Formation of discrete, functional assemblies and informational polymers through the hydrogen-bonding preferences of calixarene aryl and sulfonyl tetraureas

Article abstract of DOI:10.1021/ja974091k

Derivatives of the calix[4]arenes in the cone conformation featuring either aryl urea or sulfonyl urea functions on their larger (upper) rims dimerize through hydrogen bonding to give molecular capsules. The capsules act as hosts that reversibly bind smal

Full text of DOI:10.1021/ja974091k

J. Am. Chem. Soc. 1998, 120, 3657-3663
3657
Formation of Discrete, Functional Assemblies and Informational
Polymers through the Hydrogen-Bonding Preferences of Calixarene
Aryl and Sulfonyl Tetraureas
Ronald K. Castellano†,‡ and Julius Rebek, Jr.*,‡
Contribution from the Department of Chemistry, Massachusetts Institute of Technology,
Cambridge, Massachusetts 02139, and The Skaggs Institute for Chemical Biology and Department of
Chemistry, The Scripps Research Institute, La Jolla, California 92037
ReceiVed December 2, 1997
Abstract: Derivatives of the calix[4]arenes in the cone conformation featuring either aryl urea or sulfonyl
urea functions on their larger (upper) rims dimerize through hydrogen bonding to give molecular capsules.
The capsules act as hosts that reversibly bind smaller molecule guests in organic media. Heterodimers form
when both aryl and sulfonyl ureas are present, and the heterodimers form exclusiVely with respect to the
homodimers. The heterodimerization encodes information at the molecular level and allows the predictable
formation of discrete aggregates of nanometer dimensions. Evidence for the reversible assembly of these
structures is provided by 1H NMR, guest encapsulation studies, and gel permeation chromatography. Covalent
attachment of these calixarene aryl and sulfonyl ureas at their smaller (lower) rims leads to polymeric assemblies
in which the informational content is preserved.
Introduction
Calixarenes with urea functions attached to their larger (upper)
rims dimerize reversibly in organic solvents and create capsules
(1‚1, Figure 1).1-3 This dimerization is driven by the formation
of intermolecular hydrogen bonds between urea functions in a
cyclic “head-to-tail” arrangement. Small-molecule guests of
suitable size and shape (e.g., benzene, camphor) are reversibly
encapsulated in these host spaces on a time scale that is slow
in NMR spectroscopic measurements. Covalent attachment of
two calixarene subunits at their smaller (lower) rims leads to
the formation of functional polymeric capsules, or polycaps.4
It has been observed that homodimeric capsules of aryl urea
derivatives (1a‚1a, Figure 2) and homodimeric capsules of
sulfonyl urea derivatives3a (1b‚1b) disproportionate to form
heterodimers (1a‚1b, hereinafter referred to as 2) exclusively.5
Two reasons for this preference come to mind. First, the
increased acidity of the sulfonyl urea -NH proton6 complements
the relative basicity of the aryl urea. Additionally, and perhaps
Figure 1. Calix[4]arene tetraurea derivatives dimerize through hy-
drogen bonds in a “head-to-tail” fashion to form capsules 1‚1. (Some
of the ureas have been omitted in the structure for clarity.)
more significantly, a NOESY spectrum of 2 (see the Supporting
Information) shows NOE contacts between the aryl groups of
both ureas in the heterodimer. These aryl-aryl interactions are
apparently stabilizing, since corresponding structures bearing
alkyl ureas show less than 10% heterodimerization with sulfonyl
urea partners.7 Whatever the cause, the selective dimerization
represents encoded information at the molecular level. We
report here the consequences of this information in the formation
of discrete molecular assemblies of nanometer dimensions8 and
those of a larger and polymeric scale.9
* Address correspondence to this author at The Scripps Research Institute.
† Massachusetts Institute of Technology.
‡ The Scripps Research Institute.
(1) (a) Shimizu, K. D.; Rebek, J., Jr. Proc. Natl. Acad. Sci. U.S.A. 1995,
92, 12403-12407. (b) Hamann, B. C.; Shimizu, K. D.; Rebek, J., Jr. Angew.
Chem., Int. Ed. Engl. 1996, 35, 1326-1329. (c) Castellano, R. K.;
Rudkevich, D. M.; Rebek, J., Jr. J. Am. Chem. Soc. 1996, 118, 10002-
10003.
(2) (a) Mogck, O.; Bo¨hmer, V.; Vogt, W. Tetrahedron 1996, 52, 8489-
8496. (b) Mogck, O.; Paulus, E. F.; Bo¨hmer, V.; Thondorf, I.; Vogt, W. J.
Chem. Soc., Chem. Commun. 1996, 2533-2534. (c) Mogck, O.; Pons, M.;
Bo¨hmer, V.; Vogt, W. J. Am. Chem. Soc. 1997, 119, 5706-5712.
(3) (a) Scheerder, J. The Complexation of Anions by Neutral Calixarenes
Derivatives. Thesis, University of Twente, Enschede, The Netherlands, 1995.
(b) Scheerder, J.; Vreekamp, R. H.; Engbersen, J. F. J.; Verboom, W.; van
Duynhoven, J. P. M.; Reinhoudt, D. N. J. Org. Chem. 1996, 61, 3476-
3481. (c) Vreekamp, R. H.; Verboom, W.; Reinhoudt, D. N. J. Org. Chem.
1996, 61, 4282-4288.
Results and Discussion
Formation of Discrete Assemblies. When the polycap
species 3a4 (Figure 3) is treated with a stoichiometric amount
(6) The pKa’s of aryl sulfonyl ureas are estimated to be between 5.5 and
7.5: Deprez, P.; Guillaume, J.; Becker, R.; Corbier, A.; Didierlaurent, S.;
Fortin, M.; Frechet, D.; Hamon, G.; Heckmann, B.; Heitsch, H.; Kleemann,
H.-W.; Vevert, J.-P.; Vincent, J.-C.; Wagner, A.; Zhang, J. J. Med. Chem.
1995, 38, 2357-2377.
(4) Castellano, R. K.; Rudkevich, D. M.; Rebek, J., Jr. Proc. Natl. Acad.
Sci. U.S.A. 1997, 94, 7132-7137.
(5) Castellano, R. K.; Kim, B. H.; Rebek, J., Jr. J. Am. Chem. Soc. 1997,
119, 12671-12672.
S0002-7863(97)04091-2 CCC: $15.00 © 1998 American Chemical Society
Published on Web 04/02/1998

3658 J. Am. Chem. Soc., Vol. 120, No. 15, 1998
Castellano and Rebek
Figure 2. Combination of aryl urea homodimer 1a‚1a and sulfonyl
urea derivative 1b‚1b gives exclusive formation of the corresponding
heterodimer 2 (all dimers shown with encapsulated solvent guest). Only
1
the downfield portions of the H NMR spectra in CDCl3 are shown.
Figure 4. Structures 2 and 4-6 form as well-defined, discrete
assemblies in CDCl3. The heterodimerization of aryl ureas with sulfonyl
ureas drives the assembly and the sharp traces observed in GPC analysis
suggest stable species.
Figure 3. Covalent attachment of two tetraurea calixarenes at their
lower rims gives new bifunctional subunits. These reversibly form
polymeric capsules or discrete assemblies with their complements in
solution.
of sulfonyl urea 1b5 in CDCl3, the “dumbbell” system 4 (Figure
Figure 5. Graphical depiction of the symmetry associated with
assemblies 4-6.
