A general method for obtaining calix[4]arene derivatives in the 1,2-alternate conformation

Article abstract of DOI:10.1016/j.tet.2016.08.028

The 1,2-alternate conformation, so far the least accessible atropisomer of calix[4]arene, is now easily available on a gram scale. The entire synthetic sequence consists of only two steps—(a) proximal dialkylation (R¹-I, NaH/DMF), and (b) another subsequent dialkylation (R²-I, Me₃SiOK/THF). The selection of appropriate base/solvent combinations in both stages was the key prerequisite for the successful preparation of the 1,2-alternate conformers, which are available without the use of any protecting groups.

Full text of DOI:10.1016/j.tet.2016.08.028

Tetrahedron 72 (2016) 6348e6355
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A general method for obtaining calix[4]arene derivatives in the
1,2-alternate conformation
a
b
a,
*
ꢀ
ꢀ
Petr Slavík , Vaclav Eigner , Pavel Lhotak
a
ꢀ
Department of Organic Chemistry, University of Chemistry and Technology, Prague (UCT), Technicka 5, 166 28 Prague 6, Czech Republic
Department of Solid State Chemistry, University of Chemistry and Technology, Prague (UCT), Technicka 5, 166 28 Prague 6, Czech Republic
b
ꢀ
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 May 2016
Received in revised form 28 July 2016
Accepted 9 August 2016
Available online 13 August 2016
The 1,2-alternate conformation, so far the least accessible atropisomer of calix[4]arene, is now easily
available on a gram scale. The entire synthetic sequence consists of only two stepsd(a) proximal dia-
lkylation (R1-I, NaH/DMF), and (b) another subsequent dialkylation (R2-I, Me3SiOK/THF). The selection of
appropriate base/solvent combinations in both stages was the key prerequisite for the successful prep-
aration of the 1,2-alternate conformers, which are available without the use of any protecting groups.
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Calixarene
Conformation
Alkylation
1,2-Alternate
Partial cone
Conformational mobility
1. Introduction
supramolecular systems.2 Unfortunately, until recently, a broader
application of the 1,2-alternates has been hindered by our limited
Calix[n]arenes1 represent highly versatile macrocyclic com-
pounds as can be demonstrated by their widespread applications as
building blocks and/or molecular scaffolds in supramolecular
chemistry. The simple preparation of these compounds, almost
limitless freedom in their derivatization and excellent complexa-
tion abilities make calixarenes a highly desirable choice in the
design of new receptors. Probably, the most attractive feature of
these macrocycles is the tuneable 3D shape of their molecules,
which is extremely useful in the design and synthesis of novel re-
ceptors. Thus, the introduction of bulky substituents (R¼propyl or
any higher alkyl group) at the phenolic subunits of calix[4]arene
leads to the immobilisation of the macrocyclic skeleton into four
basic conformations (atropisomers) called cone, partial cone, 1,2-
alternate and 1,3-alternate (Scheme 1).
knowledge of their chemistry, in particular, by the lack of a general
synthetic methodology. Thus, the 1,2-alternate conformation can be
prepared using rather unusual alkylation agents, like 2-
pyridylmethyl chloride (a
-picolyl chloride),3 or by the formation
of short proximal bridges using oligoethylene glycol ditosylates.4
Another, even rarer approach, is based on the steric
The chemistry of the cone, partial cone and 1,3-alternate con-
formations has recently been well established, and all three atro-
pisomers are accessible on
a multigram scale via direct
stereoselective alkylation of parent calix[4]arenes. Consequently,
the three conformations are frequently used in the design of novel
receptors, self-assemblies or more sophisticated calixarene-based
Scheme 1. The four basic conformers (atropisomers) of calix[4]arene.
* Corresponding author. Fax: þ420 220 444 288; e-mail address: lhotakp@vscht.cz
ꢀ
(P. Lhotak).
http://dx.doi.org/10.1016/j.tet.2016.08.028
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

P. Slavík et al. / Tetrahedron 72 (2016) 6348e6355
6349
destabilization of the cone conformation of unsubstituted calix[4]
arene by introducing substituents on the methylene bridges.5
In our previous work6 we showed that calix[4]arenes immobi-
lised in the 1,2-alternate conformation can be prepared on a multi-
gram scale using a simple dialkylation/dialkylation procedure.6
Thus, alkylation of starting p-tert-butylcalixarene with propyl
bromide/NaOH in a DMSOꢀH2O mixture gave a proximally dipro-
pylated derivative, which could be subsequently alkylated to give
the corresponding 1,2-alternate. Surprisingly, this procedure did
not work with de-tert-butylated calixarene 1 leaving the corre-
sponding 1,2-alternates unavailable. In this paper we report on
a simple and general synthetic procedure that selectively provides
the 1,2-alternate derivatives with unsubstituted upper rims, hence,
paving the way for their applications in supramolecular chemistry.
Fig. 1. X-ray structure of compound 2 showing the interactions of the CH2Cl2 molecule
with the cavity, a) side view, b) same from above.
propyne) led to the isolation of compound 4 (44% yield) with free
propargyl groups.
2. Results and discussion
The structure of the dialkylated compounds was confirmed by
1H NMR spectra and reflected the expected symmetry of these
compounds. Thus, the presence of three well resolved doublets at
4.61 ppm, 4.50 ppm and 4.36 ppm in a 1:2:1 ratio with typical
geminal coupling constants (J¼12.5e13.3 Hz) for the axial protons
of the methylene bridges clearly supported that compound 4
(400 MHz, CDCl3, 293 K) was proximally alkylated and adopted the
cone conformation.
The synthesis starts with a proximal dialkylation of starting calix
[4]arene 1 (Scheme 2). We employed a subtle modification of the
reaction conditions7 recently described for the preparation of
compound 2. Thus, calixarene 1 was dissolved in dry DMF and
reacted with NaH (3.6 equiv), stirred for 15 min at room tempera-
ture and then treated with 1-iodopropane (2.15 equiv) as the
alkylating agent. The reaction is surprisingly regioselective and
proximally disubstituted isomer 2 was obtained in 54% yield using
just simple precipitation of the crude reaction product from
a MeOHeCH2Cl2 mixture (up to 5.0 g scale). This was highly desired
as easy isolation without column chromatography step is an im-
portant prerequisite for large scale synthesis.
To show the general applicability of these reaction conditions,
we carried out a similar alkylation using 1-iodobutane. The corre-
sponding proximal dibutoxy derivative 3 was isolated in 30% yield.
