Two structural types of 1,3-alternate tetrapropoxycalix[4]arene derivatives in the solid state

Article abstract of DOI:10.1039/b505454k

The solid state structures of seven tetrapropoxycalix[4]arene derivatives immobilised in a 1,3-alternate conformation were determined using single-crystal X-ray crystallography. The cavity shapes of investigated derivatives (upper rim unsubstituted, dista

Full text of DOI:10.1039/b505454k

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A R T I C L E
Two structural types of 1,3-alternate tetrapropoxycalix[4]arene
derivatives in the solid state
a
b
b
b
c
Jan S y´ kora,* Jan Budka, Pavel Lhot a´ k, Ivan Stibor and Ivana C ´ı sa rˇ ov a´
a
Institute of Chemical Process Fundamentals, Rozvojova 135, 165 02 Prague 6, Czech Republic.
E-mail: sykora@icpf.cas.cz; Fax: +420-220920661; Tel: +420-220390307
Department of Organic Chemistry, Institute of Chemical Technology, Technicka 5, 166 28
Prague 6, Czech Republic. E-mail: budkaj@vscht.cz, lhotakp@vscht.cz, stibori@vscht.cz;
Fax: +420-220444280; Tel: +420-220444288
b
c
Department of Inorganic Chemistry, Charles University, Hlavova 8, 128 43 Prague 2, Czech
Republic. E-mail: cisarova@natur.cuni.cz
Received 19th April 2005, Accepted 19th May 2005
First published as an Advance Article on the web 13th June 2005
The solid state structures of seven tetrapropoxycalix[4]arene derivatives immobilised in a 1,3-alternate conformation
were determined using single-crystal X-ray crystallography. The cavity shapes of investigated derivatives (upper rim
unsubstituted, distally di-substituted and tetra-substituted) and the nature of intermolecular interactions in
molecular packing were compared. The results indicate that there are only two structural types adopted by basic
tetrapropoxycalix[4]arene derivatives in the 1,3-alternate conformation.
Introduction
of symmetrical tetrapropoxycalix[4]arenes were synthesised for
this purpose (Scheme 1). Suitable single crystals were grown and
proven by X-ray crystallography.†
Calixarenes represent
a versatile class of macrocyclic
1–4
compounds. Some of them are readily available from cheap
starting materials and can easily be used as building blocks for
the design of more sophisticated supramolecular systems with
specific properties. Among them, calix[4]arenes have received
the most attention due to their accessibility and controllable
Further tetrapropoxy derivatives were searched for in the
Cambridge Structure Database (CSD version 5.26, February
2005 release). Among more than 600 structures of calix[4]arene
derivatives, we found 61 derivatives with propoxy groups,
but only four of them in the 1,3-alternate conformation.
Unfortunately these structures could not be included in the
conformational study because they didn’t represent structures
of free calix[4]arene but rather complexes or solvates. As the
complexed molecules or ions are affecting the final shape of the
calixarene cavity we left these structures out of consideration.
5
molecular architecture as well as diverse complexation abilities.
Generally, calix[4]arenes are compounds created by four
phenolic units connected by methylene bridges in 2,6-positions,
thus forming a small cavity. They can adopt four conformers
depending on the mutual orientation of the aromatic rings
around the cavity. Depending on this orientation, these are cone,
partial cone, 1,2-alternate and 1,3-alternate conformers.
The 1,3-alternate derivatives of calix[4]arene offer several
unique properties. They are relatively rigid molecules pos-
sessing high symmetry. A distal pair of aromatic units is well
Results and discussion
6
Conformation analysis
The basic skeleton of every determined structure was numbered
according to the rules of calix[4]arene nomenclature (Fig. 1).
Furthermore, the propoxy groups were numbered (C33–C44)
while the substituents on the aromatic part were numbered as
the last. Every quarter of the calix[4]arene derivative was labeled
with a lower case letter to distinguish individual substituents
for the purpose of intermolecular interaction comparison; Pr(b)
means the propoxy group on the aromatic ring b (C3–C7, C28).
Conformational analysis consisted of (i) comparison of the
distance between distal aromatic rings (C23–C11 and C5–C17),
preorganized for the complexation of soft cations via cation–p
interactions. A feasible derivatisation of a 1,3-alternate skeleton
7
enables the construction of “both-sides” ditopic receptors for
8
,9
10
cations and anions. The 1,3-alternate calix[4]arenes could be
11
12
used as a “core” in dendrimers and oligomacrocycles. Their
tubular shape also invokes the idea of forming the channels in
the solid state based on non-covalent interactions.
7,13,14
All these extremely interesting characteristics are definitely
associated with the conformation of these semi-rigid molecules.
In this paper, we report on the results of the solid-state
conformational analysis of several 1,3-alternate calix[4]arene
derivatives.
We were concerned with 1,3-alternate derivatives substituted
on the phenolic part (lower rim) by four propoxy groups.
It is known that this group is sufficient for stabilizing the
system in the desired conformation. Furthermore, we considered
symmetrically substituted calix[4]arenes on the aromatic part
(ii) calculation of the dihedral angle between the plane defined
by the aromatic ring and the plane defined by four methylene
bridges (C2–C8–C14–C20), and (iii) calculation of the torsion
angle of these groups.
