25,26-Dialkoxycalix[4]arenes. Part 2: 1-Alkoxy-3-benzoyloxy route

Article abstract of DOI:10.1016/j.tet.2011.03.048

Benzoylation of calix[4]arene monoalkyl ethers with benzoyl chloride yielded the corresponding 3-benzoates and/or 2,3-dibenzoates in different reaction conditions. A simple recrystallization process was able to isolate the 3-benzoates in good yield. In th

Full text of DOI:10.1016/j.tet.2011.03.048

Tetrahedron 67 (2011) 3936e3944
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25,26-Dialkoxycalix[4]arenes. Part 2: 1-Alkoxy-3-benzoyloxy route
*
Cheng-Han Kuo, Jun-Ren Huang, Hui-Ru Chen, Pei-Yu Chen, Chien-Hung Lin, Lee-Gin Lin
Institute of Applied Chemistry, Chinese Culture University, Taipei 11114, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
Benzoylation of calix[4]arene monoalkyl ethers with benzoyl chloride yielded the corresponding 3-ben-
zoates and/or 2,3-dibenzoates in different reaction conditions. A simple recrystallization process was able
to isolate the 3-benzoates in good yield. In the presence of NaH as reaction base, the 1-alkoxy-3-benzoy-
loxycalixarenes were alkylated with active alkyl halides at proximal position and yielded the corresponding
1,2-dialkoxy derivatives. Basic hydrolysis of compounds afforded the expected 25,26-dialkoxycalix[4]
arenes. For the less active alkyl halides, alkylation of 1-alkoxy-3-benzoyloxycalix[4]arenes afforded
both the 1,2-dialkoxy derivatives and the benzoyl-migrated 1,3-dialkoxy derivatives. Only the highly
symmetrical 1,3-diethoxy-2-benzoyloxycalix[4]arene was able to be isolated upon the deliberate
recrystallization process. After basic hydrolysis of the dialkylated crude products, 25,26-dialkoxycalix[4]-
arenes were chromatographic separated.
Received 29 November 2010
Received in revised form 7 March 2011
Accepted 17 March 2011
Available online 25 March 2011
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
1,2-dialkoxy-3-benzoyloxy products. Therefore, the easy accessible
1-alkoxy-3-benzoyloxycalix[4]arenes turned out to be the potential
In the literature reported, the calixarene’s ether derivatives
were prepared either in a one-step process (the tetra-alkyl ethers,1
the 1,3-dialkyl ethers,2 and the monoalkyl ethers3) or in multi-step
procedure (the monoalkyl ethers4 and the trialkyl ethers5). How-
ever, the attempt to convert the calix[4]arene’s monoalkyl ethers
into their 1,2-dialkyl ether derivatives by direct etherification pro-
cess was shown to be almost impossible. Therefore, a multi-step
procedure with an ester protecting group was required for the
preparation of calix[4]arene’s 1,2-dialkyl ethers.
candidates for the preparation of 1,2-dialkoxycalix[4]arenes.
It was then proposed that, as shown in Fig. 1, the 1,2-dialk-
oxycalix[4]arenes could be prepared by monoetherification of 1-
alkoxy-3-benzoyloxycalix[4]arenes following with cleavage of the
benzoate-protecting group in basic hydrolysis reaction. This syn-
thetic procedure will be described in the second section of this
paper. We will also report a benzoyl-migration phenomena in
1-alkoxy-3-benzoyloxycalix[4]arene systems.
In our previous report,6 we had shown that the acetate pro-
tecting group was migrated predominant in the etherification re-
action when the less active alkyl halides were used. The resulting
low productive yield suggested that the proposed 2,3-diacetate
synthetic route was not suitable for the preparation of several 1,2-
dialkoxycalix[4]arenes. Therefore, a more stable benzoate moiety,
which might not migrate as fast as acetate, was selected as the
protecting group. In the first section of this paper, we will report
a simple synthetic procedure to convert the monoalkoxycalix[4]-
arenes into their 3-benzoate derivatives.
It is easy to recognize that both of the available ‘lower rim’
positions were proximal to the existent alkoxy group in the struc-
ture of 1-alkoxy-3-benzoyloxycalix[4]arene. It is also anticipated
that the presence of the large steric hindrance benzoate moieties in
the 1-alkoxy-3-benzoyloxy’s structures might restrict the forma-
tion of the fourth ‘lower rim’ ether linkage and yield only the
2. Results and discussion
2.1. Benzoylation of calix[4]arene monoalkyl ethers
As reported in the literature4a, the tribenzoated calix[4]arene
monoallyl ether was prepared as a reaction intermediate during the
synthesis of calix[4]arene monoallyl ether. It was therefore believed
that the calix[4]arene monoalkyl ethers should be able to react with
benzoyl chloride to give the corresponding tribenzoated products.
However, when calix[4]arene monoalkyl ethers 1e5 were treated
with benzoyl chloride in a standard acylation conditions, the
3-benzoated products 6e10 and/or dibenzoated products 11e15
were the only isolated products, as shown in Scheme 1. It was noticed
that the tribenzoated products were not detected evenwith a further
increasing of benzoylation period and/or the amount of benzoyl
chloride. We believed that, as in previous observed systems,5e7 the
steric hindrance of the benzoate moieties inhibited the introduction
of the fourth substituent onto the tri-substituted calix[4]arenes and
failed to yield the 1-alkoxy-2,3,4-tribenzoate products.
* Corresponding author. E-mail address: lglin@faculty.pccu.edu.tw (L.-G. Lin).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.03.048

C.-H. Kuo et al. / Tetrahedron 67 (2011) 3936e3944
3937
CH2
CH2
CH2
CH2
Etherification with R-X, base
O
OR
OH
OH
C=O
Ph
CH2
CH2
CH2
CH2
O
OR
OR
OH
C=O
Ph
CH2
CH2
Hydrolysis with base, H2O
OH
OR
2
2
Fig. 1. A proposed synthetic route for the 1,2-dialkoxycalix[4]arenes.
CH2
CH2
CH2
CH2
CH2
CH2
PhCOCl
C5H5N
O
OR
OH
3
OR
OH
OH
C=O
Ph
R = -CH2CH3
-CH2CH2CH3
R = -CH2CH3
-CH2CH2CH3
1
2
3
4
5
6
7
-CH2CH2CH2CH3
-CH2CH=CH2
-CH2Ph
-CH2CH2CH2CH3
-CH2CH=CH2
-CH2Ph
8
9
10
CH2
CH2
CH2
CH2
excess PhCOCl, C5H5N
2-3 hours
O
O
OR
OH
C=O
Ph
C=O
Ph
Conformation unknown
R = -CH2CH3
11
-CH2CH2CH3
12
13
14
15
-CH2CH2CH2CH3
-CH2CH=CH2
-CH2Ph
Scheme 1. Synthetic scheme for benzoylation of 1-alkoxycalix[4]arenes 1e5.
The 3-benzoates 6e10 were easy to prepare by treating mono-
alkyl ethers 1e5 with benzoyl chloride in pyridine for 30 min. A
simple recrystallization afforded the monobenzoated products in
over 50% yield. Base on pervious 3-acetate cases,6 it was not too
complex to assign the structure of those monobenzoate products as
1-alkoxy-3-benzoates 6e10 with an aid from high field NMR and
2D NMR spectrum.
Dibenzoylation of monoalkyl ethers 1e5 was achieved by treating
with large excess of benzoyl chloride for 2 h. From the previous char-
acterized 3-benzoate products 6e10, it was known that the second
benzoate moiety had to link to the 2-position and yielded 1-alkoxy-2,3-
dibenzoate products 11e15. Regardless of the structural conformation,
the 1-alkoxy-2,3-dibenzoates 11e15 possessed no symmetry element,
and therefore, very complex 1H NMR spectral patterns were observed.
Although it was impossible to assign all the 1H NMR spectral signals, but
the increasing of 10 aromatic hydrogens verified the dibenzoate
structures. The 13C-chemical shift of the calix[4]arene’s methylene
carbon seemed to imply that the 1-alkoxy-2,3-dibenzoates 11e15 hold
the ‘up-down-up’ conformational arrangement,8 but all the other
available spectral data did not provide solid evidence to establish the
exact conformational structure of the products 11e15.