We mention that the same compound was already prepared by Lin
et al.8 using a very complicated procedure. Thus, the starting cal-
ixarene 1 was (i) monoalkylated, (ii) monobenzoylated into the
distal position (52% yield), (iii) monoalkylated once again, and (iv)
deprotected by hydrolysis of the benzoyl group (11% overall yield
for last two steps). Interestingly, similar direct alkylation employing
Moreover, the structure of dipropoxy derivative 2 was un-
equivocally assigned using single crystal X-ray analysis. The com-
pound crystalized in the monoclinic system, space group P21/n as
a 1:1 complex with CH2Cl2. The cavity of the calixarene is filled with
a solvent molecule (Fig. 1) with close contacts between the hy-
drogen atoms of the CH bonds (CH2Cl2) and the neighbouring ar-
omatic subunits. The distances between the hydrogen atoms and
ꢁ
ꢁ
the phenolic planes 2.397 A and 2.567 A indicated the complex is
held together by the CeHe interactions.
p
To find the most suitable conditions for the formation of the 1,2-
alternate conformation, dipropoxy derivative 2 was screened for an
optimal base/solvent/temperature combination. Obviously, sub-
sequent propylation of 2 could lead to three different conformers:
1,2-alternate 5a, partial cone 5b and cone 5c. Fortunately, all these
isomers possess well resolved signals in the aromatic region of their
a
protected propargyl bromide (3-bromo-1-(trimethylsilyl)-1-
Scheme 2. Synthesis of calix[4]arenes in the 1,2-alternate conformation.

6350
P. Slavík et al. / Tetrahedron 72 (2016) 6348e6355
1H NMR spectra allowing easy assignment of the conformations
formed, including their molar ratios in the crude products. Small
scale alkylations with 1-iodopropane (30 mg of dipropoxy com-
pound 2) were carried out using various reaction conditions com-
monly applied in calixarene chemistry (collected in Table 1). As
expected, applying standard NaH/DMF conditions (Run 1) led ex-
clusively to the cone conformation 5c, while Cs2CO3/MeCN (Run 2)
provided a high percentage of the partial cone 5c. On the other
hand, combinations of KH/DMF, K2CO3/DMF, Me3SiOK/DMF and t-
BuOK/toluene (Runs 3e4, 12) were found to be unsuitable as they
yielded complex reaction mixtures containing unreacted 2 together
with partly and fully alkylated products. Very promising results
were achieved with Me3SiOK/THF leading to a mixture of 5a and 5b
with a desirable amount of the 1,2-alternate atropisomer present-
ing in the crude products (Runs 6 and 7), similar results were also
observed for Me3SiOK/THF and t-BuOK/THF. Interestingly, Me3SiOK
or t-BuOK in benzene (Runs 10 and 11) gave an even higher molar
ratio of 5a. Unfortunately, in both cases a small amount of the cone
conformer 5c was also formed which substantially hindered iso-
lation of 5a in a pure form as the Rf values for 5a and 5c were es-
sentially identical on a silica gel column. As a result, large scale
preparation of the 1,2-alternate conformer was carried out using
Me3SiOK in THF at room temperature.
dibutyloxy 7a 1,2-alternates (both isolated in 51% yield) together
with the partial cone isomers 6b, 7b (both 41%). Applying a longer
alkyl group (using 1-hexyl iodide) led to higher selectivity for the
1,2-alternate conformer although in slightly lower overall yieldd8a
(44%), 8b (20%). As shown in Table 2, the best selectivity for the 1,2-
alternate was achieved employing propargyl bromide. This alky-
lating agent furnished 67% of 11a, while the partial cone conformer
11b was obtained in only 18% yield. In all these examples, the 1,2-
alternates possessed higher Rf values than the corresponding par-
tial cone isomers and both conformers could be easily separated
using column chromatography on silica gel. Treatment with allyl
bromide (Run 6) or benzyl bromide (Run 8) gave a corresponding
mixtures of conformations with the 1,2-alternate (10a:10b¼58:42,
12a:12b¼63:37) prevailing, but unfortunately, these mixtures
could not be efficiently separated using column chromatography on
silica gel.
The 1H NMR spectra of the resulting 1,2-alternate conformers
were fully in agreement with the expected C2h symmetry. Thus, the
pair of doublets in the 1H NMR spectrum of 6a (CDCl3) at 3.17 ppm
(J¼12.5 Hz) and 4.21 ppm (J¼12.5 Hz) represent the methylene
bridge fenced by two syn-oriented phenolic moieties (equatorial
and axial protons possessing a geminal coupling constant from the
conical fragments of the molecule). On the other hand, the singlet
at 3.91 ppm clearly showed the presence of the methylene bridge
surrounded by two identical aromatic subunits with an anti-
orientation (the 1,3-alternate segment of the molecule). Similar
structural features can be seen in all the remaining molecules
possessing the 1,2-alternate conformationde.g., two pairs of dou-
blets at 3.18, 3.19, 4.20 and 4.23 ppm for 7a indicating lower
symmetry due to the presence of two different alkyl groups (n-
propyl and n-butyl).
The structures of several 1,2-alternate products were also un-
ambiguously assigned using single crystal X-ray analysis. Com-
pounds 5a (Fig. 2a) and 7a (Fig. 2b) crystalized in the triclinic
system, space group P-1, compounds 10a (Fig. 2c) and 12a (Fig. 2d)
crystalized in the monoclinic system, space group P21/n or P21/c,
respectively, and in all cases without any solvent molecules in the
crystal lattice.
Table 1
Screening of reaction conditions for the alkylation of compound 2
Reaction conditionsa
Conformer distrib.b
Base
Solvent
Temp [ꢁC]
Time [h]
5a
5b
5c
1
2
3
4
5
6
7
8
NaH
Cs2CO3
KH
DMF
MeCN
DMF
DMF
MeCN
THF
THF
THF
THF
rt
Reflux
90
90
90
rt
Reflux
rt
Reflux
Reflux
Reflux
Reflux
24
120
120
100
120
24
24
24
24
24
0
0
90
100
10
0
c
c
c
K2CO3
Me3SiOK
Me3SiOK
Me3SiOK
KHMDS
t-BuOK
t-BuOK
Me3SiOK
t-BuOK
51
53
52
54
74
49
47
48
46
24
26
0
0
0
0
2
2
9
10
11
12
C6H6
C6H6
Toluene
24
24
72
c
a
Five equivalents of base and propyl iodide were used.
1H NMR spectrum, 400 MHz, CDCl3.
Incomplete reaction (unreacted starting compound, and/or trialkylated and
b
c
tetraalkylated products).
The results of the synthesis of 1,2-alternates on a preparative
scale are collected in Table 2. In all cases, starting calixarenes 2 or 3
were stirred with the corresponding alkylating agent (5 equiv) and
Me3SiOK as a base (5 equiv) in THF at room temperature for 1e3
days. Tetrapropoxy 1,2-alternate 5a was obtained in 51% yield ac-
companied by the partial cone isomer 5b (44%). Very similar results
were shown for tetrabutyloxy 6a and for the mixed dipropoxy
Table 2
Synthesis of the 1,2-alternate conformation
Run
Starting calix[4]arene
Alkylating agenta
Xa (yield)b
Xb (yield)b
1
2
3
4
5
6
7
8
2
3
2
2
2
2
2
2
n-Pr-I
n-Bu-I
n-Bu-I
n-Hex-I
Et-I
Allyl-Br
Propargyl-Br
Benzyl-Br
5a (51)
6a (52)
7a (52)
8a (44)
9a (53)
10a (58)c
11a (67)
12a (63)c
5b (44)
6b (41)
7b (41)
8b (20)
9b (35)
10b (42)c
11b (18)
12b (37)c
a
5 equiv. Me3SiOKþ5 equiv alkylating agent in THF, 1 day stirring at room
temperature.
b
c
Isolated yields after chromatography.
