Adamantane-bearing benzylamines and benzylamides: Novel building blocks for supramolecular systems with finely tuned binding properties towards β-cyclodextrin

Article abstract of DOI:10.1080/10610278.2013.783916

Novel building blocks for the synthesis of supramolecular components based on adamantane-bearing benzylamines were prepared. The binding properties of these amines and the corresponding acetamides towards β-cyclodextrin (β-CD) were studied using mass spectrometry, NMR spectrometry, isothermal titration calorimetry and semi-empirical calculations. It was found that all of the examined guests predominantly formed 1:1 inclusion complexes in an enthalpy-driven manner with association constants of the order of 10 ²-10³ M^-1. Stronger binding to the β-CD cavity was observed for guests with a longer spacer between the adamantane and benzene moieties and/or a 1,4-disubstituted benzene ring.

Full text of DOI:10.1080/10610278.2013.783916

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Adamantane-bearing benzylamines and benzylamides:
novel building blocks for supramolecular systems with
finely tuned binding properties towards β-cyclodextrin
Michal Rouchal a , Alena Matelová a , Fabiana Pires de Carvalho a , Robert Bernat a , Dragan
a
Grbić , Ivo Kuřitka b , Martin Babinský c , Radek Marek c , Richard Čmelík d & Robert Vícha
a
a Department of Chemistry, Faculty of Technology, Tomas Bata University in Zlín, Náměstí T.
G. Masaryka 275, 762 72, Zlín, Czech Republic
b Polymer Centre, Faculty of Technology, Tomas Bata University in Zlín, Náměstí T. G.
Masaryka 275, 762 72, Zlín, Czech Republic
c CEITEC – Central European Institute of Technology, Masaryk University, Kamenice 5, 625
00, Brno, Czech Republic
d Institute of Analytical Chemistry, v. v. i., Academy of Sciences of the Czech Republic,
Veveří 97, 602 00, Brno, Czech Republic
Published online: 15 Apr 2013.
To cite this article: Michal Rouchal , Alena Matelová , Fabiana Pires de Carvalho , Robert Bernat , Dragan Grbić , Ivo
Kuřitka , Martin Babinský , Radek Marek , Richard Čmelík & Robert Vícha (2013): Adamantane-bearing benzylamines and
benzylamides: novel building blocks for supramolecular systems with finely tuned binding properties towards β-cyclodextrin,
Supramolecular Chemistry, DOI:10.1080/10610278.2013.783916
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Supramolecular Chemistry, 2013
http://dx.doi.org/10.1080/10610278.2013.783916
Adamantane-bearing benzylamines and benzylamides: novel building blocks for supramolecular
systems with finely tuned binding properties towards b-cyclodextrin
a
Michal Rouchal , Alena Matelova , Fabiana Pires de Carvalho , Robert Bernat , Dragan Grbic , Ivo Kuritka ,
a
a
a
a
b
´
´
ˇ
c
Martin Babinsky , Radek Marek , Richard Cmelık and Robert Vıcha *
c
d
a
ˇ
´
´
´
a
´
´
´
ˇ ´
ˇ ´
´
´
Department of Chemistry, Faculty of Technology, Tomas Bata University in Zlın, Namestı T. G. Masaryka 275, 762 72 Zlın, Czech
b
Republic; Polymer Centre, Faculty of Technology, Tomas Bata University in Zlın, Namestı T. G. Masaryka 275, 762 72 Zlın, Czech
´
Republic; CEITEC – Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic;
ˇ´
Institute of Analytical Chemistry, v. v. i., Academy of Sciences of the Czech Republic, Veverı 97, 602 00 Brno, Czech Republic
c
d
(Received 19 October 2012; final version received 31 December 2012)
Novel building blocks for the synthesis of supramolecular components based on adamantane-bearing benzylamines were
prepared. The binding properties of these amines and the corresponding acetamides towards b-cyclodextrin (b-CD) were
studied using mass spectrometry, NMR spectrometry, isothermal titration calorimetry and semi-empirical calculations. It
was found that all of the examined guests predominantly formed 1:1 inclusion complexes in an enthalpy-driven manner with
association constants of the order of 102–103 M21. Stronger binding to the b-CD cavity was observed for guests with a
longer spacer between the adamantane and benzene moieties and/or a 1,4-disubstituted benzene ring.
Keywords: adamantane; amines; cyclodextrins; binding properties; host–guest systems
1. Introduction
These interactions have been used to construct cyclic
or linear supramolecular co-polymers consisting of b-CD
dimers and homo-ditopic adamantane-based guest dimers
(4). In addition, the formation of hydrogels from
adamantane-based hetero-ditopic units and b-CD has
been described (5). Comb-shaped assemblies based on a
CD-modified polyacrylate backbone with reversibly
grafted adamantane-terminated polyacrylate chains have
been studied (6). The hydrophilic b-CD duplex has been
used for the non-covalent cross-linkage of adamantane-
grafted chitosan (7). The interactions between ditopic
adamantane guests and tritopic b-CD hosts (8), as well as
the aggregation of functionalised dendrons leading to
tubular vesicles, have been studied (9). The formation of
microcapsules for the pH-driven drug release based on the
interaction between CD-grafted dextran and 1-adamantyl-
grafted poly(aspartic amide) has been described (10).
Furthermore, the interactions between the chains of
modified dextran and poly[methyl vinyl ether-alt-(maleic
anhydride)] (11), poly(ethylene glycol) (12), polyacrylate
(13) or hyaluronic acid (14) have been studied, and the
developed systems have then been used for the formation
of multilayer films (15). Because of the strong binding
between the adamantane scaffold and b-CD, simple
adamantane derivatives (mostly AdNH2 or AdCOOH,
Ad ¼ 1–adamantyl) are used to control supramolecular
aggregation (16). Although the above-mentioned papers
primarily describe the results of basic binding behaviour
studies, it is easy to imagine future applications including
Many examples of host–guest systems based on the
interactions between adamantane-bearing guests and b-
cyclodextrin (b-CD) can be found in the recent literature.
The geometric and electronic properties of both the host
and guest components play important roles in the
complexation process. The non-polar adamantyl moiety,
C10H15, consists of three fused cyclohexane rings in a
classical chair conformation and has an almost ideal
˚
spherical shape with an atom-to-atom diameter of 7.2 A.
b-CD is a macrocycle composed of seven glucopyranoside
units in the 4C1 conformation connected via a-1,4-
glycosidic bonds. Its geometry is usually described as
bottomless cap or doughnut with a wide secondary rim
(occupied by secondary OH groups at the C2 and C3
positions) and a narrow primary rim (occupied by primary
OH groups at the C6 positions). The hydrophobic cavity is
lined with H5, H3 and glycosidic O-atoms and has an
˚
internal diameter of approximately 6.5 A (1).
Although there are rare instances of the binding of
some guests on the CD portal (2) or outside the CD cone
(3), we are unaware of any demonstration of such binding
modes for adamantane-based guests. Owing to the
lipophilic character of both the adamantane scaffold and
the CD cavity, in conjunction with their complementary
geometries, adamantane and b-CD primarily form
inclusion complexes in solution, with the adamantane
cage more or less buried inside the CD cavity.
*Corresponding author. Email: rvicha@ft.utb.cz
q 2013 Taylor & Francis

