Kemp's triacid attached to octa-O-methyl resorc[4]arenes: conformations in solution and comparative binding studies with various 2-amino pyridines

Article abstract of DOI:10.1016/j.tet.2008.01.138

We synthesized the new supramolecular host molecules 7 and 13 based on functionalized resorcarenes bearing Kemp's triacid. Conformations in solution have been investigated and the influence of intra- and intermolecular hydrogen bonds from the triacid was

Full text of DOI:10.1016/j.tet.2008.01.138

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Tetrahedron 64 (2008) 3813e3825
www.elsevier.com/locate/tet
Kemp’s triacid attached to octa-O-methyl resorc[4]arenes:
conformations in solution and comparative binding
studies with various 2-amino pyridines
Ion Stoll a, Andreas Mix b, Alexander B. Rozhenko c, Beate Neumann b,
Hans-Georg Stammler b, Jochen Mattay a,
*
a Organische Chemie I, Fakulta¨t fu¨r Chemie, Universita¨t Bielefeld, Postfach 100131, 33501 Bielefeld, Germany
b Anorganische Chemie III, Universita¨t Bielefeld, Postfach 100131, 33501 Bielefeld, Germany
c Institute of Organic Chemistry, Department of Chemistry, National Academy of Sciences of Ukraine, 5 Murmanskaya Street, 02660 Kiev, Ukraine
Received 11 January 2008; received in revised form 29 January 2008; accepted 31 January 2008
Available online 6 February 2008
Abstract
We synthesized the new supramolecular host molecules 7 and 13 based on functionalized resorcarenes bearing Kemp’s triacid. Conformations
in solution have been investigated and the influence of intra- and intermolecular hydrogen bonds from the triacid was shown by low temperature
and DOSY NMR experiments. The results of host 7 are supported by DFT calculations. The binding behaviour of 7 towards different 2-amino
pyridines in chloroform has been investigated by NMR titrations. The association constants reach from K¼207 Mꢀ1 for 2-amino-5-cyano pyridine
to K¼1551 Mꢀ1 for 2-amino-4-methyl pyridine. The association constants of the formed complexes of 7 with 2-amino pyridines were compared
with those of the simple host systems 14 and 15 in order to evaluate the influence of the attached resorcarene host.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Calixarenes; Supramolecular chemistry; 2-Amino pyridine; Hydrogen bonds
1. Introduction
molecular capsules of various size in the solid state7,8 and in so-
lution.9 For example, these giant hexameric capsules have been
reported to encapsulate various guest molecules even in the gas
phase in addition to the formation of smaller complexes depend-
ing on the conditions used.10,11
Kemp’s triacid1 is a well known building block in supramo-
lecular chemistry. The concave molecule shape was used for
constructing various systems capable for molecular recognition
such as rigid molecular clefts2 and flexible receptors3 with con-
vergent functional groups of different size. In addition, the in-
teraction of aromatic imides based on Kemp’s triacid with
adenine was investigated in polar and non-polar solvents and
the role of p-stacking and hydrogen bonding in molecular rec-
ognition was determined.4 These recognition phenomena are
supplemented by substrate orientation which becomes very
meaningful in catalysis.5 Resorc[4]arenes,6 a special type of
calix[4]arene derived from resorcinol, are known to form
Cavitands12 and carcerands13 are additional examples of
resorc[4]arene based supramolecular host systems. Whereas
non-functionalized resorc[4]arenes are dominated by hydrogen
bonding as driving force for complex formation and aggrega-
tion for the latter ones the resorcinol hydroxyl groups are func-
tionalized and therefore p-interaction and electron donation
become more important in their hosteguest chemistry. Cavi-
tands and carcerands are conformationally fixed contrary to
octa-O-methyl resorc[4]arenes giving rise to more flexible cav-
ities. In a combination of these two components, the calixarene
platform and the triacid moiety, a few systems are known with
different hosteguest interactions depending on the dimension
of their cavities.14e16 Analogously, our approach was to use
* Corresponding author. Tel.: þ49 521 106 2072; fax: þ49 521 106 6417.
E-mail address: oc1jm@uni-bielefeld.de (J. Mattay).
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.01.138

3814
I. Stoll et al. / Tetrahedron 64 (2008) 3813e3825
the triacid for molecular recognition and orientation by hydro-
gen bonding and to investigate the utilization of the resorc[4]-
arene cavity for further recognition phenomena by the above
described properties. In this work we present the synthesis of
two host systems 7 and 13 with a flexible resorc[4]arene cavity
combined with Kemp’s triacid. We also present studies on the
conformation of the host systems in solution and on the forma-
tion of complexes of 7 with various 2-amino pyridines.
selective cleavage of only one of the methoxy groups leading
to the phenolic alcohol 3b as byproduct (Scheme 2). By treat-
ment of the crude product with diazomethane in a mixture of
chloroform/methanol the alcohol 3 is obtained exclusively.
In the next step the benzylic alcohol is substituted by bromine
using phosphorus tribromide in very good yield. Resorc[4]arene
4 gives the benzylic phthalimide 5 and afterwards the
R = C11H23
OH
2. Results and discussion
O
OH
2.1. Synthesis
O
O
O
2.1.1. Synthesis of the host system 7
R
R
Starting from C-undecyltetrabromooctahydroxy-resorc-
[4]arene17 1 the host system 7 is prepared by a six-step synthe-
sis (Scheme 1).18,19 Treatment of 1 with 1 equiv n-butyllithium
followed by reaction with methyl chloroformate leads to the
mono functionalized resorc[4]arene 2. The reduction of the
methyl ester in the next step is crucial. Beside the formation
of desired benzylic alcohol 3 a side reaction emerges by
R
R
O
O
O
3b
Scheme 2. Byproduct 3b.
O
O
OH
Br
O
O
O
O
O
O
O
O
Br
O
O
O
O
O
R1
R1
O
R1
R1
O
R1
R1
R1
R1
R1
R1
R1
R1
O
O
(a)
(c)
(b)
Br
Br
O
4
O
O
O
O
O
O
O
O
2
2
2
R
R
R
1
2: R2=Br
8: R2=C(O)OMe
3: R2=H
4:R2=H
9: R2=CH2OH
10: R2=CH2Br
R =C11H23
OH
O
OH
O
O
O
O
N
N
N
NH2
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
R1
R1
O
O
R1
R1
R1
R1
O
R1
R1
R1
R1
R1
R1
R1
R1
R1
R1
(d)
(e)
(f)
O
O
O
O
O
O
O
O
O
O
O
O
O
2
2
R
R
N
O
O
HO
5: R2=H
11: R2=CH2Phth
6: R2=H
12: R2=CH2NH2
7
13
Scheme 1. Synthesis of host systems 7 and 13. (a) (i) n-butyllithium, THF, ꢀ78 ꢁC, 2 h; (ii) methyl chloroformate, 12 h, rt; (b) (i) LiAlH4, THF, 3.5 h, 60 ꢁC; (ii)
12 h, rt; (c) PBr3, CH2Cl2, 2 h, rt; (d) potassium phthalimide, hexadecyltributylphosphonium bromide, toluene, 2 h reflux; (e) H2NNH2$H2O, EtOH/THF (17:3),
reflux, 12 h; (f) 5-(chloroformyl)-cis,cis-1,3,5-trimethylcyclohexane-1,3-dicarboxylic anhydride, DMAP, pyridine, 17 h, 90 ꢁC.

I. Stoll et al. / Tetrahedron 64 (2008) 3813e3825
3815
corresponding amine 6. Kemp’s triacid was prepared by a proce-
dureknownfromtheliterature20,21 andtransformedto5-(chloro-
formyl)-cis,cis-1,3,5-trimethylcyclohexane-1,3-dicarboxylic
anhydride1 to give 7 by condensation with the amine 6. Crystals
of 7 were obtained from ethanol but an X-ray analysis was not
successful so far.
Summarizing, these three compounds (7, 14 and 15) pro-
vide a scale of host molecules to study different modes of
complexation by different host amplifications of the triacid
moiety.
2.2. Host conformations in solution
2.1.2. Synthesis of host 13
2.2.1. Resorcarene 7: an intramolecular hydrogen bond
The rccc-resorc[4]arene moiety of host 7 provides a flexible
cavity of which various conformations have been well de-
The resorcarene based host 13 was prepared analogously to
host 7. In the first step the resorcarene is functionalized twofold
by treatment with 2 equiv n-butyllithium. The reaction mixture
is equilibrated for 2 h to give exclusively the oppositely function-
alized arenes. In the next step no cleavage of a methoxy group
occurs. This reaction was carried out several times for 3 and 9
andonlyfor themonofunctionalizedresorcarene3bondcleavage
happens. Further reaction steps take place in good yields to give
host 13. Also single crystals of host 13 were obtained from
acetone but an X-ray analysis was not successful.
1
scribed earlier.23e25 The H NMR spectra of 7 are in agree-
ment with a Cs symmetry. The resonances of the three upper
rim aromatic protons are in a 2:1 distribution with very small
differences in the chemical shift (0.015 ppm) and the reso-
nances of the four lower rim aromatic protons show a 2:1:1
ratio.
There are also two triplets of respective two chemical iden-
tical methine protons with only very small difference of the
chemical shift (0.03 ppm). We assume that an equilibrium
geometry of host 7 is made up of two interconverting boat con-
formations giving in average a cone like conformation at the
NMR time scale as it is commonly reported for resorc[4]-
arenes (Fig. 2a and b).
2.1.3. Synthesis of reference hosts 14 and 15
For hosteguest studies (see Section 3) two further host
molecules were synthesized (Scheme 3). Compound 14 was
prepared using a slightly different procedure as reported in
the literature.22 Compound 15 was prepared analogously to
7. Single crystals of 15 were obtained from chloroform/meth-
anol 1:1 and the X-ray analysis shows an intermolecular
hydrogen bond in the solid state (Fig. 1).
The most favourable conformations of the model 7a corre-
sponding to the above mentioned interconversion process have
been calculated at the DFT (RI-BP-86) level of approximation.
The lower rim n-undecyl groups were replaced by methyl
CH3
CH3
CH3
H
CH3
H
H3C
H3C
H
H
O
O
O
OH
OH
N
N
O
O
O
CH3
O
CH3
H3C
O
H
14
15
Scheme 3. Molecular host systems 14 and 15. Bold protons are monitored for
the determination of association constants (see Section 3).
Figure 2. (a) Calculated structure 7a-1 as model for a conformer of 7; (b)
calculated structure 7a-2 as model for a conformer of 7. A hydrogen bond
from the carbon acid to a methoxy oxygen is pictured by the dashed line.
Figure 1. X-ray structure of 15.

