Lanthanide(III) nitrobenzenesulfonates and p-toluenesulfonate complexes of lanthanide(III), iron(III), and copper(II) as novel catalysts for the formation of calix[4]resorcinarene

Article abstract of DOI:10.1016/j.tet.2007.06.090

Lanthanide(III) salts of p-toluenesulfonic acid [lanthanide(III) tosylates, Ln(TOS)₃] and nitrobenzenesulfonic acid [Ln(NBSA)₃], and p-toluenesulfonate complexes of iron(III) and copper(II) were prepared, characterized, and examined

Full text of DOI:10.1016/j.tet.2007.06.090

Tetrahedron 63 (2007) 9063–9070
Lanthanide(III) nitrobenzenesulfonates and p-toluenesulfonate
complexes of lanthanide(III), iron(III), and copper(II) as novel
catalysts for the formation of calix[4]resorcinarene
a
b
b
a
Karen Deleersnyder, Hasan Mehdi, Istv ꢀa n T. Horv ꢀa th, Koen Binnemans
a,
*
and Tatjana N. Parac-Vogt
a
Katholieke Universiteit Leuven, Department of Chemistry, Celestijnenlaan 200F, B-3001 Leuven, Belgium
b
E o€ tv o€ s University, Department of Chemical Technology and Environmental Chemistry,
P aꢀ zm aꢀ ny Pe´ter Se´t aꢀ ny 1/A, H-1117 Budapest, Hungary
Received 2 May 2007; revised 18 June 2007; accepted 27 June 2007
Available online 4 July 2007
3 3
Abstract—Lanthanide(III) salts of p-toluenesulfonic acid [lanthanide(III) tosylates, Ln(TOS) ] and nitrobenzenesulfonic acid [Ln(NBSA) ],
and p-toluenesulfonate complexes of iron(III) and copper(II) were prepared, characterized, and examined as catalysts for the synthesis of
resorcinol-derived calix[4]resorcinarenes. The reaction of resorcinol with benzaldehyde yields two isomers, the all-cis isomer (rccc) and the
cis-trans-trans isomer (rctt) with the relative isomer ratios depending on the reaction conditions. However, in the reaction of resorcinol with oc-
3
tanal only one isomer, the all-cis isomer, is formed in high yields with less than 0.1 mol % of Yb(TOS) . Examination of lanthanide(III) tosylates
and lanthanide(III) nitrobenzenesulfonates revealed that ytterbium(III) 4-nitrobenzenesulfonate [ytterbium(III) nosylate, Yb(4-NBSA) ] and
3
ytterbium(III) 2,4-dinitrobenzenesulfonate [Yb(2,4-NBSA) ] are the most active catalysts. The catalysts could be easily recovered and re-
3
used several times for resorcinarene formation without loss of efficiency. Surprisingly good results were also obtained with iron(III) and
copper(II) p-toluenesulfonates. Besides optimizing the reaction conditions, new insights into the reaction mechanism were also obtained.
Ó 2007 Elsevier Ltd. All rights reserved.
1
. Introduction
However, this synthetic procedure requires the use of large
quantities of acid, leading to excessive waste streams that
are environmentally unfriendly and expensive to deal with.
A solvent-free synthesis of resorcinarenes using p-toluene-
Adolf von Baeyer reported already in 1872 that the addition
of concentrated sulfuric acid to a mixture of benzaldehyde
and resorcinol gave a red-colored product. In 1968, Erdtman
finally proved the cyclic tetrameric structure of these conden-
sation products by single crystal X-ray diffraction analysis.
As the official IUPAC name of this type of compounds is very
complicated, they are commonly called calixarenes, refer-
ring to the resemblance of the shape of one of the conformers
1
8
sulfonic acid as the catalyst has also been reported. In addi-
tion, some conventional Lewis acids like BF $OEt , AlCl ,
3
2
3
2
and SnCl have been used in the synthesis of aromatic alde-
4
9
hyde-derived resorcinarenes. Although these Lewis acids
are usually efficient catalysts, they have several drawbacks:
they need to be used in at least stoichiometric amounts, they
are easily deactivated by water, and they cannot be recycled
or reused. More recently, trifluoromethanesulfonate salts,
3
to a type of Greek vase called a calix crater.
1
0
Calix[4]resorcinarenes (resorcinarenes), the resorcinol-
derived calixarenes, are versatile host compounds for ions,
sugars, and organic molecules. Therefore they serve as
starting materials for a variety of cavitands and other macro-
cyclic host compounds. They have also found application
as stationary phases in HPLC. Furthermore, they can ex-
hibit liquid-crystalline behavior by appropriate choice of
the R groups on the resorcinarene. Resorcinarenes are tradi-
tionally prepared by the mineral acid-catalyzed condensa-
tion of resorcinol with an aliphatic or aromatic aldehyde.
the so-called triflates, such as ytterbium(III) triflate and
1
1
bismuth(III) triflate, have been described as efficient cata-
lysts for the synthesis of calix[4]resorcinarenes. An impor-
tant property of triflate catalysts is their compatibility with
water and other protic solvents. After work-up, the catalysts
can easily be recycled and reused without significant loss of
activity. However, the triflate salts have some major disad-
vantages including their relatively high cost and the fact
that one needs to handle for their preparation the highly
corrosive triflic acid.