Separation failed, the ratio of conformers was assigned using the 1H NMR
Fig. 2. X-ray structures of several 1,2-alternate conformations: a) 5a, b) 7a, c) 10a, d)
12a.
spectra of crude products.

P. Slavík et al. / Tetrahedron 72 (2016) 6348e6355
6351
It is well documented1 that the presence of four propyl groups
on the lower rim of calix[4]arene leads to the immobilization of
a given conformation as the propyl groups are sufficiently bulky
substituents to hinder rotation of the phenolic subunits through
the macrocyclic cavity. To confirm the conformational mobility in
the 1,2-alternate series we prepared compounds proximally bearing
two propyl and two ethyl groups. Using our general alkylation
procedure the corresponding 1,2-alternate 9a was prepared in 53%
yield, accompanied again by the partial cone conformer 9b (35%).
Both conformations were easily separated using column chroma-
tography indicating the conformations are stable on a laboratory
time scale at ambient temperature. Indeed, the 1H NMR spectra of
9a or 9b in CDCl3 at 25 ꢁC did not reveal any conformational in-
terconversion of these isomers. On the other hand, heating of 9a to
130 ꢁC for 2 days (in CDCl2eCDCl2) led to a mixture of all three
theoretically possible isomers (showing that, obviously, only Et
groups can rotate through the annulus). In the independent ex-
periment 9b gave the identical mixture of isomers indicating that
a thermodynamic equilibrium was achieved (Fig. 3). Integration of
the resulting mixture showed the presence of the partial cone (56%),
cone (28%), and 1,2-alternate (16%) conformers reflecting the rela-
tive thermodynamic stabilities of the corresponding conformations
under the given conditions.
N,N’-dimethylformamide used for the reactions were dried with
CaH2 or MgSO4 and stored over molecular sieves. THF was dried
using the sodium/benzophenone method. Melting points were
measured on Heiztisch Mikroskop-Polytherm A (Wagner & Munz,
Germany) and were not corrected. The IR spectra were measured
on an FTIR spectrometer Nicolet 740 in KBr transmission mode.
NMR spectra were recorded on spectrometers Varian Gemini 300
(1H: 300 MHz, 13C: 75 MHz) and Agilent 400-MR DDR2 (1H:
400 MHz, 13C: 100 MHz). Chemical shifts (
d) are expressed in parts
per million and are referenced to the residual peak of solvent or
TMS as an internal standard, coupling constants (J) are in hertz. The
mass analyses were performed using ESI on an FT-MS (LTQ Orbitrap
Velos) spectrometer. Purity of the substances and courses of the
reactions were monitored by thin layer chromatography (TLC) us-
ing silica gel 60 F254 on aluminium-backed sheets (Merck) and
analyzed at 254 or 365 nm. Preparative TLC chromatography was
carried out on a Chromatotron (Harrison Research) with plates
covered by Silica gel 60 GF254 (Merck).
4.2. General procedure for proximal dialkylation
Calixarene 1 was dissolved in dry DMF and NaH (3.6 equiv) was
carefully added. The solution was stirred at room temperature for
15 min. Then, the alkylating agent (2.15 equiv) was added dropwise
and the resulting solution was stirred for 2 h at room temperature.
The reaction mixture was carefully quenched by aqueous 1 M HCl
and to this mixture dichloromethane was added. The organic layer
was separated, washed with water and dried over magnesium
sulfate. Solvent was removed under reduced pressure to yield the
crude product which was purified by precipitation from a CH2Cl2/
MeOH mixture. Depending on the scale of the reaction, this step
can be replaced by column chromatography or by preparative thin
layer chromatography on silica gel.
4.2.1. Synthesis of 25,26-dihydroxy-27,28-dipropoxycalix[4]arene
(2). Compound 2 was prepared according to the general procedure
for proximal alkylation using 1.06 g (2.50 mmol) of calixarene 1,
0.36 g (9.01 mmol) of NaH (60% dispersion in mineral oil) and
0.53 ml (5.38 mmol) of 1-iodopropane. Compound 2 (0.68 g, 54%)
was obtained as a white powder by simple precipitation of the
crude product from a MeOHeCH2Cl2 mixture. The analytical data
was in agreement with previously published data.7
1H NMR (400 MHz, CDCl3, 293 K)
d (ppm): 8.99 (s, 2H, AreOH),
7.06 (dd, 2H, J¼7.8, 1.6 Hz, AreH), 7.01e6.96 (m, 6H, AreH), 6.79 (t,
2H, J¼7.4 Hz, AreH), 6.63 (t, 2H, J¼7.8 Hz, AreH), 4.55 (d, 1H,
J¼12.5 Hz, AreCH2eAr), 4.34 (d, 3H, J¼12.9 Hz, AreCH2eAr),
4.13e4.05 (m, 2H, OeCH2), 3.94e3.86 (m, 2H, OeCH2), 3.41 (d, 1H,
J¼12.5 Hz, AreCH2eAr), 3.40 (d, 2H, J¼12.9 Hz, AreCH2eAr), 3.36
(d, 1H, J¼13.3 Hz, AreCH2eAr), 2.22e2.06 (m, 4H, OeCH2eCH2),
1.16 (t, 6H, J¼7.4 Hz, OeCH2eCH2eCH3).
Fig. 3. Aromatic region of the 1H NMR spectra of: a) pure 9b, c) pure 9a, b) spectrum
obtained after 47 h heating of 9a to 130 ꢁC (400 MHz, CDCl2eCDCl2), - partial cone, ,
1,2-alternate, : cone.
3. Conclusions
4.2.2. Synthesis of 25,26-dihydroxy-27,28-dibutoxycalix[4]arene
(3). Compound 3 was prepared according to the general procedure
for proximal alkylation by reacting 1.05 g (2.50 mmol) of calixarene
1, 0.36 g (9.01 mmol) of NaH (60% dispersion in mineral oil) and
0.71 ml (5.3 mmol) of 1-iodobutane. Compound 3 (0.38 g, 30%) as
a white powder was obtained by simple precipitation of the crude
product from a MeOHeCH2Cl2 mixture. Another portion of product
(15% yield) can be obtained by column chromatography of the
mother liquor remaining after the precipitation. The analytical data
was in agreement with previously published data.8
In conclusion, the upper rim unsubstituted calix[4]arenes
immobilised in the 1,2-alternate conformation are now easily ac-
cessible using a proximal dialkylation/dialkylation strategy. Careful
selection of the appropriate base/solvent combination in each step
enables the synthesis of the 1,2-alternates on a gram scale. This
paves the way for potential applications of this least accessible
conformation of calix[4]arene in supramolecular chemistry.
