Conformational properties of C2v-symmetrical resorcin[4]arene tetraethers

Article abstract of DOI:10.1002/poc.1023

Resorcin[4]arene tetraether derivatives, in which a resorcinol unit and a 1,3-dialkoxybenzene unit are incorporated in an alternating order, were synthesized by the Sc(OTf)3 catalyzed '2 + 2' fragment condensation. The conformational properties were studied using variable temperature ¹H-NMR spectroscopy, indicating that the resorcinarenes are flexible at room temperature but frozen in the cone formation at -90°C in CD ₂Cl₂, and they interconvert between two equivalent cone conformations with an energy barrier of ΔGc^? = 10.2-10.5 kcal mol^-1. These values are slightly lower than that for the resorcin[4]arene containing four 2-hexylresorcinol units. The cone conformation is stabilized by intramolecular hydrogen bonds between the OH hydrogen and ether oxygen, which is evidenced by the low frequencies (3423-3434 cm^-1) of the OH-stretching vibrations in CDCl₃ solution. Copyright

Full text of DOI:10.1002/poc.1023

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
J. Phys. Org. Chem. 2006; 19: 214–218
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/poc.1023
Conformational properties of C2v-symmetrical
resorcin[4]arene tetraethers
*
Osamu Morikawa, Eiichi Iyama, Tomoyoshi Oikawa, Kazuhiro Kobayashi and Hisatoshi Konishi
Department of Materials Science, Faculty of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan
Received 16 August 2005; revised 14 December 2005; accepted 20 December 2005
ABSTRACT: Resorcin[4]arene tetraether derivatives, in which a resorcinol unit and a 1,3-dialkoxybenzene unit are
incorporated in an alternating order, were synthesized by the Sc(OTf)3 catalyzed ‘2 þ 2’ fragment condensation. The
conformational properties were studied using variable temperature 1H-NMR spectroscopy, indicating that the
resorcinarenes are flexible at room temperature but frozen in the cone formation at ꢀ90 8C in CD2Cl2, and they
interconvert between two equivalent cone conformations with an energy barrier of DGcz ¼ 10.2–10.5 kcal molꢀ1
.
These values are slightly lower than that for the resorcin[4]arene containing four 2-hexylresorcinol units. The cone
conformation is stabilized by intramolecular hydrogen bonds between the OH hydrogen and ether oxygen, which is
evidenced by the low frequencies (3423–3434 cmꢀ1) of the OH-stretching vibrations in CDCl3 solution. Copyright
# 2006 John Wiley & Sons, Ltd.
Supplementary electronic material for this paper is available in Wiley Interscience at http://www.interscience.
wiley.com/jpages/0894-3230/suppmat/
KEYWORDS: conformation analysis; hydrogen bonding; resorcinarenes; calixarenes; variable temperature NMR
INTRODUCTION
cone conformation, which is stabilized by four intramo-
lecular hydrogen bonds between adjacent OH groups. For
this compound, the barrier of the conformational
inversion is 12.0 kcal molꢀ1 in CDCl3.14 The circular
array of hydrogen bonds is responsible for the greater
conformational stability for A. Therefore, since the partial
replacement of OH groups by OCH3 groups leads to a
decrease in the number of hydrogen bonds and the
breakdown of the hydrogen bonding array, this structural
change significantly influences both the static and
dynamic stereochemistries of the resulting systems.15–
Polyhydroxy[14]metacyclophanes, such as calix[4]arenes
(A) and resorcin[4]arenes (B), are readily available
macrocycles, and are widely used in the fields of
supramolecular chemistry.1–6 Extensive studies on their
conformational properties have been conducted for many
years.7–10 The hydrocarbon framework of [14]metacy-
clophane is very conformationally flexible, and there are
six extreme conformations, designated ‘cone (crown),’
‘flattened cone (boat),’ ‘partial cone,’ ‘1,3-alternate,’ ‘1,2-
alternate,’ and ‘chair.’11–13 The relative stabilities of the
conformational isomers and the energy barrier for the
interconversion between them are largely dependent upon
the substituents at the intra-annular and extra-annular
positions of the macrocycles. Especially, the intramole-
cular hydrogen bondings between the phenolic hydroxyl
groups on the neighboring aromatic rings play an
important role in determining the conformational proper-
ties (Scheme 1).
19
We are interested in the conformational properties of
the resorcin[4]arene tetraethers (C), in which a resorcinol
unit and a 1,3-dialkoxybenzene unit are incorporated in
an alternating order. In this case, the number of the
hydrogen bondings is the same as for (B), and the
functionalization of the OH groups at the extra-annular
positions does not sterically hinder the inversion of the
macrocycles. We now describe the first ‘2 þ 2’ fragment
synthesis of ABAB-type resorcin[4]arenes and their
conformational properties in solution.
Calix[4]arene (A; R ¼ tert-Bu) possessing four OH
groups at the intra-annular positions adopts a cone
conformation stabilized by a circular array of hydrogen
bonds, which undergoes a cone-to-cone inversion process
(Scheme 2) with a barrier of 15.7 kcal molꢀ1 in CDCl3.7
Also, resorcin[4]arene (B; R ¼ n-hexyl) possessing eight
OH groups at the extra-annular positions exists in the
RESULTS AND DISCUSSION
Synthesis
We have previously demonstrated that the Sc(OTf)3
catalyzed cyclocondensation of 2,4-dialkoxybenzyl
alcohols produced resorcinarene octaethers in good
yields.20,21 Based on this study, the ABAB-type
*Correspondence to: H. Konishi, Department of Materials Science,
Faculty of Engineering, Tottori University, 4-101 Koyama-minami,
Tottori 680-8552, Japan.
E-mail: konis@chem.tottori-u.ac.jp
Copyright # 2006 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2006; 19: 214–218