It should be also noted that compounds 11e15 seemed to
transform slowly into another isomeric forms during the extended
reaction period. A further study was required to determine whether
the transformed products were either the structural isomer or the
conformational isomer of the 1-alkoxy-2,3-dibenzoates 11e15. It is
believed that the extended study of the subject will not only reveal
the essential of the transformation, but also be able to determine
the conformational structure of all the possible 1-alkoxy-2,3-
dibenzoate isomers.

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C.-H. Kuo et al. / Tetrahedron 67 (2011) 3936e3944
2.2. Preparation of 1,2-dialkoxycalix[4]arenes with active
alkyl halides
The integral ratio and the splitting pattern of the methylene
hydrogen provided the needed information to confirm the structure of
product 17 as 1,2-dibenzyloxy-3-benzoyloxycalix[4]arene. The other
etherification product 16 was assigned as 1,2-diallyloxy-3-
benzoyloxycalix[4]arenebasedon the similarityof the spectralfeature.
The FAB-MS provided further evidences for the existing of the second
alkoxy moiety.
After the second alkoxy group was introduced, the 1,2-dialkoxy
compounds 16 and 17 were subjected to basic hydrolysis to remove
the ‘lower rim’ benzoate-protecting group as proposed in Fig.1. One
of the hydrolysis product, compound 19, was identical to the
previously synthesis compound, the syn-1,2-dibenzyloxycalix[4]-
arene.6 The other hydrolysis product 18 was assigned as syn-1,2-
Itwasreported6 previouslythatarefluxingwith1.5MequivofNaH
and excess alkyl halides in acetonitrile for 14 h was able to introduce
the second alkoxygroup onto 1-dialkoxy-2,3-diacetoxycalix[4]arenes
and yielded the expected 1,2-dialkoxy-3,4-diacetoxycalix[4]arenes.
Therefore, the same reaction conditions were applied to the 1-alkoxy-
3-benzoyloxycalix[4]arene systems. In the two active alkyl halide
cases, the benzyl bromide and allyl bromide, the resulting products
contained only one major component, and a simple recrystallization
was able to isolate the expected 1,2-dialkoxy-3-benzoyloxycalix[4]-
arenes 16 and 17, respectively (Scheme 2).
CH2
CH2
CH2
CH2
NaH, R-X, CH3CN
O
OR
OH
OH
C=O
Ph
-CH2CH=CH2
-CH2Ph
9
R=
10
CH2
CH2
CH2
CH2
O
OR
OR
OH
C=O
Ph
-CH2CH=CH2
-CH2Ph
16 R=
17
CH2
CH2
NaOH
OH
OR
2
2
EtOH-THF-H2O
-CH2CH=CH2
-CH2Ph
18 R=
19
Scheme 2. Synthetic scheme for the 1,2-dialkoxycalix[4]arenes 18 and 19.
Both products 16 and 17 contained no symmetrical element, and
hence, it was uncertain whether the structure of the products could be
properly assigned from the 1H NMR spectrum. When the spectrum of
product 17 was taken, it was surprised to find that the splitting pattern
of the calix[4]arene’s methylene and benzyloxy’s methylene moieties
was well-resolved. A total of 12 doublets were displayed for 12 dif-
ferent methylene hydrogens (eight calix[4]arene’s methylene hydro-
gens and four benzyloxy’s methylene hydrogens), as shown in Fig. 2.
diallyloxycalix[4]arene based on the similarity of the spectral fea-
ture with the earlier reported 200 MHz NMR spectrum.9
2.3. Preparation of 1,2-dialkoxycalix[4]arenes with less active
alkyl halides
It was shown previously6 that two isomeric dialkoxy products
were produced in various amounts on the etherification of 1-alkoxy-
Fig. 2. The 1H NMR spectrum of 1,2-dibenzyloxy-3-benzoyloxycalix[4]arene 17.

C.-H. Kuo et al. / Tetrahedron 67 (2011) 3936e3944
3939
2,3-diacetoxycalix[4]arenes. Similar results were also observed in the
lessactive alkyl halides, and mixtures of products weredetected when
compounds 6e8 were refluxed with 1.5 M equiv of NaH and excess
alkylhalides inacetonitrile(Scheme 3). TheTLC analysis indicated that
the crude product mixtures contained, along with other minor visible
components, a small amount of starting material and two new major
products. By careful examination of the integral ratio of the alkoxy
protons, it was possible to propose that both major compounds were
the dialkoxy derivatives.
and produced both the benzoate-migrated 1,3-dialkoxy products
and non-migrated 1,2-dialkoxy products.
Although the 50% productive yield of the 1,2-dialkoxycalix[4]-
arenes’ precursor was higher than quarterly amount in the diacetate
cases,6 but it was easily recognizable that a less-prone-to-migrate
protecting group was essential for the preparation of 1,2-dialkox-
ycalix[4]arenes. Further investigations on the less-prone-to-migrate
protecting groups, e.g., silyl ethers,10 electron-withdrawing benzo-
ates, and electron-releasing benzoates, are under study in our
laboratory.
In the most accessible 1,2-diethoxy cases, a simple but very slow
recrystallization process was able to crystallize one of the higher
symmetrical components, compound 20, from the product mixture
in a small amount (Scheme 4). Itshould be noted thatthe crystallized
product 20 would be contaminated by the other isomer, if the re-
crystallization process proceeded too fast and/or too long. The NMR
spectral pattern suggested that the molecular structure of product
20 contained a planar symmetry element. It was known clearly that
the structure of 1,2-diethoxy-3-benzoyloxycalix[4]arene contained
no symmetryelements, therefore, the structure of compound 20 had
to be benzoyl-migrated 1,3-diethoxy-2-benzoyloxycalix[4]arene.
The integral ratio between ethoxy’s protons and aromatic protons
supported the structural assignment of product 20. Further efforts
on the purification by recrystallization, unfortunately, failed to iso-
late any trace of the other isomeric components in pure form.
CH2
CH2
CH2
CH2
O
OR
OH
OH
C=O
Ph
-CH2CH3
R=
6
7
8
-CH2CH2CH3
-CH2CH2CH2CH3
NaH, R-X, CH3CN
CH2
CH2
CH2
CH2
Approximate 1:1 mixture of
1,2-dialkoxy-3-benzoyloxycalix[4]arene
and
O
OCH2CH3
OH
OH
C=O
Ph
1,3-dialkoxy-2-benzoyloxycalix[4]arene
6
NaOH,
EtOH-THF-H2O
NaH, R-X, CH3CN
CH2
CH2
CH2
OCH2CH3
CH2
CH2
CH2
O
OCH2CH3
OH
OH
OR
2
2
C=O
Ph
benzoyl-migrated 20 (by simple recrystallization)
-CH2CH3
22 R=
23
-CH2CH2CH3
+
-CH2CH2CH2CH3
24
Scheme 3. Synthetic scheme for the 1,2-dialkoxycalix[4]arene 22e24.
CH2
CH2
CH2
CH2
Unlike the diacetate cases, the amount of each component could
not be evaluated from the acetate’s signals. Fortunately, the 1H NMR
spectra of these reaction crude products displayed three well-de-
fined triplets for the alkoxy’s methyl groups, and the integral ratio
of these triplets could be used to replace the non-existent acetate’s
signal in the estimation procedure. The integral ratio of these
triplets displayed in approximate 2:1:1 in all cases, it was soon
realized that the two equal intensity triplets arose from the two
asymmetrical alkoxy moieties from the 1,2-dialkoxy derivative and
the other triplet had to arise from a symmetrical 1,3-dialkoxy
product. The 2:1:1 integral ratio also suggested that the two new
products were produced in an approximately equal amount. It was
then proposed, as in previous diacetate cases, that the benzoate
moieties were partially migrated during the etherificaton reaction
O
OCH2CH3
OCH2CH3
OH
C=O
Ph
non-migrated 21 (by chromatographic separation)
Scheme 4. Products isolated from ethylation of 1-ethoxy-3-benzoyloxycalix[4]arene 6.
