Synthesis of chiral calix[4]arenes bearing aminonaphthol moieties and their use in the enantiomeric recognition of carboxylic acids

Article abstract of DOI:10.1039/c0ob00399a

Two armed chiral calix[4]arenes 8-16 functionalized at the lower rim with chiral aminonaphthol units have been prepared and the structures of these receptors characterized by FTIR, ¹H, and ¹³C, DEPT and COSY NMR spectroscopy and elem

Full text of DOI:10.1039/c0ob00399a

View Article Online / Journal Homepage / Table of Contents for this issue
Organic &
Biomolecular
Chemistry
Dynamic Article Links
Cite this: Org. Biomol. Chem., 2011, 9, 571
www.rsc.org/obc
PAPER
Synthesis of chiral calix[4]arenes bearing aminonaphthol moieties and their
use in the enantiomeric recognition of carboxylic acids†
Mustafa Durmaz, Mustafa Yilmaz and Abdulkadir Sirit*
Received 8th July 2010, Accepted 20th September 2010
DOI: 10.1039/c0ob00399a
Two armed chiral calix[4]arenes 8–16 functionalized at the lower rim with chiral aminonaphthol units
have been prepared and the structures of these receptors characterized by FTIR, 1H, and 13C, DEPT
and COSY NMR spectroscopy and elemental analysis. The enantioselective recognition of these
receptors with various carboxylic acids has been studied by 1H NMR and UV/Vis spectroscopy. The
receptors exhibited different chiral recognition abilities towards the enantiomers of racemic materials
and formed 2 : 1 or 1 : 1 complexes between host and guest. It was also demonstrated that chiral
calix[4]arenes 9 and 16 could be used as chiral NMR solvating agents to determine the enantiomeric
purity of mandelic acid.
receptors for selective recognition of ions and neutral molecules.7
Introduction
The introduction of chirality into calixarene framework by
Molecular recognition is a very important concept due to the
attaching chiral units at one of the calix rims offers the pos-
role of chirality in many biological processes.1 Because natural
sibility of studying chiral recognition phenomena in host–guest
interactions.8 Therefore our interest focused on new methods of
synthesizing enantiomerically pure calixarenes.
living systems are mostly composed of chiral biological molecules,
which exist only in one of the possible enantiomeric forms,
they interact differently with each stereoisomer of a racemic
drug, as well as metabolize each enantiomer by way of a
separate pathway to produce different pharmacological activities.
Therefore, one stereoisomer may produce the desired therapeutic
activities, while the other may be inactive or produce harmful
effects. Detailed understanding of the interactions between bio-
logical molecules will be helpful for the development of novel
enantioselective sensors, asymmetric catalysts and other molecular
devices.2
In recent years, we have reported the synthesis of novel
chiral calix[4]arenes containing various functionalities including
amides,9 Schiff bases,10 and quaternary ammonium salts11 as well
as their catalytic activities and enantiomeric recognition properties
toward chiral amines and amino acid derivatives. In the present
study, we report the synthesis of novel calix[4]arene derivatives
bearing chiral aminonaphthol moieties at the lower rim and their
recognition abilities for carboxylic acids by 1H NMR and UV-Vis
spectroscopy.
Chiral carboxylic acids and their derivatives are organic
molecules involved in a wide variety of biological processes and
also play an important role in the area of design and preparation
of pharmaceuticals, as they are part of the synthesis process in
the production of drug intermediates and protein-based drugs.3
The growing use of enantiomerically pure chiral carboxylic acids
has given rise to the need for the development of fast and
accurate methodologies for the determination of the enantiomeric
composition of chiral carboxylic acids.4
The widespread research on molecular recognition of guests
by artificial receptors has stimulated chemists to design chiral
macrocyclic ligands for chiral recognition and chiral catalysis.5,6
Calixarenes are versatile platforms in constructing supramolecular
Results and discussion
Design and synthesis of calix[4]arene based receptors
This work is mainly focused on the synthesis and application of
chiral calix[4]arene derivatives bearing aminonaphthol moieties.
For the desired goal, first, a Mannich reaction was carried out,
using a chiral or achiral amine, b-naphthol and benzaldehyde
as starting materials, to yield the aminonaphthols 1–4 (Fig. 1).
Compounds 1–3 were synthesized stereoselectively under solvent
free conditions, starting from benzaldehyde, 2-naphthol and (R)-
1-phenylethylamine or (R)-1-(2-naphthyl)-ethylamine respectively
accordingto the literatureprocedures.12 The pyrrolidinyl derivative
of racemic aminonaphthol 4 was easily prepared using ben-
Department of Chemistry, Selc¸uk University, 42099, Konya, Turkey.
E-mail: asirit42@yahoo.com; Fax: +903323238225; Tel: +903323238220/
5822
◦
zaldehyde, 2-naphthol and pyrrolidine in ethanol at 78 C.13
Racemic aminonaphthol derivative 4 was resolved using L-(+)-
tartaric acid and enriched in the (R)-(-)enantiomer (97% ee).
Then, coupling of the aminonaphthols with the corresponding
† Electronic supplementary information (ESI) available: 1H, 13C, DEPT
and COSY NMR spectra of compounds, 1H NMR and UV/Vis titration
data. See DOI: 10.1039/c0ob00399a
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 571–580 | 571
©

View Article Online
Fig. 1 Chiral aminonaphthol derivatives appended to calix[4]arene.
calix[4]arene dibromide derivatives 5–714 in DMF with anhydrous
K2CO3 at room temperature led to the formation of the chiral
calix[4]arene derivatives in moderate to good yields (Scheme 1).
The products were characterized by a combination of 1H NMR,
13C NMR, FTIR and elemental analysis.
The stereogenic centers of receptors disturb the planar sym-
metry of the parent rings, resulting in more aromatic carbon
signals in the 13C NMR spectra of the receptors. This pattern is
similar to those observed in the 13C NMR spectra of other chiral
calix[4]arenes.15 The 1H NMR spectra of chiral calix[4]arenes
exhibit two sets of doublets due to the bridging methylene
protons and two sets of singlets due to the tert-butyl groups. This
indicates that chiral p-tert-butylcalix[4]arene derivatives adopt a
cone conformation in CHCl3.
displaying any resolution (Fig. 3e–g). As a result of diastereomeric
complexation, clear signal splitting (d = 4.90 and 4.86 ppm for host
9, d = 5.01 and 4.99 ppm for host 14 and d = 4.99 and 4.96 ppm
for host 16; Fig. 3b, Fig. 3d and Fig. 3c) with an upfield shift of
the signal of the benzylic proton of racemic mandelic acid (d =
5.25 ppm; Fig. 3a) was observed. The C O stretch (1716 cm-1 for
mandelic acid) disappeared in the FTIR spectra of a 1 : 1 mixture
of 9 and mandelic acid, and the observed intensities increased
at 1624 cm-1 (the COO- stretch) which demonstrated that the
carboxyl group of the acid was ionized.
