Selective formation of the rctt chair stereoisomers of octa-O-alkyl resorcin[4]arenes using Bronsted acid catalysis

Article abstract of DOI:10.1039/b714735j

New synthetic conditions are described for the fully selective formation of the rctt chair stereoisomers of octa-O-alkyl resorcin[4]arenes; these offer a clean route into the chair conformer of these interesting receptor molecules. Bronsted acid catalysis in acetic acid solutions results in the formation of the single isomer when 1,3-dimethoxybenzene is heated at 80 °C with a range of aldehydes, straight- and branched-chain or aromatic, and with an aldehyde synthon. An investigation of reaction conditions indicated that, in this case, the rctt chair stereoisomer was the thermodynamic product, a result confirmed by molecular modelling studies that show that this stereoisomer is of lower energy than the expected rccc boat stereoisomer. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.

Full text of DOI:10.1039/b714735j

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PAPER
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Selective formation of the rctt chair stereoisomers of octa-O-alkyl
resorcin[4]arenes using Brønsted acid catalysisw
Deborah Moore,a Graeme W. Watson,a Thorfinnur Gunnlaugsson*a and
Susan E. Matthews*b
Received (in Durham, UK) 25th September 2007, Accepted 10th January 2008
First published as an Advance Article on the web 4th February 2008
DOI: 10.1039/b714735j
New synthetic conditions are described for the fully selective formation of the rctt chair
stereoisomers of octa-O-alkyl resorcin[4]arenes; these offer a clean route into the chair conformer
of these interesting receptor molecules. Brønsted acid catalysis in acetic acid solutions results in
the formation of the single isomer when 1,3-dimethoxybenzene is heated at 80 1C with a range of
aldehydes, straight- and branched-chain or aromatic, and with an aldehyde synthon. An
investigation of reaction conditions indicated that, in this case, the rctt chair stereoisomer was the
thermodynamic product, a result confirmed by molecular modelling studies that show that this
stereoisomer is of lower energy than the expected rccc boat stereoisomer.
been reported; however, these have shown them to be useful
Introduction
new host molecules with a wide range of applications. Hence,
they are able to complex alkali-metal,8 transition-metal9 and
The field of supramolecular chemistry has generated many
organic cations,8 can be used to bind neutral electron-accep-
elegant examples of macrocyclic structures capable of func-
tioning as hosts for molecular recognition and sensing.1 Of
tors,8,10 have been used for chiral recognition (when carrying
such structures, the resorcin[n]arene 12 (the general structure
chiral substituents)11 and have the potential for the develop-
for n = 4 is depicted in Fig. 1) are particularly attractive
ment of more complex structures through selective functiona-
lisation of the methylene bridges.12
building blocks for supramolecular chemists, as they possess
highly symmetrical ‘bowl’ shape cavities, can be tailored to
different sizes (by changing the number of aryl units),3,4 can
and a large range of aldehydes using Brønsted-acid cataly-
Resorcin[4]arenes can readily be prepared from resorcinol
readily be functionalised5,6 and consequently can be employed
sis.13,14 To date, derivatives featuring methoxy substituents
in the formation of larger self-assembled structures.7 It is,
have only been prepared by Lewis-acid catalysis of 1,3-
therefore, somewhat surprising that octa-O-alkyl resorcin-
dimethoxybenzene–aldehyde mixtures in chloroform or
diethyl ether (SnCl4)15 or of 2,4-dimethoxycinnamates (BF3Á
[4]arenes, in which the hydroxy groups are masked, such as
Et2O).16 Similar approaches have also been used for the
2, are a relatively unexplored variation on the resorcin[4]arene
preparation of hybrid alkoxy/hydroxy analogues,17–19 the
system. To date, only a few studies on their applications have
parent resorcin[4]arene20–23 which is unavailable through
acid-catalysed condensation of resorcinol with formaldehyde,
ring expanded derivatives featuring between five and nine
aromatic units,24 and confused cyclotetramers25 in which an
aromatic ring is connected through the 2–6 positions. Inter-
estingly, it has been reported that mineral-acid catalysed
reactions fail to yield the cyclic tetramers (o1% yield) under
standard conditions with 1,3-dimethoxybenzene.14
As part of a synthetic programme focussed on selective
derivatisation of the methylene bridge residues of resorcin-
[4]arenes,26 we investigated the synthesis of octa-O-alkyl
resorcin[4]arenes bearing hydroxy-containing residues at the
methylene bridges. In this paper, we report the first example of
Fig. 1 Resorcin[4]arenes and octa-O-alkyl resorcin[4]arenes.
selective formation of the rctt chair stereoisomer in acetic
acid–H2SO4 or acetic acid–HCl mixtures and propose that this
isomer is the thermodynamic product under Brønsted-acid-cata-
lysis, an unprecedented observation in resorcinarene chemistry.
a School of Chemistry, Trinity College, University of Dublin, Dublin 2,
Ireland. E-mail: gunnlaut@tcd.ie
b School of Chemical Sciences and Pharmacy, University of East
Anglia, Norwich, UK NR4 7TJ. E-mail: susan.matthews@uea.ac.uk;
Fax: 44 1603-592003; Tel: 44 1603 595986
Results and discussion
w Electronic supplementary information (ESI) available: Character-
isation of rccc-boat isomers and of acylated derivatives. See DOI:
10.1039/b714735j
Our initial studies focussed on the reaction of 4-hydroxyben-
zaldehyde with 1,3-dimethoxybenzene to prepare octa-O-alkyl
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Fig. 2
resorcin[4]arenes 3 bearing aromatic hydroxy groups on the
methylene bridge positions as both the rccc boat 3a and rctt
chair 3b stereoisomers (Fig. 2).
Stereoisomers of octa-O-alkyl resorcin[4]arenes
The condensation reaction of resorcinol or dialkoxybenzenes
with aldehydes, other than formaldehyde, results in cyclic
tetramers which may exist as a number of different stereo-
isomers.1 These stereoisomers can be categorised through (i)
the configuration at each methylene bridge position, (ii) the
conformation adopted by the aromatic residues and (iii) the
relative position, axial or equatorial, of each residue at the
methylene bridge position. Of the many possible stereoisomers
three; the rccc boat (crown), the rctt chair and rcct diamond
(Fig. 3), have been isolated in the case of reactions between
resorcinol and aldehydes with the additional rccc saddle, a
conformational isomer of the rccc boat, having been reported
for octa-O-alkyl derivatives where rotation of the aromatic
residues is restricted. In addition, the rccc boat is often
observed as the C2v flattened boat conformational isomer in
1H NMR and X-ray crystal structure studies.