2
M. Rouchal et al.
drug delivery and controlled release, viscosity control and
sensors. Some very interesting examples of the inter-
actions between the adamantane cage and b-CD on a
macroscopic scale have recently been published (17). In
addition, some immunosorbents based on the interactions
between modified polymers have already been developed
for chromatographic applications (18a) and solid phase
extraction material (18b).
Furthermore, the ability of the adamantane moiety to
form inclusion complexes with b-CD is frequently used in
drug design to produce novel biologically active
adamantylated compounds with enhanced transport
properties and/or cytotoxicity (19). However, a reduction
of the desired biological activity has been clearly
documented when the introduced adamantane scaffold
lacked a sufficiently long spacer between adamantane and
the active site of the drug (20).
Scheme 1. Synthesis of starting ketones.
not increase the yield of product 2 significantly. Higher
amounts of NBS led to the formation of undesired geminal
dibromoderivatives.
In the second step, bromoketones 2 were treated with
sodium azide (10.0 equiv.) in dry acetone according to the
conditions described by Seong (22), and the desired
azidoketones 3 were isolated in good to excellent yield.
Several types of reducing agents [e.g. triphenylpho-
sphine (23), triethylphosphite (24), propane-1,3-dithiol
(25), zinc in acetic acid (26), FeCl3/NaI in MeCN (27),
complex hydrides (28), FeSO4/NH3 in MeOH (29) and
Na2S in MeOH (30)] under various reaction conditions
were unsuccessfully utilised for the preparation of
benzylamines 4. Finally, compounds 4a–d were smoothly
prepared via the reaction of the corresponding azidoke-
tones 3 with carbonyl iron powder as a reducing agent in a
methanol:hydrochloric acid solution at room temperature.
The benzylamines 4b–d were isolated either as the free
bases after adjusting the pH and extracting or as the
hydrochlorides via treatment of the methanol solution of
the corresponding amine with dry gaseous hydrogen
chloride. Compound 4a was isolated in excellent yield
(97%) as a free base, but attempts to isolate the
corresponding hydrochloride resulted in a colourless
liquid. Moreover, the free base of compound 4a was
rather unstable, in contrast to benzylamines 4b–d, and
began to solidify within a few minutes at room
temperature. This instability of amine 4a, together with
some difficulties accompanying the isothermal titration
calorimetry (ITC) experiments with amines 4 (see
discussion below), led us to transform amines 4 into the
corresponding acetamides 5. In addition, the adamanty-
lated amines 4 were intended to be linked to the final
supramolecular components via an amide bond, which is
better mimicked by amides 5. Amides 5 were prepared via
the smooth reaction of amines 4 with acetic anhydride in
pyridine at room temperature. The entire synthetic
pathway is depicted in Scheme 2.
It should be noted that approximately one-half of the
papers mentioned above describe guest components based
on AdNH2. Other frequently used adamantane building
blocks are AdOH, AdCH2OH, 2-(1-adamantyl)ethyla-
mine, AdCH2COOH and 1-(1-adamantyl)-2-bromoetha-
none. It is reasonable to suppose that the electronic and
steric properties of the linkage between adamantane and,
for example, polymer backbone or pharmacophore can
significantly affect binding to the CD cavity. For these
reasons, novel adamantane building blocks are required.
Considering the appropriate amino derivatives that are
widely used as adamantane building blocks, we describe in
this paper a convenient synthetic method for benzylamines
that bear an adamantane moiety, which can be used for the
synthesis of fine-tuned components for supramolecular
assemblages or drug modification. Thermodynamic data of
the host–guest interactions of the corresponding acet-
amides with b-CD based on calorimetric and NMR
titrations, as well as the complex geometry, are discussed.
2. Results and discussion
2.1. Chemistry
The starting materials for this study, ketones 1a–d, were
prepared in satisfactory yields according to a previously
described procedure (21) using acyl chlorides and the
corresponding Grignard reagents in the presence of a
catalytic amount of metal halide (Scheme 1).
Radical bromination of ketones 1 using 1.0 equiv. of N-
bromosuccinimide (NBS) in dry tetrachloromethane at
80–858C for the required time (monitoring by TLC)
provided bromoketones 2 in approximately 70% yield.
The reaction was initiated with a catalytic amount of
benzoyl peroxide and irradiation with a tungsten lamp. In
all cases, the starting material was not consumed
completely when 1.0 equiv. of NBS was used. However,
the addition of up to 1.2 equiv. of brominating agent did
The ability of the prepared amines 4 and amides 5 to
form supramolecular complexes with b-CD and the
properties of the complexes were further studied.
Qualitative ESI-MS analysis was used to detect the
supramolecular aggregates in solution and to study their

Supramolecular Chemistry
3
all the examined amides 5a–d, the signals of the proton
associates were accompanied by signals at an m/z ratio
twice as high minus unity (Table 1). We assigned these
signals to H-bonded dimers associated with a single
proton. Subsequent analyses of the ligand–cyclodextrin
mixtures revealed that the protonated guest, a sodium
adduct of b-CD and the protonated 1:1 host–guest
aggregates were present in the gas phase. With amide 5a,
an additional aggregate of the amide with b-CD and Naþ
was observed and successfully trapped. As illustrated for
the equimolar mixture of amide 5d with b-CD in Figure
1(a), some further minor signals were observed and
assigned to the products of either host or guest cleavage
during the ESI process. In accordance with the well-known
dissimilar stabilities of [b-CD þ H]þ and [b-CD þ Na]þ,
the corresponding aggregates of 5·b-CD with Hþ and with
Naþ displayed markedly different fragmentation patterns
during treatment under collision-induced dissociation
(CID) conditions. Although the positive ion [5·b-
CD þ H]þ lost the neutral amide 5 to produce the singly
positively charged ion [b-CD þ H]þ, which subsequently
released four glucose units to produce signals at m/z 973,
811, 649 and 487 as demonstrated with further tandem
mass spectrometry (Figure 1(b)), the sodium adduct [5·b-
CD þ Na]þ lost the neutral amide 5 to yield solely the
sodium adduct of b-CD at m/z 1157, and further
fragmentation products were not detected. In addition,
the supramolecular aggregates of amides 5 were also
observable in the negative-ion mode (Figure 1(c)). In this
case, the ions [b-CD 2 2H]22, [5–H]2, [b-CD 2 H]2
and [5·b-CD 2 H]2 were usually observed. The fragmen-
tation of the supramolecular aggregate [5·b-CD 2 H]2 led
exclusively to the release of neutral amide 5 to yield the
[b-CD 2 H]2 ion (Figure 1(d)). The MS data obtained
clearly demonstrate that all of the studied amides 5 and
amines 4b–d form 1:1 supramolecular aggregates with
b-CD in methanol–water solution, which were success-
fully transferred and detected in the gas phase using ESI.
Scheme 2. Reaction pathway leading to adamantylated amides.
fragmentation in the gas phase. The thermodynamic
parameters of the complexation reactions were determined
using NMR and ITC titrations, and the spatial arrangement
of the aggregates was studied through 2D NMR
spectrometry and theoretical calculations.
2.2. Mass spectrometry
The individual guests 4 and 5, as well as their equimolar
mixtures with b-CD, were studied in the gas phase with a
mass spectrometer equipped with an electrospray ionis-
ation source (ESI-MS). The pseudomolecular ions
[M þ H]þ predominated in the first-order mass spectra
of all of the examined guests. In the case of amine 4c and
Table 1. Important signals observed in the positive-ion mode ESI mass spectra.
Exact mass
Ligand analysis
Mixture analysis
Single þ H
Dimer þ H
Single þ Na
b-CD þ amine þH
Compound
Calc.
Found
Calc.
Found
Calc.
Found
Calc.
Found
4b
4c
4d
5a
5b
5c
5d
270.2
284.2
284.2
312.2
312.2
326.2
326.2
270.1
284.1
284.1
312.1
312.2
326.3
326.3
539.4
567.4
567.4
623.4
623.4
651.4
651.4
–
292.2
306.2
306.2
334.2
334.2
348.2
348.2
–
1404.6
1418.6
1418.6
1446.6
1446.6
1460.6
1460.6
1404.6
1418.5
1418.6
1446.5
1446.8
1460.7
1460.7
567.4
–
623.3
623.5
651.5
651.5
306.0
–
334.1
334.2
348.2
348.3

4
M. Rouchal et al.
Figure 1. ESI-MS spectra of the mixtures of 5d and b-CD in the positive-ion (a) and negative-ion (c) mode; ESI-MS/MS spectra of ions
at m/z 1460 (b) and 1458 (d). Precursor ions are marked with a bold downward arrow.
2.3. Binding thermodynamics
the very small CIS of the signals of the shielded H-atoms
and overlapping of the signals of the deshielded H-atoms.
Therefore, all of the NMR titration data are based only on
the unambiguously observed signal of the H-atom at
position 3. The stoichiometry of the studied complexes
was estimated using the Job method (31) as applied to the
NMR data. The prepared amides 5 form 1:1 complexes
with b-CD under the experimental conditions, as clearly
demonstrated for amide 5d in Figure 2 (right).
NMR spectrometry was used to determine the stoichi-
ometry of the complexes and the binding constants K. All
of the examined host–guest systems follow the fast
exchange mode on the NMR timescale. The complexation-
induced shifts (CIS) were clearly seen in the spectra of the
host–guest systems in a D2O:[D6]DMSO mixture. As it is
shown for amide 5d in Figure 2 (left), the complexation
caused a deshielding of the adamantane hydrogen atoms at
positions 2, 3 and 4 (for atom numbering, see Figure 3) and
a shielding of hydrogen atoms at positions 5, 8 and 9.
Nevertheless, the NMR data were often compromised by
Considering the 1:1 stoichiometry of the studied
complexes, the NMR titration data were fitted to the
theoretical rectangular hyperbola (Equation (1)), and the

Supramolecular Chemistry
5
1
Figure 2. Stacking plot of a portion of the H NMR spectra (left) and Job plot (right) for amide 5d and b-CD mixture. Significant
parameters [xCD (molar fraction of CD), FDMSO (volume fraction of DMSO) and temperature] are given above each line. Signals of the
host and guest nuclei are labelled as H for b-CD and G for guest. The assignment of signals corresponds with the atom numbering in
Figure 3.
values of CISmax and K were obtained using a standard
least squares regression process (for further details, see
Section 4).
to the formation of higher order aggregates within the wide
range of initial concentrations in the studied solutions. The
only successful NMR titration was done with amine 4d.
The comparison of the binding constant value for amine
4d and the corresponding amide 5d implies a marginal role
of the free amino group in complex stabilisation via
hydrogen bonding. Further thermodynamic parameters
were obtained from ITC experiments. Standard treatment
of the ITC data for amides 5a–c (using a one-binding-site
model with three parameters, n, K and DH) did not lead to
CISmaxꢀKꢀcb-CD
CIS ¼
:
ð1Þ
1 þ Kꢀcb-CD
The calculated K values are listed in Table 2. It should
be noted that satisfactory fits to a theoretical model were
not accomplished for amines 4. We attributed this failure
Figure 3. A portion of the ROESY spectrum of a 1:1 mixture of guest 5b with b-CD (left frame) and a portion of the gs-HMQC-ROESY
spectrum of a 1:1 mixture of guest 5d with b-CD (right frame). Signals of the host and guest nuclei are labelled as H for b-CD and G for
guest.