In order to investigate the role of a spacer between the basic
nitrogen atom and the calixarene backbone, we also synthesized
chiral calixarenes (8, 10 and 15) containing different methylene
spacers. Although the methine proton signals of racemic mandelic
acid split into two singlets with these hosts, the chemical shift
non-equivalencies (DDd) were lower (Table 1, entry 1, 3 and
8). From the results shown in Table 1, it can be observed
that the chiral receptors with a three-methylene spacer afforded
relatively better results than the others. In addition, different
proportions of both enantiomers of mandelic acid were treated
with 9 and 16, and different signal intensities for both (S)- and (R)-
mandelic acid were observed depending on the proportions (Fig.
4). These results clearly indicate that these chiral calix[4]arenes
could be used as chiral NMR solvating agents to determine
the enantiomeric purity of mandelic acid at appropriate tempe-
rature.
Enantiomeric recognition study of chiral calix[4]arenes for racemic
carboxylic acids by 1H NMR spectroscopy
Chiral macrocyclic compounds have been recognized as success-
ful and promising chiral receptors for molecular recognition,
mainly due to their inherent reduced flexibility and complexation
ability.16 With the optically pure calix[4]arene derivatives bearing
aminonaphthol moieties in hand, we then studied the chiral
recognition ability of these receptors toward racemic carboxylic
acids, mandelic acid, o-chloro mandelic acid, dibenzoyl tartaric
acid, hydroxyisovaleric acid and 2-chloropropionic acid (a–e)
shown in Fig. 2. Because the signals of the methine or methyl
hydrogens of all these guests do not overlap with the peaks of the
other proton signals in their 1H NMR spectra after they interact
with the host molecules, they are ideal probes for the present study.
Furthermore, 1H NMR titration studies of the chiral
calix[4]arenes 9 and 16 with different molar ratios of (R)- or (S)-
mandelic acid were examined (Fig. 5). Even in the presence of a
less than stoichiometric amount of 16, different chemical shifts of
the benzylic proton of (R)- and (S)-mandelic acid were observed.
Interestingly, the degree of signal separation of both guests did not
depend on the molar ratio of chiral calix[4]arene/guest, although
many chiral solvating agents depend greatly on the molar ratio of
the chiral agent.
1
Preliminary H NMR studies of the chiral calix[4]arenes were
performed with equimolar amounts of racemic mandelic acid.17,18
When the solution of racemic mandelic acid (10 mM in CDCl3)
was gradually added to the 10 mM solution of hosts 11–13 in
CDCl3, the CH proton signal of guest a moved to upfield without
Fig. 2 Chemical structures of the guests employed.
This journal is
572 | Org. Biomol. Chem., 2011, 9, 571–580
The Royal Society of Chemistry 2011
©

View Article Online
Scheme 1 Reagents and conditions: (i)–(iv) Appropriate chiral aminonaphthol 1–4, K2CO3, DMF, rt.
Also the magnitude of the upfield shifts of the signals of the ben-
zylic proton gradually increased with an increase in the molar ratio
of calixarenes. However, the addition of more than two equimolar
amount of compounds 9 and 16 showed no further change in the
chemical shifts of the mandelic acids. These results indicate that
chiral calix[4]arenes 9 and 16 and mandelic acid form a 2 : 1 com-
plex (see Supplementary Information for the Job plot analysis†).
Also the stoichiometry of the complexes between the receptors
and the guest c (rac-dibenzoyltartaric acid) was determined by a
continuous variation plot. The total concentration of the hosts
and the guest was kept constant (10 mM) in CDCl3, whilst the
molar fraction of the guest {[G]/([H]+[G])} was continuously
varied. The Job plots of 16 with (L)- and (D)-dibenzoyltartaric
acid are illustrated in Fig. 6. A minimum of DdX at X = 0.5 was
observed when the molar ratio of the compound 16 and (L)- or
(D)-dibenzoyltartaric acid was 1 : 1, which indicated that host 16
and the guest formed 1 : 1 instantaneous complexes. It is apparent
that the chemical shift changes of (L)-dibenzoyltartaric acid were
greater than that of the corresponding (D)-dibenzoyltartaric acid
in the presence of compound 16.
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 571–580 | 573
©

View Article Online
Table 1 Chemical shift changes (Dd) and non-equivalencies (DDd) of the
methine proton of guest a in the presence of chiral hosts by 1H NMR
spectroscopy (400 MHz) in CDCl3 at 25 ◦
C
Entry Host Guest Ratio Dd (ppm) DDd (ppm) Enantiomera
1
2
3
4
5
6
7
8
9
8
a
a
a
a
a
a
a
a
a
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
—
—
—
0.308
0.212
0.177
—
—
—
0.012
0.042
0.003
—
—
—
0.020
0.025
0.030
(S)
(S)
(S)
—
—
—
(S)
(S)
(S)
9
10
11
12
13
14
15
16
a Enantiomer showing higher upfield shift.
Fig. 4 1H NMR spectra of different enantiomeric ratios of mandelic acid
in the presence of 9 in CDCl3 at 25 ◦C [mandelic acid/9 = 1 : 1].
Fig. 3 1H NMR spectra of racemic mandelic acid in the absence and
presence of chiral hosts in CDCl3 at 25 ◦C [mandelic acid/host = 1 : 1].
Fig. 5 1H NMR titration curves of compound 16 with (R)- and
(S)-mandelic acids.
Next, we examined the relationship between the absolute
configuration and the upfield shift of the proton signals of the
carboxylic acids in the presence of hosts. For all the tested
compounds, the signals of the (S)-enantiomer appeared at a higher
magnetic field than that of the (R)-enantiomer in the presence of
hosts (Table 1).
A variety of racemic carboxylic acids (Fig. 1, (b–e)) were chosen
as guests to screen the potential of 9, 14 and 16 as chiral shift
reagents by using 1H NMR spectroscopy. Table 2 shows chemical
shift non-equivalencies (DDd) of the guests in the presence of chiral
hosts. Generally for the carboxylic acids tested b–d, the signals for
the protons attached to the stereogenic center were split. While the
methyl proton signal of e was efficiently split into two doublets with
chiral host 16, the CH proton signal was split into two quartets
with chiral hosts 9 and 14.
The formation of diastereomeric host–guest complexes possibly
occurs through interaction of the basic nitrogen atom in chiral
receptors and the carboxyl group in the chiral carboxylic acid.
The protonated amine groups would lead to the formation of the
corresponding diastereomeric salt with chiral carboxylic acids.
Though the number of recognition sites that are necessary for
producing chiral recognition is due to the shape of the receptor,
574 | Org. Biomol. Chem., 2011, 9, 571–580
This journal is
The Royal Society of Chemistry 2011
©

View Article Online
Table 2 Chemical shift non-equivalencies (DDd) of the methine and a-methyl protons of guests in the presence of chiral hosts by 1H NMR spectroscopy
(400 MHz) in CDCl3 at 25 ◦
C
Acid
Proton spectra
Compound 9 spectra
Compound 14 spectra
Compound 16 spectra
b
a-H
c
a-H
a-H
d
e
a-H or CH3
minimum of three of the possible recognition groups (phenoxy
oxygen, amine nitrogen, phenyl groups and hydroxy groups) in
order to exhibit enantioselective binding to the chiral carboxylic
acids. Among the guest molecules, mandelic acid derivatives
contain a hydroxy group at the a-position of the carbonyl group.
