-10
diester 1c and we show that cryptand 12, derived from 1c, is a
better host for both guests 3 and 4 than dibenzo-24-crown-8-
derived cryptand 76d and nearly as good as bis(m-phenylene)-
32-crown-10-derived cryptand 8 for paraquats (3). Interestingly
cryptand 12 complexes diquat (4) more powerfully than any
previously reported host.
To produce supramolecular polymers one must have a
synthetically available system with good solubility and very high
association constants.7e,8 In this paper we report a synthetically
accessible host which does not have the significant solubility
issues of the cyclodextrin and cucurbituril systems,9 and binds
paraquat and diquat well enough to afford true supramolecular
Results and Discussion
Synthesis of Cryptand 12. We previously reported the
synthesis of methyl 3-hydroxy-4-benzyloxybenzoate (9) from
the methyl 3,4-dihydroxy benzoate.5e The coupling of 9 with
tetra(ethylene glycol) ditosylate to make dimer 10 proceeds
quickly and in high yield (Scheme 1). The hydrogenolysis of
dibenzyl ether 10 affording the key bisphenol 11 is complete
within a couple of hours with quantitative yield. The cyclization
of bisphenol 11 with tetra(ethylene glycol) ditosylate is tem-
plated well in refluxing acetonitrile by the highly soluble KPF6
and poorly soluble K2CO3, affording the desired crown ether
diester 1c in 93% yield by mixing the components from the
start, i.e., without resorting to pseudo-high dilution. The yield
in this cyclization is higher than that reported (89%) for the
24-membered analog 2a;5e however, in the latter case the potas-
sium salt was isolated in quantitative yield. Given the relative
association constants for potassium ion with dibenzo-24-crown-8
(5) (a) Gibson, H. W.; Nagvekar, D. S. Can. J. Chem. 1997, 75, 1375–1384.
(b) Bryant, W. S.; Guzei, I. A.; Rheingold, A. L.; Gibson, H. W. Org. Lett.
1999, 1, 47–50. (c) Jones, J. W.; Zakharov, L. N.; Rheingold, A. L.; Gibson,
H. W. J. Am. Chem. Soc. 2002, 124, 13378–13379. (d) Huang, F.; Zakharov,
L. N.; Rheingold, A. L.; Jones, J. W.; Gibson, H. W. Chem. Commun. 2003,
2122–2123. (e) Gibson, H. W.; Wang, H.; Bonrad, K.; Jones, J. W.; Slebodnick,
C.; Zackharov, L. N.; Rheingold, A. L.; Habenicht, B.; Lobue, P.; Ratliff, A. E.
Org. Biomol. Chem. 2005, 3, 2114–2121. (f) Huang, F.; Guzei, I. A.; Jones,
J. W.; Gibson, H. W. Chem. Comm. 2005, 1693–1695. (g) Huang, F.; Zakharov,
L. N.; Rheingold, A. L.; Ashraf-Khorassani, M.; Gibson, H. W. J. Org. Chem.
2005, 70, 809–813, and references therein.
(6) (a) Bryant, W. S.; Jones, J. W.; Mason, P. E.; Guzei, I.; Rheingold, A. L.;
Fronczek, F. R.; Nagvekar, D. S.; Gibson, H. W. Org. Lett. 1999, 1, 1001–
1004. (b) Huang, F.; Switek, K. A.; Zakharov, L. N.; Fronczek, F. R.; Slebodnick,
C.; Lam, M.; Golen, J. A.; Bryant, W. S.; Mason, P. E.; Rheingold, A. L.; Ashraf-
Khorassani, M.; Gibson, H. W. J. Org. Chem. 2005, 70, 3231–3241. (c) Huang,
F.; Slebodnick, C.; Switek, K. A.; Gibson, H. W. Chem. Commun. 2006, 1929–
1931. (d) Gibson, H. W.; Wang, H.; Slebodnick, C.; Merola, J.; Kassel, W. S.;
Rheingold, A. L. J. Org. Chem. 2007, 72, 3381–3393. (e) Huang, F.; Slebodnick,
C.; Switek, K. A.; Gibson, H. W. Tetrahedron 2007, 63, 2829–2839. (f) Huang,
F.; Slebodnick, C.; Mahan, E. J.; Gibson, H. W. Tetrahedron 2007, 63, 2875–
2881. (g) Pederson, A. M.-P.; Vetor, R. C.; Rouser, M. A.; Huang, F.; Slebodnick,
C.; Schoonover, D. V.; Gibson, H. W. J. Org. Chem. 2008, 73, 5570–5573, and
references therein.
(7) (a) Huang, F.; Gibson, H. W. Prog. Polym. Sci. 2005, 30, 982–1018. (b)
Huang, F.; Gibson, H. W. Chem. Commun 2005, 1696–1698. (c) Gibson, H. W.;
Ge, Z.; Huang, F.; Jones, J. W.; Lefebvre, H.; Vergne, M. J.; Hercules, D. M.
Macromolecules 2005, 38, 2626–2637. (d) Huang, F.; Nagvekar, D. S.;
Slebodnick, C.; Gibson, H. W. J. Am. Chem. Soc. 2005, 127, 484–485. (e) Huang,
F.; Nagvekar, D. S.; Zhou, X.; Gibson, H. W. Macromolecules 2007, 40, 3561–
3567, and references therein.
(8) Sijbesma, R. P.; Beijer, F. H.; Brunsveld, L.; Folmer, B. J. B.; Hirschberg,
J. H. K. K.; Lange, R. F. M.; Lowe, J. K. L.; Meijer, E. W. Science 1997, 278,
1601–1604.