Although, the structure of product 20 was assigned as 1,3-
diethoxy-2-benzoyloxycalix[4]arene, but the spectrum pattern of
product 20 was different from the known compounds which were
reported earlier by treating 1,3-dialkoxycalix[4]arene with benzoyl
chloride in pyridine at ice bath temperature.5 A noticeable spectral
difference between compound 20 and monobenzoated 1,3-di-
alkoxycalix[4]arene indicated that the two sets of compounds were

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C.-H. Kuo et al. / Tetrahedron 67 (2011) 3936e3944
isomeric conformers. The exact conformation of product 20 will be
discussed in the next section.
ethoxy groups in syn arrangement. The lack of any anti-isomer sug-
gested that the breaking of cyclic orthobenzoate ring and the formation
of ether linkage were not gone through a stepwise fashion. Therefore,
the exact structure of compound 20 was able to assign as in all-syn
conformation. The earlier prepared monobenzoated 1,3-dialkoxycalix-
[4]arene,5 which was conformational isomer of compound 20, had to
consist of ‘up-down-up’ arrangement.11 This ‘up-down-up’ structure
was agreed with our earlier proposed structure.5
After compound 20 was partially crystallized and collected, the
mother solution was subjected to column chromatography to re-
trieve product 21. The non-migrated 1,2-diethoxy product 21 con-
tained no symmetrical element as compounds 16 and 17, therefore,
a similar 1H NMR spectral feature as previous spectrum (Fig. 2) was
able to assign the structure of product 21 as 1,2-diethoxy-3-ben-
zoyloxy-calix[4]arene.
A standard basic hydrolysis was also performed on the similar
remained crude materials. When the hydrolysis products were
recrystallized from CHCl3 and CH3OH, rod-like crystals and a small
amount of powder solids were collected. The rod-like crystals,
which were not adhered on the filter paper, were easy to separate
from the powder solid. The crude crystals were then recrystallized
again, and the resulting compound 22 was subjected to the 1H NMR
spectral analysis.
C
O
O
OH
CH2
RO
CH2
CH2
Similar to the 1H NMR spectrum of product 19, hydrolysis
product 22 also displayed three pairs of doublets with the integral
ratio of 1:1:2 for the calix[4]arene’s methylene hydrogen. The
ethoxy’s methylene hydrogens, which also experienced a different
magnetic environment, emerged into two sets of multiplets. The
existence of two ethoxy moieties was further supported by the MS
measurement, therefore, the structure of compound 22 was
assigned confidently as 1,2-diethoxycalix[4]arene.
CH2
OH
base
CH3CN
-
O
C
less
C
At the meantime, it was found that the benzoyl-migrated 1,3-
dialkoxy products were not always crystallized as expected and the
quantity of the desired non-migrated 1,2-dialkoxy products was also
varied in the mother solution. Therefore, a decision was made to
carry out the basic hydrolysis reaction directly without any prior
purification on the etherification crude products (Scheme 3). In all
threelessactivealkylhalidecases, allthreehydrolyzedcrudeproduct
mixtures contained different sets of trio-products. The highest Rf
components, which existed in a small amount, were shown to be the
calix[4]arene monoalkyl ether in all three cases. The other two
components, which existed in an approximately equal amount as
their benzoated predecessor, were distinguishable on the TLC anal-
ysis. Therefore, the hydrolysis crude products were subjected to the
chromatographic separation to isolate the 1,2-dialkoxycalix[4]-
arenes 22e24. In the chromatographic separation, the 1,2-dialkoxy
products 22e24 were eluented last following the monoalkoxy and
1,3-dialkoxy products, and the overall isolating yields were in the
range of10%. Whereas, theisolating yieldswere somewhat higherfor
their corresponding benzoyl-migrated 1,3-dialkoxy products.
Similar to the 1H NMR spectrum of the earlier isolated hydro-
lysis product 22, three pairs of doublets with the integral ratio of
1:1:2 for the calix[4]arene’s methylene hydrogen, a distinct spectral
feature for 1,2-disubstituted calix[4]arenes, was observed on the
spectra of products 23e24. The alkoxy’s methylene hydrogens of
products 23e24, as in the 1,2-diethoxy case, also emerged into two
sets of multiplets. The MS provided further characterization data to
support the structural assignment for compounds 23e24.
O
O
hindered
side
.
O
-
O
O
formation of
cyclic
CH2
CH2
RO
CH2
RO
CH2
orthobenzoate
intermediate
CH2
CH2
CH2
CH2
OH
OH
R-X
R-X
OR
C
C
OR
O
O
O
O
CH2
CH2
RO
RO
CH2
CH2
CH2
CH2
CH2
CH2
OH
OH
Fig. 3. Proposed mechanism for the intramolecular benzoyl-migration.
Investigation on the benzoyl-migrated behavior of the other 1-
alkoxy-3-benzoyloxycalix[4]arenes is under study in this labora-
tory. It should be point out that such study may shed light on the
exact structure of the 1-alkoxy-2,3-dibenzoyloxycalix[4]arenes,
a conformational problem, which is unsolved in the first section of
this paper. Furthermore, in order to verify the proposed acyl-mi-
grated mechanism, the evaluation of the benzoyl-migration rates
on electron-releasing p-methoxybenzoate group and electron-
withdrawing p-nitrobenzoate group are also under examination.
2.4. Mechanism for the etherification of 1-alkoxy-3-
benzoyloxycalix[4]arenes in basic conditions
Based on the results from various etherification conditions, we
speculated that a stronger base NaH enhanced the nucleophilicity
of the calix[4]arene anion, and achieved the preparation of the 1,2-
dialkoxy products. Whereas, a weak base K2CO3 preferred the for-
mation of the cyclic orthobenzoate-like anionic intermediates, and
hence, yielded the benzoyl-migrated products.
In the cyclic orthobenzoate-like anionic intermediate path, the alkyl
halides were probably approached from the less hindered 3-position
side, as shown in Fig. 3, and produced the benzoyl-migrated products. It
should be noted that the isolated benzoyl-migrated product 20 had two
3. Experimental12
3.1. General procedure for the monobenzoylation of
calix[4]arene monoalkyl ethers
A slurry of 0.50 g of calix[4]arene monoalkyl ethers 1e5 was
dissolved in 15 mL of pyridine, and 0.5 mL of benzoyl chloride was

C.-H. Kuo et al. / Tetrahedron 67 (2011) 3936e3944
3941
then added dropwisely at ice bath temperature. The reaction
mixture was stirred for 30 min, and the solvent was removed by
rotory evaporatory to leave an oily residue. The organic materials
were taken up by 50 mL of CHCl3 and washed with 20 mL of 1N HCl
twice followed with 100 mL of saturated NaHCO3 solution and
100 mL of distillated water. The organic solvent was then removed
from the organic portion to leave an off white residue. Recrystal-
lized from CHCl3 and CH3OH yielded the corresponding mono-
benzoylated products 6e10.
119.5, 119.3, 32.5, 32.0, 31.9; FAB-MS m/e: 568 (Mþ); HRMS (FAB)
m/e: calcd for C38H32O5: 568.2250; found: 568.2244.
3.1.5. 25-Benzoyloxy-27-benzyloxy-26,28-dihydroxycalix[4]arene
(10). An amount of 0.39 g (64.5%) of colorless fine crystals was
collected from 0.50 g (0.97 mmol) of calix[4]arene monobenzyl
ether 5: mp 238e240 ꢀC; 1H NMR (CDCl3) 8.36e8.39 (dd, 2H, Ar0H),
d
7.60e7.70(m, 3H, Ar0H, and Ar00H), 7.38e7.50 (m, 5H, Ar0H, and Ar00H),
6.67e7.08 (m,12H, ArH, and ArOH), 5.12 (s, 2H, OCH2Ar00), 4.20e4.24
(d, J¼13.6 Hz, 2H, ArCH2Ar), 4.04e4.01 (d, J¼13.2 Hz, 2H, ArCH2Ar),
3.45e3.49 (d, J¼13.6 Hz, 2H, ArCH2Ar), 3.36e3.40 (d, J¼13.2 Hz, 2H,
3.1.1. 25-Benzoyloxy-27-ethoxy-26,28-dihydroxycalix[4]arene
(6). An amount of 0.42 g (68%) of colorless fine crystals was
collected from 0.50 g (1.11 mmol) of calix[4]arene monoethyl
ArCH2Ar); 13C NMR (CDCl3)
d 165.4, 153.0, 151.5, 145.2, 136.0, 133.4,
132.7,132.3,130.6,129.5,129.4,129.1,128.9,128.8,128.6,128.5,127.9,
127.2, 126.2, 126.0, 119.5, 79.0, 31.8; FAB-MS m/e: 619 (Mþþ1);
HRMS(FAB) m/e: calcd for C42H34O5þHþ: 619.2484; found:
619.2488.