This oxygen function may act as an additional binding site and play
a crucial role for chiral recognition. Since the methine protons are
adjacent to the hydroxy group, these protons must be significantly
influenced by the possible recognition groups of the chiral hosts.
UV spectral titrations
UV-Vis spectroscopic method is a convenient and widely used
method for the study of binding phenomena.20 When the re-
ceptors absorb light at different wavelengths in the free and
complexed states, the differences in the UV-Vis spectra may suffice
for the estimation of molecular and enantiomeric recognition
thermodynamics. In order to obtain the association constants
(K) and the thermodynamic quantities (DH and DS) for the
stoichiometric 1 : 1 inclusion complexation of 9 and 16 with
(D)- or (L)-dibenzoyltartaric acid, spectrophotometric titrations
Fig. 6 Job plots of 16 with (L)- and (D)-dibenzoyltartaric acid [X =
molar fraction of dibenzoyltartaric acid, Dd = chemical shift change of
the methine proton of (L)- and (D)-dibenzoyltartaric acid]. (ꢀ) With pure
(L)- dibenzoyltartaric acid, (ꢀ) with pure (D)-dibenzoyltartaric acid.
three ordinary recognition sites are required in the receptor
molecules.19 In this study, chiral calix[4]arenes interact with a
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 571–580 | 575
©

View Article Online
have been performed in CHCl3 at 25–35 ◦C. Upon addition of
(L)-dibenzoyltartaric acid to t◦he CHCl3 solution containing chiral
receptor 9 (1.0 ¥ 10-5 M, 25 C), the absorbance of 9 at 241 nm
decreased and the one at 285 nm increased, with an isosbestic
point at 248 nm (Fig. 7). A similar spectral change was observed
when the other receptor was used as host and was believed to be
due to hydrogen bonding and p–p stacking.
The free-energy change (DG) for inclusion complexes formed
by chiral calix[4]arene derivatives and guest carboxylic acid is
calculated from the equilibrium constant K by eqn (3):
(3)
DG = -RT ln K
and is related to the enthalpic and entropic changes (DH and DS)
through the Gibbs–Helmholtz equation [eqn (4)]. Combining eqn
(3) and (4), we obtain eqn (5) which describes the temperature
dependence of K. Thus, plots of the ln K values as a function of
the inverse of temperature gave good linear relationships for the
working temperature range (Fig. 9).
(4)
(5)
DG = DH -TDS
ln K = -DH/RT + DS/R
Fig. 7 UV/Vis spectra of chiral calix[4]arene 9 (1.00 ¥ 10-5 M) in the
presence of (L)-dibenzoyltartaric acid (0.10–3.00 ¥ 10-4 M) in CHCl3.
The complexation of carboxylic acid derivative (G) with chiral
calix[4]arene (H) is expressed by eqn (1):
K
ꢂꢀ
(1)
ꢀꢀꢀꢁ
H+G
H⋅G
Fig. 9 The plot of ln K versus 1/T for the host–guest complexation of 9
and (L)-DBTA in CHCl3 at 25 ◦C.
Under the conditions employed, the concentration of
calix[4]arene derivatives (1.00 ¥ 10-5 M) is much smaller than
that of guest, i.e. [H]0 ꢀ [G]0. Therefore, the stability constant of
the supramolecular system formed can be calculated according to
the modified Hildebrand–Benesi equation,21 eqn (2), where [G]0
denotes the total concentration of carboxylic acid, [H]0 refers
to the total concentration of calix[4]arene derivative, De is the
difference between the molar extinction coefficient for the free and
complexed calix[4]arene derivative, DA denotes the changes in the
absorption of the modified calix[4]arene on adding carboxylic acid
derivative.
The association constants (K), the free-energy change (-DG0)
calculated from the slope and the intercept, and the thermo-
dynamic parameters are summarized in Table 3, along with
the enantioselectivity KL/KD for the complexation of D/L-
dibenzoyltartaric acid by these hosts.
UV-Vis spectroscopic studies indicate that chiral receptors 9
and 16 show strong binding and good recognition ability for the
enantiomers of dibenzoyltartaric acid. This is presumably due to
multiple hydrogen bonding and p–p stacking interactions between
the receptor and the aromatic side chain of the guest. From the
data shown in Table 3, all hosts have greater K values toward the
(L)-enantiomer of dibenzoyltartaric acid than the (D)-enantiomer,
which is probably due to the more complementary structure of the
(L)-enantiomer with receptors. Table 3 also shows the enantiomeric
discrimination of the guest c, characterized by the value of KL/KD,
which are 2.27 and 1.40 for chiral calix[4]arene receptors 9 and 16.
It was found that chiral calix[4]arene 9 containing a secondary
amine moiety and an extra aromatic ring gave stronger binding
and better recognition ability for the guest when compared with
receptor 16. As can be recognized readily from Table 3, all the
values of the enthalpy changes (DH◦) and the entropy changes
(DS◦) of the resulting complexes are positive. These results indicate
that the complexation of chiral calix[4]arenes (9 and 16) with D/L-
dibenzoyltartaric acid is driven predominantly by the favorable
entropic change, typically showing large positive entropy changes
(DS◦ = 341.68–377.81 J mol-1) and somewhat smaller positive
enthalpy changes (DH◦ = 83.80–94.87 kJ mol-1). One possible
explanation for the complexation of the large entropy driving force
1/DA = 1/KDe[H]0[G]0 + 1/De[H]0
(2)
For all guest molecules examined, plots of calculated 1/DA
values as a function of 1/[G]0 values give good straight lines,
supporting the 1 : 1 complex formation. Typical plots are shown
for the complexation of compound 9 with (L)-DBTA in Fig. 8.
Fig. 8 Typical Benesi–Hildebrand plot of 1/DA versus 1/[G]0.
576 | Org. Biomol. Chem., 2011, 9, 571–580
This journal is
The Royal Society of Chemistry 2011
©

View Article Online
Table 3 Binding constants (K), enantioselectivities (KL/KD) and thermodynamic parameters for the complexation of (L)- and (D)-dibenzoyltartaric acid
with the chiral hosts 9 and 16 in CHCl3 at 25 ◦
C
Entry
Host
Guest
K¥103/M-1
KL/KD
2.27
-DG/kJ mol-1
-DDGa
1.87
DH/kJ mol-1
DDHb
2.09
DS/J mol-1
DDSc
13.32
21.78
1
2
3
4
9
9
16
16
(D)-DBTA
(L)- DBTA
(D)-DBTA
(L)- DBTA
1.41 0.03
3.20 0.06
0.91 0.02
1.27 0.05
18.03 0.18
19.90 0.22
17.00 0.26
17.72 0.34
83.80 0.92
85.89 1.35
89.10 0.75
94.87 1.43
341.68 6.07
355.00 7.68
356.03 5.42
377.81 8.17
1.40
0.72
5.77
a DDG = DGL - DGD. b DDH = DHL - DHD. c DDS = DSL - DSD.
is that both dissociated guest and free calix[4]arene derivatives are
heavily solvated by hydrogen-bonding interactions.
was dried over MgSO4, filtered, evaporated and purified by flash
chromatography.