Fig. 3 Common diastereoisomers and conformers of resorcin[4]-
arenas.
has proved successful in forming the parent resorcin[4]arene
using paraformaldehyde in 2-ethoxyethanol.22
The condensation was initially investigated using the stan-
dard conditions for the formation of resorcin[4]arenes, cata-
lytic HCl in boiling ethanol (Table 2). Short reaction times
resulted in the formation of a mixture of both boat and chair
isomers, whereas increasing the reaction time, led to a slight
increase in the formation of the rctt chair but did not give
complete selectivity. Equally using a high pressure reaction at
150 1C did not significantly alter the ratio of the products and
reducing the temperature to decrease the reaction rate resulted
in failure to condense.
Lewis acid-catalysed reactions
Iwanek and Syzdol15 have described the selective formation of
the rccc boat stereoisomer of octa-O-methylresorcin[4]arenes
from branched-chain aldehydes when using SnCl4, a Lewis
acid catalyst, in chloroform. Other Lewis acids resulted in
more complex mixtures in which the rcct diamond was the
major contaminating isomer (43–62%), while trace amounts
of the chair compound could also be isolated in most cases.
Following these experimental conditions we were unable to
isolate a single conformer. Instead a mixture of two isomers
was observed, not only the expected boat but also the rctt
chair stereoisomer (vide infra) (Table 1). Changing the solvent
to diethyl ether, a solvent reported to be more suited to
reactions with straight-chain aldehydes,15b indicated that
lengthening the reaction time could significantly alter the
product distribution in favour of the boat isomer but it was
still not the sole product. In all cases, there was no evidence for
the formation of the diamond stereoisomer.
It has been noted that the parent resorcin[4]arene can be
prepared from 1,3-dimethoxybenzene and paraformaldehyde
using a sulfuric acid–acetic acid mixture at room tempera-
ture.27 Using similar conditions with 4-hydroxybenzaldehyde
again gave a mixture of two isomers.
The 1H NMR (DMSO-d6) for this mixture clearly shows the
presence of the two isomers through the appearance of two
non-equivalent singlets in the characteristic peak range
(d 4.9–5.5) for the methylene bridge hydrogen (Fig. 4(a)).
Additionally, two series of peaks, with integrals corresponding
Table 1 Distribution of conformers of 3 formed using SnCl4 cata-
lysisa
Solvent
t/h
Ratio boat : chair conformers
Overall yield (%)
CHCl3
CHCl3
Et2O
Et2O
Et2O
a
16 28 : 72
61
69
70
76
75
Brønsted acid-catalysed reactions
72 37 : 63
16 4 : 6
72 3 : 1
Following from these results, we decided to re-investigate the
use of Brønsted-acid catalysts in the formation of octa-O-alkyl
resorcin[4]arenes. While this has been reported previously to
give exceptionally low yields (o1%)14 of the cyclic tetramer, it
334 3 : 1
SnCl4, 25 1C.
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Table 2 Distribution of conformers of 3 formed using HCl in ethanol
Table 3 Distribution of conformers of 3 formed using protic acid
catalysisa
T/1C
t/h
Ratio boat : chair conformers
Overall yield (%)
Catalyst
T/K
Boat (%)
Chair (%)
Overall yield (%)
À20
0
75
75
75
a
16
16
5
16
72
—
—
25 : 75
21 : 79
21 : 79
0a
0a
70
68
73
None
HCl
H2SO4
HNO3
CF3COOH
HCl
25
80
80
80
80
25
25
25
25
0
0
0
0
0
33.3
67
0
0
100
100
0
0
54
50
0
0
0
Unreacted starting material isolated.
66.6
33
0
55
50
0
H2SO4
HNO3
CF3COOH
a
to the two individual bridge signals, can be identified, leading
to the conclusion that the mixture contains both boat and
chair isomers (vide infra).
0
0
0
20 ml acetic acid, ca. 10 meq. H+ 18 h.
However, when the reaction was carried out at 80 1C the
chair isomer was formed exclusively (Fig. 4(b)). This assign-
be directly related to their strength. The lack of condensation
with TFA is particularly interesting, as Urbaniak and Iwa-
nek30 have noted that halogenoacetic acids can cause isomer-
isation of octa-O-alkyl resorcin[4]arenes. In that case, addition
of the acid to a CHCl3 solution of an rccc boat octa-O-methyl
resorcin[4]arene, which had been prepared by Lewis-acid
condensation, resulted, after 48 h, in a product which was a
mixture of the rcct diamond and rccc boat isomers with the
chair being an additional minor component (B10%).
While we have shown that the rctt chair conformer could
readily be prepared selectively at high temperature, it can also
be obtained by separation from the isomeric mixture formed at
low temperature, by hot filtration from a methanolic solution.
However, isolation of the pure boat form from the mixture is
more problematic, with the hot filtration method resulting in
B10% contamination by the chair conformer. Esterification
of the phenolic hydroxy group leads to compounds with
enhanced solubility which can be separated by flash column
chromatography. Reaction with butanoic anhydride and chro-
matography (CHCl3–EtOAc 95 : 5) of the product 21 proved
more successful than separation of the acetates 20. Hydrolysis
with ethanolic potassium hydroxide then yielded the pure boat
stereoisomer (Fig. 4(c)). The 1H NMR (DMSO-d6) gives clear
1
ment was confirmed by H NMR analysis of 2b which was in
agreement with spectra of previously describe rctt chair con-
figurations.28,29 A single resonance for the bridging Ha proton
is observed but the presence of four signals for the ring
aromatic groups (Hb and Hc) indicates two different types of
resorcinol units and an rctt configuration of the methylene
bridge substituents. The spectra showed no changes upon
heating to 60 1C, indicating that the conformation was rigid
and thus confirming the presence of a chair, rather than a C2v
temperature-dependent flattened boat. The spectrum was ad-
ditionally assigned using comparisons with NOE experiments
on the acylated derivative 20. It is worth noting that, in the
case of the derivatives 20 and 21, the purified rccc-boat
conformer was seen as the C2v flattened boat on the 1H
NMR time scale (Fig. S1, ESIw).
Consideration of the reaction conditions showed that the
addition of a stronger acid catalyst was essential, as no
condensation was observed in acetic acid alone, and that the
catalysis could also be achieved with HCl but not by TFA or
HNO3 (Table 3). With the two latter acids, only the original
starting materials were isolated, even after longer reaction
times. Thus the catalytic activity of the Brønsted acids cannot
1
Fig. 4 Expansion of the aromatic region of the H NMR (400 MHz) in DMSO-d6 spectra of 3. (a) Products isolated from reaction at 25 1C in
acetic acid using H2SO4 catalysis, showing the presence of 3a and 3b, (b) purified chair conformer 3b, (c) purified boat conformer 3a.