(average 7.6 × 103 M-1
)
11 and dibenzo-30-crown-10 (average
4.3 × 104 M-1
)
12 in acetonitrile and the fact that the reactions
(10) (a) Savage, S. A.; Smith, A. P.; Fraser, C. L. J. Org. Chem. 1998, 63,
10048–10051. (b) Lu¨tzen, A.; Hapke, M. Eur. J. Org. Chem. 2002, 2292–2297.
(c) Lu¨tzen, A.; Hapke, M.; Staats, H.; Bunzen, J. Eur. J. Org. Chem. 2003, 394,
8–3957. (d) Newkome, G. R.; Patri, A. K.; Holder, E.; Schubert, U. S. Eur. J.
Org. Chem. 2004, 235–254.
(11) (a) Takeda, Y. Bull. Chem. Soc. Jpn. 1983, 56, 3600–3602. (b) Takeda,
Y.; Kudo, Y.; Fujiwara, S. Bull. Chem. Soc. Jpn. 1985, 58, 1315–1316. (c)
Tawarah, K. M.; Mizyed, S. A. J. Solution Chem. 1989, 18, 387–401. (d)
Chantooni, M. K., Jr.; Roland, G.; Kolthoff, I. M. J. Solution Chem. 1988, 17,
175–189. (e) Izatt, R. M.; Pawlak, K.; Bradshaw, J. S.; Bruening, R. L. Chem.
ReV. 1991, 91, 1720–2085.
(12) (a) Massaux, J.; Roland, G.; Desereux, J. F. J. Solution Chem. 1982,
11, 549–555. (b) Chantooni, M. K., Jr.; Roland, G.; Kolthoff, I. M. J. Solution
Chem. 1988, 17, 175–189.
(9) (a) Nepogodiev, S. A.; Stoddart, J. F. Chem. ReV 1998, 98, 1959–1976.
(b) Kim, K.; Selvapalam, N.; Ko, Y. H.; Park, K. M.; Kim, D.; Kim, J. Chem.
Soc. ReV. 2007, 36, 267–279.
J. Org. Chem. Vol. 73, No. 22, 2008 9095

Pederson et al.
SCHEME 1. Synthesis of 12a
a (i) Ts(OCH2CH2)4OTs, 2 equiv K2CO3, CH3CN, reflux/12 h, 93%; (ii) H2, Pd/C, 99%; (iii) Ts(OCH2CH2)4OTs, 1 equiv KPF6, 5 equiv K2CO3, CH3CN,
reflux/12 h, 93%; (iv) LiAlH4, THF, 94%; (v) CH2Cl2/pyridine, pseudo-high dilution, 25°C, 6 days, 44%.
were carried out at 44 and 57 mM, respectively, it is not
surprising that the yield of 1c may be higher. The overall yield
of 1c from 9 is 86% and the synthesis was accomplished in
less than 3 days; Huang et al. reported the preparation of 1c
via tetra(ethylene glycol) dichloride with K2CO3 only (no KPF6)
over a period of 9.5 days in 44% overall yield.13 The structure
of 1c was confirmed by 1H NMR and positive ion high
resolution fast atom bombardment mass spectrometry (FAB-
MS).
structure of 1214 shows that it is slightly collapsed, but its cavity
is accessible (Figure 2); the structure shows an absence of
solvent molecules around or in the cryptand. The catechol rings
are offset by about 3.1 Å, nonparallel by 18.72°, and the
centeroid-centeroid distance is 5.458 Å.
Complexation of Paraquat Diol (3a) by Cryptand 12. The
complex 12·3a is yellow due to charge transfer interactions
between the electron rich benzo rings of the host and the electron
deficient pyridinium rings of the guest; the host and guest are
colorless individually. The strength of complexation was
measured by isothermal titration calorimetry (ITC); ∆H )
-13((1) kcal/mol and an association constant (Ka) of 1.0((0.1)
× 105 M-1 were determined in acetone at 22 °C. The 1:1
stoichiometry of the complex was also confirmed by FAB-MS:
m/z 1118.3832 [12·3a - PF6]+ (error 1.6 ppm); no other
stoichiometries were detected. 1D NOE experiments show the
through-space interactions of HR and Hꢀ of the guest (2a) with
the aromatic and ethyleneoxy protons of the host (12) in the
solution phase.
The crown ether diester 1c was converted in high yield to
the diol 1d via reaction with lithium aluminum hydride in dry
THF. Diol 1d was reacted with pyridine 2,6-dicarboxylic acid
chloride under pseudo-high dilution conditions, leading to pure
1
cryptand 12 in 44% yield. FAB-MS and H NMR of crude 12
demonstrated the presence of a complex with the pyridinium
ion; based on this observation, we are working on templation
to increase the yield of this final step.
The 1H NMR spectrum of cryptand 12 shows that it has the
same C2 symmetry as 24-crown analog 7;6d the signal for the
benzylic methylene hydrogens is a singlet and the two non-
equivalent ethyleneoxy arms are well-resolved (Figure 1). 12
was also analyzed by FAB-MS: m/z 727.2874 (error 4.7 ppm)
for [12]+.