ether 1: mp 302e304 ꢀC; 1H NMR (CDCl3)
d 8.48e8.50 (dd, 2H,
Ar0H), 7.63e7.66 (t, J¼7.6 Hz, 1H, Ar0H), 7.50e7.54 (m, 2H, Ar0H),
7.17 (s, 1H, ArOH), 6.69e7.06 (m, 12H, ArH), 4.19e4.23
(q, J¼7.0 Hz, 2H, OCH2CH3), 4.10e4.14 (d, J¼13.2 Hz, 2H,
ArCH2Ar), 4.08e4.11 (d, J¼13.6 Hz, 2H, ArCH2Ar), 3.54e3.57
(d, J¼13.6 Hz, 2H, ArCH2Ar), 3.39e3.42 (d, J¼13.2 Hz, 2H,
ArCH2Ar), 1.82e1.85 (t, J¼7.0 Hz, 3H, OCH2CH3); 13C NMR (CDCl3)
3.2. General procedure for the dibenzoylation of
calix[4]arene monoalkyl ethers
d
165.6, 152.9, 150.7, 145.4, 133.5, 132.9, 132.5, 130.7, 129.8, 129.6,
A slurry of 0.50 g of calix[4]arene monoalkyl ethers 1e5 was
dissolved in 20 mL of pyridine, and 4.0 mL of benzoyl chloride was
then added dropwiselyat ice bath temperature. The reaction mixture
was stirred for 2 h, and the solvent was removed by rotory evapo-
ratorytoleaveanoilyresidue. Theorganicmaterialsweretakenupby
50 mL of CHCl3, and washed with 20 mL of 1N HCl twice followed
with 100 mL of saturated NaHCO3 solution and 100 mL of distillated
water. The organic solvent was then removed from the organic por-
tion to leave an off white residue. Recrystallized from CHCl3 and
CH3OH yielded the corresponding dibenzoylated products 11e15.
129.0, 128.9, 128.6, 128.4, 126.5, 126.4, 126.0, 119.5, 72.7, 32.1,
31.9, 15.3; FAB-MS m/e: 556 (Mþ); HRMS (FAB) m/e: calcd for
C37H32O5: 556.2250; found: 556.2242.
3.1.2. 25-Benzoyloxy-27-propoxy-26,28-dihydroxycalix[4]arene
(7). An amount of 0.48 g (78%) of colorless fine crystals was col-
lected from 0.50 g (1.07 mmol) of calix[4]arene monopropyl ether
2: mp 256e258 ꢀC; 1H NMR (CDCl3)
d
8.50e8.53 (dd, 2H, Ar0H),
7.64e7.69 (m, 1H, Ar0H), 7.52e7.56 (m, 2H, Ar0H), 6.67e7.16 (m, 14H,
ArH, and ArOH), 4.07e4.14 (m, 6H, OCH2CH2CH3, and ArCH2Ar),
3.50e3.55 (d, J¼14 Hz, 2H, ArCH2Ar), 3.41e3.37 (d, J¼13.2 Hz, 2H,
ArCH2Ar), 2.18e2.24 (m, OCH2CH2CH3), 1.33e1.38 (t, J¼7.4 Hz,
3.2.1. 25,26-Dibenzoyloxy-27-ethoxy-28-hydroxycalix[4]arene
(11). An amount of 0.25 g (34%) of colorless fine crystals was col-
lected from 0.50 g (1.11 mmol) of calix[4]arene monoethyl ether 1:
OCH2CH2CH3); 13C NMR (CDCl3)
d 165.6, 152.9, 150.8, 145.4, 133.5,
132.6, 132.3, 132.2, 130.6, 130.5, 129.7, 129.6, 129.2, 129.1, 128.9,
128.6, 128.4, 128.1, 126.6, 126.2, 126.0, 119.4, 79.0, 32.4, 31.8, 23.4,
11.0; FAB-MS m/e: 571 (Mþþ1); HRMS (FAB) m/e: calcd for
C38H34O5þHþ: 571.2484; found: 571.2493.
248e250 ꢀC; 1H NMR (CDCl3) 8.00e8.02 (m, 3H, Ar0H, and ArOH),
d
7.56e7.60 (t, J¼7.2 Hz, 1H, Ar0H), 7.36e7.40 (t, J¼7.8 Hz, 2H, Ar0H),
6.16e7.25 (m, 17H, ArH, and Ar0H), 4.17e4.21 (m, 1H, OCH2CH3),
4.07e4.10 (d, J¼12.8 Hz, 1H, ArCH2Ar), 3.81e3.99 (m, 5H, ArCH2Ar,
and OCH2CH3), 3.73e3.77 (d, J¼16.4 Hz,1H, ArCH2Ar), 3.46e3.50 (d,
J¼14.0 Hz, 1H, ArCH2Ar), 3.25e3.28 (d, J¼12.8 Hz, 1H, ArCH2Ar),
3.1.3. 25-Benzoyloxy-27-butoxy-26,28-dihydroxycalix[4]arene
(8). An amount of 0.32 g (52.5%) of colorless fine crystals was
collected from 0.50 g (1.04 mmol) of calix[4]arene monobutyl
1.47e1.51 (t, J¼7.2 Hz, 3H, OCH2CH3); 13C NMR (CDCl3)
d 164.9,
163.3, 153.1, 148.1,146.6, 133.2,133.1,133.0, 132.8, 132.5, 132.3, 131.8,
130.7, 130.1, 130.0, 129.7, 129.6, 129.5, 129.3, 129.3, 128.6, 128.5,
128.2, 128.1, 128.1, 127.9, 127.2, 126.2, 125.3, 125.0, 119.2, 69.4, 37.8,
31.7, 31.2, 15.1; FAB-MS m/e: 661 (Mþþ1); HRMS (FAB) m/e: calcd
for C44H36O6þHþ: 661.2590; found: 661.2599.
ether 3: mp 243e245 ꢀC; 1H NMR (CDCl3)
d 8.50e8.53 (dd, 2H,
Ar0H), 7.62e7.78 (m, 1H, Ar0H), 7.52e7.62 (m, 2H, Ar0H), 6.67e7.16
(m, 14H, ArH and, ArOH), 4.10e4.14 (m, 6H, OCH2CH2CH2CH3, and
ArCH2Ar), 3.51e3.54 (d, J¼13.6 Hz, 2H, ArCH2Ar), 3.36e3.40 (d,
J¼13.2 Hz, 2H, ArCH2Ar), 2.15e2.20 (m, 2H, OCH2CH2CH2CH3),
1.70e1.76 (m, 2H, OCH2CH2CH2CH3), 1.10e1.15 (t, J¼7.4 Hz, 3H,
3.2.2. 25,26-Dibenzoyloxy-27-propoxy-28-hydroxycalix[4]arene
(12). An amount of 0.33 g (46%) of colorless fine crystals was col-
lected from 0.50 g (1.07 mmol) of calix[4]arene monopropyl ether 2:
OCH2CH2CH2CH3); 13C NMR (CDCl3)
d 165.6, 152.9, 153.0, 151.0,
145.4, 133.4, 132.7, 132.4, 130.7, 130.5, 129.8, 129.0, 128.9, 128.6,
128.5, 128.4, 126.6, 126.2, 126.0, 119.5, 32.0, 31.8, 19.2, 14.1; FAB-
MS m/e: 585 (Mþþ1); HRMS (FAB) m/e: calcd for C39H36O5þHþ:
585.2641; found: 585.2639.