4) emerges. The assembly process occurs rapidly and is
1
complete within minutes of mixing. The H NMR spectrum
shows four singlets at low field corresponding to the four
different -NâH (Figure 1) protons of the sulfonyl urea portion
that caps the system.10 At first glance, only two singlets might
be anticipated from the symmetry of the assembly, but a closer
look reveals that the situation is more complicated. Certainly,
the centerpiece of the “dumbbell”, e.g. 3a, as a monomeric
species should (and does) show three signals for the -NâH urea
protons that reflect the structure’s plane of symmetry (depicted
as A in Figure 5, where three of the four substituents are
equivalent). Likewise, monomeric 1b shows one signal for
these protons (depicted as B in Figure 5, where all substituents
are equivalent). Upon assembly into a “dumbbell,” a sense of
directionality in the urea functions is introduced: the “head-
to-tail” arrangements of the ureas can be clockwise or coun-
terclockwise, giving rise to cycloenantiomers11 (C and C′) of
(7) Castellano, R. K.; Kim, B. H.; Rebek, J., Jr. Unpublished results.
(8) (a) Seto, C. T.; Whitesides, G. M. J. Am. Chem. Soc. 1993, 115,
905-916. (b) Seto, C. T.; Mathias, J. P.; Whitesides, G. M. J. Am. Chem.
Soc. 1993, 115, 1321-1329. (c) Seto, C. T.; Whitesides, G. M. J. Am. Chem.
Soc. 1993, 115, 1330-1340. (d) Mathias, J. P.; Seto, C. T.; Simanek, E.
E.; Whitesides, G. M. J. Am. Chem. Soc. 1994, 116, 1725-1736. (e)
Mathias, J. P.; Simanek, E. E.; Whitesides, G. M. J. Am. Chem. Soc. 1994,
116, 4326-4340. (f) Mammen, M.; Simanek, E. E.; Whitesides, G. M. J.
Am. Chem. Soc. 1996, 118, 12614-12623. (g) Simanek, E. E.; Li, X.; Choi,
I. S.; Whitesides, G. M. Cyanuric Acid and Melamine: A Platform for the
Construction of Soluble Aggregates and Crystalline Materials in Compre-
hensiVe Supramolecular Chemistry; Atwood, J. L., Davies, J. E. D.,
MacNicol, D. D., Vo¨gtle, F., Lehn, J.-M., Eds.; Pergamon: Oxford, U.K.,
1996; Vol. 9: Templating, Self-Assembly, and Self-Organization (Sauvage,
J.-P., Hosseini, N. W., Eds.), pp 595-622. (h) Simanek, E. E.; Isaacs, L.;
Li, X.; C, W. C. C.; Whitesides, G. M. J. Org. Chem. 1997, 62, 8994-
9000. (i) Reinhoudt, D. N.; Rudkevich, D. M.; Huck, W. T. S.; Kenis, P.
J. A.; Vreekamp, R. H. A Modular Approach to Large Functional Structures
in Modular Chemistry; Michl, J., Ed.; Kluwer Academic Publishers:
London, 1997; pp 575-585.
(9) (a) Kotera, M.; Lehn, J.-M.; Vigneron, J.-P. J. Chem. Soc., Chem.
Commun. 1994, 197-199. (b) Lange, R. F. M. Multiple Hydrogen Bonding
in Reversible Polymer Networks. Thesis, Eindhoven University of Technol-
ogy, Eindhoven, The Netherlands, 1997. (c) 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.
(10) These assignments are based on NOESY and ROESY spectra of 2.
See the Supporting Information for details.

Functional Assemblies and Informational Polymers
J. Am. Chem. Soc., Vol. 120, No. 15, 1998 3659
Scheme 1
the complex. When these pictorial representations are applied
to the analysis of 4-6, it becomes apparent that each urea in
these assemblies is in a magnetically inequivalent environment,
and a total of 16 urea protons can be observed in their respective
1H NMR spectra (eight from the centerpiece and eight from
the caps).12 The peak at 9 ppm arises from the amide -NH
resonance of the central spacer where X ) p-C6H4 (Figure 3).
Figure 6. Discrete assemblies 2 and 4-6 encapsulate a polycyclic
1
guest 20. Their H NMR spectra in p-xylene-d10 show the expected
-NâH resonances at low field and several strongly shielded resonances
from the encapsulated guest.
Through synthetic methods similar to those devised for 3a,
the bis(tetrasulfonyl urea) 3b was prepared (Scheme 1). Phenol
7 was prepared from the parent p-tert-butylcalix[4]arene via
alkylation with 1-iododecane using a procedure described by
Shinkai and co-workers.13 Subsequent alkylation with ethyl
bromoacetate, nitration, and reduction yielded the tetraamine
10. Treatment of the amine with p-toluenesulfonyl isocyanate
followed by saponification of the ethyl ester gave the versatile
intermediate acid 12. Finally, coupling of 2 equiv of the acid
to 1,8-diaminooctane using PyBOP14 provided 3b in good yield.
Addition of 2 equiv of 1a to this polymeric species gives the
inverted “dumbbell” 5 (Figure 4), in which the central sulfonyl
ureas are capped by aryl ureas. Again, no other species can be
Scheme 2
triacid 15 to give the complete centerpiece of assembly 6, shown
in Scheme 3 as 19. Addition of CDCl3 to this compound
produces an uncharacterized insoluble gel, presumably through
the formation of cross-linked polycaps. In contact with aromatic
solvents such as benzene and p-xylene, it exists as an insoluble
powder. Nonetheless, sonication of 1b with the gel in CDCl3
yields a homogeneous solution, and the capped derivative 6
emerges as the only species detectable by 1H NMR (Figure 4).
Again the characteristic four signals for the -NâH protons of
the cap are observed.
1
detected in the H NMR spectrum.
More complicated systems follow in two-dimensional as-
semblies, as in 6 (Figure 4). The components of this system
are derived from 1,3,5-triethynylbenzene 13, which was made
through known acetylene coupling chemistry from 1,3,5-
tribromobenzene.15 Subsequent coupling to ethyl 4-iodoben-
zoate (Scheme 2) using Sonogashira’s conditions16 gave the
corresponding triester 14, which was then saponified to afford
the rigid, C3-symmetric triacid 15. The calixarene subunit of 6
was prepared as shown in Scheme 3. The previously described
monoacid 164 was coupled to mono-BOC-protected p-xylylene-
diamine17 with PyBOP to give 17. Deprotection with HCl(g)
gave the amine salt 18, which was subsequently coupled to the
Further Characterization: Guest Encapsulation and GPC
Analysis. Functional characterization of these systems involved
the study of their guest encapsulation behavior, and physical
characterization was possible through the use of gel permeation
chromatography (GPC) analysis. Addition of the pentacyclic
dione 20 (Figure 6) to solutions of 2 and 4-6 in p-xylene-d10
(11) (a) Prelog, V.; Gerlach, H. HelV. Chim. Acta 1964, 47, 2288-2294.
(b) Yamamoto, C.; Okamoto, Y.; Schmidt, T.; Ja¨ger, R.; Vo¨gtle, F. J. Am.
Chem. Soc. 1997, 119, 10547-10548 and references therein.
