25,26-Dialkoxycalix[4]arenes. Part 1: 25-Alkoxy-26,27-diacetoxy route

Article abstract of DOI:10.1016/j.tet.2011.03.010

Acetylation of calix[4]arene 1,3-dialkyl ethers yielded the corresponding monoacetates. The ¹H NMR spectral analysis indicated that the products' alkoxy moieties were 'rotation restricted'. Acylation of calix[4]arene monoalkyl ethers with acety

Full text of DOI:10.1016/j.tet.2011.03.010

Tetrahedron 67 (2011) 3238e3247
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25,26-Dialkoxycalix[4]arenes. Part 1: 25-Alkoxy-26,27-diacetoxy route
Fung-Ying Wu, Kai-Fu Chang, Cheng-Han Kuo, Kuan-Chih Chen, Kuo-Chang Lee, Chiun-Shiang Huang,
*
Yung-Sheng Chiang, 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
Acetylation of calix[4]arene 1,3-dialkyl ethers yielded the corresponding monoacetates. The 1H NMR
spectral analysis indicated that the products’ alkoxy moieties were ‘rotation restricted’. Acylation of calix
[4]arene monoalkyl ethers with acetyl chloride yielded monoacetates and/or 2,3-diacetates in different
reaction conditions. A simple recrystallization process was able to isolate 2,3-diacetates in good yield.
The 1H NMR spectra of the diacetylated products indicated that those compounds also possessed the
‘rotation restricted’ alkoxy moieties. In the presence of K2CO3 as reaction base, alkylation of 2,3-diac-
etates produced the acetyl-migrated 1,3-dialkyloxy derivatives. Basic hydrolysis of the acetyl-migrated
compounds yielded the known 1,3-dialkoxycalix[4]arenes. In the presence of NaH as reaction base, 2,3-
diacetates were alkylated with and without the acetyl-migration. For the highly reactive benzyl bromide
and allyl bromide, the majority of alkylation proceeded without acetyl-migration. In the other alkyl
halides, the products were the acetyl-migrated 1,3-dialkoxy derivatives along with less than one-fourth
the amount of non-migrated 1,2-dialkoxy derivatives.
Article history:
Received 29 November 2010
Received in revised form 22 February 2011
Accepted 3 March 2011
Available online 9 March 2011
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
a three-step synthetic procedure for the preparation of 25,26-
dibenzyloxycalix[4]arene and the acetyl-migration phenomena in
Calixarenes1 can be functionalized in either the ‘upper rim’ or
the ‘lower rim’. In the lower rim’s functionalization, the phenolic
hydroxy groups were usually converted into ester or ether moieties.
Among them, the ether derivatives were the most studied subjects,
and the tetra-alkoxy derivatives were the first ‘lower rim’ func-
tionalized calix[4]arenes to be prepared.2 The 1,3-dialkoxy de-
rivatives were later reported by Reinhoudt3 in a one-step process,
whereas, the other alkoxy derivatives, monoalkyl ethers4 and the
trialkyl ethers,2b,5 were all prepared in multi-step procedures. The
calix[4]arene monoalkyl ethers were later found to be achievable in
a single step by applying NaOCH3 and/or K2CO3 as the reacting
base.6,7 However, to this day, the 1,2-dialkoxy derivatives can only
be found in the active alkyl halide cases, e.g., allyl bromide8 and
benzyl bromide,9 or in the tert-butylcalix[4]arene system.10
In this paper, we will report a general synthetic procedure to
convert the monoalkoxy-calix[4]arenes into their corresponding
2,3-diacetate derivatives. Since the only available position for the
further ether linkage was proximal to the existent alkoxy group in
the 2,3-diacetate products, it was reasonable to propose that
etherification of 25-alkoxy-26,27-diacetoxycalix[4]arenes follow-
ing with basic hydrolysis would be able to produce the corre-
sponding 25,26-dialkoxycalix[4]arenes. Therefore, We will report
25-alkoxy-26,27-diacetoxycalix[4]arene systems.
2. Results and discussion
2.1. Acetylation of calix[4]arene 1,3-dialkyl ethers
In our earlier research work on the synthesis of calix[4]arene
trialkyl ethers, we developed a four-step synthetic procedure with
benzoate as a protecting group.5f We had noticed that the alkoxy’s
first methylene hydrogens were always displayed as two sets of
multiples with equal intensity after the introducing of the benzoate
group. Since the benzoate protecting groups were removed at the
final stage of the synthesis, the conformation of the intermediate
was only rationally assigned as ‘up-down-up’11 without any further
pursued at that time. Recently, some interesting results were ob-
served during the search for the possible synthetic pathways for the
calix[4]arene 1,2-dialkyl ethers. Therefore, we decided to in-
vestigate the conformation for all the available acylated calix[4]
arene alkyl ethers.
When calix[4]arene 1,3-dialkyl ethers 1e5 were treated with
less hindered acetyl chloride in pyridine at ice bath temperature
(Scheme 1), the resulting products 6e10 displayed, as their
benzoated counterparts, two sets of multiples with equal intensity
at
d 3.78 and 3.99 for the alkoxy’s first methylene hydrogens.
* Corresponding author. E-mail address: lglin@faculty.pccu.edu.tw (L.-G. Lin).
However, when the products were subjected to 2D COSY spectral
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.03.010

F.-Y. Wu et al. / Tetrahedron 67 (2011) 3238e3247
3239
Scheme 1. Synthetic scheme for 1,3-dialkoxy-2-acetoxycalix[4]arenes 6e10.
measurement, to our surprise, the 2D COSY spectrum (Fig. 1) in-
2.2. Acetylation of calix[4]arene monoalkyl ethers
dicated that the two sets of alkoxy’s first methylene hydrogen
signals actually arose from the protons on the same methylene
moieties. This result indicated that the free rotation on the alkoxy
CeO single bonds had to have ceased in NMR time scale in order for
the creation of two different magnetic environments for the
methylene’s protons, and hence, to display two multiples with
different chemical shifts on the spectrum. Since the acetylated
products possessed a sharp melting point and displayed a single
spot upon TLC analysis, the same ‘up-down-up’ conformers were
assigned to the products 6e10 based on our earlier judgment in the
triallyloxycalix[4]arene system.5f We will demonstrate that, in Part
II of this series, the products 6e10 were properly assigned.
Asin thepreviouslyacetylationcases, whena standard acetylation
reaction condition was applied on calix[4]arene monoalkyl ethers
11e15, no trace of tetra-substituent triacetated products were
detected even with a further increasing of acetylation period and/or
the amount of acetyl chloride. The only isolated products were the
corresponding monoacetates 16e20 and/or 2,3-diacetates 21e25
(Scheme 2). We believed, as in previous systems, that the steric hin-
drance inhibited the introduction of the fourth substituent onto the
tri-substituent calix[4]arenes in the reaction conditions.
In the acetylation of calix[4]arene monoalkyl ethers 11e15, the
monoacetated products 16e20 were isolated in over 40% yield when
the reaction was performed with a small amount of acetyl chloride
for 10 min. Whereas, the 2,3-diacetate products 21e25 could be
afforded in an easier purification process and higher isolation yield
by applying larger amount of acetyl chloride and a longer reaction
period upon calix[4]arene monoalkyl ethers 11e15.
2.3. Spectral analysis of monoalkoxy-calix[4]arene 2,3-
diacetates 21e25
The 1H NMR spectra of the monoacetates 16e20 displayed
a similar spectral pattern as starting materials 11e15 with an extra
sharp singlet at d 2.5 (being a normal chemical shift position for the
acetate’s methyl hydrogen) for the newly introduced acetate moi-
eties. Since only the 3-monoacetate derivates possessed the same
symmetry elements as the starting materials 11e15, therefore, it
was easy to assign the structure of the monoacetates 16e20 as 25-
alkxoy-27-acetoxycalix[4]arenes.
It was known that both the alkoxy and the acetyl groups are able
to hinder the ‘through-the-annulus’ free rotation, and hence, the
introduction of the second acetate moieties will then create a chiral
plane and greatly reduce the symmetry of the 2,3-diacetate prod-
ucts 21e25. In the lack of any symmetry element in those 2,3-
diacetate products, eight sets of doublets for the calixarene’s eight
methylene hydrogens and two sharp singlets (d 2.1 and 1.1) for the
two different acetate moieties were observed. It was interesting to
notice that the second acetate moiety was shifted upfield from their
normal position by approximately 1 ppm, and this strong shielding
effect could only be arisen from the opposite and/or the adjacent
calix[4]arene’s phenolic rings. This observation suggested that in
order to be shielded by calix[4]arene’s aromatic rings the second
acetate moiety had to be anti- to the other ‘lower rim’ substituents.
