Synthesis, conformation, and binding properties of resorcarene tetrasulfonates. Asymmetric reorganization of pendant sulfonyl groups via intramolecular S=O---H-O hydrogen bonds

Article abstract of DOI:10.1021/jo981751a

The regioselective reaction of resorcarene octaols 1 with 4 equiv of arylsulfonyl chlorides and Et₃N in MeCN gives in 30-60% yield the C(2v) symmetrical tetrasulfonates 3. The mild electrophilic substitution (aminomethylation, bromination) of resorcarene tetrasulfonates 3 and tetraphosphates 2 takes place only in the 2-positions of unsubstituted resorcinol rings yielding distally disubstituted resorcarenes 4. The acylation of hydroxy groups in compounds 2 and 3 gives C(2v) symmetrical octaesters 5 including large resorcarene tetracrown-ethers. In the minimized boat conformation of tetrasulfonates 3 the two unsubstituted resorcinol rings are vertical and the sulfonyl fragments are arranged in a C₂ symmetrical manner via intramolecular S=O---H-O hydrogen bonds. This structure is proved by NMR and IR spectroscopy. In the case of tetrasulfonate 3c the two enantiomeric conformations interconvert in CDCl₈ with ΔG* = 11.6 kcal/mol. This is in agreement with the ΔE* value predicted by molecular mechanics in vacuo.

Full text of DOI:10.1021/jo981751a

9510
J . Org. Chem. 1998, 63, 9510-9516
Syn th esis, Con for m a tion , a n d Bin d in g P r op er ties of Resor ca r en e
Tetr a su lfon a tes. Asym m etr ic Reor ga n iza tion of P en d a n t Su lfon yl
Gr ou p s via In tr a m olecu la r SdO- - -H-O Hyd r ogen Bon d s
Oleg Lukin,† Alexander Shivanyuk,*,‡ Vladimir V. Pirozhenko,§ Ivan F. Tsymbal,§ and
Vitaly I. Kalchenko§
Institut fu¨r Organische Chemie, J ohannes Gutenberg-Universita¨t Mainz, J . J . Becher Weg 34 SB1,
D-55099 Mainz, Germany, Institute of Organic Chemistry, Polish Academy of Science, 01-224 Warsaw,
ul. Kasprzaka 44, Poland, and Institute of Organic Chemistry National Academy of Sciences of Ukraine,
Murmans’ka Street 5, 253-660 Kyiv 94, Ukraine
Received August 26, 1998
The regioselective reaction of resorcarene octaols 1 with 4 equiv of arylsulfonyl chlorides and Et3N
in MeCN gives in 30-60% yield the C2v symmetrical tetrasulfonates 3. The mild electrophilic
substitution (aminomethylation, bromination) of resorcarene tetrasulfonates 3 and tetraphosphates
2 takes place only in the 2-positions of unsubstituted resorcinol rings yielding distally disubstituted
resorcarenes 4. The acylation of hydroxy groups in compounds 2 and 3 gives C2v symmetrical
octaesters 5 including large resorcarene tetracrown-ethers. In the minimized boat conformation
of tetrasulfonates 3 the two unsubstituted resorcinol rings are vertical and the sulfonyl fragments
are arranged in a C2 symmetrical manner via intramolecular SdO- - -H-O hydrogen bonds. This
structure is proved by NMR and IR spectroscopy. In the case of tetrasulfonate 3c the two
enantiomeric conformations interconvert in CDCl3 with ∆G* ) 11.6 kcal/mol. This is in agreement
with the ∆E* value predicted by molecular mechanics in vacuo.
In tr od u ction
tetraphosphates (structure A) having the chair and
diamond conformation.11 This interpretation, however
proved to be entirely incorrect and later the C2v sym-
metrical structure 2 was unambiguously established.12
Previously, we have reported the conditions for the
similar tetrasulfonation only for resorcarene 1a .13 Al-
though some of the tetraphosphates and tetrasulfonates
Resorcarenes 11 are readily available by acid catalyzed
condensation of resorcinol with various aldehydes. The
rccc isomers are effectively used as receptors for biologi-
cally important molecules2 as well as for the creation of
covalent and self-assembling molecular containers.3,4 To
modify the conformational behavior and binding proper-
ties of resorcarenes, chemical modifications can be per-
formed. Many examples of complete derivatizations5 of
hydroxy groups and electrophilic substitutions in reactive
resorcinol rings6 have been reported in the literature.
Several cases of partial reactions including bridging of
the neighboring hydroxy groups,7 alkylations,8 and bro-
(6) (a) Cram, D. J .; Karbach, S.; Kim, H.-E.; Knobler, C. B.;
Maverick, E. F.; Ericson, J . L.; Helgeson, R. C. J . Am. Chem. Soc. 1988,
110, 2229-2237. (b) Manabe, O.; Asakura, K.; Nishi, T.; Shinkai, S.
Chem. Lett. 1990, 1219-1222. (c) Matsushita, Y.; Matsui, T. Tetrahe-
dron Lett. 1993, 34, 7433-7437. (d) Schneider, U.; Schneider, H.-J .
Chem. Ber. 1994, 127, 7, 2455-2459. (d) Airola, K.; Bo¨hmer, V.; Paulus,
E. F.; Rissanen, K.; Schmidt, C.; Thondorf, I.; Vogt, W. Tetrahedron
1997, 53, 10709-10724. (e) Iwanek, W.; Mathay, J . Liebigs Anal. 1995,
1463-1469. (f) Konishi, H.; Yamaguchi, H.; Miyashiro, M.; Kobayashi,
K.; Morikawa, O. Tetrahedron Lett. 1996, 37, 8547-8548.