The complexation of 3a with 12 was also investigated via
1H NMR spectroscopy (Figure 3). The aromatic signals of
(20) Yellow blocks (0.07 × 0.24 × 0.27 mm3) of 12 · 3a crystallized from
acetone/pentane by vapor diffusion at room temperature. The chosen crystal was
centered on the goniometer of an Oxford Diffraction Xcalibur S diffractometer
operating with Mo KR radiation. The data collection routine, unit cell refinement,
and data processing were carried out with the program CrysAlis.15 The Laue
Single crystals of cryptand 12 were grown by slow evapora-
tion of a 9:1 (v:v) chloroform:acetone solution at rt. The crystal
j
(13) He, C.; Shi, Z.; Zhou, Q.; Li, S.; Li, N.; Huang, F. J. Org. Chem. 2008,
73, 5872–5880.
symmetry was consistent with the triclinic space groups P1 and P1. The structure
was solved by direct methods and preliminary refinements performed in both
18
(14) Colorless plates (0.24 × 0.19 × 0.05 mm3) of 12 crystallized from 9:1
chloroform/acetone by slow evaporation at room temperature. The chosen crystal
was centered on the goniometer of an Oxford Diffraction Gemini S Ultra
diffractometer operating with Cu KR radiation. The data collection routine, unit
cell refinement, and data processing were carried out with the program
P1 and P1 using SHELXTL NT. The original refinement models in both P1
j
j
and P1 suggested the same disorder in the crystal structure. Therefore, the higher
symmetry space group, P1, was chosen. The asymmetric unit of the structure
j
comprises two host-guest complexes, two water molecules and one acetone
molecule. The final refinement model involved anisotropic displacement
parameters for all ordered non-hydrogen atoms and a riding model for all
hydrogen atoms. The hydrogen atoms from the water molecules could not be
located in the residual electron density map and were not included in the
refinement. Two-position disorder models were used for the arm of one host
molecule, one guest molecule, and two PF6-. The disordered atoms in the arm
of a host molecule were refined isotropcially to relative occupancies of 0.640(7)
CrysAlisPro.15 The Laue symmetry was consistent with the triclinic space groups
2
j
j
P1 and P1. The centric space group P1 was chosen based on the |E -1| value
(|E2-1| ) 1.052). The structure was solved by direct methods using SIR9716
via the WinGX graphical user interface17 and refined using SHELXL-97.18 The
asymmetric unit of the structure comprises one cryptand 12 molecule. The final
refinement model involved anisotropic displacement parameters for non-hydrogen
atoms and a riding model for all hydrogen atoms.
-
and 0.360(7). Both disordered PF6 were refined anisotropically. The relative
-
(15) CrysAlisPro, v1.171.32; Oxford Diffraction: Wroclaw, Poland, 2007.
(16) Altomare, A.; Burla, M. C.; Camalli, G.; Cascarano, G.; Giacovazzo,
C.; Guagliardi, A.; Moliteri, A. G. G.; Polidori, G.; Rizzi, R. J. Appl. Crystallogr.
1999, 32, 115–119.
occupancies of the P4 containing PF6 refined to 0.46(2) and 0.54(2). The P3
containing PF6- is disordered near an inversion center such that PF6- cannot be
in both positions at once, so the occupancies were constrained to 0.50. The
-
disorder in the guest molecule is coupled to the disorder in this PF6 and the
(17) Farrugia, L. J. J. Appl. Crystallogr. 1999, 32, 837–838.
occupancies of the guest were also constrained to 0.50. This guest molecule
was refined isotropically. After modeling the disorder, a region with weak residual
electron density peaks (1-2 e-/Å3) could not be modeled as anything chemically
reasonable and the peaks were assumed to arise from partially evaporated solvent.
The SQUEEZE subroutine of the PLATON program package was used and a
total of 8 e- was subtracted from 284.8 Å3 of void space.21
(18) Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112–122.
(19) Tsukube, H.; Furuta, H.; Odani, A.; Takeda, Y,; Kudo, Y.; Inoue, Y.;
Liu, Y.; Sakamoto, H.; Kimura, K. In ComprehensiVe Supramolecular Chemistry;
Atwood, J. L., Davies, J. E. D., MacNicol, D. D., Vo¨gtle, F., Eds.; Pergamon
Press: London. 1996; Vol. 8, pp 425-482.
9096 J. Org. Chem. Vol. 73, No. 22, 2008

cis-Dicarbomethoxy-dibenzo-30-crown-10
FIGURE 1. 1H NMR spectrum (400 MHz) of cryptand 12 in CDCl3.
FIGURE 2. Top and side views of the X-ray crystal structure of 12.
cryptand 12 are shifted upfield upon complexation, as usually
observed in such complexes.4-6 The similarity of the results
for 1:1 compared to 1:70 host:guest stoichiometry shows that
binding is strong. With such strong binding (Ka > 104 M-1),
the association constant cannot be accurately determined by 1H
NMR directly.19 The complexation of guest 3a by host 12 was
molecule which is then strongly interacting with two Hꢀs of 3a
[similar to the 12·3b dimorphs described below (Figure 5)];
we have reported similar findings previously.6a In dimorph II
one end of the guest resides in the cavity of the crown ether
macrocycle of 12 and the guest lies at an oblique angle with
respect to the pyridyl ring; the pyridyl-N is interacting with an
HR (shown by line e) and an Hꢀ (shown by line f) of 3a; the
third oxygen of the 3-position arm of host 12 is interacting with
an HR (shown by line h) and N+CH2 (shown by line i), and the
4-position arm is interacting with an HR (shown by line g).
Complexation of Dimethyl Paraquat (3b) with Cryptand 12.
The complex 12·3b is yellow due to charge transfer interactions
between the electron rich benzo rings of the host and the electron
poor pyridinium rings of the guest. The strength of complexation
was measured by ITC; ∆H ) -14((1) kcal/mol and an
association constant (Ka) of 2.0((0.2) × 105 M-1 were
determined in acetone at 22 °C. The 1:1 stoichiometry of the
complex was confirmed by FAB-MS: m/z 1058.3671[12·3b -
PF6]+ (error 3.0 ppm); no other stoichiometries were detected.
1D NOE experiments show the through-space interactions of
1
also investigated by H NMR in DMSO-d6: Ka ) 125 ((25)
M-1 which is impressive in this competitive hydrogen bonding,
polar solvent.