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identification of the rccc boat configuration,28,29 in which all
resorcinol units and substituents are identical, featuring single
peaks for the bridging proton (Ha) and for each of the
aromatic peaks (Hb and Hc) and a pair of doublets for the
4-hydroxybenzyl substituents (Hd and He). Comparison of the
mass spectrometric data for the two stereoisomers provides a
preliminary indication of different binding abilities for group 1
metals, with the rccc boat showing the presence of both
sodium and potassium complexes while the rctt chair shows
minimal complexation of potassium and diminished com-
plexation of sodium (Fig. 2 and 3, ESIw).
protons, two for the acetyl protons and a quartet for the CH
bridging proton.
Additionally, when using the branched-chain aliphatic iso-
valeraldehyde the condensation at high temperature again
results in exclusive formation of the rctt chair isomer (Table 5,
15). This isomer has previously been reported only as a minor
component (maximum 10% with AlCl3) in Lewis-acid cata-
lysed condensation reactions15 which tend to favour the
formation of the boat and diamond.
Octa-O-methyl resorcin[4]arenes featuring o-hydroxyalkyl
substituents at the methylene bridge have been prepared
previously through post-condensation reduction of CH2CO2R
esters of the corresponding octa-O-methylresorcin[4]arenes,
which in turn had been prepared by the reaction of
2,4-dimethoxycinnamates with BF3ÁEt2O.31 In that case, while
three separate isomers could be characterised from the initial
condensation [an rccc-boat, a rcct diamond-like structure and
a rccc 1,3-alternate (or saddle) conformation], treatment with
LiAlH4 resulted in only the boat and diamond o-hydroxyalkyl
derivatives being isolated.
Generality of reaction
With this important result in hand, the generality of this
stereoisomerically selective reaction for synthesis of other
octa-O-alkyl resorcin[4]arenes was explored (Table 4, Scheme
1). Condensation reactions under these new synthetic condi-
tions with a series of aldehydes and masked aldehydes were
investigated to determine the role of hydrogen bonding inter-
actions and steric bulk in directing the formation of products.
Reaction with a long chain O-alkyl derivative of 4-hydro-
xybenzaldehyde, where there is no possibility of intra or inter-
molecular hydrogen bonding, yielded 13. This reaction gave
consistent results at 80 1C (100% rctt chair formation) and
showed further selectivity for the chair conformer under low-
temperature (25 1C) conditions, indicating that the results
obtained for 3 are not solely a result of hydrogen bonding.
Equally, when using a simple straight-chain aliphatic alde-
hyde such as acetaldehyde, full selectivity for the rctt chair was
again achieved at high temperature. This leads to the conclu-
sion that the previously observed selectivity is not only a
consequence of steric interactions between the large aryl units.
The reaction of acetaldehyde with 1,3-dimethoxybenzene has
been reported14 to yield the boat stereoisomer, in very low
yield, when the condensation is performed in methanolic HCl
for 1 h. Comparison of the 1H NMR spectroscopic data for 14
with those reported (Table 5) confirms the formation of a
different stereoisomer under our high-temperature conditions
and the formation of a mixture of the previously reported and
new isomer at room temperature. This is clearly shown by the
appearance of four separate signals for the aromatic ring
This makes the results obtained for the reaction of
1,3- dimethoxybenzene and 2,3-dihydrofuran, an enol–ether
masked aldehyde, particularly interesting. While Lewis-acid
catalysis (SnCl4/CHCl3) failed to yield any cyclic tetramer, a
single isomer was isolated both at room temperature (albeit in
low 17% yield) and on heating to 60 1C using HCl catalysis in
acetic acid. Comparison of the spectroscopic data for 16 (Fig. 5)
with the published data for the similar boat and diamond shows
this to be a previously unobtainable conformer, which can be
formed in a single-step reaction. This was identified as a C2-
symmetrical structure on the basis of its 1H NMR spectrum. In
this spectrum, there is a doubling of all aromatic proton signals,
while the bridging proton gives a single triplet, confirming that it
is the rctt isomer in the chair conformation.
Thus the selective formation of rctt chair stereoisomers of
octa-O-methyl resorcin[4]arenes proceeds in excellent yield for
a wide range of aldehydes under these newly developed
synthetic conditions, opening up the chemistry of these mole-
cules for further development for diverse applications. How-
ever, it should be noted that the use of the highly sterically
demanding and less reactive 3,5-dihydroxybenzaldehyde failed
to yield any cyclic product in this reaction.
Table 4 Application of conditions to other substratesa
R1
H
R2
R3
T/1C
Boat (%)
Chair (%)
Overall yield (%)
13
14
15
16
17
18
19
a
Me
4-C6H4OC8H17
25
80
25
80
25
80
25
60
25
80
25
80
25
80
17
0
40
0
48
0
0
83
100
60
100
52
100
100
100
—
—
—
21
54
91
70
H
Me
Me
Me
Me
Me
Bn
CH3
H
CH2CH(CH3)2
CH2CH2CH2OH
3,5-C6H3(OH)2
4-C6H4OH
4-C6H4OH
b
88
30.5
17.4b
61.4b
H
0
c
H
—
—
—
—
—
17
—
—
c
c
OMe
H
—
—
c
—
—
83
c
—
76
20 ml acetic acid, 0.0102 mmol H+, 18 h. HCl catalysis. Starting materials isolated.
c
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Scheme 1 General scheme for the reaction of aldehydes with alkylated resorcinols.
To investigate further that the selective formation of the rctt
chair was not solely a property of the alkoxybenzene, we first
examined the reaction of 1,3-dibenzoxybenzene with 4-hydro-
xybenzaldehyde. In this case, no condensation was seen at
lower temperatures. However, upon heating (80 1C) a mixture
of the two isomers was observed which was biased in an B4 : 1
ratio in favour of the chair. This suggests that similar results
could be obtained with a wide range of dialkoxybenzenes,
although the actual product distribution may be affected by
steric effects with larger O-alkyl groups. In contrast, when
1,2,3-trimethoxybenzene, a pyrogallol analogue, is used in the
condensation reaction, no product was observed under either
set of reaction conditions. This lack of reactivity is in line with
the results observed by Iwanek et al.8 using SnCl4 catalysis,
where only the parent pyrogallorene could be formed through
the reaction of 1,2,3-trimethoxybenzene with trioxane, and
reactions with aliphatic aldehydes failed to yield cyclic
tetramers.