(7) (a) Cram, D. J .; Tunstad, L. M.; Knobler, C. J . Org. Chem. 1992,
57, 7, 528-535. (b) Cram, D. J .; Tanner, M. E.; Bryant, J . A.; Knobler,
C. B. J . Am. Chem. Soc. 1992, 114, 8-7765.
(8) Konishi, H.; Tamura, T.; Ohkubo, H.; Kobayashi, K.; Morikawa,
O. Chem. Lett. 1996, 685-686.
(9) Konishi, H.; Nakamaru, H.; Nakatani, H.; Ueyama, T.; Koba-
yashi, K.; Morikawa, O. Chem. Lett. 1997, 185-186.
(10) (a) Sorrel, T. N.; Richards, J . L. Synlett 1992, 155-156. (b)
Timmerman, P.; Mook, M. J . A.; Verboom, W.; Hummel, G. J .;
Harkema, S.; Reinhoudt, D. N. Tetrahedron Lett. 1992, 33, 3377-3380.
(11) (a) Markovsky, L. N.; Rudkevich, D. M.; Kalchenko, V. I. Zh.
Obshch. Khim. (Russ.) 1990, 60, 2799-2800. (b) Markovsky, L. N.;
Kalchenko, V. I.; Rudkevich, D. M.; Shivanyuk A. N. Mendeleev
Commun. 1992, 106-108. (c) Markovsky, L. N.; Kalchenko, V. I.;
Rudkevich, D. M.; Shivanyuk, A. N. Phosphorus Silicon Sulfur 1993,
75, 59-62.
9
mination have also been described. Partially bridged
cavitands undergo further regioselective substitutions in
the neighboring resorcinol rings.10
Regioselective phosphorylation of rccc-resorcarenes 1
was first reported to give the C4 symmetrical resorcarene
† PAS.
‡ University of Mainz.
§ NASU.
(1) For recent review on resorcarenes see: Timmerman, P.; Ver-
boom, W.; Reinhoudt, D. N. Tetrahedron 1996, 52, 2663-2704.
(2) (a) Kurihara, K.; Ohto, K.; Tanaka, Y.; Aoyama, Y.; Kunitaka,
T.; J . Am. Chem. Soc. 1988, 110, 623-624. (c) Tanaka, Y.; Kato, Y.;
Aoyama, Y. J . Am. Chem. Soc. 1990, 112, 2807-2808. (d) Kobayashi,
K.; Asakuwa, Y.; Kato, Y.; Aoyama, Y. J . Am. Chem. Soc. 1992, 114,
10307-10313. (e) Murayama, K.; Aoki, K. Chem. Commun. 1997, 119-
120.
(3) Cram, D. J .; Cram, J . M. Container Molecules and Their Guests;
Stoddart, J . F., Ed.; Monographs in Supramolecular Chemistry; The
Royal Society of Chemistry: Cambridge, U.K., 1994.
(4) (a) Chapman, R. G.; Sherman, J . C. Tetrahedron 1997, 53,
15911-15945. (b) MacGillivray, L. R.; Atwood, J . L. Nature 1997, 389,
469-472.
(5) (a) Xu, W.; Rourke, J . P.; Vittal, J . J .; Puddephat, R. J . J . Am.
Chem. Soc. 1993, 115, 6456-6457. (b) Lippmann, T.; Wilde, H.;
Dalcanale, E.; Mavilla, L.; Mann, G.; Heyer, U.; Spera, S. J . Org. Chem.
1995, 60, 253-242. (c) Mann, G.; Hennig, L.; Weinelt, F.; Mu¨ller, K.;
Meusinger, R.; Zahn, G.; Lippmann, T. Supramol. Chem. 1994, 3, 101-
113.
(12) (a) Kalchenko, V. I.; Rudkevich, D. M.; Shivanyuk, A. N.;
Pirozhenko, V. V.; Tsymbal, I. F.; Markovsky, L. N Zh. Obshch. Khim.
(Russ.) 1994, 64, 731; Chem. Abstr. 1995, 122, 314652u. (b) Kalchenko,
V. I.; Shivanyuk, A. N.; Pirozhenko, V. V.; Markovsky, L. N. Zhurn.
Obshch. Khim. (Russ) 1994, 64, 1562-1563; Chem. Abstr. 1995, 122,
314654 w. (c) Shivanyuk, A. N.; Kalchenko, V. I.; Pirozhenko, V. V.;
Markovsky, L. N. Zhurn. Obshch. Khim. (Russ.) 1994, 64, 1558; Chem.
Abstr. 1995, 122, 314625u. (d) Lipkowski, J .; Kalchenko, O. I.;
Slowikowska, J .; Kalchenko, V. I.; Lukin, O. V.; Markovsky, L. N.;
Nowakowsky, R. J . Phys. Org. Chem. 1998, 11, 426-435.
(13) Lukin, O. V.; Pirozhenko, V. V.; Shivanyuk, A. N. Tetrahedron
Lett. 1995, 36, 7725-7728.
10.1021/jo981751a CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/13/1998

Resorcarene Tetrasulfonates
Sch em e 1
J . Org. Chem., Vol. 63, No. 25, 1998 9511
of resorcarenes can be prepared in gram quantities their
binding properties and dynamic stereochemistry still
remain unexplored.