4. Experimental
4.1. General
1H NMR (400 MHz, CDCl3, 293 K)
d (ppm): 9.00 (s, 2H, AreOH),
7.15e7.06 (m, 2H, AreH), 7.06e6.98 (m, 6H, AreH), 6.83 (t, 2H,
J¼7.4 Hz, AreH), 6.67 (t, 2H, J¼7.4 Hz, AreH), 4.59 (d, 1H, J¼12.1 Hz,
AreCH2eAr), 4.45e4.36 (m, 3H, AreCH2eAr), 4.20e4.12 (m, 2H,
OeCH2), 4.03e3.94 (m, 2H, OeCH2), 3.49e3.36 (m, 4H, AreCH2eAr),
All chemicals were purchased from commercial sources and
used without further purification. 1,2-Dichloroethane, CH2Cl2 and

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P. Slavík et al. / Tetrahedron 72 (2016) 6348e6355
2.27e2.02 (m, 4H, OeCH2eCH2), 1.74e1.56 (m, 4H, OeCH2e-
CH2eCH2), 1.12 (t, 6H, J¼7.4 Hz, OeCH2eCH2eCH2eCH3). 13C NMR
general procedure using 0.10 g (0.19 mmol) of calixarene 3, 0.12 g
(0.94 mmol) of potassium trimethylsilanolate (90% purity), and
0.13 ml (0.94 mmol) of 1-iodobutane. The crude reaction mixture
was purified by preparative TLC on silica gel (hexane:CH2Cl2 3:2, v/
v) to give the title compounds 6a (0.064 g, 52%, white powder) and
6b (0.050 g, 41%, white powder).
(100 MHz, CDCl3, 293 K) d (ppm): 153.5,151.2,134.7,134.2,129.4,129.1
(2ꢂ),128.8 (2ꢂ),128.0,124.8,120.6,76.7, 32.1, 32.0,31.8,30.0,19.3,14.1.
4.2.3. Synthesis of 25,26-dihydroxy-27,28-dipropargyloxycalix[4]
arene (4). Compound 4 was prepared according to the general
procedure for proximal alkylation using 0.53 g (1.26 mmol) of cal-
ixarene 1, 0.18 g (4.52 mmol) of NaH (60% dispersion in mineral oil)
and 0.44 ml (2.7 mmol) of 3-bromo-1-(trimethylsilyl)-1-propyne.
After the workup, the unprotected title compound was obtained
(0.28 g, 44%) as a white powder using preparative TLC on silica gel
(hexane:CH2Cl2 1:2, v/v). Mp 166e167 ꢁC. 1H NMR (400 MHz, CDCl3,
4.3.2.1. Data for 1,2-alternate 6a. Mp 86.5e88 ꢁC. 1H NMR
(CDCl3, 400 MHz, 293 K)d (ppm): 7.14e7.03 (m, 8H, AreH), 6.89e6.82
(m, 4H, AreH), 4.21 (d, 2H, J¼12.5 Hz, AreCH2eAr), 3.91 (s, 4H,
AreCH2eAr), 3.47e3.34 (m, 8H, OeCH2), 3.17 (d, 2H, J¼12.5 Hz,
AreCH2eAr), 1.27e1.15 (m, 4H, OeCH2eCH2), 1.14e1.01 (m, 8H,
OeCH2eCH2eCH2),
0.93e0.78
(m,
16H,
293 K)
d
(ppm): 7.08e7.01 (m, 4H, AreH), 6.97 (d, 4H, J¼7.4 Hz,
OeCH2eCH2þOeCH2eCH2eCH2eCH3). 13C NMR (CDCl3, 100 MHz,
AreH), 6.88e6.82 (m, 2H, AreH), 6.67e6.61 (m, 2H, AreH), 4.96 (dd,
2H, J¼15.7, 2.4 Hz, OeCH2), 4.87 (dd, 2H, J¼15.7, 2.4 Hz, OeCH2), 4.61
(d, 1H, J¼12.5 Hz, AreCH2eAr), 4.50 (d, 2H, J¼13.3 Hz, AreCH2eAr),
4.36 (d, 1H, J¼13.3 Hz, AreCH2eAr), 3.47e3.36 (m, 4H, AreCH2eAr),
2.66 (t, 2H, J¼2.4 Hz, OeCH2eCeCH). 13C NMR (100 MHz, CDCl3,
293 K) d (ppm): 156.6,134.6,132.9,129.2,129.8,121.9, 72.9, 38.2, 31.7,
28.9, 19.1, 14.1. IR (KBr)
n
1457.2 cmꢀ1. HRMS-ESIþ (C44H56O4) m/z
calcd: 649.42514 [MþH]þ, 671.40708 [MþNa]þ, 687.38102 [MþK]þ,
found: 649.42631 [MþH]þ, 671.40758 [MþNa]þ, 687.38060 [MþK]þ.
293 K)
d
(ppm): 152.7, 151.0, 134.8 (2ꢂ), 129.4, 129.3, 129.1, 129.0,
4.3.2.2. Data for partial cone 6b. Mp 116e118 ꢁC. 1H NMR
128.8, 128.2, 125.6, 120.9, 79.2, 76.5, 62.5, 32.1, 31.9 (2ꢂ). IR (KBr)
n
(CDCl3, 400 MHz, 293 K)
d
(ppm): 7.23 (d, 2H, J¼7.3 Hz, AreH), 7.09
(cmꢀ1): 2122.7, 1462.7. HRMS-ESI (C34H28O4) m/z calcd: 501.20604
[MþH]þ, 523.18798 [MþNa]þ, 539.16192 [MþK]þ, found: 501.20611
[MþH]þ, 523.18837 [MþNa]þ, 539.16221 [MþK]þ.
(d, 2H, J¼7.3 Hz, AreH), 6.97e6.80 (m, 4H, AreH), 6.44 (t, 2H,
J¼7.6 Hz, AreH), 6.26 (dd, 2H, J¼7.6, 1.8 Hz, AreH), 4.07 (d, 2H,
J¼13.2 Hz, AreCH2eAr), 3.84e3.74 (m, 4H, OeCH2), 3.65 (s, 4H,
AreCH2eAr), 3.64e3.52 (m, 2H, OeCH2), 3.40e3.30 (m, 2H,
OeCH2), 3.05 (d, 2H, J¼13.5 Hz, AreCH2eAr), 1.97e1.78 (m, 6H,
CH2), 1.64e1.36 (m, 6H, CH2), 1.20e1.09 (m, 2H, eCH2), 1.07e0.97
(m,12H, OeCH2eCH2eCH2eCH3). 13C NMR (CDCl3, 100 MHz, 293 K)
4.3. General procedure for the synthesis of calix[4]arenes in
the 1,2-alternate conformation
Proximally dialkylated calix[4]arene was dissolved in dry THF
and stirred at room temperature. To this solution potassium tri-
methylsilanolate (5 equiv, 90% purity) was added and stirred for
another 30 min. The alkylating agent (5 equiv) was then added and
the mixture was stirred at room temperature for 1e3 days. The
course of reaction was monitored by TLC. After disappearance of the
starting compound aqueous 1 M HCl was added, and the mixture
was extracted with CH2Cl2. The organic layer was washed with
water and dried over MgSO4. The solvent was removed under re-
duced pressure to yield the crude product which was purified by
preparative chromatography to separate the conformers.