acid results in formation of the boat. This preference for the
boat conformer has been related to the ability to form the
maximum number of hydrogen bonds between the resorcinol
units with the minimum steric interference between the
substituents at the methylene-bridge positions.1,14
In the case of octa-O-alkyl resorcin[4]arenes, the major
driving force to the formation of the boat, the presence of
an array of hydrogen bonds between the resorcinol units, is no
longer an important factor. In the previous synthetic accounts
where Lewis acids have been used, stereoisomer mixtures have
been observed. In the cases of catalysis by SOCl2, POCl3 and
AlCl3 the rcct diamond isomer has been the preferentially
formed product: selectivity for the boat is only observed when
SnCl4 is used, a result that has been ascribed to templation by
complexation of the metal ions to the ether oxygens.15
In view of these previous reports, the isolation of the rctt
chair from the reactions of 1,3-dimethoxybenzene with a range
of aldehydes is initially somewhat surprising. While in the
majority of cases this reaction is heterogeneous, identical
results in favour of the rctt chair stereoisomer are observed
even when the reaction conditions are homogeneous, as in the
case of 14. In this Brønsted-acid catalysed reaction, potentially
templating metal and potential hydrogen bonding arrays
between the aromatic units are absent. This suggests that, in
this case, the thermodynamically more stable isomer may be a
result of minimised steric interactions, i.e. is one in which the
O-methylresorcinol units are as far apart as possible both from
themselves and, through a rctt configuration at the methylene
bridge positions, from the side chains.
Selectivity of the reaction
In this study, we have observed selectivity for the formation of
the rctt chair isomer of octa-O-alkyl resorcin[4]arenes for a
range of aldehydes and resorcinol derivatives. In the synthesis
of resorcin[4]arenes under homogeneous conditions where
there is no protection of the phenolic OH groups, the chair
is considered to be the kinetic product which is only observed
in the early part of the reaction, whereas the rccc boat is the
thermodynamic product. The situation is more complex in
heterogeneous reactions,1,14 where the solubility of each iso-
mer can affect the distribution of products, but it has still been
shown that prolonged treatment of the rctt chair isomer with
To investigate whether this chair arrangement was particu-
larly stable in comparison to the boat, which is only formed at
1
Table 5 Comparison of H NMR data for 14 and 15 (CDCl3) with previously reported data for isolated stereoisomers
Compound
Stereoisomer
Spectrum
Ref.
14
rctt chair
rccc boat
6.56 (s), 6.44 (s), 6.41 (s), 6.36 (s) 4.59 (q), 3.87 (s), 3.79 (s), 1.45 (d)
6.50 (s), 6.46 (s), 4.47 (q), 3.61 (s), 1.32 (d)
This study
14
15
rctt chair
rctt chair
rccc boat
rcct diamond
6.96 (s), 6.51 (s), 6.43 (s), 6.27 (s), 4.69 (m), 3.91 (s), 3.65 (s), 1.62 (m), 1.43 (m), 0.85 (d)
6.93 (s), 6.59 (s), 6.40 (s), 6.25 (s), 4.66 (m), 3.88 (s), 3.62 (s), 1.60 (m), 1.42 (m), 0.82 (d)
6.60 (s), 6.32 (s), 4.60 (t), 3.60 (s), 1.69 (dd), 1.55 (m), 0.91 (d)
7.66 (s), 6.52 (s), 6.43 (s), 6.36 (s), 5.23 (t), 4.76 (m), 3.86 (s), 3.83 (s), 3.76 (s), 3.58 (s),
1.82 (m), 1.55 (m), 1.33 (m), 0.89 (m), 0.79 (m), 0.55 (d)
This study
15
15
15
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Fig. 5 1H NMR spectrum of 16 in CDCl3 (side-chain signals not shown).
lower temperatures, we undertook hybrid density functional
theory calculations at the B3LYP level with a 6-31G(d) basis
set in the Gaussian 03 package.32 Calculations were performed
on a range of starting conformations of the two fixed config-
urations (rccc and rctt) of 14, which features methyl residues at
the methylene bridges. The minimised conformations are
shown in Fig. 6 with the energies in Table 6. The calculations
predict an energy difference of 1.2 kJ molÀ1, in favour of the
chair conformation, in line with our experimental results.
Inspection of the optimised conformer for 14a shows that
the octa-O-methyl resorcin[4]arene exists in a flattened boat
arrangement. The angles between the flattened aromatic units
are 01 with the methyl groups orientated above the plane such
that a methyl hydrogen atom interacts with a methoxy oxygen
on the adjacent ring. For 14b, a normal chair conformation is
obtained, once again with the methyl groups on the co-planar
rings orientated to maximize their interaction with adjacent
methoxy groups.
Table 6 Comparison of energy of minimised conformations of 14
and 22
Stereoisomer
14
22
rccc Boat (Hartrees)
rctt Chair (Hartrees)
Chair À Boat (kJ molÀ1
À2154.88076 (14a) À1840.461459 (22a)
À2154.881482 (14b) À1840.443855 (22b)
)
À1.2
46.2
To ensure validation of the results obtained for 14a and 14b,
calculations were also performed on the known analogous
resorcin[4]arenes 22a and 22b which have been shown exper-
imentally to exist preferentially in the rccc boat stereoi-
somer.1,14 The optimised conformations are shown in Fig. 7,
Fig. 7 Predicted structure of (a) 22a and (b) 22b using B3LYP/
6-31G(d).
with the corresponding energies in Table 6. As expected, the
lower energy macrocycle has a rccc configuration with adop-
tion of the boat conformation. This achieves maximum hydro-
gen bonding (1.92 A), with the angle between opposite
aromatic units being 771. In contrast, the higher energy rctt
configuration adopts a chair conformation with minimal
hydrogen bonding (3.25 A). To quantify the effect of the
hydrogen bonding MM3 calculations were carried out using
the Cache Package.33 These calculations indicate that the
hydrogen bonding stabilizes the rccc configuration by over
30 kJ molÀ1. This confirms that H bonding is a significant
driving force in the adoption of the rccc conformation for 22, a
factor which is absent for 14.
Conclusions
Condensation reactions of 1,3-dimethoxybenzene with a di-
verse series of aldehydes using Brønsted-acid catalysis in acetic
Fig. 6 Predicted structure of (a) 14a and (b) 14b using B3LYP/
6-31G(d).
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acid at 80 1C lead exclusively to the formation of the rctt chair
stereoisomer of the octa-O-alkyl resorcin[4]arenes. Unlike
previously reported methods for the formation of the rccc
boat stereoisomer,15 the new reaction conditions are applic-
able over a wide range of starting aldehydes, including
branched- and straight-chain aliphatic aldehydes, aromatic
aldehydes and even the masked aldehyde 2,3-dihydrofuran.