Crystals of 12·3a were grown by vapor diffusion of pentane
into an acetone solution of the complex at rt. The crystal
structure (Figure 4) reveals two distinct dimorphs.20 In dimorph
I the pyridyl-N is interacting with two Hꢀs (shown by lines a
and b) of 3a, which is threaded through the cavity nearly
orthogonal to the pyridyl ring; the 3-position arm of 12 is
interacting with one HR (shown by line c) and one N+CH2
(shown by line d) of 3a, and the 4-position ethyleneoxy arm of
12 is not interacting with 3a, but is interacting with a water
(21) Spek, A. L. J. Appl. Crystallogr. 2003, 36, 7–13.
J. Org. Chem. Vol. 73, No. 22, 2008 9097

Pederson et al.
1
FIGURE 3. Partial H NMR spectra of cryptand 12 and paraquat diol (3a) in acetone-d6 at 23 °C. (a) 1.00 mM 12, (b) 1.00 mM 12 and 3a, (c)
1.00 mM 12 and 70.0 mM 3a, (d) 1.00 mM 3a.
HR and Hꢀ of the guest with the aromatic and ethyleneoxy
protons of host 12 in the solution phase.
arms to interact with the guest, while the meta-orientation of
the ethyleneoxy units in the latter does allow such interaction.
Complexation of Diquat (4) with Cryptand 12. This system
was examined on the basis that the broader diquat molecule
might engage both ethyleneoxy arms of cryptand 12, affording
a “tighter binding” than with the narrower paraquats (3). The
complex 12·4 is orange-red due to charge transfer interactions
between the electron rich benzo rings of the host and the electron
deficient pyridinium rings of the guest. The strength of com-
plexation was measured by ITC; ∆H ) -14((1) kcal/mol and
Ka ) 1.9((0.6) × 106 M-1 were determined in acetone at 25
°C. This is the highest association constant ever reported for
guest 4; previously we reported that the bis(m-phenylene)-32-
crown-10-based cryptand 8 binds diquat (4) with Ka ) 3.3 x105
M-1 (acetone, 22 °C) measured by a competitive NMR
method.6e With regard to our overall aim of constructing
supramolecular polymers this is a significant improvement; for
example, in a system comprised of complementary homoditopic
monomers at 10 mM concentration, the dihost with individual
Ka ) 3.3 × 105 M-1 would produce oligomeric material
containing on average only 57 repeat units (n), while the new
cryptand-based dihost would lead to a true polymeric species
with n ) 1.4 × 102 repeat units (calculated from n )
{Ka[conc]}1/2).7e,8 Moreover, the development of a facile
Crystals of 12·3b were grown by vapor diffusion of pentane
into an acetone solution of the complex at rt. The crystal
structure (Figure 5) shows that the complex exists as two
dimorphs in the solid state.22 However, unlike the situation with
12·3a the dimorphs have only subtle differences in the
cryptand’s ethyleneoxy arms. The pyridyl-N interacts with two
Hꢀ of dimethyl paraquat (shown by lines a, b, e and f) and the
3-position arm of 12 interacts with one HR (shown by lines c
and g) and one of the methyl protons (shown by lines d and h)
of 3b in both dimorphs. The solid phase structure shows that
the 4-position ethyleneoxy arm of cryptand 12 does not interact
with guest 3b in either dimorph which is the same as in the
complex 12·3a (Figure 4). We believe this is the reason the
association constant values of dibenzo-30-crown-8-derived
cryptand 12 with these paraquat species are less than the one
from our previously reported highly associating, analogous
bis(m-phenylene)-32-crown-10-based cryptand 8 (Ka ) 5 × 106
M-1);6b the ortho-linkage in 12 does not allow both ethyleneoxy
(22) Yellow plates (0.03 × 0.17 × 0.23 mm3) of 12 · 3b crystallized from
acetone/ethyl acetate at room temperature. The chosen crystal was centered on
the goniometer of an Oxford Diffraction Gemini S diffractometer operating with
Cu KR radiation. The data collection routine, unit cell refinement, and data
processing were carried out with the program CrysAlis.15 The Laue symmetry
was consistent with the triclinic space groups P1 and P1. The centric space
(23) Orange plates (0.07 × 0.15 × 0.20 mm3) of 12 · 4 crystallized from
acetone/pentane by vapor diffusion at room temperature. The chosen crystal was
centered on the goniometer of an Oxford Diffraction Gemini S diffractometer
operating with Mo KR radiation. The data collection routine, unit cell refinement,
and data processing were carried out with the program CrysAlis.15 The Laue
j
2
2
j
group P1 was chosen based on the |E -1| value (|E -1| ) 1.027). The structure
was solved by direct methods and refined using SHELXTL NT.18 The asymmetric
unit of the structure comprises 2 host-guest complexes, 3 water molecules, and
2.7 acetone molecules. The final refinement model involved anisotropic displace-
ment parameters for non-hydrogen atoms and a riding model for all hydrogen
atoms. The hydrogen atoms from the water molecules could not be located in
the residual electron density map and were not included in the refinement. The
original refinement model suggested substantial disorder in the crystal structure.
A 2-position disorder model was used for one arm of a host molecule and the
P3 containing PF6 anion; because this disorder was located near an inversion
center, both positions cannot be occupied simultaneously and the relative
occupancies were constrained to 50%. Atom C(13) of a host molecule was
modeled as 2-position disorder with relative occupancies 0.627(15) and 0.373(15).
The P(4) containing PF6 anion was also modeled as 2-position disorder with
relative occupancies 0.572(10) and 0.428(10). The displacement ellipsoid drawing
suggested additional disorder in the P(5) containing PF6 anion and two acetone
molecules. Attempts to model this disorder did not improve the refinement and
were abandoned. Because of extremely large thermal parameters, the occupancy
of the acetone molecule containing O(34) was allowed to refine and converged
to 0.695(12).
j
group was consistent with the triclinic space groups P1 and P1. The structure
18
j
was solved direct methods in both P1 and P1 and refined using SHELXTL NT.