3816
I. Stoll et al. / Tetrahedron 64 (2008) 3813e3825
groups. Herein, the conformation 7a-1 is slightly preferred.
The total energy of the alternative conformation 7a-2 is only
1.8 kcal/mol higher. For both conformers a formation of an in-
tramolecular C(O)OeH/O hydrogen bond has been revealed.
Beyond the hydrogen bonds illustrated in Figure 2a and b
(7a-1 and 7a-2), conformations with intramolecular hydrogen
bonds to the vicinal resorcinol methoxy oxygens are also im-
portant (7b). The structure 7b (Fig. 3) is only 0.5 kcal/mol
higher in energy as the structure 7a-1.
a) 298 K
b) 233 K
c) 203 K
12.6
d) 203 K
after
addition of
methanol-d4
6.0
(ppm)
Figure 3. Calculated structure 7b as model for a conformer of 7. A hydrogen
bond from the acid to a vicinal resorcinol methoxy oxygen is pictured by the
dashed line.
Figure 4. Aromatic region of the 1H NMR spectra of 7 (600 MHz, CD2Cl2) at
(a) 298 K; (b) 233 K; (c) 203 K, left: down field region of spectrum (c); (d)
203 K, after addition of a small amount of methanol-d4.
To investigate the influence of the intramolecular hydrogen
bonds the analogous carboxylic methyl ester 16 has been syn-
thesized (Scheme 4). As expected the methyl ester 16 shows
Cs symmetry at the H NMR time scale as well. Interestingly
both compounds show a remarkable difference in the temper-
ature dependence of the conformations formed in solution.
intramolecular hydrogen bond between the carboxylic acid
and an oxygen of a methoxy group. At 203 K the interconver-
sion of different conformers becomes separated at the NMR
time scale and the signal sets are adjusted. The 1H NMR spectra
at 203 K seem to consist of more than just two isomers. Because
of the not clear assignment of the signals at this temperature we
were not able to quantify the energy of the interconversion
barrier of 7.
1
OH
O
O
O
To avoid intramolecular hydrogen bonding a small amount
of methanol is added. The spectrum is sharpened again and al-
most matches the spectrum at room temperature (Fig. 4d). For
comparison the 1H NMR spectrum in acetone, which is known
to avoid intramolecular hydrogen bonding, is given in Section
O
O
N
N
O
O
O
O
O
O
O
O
1
O
O
O
O
5 as well. The H NMR spectrum of the methyl ester 16 at
R
R
R
R
(a)
R
R
R
R
O
O
a) 303 K
O
O
O
O
Solvent signal
R =C11H23
7
16
Scheme 4. Synthesis of the acid ester 16. (a) MeOH/CHCl3 (1:1), CH2N2.
The temperature dependence of the 1H NMR spectra of 7 is
given in Figure 4. Only the aromatic region of the spectrum is
shown. At room temperature the spectrum shows the above
described profile, the chemical shifts are given in Section 5.
With decreasing temperature (233 K) the signals are ex-
tremely broadened due to the slow dynamics of the interconver-
sion process between the different conformers. At 203 K a peak
at very low field (12.66 ppm) appears. This indicates a low elec-
tron density of the corresponding proton and is assigned to an
b) 203 K
7.0
6.6
6.2
5.8
5.4
5.0
4.6
4.2
3.8
Figure 5. 1H NMR spectra of 16 (600 MHz, CD2Cl2) at (a) 303 K; (b) 203 K.

I. Stoll et al. / Tetrahedron 64 (2008) 3813e3825
3817
room temperature and at 203 K is given in Figure 5. The reso-
nances at low temperature are broadened and shifted but the
original shape of the spectrum is still remained. In conclusion,
the carboxylic acid resorcarene 7 shows a relatively high inter-
conversion barrier in comparison to the ester 16 and we as-
sume that this is caused by intermolecular hydrogen bonds.
In these conformations the acid moiety points towards the re-
sorcarene cavity and the resorcarene exhibits a boat conforma-
tion with Cs symmetry.
CDCl3, 600 MHz
a)
b)
A similar influence on the conformation of other hydrogen-
bonded supramolecular systems was reported by Chung et al.
as well.26
after addition of
CD3OD
c)
2.2.2. Resorcarene 13: intermolecular hydrogen bonding
The resorcarene 13 also provides an interesting behaviour
in solution. At room temperature in chloroform no evidence
for intramolecular hydrogen bonding to a methoxy oxygen
or to the opposite carboxylic acid was found. The spectrum al-
most matches the spectrum in acetone which is known to avoid
hydrogen bonding. At room temperature a white solid slowly
precipitates from the satd acetone soln. This precipitate can
be dissolved in chloroform or dichloromethane and shows a re-
markable different NMR spectrum (Figs. 6 and 7). The differ-
ence is most demonstrative for the methoxy groups which
appear from 3.0 to 4.0 ppm.
7.2
6.4
5.6
4.8
4.0
3.2
2.4
1.6
Figure 7. (a) 1H NMR spectra of 13 (600 MHz, CDCl3); (b) after one week in
chloroform solution; (c) 16 h after addition of a small amount of methanol-d4.
Since an intramolecular hydrogen bond would not change
the diffusion coefficient upon addition of methanol these re-
sults clearly indicate intermolecular aggregation of 13. Due
to the broadened resonances apparently a dynamic equilibrium
prevails in solution. This might happen between intermolecu-
lar hydrogen bond aggregates of different size. Therefore on
the NMR time scale only an average diffusion coefficient
was detected.
3. Hosteguest chemistry in solution. NMR titrations:
quantitative binding studies
Solvent signal
a)
Association constants for the complex formation of the
hosts 7, 14 and 15 with various 2-amino pyridines in chloro-
form were determined by NMR titrations. The guest molecules
for hosteguest studies were commercially purchased (for de-
tails see Section 5) besides amino pyridine 17 which was pre-
pared according to the literature.28,29 The determined binding
constants are summarized in Table 1. For all titrations the
coefficient of determination is higher than 0.99 and the given
errors are the twofold standard deviation. For host 7 the
resonances used for monitoring are the two magnetic equiva-
lent equatorial protons of the Kemp’s triacid moiety (HKemp),
which appear at 2.64 ppm and the lower rim proton of the re-
sorcarene scaffold (Harom), which appears at 6.47 ppm in the
1H NMR spectrum. A graphic assignment can be found in Sec-
tion 5 (Scheme 5). The determined association constants for
the different protons are in good agreement within the experi-
mental error and prove the experimental consistency with one
exception (see below). In case of 2-amino pyridines the largest
association constants are obtained for the more electron rich
guests up to Ka¼1551 Mꢀ1 (2-amino-4-methyl pyridine).
The association constants for less electron rich amino pyr-
idines range from 200 to 600 Mꢀ1, they are significantly
smaller than for the amino pyridines without electronegative
substituents. The substitution pattern of the guests does not af-
fect the association constants in a distinct way as shown for
the methyl and trifluoromethyl substituted 2-amino pyridines.
Within the experimental error, they do not vary significantly.
b)
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0
Figure 6. 1H NMR spectra of 13 (500 MHz, CD2Cl2) (a) 16 h after addition of
a small amount of methanol-d4; (b) precipitate from acetone dissolved in
methylene chloride.
After addition of a small amount of methanol the spectrum
can be transferred into the origin shape. This proves that no
reaction occurred and that the interaction is driven by hydro-
gen bonding. To investigate whether intra- or intermolecular
hydrogen bonding takes place DOSY NMR experiments
were carried out. For a better comparability to the literature
the DOSY experiments were carried out in chloroform. The
1H NMR spectrum in chloroform is broadened in comparison
to the dichloromethane spectrum but the similar shape remains
(Fig. 7). Even though, without methanol addition the spectrum
merges within few days the spectrum of the monomer of 13.
DOSY NMR measurements of spectra (b) and (c) in chlo-
roform were carried out at 295.4 K. For spectrum (b) a diffu-
sion coefficient of 0.35ꢂ10ꢀ5 cm2 sꢀ1 was determined and for
spectrum (a) after methanol addition a diffusion coefficient of
0.62ꢂ10ꢀ5 cm2 sꢀ1. These diffusion coefficients are in a typi-
cal magnitude of resorcarenes and resorcarene assemblies.27