The presence of the expected competing rccc boat stereoisomer
in lower-temperature reactions leads to the conclusion that, in
the synthesis of octa-O-alkyl resorcin[4]arenes in which there is
no templating metal or the possibility of positive hydrogen-
bonding interactions, the rctt chair is the thermodynamic
product. This result has been confirmed using quantum che-
mical calculation studies which indicate that the rctt chair
stereoisomer is, indeed, the lower energy product.
ArH), 6.17 (s, 2H, ArH), 5.97 (s, 2H, ArH), 5.49 (s, 4H,
ArCH), 3.64 (s, 12H, OCH3), 3.59 (s, 12H, OCH3); 13C NMR
(100 MHz, DMSO-d6) d 185.5, 178.6, 155.6, 154.8, 132.6,
129.7, 125.1, 123.5, 114.1, 55.7, 55.6; nmax 1609, 1582, 1504,
1452, 1437, 1199, 1093, 1030 cmÀ1; mp 320 1C (decomp.);
MALDI m/z (relative intensity) 968.4 ((M À H, 92), 991.4
(M + Na, 100), 1007.3 (M + K, 35).
rccc-Boat. 1H NMR (400 MHz, DMSO-d6) d 9.4 (s, 4H,
OH), 6.53 (d, J = 8.5 Hz, 8H, ArH), 6.47 (d, J = 8.5 Hz, 8H,
ArH), 6.36 (s, 4H, ArH), 6.13 (s, 4H, ArH), 5.45 (s, 4H,
ArCH), 3.60 (s, 12H, OCH3); 13C NMR (100 MHz,
DMSO-d6) d 154.9, 154.8, 133.5, 129.5, 129.4, 114.4, 114.3,
114.2, 55.7, 41.6; nmax 1611, 1582, 1509, 1499, 1542, 1438,
1200, 1095 cmÀ1; mp 280–285 1C; MALDI m/z (relative
intensity) 968.4 (M À H, 100), 991.4 (M + Na, 93).
Experimental
Compound 13. Method 3 was applied to 1,3-dimethoxyben-
zene (0.5 cm3, 3.8 mmol) and 4-octyloxybenzaldehyde (0.89 g,
3.8 mmol) using H2SO4 (H+ 8.36 meq.). The crude products
of these reactions were isolated by filtration as pale blue
powders.
All chemicals were obtained from Sigma-Aldrich, Fluka, Lan-
caster or Acros Organics and, unless specified, were used
without further purification. Deuterated solvents for NMR
use were purchased from Apollo. NMR spectra were recorded
at 273 K, except when stated otherwise, using a Bruker DPX-
400 Avance spectrometer, operating at 400.13 MHz (proton)
and 100.6 MHz (carbon), Shifts are referenced relative to the
internal solvent signals. Melting points were determined using
IA9000 digital melting point apparatus and are uncorrected.
Method 3 (80 1C): overall yield 54%, chair isomer 100%
Method 3 (25 1C): overall yield 21%, chair : boat 8.3 : 1.7
1
rctt-Chair. H NMR (400 MHz, CDCl3) d 6.58 (d, J = 8.0
Hz, 8H, ArH), 6.49 (d, J = 8.0 Hz, 8H, ArH), 6.46 (s, 2H,
ArH), 6.41 (s, 2H, ArH), 6.21 (s, 2H, ArH), 5.83 (s, 2H, ArH),
5.69 (s, 4H, ArCH), 3.84 (t, J = 6.5 Hz, 8H, OCH2), 3.71 (s,
12H, OCH3), 1.75 (m, 8H, OCH2CH2), 1.2–1.5 (m, 40H,
(CH2)5CH3), 0.91 (t, J = 7 Hz, 12H, CH3); 13C NMR (100
MHz, CDCl3) 183.0, 156.3, 155.5, 155.1, 134.5, 129.5, 127.8,
125.0, 124.2, 112.9, 96.1, 94.9, 67.3, 55.9, 55.4, 41.5, 31.4, 29.2,
29.1, 28.9, 25.7, 22.4, 13.7; nmax 2929, 2852, 1609, 1584, 1508,
1202, 1038 cmÀ1; mp 245–250 1C. Anal. Calc. for C92H120O12:
C: 77.80, H: 8.45. Found: C: 77.93, H: 8.53%.
1
(ESI H NMR data for rccc boat stereoisomers at 25 1C).
General methods for the preparation of octa-O-alkyl
resorcin[4]arenes
Method 1: Condensation in the presence of SnCl4. 1,3-Di-
methoxybenzene (2.00 cm3, 15.3 mmol) and 4-hydroxybenzal-
dehyde (1.86 g, 15.3 mmol) were added to SnCl4 (1.78 cm3,
15.3 mmol) in either Et2O or CHCl3 (20 cm3). The reaction
mixture was stirred at 25 1C for 16 or 72 h. The product was
isolated by filtration and washed with Et2O to yield the crude
mixture of isomers as a purple powder.
Compound 14. Method 3 was applied to 1,3-dimethoxyben-
zene (0.5 cm3, 3.8 mmol) and acetaldehyde (0.168 g, 3.82
mmol) using H2SO4 (H+ 8.36 meq.). The crude products of
these reactions were isolated by filtration as pale blue powders.
Method 3 (80 1C): overall yield 70%, chair isomer 100%
Method 3 (25 1C): overall yield 91%, chair : boat 6 : 4
Method 2: Condensation with HCl in ethanol. Aq. HCl (9 M,
0.8 cm3) was added dropwise to a stirred solution of 1,3-
dimethoxybenzene (0.5 cm3, 3.82 mmol) and 4-hydroxyben-
zaldehyde (0.46 g, 3.82 mmol) in EtOH (6.25 cm3). The
mixture was then allowed to stir at reflux for 16 or 72 h.
The mixture was allowed to cool to room temperature and
then filtered to yield the crude mixture of isomers as a purple
powder.
rctt-Chair. 1H NMR (400 MHz, CDCl3) d 6.56 (s, 2H,
ArH), 6.44 (s, 4H, ArH), 6.41 (s, 4H, ArH), 6.36 (s, 4H,
ArH), 4.59 (q, J = 7.0 Hz, J = 7.0 Hz, 4H, ArCH), 3.87 (s,
12H, OCH3), 3.79 (s, 12H, OCH3), 1.45 (d, J = 7.50 Hz, 12H,
CHCH3); 13C NMR (100 MHz, CDCl3) d 156.7, 155.5, 127.7,
127.6, 126.9, 123.6, 97.5, 96.4, 56.4, 56.3, 44.3, 33.5, 26.0, 23.8,
22.2; nmax 2946, 2923, 2853, 1465, 1297, 1201, 1037 cmÀ1; mp
320–322 1C.