To verify the spatial relationship between three ‘lower rim’ sub-
stituents, a 2D-NOSEY was taken for compound 21. The spectrum
indicated that the two acetate’s methyl groups were not space rela-
Fig. 1. 2D COSY spectrum of 25-acetoxy-26,28-dipropoxycalix[4]arene (7).
A further study indicated that the 1,3-diacetylated products
were not produced in more severe reaction conditions, e.g., higher
temperature, longer reaction period, and/or larger amounts of
acetyl chloride. It was believed that the steric hindrance of the tri-
substituent calix[4]arenes prohibited the formation of the fourth
‘lower rim’ ester linkage in acidic or weaker basic conditions.
However, in the later section of this paper, we will demonstrate that
the 1,3-diacetylated derivatives could be prepared in a very strange
fashion.
tive, and the ethoxy’s methylene hydrogen interacted only with d 2.1
acetate’s signal. This observation implicated that the compound 21
holds the ‘up-down-up’ arrangement. The chemical shift of the calix
[4]arene’s methylene carbon (at
d 37.9, 37.8, 31.8, and 31.4) also

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F.-Y. Wu et al. / Tetrahedron 67 (2011) 3238e3247
Scheme 2. Synthetic scheme for acetylation of 1-alkoxycalix[4]arenes 11e15.
supported the ‘up-down-up’ structure assignment.12 Based on
those results, the conformation of the compounds 21e25 was
assigned as 25-alkoxy-anti-26-acetoxy-syn-27-acetoxycalix[4]are-
nes. The structure of the compounds 21e25 will be further proven on
the later section of this paper. The spectra of compounds 21e25 also
displayed, as in the previous compounds 6e10, two sets of multiples
for the alkoxy’s first methylene hydrogens (Fig. 2), and a restricted
free rotation of the alkoxy CeO single bond was also proposed to
clarify the existence of two multiples.
arenes 21e25. When compounds 21e25 were refluxed with large
amounts of NaH and alkyl halides in acetonitrile overnight, a stan-
dard procedure for introducing the fourth ether linkage onto the
calix[4]arene,5,6 it was found that all the acetate moieties were
removed and tetraalkoxycalix[4]arenes were the only isolated
products. A conclusion, which was later found to be inappropriate,
was rapidly reached that the strength of the reaction base had to be
reduced in order to keep the acetate moieties unaffected. A weaker
base, K2CO3, was then chosen to replace the NaH in the reaction.
When compounds 21e25 were refluxed with K2CO3 and excess
alkyl halides in acetonitrile, over 50% of the yield of the new
products 26e30 was isolated as colorless crystals (Scheme 3). Not
only the 1H NMR spectra of products 26e30 displayed two acetate’s
sharp singlets, which indicated that the reaction conditions did not
cleave any acetate moieties; but the spectral integral ratio of the
alkoxy’s hydrogen also suggested that the second alkoxy moiety
was present. Even though the splitting pattern of the calix[4]are-
ne’s methylene hydrogens suggested that products 26e30 pos-
sessed a planar symmetry element, which was not totally in
agreement with the 1,2-dialkoxy-3,4-diacetoxy structural ar-
rangement, the products 26e30 were still assigned as 1,2-dialkoxy-
3,4-diacetoxycalix[4]arenes at this stage. The structure assignment
was soon proven to be incorrect when products 26e30 were basic
hydrolyzed.
2.4. Etherification of 1-alkoxy-2,3-diacetoxycalix[4]arenes
with K2CO3
According to our proposed synthetic route, the first step of the
synthesis was etherification of 1-alkoxy-2,3-diacetoxycalix[4]
After the introduction of the second ether linkage, compounds
26e30 were subjected to basic hydrolysis as in our proposed syn-
thetic route. Instead of isolating the expecting 1,2-dialkoxycalix[4]
arenes, it was a surprise to recognize that the hydrolysis products
were the known compounds,3 1,3-dialkoxycalix[4]arenes 31e35.
Since the basic hydrolysis conditions had no effect on the ether
linkage, the hydrolysis products had to be derived from 1,3-dia-
lkoxy-2,4-diacetoxycalix[4]arenes. This result suggested that the
actual structure of products 26e30 were not the expected 1,2-
dialkoxy-3,4-diacetoxycalix[4]arenes, but were the acetyl-mi-
grated 1,3-dialkoxy-2,4-diacetoxycalix[4]arenes, as shown in Fig. 3.
As described in the beginning of this reported, a direct acety-
lation of 1,3-dialkoxycalix[4]arenes was not able to produce the
2,4-diacetated products. However, this acetyl-migrated ether-
ification provided a strange pathway for the preparation of the
tetra-substituent 2,4-diacetated products 26e30 in ‘partial cone’
conformation.
Fig. 2. 2D COSY spectrum of 25,26-diacetoxy-27-propoxy-28-hydroxycalix[4]arene (22).

F.-Y. Wu et al. / Tetrahedron 67 (2011) 3238e3247
3241
Scheme 3. Etherification of 1-alkoxy-2,3-diacetoxycalix[4]arenes 21e25.
CH3
C=O
O
CH2
CH2
CH2
CH2
O
OR
OR
C=O
CH3
migration of "lower rim" acetyl group
26
R = -CH2CH3
27
-CH2CH2CH3
28
-CH2CH2CH2CH3
29
-CH2CH=CH2
30
-CH2Ph
Fig. 3. Conformational structure of acetyl-migrated 1,3-dialkoxy-2,4-diacetoxycalix[4]
arenes 26e30.
2.5. Mechanism for the formation of 1,3-dialkoxy-2,4-
diacetoxycalix[4]arenes 26e30
An acetyl-migration proceeding the ether linkage formation was
essential for the conversion of 1-alkoxy-2,3-diacetoxycalix[4]are-
nes 21e25 into 1,3-dialkoxy-2,4-diacetoxycalix[4]arenes 26e30.
Therefore, we speculated that a cyclic orthoacetate-like anionic
intermediate was present during the etherification reaction, as
shown in Fig. 4. In such a structural configuration, the alkyl halide
substrates would be more favorable to approach the intermediates
from the less hindered 3-position side at the final stage and yielded
the 1,3-dialkoxy products 26e30. Gutsche and his co-worker had
also reported a similar acyl-migrated phenomenon in the calix[4]
arene 1,3-dibenzoate system.13
The 1H NMR spectra of compounds 26e30 indicated that these
etherification products belonged to Cv symmetry point group with
two different acetate groups. A ‘partial cone’ conformation with
Fig. 4. Proposed mechanism for the formation of 1,3-dialkoxy-2,4-diacetoxycalix[4]
arenes.

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F.-Y. Wu et al. / Tetrahedron 67 (2011) 3238e3247
two acetate moieties ‘anti’ to each other was the only reasonable
structure for compounds 26e30. It was known that any sub-
stituents that were larger than the ethyl group would not be able to
rotate through the calix[4]arene’s annulus at room temperature.14
Therefore, the two acetate moieties would also have to be ‘anti’ to
each other in the structure of starting compounds 21e25. This re-
sult was fully agreed with our previous assignment on the structure
of 1-alkoxy-2,3-diacetoxycalix[4]arenes 21e25.
It should be noted that all the isolated acetyl-migrated products
had two alkoxy groups in syn arrangement. The lack of any anti-
isomer suggested that the breaking of cyclic orthoacetate ring and
the formation of ether linkage occurred in a concerted fashion.
2.6. Formation of 1,2-dialkoxy-3,4-diacetoxycalix[4]arenes
It was shown that the K2CO3 reaction conditions failed to yield
the expected 1,2-dialkoxy-3,4-diacetoxycalix[4]arenes, and there-
fore, the direction of the reaction condition adjustment had to shift
to the quantity of NaH and reaction periods. After a few trials on the
amount of NaH and reaction times, it was found that a refluxing
with 1.5 M equiv of NaH and excess alkyl halides in acetonitrile for
14 h was able to introduce the second alkoxy group onto the desired
2-position and yielded the corresponding 1,2-dialkoxy-3,4-diac-
etoxycalix[4]arenes (Scheme 4).