3818
I. Stoll et al. / Tetrahedron 64 (2008) 3813e3825
Table 1
Association constants for the complex formation of hosts 7, 14 and 15 with various 2-amino pyridines (K/Mꢀ1
)
Guest
7
14
15
Harom
HKemp
HKemp
Harom
HKemp
N
No
Consistency
6290ꢃ812
1872ꢃ324
7905ꢃ1424
1035ꢃ156
6591ꢃ1730
NH2
N
NH2
1176ꢃ100
1018ꢃ116
558ꢃ54
1287ꢃ188
843ꢃ100
N
NH2
d
1493ꢃ130
823ꢃ152
918ꢃ152
362ꢃ50
17
N
NH2
d
356ꢃ34
345ꢃ42
361ꢃ82
F3C
N
NH2
296ꢃ52
CF3
N
NH2
1377ꢃ98
1551ꢃ62
d
1382ꢃ110
1446ꢃ100
207ꢃ46
HC3
N
NH2
CH3
N
NH2
N
N
NH2
413ꢃ18
301ꢃ54
d
N
N
NH2
271ꢃ34
F
However, the association constant for 2-amino-4-cyano pyr-
idine is twice as large as for 2-amino-5-cyano pyridine. Not
for all titrations both host protons can be fitted due to small
change in chemical shift and the larger relative experimental
error.
For comparison the association constants for complexes of
host 14 and 15 with selected amino pyridines are determined
as well. In general, the complexes of host 14 with 2-amino pyr-
idines show the largest association constants. The fitted protons
are the magnetic equivalent equatorial protons of the triacid at
2.62 ppm (HKemp) (see Scheme 3, bold). The complexes of 15
with 2-amino pyridines also exceed the complexes of 7 but
the association constants are notably smaller than for the com-
plexes of 14. Again the resonances used for monitoring are the
equatorial Kemp’s triacid protons at 2.67 ppm (HKemp) and the
aromatic proton at 7.08 ppm (Harom) (bold protons in Scheme
3), which were in good agreement within the experimental er-
ror. The association constants for the complexes with 1-amino
isoquinoline must be treated carefully. The experimentally de-
termined association constants for the different protons of host
7 are not consistent. Therefore isomeric complexes have to be
11 10
8
9
HO
O
O
O
NO
O
4
b
O
c
O
5
O
O
O
a
O
d
C
11H23
6
3
2
1
C11H23
C11H23
7
H23C11
Scheme 5. Graphical assignment of the 1H NMR of host 7.

I. Stoll et al. / Tetrahedron 64 (2008) 3813e3825
3819
taken into account for 7. In this case microscopic binding con-
stants cannot be determined. Despite these limitations it can be
established that 1-amino isoquinoline is the strongest binding
partner for the hosts 14 and 15 of the complexes studied here.
In conclusion, the largest association constants for all three
host systems are obtained for the complexes with electron
rich guests. The influence of the substitution pattern of the
2-amino pyridines plays a minor role.
Also NMR titration experiments of the monomer of host 13
with 2-aminopyrimidines were carried out. Surprisingly, by
the shape of the binding isotherm a 1:1 complex of the host
13 and an aminopyrimidine can be excluded (Fig. 9). In con-
sideration of the results of the titration experiments with host 7
and the difficult evaluation of higher complex stoichiometries
in equilibrium these experiments were not pursued.
were added and spectra were recorded after each addition until
complex saturation. The obtained titration curves were solved
by non-linear fitting by iterative solution of Eq. 1.
0
ðdH ꢀ dCÞ 1
1
@
dobs
¼
½Hꢄ0þ½Gꢄ þ
½Hꢄ0
2
K
1
sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
ꢀ
ꢁ
2
1
A
ꢀ
½Hꢄ0þ½Gꢄ þ
ꢀ4½Hꢄ0½Gꢄ ꢀ dH
ð1Þ
K
Eq. 1 describes the relation between the observed chemical
shift dobs and the association constant K. [H]0 is the host con-
centration and [G] the guest concentration. The chemical shift
of the host dH was measured in absence of a guest. The chemi-
cal shift of the formed complex dC was treated as floating
parameter. An elaborated derivation of Eq. 1 and further infor-
mation are reported in the literature.30e32 As an example the
titration curve for the complex formation of 7 with 2-amino
pyridine is shown in Figure 8. The shape of the binding iso-
therms for all titrations clearly shows a 1:1 complex stoichio-
metry, which is assured by a representative Job-plot33 for the
complex of 7 with 2-amino pyridine (Fig. 8, insertion).
4. Conclusion
We presented the synthesis of a mono and a distal function-
alized octamethoxy resorcarene attached to Kemp’s triacid. The
conformation of the hosts 7 and 13 in solution has been inves-
tigated. It is shown by low temperature NMR and by compari-
son with the corresponding methyl ester 16 that intramolecular
hydrogen bonding from the triacid to the resorcarene is crucial
for the structure of host 7 in solution. The results are supported
by DFT calculations. We also have shown by DOSY NMR
experiments that host 13 forms aggregates in solution driven
by intermolecular hydrogen bonding.
The association constants for the complexes of 7 with var-
ious 2-amino pyridines in chloroform have been determined
by NMR titration clearly showing the influence of electron do-
nating and electron withdrawing substituents over a large scale
of guest molecules. Association constants for complexes of se-
lected 2-amino pyridines with smaller host molecules 14 and
15 were determined as well. The initial idea was to pre-orga-
nize a hosteguest complex by hydrogen bonding of the triacid
moiety to the guest molecule and to investigate the influence
of the attached host, i.e., the resorcarene to provide a pocket
like cavity for the guest. A cooperative binding of the triacid
moiety and the attached host would have increased the associ-
ation constant for at least one order of magnitude. However,
based on our measurements we certainly can exclude such
a cooperative binding by the triacid and the resorcarene or
dimethoxy resorcinol moieties.
Experiments were carried out at 300 K. Spectra were re-
corded at a guest/host ratio of 0.2, 0.4, 0.6, 0.8, 1, 2, 3, 4, 5, 7,
9, 11, 13, 15, 20, 25 and 45. In the case of 2-amino-4-cyano pyr-
idineand2-amino-5-cyanopyridine0.05 Mstock solutionswere
prepared due to the weak solubility. Because of the limited vol-
ume of the NMR tube only 25 guest equivalents were added
but complex saturation was reached. Amino pyridines were
commercially purchased from Alfa Aeser (2-amino-5-methyl
pyridine (99%), 2-amino-4-methyl pyridine (98%), 2-amino-5-
(trifluoro)methyl pyridine (97%), 2-amino-4-(trifluoro)methyl
pyridine (99%), 2-amino-5-cyano pyridine (98%), 2-amino-4-
cyano pyridine (97%) and 2-amino-5-fluoro pyridine (97%))
and Aldrich (2-Amino pyridine (99%) and 1-amino isoquinoline
(99%)) and used as received. For the Job-plot stock solutions
(c¼4.3ꢂ10ꢀ3 M) of the host 7 and 2-amino pyridine were
1640
1630
16
1620
1610
1600
14
12
10
8
5. Experimental section
6
4
2
5.1. General methods
0
0.0 0.2 0.4 0.6 0.8 1.0
1590
mole fraction of host 7
5.1.1. General procedure for NMR titrations
A solution of the host system was prepared in deuterated
chloroform (c¼3ꢂ10ꢀ3 M). Deuterated chloroform was pur-
chased from Acros Organics and used as received. 0.7 mL of
the host solution was transferred to a 5ꢂ178 mm NMR tube
1580
0
10
2
equivalents of 2-amino pyridine
3
40
50
Figure 8. Measured ( ) and calculated (solid line) chemical shift of the host
resonances of 7 upon addition of 2-amino pyridine (initial chost¼3ꢂ10ꢀ3 M)
in deuterated chloroform. Insertion: Job-plot for the complex of 7 with
2-amino pyridine (coverall¼4.3ꢂ10ꢀ3 M).
1
and a H NMR spectrum was recorded on a Bruker Avance
600 spectrometer with internal standard (CHCl3, 7.24 ppm).
Then aliquots of a 0.1 M stock solution of an amino pyridine