25,27-Bis[(1-((R)-phenyl{[(1¢R)-1¢-phenylethyl]amino}-methyl)-
naphthalen-2-yloxy)ethoxy]-26,28-dihydroxy-5,11,17,23-tetra-
(tert-butyl)calix[4]arene (8). The crude product was purified by
Conclusions
In this study, novel chiral calix[4]arenes bearing aminonaphthol
moieties were developed for the recognition of various chiral
carboxylic acids. The chiral calix[4]arenes 9 and 16 could be used
as chiral NMR solvating agents to determine the enantiomeric
purity of mandelic acid at ambient temperature. Further studies
of the chiral calix[4]arenes to allow asymmetric catalysis are now
in progress in our laboratory.
flash chromatography on silica gel (EtOAc/Hexane 1 : 25) to
◦
afford 8 as a white solid. Yield 45%; Mp 142–144 C; [a]D25
=
+28.0 (c 1, CHCl3). IR (KBr): 3353, 2957, 1622, 1235, 1028, 749,
700 cm-1; 1H-NMR (400 MHz, CDCl3): d (ppm) 7.73 (d, 2H, J =
7.4 Hz, ArH), 7.66 (d, 4H, J = 9.0 Hz, ArH), 7.43 (d, 4H, J =
7.5 Hz, ArH), 7.37–7.29 (m, 10H, ArH + ArOH), 7.26–7.16 (m,
6H, ArH), 7.14–7.03 (m, 12H, ArH), 6.81–6.77 (m, 4H, ArH),
5.62 (bs, 2H, NHCH), 4.67–4.57 (m, 2H, CHCH3), 4.31 (d, 2H,
J = 13.1 Hz, ArCH2Ar), 4.23 (d, 2H, J = 12.9 Hz, ArCH2Ar), 3.88–
3.58 (m, 8H, OCH2CH2O) 3.25 (d, 4H, J = 12.9 Hz, ArCH2Ar),
2.85–2.60 (br, 2H, NH), 1.31 (s, 18H, C(CH3)3), 1.13 (d, 6H, J =
6.1 Hz, CHCH3), 0.91 (s, 18H, C(CH3)3); 13C-NMR (100 MHz,
CDCl3): d (ppm): 155.1, 150.7, 150.1, 147.1, 146.7, 141.7, 132.8,
132.5, 129.8, 129.5, 128.9, 128.5, 128.3, 128.0, 127.9, 127.3, 126.8,
126.7, 125.9, 125.6, 125.4, 125.3, 124.1, 89.5, 74.2, 69.1, 58.7, 55.8,
54.9, 34.2, 34.1, 32.1, 32.0, 31.8, 31.3, 26.2, 22.9, 14.4. Anal. Calcd
for C98H106N2O6 (1407.90): C, 83.60, H, 7.59, N, 1.99%. Found: C,
83.84; H, 7.36; N, 1.72%.
Experimental
General
Melting points were determined on an Electrothermal 9100
apparatus in a sealed capillary and are uncorrected. H and 13C
1
NMR spectra were recorded at room temperature on a Varian
400 MHz spectrometer in CDCl3. IR spectra were obtained on
a Perkin Elmer Spectrum 100 FTIR spectrometer using KBr
pellets. UV/Vis spectra were measured with a Perkin Elmer
Lambda 25 spectrometer. Optical rotations were measured on an
Atago AP-100 digital polarimeter. The HPLC measurements were
carried out on Agilent 1100 equipment connected with a Zorbax
RX-C18 column. Elemental analyses were performed using a
Leco CHNS-932 analyzer. Analytical TLC was performed using
Merck prepared plates (silica gel 60 F254 on aluminium). Flash
chromatography separations were performed on a Merck Silica
Gel 60 (230–400 Mesh). All reactions, unless otherwise noted, were
conducted under a nitrogen atmosphere. All starting materials and
reagents used wereof standard analyticalgrade fromFluka, Merck
and Aldrich and used without further purification. Toluene was
distilled from CaH2 and stored over sodium wire. Other commer-
cial grade solvents were distilled, and then stored over molecular
sieves. The drying agent employed was anhydrous MgSO4.
25,27-Bis[(1-((R)-phenyl{[(1¢R)-1¢-phenylethyl]amino}-methyl)-
naphthalen-2-yloxy)propoxy]-26,28-dihydroxy-5,11,17,23-tetra-
(tert-butyl)calix[4]arene (9). The crude product was purified by
flash chromatography on silica gel (EtOAc/Hexane 1 : 20) to
afford compound 9 as a white solid. Yield 70%; Mp 132–135 ◦C;
[a]2D5 = +25.0 (c 2, CHCl3). IR (KBr): 3340, 2956, 1623, 1238, 1068,
1
749, 699 cm-1; H NMR (400 MHz, CDCl3): d (ppm) 7.67–7.65
(m, 2H, ArH), 7.60 (s, 2H, ArOH), 7.56 (d, 4H, J = 9.0 Hz, ArH),
7.30 (d, 4H, J = 7.5 Hz, ArH), 7.24–7.19 (m, 8H, ArH), 7.17–7.13
(m, 6H, ArH), 7.10 (d, 2H, J = 7.0 Hz, ArH), 7.07–6.96 (m, 8H,
ArH), 6.93–6.87 (m, 2H, ArH), 6.79–6.77 (m, 4H, ArH), 5.52
(bs, 2H, NHCH), 4.31 (q, 2H, J = 6.6 Hz, CHCH3), 4.17 (d, 2H,
J = 12.7 Hz, ArCH2Ar), 4.06 (d, 2H, J = 12.9 Hz, ArCH2Ar),
3.82 (b, 2H, OCH2), 3.75–3.69 (m, 2H, OCH2), 3.60–3.58 (m, 2H,
OCH2), 3.49 (q, 2H, J = 6.5 Hz, OCH2), 3.20 (d, 4H, J = 12.9 Hz,
ArCH2Ar), 1.99–1.92 (m, 2H, OCH2CH2CH2O), 1.83–1.77 (m,
2H, OCH2CH2CH2O), 1.21 (s, 18H, C(CH3)3), 1.10 (d, 6H, J =
6.5 Hz, CHCH3), 0.95 (s, 18H, C(CH3)3); 13C NMR (100 MHz,
CDCl3): d (ppm): 153.8, 149.6, 148.5, 146.0, 145.2, 144.3, 140.5,
131.8, 131.6, 128.2, 127.6, 127.2, 126.8, 126.7, 126.6, 126.1, 125.7,
125.5, 125.3, 124.7, 124.6, 122.4, 71.6, 64.8, 54.6, 33.0, 32.8, 30.9,
30.8, 30.7, 30.1, 29.0, 25.0. Anal. Calcd for C100H110N2O6 (1435.95):
C, 83.64, H, 7.72, N, 1.95%. Found: C, 83.80; H, 7.50; N, 1.82%.
Syntheses
General procedure for the synthesis of compounds 8–16. Com-
pounds 8–16 were synthesized using a modified procedure origi-
nally reported by Zhang et al.22 To a suspension of appropriate
aminonaphthol (1 mmol) and K2CO3 1.38 g (10 mmol) in dry
DMF (15 mL) was added a solution of p-t-butylcalix[4]arene
dibromide derivatives (0.5 mmol) in dry DMF (15 mL) dropwise.
