Synthesis of a phloroacetophenon[4]arene consisting of four isomers via the one-pot, acid-catalysed condensation of phloroacetophenone with benzaldehyde

Article abstract of DOI:10.1080/10610278.2013.822969

A phloroacetophenon[4]arene (3) consisting of four isomers was synthesised for the first time via the condensation of phloroacetophenone and benzaldehyde in a one-pot reaction with refluxing toluene in the presence of catalytic amounts of TsOH·H2O for a maximum yield of 64%. The conformational elucidation of four isomers (3a-d) by ¹H NMR spectroscopy and X-ray crystal structure analysis showed them to be cone, partial cone, 1,3-alternate and 1,2-alternate types of conformations, respectively. 2013

Full text of DOI:10.1080/10610278.2013.822969

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Synthesis of a phloroacetophenon[4]arene
consisting of four isomers via the one-pot, acid-
catalysed condensation of phloroacetophenone with
benzaldehyde
Akihito Yashiroa, Keita Onoderaa, Chunlei Lia, Yukiko Suzukia, Hiroshi Katagiria & Shingo
Satoa
a Graduate School of Science and Engineering, Yamagata University, 4-3-16 Jonan,
Yonezawa-shi, Yamagata, 992-8510, Japan
Published online: 21 Aug 2013.
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To cite this article: Akihito Yashiro, Keita Onodera, Chunlei Li, Yukiko Suzuki, Hiroshi Katagiri & Shingo Sato (2014)
Synthesis of a phloroacetophenon[4]arene consisting of four isomers via the one-pot, acid-catalysed condensation of
phloroacetophenone with benzaldehyde, Supramolecular Chemistry, 26:1, 48-53, DOI: 10.1080/10610278.2013.822969
To link to this article: http://dx.doi.org/10.1080/10610278.2013.822969
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Supramolecular Chemistry, 2014
Vol. 26, No. 1, 48–53, http://dx.doi.org/10.1080/10610278.2013.822969
Synthesis of a phloroacetophenon[4]arene consisting of four isomers via the one-pot,
acid-catalysed condensation of phloroacetophenone with benzaldehyde
A k i h i t o Y a s h i ro , K e i t a O n o d e r a , C h u n l e i L i , Y u k ik o S u z u k i, H i r o s h i K a t a g ir i a n d S h i n g o S a t o *
Graduate School of Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa-shi, Yamagata 992-8510, Japan
(Received 15 March 2013; final version received 17 June 2013)
A p h l o r o a c e t o ph e n o n [4 ] a r en e ( 3) consisting of four isomers was synthesised for the first time via the condensation of
phloroacetophenone and benzaldehyde in a one-pot reaction with refluxing toluene in the presence of catalytic amounts of
TsOH· H2O for a maximum yield of 64%. The conformational elucidation of four isomers (3a–d) by 1H NMR spectroscopy
and X-ray crystal structure analysis showed them to be cone, partial cone, 1,3-alternate and 1,2-alternate types of
conformations, respectively.
Keywords: p hl o r o a c e t o p he n on [ 4 ] a r e n e ; f o ur i s o m e r s ; c o n f o r ma t i o n a l e l u c i d a t i on ; h y d r og e n b o n di n g
1. Introduction
C-acylated phloroglucinol, phloroacetophenone would
behave like a resorcinol in the reaction.
T he re a re m an y r ep or ts (1) on the synthesis and the
functionality of cyclic oligomers consisting of a phenol
analogue, whereby the compounds taking a calix structure
are referred to as ‘calixarene’. These were mainly
synthesised by the condensation between phenols such as
p-tert-butylphenol (2) or resorcinol (3) or pyrogallol (4) and
an alkyl- and aryl aldehyde such as formaldehyde or
benzaldehyde (5). Although there are many reports on the
chemical modification of a p-tert-butylcalix[4]arene or
resorcin[4]arene, there are no reports on the synthesis of
cyclic oligomers that consist of a phloroglucinol (benzene
1,3,5-triol). We previously reported the first synthesis of a
cyclic tetramer and hexamer (1 and 2, Figure 1) with
alternately arranged phloroglucinols and p-tert-butylphe-
nols, and explored the chemical and inclusion properties of
1 (6). It appeared that the phloroglucinol moiety in 1 had
partially taken a keto-form under alkaline conditions (6a).
However, despite many efforts, the synthesis of a cyclic
oligomer that is consisting only of phloroglucinol has not
been achieved because oligomerisation proceeded prefer-
entially because of a high reactivity at the 2,4,6-positions. It
could not be synthesised by the same approach as resorcin
[4]arene, which is achieved by acid-catalysed condensation
between resorcinol and aldehyde (3). Based on the reasons
given earlier, we formulated our hypothesis on the reactivity
of the phloroglucinol as follows: if one of the 2,4,6-
positions of phloroglucinol is acylated, its C-alkylated site
will decrease to two from three, one of the three phenolic
hydroxyls will form a chelation with an acyl–carbonyl
group, and because taking a keto-form is difficult, the
O n t h e b a s i s o f t h i s h y p o t h e s i s , w e a t t e m pt e d t he
s y n t h e s i s o f a c y c l i c o l i g o m e r c o n s i s t i n g o f o n l y
p h l o r o a c e t o p h e n o n e . W e d e s c r ib e h e r e t h e fi r s t o ne -p o t
s y n t h e si s o f a c y c li c t e t r a m e r 3 (Figure 1) consisting of
phloroacetophenone and benzaldehyde, which hereafter
will be called a ‘phloroacetophenon[4]arene’.
2. Results and discussion
2.1 Synthesis
A l t h o u g h o u r a t t e m p t s t o w a r d s t h e s y n t h e s i s o f a c y c l i c
o l i g o m e r t h a t c o n s i s t e d o f o n l y a p h l o r o g l u c i n o l h a v e
b e e n u n s u c c e s s f u l , a n a c i d - c a t a l y s e d c o n d e n s a t i o n o f
p h l o r o a c e t o p h e n o n e w i t h b e n z a l d e h y d e o n t h e b a s e o f
t h e p r e v i o u s l y m e n t i o n e d h y p o t h e s i s g a v e t h e d e s i r e d
c y c l i c t e t r a m e r . B e c a u s e o n e o f t h e t h r e e r e a c t i o n s i t e s o f
p h l o r o g l u c i n o l w a s fi l l e d w i t h a n a c e t y l g r o u p , i t w a s
a s s u m e d t h a t p h l o r o a c e t o p h e n o n e b e h a v e d l i k e r e s o r c i
-
n o l . T h i s r e a c t i o n w a s a c h i e v e d w i t h a n o r m a l a n d
p r a c t i c a l c o n c e n t r a t i o n ( 0 . 5 M ) a n d r e a c t i o n t i m e
( 1 0 m i n ) u s i n g e q u i m o l a r a m o u n t s o f p h l o r o a c e t o p h e
-
n o n e a n d b e n z a l d e h y d e i n r e fl u x i n g t o l u e n e i n t h e
p r e s e n c e o f a c a t a l y t i c a m o u n t ( 0 . 1 5 e q u i v . ) o f p-toluene-
sulfonic acid monohydrate (TsOH·H2O), whereas com-
pounds 1 and 2 were synthesised by stepwise synthesis.
The substrates disappeared after 5 min, and the reaction
mixture was readily separable to only the corresponding
cyclic tetramer from some chained oligomers by silica
gel column chromatography (solvent: chloroform), which
* C o rr e sp o n d i n g a u t h o r . E m a i l: s h i ng o - s@ y z . y a m a g at a- u . a c . j p
q 2 0 1 3 T a y l o r & F r a n c i s