Preliminary refinements suggested disorder with both space groups; the centric
j
space group P1 was chosen. In P1, the asymmetric unit of the structure comprises
one crystallographically independent [C37H45NO14 · C12H12N2][PF6]2. The final
refinement model involved anisotropic displacement parameters for all non-
hydrogen atoms except the fluorine atoms of the PF6 anions. A riding model
was used for all hydrogen atoms. Residual electron density maps suggested
substantial disorder of the PF6 anions and disorder in the host molecule. One
PF6 anion was modeled with 3-position disorder with relative occupancies that
refined to 0.516(4), 0.296(8), and 0.188(8). The second PF6 anion was modeled
with 2-position disorder with occupancies that refined to 0.500(5). Both anions
were restrained to be octahedral using the SADI command in SHELXL-97.
Although the displacement ellipsoids of the host molecule suggest additional
disorder, discrete disorder sites in the host could not be found and attempts to
model this disorder were abandoned.
9098 J. Org. Chem. Vol. 73, No. 22, 2008

cis-Dicarbomethoxy-dibenzo-30-crown-10
FIGURE 5. Top (A and C) and side (B and D) views of the X-ray
-
crystal structure of the dimorphs of 12·3b. The PF6 counterions,
solvent molecules, and hydrogens of 12 were omitted. Five atoms of
the 3-position ethyleneoxy arm of 12 of dimorph I (A and B) are
disordered; only one atom of the 3-position ethyleneoxy arm of 12 of
dimorph II (C and D) is disordered. All PF6- counterions are disordered.
C· · ·O(N) distances (Å) and angle (°) for H-bonds: a 3.627, 173.0; b
3.561, 170.2; c 3.082, 165.6; d 3.581, 154.6; e 3.338, 168.0; f 3.609,
165.6; g 3.169, 166.2; h 3.319, 141.2. In both dimorphs, both of the
ester sp3-oxygens of host 12 have weak interactions with Hꢀ of guest
3b; the C· · ·O distances vary from 3.078-3.612 Å and angles vary
from 111-134°. The catechol rings of I and II are stacked and the
centroid-centroid distances (Å) are 6.932 and 6.829, respectively. The
distances (Å) between the catechol centroids and the plane of the guest
molecule are 3.384 and 3.515 for dimorph I and 3.380 and 3.520 for
dimorph II. The angles (°) between the catechol rings and the plane of
the guest molecule are 3.83 and 5.92 for dimorph I and 4.13 and 6.05
for dimorph II. The red double-headed arrow in A and C shows the
4-position ethyleneoxy arm of cryptand 12 of both dimorphs that is
too far away to directly interact with 3b; this arm is holding a water
molecule. The red spheres show the oxygen atom of the water [dimorph
I: O · · · O distances (Å) 2.891 and 2.923; O · · · O · · · O angle 110.9°;
dimorph II: O · · ·O distances (Å) 2.838 and 2.860; O · · ·O· · ·O angle
105.9°] which is closely interacting with two Hꢀs of 3b [dimorph I:
C...O distances (Å) and C-H· · ·O angles (°): 3.306, 173.1 and 3.416,
178.6; dimorph II: C · · ·O distances (Å) and C-H· · ·O angles (°): 3.286,
168.5 and 3.186, 174.8].
FIGURE 4. Top (A and C) and side (B and D) views of the X-ray
-
crystal structure of the dimorphs of 12·3a. The PF6 counterions,
solvent molecules, and hydrogens of 12 were omitted. Dimorph I (A
and B) is not disordered. Both guest 3a and the 4-position ethyleneoxy
arm of 12 are disordered (disorder in 3a not shown) in dimorph II (C
-
and D). All PF6 counterions are disordered. C· · ·O(N) distances (Å)
and angles (°) for H-bonds: a 3.568, 176.7; b 3.483, 170.3; c 3.085,
167.3; d 3.380, 150.4; e 3.231, 139.3; f 3.528, 109.5; g 3.173, 133.2;
h 3.782, 134.9; i 3.104, 169.3. The disordered guest, 3a, has similar
interactions (e, g, h, i) with 12 of dimorph II. In dimorph I, both of the
ester sp3-oxygens of host 12 have weak interactions with Hꢀ of 3a; the
C· · ·O distances vary from 3.172-3.577 Å and the angles vary from
116-128°. The catechol rings of dimorphs I and II are stacked and
the centroid-centroid distances (Å) are 6.903 and 6.813, respectively.
The distances (Å) between the catechol centroids and the plane of the
guest molecule are 3.365 and 3.437 for dimorph I and 3.358 and 3.449
for dimorph II. The angles (°) between each catechol and the plane of
the guest molecule are 4.35 and 7.67 for dimorph I and 3.69 and 3.71
for dimorph II. The red double-headed arrow in A shows the 4-position
ethyleneoxy arm of 12 of dimorph I that is too far away to interact
with 3a directly; this arm is holding a water molecule, the red sphere
shows the oxygen atom of water [O · · ·O distances (Å) 2.865 and 2.867;
O· · ·O· · ·O angle 108.9°] which is closely interacting with two Hꢀs of
3a [C· · ·O distances (Å) and C-H· · ·O angles (°) are: 3.235, 176.6
and 3.263, 175.6].
synthesis of precursor 1c for 12 also represents a significant
advance versus the tedious preparation of precursor 5a for 8.
The 1:1 stoichiometry of the 12·4 complex was confirmed by
FAB-MS: m/z 1056.3531 [12·4 - PF6]+ (error 4.6 ppm); no
other stoichiometry was detected. 1D NOE experiments show
the through-space interactions of the guest′s ethylene protons
with the ethyleneoxy protons of host 12 in the solution phase.