The mixture was stirred at room temperature for 48 h. Then it was
poured into 50 mL water and extracted with toluene (10 mL ¥ 3),
washed with water (10 mL) and brine (10 mL). The organic phase
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 571–580 | 577
©

View Article Online
CHCH3), 3.39 (d, 2H, J = 12.9 Hz, ArCH2Ar), 3.32 (d, 2H, J =
13.1 Hz, ArCH2Ar), 2.37–2.29 (m, 4H, OCH2CH2CH2O), 2.00
(s, 6H, NCH3), 1.36 (d, 6H, J = 6.6 Hz, CHCH3), 1.31 (s, 18H,
C(CH3)3), 1.07 (s, 18H, C(CH3)3); 13C NMR (100 MHz, CDCl3):
d (ppm): 154.1, 151.0, 150.0, 147.4, 143.7, 142.2, 141.9, 133.4,
133.1, 133.0, 129.6, 129.4, 128.6, 128.5, 128.2, 128.1, 127.9, 126.7,
126.4, 125.9, 125.5, 123.4, 123.3, 114.1, 97.0, 73.6, 65.8, 64.4, 57.0,
34.3, 34.1, 33.8, 32.3, 32.2, 31.9, 31.3, 30.7, 14.3. Anal. Calcd for
C102H114N2O6 (1464.00): C, 83.68, H, 7.85, N, 1.91%. Found: C,
83.92; H, 7.46; N, 1.83%.
25,27-Bis[(1-((R)-phenyl{[(1¢R)-1¢-phenylethyl]amino}-methyl)-
naphthalen-2-yloxy)butoxy]-26,28-dihydroxy-5,11,17,23-tetra-
(tert-butyl)calix[4]arene (10). The crude product was purified
by flash chromatography on silica gel (EtOAc/Hexane 1 : 15) to
afford compound 10 as a white solid. Yield 54%; Mp 128–131 ◦C;
[a]2D5 = +22.0 (c 1.4, CHCl3). IR (KBr): 3360, 2953, 1623, 1239,
1028, 753, 700 cm-1; 1H NMR (400 MHz, CDCl3): d (ppm) 7.78 (d,
2H, J = 9.1 Hz, ArH), 7.63 (d, 4H, J = 9.1 Hz, ArH), 7.45–7.43 (m,
6H, ArH), 7.36–7.06 (m, 26H, ArH + ArOH), 6.84 (s, 4H, ArH),
5.64 (s, 2H, NCH), 4.28 (d, 2H, J = 13.1 Hz, ArCH2Ar), 4.26 (d,
2H, J = 13.0 Hz, ArCH2Ar), 4.17–4.12 (m, 2H, OCH2), 3.87–3.80
(m, 6H, OCH2(CH2)2CH2O), 3.62 (q, 2H, J = 6.5 Hz, CHCH3),
3.36 (d, 2H, J = 13.0 Hz, ArCH2Ar), 3.35 (d, 2H, J = 13.0 Hz,
ArCH2Ar), 1.89–1.84 (m, 4H, OCH2(CH2)2CH2O), 1.83–1.73 (m,
4H, OCH2(CH2)2CH2O), 1.34 (s, 18H, C(CH3)3), 1.23 (d, 6H, J =
6.6 Hz, CHCH3), 1.00 (s, 18H, C(CH3)3); 13C NMR (100 MHz,
CDCl3): d (ppm): 155.1, 151.0, 150.1, 147.1, 146.6, 145.6, 141.7,
132.8, 129.4, 128.9, 128.5, 128.0, 127.4, 127.0, 126.9, 126.6, 126.0,
125.7, 125.6, 125.3, 123.6, 114.9, 55.9, 34.2, 34.1, 32.0, 31.3, 26.7,
26.4, 26.3. Anal. Calcd for C102H114N2O6 (1464.00): C, 83.68, H,
7.85, N, 1.91%. Found: C, 83.86; H, 7.62; N, 1.80%.
25,27-Bis[(1-((R)-phenyl{methyl[(1¢R)-1¢-phenylethyl]amino}-
methyl)naphthalen-2-yloxy)butoxy]-26,28-dihydroxy-5,11,17,23-
tetra(tert-butyl)calix[4]arene (13). The crude product was puri-
fied by flash chromatography on silica gel (EtOAc/Hexane 1 : 15)
to afford compound 13 as a white solid. Yield 48%; Mp 130–
◦
134 C; [a]2D5 = -14.0 (c 2, CHCl3). IR (KBr): 3335, 2954, 1624,
1238, 746, 699 cm-1; 1H NMR (400 MHz, CDCl3): d (ppm) 9.45
(d, 2H, J = 9.6 Hz, ArH), 7.58–6.74 (m, 40H, ArH + ArOH), 5.80
(s, 2H, NCH), 4.29 (d, 2H, J = 12.9 Hz, ArCH2Ar), 4.27 (d, 2H,
J = 12.9 Hz, ArCH2Ar), 4.19–4.06 (m, 6H, OCH2 + CHCH3),
4.00 (br s, 4H, OCH2(CH2)2CH2O), 3.29 (d, 2H, J = 12.9 Hz,
ArCH2Ar), 3.28 (d, 2H, J = 13.1 Hz, ArCH2Ar), 2.17 (br s, 8H,
OCH2(CH2)2CH2O), 1.91 (s, 6H, NCH3), 1.28 (d, 6H, J = 6.8 Hz,
CHCH3), 1.23 (s, 18H, C(CH3)3), 0.91 (s, 18H, C(CH3)3); 13C
NMR (100 MHz, CDCl3): d (ppm): 154.3, 151.0, 150.1, 147.2,
143.7, 142.7, 141.8, 133.4, 132.9, 129.7, 129.5, 128.6, 128.5, 128.4,
128.2, 128.0, 126.8, 126.6, 126.4, 126.0, 125.8, 125.4, 123.9, 114.4,
69.0, 64.1, 56.9, 34.2, 34.1, 33.7, 32.1, 32.0, 31.3, 27.3, 27.0, 13.5.
Anal. Calcd for C104H118N2O6 (1492.06): C, 83.72, H, 7.97, N,
1.88%. Found: C, 83.91; H, 7.84; N, 1.76%.