4
5
6
7
In a pursuit of lanthanide(III) catalysts, which do not require
the use of hazardous or costly compounds, we recently
examined lanthanide(III) salts of non-corrosive aromatic
Keywords: Catalysis; Lanthanides; Lewis acids; Macrocycles; Rare earths.
*
Corresponding author. Fax: +32 16 327992; e-mail: tatjana.vogt@chem.
kuleuven.be
0
040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.06.090

9064
K. Deleersnyder et al. / Tetrahedron 63 (2007) 9063–9070
sulfonic acids, such as p-toluenesulfonic acid and nitrobenz-
enesulfonic acids as catalysts for the nitration of aromatic
and six water molecules occupy the first coordination
sphere, while the third tosylate anion appears in the second
coordination sphere. Structural studies on copper(II) tosy-
1
2–14
15
17
compounds and for the acylation of alcohols. The
aromatic sulfonic acids are much weaker acids than triflic
acid (p-toluenesulfonic acid is, for example, about 10 times
late revealed that this complex crystallizes with six mole-
cules of water in the first coordination sphere. To the
6
17
1
6
weaker acid than triflic acid), and therefore their com-
plexes with lanthanides are expected to be significantly
weaker Lewis acids than the lanthanide(III) triflates. How-
ever, our recent studies revealed that their catalytic
best of our knowledge, the crystal structure of iron(III) tosy-
late is not known, but studies on iron(II) tosylate indicate
that three tosylate ions bind to iron(II) in a bidentate fash-
1
7
ion. Comparison of infrared spectra of iron(II) tosylate
and iron(III) tosylate, implied that iron(III) is also six-coor-
dinated by three tosylate anions.
1
2–15
efficiency was comparable to that of the triflate salts.
This prompted us to further exploit the inexpensive and con-
venient lanthanide(III) tosylates and lanthanide(III) nitro-
benzenesulfonates as alternatives for the lanthanide(III)
triflates. In this study we demonstrate that lanthanide(III)
tosylates and lanthanide(III) nitrobenzenesulfonates can be
used as efficient, inexpensive, recyclable, and environmen-
tally friendly catalysts for the synthesis of calix[4]resorcin-
arenes. In addition, we demonstrate that copper(II) and
iron(II) complexes of p-toluenesulfonic acid also efficiently
catalyze formation of calixarenes.
The elemental analysis results of the investigated complexes
(see Section 4) indicated that upon drying the crystalline
ꢀ
solid at 50 C in vacuo, some water molecules of crystalliza-
tion are lost, but the complexes still contain one to four
molecules of water. Consequently, infrared spectral data of
the complexes showed strong and broad absorption in the
ꢁ
1
region between 3200 and 3600 cm , corresponding to the
–OH stretching of water molecules.
Since it is known that p-toluenesulfonic acid itself is a good
catalyst for the formation of calixarenes, it is important to
8
2
. Results and discussion
demonstrate the absence of trace amounts of free acid in the
lanthanide(III)catalyst. Theinfraredspectraoflanthanide(III)
complexes showed that the broad infrared absorption band
2
.1. Synthesis and characterization of the catalysts
ꢁ
1
Lanthanide(III) salts of p-toluenesulfonic acid, [Ln(TOS)3]
with Ln¼Yb, La, Nd, Gd, Y, 3-nitrobenzenesulfonic acid,
between 2400 and 3100 cm , typical for the OH stretching
1
8
mode of protonated benzenesulfonic acid, was absent in all
cases. Furthermore, the aqueous solution of lanthanide(III)
complexes always had a close-to-neutral pH (pHz6), which
further confirms the absence of free p-toluenesulfonic or
nitrobenzenesulfonic acid in the isolated lanthanide(III)
salts. The absence of free p-toluenesulfonic acid in Fe(TOS)3
[
(
(
Yb(3-NBSA) ], 4-nitrobenzenesulfonic acid, [Yb-
3
4-NBSA) ], and 2,4-dinitrobenzenesulfonic acid, [Yb-
3
2,4-NBSA) ], (Scheme 1) were prepared by reaction of
3
the acid with the corresponding lanthanide(III) oxide.
and Cu(TOS) was also confirmed by similar method.
2
SO3-
SO3-
SO3-
SO3-
NO2
2
.2. Formation of resorcinarenes
NO2
NO2
NO2
2,4-NBSA
Herein we report the formation of calix[4]resorcinarenes
through lanthanide(III) tosylate and nitrobenzenesulfonate
catalyzed condensation of resorcinol with an aromatic or
an aliphatic aldehyde (Scheme 2). During this reaction,
only the tetrameric resorcinarene and water are formed.
The tetrameric nature of the compounds was confirmed by
mass-spectrometric analysis. Of the four diastereoisomers
formed, we observed the all-cis (rccc) isomer (3a) and the
cis-trans-trans (rctt) isomer (4a) in the reactions with benz-
aldehyde, with a relative ratio depending on the reaction
CH3
TOS
3-NBSA
4-NBSA
Scheme 1. Aromatic sulfonates used as counterions for lanthanide(III)
catalysts.