Crystals of 12·4 were grown by vapor diffusion of pentane
into an acetone solution of the complex at rt. The crystal
structure23 shows all four ethylene protons of guest 4 have
bifurcated H-bond interactions (shown by lines c/d, e/f, g/h,
i/j), engaging both of the ethyleneoxy arms of cryptand 12, as
anticipated. H6 of guest 4 is also interacting with an ethyleneoxy
arm of host 12 (shown by line k). The pyridyl nitrogen of host
12 interacts with H5 (shown by line b) and H6 (shown by line
a) of guest 4. The other 6-, 5-, and both of the 4-position protons
of guest 4 are not bound to host 12 in the solid state.
the association constant was estimated via 1H NMR-based
competitive complexation to be 5.0 × 106 M-1 (22 °C, acetone-
d6).6b In order to standardize our methods we retested this system
using ITC and found Ka ) 1.6((0.6) × 106 M-1 and ∆H )
15((1) kcal/mol (acetone, 25 °C).
Conclusions
In conclusion, a high yielding, regiospecific synthesis of
cis(4,4′)-di(carbomethoxybenzo)-30-crown-10 (1c) was reported.
The diester crown ether was converted via the diol 1d to the
pyridyl cryptand 12, which binds paraquats (3) well (Ka g 105
M-1) and diquat (4) better than any other host reported to date
(Ka ) 1.9 × 106 M-1) in acetone. The complexation of dibenzo-
30-crown-10-based cryptand 12 with diquat 4 is at least as strong
as bis(m-phenylene)-32-crown-10-derived cryptand 8 with
paraquat 3b, but the synthesis of the 30-crown presursor 1c is
much less time-consuming and higher yielding than synthesis
of the 32-crown precursor 5a. The 1:1 nature of the complexes
of new cryptand 12 with paraquats and diquats (3 and 4) was
Complexation of 3b with 8. The complex of dimethyl
paraquat (3b) and bis(m-phenylene)-32-crown-10-derived cryptand
8 was previously described via its X-ray crystal structure and
J. Org. Chem. Vol. 73, No. 22, 2008 9099

Pederson et al.
CH3OH]+; 612.2, 55% [10 + H - OCH3 - CH3OH]+; 613, 21%
[10 + H - OCH3 - CH3OH + 1]+; 614, 6% [10 + H - OCH3 -
CH3OH + 2]+; 643.2, 15% [10 - OCH3]+; 644.2, 100% [10 + H
- OCH3]+; 645, 36% [10 + H - OCH3 + 1]+; 646, 8% [10 + H
- OCH3 + 2]+; 674.3, 5% [10]+; 675.3, 40% [10 + H]+; 676,
23% [10 + H + 1]+; 677, 8% [10 + H + 2]+. HR FAB MS (NBA/
PEG): m/z 674.2712 [10]+, calcd for C38H42O11 674.2727, error
2.3 ppm.
Tetra(ethylene glycol) Bis(2-hydroxy-5-carbomethoxyphenyl)
Ether (11). To a solution of dibenzyl ether 10 (13.50 g, 20.00 mmol)
in CH2Cl2 (100 mL) was added 10% Pd/C (0.20 g). The suspension
was shaken under H2 atmosphere (50 psi) at rt. After 12 h, TLC
showed complete conversion to product. The catalyst was removed
by filtration. The filtrate was concentrated to give a white solid,
1
9.81 g (99%), mp 60.8-62.3 °C; H NMR (CDCl3, 400 MHz) δ
4
8.24 (br s, 2H), 7.62 (dd, JHH ) 2 Hz,3JHH ) 8 Hz, 2H), 7.53 (d,
3
4JHH ) 2 Hz, 2H), 6.90 (d, JHH ) 8 Hz, 2H), 4.30 (m, 4H), 3.86
(m, 10H), 3.70 (m, 8H). LR FAB MS (NBA) of 11: m/z 463, 11%
[11 - OCH3]+; 464, 100% [11 + H - OCH3]+; 465, 25% [11 +
H - OCH3 + 1]+; 466, 5% [11 + H - OCH3 + 2]+; 468, 33%
[11 + H + Na - H2O - CH3OH]+; 469, 10% [11 + H + Na -
H2O - CH3OH + 1]+; 470, 4% [11 + H + Na - H2O - CH3OH
+ 2]+; 495, 20% [11 + H]+; 496, 33% [11 + H + 1]+; 497, 10%
[11 + H + 2]+; 499, 10% [11 + Na -- H2O]+; 500, 12% [11 +
Na - H2O + 1]+; 501, 4% [11 + Na - H2O + 2]+; 518, 4% [11
+ H + Na]+. HR FAB MS (NBA/PEG): m/z 494.1748 [11]+, calcd
for C24H30O11 494.1788, error 8.1 ppm.
FIGURE 6. X-ray crystal structure of 12·4. The PF6- counterions and
-
hydrogens of 12 were omitted. The PF6 counterions are disordered.
C-H· · ·O(N) distances (Å) and angles (°) for H-bonds: a 3.712, 125.3;
b 3.668, 128.81; c 3.240, 166.8; d 3.288, 112.9; e 3.314, 152.7; f 3.461,
121.4; g 3.355, 152.3; h 3.175, 129.1; i 3.289, 129.4; j 3.094, 135.2;
k 3.257, 147.3. Both of the ester sp3-oxygen atoms of host 12 have
weak interactions with H6 of 4; the C · · ·O distances (Å) and angles (°)
are 3.510, 98.0 and 3.358, 105.0. The catechol rings of 12 are stacked
and the centroid-centroid distance is 7.019 Å. The distances (Å) between
the catechol centroids and the plane of the guest molecule are 3.442
and 3.501. The angles (°) between the catechol rings and the plane of
the guest molecule are 5.05 and 11.53.
cis(4,4′)-Di(carbomethoxybenzo)-30-crown-10 (1c). Bisphenol 11
(16.80 g, 33.97 mmol) and tetra(ethylene glycol) ditosylate (17.07
g, 33.96 mmol) were dissolved in CH3CN (600 mL). KPF6 (6.75
g, 36.6 mmol) and K2CO3 (23.80 g, 172.1 mmol) were added to
the solution. The refluxing mixture was stirred under N2 for 16 h.
