Conformational features and recognition properties of a conformationally blocked calix[7]arene derivative

Article abstract of DOI:10.1002/chem.201102179

The shaping of a calix[7]arene macrocycle into cone-like structure 3, through exhaustive alkylation of doubly bridged calix[7]arene derivative 2 with bulky groups, has been investigated. Conformational details about the structure adopted by calix[7]arene derivative 3 in solution have been obtained by using chemical shift surface maps, as previously reported by our group. Thus, chemical shift contour plots indicated that 3 adopted a cone-shaped structure in solution analogous to that adopted by the known p-tert-butylcalix[7]arene heptacarboxylic acid derivative 4. Interestingly, the X-ray structure of derivative 3 showed a high degree of similarity to the theoretical structure, which confirmed the validity of the contour plots method. The preorganized calix[7]arene host 3 showed interesting recognition abilities toward both organic and alkali cations. In fact, an unprecedented endo-cavity complexation of linear and branched alkyl ammonium cations with a larger calix[7]arene host was evidenced. A comparable affinity for branched tBuNH₃⁺ and linear nBuNH₃⁺ guests was observed. Pursuing the weak: The first example of a completely rigidified calix[7]arene derivative (see figure) shows interesting recognition abilities toward cationic guests. In particular, an endo-calix complexation of alkylammonium guests was observed when they are coupled to the "superweak" tetrakis[3,5-bis(trifluoromethyl) phenyl]borate anion. Copyright

Full text of DOI:10.1002/chem.201102179

FULL PAPER
DOI: 10.1002/chem.201102179
Conformational Features and Recognition Properties of a Conformationally
Blocked Calix[7]arene Derivative
Carmine Gaeta,*[a] Carmen Talotta,[a] Francesco Farina,[a] Gaetano Campi,[b]
Mercedes Camalli,[b] and Placido Neri[a]
Abstract: The shaping of a calix[7]ar-
ene macrocycle into cone-like structure
3, through exhaustive alkylation of
doubly bridged calix[7]arene derivative
2 with bulky groups, has been investi-
gated. Conformational details about
the structure adopted by calix[7]arene
derivative 3 in solution have been ob-
tained by using chemical shift surface
maps, as previously reported by our
group. Thus, chemical shift contour
plots indicated that 3 adopted a cone-
shaped structure in solution analogous
to that adopted by the known p-tert-bu-
tylcalix[7]arene heptacarboxylic acid
derivative 4. Interestingly, the X-ray
structure of derivative 3 showed a high
degree of similarity to the theoretical
structure, which confirmed the validity
of the contour plots method. The pre-
organized calix[7]arene host 3 showed
interesting recognition abilities toward
both organic and alkali cations. In fact,
an unprecedented endo-cavity com-
plexation of linear and branched alkyl
ammonium cations with a larger cal-
ix[7]arene host was evidenced. A com-
Keywords: calixarenes · conforma-
tional analysis · host–guest systems ·
molecular recognition · structure
elucidation
+
parable affinity for branched tBuNH3
+
and linear nBuNH3 guests was ob-
served.
Introduction
amples of 1,4-singly[9] and 1,4:2,3-doubly[10] bridged calix[7]-
arenes were obtained in yields of up to 72 and 76%, respec-
tively. More recently, examples of monosubstituted,[11] singly
Recent advances in macrocyclic chemistry have made it pos-
sible to develop highly preorganized receptors able to recog-
nize specific guests. In this regard, calix[n]arene[1] macrocy-
cles have become one of the leading host systems and are
currently the most studied receptors in the context of molec-
ular recognition.[2] The main reason for this success, apart
from their ready availability, is their easy chemical modifica-
tion,[3] which allows the generation of new related systems
with improved or profoundly different supramolecular prop-
erties. Thus, several calixarene hosts have been reported
that showed interesting recognition abilities toward electro-
neutral[4] and charged anionic[5] or cationic[6] guests.
The large majority of these studies have been conducted
on the even-membered “major” calix[n]arenes (n=4, 6, 8),[1]
whereas the odd-membered “minor” calix[7]arene[7] macro-
cycle has been scarcely studied. In fact, concerning chemical
modification, we reported a procedure to achieve the
diacetylamido-bridged,[11]
and
multiply
diphosphate-
bridged[12] calix[7]arenes were reported by Chen and co-
workers. Regarding the supramolecular properties of the
calix[7]arene macrocycle, our group has reported on the
binding ability of a water-soluble p-sulfonatocalix[7]arene[13]
derivative toward organic quaternary ammonium cations.
Successively, molecular capsules based on p-sulfonatoca-
lix[7]arene and a dicationic Diquat guest have been ob-
tained in the solid state.[14]
Very recently,[15] we have reported on the endo-cavity
complexation of large calix
lammonium cations coupled to the weakly coordinating
tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (TFPB)
anion.[16] In particular, we showed that no hint of complexa-
tion of [n-butylammonium][TFPB] was observed for scarce-
ACHTUNGTRNE[NUNG 6,7]arene derivatives with alky-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
ly preorganized calix[7]arene derivatives. To overcome this
kind of problem, we decided to resort to intramolecular
bridging as a very convenient method to shape and preor-
ganize larger calixarene macrocycles.[17,18] Thus, we focused
our attention on doubly bridged calix[7]arene derivatives,[10]
such as 2 (Scheme 1), in which the presence of two short
bridges at the 1,4- and 2,3-positions led to a high level of
preorganization and suggested potential applications as mo-
lecular hosts in supramolecular chemistry. The 1,4-bridging
gives rise to two different tetra- and trimeric subunits in 2
defined by the four alkylated and the three unalkylated
phenol rings, respectively. Naturally, the presence of unalky-
lated OH groups at the lower rim of the trimeric subunit of
2 leaves residual mobility due to their through-the-annulus
1,2,4,6-tetra-O-substitution of p-tert-butylcalix[7]arene
1
(Scheme 1) with high selectivity.[8] Successively, the first ex-
[a] Dr. C. Gaeta, Dr. C. Talotta, Dr. F. Farina, Prof. P. Neri
Dipartimento di Chimica e Biologia
Universitꢀ degli Studi di Salerno, Via Ponte don Melillo
84084 Fisciano (Italy)
Fax : (+39)0899-696-03
E-mail: cgaeta@unisa.it
[b] Dr. G. Campi, Dr. M. Camalli
Istituto di Cristallografia, CNR
Via Salaria Km 29.300
00015 Moterotondo Scalo (Italy)
Chem. Eur. J. 2012, 18, 1219 – 1230
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Scheme 1. Synthesis of 1,4:2,3-doubly bridged calix[7]arene derivative 3. Ts=tosyl.
passage, which could be cur-
tailed by the introduction of
sufficiently bulky groups.
Herein, we wish to report the
first example of complete rigid-
ification of the calix[7]arene
macrocycle and the consequent
study of the complexation of
cationic guests induced by the
presence of the weakly coordi-
nating[16] TFPB counterion.
Results and Discussion
Synthesis: Compound 2 was obtained in good yields by
direct alkylation of 1 with di(ethylene glycol) ditosylate by
following the procedure previously reported by us
(Scheme 1).[10] 1D and 2D NMR spectroscopy studies re-
vealed that 2 adopted an all-syn conformation, similar to the
double-cone pinched conformation of 1,[10,19] which was char-
acterized by a syn combination of the tetra- (cone-like) and
trimeric (3/4-cone-like) subunits (see Figure 1).