Single crystal studies of lanthanide(III) tosylates showed
that with the exception of the La(III) complex, in which
nine water molecules are found in the first coordination
sphere, in most of the other lanthanides two tosylate anions
HO
OH
HO
OH
R
R
R
R
HO
OH HO
OH
OH
O
HO
OH
R
H
HO
OH
HO
1a: R = Ph
R
2
R
R
R
1b: R = C H
7
15
OH
HO
HO
OH
3
a: R = Ph
4a: R = Ph
(rctt)
3b: R = C H
7
15
(rccc)
Scheme 2. Formation of calix[4]resorcinarene through lanthanide(III) tosylate and nitrobenzenesulfonate catalyzed condensation of resorcinol with an aromatic
or an aliphatic aldehyde.

K. Deleersnyder et al. / Tetrahedron 63 (2007) 9063–9070
9065
conditions used. Only in the case of short reaction times (4 h
2.4. Influence of the reaction time
or less) or low catalyst concentration (0.1 mol %), a small
amount of a third product is formed. Based on the NMR
data this product is likely one of the other possible isomers,
however, the exact structure of the product was not further
investigated. In the reactions with octanal only the all-cis
isomer (3b) is formed, although after shorter reaction times,
usually 4–12 h, a small amount of a less thermodynamically
stable isomer could also be formed. The configuration of the
isomers has previously been determined by X-ray diffraction
analysis and our NMR spectra are in agreement with the lit-
Since the screening of the different lanthanide(III) tosylates
revealed that the ytterbium(III) complexes are the most pow-
erful catalysts in the lanthanide(III) series, ytterbium(III)
nitrobenzenesulfonates were examined as catalysts for the
formation of resorcinarenes with benzaldehyde or octanal.
When performing the condensation reaction of resorcinol
with octanal in the presence of 2 mol % of ytterbium(III)
tosylate or nosylate (abbreviation for 4-nitrobenzenesulfo-
nate), the yields are 93–95% after 24 h. The yields and
isomer distributions in the reaction of benzaldehyde using
4
c,19
erature data.
Although the use of an inert atmosphere is
frequently recommended for the formation of resorcinar-
enes, our experiments indicate that there is no difference
in yields or isomer distribution in the reactions performed
under argon, nitrogen or in the air atmosphere. Therefore,
the reactions can be performed in a simple reflux setup,
open to the air.
ytterbium(III) 3-nitrobenzenesulfonate [Yb(3-NBSA) ], yt-
3
terbium(III) 4-nitrobenzenesulfonate [Yb(4-NBSA) ], and
3
ytterbium(III) 2,4-dinitrobenzenesulfonate [Yb(2,4-NBSA)3]
are summarized in Table 2. Only minor differences in total
yield are observed for the different catalysts. As can be seen
in Table 2 and Figure 1, after a certain time the largest amount
of rccc isomer is formed when using Yb(4-NBSA) . Further-
3
2
.3. Influence of the lanthanide ion
more, the amount of rccc isomer can be increased by increas-
ing the reaction time. This is consistent with the previous
findings in which Yb(OTf) was used as the catalyst, al-
though this catalyst more efficiently catalyzed the formation
of the pure rccc isomer.
1
0
In order to find the most suitable lanthanide(III) ion for the
calix[4]resorcinarene formation, a range of lanthanide(III)
tosylates were examined as potential catalysts. As can be
seen in Table 1, only small differences in yield and isomer
distribution are observed for the reaction with benzaldehyde
using different lanthanide(III) tosylates. While 93% of resor-
cinarene is formed after 24 h by using 5 mol % of Yb(TOS)3,
and 84% of resorcinarene is formed when using La(TOS)3.
In contrast, surprisingly large differences are observed for
3
Table 2. Effect of the counterion (tosylate and nitrobenzenesulfonate) in
function of time on the ytterbium(III) catalyzed formation of resorcinarenes
with benzaldehyde
a
Time (h)
Yield (rccc:rctt) (%)
the reaction with octanal. The use of Yb(TOS) leads to
3
TOS
3-NBSA
4-NBSA
2,4-NBSA
9
2% of resorcinarene, while only 11% of the product is
formed when using La(TOS) as the catalyst. This trend
4
90 (32:68)
93 (42:58)
95 (51:49)
96 (64:36)
96 (86:14)
80 (40:60)
87 (45:55)
89 (47:53)
90 (64:36)
95 (65:35)
68 (46:54)
>98 (61:39)
>98 (73:27)
>98 (86:14)
>98 (96:4)
86 (40:60)
92 (45:55)
>98 (57:43)
>98 (70:30)
>98 (72:28)
3
2
4
4
8
over the lanthanide series is consistent with our previous
studies involving lanthanide(III) tosylates in the acetylation
of alcohols. Solution studies have shown that the solid-
state structure, which shows clear structural differences
96
216
1
5
a
Yb catalyst (5 mol %), at reflux temperature; TOS¼p-toluenesulfonate, 3-
NBSA¼3-nitrobenzenesulfonate, 4-NBSA¼4-nitrobenzenesulfonate,
2,4-NBSA¼2,4-dinitrobenzenesulfonate.
1
7,20
across the lanthanide(III) series,
was not preserved in
acetic acid. In strongly coordinating solvents, such as water,
the structures of all lanthanide(III) tosylates are the same
since the coordinating solvent displaces the tosylate ligands
2
1
from the first coordination sphere. Ethanol coordinates
strongly enough to the lanthanide ion to displace the tosylate
ligands to the second coordination sphere, so that the first
coordination sphere around the lanthanide(III) is occupied
by ethanol molecules only. In this case, a smaller ionic radius
of trivalent lanthanide ion leads to a larger charge-to-size
ratio, Z/r, which in turn results in a stronger polarizing power
of the lanthanide(III) center, a stronger Lewis acidity, and
hence higher reaction yields.