We can find two basic types of cavity shape among the
1
,3-alternate derivatives studied. More than half of the studied
calix[4]arenes (8, 9, 11, 12) adopt the first, closed cavity type
Table 1). The cavity of these derivatives is nearly closed on both
sides and propoxy groups are turned into the space making
(
(
upper rim) as themostconvenientmolecules for conformational
analysis. Weintendedto compare the cavitysize, cavityshape and
intermolecular interactions in the molecular packing of these
derivatives. Di-tert-butyl-7, dibromo-8, diphenyl-9 as represen-
tatives of distally di-substituted tetrapropoxycalix[4]arene and
tetra-tert-butyl-10, unsubstituted tetrapropoxycalix[4]arene 11,
tetrabromo-12 and tetraphenyl-13 derivatives as representatives
†
CCDC reference numbers 178413–178416, 267155–267157. See
http://www.rsc.org/suppdata/ob/b5/b505454k/ for crystallographic
data in CIF or other electronic format.
2
5 7 2
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 5 7 2 – 2 5 7 8
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5

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Scheme 1 (a) Phenol, AlCl
d) propyl iodide, Cs CO , acetone, reflux, (e) from 4, 2.2 eq. Br
iodide, [Ni(dppe)]Cl
acid, Pd(PPh
3
, toluene, rt, (b) propyl iodide, 1.1 eq. K
2
CO
3
, acetone, reflux, (c) from 3, AlCl
3
, dichloromethane, toluene, rt,
SiOK, THF, rt, (g) phenylmagnesium
(
2
3
2
, chloroform, rt, (f) propyl iodide, (CH
, ether, reflux, (h) 1. Bu –Li, THF, −78 C, 2. zinc chloride, THF, –78 C, 3. phenyl iodide, THF, Pd(PPh
3
)
3
t
◦
◦
2
3 4
) , rt, (i) phenylboronic
◦
3
)
4
, toluene–methanol, 100 C, (j) propyl iodide, Cs
2
CO
3
, acetone, reflux, (k) from 11, NBS, butan-2-one, rt.
groups and neighbouring aromatic rings (Fig. 2). The structure
of 7 represents such an intermediate state. Two of the three
molecules creating an independent part of the unit cell adopt
the wide open type of structure but the shape of the last molecule
is much more similar to the closed type. The differences between
both types are clearly demonstrated in Fig. 3.
The torsion angle of the methylene bridges acquires higher
values in open conformers. Compound 13 represents the most
◦
distorted structure with a torsion angle equal to 12 (Table 1).
Values of dihedral angles in the closed conformers vary only
◦
slightly, within the range of 2.5 for each structure. These
varieties are significantly higher for open conformers (Table 2).
Furthermore, the investigated crystal structures were com-
pared with the shape of the ideal 1,3-alternate conformer that
adopts an S4 symmetry; it has a four-fold inversion axis passing
through the cavity center, its methylene bridges are lying in the
plane creating a square and all aromatic units are tilted by the
same angle.
Fig. 1 Schematic overview of basic skeleton numbering.
Table 1 Torsion angles and distances at the aromatic part
◦
a
Distance/ A˚ a
C5–C17
Torsion angle/
Structure no.
C2–C8–C14–C20
C11–C23
7
7
7
8
9
1
1
1
1
(1)
(2)
(3)
5.4
7.0
5.2
0.8
3.1
6.5
0.4
0
7.19
7.27
5.53
4.60
4.54
7.22
4.33
4.75
7.19
7.45
7.58
6.06
4.49
4.35
7.22
4.31
4.69
7.32
Table 2 Dihedral angles of aromatic rings and plane C2–C8–C14–C20
◦
a
Dihedral angle/
Structure no.
a
b
c
d
0
1
2
3
7
7
7
8
9
1
11
12
1
(1)
(2)
(3)
118.9
124.7
96.7
80.7
79.8
113.9
77.5
83.8
119.3
109.8
91.4
79.4
77.8
107.8
77.4
82.2
111.2
109.0
95.8
79.7
—
109.3
—
106.3
117.2
93.6
79.5
—
118.5
—
12.0
a
Distances and angles calculated with ORTEPIII.
0
the top of the cavity more accessible for the next calixarene
unit.
The second type, the wide open cavity, is adopted by the rest
of the molecules (7, 10, 13). The stability of the open cavity is
provided by intramolecular CH–p interactions between propoxy
81.5
112.7
82.3
112.2
3
111.1
113.5
a
Calculated with PARST97.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 5 7 2 – 2 5 7 8
2 5 7 3

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At first sight, both types seem to be closed to the ideal S4
shape. In detail, it’s obvious that the individual inner symmetry is
much lower. Thus, compounds 7, 8, 10, 13 possess C1 symmetry,
derivative 12 has C symmetry, while calixarenes 9 and 11 exhibit
v
C2 symmetry.
Intermolecular interactions
It is generally known that classical calix[4]arenes and thia-
calix[4]arenes (the phenols are connected via four sulfur atoms
instead of CH groups) in the 1,3-alternate conformation are
2
15
inclined to form infinite channels in the solid state. This
property is in fact predetermined by the shape of these molecules.
Indeed, there are only two exceptions among studied derivatives,
compounds 7 and 13; both adopt the open type of structure.
As it is evident, e.g. from the molecular packing of 11
(Fig. 4), molecules in the 1,3-alternate conformation simply
interlock like a box of bricks in the solid state. Hydrogens
in para positions are attracted into the cavity of the next
calixarene unit. The shortest distance CH · · · C(arom) is less
˚
than 3.15 A. The other derivatives behave similarly depending on
the substitution. Generally, if the substituent is attracted towards
the next calix[4]arene cavity, the molecules will likely adopt
the closed cavity shape and form infinite channels (compare
Fig. 4). Otherwise, the CH–p interactions of propoxy groups or
methylene bridges become the most important interactions in
the molecular packing (Table 3) and the molecules adopt the
more distorted open cavity shape. The CH–p interactions were
considered only when a hydrogen atom was localised directly
16
˚
Fig. 2 Detail of intramolecular CH–p interactions in structure 13
adopting the open cavity shape.
above the aromatic ring at a distance shorter than 3.2 A. It
has been proved that the CH–p interactions play a crucial role
in the molecular packing of both structural types adopted by
1
,3-alternate tetrapropoxycalix[4]arene. The significant CH–p
contacts are summarized in Table 3.