3820
I. Stoll et al. / Tetrahedron 64 (2008) 3813e3825
prepared. Aliquots of the host solution varying from 0 to 480 ml
were transferred to NMR tubes. The stock solution of the guest
was added to complete the volume to 600 ml. A spectrum was re-
corded for each sample on a Bruker DRX 500 spectrometer. For
evaluation of NMR spectra Bruker 1D NMR software was used.
Forhosteguesttitrationsof host13stocksolutionswiththesame
concentrations for the host and the guest as mentioned for the ti-
trationsof 7wereprepared inchloroform. Titrationswerecarried
out with 2-aminopyrimidine, 2-amino-5-phenyl-aminopyrimi-
dine and a-naphthyl-aminopyrimidine. The binding isotherm
of the titration of host 13 with 2-aminopyrimidine is shown in
Figure 9 which is representative for the shape of the isotherms
of the other titrated aminopyrimidines.
(3ꢂ). Dry DMF (250 mL) was added and following a solution
of rccc-5,11,17,23-tetrabromo-2,8,14,20-tetra-(n-undecyl)-
resorc[4]arene18,43 (15.4 g, 10.8 mmol) and iodomethane
(12.2 mL, 27.6 g, 195 mmol) in dry DMF was added slowly
to keep the temperature below 35 ꢁC. The mixture was stirred
for 1 day at room temperature. Iodomethane (5 mL, 11.4 g,
80 mmol) was added and the mixture was stirred at 50 ꢁC
for additional 1 day. At room temperature ethanol (20 mL)
was added to dispose the excess of sodium hydride. The
solvent was removed in vacuo and the residue was dissolved
in chloroform (500 mL) and satd NH4Cl soln (300 mL). The
aqueous phase was extracted with chloroform (2ꢂ) and the
organic layer was washed with water (3ꢂ) and dried over
MgSO4. The solvent was removed in vacuo and after recrystal-
lization from 2-propanol the pure product was obtained as col-
ourless crystals (15 g, 9.78 mmol, yield: 91%). Mp: 79 ꢁC; 1H
NMR (CDCl3, 500 MHz, 27 ꢁC): d¼6.50 (br s, 4H, ArH), 4.43
2625
2620
2615
2610
2605
2600
2595
2590
2585
3
(t, J¼7.4 Hz, 4H, ArCHAr), 3.64 (s, 24H, COOCH3), 1.88e
1.78 (m, 8H, CHCH2), 1.36e1.17 (m, 72H, CH2), 0.84 (t,
3J¼7.0 Hz, 12H, CH3) ppm; 13C NMR (CDCl3, 125 MHz,
27 ꢁC): d¼154.3, 134.6, 125.5, 113.1, 60.6, 38.6, 35.0, 31.9,
29.8, 29.8, 29.7, 29.7, 29.7, 29.4, 28.4, 22.7, 14.1 ppm;
HRMS: m/z calcd for C80H124O8Br4þNH4 [MþNH4]þ
1546.63680; found 1546.63432; IR (KBr): ~n ¼ 2923, 2855,
1468, 1418, 1392, 1327, 1296, 1229, 1189, 1151, 1090,
0
10
20
30
equivalents of 2-aminopyrimidine
40
50
1039, 1003, 967, 917, 896, 777, 720 cmꢀ1
.
Figure 9. Measured chemical shift of host 13 upon addition of 2-aminopyrimi-
dine (initial chost¼3ꢂ10ꢀ3 M) in deuterated chloroform.
5.2.2. rccc-5,11,17-Tribromo-23-[methoxycarbonyl]-
5.1.2. Details of calculations
4,6,10,12,16,18,22,24-octa-O-methyl-2,8,14,20-tetra-
All calculations were performed with the TURBOMOLE set
ofprograms.34,35 Structureswereoptimizedwithoutanysymme-
try restrictions. The standard split-valence SV(P)basissets36 and
DFT BP8637,38 functional were used for calculations in combi-
nation with the high integration accuracy (grid¼5) and conver-
gence criterion (scfconv¼1ꢂ10ꢀ8). For more performance, the
RI (Resolution of the Identity)39e41 algorithm was employed
for all calculation routines. No vibration frequency calculations
were made, due to the large size of the investigated structures.
The single-point energy calculations were performed with the
optimized structures using the TZV basis sets of triple-zeta qual-
ity suggested by Ahlrichs et al.:36 (11s6p)/[5s3p] for C, N, O and
F contracted as {62111/411} and (5s)/[3s] for H with contraction
{311}. The basis sets were expanded by addition of the polariza-
tion functions (the TZVP basis sets standard within the TURBO-
MOLE packet) formed as the TZV basis sets plus one set of three
p-functions for hydrogen and one set of five d-functions for the
other elements. The VMD program packet42 was used for the
graphical presentation of the calculated structures.
(n-undecyl)-resorc[4]arene (2)
A solution of resorc[4]arene (1) (1.19 g, 0.78 mmol) in
50 mL anhydrous THF under argon-atmosphere was cooled
to ꢀ78 ꢁC and n-butyllithium (0.49 mL of a 1.6 M solution
in hexanes, 0.78 mmol) was added rapidly. After 2 h methyl
chloroformate (1 mL, 12.9 mmol) was added and the mixture
was allowed to warm to room temperature within 12 h. Meth-
anol (5 mL) was added and the solvent was removed in vacuo.
The residue was dissolved in CHCl3 and the organic layer
was washed with water (3ꢂ), and was dried over anhydrous
MgSO4. Evaporation gave the crude product as yellow oil.
After column chromatography (SiO2, cyclohexane/ethyl ace-
tate, 4:1) the pure product was obtained as colourless solid
(0.8 g, 0.53 mmol, yield: 68%). Mp: 62e64 ꢁC; 1H NMR
(CDCl3, 500 MHz, 27 ꢁC): d¼6.61 (br s, 2H, ArH), 6.55 (br
s, 2H, ArH), 4.45 (t, 3J¼7.5 Hz, 2H, ArCHAr), 4.40 (t,
3J¼7.5 Hz, 2H, ArCHAr), 3.89 (s, 3H, COOCH3), 3.63 (br
s, 12H, OCH3), 3.61 (br s, 12H, OCH3), 1.87e1.79 (m, 8H,
CHCH2), 1.34e1.16 (m, 72H, CH2), 0.84 (t, 3J¼6.9 Hz,
12H, CH3) ppm; 13C NMR (CDCl3, 125 MHz, 27 ꢁC):
d¼167.5, 154.3, 154.3, 153.9, 134.6, 128.0, 125.5, 125.5,
122.5, 113.2, 113.1, 61.9, 60.6, 60.5, 52.5, 38.5, 37.8, 35.1,
35.1, 31.9, 29.8, 29.7, 29.7, 29.3, 28.4, 28.4, 22.7, 14.1 ppm;
HRMS: m/z calcd for C82H128O10Br3þHþ [MþH]þ
1509.70521; found 1509.70431; IR (KBr): ~n ¼ 2956, 2922,
2851, 1736, 1580, 1470, 1456, 1420, 1396, 1291, 1261,
5.2. Synthetic procedures
5.2.1. rccc-5,11,17,23-Tetrabromo-4,6,10,12,16,18,22,24-
octa-O-methyl-2,8,14,20-tetra-(n-undecyl)-resorc[4]-
arene (1)
Sodium hydride (60%) in paraffin (5.2 g, 3.0 g pure sodium
hydride, 127 mmol) under argon was washed with n-pentane
1039, 1009, 800 cmꢀ1
.