(12) The spectra of 4-6 in Figure 4 are quite sharp although they
represent diastereomers of the complexes which differ by the clockwise/
counterclockwise array of the ureas on their ends. Apparently this level of
information is not communicated between the ends of the assemblies.
(13) Iwamoto, K.; Araki, K.; Shinkai, S. J. Org. Chem. 1991, 56, 4955-
4962.
1
shows upfield encapsulated guest resonances by H NMR. In
all cases the anticipated stoichiometry of the guest is observed,
i.e. one guest molecule for 2, two for either 4 or 5, etc.
Assembly 6 is the most complex, as it is comprised of four
molecules as the host species and three guest molecules.
(14) Coste, J.; Le-Nguyen, D.; Castro, B. Tetrahedron Lett. 1990, 31,
205-208.
Whitesides and co-workers have introduced the application
of GPC in the characterization of discrete hydrogen-bonded
(15) Weber, E.; Hecker, M.; Koepp, E.; Orlia, W.; Czugler, M.; Cso¨regh,
I. J. Chem. Soc., Perkin Trans. 2 1988, 1251-1257.
(16) Takahashi, S.; Kuroyama, Y.; Sonogashira, K.; Hagihara, N.
Synthesis 1980, 627-630.
(17) Smith, J.; Liras, J. L.; Schneider, S. E.; Anslyn, E. V. J. Org. Chem.
1996, 61, 8811-8818.

3660 J. Am. Chem. Soc., Vol. 120, No. 15, 1998
Castellano and Rebek
Scheme 3
Figure 8. Aryl urea polycaps (a) and sulfonyl urea polycaps (b) in
CDCl3 disproportionate to give alternating subunits (c). The self-
complementary subunit 3c in CDCl3 assembles as polycaps of predict-
able “head-to-tail” sequence (d). Only the downfield portion of the 1H
NMR spectra in CDCl3 is shown.
Figure 7. Linear correlation between molecular weight and retention
time is observed for a variety of standards (filled squares). Assemblies
2 and 4-6 deviate slightly from the calibration line due, in part, to
differences in shape and functional groups.
of 3a,b should lead to polycaps of alternating subunits. Figure
8c shows the result of the experiment; indeed, only -NâH
resonances from the aryl urea-sulfonyl urea interaction are
observed in the 1H NMR spectrum clustered around 10.6 ppm.
Likewise, the self-complementary derivative, 3c, is expected
to polymerize “head-to-tail” with alternating aryl urea and
sulfonyl urea rims. This system was prepared from combination
of amine 18 with acid 22 ()12 with propyl rather than decyl
chains on the lower rim). Acid 22 was made from its
corresponding ethyl ester 21, available in one step from the
known tetraamine.4 Polycaps do in fact form in this system
(Figure 8d), and the spectrum closely resembles that of the
alternating 3a‚3b (Figure 8c). Again, no telltale signals for
capsules of the aryl urea-aryl urea neighbors are detectable by
1H NMR. Unfortunately, GPC studies on these systems are
less reliable as their molecular weights exceed the exclusion
limit of the GPC column.19
complexes.8 This method offers information regarding ag-
gregate stability and, in some cases, molecular weight. Struc-
tures 2 and 4-6 give sharp GPC traces (Figure 4) in CHCl3
reflecting their relative stability versus, for example, dimers
1a‚1a and 1b‚1b, which offer broader traces (see the Supporting
Information). To correlate retention time with molecular weight,
a standardization curve (Figure 7) was obtained from eight
polystyrene standards, three monomeric calixarene derivatives,
and two substituted benzenes (see the Supporting Information
for structures). Although assemblies 2 and 4-6 fall slightly
off the calibration line, their homology makes their retention
times reliably consistent and gives further evidence for the
assignment of structure.18
“Smart” Polymers. The information offered by the aryl
urea-sulfonyl urea heterodimerization can be used for pro-
grammed, or “smart” polymers (Figure 8). As previously
reported,4 calixarene 3a forms linear polycaps in organic
solvents (Figure 8a), as does 3b (Figure 8b). Representative
1H NMR spectra show the -NâH protons of each clustered
around 9.4 and 10.2 ppm, respectively. The heterodimerization
tendency of aryl and sulfonyl ureas predicts that a combination
Outlook. The preference of the aryl urea-sufonyl urea
associations represents information in the sense of a binary code.
As such, it suggests a new type of informational polymer that
differs from those found in nature. We will report on the
development of such systems in due course.
(19) The exclusion limit of the column used is ≈30 kDa (based on
polystyrene standards), which corresponds to a retention time on the order
of 6.3 min. Beyond this point there no longer exists a linear correlation
between molecular weight and retention time. All of the polymeric systems
investigated have retention times below this limit, thereby precluding
molecular weight assignments. Additionally, polycap traces tended to be
prohibitively broad, preventing even direct comparison to polystyrene
standards.
(18) Differences in both shape and functional groups from the standards
make the rentention times of assemblies 2 and 4-6 necessarily deviate from
the standard calibration line. These assemblies are, however, similar to each
other in these regards, making molecular weight estimations reasonable,
although only in a comparative sense (see ref 8).

Functional Assemblies and Informational Polymers
J. Am. Chem. Soc., Vol. 120, No. 15, 1998 3661
for 14 h. Most of the solvent was removed in vacuo, and the residue
was dissolved in CHCl3 (200 mL). The organic layer was washed with
1 M HCl (250 mL) and water (250 mL) and dried over MgSO4.
Following filtration and concentration, the resulting oil was dried under
high vacuum. The oil was dissolved in a minimum amount of 60:1
hexanes/EtOAc and added to a SiO2 column (800 mL) and eluted with
50:1 hexanes/EtOAc (Rf ) 0.36). The desired product (8.0 g, 88%)
was isolated as a clear, colorless oil: 1H NMR (300 MHz, CDCl3) δ
6.91 (s, 2H), 6.90 (s, 2H), 6.63 (m, 4H), 4.85 (s, 2H), 4.67 (d, 2H, J
) 12.7 Hz), 4.38 (d, 2H, J ) 12.4 Hz), 4.18 (q, 2H, J ) 7.1 Hz),
3.87-3.71 (m, 6H), 3.16 (d, 2H, J ) 13.0 Hz), 3.12 (d, 2H, J ) 12.6
Hz), 2.10 (m, 2H), 1.93 (m, 4H), 1.37-1.18 (m, 45H), 1.18 (s, 9H),
1.17 (s, 9H), 0.97 (s, 18H), 0.90-0.86 (m, 9 H); 13C NMR (CDCl3) δ
170.90, 154.21, 153.52, 153.43, 144.88, 144.61, 144.21, 134.77, 134.27,
133.21, 133.04, 125.52, 125.14, 124.79, 124.76, 75.62, 75.38, 70.60,
60.13, 33.82, 33.80, 33.60, 31.91, 31.88, 31.53, 31.48, 31.42, 31.23,
30.88, 30.41, 30.29, 30.07, 29.94, 29.85, 29.81, 29.73, 29.69, 29.39,
29.33, 26.28, 26.19, 22.61, 14.13, 14.00; IR (thin film) 2956, 2924,
2854, 1766, 1481, 1467, 1361, 1200, 1072, 870 cm-1; HRMS (FAB;
M + Cs+) calcd for C78H122O6Cs 1287.8296, found 1287.8359.