25,27-Bis[(1-((R)-phenyl{methyl[(1¢R)-1¢-phenylethyl]amino}-
methyl)naphthalen-2-yloxy)ethoxy]-26,28-dihydroxy-5,11,17,23-
tetra(tert-butyl)calix[4]arene (11). The crude product was puri-
fied by flash chromatography on silica gel (EtOAc/Hexane 1 : 25)
to a◦fford compound 11 as a white solid. Yield 40%; Mp 123–
126 C; [a]2D5 = –19.0 (c 0.5, CHCl3). IR (KBr): 3385, 2954, 1623,
1263, 746, 699 cm-1; 1H NMR (400 MHz, CDCl3): d (ppm) 9.55
(d, 2H, J = 8.8 Hz, ArH), 7.69 (d, 4H, J = 7.2 Hz, ArH), 7.56–
7.54 (m, 2H, ArH), 7.51–7.43 (m, 4H, ArH), 7.36–7.24 (m, 10H,
ArH), 7.23–7.16 (m, 6H, ArH+ ArOH), 7.13–7.06 (m, 8H, ArH),
7.00–6.96 (m, 2H, ArH), 6.87–6.85 (m, 4H, ArH), 5.90 (s, 2H,
NCH), 4.67–4.62 (m, 2H, OCH2), 4.50 (d, 2H, J = 12.9 Hz,
ArCH2Ar), 4.47 (d, 2H, J = 13.1 Hz, ArCH2Ar), 4.45–4.38 (m,
6H, OCH2CH2O), 4.21 (q, 2H, J = 6.8 Hz, CHCH3), 3.41 (d, 2H,
J = 13.1 Hz, ArCH2Ar), 3.38 (d, 2H, J = 13.1 Hz, ArCH2Ar), 2.03
(s, 6H, NCH3), 1.35 (d, 6H, J = 6.9 Hz, CHCH3), 1.33 (s, 18H,
C(CH3)3), 1.00 (s, 18H, C(CH3)3); 13C NMR (100 MHz, CDCl3): d
(ppm): 154.1, 150.8, 150.1, 147.4, 143.6, 142.9, 141.8, 133.4, 132.8,
132.7, 130.1, 129.6, 128.6, 128.4, 128.2, 128.0, 127.9, 126.9, 126.7,
126.4, 126.1, 126.0, 125.9, 125.5, 124.7, 123.8, 115.0, 74.7, 68.3,
64.3, 57.0, 34.2, 34.1, 33.8, 32.1, 31.9, 31.3, 13.8. Anal. Calcd for
C100H110N2O6 (1435.95): C, 83.64, H, 7.72, N, 1.95%. Found: C,
83.86; H, 7.38; N, 1.81%.
25,27-Bis[(1-((R)-phenyl{[(1¢R)-1¢-naphthylethyl]amino}-methyl)-
naphthalen-2-yloxy)propoxy]-26,28-dihydroxy-5,11,17,23-tetra-
(tert-butyl)calix[4]arene (14). The crude product was purified
by flash chromatography on silica gel (EtOAc/Hexane 1 : 15) to
afford compound 14 as a white solid. Yield 73%; Mp 144–146 ◦C;
[a]2D5 = -12.6 (c 2, CHCl3). IR (KBr): 3346, 2955, 1621, 1237, 777,
1
699 cm-1; H NMR (400 MHz, CDCl3): d (ppm) 8.01–7.65 (m,
16H, ArH), 7.54–7.45 (m, 6H, ArH), 7.37 (t, 2H, J = 7.2 Hz,
ArH), 7.30–7.09 (m, 18H, ArH + ArOH), 6.92 (s, 4H, ArH), 5.83
(br s, 2H, NHCH), 4.49 (q, 2H, J = 6.2 Hz, CHCH3), 4.40 (br,
2H, ArCH2Ar), 4.24 (br, 4H, OCH2), 4.12 (d, 2H, J = 12.7 Hz,
ArCH2Ar), 3.67 (br, 2H, OCH2), 3.47 (br, 2H, OCH2), 3.34 (d,
4H, J = 12.9 Hz, ArCH2Ar), 1.90–1.64 (m, 2H, OCH2CH2CH2O),
1.62–1.44 (m, 2H, OCH2CH2CH2O), 1.38 (br s, 24H, CHCH3 +
C(CH3)3), 1.14 (s, 18H, C(CH3)3); 13C NMR (100 MHz, CDCl3):
d (ppm): 155.2, 150.8, 150.0, 149.7, 147.4, 145.6, 141.9, 134.2,
133.1, 133.0, 131.8, 129.6, 128.9, 128.2, 128.1, 127.9, 127.2, 126.8,
126.5, 126.2, 126.0, 125.8, 125.7, 125.5, 125.4, 125.3, 123.5, 72.7,
65.7, 54.6, 34.3, 34.1, 32.1, 32.0, 31.4, 29.9, 25.3. Anal. Calcd for
C108H114N2O6 (1536.07): C, 84.45, H, 7.48, N, 1.82%. Found: C,
84.90; H, 7.28; N, 1.95%.
25,27-Bis[(1-((R)-phenyl{methyl[(1¢R)-1¢-phenylethyl]amino}-
methyl)naphthalen-2-yloxy)propoxy]-26,28-dihydroxy-5,11,17,23-
tetra(tert-butyl)calix[4]arene (12). The crude product was puri-
fied by flash chromatography on silica gel (EtOAc/Hexane 1 : 20)
to afford compound 12 as a white solid. Yield 58%; Mp 182–
◦
184 C; [a]2D5 = -21.0 (c 1, CHCl3). IR (KBr): 3320, 2959, 1623,
1266, 1238, 740, 699 cm-1; 1H NMR (400 MHz, CDCl3): d (ppm)
9.60 (d, 2H, J = 8.8 Hz, ArH), 7.96 (s, 2H, ArH), 7.64 (d, 4H, J =
7.8 Hz, ArH), 7.55–7.43 (m, 6H, ArH), 7.33–7.22 (m, 10H, ArH
+ ArOH), 7.16–6.93 (m, 18H, ArH), 5.77 (s, 2H, NCH), 4.40 (d,
2H, J = 12.9 Hz, ArCH2Ar), 4.32 (d, 2H, J = 13.1 Hz, ArCH2Ar),
4.20–4.10 (m, 8H, OCH2CH2CH2O), 4.00 (q, 2H, J = 6.6 Hz,
25,27-Bis[(1-((R)-(a-pyrrolidinylbenzyl))naphthalen-2-yloxy)-
ethoxy]-26,28-dihydroxy-5,11,17,23-tetra(tert-butyl)-calix[4]arene
(15). The crude product was purified by flash chromatography
on silica gel (EtOAc/Hexane 1 : 15) to afford compound 15 as
◦
a white solid. Yield 42%; Mp 157–159 C; [a]2D5 = -64.0 (c 0.5,
578 | Org. Biomol. Chem., 2011, 9, 571–580
This journal is
The Royal Society of Chemistry 2011
©

View Article Online
CHCl3). IR (KBr): 3374, 2956, 1624, 1233, 1084, 748, 700 cm-1;
1H NMR (400 MHz, CDCl3): d (ppm) 9.46 (d, 2H, J = 8.8 Hz,
ArH), 7.66 (d, 6H, J = 7.8 Hz, ArH), 7.58 (d, 2H, J = 9.0 Hz,
ArH), 7.44–7.41 (m, 4H, ArH + ArOH), 7.31–7.27 (m, 2H,
ArH), 7.20–7.01 (m, 12H, ArH), 6.87 (s, 4H, ArH), 5.69 (s,
2H, NCH), 4.62–4.61 (m, 4H, ArCH2Ar), 4.57–4.42 (m, 8H,
OCH2CH2O), 3.43 (d, 2H, J = 13.1 Hz, ArCH2Ar), 3.32 (d, 2H,
J = 12.5 Hz, ArCH2Ar), 2.58–2.56 (m, 4H, NCH2), 2.30–2.26 (m,
4H, NCH2), 1.54 (br, 8H, CH2), 1.30 (s, 18H, C(CH3)3), 1.00 (s,
18H, C(CH3)3); 13C NMR (100 MHz, CDCl3): d (ppm): 153.4,
150.9, 150.0, 147.3, 144.4, 141.6, 133.3, 133.1, 132.7, 129.9, 129.3,
128.3, 128.2, 128.0, 127.6, 127.0, 126.2, 126.0, 125.7, 125.6, 125.4,
125.3, 123.7, 114.2, 74.9, 68.3, 66.6, 53.6, 34.2, 34.0, 32.5, 32.0,
31.8, 31.3, 23.8, 23.6. Anal. Calcd for C90H102N2O6 (1307.78): C,
82.66, H, 7.86, N, 2.14%. Found: C, 82.94; H, 7.68; N, 2.01%.