When compounds 21e25 were etherified in the modified reaction
conditions, two isomeric dialkoxy derivatives were afforded in vari-
ous amounts. The 1H NMR spectra of these reaction crude products all
displayed two pairs of the acetate’s singlets. It was shown previously
that the 1,3-dialkoxy products 26e30 displayed two sharp singlets at
d
1.5 and 1.9 for the acetate moieties. It was therefore reasonable to
assume thatthe otherpairof signalsat 1.2and 1.5arosefromthe1,2-
d
dialkoxy products. The integral ratio of those acetate’s signals also
provided an adequate information to estimate the composition of the
crude product. In the two active alkyl halide cases, the allyl bromide
and benzyl bromide, the crude products contained approximately a 3
to 1 ratio of 1,2-dialkoxy products and 1,3-dialkoxy products, re-
spectively. Inthe cases ofotherlessreactivealkyl halides, the opposite
results were observed, i.e., the 1,3-dialkoxy products 26e28 were
afforded in approximately 75% and the amount of the desired 1,2-
alkyloxy products 36e38 was less than one-fourth.
We speculated that after the weak base, K2CO3, neutralized the
calix[4]arene’s phenolic hydroxy moieties into an anion form, the
resulting weak nucleophile could only attack the adjacent acetate
group and produced the cyclic intermediate. Whereas, the stronger
base, NaH, was able to convert the calix[4]arene into a better nu-
cleophile, and hence, increased the rate of the ether formation. As
the composition of the crude products might suggest, the rate of the
ether formation ke was approximately three times faster than the
rateof the cyclic intermediateformation kc in the cases of activealkyl
halides. However, the reaction rate seemed to be reversed in the less
reactive alkyl halide cases, and the production of the desired 1,2-
dialkoxy products was less than one-quarter. The productive yield,
not the isolating yield, of less than 25% clearly indicated that the
proposed synthetic route was not acceptable for the preparation of
Scheme 4. Synthetic scheme for 1,2-dialkoxy-3,4-diacetoxycalix[4]arenes 36e40.
were always crystallized together and the isolation of product 39
was not achieved. Fortunately, a new approach that will be illus-
trated in Part II of this series eliminated the necessity of the chro-
matographic separation.
2.7. Basic hydrolysis of 1,2-dibenzyloxy-3,4-diacetoxycalix[4]
arenes
1,2-dialkoxycalix[4]arenes. Therefore,
a
new approach was
developed and will be illustrated in Part II of this series.
For the allyl bromide and benzyl bromide cases, the crude
products contained approximately three quarters of the desired
1,2-dialkoxy products 39 and 40. Hence, the recrystallization pro-
cess was applied to purify the desired products. During the re-
crystallization process, it was noticed that the more symmetrical
1,3-dialkoxy side products were always crystallized first. In the
benzyl bromide case, the 1,3-dibenzyloxy product 30 was crystal-
lized as the first crop, and further concentrations of the mother
solution yielded 1,2-dibenzyloxy-3,4-diacetoxycalix[4]arene 40. In
the allyl bromide case, the two diallyloxy isomeric pairs 29 and 39
After the isolation of 1,2-dibenzyloxy 40 was achieved, product
40 was subjected to basic hydrolysis to remove the ‘lower rim’
acetate protecting groups as shown in Scheme 5.
The hydrolysis product, syn-1,2-dibenzyloxycalix[4]arene (41),
also possessed a symmetrical plane as its isomeric 1,3-dibenzyloxy
countpart 35. However, the symmetrical plane bisected the two
isomeric dibenzyloxy compounds differently, and the 1H NMR
spectrum of 1,2-dibenzyloxy 41 was expected to be very different
from its isomeric 1,3-dibenzyloxy countpart 35. The 1H NMR
spectrum of the syn-1,3-dibenzyloxycalix[4]arene 35 displayed one

F.-Y. Wu et al. / Tetrahedron 67 (2011) 3238e3247
3243
was then added dropwisely at room temperature. The reaction
mixtureswerestirredfor 24 h, andthesolventwasremovedbyrotory
evaporatorytoleaveanoilyresidue. Theorganicmaterialsweretaken
up by 50 mL of CHCl3, and washed with 20 mL of 1 N HCl twice
followed with 100 mL of saturated NaHCO3 solution and 100 mL of
distillated water. The organic solvent was removed to leave a pale
yellow solid. Chromatographic separation (eluent: EtOAc/n-hexane
＝1:4), following by recrystallization from CHCl3 and CH3OH yielded
the corresponding monoacetylated products 6e10.
3.1.1. 25-Acetoxy-26,28-diethoxycalix[4]arene (6). An amount of
0.24 g (13%) of colorless fine crystals was collected from 1.68 g
(3.50 mmol) of calix[4]arene diethyl ether 1: mp 230e231 ꢀC; 1H
NMR (CDCl3)
d
7.28 (d, J¼7.6 Hz, 2H, ArH), 7.21 (s, 1H, ArOH), 7.16 (t,
J¼7.6 Hz, 1H, ArH), 7.07 (d, J¼7.5 Hz, 2H, ArH), 6.90 (d, J¼7.5 Hz, 2H,
ArH), 6.82 (d, J¼6.6 Hz, 2H, ArH), 6.73 (t, J¼7.5 Hz, 2H, ArH), 6.69 (t,
J¼7.5 Hz, 1H, ArH), 4.10 (d, J¼13.1 Hz, 2H, ArCH2Ar), 3.97e4.01 (m,
2H, OCH2CH3), 3.94 (d, J¼15.7 Hz, 2H, ArCH2Ar), 3.74e3.82 (m, 2H,
OCH2CH3), 3.64 (d, J¼15.7 Hz, 2H, ArCH2Ar), 3.28 (d, J¼13.2 Hz, 2H,
ArCH2Ar), 1.34 (s, 3H, COCH3), 1.27 (t, J¼7 Hz, 6H, OCH2CH3); 13C
NMR (CDCl3)
d 168.7, 154.4, 153.1, 148.1, 134.1, 133.0, 132.9, 132.8,
129.6, 129.5, 129.0, 128.7, 128.5, 128.1, 127.6, 124.9, 123.5, 118.8, 69.2,
37.9, 31.2, 20.4, 15.1; FAB-MS m/e: 522 (Mþ); HRMS (FAB) m/e: calcd
for C34H34O5: 522.2406; found: 522.2394.
Scheme 5. Synthetic scheme for 1,2-dibenzyloxycalix[4]arene 41.
3.1.2. 25-Acetoxy-26,28-dipropoxycalix[4]arene (7). An amount of
0.22 g (11%) of colorless fine crystals was collected from 1.79 g
(3.52 mmol) of calix[4]arene dipropyl ether 2: mp 238e239 ꢀC; 1H
pair of doublets for the calix[4]arene’s methylene hydrogen and
one sharp singlet for the benzyloxy’s methylene hydrogen.
Whereas, the 1H NMR spectrum of syn-1,2-dibenzyloxycalix[4]
arene displayed (as shown in Fig. 5) three pairs of doublets with an
integral ratio of 1:1:2 for the same calix[4]arene’s methylene hy-
drogen. The benzyloxy’s methylene hydrogens, which experienced
a different magnetic environment, also emerged as a predictive pair
of doublets. The FAB-MS provided a strong support for the existing
of the two benzyloxy moieties of the compound 41. An alternate
synthetic approach for the preparation of 1,2-dibenzyloxycalix[4]
arene (41) will also be described in Part II of this series.
NMR (CDCl3)
d
7.43 (s, 1H, ArOH), 7.26 (d, J¼7.6 Hz, 2H, ArH), 7.14 (t,
J¼7.6 Hz, 1H, ArH), 7.08 (d, J¼7.5 Hz, 2H, ArH), 6.93 (d, J¼7.6 Hz, 2H,
ArH), 6.82 (d, J¼6.4 Hz, 2H, ArH), 6.75 (t, J¼7.5 Hz, 2H, ArH), 6.69 (t,
J¼7.4 Hz, 1H, ArH), 4.12 (d, J¼13.2 Hz, 2H, ArCH2Ar), 3.90e3.98 (m,
4H, ArCH2Ar and OCH2CH2CH3), 3.58e3.69 (m, 4H, ArCH2Ar and
OCH2CH2CH3), 3.28 (d, J¼13.2 Hz, 2H, ArCH2Ar), 1.65e1.74 (m, 4H,
OCH2CH2CH3), 1.20 (s, 3H, COCH3), 0.94 (t, J¼7.4 Hz, 6H,
OCH2CH2CH3); 13C NMR (CDCl3)
d 168.8, 154.6, 153.4, 148.0, 133.9,
133.0,132.8,129.6,129.5,128.6,128.3,128.0,125.0,123.5,118.6, 75.1,
37.9, 31.2, 23.2, 20.3, 10.5.