Supramolecular Chemistry
4
9
O
OH
HO
OH
OH
HO
HO
HO
HO
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH HO
OH
O
OH
OH
HO
HO
HO
OH
HO
OH
O
OH
HO
HO
OH
O
1
2
3
F i g u r e 1 . T h e s y n t h e s i s e d c y c l i c o l i go m e r s c o n t a in i n g p h l o r og l u c i n o l .
was afforded in a yield of 35% (Table 1). Phloroaceto-
phenone also reacted with p-anisaldehyde or 2-naphthal-
dehyde to give the corresponding phloroacetophenon[4]
arene in the same yields. However, it did not react with the
other benzaldehydes such as p-hydroxybenzaldehyde,
p-phenylbenzaldehyde, o-nitrobenzaldehyde or 1-naphth-
aldehyde, or with any aliphatic aldehydes such as formal-
dehyde or alkylaldehyde. Benzaldehyde reacted neither
with phloroacetophenone derivatives in which a hydroxyl
group was protected nor with alkylated phloroglucinols
such as those containing an ethyl group in place of an
acetyl group.
N e x t , o p t i m u m a m o u n t o f a c a t a l y s t p-TsOH·H2O was
examined (Table 3). When the amount of p-TsOH·H2O
was doubled (0.30 equiv.), the yield was improved to 40%;
however, the use of more amount (0.50 equiv.) decreased
the yield to 30%. The change in the amounts of
p-TsOH·H2O had no significant influence on the yield.
E xp lo ra ti on o f t he o pti mu m c on ce nt ra ti on o f p hl or oa
-
c et op he no ne a nd b en za ld eh yd e o n t he reacti on i n reflu xi ng
t ol ue ne i n t he p re se nc e o f p-TsOH·H2O (0.15 equiv.) showed
that the more dilute concentration gave a higher yield
(Table 4, runs 4 and 5). When the concentration used was
34mM, the yield was maximum 63%, and when with
3.4 mM, the yield was about the same, at 64%.
T h e u s e o f e it h e r H C l o r y t t e rb i u m (I I I ) t r i flu o r o m e t h a
-
n e su l f o n a te [ Y b( O T f) ] , w h i c h w a s u s e d a s a c a t a l y s t i n
T o s u m m a r i s e t h e r e a c t i o n c o n d i ti o n s , i t a p p e a r ed t ha t
p h l o r o a c e t o p h e n o n [ 4 ] a r e n e w a s p r o d u c e d i n a 6 4% y ie l d
a f t e r t h e 4 - h r e fl u x in g o f a c o n c e n t r a t i o n o f 3 .4 m M
s u b s t r a t e s i n t o l u e n e i n t h e p r e s e n c e o f 0 . 1 5 e q ui v . o f
p-TsOH·H2O. Although the yield of 3 was changed by a
change in either the solvent or catalyst, the product ratio of
the four isomers was scarcely changed from ca.
3a:3b:3c:3d ¼ 13:61:12:14, as determined by HPLC
analysis [column: silica gel, solvent system: toluene–
AcOEt–AcOH ¼ 65:30:5, flow rate: 1 ml/min, detection:
UV310 nm, Rt: 1.97 min (3a), 4.39 min (3b), 6.38 min (3c)
and 16.91 min (3d)].
3
t h e s y n th e s i s o f r e s o r c i n a r e n e (3f), was never successful.
The use of sulfonic acid derivatives like H2SO4, CH3SO3H
or CF3SO3H in the place of TsOH·H2O afforded 3 in the
same yield. The use of protic solvents such as ethanol or
aprotic polar solvents such as acetonitrile and 1,4-dioxane
gave no or little yield (Table 2). Aprotic non-polar solvents
with high-boiling temperatures such as toluene, ethylben-
zene or chlorobenzene gave higher yields.
T a b l e 1 . S y n t h e s i s o f 3 in the presence of some catalysts.
O
CHO
HO
OH
T a b l e 2 . S y n t he s is o f 3 catalysed by p-TsOH·H2O (0.15 equiv.)
in some refluxing solvents.
reflux
+
3
C o n c e n t ra t i on
( m M )
T i m e
( m i n )
OH
R
u
n
S
o
l
v
e
n
t
Y
i
e
l
d
(
%
)
1 equiv
1 equiv
1
2
3
4
5
6
7
8
T o l u e n e
E t h a n o l
C H C N
1 , 4 - Di o x a n e
B e n z e n e
E t h y l be n z e n e
X y l e n e s
C h l o r ob e n z e n e
5 0 0
5 0 0
5 0 0
5 0 0
5 0 0
5 0 0
5 0 0
5 0 0
1 0
1 0
6 0
3 0
1 0
1 0
1 0
1 0
3 5
0
T r a c e
T r a c e
1 7
C a t a l y s t
( e q u i v . )
C o nc e n t r a t i o n
( m M)
Y i e l d
( % )
R u n
1
S
o
l
v
e
n
t
T i m e
5 m i n
3
p-TsOH·H2O T o l ue n e
(0.15)
5
0
0
3 5
0
2 3
1 0
2
3
Y b ( O Tf )
( 0 . 1 5 )
T
o
l
u
e
n
e
5
0
0
2 0 m i n
1 6 h
3
a
3
8
C o n c e n t r a t e d E t ha no l
H C l ( 1 . 9 2 )
1
0
0
0
0
a p-TsOH·H2O (0.30 equiv.).