Evaluation of the stoichiometric ratio of the host–guest complex
(Job plots)
The stoichiometry of the complex between chiral hosts and
enantiomers of carboxylic acids was determined by a continuous-
variation plot (Job plot).23 Equimolar amounts of host and
guest compounds were dissolved in CDCl3. These solutions were
distributed among nine NMR tubes, with the molar fractions X of
host and guest in the resulting solutions increasing (or decreased)
from 0.1 to 0.9 (and vice versa). The complexation induced shifts
(Dd) were multiplied by X and plotted against X itself.
Acknowledgements
This work was supported by the Scientific and Technical Re-
search Council of Turkey (TUBITAK–109T167) and Research
Foundation of Selc¸uk University (BAP–10101005). The provision
of PhD studentship to M.D. by TUBITAK-BIDEB is gratefully
acknowledged.
25,27-Bis[(1-((R)-(a-pyrrolidinylbenzyl))naphthalen-2-yloxy)-
propoxy]-26,28-dihydroxy-5,11,17,23-tetra(tert-butyl)-calix[4]-
arene (16). The crude product was purified by flash chromatog-
raphy on silica gel (EtOAc/Hexane 1 : 15) to afford compound
◦
16 as white crystals. Yield 60%; Mp 140–142 C; [a]2D5 = -30.0 (c
Notes and references
1, CHCl3). IR (KBr): 3353, 2955, 2867, 1622, 1596, 1484, 1235,
748, 699 cm-1; 1H NMR (400 MHz, CDCl3): d (ppm) 9.40 (d, 2H,
J = 8.8 Hz, ArH), 8.00 (s, 2H, ArOH), 7.68–7.43 (m, 12H, ArH),
7.28–6.89 (m, 16H, ArH), 5.60 (s, 2H, NCH), 4.45–4.40 (m, 6H,
ArCH2Ar + OCH2), 4.33–4.22 (m, 6H, OCH2), 3.42 (dd, 4H, J1
and J2 = 12.9 Hz, ArCH2Ar), 2.63–2.61 (m, 4H, NCH2), 2.47 (p,
4H, J = 6.0 Hz, OCH2CH2CH2O), 2.40–2.37 (m, 4H, NCH2), 1.72
1 (a) A. H. Beckett, Biochem. Soc. Trans., 1991, 19, 443–446; (b) F. Hof,
S. L. Craig, C. Nuckolls and J. Jr,. Rebek, Angew. Chem., Int. Ed., 2002,
41, 1488–1508; (c) G. A. Hembury, V. V. Borovkov and Y. Inoue, Chem.
Rev., 2008, 108, 1–73.
2 (a) Y. Kubo, S. Maeda, T. Sumio and M. Kubo, Nature, 1996, 382,
522–524; (b) J. K. M. Sanders, Chem.–Eur. J., 1998, 4, 1378–1383;
(c) Y. Murakami, J. Kikuchi, Y. Hisaeda and O. Hayashida, Chem.
Rev., 1996, 96, 721–758; (d) W. L. Wong, K. H. Huang, P. F. Teng, C. S.
Lee and H. L. Kwong, Chem. Commun., 2004, 384–385; (e) K. Jennings
and D. Diamond, Analyst, 2001, 126, 1063–1067; (f) E. A. Meyer, R. K.
Castellano and F. Diederich, Angew. Chem., Int. Ed., 2003, 42, 1210–
1250; (g) X. Kuoxi, B. Zhanwei, H. Kejing, Z. Jin and W. Chaojie, Chin.
J. Chem., 2010, 28, 803–810.
(br, 8H, CH2), 1.34 (s, 18H, C(CH3)3), 1.09 (s, 18H, C(CH3)3); 13
C
NMR (100 MHz, CDCl3): d (ppm): 23.9, 30.8, 31.4, 32.0, 32.4,
34.2, 34.4, 54.1, 66.0, 66.7, 73.5, 114.5, 123.5, 124.8, 125.5, 126.0,
126.3, 126.7, 127.9, 128.1, 128.2, 128.4, 129.4, 129.7, 133.2, 141.9,
144.4, 147.5, 149.9, 151.1, 153.7. Anal. Calcd for C92H106N2O6
(1335.84): C, 82.72, H, 8.00, N, 2.10%. Found: C, 82.90; H, 7.91;
N, 2.04%.
3 (a) G. M. Coppola and H. F. Schuster, a-Hydroxyl Acids in Enantioselec-
tive Synthesis, VCH, Weinheim, 1997; (b) S. Hanessian, Total Synthesis
of Natural Products: The Chiron Approach, Pergamon, Oxford, 1983;
(c) N. M. Maier, P. Franco and W. Lindner, J. Chromatogr., A, 2001,
906, 3–33.
4 E. L. Eliel and S. H. Wilen, Stereochemistry of Organic Compounds,
John Wiley & Sons, New York, 1994.
NMR host–guest titrations
5 (a) J. M. Lehn, Supramolecular Chemistry: Concepts and Perspectives,
VCH, Weinheim, 1995; (b) J. Bois, I. Bonnamour, C. Duchamp, H.
Parrot-Lopez, U. Darbost and C. Felix, New J. Chem., 2009, 33, 2128–
2135; (c) G. Uccello-Barretta, M. G. Berni and F. Balzano, Tetrahedron:
Asymmetry, 2007, 18, 2565–2572.
Samples for analysis were obtained by mixing equimolar amounts
of chiral hosts with the guests in CDCl3, making the concentra-
tions of the hosts (or guests) normally 10 mM. For NMR titrations
the guest compound was dissolved in an appropriate amount of
solvent and the resulting solution evenly distributed among 10
NMR tubes. The first NMR tube was sealed without any host.
The host compound was also dissolved in the appropriate amount
of solvent and added in increasing amounts to the NMR tubes, so
that solutions with the following relative amounts (equiv) of host
versus guest compound (concentration was 6.0 ¥ 10-2 M) were
obtained: 0, 0.20, 0.40, 0.60, 0.80, 1.00, 1.20, 2.00, 3.00, 4.00, 6.00,
10.00.
6 (a) W. Guo, J. Wang, C. Wang, J.-Q. He, X.-W. He and J.-P. Cheng,
Tetrahedron Lett., 2002, 43, 5665–5667; (b) Y. He, Y. Xiao, L. Meng,
Z. Zeng, X. Wu and C.-T. Wu, Tetrahedron Lett., 2002, 43, 6249–6253;
(c) S. Shirakawa and S. Shimizu, New J. Chem., 2010, 34, 1217–1222.
7 (a) A. Ikeda and S. Shinkai, Chem. Rev., 1997, 97, 1713–1734; (b) C.