Figure 1. The most common X-ray structures presently found for the cal-
ix[7]arene macrocycle: a) X-ray crystal structure of 1 defined as double-
cone pinched conformation;[22a] p-tert-butyl groups and hydrogen atoms
^
are omitted for clarity. ~ and : The calix[7]arene phenol rings forming
the tetra- (cone-like) and trimeric (3/4-cone-like) subcavities, respective-
ly. b) X-ray crystal structure of p-ethylcalix[7]arene defined as a pleated-
loop/cone conformation;[22b] p-ethyl groups and hydrogen atoms are omit-
ted for clarity. c) X-ray crystal structure of p-tert-butylcalix[7]arene-hep-
tacarboxylic acid derivative 4;[22e] p-tert-butyl and carboxy groups and hy-
drogen atoms are omitted for clarity. d) X-ray crystal structure of the
complex formed by p-benzylcalix[7]arene with a uranyl cation in pres-
The presence of two short bridges at the 1,4- and 2,3-posi-
tions of the tetrameric cone-like subcavity leads to its rigidi-
1
fication, while variable-temperature (VT) H NMR studies
confirmed the expected residual conformational mobility of
the trimeric 3/4-cone-like subcavity.[10] Interestingly, with re-
spect to the original 28-membered ring of parent 1, the tri-
meric 3/4-cone-like sub-ring of 2 is scaled down to a 24-
membered ring. In similar previous work,[20] it was shown
that the conformational rigidification of a 23-membered
sub-ring of a 1,5-tetramethylene-bridged calix[8]arene deriv-
ative was possible by curtailing the oxygen-through-the-an-
nulus route when sufficiently bulky groups were appended
at the lower rim of the calix[8]arene macrocycle.
In a similar way, we have now attempted the rigidification
of the trimeric 3/4-cone-like subunit of 2 by the introduction
of bulky tert-butoxycarbonylmethyl groups at the OH func-
tionalities. Exhaustive alkylation of 2 occurred smoothly by
using a large excess of tert-butylbromoacetate (Scheme 1)
ence of 1,4-diazabicycloACTHNUTRGNE[NUG 2.2.2]octane (DABCO) (H atoms, uranyl and
HDABCO+ cations, and solvent molecules are omitted for clarity).[22d]
and NaH as a base in a mixture of dry THF/DMF (5:1, v/v)
as the solvent at 1008C for 3 h. After standard workup,
product 3 was isolated by column chromatography. The
structure of 3 was assigned by means of spectral analysis. In
particular, the presence of a pseudomolecular ion signal at
m/z 1617 in the ESI+ mass spectrum confirmed the molecu-
1
lar formula. H and 13C NMR spectra of 3 in CDCl3 showed
the presence of a symmetry plane bisecting one aromatic
ꢀ
ring and the opposite ArCH2Ar group (Ar CH2 symmetry).
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Chem. Eur. J. 2012, 18, 1219 – 1230

A Conformationally Blocked Calix[7]arene Derivative
FULL PAPER
1
Thus, six tBu singlets were present in the H NMR spectrum
(CDCl3, 400 MHz, 298 K) at d=0.70, 1.07, 1.32, 1.34, 1.48,
and 1.57 ppm (2:2:2:1:2:1 ratio), while the ArCH2Ar groups
gave rise to four sharp AX systems at d=3.44/3.51 (J=
15.1 Hz), 3.89/4.22 (J=17.2 Hz), 4.60/4.63 (J=15.2 Hz), and
3.34/5.07 ppm (J=13.1 Hz). The 13C NMR spectrum dis-
played four signals at d=28.1, 29.9, 30.2, and 30.8 ppm rela-
tive to methylene carbon atoms, while two characteristic res-
onances (2:1 ratio) relative to the two carbonyl groups were
present at d=168.4 and 168.0 ppm.
VT NMR studies (400 MHz, TCDE) indicated high con-
formational stability of 3 and, in particular, with respect to
the trimeric 3/4-cone-like subcavity. In fact, no hint of coa-
lescence was observed in the VT 1H NMR spectra upon
heating to 400 K. This conformational stability was con-
firmed by prolonged heating in toluene at reflux (up to 4 d),
which showed no change in the 1H NMR spectrum of 3.
This result proves that the tert-butyl-through-the-annulus
passage is inhibited in 3 as a result of the small dimension
of the trimeric (3/4-cone-like) subcavity and that the tert-bu-
toxycarbonylmethoxy substituent is bulky enough to prevent
the oxygen-through-the-annulus route.
Definition of the conformation of 3 through theoretically
1
computed H Dd and 13C chemical shift surfaces: The con-
formational features of the larger calix[n]arenes (n=6–8)[21]
become increasingly more complex with the increasing
number, n, of aryl rings. In fact, an exponentially increasing
number of conformations become possible through the in-
creased number of possible combinations of the syn/anti dis-
positions of the aryl rings, joined to their possible inward/
outward orientations. Thus, eight extreme conformations are
possible for a calix[7]arene macrocycle if a simple “up” or
“down” orientation of phenol rings is assumed, but the
number is higher if the “out”, “inward”, and “outward” in-
clinations of the phenol rings are also considered.[7] To con-
firm the high conformational complexity of the calix[7]arene
macrocycle, to date, eight different solid-state structures
have been determined by X-ray crystallography. The corre-
sponding most common conformations of calix[7]arene skel-
eton are reported in Figure 1.[22]
Naturally, in the case of derivative 3, the presence of two
short bridges at the lower rim requires syn orientation be-
tween aryl rings E and D and a syn/outward geometry be-
tween rings F and C (Scheme 1). Both conformational re-
quirements are compatible with each of the conformations
reported in Figure 1. Therefore, to shed light on the confor-
mational preferences of 3, we decided to resort to a pro-
posed novel method for the assessment of calixarene confor-
mations based on the QM GIAO calculation of 13C and
1H NMR chemical shift values of ArCH2Ar groups.[23] In
particular, following the reported indications, we used the
published chemical shift surface maps[23b] in which the 1H
Dd (Figure 2a) and 13C d (Figure 2b) values of the calixar-
ene ArCH2Ar groups are correlated with the f and c torsion
Figure 2. Contour plot representations of the 1H Dd (a) and 13C (b) chem-
ical shift values [ppm] of the ArCH2Ar group versus the f and c torsion
angles [8].[23] c) Computer-assisted graphical superimposition of the lines
relative to experimental 1H Dd=1.2 ppm and 13C=30.0 ppm values for
methylene group 2 (Scheme 1 and Table 1); other lines of the contour
plots have been omitted for clarity.
imposition of the relative maps (Figure 2c) allowed us to
obtain a series of possible combinations of f and c torsion
ꢀ
ꢀ
angles of the Ar CH2 Ar bonds.