Fig. 3 (a) Structures adopting the closed cavity type (white-8, red-9, grey-11, blue-12) and molecule 7(3) (yellow) representing such an intermediate
state, (b) the open cavity shape (grey-7, yellow-10, red-13).
Fig. 4 The various infinity channel types created by 1,3-alternate tetrapropoxycalix[4]arene derivatives (a) 8, (b) 9, (c) 10, (d) 11, (e) 12.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 5 7 2 – 2 5 7 8
2
5 7 4

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Table 3 CH–p contacts in the crystal structures of 1,3-alternate tetrapropoxycalix[4]arene derivatives
Structure
t
Ar—aromatic ring, Bu —tert-butyl group, Mb—methylene bridge,
Pr—propoxy group, Ph—phenyl group
Distance/ A˚ c
CH–p interaction
7
8
10
13
t
t
Bu (1c)–Ar(3d)
2.79
2.80
2.84
2.80
2.88
2.80
2.98
2.94
2.78
2.89
2.87
2.90
Pr(a)–Ar(b)
Pr(c)–Ar(d)
3.09
2.94
Bu (b)–Ar(a)
2.91
3.07
3.05
2.82
2.89
Ar(d)–Ar(b)
Mb(a)–Ph(c)
Mb(b)–Ar(a)
Ph(a)–Ph(d)
Ph(b)–Ph(a)
Ph(c)–Ar(c)
Ph(d)–Ph(b)
Ph(d)–Ph(b)
3.11
2.99
3.03
3.04
3.10
3.09
3.00
3.09
2.99
2.94
2.80
2.78
t
t
Bu (2c)–Ar(3b)
Bu (c)–Ar(d)
a
Mb(2c)–Ar(1b)
Mb(3b)–Ar(2c)
Mb(3d)–Ar(1c)
Pr(a)–Ar(d)
a
9
Pr(d)–Ar(a)
a
Mb(c)–Ph(a)
2.83
2.83
Pr(d)–Ar(c)
a
b
Pr(1a)–Ar(1d)
Mb(a) –Ph(c)
a
Pr(1b)–Ar(1c)
12
Pr(1d)–Ar(2b)
Pr(c)–Ar(b)
2.88
2.88
a
b
a
Pr(2a)–Ar(2b)
Pr(c)–Ar(b)
Pr(a)–Ar(d)
a
a
Pr(2a)–Ar(2d)
Pr(b)–Ar(a)
a
Pr(2b)–Ar(1d)
Pr(c)–Ar(b)
a
a
Pr(2d)–Ar(2a)
Pr(d)–Ar(c)
a
b
c
Intramolecular interaction. Generated by the symmetry. Calculated in PARST97.
Conclusion
CDCl
3
; Me
4
Si) 8.05 (2H, s, OH), 7.03 (4H, d, J 7.2, Ar–H), 6.86
(
4H, s, Ar–H), 6.62 (2H, t, J 7.2, Ar–H), 4.31 (4H, d, J 12.6,
Some general conformational rules for 1,3-alternate
tetrapropoxycalix[4]arene derivatives in the solid state can
be derived from the comparison of studied crystal structures.
Irrespective of the substituent on the aromatic part of the 1,3-
alternate tetrapropoxycalix[4]arene, only two different cavity
shapes were found in the crystal structures studied. The cavity
of the 1,3-alternates (unsubstituted, distally di-substituted
and tetra-substituted tetrapropoxycalix[4]arene derivatives) is
either open or closed, both in a narrow range of dihedral angle
between the plane defined by the aromatic ring and the plane
defined by four methylene bridges.
The internal cavity parameters differ only slightly among the
representatives of each group. The open type is more distorted
but both types are closed to S4 symmetry. The closed type is
preferred in structures creating infinite channels in the solid state.
Both groups then apply different intermolecular interactions in
molecular packing.
Ar–CH
2.6, Ar–CH
6H, t, J 7.2, 2 × CH
2
–Ar ax), 3.95 (4H, t, J 6.6, 2 × OCH
2
), 3.34 (4H, d, J
CH ), 1.26
1
(
2
–Ar eq), 2.08–2.02 (4H, m, 2 × OCH
2
2
3
), 1.03 (18H, s, 2 × tert-Bu).
5
,17-Di-tert-butyl-25,26,27,28-tetrapropoxycalix[4]arene (1,3-
alternate) 7 and 5,17-di-tert-butyl-25,26,27,28-tetrapropoxy-
25
calix[4]arene (partial cone) 7b . A mixture of derivative 5
115 mg, 0.19 mmol), caesium carbonate (240 mg, 0.75 mmol)
(
and of propyl iodide (0.11 ml, 1.14 mmol) was refluxed in 20 ml
of dry acetone. The reaction was monitored by TLC. After
4
8 hours, the mixture was cooled, evaporated to dryness, and
dissolved in a mixture of 20 ml of chloroform and 15 ml of 1 M
HCl. The organic layer was separated and the aqueous layer
was extracted twice with 15 ml of chloroform. The chloroform
layers were combined, washed with water and dried over
magnesium sulfate. After filtration, the mixture was evaporated
to dryness and separated by preparative TLC (petroleum ether–
ethyl acetate 15 : 1) to yield 34 mg (26%) of 1,3-alternate 7
The results of our conformational analysis can be used for the
rational design of novel 1,3-alternate calix[4]arenes possessing
interesting properties in the solid state, e.g. crystal engineering.