d
(ppm): 157.5, 157.2, 155.6, 137.0, 133.9, 133.4, 132.1, 130.3, 129.3,
128.9, 128.3, 122.0 (2ꢂ), 121.4, 74.1, 74.0, 72.9, 35.8, 33.0, 32.8, 31.0,
30.5, 19.6, 19.4, 18.9, 14.3, 14.2, 14.0. IR (KBr)
n
1454.2 cmꢀ1. HRMS-
ESIþ (C44H56O4) m/z calcd: 666.45169 [MþNH4]þ, 671.40708
[MþNa]þ, 687.38102 [MþK]þ, found: 666.45251 [MþNH4]þ,
671.40752 [MþNa]þ, 687.38065 [MþK]þ.
4.3.3. Synthesis of 25,26-dipropoxy-27,28-di-butoxycalix[4]arene-
1,2-alt (7a) and paco (7b). Compound 7a was prepared according
to the general procedure using 0.11 g (0.21 mmol)of calixarene 2,
0.13 g (1.04 mmol) of potassium trimethylsilanolate (90% purity),
and 0.14 ml (1.04 mmol) of 1-iodobutane. The crude reaction
mixture was purified by preparative TLC on silica gel (hexane:
CH2Cl2 2:1, v/v) to give the title compounds 7a (0.067 g, 52%, white
powder) and 7b (0.053 g, 41%, white powder).
4.3.1. Synthesis of 25,26,27,28-tetrapropoxy-calix[4]arenes-1,2-alt
(5a) and paco (5b). Compound 5a was prepared according to the
general procedure using 0.31 g (0.62 mmol) of calixarene 2, 0.61 g
(3.08 mmol) of potassium trimethylsilanolate (90% purity), and
0.30 ml (3.08 mmol) of 1-iodopropane. The crude reaction mixture
was purified by column chromatography on silica gel (hexane:
CH2Cl2 5:1, v/v) to give the title compounds 5a (0.19 g, 51%, white
powder) and 5b (0.16 g, 44%, white powder).
4.3.3.1. Data for 1,2-alternate 7a. Mp 86e87 ꢁC. 1H NMR
(CDCl3, 400 MHz, 293 K)
d (ppm): 7.15e7.03 (m, 8H, AreH),
6.90e6.82 (m, 4H, AreH), 4.23 (d, 1H, J¼12.5 Hz, AreCH2eAr), 4.20
(d, 1H, J¼12.5 Hz, AreCH2eAr), 3.91 (s, 4H, AreCH2eAr), 3.46e3.34
(m, 8H, OeCH2), 3.19 (d, 1H, J¼12.5 Hz, AreCH2eAr), 3.18 (d, 1H,
J¼12.5 Hz, AreCH2eAr), 1.31e1.16 (m, 4H), 1.15e1.03 (m, 4H),
1.03e0.93 (m, 2H) 0.89e0.76 (m, 2H), 0.84 (t, 6H, J¼7.4 Hz, eCH3),
0.64 (t, 6H, J¼7.4 Hz, eCH3). 13C NMR (CDCl3, 100 MHz, 293 K)
4.3.1.1. Data for 1,2-alternate 5a. Mp 140.5e142 ꢁC. 1H NMR
(CDCl3, 400 MHz, 293 K) d (ppm): 7.12e7.03 (m, 8H, AreH), 6.84 (t, 4H,
J¼7.4 Hz, AreH), 4.21 (d, 2H, J¼12.5 Hz, AreCH2eAr), 3.89 (s, 4H,
AreCH2eAr), 3.41e3.32 (m, 8H, OeCH2), 3.18 (d, 2H, J¼12.5 Hz,
AreCH2eAr), 1.30e1.15 (m, 4H, OeCH2eCH2), 1.02e0.86 (m, 4H,
OeCH2eCH2), 0.63 (t, 12H, J¼7.4 Hz, OeCH2eCH2eCH3). 13C NMR
d
(ppm): 156.6 (2ꢂ), 134.6, 134.5, 132.9 (2ꢂ), 129.3, 128.9, 128.8,
122.0,121.8 (2ꢂ), 74.7, 73.0, 38.1, 31.6, 28.9, 22.8 (2ꢂ), 19.1, 14.1, 10.3.
IR (KBr) n
1457.2 cmꢀ1. HRMS-ESIþ (C42H52O4) m/z calcd: 638.42039
(CDCl3, 100 MHz, 293 K)
121.8, 74.7, 38.1, 29.0, 22.7, 10.3. IR (KBr)
d
(ppm): 156.6, 134.6, 132.9, 129.3, 128.3,
1456.1 cmꢀ1. HRMS-ESIþ
[MþNH4]þ, 643.37578 [MþNa]þ, 659.34972 [MþK]þ, found:
n
638.42072 [MþNH4]þ, 643.37585 [MþNa]þ, 659.34930 [MþK]þ.
(C40H48O4) m/z calcd: 593.36254 [MþH]þ, 610.38909 [MþNH4]þ,
615.34448 [MþNa]þ, 631.31842 [MþK]þ, found: 593.36267 [MþH]þ,
610.38971 [MþNH4]þ, 615.34442 [MþNa]þ, 631.31775 [MþK]þ.
4.3.3.2. Data for partial cone 7b. Mp 135e138 ꢁC. 1H NMR
(CDCl3, 400 MHz, 293 K) d (ppm): 7.28e7.22 (m, 2H, AreH), 7.11 (d,
2H, J¼7.4 Hz, AreH), 6.99e6.87 (m, 4H, AreH), 6.46 (t, 2H, J¼7.4 Hz,
AreH), 6.28 (d, 2H, J¼7.8 Hz, AreH), 4.10 (d, 2H, J¼13.3 Hz, Are-
CH2eAr), 3.86e3.74 (m, 4H, OeCH2), 3.68 (s, 4H, AreCH2eAr),
3.65e3.53 (m, 2H, OeCH2), 3.37e3.29 (m, 2H, OeCH2), 3.07 (d, 2H,
J¼13.3 Hz, AreCH2eAr), 1.98e1.80 (m, 6H), 1.66e1.48 (m, 4H),
1.46e1.35 (m, 2H), 1.11 (t, 3H, J¼7.4 Hz, eCH3), 1.09e1.01 (m, 6H,
4.3.1.2. Data for partial cone 5b. The analytical data were in
agreement with previously published data.9
4.3.2. Synthesis of 25,26,27,28-tetrabutoxy-calix[4]arenes-1,2-alt
(6a) and paco (6b). Compound 6a was prepared according to

P. Slavík et al. / Tetrahedron 72 (2016) 6348e6355
6353
eCH3), 0.73 (t, 3H, J¼7.4 Hz, eCH3). 13C NMR (CDCl3, 100 MHz,
128.7, 122.0,121.8, 74.6, 68.0, 38.1, 29.1, 28.9, 22.8,14.9,10.3. IR (KBr)
293 K)
d
(ppm): 157.6, 157.1, 155.6 (2ꢂ), 137.1, 134.0, 133.4, 132.1,
n .