Method 3: Condensation in acetic acid. 1,3-Dimethoxyben-
zene (0.528 g, 3.82 mmol) and the aldehyde (3.82 mmol) were
stirred together in acetic acid (20 cm3) in the presence or
absence of H+ (8.36–13.90 meq.) from a catalytic Brønsted
acid at 25 or 80 1C for 18 h. The reaction mixture was cooled
and the resulting precipitate isolated by filtration. If no pre-
cipitation occurred, water (50 ml) was added to the reaction
mixture to aid precipitation.
Compound 1510. Method 3 was applied to 1,3-dimethoxy-
benzene (0.5 cm3, 3.8 mmol) and isovaleraldehyde (0.41 ml,
0.329 g, 3.82 mmol) using H2SO4 (H+ 8.36 meq.). The crude
products of these reactions were isolated by filtration as off-
white powders.
Compound 3
1
rctt-Chair. H NMR (400 MHz, DMSO-d6) d 8.79 (s, 4H,
OH), 6.60 (s, 2H, ArH), 6.46 (s, 2H, ArH), 6.36 (m, 16H,
Method 3 (80 1C): overall yield 30.5%, chair isomer 100%
Method 3 (25 1C): overall yield 88.1%, chair : boat 5.2 : 4.8
ꢀc
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rctt-Chair. 1H NMR (400 MHz, CDCl3) d 6.96 (s, 2H,
ArH), 6.51 (s, 2H, ArH), 6.43 (s, 2H, ArH), 6.27 (s, 2H,
ArH) 4.69 (m, 4H, ArCH), 3.91 (s, 12H, OCH3), 3.65 (s, 12H,
OCH3), 1.62 (m, 8H, CH2), 1.43 (m, 4H, CH), 0.85 (d, J = 6.0
Hz, 24H, CH(CH3)2); 13C NMR (100 MHz, CDCl3) d 156.1,
154.9, 127.1, 127.0, 126.3, 123.0, 96.9, 95.7, 55.8, 55.7, 43.7,
32.8, 25.4, 23.1, 21.6.
CHCl3 (20 cm3). The reaction mixture was heated at reflux for
18 h. After cooling, MeOH (30 cm3) was added slowly and the
resultant precipitate was collected by filtration and washed
with Et2O (40 cm3) to give the chair isomer as an off-white
powder. The filtrate was evaporated to dryness and the residue
stirred in Et2O. This suspension was filtered off and the
isolated powder was further purified by column chromatogra-
phy (CHCl3–EtOAc 95 : 5) to give the boat isomer as a yellow
powder. chair 31%, boat 26%.
Compound 16. Aq. HCl (9 M, 1 cm3) was added dropwise to
a solution of 1,3-dimethoxybenzene (0.5 cm3, 3.8 mmol) and
2,3-dihydrofuran (0.289 cm3, 3.82 mmol) in acetic acid (20
cm3). The reaction mixture was then heated at 60 1C over-
night. After cooling, the product was isolated by filtration and
washed with Et2O to yield a white powder (0.489 g, 61.4%).
1
rctt-Chair. H NMR (400 MHz, CDCl3) d 6.70 (d, J = 8.5
Hz, 8H, ArH), 6.65 (d, J = 8.5 Hz, 8H, ArH), 6.44 (s, 2H,
ArH), 6.41 (s, 2H, ArH), 6.19 (s, 2H, ArH), 5.76 (s, 4H,
ArCH), 5.69 (s, 2H, ArH), 3.71 (s, 12H, OCH3), 3.69 (s, 12H,
OCH3), 2.52 (t, J = 7.0 Hz, 8H, COCH2), 1.80 (m, 8H,
CH2CH2CH3), 1.06 (t, J = 7.5 Hz, 12H, CH2CH3); 13C
NMR (100 MHz, CDCl3) d 171.5, 155.6, 155.4, 147.9, 140.1,
131.1, 129.4, 128.0, 123.9, 123.6, 119.7, 95.5, 94.7, 55.6, 55.4,
41.6, 35.9, 18.0, 13.3; nmax 2966, 2935, 2878, 2832, 1751, 1612,
1586, 1502, 1451 cmÀ1; mp 334–337 1C. Anal. Calc. for
C76H80O16: C: 73.06, H: 6.45. Found: C: 73.08, H: 6.47%.
rctt-Chair. 1H NMR (400 MHz, CDCl3) d 6.89 (s, 2H,
ArH), 6.50 (s, 2H, ArH), 6.41 (s, 2H, ArH), 6.30 (s, 2H,
ArH), 4.57 (t, J = 7.5 Hz, ArCH), 4.01 (t, J = 6.5, 8H,
CH2OH), 3.90 (s, 12H, OCH3), 3.68 (s, 12H, OCH3), 1.74 (m,
8H, CHCH2), 1.54 (m, 8H, CH2CH2OH); 13C NMR (100
MHz, CDCl3) d 156.1, 155.3, 126.5, 126.3, 125.8, 122.6, 96.2,
95.3, 64.3, 55.6, 55.5, 34.7, 30.5, 30.3, 26.5; nmax 2940, 2837,
1735, 1608, 1578, 1496, 1439, 1243, 1203, 1027, 889 cmÀ1; mp
236–238 1C.
rccc-Boat. 1H NMR (400 MHz, CDCl3) d 6.78 (m, 16H,
ArH), 6.42 (s, 2H, ArH), 6.23 (s, 2H, ArH), 6.10 (s, 2H, ArH),
5.82 (s, 2H, ArH), 5.73 (s, 4H, ArCH), 3.62 (s, 12H, OCH3),
3.51 (s, 12H, OCH3), 2.55 (t, J = 7.5 Hz, 8H, COCH2), 1.83
(sextet, 8H, CH2CH2CH3), 1.09 (t, J = 7 Hz, CH2CH3); 13C
NMR (100 MHz, CDCl3) d 171.5, 155.8, 155.5, 148.0, 140.9,
132.3, 129.2, 127.9, 123.9, 123.6, 120.0, 95.9, 95.6, 55.6, 41.9,
35.9, 18.1, 13.3; nmax 2963, 2936, 2877, 2832, 1752, 1502, 1299,
1244, 1165 cmÀ1; mp 261–263 1C. Anal. Calc. for C76H80O16:
C: 73.06, H: 6.45. Found: C: 72.56, H: 6.42%.