Here we describe the synthesis and unique conforma-
tional properties of C2v symmetrical resorcarene tetra-
sulfonates. We demonstrate also that resocarene tetera-
sulfonates and teteraphosphates can be employed as a
molecular platform for the design of complex cation
receptors containing several binding units of different
types.
F igu r e 1. 1H NMR spectrum of tetratosylate 3e (400 MHz,
CDCl3). NOE are shown with arrows: Hj(Hd) ) 3.2%, Hf(Hd)
) 1.8%, Hg(Hc) ) 2.4%; Hh(Hc) ) 4.3%, Ha(Hh) ) 0.5%.
Ch a r t 1
Resu lts a n d Discu ssion
Syn th esis a n d Str u ctu r e. The addition of Et3N (4
equiv) to a solution of octaol 1 in MeCN gave a slightly
red precipitate. Although these extremely insoluble
solids could not be identified they are most probably the
salts of the rather acidic14 resorcarenes 1 and Et3N.15
After the addition of arylsulfonyl chloride (4 molar equiv)
the reaction mixture became homogeneous and after a
while the precipitate of 3‚2Et3NHCl was formed (Scheme
crystal X-ray analysis of bis-benzoxazine derivatives of
3a .16 In the case of the pentyl analogue 3e one doublet
of doublets corresponds to the methyne protons of the
bridges due to coupling with the diastereotopic protons
of the neighboring methylene groups that appear in turn
as two well-separated multiplets (Figure 1). The 13C
NMR spectra of compounds 3 contain two signals corre-
sponding to the carbon atoms in the 2-positions of the
unsubstituted (δ ) 103 ppm) and diacylated (δ ) 114
ppm) resorcinol rings. This conclusion is additionally
supported by comparison with 13C NMR spectra of
resorcarene 1a (δ ) 101 ppm) and octatosylate 5g (δ )
114 ppm).
1
1). TLC analysis and H NMR spectra showed that the
filtrate contained many partially acylated resorca-
renes that could not be identified.
The highest yields of tetrasulfonates were reached for
resorcarene 1a while in the case of more lypophilic
(soluble) compounds 1d ,e no individual product could be
isolated. The tetraacylation with p-chlorobenzene sul-
fonyl chloride had considerably lower yield compared to
the reaction with tosyl chloride (31 and 53%) while in
the case of nosyl chloride the reaction was not regioslec-
tive. Many attempts to perform partial and complete
sulfonation of resorcarene 1a with benzo-15-crown-5-
sulfonyl chloride also failed.
The tetrasulfonates 3a -c and tetraphosphates 2b,d
(Chart 1) undergo acid-catalyzed aminomethylation with
secondary amines or bromination with N-bromsuccinim-
ide to give the diamines 4a -d ,g and dibromide 4e (Chart
2). The reason for this regioselectivity is apparently the
much higher reactivity of unsubstituted resorcinol rings
over diacylated ones. The three singlets for the protons
The structure of tetrasulfonates 3 could be unambigu-
1
ously proved by H and 13C NMR spectroscopy and by
1
FD-mass spectrometry. The H NMR spectrum of tet-
ratosylate 3a contains four singlets for the protons of
resorcinol rings, one doublet and one quartet for the
protons of the bridges and one set of signals for the tosyl
fragments in accordance with a C2v symmetrical struc-
ture. This structure was confirmed proved by single-
1
of resorcinol rings in the H NMR spectra of compounds
4 are entirely consistent with the proposed structure.
The acylation of tetrasulfonates 3a and 3c and tetra-
phosphates 2b and 2e with tosyl chloride, acetyl chloride,
(14) Schneider, H.-J .; Gutes, D.; Schneider, U. J . Am. Chem. Soc.
1988, 110, 6449-6454.
(15) MacGillivray, L. R.; Atwood, J . L. J . Am. Chem. Soc. 1997, 119,
9, 6931-6932.
(16) Shivanyuk, A.; Schmidt, C.; Bo¨hmer, V.; Paulus, E. F.; Lukin,
O. V.; Vogt, W. J . Am. Chem. Soc. 1998, 120, 4319-4326.

9512 J . Org. Chem., Vol. 63, No. 25, 1998
Lukin et al.
Ch a r t 2
Ch a r t 3
F igu r e 2. 1H NMR spectrum of tetrasulfonate 3c (200 MHz,
CDCl3): (a) at 295 K; (b) at 203 K.
Dyn a m ic Ster eoch em istr y. The 1H NMR spectra
and NOE (Figure 1) suggest that in solution compounds
3 exist in one boat conformation. The singlets for the
protons of the lower rim of the calixarene skeleton are
strongly separated (∆δ ) 1.0 ppm) which is characteristic
of the rccc boat conformation. By analogy with known
rccc-octaesters18 of resorcarenes, one can conclude that
the high-field signal corresponds to the protons of the
horizontal resorcinol rings. However, it was not possible
to establish from NMR which of the two boat conforma-
tions (with horizontal or vertical free resorcinol rings) is
actually present in the solution.