5,11,17,23-Tetranitro-25,26,27-tris(decyloxy)-28-[(ethoxycarbonyl)-
methoxy]calix[4]arene (9). The calixarene 8 (7.95 g, 6.88 mmol) was
dissolved in CH2Cl2 (100 mL) and glacial acetic acid (100 mL). To
this colorless solution was added fuming HNO3 (30 mL), resulting in
a color change to an opaque purple/black. After 2 h, the clear yellow/
orange solution was treated with water (250 mL) and stirred for 10
min. The organic layer was separated off, washed with water (300
mL), dried over MgSO4, and filtered. Evaporation of the filtrate to
dryness gave a yellow oil which upon trituration with MeOH yielded
5.83 g (5.52 mmol, 76%) of the desired product as a pale yellow
powder: 1H NMR (300 MHz, CDCl3) δ 7.82 (s, 4H), 7.34 (m, 4H),
4.75 (s, 2H), 4.75 (d, 2H, J ) 14.2 Hz), 4.51 (d, 2H, J ) 13.9 Hz),
4.22 (q, 2H, J ) 7.2 Hz), 4.02-3.88 (m, 6H), 3.45 (d, 2H, J ) 15.2
Hz), 3.40 (d, 2H, J ) 15.4 Hz), 1.89-1.85 (m, 6H), 1.56-1.27 (m,
45H), 0.90-0.86 (m, 9H); 13C NMR (CDCl3) δ 168.68, 162.37, 161.34,
161.01, 143.36, 143.00, 136.08, 135.92, 134.94, 134.83, 124.61, 124.46,
123.74, 123.73, 76.47, 76.43, 70.53, 61.17, 31.79, 31.30, 30.94, 30.13,
30.02, 29.72, 29.64, 29.60, 29.55, 29.26, 29.24, 26.00, 25.71, 22.55,
14.05, 13.95; IR (thin film) 2926, 2854, 1770, 1585, 1522, 1462, 1347,
1188, 1096, 900, 745 cm-1; HRMS (FAB; M + Cs+) calcd for
C62H86N4O14Cs 1243.5195, found 1243.5261.
5,11,17,23-Tetraamino-25,26,27-tris(decyloxy)-28-[(ethoxycarbonyl)-
methoxy]calix[4]arene (10). To the tetranitro compound 9 (0.15 g,
0.13 mmol) in toluene (20 mL) was added Raney nickel (cat.) under
H2 (atm). The mixture was heated to 50 °C for 1.5 h prior to filtration
through a Celite pad. Concentration of the filtrate to dryness yielded
the reduction product as a brown solid which was used without further
purification (0.0903 g, 69%): 1H NMR (300 MHz, CDCl3) δ 6.26 (s,
2H), 6.24 (s, 2H), 5.87 (s, 4H), 4.64 (s, 2H), 4.52 (d, 2H, J ) 13.4
Hz), 4.30 (d, 2H, J ) 13.1 Hz), 4.16 (q, 2H, J ) 7.1 Hz), 3.82-3.64
(m, 6H), 3.18 (s, 8H), 2.97 (d, 4H, J ) 13.7 Hz), 2.91 (d, 4H, J )
13.3 Hz), 1.83-1.79 (m, 6H), 1.42-1.24 (m, 45H), 0.90-0.86 (m,
9H); 13C NMR (CDCl3) δ 170.70, 150.53, 149.49, 149.34, 140.86,
140.67, 140.42, 136.54, 136.26, 134.72, 134.64, 115.88, 115.73, 115.52,
75.26, 75.17, 70.14, 59.92, 31.79, 31.77, 31.32, 30.90, 30.07, 30.03,
29.84, 29.76, 29.71, 29.69, 29.58, 29.26, 29.22, 26.26, 25.99, 22.51,
14.04, 13.90; IR (thin film) 3350, 2924, 2853, 1765, 1608, 1468, 1379,
1216, 1184, 1078, 853 cm-1; HRMS (FAB; M + Cs+) calcd for
C62H94N4O6Cs 1123.6228, found 1123.6279.
Experimental Section
General. All chemicals were used without further purification unless
otherwise specified. Proton (1H) NMR spectra were recorded on Bruker
DRX-600 (600 MHz) or AM-300 (300 MHz) spectrometers. Carbon
(13C) spectra were recorded on a Bruker DRX-600 (151 MHz)
spectrometer. IR spectra were recorded on a Perkin-Elmer Paragon
1000PC FT-IR spectrometer. The fast atom bombardment (FAB)
positive ion mass spectra were obtained on a VG ZAB-VSE double-
focusing high-resolution mass spectrometer equipped with a cesium
ion gun. Matrix-assisted laser desorption/ionization (MALDI) mass
spectrometry experiments were performed on a PerSeptive Biosystems
Voyager-Elite mass spectrometer with delayed extraction. Electrospray
ionization (ESI) mass spectrometry experiments were performed on
an API III Perkin-Elmer SCIEX triple-quadrupole mass spectrometer.
Dichloromethane (CH2Cl2) and tetrahydrofuran (THF) were passed
through columns of activated aluminum oxide as described by Grubbs
and co-workers20 prior to use.
GPC Measurements. GPC measurements were performed using a
TosoHaas (Montgomeryville, PA) G3000-HHR column (no. 17355)
equipped with a HHR-L guard column (no. 17368). HPLC-grade
chloroform was purchased from Aldrich Chemical Co. and used without
further purification. The column was connected to a Waters HPLC
system equipped with a 717 autosampler, 600 controller, and 996
photodiode array (PDA) detector. GPC traces are shown within the
wavelength range 245-265 nm. Representative samples were injected
with toluene as a standard (retention time in CHCl3 ) 12.2 min).
Retention times given for 2 and 4-6 are the average of three to five
runs. All polystyrene standards were purchased from Aldrich Chemical
Co. with the exception of MW 5970 and 9100, which were purchased
from TosoHaas.
5,11,17,23-Tetra-tert-butyl-25,26,27-tris(decyloxy)-28-hydroxycalix-
[4]arene (7).13 A 500-mL round-bottomed flask was charged with the
parent p-tert-butylcalixarene (10.0 g, 15.4 mmol), Ba(OH)2‚8H2O (17
g, 54 mmol), BaO (16 g, 24 mmol), and DMF (200 mL). The alkylating
agent, 1-iododecane (100 mL, 462 mmol), was then added, and the
resulting mixture was vigorously stirred at room temperature. After
24 h, TLC (70:1 hexanes/EtOAc) revealed a complex mixture. The
DMF was removed in vacuo, and the remaining residue was partitioned
between CHCl3 (300 mL) and water (300 mL) and stirred for several
minutes. The organic layer was separated, washed with water (500
mL), dried over MgSO4, and filtered. Concentration of the filtrate gave
the product as a solution in excess 1-iododecane. This solution was
added directly to an SiO2 column (800 mL) to remove the excess reagent
(hexanes f 70:1 hexanes/EtOAc). All fractions containing the desired
product (Rf ) 0.3) were combined and concentrated to a yellow oil.