mp 254e258 ꢀC; 1H NMR (CDCl3)
d
8.01e8.02 (d, J¼7.2 Hz, 2H, Ar0H),
7.90 (s, 1H, ArOH), 7.58e7.62 (t, J¼7.4 Hz, 1H, Ar0H), 7.38e7.41 (t,
J¼7.6 Hz, 2H, Ar0H), 6.18e7.25 (m,17H, ArH, and Ar0H), 3.72e4.14 (m,
8H, ArCH2Ar, and OCH2CH2CH3), 3.48e3.52 (d, J¼14.0 Hz, 1H,
ArCH2Ar), 3.28e3.31 (d, J¼12.8 Hz, 1H, ArCH2Ar), 1.95e2.02 (m, 1H,
OCH2CH2CH3), 1.87e1.94 (m, 1H, OCH2CH2CH3), 1.14e1.18 (t,
3.1.4. 25-Benzoyloxy-27-allyloxy-26,28-dihydroxycalix[4]arene
(9). An amount of 0.37 g (60%) of colorless fine crystals was col-
lected from 0.50 g (1.08 mmol) of calix[4]arene monoallyl ether 4:
J¼7.4 Hz, 3H, OCH2CH2CH3); 13C NMR (CDCl3
) d 164.9, 163.4, 153.1,
mp 212e214 ꢀC; 1H NMR (CDCl3
)
d
8.58e8.46 (dd, 2H, Ar0H),
152.4,148.1,133.2,133.1,132.6,132.5,132.4,131.8,130.2,129.8,129.5,
129.4,129.3,128.8,128.6,128.3,128.2,128.1,127.9,127.2,126.2,125.3,
125.0,119.2, 37.8, 31.7, 31.1, 23.0, 10.7; FAB-MS m/e: 674 (Mþ); HRMS
(FAB) m/e: calcd for C45H38O6: 674.2668; found: 674.2665.
7.51e7.79 (m, 3H, Ar0H), 6.67e7.21 (m, 14H, ArH, and ArOH),
6.29e6.56 (m, 1H, OCH2CH]CH2), 5.71e5.88 (dd, 1H, OCH2CH]
CH2), 5.53e5.65 (dd, 1H, OCH2CH]CH2), 4.58e4.76 (m, 2H,
OCH2CH]CH2), 4.14e4.18 (d, J¼14.0 Hz, 2H, ArCH2Ar), 4.12e4.16 (d,
J¼13.2 Hz, 2H, ArCH2Ar), 3.52e3.56 (d, J¼14.0 Hz, 2H, ArCH2Ar),
3.2.3. 25,26-Dibenzoyloxy-27-butoxy-28-hydroxycalix[4]arene
(13). Anamountof0.35 g(49%) ofcolorlessfinecrystals wascollected
from 0.50 g (1.04 mmol) of calix[4]arene monobutyl ether 3: mp
3.40e3.44 (d, J¼13.2 Hz, 2H, ArCH2Ar); 13C NMR (CDCl3
) d 165.5,
153.0, 151.0, 145.4, 133.5, 132.8, 132.4, 132.3, 132.1, 130.7, 130.6,
129.6, 129.2, 129.1, 128.9, 128.6, 128.5, 128.1, 126.8, 126.2, 126.1,
256e258 ꢀC; 1H NMR (CDCl3)
d
8.02e8.04 (d, J¼7.2 Hz, 2H, Ar0H), 7.90

3942
C.-H. Kuo et al. / Tetrahedron 67 (2011) 3936e3944
(s, 1H, ArOH), 7.60e7.64 (t, J¼7.6 Hz, 1H, Ar0H), 7.40e7.45 (t, J¼7.8 Hz,
2H, Ar0H), 6.21e7.28 (m, 17H, ArH, and Ar0H), 3.74e4.14 (m, 8H,
ArCH2Ar, and OCH2CH2CH2CH3), 3.47e3.51 (d, J¼13.6 Hz, 1H,
ArCH2Ar), 3.27e3.30 (d, J¼12.8 Hz, 1H, ArCH2Ar), 1.92e2.02 (m, 1H,
OCH2CH2CH2CH3),1.75e1.90 (m,1H, OCH2CH2CH2CH3),1.50e1.57 (m,
2H, OCH2CH2CH2CH3), 1.05e1.09 (t, J¼7.4 Hz, 3H, OCH2CH2CH2CH3);
(m, 5H, OCH2CH]CH2, and ArCH2Ar), 4.23e4.30 (2d, 2H, ArCH2Ar),
4.08e4.12 (d, J¼12.8 Hz, 1H, ArCH2Ar), 3.44e3.47 (d, J¼12.8 Hz, 1H,
ArCH2Ar), 3.26e3.38 (3d, 3H, ArCH2Ar); 13C NMR (CDCl3)
d 166.0,
155.1,153.3,152.6,146.0,136.8,136.3,134.7,134.1,133.5,133.3,132.9,
132.6,132.1,131.1,130.6,130.0,129.1,129.0,128.9,128.9,128.8,128.5,
128.5,128.4,128.0,127.8,127.6,125.0,124.6,123.5,119.5,118.4,117.9,
75.2, 31.9, 31.4; FAB-MS m/e: 609 (Mþþ1); HRMS (FAB) m/e: calcd for
C41H36O5þHþ: 609.2641; found: 609.2645.
13C NMR (CDCl3)
d 164.9, 163.4, 153.1, 152.5, 148.1, 146.7, 133.2, 133.2,
133.1, 132.6, 132.5, 132.4, 131.8, 130.7, 130.2, 129.8, 129.6, 129.4, 129.3,
128.8, 128.6, 128.3, 128.2, 128.1, 128.0, 127.2, 126.2, 125.3, 119.2, 74.0,
37.9, 31.7, 31.6, 31.1,19.0,14.1; FAB-MS m/e: 689 (Mþþ1); HRMS (FAB)
m/e: calcd for C46H40O6þHþ: 689.2903; found: 689.2902.
3.3.2. 25,26-Dibenzyloxy-27-benzoyloxy-28-dihydroxycalix[4]arene
(17). An amount of 0.20 g (35%) of colorless crystals was afforded
form 0.50 g (0.81 mmol) of monobenzyloxy compound 10: mp
3.2.4. 25,26-Dibenzoyloxy-27-allyloxy-28-hydroxycalix[4]arene
(14). An amount of 0.22 g (30%) of colorless fine crystals was col-
lected from 0.50 g (1.08 mmol) of calix[4]arene monoallyl ether 4:
244e246 ꢀC; 1H NMR (CDCl3) 8.54e8.56 (d, 2H, Ar0H), 7.64e7.66
d
(t, 1H, Ar0H), 7.53e7.57 (t, 2H, Ar0H), 6.52e7.48 (m, 22H, ArH, and
Ar00H), 5.94 (s, 1H, ArOH), 5.05e5.08 (d, J¼12.8 Hz, 1H, OCH2Ar00),
4.94e4.97 (d, J¼12.8 Hz, 1H, OCH2Ar00), 4.83e4.87 (2d, 2H,
OCH2Ar00), 4.25e4.29 (d, J¼12.8 Hz, 1H, ArCH2Ar), 4.16e4.19
(d, J¼12.8 Hz, 1H, ArCH2Ar), 4.02e4.05 (d, J¼12.8 Hz, 1H, ArCH2Ar),
3.84e3.88 (d, J¼12.8 Hz, 1H, ArCH2Ar), 3.23e3.28 (2d, 2H,
ArCH2Ar), 3.18e3.20 (d, J¼12.8 Hz, 1H, ArCH2Ar), 2.95e2.98
mp 238e240 ꢀC; 1H NMR (CDCl3)
d
8.00e8.02 (d, J¼8.4 Hz, 2H, Ar0H),
7.71 (s, 1H, ArOH), 7.59e7.63 (t, J¼7.4 Hz, 1H, Ar0H), 7.40e7.44
(t, J¼7.6 Hz, 2H, Ar0H), 6.21e7.25 (m, 17H, ArH, and Ar’H), 6.05e6.16
(m, 1H, OCH2CH]CH2), 5.40e5.48 (m, 2H, OCH2CH]CH2),
4.67e4.70 (dd, 1H, OCH2CH]CH2), 4.31e4.36 (dd, 1H, OCH2CH]
CH2), 4.08e4.11 (d, J¼13.2 Hz,1H, ArCH2Ar), 4.02e4.06 (d, J¼16.4 Hz,
1H, ArCH2Ar), 4.00e4.04 (d, J¼14.0 Hz, 1H, ArCH2Ar), 3.90e3.93
(d, J¼15.6 Hz, 1H, ArCH2Ar), 3.84e3.88 (d, J¼16.4 Hz, 1H, ArCH2Ar),
3.75e3.79 (d, J¼15.6 Hz, 1H, ArCH2Ar), 3.48e3.51 (d, J¼14.0 Hz, 1H,
ArCH2Ar), 3.27e3.30 (d, J¼13.2 Hz, 1H, ArCH2Ar); 13C NMR (CDCl3)
(d, J¼12.8 Hz, 1H, ArCH2Ar); 13C NMR(CDCl3)
d 166.0, 154.2, 153.3,
152.4, 146.0, 136.8, 136.6, 136.4, 134.3, 133.4, 133.0, 132.6, 132.3,
131.5,130.7,130.3,130.1,129.2,129.1,128.9,128.7,128.7,128.6,128.6,
128.4, 127.9, 127.8, 127.6, 127.6, 126.4, 125.0, 124.6, 123.4, 119.6, 78.1,
31.7, 31.4, 31.3, 31.0; FAB-MS m/e: 709 (Mþþ1); HRMS (FAB) m/e:
calcd for C49H40O5: 708.2877; found: 708.2867.