1
To apply this strategy, a complete assignment for both H
and 13C NMR spectra of 3 was obtained at room tempera-
ture by means of a detailed 1D and 2D NMR spectroscopy
study (COSY, HSQC, and HMBC 2D spectra, 400 MHz,
CDCl3). Consequently, for each methylene group (2/38, 8/32,
14/26 and 20; see Scheme 1 and Table 1), the simultaneous
fitting of the corresponding coupled experimental 1H Dd
and 13C d values (Table 1) in the contour plots (Figure 2)
was obtained through computer-assisted graphical superim-
1
position[24] (see Figure 2c) of the relative H Dd and 13C d
lines. As an example, Figure 2 illustrates the case of the
1
methylene group at position 2/38: H Dd=1.2 ppm and 13C
d=30.0 ppm. Thus, through the coordinates of each inter-
section point, we obtained f and c torsion angles values of
+75/ꢀ8 and ꢀ75/+88. By repeating this procedure for the
remaining positions, we obtained the f and c torsion angle
values reported in Table 1. These data were then used in a
modeling program (Maestro 4.1) to build the possible con-
formers starting with an open-chain calix[7]arene skeleton.
The first, obvious criterion followed to select compatible
conformers was to discard those arrangements that lacked
ꢀ
ꢀ
angles of the Ar CH2 Ar bonds. Thus, simultaneous fitting
1
of experimental H Dd and 13C d values obtained by super-
Chem. Eur. J. 2012, 18, 1219 – 1230
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1221

C. Gaeta et al.
Table 1. f And c torsion angles derived by fitting of the experimental
[a]
Dd 1H and 13C[a] d values for the methylene groups of 3 on the corre-
sponding chemical shift surface.
Atom number
d
(13C)[a]
Dd(1H)[a]
fcalcd [8]
ccalcd [8]
exptl
exptl
A
ACHTUNGTRENNUNG
+75
ꢀ75
ꢀ8
+8
+17.5
ꢀ17.5
+2
2 and 38
8 and 32
14 and 26
20
30.0
30.8
30.2
28.1
+87.5
ꢀ87.5
+73
ꢀ73
0.34
1.09
1.73
ꢀ2
+75
ꢀ75
ꢀ25
+25
[a] The complete NMR signal assignment leading to Dd 1H and 13C d
values for the methylene groups of 3 was obtained by means of a detailed
1D and 2D NMR spectroscopy study (COSY, HSQC, and HMBC 2D
1
NMR spectra, 400 MHz, 298 K, CDCl3). Dd H values were calculated as
the distance on the ppm scale between the two doublets of each AX
system of ArCH2Ar groups of 3.
Table 2. Sequence of f and c torsion angles.
Torsion angles[a] [8]
3[b,c]
3a
3b[d]
4[e,f]
f: C42-C1-C2-C3
c: C1-C2-C3-C4
f: C6-C7-C8-C9
c: C7-C8-C9-C10
+87.9
ꢀ37.1
+10.8
ꢀ80.6
+90.7
ꢀ20.3
+56.3
ꢀ73.1
+46.3
ꢀ88.9
+78.8
+4.0
+75.0
ꢀ8.0
+90.5
ꢀ32.0
+7.3
+122.5
ꢀ37.7
+1.4
closure of the calix[7]arene macrocycle. In this way, only the
following sequence of torsion angle values was obtained
(Table 1): +75/ꢀ8, +17.5/ꢀ87.5, +73/+2, +25/ꢀ75, ꢀ2/
ꢀ73, +87.5/ꢀ17.5, and +8/ꢀ758.
+17.5
ꢀ87.5
+73.0
+2.0
ꢀ84.9
+96.5
ꢀ28.5
+53.2
ꢀ84.4
+46.5
ꢀ84.2
+83.6
+5.2
ꢀ108.6
+77.2
ꢀ31.3
+81.2
ꢀ50.1
+41.0
ꢀ105.6
+68.0
+5.0
f: C12-C13-C14-C15
c: C13-C14-C15-C16
f: C18-C19-C20-C21
c: C19-C20-C21-C22
f: C24-C25-C26-C27
c: C25-C26-C27-C28
f: C30-C31-C32-C33
c: C31-C32-C33-C34
f: C36-C37-C38-C39
c: C37-C38-C39-C40
+25.0
ꢀ75.0
ꢀ2.0
Thus, from this sequence of torsion angle values, crude
model 3a was obtained (Figure 3a), which showed a high
degree of similarity (see superimposition in Figure 3c) to
the crystal structure of p-tert-butylcalix[7]arene heptacar-
boxylic acid[22d] derivative 4 reported in Figure 1c. The high
ꢀ73.0
+87.5
ꢀ17.5
+8.0
+25.0
ꢀ85.5
+38.1
ꢀ98.8
+32.7
ꢀ91.1
ꢀ75.0
[a] For the numbering, see Scheme 1. [b] X-ray structure of 3. [c] The
rmsd value with respect to 3a is 208. [d] The rmsd value with respect to
3a is 228. [e] The rmsd value with respect to 3a is 298. [f] The rmsd value
with respect to 3 is 178.
clined outward, while the distal B and G rings of the trimer-
ic subunit are oriented inward. Furthermore, in the calix[7]-
arene skeleton shown in Figure 3a, the A and B rings (and
the equivalent A and G rings) were syn oriented in accord-
1
ance with the experimental 13C d and H Dd values of meth-
ylene group 2 (Table 1 and Scheme 1).[25]
Analogously, a syn orientation was found for the couples
of adjacent rings C/D (E/F) and D/E. Finally, an out orienta-
tion was found for crown-3-bridged C and F rings in accord-
Figure 3. a) Crude model (Maestro 4.1) 3a obtained by imposing the f
and c torsion angle values reported in Table 1 on the calix[7]arene skele-
ton of 3. b) Lowest MM3 energy conformation 3b (MacroModel 9.0,
CHCl3 GB/SA implicit model solvent) obtained from 3a. c) Superimposi-
tion (rmsd=0.96 ꢂ) of 3a (light gray) and the X-ray structure (dark
gray) of 4. d) Superimposition (rmsd=0.86 ꢂ) of 3a (white) and 3b
(black). tert-Butyl groups and substituents at the lower rim are omitted
for clarity.
1
ance with an experimental H Dd value of 0.34 ppm relative
to the pertinent ArCH2Ar protons in 8.
As previously reported,[23a] there is a logical relationship
between the canting angle[26] of a calixarene aromatic ring
1
and the corresponding H and 13C NMR data. In particular,
1
we have deduced that the higher H Dd values are predicted
degree of similarity between 3a and 4 was confirmed by a
root-mean-square deviation (rmsd) value of 0.96 ꢂ for the
superimposition (Figure 3c) and by a rmsd value of 298 for
the corresponding torsion angles f and c given in Table 2.
In fact, analogously to 4, crude-model 3a displays all cal-
ixarene oxygen atoms on the same side of the molecule,
with the two bridged F and C rings of tetrameric portion in-
for a canting angle, q, ranging from +50 to +1008, corre-
sponding to a cone conformation, with a maximum with re-
gards to a “standing-up” situation for q =798. Thus, the high
experimental 1H Dd value of 1.73 ppm observed for
ArCH2Ar protons in 20 corresponds to a canting angle of
103 and 868 for the adjacent D and E rings, respectively. In
addition, in the theoretical crude-model 3a (Figure 3a) the
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A Conformationally Blocked Calix[7]arene Derivative
FULL PAPER
B, D, E, and G rings (Scheme 1) were bent inward toward
the calix[7]arene cavity, showing a canting angle of 125, 103,
86, and 1208, respectively, while the A, C, and F rings were
oriented outward with a canting angle of 69, 59, and 608, re-
spectively. Experimentally, an unusually shielded signal at
d=0.70 ppm was present in the 1H NMR spectrum of 3
(CDCl3, 400 MHz, 298 K) relative to the tBu groups of B
and G rings, which was indicative of the self-inclusion of this
group inside the calix cavity and suggesting an inward orien-
tation of B and G rings in accordance with 3a.