The oil was again subjected to SiO2 chromatography (70:1 Hex/EtOAc,
1200 mL). Fractions containing only the desired product were
combined and evaporated to give the pure product as a viscous, pale
yellow oil (9.65 g, 59%): 1H NMR (600 MHz, CDCl3) δ 7.13 (s, 2H),
7.05 (s, 2H), 6.52 (d, 2H, J ) 2.3 Hz), 6.51 (d, 2H, J ) 2.4 Hz), 5.72
(s, 1H), 4.37 (d, 2H, J ) 12.6 Hz), 4.33 (d, 2H, J ) 13.1 Hz), 3.89 (m,
2H), 3.78 (m, 4H), 3.23 (d, 2H, J ) 13.2 Hz), 3.16 (d, 2H, J ) 12.6
Hz), 2.30 (m, 2H), 1.98-1.84 (m, 4H), 1.37-1.18 (m, 42H), 1.33 (s,
9H), 1.33 (s, 9H), 0.90-0.88 (m, 9 H), 0.83 (s, 18H); 13C NMR (CDCl3)
δ 154.14, 151.95, 150.86, 145.51, 145.06, 141.35, 136.11, 132.34,
132.00, 129.45, 125.64, 125.01, 124.80, 124.70, 76.34, 74.87, 34.02,
33.73, 33.55, 31.93, 31.86, 31.67, 31.59, 31.50, 31.25, 31.03, 30.97,
30.23, 29.99, 29.75, 29.64, 29.62, 29.40, 29.28, 26.24, 26.16, 22.64,
22.60, 22.55, 14.01; IR (thin film) 3545, 2956, 2924, 2854, 1483, 1467,
1362, 1202, 871 cm-1; HRMS (FAB; M + Cs+) calcd for C74H116O4-
Cs 1201.7928, found 1201.7997.
5,11,17,23-Tetrakis(tosylurea)-25,26,27-tris(decyloxy)-28-[(ethoxy-
carbonyl)methoxy]calix[4]arene (11). The tetraamino compound 10
(0.090 g, 0.091 mmol) was dissolved in dry CH2Cl2 (15 mL) under
N2. To the homogeneous solution was added p-toluenesulfonyl
isocyanate (70 µL, 0.46 mmol), and the reaction was stirred at room
temperature for 4 h. The solvent was then removed in vacuo, and the
resulting solid was triturated with MeOH. This process was repeated,
and the resulting suspension was filtered. The urea (0.145 g, 90%)
was used without further purification: H NMR (600 MHz, DMF-d7) δ
10.39 (bs, 2H), 10.26 (bs, 2H), 8.67 (s, 1H), 8.66 (s, 1H), 8.44 (s, 2H),
7.97 (d, 4H, J ) 8.2 Hz), 7.93 (d, 4H, J ) 8.3 Hz), 7.49 (d, 4H, J )
8.2 Hz), 7.46 (d, 4H, J ) 8.2 Hz), 6.89 (s, 2H), 6.88 (s, 2H), 6.54 (s,
5,11,17,23-Tetra-tert-butyl-25,26,27-tris(decyloxy)-28-[(ethoxycar-
bonyl)methoxy]calix[4]arene (8). The alcohol 7 was suspended in
anhydrous DMF (20 mL) and THF (80 mL) under N2 prior to the
addition of 1.3 g (31 mmol) of NaH (60% dispersion in mineral oil).
The mixture was heated to 50 °C for 1 h to effect complete
deprotonation. To the cloudy mixture was added ethyl bromoacetate
(3.5 mL, 31 mmol), and stirring was continued at the above temperature
(20) Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.;
Timmers, F. J. Organometallics 1996, 15, 1518-1520.

3662 J. Am. Chem. Soc., Vol. 120, No. 15, 1998
Castellano and Rebek
4H), 4.74 (s, 2H), 4.58 (d, 2H, J ) 13.3 Hz), 4.34 (d, 2H, J ) 13.0
Hz), 3.84 (m, 2H), 3.81-3.72 (m, 4H), 3.08 (d, 2H, J ) 14.0 Hz),
3.06 (d, 2H, J ) 13.6 Hz), 2.45 (s, 6H), 2.44 (s, 6H), 1.92-1.84 (m,
6H), 1.46-1.24 (m, 44H), 1.25 (t, 3H, J ) 7.2 Hz), 0.91-0.86 (m,
9H); 13C NMR (DMF-d7) δ 170.88, 153.87, 153.41, 152.99, 150.48,
145.23, 145.17, 138.77, 138.73, 136.44, 136.29, 135.40, 135.32, 133.82,
133.52, 133.20, 130.54, 130.50, 128.88, 128.84, 120.48, 120.45, 120.29,
120.24, 76.20, 71.42, 60.97, 32.67, 32.65, 32.03, 31.54, 30.97, 30.91,
30.76, 30.65, 30.60, 30.51, 30.49, 30.13, 27.17, 26.99, 23.33, 21.52,
14.66, 14.46; IR (thin film) 3350, 2924, 2854, 1762, 1694, 1599, 1550,
1464, 1343, 1218, 1162, 1091, 895, 667 cm-1; LRMS (ESI; M + Na+
fractions gave the product as a pale yellow powder (0.181 g, 23%):
1H NMR (300 MHz, CDCl3) δ 8.05 (d, 6H, J ) 6.7 Hz), 7.71 (s, 3H),
7.59 (d, 6H, J ) 6.8 Hz), 4.40 (q, 6H, J ) 7.2 Hz), 1.41 (t, 9H, J )
7.2 Hz); 13C NMR (CDCl3) δ 166.11, 134.66, 131.66, 130.35, 129.64,
127.22, 123.82, 90.23, 90.05, 61.17, 14.18; IR (thin film) 2983, 2890,
2247, 1715, 1695, 1604, 1404, 1366, 1307, 1276, 1175, 1128, 1107,
1019, 918, 768, 732 cm-1; HRMS (FAB; M + H+) calcd for C39H31O6
595.2121, found 595.2140.
4-{2-{3,5-Bis[2-(4-carboxyphenyl)-1-ethynyl]phenyl}-1-ethynyl}-
benzoic acid (15). The ester 14 (0.150 g, 0.252 mmol) was dissolved
in a mixture of THF (4 mL) and H2O (0.6 mL). To this was added
LiOH‚H2O (0.212 g, 5.04 mmol), and the mixture was stirred at room
temperature. H2O (2 mL) was added over the course of several hours
as the ester reacted and solubility increased. After 14 h, the reaction
was determined complete by TLC (EtOAc). The solution was poured
into 40 mL of H2O and acidified with 1 M HCl. Evaporation of all
solvents gave the crude product (0.138 g, quantitative) as a tan powder.
Trituration with MeOH gave the pure triacid as a white powder (0.063
g, 49%): 1H NMR (600 MHz, DMSO-d6) δ 13.22 (bs, 3H), 8.00 (d,
6H, J ) 8.3 Hz), 7.88 (s, 3H), 7.72 (d, 6H, J ) 8.3 Hz): 13C NMR
(DMSO-d6) δ 166.91, 134.67, 131.95, 131.19, 129.81, 126.14, 123.54,
90.34, 89.88; IR (thin film) 3007 (b), 2209, 1723, 1693, 1605, 1581,
1558, 1417, 1312, 1280, 1176, 1108, 1017, 877, 857, 770 cm-1. LRMS
(ESI; M - H) calcd for C33H18O6 509, found 509.
+
13C) calcd for C94H122N8O18S4Na 1752, found 1752.