CONFORMATIONAL PROPERTIES OF C2v-SYMMETRICAL RESORCINARENES
215
Scheme 1. Calix[4]arene (A) and ABAB-type resorcine[4]arene tetraether (C)
resorcin[4]arenes were prepared in a ‘2 þ 2’ fragment
synthesis as shown in Scheme 3. Although a variety of
regioselectively substituted calixarenes with well-defined
structures have been prepared by fragment synthesis,22
this methodology has been scarcely used for the
construction of resorcinarenes. For example, resorci-
n[4]arenes bearing alternating substituents at their
bridging positions were synthesized.23 However, the
direct synthesis of ABAB type resorcin[4]arenes con-
sisting of different resorcinol units has not been reported.
Scheme 2. Cone-to-cone interconversion in[14]metacyclo-
phane system, and intraannular (Hin), extraannular (Hex),
axial (Hax), and equatorial (Heq) protons in the cone
conformer
Scheme 3. ‘2 þ 2’ Fragment synthesis of resorcin[4]arene tetraethers. Reagents and sol-
vents: (i) NaBH4, EtOH; (ii) 2-propylresorcinol, Sc(OTf)3, MeCN; (iii) POCl3, DMF; (iv) NaBH4,
EtOH; (v) Sc(OTf)3, MeCN
Copyright # 2006 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2006; 19: 214–218