3. Experimental15
3.1.3. 25-Acetoxy-26,28-dibutoxycalix[4]arene (8). An amount of
0.36 g (17.5%) of colorless fine crystals was collected from 1.87 g
(3.49mmol)ofcalix[4]arenedibutylether3: mp 194e195 ꢀC;1HNMR
3.1. General procedure for the monoacetylation of calix[4]
arene dialkyl ethers
(CDCl3)
d
7.43 (s,1H, ArOH), 7.26(d, J¼7.6Hz, 2H, ArH), 7.14(t, J¼7.8 Hz,
1H, ArH), 7.07(d, J¼7.2Hz,2H, ArH),6.92(d, J¼7.6Hz, 2H, ArH),6.82(d,
J¼7.2 Hz, 2H, ArH), 6.73 (t, J¼7.8 Hz, 2H, ArH), 6.69 (t, J¼7.4 Hz, 1H,
ArH), 4.11 (d, J¼13.2 Hz, 2H, ArCH2Ar), 3.92e3.98 (m, 4H, ArCH2Ar
A slurry of approximate 3.50 mmol of calix[4]arene dialkyl ethers
1e5 was dissolved in 20 mL of pyridine, and 5.0 mL of acetyl chloride
Fig. 5. The 1H NMR spectrum of the syn-1,2-dibenzyloxycalix[4]arene 41.

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F.-Y. Wu et al. / Tetrahedron 67 (2011) 3238e3247
and OCH2CH2CH2CH3), 3.62e3.69 (m, 4H, ArCH2Ar and
OCH2CH2CH2CH3), 3.28 (d, J¼13.2 Hz, 2H, ArCH2Ar), 1.57e1.75 (2m,
4H, OCH2CH2CH2CH3), 1.35e1.48 (m, 4H, OCH2CH2CH2CH3), 1.22 (s,
3H, COCH3), 0.95 (t, J¼7.2 Hz, 6H, OCH2CH2CH2CH3); 13C NMR (CDCl3)
collected from 0.50 g (1.07 mmol) of calix[4]arene monopropyl
ether 12: mp 282e284 ꢀC; 1H NMR (CDCl3)
6.98e7.19 (m, 6H, ArH
d
and ArOH), 6.85e6.88 (d, J¼7.6 Hz, 2H, ArH), 6.77e6.80 (d, J¼7.6 Hz,
2H, ArH), 6.61e6.80 (m, 4H, ArH), 4.06e4.10 (d, J¼13.6 Hz, 2H,
ArCH2Ar), 3.94e4.01 (m, 4, ArCH2Ar and OCH2CH2CH3), 3.40e3.44
(d, J¼13.6 Hz, 2H, ArCH2Ar), 3.30e3.34 (d, J¼13.6 Hz, 2H, ArCH2Ar),
2.45 (s, 3H, COCH3), 2.00e2.06 (m, 2H, OCH2CH2CH3), 1.21e1.25 (t,
d
168.8, 154.6, 153.4, 148.0, 133.9, 133.0, 132.8, 129.6, 129.5, 128.6,
128.3, 128.0, 124.9, 123.5, 118.7, 73.4, 37.9, 32.0, 31.2, 20.3, 19.2, 14.1.
3.1.4. 25-Acetoxy-26,28-diallyloxycalix[4]arene (9). An amount of
0.30 g (15.5%) of colorless fine crystals was collected from 1.76 g
(3.49 mmol) of calix[4]arene diallyl ether 4: mp 218e219 ꢀC; 1H NMR
J¼7.4 Hz, OCH2CH2CH3); 13C NMR (CDCl3)
d 169.6, 152.8, 151.2,
144.9, 133.0, 132.4, 129.4, 128.7, 128.6, 128.5, 127.2, 126.2, 126.0,
119.6, 31.81, 31.7, 23.3, 21.7, 10.6; FAB-MS m/e: 508 (Mþ); HRMS
(FAB) m/e: calcd for C33H32O5: 508.2250; found: 508.2263.
(CDCl3)
d
7.25 (d, J¼6.9 Hz, 2H, ArH), 7.13 (s,1H, ArOH), 7.10 (t, J¼7.9 Hz,
1H, ArH), 7.07(d, J¼7.5Hz,2H, ArH),6.92(d,J¼7.0Hz, 2H, ArH), 6.84(d,
J¼7.2 Hz, 2H, ArH), 6.76 (t, J¼7.5 Hz, 2H, ArH), 6.69 (t, J¼7.5 Hz, 1H,
ArH), 5.92e5.99 (m, 1H, OCH2CH]CH2), 5.26 (dd, J¼17.2, 1.6 Hz, 2H,
OCH2CH]CH2), 5.18 (dd, J¼10.6, 1.3 Hz, 2H, OCH2CH]CH2),
4.47e4.50 (m, 2H, OCH2CH]CH2), 4.22 (dd, J¼5.3, 12.9 Hz, 2H,
OCH2CH]CH2), 4.08 (d, J¼13.2 Hz, 2H, ArCH2Ar), 3.94 (d, J¼15.6 Hz,
2H, ArCH2Ar), 3.66 (d, J¼15.7 Hz, 2H, ArCH2Ar), 3.27 (d, J¼13.2 Hz, 2H,
3.2.3. 25-Acetoxy-27-butoxy-26,28-dihydroxycalix[4]arene (18). An
amount of 0.25 g (46%) of colorless fine crystals was collected from
0.50 g (1.04 mmol) of calix[4]arene monobutyl ether 13: mp
262e264 ꢀC; 1H NMR (CDCl3)
d 7.08e7.20 (m, 6H, ArH and ArOH),
6.90e6.92 (d, J¼7.6 Hz, 2H, ArH), 6.83e6.86 (d, J¼7.6 Hz, 2H, ArH),
6.68e6.78 (m, 4H, ArH), 4.04e4.18 (m, 6H, ArCH2Ar and
OCH2CH2CH2CH3), 3.49e3.53 (d, J¼13.6 Hz, 2H, ArCH2Ar), 3.39e3.43
(d, J¼13.6 Hz, 2H, ArCH2Ar), 2.54 (s, 3H, COCH3), 2.06e2.08 (m, 2H,
OCH2CH2CH2CH3), 1.80e1.82 (m, 2H, OCH2CH2CH2CH3), 1.10e1.15 (t,
ArCH2Ar), 1.41 (s, 3H, COCH3); 13C NMR (CDCl3)
d 168.7, 154.1, 153.2,
147.9, 134.0, 132.9, 132.8, 130.0, 129.6, 128.7, 128.1, 128.0, 125.1, 123.7,
118.7, 117.2, 73.9, 37.8, 31.1, 20.5; FAB-MS m/e: 546 (Mþ).
J¼7.3 Hz, OCH2CH2CH2CH3); 13C NMR (CDCl3)
d 169.5, 152.8, 151.1,
3.1.5. 25-Acetoxy-26,28-dibenzyloxycalix[4]arene (10). An amount
of 0.28 g (14.5%) of colorless fine crystals was collected from 1.81 g
(3.14 mmol) of calix[4]arene dibenzyl ether 5: mp 205e206 ꢀC; 1H
144.9, 132.9, 132.3, 129.4, 128.7, 128.6, 128.5, 127.1, 126.2, 125.9, 119.5,
32.1, 31.8, 31.7, 20.6, 19.3, 14.0; FAB-MS m/e: 522 (Mþ); HRMS (FAB)
m/e: calcd for C34H34O5: 522.2406; found: 522.2410.