d
164.9, 163.4, 153.0, 152.3, 148.1, 146.7, 133.2, 133.1, 132.7, 132.6,
132.5,132.5,132.4,131.8,130.8,130.2,130.2,129.9,129.5,129.5,129.3,
129.0,128.6,128.4,128.2,128.1,128.0,127.3,126.2,125.4,125.3,125.2,
119.2, 119.2, 75.0, 37.9, 37.8, 31.8, 31.2.
3.4. General procedure for the basic hydrolysis of 1,2-
dialkoxy-3-benzoyloxycalix[4]arenes 16e17
3.2.5. 25,26-Dibenzoyloxy-27-benzyloxy-28-hydroxycalix[4]arene
(15). An amount of 0.20 g (28%) of colorless fine crystals was col-
lected from 0.50 g (0.97 mmol) of calix[4]arene monobenzyl ether
A slurry of approximate 0.20 g of 1,2-dialkoxy-3-benzoyl-
oxycalix[4]arenes 16e17 and 2.00 g of 25% NaOH was refluxed in
a mixture of 10 mL of C2H5OH and 30 mL of THF for 24 h. The
solvent was removed by rotory evaporatory and the organic ma-
terials were taking up by 50 mL of CHCl3. The solution was washed
in sequence with 20 mL of 1N HCl and 100 mL of distillated water,
and the solvent was then removed to leave a colorless solid. Re-
crystallization from CHCl3 and CH3OH yielded the corresponding
hydrolysis products 18e19.
5: mp 264e268 ꢀC; 1H NMR (CDCl3)
d
7.97e8.01 (dd, 2H, Ar0H),
7.59e7.60 (t, 1H, Ar0H), 6.22e7.38 (m, 25H, ArH, Ar0H, Ar00H, and
ArOH), 5.18e5.21 (d, J¼11.6 Hz, 1H, OCH2Ar00), 4.86e4.89
(d, J¼11.6 Hz, 1H, OCH2Ar00), 4.06e4.10 (d, J¼12.8 Hz, 1H, ArCH2Ar),
4.01e4.05 (d, J¼16.4 Hz, 1H, ArCH2Ar),3.79e3.92 (3d, 3H, ArCH2Ar),
3.73e3.77 (d, J¼16.4 Hz, 1H, ArCH2Ar), 3.25e3.31 (2d, 2H,
ArCH2Ar); 13C NMR (CDCl3)
d 164.9, 163.5, 153.0, 152.7, 148.1, 146.7,
135.8, 133.2, 133.1, 133.0, 132.8, 132.7, 132.5, 132.5, 131.8, 130.7,
130.3, 130.2, 130.2, 129.6, 129.5, 129.3, 129.3, 129.2, 128.8, 128.6,
128.4, 128.1, 127.3, 126.3, 125.3, 125.2, 125.1, 119.2, 38.0, 37.8, 31.7,
31.1; FAB-MS m/e: 723 (Mþþ1); HRMS (FAB) m/e: calcd for
C49H38O6þHþ: 723.2747; found: 723.2740.
3.4.1. 25,26-Diallyloxy-27,28-dihydroxycalix[4]arene (18). An amo-
unt of 0.09 g (49%) of colorless crystals was afforded form 0.22 g
(0.36 mmol) of diallyloxy compound 16: mp 155e160 ꢀC; 1H NMR
(CDCl3)
d 8.72 (s, 2H, ArOH), 6.59e7.06 (m, 12H, ArCH2Ar),
6.34e6.43 (m, 2H, OCH2CH]CH2), 5.57e5.60 (dd, J¼16.4, 0.8 Hz,
2H, OCH2CH]CH2), 5.39e5.43 (dd, J¼11.2, 0.8 Hz, 2H, OCH2CH]
CH2), 4.66e4.67 (m, 2H, OCH2CH]CH2), 4.49e4.53 (m, 3H,
OCH2CH]CH2, and ArCH2Ar), 4.32e4.36 (d, J¼13.2 Hz, 3H,
3.3. General procedure for the alkylation of 1-alkoxy-3-
benzoyloxycalix[4]arenes 9e10 in the present of NaH
ArCH2Ar), 3.34e3.43 (m, 4H, ArCH2Ar); 13C NMR (CDCl3)
d 153.1,
A slurry of approximate 0.50 g of 1-alkoxy-3-benzoyloxycalix[4]-
arenes 9e10, 0.05 g of 60% NaH, and 4 mol equiv of alkyl halides was
refluxedin50mLofCH3CNfor3 h. Thesolvent wasremoved byrotory
evaporatory and the organic materials were taken up by 30 mL of
CHCl3. The organic solutionwaswashed insequencewith20mL of1N
HCl and 100 mL of distillated water. The organic solvent was then
concentrated and recrystallized from CHCl3 and CH3OH to afford the
corresponding products 16e17.
151.0, 134.6, 134.3, 133.5, 129.2, 129.1, 129.0, 128.7, 128.7, 128.0,
124.9, 120.6, 119.1, 77.3, 31.9, 31.7, 30.4.
3.4.2. 25,26-Dibenzyloxy-27,28-dihydroxycalix[4]arene
(19). An
amount of 0.08 g (41%) of colorless crystals was afforded form
0.23 g (0.32 mmol) of dibenzyloxy compound 17: mp 230e232 ꢀC;
1H NMR (CDCl3)
d 8.93 (s, 2H, ArOH), 6.56e7.51 (m, 22H, ArH, and
Ar0H), 5.05e5.08 (d, J¼11.2 Hz, 2H, OCH2Ar’), 4.87e4.90 (d,
J¼11.2 Hz, 2H, OCH2Ar’), 4.47e4.50 (d, J¼12.4 Hz, 1H, ArCH2Ar),
4.23e4.26 (d, J¼13.2 Hz, 1H, ArCH2Ar), 4.10e4.13 (d, J¼12.8 Hz,
2H, ArCH2Ar), 3.33e3.36 (d, J¼13.2 Hz, 2H, ArCH2Ar), 3.22e3.25
3.3.1. 25,26-Diallyloxy-27-benzoyloxy-28-dihydroxycalix[4]arene
(16). An amount of 0.21 g (39%) of colorless crystals was afforded
form 0.50 g (0.88 mmol) of monoallyloxy compound 9: mp
(d, J¼12.8 Hz, 2H, ArCH2Ar); 13C NMR (CDCl3)
d 153.1, 151.0, 136.5,
134.6, 134.4, 129.2, 129.1, 128.9, 128.8, 128.7, 128.6, 128.5, 128.4,
128.0, 124.9, 120.4, 78.4, 31.8, 30.5.
166e172 ꢀC; 1H NMR (CDCl3)
d
8.48e8.50 (d, 2H, Ar0H),7.62e7.65
(t, 1H, Ar0H), 7.52e7.55 (t, 2H, Ar0H), 6.55e7.15 (m, 12H, ArH),
6.26e6.33(m,1H, OCH2CH]CH2), 6.10e6.16 (m,1H, OCH2CH]CH2),
5.86 (s, 1H, ArOH), 5.53e5.57 (d, 1H, OCH2CH]CH2), 5.38e5.41
(d,1H, OCH2CH]CH2), 4.83e4.93 (m, 2H, OCH2CH]CH2), 4.41e4.63
3.4.3. 25,27-Diethoxy-26-benzoyloxy-28-hydroxycalix[4]arene
(20). A slurry of 0.46 g (0.83 mmol) of 1-ethoxy-3-benzoyloxycalix-

C.-H. Kuo et al. / Tetrahedron 67 (2011) 3936e3944
3943
[4]arenes (6), 0.07 g of 60% NaH, and 0.59 g (3.78 mmol) of ethyl
iodide was refluxed in 50 mL of CH3CN for 16 h. The solvent was
removedbyrotoryevaporatoryandtheorganicmaterialsweretaken
up by 30 mL of CHCl3. The organic solution was washed in sequence
with 20 mL of 1N HCl and 100 mL of distillated water. The organic
solvent was then concentrated and slow recrystallized from CHCl3
and CH3OH to afford 0.05 g (10%) of colorless crystals 20: mp
of CHCl3. The organic solution was washed with 100 mL of distillated
water, and the solvent was removed to leave a pale yellow solid.