6
M. Rouchal et al.
Table 2. Thermodynamic parameters of complexations.
ITC
NMR
K (M21
Compound
)
K (M21
)
2DH (kJ mol21
)
2DS (J mol21 K)
n
5a
5b
5c
5d
5d
5db
4d
538 ^ 70
767 ^ 75
1206 ^ 107
1721 ^ 34
–
128 ^ 4
258 ^ 9
219 ^ 5
329 ^ 3
329 ^ 20
–
26.3 ^ 0.6
28.1 ^ 0.7
31.0 ^ 0.4
35.2 ^ 0.2
35.3 ^ 4
(28)c
46
46
59
67
1a
1a
1a
1a
1.00 ^ 0.09
68
439 ^ 30
1142 ^ 128
(34)c
–
–
–
–
–
Note: T ¼ 303 K.
a The stoichiometry was predicted to be 1:1 using the ITC data treatment parameter n ¼ 1.
b T ¼ 333 K.
c See Section 4.
satisfactory results. Only iteration of the data for
compound 5d converged to reasonable values. However,
we have previously shown predominantly 1:1 stoichi-
ometry using NMR data under essentially the same
conditions as those used for the calorimetric titrations.
Therefore, we decided to fix the iteration parameter at
n ¼ 1. Thus, we obtained the thermodynamic parameters
given in Table 2. Comparison of the thermodynamic
parameters obtained for amide 5d with and without a fixed
n (Table 2) suggests that the presumption of 1:1 aggregates
was justified. The slightly higher entropy loss in the case of
amides 5c and 5d can be attributed to the more constrained
guest conformation inside the CD cavity. These data allow
us to conclude that all of the examined guests bind in an
enthalpy-driven manner. The elongation of the spacer
between the adamantane moiety and the benzene ring
leads to the formation of more stable aggregates. Further
fine tuning of the binding strength can be accomplished by
choosing appropriate substitution on the benzene ring. The
para-substituted amides form more stable complexes;
meta-substituted amides form less stable complexes.
The common simple adamantane derivatives, inde-
pendently on their charge, displayed association constants
with b-CD around 104. Typically, for AdCOO2 and
AdNHþ3 , K was estimated to be of 1.6 £ 104 and
8.3 £ 103 M21, respectively (32). For compounds with
the adamantane cage linked to some bulkier moiety or
polymer backbone, weaker binding was reported. For
example, N-(1-adamantyl)pyridinium bromide binds the
b-CD with K ¼ 1.9 £ 103 M21 (4a). Nevertheless, these
values were obtained in pure or buffered water. Owing to
low solubility of our ligands in water, we carried out all
titrations in H2O:DMSO (1:3, v:v) mixture in which the
contribution of hydrophobic effect is significantly
weakened. We carried out calorimetric titration of
AdNH2·HCl in phosphate buffer (pH 7.00) and in
H2O:DMSO mixture to be able to estimate the solvent
influence on the K value. The respective association
constants are 1.5 £ 104 and 2 £ 102 M21. As can be seen,
the binding is of two orders stronger in water. We believe
that this trend is applicable also for our new ligands to
sound their binding strength towards b-CD in water
similar to other conventional adamantane derivatives.
When carrying out the NMR titration of amide 5d with
b-CD, we observed a large separation between the signals
of the initially enantiotopic hydrogen atoms at position 5
(for C-atom numbering, see Figure 3) with an increased
proportion of b-CD as the spin system was changed from A2
to AB (Figure 2(a)–(c)). We attempted to understand the
nature of this phenomenon by carrying out additional
measurements. Increasing the temperature led to coalesc-
ence at approximately 608C (Figure 2(d),(e)). However,
when we increased the proportion of b-CD, while
concomitantly holding the mixture at 608C, the signal
split again (Figure 2(f)). Finally, lines g–j in Figure 2
demonstrate the increased signal separation observed with
increasing proportions of water in the mixed solvent. All of
these observations suggest that the signal splitting could be
attributed to the amount of complexed amide in the mixture.
We postulate that amide 5d (similar but significantly
smaller signal splitting was also observed with amide 5c)
predominantly adopts a particular conformation within the
b-CD cavity, which belongs to the C1 symmetry point group
and is fixed via interactions with b-CD. In such a situation,
the hydrogen atoms at carbon 5 become non-equivalent due
to the adjacent strongly anisotropic carbonyl group (see the
calculated model in Figure 4). These observations clearly
indicate that particular guest conformations may be locked
inside a suitable cavity via weak van der Waals interactions
and/or a steric hindrance.
2.4. Complex geometry
Owing to geometrical properties of the b-CD cavity (i.e.
wider secondary rim, narrower primary rim and central
constriction caused by H3 and H5 H-atoms), there are four
principal arrangements of an inclusion complex of
adamantane guest with b-CD. The adamantane cage can

Supramolecular Chemistry
7
A partial ROESY spectrum of an equimolar mixture of
amide 5b with b-CD and a schematic drawing of the
suggested complex geometry including the observed
interactions is depicted in Figure 3 (left). Furthermore,
we attempted to support this arrangement by applying a
1
2D H–13C gs-HMQC-ROESY experiment. As Figure 3
(right) shows for amide 5d, the interactions between CD
carbon 3 and the amide H-atoms 2, 3 and 4, between CD
carbon 5 and the amide H-atoms 2 and 8 and between CD
carbon 6 and the amide H-atoms 2, 8 and 9 were clearly
observed. These data led us to suggest a very similar
arrangement for the 5d·b-CD complex (Figure 3, right) as
that discussed above for amide 5b.
Finally, the geometry of the inclusion complexes was
calculated in a manner described previously (34). The
particular amide was positioned stepwise along the seven-fold
axis of b-CD to simulate threading the guest molecule through
the CD cavity. The geometries were initially optimised using a
semi-empirical PM3 method, and single point energies were
subsequently calculated at DFT level of theory. The
arrangement with the maximum difference between the
energy of the complex and sum of the energies of the guest and
host calculated separately was considered to be the closest to
the predominant actual complex geometry. A typical result
obtained for amide 5d is depicted in Figure 4. The calculated
geometry agrees well with the experimental data.
Figure 4. A calculated model of the 5d·b-CD inclusion
complex. H-atoms are omitted for clarity with the exception of
AdCH2, which were commented in the text.
occupy secondary (S) or primary (P) rim and in both cases,
the residue of the guest molecule can either thread the
cavity in a pseudorotaxane manner (I – interior) or
protrude to the outer environment (E – exterior) (33, 34).
As the adamantane cage better fits the wider secondary
rim, the positioning of adamantane-based guest molecule
in the primary rim has been rarely reported. Although the
host–guest complex of 1-adamantylammonium and
modified b-CD with the PE geometry was observed only
when the secondary rim was blocked by the positively
charged aminogroup (33), the PI arrangement has not been
reported to the best of our knowledge. The adamantane-
based guests with long non-polar substituent adopt
predominantly the SI geometry (34, 35c). However,
when the SI arrangement was obstructed by either host
(e.g. the cyclodextrins are frequently linked to the polymer
backbone via C6 carbon) or guest (e.g. two adamantane
cages linked with a short spacer) form, the preferable
geometry was reported to be of SE (4a,b, 35).
3. Conclusion
In conclusion, we described a convenient synthetic method
leading to versatile adamantane-bearing building blocks,
which could be subsequently used to prepare components
for supramolecular systems. In addition to full character-
isation of all of the novel compounds by spectral methods,
we studied the binding behaviour of four guests towards b-
CD using mass spectrometry, NMR and calorimetric
titrations. The association constants were found to be of
the order of 102–103 M21, and a relationship between the
guest structure and the binding strength was clearly
observed. Binding of the guest into the b-CD cavity was
improved with a longer non-polar spacer separating the
adamantane scaffold from the rest of the molecule and/or a
‘linear’ arrangement (i.e. para substitution of the central
benzene ring) of the guest molecule.
Although the distinguishing of S and P binding mode is
reasonable from a geometrical point of view, it should be
notedthat the adamantane cage is usually deeply buried into
the CD cavity with the centre of gravity of 10 adamantane
carbons being close to the best plane of seven etheric
oxygen atoms of b-CD. In addition, the analyses of NOE
data including only adamantane H-atoms can be rather
confused by means of significant sterically driven deviation
of the three-folded axes of adamantane substituent from the
seven-folded axes of cyclodextrin ring.
The 2D NMR ROESY spectra indicate that all of the
examined amides 5 interact with the b-CD unit
predominantly by inclusion within the internal cavity.
We clearly observed interactions between the inner H-
atoms at carbons 3 and 5 with adamantane H-atoms 2, 3
and 4. The additional cross-peaks that relate to interactions
between the aromatic guest H-atoms and the H-atoms at
position 5 in CD indicate that the aromatic part of the guest
molecule protrudes from the primary rim of cyclodextrin.
4. Experimental section
4.1. General
All solvents, reagents and starting compounds (except
those mentioned below) were of analytical grade,
purchased from commercial sources and used without
further purification. Adamantane-1-carbonyl chloride and
3-methylbenzoyl chloride were prepared according to a
previously published procedure (21). Melting points were