◦
(
9
R
F
= 0.7), mp 204–206 C (ethyl acetate), found: C, 81.2; H,
+
.1; M , 704.6. C48
H
64
4
O requires C 81.8; H 9.15%; M, 704.5).
d
H
(300 MHz; CDCl
3
; Me Si) 6.99 (4H, d, J 7.2, Ar–H), 6.97
4
Experimental
(4H, s, Ar–H), 6.75 (2H, t, J 7.7, Ar–H), 3.76 (8H, s, Ar–CH –
2
Ar), 3.36 (4H, t, J 7.7, 2 × OCH
2
), 3.35 (4H, t, J 7.7, 2 × OCH
CH
), 1.25 (18H, s, 2 × tert-Bu),
), and
= 0.85), mp 180–
requires
Si) 7.23 (2H, d, J
.2, Ar–H), 7.08 (2H, d, J 7.2, Ar–H), 6.89 (2H, t, J 7.2, Ar–H),
.86 (2H, d, J 2.2, Ar–H), 6.51 (2H, d, J 2.7, Ar–H), 4.05 (2H,
–Ar), 3.80–3.72 (2H, m, OCH ), 3.74–3.60
–Ar), 3.62 (2H, t, J 7.7, OCH ), 3.51–3.43 (2H,
), 3.39–3.33 (2H, m, OCH ), 3.04 (2H, d, J 12.6, Ar–
–Ar), 1.90–1.78 (6H, m, 3 × OCH CH ), 1.52–1.43 (2H, m,
OCH CH
), 1.01 (18H, s, 2 × tert-Bu), 1.03 (6H, t, J 7.7, 2 ×
CH ), 0.95 (3H, t, J 7.2, CH ), 0.71 (3H, t, J 7.7, CH ).
2
),
Synthesis
1
0
2
1
.27–1.16 (8H, m, 4 × OCH
2
2
.71 (6H, t, J 7.7, 2 × CH
3
), 0.69 (6H, t, J 7.7, 2 × CH
3
Compounds prepared according to published methods:
1
7
4 mg (18%) of partial cone isomer 7b (R
F
5
,11,17,23-tetra-tert-butylcalix[4]arene-25,26,27,28-tetraol 1,
◦
18,19
82 C (ethyl acetate), found: C, 81.5; H, 9.1. C48
H
64
O
4
calix[4]arene-25,26,27,28-tetraol 2,
butyl-6,28-dipro-poxycalix[4]arene-25,27-diol 3, 26,28-dipro-
poxycalix[4]arene-25,27-diol 4,
poxycalix[4]arene-25,27-diol 6,
5,11,17,23-tetra-tert-
20
C 81.8; H 9.15%). d
H
(300 MHz; CDCl
3
; Me
4
2
1,22
7
6
11,23-dibromo-26,28-dipro-
3
2
5,11,17,23-tetra-tert-butyl-
24
d, J 12.7, Ar–CH
4H, m, Ar–CH
m, OCH
CH
2
2
2
2
5,26,27,28-tetrapropoxycalix[4]arene (1,3-alternate) 2 10,
5
(
2
2
5,26,27,28-tetrapropoxycalix[4]arene (1,3-alternate) 11.
2
2
5
.
,17-Di-tert-butyl-26,28-dipropoxycalix[4]arene-25,27-diol
Aluminium chloride (0.6 g, 3.3 mmol) was stirred in 4 ml
26
2
2
2
5
2
2
of dry dichloromethane for 15 minutes. Then, the solution of
derivative 3 (0.5 g, 1.36 mmol) in 12 ml of dry toluene was
added. The mixture was stirred vigorously and the course of the
reaction was monitored by TLC (petroleum ether–ethyl acetate
3
3
3
5,17-Dibromo-25,26,27,28-tetrapropoxycalix[4]arene
(1,3-
alternate) 8. Derivative 6 (8.0 g, 12 mmol) and 7.7 g (60 mmol,
1
1
1
5 : 1). After 25 minutes, the mixture was dissolved in 15 ml of
M HCl, stirred for 10 minutes and then extracted with 3 ×
0 ml of ethyl acetate. The extracts were combined, washed with
5 equivalents) of potassium trimethylsilanolate were dissolved
◦
in 150 ml of dry tetrahydrofuran. After cooling to −5 C, 5.8 ml
(60 mmol) of propyl iodide were added dropwise over a period
of 20 minutes. The mixture was stirred at room temperature for
5 days. Then, 150 ml of 1 M HCl were added and the mixture
was extracted with 4 × 50 ml of chloroform. The organic layers
were combined, dried over magnesium sulfate, filtered and
evaporated to dryness. Crude product was precipitated from
brine and water, dried over magnesium sulfate and evaporated
to dryness. The preparative TLC (petroleum ether–ethyl acetate
15 : 1, R
F
= 0.75) yielded 115 mg (28%) of title compound 5
◦
as a white solid, mp 204–207 C (ethyl acetate), found: C, 81.0;
H, 8.5. C42
H
52
O
4
requires: C, 81.25; H 8.4%). d (300 MHz;
H
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 5 7 2 – 2 5 7 8
2 5 7 5

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chloroform–methanol to give 6.66 g (74%) of derivative 8, mp
5,11,17,23-Tetrabromo-25,26,27,28-tetrapropoxycalix[4]arene
(1,3-alternate) 12 . A mixture of derivative 11 (2.0 g,
◦
+
30
2
48–251 C (THF), found: C, 63.7; H, 6.2; Br 21.0; M 747.3.