NMR (CDCl3)
d
7.25e7.35 (m, 10H, Ar0H), 7.09 (s, 1H, ArOH), 7.04 (d,
J¼7.4 Hz, 4H, ArH), 6.94 (d, J¼7.5 Hz, 2H, ArH), 6.88 (d, J¼6.5 Hz, 2H,
ArH), 6.84 (t, J¼7.6 Hz, 1H, ArH), 6.79 (t, J¼7.5 Hz, 2H, ArH), 6.67 (t,
J¼7.4 Hz,1H, ArH), 5.08 (d, J¼12 Hz, 2H, ArOCH2Ar0), 4.78 (d, J¼12.0 Hz,
2H, ArOCH2Ar0), 4.04 (d, J¼13.2 Hz, 2H, ArCH2Ar), 3.92 (d, J¼15.5 Hz,
2H, ArCH2Ar), 3.67 (d, J¼15.5 Hz, 2H, ArCH2Ar), 3.21 (d, J¼13.3 Hz, 2H,
3.2.4. 25-Acetoxy-27-allyloxy-26,28-dihydroxycalix[4]arene
(19). An amount of 0.22 g (40%) of colorless fine crystals was col-
lected from 0.50 g (1.08 mmol) of calix[4]arene monoallyl ether 14:
mp 222e224 ꢀC; 1H NMR (CDCl3)
d 7.08e7.18 (m, 6H, ArH and
ArOH), 6.91e6.93 (d, J¼7.6 Hz, 2H, ArH), 6.84e6.86 (d, J¼7.6 Hz, 2H,
ArH), 6.70e6.79 (m, 4H, ArH), 6.15e6.35 (m, 1H, OCH2CH]CH2),
5.69e5.74 (dd, 1H, OCH2CH]CH2), 5.43e5.46 (dd, 1H, OCH2CH]
CH2), 4.55e4.60 (m, 2H, OCH2CH]CH2), 4.15e4.18 (d, J¼13.6 Hz,
2H, ArCH2Ar), 3.95e4.03 (d, J¼13.6 Hz, 2H, ArCH2Ar), 3.47e4.50 (d,
J¼13.6 Hz, 2H, ArCH2Ar), 3.38e3.42 (d, J¼13.6 Hz, 2H, ArCH2Ar),
ArCH2Ar), 1.44 (s, 3H, COCH3); 13C NMR (CDCl3)
d 168.7, 154.4, 153.4,
147.9, 137.0, 133.9, 133.0, 132.9, 129.9, 129.8, 128.8, 128.3, 128.1, 127.9,
127.6, 127.2, 127.1, 125.1, 123.9, 118.6, 75.2, 37.9, 31.1, 20.6; FAB-MS m/e:
646 (Mþ); HRMS (FAB) m/e: calcd for C44H38O5: 646.2720; found:
646.2730.
2.53 (s, 3H, COCH3); 13C NMR (CDCl3)
d 169.5, 152.7, 151.1, 144.9,
3.2. General procedure for the monoacetylation of calix[4]
arene monoalkyl ethers
133.0, 132.4, 132.1, 129.4, 128.8, 128.7, 128.6, 128.5, 127.4, 126.3,
126.0, 119.6, 118.7, 31.9, 31.8, 20.8; FAB-MS m/e: 506 (Mþ); HRMS
(FAB) m/e: calcd for C33H30O5: 506.2093; found: 506.2094.
A slurry of 0.50 g of calix[4]arene monoalkyl ethers 11e15 was
dissolved in 10 mL of pyridine, and 0.2 mL of acetyl chloride was then
added dropwisely at ice bath temperature. The reaction mixtures
were stirred for 10 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 1 N HCl twice fol-
lowed with 100 mL of saturated NaHCO3 solution and 100 mL of dis-
tillated water. Theorganic solvent was then removed from the organic
portion to leave an off white residue. Recrystallized from CHCl3 and
CH3OH yielded the corresponding monoacetylated products 16e10.
3.2.5. 25-Acetoxy-27-benzyloxy-26,28-dihydroxycalix[4]arene
(20). An amount of 0.24 g (44%) of colorless fine crystals was col-
lected from 0.50 g (0.97 mmol) of calix[4]arene monobenzyl ether
15: mp 264e266 ꢀC; 1H NMR (CDCl3)
d
7.67e7.70 (m, 2H, Ar0H),
7.38e7.5 (m, 3H, Ar0H), 7.05e7.12 (m, 6H, ArH and ArOH), 6.95e6.98
(d, J¼7.6 Hz, 2H, ArH), 6.86e6.88 (d, J¼7.6 Hz, 2H, ArH), 6.65e6.85
(m, 4H, ArH), 5.09 (s, 2H, OCH2Ar0), 4.21e4.25 (d, J¼13.6 Hz, 2H,
ArCH2Ar), 4.21e4.25 (d, J¼13.6 Hz, 2H, ArCH2Ar), 3.92e3.96 (d,
J¼13.2 Hz, 2H, ArCH2Ar), 3.45e3.49 (d, J¼12.4 Hz, 2H, ArCH2Ar),
3.35e3.89 (d, J¼13.2 Hz, 2H, ArCH2Ar), 2.36 (s, 3H, COCH3); 13C
3.2.1. 25-Acetoxy-27-ethoxy-26,28-dihydroxycalix[4]arene (16). An
amount of 0.28 g (51%) of colorless fine crystals was collected from
0.50 g (1.11 mmol) of calix[4]arene monoethyl ether 11: mp
NMR (CDCl3) d 169.3, 152.7, 151.1, 144.6, 135.8, 133.2, 132.4, 129.5,
128.8, 128.7, 128.5, 128.4, 128.2, 127.5, 126.5, 126.2, 119.7, 78.7, 31.9,
31.8, 20.56; FAB-MS m/e: 557 (Mþþ1); HRMS (FAB) m/e: calcd for
C37H32O5þHþ: 557.2328; found: 557.2321.
241e243 ꢀC; 1H NMR (CDCl3)
d 7.01e7.19 (m, 6H, ArH and ArOH),
6.93e6.97 (d, J¼7.2 Hz, 2H, ArH), 6.85e6.88 (d, J¼7.6 Hz, 2H, ArH),
6.68e6.81 (m, 4H, ArH), 4.10e4.18 (m, 4H, ArCH2Ar and OCH2CH3),
4.03e4.06 (d, J¼13.2 Hz, 2H, ArCH2Ar), 3.48e3.52 (d, J¼14.0 Hz, 2H,
ArCH2Ar), 3.37e3.41 (d, J¼14.0 Hz, 2H, ArCH2Ar), 2.53 (s, 3H, COCH3),
3.3. General procedure for the diacetylation of calix[4]arene
monoalkyl ethers
1.65e1.69 (t, J¼7.0 Hz, OCH2CH3); 13C NMR (CDCl3)
d
169.7, 152.6,
A slurry of 0.50 g of calix[4]arene monoalkyl ethers 11e15 was
dissolved in 20 mL of pyridine, and 2.0 mL of acetyl chloride was
then added dropwisely at ice bath temperature. The reaction
mixtures were stirred for 2 h, 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 1 N
HCl twice followed with 100 mL of saturated NaHCO3 solution and
151.1, 144.0, 133.1, 132.5, 129.4, 128.9, 128.8, 128.6, 128.4, 127.3, 126.2,
126.1,119.7, 72.6, 31.8, 20.8,15.1; FAB-MS m/e: 494 (Mþ); HRMS (FAB)
m/e: calcd for C32H30O5: 494.2093; found: 494.2094.
3.2.2. 25-Acetoxy-27-propoxy-26,28-dihydroxycalix[4]arene
(17). An amount of 0.26 g (47.5%) of colorless fine crystals was

F.-Y. Wu et al. / Tetrahedron 67 (2011) 3238e3247
3245
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 diacety-
lated products 21e25.
ArH, and Ar0H), 5.22 (d, J¼11.2 Hz, 1H, OCH2Ar0), 4.82 (d, J¼11.6 Hz,
1H, OCH2Ar0), 4.08 (d, J¼16.4 Hz, 1H, ArCH2Ar), 3.82e4.00 (m, 4H,
ArCH2Ar), 3.75 (d, J¼16.0 Hz, 1H, ArCH2Ar), 3.47 (d, J¼14.0 Hz, 1H,
ArCH2Ar), 3.26 (d, J¼12.8 Hz, 1H, ArCH2Ar), 2.10 (s, 3H, COCH3), 1.23
(s, 3H, COCH3); 13C NMR (CDCl3)
d 169.5, 168.5, 153.1, 152.8, 148.2,
3.3.1. 25,26-Diacetoxy-27-ethoxy-28-hydroxycalix[4]arene (21). An
amount of 0.40 g (67.5%) of colorless fine crystals was collected
from 0.50 g (1.11 mmol) of calix[4]arene monoethyl ether 11: mp
146.9, 135.7, 133.7, 133.6, 133.3, 132.9, 131.9, 130.0, 129.6, 129.5,
129.4, 129.1, 128.5, 128.4, 128.3, 128.1, 128.0, 127.6, 126.2, 125.4,
125.2, 119.2, 75.6, 38.0, 37.9, 31.8, 31.4, 20.7, 20.2; FAB-MS m/e: 599
(Mþþ1); HRMS (FAB) m/e: calcd for C39H34O6þHþ: 599.2434;
found: 599.2436.