1
00
90
8
7
6
5
4
3
0
0
0
0
0
0
Table 1. Effect of the lanthanide(III) ion on the formation of calix[4]resor-
cinarene
TOS
a
20
3
-NBSA
4
-NBSA
Ln ion
Benzaldehyde
Octanal
10
2,4-NBSA
Yield (%)
rccc:rctt (%)
Yield (%)
0
0
50
100
Time (hours)
150
200
250
La
Gd
Yb
Y
84
81
93
84
38:62
36:64
42:58
33:67
11
30
92
75
Figure 1. Amount of rccc isomer as a function of the time and the counter-
ion. The amount of rccc (all-cis) isomer is monitored as a function of time
for the formation of benzaldehyde-based resorcinarenes with ytterbium(III)
catalysts.
a
Lanthanide(III) p-toluenesulfonate (5 mol %), after 24 h, at reflux
temperature.

9066
K. Deleersnyder et al. / Tetrahedron 63 (2007) 9063–9070
2.5. Effects of temperature and catalyst loading on the
extent of resorcinarene formation
impurity the weight of the recovered catalyst is somewhat
higher than the weight of catalyst used in the first run. In
combination with the small catalyst loading required for
quantitative reaction, we can conclude that this condensation
reaction, catalyzed by lanthanide(III) tosylates and various
nitrobenzenesulfonates, is a real catalytic system.
The influence of temperature was studied for the reactions
with benzaldehyde and octanal. For the reaction with octanal
we could not isolate any resorcinarene when the reaction was
ꢀ
performed at room temperature or at 50 C. However, the re-
action with benzaldehyde resulted in resorcinarene forma-
tion at room temperature, although with lower yields and
less rccc isomer formed. Reaction for 48 h at room temper-
ature leads to 80% of yield with 36% of rccc isomer. In order
to further optimize the reaction conditions, we also studied
the effect of catalyst amount on both condensation reactions.
As can be seen from Table 3, good yields are achieved by us-
2.7. Use of transition metals and other acidic catalysts
Since copper(II) complexes with some sulfate ligands are
2
2
also known to be good Lewis acid catalysts, we set out
to test the activity of several transition metal tosylates as cat-
alysts for the formation of calixarenes. Iron(III) tosylate is
commercially available at relatively low price and copper(II)
tosylate was prepared following the procedure applied for
the synthesis of lanthanide(III) tosylates. The reactions of
resorcinol with octanal and benzaldehyde catalyzed by
5 mol % Cu(TOS) and Fe(TOS) are shown in Table 5. In
ing only 0.1 mol % Yb(TOS) . However, in the reaction of
3
benzaldehyde a small amount of a third isomer was formed
when less than 0.1 mol % of Yb(TOS) was used. For the
3
condensation with benzaldehyde, an increase to 5 mol %
of Yb(TOS) resulted also in a larger amount of rccc isomer,
2
3
all cases nearly quantitative conversion was obtained after
24 h of reaction. Furthermore, remarkably high amount of
all-cis isomer was formed in the reaction with iron(III) tosy-
late. As a comparison, the reported reaction with 8 mol % of
ytterbium(III) triflate achieves around 46% of all-cis isomer
after 48 h of reaction. This exceptionally high amount of all-
cis isomer can probably be explained by a strong Lewis acid-
ity of iron(III) that results from its high charge-to-size ratio.
Moreover, in the reaction of resorcinol with octanal the
initial reaction rates are higher with copper(II) and iron(III)
tosylate compared to lanthanide(III) tosylates. By using
copper(II) and iron(III) tosylate 91–94% of resorcinarene
was formed after 6 h of reaction while in the case of ytterbium-
(III) tosylate 18 h of reaction was necessary to obtain the
same yield. Furthermore, these catalysts can also be recov-
ered and reused.
3
but in this case the total yield and amount of rccc isomer are
almost not improved when increasing the catalyst load to
1
0 mol %. Furthermore, in the reaction of octanal with resor-
cinol, 84% of resorcinarene was formed after 24 h by using
.1 mol % of Yb(TOS) while no resorcinarene could be iso-
0
3
lated without using a catalyst. The use of higher catalytic
amounts leads to a slight increase in yield: 92% by using
5
mol % under the same reaction conditions.
Table 3. The effect of the ytterbium(III) tosylate loading on the formation of
resorcinarenes with benzaldehyde and octanal
a
Catalyst load
mol %)
Benzaldehyde
Yield (%) rccc:rctt (%)
Octanal
(
Yield (%)
None
2
71
88
88
93
n.d.
0
84
86
92
92
0
1
2
5
.1
32:68
33:67
34:66
42:58
The reaction yields obtained by using transition metal and
lanthanide tosylates were compared with those when tradi-
tional mineral acid such as HCl was used. Nowadays the
mineral acid HCl is used in equimolar amounts to promote
the formation of resorcinarenes. We compared our results
to the one obtained in the reaction of resorcinol with benz-
aldehyde or octanal in the presence of 500 mL of 37% HCl,
which corresponds almost to an equimolar amount com-
pared to the other reactants. As can be seen in Table 5, the
reactions promoted by HCl are faster and in the reaction
with benzaldehyde more all-cis isomer is formed. On the
a
After 24 h, at reflux temperature.