I. Stoll et al. / Tetrahedron 64 (2008) 3813e3825
3821
5.2.3. rccc-5-Hydroxymethyl-4,6,10,12,16,18,22,24-octa-O-
methyl-2,8,14,20-tetra-(n-undecyl)-resorc[4]arene (3)
butylphosphonium bromide in toluene (20 mL) was refluxed
for 3 h. The solvent was evaporated in vacuo and the residue
dissolved in CH2Cl2. The solution was washed with 1 N
NaOH and dried over anhydrous MgSO4. The solvent was
removed under reduced pressure and the crude product was
purified by column chromatography (SiO2, cyclohexane/ethyl
acetate, 3:1) yielding a colourless solid (0.19 g, 0.14 mmol,
yield: 45%). Mp: 56e58 ꢁC; 1H NMR (CDCl3, 500 MHz,
27 ꢁC): d¼7.87e7.61 (m, 4H, ArH), 6.70 (s, 1H, ArH), 6.66
(s, 1H, ArH), 6.57 (s, 2H, ArH), 6.30 (s, 2H, ArH), 6.27
A mixture of resorc[4]arene (2) (1 g, 0.66 mmol) and LiAlH4
(150 mg, 4 mmol)inanhydrousTHF (30 mL)underargon-atmo-
sphere was refluxed for 3.5 h and additional LiAlH4 (100 mg,
2.6 mmol) was added. The mixture was stirred for 12 h at room
temperature and treated with methanol (10 mL). HCl (2 M)
was added until the mixture became acidic. The mixture was ex-
tractedwith CHCl3 (3ꢂ). Theorganiclayer waswashed withsatd
NaHCO3 soln and brine, and was dried over anhydrous MgSO4.
After evaporation the product (0.71 g, 0.57 mmol, yield: 86%)
was obtained as white solid. The product can be recrystallized
3
(s, 1H, ArH), 4.84 (s, 2H, ArCH2), 4.42 (t, J¼7.5 Hz, 4H,
ArCHAr), 3.60 (s, 6H, OCH3), 3.59 (s, 6H, OCH3), 3.58 (s,
6H, OCH3), 3.39 (s, 6H, OCH3), 1.84e1.68 (m, 8H,
CHCH2), 1.33e1.10 (m, 72H, CH2), 0.85 (t, 3J¼6.9 Hz,
12H, CH3) ppm; 13C NMR (CDCl3, 125 MHz, 27 ꢁC):
d¼167.9, 156.0, 155.7, 155.5, 134.3, 133.8, 133.5, 132.4,
126.8, 126.5, 126.2, 126.1, 125.7, 124.9, 123.6, 122.9,
120.8, 96.5, 95.5, 61.1, 56.2, 55.6, 36.1, 35.5, 25.4,
34.6, 33.2, 31.9, 30.0, 30.0, 29.9, 29.8, 29.7, 29.7,
29.4, 28.2, 28.1, 22.7, 14.1 ppm; HRMS: m/z calcd for
1
from acetone. Mp: 87e89 ꢁC; H NMR (CDCl3, 600 MHz,
27 ꢁC): d¼6.95 (s, 1H, ArH), 6.91 (s, 1H, ArH), 6.42 (s, 2H,
ArH), 6.32 (s, 2H, ArH), 6.14 (s, 1H, ArH), 4.56 (s, 2H,
ArCH2), 4.48 (t, 3J¼7.4 Hz, 2H, ArCHAr), 4.42 (t, 3J¼7.4 Hz,
2H, ArCHAr), 3.76 (s, 6H, OCH3), 3.75 (s, 6H, OCH3), 3.46 (s,
6H, OCH3), 3.26 (s, 6H, OCH3), 1.87e1.72 (m, 8H, CHCH2),
1.35e1.17 (m, 72H, CH2), 0.85 (t, 3J¼7.2 Hz, 12H, CH3) ppm;
13C NMR (CDCl3, 125 MHz, 27 ꢁC): d¼155.9, 155.8, 155.4,
155.1, 133.1, 127.4, 126.6, 126.4, 126.2, 123.9, 96.0, 95.5,
61.3, 56.5, 56.2, 55.8, 55.4, 35.9, 35.3, 35.0, 34.7, 31.9, 30.0,
29.9, 29.8, 29.7, 29.4, 28.2, 28.2, 22.7, 14.1 ppm; HRMS: m/z
calcd for C81H130O9þNHþ4 [MþNH4]þ 1265.00531; found
1265.00765; IR (KBr): ~n ¼ 3456, 2922, 2853, 1611, 1580,
C89H133O10NþNaþ
1459, 1439, 1398, 1351, 1299, 1201, 1040 cmꢀ1
[MþNa]þ
1398.98217;
found
1398.98139; IR (KBr): ~n ¼ 2924, 2854, 1719, 1655, 1499,
.
5.2.6. rccc-5-Aminomethyl-4,6,10,12,16,18,22,24-octa-O-
methyl-2,8,14,20-tetra-(n-undecyl)-resorc[4]arene (6)
1506, 1467, 1299, 1202, 1095, 1040, 904, 818, 722 cmꢀ1
.
A solution of resorc[4]arene (5) (0.86 g, 0.62 mmol) in a
mixture of ethanol and THF (17:3, 50 mL) was treated with hy-
drazine hydrate (2 mL, approx. 27 mmol pure hydrazine) and
refluxed for 12 h. The solution was cooled to 0 ꢁC and concd
HCl (1.5 mL) was added. The solution was stirred for additional
2 h under ice cooling and concd NaOH was added till pH>10.
The precipitate was filtered off and washed with concd NaOH
and cold ethanol. The colourless solid (0.7 g, 0.56 mmol, yield:
90%) was dried in vacuo. Mp: 125 ꢁC; 1H NMR (CDCl3,
500 MHz, 27 ꢁC): d¼6.92 (s, 1H, ArH), 6.90 (s, 1H, ArH),
6.42 (s, 2H, ArH), 6.30 (s, 2H, ArH), 6.12 (s, 1H, ArH), 4.47
(t, 3J¼7.4 Hz, 2H, ArCHAr), 4.42 (t, 3J¼7.4 Hz, 2H, ArCHAr),
3.77 (s, 6H, OCH3), 3.76 (s, 6H, OCH3), 3.62 (s, 2H, ArCH2),
3.46 (s, 6H, OCH3), 3.19 (s, 6H, OCH3), 1.90e1.70 (m, 8H,
5.2.4. rccc-5-Bromomethyl-4,6,10,12,16,18,22,24-octa-O-
methyl-2,8,14,20-tetra-(n-undecyl)-resorc[4]arene (4)
A solution of resorc[4]arene (3) (0.49 g, 0.39 mmol) in dry
dichloromethane (20 mL) was treated with phosphonium tribro-
mide (0.23 g, 0.85 mmol). The solution turned slightly pink. The
reaction mixture was stirred for 2 h at room temperature and
2-propanol (5 mL) was added. The solution was washed with
satd NaHCO3 soln and brine, and dried over anhydrous
MgSO4. Evaporation of the solvent afforded the product
(0.47 g, 3.6 mmol, yield: 92%) as colourless solid. Mp: 79e
1
80 ꢁC; H NMR (CDCl3, 500 MHz, 27 ꢁC): d¼7.03 (s, 1H,
ArH), 6.96 (s, 1H, ArH), 6.44 (s, 2H, ArH), 6.28 (s, 2H, ArH),
3
6.15 (s, 1H, ArH), 4.57 (s, 2H, ArCH2), 4.49 (t, J¼7.4 Hz,
3
3
2H, ArCHAr), 4.40 (t, J¼7.4 Hz, 2H, ArCHAr), 3.80 (s, 6H,
CHCH2), 1.38e1.14 (m, 72H, CH2), 0.85 (t, J¼6.9 Hz, 12H,
13
OCH3), 3.79 (s, 6H, OCH3), 3.47 (s, 6H, OCH3), 3.32 (s, 6H,
OCH3), 1.90e1.72 (m, 8H, CHCH2), 1.42e1.13 (m, 72H,
CH3) ppm; C NMR (CDCl3, 125 MHz, 27 ꢁC): d¼155.9,
155.7, 155.3, 155.1, 133.0, 129.6, 127.4, 126.8, 126.4, 125.3,
123.8, 96.0, 95.1, 60.9, 56.2, 55.7, 55.4, 36.8, 36.1, 35.3,
35.0, 34.7, 31.9, 30.0, 30.0, 29.9, 29.8, 29.7, 29.4, 28.2, 22.7,
14.1 ppm; HRMS: m/z calcd for C81H131NO8þHþ [MþH]þ
1246.99475; found 1246.99483; IR (KBr): ~n ¼ 3449, 2922,
2852, 1610, 1579, 1507, 1466, 1400, 1299, 1200, 1097, 1039,
3
CH2), 0.84 (t, J¼6.9 Hz, 12H, CH3) ppm; 13C NMR (CDCl3,
125 MHz, 27 ꢁC): d¼156.2, 155.9, 155.8, 155.1, 132.9, 128.3,
127.8, 126.4, 126.3, 126.2, 125.0, 122.8, 95.9, 95.3, 61.3, 56.2,
55.7, 55.1, 36.1, 35.6, 35.0, 34.4, 31.9, 30.0, 29.9, 29.8, 29.8,
29.7, 29.7, 29.7, 29.7, 29.4, 28.3, 28.1, 25.3, 22.7, 14.1 ppm;
HRMS: m/z calcd for C81H129O8BrþNHþ4 [MþNH4]þ
1326.92091; found 1326.92150; IR (KBr): ~n ¼ 2921,
2852, 1611, 1582, 1506, 1467, 1299, 1202, 1042, 903, 811,
903, 819, 720 cmꢀ1
.
5.2.7. Kemp’s acid resorc[4]arene (7)
720 cmꢀ1
.
A solution of the resorc[4]arene (6) (0.7 g, 0.56 mmol),
5-(chloroformyl)-cis,cis-1,3,5-trimethylcyclohexane-1,3-dicarb-
oxylic anhydride (0.18 g, 70 mmol) and a catalytic amount of
4-dimethylamino pyridine in pyridine (20 mL) was heated to
90 ꢁC for 17 h. The solvent was removed invacuo and the residue
was dissolved in CHCl3. The organic layer was washed with 2 N
5.2.5. rccc-5-Phthalimidomethyl-4,6,10,12,16,18,22,24-octa-
O-methyl-2,8,14,20-tetra-(n-undecyl)-resorc[4]arene (5)
A mixture of the resorc[4]arene (4) (0.41 g, 0.31 mmol),
potassium phthalimide (0.3 g, 1.62 mmol) and hexadecyltri-