257e259 ꢀC; 1H NMR (CDCl3)
d 7.73 (s, 1H, ArOH), 6.68e7.28 (m,
12H, ArH), 3.68e4.14 (m, 8H, ArCH2Ar and OCH2CH3), 3.45 (d,
J¼14.0 Hz, 1H, ArCH2Ar), 3.25 (d, J¼12.8 Hz, 1H, ArCH2Ar), 2.09 (s,
3H, COCH3), 1.28 (t, J¼7.0 Hz, 3H, OCH2CH3), 1.10 (s, 3H, COCH3); 13
C
3.4. General procedure for the alkylation of 1-monoalkoxy-
2,3-diacetoxycalix[4]arenes 21e25 in the present of K2CO3
NMR (CDCl3)
d
169.5, 168.4, 152.9, 152.5, 148.2, 146.8, 133.8, 133.7,
133.1, 132.9, 132.7, 131.8, 129.6, 129.5, 129.4, 129.2, 128.9, 128.3,
128.0,127.9,126.6,125.2,125.1,119.3, 69.0, 37.9, 37.8, 31.8, 31.4, 20.6,
19.9, 14.6; FAB-MS m/e: 537 (Mþþ1); HRMS (FAB) m/e: calcd for
C34H32O6þHþ: 537.2277; found: 537.2279.
A slurry of approximate 0.50 g of 1-monoalkoxy-2,3-diacetox-
ycalix[4]arenes 21e25, 1.00 g of K2CO3, and 2 mL of alkyl halide was
refluxed in 50 mL of CH3CN for 24 h. The solvent was removed and
the organic materials were taken up by 50 mL of CHCl3. The solu-
tion was washed in sequence with 20 mL of 1 N HCl and 100 mL of
distillated water, and the solvent was then removed to leave a col-
orless solid. Recrystallization from CHCl3 and CH3OH yielded the
corresponding dialkoxy products 26e30.
3.3.2. 25,26-Diacetoxy-27-propoxy-28-hydroxycalix[4]arene
(22). An amount of 0.25 g (42%) of colorless fine crystals was col-
lected from 0.50 g (1.07 mmol) of calix[4]arene monopropyl ether
12: mp 234e236 ꢀC; 1H NMR (CDCl3)
d 7.69 (s, 1H, ArOH), 6.69e7.27
(m, 12H, ArH), 3.67e4.07 (m, 8H, ArCH2Ar and OCH2CH2CH3), 3.45
(d, J¼13.6 Hz, 1H, ArCH2Ar), 3.24 (d, J¼12.8 Hz, 1H, ArCH2Ar), 2.09
(s, 3H, COCH3), 1.71e1.75 (m, 2H, OCH2CH2CH3), 1.10 (s, 3H, COCH3),
3.4.1. 25,27-Diethoxy-26,28-diacetoxycalix[4]arene (26). An amount
of 0.37 g (71%) of colorless crystals was afforded from 0.50 g
(0.93 mmol) of monoethoxy compound 21: mp>300 ꢀC (dec); 1H
0.95 (t, J¼7.6 Hz, OCH2CH2CH3); 13C NMR (CDCl3)
d 169.5, 168.5,
153.0, 152.7, 148.2, 146.8, 133.7, 133.5, 133.2, 133.0, 132.8, 131.8,
129.7, 129.5, 129.4, 129.3, 129.1, 128.3, 128.0, 127.9, 126.3, 125.2,
125.1, 125.0, 119.1, 75.3, 37.9, 37.8, 31.8, 31.3, 22.8, 20.6, 20.0, 10.4;
FAB-MS m/e: 551 (Mþþ1); HRMS (FAB) calcd for C35H34O6þHþ:
551.2434; found: 551.2432.
NMR (CDCl3) d 6.62e7.29 (m, 12H, ArH), 3.85e3.89 (m, 6H, ArCH2Ar
and OCH2CH3), 3.64e3.69 (m, 2H, OCH2CH3), 3.53e3.57 (d,
J¼14.8 Hz, 2H, ArCH2Ar), 3.18e3.21 (d, J¼14.8 Hz, 2H, ArCH2Ar), 1.91
(s, 3H, COCH3), 1.56 (s, 3H, COCH3), 1.35e1.37 (t, J¼7.2 Hz, 6H,
OCH2CH3); 13C NMR (CDCl3)
d 171.9, 168.7, 155.2, 148.8, 148.1, 135.5,
134.0, 133.3, 132.4, 130.4, 129.4, 129.3, 128.5, 125.5, 125.0, 122.3, 69.9,
37.6, 30.6, 21.8, 21.4, 15.77; FAB-MS m/e: 565 (Mþþ1); HRMS (FAB)
m/e: calcd for C36H36O6þHþ: 565.2590; found: 565.2588.
3.3.3. 25,26-Diacetoxy-27-butoxy-28-hydroxycalix[4]arene (23). An
amount of 0.36 g (61%) of colorless fine crystals was collected from
0.50 g (1.04 mmol) of calix[4]arene monobutyl ether 13: mp
201e203 ꢀC; 1H NMR (CDCl3)
d
7.69 (s, 1H, ArOH), 6.70e7.28 (m,
3.4.2. 25,27-Dipropoxy-26,28-diacetoxycalix[4]arene (27). An amount
of 0.37 g (69%) of colorless crystals was afforded from 0.50
(0.91 mmol) g of monopropoxy compound 22: mp 216e218 ꢀC; 1H
12H, ArH), 3.68e4.15 (m, 8H, ArCH2Ar and OCH2CH2CH2CH3), 3.45
(d, J¼13.6 Hz, 1H, ArCH2Ar), 3.24 (d, J¼12.8 Hz, 1H, ArCH2Ar), 2.09
(s, 3H, COCH3), 1.71e1.79 (m, 1H, OCH2CH2CH2CH3), 1.61e1.70 (m,
1H, OCH2CH2CH2CH3), 1.38e1.45 (m, 2H, OCH2CH2CH2CH3), 1.13 (s,
3H, COCH3), 0.94 (t, J¼7.4 Hz, 3H, OCH2CH2CH2CH3); 13C NMR
NMR (CDCl3)
d
6.63e7.31 (m, 12H, ArH), 3.88e3.92 (d, J¼13.6 Hz, 4H,
ArCH2Ar), 3.73e3.78 (m, 2H, OCH2CH2CH3), 3.50e3.59 (m, 4H,
ArCH2Ar and OCH2CH2CH3), 3.20e3.23 (d, J¼13.2 Hz, 2H, ArCH2Ar),
1.94 (s, 3H, COCH3), 1.79e1.85 (m, 4H, OCH2CH2CH3), 1.56 (s, 3H,
COCH3), 0.95e1.02 (t, J¼7.2 Hz, 6H, OCH2CH2CH3); 13C NMR (CDCl3)
(CDCl3)
d 169.4, 168.4, 153.0, 152.8, 148.2, 146.8, 133.7, 133.5, 133.2,
133.0, 132.8, 131.8, 129.7, 129.5, 129.4, 129.3, 129.1, 128.3, 128.0,
127.8, 126.3, 125.2, 125.1, 125.0, 119.1, 73.7, 37.9, 37.8, 31.8, 31.6, 31.3,
20.5, 20.0, 19.0, 14.0; FAB-MS m/e: 565 (Mþþ1); HRMS (FAB) m/e:
calcd for C36H36O6þHþ: 565.2590; found: 565.2599.
d
171.9,168.7,155.4,148.9,148.1,135.5,134.0,133.2,132.2,130.4,129.5,
129.4, 128.5, 125.5, 125.0, 122.2, 77.3, 77.0, 76.7, 76.6, 37.5, 30.6, 23.4,
21.5, 21.5, 10.6; FAB-MS m/e: 593 (Mþþ1); HRMS (FAB) m/e: calcd for
C38H40O6þHþ: 593.2903; found: 593.2906.