Refinement of 3a was obtained through molecular me-
chanics calculations (MM3 Force Field, CHCl3 GB/SA im-
plicit model solvent).[27] The obtained lowest-energy struc-
ture, 3b (Figure 3b), showed only small differences with re-
spect to 3a (Figure 3a), as demonstrated by a rmsd value of
0.86 ꢂ for the superimposition (Figure 3d) and by a rmsd
value of 228 for the corresponding torsion angles f and c
given in Table 2.
Figure 5. Left: Superimposition (rmsd=0.60 ꢂ) of the X-ray structure
(dark gray) of 3 and X-ray structure (light gray) of 4. Right: Superimpo-
sition (rmsd=0.90 ꢂ) of the X-ray structure (black) of 3 and crude
model 3a (white).
As proposed by Ugozzoli and Andreetti,[28] an accurate
description of larger calixarene conformations can be ob-
ꢀ
tained by means of f and c torsion angle values of Ar
ꢀ
CH2 Ar bonds. Thus, when two adjacent aryl rings have a
syn orientation, the signs of the f and c angles are opposite,
whereas they are the same for the anti orientation. Exami-
nation of the f and c torsion angles reveals that the solid-
state conformation of 3 is characterized by the following
signs: + ꢀ, + ꢀ, + ꢀ, + ꢀ, + ꢀ, + +, + ꢀ, similar to that
of 4 in Figure 1c. The high degree of similarity between the
X-ray structures of 3 and 4 was confirmed by a rmsd value
of 178 for the corresponding torsion angles f and c given in
Table 2.
Single-crystal X-ray analysis: Slow crystallization of 3 from
a two-component mixture (MeOH/CHCl3) afforded color-
less crystals, which were suitable for single-crystal X-ray
analysis.
Interestingly, derivative 3 adopts a conformation in the
solid state (Figure 4) very similar both to that predicted by
1H and 13C chemical shifts surfaces (Figure 3) and to that
adopted by p-tert-butylcalix[7]arene heptacarboxylic acid 4
(Figure 1c); this was confirmed by a rmsd value of 0.6 ꢂ for
the superimposition of the X-ray structures of 3 and acid 4
(Figure 5, left).
Interestingly, the solid-state assembly of 3 gives rise to a
bilayer-type supramolecular architecture with alternating
oxygen-rich polar zones and lipophilic tert-butyl regions
(Figure 6). In particular, calix[7]arene molecules of 3 are
flanked to give a columnar arrangement that runs along the
diagonal of the a,b plane. Two columns of 3 are stacked on
each other through the facing of lipophilic tert-butyl regions
(Figure 6a). These subunits are stacked along the c axis
through the facing of lower-rim regions (Figure 6b). Inter-
estingly, inspection of the 2D packing in the a,b plane re-
Figure 4. Side view (left) and top view (right) of the X-ray structure of
calix[7]arene derivative 3. Hydrogen atoms are omitted for clarity.
In a similar way, the high degree of similarity between
theoretical 3a (Figure 3a) and the X-ray structure of 3
(Figure 4) was confirmed by a rmsd value of 0.90 ꢂ for their
superimposition (Figure 5, right) and by a rmsd value of 208
for the corresponding torsion angles f and c given in
Table 2. In analogy to 3a (Figure 3a), in the X-ray structure
of 3 (Figure 4) aromatic rings B, D, E, and G were bent
inward towards the calix[7]arene cavity with a canting angle
of 103 (Dq=qcrude-modelꢀqX-ray structure =228), 102 (Dq =1), 94
(Dq =ꢀ8), and 1078 (Dq=138), respectively. The canting
angle values regarding rings A, C, and F, were 62 (Dq =78),
35 (Dq =24), and 368 (Dq=248), respectively.
Figure 6. View of the bilayer-type 3D architecture along the diagonal of
the a,b plane.
Chem. Eur. J. 2012, 18, 1219 – 1230
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1223

C. Gaeta et al.
vealed that molecules of 3 (Figure 7) fit to form a close-
packed arrowhead-motif favored by perfect structural com-
plementarity between the triangular shapes.
resonances in the upfield negative region of the spectrum
(Figure 8b).
This latter is a clear indication that 5a gave endo-calix
complexation with the alkyl chain shielded by the aromatic
rings. Complex formation was also confirmed by an ESI+
mass spectrum, which gave as the base peak a value of m/z
+
1690, corresponding to supramolecular ion nBuNH3 ꢁ3. A
COSY-45 spectrum (Figure 9) allowed a complete confident
Figure 7. Arrowhead motif derived by the 2D packing of 3 in the a,b
plane.
Binding abilities of 3 toward alkylammonium guests 5a–d:
1H NMR experiments showed interesting recognition prop-
erties
for
calix[7]arene
derivative
3
toward
[alkylammonium]ACHTUNGTRENNUNG[TFPB] salts 5a–d. In particular, the addi-
tion of the TFPB salt of n-butylammonium cation (5a) to a
solution of 3 in CDCl3 resulted in significant changes in the
1H NMR spectrum (Figure 8a). The most evident ones were
the appearance of a new set of signals due to the formation
+
of the nBuNH3 ꢁ3 complex and the presence of n-butyl
Figure 9. COSY-45 spectrum of an equimolar solution (3 mm) of 3 and
5a.
+
+
assignment of all nBuNH3 resonances. Thus, NH3 group
at d=4.93 ppm correlates with a protons at d=0.22 ppm,
which in turn is coupled with a b methylene group at d=
ꢀ0.05 ppm, which presents a cross-peak with g protons at
d=ꢀ0.27 ppm, finally coupled with the d methyl group at
d=ꢀ2.11 ppm (Figure 9). In this way, it is clear that the n-
butyl protons that experience the highest complexation in-
duced shift (CIS) are those at the d position, which undergo
an upfield shift of 4.07 ppm, while the n-butyl protons at the
a-, b-, and g-positions experience CISs of 2.62, 1.40 and
1.52 ppm, respectively. Interestingly, the CIS of the d pro-
tons of guest 5a (Dd=4.07 ppm) was significantly higher
with respect to that previously observed for analogous pro-
Figure 8. 1H NMR spectra (CDCl3, 400 MHz, 298 K) of a) 3, b) an equi-
molar solution (3 mm) of 3 and 5a, c) an equimolar solution (3 mm) of 3
and 5b, d) an equimolar solution (3 mm) of 3 and 5c, and e) an equimolar
solution (3 mm) of 3 and 5d. For definitions of a, b, g, and d, see struc-
tures of 5a–5d.
+
tons in endo-cavity complexation of an nBuNH3 guest with
calix[6]arene hosts (Dd=1.96 ppm).[15a] It is very likely that,
1224
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ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 1219 – 1230

A Conformationally Blocked Calix[7]arene Derivative
FULL PAPER
+
+
in the nBuNH3 ꢁ3 complex, the guest is able to penetrate
association constant for the sBuNH3 ꢁ3 complex of 6.2ꢃ
more deeply into the calix[7]arene cavity of 3 and is driven
by hydrogen-bond formation between the carbonyl groups
at the lower rim of 3 and the ammonium group of guest 5a.