3822
I. Stoll et al. / Tetrahedron 64 (2008) 3813e3825
HCl and 2 N NaOH and the solvent was removed under reduced
pressure. The crude product was purified by column chromatog-
raphy(SiO2, cyclohexane/ethylacetate, 1:1)yieldinga colourless
solid (0.34 g, 0.23 mmol, yield: 41%). Mp: 79e81 ꢁC; 1H NMR
(CDCl3, 500 MHz, 27 ꢁC): d¼6.67 (s, 2H, ArH, lower rim, H1),
6.53 (s, 1H, ArH, lower rim, H2), 6.47 (s, 1H, ArH, lower rim,
H3), 6.29 (s, 2H, ArH, upper rim, H4), 6.27 (s, 1H, ArH, upper
rim, H5), 4.84(s, 2H, ArCH2R),4.41(t, 3J¼7.4 Hz, 2H, ArCHAr,
H6), 4.38(t, 3J¼7.4 Hz, 2H, ArCHAr, H7), 3.62(s, 6H, OCH3 a),
3.55(s, 6H, OCH3 b), 3.53(s, 6H, OCH3 c), 3.35(s, 6H, OCH3 d),
ꢀ78 ꢁC and n-butyllithium (9 mL of a 1.6 M solution in hex-
anes, 14.4 mmol) was added rapidly. After 2 h methyl chloro-
formate (8 mL, 103.2 mmol) was added and the mixture was
allowed to warm to room temperature within 12 h. Methanol
(10 mL) was added and the solvent was removed in vacuo.
The residue was dissolved in CHCl3 and the organic layer
was washed with water (3ꢂ), and was dried over anhydrous
MgSO4. Evaporation gives the crude product as yellow oil.
After column chromatography (SiO2, cyclohexane/ethyl ace-
tate, 4:1) the pure product was obtained as colourless solid
2
1
2.64 (d, J¼13.8 Hz, 2H, Kemp’s acid CH2 eq, H8), 1.97 (d,
(4.7 g, 3.2 mmol, yield: 48%). Mp: 76 ꢁC; H NMR (CDCl3,
2J¼12.6 Hz, 1H, Kemp’s acid CH2 eq, H9), 1.89e1.63 (m, 8H,
CHCH2), 1.40e1.13 (m, 76H, CH2; Kemp’s acid CH2 ax, H10,
CH3 Kemp’s acid), 1.18 (s, 6H, CH3 Kemp’s acid), 1.10 (d,
2J¼14.4 Hz, 2H, Kemp’s acid CH2 ax, H11), 0.85 (t,
500 MHz, 27 ꢁC): d¼6.75 (br s, 2H, ArH), 6.46 (br s, 2H,
ArH), 4.43 (t, 3J¼7.5 Hz, 4H, ArCHAr), 3.92 (s, 6H,
COOCH3), 3.69 (s, 12H, OCH3), 3.54 (s, 12H, OCH3),
1.87e1.79 (m, 8H, CHCH2), 1.34e1.16 (m, 72H, CH2),
0.84 (t, 3J¼6.9 Hz, 12H, CH3) ppm; 13C NMR (CDCl3,
125 MHz, 27 ꢁC): d¼167.5, 154.6, 153.7, 133.8, 128.1,
125.5, 122.5, 113.3, 62.0, 60.5, 52.6, 37.7, 35.1, 31.9, 29.8,
29.7, 29.7, 29.7, 29.4, 28.4, 22.7, 14.1 ppm; HRMS: m/z calcd
for C84H130O12Br2þNaþ [MþNa]þ 1511.78212; found
1511.78396; IR (KBr): ~n ¼ 2924, 2852, 1727, 1584, 1467,
1438, 1421, 1333, 1296, 1279, 1265, 1233, 1197, 1154,
1
3J¼6.9 Hz, 12H, CH3) ppm; H NMR ((CD3)2CO, 500 MHz,
27 ꢁC): d¼10.79 (br, 1H, COOH), 6.92 (s, 2H, ArH, lower
rim), 6.61 (s, 1H, ArH, lower rim), 6.54 (s, 1H, ArH, lower
rim), 6.52 (s, 1H, ArH, upper rim), 6.45 (s, 2H, ArH, upper rim),
3
4.89 (s, 2H, ArCH2), 4.56 (t, J¼7.5 Hz, 2H, ArCHAr), 4.48
(t, 3J¼7.5 Hz, 2H, ArCHAr), 3.74 (s, 6H, OCH3), 3.60 (s, 6H,
OCH3), 3.58 (s, 6H, OCH3), 3.49 (s, 6H, OCH3), 2.57 (d,
2
2J¼13.2 Hz, 2H, Kemp’s acid CH2 eq), 1.97 (d, J¼12.6 Hz,
1118, 1090, 1063, 1031, 1002, 909, 892, 722 cmꢀ1
.
1H, Kemp’s acid CH2 eq), 1.90e1.67 (m, 8H, CHCH2), 1.43
2
(d, J¼12.6 Hz, 1H, Kemp’s acid CH2 ax), 1.37e1.21 (m,
5.2.9. rccc-5,17-Bis-(hydroxymethyl)-4,6,10,12,16,18,
22,24-octa-O-methyl-2,8,14,20-tetra-(n-undecyl)-resorc[4]-
arene (9)
74H, CH2; Kemp’s acid CH2 ax), 1.20 (s, 3H, CH3 Kemp’s
acid), 1.18 (s, 6H, CH3 Kemp’s acid), 0.86 (t, 3J¼6.9 Hz,
12H, CH3) ppm; 1H NMR (CD2Cl2, 600 MHz, 27 ꢁC): d¼6.88
(s, 2H, ArH, lower rim), 6.52 (s, 1H, ArH, lower rim), 6.46 (s,
1H, ArH, lower rim), 6.39 (s, 1H, ArH, upper rim), 6.30 (s,
2H, ArH, upper rim), 4.86 (s, 2H, ArCH2), 4.46 (t, 3J¼7.5 Hz,
A mixture of LiAlH4 (190 mg, 5 mmol) and resorc[4]arene
(8) (3.62 g, 2.43 mmol) in anhydrous THF (100 mL) was stirred
at room temperature for 0.5 h and subsequently at 60 ꢁC for 4 h.
Additional LiAlH4 (190 mg, 5 mmol) was added and stirred for
4 h at 60 ꢁC. At room temperature methanol (10 mL) and hy-
drochloric acid (2 M) were added until the mixture became
acidic. The mixture was extracted with CHCl3 (3ꢂ). The or-
ganic layer was washed with satd NaHCO3 soln and brine
and was dried over anhydrous MgSO4. After evaporation the
product (2.18 g, 2.14 mmol, yield: 88%) was obtained as white
solid. The product can be recrystallized from acetone. Mp:
3
2H, ArCHAr), 4.40 (t, J¼7.9 Hz, 2H, ArCHAr), 3.74 (s, 6H,
OCH3), 3.60 (s, 6H, OCH3), 3.58 (s, 6H, OCH3), 3.50 (s, 6H,
2
OCH3), 2.61 (d, J¼13.5 Hz, 2H, Kemp’s acid CH2 eq), 1.98
(d, 2J¼12.9 Hz, 1H, Kemp’s acid CH2 eq), 1.92e1.56 (m, 8H,
CHCH2), 1.41e1.20 (m, 78H, CH2; Kemp’s acid CH2 ax,
CH3, Kemp’s acid CH2 ax), 1.16 (s, 6H, CH3 Kemp’s acid),
0.87 (t, 3J¼6.9 Hz, 12H, CH3) ppm; 1H NMR (CD2Cl2,
600 MHz, ꢀ70 ꢁC): d¼12.66, 7.18, 6.44, 6.41, 6.31, 6.28,
6.19, 6.14, 6.09, 5.87, 5.26, 4.87, 4.51, 4.43, 4.36, 4.31, 4.23,
4.16, 4.09, 3.87, 3.74, 3.62, 3.59, 3.52, 3.44, 3.37, 2.54, 2.36,
2.24, 2.14, 1.99, 1.92, 1.83, 1.78, 1.49, 1.45, 1.12, 0.78 ppm;
13C NMR (CDCl3, 125 MHz, 27 ꢁC): d¼177.4, 175.7, 156.1,
155.7, 155.6, 155.2, 133.9, 126.4, 126.1, 125.5, 125.5, 125.4,
122.5, 97.0, 95.4, 61.1, 56.2, 55.7, 44.3, 43.1, 41.7, 40.4,
36.1, 35.4, 35.0, 34.6, 31.9, 30.4, 30.0, 29.9, 29.9, 29.8,
29.7, 29.4, 28.2, 28.0, 25.9, 22.7, 14.1 ppm; HRMS: m/z
calcd for C93H145NO12þNaþ [MþNa]þ 1491.06590; found
1491.06629; IR (ATR): ~n ¼ 3477 ðbrÞ, 3194 (br), 2963, 2852,
1730, 1705, 1678, 1611, 1582, 1502, 1462, 1378, 1297, 1201,
1
72 ꢁC; H NMR (CDCl3, 500 MHz, 27 ꢁC): d¼6.97 (s, 2H,
ArH), 6.42 (s, 2H, ArH), 6.35 (s, 2H, ArH), 4.53 (s, 4H,
ArCH2), 4.48 (t, 3J¼7.2 Hz, 4H, ArCHAr), 3.77 (s, 12H,
OCH3), 3.40 (s, 12H, OCH3), 1.87e1.72 (m, 8H, CHCH2),
1.36e1.17 (m, 72H, CH2), 0.85 (t, 3J¼6.9 Hz, 12H, CH3) ppm;
13C NMR (CDCl3, 125 MHz, 27 ꢁC): d¼155.6, 155.4, 133.0,
126.9, 126.5, 126.5, 126.3, 95.4, 61.5, 56.3, 55.7, 35.7, 35.1,
31.9, 29.3, 29.9, 29.8, 29.7, 29.4, 28.1, 22.7, 14.1 ppm;
HRMS: m/z calcd for C82H132O10þNaþ [MþNa]þ
1299.97127; found 1299.97187; IR (KBr): ~n ¼ 3531, 3437,
2923, 2854, 1704, 1613, 1582, 1503, 1466, 1426, 1401, 1366,
1298, 1262, 1202, 1090, 1028, 904, 876, 805, 720, 686 cmꢀ1
.
1164, 1091, 1039, 817, 755 cmꢀ1
.
5.2.10. rccc-5,17-Bis-(bromomethyl)-4,6,10,12,16,18,22,24-
octa-O-methyl-2,8,14,20-tetra-(n-undecyl)-resorc[4]-
arene (10)
A solution of resorcarene (9) (1.14 g, 0.89 mmol) in dry di-
chloromethane (50 mL) was treated with phosphonium tribro-
mide (0.96 g, 3.55 mmol). The reaction mixture was stirred for
5.2.8. rccc-5,17-Dibromo-11,23-bis-[methoxycarbonyl]-
4,6,10,12,16,18,22,24-octa-O-methyl-2,8,14,20-tetra-
(n-undecyl)-resorc[4]arene (8)
A solution of resorc[4]arene (1) (10.1 g, 6.6 mmol) in anhy-
drous THF (450 mL) under argon-atmosphere was cooled to