After cooling, the mixture was filtered and the solvent was
evaporated. The material was partitioned between chloroform and
water; the organic phase was washed with water, NaCl (sat. aq.),
dried with sodium sulfate, filtered, and the solvent was removed.
Column chromatography (neutral alumina, 1/1 v/v CHCl3/hexanes)
yielded a white solid (20.61 g, 93%), mp 110.8-111.4 °C. We
believe the melting point Huang et al.13 report for 1c (149-150
°C) is likely that of the potassium salt complex with 1c. 1H NMR
confirmed by MS, ITC fittings, CPK modeling, and solid state
structures. As other groups have improved the synthesis of
functional 2,2′-bipyridines, the synthesis of derivatives of diquat
4 will lead to supramolecular polymers based on their molecular
recognition by appropriate derivatives of host 12. We are
currently exploring the synthesis of cryptands based on the
derivatives of the regioisomers of di(carbomethoxybenzo)-27-
crown-9 as further improved hosts for paraquat guests. With
synthetically available hosts with high association constants with
paraquats and diquats in hand we will be able to produce true
supramolecular polymers (DP g 100).
3
4
(CDCl3, 400 MHz) δ: 7.63 (dd, JHH ) 8 Hz, JHH ) 2 Hz, 2H),
7.52 (d,4JHH ) 2 Hz, 2H), 6.85 (d, JHH ) 8 Hz, 2H), 4.18 (m,
3
8H), 3.88 (m, 14H), 3.78 (m, 8 H), 3.69 (m, 8H). LR FAB MS
(NBA/PEG) of crude 1c: m/z 691.7, 100% [1c + K]+; 692.7, 35%
[1c + K + 1]+; 693.7, 17% [1c + K + 2]+; 694.7, 4% [1c + K+
3]+. HR FAB MS of crude 1c (NBA/PEG): m/z 691.2352 [1c +
K]+, calc. for C32H44O14K 691.2368, error 2.3 ppm. LR FAB MS
(NBA) of 1c: m/z 622, 100% [1c + H - OCH3]+; 623, 34% [1c +
H - OCH3 + 1]+; 624, 13% [1c + H - OCH3 + 2]+; 653, 55%
[1c]+; 654, 68% [1c + H]+; 655, 21% [1c + H + 1]+; 672, 81%
[1c + H + H2O]+; 673, 28% [1c + H + H2O + 1]+. HR FAB MS
(NBA/PEG): m/z 652.2701 [1c]+, calcd for C32H44O14 652.2731,
error 4.6 ppm.
Experimental Section
Tetra(ethylene glycol) Bis(2-benzyloxy-5-carbomethoxyphenyl)
Ether (10). A solution of phenol 95e (22.49 g, 87.07 mmol), K2CO3
(24.80 g, 179.3 mmol) and tetra(ethylene glycol) ditosylate24 (22.01
g, 43.79 mmol) in CH3CN (400 mL) was stirred at reflux for 12 h.
The solids were filtered and solvent was removed in Vacuo; the
residue was partitioned between water and ethyl acetate. The water
layer was extracted with ethyl acetate (3×). The combined ethyl
acetate solution was washed with water and saturated NaCl solution,
and dried over anhydrous Na2SO4. After concentration in Vacuo,
the material was purified via column chromatography (silica/1:1
ethyl acetate:hexanes). A white solid was obtained, 27.34 g (93%),
cis(4,4′)-Di(hydroxymethylbenzo)-30-crown-10 (1d). Diester 1c
(4.00 g, 6.12 mmol) was dissolved in THF (200 mL, distilled from
Na). LiAlH4 (0.46 g, 12 mmol) was slowly added over 1 h. The
mixture was stirred for an additional 12 h and then worked up using
the Fieser and Fieser method.25 1d was isolated as a white solid
1
4
mp 68.7-69.3 °C. H NMR (CDCl3, 400 MHz) δ 7.62 (dd, JHH
4a
1
3
4
(3.43 g, 94%), mp 89.7-92.0 °C (lit. mp 91-94 °C ). H NMR
(CDCl3, 400 MHz) δ: 6.92 (s, 2H), 6.85 (m, 4H), 4.57 (s, 4H),
4.13 (m, 8H), 3.87 (m, 8H), 3.67 (m, 16H). LR FAB MS (NBA)
of 1d: m/z 580.24, 94% [1d + H - OH]+; 581.2, 14% [1d + H -
OH + 1]+; 597.3, 100% [1d + H]+; 598.3, 13% [1d + H + 1]+;
620, 31% [1d + Na]+; 621, 10% [1d + Na + 1]+. HR FAB MS
(NBA/PEG): m/z 596.2848 [1d]+, calcd for C30H44O12 596.2833,
error 2.5 ppm.