8
M. Rouchal et al.
measured on a Kofler block and are uncorrected.
Elemental analyses (C, H and N) were determined with a
Thermo Fisher Scientific Flash EA 1112. Retention times
were determined using TLC plates (Alugram Sil G/UV
from Macherey-Nagel) and petroleum ether/ethyl acetate
was used as the mobile phase. Four systems of mobile
phases were used (v/v): system a (1/1); system b (4/1);
system c (8/1) and system d (16/1). NMR spectra were
recorded at 258C on a Bruker Avance 500 spectrometer
operating at frequencies of 500.13 MHz (1H) and
125.77 MHz (13C) and a Bruker Avance 300 spectrometer
operating at frequencies of 300.13 MHz (1H) and
v/v). Clear mixtures were introduced into the ion source at
a flow rate of 3 ml/min via a metal capillary held at high
voltage (^3.5 kV). The other instrumental conditions
were as follows: the drying gas temperature was 2508C, the
drying gas flow was 5 l/min, and the nebuliser pressure was
41.37 kPa. Nitrogen was used for nebulisation and drying.
The nozzle-skimmer potential and octopole potential were
modified and optimised before each experiment. The
tandem mass spectra were collected using CID with He as
the collision gas after isolation of the required ions. The
ITC measurements were carried out in a DMSO:H2O (3:1,
v/v) solvent mixture using a VP-ITC MicroCal instrument
at 308C. The concentrations of the host in the cell and the
guest in the microsyringe were approximately 0.9–1.5 and
9–17 mM, respectively. The raw experimental data were
analysed with MicroCal ORIGIN software. The heats of
dilution were taken into account for each guest compound.
The data were fitted to a theoretical titration curve using
the ‘one set of binding sites’ model.
1
75.77 MHz (13C). H and 13C NMR chemical shifts were
referenced to the signal of the solvent [1H: d(residual
CHCl3) ¼ 7.27 ppm, d(residual [D5]DMSO) ¼ 2.50 ppm;
13C: d(CDCl3) ¼ 77.23 ppm, d([D6]DMSO) ¼ 39.52
ppm]. The mixing time for the NOESY experiment was
adjusted to 700 ms and the spin-lock for ROESY was
1
adjusted to 400 ms. The 2D H–13C gs-HMQC–ROESY
spectrum (36) was measured at resonance frequencies of
600.15 MHz (1H) and 150.67 MHz (13C). The HMQC step
1
was adjusted for JH–C ¼ 145 Hz with a subsequent
4.2. General procedure for ketones 1 preparation
ROESY spin-lock of 400 ms. The spectrum was recorded
in phase-sensitive mode using the echo–antiecho protocol
(37). NMR titration experiments were carried out as
follows. The solution of guest was titrated with stock
solution of b-CD. Complexation-induced shifts (CIS)
were calculated as CIS ¼ jdobserved 2 dfree guestj. Accord-
ing to Benesi–Hildebrand approach, CIS values were
plotted against total concentration of b-CD (cb-CD) and
data were fitted to a theoretical rectangular hyperbole
(Equation (1)) via the routine least square regression
process using MicroCal Origin software. The CISmax
describes coordinate of horizontal asymptote with the
meaning of chemical shift of particular 1H in the
Ketones 1a–d were prepared from the corresponding
Grignard reagent and acyl chloride in the presence of a
catalyst (21). In all cases, the desired product and a Grignard
dimer as a co-product were observed. The dimers were
separated from the mixture by column chromatography
(system b). The spectral data for ketones 1b (yield 77%) and
1a (yield 76%) correspond with the literature (21, 38).
4.2.1. 2-(1-Adamantyl)-1-(4-methylphenyl)ethanone (1d)
Compound 1d was isolated as colourless crystals in the
yield of 82%. M.p. 62–648C, Rf 0.37 (system d), anal.
calcd for C19H24O: C, 85.03; H, 9.01%; found C, 84.87%;
complexed guest molecule (CISmax ¼ jdcomplexed guest
2
1
H, 8.95%. H NMR (CDCl3): d 1.66 (m, 12H, CH2(Ad)),
d
j) and K (an association constant) is the slope for the
free guest
1.95 (m, 3H, CH(Ad)), 2.41 (s, 3H, PhCH3), 2.69 (s, 2H,
CH2CO), 7.24 (d, J ¼ 7.9 Hz, 2H, Ph), 7.85 (d, J ¼ 8.0 Hz,
2H, Ph) ppm. 13C NMR (CDCl3): d 21.7(CH3), 28.9(CH),
37.0(CH2), 43.2(CH2), 51.3(C), 128.7(CH), 129.3(CH),
136.7(C), 143.6(C), 200.0(CO) ppm. IR (KBr): 3066(w),
3027(w), 2899(s), 2846(s), 1659(s), 1604(s), 1571(w),
1449(m), 1323(m), 1308(m), 1268(s), 1183(m), 1152(w),
1119(m), 1017(w), 975(w), 842(w), 813(m), 761(m),
582(w) cm21. GC-MS (EI, 75eV); m/z (%): 41(11), 55(6),
65(14), 67(6), 77(9), 79(13), 91(47), 92(8), 93(9), 105(7),
119(100), 120(9), 135(11), 253(46), 254(9), 268(Mþ, 8).
CIS ¼ 0. For further details, see (31) and references
therein. The values of DH and DS were calculated from
NMR data using the van’t Hoff equation with –DH/R as
the slope and DS/R as the intercept of the straight line
obtained from linear regression of the plot of ln K versus
1/T. The IR spectra were recorded with a Mattson 3000 FT-
IR using a KBr disc. GC-MS analyses were run on a
Shimadzu QP-2010 instrument using a Supelco SLB-5 ms
(30 m, 0.25 mm) column with He as the carrier gas in
constant linear flow mode (38 cm s21), 1008C for 7 min,
258C min21 to 2508C, then held for the required time. Only
the peaks with relative abundances exceeding 5% are
listed. The electrospray mass spectra were recorded with
an Esquire LC ion-trap mass spectrometer (Bruker
Daltonics, Bremen, Germany) equipped with an ESI
source. Sample solutions were prepared immediately
before each experiment by mixing b-CD and the
individual amine:amide (8.8 mM in methanol:water, 1:1,
4.2.2. 2-(1-Adamantyl)-1-(3-methylphenyl)ethanone (1c)
Compound 1c was isolated as colourless liquid in the yield
of 75%. Rf 0.17 (system a), anal. calcd for C19H24O: C,
85.03%; H, 9.01%; found C, 85.22%; H, 8.92%. 1H NMR
(CDCl3): d 1.66 (m, 12H, CH2(Ad)), 1.95 (m, 3H,