The pale yellow solid material was then refluxed with 2.00 g of
25% NaOH in a mixture of 10 mL of C2H5OH and 30 mL of THF for
24 h to remove the benzoate moieties. The solvent was removed
and the organic materials were taken up with 50 mL of CHCl3. The
organic solution was washed with 20 mL of 1N HCl and 100 mL of
distillated water, and the organic solvent was removed to leave
a colorless solid. Chromatographic separation, following by re-
crystallization from CHCl3 and CH3OH yielded the corresponding
hydrolysis products 22e24.
258e260 ꢀC; 1H NMR (CDCl3) 8.91e8.93 (d, 2H, Ar0H), 7.63e7.66 (t,
d
1H, Ar0H), 7.58e7.61 (t, 2H, Ar0H), 7.41 (s, 1H, ArOH), 6.57e7.27 (m,
12H, ArH), 4.28e4.32 (d, J¼13.2 Hz, 2H, ArCH2Ar), 4.17e4.20
(d, J¼12.8 Hz, 2H, OCH2CH3), 3.61e3.63(m, 4H, OCH2CH3), 3.34e3.37
(d, J¼12.8 Hz, 4H, ArCH2Ar), 0.82e0.85 (t, J¼7.2 Hz, 6H, OCH2CH3);
13C NMR (CDCl3)
d
167.4,153.4,152.9,146.8,135.6,133.3,133.1,132.9,
3.5.1. 25,26-Diethoxy-27,28-dihydroxycalix[4]arene (22) by chro-
matographic separation. An amount of 0.49 g of etherification crude
products was collected from 0.54 g (0.97 mmol) of compound 6.
Chromatographic separation (eluent: EtOAc/n-hexane＝1:15) of
the crude product afforded 0.12 g (26%) of colorless crystals in
second fraction which was shown to be identical to the previous
known 1,3-diethoxycalix[4]arene. An amount of 0.06 g (13%) of
colorless fine crystals was collected in the third section. The melt-
ing point and the spectral feature of the colorless crystals were
identical to the previous prepared product 22.
132.8,129.5,128.7,128.5,128.4,128.2,128.1,127.9,126.1,124.0,118.7,
72.0, 31.2, 30.4, 14.9; FAB-MS m/e: 584 (Mþ); HRMS (FAB) m/e: calcd
for C39H36O5: 584.2563; found: 584.2553.
3.4.4. 25,26-Diethoxy-27-benzoyloxy-28-hydroxycalix[4]arene
(21). The mother solution of the pervious recrystallization pro-
cedure was concentrated to leave a pale yellow solid material.
Chromatographic separation (eluent: EtOAc/n-hexane＝1：7) fol-
lowing by recrystallization from CHCl3 and CH3OH afforded 0.10 g
(20.5%) of colorless crystals 21: mp 196e200 ꢀC; 1H NMR (CDCl3)
d
8.48e8.50 (d, 2H, Ar0H), 7.63e7.66 (t, 1H, Ar0H), 7.52e7.56 (t, 2H,
3.5.2. 25,26-Dipropoxy-27,28-dihydroxycalix[4]arene (23) by chro-
matographic separation. An amount of 0.49 g of etherification crude
products was collected from 0.50 g (0.88 mmol) of compound 7.
Chromatographic separation (eluent: EtOAc/n-hexane＝1：20) of
the crude product afforded 0.10 g (22%) of colorless crystals in
second fraction which was shown to be identical to the previous
known 1,3-dipropoxycalix[4]arene. An amount of 0.07 g (15.5%) of
off-white crystals was collected as compound 23: mp 197e198 ꢀC;
Ar0H), 7.24 (s, 1H, ArOH), 6.52e7.17 (m, 12H, ArH), 4.42e4.45
(d, J¼13.2 Hz, 1H, ArCH2Ar), 4.22e4.27 (2d, 2H, ArCH2Ar), 4.08e4.11
(d, J¼13.6 Hz, 1H, ArCH2Ar), 3.95e4.06 (m, 4H, OCH2CH3),
3.41e3.45 (d, J¼13.6 Hz, 1H, ArCH2Ar), 3.31e3.35 (d, J¼13.6 Hz, 1H,
ArCH2Ar), 3.24e3.28 (2d, 2H, ArCH2Ar), 1.59e1.62 (t, J¼7.0 Hz, 3H,
OCH2CH3), 1.36e1.39 (t, J¼7.2 Hz, 3H, OCH2CH3); 13C NMR (CDCl3)
d
166.1, 155.9, 153.3, 152.9, 146.1, 136.7, 136.4, 134.3, 133.4, 133.1,
132.8, 132.1, 131.3, 130.6, 130.0, 129.4, 129.3, 129.2, 129.0, 128.8,
128.7, 128.5, 128.4, 127.7, 127.5, 124.9, 124.4, 123.3, 119.6, 71.8, 69.8,
31.5, 31.4, 31.2, 30.8, 15.6, 15.5; FAB-MS m/e: 585 (Mþþ1); HRMS
(FAB) m/e: calcd for C39H36O5þHþ: 585.2641; found: 585.2651.
1H NMR (CDCl3)
d
8.96 (s, 2H, ArOH), 7.02e7.04 (d, J¼7.6 Hz, 2H,
ArH), 6.93e6.98 (m, 6H, ArH), 6.74e6.78 (t, J¼7.6 Hz, 2H, ArH),
6.58e6.62 (t, J¼7.6 Hz, 2H, ArH), 4.52e4.55 (d, J¼12.0 Hz, 1H,
ArCH2Ar), 4.31e4.35 (d, J¼13.2 Hz, 3H, ArCH2Ar), 4.05e4.11 (m, 2H,
OCH2CH2CH3), 3.85e3.92 (m, 2H, OCH2CH2CH3), 3.33e42 (3d, 4H,
ArCH2Ar), 2.12e2.18 (m, 4H, OCH2CH2CH3), 1.15e1.19 (t, J¼7.4 Hz,
3.4.5. 25,26-Diethoxy-27,28-dihydroxycalix[4]arene (22) by re-
crystallization. The mother solution of the recrystallization pro-
cedure for compound 20 was concentrated to leave a pale yellow
solid material. The solid material was then refluxed with 2.00 g of
25% NaOH in a mixture of 10 mL of C2H5OH and 30 mL of THF for 24 h.
The solvent was removed and the organic materials were dissolved
in 50 mLof CHCl3. The solutionwas washed with 20 mLof 1NHCl and
100 mL of distillated water, and the organic solvent was then re-
moved to leave a colorless solid. Recrystallization from CHCl3 and
CH3OH precipitated a mixtureof rod-like crystals and powder solids.
The rod-like crystals were collected and recrystallized from CHCl3
and CH3OH to give 0.11 g (27.5%) of colorless crystals 22: mp
6H, OCH2CH2CH3); 13C NMR (CDCl3)
d 153.4, 151.2, 134.6, 134.1,
129.4, 129.1, 129.0, 128.8, 128.7, 128.0, 124.7, 120.1, 78.3, 31.9, 31.8,
29.9, 23.2, 10.3; FAB-MS m/e: 509 (Mþþ1); HRMS (FAB) m/e: calcd
for C34H36O4þHþ: 509.2692; found: 509.2687.
3.5.3. 25,26-Dibutoxy-27,28-dihydroxycalix[4]arene (24) by chro-
matographic separation. An amount of 0.58 g of etherification crude
products was collected from 0.50 g (0.86 mmol) of compound 8.