1
At room temperature the H NMR spectrum of 3c is
and benzo-15-crown-5-sulfonyl chloride readily gave the
C2v symmetrical octaesters 517 (Chart 3). The structure
of large receptor molecules 5d-f having molecular weights
in the range 2.5-2.6 kDa could be definitely proved by
1H NMR spectroscopy. The 1H NMR spectra of com-
pounds 5d -f measured in CDCl3 at room temperature
are broad and featureless while in DMSO-d6, acetone-
d6, and benzene-d6 they are well resolved and again
consistent with C2v symmetrical structure. This solvent
effect could be caused by formation of a hydrogen bonded
complex between the crown-ether fragments and chloro-
form molecules. The reactions of tetraphosphates 2a and
2c with acetyl chloride and tosyl chloride failed due to
their poor solubility in most of organic solvents (except
for DMF, DMSO, etc.)
consistent with the C2v symmetrical structure (Figure 2a)
while at -60 °C the C2 symmetrical pattern is observed
(Figure 2b). Namely the cooling results in doubling of
the signals for the protons of hydroxy groups, the bridges,
and mesityl fragments. In contrast the four singlets for
the protons of the lower rim do not change considerably
either in their shape or in their position within the
temperature range 295-205 K, therefore excluding boat-
boat transition.19 Only the signal for the protons of
unsubstituted resorcinol rings (upper rim) is shifted
upfield by about 0.2 ppm. The signals for the methyne
protons of the bridges coalesce at 247 K (200 MHz, CDCl3)
which corresponds to ∆G* of 11.6 kcal/mol.20 Almost the
same ∆G* (11.2 kcal/mol) was found in toluene-d8 while
Hydrolysis of tetratosylate 3a by KOH in MeOH-H2O
at 60 °C gave quantitatively octaol 1a . However, it was
not possible to remove ether the tosyl or phosphoryl
groups from the disubstituted compounds 4. Thus the
phosphoryl and arylsulfonyl groups cannot be used as
protecting groups in the rational synthesis of partly
substituted resorcarenes.
(18) (a) Ho¨gberg, A. G. S. J . Am. Chem. Soc. 1980, 102, 6046-6050.
(b) Ho¨gberg, A. G. S. J . Org. Chem. 1980, 45, 4498-4500. (c) Abis, L.;
Dalcanale, E.; Du vosel, A.; Spera, S. J . Chem. Soc., Perkin Trans. 2
1990, 2075-2080. (d) Abis, L.; Dalcanale, E.; Du vocel, A.; Spera, S.
J . Org. Chem. 1988, 53, 5475-5479. (e) Shivanyuk, A. N.; Pirozhenko,
V. V.; Kalchenko, V. I.; Markovsky, L. N. J . Chem. Res. (S) 1995, 374-
375.
(19) In the case of resorcarene octatosylates the boat- boat transition
took place: Kalchenko, V. I.; Solov’yov, A. V.; Gladun, N. R.; Shivanyuk,
A. N.; Atamas’, L. I.; Pirozhenko, V. V.; Markowsky, L. N.; Lipkowski,
J .; Simonov, Yu. A. Supramol. Chem. 1997, 8, 269-297
(20) Gutowski, H. S.; Holm, C. H. J . Chem. Phys. 1956, 25, 1228-
1233.
(17) About resorcarene crown-ethers, see for example: Beer, P. D.;
Tite, E. L.; Ibbotson, A. J . Chem. Soc., Chem. Commun. 1989, 1874-
1876.

Resorcarene Tetrasulfonates
J . Org. Chem., Vol. 63, No. 25, 1998 9513
F igu r e 3. Simultaneous (SM) and stepwise (SW) pathways for the interconversion between C2 symmetrical enantiomeric
conformations of 3. R and S refer to the clockwise and counterclockwise orientation of the sulfonyl groups, respectively. Hydrogen
bonds are shown in dotted lines.
in pyridine-d5 (acceptor of hydrogen bonds) no dynamics
were observed up to 213 K. This process is much faster
(∆G* < 10 kcal/mol) for the less sterically hindered
and two S-carbon atoms of the bridges. The propeller-
like arrangement of the sulfonyl fragments “induces” the
chirality of the whole molecule, making the R- and
S-bridging atoms inequivalent. The sulfur atoms also
become chiral since one of the SdO oxygens forms the
hydrogen bond while the other does not.
The second minimized conformation of 3a and 3c with
vertical diacylated resorcinol rings (Figure 4a) was found
to be about 8 kcal/mol less advantageous. This difference
may be attributed partly to the formation of only two
intramolecular hydrogen bonds SdO---H-O.
The results of dynamics NMR studies of resorcarene
3c could be explained by the exchange between two
enantiomeric structures differing only in handedness of
the propeller-like arrangement of four sulfonyl fragments.
The simultaneous and stepwise rotations around ArSO2-
OAr′ bonds were considered as possible pathways for this
interconversion (Figure 3).
In the simultaneous route all four torsion angles
ArSO2-O-Ar′ were constrained every 10° in the range
-170 to 70°, while the rest of molecule was minimized.
As a result of this procedure the four arylsulfonyl
fragments are moving like molecular wind screen wipers.
The potential energy surface of this mechanism has a
single transition state (Figure 5) with the ∆E* of 7.5 for
3a and 11.5 kcal/mol for 3c which is comparable with
the experimental values of ∆G*.
1
tetratosylate 3a since only broadening of the H NMR
signals was observed at 213 K (CDCl3, 200 MHz).
The IR spectra of 3b and 3c measured in CH2Cl2 and
CCl4 contain two clear-cut bands for the OH groups (3410
and 3475 cm-1). The independence of the IR spectra on
the concentration and temperature (22-70 °C) reflects
the formation of two types of intramolecular hydrogen
bonds SdO---H-O that are slightly different in strength.
The above results could be generally explained by
interconversion of two C2 symmetrical conformers of 3c
different only in the arrangement of hydrogen-bonded
sulfonyl fragments. To verify this hypothesis we have
performed molecular mechanics studies of tetrasulfonates
3a and 3c.