I. Stoll et al. / Tetrahedron 64 (2008) 3813e3825
3823
2 h at room temperature and 2-propanol (5 mL) was added.
The solution was washed with satd NaHCO3 soln and brine
and dried over anhydrous MgSO4. The solvent was removed
in vacuo and the crude product was recrystallized from ace-
tone to afford the product (1.00 g, 0.71 mmol, yield: 80%)
as colourless solid. Mp: 101 ꢁC; 1H NMR (CDCl3,
500 MHz, 27 ꢁC): d¼6.96 (s, 2H, ArH), 6.62 (s, 2H, ArH),
0.64 mmol, yield: 94%). Mp: 97 ꢁC; 1H NMR (CDCl3,
500 MHz, 27 ꢁC): d¼6.86 (s, 2H, ArH), 6.50 (s, 2H, ArH),
3
6.40 (s, 2H, ArH), 4.50 (t, J¼7.5 Hz, 4H, ArCHAr), 3.73 (s,
12H, OCH3), 3.64 (s, 2H, ArCH2), 3.38 (s, 12H, OCH3),
1.89e1.70 (m, 8H, CHCH2), 1.36e1.13 (m, 72H, CH2), 0.85
3
(t, J¼6.9 Hz, 12H, CH3) ppm; 13C NMR (CDCl3, 125 MHz,
27 ꢁC): d¼155.4, 155.2, 133.2, 128.8, 126.4, 126.3, 125.5, 95.5,
61.1, 55.7, 36.7, 35.7, 35.4, 31.9, 29.9, 29.8, 29.8, 29.7, 29.4,
28.1, 22.7, 14.1 ppm; HRMS: m/z calcd for C82H134O8N2þHþ
[MþH]þ 1276.02130; found 1276.02343; IR (KBr): ~n ¼ 2918,
2849, 1658, 1609, 1578, 1503, 1465, 1296, 1197, 1087, 1032,
3
6.38 (s, 2H, ArH), 4.54 (s, 4H, ArCH2), 4.51 (t, J¼7.2 Hz,
4H, ArCHAr), 3.71 (s, 12H, OCH3), 3.57 (s, 12H, OCH3),
1.90e1.72 (m, 8H, CHCH2), 1.36e1.13 (m, 72H, CH2), 0.85
3
(t, J¼6.9 Hz, 12H, CH3) ppm; 13C NMR (CDCl3, 125 MHz,
27 ꢁC): d¼155.8, 155.7, 133.6, 128.0, 126.1, 125.7, 125.0,
95.8, 61.4, 55.6, 35.9, 35.5, 31.9, 29.9, 29.8, 29.8, 29.7,
29.4, 28.2, 24.5, 22.7, 14.1 ppm; HRMS: m/z calcd for
C82H130O8Br2þNaþ [MþNa]þ 1423.80247; found 1423.80506;
IR (KBr): ~n ¼ 2925, 2855, 1614, 1574, 1503, 1468, 1424,
1402, 1301, 1229, 1201, 1145, 1120, 1082, 1034, 1007, 898,
1011, 891, 821, 720, 513 cmꢀ1
.
5.2.13. Kemp’s acid resorc[4]arene (13)
A solution of the resorc[4]arene (12) (92 mg, 0.07 mmol),
5-(chloroformyl)-cis,cis-1,3,5-trimethylcyclohexane-1,3-dicarb-
oxylic anhydride (44 mg, 0.17 mmol) and a catalytic amount
of 4-dimethylamino pyridine in pyridine (30 mL) was refluxed
for 5 h. The solvent was removed in vacuo and the residue was
dissolved in CHCl3. The organic layer was washed with 2 N
HCl and 2 N NaOH and the solvent was removed under reduced
pressure. The crude product was purified by column chromatog-
raphy (SiO2, cyclohexane/ethyl acetate, 7.5%) yielding a
colourless solid (102 mg, 0.06 mmol, yield: 86%). Mp: 140e
821, 771, 720, 629 cmꢀ1
.
5.2.11. rccc-5,17-Bis-[(phthalimido)-methyl]-4,6,10,12,16,
18,22,24-octa-O-methyl-2,8,14,20-tetra-(n-undecyl)-
resorc[4]arene (11)
A mixture of resorcarene (10) (420 mg, 0.30 mmol), potas-
sium phthalimide (175 mg, 0.94 mmol) an 18-crown-6 (34 mg,
0.18 mmol) in THF (50 mL) was refluxed for 12 h. Water
(50 mL) was added and the aqueous phase extracted with chlo-
roform (3ꢂ). The organic layer was washed with brine and
dried over anhydrous MgSO4. The solvent was removed and
the crude product filtrated over silica gel (cyclohexane/ethyl
acetate, 3:2). After recrystallization from acetone the product
was obtained as colourless solid (258 mg, 0.17 mmol, yield:
56%). Mp: 197e198 ꢁC; 1H NMR (CDCl3, 500 MHz,
27 ꢁC): d¼7.82e7.78 (m, 4H, ArH), 7.67e7.63 (m, 4H,
ArH), 6.87 (s, 2H, ArH), 6.49 (s, 2H, ArH), 6.21 (s, 2H,
ArH), 4.95 (s, 2H, ArCH2), 4.40 (t, 3J¼7.2 Hz, 4H, ArCHAr),
3.60 (s, 12H, OCH3), 3.47 (s, 12H, OCH3), 1.88e1.65 (m, 8H,
1
145 ꢁC; H NMR (CDCl3, 500 MHz, 27 ꢁC): d¼6.94 (s, 2H,
ArH), 6.15 (s, 2H, ArH), 6.13 (s, 2H, ArH), 4.95 (s, 4H,
ArCH2), 4.31 (t, 3J¼6.9 Hz, 4H, ArCHAr), 3.65 (s, 12H,
OCH3), 3.36 (s, 12H, OCH3), 2.68 (d, 2J¼13.8 Hz, 4H, Kemp’s
acid CH2 eq), 2.00 (d, 2J¼13.2 Hz, 2H, Kemp’s acid CH2 eq),
1.77e1.90 (m, 4H, CH2), 1.59e1.73 (m, 4H, CH2), 1.02e1.42
(m, 96H, CH2, Kemp’s acid CH2 ax, CH3 Kemp’s acid), 0.85
3
(t, J¼6.9 Hz, 12H, CH3) ppm; 13C NMR (CDCl3, 125 MHz,
27 ꢁC): d¼177.8, 175.7, 156.3, 154.7, 135.2, 126.5, 125.1,
124.4, 122.5, 97.3, 61.1, 55.6, 44.4, 43.2, 41.8, 40.4, 36.5,
35.4, 35.1, 31.9, 30.5, 30.0, 29.9, 29.8, 29.7, 29.4, 28.2, 26.0,
22.7, 14.1 ppm. HRMS: m/z calcd for C106H162O16N2þHþ
[MþH]þ 1720.19971; found 1720.19918; IR (KBr): ~n ¼ 3512
(br), 3196 (br), 2921, 2851, 1728, 1703, 1678, 1612, 1581,
1506, 1461, 1378, 1297, 1262, 1202, 1167, 1090, 1035, 1011,
3
CHCH2), 1.35e1.05 (m, 72H, CH2), 0.85 (t, J¼6.9 Hz, 12H,
13
CH3) ppm; C NMR (CDCl3, 125 MHz, 27 ꢁC): d¼168.0,
156.0, 155.4, 134.6, 133.5, 132.4, 126.6, 126.1, 125.0,
123.0, 120.9, 96.6, 61.2, 55.5, 36.1, 35.7, 33.3, 31.9, 29.9,
29.8, 29.7, 29.7, 29.4, 28.2, 22.7, 14.1 ppm; HRMS: m/z calcd
for C98H138O12N2þNHþ4 [MþNH4]þ 1553.05880; found
1553.05859; IR (KBr): ~n ¼ 2920, 2851, 1772, 1713, 1610,
1580, 1499, 1465, 1389, 1324, 1296, 1199, 1087, 1036,
804, 755, 729 cmꢀ1
.
5.2.14. 1,3,5,7-Tetramethyl-2,4-dioxo-3-aza-bicyclo[3.3.1]-
nonane-7-carboxylic acid (14)
5-(Chloroformyl)-cis,cis-1,3,5-trimethylcyclohexane-1,3-di-
carboxylic anhydride (0.14 g, 54 mmol), methyl ammonium
chloride (0.85 mg, 1.3 mmol) and a catalytic amount of 4-dime-
thylamino pyridine in pyridine (10 mL) were heated to 60 ꢁC
for 3 h. The solvent was evaporated in vacuo and the precipitate
was dissolved in 6 N HCl and extracted with overall 35 mL
chloroform (5ꢂ). The solvent was removed and the obtained
solid was recrystallized from acetone to afford colourless
crystals (0.52 g, 19 mmol, yield: 35%); 1H NMR (CDCl3,
500 MHz, 27 ꢁC): d¼2.92 (s, 3H, NCH3), 2.62 (d,
1006, 953, 900, 819, 796, 714, 532, 502 cmꢀ1
.
5.2.12. rccc-5,17-Bis-(aminomethyl)-4,6,10,12,16,18,22,24-
octa-O-methyl-2,8,14,20-tetra-(n-undecyl)-
resorc[4]arene (12)
A solution of resorcarene (11) (1.04 g, 0.68 mmol) in a mix-
ture of THF and ethanol (7:3, 50 mL) was treated with hydr-
azine hydrate (3 mL, ca. 40 mmol pure hydrazine) and refluxed
for 12 h. At room temperature concd HCl (1.5 mL) was added
and stirred for 2 h. Under ice cooling concd NaOH was added
until pH>10. The THF was removed in vacuo and the precip-
itate was filtered off and washed with concd NaOH and cold eth-
anol to afford the product as colourless solid (816 mg,
2
2J¼13.2 Hz, 2H, Kemp’s acid CH2 eq), 1.94 (d, J¼13.2 Hz,
2
1H, Kemp’s acid CH2 eq), 1.36 (d, J¼13.3 Hz, 1H, Kemp’s
acid CH2 ax), 1.25 (s, 6H, CH3), 1.25 (s, 3H, CH3), 1.17
2
(d, J¼13.3 Hz, 2H, Kemp’s acid CH2 ax) ppm; IR (ATR):