Supramolecular Chemistry
9
CH(Ad)), 2.42 (s, 3H, PhCH3), 2.71 (s, 2H, COCH2), 7.30–
7.35 (m, 2H, Ph), 7.73–7.76 (m, 2H, Ph) ppm. 13C NMR
(CDCl3): d 21.6(CH3), 28.9(CH), 34.1(C), 37.0(CH2),
43.2(CH2), 51.4(COCH2), 125.9(CH), 128.4(CH),
129.0(CH), 133.6(CH), 138.4(C), 139.2(C), 200.6(CO)
ppm. IR (KBr): 2902(s), 2847(s), 2674(w), 2657(w),
1671(s), 1602(w), 1584(w), 1450(m), 1343(w), 1317(w),
1267(s), 1237(w), 1190(w), 1151(w), 1098(w), 1041(w),
804(w), 777(w), 754(m), 693(m) and 607(w) cm21. GC-
MS (EI, 75 eV); m/z (%): 41(8), 55(5), 65(11), 67(5), 77(7),
79(11), 91(43), 92(8), 93(9), 119(100), 120(9), 134(5),
135(17), 250(5), 253(15), 268(Mþ, 24) and 269(5).
calcd for C18H21BrO: C, 64.87%; H, 6.35%; found C,
1
64.59%; H, 6.23%. H NMR (CDCl3): d 1.76 (m, 6H,
CH2(Ad)), 2.02 (m, 6H, CH2(Ad)), 2.09 (m, 3H, CH(Ad)),
4.50 (s, 2H, CH2Br), 7.42 (d, J ¼ 7.9 Hz, 2H, Ph), 7.54 (d,
J ¼ 7.9 Hz, 2H, Ph) ppm. 13C NMR (CDCl3): d 28.3(CH),
32.7(CH2), 36.7(CH2), 39.3(CH2), 47.2(C), 127.8(CH),
128.8(CH), 139.7(C), 139.9(C), 209.6(CO) ppm. IR
(KBr): 2924(s), 2905(s), 2852(s), 2658(w), 1669(s),
1605(w), 1453(w), 1403(w), 1274(m), 1243(m),
1226(m), 1176(w), 1108(m), 988(m), 951(w), 930(w),
846(w), 788(w), 683(w), 619(m), 595(w) and 557(w)
cm21. GC-MS (EI, 75 eV); m/z (%): 43(6), 67(5), 77(5),
79(13), 89(6), 93(13), 107(8), 118(15), 135(100), 136(11)
and 332(Mþ, ,1).
4.3. General procedure for the synthesis of
benzylbromides 2a–d
4.3.3. 2-(1-Adamantyl)-1-[3-(bromomethyl)phenyl]
ethanone (2c)
The corresponding ketone 1 (47.1 mmol) was dissolved in
100 ml of dry tetrachloromethane, and NBS (8.54 g,
48.0 mmol) was added in one portion to this solution. The
reaction was initiated by the addition of a catalytic amount
of benzoyl peroxide and irradiation with a tungsten
lamp. The mixture was stirred and refluxed for 8 h, and the
reaction progress was monitored by TLC during this time.
After this period, the succinimide was filtered off, and the
filtrate was evaporated under vacuum. The desired product
was obtained after purification of the crude product by
column chromatography (system c).
Compound 2c was isolated as colourless liquid in the yield
of 82%. Rf 0.45 (system c), anal. calcd for C19H23BrO: C,
65.71%; H, 6.68%; found C, 65.58%; H, 6.65%. 1H NMR
(CDCl3): d 1.65 (m, 12H, CH2(Ad)), 1.94 (m, 3H,
CH(Ad)), 2.71 (s, 2H, CH2CO), 4.52 (s, 2H, CH2Br), 7.42
(t, J ¼ 7.6 Hz, 1H, Ph), 7.56 (d, J ¼ 7.6 Hz, 1H, Ph), 7.86
(t, J ¼ 7.6 Hz, 1H, Ph), 7.95 (s, 1H, Ph) ppm. 13C NMR
(CDCl3): d 28.8(CH), 32.8(CH2), 34.1(C), 36.9(CH2),
43.1(CH2), 51.4(CH2), 128.5(CH), 128.9(CH), 129.1(CH),
133.3(CH), 138.4(C), 139.4(C), 199.6(CO) ppm. IR
(KBr): 2901(s), 2846(s), 1673(s), 1600(w), 1449(m),
1312(w), 1168(w), 1216(w), 1143(w), 1094(w), 807(w),
762(w) and 692(s) cm21. GC-MS (EI, 75 eV); m/z (%):
41(12), 55(7), 65(5), 67(9), 77(11), 79(21), 81(6), 89(14),
90(31), 91(26), 92(9), 93(16), 105(7), 107(8), 118(21),
119(26), 133(8), 135(40), 136(5), 196(19), 198(20),
253(11), 267(100), 268(21), 346(Mþ, 3) and
348(Mþ þ 2, 3).
4.3.1. 1-Adamantyl-[3-(bromomethyl)phenyl]
methanone (2a)
Compound 2a was isolated as colourless liquid in the yield
of 80%. The oily material slowly crystallised at 2 158C.
M.p. 48–508C, Rf 0.42 (system c), anal. calcd for
C18H21BrO: C, 64.87%; H, 6.35%; found C, 64.78%; H,
6.21%. 1H NMR (CDCl3): d 1.76 (m, 6H, CH2(Ad)), 2.01
(m, 6H, CH2(Ad)), 2.09 (m, 3H, CH(Ad)), 4.50 (s, 2H,
CH2Br), 7.34–7.50 (m, 3H, Ph), 7.54 (s, 1H, Ph) ppm. 13
C
NMR (CDCl3): d 28.3(CH), 33.0(CH), 36.7(CH2),
39.3(CH2), 47.2(C), 127.1(CH), 127.9(CH), 128.6(CH),
130.8(CH), 137.9(C), 140.4(C), 209.8(CO) ppm. IR
(KBr): 2905(s), 2850(s), 2678(w), 2657(w), 1664(s),
1598(w), 1452(m), 1344(w), 1276(m), 1214(m),
1194(w), 1175(m), 1104(w), 1004(m), 802(w), 763(w),
733(w), 695(m), 625(w), 568(w) cm21. GC-MS (EI,
75 eV); m/z (%): 41(8), 55(6), 67(8), 77(7), 79(22), 81(6),
89(7), 90(10), 91(10), 93(18), 107(10), 118(5), 135(100),
136(11) and 332(Mþ, ,1).
4.3.4. 2-(1-Adamantyl)-1-[4-(bromomethyl)phenyl]
ethanone (2d)
Compound 2d was isolated as colourless crystals in the
yield of 55%. M.p. 85–888C, Rf 0.22 (system d), anal.
calcd for C19H23BrO: C, 65.71%; H, 6.68%; found C,
1
65.48%; H, 6.52%. H NMR (CDCl3): d 1.66 (m, 12H,
CH2(Ad)), 1.96 (m, 3H, CH(Ad)), 2.71 (s, 2H, CH2CO),
4.51 (s, 2H, CH2Br), 7.48 (d, J ¼ 8.6 Hz, 2H, Ph), 7.93 (d,
J ¼ 8.6 Hz, 2H, Ph) ppm. 13C NMR (CDCl3): d 28.9(CH),
32.4(CH2), 34.2(C), 37.0(CH2), 43.2(CH2), 51.5(CH2),
129.1(CH), 129.3(CH), 138.9(C), 142.5(C), 199.7(CO)
ppm. IR (KBr): 2900(s), 2846(m), 2672(w), 2657(w),
1670(s), 1604(w), 1571(w), 1446(w), 1411(w), 1346(w),
1322(w), 1286(w), 1262(m), 1204(w), 1179(w), 1152(w),
1094(w), 1015(w), 977(w), 861(w), 816(w), 782(w),
709(w), 667(w) and 601(m) cm21. GC-MS (EI, 75 eV);
4.3.2. 1-Adamantyl-[4-(bromomethyl)phenyl]
methanone (2b)
Compound 2b was isolated as colourless crystals in the
yield of 72%. M.p. 60–628C, Rf 0.49 (system c), anal.

10
M. Rouchal et al.
m/z (%): 40(5), 41(41), 43(6), 51(6), 53(15), 55(24),
63(11), 64(5), 65(24), 66(5), 67(26), 69(6), 77(35), 78(12),
79(59), 80(8), 81(17), 89(33), 90(78), 91(92), 92(24),
93(41), 104(16), 105(20), 107(16), 118(70), 119(100),
120(9), 133(22), 134(21), 135(45), 136(5), 169(6),
197(20), 199(19), 253(43), 254(9), 267(89) and 268(21).
987(w), 950(w),927(w), 834(w), 799(w),738(w)and685(w)
cm21. GC-MS (EI, 75eV); m/z (%): 55(8), 67(10), 77(14),
79(21), 81(6), 91(6), 93(20), 107(10), 118(7), 135(100),
136(10), 239(10), 267(Mþ–N2, 2) and 295(Mþ, 1).
4.4.3. 2-(1-Adamantyl)-1-[3-(azidomethyl)phenyl]
ethanone (3c)
4.4. General procedure for the synthesis of azides 3a–d
Compound 3c was isolated as colourless crystals in the
yield of 97%. The analytical sample was further crystal-
lised from hexane. M.p. 60–628C, Rf 0.22 (system d), anal.
calcd for C19H23N3O: C, 73.76%; H, 7.49%; N, 13.58%;
found C, 73.65%; H, 7.23%; N, 13.78%. 1H NMR
(CDCl3): d 1.66 (m, 12H, CH2(Ad)), 1.94 (m, 3H,
CH(Ad)), 2.72 (s, 2H, CH2CO), 4.42 (s, 2H, CH2N3), 7.44–
7.52 (m, 2H, Ph) and 7.89–7.92 (m, 2H, Ph) ppm. 13C NMR
(CDCl3): d 28.9(CH), 34.1(C), 37.0(CH2), 43.1(CH2),
51.5(CH2), 54.6(CH2), 128.0(CH), 128.5(CH), 129.2(CH),
132.4(CH), 136.1(C), 139.6(C) and 199.9(CO) ppm. IR
(KBr): 2905(s), 2847(s), 2099(s), 1673(s), 1602(w),
1449(m), 1344(w), 1311(w), 1266(m), 1189(w), 1148(w),
1095(w), 979(w), 925(w), 806(w), 757(w), 723(w),
The appropriate bromide (2.72 mmol) was dissolved in
10ml of dry acetone, and sodium azide (1.77 g, 27.2mmol)
was added to this solution in one portion. The reaction
mixture was refluxed under an Ar atmosphere until TLC
indicated the complete disappearance of the starting material
(6–8 h). Subsequently, the mixture was diluted with water
and extracted six times with diethyl ether. The combined
organic layers were dried over sodium sulphate. Evaporation
of the solvent under vacuum followed by purification via
column chromatography (system c) provided the desired
product.
695(m), 695(w), 649(w) and 610(w) cm21
.
4.4.1. 1-Adamantyl-[3-(azidomethyl)phenyl]methanone
(3a)
Compound 3a was isolated as colourless liquid in the yield
of 73%. Rf 0.24 (system d), anal. calcd for C18H21N3O: C,
73.19%; H, 7.17%; N, 14.23%; found C, 73.08%; H,
4.4.4. 2-(1-Adamantyl)-1-[4-(azidomethyl)phenyl]
ethanone (3d)
1
7.32%; N, 14.17%. H NMR (CDCl3): d 1.76 (m, 6H,
Compound 3d was isolated as colourless solid in the yield
of 77%. M.p. 25–278C, Rf 0.33 (system b), anal. calcd for
C19H23N3O: C, 73.76%; H, 7.49%; N, 13.58%; found C,
73.82%; H, 7.12%; N, 13.55%. 1H NMR (CDCl3): d 1.66
(m, 12H, CH2(Ad)), 1.95 (m, 3H, CH(Ad)), 2.72 (s, 2H,
CH2CO), 4.42 (s, 2H, CH2N3), 7.40 (d, J ¼ 8.3 Hz, 2H,
Ph), 7.96 (d, J ¼ 8.3 Hz, 2H, Ph) ppm. 13C NMR (CDCl3):
d 28.9(CH), 34.2(C), 36.2(CH2), 43.2(CH2), 51.5(CH2),
54.5(CH2), 128.2(CH), 127.1(CH), 138.9(C), 140.4(C),
199.8(CO) ppm. IR (KBr): 2903(s), 2847(s), 2099(s),
1671(s), 1608(m), 1573(w), 1504(w), 1450(w), 1412(w),
1345(w), 1287(w), 1262(m), 1209(w), 1178(w), 1149(w),
1014(w), 978(w), 915(w), 851(w), 813(w) and 764(w)
cm21. GC-MS (EI, 75 eV); m/z (%): 41(16), 51(7), 53(5),
55(9), 67(12), 76(6), 77(39), 78(6), 79(26), 81(8), 91(21),
92(9), 93(20), 103(6), 104(28), 105(13), 107(9), 132(100),
133(11), 135(32), 252(6), 253(23), 264(9), 280(6),
281(Mþ–N2, 75) and 282(16).
CH2(Ad)), 2.01 (m, 6H, CH2(Ad)), 2.09 (m, 3H, CH(Ad)),
4.39 (s, 2H, CH2N3), 7.41–7.51 (m, 4H, Ph) ppm. 13C
NMR (CDCl3): d 28.3(CH), 36.7(CH2), 39.3(CH2),
47.2(C), 54.7(CH2), 126.9(CH), 127.0(CH), 128.7(CH),
129.8(CH), 135.7(C), 140.6(C) and 205.2(CO) ppm. IR
(KBr): 2905(s), 2851(s), 2678(w), 2659(w), 2098(s),
1672(s), 1601(w), 1584(w), 1452(m), 1344(m), 1273(m),
1245(m), 1194(w), 1172(m), 1104(w), 999(m), 972(w),
935(w), 887(w), 803(w), 782(w), 732(w), 711(w) and
650(w) cm21
.
4.4.2. 1-Adamantyl-[4-(azidomethyl)phenyl]methanone
(3b)
Compound 3b was isolated as colourless crystals in the
yield of 70%. M.p. 35–368C, Rf 0.45 (system c), anal.
calcd for C18H21N3O: C, 73.19%; H, 7.17%; N, 14.23%;
found C, 73.36%; H, 7.26%; N, 13.95%. 1H NMR
(CDCl3): d 1.76 (m, 6H, CH2(Ad)), 2.02 (m, 6H,
CH2(Ad)), 2.09 (m, 3H, CH(Ad)), 4.39 (s, 2H, CH2N3),
7.35 (d, J ¼ 7.9 Hz, 1H, Ph), 7.58 (d, J ¼ 7.9 Hz, 1H, Ph)
ppm. 13C NMR: d 28.4(CH), 36.8(CH2), 39.3(CH2),
47.2(C), 54.6(CH2), 128.8(CH), 128.0(CH), 137.8(C),
139.7(C) and 204.8(CO) ppm. IR (KBr): 2910(s), 2851(s),
2098(s), 1657(s), 1605(w), 1452(w), 1428(w), 1408(w),
1344(w), 1295(w), 1270(w), 1233(w), 1173(w), 1103(w),
4.5. General procedure for the synthesis of benzylamines
4a–d
The corresponding azide(1.88 mmol) was dissolved in20ml
of methanolic HCl (1–2 M), and iron powder (203mg,
3.64mmol) was added to this solution in one portion. The
reaction mixture was stirred at room temperature, and
another portionofcarbonyliron(3.64 mmol)wasaddeduntil