Many local energy minima are possible for compounds
3 that are different in the conformation of the resorcarene
skeleton and the arrangement of sulfonyl groups. The
structures of tetrasulfonates 3a and 3c were minimized
by MMX force field starting from the two boat conforma-
tions with parallel and coplanar unsubstituted resorcinol
rings. The energy barrier between these conformations
was sufficiently high to prevent their interconversion
during the geometry optimization.
The lowest energy corresponds to the boat conforma-
tion having horizontal diacylated resorcinol rings and C2
symmetrical propeller-like orientation of the four sulfonyl
fragments (Figure 3). Two pairs of intramolecular hy-
drogen bonds SdO‚‚‚H-O (O‚‚‚O of 2.9 and 3.1 Å) are
predicted for this structure. It is important to note that
a similar arrangement of the sulfonyl fragments was
experimentally found in the X-ray crystal structures of
bis-benzoxazine derivatives of tetratosylate 3a .17 The
time-averaged structure of 3 is a mesoform with two R-
In a stepwise pathway the rotation procedure was
applied separately to each arylsulfonyl fragment so that
finally three intermediates and four transition states
were obtained (Figures 3 and 5). In this case two routes
are possible, namely, R-I1-I21-I3-S or R-I1-I22-I3-S
whose energetic characteristics are summarized in the
Table 1. Apparently two of those intermediates (I1 and
I3) are chiral (antipodes) while the two others (I21 and
I22) are mesoforms. It is important to note that the

9514 J . Org. Chem., Vol. 63, No. 25, 1998
Lukin et al.
F igu r e 4. Minimized conformations of tetratosylate 3a (the second) and diamine 4a trans form (b) and cis form (c).
pendant arylsulfonyl fragments in molecules 3 and
molecular chirality.22 The two sp2 oxygens of the sulfonyl
group appear to be crucial for this process since in the
case of tetraphosphates 2 no dynamics could be detected
1
by H NMR spectroscopy.
Com p lexa tion Stu d ies
Compounds 5d -f are able to complex alkali cations
F igu r e 5. Potential energy profiles of the simultaneous (a)
and stepwise (b) pathways.
and NH4 in acetone THF and CHCl3. The 1H NMR
+
titration of tetraphosphates 5d and 5e by picrates of Na+,
+
K+, Cs+, Rb+, and NH4 showed systematic changes in
activation energy per sulfonyl fragment (∆E*/4) for the
simultaneous mechanism is considerably lower than the
average value of the four activation energies for the
stepwise pathway (∆E*a). Thus it is reasonable to
assume that the interconversion between two enantio-
meric conformers of 3 is realized via the cooperative
simultaneous route.
the shape and position of the signals corresponding to
the protons of the phosphoryl groups, benzo crown-ether
fragments and resorcarene skeleton. The strongest ef-
fects were observed in the case of KPic. For example
after addition of 2 equiv of KPic all the resonances for
the aryl rings of benzo-15-crown-5 were transformed into
one broad singlet.
The 31P NMR signal of 5d and 5e was shifted downfield
by about 1 ppm upon titration with MPic clearly showing
saturation. However, no reliable thermodynamic param-
eters could be obtained from these dilution experiments,
most probably, due to the presence of more than one
complex under the host-guest ratios studied.
Inspection of CPK- models and MM- calculations for
the receptors 5d -f showed that complexation of the
cations can be realized in several ways (Figure 5).
A. Sandwich-like complex with two crown-ether frag-
ments connected to the same resorcinol ring.
B. Sandwich-like complex with two crown-ether frag-
ments connected to the opposite resorcinol rings. This
type of complexation is possible only when the receptor
adopts the boat conformation with vertical sulfonated
resorcinol rings.
C. Lariat complex with one crown-ether fragment and
neighboring PdO or SdO groups.
To reveal the mode of 1:1 cation complexation we have
carried out a UV study of interaction of MPic with excess
of the ligand.
1
The H NMR spectrum of diamine 4c recorded at 213
K contains a double set of the signals for the methyne
protons of the bridges, hydroxy groups (12.2, 7.01 ppm)
and diethylamino fragments. Two doublets with J ) 14.4
Hz for the benzyl protons of the aminomethyl groups
reveal that rotation around the Ar-CH2 bond is slow on
the NMR time scale at this temperature.21 The three
sharp singlets for the protons of resorcinol rings allow
the conclusion that the “frozen” conformation has C2
symmetry. The coalescence data for the protons of the
bridging carbon atoms give a ∆G* value of 11.1 kcal/mol
which is comparable to that found for the dynamics of
tetrasulfonate 3c. The IR study of 4c in CH2Cl2 and CCl4
solutions reveals again intramolecular hydrogen bonding.
However in contrast to 3b and 3c the two bands for the
hydroxy groups are quite distant, most probably due to
the large difference in the strength between SdO---H-O
(ν ) 3511 cm-1) and O-H---N (ν ) 2800 cm-1) hydrogen
bonds.
Indeed the molecular mechanics calculations predict
intramolecular hydrogen bonds between the hydroxy
groups and the nitrogen atoms for both C2 and Cs
symmetrical conformations of diamine 4c (Figure 4b,c).
However, the latter is by 3 kcal/mol less advantageous
than the former, probably due to the stronger sterical
and electrostatic repulsion between diethylamino moi-
eties.