1456.6 cmꢀ1 HRMS-ESIþ (C38H44O4) m/z calcd: 582.35779
130.4 (2ꢂ), 129.3, 128.9, 128.3, 122.1, 121.6, 121.4, 76.1, 75.5, 74.1,
[MþNH4]þ, 587.31318 [MþNa]þ, 603.28712 [MþK]þ, found:
72.9, 35.8, 33.0, 32.8, 30.5, 23.8, 22.3, 19.6, 19.5, 14.2, 14.1, 10.9, 9.3.
582.35866 [MþNH4]þ, 587.31364 [MþNa]þ, 715.28683 [MþK]þ.
IR (KBr)
n .
1453.8 cmꢀ1 HRMS-ESIþ (C42H52O4) m/z calcd:
638.42039 [MþNH4]þ, 643.37578 [MþNa]þ, 659.34972 [MþK]þ,
found: 638.42132 [MþNH4]þ, 643.37647 [MþNa]þ, 659.34954
[MþK]þ.
4.3.5.2. Data for partial cone 9b. Mp 230e232 ꢁC. 1H NMR
(CDCl3, 400 MHz, 293 K)
d
(ppm): 7.22 (d, 2H, J¼7.4 Hz, AreH), 7.09
(d, 2H, J¼7.4 Hz, AreH), 6.96e6.86 (m, 4H, AreH), 6.49e6.41 (m,
2H, AreH), 6.34e6.26 (m, 2H, AreH), 4.08 (d, 1H, J¼12.9 Hz,
AreCH2eAr), 4.06 (d, 1H, J¼12.6 Hz, AreCH2eAr), 3.91e3.81 (m,
3H, OeCH2), 3.80e3.71 (m, 1H, OeCH2), 3.70e3.60 (m, 5H,
OeCH2þAreCH2eAr), 3.58e3.48 (m, 1H, OeCH2), 3.36e3.27 (m,
2H, OeCH2), 3.05 (dd, 2H, J¼12.9, 2.4 Hz, AreCH2eAr), 1.92e1.82
(hex, 2H, J¼7.4 Hz, OeCH2eCH2), 1.49e1.34 (m, 8H,
OeCH2eCH2þCH3), 1.09 (t, 3H, J¼7.4 Hz, CH3), 0.71 (t, 3H, J¼7.4 Hz,
4.3.4. Synthesis of 25,26-dipropoxy-27,28-dihexyloxycalix[4]arene-
1,2-alt (8a) and paco (8b). Compound 8a was prepared according
to the general procedure using 0.077 g (0.15 mmol) of calixarene 2,
0.098 g (0.76 mmol) of potassium trimethylsilanolate (90% purity),
and 0.11 ml (0.76 mmol) of 1-iodohexane. The crude reaction
mixture was purified by preparative TLC on silica gel (hex-
ane:CH2Cl2 5:1, v/v) to give the title compounds 8a (0.046 g, 44%,
white powder) and 8b (0.021 g, 20%, white powder).
CH3). 13C NMR (CDCl3, 100 MHz, 293 K)
d (ppm): 157.3, 157.1, 155.6,
155.4, 137.0 (2ꢂ), 134.1, 134.0, 133.5, 133.4, 132.2, 132.0, 130.7, 130.5,
129.6, 129.5, 128.9, 128.8, 128.3 (2ꢂ), 122.1, 121.6, 121.4, 121.3, 76.1,
75.5, 69.3, 67.7, 36.2, 36.0, 30.5, 30.4, 23.8, 22.1, 16.1, 15.9, 10.9, 9.3.
4.3.4.1. Data for 1,2-alternate 8a. Mp 58e60 ꢁC. 1H NMR
(CDCl3, 400 MHz, 293 K)
d
(ppm): 7.11e6.98 (m, 8H, AreH), 6.82 (dt,
IR (KBr) n
1452.8 cmꢀ1. HRMS-ESIþ (C38H44O4) m/z calcd: 582.35779
4H, J¼7.4, 1.2 Hz, AreH), 4.21e4.13 (m, 2H, AreCH2eAr), 3.87 (s, 4H,
AreCH2eAr), 3.41e3.29 (m, 8H, OeCH2), 3.15 (d, 1H, J¼12.5 Hz,
AreCH2eAr), 3.14 (d, 1H, J¼12.5 Hz, AreCH2eAr), 1.30e0.91 (m,
16H, CH2), 0.89 (t, 6H, J¼7.0 Hz, CH3), 0.83e0.63 (m, 4H, CH2), 0.59
[MþNH4]þ, 587.31318 [MþNa]þ, 603.28712 [MþK]þ, found:
582.35905 [MþNH4]þ, 587.31382 [MþNa]þ, 715.28693 [MþK]þ.
4.3.6. Synthesis of 25,26-diallyloxy-27,28-propoxycalix[4]arene-1,2-
alt (10a) and paco (10b). A mixture of compounds 10a and 10b
was prepared according to the general procedure using 0.035 g
(0.069 mmol) of calixarene 2, 0.044 g (0.340 mmol) of potassium
trimethylsilanolate (90% purity), and 0.030 ml (0.34 mmol) of allyl
bromide. The 1H NMR analysis of the crude product (0.040 g)
showed the presence of 10a and 10b conformers in a 58:42 ratio
(see Supplementary data). This mixture was purified by repeated
preparative thin layer chromatography on silica gel, unfortunately,
we were not able to isolate pure desired 1,2-alternate conformer
10a. However, we were able to obtain a single crystal of compound
10a (CH2Cl2/methanol) suitable for X-ray analysis.
(t, 6H, J¼7.4 Hz, CH3). 13C NMR (CDCl3, 100 MHz, 293 K)
d (ppm):
156.6, 156.5, 134.6, 134.5, 132.9, 129.2 (2ꢂ) 128.8 (2ꢂ), 121.9, 121.8,
74.6, 73.3, 38.1, 31.9, 29.4, 29.0, 28.9, 25.6, 22.8, 22.7, 14.1, 10.3. IR
(KBr)
n
1457.3 cmꢀ1. HRMS-ESIþ (C46H60O4) m/z calcd: 694.48299
[MþNH4]þ, 699.43838 [MþNa]þ, 715.41232 [MþK]þ, found:
694.48354 [MþNH4]þ, 699.43872 [MþNa]þ, 715.41178 [MþK]þ.