Br requires C 64.0; H 6.2; Br 21.3%; M, 748.18).
(300 MHz; CDCl ; Me Si) 7.17 (4H, s, Ar–H), 6.98 (4H,
d, J 7.2, Ar–H), 6.69 (2H, t, J 7.2, Ar–H), 3.61 (4H, t, J 6.6,
× OCH ), 3.58 (8H, s, Ar–CH –Ar), 3.46 (4H, t, J 6.6, 2 ×
OCH CH ), 1.62–1.52 (4H, d
), 1.72–1.65 (4H, d m, 2 × OCH
m, 2 × OCH CH ), 1.01 (6H, t, J 7.2, 2 × CH ), 0.87 (6H, t, J
.2, 2 × CH ).
C
40
H
46
O
4
2
3.37 mmol) and N-bromosuccinimide (6.0 g, 33.7 mmol, 10
equiv.) in 100 ml of butan-2-one was stirred at room temperature
for 5 days. The precipitate formed was filtered off to give 2.68 g
d
H
3
4
◦
2
2
2
(88%) of derivative 12, mp 354–356 C (from THF), found: C,
2
2
2
52.8; H, 4.9; Br 34.3. C40
35.2%). d (300 MHz; CDCl
(8H, t, J 6.6, 4 × OCH ), 3.54 (8H, s, Ar–CH
m, 4 × OCH CH ), 0.99 (12H, t, J 7.7, 4 × CH
H
44
O
; Me
4
Br
4
4
requires C 52.9; H 4.9; Br
Si) 7.15 (8H, s, Ar–H), 3.56
–Ar), 1.66 (8H,
).
2
2
3
H
3
7
3
2
2
2
2
3
5,17-Diphenyl-25,26,27,28-tetrapropoxycalix[4]arene (1,3-
5
,11,17,23-Tetraphenyl-25,26,27,28-tetrapropoxycalix[4]arene
alternate) 9.
28
(
1,3-alternate) 13 . To a solution of 0.5 g (0.55 mmol) of
27
Method A . A mixture of derivative 8 (100 mg, 0.13 mmol)
and 10 mg (0.02 mmol) of [Ni(dppe)]Cl was dissolved in 50 ml
◦
derivative 12 in 10 ml of dry THF cooled to −78 C were injected
2
3
.2 ml of 1.7 M tert-butyllithium in pentane (5.5 mmol, 10
of dry diethyl ether. The reaction flask was evacuated 4 times
and filled with argon. A solution of phenylmagnesium bromide
◦
equiv.) and the yellow solution was stirred at −78 C for 1 hour.
During this period, a solution of freshly fused ZnCl
2
(1.02 g,
(
0.4 ml of 3 M, 1.2 mmol) in diethyl ether was injected via a
7
.5 mmol, 14 equiv.) in 5 ml of dry THF was prepared, and
septum and the mixture was refluxed for 48 hours. The ether
was evaporated and the mixture was dissolved in 50 ml of
dichloromethane and washed with 30 ml of 1 M HCl. The
organic layer was separated, neutralized by 30 ml of 2 M
then cannulated into the reaction mixture. After the addition,
the cooling bath was removed and the colorless solution was
stirred at room temperature for 30 minutes. The organozinc salt
solution was then cannulated into a flask containing phenyl
Na
2
CO
3
, washed with 2 × 20 ml of water and dried over
iodide (0.85 ml, 7.5 mmol) and Pd(PPh
3
4
) (15 mg, 0.014 mmol)
magnesium sulfate. The mixture was filtered and evaporated to
dryness to give 126 mg of crude product, which was purified by
preparative TLC (petroleum ether–chloroform 3 : 1) to remove
in 10 ml of dry THF. The reaction mixture was stirred in the
dark at room temperature for 12 hours and then poured into
5
0 ml of 4 M HCl and extracted with 3 × 20 ml of chloroform.
The combined organic layers were washed successively with
0 ml of brine, 20 ml of a 10% solution of Na SO and water,
the diphenyl (R
of derivative 9 (R
F
= 1.0). The second fraction yielded 34 mg (34%)
◦
F
= 0.45), mp 228–231 C (ethyl acetate), found:
2
2
3
+
C, 83.2; H, 7.6; M 744.7. C52
44.42). d (300 MHz; CDCl
4H, s, Ar–H), 7.17 (6H, m, Ar–H), 7.05 (4H, d, J 7.2, Ar–H),
.73 (2H, t, J 7.2, Ar–H), 3.71 (8H, s, Ar–CH –Ar), 3.59 (4H, t,
J 6.8, 2 × OCH ), 3.57 (4H, t, J 6.8, 2 × OCH ), 1.65–1.54 (8H,
m, 4 × OCH CH ), 0.92 (6H, t, J 7.6, 2 × CH ), 0.79 (6H, t, J
.6, 4 × CH ).
H
56
O
4
requires C 83.8; H 7.6%; M,
dried over magnesium sulfate and then evaporated to dryness.