Addition of receptor 5d (10 molar equiv) to the solution
of alkali and ammonium picrates in THF resulted in
considerable bathochromic shifts (∆λmax) of the absorption
maximum for the picrate anion (see Table 2) due to the
separation of contact ion pair M+Pic-. The strongest
shifts were observed for KPic (24 nm) and RbPic (20 nm),
while relatively small or no changes were found for LiPic
In conclusion the intramolecular hydrogen bonds
SdO- - -H-O result in asymmetric reorganization of four
(22) About the “supramolecular chirality” in the crystalline state
via intermolecular hydrogen bonding between achiral compounds,
see: Suarez, M.; Branda, N.; Lehn, J .-M.; Decian, A.; Fischer, J . Helv.
Chim. Acta 1998, 81, 1-13.
(21) This rotation is much more hindered in the completely ami-
nomethylated resorcarenes: Leigh, D. A.; Linnane, P.; Pritchard, R.
G.; J ackson, G. J . Chem. Soc. Chem. Commun. 1994, 389-390.

Resorcarene Tetrasulfonates
J . Org. Chem., Vol. 63, No. 25, 1998 9515
Ta ble 1. En er getic Ch a r a cter istics (in k ca l/m ol) for th e In ter con ver sion of Tetr a su lfon a tes 3a ,c
∆E1*
∆E1
∆E2*
∆E2
∆E3*
∆E3
∆E4*
∆E4
3.5
3a
route 1
route 2
3
3
2
2
3.5
4.5
2.5
4
4
4.5
2.5
2.5
3.5
3.5
3.875
∆E*/4
min (4∆E*a - ∆E*)
1.87
6.5
3c
route 1
route 2
4
4
3
3
5
7
0.5
6
3.5
8.5
3
3
5
5
4.375
6.125
∆E*/4
min (4∆E*a - ∆E*)
2.875
6
Ta ble 2. Absor p tion Ma xim a for P icr a te An ion λm a x a n d
Th eir Ba h och r om ic Sh ifts ∆λm a x In d u ced by
Com p lexa tion of Recep tor s 5d ,f a n d Mod el Com p ou n d 6
w ith MP ic in THF
asymmetric arrangement of all arylsulfonyl fragments
which is unprecedented in the chemistry of resorcarenes.
Exp er im en ta l Section
cation
1
Rea gen ts a n d Meth od s. The H and 13 C NMR, 1H NOE,
+
ligand
Li+
Na+
K+
Rb+
Cs+
NH4
HETCOR, and APT spectra were recorded with Varian XR-
300 (300 and 75.4 MHz), Varian-200 (200 and 50.0 MHz),
Bruker 200 (200 and 50 MHz), and Bruker 400 (400 and 100
MHz) instruments with TMS as internal standard. The 31P
NMR spectra were recorded by Bruker WP-200 (81.026 MHz)
5d b
5fb
6c
348[1] 356[5] 380[24] 376[20] 372[12] 362[12]
347[0] 354[3] 369[12] 376[20]
368[8]
360[0]
357[7]
350[0]
347[0] 354[3] 369[12]
356[0]
a
b
Concentration of MPic ) 2 × 10-4 M. MPic/ligand ) 1:10.
1
with 85% H3PO4 as external standard. The H and 13C NMR
c MPic/ligand ) 1:20.
spectra in CCl4 were recorded using a capillary with TMS. The
UV and IR spectra were measured by Specord M-40 and
Specord M-80 instruments, respectively. FD mass spectra
were recorded with a Finnigan MAT 90 (5 kV/10 mA/min).
Melting points were determined with a MEL TEMP 2 capillary
melting point apparatus and are uncorrected. Compounds 1
were obtained by known procedures.23
Gen er a l P r oced u r e for Tetr a su lfon yla tion of Resor -
ca r en es. To a solution of resorcarene 1a (5.45 g, 0.01 mol) in
dry MeCN (100-150 mL) Et3N (4.04 g, 0.04 mol) was added.
A slightly red precipitate was formed, and the reaction mixture
was stirred for 15 min. A solution of tosyl chloride (7.68 g,
0.04 mol) in MeCN (50 mL) was added immediately to the
suspension of precipitate, and the reaction mixture was
intensively stirred to facilitate disolution of the precipitate.
In 2-3 min a colorless precipitate formed. The reaction
mixture was stirred at room temperature for 12 h, the
precipitate formed was filtered off, washed with MeCN (2 ×
20 mL) water and dried in a vacuum. The product obtained
in this way is a complex of tetratosylate 2a with 2 equiv of
Et3NHCl. The salt ether was removed by reprecipitation of a
DMF solution of the complex with water or by chloroform/
water extraction.
F igu r e 6. Possible mechanisms for the complexation of the
cation by resorcarene tetracrown ethers.
and NaPic. The tetracrown-ether 5f showed similar
effects; however, in the case of KPic, the ∆λmax was two
times smaller under exactly the same conditions.
In the model expereiment the addition of bis crown-
ether 6 (isolated binding unit of type A) to the solution
of KPic in THF induced ∆λmax of 12 nm however no
changes were detected for the other cations. These
results suggest that complexes tetracrown-ethers 5d -f
with Rb+, Cs+, and NH4+, are of type B or (and) C (Figure
6).
The reaction with nosyl chloride and benzo-15-crown-5-
sulfonyl chloride were carried out in
a similar manner.
However, after addition of sulfonyl chloride no precipitate was
formed. The reaction mixture was evaporated in vacuo. The
1
TLC analysis and H NMR spectroscopy showed that insepa-
rable mixtures of many partially acylated compounds were
formed.