3.3.4. 25,26-Diacetoxy-27-allyloxy-28-hydroxycalix[4]arene
(24). An amount of 0.23 g (39%) of colorless fine crystals was col-
lected from 0.50 g (1.08 mmol) of calix[4]arene monoallyl ether 14:
3.4.3. 25,27-Dibutoxy-26,28-diacetoxycalix[4]arene (28). An amount
of 0.25 g (45%) of colorless crystals was afforded from 0.50 g
(0.88 mmol) of monobutoxy compound 23: mp 178e180 ꢀC; 1H NMR
mp 206e208 ꢀC; 1H NMR (CDCl3)
d 7.44 (s, 1H, ArOH),6.68e7.28 (m,
12H, ArH), 5.83e5.96 (m, 1H, OCH2CH]CH2), 5.15e5.24 (m, 2H,
OCH2CH]CH2), 4.53e4.61 (m, 1H, OCH2CH]CH2), 4.21e4.28 (m,
1H, OCH2CH]CH2), 3.67e4.03 (m, 6H, ArCH2Ar), 3.44 (d, J¼13.6 Hz,
1H, ArCH2Ar), 3.24 (d, J¼13.2 Hz, 1H, ArCH2Ar), 2.11 (s, 3H, COCH3),
(CDCl3)
d
6.64e7.29 (m, 12H, ArH), 3.86e3.91 (2d, J¼13.4 Hz, 4H,
ArCH2Ar), 3.73e3.81 (m, 2H, OCH2CH2CH2CH3), 3.53e3.59 (m, 4H,
ArCH2Ar and OCH2CH2CH2CH3), 3.19e3.22 (d, J¼13.2 Hz, 2H,
ArCH2Ar), 1.93 (s, 3H, COCH3), 1.75e1.78 (m, 4H, OCH2CH2CH2CH3),
1.54 (s, 3H, COCH3), 1.38e1.44 (m, 4H, OCH2CH2CH2CH3), 0.94e0.98
1.18 (s, 3H, COCH3); 13C NMR (CDCl3)
d 169.5, 168.5, 153.0, 152.4,
148.2, 146.9, 133.7, 133.6, 133.1, 132.8, 131.9, 131.6, 129.8, 129.6,
129.5, 129.4, 129.3, 128.4, 128.0, 126.3, 125.4, 125.3, 125.2, 119.3,
118.1, 73.84, 37.9, 37.8, 35.1, 31.7, 31.4, 20.7, 20.4, 20.1; FAB-MS m/e:
549 (Mþþ1); HRMS (FAB) m/e: calcd for C35H32O6þHþ: 549.2277;
found: 549.2274.
(t, J¼7.2 Hz, 3H, OCH2CH2CH2CH3); 13C NMR (CDCl3)
d 172.9, 168.7,
155.4, 148.8,148.1, 135.5,134.0, 133.2,132.2, 130.4, 129.5, 129.4, 128.5,
125.5, 125.0, 122.2, 74.7, 37.5, 32.2, 30.6, 21.5, 19.3, 13.9.
3.4.4. 25,27-Diallyloxy-26,28-diacetoxycalix[4]arene (29). An amount
of 0.29g (54%) of colorless crystals was afforded from 0.50 g
(0.91 mmol) of monoalloxy compound 24: mp 210e212 ꢀC; 1H NMR
(CDCl3) d 6.64e7.29 (m, 12H, ArH), 6.05e6.17 (m, 2H, OCH2CH]CH2),
5.24e5.34 (2d, 4H, OCH2CH]CH2), 4.26e4.32 (m, 2H, OCH2CH]
CH2), 4.12e4.18 (m, 2H, OCH2CH]CH2), 3.87e3.91 (d, J¼13.2 Hz, 4H,
3.3.5. 25,26-Diacetoxy-27-benzyloxy-28-hydroxycalix[4]arene
(25). An amount of 0.26 g (45%) of colorless fine crystals was col-
lected from 0.50 g (0.97 mmol) of calix[4]arene monobenzyl ether
15: mp 225e227 ꢀC; 1H NMR (CDCl3)
d 6.70e7.45 (m, 18H, ArOH,

3246
F.-Y. Wu et al. / Tetrahedron 67 (2011) 3238e3247
ArCH2Ar), 3.54e3.59 (d, J¼13.2 Hz, 2H, ArCH2Ar), 3.19e3.23 (d,
organic solution was washed in sequence with 20 mL of 1 N HCl and
100 mL of distillated water. The organic solvent was then concen-
trated and recrystallized from CHCl3 and CH3OH to afford the
mixture of acetyl-migrated 1,3-dialkoxy 26e30 and non-migrated
1,2-alkoxy 36e40, respectively, in various amount. Product 40 was
the only compound, which could be purified by a simple crystalli-
zation procedure.
J¼13.2 Hz, 2H, ArCH2Ar), 1.89 (s, 3H, COCH3), 1.52 (s, 3H, COCH3); 13
C
NMR (CDCl3)
d 171.8, 168.6, 154.9, 148.7, 148.1, 135.4, 133.9, 133.8,
133.3, 132.5, 130.5, 129.5, 129.3, 128.5, 125.5, 125.0, 122.6, 118.8, 75.7,
37.6, 30.8, 21.9, 21.4; FAB-MS m/e: 589 (Mþþ1); HRMS (FAB) m/e:
calcd for C38H36O6þHþ: 589.2590; found: 589.2597.
3.4.5. 25,27-Dibenzyloxy-26,28-diacetoxycalix[4]arene
amount of 0.34 g (59%) of colorless crystals was afforded from
0.50 (0.83 mmol) of monobenzyloxy compound 25: mp
222e224 ꢀC; 1H NMR (CDCl3) 6.66-7.36 (m, 22H, ArH and Ar0H),
(30). An
3.6.1. 25,26-Dibenzyloxy-27,28-diacetoxycalix[4]arene (40). A slurry
of 0.50 g (0.83 mmol) of compound 25, 0.05 g of 60% NaH, and
0.28 g (1.67 mmol) of benzyl bromide was refluxed in 50 mL of
CH3CN for 14 h. The solvent was removed and the organic materials
were taken up by 50 mL of CHCl3. The solution was washed with
20 mL of 1 N HCl and 100 mL of distillated water twice, and the
g
d
4.69e4.72 (d, J¼10.4 Hz, 2H, OCH2Ar0), 4.62e4.65 (d, J¼10.4 Hz, 2H,
OCH2Ar0), 3.83e3.86 (d, J¼13.6 Hz, 2H, ArCH2Ar), 3.75e3.79 (d,
J¼14.6 Hz, 2H, ArCH2Ar), 3.49e3.53 (d, J¼14.6 Hz, 2H, ArCH2Ar),
3.09e3.12 (d, J¼13.6 Hz, 2H, ArCH2Ar), 1.93 (s, 3H, COCH3), 1.09 (s,
solvent was then removed to leave
a colorless solid. Re-
3H, COCH3); 13C NMR (CDCl3)
d
172.0, 169.0, 155.1, 149.0, 148.4,
crystallization from CHCl3 and CH3OH afforded the first crops as
1,3-dialkoxy products 30. The mother solution was further con-
centration to precipitate second crops of solid. Further re-
crystallization from CHCl3 and CH3OH yielded 0.22 g (28％) of
136.6, 135.7, 133.9, 133.8, 132.8, 130.7, 129.9, 129.8, 129.7, 128.8,
128.7, 125.8, 125.1, 122.8, 77.9, 77.4, 77.3, 76.6, 37.8, 31.0, 21.7, 21.4;
FAB-MS m/e: 689 (Mþþ1); HRMS (FAB) m/e: calcd for
C46H40O6þHþ: 689.2903; found: 689.2901.
colorless crystals 40: mp 240e245 ꢀC; 1H NMR (CDCl3)
d 6.89e7.30
(m, 22H, ArH and Ar0H), 4.65 (s, 2H, OCH2Ar0), 4.61e4.64
(d, J¼11.8 Hz, 1H, OCH2Ar0), 4.55e4.58 (d, J¼11.8 Hz, 1H, OCH2Ar0),
4.04e4.07 (d, J¼12.8 Hz, 1H, ArCH2Ar), 3.82e3.85 (d, J¼12.8 Hz, 1H,
ArCH2Ar), 3.51e3.65 (m, 3H, ArCH2Ar), 3.48e3.52 (d, J¼15.6 Hz, 1H,
ArCH2Ar), 3.14e3.17 (d, J¼12.8 Hz, 1H, ArCH2Ar), 2.96e2.99 (d,
3.5. General procedure for the basic hydrolysis of dialkoxy-
diacetoxycalix[4]arene 26e30
A slurry of dialkoxy-diacetoxycalix[4]arene ethers 26e30 and
2.00 g of NaOH was refluxed in a mixture of 10 mL of C2H5OH and
50 mL of THF for 24 h. The solvent was removed by rotory
evaporatory and the organic materials were taken 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 re-
moved to leave a colorless solid. Recrystallization from CHCl3 and
CH3OH yielded the corresponding 1,3-dialkoxycalix[4]arenes
31e35.