4.3.4.2. Data for partial cone 8b. Mp 74e76 ꢁC. 1H NMR (CDCl3,
400 MHz, 293 K)
d
(ppm): 7.23 (d, 2H, J¼7.4 Hz, AreH), 7.10 (d, 2H,
J¼7.4 Hz, AreH), 6.97e6.84 (m, 4H, AreH), 6.43 (t, 2H, J¼7.4 Hz,
AreH), 6.25 (dd, 2H, J¼7.4, 1.2 Hz, AreH), 4.08 (d, 1H, J¼13.3 Hz,
AreCH2eAr), 4.07 (d, 1H, J¼13.3 Hz, AreCH2eAr), 3.84e3.72 (m,
4H, OeCH2), 3.65 (s, 4H, AreCH2eAr), 3.62e3.51 (m, 2H, OeCH2),
3.34e3.27 (m, 2H, OeCH2), 3.05 (d, 2H, J¼13.7 Hz, AreCH2eAr),
1.97e1.79 (m, 6H, CH2), 1.60e1.32 (m, 18H, CH2), 1.10 (t, 3H,
J¼7.4 Hz, CH3), 0.98e0.92 (m, 6H, CH3), 0.91e0.75 (m, 4H, CH2),
0.71 (t, 3H, J¼7.4 Hz, CH3). 13C NMR (CDCl3, 100 MHz, 293 K)
4.3.7. Synthesis of 25,26-dipropargyloxyoxy-27,28-propoxycalix[4]
arene-1,2-alt (11a) and paco (11b). Compound 11a was prepared
according to the general procedure using 0.048 g (0.094 mmol) of
calixarene 2, 0.070 g (0.47 mmol) of potassium trimethylsilanolate
(90% purity), and 0.050 ml (0.47 mmol) of propargyl bromide (80%
in toluene). The crude reaction mixture was purified by preparative
TLC on silica gel (hexane:CH2Cl2 1:1, v/v) to give the title com-
pounds 11a (0.037 g, 67%, white powder) and 11b (0.010 g, 18%,
white powder).
d
(ppm): 157.6, 157.1, 155.6 (2ꢂ), 137.0, 134.0, 133.4, 132.0, 130.4,
129.3, 128.9, 128.3, 122.0, 121.5, 121.4, 76.1, 75.5, 74.4, 73.1, 35.8, 31.9
(2ꢂ), 30.9, 30.7, 26.2, 25.9, 23.8, 22.7 (2ꢂ), 22.3, 14.1 (2ꢂ), 10.9, 9.3.
IR (KBr) n
1454.1 cmꢀ1. HRMS-ESIþ (C46H60O4) m/z calcd: 694.48299
[MþNH4]þ, 699.43838 [MþNa]þ, 715.41232 [MþK]þ, found:
694.48394 [MþNH4]þ, 699.43908 [MþNa]þ, 715.41217 [MþK]þ.
4.3.7.1. Data for 1,2-alternate 11a. Mp 160e162 ꢁC. 1H NMR
(CDCl3, 400 MHz, 293 K)
d
(ppm): 7.16 (d, 4H, J¼7.8 Hz, AreH), 7.05
4.3.5. Synthesis of 25,26-diethoxy-27,28-propoxycalix[4]arene-1,2-
alt (9a) and paco (9b). Compound 9a was prepared according to
the general procedure using 0.079 g (0.16 mmol) of calixarene 2,
0.10 g (0.78 mmol) of potassium trimethylsilanolate (90% purity),
and 0.07 ml (0.78 mmol) of 1-iodoethane. The crude reaction
mixture was purified by preparative TLC on silica gel (hex-
ane:CH2Cl2 1:1, v/v) to give the title compounds 9a (0.046 g, 53%,
white powder) and 9b (0.031 g, 35%, white powder).
(dd, 2H, J¼7.4, 1.6 Hz, AreH), 6.97 (dd, 2H, J¼7.4, 1.6 Hz, AreH),
6.90e6.84 (m, 4H, AreH), 4.48 (d, 1H, J¼12.9 Hz, AreCH2eAr), 4.14
(d, 1H, J¼12.9 Hz, AreCH2eAr), 4.04 (d, 2H, J¼16.0 Hz, AreCH2eAr),
3.95 (m, 4H, OeCH2eCeCH), 3.85 (d, 2H, J¼16.0 Hz, AreCH2eAr),
3.37e3.22 (m, 5H, OeCH2þAreCH2eAr), 3.16 (d, 1H, J¼12.9 Hz,
AreCH2eAr), 2.33 (t, 2H, J¼2.4 Hz, OeCH2eCeCH), 1.25e1.12 (m,
2H, OeCH2eCH2), 0.77e0.65 (m, 2H, OeCH2eCH2), 0.62 (t, 6H,
J¼7.0 Hz, OeCH2eCH2eCH3). 13C NMR (CDCl3, 100 MHz, 293 K)
d
(ppm): 156.2, 154.7, 135.3, 135.1, 133.8, 132.9, 129.9, 129.4, 128.8,
4.3.5.1. Data for 1,2-alternate 9a. Mp 95e97 ꢁC. 1H NMR (CDCl3,
128.7, 122.8,122.5, 80.8, 75.4, 74.1, 59.8, 37.4, 30.2, 29.5, 22.3,10.1. IR
400 MHz, 293 K)
d
(ppm): 7.15e7.02 (m, 8H, AreH), 6.85e6.81 (m,
(KBr) n
2123.1, 1454.9 cmꢀ1. HRMS-ESIþ (C40H40O4) m/z calcd:
4H, AreH), 4.23 (d, 1H, J¼12.5 Hz, AreCH2eAr), 4.17 (d, 1H,
J¼12.5 Hz, AreCH2eAr), 3.90 (s, 4H, AreH), 3.46 (q, 4H, J¼7.04 Hz,
OeCH2), 3.42e3.36 (m, 4H, OeCH2), 3.21e3.13 (m, 2H, Are-
CH2eAr), 1.30e1.16 (m, 2H, OeCH2eCH2), 1.07e0.94 (m, 2H,
OeCH2eCH2), 0.67 (t, 6H, J¼7.04 Hz, OeCH2eCH3), 0.61 (t, 6H,
J¼7.4 Hz, OeCH2eCH2eCH3). 13C NMR (CDCl3, 100 MHz, 293 K)
602.32649 [MþNH4]þ, 607.28188 [MþNa]þ, 623.25582 [MþK]þ,
found: 602.32642 [MþNH4]þ, 607.28134 [MþNa]þ, 623.25429
[MþK]þ.