Supramolecular Chemistry
11
the starting material had completely disappeared (according
toTLC).Thesolventwasthenremovedundervacuum, 30ml
of 7% NaOH (water solution) was added, and the water layer
was extracted with diethyl ether (5 £ 10ml). The collected
organic portions were washed with brine (3 £ 10ml), dried
over sodium sulphate and evaporated under vacuum. The
purified product (column chromatography, system d) was
generally isolated as a colourless liquid, which was
subsequently converted to the hydrochloride.
(KBr): 3340(w), 2901(s), 2847(m), 1671(s), 1600(w),
1451(m), 1317(m), 1267(m), 1190(w), 1148(w), 807(w),
757(w), 695(m) and 469(m) cm21. GC-MS (free base) (EI,
75 eV); m/z (%): 41(6), 55(5), 67(6), 77(21), 79(19), 91(10),
93(11), 104(8), 105(11), 106(22), 107(7), 118(19), 119(5),
134(100), 135(27), 253(14), 266(67) and 267(14).
4.5.4. 2-(1-Adamantyl)-1-[4-(aminomethyl)phenyl]
ethanone hydrochloride (4d)
Compound 4d was isolated as a colourless crystalline
powder in the yield of 85%. M.p. 220–2228C, Rf (free base)
0.24 (MeOH:CHCl3, 3:1, v:v), anal. calcd for C19H26ClNO:
C, 71.34%; H, 8.19%; N, 4.38%; found C, 71.48%; H,
8.13%; N, 4.72%. 1H NMR ([D6]DMSO, 2.50ppm): d 1.58
(m, 12H, CH2(Ad)), 1.88 (m, 3H, CH(Ad)), 2.74 (s, 2H,
CH2CO), 4.08(s, 2H, CH2NH3), 7.65(s, 2H, Ph), 7.98(s, 2H,
Ph) and 8.66 (bs, 3H, NH3) ppm. 13C NMR ([D6]DMSO,
39.5ppm): d 28.0(CH), 33.4(C), 36.2(CH2), 41.6(CH2),
42.2(CH2), 50.4(CH2), 128.3(CH), 129.0(CH), 138.2(C),
138.9(C), 199.3(CO) ppm. IR (KBr): 2901(s), 2847(s),
2674(w), 2611(w), 1670(s), 1611(m), 1450(m), 1417(w),
1264(m), 1218(w), 1179(w), 1121(w), 1100(w), 1009(w),
983(w), 915(w), 825(w), 668(w) and 587(w) cm21. GC-MS
(free base) (EI, 75eV); m/z (%): 41(8), 55(7), 67(7), 77(15),
79(19), 89(20), 91(15), 92(5), 93(12), 104(7), 105(24),
106(15), 107(6), 134(100), 135(24), 253(62), 254(12),
266(42) and 267(10).
4.5.1. 1-Adamantyl-[3-(aminomethyl)phenyl]methanone
(4a)
Compound 4a was isolated as colourless liquid in the yield
of 97%. Rf 0.25 (system a). GC-MS (EI, 75 eV); m/z (%):
41(5), 67(8), 77(11), 79(19), 91(5), 93(18), 106(10),
107(12), 134(14), 135(100), 136(11), 241(22), 252(7) and
269(Mþ, 2).
4.5.2. 1-Adamantyl-[4-(aminomethyl)phenyl]methanone
hydrochloride (4b)
Compound 4b was isolated as colourless crystalline powder
in the yield of 68%. M.p. 200–2048C, Rf (free base) 0.79
(MeOH:CHCl3, 3:1, v:v), anal. calcd for C18H24ClNO: C,
70.69%; H, 7.91%; N, 4.58%; found C, 70.48%; H, 7.85%;
N, 4.32%. 1H NMR ([D6]DMSO, 2.50ppm): d 1.69 (m, 6H,
CH2(Ad)), 1.90 (m, 6H, CH2(Ad)), 2.01 (m, 3H, CH(Ad)),
4.05 (s, 2H, CH2NH3), 7.57 (m, 4H, Ph) and 8.52 (s, 3H,
NH3) ppm. 13C NMR ([D6]DMSO, 39.5ppm): d 27.2(CH),
35.7(CH2), 38.1(CH2), 41.5(CH2), 45.8(C), 126.8(CH),
128.4(CH), 135.8(C), 138.7(C) and 208.5(CO) ppm. IR
(KBr): 3034(w), 2906(s), 2849(w), 1733(w), 1690(s),
1613(w), 1595(w), 1493(m), 1452(m), 1382(w), 1343(w),
1273(w), 1240(m), 1178(w), 1103(w), 1070(w), 989(m),
931(w), 849(m) and 636(m) cm21. GC-MS (free base) (EI,
75eV); m/z (%): 79(18), 81(5), 89(7), 91(5), 93(16), 105(5),
106(6), 107(10), 134(21), 135(100), 136(11), 252(10) and
269(Mþ, 2).
4.6. General procedure for the synthesis of acetamides 5
The corresponding benzylamine 4 (0.9 mmol) was
dissolved in 45 ml of pyridine, and 0.15 ml of acetic
anhydride was added to this solution. The mixture was
stirred for 12 h at room temperature and then poured onto
crushed ice. The water layer was extracted with diethyl
ether (5 £ 10 ml), and the combined organic layers were
dried over sodium sulphate and evaporated under vacuum.
The desired acetamide 5 was obtained after purification of
the crude product by column chromatography (system a).
4.5.3. 2-(1-Adamantyl)-1-[3-(aminomethyl)phenyl]
ethanone hydrochloride (4c)
4.6.1. N-[3-(1-adamantylcarbonyl)benzyl]acetamide (5a)
Compound 4c was isolated as a pale yellow crystalline
powder in the yield of 91%. M.p. 163–1678C, Rf (free base)
0.27 (system a), anal. calcd for C19H26ClNO: C, 71.34%; H,
8.19%; N, 4.38%; found C, 71.12%; H, 8.08%; N, 4.53%.
1H NMR (CDCl3): d 1.60 (m, 12H, CH2(Ad)), 1.88 (s, 3H,
CH(Ad)), 2.64 (s, 2H, CH2CO), 4.18 (s, 2H, CH2NH2), 7.36
(t, J ¼ 7.6 Hz, 1H, Ph), 7.71 (d, J ¼ 7.6 Hz, 1H, Ph), 7.79
(d, J ¼ 7.6 Hz, 1H, Ph) and 8.09 (m, 1H, Ph), 8.63 (bs, 3H,
NH3) ppm. 13C NMR (CDCl3): d 28.9(CH), 34.2(C),
36.9(CH2), 43.5(CH2), 51.5(CH2), 129.2(CH), 129.3(CH),
133.6(CH), 134.0(CH), 139.3(C) and 200.7(CO) ppm. IR
Compound 5a was isolated as a colourless crystalline
powder in the yield of 83%. M.p. 105–1108C, Rf 0.31
(system a), anal. calcd for C20H25NO2: C, 77.14%; H,
8.09%; N, 4.50%; found C, 76.95%; H, 8.18%; N, 4.22%.
1H NMR (CDCl3): d 1.74 (m, 6H, CH2(Ad)), 1.98–2.07
(m, 12H, CH2 (Ad) þ CH(Ad) þ CH3CO), 4.42 (d,
J ¼ 5.6 Hz, 2H, CH2NH), 6.10 (bs, 1H, NH), 7.34–7.43
(m, 4H, Ph) ppm. 13C NMR (CDCl3): d 23.4(CH3),
28.3(CH), 36.7(CH2), 39.3(CH2), 43.6(CH2), 47.1(C),
126.1(CH), 126.5(CH), 128.4(CH), 129.7(CH), 138.6(C),
140.3(C), 170.2(NHCO) and 210.4(CO) ppm. IR (KBr):