J¼12.8 Hz,1H, ArCH2Ar),1.50 (s, 3H, COCH3),1.23 (s, 3H, COCH3); 13
C
NMR (CDCl3)
d 170.2, 168.5, 155.2, 155.0, 148.6, 146.3, 137.5, 137.0,
135.8, 135.0, 134.9, 134.3, 133.7, 132.7, 132.4, 131.6, 130.1, 129.4,
129.3, 129.1, 128.9, 128.8, 128.6, 128.5, 128.5, 128.1, 128.1, 128.0,
127.3, 125.0, 124.8, 123.6, 122.7, 76.1, 37.9, 37.6, 30.6, 30.1, 20.2, 20.0;
FAB-MS m/e: 689 (Mþþ1); HRMS (FAB) m/e: calcd for
C46H40O6þHþ: 689.2903; found: 689.2890.
3.6.2. 25,26-Dibenzyloxy-27,28-dihydroxycalix[4]arene (41). A slurry
of0.38 g (0.69 mmol) of 1,2-dibenzyloxy compound 40 and 8.00 g of
25% NaOH was refluxed in a mixture of 10 mL of C2H5OH and 50 mL
of THF for 24 h. The solvent was removed by rotory evaporatory and
the organic materials were taken up by 50 mL of CHCl3. The solution
was washed with 20 mL of 1 N HCl and 100 mL of distillated water
twice, and the solvent was then removed to leave a colorless solid.
Recrystallization from CHCl3 and CH3OH yielded 0.22 g (65%) of
3.5.1. 25,27-Diethoxy-26,28-dihydroxycalix[4]arene (31). An amount
of 0.15 g (38%) of colorless fine crystals was collected from 0.47 g
(0.83 mmol) of compound 26: mp 254e256 ꢀC. The 1H NMR was
identical to the known compound.
3.5.2. 25,27-Dipropoxy-26,28-dihydroxycalix[4]arene (32). An amount
of 0.14 g (75%) of colorless fine crystals was collected from 0.22 g
(0.37 mmol) of compound 27: mp 256e258 ꢀC. The 1H NMR was
identical to the known compound.
colorless crystals 41: 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, OCH2Ar0), 4.87e4.90 (d, J¼11.2 Hz, 2H, OCH2Ar0), 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 (d, J¼12.8 Hz, 2H, ArCH2Ar); 13C NMR (CDCl3)
3.5.3. 25,27-Dibutoxy-26,28-dihydroxycalix[4]arene (33). An amount
of 0.10 g (64%) of colorless fine crystals was collected from 0.18 g
(0.29 mmol) of compound 28: mp 212e216 ꢀC. The 1H NMR was
identical to the known compound.
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; FAB-MS m/e:
605 (Mþþ1); HRMS (FAB) m/e: calcd for C42H36O4þHþ: 605.2692;
found: 605.2708.
3.5.4. 25,27-Diallyloxy-26,28-dihydroxycalix[4]arene (34). An amount
of 0.22 g (76%) of colorless fine crystals was collected from 0.34 g
(0.58 mmol) of compound 29: mp 208e210 ꢀC. The 1H NMR was
identical to the known compound.
Acknowledgements
3.5.5. 25,27-Dibenzyloxy-26,28-dihydroxycalix[4]arene
(35). An
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
(Grant NSC-94-2113-M034-002 and NSC-95-2113-M034-001) is
gratefully acknowledged.
amount of 0.15 g (45%) of colorless fine crystals was collected from
0.38 g (0.55 mmol) of compound 30: mp 230e232 ꢀC. The 1H NMR
was identical to the known compound.
3.6. General procedure for the alkylation of 1-monoalkoxy-
2,3-diacetoxycalix[4]arenes 21e25 in the present of NaH
Supplementary data
A slurry of approximate 0.50 g of 1-monoalkoxy-2,3-diacetox-
ycalix[4]arenes 21e25, 0.05 g of 60% NaH, and 1 mL of alkyl halide
was refluxed in 50 mL of CH3CN for 14 h. The solvent was removed
and the organic materials were taken up by 50 mL of CHCl3. The
Copies of 1H and 13C NMR spectra of compounds 6e35, 40 and
41 are available. Supplementary data related to this article can be
found online at doi:10.1016/j.tet.2011.03.010.

F.-Y. Wu et al. / Tetrahedron 67 (2011) 3238e3247
3247
6. Shu, C.-M.; Chung, W.-S.; Wu, S.-H.; Ho, Z.-C.; Lin, L.-G. J. Org. Chem. 1999, 64,
2673e2679.
7. One-step procedure with chromatographic separation: (a) Groenen, L. C.; Ruel,
B. H. M.; Casnati, A.; Verboom, W.; Pochini, A.; Ungaro, R.; Reinhoudt, D. N.
Tetrahedron 1991, 47, 8379e8384; (b) Araki, K.; Iwamoto, K.; Shinkai, S.; Mat-
suda, T. Bull. Chem. Soc. Jpn. 1990, 63, 3480e3485.
References and notes
€
€
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Compounds; Topics in Inclusion Science 3; Vicens, J., Bohmer, V., Eds.; Kluwer:
Dordrecht, 1991; (d) Groenen, L. C.; Reinhoudt, D. N. In Supramolecular Chem-
istry; Balzani, V., de Cola, L., Eds.; Kluwer: Dordrecht, 1991; pp 51e70; (e) Po-
8. Shu, C.-M.; Yuan, T.-S.; Ku, M.-C.; Ho, Z.-C.; Liu, W.-C.; Tang, F.-S.; Lin, L.-G.
Tetrahedron 1996, 52, 9805e9818.
€
€
9. (a) Groenen, L. C.; Ruel, B. H. M.; Casnati, A.; Timmerman, P.; Verboom, W.;
Harkema, S.; Pochini, A.; Ungaro, R.; Reinhoudt, D. N. Tetrahedron Lett. 1991, 32,
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L., Ungaro, R., Eds.; Imperial College: London, UK, 2000; (h) Calixarenes 2001;
Asfari, Z., Bhmer, V., Harrowfield, J., Vicens, J., Eds.; Kluwer: Dordrecht, The
Netherlands, 2001.
2. (a) Gutache, C. D.; Dhawan, B.; Levine, J. A.; No, K. H.; Bauer, L. J. Tetrahedron
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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.
ꢀ
12. Jaime, C.; de Mendoza, J.; Prados, P.; Nieto, P. M.; Sanchez, C. J. Org. Chem. 1991,
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15. 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) andareuncorrected.
1H NMR spectra are recorded on Varian 400-MR 400 MHz FT-NMR spectrometer
4.
A multi-step process: (a) Gutsche, C. D.; Lin, L.-G. Tetrahedron 1986, 42,
1633e1640; (b) Casnati, A.; Arduini, A.; Ghidini, E.; Pochini, A.; Ungaro, R.
Tetrahedron 1991, 47, 2221e2228.
5. A multi-step process: (a) Iwamoto, K.; Araki, K.; Shinkai, S. J. Org. Chem. 1991,
56, 4955e4962; (b) Iwamoto, K.; Araki, K.; Shinkai, S. Tetrahedron 1991, 47,
4325e4342; (c) Pappalardo, S.; Giunta, L.; Foti, M.; Ferguson, G.; Gallagher, J. F.;
Kaitner, B. J. Org. Chem. 1992, 57, 2611e2624; (d) Iwamoto, K.; Shimizu, H.;
Araki, K.; Shinkai, S. J. Am. Chem. Soc. 1993, 115, 3997e4006; (e) Ferguson, G.;
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(f) Ho, Z.-C.; Ku, M.-C.; Shu, C.-M.; Lin, L.-G. Tetrahedron 1996, 52, 13189e13200.
and chemical shifts are reported as
d
values in ppm relative toTMS (
d
¼0.00). FAB-
MS and HRMS (FAB) spectra were taken on a Finnigan/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 outon MachereyeNagel aluminum back silica
gel 60 F254 plates (absorbant thickness 0.2 mm).