2
.6. Recovery and reuse of the lanthanide(III) catalyst
After quenching the reaction mixture with water, the resorci-
narene was filtered off and washed with water. The catalysts
could be easily recovered from the filtrate by evaporating the
1
water under reduced pressure. The H NMR spectrum of the
recovered Yb(TOS)3 showed a very small amount of
impurity compared to the spectrum of the freshly prepared
Yb(TOS) . But as can be seen in Table 4, the presence of
Table 5. The effect of the metal ion and its counterion on the formation of
calix[4]resorcinarene
a
3
this impurity—a few percent of unreacted resorcinol and
octanal—has no negative influence on the reactivity of the
catalyst in the subsequent runs. Due to this small amount of
Catalyst
Benzaldehyde
Octanal
Yield (%)
rccc:rctt (%)
Yield (%)
La(TOS)
Cu(TOS)
Fe(TOS)
Yb(TOS)
Yb(3-NBSA)
Yb(4-NBSA)
3
84
91
95
93
38:62
48:52
73:27
42:58
45:55
61:39
57:43
11
93
96
95
91
96
96
95
3
Table 4. Recovery and reuse of ytterbium(III) tosylate after the reaction of
resorcinol with octanal
a
3
3
3
87
Run
Yield (%)
3
Recovered Yb(TOS) (%)
3
>98
>98
>98/81
1
2
3
95
96
94
>98
>98
>98
Yb(2,4-NBSA)
HCl
3
b
c
c
100:0/60:40
a
Catalyst (5 mol %), after 24 h, at reflux temperature.
Addition of equimolar amount of HCl.
After 1 h.
a
b
c
After 24 h, at reflux temperature, the recovered amount of catalyst is each
time compared to the initial 5 mol % of Yb(TOS) used in the first run.
3

K. Deleersnyder et al. / Tetrahedron 63 (2007) 9063–9070
9067
other hand, tosylate complexes of transition metals and lan-
thanides are beneficial for several reasons: they are not re-
quired in stoichiometric amounts but in catalytic amounts
as small as 0.1 mol % are sufficient, they can be easily recov-
ered and reused several times without loss of activity, and
hence they avoid the consumption of strong acids.
similar catalytic properties as triflate salts, it can be expected
that tosylates also can catalyze the acetal formation in the
presence of an excess of ethanol. Furthermore, a new absorp-
ꢁ
1
tion band that appeared at 1011 cm is consistent with the
C–O single bond absorption characteristic of acetals. The
intensity of this absorption band increases upon addition
of Yb(TOS) , consistent with the Yb(TOS) -catalyzed
3
3
2
.8. Postulated mechanism for the lanthanide(III)
formation of the acetal.
tosylate and nitrobenzenesulfonate catalyzed formation
of calix[4]resorcinarenes
The catalytic reaction followed by proton NMR spectros-
ꢀ
copy was recorded in deuterated ethanol at 65 C (Fig. 3).
Barrett and co-workers proposed in their study on Yb(OTf)3-
catalyzed formation of resorcinarenes that once the resorci-
narene is formed, it (reversibly) binds to Yb(OTf) , thus
Addition of octanal to an ethanolic solution of resorcinol re-
sulted in formation of a small peak around 4.5 ppm, consis-
tent with acetal formation (Scheme 3, step A). Upon addition
3
generating a complex, which liberates triflic acid, or is itself
acidic enough to promote protodealkylation and hence iso-
merization. Although the above work clearly demonstrates
the Brønsted acid nature of the isomerization of resorcinar-
enes, it is not clear how the initial resorcinol–aldehyde bond
formation is initiated.
of 5 mol % of Yb(TOS) the proton signal of the aldehyde
3
group nearly completely disappeared while the signal
around 4.5 ppm that can be attributed to the CH-proton of
the acetal strongly increases. Furthermore, peaks of the re-
maining octanal are broadened upon addition of Yb(TOS)3,
which indicates coordination of the carbonyl group to para-
magnetic ytterbium(III) ion (Scheme 3, step B). Unfortu-
nately, it was not possible to follow the disappearance of
acetal peak as the reaction proceeded, due to overlap with
the peak of water that is formed in the course of reaction.
The spectrum shown in Figure 3c corresponds to the reaction
mixture after 11 h of reaction. As it can be seen in the aro-
matic NMR region at this stage of the reaction several calix-
arene isomers are formed, however, after 24 h of reaction
only the all-cis isomer is present in solution.