Compound 20
rccc-Boat. A catalytic amount of pyridine (0.5 cm3) was
added to a solution of 3 (0.467 g, 0.48 mmol) in acetic
anhydride (20 cm3). The reaction mixture was heated at reflux
for 3 h. After complete cooling, MeOH (20 cm3) was slowly
added to aid precipitation. The precipitate was isolated by
filtration and washed with MeOH (50 cm3) to yield the
acylated mixture of conformers as a white powder. This crude
product was then purified by column chromatography
(CHCl3–EtOAc 4 : 1) to give the boat isomer as a white
powder (0.07 g, 15%). 1H NMR (400 MHz, CDCl3) d 6.78
(dd, J = 9 Hz, 16H, ArH), 6.43 (s, 2H, ArH), 6.22 (s, 2H,
ArH), 6.22 (s, 2H, ArH), 6.07 (s, 2H, ArH), 5.79 (s, 2H, ArH),
5.73 (s, 4H, ArCH), 3.66 (s, 12H, OCH3), 3.52 (s, 12H, OCH3),
2.33 (s, 12H, OCCH3).
Acknowledgements
The authors would like to thank the EPSRC Mass Spectro-
metry Service, University of Swansea and Dr John O’Brien,
TCD, for help with spectroscopic measurements. This work
was funded by Enterprise Ireland, University of East Anglia
and Trinity College, University of Dublin.
rctt-Chair. A catalytic amount of pyridine (1 cm3) was
added to a solution of 3b (1.00 g, 1.03 mmol) in acetic
anhydride (20 cm3). The reaction mixture was then heated at
reflux for three hours. After complete cooling, MeOH (30 cm3)
was added slowly to aid precipitation. The precipitate was
isolated by filtration and washed with MeOH (70 cm3) to yield
the desired product as a white powder (0.98 g, 93%). 1H NMR
(400 MHz, CDCl3) d 6.71 (d, J = 8.5 Hz, 8H, ArH), 6.65 (d,
J = 8.5 Hz, 8H, ArH), 6.45 (s, 2H, ArH), 6.41 (s, 2H, ArH),
6.18 (s, 2H, ArH), 5.76 (s, 4H, ArCH), 5.64 (s, 2H, ArH), 3.72
(s, 12H, OCH3), 3.69 (s, 12H, OCH3), 2.29 (s, 12H, OCCH3);
13C NMR (100 MHz, CDCl3) d 168.7, 155.6, 155.4, 147.9,
141.5, 140.2, 131.2, 129.4, 128.0, 123.8, 119.7, 95.5, 94.6, 55.6,
55.4, 41.6, 30.5; nmax 2943, 2837, 1733, 1609, 1583, 1503, 1463,
1291, 1200, 1033 cmÀ1; mp 351–353 1C. Anal. Calc. for
C68H64O16Á2CH3CO2COCH3: C: 68.05, H: 5.71. Found: C:
67.79, H: 5.43%.
References
1 (a) M. H. Filby and J. W. Steed, Coord. Chem. Rev., 2006, 250,
3200; (b) C. Redshaw, Coord. Chem. Rev., 2003, 244, 45; (c) T.
Gunnlaugsson, M. Glynn, G. M. Tocci, P. E. Kruger and F. M.
Pfeffer, Coord. Chem. Rev., 2006, 250, 3094; (d) S. E. Matthews and
P. D. Beer, Supramol. Chem., 2005, 17, 411; (e) E. Quinlan, S. E.
Matthews and T. Gunnlaugsson, Tetrahedron Lett., 2006, 47, 9333;
(f) E. Quinaln, S. E. Matthews and T. Gunnlaugsson, J. Org.
Chem., 2007, 72, 7497.
2 (a) P. Timmermann, W. Verboom and D. N. Reinhoudt, Tetra-
hedron, 1996, 52, 2663; (b) B. Botta, M. Cassani, I. D’Acquarica,
D. Misiti, D. Subissati and G. Delle Monache, Curr. Org. Chem.,
2005, 9, 337; (c) B. Botta, M. Cassani, I. D’Acquarica, D. Misiti,
D. Subissati, G. Zappia and G. Delle Monache, Curr. Org. Chem.,
2005, 9, 1167.
3 (a) H. Konishi, K. Ohata, O. Morikawa and K. Kobayashi, J.
Chem. Soc., Chem. Commun., 1995, 309; (b) H. Konishi, T.
Nakamura, K. Ohatu, K. Kobayashi and O. Morikawa, Tetrahe-
dron Lett., 1996, 37, 7383.
4 C. Naumann, E. Roman, C. Peinador, T. Ren, B. O. Patrick, A. E.
Kaifer and J. C. Sherman, Chem.–Eur. J., 2001, 7, 1637.
5 (a) R. Arnecke, V. Bohmer, E. F. Paulus and W. Vogt, J. Am.
Chem. Soc., 1995, 117, 3286; (b) C. Schmidt, T. Straub, D. Falabu,
Compound 21. Pyridine (0.5 cm3) was added to 2 (1.00 g,
1.03 mmol) and butanoic anhydride (2.00 cm3, 11.7 mmol) in
ꢀc
This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2008
New J. Chem., 2008, 32, 994–1002 | 1001

View Article Online
E. F. Paulus, E. Wegelius, E. Kolehmainen, V. Bohmer and K.
Rissanen, Eur. J. Org. Chem., 2000, 3937.
18 J. Y. Boxhall, P. C. Bulman Page, M. R. J. Elsegood, Y. Chan, H.
Heaney, K. E. Holmes and M. J. McGrath, Synlett, 2003, 1002.
19 O. Morikawa, E. Iyama, T. Oikawa, K. Kobayashi and H.
Konishi, J. Phys. Org. Chem., 2006, 19, 214.
20 O. M. Falana, E. Al-Farhan, P. M. Keehn and R. Stevenson,
Tetrahedron Lett., 1994, 35, 65.
21 H. Konishi, H. Sakakibara, K. Kobayashi and O. Morikawa, J.
Chem. Soc., Perkin Trans. 1, 1999, 2583.
22 (a) J. Stursa, H. Dvorakova, J. Smirdrkal, H. Petrickova and J.
Moravcova, Tetrahedron Lett., 2004, 45, 2043; (b) H. Dvorakova,
J. Stursa, M. Cajan and J. Moravcova, Eur. J. Org. Chem., 2006,
4519.
23 (a) D. Li, T. Kusunoki, T.-A. Yamagishi and Y. Nakamoto,
Polym. Bull., 2002, 47, 493; (b) D. Li, T. Kusunoki, T.-A. Yama-
gishi and Y. Nakamoto, Polym. Bull., 2002, 48, 423.
24 O. Morikawa, T. Ishizaka, H. Sakakibara, K. Kobayashi and H.
Konishi, Polym. Bull., 2005, 53, 97.