3824
I. Stoll et al. / Tetrahedron 64 (2008) 3813e3825
~n ¼ 2964, 2930, 1701, 1668, 1467, 1449, 1427, 1408, 1378,
795, 754, 620, 585, 563 cmꢀ1
(s, 1H, ArH, upper rim), 6.31 (s, 2H, ArH, upper rim), 4.84
3
1358, 1379, 1273, 1233, 1209, 1116, 1094, 941, 886, 841,
.
(s, 2H, ArCH2), 4.46 (t, J¼7.5 Hz, 2H, ArCHAr), 4.41 (t,
3J¼7.2 Hz, 2H, ArCHAr), 3.72 (s, 6H, OCH3), 3.62 (s, 6H,
OCH3), 3.61 (s, 6H, OCH3), 3.47 (s, 6H, OCH3), 2.61 (d,
2
5.2.15. 3-(2,6-Dimethoxy)benzyl-1,5,7-trimethyl-2,4-dioxo-
3-aza-bicyclo[3.3.1]nonane-7-carboxylic acid (15)
2J¼13.2 Hz, 2H, Kemp’s acid CH2 eq), 1.95 (d, J¼12.2 Hz,
1H, Kemp’s acid CH2 eq), 1.88e1.63 (m, 8H, CHCH2),
1.41e1.18 (m, 79H, CH2; Kemp’s acid CH2 ax, CH3 Kemp’s
acid, COOCH3), 1.18 (s, 6H, CH3 Kemp’s acid), 1.12 (d,
5-(Chloroformyl)-cis,cis-1,3,5-trimethylcyclohexane-1,3-di-
carboxylic anhydride (0.11 g, 43 mmol), 2,6-dimethoxy benz-
yl amine (0.11 mg, 0.43 mmol) and a catalytic amount of
4-dimethylamino pyridine in pyridine (10 mL) were heated
to 60 ꢁC for 3 h. The solvent was evaporated in vacuo and
the precipitate was dissolved in CHCl3. The organic layer
was washed with 2 N HCl (3ꢂ) and the solvent was removed
in vacuo. The resulting precipitate was recrystallized from
chloroform/methanol (1:1) to afford colourless crystals
3
2J¼13.8 Hz, 2H, Kemp’s acid CH2 ax), 0.87 (t, J¼6.9 Hz,
1
12H, CH3) ppm; H NMR (CD2Cl2, 600 MHz, ꢀ70 ꢁC):
d¼7.18 (s, 2H, ArH), 6.45 (s, 1H, ArH), 6.28 (s, 1H, ArH),
6.19 (s, 1H, ArH), 6.14 (s, 2H, ArH), 4.89 (s, 2H, ArCH2),
4.42 (2H, ArCHAr), 4.32 (2H, ArCHAr), 3.86 (s, 6H, OCH3),
3.75 (s, 6H, OCH3), 3.62 (s, 6H, OCH3), 3.59 (s, 6H, OCH3),
2.54 (2H, Kemp’s acid CH2 eq), 1.93 (1H, Kemp’s acid CH2
eq), 1.90e1.70 (m, 8H, CHCH2), 1.36e0.93 (m, 87H, CH2;
Kemp’s acid CH2 ax, CH3 Kemp’s acid, COOCH3, CH3 Kemp’s
1
(44 mg, 11 mmol, yield: 26%); H NMR (CDCl3, 600 MHz,
3
3
27 ꢁC): d¼7.08 (t, J¼8.3 Hz, 1H, ArH), 6.45 (d, J¼8.3 Hz,
2H, ArH), 4.85 (s, 2H, NCH2R), 3.73 (s, 6H, OCH3), 2.67
(d, 2J¼13.2 Hz, 2H, Kemp’s acid CH2 eq), 1.87 (d,
1
acid, Kemp’s acid CH2 ax), 0.79 (12H, CH3) ppm; H NMR
(CDCl3, 500 MHz, 27 ꢁC): d¼6.62 (s, 2H, ArH, lower rim),
6.57 (s, 1H, ArH, lower rim), 6.51 (s, 1H, ArH, lower rim),
6.29 (s, 2H, ArH, upper rim), 6.25 (s, 1H, ArH, upper
rim), 4.82 (s, 2H, ArCH2), 4.43e4.36 (m, 4H, ArCHAr), 3.59
(s, 6H, OCH3), 3.57 (s, 6H, OCH3), 3.56 (s, 6H, OCH3), 3.30
2J¼12.9 Hz, 1H, Kemp’s acid CH2 eq), 1.31 (d, J¼12.8 Hz,
2
1H, Kemp’s acid CH2 ax), 1.26 (s, 3H, CH3), 1.23 (s, 6H,
2
CH3), 1.14 (d, J¼14.0 Hz, 2H, Kemp’s acid CH2 ax) ppm;
1H NMR (MeOD, 500 MHz, 27 ꢁC): d¼7.12 (t, J¼8.2 Hz,
3
1H, ArH), 6.54 (d, 3J¼8.2 Hz, 2H, ArH), 4.83 (s, 2H,
(s, 6H, OCH3), 2.65 (d, J¼13.8 Hz, 2H, Kemp’s acid CH2
2
2
NCH2R), 3.73 (s, 6H, OCH3), 2.56 (d, 2J¼13.2 Hz, 2H,
eq), 1.95 (d, J¼12.6 Hz, 1H, Kemp’s acid CH2 eq), 1.85e
2
Kemp’s acid CH2 eq), 1.85 (d, J¼12.6 Hz, 1H, Kemp’s acid
1.65 (m, 8H, CHCH2), 1.35e1.12 (m, 76H, CH2; Kemp’s
acid CH2 ax, CH3 Kemp’s acid), 1.18 (s, 6H, CH3 Kemp’s
acid), 1.17 (s, 3H, COOCH3), 1.12 (d, 2J¼13.8 Hz, 2H, Kemp’s
CH2 eq), 1.45 (d, 2J¼13.2 Hz, 1H, Kemp’s acid CH2 ax),
2
1.24 (d, J¼13.8 Hz, 2H, Kemp’s acid CH2 ax), 1.20 (s, 3H,
CH3), 1.19 (s, 6H, CH3) ppm; 13C NMR (MeOD, 125 MHz,
27 ꢁC): d¼178.9, 178.1, 159.8, 129.0, 114.4, 105.1, 56.1,
45.2, 43.9, 42.9, 41.4, 35.4, 30.8, 26.1 ppm; HRMS: m/z calcd
for C21H27NO6þNaþ [MþNa]þ 412.17306; found 412.17313;
IR (ATR): ~n ¼ 2982, 2962, 2932, 1724, 1697, 1678,
1590, 1464, 1381, 1361, 1324, 1278, 1245, 1213, 1175,
1106, 1034, 1002, 973, 948, 767, 707, 659, 617, 586,
534 cmꢀ1. Crystal size 0.30ꢂ0.28ꢂ0.19 mm3, monoclinic,
acid CH2 ax), 0.85 (t, J¼6.9 Hz, 12H, CH3) ppm; 13C NMR
3
(CD2Cl2, 125 MHz, 27 ꢁC): d¼176.0, 175.9, 156.5, 156.2,
155.9, 155.5, 134.8, 126.9, 126.4, 126.3, 125.4, 125.3, 124.5,
123.4, 96.8, 96.1, 77.9, 56.2, 56.1, 55.8, 52.3, 44.6, 43.3,
42.4, 40.6, 36.3, 36.3, 35.4, 35.2, 35.2, 32.3, 30.5, 30.3, 30.2,
30.1, 30.1, 30.0, 29.8, 28.6, 28.4, 26.1, 23.0, 14.2 ppm;
HRMS: m/z calcd for C94H147NO12þNaþ [MþNa]þ
1505.08155; found 1505.08308.
˚
P21/c, a¼15.5794(3), b¼8.5107(2), c¼15.7755(3) A, b¼
108.5925(12) , Z¼4, V¼1982.53(7) A , rcalcd¼1.305 mg mꢀ3
,
5.2.17. 5-Phenyl-2-amino pyridine (17)
3
ꢁ
˚
Qmax¼27.5ꢁ, m¼0.095 mmꢀ1, F(000)¼832, 361 parameters,
R1¼0.0368, wR2¼0.0946 (for 3844 reflections [I>2s(I)]),
R¼0.0446, wR(F2)¼0.0998 (for 4519 unique reflections),
2-Amino-5-chloro pyridine (1 g, 7.78 mmol), boronic acid
(1.42 g, 11.7 mmol, 1.5 equiv) and potassium phosphate
were solved in toluene and have been degassed by pumpe
freezeethaw (three cycles). Palladium acetate (17.5 mg,
0.078 mmol, 1%) and dicyclohexyl-(2,6-dimethoxy-biphenyl-
2-yl)-phosphane (63.9 mg, 0.16 mmol, 2%) were added
and the suspension was degassed by additional two pumpe
freezeethaw cycles. The suspension was heated in a sealed
tube to 100 ꢁC for 17 h and filtrated. The precipitate was
washed with ethyl acetate (2ꢂ) and the filtrate was washed
with 2 N NaOH (3ꢂ) and satd NaCl soln and the solvent
was removed in vacuo. The crude product was purified by col-
umn chromatography (SiO2, cyclohexane/ethyl acetate, 3:2)
yielding a colourless solid (0.95 g, 5.6 mmol, yield: 72%);
ꢀ3
˚
R(int)¼0.033, Dr(min/max)¼ꢀ0.262/0.342 e A
.
CCDC
664625 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data via www.ccdc.cam.
ac.uk/data_request/cif.
5.2.16. Kemp’s acid ester resorc[4]arene (16)
A solution of resorc[4]arene (7) (7 mg, 4.8 mmol) in CHCl3/
MeOH (1:1, 5 mL) was treated with a 0.02 M solution of diazo-
methane in diethyl ether (0.2 mL, 4 mmol) and stirred for
30 min at room temperature. Acetic acid (0.05 mL) was added
and the organic layer was washed with satd NaHCO3 soln. The
solvent was removed in vacuo to give the product as colourless
solid (7 mg, 4.7 mmol, yield: 98%); 1H NMR (CD2Cl2,
600 MHz, 27 ꢁC): d¼6.85 (s, 2H, ArH, lower rim), 6.56
(s, 1H, ArH, lower rim), 6.50 (s, 1H, ArH, lower rim), 6.38
4
1H NMR (CDCl3, 500 MHz, 27 ꢁC): d¼8.31 (d, J¼2.5 Hz,
1H), 7.65 (dd, 3J¼8.8 Hz, 4J¼2.5 Hz, 1H), 7.49 (d,
3
3
3J¼6.9 Hz, 2H), 7.40 (dd, J¼8.2 Hz, J¼8.2 Hz, 2H), 7.29
(t, 3J¼7.5 Hz, 1H), 6.56 (d, 3J¼8.8 Hz, 1H), 4.53 (s, 2H,
NH2) ppm.

I. Stoll et al. / Tetrahedron 64 (2008) 3813e3825
3825
21. Bergmann, H. Ph.D. Thesis, Universitat Marburg, Marburg, 2001;
¨
¨
Aechtner, T. Ph.D. Thesis, TU Munchen, Munchen, 2002.
Acknowledgements
¨
22. Nowick, J. S.; Feng, Q.; Tjivikua, T.; Ballester, P.; Rebek, J., Jr. J. Am.
Chem. Soc. 1991, 113, 8831e8839.
Financial support from the Deutsche Forschungsgemein-
schaft and the University of Bielefeld’s Innovationsfonds
is gratefully acknowledged. The authors also thank Prof. Dr.
Thorsten Bach (Technical University Munich) for providing
detailed protocols for the synthesis of Kemp’s triacid.
23. Hogberg, A. G. S. J. Am. Chem. Soc. 1980, 102, 6046e6050.
24. Hogberg, A. G. S. J. Org. Chem. 1980, 45, 4498e4500.
25. Abis, L.; Dacanale, E.; Du Vosel, A.; Spera, S. J. Org. Chem. 1988, 53,
5475e5479.
´
26. Chang, C. K.; Liang, Y.; Aviles, G.; Peng, S.-M. J. Am. Chem. Soc. 1995,
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