The residue (0.9 g) was separated by column chromatography
on silica gel. The excess of phenyl iodide was removed using
petroleum ether as an eluent. The second fraction, obtained
using a petroleum ether–chloroform 3 : 1 mixture, contained
7
H
3
; Me
4
Si) 7.33 (4H, m, Ar–H), 7.21
(
6
2
2
2
2
2
3
0
3
.25 g of crude product. The pure title compound 13 (0.15 g,
7
3
1%) was isolated by subsequent preparative TLC (petroleum
◦
28
Method B . To a solution of derivative 8 (0.5 g, 0.67 mmol)
ether–chloroform 1 : 1, R
F
= 0.45–0.55). Mp 278–280 C (from
◦
+
in 10 ml of dry THF cooled to −78 C, 2.3 ml of 1.7 M tert-
ethyl acetate), found: C, 85.2; H, 7.1%; M 896.8. C64
H
64
O
4
butyllithium in pentane (4.0 mmol, 6 equiv.) were injected and
requires C 85.7; H 7.2%; M, 896.48). d
Me
m, Ar–H), 3.77 (8H, s, Ar–CH
OCH
), 1.58–1.51 (8H, m, 4 × OCH
4 × CH ).
H
(400 MHz; CDCl
3
;
◦
the resulting yellow solution was stirred at −78 C for 1 hour.
4
Si) 7.37 (8H, m, Ar–H), 7.23 (8H, s, Ar–H), 7.17 (12H,
–Ar), 3.61 (8H, t, J 7.2, 4 ×
CH ), 0.78 (12H, t, J 7.2,
During this period, a solution of 0.82 g (6.0 mmol, 9 equiv.) of
2
freshly fused ZnCl
2
in 5 ml of dry THF was prepared, which was
2
2
2
then cannulated into the reaction mixture. After the addition
was complete, the cooling bath was removed and the colourless
solution was stirred at room temperature for 30 minutes. The
resulting organozinc salt solution was then cannulated into
a flask containing 0.67 ml of phenyl iodide (6.0 mmol) and
3
Crystal structure determination
The single crystals of 7, 9, 10, 11 and 12 were measured on a No-
nius Kappa CCD diffractometer with graphite monochromated
Mo–Ka radiation. Single crystals of 8 and 13 were measured on
an Enraf-Nonius CAD4 with graphite monochromated Cu–Ka
1
0 mg (0.01 mmol) of Pd(PPh
3
4
) in 10 ml of dry THF. The
mixture was stirred at room temperature for 12 hours in the
dark, then dissolved in 50 ml of 4 M HCl and extracted with
31
radiation. The structures were solved by direct methods and
3
× 20 ml of chloroform. The combined organic layers were
successively washed with 20 ml of brine, 20 ml of a 10% solution
of Na SO and water, dried over magnesium sulfate and then
32
were refined by full matrix least-squares on F values.
−
1
X-Ray data for 7.
C
48
H
64
O
4
, M = 705.04 g mol , monoclinic
2
3
evaporated to dryness. The crude product (0.7 g) was purified
by column chromatography using petroleum ether to remove
the excess of phenyl iodide and then by using a mixture of
petroleum ether–chloroform 3 : 1 to yield 0.24 g (49%) of title
compound 9.
system, space group P21/c, a = 13.9231(1), b = 35.1563(2), c =
3
˚
˚
25.7578(2) A, b = 94.5875(3), Z = 12, V = 12567.7(1) A , D
c
=
−
3
−1
1.12 g cm , l(Mo–Ka) = 0.7 mm , crystal dimensions of 0.3 ×
0.3 × 0.2 mm, T = 150(2) K. All heavy atoms were refined
anisotropically. Hydrogen atoms were placed from expected
geometry and were not refined. This model converged to final
29
Method C . A mixture of derivative 8 (0.4 g, 0.54 mmol),
Pd(PPh (250 mg, 0.23 mmol) and phenylboronic acid (153 mg,
.26 mmol) was dissolved under an atmosphere of argon in
R = 0.0765 and R
w
= 0.0799 using 17406 independent reflections
3
)
4
◦
(
h
max = 25.4 ). CCDC reference number 267155.†
1
1
−
1
0 ml of dry toluene and 1 ml of dry methanol and the reaction
X-Ray data for 8.
C
40
¯
H
46
O
4
Br
2
, M = 750.61 g mol , triclinic
◦
mixture was heated at 100 C. After 15 minutes, 2 ml of a 2 M
system, space group P1, a = 10.055(2), b = 13.297(2), c =
˚
solution of Na
2
CO
3
were added and heating was continued for
15.802(3) A, a = 75.12(1), b = 74.15(2), c = 69.45(1), Z =
3
−3
−1
˚
4
0 hours. After cooling, the mixture was dissolved in 100 ml
2, V = 1872.5(6) A , D = 1.33 g cm , l(Cu–Ka) = 30.4 mm ,
c
of 1 M HCl and extracted with 3 × 20 ml of chloroform. The
crystal dimensions of 0.1 × 0.1 × 0.1 mm, T = 293 K. All
heavy atoms were refined anisotropically. Hydrogen atoms were
placed from expected geometry and were not refined. Disorder of
bromine atoms was modeled. The refinement converged to final
combined organic layers were washed successively with water,
2
0 ml of brine, and again with water and dried over magnesium
sulfate. After evaporation, the residue was purified using column
chromatography on silica gel (petroleum ether–chloroform 4 :
R = 0.0736 and R
w
= 0.0701 using 2567 independent reflections
◦
1
) to yield 0.14 g (36%) of derivative 9.
(hmax = 60 ). CCDC reference number 178413.†
2
5 7 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 5 7 2 – 2 5 7 8

View Article Online
−
1
th
X-Ray data for 9.
C
52
H
56
O
4
, M = 745.02 g mol , monoclinic
3 Z. Asfari and J. Harrowfield, Calixarenes 50 Anniversary:
system, space group C2/c, a = 24.088(1), b = 12.665(1), c =
Commemorative Issue, Kluwer Academic Publishers, Dordrecht,
1994.