4.3.7.2. Data for partial cone 11b. Mp 171e172 ꢁC. 1H NMR
(CDCl3, 400 MHz, 293 K)
7.24 (dd, 1H, J¼7.8, 1.6 Hz, AreH), 7.12e7.06 (m, 2H, AreH),
d
(ppm): 7.33 (dd, 1H, J¼7.4, 1.6 Hz, AreH),
d
(ppm): 156.6, 156.3, 134.9, 134.6, 133.0, 132.9, 129.2 (2ꢂ), 128.8,

6354
P. Slavík et al. / Tetrahedron 72 (2016) 6348e6355
7.05e7.00 (m, 2H, AreH), 6.95 (t, 1H, J¼7.4 Hz, AreH), 6.90 (t, 1H,
J¼7.4 Hz, AreH), 6.54 (t, 1H, J¼7.4 Hz, AreH), 6.47 (t, 1H, J¼7.4 Hz,
AreH), 6.37 (dd, 1H, J¼7.8, 1.6 Hz, AreH), 6.31 (dd, 1H, J¼7.4, 1.6 Hz,
AreH), 4.49e4.35 (m, 4H, OeCH2eCeCH), 4.10 (d, 1H, J¼13.3 Hz,
AreCH2eAr), 4.09 (d, H, J¼13.0 Hz, AreCH2eAr), 3.82e3.64 (m, 5H,
OeCH2þAreCH2eAr), 3.59e3.51 (m, 1H, OeCH2), 3.38e3.28 (m,
2H, OeCH2), 3.09 (d, 1H, J¼13,3 Hz, AreCH2eAr), 3.07 (d, 1H,
J¼13,3 Hz, AreCH2eAr), 2.51 (t, 1H, J¼2.4 Hz, OeCH2eCeCH), 2.50
(t, 1H, J¼2.4 Hz, OeCH2eCeCH), 1.92e1.80 (m, 2H, OeCH2eCH2),
1.45e1.31 (m, 2H, OeCH2eCH2), 1.08 (t, 3H, J¼7.4 Hz, OeCH2e-
CH2eCH3), 0.72 (t, 3H, J¼7.4 Hz, OeCH2eCH2eCH3). 13C NMR
reduction and absorption correction were done using Apex3 soft-
ware.10 The structures 5a and 12a were measured using Xcalibur PX
with an Onyx CCD detector and graphite monochromated Cu K
a
ꢁ
(l¼1.54184 A) radiation. The data reduction and absorption cor-
rection were done using CrysAlis PRO software.11 The structures
2$CH2Cl2, 5a, 10a and 12a were solved by direct methods12 and the
structure 7a was solved by charge flipping methods.13 The struc-
tured were refined by full matrix least squares on F squared value
using Crystals software.14 MCE software15 was used for visualiza-
tion of the electron density maps. The positions of the disordered
functional groups were found in difference Fourier maps; the bond
lengths and angles were restrained. The overall occupancy of the
disordered functional groups was constrained to 1. According to
common practice the hydrogen atoms attached to the carbon atoms
were placed geometrically with Uiso(H) in the range of 1.2e1.5 Ueq
for parent atom (C). For further information on crystal structures
and data collection see Table 3.
(CDCl3, 100 MHz, 293 K)
d (ppm): 157.0, 156.3, 155.5, 154.4, 136.9,
136.7, 134.3, 134.1, 133.6, 133.4, 132.3, 131.8, 130.8, 130.7, 129.5,
129.4, 129.1, 128.7, 128.6, 128.4, 122.7, 122.6, 122.3, 121.6, 76.1, 75.6,
74.6, 74.4, 60.9, 59.3, 36.2, 36.1, 30.8, 30.4, 23.8, 22.1, 10.9, 9.4. IR
(KBr)
n
2123.1, 1453.6 cmꢀ1. HRMS-ESIþ (C40H40O4) m/z calcd:
602.32649 [MþNH4]þ, 607.28188 [MþNa]þ, 623.25582 [MþK]þ,
Table 3
The information on crystal structures and data collection
Compound
2$CH2Cl2
34$H36$O4, C$H2$Cl2
5a
7a
10a
12a
Formula
C
C
40$H48$O4
C42$H52$O4
C
40$H44$O4
C48$H48$O4
Mr
593.59
Monoclinic
P21/n
11.6864 (3)
14.6226 (3)
18.1551 (4)
90
101.0873 (9)
90
592.82
Triclinic
P-1
620.87
Triclinic
P-1
588.79
Monoclinic
P21/n
10.8996 (2)
19.7499 (4)
15.3146 (3)
90
95.5843 (9)
90
3281.07 (11)
4
688.91
Monoclinic
P21/c
10.5744 (2)
18.5382 (4)
39.8504 (10)
90
93.760 (2)
90
Crystal system
Space group
ꢁ
a (A)
9.5234 (3)
18.5382 (6)
19.0955 (4)
85.559 (2)
85.451 (2)
86.181 (3)
3344.33 (17)
4
9.4668 (11)
10.8903 (14)
18.778 (2)
80.119 (4)
82.721 (3)
70.323 (3)
1790.9 (4)
2
ꢁ
b (A)
ꢁ
c (A)
a
b
g
(ꢁ)
(ꢁ)
(ꢁ)
3
ꢁ
V (A )
Z
3044.54 (12)
4
7795.1 (3)
8
T (K)
180
1.295
2.22
180
1.177
0.58
180
1.151
0.56
180
1.192
0.59
180
1.174
0.57
Dcalcd (g cmꢀ3
)
m
(mmꢀ1
)
Reflections used
Independent (Rint
29,831
5518 (0.060)
5279
28,112
13,453 (0.042)
10,837
22,594
6505 (0.049)
6127
49,970
6013 (0.053)
5763
63,509
16,023 (0.042)
11,746
)
Observed [I>2
s(I)]
Parameters/restrains
398/34
820/58
452/68
0.64/ꢀ0.48
1.14
425/28
0.56/ꢀ0.48
1.06
965/28
0.29/ꢀ0.32
1.01
ꢀ ꢁꢀ3
Drmax
/
Drmin (e
A
)
0.78/ꢀ0.54
0.60/ꢀ0.51
GOF
0.89
0.91
R/wR
CCDC number
0.072/0.180
1478270
0.074/0.165
1478271
0.092/0.206
1478272
0.067/0.155
1478273
0.061/0.150
1478274
found: 602.32621 [MþNH4]þ, 607.28114 [MþNa]þ, 623.25442
[MþK]þ.
Acknowledgements
The authors wish to thank the Czech Science Foundation (grant
Nr. 16-13869S and 16-10035S) and Specific University Research
(MSMT No 20-SVV/2016).
4.3.8. Synthesis of 25,26-dibenzyloxy-27,28-propoxycalix[4]arene-
1,2-alt (12a) and paco (12b). A mixture of compounds 12a and 12b
was prepared according to the general procedure using 0.072 g
(0.14 mmol) of calixarene 2, 0.091 g (0.71 mmol) of potassium tri-
methylsilanolate (90% purity), and 0.085 ml (0.71 mmol) of benzyl
bromide. The 1H NMR analysis of the crude product (0.077 g)
showed the presence of 12a and 12b conformers in a 63:37 ratio
(see Supplementary data). This mixture was purified by repeated
preparative TLC on silica gel, unfortunately, we were not able to
isolate pure desired 1,2-alternate conformer 12a. On the other hand,
we were able to obtain a single crystal of compound 12a (CH2Cl2/
methanol) suitable for X-ray analysis.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2016.08.028.
References and notes
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