1
0
We performed in situ infrared experiments to gain more in-
sight into the initial interactions between the aldehyde and
Yb(TOS) . Octanal could be monitored following the car-
3
ꢁ
1
bonyl absorption band at 1721 cm . Unfortunately, it was
not possible to follow the formation of resorcinarene with
in situ infrared spectroscopy, since the vibration bands of
the C–C bonds in the resorcinarene, such as, for example,
the band at 1603 cm , fall in the same region as the vibra-
tion bands of the C–C bonds in resorcinol, leading to strong
overlapping. Figure 2 shows the most interesting part of re-
corded in situ infrared spectra, which shows the step-by-step
ꢁ
1
In summary, the in situ infrared and proton NMR measure-
ments established that lanthanide(III) tosylates and nosy-
lates catalyze acetal formation in the reaction between the
aldehyde and ethanol. Once the acetal is formed, the reaction
proceeds similarly to the build-up sequence postulated by
Weinelt and Schneider for the acid-catalyzed condensation
reaction between resorcinol and acetaldehyde in methanol/
addition of octanal, Yb(TOS) , and resorcinol to an etha-
3
nolic solution. By addition of 5 mol % of Yb(TOS) , the in-
3
ꢁ
1
tensity of carbonyl absorption band of octanal at 1721 cm
strongly decreased. This cannot originate from a full coordi-
nation of ytterbium to octanal since Yb(TOS) was present
3
in only 5 mol %. Rather, Yb(TOS) -catalyzed acetal forma-
3
2
4
HCl. The acid-catalyzed condensation has frequently
been interpreted in terms of cationic intermediates and elec-
trophilic aromatic substitution, but our experiments indi-
tion can be expected (Scheme 3, step A). The ability of
Sc(OTf) to catalyze the acetal formation at an early reaction
3
3
stage has been described in the Friedel–Crafts alkylation
of aromatics with arenecarbaldehydes in the presence of
cate that the lanthanide(III) catalyst is responsible for
more than simple coordination to the aldehyde. In fact, if
ethanol is used as a solvent, the lanthanide ion plays a dual
2
3
1
,3-propanediol. Since the lanthanide(III) tosylates have
+
resorcinol
+
Yb(TOS)3
+
octanal
Figure 2. In situ infrared spectra of the Yb(TOS)
information on the initial interaction of Yb(TOS)
tion of octanal (1721 cm ) is observed.
3
-catalyzed reaction of octanal and resorcinol in the presence of an excess of ethanol. Only the part giving
is depicted. At the addition of Yb(TOS) catalyst, an immediate decrease in absorbance of the C]O absorp-
3
3
ꢁ1

9068
K. Deleersnyder et al. / Tetrahedron 63 (2007) 9063–9070
CH CH OH
Ln-catalyst
3
2
R
H
R
H
Ln-catalyst
OCH CH
O
R
H
2
3
Ln3+
Ln3+
O
O
OCH CH
2
3
R
H
HO
OH
HO
OH
2
HO
OH
OH
R
OH
HO
OH
HO
OH
R
HO
OH
R
R
HO
HO
OH
OH
R
R
HO
OH
Scheme 3. Postulated mechanism for the lanthanide catalyzed formation of calix[4]resorcinarenes.
+
+
+
+
C
B
+
+
+
Δ
Δ
Δ
A
PPM
9.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
ꢀ
Figure 3. Proton NMR spectra of formation of calix[4]resorcinarenes at 65 C. The peaks at 1.11, 3.57, and 4.40 ppm are due to ethanol and water (A): res-
orcinol (stars) and octanal (black circles) in CD CD OD result in formation of small amount of acetal (white circles), (B) after addition of 5 mol % of Yb(TOS)
white triangles) more acetal is produced and, (C): after 11 h of reaction different isomers of calix[4]resorcinarene are present in the solution (plus signs).
3
2
3
(
role (Scheme 3). Most of the octanal is conversed to the ace-
tal by lanthanide catalyzed acetal formation and the remain-
ing octanal coordinates to the lanthanide ion to form
a cationic electrophilic species, which attacks the resorcinol
to form the calix[4]resorcinarene.
associated acid, or is itself acidic enough to promote proto-
1
0
dealkylation and hence isomerization. In order to deter-
mine whether the complex itself or the liberated acid
catalyzes the isomerization, the following experiment was
performed. Benzaldehyde-derived calix[4]resorcinarene
(1 g) with a known isomer distribution was left to react
It is reasonable to assume that once some calix[4]resorcinar-
ene is formed, it binds to the lanthanide(III) tosylate or nitro-
benzenesulfonate in a way similar as proposed in the study
on Yb(OTf) -catalyzed formation of resorcinarenes. Barrett
3
and co-workers suggest that this complex liberates the
with the respective catalyst in 10 mL of ethanol just beneath
the reflux temperature. After 120 h, the calix[4]resorcinar-
ene was isolated in the usual way and the isomer distribution
was determined from the H NMR spectrum. As can be seen
in Table 6, the degree of isomerization strongly depends on
1

K. Deleersnyder et al. / Tetrahedron 63 (2007) 9063–9070
9069
Table 6. Influence of the tosylate and nitrobenzenesulfonate counterion on
the isomerization of all-cis calix[4]resorcinarene (rccc), formed from benz-
aldehyde and resorcinol, to cis-trans-trans calix[4]resorcinarene (rctt)
catalysts is both environmentally and economically advanta-
geous. These catalysts can easily be recovered after reaction
and reused several times without loss of efficiency.
a
Catalyst
rccc:rctt
a
pK of the acid
Yb(TOS)
Yb(3-NBSA)
Yb(4-NBSA)
3
45:55
55:45
55:45
54:46
71:29
ꢁ6.56
ꢁ7.25
ꢁ7.23
N.A.