Chromatographic separation (eluent: EtOAc/n-hexane＝1:20) of the
crude product afforded 0.07 g (15%) of colorless crystals in second
fraction which was shown to be identical to the previous known 1,3-
dibutoxycalix[4]arene. An amount of 0.05 g (10.5%) of colorless fine
crystals was collected as compound 24: mp 168e170 ꢀC; 1H NMR
185e190 ꢀC; 1H NMR (CDCl3)
d 8.86 (s, 2H, ArOH), 6.59e7.04 (m,12H,
ArH), 4.50e4.53 (d, J¼12.4 Hz,1H, ArCH2Ar), 4.35e4.38(d, J¼13.2Hz,
1H, ArCH2Ar), 4.31e4.34 (d, J¼12.8 Hz, 2H, ArCH2Ar), 4.19e4.23
(m, 2H OCH2CH3), 4.04e4.10 (m, 2H, OCH2CH3), 3.37e3.42 (d,
J¼13.2 Hz, 2H, ArCH2Ar), 3.34e3.38 (d, J¼12.8 Hz, 2H, ArCH2Ar),
(CDCl3)
d
8.92 (s, 2H, ArOH), 7.02e7.04(d, J¼7.6 Hz, 2H, ArH), 6.95e6.96
(m, 6H, ArH), 6.74e6.78 (t, J¼7.6 Hz, 2H, ArH), 6.58e6.62 (t, J¼7.6 Hz, 2H,
ArH), 4.51e4.54 (d, J¼12.4 Hz, 1H, ArCH2Ar), 4.33e4.36 (d, J¼13.2 Hz,
1H, ArCH2Ar), 4.31e4.34 (d, J¼12.8 Hz, 2H, ArCH2Ar), 4.07e4.13 (m, 2H,
OCH2CH2CH2CH3), 3.90e3.96 (m, 2H, OCH2CH2CH2CH3), 3.26e3.42
(3d, 4H, ArCH2Ar), 2.09e2.15 (m, 4H, OCH2CH2CH2CH3), 1.56e1.64 (m,
1.68e1.72 (t, J¼13.2 Hz, 6H, OCH2CH3); 13C NMR (CDCl3)
d 153.2,
151.2, 134.7, 134.3, 129.4, 129.3, 129.1, 128.7, 128.0, 124.8, 120.6, 71.8,
31.9, 31.8, 30.2, 15.5; FAB-MS m/e: 480 (Mþ); HRMS (FAB) m/e: calcd
for C32H32O4: 480.2301; found: 480.2293.
4H, OCH2CH2CH2CH3),1.07e1.11 (t, J¼7.2 Hz, 6H, OCH2CH2CH2CH3); 13
C
NMR (CDCl3)d152.6,150.34,134.1,133.6,128.9,128.6,128.3,127.5,124.3,
120.2, 33.1, 33.0, 32.9, 31.1, 20.5, 15.5; FAB-MS m/e: 536 (Mþ); HRMS
(FAB) m/e: calcd for C36H40O4: 536.2927; found: 536.2914.
3.5. General procedure for 1,2-dialkoxycalix[4]arene 22e24
by chromatographic separation
Acknowledgements
A slurry of approximate 0.50 g of 1-alkoxy-3-benzoyloxycalix[4]-
arenes 6e8, 0.05 g of 60% NaH, and 4 mol equiv of alkyl halides was
refluxed in 50 mL of CH3CN for 14 h. The solvent was removed by
rotory evaporatory and the organic materials were taken up by 30 mL
We thank Ms. L.-M. Hsu of NSC Instrumental Center in Taichung
for taking all the FAB-MS measurements. Financial support of this
work from the National Science Council of the Republic of China

3944
C.-H. Kuo et al. / Tetrahedron 67 (2011) 3936e3944
5. (a) Iwamoto, K.; Araki, K.; Shinkai, S. J. Org. Chem. 1991, 56, 4955; (b) Iwamoto,
K.; Araki, K.; Shinkai, S. Tetrahedron 1991, 47, 4325; (c) Pappalardo, S.; Giunta, L.;
Foti, M.; Ferguson, G.; Gallagher, J. F.; Kaitner, B. J. Org. Chem. 1992, 57, 2611; (d)
Iwamoto, K.; Shimizu, H.; Araki, K.; Shinkai, S. J. Am. Chem. Soc. 1993, 115, 3997;
(e) Ferguson, G.; Gallagher, J. F.; Giunta, L.; Neri, P.; Pappalardo, S. J. Org. Chem.
1994, 59, 42; (f) Ho, Z.-C.; Ku, M.-C.; Shu, C.-M.; Lin, L.-G. Tetrahedron 1996, 52,
13189.
(Grant NSC-94-2113-M034-002 and NSC-97-2113-M034-001) is
gratefully acknowledged.
Supplementary data
Copies of 1H and 13C NMR spectra of compounds 1e24 are
available. Supplementary data associated with this article can be
found in online version at doi:10.1016/j.tet.2011.03.048. These data
include MOL files and InChIKeys of the most important compounds
described in this article.
6. The part I of this series, and references therein.
7. Shu, C.-M.; Liu, W.-C.; Ku, M.-C.; Tang, F.-S.; Yeh, M.-L.; Lin, L.-G. J. Org. Chem.
1994, 59, 3730.
ꢀ
8. Jaime, C.; de Mendoza, J.; Prados, P.; Nieto, P. M.; Sanchez,C.J. Org. Chem.1991,56,3372.
9. Shu, C.-M.; Yuan, T.-S.; Ku, M.-C.; Ho, Z.-C.; Liu, W.-C.; Tang, F.-S.; Lin, L.-G.
Tetrahedron 1996, 52, 9805.
10. Narumi, F.; Hattori, T.; Morohashi, N.; Matsumura, N.; Yamabuki, W.; Ka-
meyama, H.; Miyan, S. Org. Biomol. Chem. 2004, 2, 890.
11. The conformational assignment is based on the relative position of the phenolic
O-substitutents. Due to the ‘through-the-annulus’ free rotation of the phenolic
hydroxy groups, the relative position of the free phenolic OH moieties are not
assigned.
References and notes
1. (a) Gutache, C. D.; Dhawan, B.; Levine, J. A.; No, K. H.; Bauer, L. J. Tetrahedron
1983, 39, 409; (b) Gutache, C. D.; Levine, J. A. J. Am. Chem. Soc. 1982, 104, 2652.
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D.; Arduini, A.; Coppi, L.; Verboom, W.; Pochini, A.; Ungaro, R.; Harkema, S.;
Reinhoudt, D. N. J. Org. Chem. 1990, 55, 5639.
12. All reagents were obtained from Commercial Chemical Companies and used
without further purification. Melting points were taken in capillary tubes on
a
Mel-Temp apparatus (Laboratory Devices, Cambridge, MA) and are un-
corrected. 1H NMR spectra are recorded on Varian 400-MR 400 MHz FT NMR
spectrometer and chemical shifts are reported as values in ppm relative to
TMS (
d
3. (a) Shu, C.-M.; Chung, W.-S.; Wu, S.-H.; Ho, Z.-C.; Lin, L.-G. J. Org. Chem. 1999, 64,
€
d
¼0.00). FAB-MS and HRMS (FAB) spectra were taken on a Finnigan/
2673; (b) Groenen, L. C.; Ruel, B. H. M.; Casnati, A.; Verboom, W.; Pochini, A.;
Thermo Quest MAT 95XL spectrometer. Chromatographic separations were
performed with Merck silica gel (230e400 mesh ASTM) on columns of 25 mm
diameter filled to height of 150 mm. TLC analyses were carried out on Ma-
chereyeNagel aluminum back silica gel 60 F254 plates (absorbant thickness 0.
2 mm).
Ungaro, R.; Reinhoudt, D. N. Tetrahedron 1991, 47, 8379; (c) Araki, K.; Iwamoto,
K.; Shinkai, S.; Matsuda, T. Bull. Chem. Soc. Jpn. 1990, 63, 3480; (d) Bottino, F.;
Giunta, L.; Pappalardo, S. J. Org. Chem. 1989, 54, 5407.
4. (a) Gutsche, C. D.; Lin, L.-G. Tetrahedron 1986, 42, 1633; (b) Casnati, A.; Arduini,
A.; Ghidini, E.; Pochini, A.; Ungaro, R. Tetrahedron 1991, 47, 2221.