216
O. MORIKAWA ET AL.
The condensation of 2-propylresorcinol with 2,4-
dialkoxybenzyl alcohols 2 in CH3CN was catalyzed by
Sc(OTf)3 to give diphenylmethanes 3 in 42–73% yields.
The Vilsmeier formylation of 3 produced the benzalde-
hydes 4 in 42–63% yields. The aldehydes were then
reduced with NaBH4 to give the dimeric components 5 in
64–82% yields. Finally, the cyclocondensation was
conducted in CH3CN in the presence of Sc(OTf)3 that
resulted in the formation of the ABAB-type cyclic
tetramers 6. Although the yields in the last step were in
the range of 7–15%, the cyclic tetramers 6a, 6b, and 6c
precipitated during the reaction and were easily obtained
as pure materials. On the other hand, compound 6d was
soluble in the reaction solvent and isolated by preparative
gel permeation chromatography (GPC). The structure and
composition of the ABAB resorcinarenes 6 were
Figure 1. 1H-NMR spectrum of the methylene region of 6a
in CD2Cl2 at different temperatures
1
confirmed by H and 13C NMR spectroscopies, FAB-
mass spectrometry, and elemental analysis.
of 6a at different temperatures is shown in Fig. 1 and the
results are summarized in Table 1. At ꢀ90 8C in this
solvent, compound 6a showed one AB quartet (3.38 and
4.01 ppm, J ¼ 14.2 Hz) arising from the four equivalent
bridging methylene groups, indicating conformational
freezing on the NMR time scale. The large chemical shift
difference between the two methylene protons
(Dd ¼ 0.63 ppm) suggests that the adjacent two aromatic
rings adopt syn arrangements. That is, the freezing
conformation should be a cone or flattened cone. These
conformations can be discriminated by examination of
the chemical shifts of the intra-annular aromatic protons
(Hin), since they significantly depend upon the orientation
of the adjacent aromatic rings. Two Hin signals in 6a,
which were assigned by two-dimensional NMR spectro-
scopy (NOESY), appeared as singlets at 6.99 and
7.25 ppm, respectively. On the other hand, the dimer
3a showed their corresponding aromatic protons at 6.90
and 7.12 ppm (Dd ¼ 0.22 ppm), respectively. Therefore,
the difference in the chemical shifts that observed for 6a
(Dd ¼ 0.26 ppm) can be primarily accounted for the
difference in the substituents at the meta-positions.
Namely, it is reasonably concluded that both Hin protons
are under the same anisotropy influence of the aromatic
rings, and that the metacyclophane framework adopts a
cone conformation with nearly C4v symmetry.
To clarify the low yields of the fragment synthesis, we
analyzed the soluble fraction of the reaction mixture
obtained from the synthesis of 6a. The GPC separation of
the soluble fraction gave various types of low linear
oligomers such as dimers and trimers. Interestingly, it was
also shown that most of these isolated oligomers had no
terminal hydroxymethyl groups. These products probably
resulted from the fragmentation of the initially formed
linear oligomers via an ipso-attack of the benzyl
cations24–26 and the dimerization of the activated benzyl
alcohols via dehydroxymethylation.27 Thus, we conclude
that the fragmentation and recombination of linear
oligomers are responsible for the low yields of the
‘2 þ 2’ fragment synthesis.
Conformational properties
The 1H-NMR spectra of 6 recorded at 30 8C showed three
singlets for the aromatic protons of the metacyclophane
core and one singlet for the bridge methylene protons,
indicating that these compounds are conformationally
flexible systems. To confirm the preferred conformation
of the cyclic tetramers, we measured their low-
temperature 1H-NMR spectra. Since compounds 6a,
6b, and 6d have good solubilities in CD2Cl2, their
conformational properties could be analyzed by variable-
temperature NMR spectroscopy. The 1H-NMR spectrum
The bridging methylene signal that appeared at a
higher field (3.38 ppm) showed an NOE correlation with
two Hin signals. Hence, the higher field signal is assigned
Table 1. Chemical shifts of the intra-annular aromatic protons (Hin) and methylene protons (Hax and Heq) at ꢀ90 8C in CD2Cl2
and the activation energies for the conformational change at the coalescence temperature (Tc)
Compound
Hin
Hax
Heq
J/Hz
DGz/kcal molꢀ1
Tc/K
6a
6b
6d
7.25/6.99
7.02/6.89
7.02/6.90
7.19
3.38
3.27
3.29
3.51
4.01
3.91
3.93
4.08
14.2
13.7
14.0
13.0
10.2
10.5
10.5
11.7
228
233
233
251
B (R ¼ n-Hexyl)a
a Reference [14]. Determined at S50 8C in CDCl3.
Copyright # 2006 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2006; 19: 214–218

CONFORMATIONAL PROPERTIES OF C2v-SYMMETRICAL RESORCINARENES
217
CONCLUSION
Resorcin[4]arene tetraether derivatives, in which a
resorcinol unit and a 1,3-dialkoxybenzene unit are
incorporated in alternating order, were synthesized by
the Sc(OTf)3 catalyzed ‘2 þ 2’ fragment condensation.
The conformational properties were studied by variable
temperature 1H-NMR and IR spectroscopy. The preferred
conformation is a cone with nearly C4v symmetry, which
is stabilized by intramolecular hydrogen bonds between
the OH hydrogen and ether oxygen. On the NMR time
scale, the resorcinarenes are flexible at room temperature,
but frozen in the cone formation at ꢀ90 8C in CD2Cl2.
Their activation energies for the interconversion between
two equivalent cone conformations are slightly lower than
that for the resorcin[4]arene containing four 2-hexylre-
sorcinol units.
Scheme 4. Intramolecular hydrogen bondings in a re-
sorcin[4]arene tetraether
Experimental procedures and spectral data for all new
compounds are available via the Internet at EPOC website.
to the axial protons (Hax) and the lower field signal is
assigned to the equatorial protons (Heq) (Scheme 2). In
contrast, in the calix[4]arene systems, the equatorial
methylene proton resonates at a higher field than the axial
ones.28,29 This is because the Heq protons of 6 is in close
proximity to the oxygen functions (OH, OR), and are in an
environment similar to the Hax of calix[4]arenes.
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