D. Gutsche, Calixarenes Revisited: Monographs in Supramolecular
Chemistry, ed. J. F. Stoddart, The Royal Society of Chemistry,
Cambridge, UK, 1998; (c) Calixarenes in Action, ed. L. Mandolini, and
R. Ungaro, Imperial College, Singapore, 2000; (d) Calixarenes 2001,
ed. Z. Asfari, V. Bo¨hmer, J. M. Harrowfield and J. Vicens, Kluwer
Academic, Dordrecht, 2001; (e) L. Mutihac, Anal. Lett., 2010, 43,
1355–1366; (f) L. Mutihac, H.-J. Buschmann, R.-C. Mutihac and E. J.
Schollmeyer, J. Inclusion Phenom. Macrocyclic Chem., 2005, 51, 1–10.
8 (a) A. Sirit and M. Yilmaz, Turk. J. Chem., 2009, 33, 159–200; (b) R.
Ludwig, Microchim. Acta, 2005, 152, 1–19; (c) A. Casnati, F. Sansone
and R. Ungaro, Acc. Chem. Res., 2003, 36, 246–254; (d) M. O. Vysotsky,
C. Schmidt and V. Bo¨hmer, in Advances in Supramolecular Chemistry,
ed. G. Gokel, JAI Press, Stanford, 2000, Vol. 7, pp. 139–233.
9 E. Kocabas, M. Durmaz, S. Alpaydin, A. Sirit and M. Yilmaz, Chirality,
2008, 20, 26–34.
UV-Vis spectral measurement
Binding constants (K) were determined on the basis of the differ-
ential UV spectrometry in chloroform. The same concentrations
of guest solution were added to the sample cell and reference cell
(light path = 1 cm). The association constants were determined at
241 nm. The concentration of the hosts is 1.00 ¥ 10-5 mol dm-3
with the increasing concentration between 0.10–3.00 ¥ 10-4 mol
dm-3 of the added guest.
10 (a) M. Durmaz, S. Alpaydin, A. Sirit and M. Yilmaz, Tetrahedron:
Asymmetry, 2006, 17, 2322–2327; (b) M. Durmaz, S. Alpaydin, A. Sirit
and M. Yilmaz, Tetrahedron: Asymmetry, 2007, 18, 900–905.
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 571–580 | 579
©

View Article Online
11 S. Bozkurt, M. Durmaz, M. Yilmaz and A. Sirit, Tetrahedron:
Asymmetry, 2008, 19, 618–623.
(d) T. Ema, D. Tanida and T. Sakai, J. Am. Chem. Soc., 2007, 129,
10591–10596; (e) F. Cuevas, P. Ballester and M. A. Pericas, Org. Lett.,
2005, 7, 5485–5487; (f) X. Yang, X. Wu, M. Fang, Q. Yuan and E.
Fu, Tetrahedron: Asymmetry, 2004, 15, 2491–2497; (g) F. Ma, L. Ai, X.
Shen and C. Zhang, Org. Lett., 2007, 9, 125–127.
12 (a) G. Palmieri, Tetrahedron: Asymmetry, 2000, 11, 3361–3373; (b) C.
Cimarelli, A. Mazzanti, G. Palmieri and E. Volpini, J. Org. Chem.,
2001, 66, 4759–4765; (c) C. Cimarelli, G. Palmieri and E. Volpini,
Tetrahedron: Asymmetry, 2002, 13, 2417–2426; (d) I. Szatma´ri, R.
Sillanpa¨a¨ and F. Fu¨lo¨p, Tetrahedron: Asymmetry, 2008, 19, 612–617.
13 M. Periasamy, M. N. Reddy and S. Anwar, Tetrahedron: Asymmetry,
2004, 15, 1809–1812.
14 Z.-T. Li, G.-Z. Ji, C.-X. Zhao, S.-D. Yuan, H. Ding, C. Huang, A.-L.
Du and M. Wei, J. Org. Chem., 1999, 64, 3572–3584.
15 (a) H. S. Yuan and Z. T. Huang, Tetrahedron: Asymmetry, 1999, 10,
429–437; (b) G.-Y. Qing, Y.-B. He, Y. Zhao, C.-G. Hu, S.-Y. Liu and X.
Yang, Eur. J. Org. Chem., 2006, 1574–1580; (c) G. Y. Qing, Y. B. He,
F. Wang, H. J. Qin, C. G. Hu and X. Yang, Eur. J. Org. Chem., 2007,
1768–1778.
18 For enantiomeric recognition of carboxylic acids by chiral calix[4]arene
derivatives, see: (a) Y. S. Zheng and C. Zhang, Org. Lett., 2004, 6,
1189–1192; (b) X. X. Liu and Y. S. Zheng, Tetrahedron Lett., 2006, 47,
6357–6360; (c) S. Shirakawa, A. Moriyama and S. Shimizu, Eur. J. Org.
Chem., 2008, 5957–5964; (d) H. N. Demirtas, S. Bozkurt, M. Durmaz,
M. Yilmaz and A. Sirit, Tetrahedron: Asymmetry, 2008, 19, 2020–2025;
(e) T. Ishi-i, M. Crego-Calama, P. Timmerman, D. N. Reinhoudt and S.
Shinkai, Angew. Chem., Int. Ed., 2002, 41, 1924–1929; (f) S. Shirakawa,
A: Moriyama and S. Shimizu, Org. Lett., 2007, 9, 3117–3119.
19 M. Kubinyi, K. Pa´l, P. Baranyai, A. Grofcsik, I. Bitter and A. Gru¨n,
Chirality, 2004, 16, 174–179.
16 (a) T. H. Webb and C. S. Wilcox, Chem. Soc. Rev., 1993, 22, 383–395;
(b) X. X. Zhang, J. S. Bradshaw and R. M. Izatt, Chem. Rev., 1997, 97,
3313–3362.
17 For enantiomeric recognition of mandelic acid by artificial chiral
receptors, see: (a) K. Tanaka and N. Fukuda, Tetrahedron: Asymmetry,
2009, 20, 111–114; (b) C. Pena, J. Gonzalez-Sabin, I. Alfonso, F.
Rebolledo and V. Gotor, Tetrahedron, 2008, 64, 7709–7717; (c) Z. Luo,
C. Zhong, X. Wu and W. Fu, Tetrahedron Lett., 2008, 49, 3385–3390;
20 (a) X. Chen, D. M. Du and W. T. Hua, Tetrahedron: Asymmetry, 2003,
14, 999–1007; (b) J. S. You, X. Q. Yu, G. L. Zhang, Q. X. Xiang, J. B.
Lan and R. G. Xie, Chem. Commun., 2001, 1816–1817.
21 H. A. Benesi and J. H. Hildebrand, J. Am. Chem. Soc., 1949, 71, 2703–
2707.
22 F. Ma, X. Shen, X. Ming, J. Wang, J. Ou-Yang and C. Zhang,
Tetrahedron: Asymmetry, 2008, 19, 1576–1586.
23 P. Job, Ann. Chim. (Paris), 1928, 9, 113–203.
580 | Org. Biomol. Chem., 2011, 9, 571–580
This journal is
The Royal Society of Chemistry 2011
©