5,11,17,23-Tetrakis(tosylurea)-25,26,27-tris(decyloxy)-28-(carboxy-
methoxy)calix[4]arene (12). The ester 11 (0.139 g, 0.0778 mmol)
was dissolved in a mixture of THF (7.5 mL) and water (1.5 mL). To
this suspension was added LiOH‚H2O (0.065 g, 1.6 mmol), and the
mixture was stirred at room temperature for 18 h. After this period,
the resulting solution was poured into 50 mL of water and treated with
1 M HCl until strongly acidic. The tan precipitate was filtered and
washed with water, yielding 0.123 g (0.0702 mmol, 90%) of the crude
acid: 1H NMR (600 MHz, DMF-d7) δ 12.65 (bs, 1H), 10.38 (bs, 2H),
10.30 (bs, 2H), 8.64 (s, 1H), 8.61 (s, 1H), 8.53 (s, 2H), 7.96 (d, 4H, J
) 8.3 Hz), 7.94 (d, 4H, J ) 8.3 Hz), 7.48 (d, 4H, J ) 7.8 Hz), 7.47
(d, 4H, J ) 7.8 Hz), 6.80 (s, 4H), 6.68 (s, 4H), 4.63 (s, 2H), 4.54 (d,
2H, J ) 13.2 Hz), 4.36 (d, 2H, J ) 12.9 Hz), 3.89-3.77 (m, 6H), 3.09
(d, 2H, J ) 13.2 Hz), 3.07 (d, 2H, J ) 12.9 Hz), 2.45 (s, 6H), 2.45 (s,
6H), 1.91-1.85 (m, 6H), 1.41-1.23 (m, 43H), 0.88-0.86 (m, 9H);
13C NMR (DMF-d7) δ 171.37, 153.08, 152.81, 152.24, 149.98, 149.95,
144.64, 138.21, 135.58, 135.40, 135.23, 135.11, 133.30, 132.93, 132.80,
129.97, 128.30, 128.29, 119.91, 119.87, 119.79, 75.80, 71.13, 32.14,
32.12, 31.44, 31.00, 30.34, 30.21, 30.15, 30.10, 30.06, 30.03, 29.94,
29.61, 26.50, 26.45, 22.79, 20.97, 13.93; IR (thin film) 3350, 2925,
2854, 1706, 1599, 1552, 1466, 1341, 1218, 1163, 1090, 1055, 894,
664 cm-1; LRMS (ESI; M + H+) calcd for C92H119N8O18S4 1752, found
1752.
BOC-Protected Calixarene (17). The acid 164 (0.543 g, 0.353
mmol) was dissolved in anhydrous DMF (10 mL) under N2. To this
solution was added PyBOP (0.221 g, 0.424 mmol), triethylamine (59
µL, 0.42 mmol), and mono-BOC-protected p-xylylenediamine17 (0.10
g, 0.424 mmol). After the mixture was stirred at room temperature
for 1 h, most of the DMF was removed in vacuo and the resulting
brown oil was diluted with CH2Cl2 (50 mL). This solution was washed
with 1 M NaOH (2 × 50 mL) and brine (2 × 50 mL). The combined
organic extracts were dried over MgSO4, filtered, and concentrated to
near dryness. Trituration with MeOH gave the product as an off-white
powder (0.504 g, 81%): 1H NMR (600 MHz, DMF-d7) δ 8.80 (t, 1H,
J ) 6.0 Hz), 8.60 (bs, 2H), 8.58 (s, 1H), 8.55 (s, 1H), 8.34 (s, 2H),
8.30 (s, 2H), 7.44 (d, 2H, J ) 8.5), 7.43 (d, 2H, J ) 8.5), 7.38 (d, 2H,
J ) 8.0 Hz), 7.34 (d, 2H, J ) 8.1 Hz), 7.28 (t, 1H, J ) 6.0 Hz), 7.26
(d, 4H, J ) 8.5 Hz), 7.20 (s, 2H), 7.18 (s, 2H), 7.13 (d, 2H, J ) 8.5
Hz), 7.12 (d, 2H, J ) 8.6 Hz), 7.05 (d, 4H, J ) 8.5 Hz), 6.63 (bs, 4H),
4.79 (s, 2H), 4.69 (d, 2H, J ) 5.9 Hz), 4.51 (d, 2H, J ) 13.5 Hz), 4.43
(d, 2H, J ) 13.2 Hz), 4.26 (d, 2H, J ) 6.2 Hz), 3.90 (m, 2H), 3.80-
3.74 (m, 4H), 3.24 (d, 2H, J ) 13.8 Hz), 3.18 (d, 2H, J ) 13.5 Hz),
2.56-2.51 (m, 8H), 1.87 (m, 2H), 1.74 (m, 4H), 1.57 (m, 8H), 1.41 (s,
9H), 1.32-1.24 (m, 32H), 0.93 (t, 3H, J ) 7.4 Hz), 0.90 (t, 6H, J )
7.4 Hz), 0.88-0.85 (m, 12H); 13C NMR (DMF-d7) δ 170.42, 156.71,
153.55, 153.51, 153.39, 153.12, 152.25, 150.95, 139.80, 138.74, 138.66,
138.61, 138.59, 136.44, 136.38, 136.33, 135.96, 135.09, 134.98, 134.86,
134.59, 133.83, 129.01, 128.86, 127.81, 127.38, 119.64, 119.45, 119.23,
119.06, 118.69, 118.67, 118.32, 78.16, 77.56, 76.62, 74.74, 43.89, 42.23,
35.13, 32.03, 31.93, 31.59, 29.33, 29.27, 28.17, 23.11, 22.93, 22.74;
IR (thin film) 3339, 3189, 3119, 2957, 2926, 2854, 1718, 1667, 1605,
1552, 1514, 1476, 1418, 1316, 1214, 1052, 1002, 848 cm-1; HRMS
(FAB; M + Cs+) calcd for C108H142N10O11Cs 1887.9914, found
1887.9993.
1,8-Bis{5,11,17,23-tetrakis(tosylurea)-25,26,27-tris(decyloxy)-28-
[(aminocarbonyl)methoxy]calix[4]arene}octane (3b). The above acid
12 (0.0742 g, 0.0423 mmol) was dissolved in anhydrous DMF (3 mL)
under N2. To this solution was added PyBOP14 (0.033 g, 0.064 mmol),
triethylamine (35 µL, 0.254 mmol), and 1,8-diaminooctane (0.0029 g,
0.020 mmol). The reaction solution was stirred for 14 h at 35 °C.
Most of the DMF was removed in vacuo, and the resulting yellow oil
was diluted to 20 mL with CHCl3. This solution was washed with 1
M HCl (2 × 30 mL) and brine (2 × 30 mL). The combined organic
extracts were dried over MgSO4, filtered, and concentrated to dryness.