) 2 Hz, JHH ) 8 Hz, 2H), 7.57 (d, JHH ) 2 Hz, 2H), 7.35 (m,
3
3
10H), 6.90 (d, JHH ) 8 Hz, 2H), 5.17 (s, 4H), 4.21 (t, JHH ) 5
Hz, 4H), 3.87 (m, 10H), 3.72 (m, 4H), 3.61 (m, 4H). LR FAB MS
(NBA) of 10: m/z 558, 45% [10 - 2 COOCH3]+; 559, 13% [10 -
2 COOCH3 + 1]+; 560, 2% [10 - 2 COOCH3 + 2]+; 584, 40%
[10 - C6H5CH2]+; 585, 19% [10 + H - C6H5CH2]+; 586, 6% [10
+ H - C6H5CH2 + 1]+; 589, 26% [10 + Li - C6H5CH3]+; 590,
9% [10 + Li - C6H5CH3 + 1]+; 611, 9% [10 - OCH3
-
(24) Ouchi, M.; Inoue, Y.; Kanzaki, T.; Hakushi, T. J. Org. Chem. 1984,
49, 1408–1412.
(25) Fieser, M.; Fieser, L.; Smith, J. G. Reagents for Organic Synthesis;
Wiley: New York, 1967.
9100 J. Org. Chem. Vol. 73, No. 22, 2008

cis-Dicarbomethoxy-dibenzo-30-crown-10
Cryptand 12. To a solution of pyridine (2.0 mL) in CH2Cl2 (2.5
L) were added crown ether diol 1d (3.47 g, 5.82 mmol) in CHCl3
(40 mL) and pyridine-2,6-dicarbonyl chloride (1.18 g, 5.78 mmol)
in CHCl3 (40 mL) simultaneously with two separate syringes via a
syringe pump at 0.50 mL/h. After addition, the reaction mixture
was stirred at rt 5 days. The solvent was evaporated. The crude
product was redissolved in CHCl3 and washed with 10% H2SO4,
water, dried with Na2SO4, filtered, and concentrated via rotary
evaporation. The residue was subjected to neutral alumina column
chromatography, eluting with 1% MeOH in CHCl3. 12 was isolated
Example of ITC Titration Methods. Stock solutions of 12 (0.53
mM, 10 mL) and the titrant 3a (13.8 mM, 5 mL) in acetone were
prepared using volumetric glassware. All titrations were run at 22
°C. The high gain (high sensitivity) system was used, and the
reference offset was set at 50% of the maximum. During each
titration, 33 injections of 3.3 µL were made. Injections were made
every 180 s with a primary filter period of 2 s, and a secondary
filter period of 4 s. The switch time for the filter periods was at
120 s. After the titration isotherm was recorded, the raw data were
reduced using commercial software and the supplied algorithms
from the manufacturer. A control titration was also completed so
that the heat of dilution from the titrant could be subtracted from
the original titration isotherm. The parameters for the control
titration were the same as those used in the original titration with the
exception that the cell solution was replaced with pure acetone.
The control isotherm was integrated using the same method as the
original titration and the energy values obtained were subtracted
from the integrated point plot of the original titration. The
integration data from the titrations were fit using the “One Set of
Sites” model; other stoichiometries yielded unsatisfactory fits of
the data.
1
as a white solid (1.86 g, 44%), mp 160.9-162.7 °C; H NMR
3
3
(CDCl3, 400 MHz): δ 8.34 (d, JHH ) 8.0 Hz, 2 H), 8.03 (t, JHH
) 8.0 Hz, 1H), 6.95 (m, 4H), 6.78 (d, 3JHH ) 8.8 Hz, 2H), 5.34 (s,
4H), 4.17 (m, 4H), 4.01 (m, 4H), 3.93 (m, 4H), 3.81 (m, 4H), 3.75
(m, 4H), 3.70 (m, 8H), and 3.64 (m, 4H). LR FAB MS (NBA) of
crude 12 (before chromatography): m/z 561, 16% [1d - H2O -
OH or 12 - C7H5NO4]+; 562, 63% [1d + H - H2O - OH or 12
+ H - C7H5NO4]+; 563, 35% [1d + H - H2O - OH + 1 or 12
+ H - C7H5NO4+ 1]+; 564, 12% [1d + H - H2O - OH + 2 or
12 + H - C7H5NO4 + 2]+; 728, 65% [12]+; 729, 100% [12 +
H]+; 730, 47% [12 + H + 1]+; 731, 14% [12 + H + 2]+; 808,
93% [12 + C5H5NH]+; 809, 42% [12 + C5H5NH + 1]+; 810, 16%
[12 + C5H5NH + 2]+; LR FAB MS (NBA) of purified 12: m/z
728, 73% [12]+; 729, 100% [12 + H]+; 730, 40% [12 + H + 1]+;
731, 13% [12 + H + 2]+; HR FAB MS (NBA/PEG): m/z 727.2874
[12]+, calcd for C37H45NO14 727.2840, error 4.7 ppm.
Acknowledgment. We acknowledge financial support of this
research by the National Science Foundation through generous
grants DMR0097126 and DMR0704076.
FAB MS Determination of the Complex 12 ·3a. HR FAB MS
(NBA/PEG): m/z 1118.3832 [12·3a - PF6]+, calc. for C37H45NO14•
C14H18O2N2PF6, 1118.3850, error 1.6 ppm.
FAB MS Determination of the Complex 12 ·3b. HR FAB MS
(NBA/PEG): m/z 1058.3671 [12·3b - PF6]+, calc. for C37H45NO14•
C12H14N2PF6, 1058.3639, error 3.0 ppm.
FAB MS Determination of the Complex 12 ·4. HR FAB MS
(NBA/PEG): m/z 1056.3531 [12·4 - PF6]+, calc. for C37H45NO14•
C12H12N2PF6, 1056.3482, error 4.6 ppm.
Supporting Information Available: Characterizations for
all compounds and complexes (NMR, MS, ITC, 1D NOESY,
and X-ray diffraction data). This material is available free of
charge via the Internet at http://pubs.acs.org.
JO801886X
J. Org. Chem. Vol. 73, No. 22, 2008 9101