4. Experimental
3
3
Yb(2,4-NBSA)
Er(OTf)
3
4
.1. Materials and methods
3
ꢂꢁ12
a
Benzaldehyde-based calix[4]resorcinarene of 1 g (44% rccc, 56% rctt),
0 mol % of hydrated lanthanide catalyst, 10 mL ethanol, 120 h at reflux
temperature.
Reagents were obtained from Aldrich Chemical Co. Inc.,
Acros Organics or Rhodia Electronics and Catalysis, and
were used without further purification. Iron(III) tosylate
was purchased from Aldrich and copper(II) tosylate was pre-
1
1
pared in the same way as the lanthanide(III) tosylates. H
the counterion. If the lanthanide-resorcinarene complex
would itself promote protodealkylation we expect no differ-
ence between the various counterions. Moreover, during this
experiment a clear decrease in pH was noticed. Thus, we can
assume that the liberated acid catalyzes the isomerization
and hence the extent of isomerization depends on the acidity
of the respective sulfonic acid formed. Since p-toluenesul-
NMR spectra were run on a Bruker Avance 300 spectro-
meter, operating at 300 MHz. Elemental analysis was per-
formed on a CE Instruments EA-1110 elemental analyzer.
Mass spectra were recorded on a Thermo Electron mass
spectrometer, type LCQ, with an electrospray ionization
source (ESI). In situ infrared spectra were obtained using
a ReactIR 1000 IR (Applied Systems Inc., Mettler Toledo).
1
6
fonic acid (pK ¼ꢁ6.56), p-nitrobenzenesulfonic acid
a
(
pK ¼ꢁ7.23), and m-nitrobenzenesulfonic acid (pK ¼
4.2. General procedure for the synthesis of Ln(TOS)3
and Ln(NBSA) complexes
a
a
2
5
ꢁ
ꢁ
7.25) are much weaker acids than triflic acid (pK <
a
3
2
6
12), they do not really catalyze the isomerization of
the all-cis isomer (rccc) to the cis-trans-trans isomer (rctt).
As shown in Table 2 and Figure 1, the smallest amounts of
rccc isomer was formed when using Yb(3-NBSA)3 or
The lanthanide(III) salts were synthesized by reaction of
1.1 equiv of the corresponding lanthanide(III) oxide and
6 equiv of p-toluenesulfonic acid in water. After stirring
the solution in boiling water for 30 min, the excess of oxide
was removed by filtration. The filtered solution was evapo-
rated to dryness and the resulting solid was dried in a vacuum
Yb(2,4-NBSA) . The lower efficiency of these two catalysts
3
may be contributed to the steric effect of the substituents on
the aromatic ring, which may form more crowded environ-
ment around the lanthanide(III) ion.
ꢀ
oven at 50 C over night. Copper(II) tosylate was prepared
from copper(II) oxide and p-toluenesulfonic acid and the
lanthanide(III) nitrobenzenesulfonates are prepared in a sim-
ilar way from the respective nitrobenzenesulfonic acid.
As these latter experiments indicate that calixarene forma-
tion results in a lanthanide–calixarene complex with con-
comitant liberation of the associated Brønsted acid, it is
evident that further formation of calixarene can also occur
autocatalytically by this liberated acid. For comparison,
the reaction between benzaldehyde and resorcinol was also
carried out in the presence of 5 mol % of p-toluenesulfonic
acid monohydrate and after 24 h of reflux in ethanol nearly
complete conversion was obtained (83% rccc isomer and
4.3. Elemental analysis results for Ln(TOS) $xH O and
3
2
Ln(NBSA) $xH O
3
2
Yb(TOS) $H O (C H S O Yb) Calcd (found): C, 35.75
3
2
21 23 3 10
(35.63);
H,
3.29
(3.69)%.
(C H S O N Yb) Calcd (found): C, 26.51 (26.47); H,
Yb(3-NBSA) $2H O
3 2
1
8 16 3 17 3
1
7% rctt isomer).
1.98 (2.06); N, 5.15 (5.41)%. Yb(4-NBSA) $3H O
3 2
(C H S O N Yb) Calcd (found): C, 25.94 (25.57); H,
18 18 3 18 3
2.18 (2.34); N, 5.04 (5.52)%. Yb(2,4-NBSA) $4H O
3 2
3. Conclusions
(C H S O N Yb) Calcd (found): C, 21.91 (21.52); H,
18 17 3 25 6
1.74 (1.65); N, 8.52 (8.57)%. La(TOS) $3H O
3 2
We have demonstrated that lanthanide(III), copper(II), and
iron(III) p-toluenesulfonates and the lanthanide(III) salts
of nitrobenzenesulfonic acids are efficient catalysts for the
condensation reaction of resorcinol with benzaldehyde or
octanal to form calix[4]resorcinarenes. Moreover, in the re-
actions with benzaldehyde, the amount of each isomer can
be tuned not only by varying the reaction time but also by
appropriate choice of the metal ion. Although p-toluenesul-
(C H S O La) Calcd (found): C, 35.70 (35.68); H, 3.85
21 27 3 12
(3.76)%. Gd(TOS) $3H O (C H S O Gd) Calcd (found):
21 27 3 12
3
2
C, 34.76 (34.60); H, 3.75 (3.70)%. Y(TOS) $H O
3
2
(C H S O Y) Calcd (found): C, 40.65 (40.56); H, 3.74
2
1 23 3 10
(4.08)%. Cu(TOS) $H O (C H S O Cu) Calcd (found):
2
2
14 16 2 7
C, 39.66 (39.71); H, 3.88 (4.78)%.