This binding mode was confirmed by the OPLS (optimized
potential for liquid simulation) lowest-energy structure of
102 mꢀ1.
Additional interesting endo-cavity complexation was ob-
tained with the more cumbersome salt 5d and 3 (Figure 8e).
In fact, in the H NMR spectrum shown in Figure 8e a sin-
glet shielded at d=ꢀ0.61 ppm (9H) can be observed that
corresponds to the endo-cavity disposition of the tBu group.
Inspection of the energy-minimized structure of the
1
the nBuNH3 ꢁ3 complex (Figure 10a and b),[27] for which it
+
+
tBuNH3 ꢁ3 complex (Figure 10c and d) revealed that the
cavity of 3 was large enough to accommodate the bulkier
+
guest 5d. An apparent association constant for the tBuNH3
ꢁ3 complex of 4.8ꢃ103 mꢀ1 was determined, which was un-
+
expectedly comparable to that of the nBuNH3 ꢁ3 complex
(5.30ꢃ103 mꢀ1). In fact, an NMR competition experiment
(Figure 11) showed that when 3 was mixed with equimolar
+
Figure 10. OPLS lowest-energy structures of nBuNH3 ꢁ3 (a and b) and
+
tBuNH3 ꢁ3 (c and d) complexes obtained by Monte Carlo conforma-
tional searches. Hydrogen atoms of 3 are omitted for clarity.
is possible to observe an n-butyl group inside the trimeric 3/
4-cone-like subcavity with the ammonium group hydrogen
bonded to both ethereal oxygen atoms and carbonyl groups.
Interestingly, the nitrogen atom sits at a distance of 0.20 ꢂ
above the mean plane of the calixarene oxygen atoms of the
trimeric 3/4-cone-like subcavity of 3; a value that is signifi-
cantly lower with respect to that previously observed for
Figure 11. 1H NMR spectrum (CDCl3, 400 MHz, 298 K) of an equimolar
solution (3 mm) of 3, 5a (3 mm), and 5d (3 mm).
mixtures of [tBuNH3]ACTHNUTRGNEN[UG TFPB] and [nBuNH3]ACHTUGNTREN[NUNG TFPB] salts
+
+
both tBuNH3 ꢁ3 and nBuNH3 ꢁ3 complexes were formed
in a 1:1 ratio. Thus, contrary to the results reported by Pap-
palardo and co-workers[31] for smaller p-tert-butylcalix[5]ar-
ene derivatives, the larger calix[7]arene derivative 3 shows a
+
endo-cavity complexation of an nBuNH3 guest with cal-
ix[6]arene hosts (0.76 ꢂ).[15a] The apparent association con-
+
stant for nBuNH3 ꢁ3 complex was determined by quantita-
1
+
tive H NMR spectroscopy analysis of a 1:1 titration mixture
comparable affinity for isomeric bulky tertiary tBuNH3
and linear nBuNH3 guests.
in CDCl3,[29] using toluene as the internal standard, to give a
+
value of 5.2ꢃ103 mꢀ1. It is noteworthy that in CDCl3 no trace
An analogous result was obtained for the complexation of
+
1
of complexation of nBuNH3 guests was observed for 3 in
guest 5c. In fact, the H NMR spectrum of a 1:1 mixture of
ꢀ
ꢀ
the presence of counterions such as Clꢀ, PF6 , and BPh4 .
the TFPB salt of 5c and 3 in CDCl3 showed a broad signal
at d=ꢀ0.62 ppm characteristic of endo-complexation of an
isopropyl group shielded by calixarene aromatic rings.
1H NMR spectroscopic quantitative analysis of a 1:1 mixture
of 3 and 5d in CDCl3 revealed an apparent association con-
This can be ascribed to the sum of two effects, namely, poor
ꢀ
solubility and the strong ion-pairing tendency of Clꢀ, PF6 ,
ꢀ
+
and BPh4 salts of nBuNH3 in CDCl3 with respect to the
more hydrophobic and weakly coordinating[16] TFPB anion.
Interestingly, interaction with 3 was also detected for iso-
+
stant for the iPrNH3 ꢁ3 complex of 3.0ꢃ103 mꢀ1. Therefore,
+
+
meric secondary sBuNH3 5b and iPrNH3 5c guests. In
compound 3 shows a comparable affinity for linear
+
+
fact, addition of solid [sBuNH3]
N
nBuNH3 and secondary iPrNH3 guests. In fact, an NMR
competition experiment showed that when 3 was mixed with
1
CDCl3 again caused dramatic changes in the H NMR spec-
trum (Figure 8c) with the appearance of resonances in the
upfield negative region of the spectrum relative to the sBu
group of the guest inside the aromatic cavity of 3. A quanti-
equimolar mixtures of [iPrNH3]ACTHNUTRGNE[UNG TFPB] and [nBuNH3]-
+
+
AHCTUNGTRENNUNG
1
tative H NMR spectroscopy experiment led to an apparent
Chem. Eur. J. 2012, 18, 1219 – 1230
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
1225

C. Gaeta et al.
Binding ability of 3 toward alkali-metal cations: Analogous-
ly to the alkylammonium guests reported above, calix[7]ar-
ene derivative 3 showed interesting complexation properties
toward alkali-metal cations. In fact, upon the addition of
0.5 equivalents of solid NaTFPB to a solution of 3 in CDCl3,
a new set of signals emerged due to the formation of the
Na+ꢁ3 complex (Figure 12a and b). Further addition of cat-
Figure 13. Corey–Pauling–Koltun (CPK) models of the OPLS lowest-
energy structures of free host 3 (left) and Na+ꢁ3 complex (right), as
found by Monte Carlo conformational searches.
These adaptive conformational changes were fully con-
firmed by molecular modeling (Figure 14). In fact, the
OPLS lowest-energy structure of Na+ꢁ3 complex
(Figure 14) shows that the cation is encapsulated inside a
Figure 14. Side views of the computer models of the OPLS lowest-energy
structure of the Na+ꢁ3 complex, as found by Monte Carlo conformation-
al searches.
cavity delimited by the three tert-butoxycarbonylmethoxy
groups and a crown-3 bridging element (Figures 13 and 14).
In particular, inspection of the free (Figure 13 left) and Na+
-complexed forms (Figure 13 right) revealed that 3 was able
to bind the Na+ guest through an induced-fit mechanism,
which originated from the residual conformational flexibility
of nonbridged aromatic rings A, B, and G of 3 (see
Scheme 1).
Figure 12. 1H NMR spectra (CDCl3, 400 MHz, 298 K) of a) 3, b) 3 after
the addition of 0.5 equivalents of NaTFPB, and c) 3 after the addition of
1 equivalent of NaTFPB.
ionic guest led to complete complexation (Figure 12c) and a
1:1 stoichiometry was determined by spectral integration.
An apparent association constant of 3.4ꢃ105 mꢀ1 was de-
termined for the Na+ꢁ3 complex by integration of the
1
1
Complete assignment for both H and 13C NMR spectra of
slowly exchanging H NMR spectrum of a 1:1 titration mix-
the Na+ꢁ3 complex in CDCl3 was obtained at room temper-
ature by means of a detailed 1D and 2D NMR spectroscopy
study (2D HSQC and HMBC spectra; 400 MHz, CDCl3).