12
M. Rouchal et al.
3250(s), 3074(s), 2905(s), 2851(s), 2678(w), 2658(w),
1679(s), 1642(s), 1563(s), 1440(m), 1373(m), 1349(w),
1299(m), 1274(m), 1249(m), 1193(w), 1172(w), 1101(w),
1032(m), 996(m), 896(w), 790(m), 733(w), 705(m),
689(w), 640(w) and 496(w) cm21. GC-MS (EI, 75 eV);
m/z (%): 43(5), 67(6), 77(5), 79(14), 93(13), 106(5),
107(9), 135(100), 136(9), 178(5), 311(Mþ, 9).
4.6.4. N-[4-(1-adamantylmethylcarbonyl)benzyl]
acetamide (5d)
Compound 5d was isolated as a colourless crystalline
powder in the yield of 43%. M.p. 84–888C, Rf 0.27
(system a), anal. calcd for C21H27NO2: C, 77.50; H, 8.36;
N, 4.30; found C, 77.38; H, 8.41; N 3.98. 1H NMR
(CDCl3): d ¼ 1.59–1.70 (m, 12H, CH2(Ad)); 1.94 (m, 3H,
CH(Ad)); 2.04 (s, 3H, COCH3); 2.68 (s, 2H, AdCH2CO);
4.47 (d, J ¼ 5.9 Hz, 2H, PhCH2NH); 6.16 (bs, 1H, NH);
7.32 (d, J ¼ 8.3 Hz, 2H, Ph) and 7.88 (d, J ¼ 5.9 Hz, 2H,
Ph) ppm. 13C NMR (CDCl3): d ¼ 23.3 (CH3), 28.9 (CH),
34.2 (C), 37.0 (CH2), 43.2 (CH2), 43.5 (CH2), 51.5 (CH2),
127.8 (CH), 129.0 (CH), 138.3 (C), 143.5 (C), 170.3
(NHCO) and 200.5 (CO) ppm. IR (KBr): 3261 (s), 3079
(s), 2903 (s), 2844 (s), 2673 (w), 2655 (w), 1652 (m), 1609
(m), 1561 (s), 1426(m), 1371 (s), 1350 (w), 1286 (s), 1263
(s), 1214 (m), 1100 (m), 1027 (s), 983 (m), 915 (w), 813
(m), 771 (m), 623 (w), 585 (s) and 511 (m) cm21. GC-MS
(EI, 75 eV); m/z (%): 41(8), 43(16), 77(14), 79(20), 93(13),
105(17), 106(15), 135(17), 176(55), 253(10), 266(100)
and 267(22).
4.6.2. N-[4-(1-adamantylcarbonyl)benzyl]acetamide (5b)
Compound 5b was isolated as a colourless crystalline
powder in the yield of 55%. M.p. 114–1178C, Rf 0.30
(system a), anal. calcd for C20H25NO2: C, 77.14; H, 8.09;
N, 4.50; found C, 77.42; H, 7.93; N, 4.37. 1H NMR
(CDCl3): d 1.69–1.79 (m, 6H, CH2(Ad)); 1.99 (m, 6H,
CH2(Ad)); 2.04 (s, 3H, COCH3); 2.07 (m, 3H, CH(Ad));
4.44 (d, J ¼ 5.6 Hz, 2H, PhCH2NH); 6.08 (bs, 1H, NH);
7.28 (d, J ¼ 7.9 Hz, 2H, Ph); 7.51 (d, J ¼ 7.9 Hz, 2H, Ph)
ppm. 13C NMR (CDCl3): d ¼ 23.3 (CH3), 28.3 (CH), 36.7
(CH2), 39.3 (CH2), 43.5 (CH2), 47.1 (C), 127.4 (CH),
127.8 (CH), 138.9 (C), 140.7 (C), 170.3 (NHCO) and
209.8 (CO) ppm. IR (KBr): 3250 (s), 3085 (s), 2904 (s),
2848 (s), 2658 (m), 1686 (s), 1646 (s), 1612 (m), 1548 (s),
1452 (s), 1421 (m), 1406 (w), 1375 (m), 1344 (w), 1292
(s), 1273 (s), 1237 (s), 1180 (m), 1122 (m), 1099 (m), 989
(s), 931 (m), 837 (w), 742 (s), 687 (m), 641 (s), 595 (s) and
495 (s) cm21. GC-MS (EI, 75 eV); m/z (%): 43(6), 67(7),
79(20), 89(5), 91(5), 93(15), 107(10), 135(100), 176(8),
311(Mþ, 9).
Acknowledgements
This work was supported by the Internal Founding Agency of
´
Tomas Bata University in Zlın, project IGA/FT/2012/016 to
A.M., M.R. and R.V., the project ‘CEITEC 2 Central European
Institute of Technology’ (CZ.1.05/1.1.00/02.0068) from the
European Regional Development Fund to R.M. and M.B. and
institutional research plan RVO:68081715 to R.C.
4.6.3. N-[3-(1-adamantylmethylcarbonyl)benzyl]
acetamide (5c)
References
Compound 5c was isolated as a colourless crystalline
powder in the yield of 74%. M.p. 115–1208C, Rf
0.30(system a), anal. calcd for C21H27NO2: C, 77.50; H,
(1) Carrazana, J.; Jover, A.; Meijide, F.; Soto, V.H.; Tato, J.V.
J. Phys. Chem. B 2005, 109, 9719–9726.
(2) (a) Chelli, S.; Majdoub, M.; Jouini, M.; Aeiyach, S.;
Maurel, F.; Chane-Ching, K.I.; Lacaze, P.-C. J. Phys. Org.
1
8.36; N, 4.30; found C, 77.24; H, 8.28; N 4.57. H NMR
(CDCl3): d 1.59–1.70 (m, 12H, CH2(Ad)); 1.94 (m, 3H,
CH(Ad)); 2.04 (s, 3H, COCH3); 2.69 (s, 2H, AdCH2CO);
4.48 (d, J ¼ 5.3 Hz, 2H, PhCH2NH); 6.17 (bs, 1H, NH);
´
Chem. 2007, 20, 30–43. (b) Carmona, T.; Gonzales-
Alvarez, M.J.; Mendicuti, F.; Tagliapierta, S.; Cravotto,
´
M.K. J. Phys. Chem. C 2010, 114, 22431–22440.
(3) Lahiani-Skiba, M.; Boulet, Y.; Youm, I.; Bounoure, F.;
7.37–7.48 (m, 2H, Ph) and 7.81–7.83 (m, 2H, Ph) ppm. 13
C
´
´
Verite, P.; Arnaud, P.; Skiba, M. J. Incl. Phenom.
Macrocycl. Chem. 2007, 57, 211–217.
NMR (CDCl3): d ¼ 23.3 (CH3), 28.9 (CH), 34.2 (C), 37.0
(CH2), 43.2 (CH2), 43.6 (CH2), 51.5 (CH2), 127.5 (CH),
127.9 (CH), 129.0 (CH), 132.4 (CH), 139.0 (C), 139.4 (C),
170.4 (NHCO) and 200.3 (CO) ppm. IR (KBr): 3251 (s),
3077 (s), 2990 (w), 2905 (s), 2846 (s), 2674 (w), 2660 (w),
1672 (s), 1644 (s), 1600 (m), 1553 (s), 1437 (s), 1371 (m),
1290 (m), 1251 (m), 1026 (m), 803 (w), 760 (m), 582 (w)
and 515 (m) cm21. GC-MS (EI, 75 eV); m/z (%): 43(18),
55(5), 67(11), 73(5), 77(23), 79(33), 81(8), 89(8), 90(7),
91(18), 43(18), 92(6), 93(22), 104(3), 105(18), 105(35),
107(17), 118(26), 119(11), 134(13), 135(100), 136(11),
148(20), 149(9), 172(7), 176(73), 177(8), 190(10), 253(93),
254(19), 266(65), 267(14) and 325(Mþ, 5).
(4) (a) Ohga, K.; Takashima, Y.; Takahashi, H.; Kawaguchi,
Y.; Yamaguchi, H.; Harada, A. Macromolecules 2005, 38,
5897–5904. (b) Leggio, C.; Anselmi, M.; Di Nola, A.;
Galantini, L.; Jover, A.; Meijide, F.; Pavel, N.V.; Tellini,
V.H.S.; Tato, J.V. Macromolecules 2007, 40, 5899–5906.
(c) Hasegawa, Y.; Miyauchi, M.; Takashima, Y.; Yama-
guchi, H.; Harada, A. Macromolecules 2005, 38, 3724–
3730.
(5) Krishan, R.; Gopidas, K.R. J. Phys. Chem. Lett. 2011, 2,
2094–2098.
(6) Bertrand, B.; Stenzel, M.; Fleury, E.; Bernard J. Polym.
Chem. 2012, 3, 377–383.
´
(7) Bistri, O.; Mazeau, K.; Auzely-Velty, R.; Sollogoub, M.
Chem. Eur. J. 2007, 13, 8847–8857.