4.4. General procedure for the lanthanide catalyzed
formation of calix[4]resorcinarenes
6
fonic and nitrobenzenesulfonic acids are about 10 times
weaker than triflic acid, their lanthanide(III) salts are strong
Lewis acids, which are able to catalyze the formation of re-
sorcinarenes. Good reaction yields are obtained after 24 h
with only 0.1 mol % of catalyst. The initial formation of
acetals as key intermediates has been confirmed. The use
of p-toluenesulfonic acid and nitrobenzenesulfonic acids
over triflic acid for the preparation of lanthanide(III)
To a stirred solution of the nonahydrated lanthanide(III)
catalyst (5 mol %, 0.318 mmol) in absolute ethanol
(10 mL) were added the resorcinol (6.36 mmol, 699 mg)
and benzaldehyde (6.36 mmol, 645 mL). This solution was
heated till just beneath the reflux temperature. After a given
period of time the solution was cooled and poured into

9070
K. Deleersnyder et al. / Tetrahedron 63 (2007) 9063–9070
distilled water (20 mL). The precipitated resorcinarene was
filtered on a dry weighed crucible and washed with water
5. Pietraszkiewicz, O.; Pietraszkiewicz, M. Pol. J. Chem. 1998,
72, 2418–2422.
(
3ꢃ10 mL). After drying the resorcinarene to constant
6. (a) Bonsignore, S.; Cometti, G.; Dalcanale, E.; Du Vosel, A.
Liq. Cryst. 1990, 8, 639–649; (b) Cometti, G.; Dalcanale, E.;
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H €o gberg, A. G. S. J. Am. Chem. Soc. 1980, 102, 6046–6050.
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Chem. 2001, 3, 280–284.
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Pieroni, O. L.; Rodriguez, N. M.; Vuano, B. M.; Cabaleiro,
M. C. J. Chem. Res., Synop. 1994, 188–189.
10. Barrett, A. G. M.; Braddock, D. C.; Henschke, J. P.; Walker,
E. R. J. Chem. Soc., Perkin Trans. 1 1999, 873–878.
11. Peterson, K. E.; Smith, R. C.; Mohan, R. S. Tetrahedron Lett.
ꢀ
weight (after about 48 h in a vacuum oven at 90 C) the cru-
cible was weighed again giving the amount of formed resor-
cinarene. To obtain the isomer distribution, a small amount
of resorcinarene was dissolved in deuterated DMSO and
1
a H NMR spectrum was recorded. The ratio was obtained
by integration of the signals at d¼5.64 (4H, benzylic hydro-
gens of rccc isomer) versus the signals at d¼5.54 (4H, ben-
zylic hydrogens of rctt isomer) and d¼5.57 (2H, ortho to OH
in rctt isomer). Electron spray ionization mass spectrometry
was performed to prove the tetrameric structure: m/e
+
+
+
(
ESI )¼793 (M+1) , 1608 (2M+Na+1) . CHN-analysis
was performed after drying the calix[4]resorcinarene for
ꢀ
8 h at 50 C in a vacuum oven: C H O $3H O Calcd
52 40 8 2
found): C, 73.74 (73.89); H, 5.47 (5.56)%.
4
(
2
003, 44, 7723–7725.
The procedures for the reactions with octanal were identical
with the only difference that these reactions were performed
at reflux temperature. CHN-analysis was also performed
12. Parac-Vogt, T. N.; Binnemans, K. Tetrahedron Lett. 2004, 45,
3137–3139.
13. Parac-Vogt, T. N.; Deleersnyder, K.; Binnemans, K. J. Alloys
Compd. 2004, 374, 46–49.
14. Parac-Vogt, T. N.; Pachini, S.; Nockemann, P.; Van Hecke, K.;
Van Meervelt, L.; Binnemans, K. Eur. J. Org. Chem. 2004,
ꢀ
after drying the calix[4]resorcinarene for 48 h at 50 C in
a vacuum oven: C H O $3H O Calcd (found): C, 71.91
5
6
80
8
2
(
71.51); H, 9.27 (9.35)%.
4
560–4566.
1
5. Parac-Vogt, T. N.; Deleersnyder, K.; Binnemans, K. Eur. J.
Org. Chem. 2005, 1810–1815.
Acknowledgements
1
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T.N.P.-V. thanks FWO-Flanders (Belgium) for the postdoc-
toral fellowship. Financial support has been provided by
the K.U. Leuven (VIS/01/006.01/2002/-06/2004 and GOA
17. (a) Faithfull, D. L.; Harrowfield, J. M.; Ogden, M. I.; Skelton,
B. W.; Third, K.; White, A. M. Aust. J. Chem. 1992, 45, 583–
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0
3/03) and by the FWO-Flanders (Krediet aan Navorsers
to K.B.). This work was performed within the framework
of a bilateral grant between Flanders and Hungary (BIL
0
4/27). The authors thank Rhodia Electronics and Catalysis
for a gift of rare-earth oxides. The donation of a ReactIR
000 instrument to E €o tv €o s University by Mettler-Toledo
1
AutoChem. Inc. is greatly appreciated.
1
9. Nakayama, T.; Takahashi, D.; Takeshi, K.; Ueda, M.
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