Trituration with MeOH gave the product as a beige powder (0.0495 g,
68%): 1H NMR (600 MHz, DMF-d7) δ 10.33 (bs, 8H), 8.59 (s, 4H),
8.58 (s, 2H), 8.54 (s, 2H), 7.96 (d, 8H, J ) 8.1 Hz), 7.94 (d, 8H, J )
8.3 Hz), 7.48-7.44 (m, 16H), 6.74 (s, 8H), 6.68 (s, 4H), 6.67 (s, 4H),
4.41 (d, 4H, J ) 13.3 Hz), 4.37 (s, 4H), 4.33 (d, 4H, J ) 12.9 Hz),
3.96-3.92 (m, 4H), 3.88-3.84 (m, 4H), 3.76 (m, 4H), 3.31-3.29 (m,
4H), 3.11 (d, 4H, J ) 13.5 Hz), 3.07 (d, 4H, J ) 13.3 Hz), 2.44 (s,
12H), 2.44 (s, 12H), 1.91-1.82 (m, 16H), 1.50 (m, 8H), 1.35-1.30
(m, 82H), 0.88-0.86 (m, 18H); IR (thin film) 3342, 2924, 2853, 1686,
1608, 1555, 1458, 1340, 1225, 1090, 1055, 892 cm-1
.
Ethyl 4-{2-{3,5-Bis{2-[4-(ethoxycarbonyl)phenyl]-1-ethynyl}-
phenyl}-1-ethynyl}benzoate (14).16 To a solution of ethyl 4-iodo-
benzoate (0.89 mL, 5.3 mmol) in diethylamine (25 mL) was added
Pd(PPh3)2Cl2 (0.047 g, 0.067 mmol) and CuI (0.038 g, 0.20 mmol)
under N2. The resulting green mixture was treated with triethynyl-
benzene15 (0.195 g, 1.33 mmol) and stirred at room temperature. After
30 min, the solution assumed a bright yellow color which gradually
changed to orange over the course of several hours.
BOC Deprotection (18). To a solution of the protected amine 17
(0.30 g, 0.17 mmol) in dioxane (30 mL) was bubbled HCl(g). After
20 min, the precipitation of a solid was observed and the deprotection
was determined complete after 50 min by TLC (20:1 CH2Cl2/MeOH).
The solvent was removed in vacuo, giving the crude amine salt which
was used without further purification (0.288 g, 99%): HRMS (FAB;
M + Cs+ - HCl) calcd for C103H134N10O9Cs 1787.9390, found
1787.9497.
After 20 h, the reaction was deemed near completion by TLC (5:1
hexanes/EtOAc; desired product Rf ) 0.4). The DEA was removed in
vacuo, and the residue was dissolved in CH2Cl2 (70 mL) and washed
with water (100 mL). The aqueous layer was back-extracted with CH2-
Cl2 (3 × 25 mL), and the combined organic layers were dried over
MgSO4 and filtered. To the filtrate was added 10 mL of SiO2 and the
solvent was removed. The preload was added to a 150-mL SiO2 column
and eluted with 6:1 hexanes/EtOAc. Evaporation of the desired
Coupling of 18 to the C3-Symmetric Spacer (19). To a solution
of the triacid 15 (0.027 g, 0.053 mmol) and PyBOP (0.088 g, 0.17
mmol) in DMF (5 mL) was added a solution of the amine 18 (0.288 g,
0.170 mmol) and NEt3 (89 uL, 0.64 mmol) in DMF (5 mL). The
homogeneous solution was stirred at room temperature for 5 h, when
the reaction was determined complete by TLC (20:1 CH2Cl2/MeOH).
The DMF was removed in vacuo, and the residue was dissolved in
CH2Cl2. Washing with 1 M HCl (2 × 30 mL) yielded an emulsion.

Functional Assemblies and Informational Polymers
J. Am. Chem. Soc., Vol. 120, No. 15, 1998 3663
Additional washing with 1 M NaOH and brine did not yield a clean
separation. The combined aqueous extracts containing the emulsion
were treated with THF, and the resulting clear, biphasic mixture was
separated off. All of the organic layers were combined (THF + CH2-
Cl2), dried over MgSO4, and filtered. The filtrate was concentrated in
vacuo, and the crude solid was chromatographed on SiO2 (160 mL,
20:1 CH2Cl2/MeOH, Rf ) 0.50). Fractions containing the lower Rf of
two product spots were combined and concentrated, giving the desired
product as a pale yellow powder (0.271 g, 94%). 1H NMR (600 MHz,
DMF-d7) δ 9.15 (t, 3H, J ) 6.0 Hz), 8.81 (t, 3H, J ) 6.2 Hz), 8.61 (s,
3H), 8.58 (s, 3H), 8.55 (s, 3H), 8.53 (s, 3H), 8.30 (s, 6H), 8.29 (s, 6H),
8.10 (d, 6H, J ) 8.3 Hz), 7.86 (s, 3H), 7.77 (d, 6H, J ) 8.3 Hz),
7.47-7.36 (m, 24H), 7.26 (d, 12H, J ) 8.4), 7.18 (d, 12H, J ) 8.0),
7.11 (d, 12H, J ) 8.3 Hz), 7.06 (d, 12H, J ) 8.4 Hz), 6.64 (s, 6H),
6.64 (s, 6H), 4.79 (s, 6H), 4.69 (d, 6H, J ) 5.6 Hz), 4.63 (d, 6H, J )
4.8 Hz), 4.51 (d, 6H, J ) 13.6 Hz), 4.43 (d, 6H, J ) 13.1 Hz), 3.90
(m, 6H), 3.80-3.75 (m, 12H), 3.24 (d, 6H, J ) 13.8 Hz), 3.18 (d, 6H,
J ) 13.8 Hz), 2.56-2.51 (m, 24H), 1.88 (m, 6H), 1.74 (m, 12H), 1.57
(m, 24H), 1.30-1.25 (m, 96H), 0.93 (t, 9H, J ) 7.4 Hz), 0.90 (t, 18H,
J ) 7.4 Hz), 0.88-0.85 (m, 36H). IR (KBr) 3326, 2926, 2855, 2208,
(DMF-d7) δ 171.52, 153.28, 152.51, 152.44, 150.00, 149.96, 144.74,
144.67, 138.25, 138.20, 136.05, 135.81, 134.83, 134.66, 133.48, 133.09,
132.75, 130.03, 129.99, 128.35, 128.30, 120.06, 119.90, 119.84, 77.50,
77.27, 71.01, 31.43, 31.01, 23.18, 20.98, 21.00, 10.26, 9.89; IR (thin
film) 3353, 3189, 2966, 2876, 1709, 1599, 1552, 1466, 1342, 1218,
1162, 1054, 890, 663 cm-1; LRMS (ESI; M - H) calcd for C71H75N8O18
1455, found 1455.