6 E. K. Kazakova, N. A. Makarova, A. U. Ziganshina, L. A. Mus-
linkina and W. D. Habicher, Tetrahedron Lett., 2000, 41, 10111.
7 (a) D. J. Cram and J. M. Cram, Container Molecules and Their
Guests, Monographs in Supramolecular Chemistry, The Royal So-
ciety of Chemistry, Cambridge, 1994; (b) J. R. Moran, S. Karbach
and D. J. Cram, J. Am. Chem. Soc., 1982, 104, 5826; (c) J. A.
Bryant, C. B. Knobler and D. J. Cram, J. Am. Chem. Soc., 1990,
112, 1254; (d) D. J. Cram, S. Karbach, H. E. Kim, C. B. Knobler, E.
F. Maverick, J. L. Ericson and R. C. Helgeson, J. Am. Chem. Soc.,
1988, 110, 2229; (e) B. C. Gibb, Chem.–Eur. J., 2003, 9, 5180.
8 W. Iwanek, M. Urbaniak and M. Bochenska, Tetrahedron, 2002,
58, 2239.
9 (a) B. Botta, G. Delle Monache, P. Ricciardi, G. Zappia, C. Seri, E.
Gacs-Baitz, P. Csokasi and D. Misiti, Eur. J. Org. Chem., 2000,
841; (b) B. Botta, G. Delle Monache, G. Zappia, D. Misiti, M.
CamillaBaratto, R. Pogni, E. Gacs-Baitz, M. Botta, F. Corelli, F.
Manetti and A. Tafi, J. Org. Chem., 2002, 67, 1178.
25 O. Morikawa, Y. Nagamatsu, A. Nishimura, K. Kobayashi and H.
Konishi, Tetrahedron Lett., 2006, 47, 3991.
10 M. Urbaniak and W. Iwanek, Tetrahedron, 1999, 55, 14459.
11 (a) A. Tafi, B. Botta, M. Botta, G. Delle Monache, A. Filippi and
M. Speranza, Chem.–Eur. J., 2004, 10, 4126; (b) B. Botta, D.
Subissati, A. Tafi, G. Delle Monache, A. Filippi and M. Speranza,
Angew. Chem., Int. Ed., 2004, 43, 4767; (c) B. Botta, F. Caprorucio,
D. Subissati, A. Tafi, M. Botta, A. Filippi and M. Speranza,
Angew. Chem., Int. Ed., 2006, 45, 2717; (d) B. Botta, F. Capor-
uscio, I. D’Acquarica, G. Delle Monache, D. Subissati, A. Tafi, M.
Botta, A. Filippi and M. Speranza, Chem.–Eur. J., 2006, 12, 8096.
12 (a) B. Botta, G. Delle Monache, M. C. De Rosa, C. Seri, E.
Benedetti, R. Iacovino, M. Botta, F. Corelli, V. Masignani, A.
Tafi, E. Gacs-Baitz, A. Santini and D. Misiti, J. Org. Chem., 1997,
62, 1788; (b) B. Botta, P. Ricciardi, C. Galeffi, M. Botta, A. Tafi, R.
Pogni, R. Iacovino, I. Garella, B. Di Blasio and G. Delle Monache,
Org. Biomol. Chem., 2003, 1, 3131.
13 (a) H. Erdtman, S. Hogberg, S. Abrahamsson and B. Nilsson,
Tetrahedron Lett., 1968, 14, 1679; (b) B. Nilsson, Acta Chem.
Scand., 1968, 22, 732.
14 F. Weinelt and H.-J. Schneider, J. Org. Chem., 1991, 56, 5527.
15 (a) W. Iwanek, Tetrahedron, 1998, 54, 14089; (b) W. Iwanek and B.
Syzdol, J. Synth. Commun., 1999, 29, 1209.
16 (a) B. Botta, P. Iacomacci, C. Di Giovanni, G. Delle Monache, E.
Gacs-Baitz, M. Botta, A. Tafi, F. Corelli and D. Misiti, J. Org.
Chem., 1992, 57, 3259; (b) I. D’Acquarica, L. Nevola, G. Delle
Monache, E. Gacs-Baitz, C. Massera, F. Ugozzoli, G. Zappia and
B. Botta, Eur. J. Org. Chem., 2006, 3652.
17 (a) M. J. Mclldowie, M. Mocerino, B. W. Skelton and A. H. White,
Org. Lett., 2000, 2, 3869; (b) M. Klaes, C. Agena, M. Kohler, M.
Inoue, T. Wada, Y. Inoue and J. Mattay, Eur. J. Org. Chem., 2003,
1404; (c) C. Schiel, G. A. Hembury, V. V. Borovkov, M. Klaes, C.
Agena, T. Wada, S. Grimme, Y. Inoue and J. Mattay, J. Org.
Chem., 2006, 71, 976; (d) K. Salorinne and M. Nissinen, Org. Lett.,
2006, 8, 5473.
26 A. J. Wright, S. E. Matthews, W. Fischer and P. D. Beer,
Chem.–Eur. J., 2001, 7, 3474.
27 G. I. Konishi, T. Matsuo and Y. Nakamato, Poster abstract 58,
8th International Conference on Calixarenes (CALIX 2005), Pra-
gue, Czech Republic.
28 A. G. S. Hogberg, J. Am. Chem. Soc., 1980, 102, 6046.
29 L. Abis, E. Dalcanale, A. Du Vosel and S. Spera, J. Org. Chem.,
1988, 53, 5475.
30 M. Urbaniak and W. Iwanek, Tetrahedron, 2004, 60, 8265.
31 B. Botta, M. C. Di Giovanni, G. Delle Monache, M. C. De Rosa,
E. Gacs-Baitz, M. Botta, F. Corelli, A. Tafi, A. Santini, E.
Benedetti, C. Pedone and D. Misiti, J. Org. Chem., 1994, 59, 1532.
32 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A.
Robb, J. R. Cheeseman, J. A. Montgomery, Jr., T. Vreven, K. N.
Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V.
Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A.
Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R.
Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O.
Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J.
B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E.
Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J.
Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J.
J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M.
C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghava-
chari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S.
Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P.
Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A.
Al-Laham, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M.
W. Gill, B. G. Johnson, W. Chen, M. W. Wong, C. Gonzalez and
J. A. Pople, GAUSSIAN 03 (Revision C.02), Gaussian, Inc.,
Wallingford, CT, 2004.
33 Cache Workstation Pro Version 6.01, Fujitsu Computer Systems,
2003.
ꢀc
This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2008
1002 | New J. Chem., 2008, 32, 994–1002