4 J. Vicens and V. B o¨ hmer, Calixarenes: A Versatile Class of Macro-
cyclic Compounds, Kluwer Academic Publishers, Dordrecht, 1991.
3
˚
3
˚
1
1
0
7.274(1) A, b = 126.477(1), Z = 4, V = 4237.5(1) A , D =
c
−
−1
.17 g cm , l(Mo–Ka) = 0.7 mm , crystal dimensions of 0.2 ×
.1 × 0.1 mm, T = 150(2) K. The independent part of the unit
5
S. Shimizu, A. Moriyama, K. Kito and Y. Sasaki, J. Org. Chem.,
003, 68, 2187.
6 For a recent review about 1,3-alternate calix[4]arenes, see: B. Pulpoka
and J. Vicens, Collect. Czech. Chem. Commun., 2004, 69, 1251.
J. Budka, P. Lhot a´ k, I. Stibor, J. S y´ kora and I. C ´ı sa rˇ ov a´ , Supramol.
Chem., 2003, 15, 353.
A. Ikeda and S. Shinkai, J. Am. Chem. Soc., 1994, 116, 3102; P. D.
Beer, M. G. B. Drew, P. A. Gale, P. B. Leeson and M. I. Ogden,
J. Chem. Soc., Dalton Trans., 1994, 3479; G. Mislin, E. Graf and
M. W. Hosseini, Tetrahedron Lett., 1996, 37, 4503; J.-A. P e´ rez-
Adelmar, H. Abraham, C. S a´ nchez, K. Rissanen, P. Prados and J. de
Mendoza, Angew. Chem., Int. Ed. Engl., 1996, 35, 1009; P. Lhotak and
S. Shinkai, J. Phys. Org. Chem., 1997, 10, 273; R. J. W. Lugtenberg,
R. J. M. Egbering, J. F. J. Engbersen and D. N. Reinhoudt, J. Chem.
Soc., Perkin Trans. 2, 1997, 1353; A. T. Macias, J. E. Norton and J. D.
Evanseck, J. Am. Chem. Soc., 2003, 125, 2351.
cell is created by one half of the molecule. All heavy atoms
were refined anisotropically. Hydrogen atoms were located from
Fourier maps and refined isotropically. This model converged
2
7
to final R = 0.0493 and R
w
= 0.0183 using 3902 independent
◦
reflections (hmax = 27 ). CCDC reference number 178414.†
8
−
1
X-Ray data for 10.
C
¯
56
H
80
O
4
, M = 817.25 g mol , triclinic
system, space group P1, a = 10.3974(2), b = 13.0709(3), c =
˚
1
2
9.4131(3) A, a = 107.941(1), b = 93.567(1), c = 97.093(1), Z =
3
−3
−1
´
˚
, V = 2476.7(1) A , D = 1.10 g cm , l(Mo–Ka) = 0.7 mm ,
c
crystal dimensions of 0.2 × 0.2 × 0.2 mm, T = 150(2) K. All
heavy atoms were refined anisotropically. Hydrogen atoms were
placed from expected geometry and were not refined. Disorder
of two tert-butyl groups was modeled. This model converged
9
For derivatives based on calix-crowns, see for example: Z. Asfari,
J. M. Harrowfield, A. N. Sobolev and J. Vicens, Aust. J. Chem., 1994,
47, 757; K. N. Koh, K. Araki and S. Shinkai, Tetrahedron Lett.,
to final R = 0.0520 and R
w
= 0.0313 using 7878 independent
◦
reflections (hmax = 27.5 ). CCDC reference number 267157.†
1
995, 36, 6095; A. Casnati, A. Pochini, R. Ungaro, F. Ugozzoli, F.
−
1
Arnaud, S. Fanni, M. J. Schwing, R. J. M. Egbering, F. de Jong and
D. N. Reinhoudt, J. Am. Chem. Soc., 1995, 117, 2767; A. Casnati,
A. Pochini, R. Ungaro, C. Bocchi, F. Ugozzoli, R. J. M. Egberink,
H. Struijk, R. Lugtenberg, F. de Jong and D. N. Reinhoudt, Chem.–
Eur. J., 1996, 2, 436; H. Zeng and B. Dureault, Talanta, 1998, 46,
1485; P. Thu e´ ry, M. Nierlich, F. Arnaud-Neu, B. Souley, Z. Asfari
and J. Vicens, Supramol. Chem., 1999, 11, 143; L. Prodi, F. Boletta,
M. Montalti, N. Zaccheroni, A. Casnati, F. Sansone and R. Ungaro,
New J. Chem., 2000, 24, 155; A. Casnati, C. Massera, N. Pelizzi,
I. Stibor, E. Pinkassik, F. Ugozzoli and R. Ungaro, Tetrahedron
Lett., 2002, 43, 7311; K. Yang, K. D. Kang, Y. Hee Park, I. S. Koo
and I. Lee, Chem. Phys. Lett., 2003, 381, 239; S. K. Kim, J. Vicens,
K.-M. Park, S. S. Lee and J. S. Kim, Tetrahedron Lett., 2003, 44,
X-Ray data for 11.
C
40
H
48
O
4
, M = 592.83 g mol , mono-
clinic system, space group C2/c, a = 25.714(1), b = 8.002(1),
3
˚
˚
c = 19.113(1) A, b = 121.01(1), Z = 4, V = 3370.7(1) A ,
−
3
−1
D
c
= 1.16 g cm , l(Mo–Ka) = 0.73 mm , crystal dimensions
of 0.2 × 0.2 × 0.3 mm, T = 150(2) K. The independent part
of the unit cell is created by one half of the molecule. All heavy
atoms were refined anisotropically. Hydrogen atoms were placed
from expected geometry and were refined isotropically. Disorder
of one propoxy group was modeled. The refinement converged
to final R = 0.0558 and R
w
= 0.0600 using 3160 independent
◦
reflections (hmax = 27.5 ). CCDC reference number 267156.†
9
93.