The complexation of KPic by receptor 5f is most
probably realized in way A since the ∆λmax is the same
as for the biscrown ether 6. The difference in ∆λmax
(KPic) for tetraphosphate 5d and tetramesityl sulfonate
5f gives a hint in a favor of lariat complexation (type C)
of K+ by 5d . This is in accordance with the fact that the
phosphoryl group is a much better donor of the electron
pair than the sulfonyl goup.
4,6,16,18-Tetr a h yd r oxy-10,12,22,24-tetr a k is(p-tolylsu l-
fon yloxy)-2,8,14,20-(tetr a m eth yl)ca lix[4]a r en e 3a . Yield
1
53%; mp 310-313 °C; H NMR (400 MHz, DMSO-d6) δ 8.69
(s, 4H), 7.80 (d, J ) 7.5 Hz, 8H), 7.50 (d, J ) 7.5 Hz, 8H), 6.91
(s, 2H), 6.85 (s, 2H), 6.84 (s, 2H), 5.93 (s, 2H), 4.30 (q, J ) 6.9
Hz, 4H), 2.39 (s, 12H), 1.20 (d, J ) 6.9 Hz, 12H); 13C NMR
(100, MHz, DMSO-d6) δ 152.90, 145.46, 143.72, 138.31, 132.83,
130.06, 127.83, 127.65, 124.02, 120.25, 112.84, 101.92, 29.66,
20.99, 20.42. MS (FD) 1160.6 (100%) [M+, 1161.3]. Anal.
Calcd for C60H56O16S4: C, 62.05; H, 4.86; S, 11.04; Found: C,
61.95; H, 4.88; S, 11.15.
Con clu d in g Rem a r k s
4,6,16,18-Tet r a h yd r oxy-10,12,22,24-t et r a k is(d i-n -p r o-
p y lp h o s p h o r y lo x y )-5,17-(m e t h y le n e d ie t h y la m in o )-
2,8,14,20-(tetr a m eth yl)ca lix[4]a r en e 4d . To a solution of
tetraphosphate 2b (0.5 g, 4.3 mmol) in EtOH (30 mL) was
The tetrasulfonates and tetraphosphates of resorca-
renes are promising molecular platforms for preorgani-
zation of various modules (for example cation binding
sites) via modiffication of the hydroxy groups and un-
substituted resorcinol rings. The intramolecular hydro-
gen bonding between the neighboring sulfonyl and hy-
droxy groups in tetrasulfonates 3 makes possible the
(23) Tunstad, L. M.; Tucker, J . A.; Dalcanale, E.; Weiser, J .; Bryant,
J . A.; Sherman, J . C.; Helgeson, R. C.; Knobler, C. B.; Cram, D. J . J .
Org. Chem. 1989, 54, 1305-1312.

9516 J . Org. Chem., Vol. 63, No. 25, 1998
Lukin et al.
added Et2NH (2 mL) and the solution was brought to reflux.
To the clear solution phormaline (40%, 3 mL) was added in
one portion followed by AcOH (0.5 mL). Reaction mixture was
stirred at room temperature for 20 h and then was poured into
water (200 mL). The emulsion formed was extracted with
ether (5 × 20 mL) and the combined ether solutions were dried
over Na2SO4 and evaporated in vacuo. Yield 63%; mp 127-
128 °C; 1H NMR (CCl4) δ 0.87 (t, J ) 7.5 Hz, 12H), 0.94, 0.96
(two t, J ) 7.8 Hz, 24H), 1.37 (d, J ) 7.1 Hz, 12H), 1.61-1. 88
(m, 16H), 2.30 (q, J ) 7.5 Hz, 8H), 3.52 (s, 4H), 3.93-4.12 (m,
16H), 4.44 (q, J ) 7.1 Hz, 4H), 6.31 (s, 2H), 6.90 (s, 2H), 7.22
(t, J ) 1.0 Hz, 2H), 9.10 (br s, 4H); 13C NMR (CCl4) δ 8.01,
9.30, 18.85, 21.64 (d, J CP 7.0 Hz), 29.36, 44.41, 48.77, 67.60
(d, J CP 7.0 Hz), 68.05 (d, J CP 7.0 Hz), 106.05, 109.82, 116.35,
121.46, 124.33, 134.52 (d, J CP 5.9 Hz), 143.79 (d, J CP 6.2 Hz),
8H). Anal. Calcd for: C72H74O20N2S4: C, 61.09; H, 5.27; S,
9.06; N, 1.98. Found: C, 61.00; H, 5.16; S, 9.22; N, 1.90.
4,6,16,18-Te t r a k is(b e n zo-15-cr ow n -5-su lfon yloxy)-
10,12,22,24-tetr a k is(d ip r op oxyp h osp h or yloxy)-2,8,14,20-
(tetr a m eth yl)ca lix[4]a r en e 5d . To a solution of tetraphos-
phate 2 (0.9 g, 0.77 mmol) in dry CHCl3 (10 mL) Et3N (0.9
mL, 6.1 mmol) was added followed by benzo 15-crown-5-
sulfonyl chloride (2.3 g, 6.3 mmol). The reaction mixture was
stirred at room temperature for 12 h. The solvent was
evaporated in vacuo, and the crude product was taken up in
THF (30 mL). A precipitate formed (Et3NHCl) was filtered
off, and the filtrate was evaporated in vacuo. The crude
product was recrystallized from diethyl ether. Yield 55%; mp
148-150 °C; 1H NMR (200 MHz, acetone-d6) δ 0.96, 0.98 (two
t, J ) 7.0 Hz, 24H), 1.40 (d, 12H, J ) 7.0 Hz), 1.65-1.85 (m,
16H), 3.69-4.24 (m, 80H), 4.57 (q, J ) 7.1 Hz, 4H), 6.20 (br s,
2H), 7.04-7.52 (m, 18H); 31P NMR (acetone-d6) δ -5.20; Anal.