Interestingly, after the addition of NaTFPB to a solution
of 3 in CDCl3, a downfield shift of the signal of the tBu
groups (Dd=1.13ꢀ0.70=0.43 ppm) belonging to the B and
G aromatic rings was observed. In addition, a downfield
shift of aromatic protons ArH4 (Scheme 1, Dd=7.17ꢀ6.70=
0.47 ppm) and ArH6 (Dd=6.96ꢀ6.36=0.40 ppm) were also
observed. These data indicate that, upon complexation, the
B and G rings of 3 switch from the previous inward orienta-
tion (Figure 13, left) to the opposite outward orientation
(Figure 13, right) with the two tert-butoxycarbonylmethoxy
groups pointing toward the Na+ guest.
ture in CDCl3. It is noteworthy that in CDCl3 no trace of
complexation of the Na+ guest was observed for 3 in the
presence of counterions such as picrate, Clꢀ, PF6 , and
ꢀ
ꢀ
BPh4 .
Analogously, the addition of solid KTFPB to a solution of
1
3 in CDCl3 caused significant changes in the H NMR spec-
trum due to the formation of the K+ꢁ3 complex
1
(Figure 15). Integration of slowly exchanging H NMR sig-
nals for both free and complexed calix[7]arene macrocycle 3
lead to an apparent association constant for the K+ꢁ3 com-
plex of 3.6ꢃ103 mꢀ1. Interestingly, compound 3 displays a se-
lectivity for sodium over potassium of 94 when expressed as
the ratio of their association constants.
1226
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ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 1219 – 1230

A Conformationally Blocked Calix[7]arene Derivative
FULL PAPER
action temperatures were measured externally. Reactions were moni-
tored by TLC on Merck silica gel plates (0.25 mm) and visualized by UV
light or by spraying with H2SO4–CeACHTUNGTRNEUNG
(SO4)2. Derivatives 1,[32] 2,[15]
+
nBuNH3 tetrakis
[3,5-bis(trifluoromethyl)phenyl]borate,[15] and sodium
ACHTUNGTRENNUNG
tetrakis
AHCTUNGTRENNUNG
cording to literature procedures. NMR spectra were recorded on a
Bruker Avance-400 spectrometer (400 (1H) and 100 MHz (13C)); chemi-
cal shifts are reported relative to the residual solvent peak (CHCl3: d=
7.26 ppm, CDCl3: d=77.23 ppm). Standard pulse programs, provided by
the manufacturer, were used for 2D COSY-45, ROESY, HMBC, and
HSQC experiments. Monte Carlo conformational searches (10000 steps)
were performed with MacroModel-9/Maestro-4.1 program using CHCl3
as the solvent (GB/SA model).
Compound 3: K2CO3 (0.88 g, 6.36 mmol) was added, under stirring, to a
solution of derivative 2 (0.41 g, 0.32 mmol) in dry CH3CN (90 mL). The
mixture was kept at reflux, under an atmosphere of argon, and after 2 h,
tert-butylbromoacetate (1.24 g, 0.94 mL, 6.36 mmol) was added. The reac-
tion was stirred at reflux for 12 h under an atmosphere of argon and the
solvent was removed under reduced pressure. The residue was dissolved
in CH2Cl2 and washed with H2O (3ꢃ50 mL). The organic layer was dried
over Na2SO4, filtered, and the solvent was removed under reduced pres-
sure. The crude product was subjected to flash chromatography on silica
gel using cyclohexane/ethyl acetate (90:10, v/v) as the solvent to give 3
(52%, 0.27 g). 1H NMR (CDCl3, 400 MHz, 298 K): d=0.70, (s, 18H; -C-
A
R
ACHTUNGTRENNUNG
A
R
ACHTUNGTRENNUNG
-OCH2CH2OCH2CH2O-), 2.86 (m, 2H; -OCH2CH2OCH2CH2O-), 3.34
(AX J=13.2 Hz, 2H; ArCH2Ar), 3.43 (AX, J=15.2 Hz, 4H; ArCH2Ar),
3.44 (brs, 2H; -OCH2COOtBu), 3.49 (AX, J=13.4 Hz, 4H; ArCH2Ar),
3.80 (m, 2H; -OCH2CH2OCH2CH2O-), 3.89 (AX, J=13.6 Hz, 4H;
ArCH2Ar), 4.08 (m, 2H; -OCH2CH2OCH2CH2O-), 4.23 (AX, J=
13.6 Hz, 4H; ArCH2Ar), 4.32 (m, 4H; -OCH2CH2OCH2CH2O-), 4.46
(AB, J=15.2 Hz, 4H; -OCH2COOtBu), 4.47 (AB, J=15.2 Hz, 4H;
-OCH2COOtBu), 4.58 (AX, J=13.4 Hz, 4H; ArCH2Ar), 4.62 (AX, J=
15.2 Hz, 4H; ArCH2Ar), 5.07 (AX, J=13.2 Hz, 2H; ArCH2Ar), 6.36
(brs, 2H; ArH), 6.70 (brs, 2H; ArH), 6.82 (brs, 2H; ArH), 7.10 (d, J=
2.4 Hz, 2H; ArH), 7.21 (s, 2H; ArH), 7.26 (brs, 2H; ArH), 7.32 ppm (d,
J=2.4 Hz, 2H; ArH); 13C NMR (CDCl3, 100 MHz, 298 K): d=28.1 (t,
Figure 15. 1H NMR spectra (CDCl3, 400 MHz, 298 K) of a) 3, b) 3 after
the addition of 0.5 equivalents of KTFPB, and c) 3 after the addition of
1 equivalent of KTFPB.
Conclusion
The first example of a completely rigidified calix[7]arene de-
rivative 3 has been synthesized; this showed interesting rec-
ognition abilities toward cationic guests. By using previously
reported chemical shift surface maps, we predicted that the
conformation adopted by 3 was similar to the X-ray struc-
ture reported for a the known p-tert-butylcalix[7]arene hep-
tacarboxylic acid (4). This prediction was fully confirmed by
single-crystal X-ray analysis of 3. Interestingly, unprecedent-
ed endo-cavity complexation by a calix[7]arene host of iso-
ArCH2), 28.3 (q, -OCH2COOC
29.8 (t, ArCH2), 30.2 (t, ArCH2), 30.8 (q, -C
(q, -C(CH3)3), 31.7 (q, -C(CH3)3), 31.8 (q, -C
34.4 (s, -C(CH3)3, 6C), 67.9 (t, -OCH2CH2OCH2CH2O-), 69.2 (t,
-OCH2COOC(CH3)3), 70.7 (t, -OCH2COOC(CH3)3), 71.4 (t,
-OCH2CH2OCH2CH2O-), 74.0 (t, -OCH2CH2OCH2CH2O-), 74.4 (t,
-OCH2CH2OCH2CH2O-), 81.9 (s, -OCH2COOC(CH3)3, 3C), 123.3 (d,
CArH), 123.5 (d, CArH), 124.2 (d, CArH), 125.8 (d, CArH), 127.7 (d, CArH),
127.9 (d, CArH), 128.4 (d, CArH), 131.6 (s, CArCH2), 132.4 (s, CArCH2),
132.8 (s, CArCH2), 131.6 (s, CArCH2), 133.7 (s, CArCH2), 134.2 (s, CArCH2,
G
ACHTUNGTRENNUNG(CH3)3),
AHCTUNGTRENNUNG
E
T
N
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
G
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
2C), 134.8 (s, CArCH2), 146.0 (s, CArCAHCNTURGENN(UG CH3)3, 4C), 146.4 (s, CArCACHTUNGTRENNUNG(CH3)3,
+
+
meric linear nBuNH3
and branched sBuNH3
and
3C), 151.6 (s, CArO, 3C), 152.4 (s, CArO), 154.7 (s, CArO), 168.0 (s, C=O),
168.4 ppm (s, C=O); ESI+-MS: m/z 1617 [M+H+]; elemental analysis
calcd (%) for C103H140O15: C 76.45, H 8.72; found: C 76.55, H 8.62.