Supramolecular Chemistry
13
(8) Galantini, L.; Jover, A.; Leggio, C.; Meijide, F.; Pavel,
N.V.; Tellini, V.H.S.; Tato, J.V.; Tortolini, C. J. Phys.
Chem. B 2008, 112, 8536–8541.
King, A.R.; Tarzia, G.; Piomelli, D. J. Med. Chem. 2008, 51,
3487–3498.
´
´ˇ
(21) Vıcha, R.; Potacek, M. Tetrahedron 2005, 61, 83–88.
(22) Seong, H.R.; Kim, D.-S.; Kim, S.-G.; Choi, H.-J.; Ahn,
K.H. Tetrahedron Lett. 2004, 45, 723–727.
¨
¨
(9) Bohm, I.; Isenbugel, K.; Ritter, H.; Branscheid, R.; Kolb, U.
Angew. Chem. Int. Ed. 2011, 50, 7896–7899.
(10) Li, C.; Luo, G.-F.; Wang, H.-Y.; Zhang, J.; Gong, Y.-H.;
Cheng, S.-X.; Zhuo, R.-X.; Zhang, X.-Z. J. Phys. Chem. C
2011, 115, 17651–17659.
(11) Layre, A.-M.; Volet, G.; Wintgens, V.; Amiel, C.
Biomacromolecules 2009, 10, 3283–3289.
(12) Osman, S.K.; Brandl, F.P.; Zayed, G.M.; Teßmar, J.K.;
(23) Vaultier, M.; Knouzi, N.; Carrie, R. Tetrahedron Lett. 1983,
24, 763–764.
(24) Koziara, A.; Osowska-Pacewicka, K.; Zawadzki, S.;
Zvierzak, A. Synthesis 1985, 1985, 202–204.
(25) Bayley, H.; Standring, D.N.; Knowles, J.R. Tetrahedron
Lett. 1978, 19, 3633–3634.
(26) Lin, W.; Zhang, X.; He, Z.; Jin, Y.; Gong, L.; Mi, M. Synth.
Commun. 2002, 32, 3279–3284.
(27) Kamal, A.; Ramana, K.V.; Ankati, H.B.; Ramana, A.V.
Tetrahedron Lett. 2002, 43, 6861–6863.
(28) (a) Rolla, F. J. Org. Chem. 1982, 47, 4327–4329. (b) Boyer,
J.H.; Ellzey, S.E. Jr. J. Org. Chem. 1958, 23, 127–129.
(c) Aelterman, W.; Tehrani, K.A.; Coppens, W.; Huy-
¨
Gopferich, A.M. Polymer 2011, 52, 4806–4812.
(13) (a) Koopmans, C.; Ritter, H. Macromolecules 2008, 41,
7418–7422. (b) Li, L.; Guo, X.; Wang, J.; Liu, P.;
Prudhomme, R.K.; May, B.L.; Lincoln, S.L. Macromole-
cules 2008, 41, 8677–8681.
´
(14) (a) Charlot, A.; Auzely-Velty, R. Macromolecules 2007, 40,
9555–9563. (b) Charlot, A.; Auzely-Velty, R. Macromole-
´
cules 2007, 40, 1147–1158.
(15) Van der Heyden, A.; Wilczewski, M.; Labbe, P.; Auzely, R.
Chem. Commun. 2006, 3220–3222.
´
brechts, T.; Kimpe, N.; Tourwe, D.; Declercq, J.-P. Eur.
J. Org. Chem. 1999, 1999, 239–250.
´
´
(29) Kamal, A.; Laxman, E.; Arifuddin, M. Tetrahedron Lett.
2000, 41, 7743–7746.
(16) (a) Goto, H.; Furusho, Y.; Yashima, E. J. Am. Chem. Soc.
2007, 129, 109–112. (b) Zawko, S.A.; Truong, Q.; Schmidt,
C.E. J. Biomed. Mater. Res. A 2008, 87, 1044–1052. (c)
Bernet, D.B.; Isenbu¨gel, K.; Ritter, H. Macromol. Rapid
Commun. 2011, 32, 397–403.
(30) Kazemi, F.; Kiasat, A.R.; Sayyahi, S. Phosphor. Sulfur
Silicon Relat. Elem. 2004, 179, 1813–1817.
(31) (a) Hirose, K. J. Incl. Phenom. Macrocycl. Chem. 2001, 39,
193–209. (b) Fielding, L. Tetrahedron 2000, 56, 6151–
6170.
(32) Rekharsky, M.V.; Inoue, Y. Chem. Rev. 1998, 98,
1875–1917, and references therein.
(33) Carrazana, J.; Jover, A.; Meijide, F.; Soto, V.H.; Tato, J.V.
J. Phys. Chem. B 2005, 109, 9719–9726.
´
(17) (a) Kaftan, O.; Tumbiolo, S.; Dubreuil, F.; Auzely-Velty,
R.; Fery, A.; Papastavrou, G. J. Phys. Chem. B 2011, 115,
7726–7735. (b) Harada, A.; Kobayashi, R.; Takashima, Y.;
Hashidzume, A.; Yamaguchi, H. Nat. Chem. 2010, 3, 34–
37.
´
(18) (a) Karakasyan, C.; Sebille, B.; Millot, M.C. J. Chromatogr.
´
´
ˇ
(34) Vıcha, R.; Rouchal, M.; Kozubkova, Z.; Kuritka, I.; Marek,
R.; Branna, P.; Cmelık, R. Supramol. Chem. 2011, 23,
B 2006, 845, 200–204. (b) Rozou, S.; Raftopoulos, P.;
Hatziantoniou, S.; Antoniadou-Vyza, E. J. Sep. Sci. 2009,
32, 3521–3528.
ˇ
´
´
663–677.
(35) (a) Leclerq, L.; Schmitzer, A.R. J. Phys. Org. Chem. 2009,
22, 91–95. (b) Tellini, V.H.S.; Jover, A.; Galantini, L.;
Meijide, F.; Tato, J.V. Acta Crystallogr., Sect. B: Struct. Sci.
2004, 60, 204–210. (c) Taura, D.; Taniguchi, Y.;
Hashidzume, A.; Harada, A. Macromol. Rapid Commun.
2009, 30, 1741–1744. (d) Liu, H.; Zhang, Y.; Hu, J.; Li, C.;
Liu, S. Macromol. Chem. Phys. 2009, 210, 2125–2137.
(36) Martin, G.E.; Crouch, R.C. J. Nat. Prod. 1991, 54, 1–70.
(37) Kay, L.E.; Keifer, P.; Saarinen, T. J. Am. Chem. Soc. 1992,
114, 10663–10665.
(19) (a) van Bommel, K.J.C.; Metselaar, G.A.; Verboom, W.;
Reinhoudt, D.N. J. Org. Chem. 2001, 66, 5405–5412. (b)
Cromwel, W.C.; Bystrom, K.; Efting, M.R. J. Phys. Chem.
1985, 89, 326–332. (c) Prashar, D.; Shi, Y.; Bandyopad-
hyay, D.; Dabrowiak, J.C.; Luk, Y.-Y. Bioorg. Med. Chem.
Lett. 2011, 21, 7421–7425. (d) Machut-Binkowski, C.;
Hapiot, F.; Ceccelli, R.; Martin, P.; Monflier, E. J. Incl.
Phenom. Macrocycl. Chem. 2007, 57, 567–572.
ˇ
(20) (a) Otyepka, M.; Krystof, V.; Havlıcek, L.; Singlerova, V.;
Strnad, M.; Koca, J. J. Med. Chem. 2000, 43, 2506–2513.
´ˇ
´
ˇ
(38) Lo Fiego, M.J.; Lockhart, M.T.; Chopa, A.B. J. Organomet.
Chem. 2009, 694, 3674–3678.
(b) Mor, M.; Lodola, A.; Rivara, S.; Vacondio, F.; Duranti,
A.; Tontini, A.; Sanchini, S.; Piersanti, G.; Clapper, J.R.;

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M. Rouchal et al.
´ ´ ˇ
Michal Rouchal, Alena Matelova, Fabiana Pires de Carvalho, Robert Bernat, Dragan Grbic, Ivo Kuritka,
ˇ
Martin Babinsky, Radek Marek, Richard Cmelık and Robert Vıcha
´
´
´
Adamantane-bearing benzylamines and benzylamides: novel building blocks for supramolecular systems with finely tuned
binding properties towards b-cyclodextrin
1–14