Calcd for C112H156O48P4S4: C, 53.32; H, 6.23; S, 5.08; P, 4.91.
Found: C, 53.55; H, 6.14; S, 5.15; P 4.72.
151.90; 31P NMR (CCl4) δ -5.15. Anal. Calcd for C66H110O20
-
P4N2:C, 57.62; H, 8.06; P, 9.01; N, 2.03. Found: C, 57.62; H,
8.06; P, 9.01; N, 2.03.
4,6,16,18-Tet r a h yd r oxy-10,12,22,24-t et r a k is(d i-n -b u -
tylp h osp h or yloxy)-5,17-d ibr om o-2,8,14,20-(tetr a m eth yl)-
ca lix[4]a r en e 4e. To a solution of the tetraphosphate 2d (1
g, 0.76 mmol) in acetone (20 mL) N-bromosuccinimide (1 g,
4.4 mmol) was added in one portion and the reaction mixture
was stirred overnight at room temperature. Solvent was
removed in vacuo and the remaining material was recrystal-
Molecu la r Mech a n ics Ca lcu la tion s. Molecular mechan-
ics calculations were performed using MMX force field as
implemented in PCMODEL 5.13.24 Geometry optimization
was accomplished with a conjugate gradient procedure. A root-
mean-square (RMS) gradient of 0.001 kcal/mol or less was
assumed as a condition of energy convergence. A value of 1.5
D was assumed for the dielectric constant.
1
lized from EtOH/H2O. Yield 84%; mp 216-218 °C; H NMR
(200 MHz, CDCl3) δ 7.84 (br s, 4H), 7.25 (s, 2H), 7.07 (s, 2H),
6.13 (s, 2H), 4.57 (q, J ) 6.8 Hz, 4H), 4.30-4.10 (m, 16H),
1.81-1.62 (m, 16H), 1.45 (d, J ) 7.16 Hz, 12H), 1.52-1.31 (m,
16H), 0.93 (t, J ) 7.3 Hz, 24H); 13C NMR (100 MHz, CDCl3) δ
13.55, 18.61, 20.05, 29.55, 32.13, 32.16, 32.30, 32.35, 68.61 (d,
J ) 6.4 Hz), 68.84 (d, J ) 6.4 Hz), 101.11, 112.0, 119.72,
123.60, 126.08, 135.67 (d, J ) 5.4 Hz), 146.1 (d, J ) 8.2 Hz),
150.18; FD-MS m/z 1471.3 (100%) [M+ 1471.2 ]. Anal. Calcd
for C64 H98O20P4Br2: C, 48.94; H, 12.72. Found: C, 49.13; H,
12.94.
For optimization of the arrangement of the arylsulfonyl
groups the dihedral driver procedure has been applied during
which two torsions for the Ar-OTs and ArO-Ts bonds were
changed with the step of 30°. From the 144 conformers, the
lowest energy one was minimized with no constrains and
taken, in turn, as starting point for the following rotations of
remaining tosyl groups.
Ack n ow led gm en t. This work was partly supported
by the International Science Foundation.
4,6,16,18-Tetr a h yd r oxy-10,12,22,24-tetr a k is(p-tolylsu l-
f o n y l o x y ) -5 ,1 7 -b i s ( N -L -p r o l y l m e t h y l ) -2 ,8 ,1 4 ,2 0 -
(tetr a m eth yl)ca lix[4]a r en e 4f. To a solution of tetratosylate
3a (0.3 g, 0.26 mmol) in ethanol (20 mL) formaline (0.5 mL,
0.26 mmol) and 2 or 3 drops of acetic acid were added. Then
a solution of L-proline (0.59 g, 5.2 mmol) in ethanol (5 mL)
was added with stirring. The mixture was stirred at reflux
for 5 min and at room temperature for 24 h. The solvent was
evaporated in vacuo, and the solid formed was recrystallized
from cold methanol. Violet solid; yield 89%; mp 180-184 °C;
1H NMR (CDCl3, 200 MHz) δ 1.34 (d, J ) 6.2 Hz, 12H), 1.78
(br, s, 4H), 2.07 (br s, 4H), 2.46 (s, 12H), 2.84 (br s, 2H), 3.33
(br s, 2H), 4.17 (s, 4H), 4.20-4.60 (m, 6H), 5.96 (s, 2H), 6.82
(s, 2H), 7.12 (s, 2H), 7.38 (d, J ) 7.2 Hz, 8H), 7.82-7.90 (m,
Su p p or tin g In for m a tion Ava ila ble: Synthetic proce-
dures, spectral and analytical data for compounds 2d , 3b-d ,
5a -c, 4a , 4b, 5e-g, and 6 (6 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, can be ordered
from ACS; see any current masthead page for ordering
information.
J O981751A
(24) (a) PCMODEL is distributed by Serena Software, Dr. Kevin E.
Gilbert, P. O. 3076, Bloomington, IN 47402. (b) Discover, version 2.9.5;
Biosym Technologies: 9685 Scranton Road, San Diego, CA 92121-4778,
May, 1994.