+
tBuNH3 cations was observed. Surprisingly, calix[7]arene
derivative 3 showed a comparable affinity for branched
+
+
X-ray crystallography: The single-crystal X-ray diffraction measurements
were collected on an XCS-Huber four-circle diffractometer (University
of Rome ꢄꢄLa Sapienza’’, Department of Chemistry,) using graphite-mon-
ochromatized MoKa radiation (0.71073 ꢂ). The crystal was sealed with its
mother liquid in Lindermann capillaries to avoid efflorescence. The cell
parameters were refined by least squares from the angular positions of 50
reflections; the data were measured at room temperature for 0.858<2q<
20.818 using a q/2q scan technique and processed to yield I and s(I)
values corrected for Lorentz, polarization, and shape anisotropy effects;
no decay effect was observed. A total of 5435 independent reflections
with Fo >3s(Fo) were processed by the direct methods, which provided
the complete structure in the P21/a space group. All non-hydrogen atoms
were refined by a full-matrix least-squares method with anisotropic ther-
mal parameters, except for three carbon atoms refined with isotropic
thermal factors due to disorder that could not be modeled. Due to the
low-quality data mentioned, we enhanced the observed reflections/pa-
tBuNH3 and linear nBuNH3 guests. In addition, the bind-
ing ability of 3 toward alkali-metal cations was also evi-
denced.
Experimental Section
General: ESI+-MS measurements were performed on a Micromass Bio-
Q triple quadrupole mass spectrometer equipped with an electrospray
ion source, using a mixture of H2O/CH3CN (1:1) and 5% HCOOH as
the solvent. Flash chromatography was performed on Merck silica gel
(60, 40–63 mm). All chemicals were of reagent grade and were used with-
out further purification. Anhydrous solvents were purchased from Al-
drich. When necessary, compounds were dried in vacuo over CaCl2. Re-
Chem. Eur. J. 2012, 18, 1219 – 1230
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
1227

C. Gaeta et al.
+
rameters ratio refinement using constraints by setting the benzene rings
as rigid bodies; the final R value was 0.10. The hydrogen atoms were in-
nBuNH3 ꢁ3 complex: Compound 3 (0.002 g, 1.23ꢃ10ꢀ3 mmol) was dis-
solved in CDCl3 (0.4 mL; 3.0ꢃ10ꢀ3 m solution). Then, a solution of n-bu-
ꢀ
tylammonium tetrakisACTHNUTRGNE[NUG 3,5-bis(trifluoromethyl)phenyl]borate salt in
cluded in geometric positions (C H=0.96 ꢂ) and given thermal parame-
CDCl3 (1.23ꢃ10ꢀ3 mmol, 6.1ꢃ10ꢀ3 m) was added and the mixture was
stirred for 15 min at room temperature. Then, the solution was trans-
ferred to an NMR tube for 1D and 2D NMR spectra acquisition.
1H NMR (CDCl3, 400 MHz, 298 K): d=ꢀ2.10 (brs, 3H; (CH2)e], ꢀ0.31
(m, 2H; (CH2)g), ꢀ0.07 (m, 2H, (CH2)b), 0.21 (m, 2H, (CH2)a), 0.85 (s,
ters equivalent to 1.3 times those of the parent atom and allowed to ride
on it. The final difference Fourier map, with a root-mean-square devia-
tion of electron density of 0.06 eꢂꢀ3 showed minimum and maximum
values of ꢀ0.47 and 0.44, respectively. Calculations were performed by
using the XCS data collection program,[33] DARX2002 data reduction
program, and ꢄꢄIl milione’ꢅ structure determination and refinement pack-
age.[34] Full details are given in Table 3.
18H; -C
N
N
ACHTUGNTREN(UNNG CH3)3), 1.49 (s,
18H; -OC
N
ACHTUNGTRENNUNG
ArCH2Ar), 3.56 (AX, J=12.4 Hz, 2H; ArCH2Ar), 3.58 (AX, J=12.8 Hz,
4H; ArCH2Ar), 3.68 (brs, 4H; -OCH2CH2OCH2CH2O-), 3.89 (AB, J=
16.9 Hz, 2H; -OCH2COOtBu), 3.70 (AB, J=16.9 Hz, 2H;
-OCH2COOtBu), 3.93 (AX, J=13.2 Hz, 4H; ArCH2Ar), 3.99 (t, J=
8.8 Hz, 4H; -OCH2CH2OCH2CH2O-), 4.24 (AX, J=14.8 Hz, 4H;
ArCH2Ar), 4.30–4.50 (overlapped, 8H), 4.35 (AX, J=13.2 Hz, 4H;
ArCH2Ar), 4.41 (AX, J=12.8 Hz, 4H; ArCH2Ar), 4.44 (AB, J=17.3 Hz,
4H; -OCH2COOtBu), 4.63 (AB, J=17.3 Hz, 4H; -OCH2COOtBu), 4.93
(brs; +NH3), 5.25 (AX, J=12.4 Hz, 2H; ArCH2Ar), 6.27 (brs, 2H;
ArH), 6.70 (brs, 2H; ArH), 7.05 (brs, 2H; ArH), 7.38–7.41 (overlapped,
8H; ArH), 7.48 (s, 4H; ArHTFPBꢀ), 7.67 ppm (s, 8H; ArHTFPBꢀ); ESI+
-MS: m/z: 1690 [nBuNH3ꢁ3]+.
Table 3. Data collection parameters for compound 3.