1-{[5,11,17,23-tetrakis(p-heptylphenyl)-25,26,27-tripropoxy-28-
[(aminocarbonyl)methoxy]calix[4]arene]-4-[5,11,17,23-tetrakis-
(tosylurea)-25,26,27-tripropoxy-28-[(aminocarbonyl)methoxy]calix-
[4]arene]}xylene (3c). The tripropoxy sulfonyl acid 22 (0.0537 g,
0.0368 mmol) was dissolved in anhydrous DMF (4 mL) under N2. To
this solution was added PyBOP (0.023 g, 0.044 mmol), and the solution
was stirred at room temperature for several minutes. In a separate flask,
the amine hydrochloride 18 (0.0623 g, 0.0368 mmol) was treated with
triethylamine (20 µL, 0.15 mmol), and this solution was transferred to
the flask containing the acid. The reaction was continued at room
temperature for 2.5 h. Most of the DMF was removed in vacuo, and
the resulting oil was diluted to 20 mL with CHCl3. This solution was
washed with 1 M HCl (2 × 50 mL) and brine (1 × 50 mL). The
organic layer was dried over MgSO4, filtered, and concentrated to
dryness. Trituration with MeOH gave the crude product as an off-
white powder (0.0791 g, 69%): 1H NMR (600 MHz, DMF-d7) δ 10.47
(s, 1H), 10.43 (s, 1H), 10.20 (s, 2H), 8.81 (t, 1H, J ) 5.7 Hz), 8.72 (s,
1H), 8.68 (s, 1H), 8.60 (t, 1H, J ) 6.1 Hz), 8.56 (s, 1H), 8.55 (s, 1H),
8.53 (s, 1H), 8.52 (s, 1H), 8.43 (s, 2H), 8.27 (s, 4H), 7.96 (s, 2H), 7.95
(s, 2H), 7.90 (d, 4H, J ) 8.3 Hz), 7.47 (d, 2H, J ) 8.2 Hz), 7.46 (d,
2H, J ) 8.3 Hz), 7.43 (d, 4H, J ) 8.0 Hz), 7.37 (d, 2H, J ) 8.2 Hz),
7.34 (d, 2H, J ) 8.2 Hz), 7.25 (d, 4H, J ) 8.4 Hz), 7.18 (s, 2H), 7.18
(s, 2H), 7.12 (d, 4H, J ) 8.5 Hz), 7.05 (d, 4H, J ) 8.5 Hz), 6.88 (s,
2H), 6.88 (s, 2H), 6.62 (s, 4H), 6.47 (s, 2H), 6.46 (s, 2H), 4.78 (s, 2H),
4.67 (d, 2H, J ) 5.9 Hz), 4.62 (s, 2H), 4.58 (d, 2H, J ) 5.8 Hz), 4.46
(d, 2H, J ) 11.2 Hz), 4.42 (d, 2H, J ) 13.4 Hz), 4.40 (d, 2H, J ) 12.9
Hz), 4.29 (d, 2H, J ) 13.1 Hz), 3.87 (m, 2H), 3.79-3.70 (m, 10H),
3.21 (d, 2H, J ) 13.8 Hz), 3.16 (d, 2H, J ) 13.4 Hz), 3.08 (d, 2H, J
) 13.8 Hz), 3.05 (d, 2H, J ) 13.5 Hz), 2.52 (m, 8H), 2.43 (s, 3H),
2.43 (s, 3H), 2.41 (s, 6H), 1.78-1.66 (m, 12H), 1.56-1.53 (m, 8H),
1.29-1.24 (m, 32H), 0.92-0.79 (m, 30H); IR (thin film) 3358, 2926,
1667, 1600, 1548, 1469, 1416, 1311, 1210, 1014 cm-1
(MALDI; Mavg) calcd for C342H414N30O30 5425, found 5427.
. LRMS
5,11,17,23-Tetrakis(tosylurea)-25,26,27-tripropoxy-28-[(ethoxy-
carbonyl)methoxy]calix[4]arene (21). Prepared similarly to 11 using
0.288 g (0.413 mmol) of the tetraamine4 and 316 µL (2.07 mmol) of
p-toluenesulfonyl isocyanate. The product was obtained as an off-
white powder and used without further purification (0.343 g, 56%):
1H NMR (600 MHz, DMF-d7) δ 10.46 (bs, 2H), 10.19 (bs, 2H), 8.72
(s, 1H), 8.71 (s, 1H), 8.41 (s, 2H), 7.98 (d, 4H, J ) 8.2 Hz), 7.92 (d,
4H, J ) 8.4 Hz), 7.50 (d, 4H, J ) 8.3 Hz), 7.46 (d, 4H, J ) 8.3 Hz),
6.94 (s, 2H), 6.93 (s, 2H), 6.47 (s, 4H), 4.74 (s, 2H), 4.58 (d, 2H, J )
13.3 Hz), 4.33 (d, 2H, J ) 13.0 Hz), 4.15 (q, 2H, J ) 7.0 Hz), 3.83-
3.66 (m, 6H), 3.08 (d, 2H, J ) 13.2 Hz), 3.06 (d, 2H, J ) 13.0 Hz),
2.46 (s, 6H), 2.44 (s, 6H), 1.92-1.82 (m, 6H), 1.23 (t, 3H, J ) 7.2
Hz), 0.98 (t, 6H, J ) 7.4 Hz), 0.93 (t, 3H, J ) 7.4 Hz); 13C NMR
(DMF-d7) δ 170.50, 153.41, 152.76, 152.68, 149.96, 149.95, 144.71,
144.63, 138.22, 138.16, 136.07, 135.89, 134.66, 134.58, 133.27, 133.00,
132.58, 130.00, 129.95, 128.34, 128.29, 119.96, 119.72, 119.69, 77.24,
77.09, 70.99, 60.44, 31.45, 30.99, 23.23, 20.98, 20.97, 14.03, 10.34,
9.90; IR (KBr) 3353, 3242 (b), 2963, 2925, 2872, 1718, 1599, 1544,
1458, 1343, 1218, 1162, 892 cm-1; LRMS (ESI; M + Na+) calcd for
C73H80N8O18Na 1508, found 1508.
5,11,17,23-Tetrakis(tosylurea)-25,26,27-tripropoxy-28-(carboxy-
methoxy)calix[4]arene (22). Prepared similarly to 12 using 0.100 g
(0.0672 mmol) of 21 and 0.056 g (1.35 mmol) of LiOH‚H2O. The
white solid obtained was used without further purification (0.086 g,
88%): 1H NMR (600 MHz, DMF-d7) δ 12.49 (bs, 1H), 10.49 (bs, 2H),
10.24 (bs, 2H), 8.75 (s, 1H), 8.73 (s, 1H), 8.46 (s, 2H), 7.98 (d, 4H, J
) 8.3 Hz), 7.93 (d, 4H, J ) 8.2 Hz), 7.49 (d, 4H, J ) 8.2 Hz), 7.46
(d, 4H, J ) 8.3 Hz), 6.94 (s, 2H), 6.94 (s, 2H), 6.55 (s, 2H), 6.55 (s,
2H), 4.67 (s, 2H), 4.54 (d, 2H, J ) 13.2 Hz), 4.36 (d, 2H, J ) 12.9
Hz), 3.85 (m, 2H), 3.77-3.68 (m, 4H), 3.10 (d, 2H, J ) 12.4 Hz),
3.08 (d, 2H, J ) 12.4 Hz), 2.45 (s, 6H), 2.44 (s, 6H), 1.90-1.82 (m,
6H), 0.96 (t, 6H, J ) 7.5 Hz), 0.91 (t, 3H, J ) 7.4 Hz); 13C NMR
2854, 1715, 1670, 1602, 1554, 1511, 1476, 1215, 1150 cm-1
.
Acknowledgment. We are grateful to the Skaggs Research
Foundation and the National Institutes of Health for financial
support. We also thank Professor Andrew Hamilton and Dr.
Abdullah Zafar (University of Pittsburgh) for helpful discussions
regarding GPC analysis and Dr. Go¨ran Hilmersson and Kent
Pryor for experimental and interpretive advice.
Supporting Information Available: Additional GPC data
and NOESY/ROESY data for 2 (6 pages, print/PDF). See any
current masthead page for ordering information and Web access
instructions.
JA974091K