−
1
10 A. Casnati, F. Bonetti, A. Sartori, L. Pirondini, R. Ungaro, COST
X-Ray data for 12.
C
40
H
44
O
4
Br
4
, M = 908.40 g mol ,
st
ACTION D11, 1 Working Group Meeting, 1999, 18; J. Budka, P.
orthorhombic system, space group Pnma, a = 23.851(1), b =
Lhot a´ k, V. Michlov a´ and I. Stibor, Tetrahedron Lett., 2001, 42, 1583;
M. Dudic, P. Lhotak, I. Stibor, K. Lang and P. Proskova, Org. Lett.,
3
˚
˚
1
1
0
2.333(1), c = 13.079(1) A, Z = 4, V = 3845.6(1) A , D
c
=
−
3
−1
.57 g cm , l(Mo–Ka) = 4.22 mm , crystal dimensions of 0.3 ×
.3 × 0.2 mm, T = 200(2) K. The independent part of the unit
2
003, 5, 149; A. Casnati, F. Bonetti, F. Sansone, F. Ugozzoli and R.
Ungaro, Collect. Czech. Chem. Commun., 2004, 69, 1063.
11 T. Nagasaki, S. Tamagaki and K. Ogino, Chem. Lett., 1997, 717; T.
Nagasaki, A. Noguchi, T. Matsumoto, S. Tamagaki and K. Ogino,
An. Quim. Int. Ed., 1997, 93, 341; A. Ikeda, M. Kawaguchi and S.
Shinkai, An. Quim. Int. Ed., 1997, 93, 408.
cell is created by one half of the molecule. All heavy atoms
were refined anisotropically. Disorder of one propoxy group was
modeled. Hydrogen atoms were located from Fourier maps and
expected geometry. Only hydrogens with full occupancies were
1
2 A. Ikeda and S. Shinkai, J. Chem. Soc., Chem. Commun., 1994, 2375;
V. Stastny, I. Stibor, H. Dvorakova and P. Lhotak, Tetrahedron, 2004,
60, 3383.
13 G. Mislin, E. Graf, M. W. Hosseini, A. De Cian, N. Kyritsakas and
J. Fischer, Chem. Commun., 1998, 2545; W. Jaunky, M. W. Hosseini,
J. M. Planeix, A. De Cian, N. Kyritsakas and J. Fischer, Chem.
Commun., 1999, 2313.
refined isotropically. This model converged to final R = 0.0327
◦
and R
w
= 0.0337 using 2353 independent reflections (hmax = 27 ).
CCDC reference number 178416.†
−
1
X-Ray data for 13.
C
64
H
64
O
4
, M = 897.21 g mol , mono-
clinic system, space group P21/c, a = 14.921(1), b = 18.436(2),
1
4 V. Sidorov, F. W. Kotch, G. Abdrakhamanova, R. Mizani, J. C.
Fettinger and J. T. Davis, J. Am. Chem. Soc., 2002, 124, 2267.
5 P. Lhot a´ k, Eur. J. Org. Chem., 2004, 8, 1675.
3
˚
˚
c = 19.880(2) A, b = 108.21(1), Z = 4, V = 5194.5(8) A ,
−
3
−1
D
0
c
= 1.15 g cm , l(Cu–Ka) = 5.4 mm , crystal dimensions of
1
.5 × 0.5 × 0.3 mm, T = 293 K. All heavy atoms were refined
16 H. Suezawa, T. Yoshida, M. Hirota, H. Takahashi, Y. Umezawa, K.
anisotropically. Hydrogen atoms were placed from expected
geometry and were not refined. This model converged to final
Honda, S. Tsuboyama and M. Nishio, J. Chem. Soc., Perkin Trans.
2
, 2001, 2053; H. Takahashi, S. Tsuboyama, Y. Umezawa, K. Honda
and M. Nishio, Tetrahedron, 2000, 56, 6185.
R = 0.1015 and R
w
= 0.0829 using 5801 independent reflections
1
1
1
7 C. D. Gutsche and M. Iqbal, Org. Synth., 1990, 68, 234.
8 C. D. Gutsche and L.-G. Lin, Tetrahedron, 1986, 42, 1633.
9 C. D. Gutsche, J. A. Levine and P. K. Sujeeth, J. Org. Chem., 1985,
◦
(
h
max = 68 ). CCDC reference number 178415.†
5
0, 5802.
Acknowledgements
2
2
2
0 K. Iwamoto, A. Yanagi, K. Araki and S. Shinkai, Chem. Lett., 1991,
3, 473.
This work was supported by the Grant Agency of the Czech
Republic (nos. 203/03/0926 and 203/02/D176). The Grant
Agency supported the purchase of the X-ray diffractometer as
well (203/99/M037).
1 A. Arduini, M. Fabbi, M. Mantovani, L. Mirone, A. Pochini, A.
Secchi and R. Ungaro, J. Org. Chem., 1995, 60, 1454.
2 J. D. Van Loon, A. Arduini, L. Coppi, W. Verboom, A. Pochini, R.
Ungaro, S. Harkema and D. N. Reinhoudt, J. Org. Chem., 1990, 55,
5
639.
2
3 A. Casnati, M. Fochi, P. Minari, A. Pochini and M. Reggiani, Gazz.
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