3
formula
Mr
C103H140O15
1618.26
a [ꢂ]
b [ꢂ]
c [ꢂ]
a [8]
17.905(4)
23.354(5)
24.111(5)
90.00
b [8]
97.84(2)
90.00
9988(4)
Na+ꢁ3 complex: Compound 3 (0.002 g, 1.23ꢃ10ꢀ3 mmol) was dissolved
g [8]
V [ꢂ3]
Z
in CDCl3 (0.4 mL; 3.0ꢃ10ꢀ3 m solution). Then, a solution of sodium
4
tetrakisACHTUNTRGNE[NUG 3,5-bis(trifluoromethyl)phenyl]borate salt in CDCl3 (1.23ꢃ
10ꢀ3 mmol, 6.1ꢃ10ꢀ3 m) was added and the mixture was stirred for 15 min
at room temperature. Then, the solution was transferred to an NMR tube
for 1D and 2D NMR spectra acquisition. 1H NMR (CDCl3, 400 MHz,
crystal system
monoclinic
1.073
1calcd [gcmꢀ3
]
F
N
3496
]
0.070
298 K): d=0.95 (s, 9H,; -C
-C(CH3)3), 1.38 (s, 18H; -C
(s, 9H, 18H; -OC(CH3)3), 1.88 (m, 2H; -OCH2CH2OCH2CH2O-), 2.34
A
ACHTUNGTRENNUNG
h,k,l min/max
resolution range [ꢂ]
reflns collected
0/17, 0/23, ꢀ23/23
1.000–23.886
10302
A
R
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
(m, 2H; -OCH2CH2OCH2CH2O-), 2.63 (m, 2H; -OCH2CH2OCH2CH2O-
), 2.88 (m, 2H; -OCH2CH2OCH2CH2O-), 3.32 (AX, J=15.2 Hz, 2H;
ArCH2Ar), 3.54 (AX, J=14.4 Hz, 4H; ArCH2Ar), 3.73 (m, 2H;
independent reflns [Rint
parameters refined
]
6195 [0.070]
754
0.0084, 1.0000, 0.0039
a,b,c, in the w=1.0/a+bFo+cFo2
weighting scheme
R, wR
-OCH2CH2OCH2CH2O-),
-OCH2CH2OCH2CH2O-),
4.02
4.18–4.31
(brt,
J=8.1 Hz,
(overlapped,
2H;
4H;
0.100, 0.146
0.885
0.001/0.000
-OCH2CH2OCH2CH2O-), 4.20 (AX, J=14.4 Hz, 4H; ArCH2Ar), 4.31 (s,
4H; -OCH2COOtBu), 4.44 (s, 2H; -OCH2COOtBu), 4.49 (AX, J=
14.4 Hz, 4H; ArCH2Ar), 5.09 (AX, J=15.2 Hz, 2H; ArCH2Ar), 6.58
(brs, 2H; ArH), 6.96 (brs, 2H; ArH), 7.02 (brs, 2H; ArH), 7.17 (brs,
2H; ArH), 7.20 (brs, 2H; ArH), 7.25 (brs, 2H; ArH), 7.28 (brs, 2H;
ArH), 7.48 (s, 4H; ArHTFPBꢀ), 7.67 ppm (s, 8H; ArHTFPBꢀ); 13C NMR
goodness of fit, S
max mean shift/error
(CDCl3, 100 MHz, 298 K): d=28.1 (q, -C
(t, ArCH2), 28.5 (t, ArCH2), 30.2 (t, ArCH2), 31.3 (q, -C
-C(CH3)3, 12C), 31.7 (q, -C(CH3)3), 32.2 (t, ArCH2), 34.3 (s, -C
4C), 34.5 (s, -C(CH3)3, 6C), 70.1, 70.6, 71.1, 71.3, 73.6, 74.0 (t, OCH2),
84.5, 84.6 (s, OC
(CH3)3), 117.6 (d, CArHTFPB), 123.8 (d, CArH), 125.4 (d,
CArH), 125.5 (d, CArH), 126.2 (d, CArH), 126.9 (d, CArH), 128.6 (d, CArH),
128.8 (d, CArH), 135.1 (d, CArHTFPB), 130.5 (s, CArCH2), 131.9 (s, CArCH2),
132.2 (s, CArCH2), 132.9 (s, CArCH2), 133.1 (s, CArCH2), 134.2 (s, CArCH2),
G
ACHTUGNTRNEN(UNG CH3)3), 28.4
CCDC-820352 contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
AHCTUNGTRENNUNG
G
G
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
General procedure for the synthesis of the ammonium TFPB salts: A so-
lution of NaTFPB[16b] (0.67 mmol) in dry methanol (2 mL) was added to
the solution of appropriate (n-butyl, sec-butyl, or isopropylammonium)
chloride salts (0.52 mmol) in dry methanol (3 mL). The resulting solution
was stirred overnight. After removing methanol by evaporation, deion-
ized water was added, and the brown solid was filtered off and dried
under vacuum for 24–48 h.
134.6 (s, CArCH2), 135.0 (s, CArCF3, 8C), 146.4 (s, CAr
CACHTUNGTRENNUNG
CAr (CH3)3), 148.1 (s, CAr (CH3)3), 148.6 (s, CArCACHTUGNRTENNGUN
C
N
C
U
CArO), 150.7 (s, CArO), 151.9 (s, CArO), 153.7 (s, CArO), 170.5 ppm (s, C=
O, 3C); ESI+ MS: m/z: 1639 [Naꢁ3]+.
ACHTUNGTRENNUNG[tBuNH3]ACHTUNGTRENNUNG
[TFPB]: 1H NMR ([D6]DMSO, 400 MHz, 298 K): d=1.21 (s,
Determination of association constant values by quantitative 1H NMR
spectroscopy analysis: The samples were prepared by dissolving 3 (1.24ꢃ
10ꢀ3 mmol) and the appropriate alkylammonium guest 5a–d (1.24ꢃ
9H; (CH3)3CNH3+), 7.70 ppm (brs, 12H; ArHTFPB); 13C NMR
([D6]DMSO, 100 MHz, 298 K): d=27.0, 51.0, 117,6, 119.9, 122.6,
125.4,128.1, 128.3, 128.6, 129.0, 134.1, 160.3, 160.7, 161.3, 161.7 ppm.
10ꢀ3 mmol) in CDCl3 (0.5 mL) containing toluene (1 mL; d=0.87 gmLꢀ1
,
A
ACHTUNGTRENNUNG
0.19m) as an internal standard. The complex concentration was evaluated
by integration of the 1H NMR signals of the toluene CH3 group versus
the shielded signals at negative values of chemical shift of the guest mol-
ecules. Equation (1)[35] was used to obtain the number of moles of the
complex:
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
([D6]DMSO, 100 MHz, 298 K): d=9.61, 17.6, 27.1, 48.3, 117.6, 121.9,
126.3, 127.9, 128.8, 129.3, 130.6, 134.1, 159.9, 160.7, 161.5, 166.3 ppm;
ACHTUNGTRENNUNG[iPrNH3]ACHTUNGTRENNUNG
[TFPB]: 1H NMR (CD3OD 400 MHz, 298 K): d=1.30 (d, J=
Ga Fa Nb Ma
Gb Fb Na Mb
ð1Þ
¼
ꢂ
ꢂ
+
6.4 Hz, 6H; (CH3)2CHNH3+), 3.41 (sept, J=6.4 Hz, 1H; (CH3)2CHNH3
), 7.71 ppm (brs, 12H; ArHTFPB); 13C NMR ([D6]DMSO, 100 MHz,
298 K): d=20.3, 43.1, 117.5, 122.7, 125.4, 128.1, 128.3, 128.6, 134.1, 160.3,
160.8, 161.3, 161.8 ppm.
in which Ga is the number of grams of toluene; Gb is the number of
grams of complex; Fa and Fb are the areas of the signals of the toluene
1228
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ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 1219 – 1230

A Conformationally Blocked Calix[7]arene Derivative
FULL PAPER
CH3 group and shielded signal of the guest, respectively; Na and Nb are
the numbers of nuclei that cause the signals (Na for toluene=3; Nb for
the guest); and Ma and Mb are the molecular masses of toluene and com-
plex, respectively.
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Neri, Mini-Rev. Org. Chem. 2004, 1, 219–231.
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1534.
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3391.
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797.
Acknowledgements
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We thank Dr. Patrizia Iannece (Dipartimento di Chimica, Universitꢀ di
Salerno) for ESI-MS measurements.
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Received: July 15, 2011
Published online: December 16, 2011
1230
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Chem. Eur. J. 2012, 18, 1219 – 1230