5 0
A. Yashiro et al.
spectra of 3b and 3d, four signals for each proton were
observed with the exception of the observation of one
singlet peak with four hydroxyls on the lower side. In the
signal from the four chelated hydroxyls, however, 3b was
separated to one and three other singlet peaks and 3d was
separated to two and two singlet peaks, respectively. From
the above analysis, it was assumed that 3b had taken a
partial cone-type conformation and 3d a 1,2-alternate-type
conformation, respectively. Because the peaks derived
from the four phenolic hydroxyls on the lower side were
observed as a singlet in all isomers, it was assumed that the
structure of the three isomers, with the exception of 3a,
taken in CDCl3 was not examples of the perfect-reverse
models depicted in Figure 2 (7), but was of half-reverse
models where a hydrogen-bonding ring network at the
lower side was not broken. Further, X-ray crystal structure
analysis showed that 3a also adopted a cone-type
conformation (see Figure 3) and that an acetone molecule
had bonded via four intermolecular hydrogen bonds
between the carbonyl oxygen of acetone and the four
hydroxyl groups of the lower side of 3a. Also possible was
four CH–p interactions between the two methyl groups of
acetone and the four benzene rings on the lower side of 3a.
Although the crystal of 3a was fragile, X-ray crystal
structure analysis showed that one of the four isomers, 3a,
had taken a calix structure and that a new characteristic
structure of the lower and upper rims had hydrogen-
bonding networks like those of p-tert-butylcalix[4]
arene and resorcinarene, respectively. Also, the lower
rim had a shallow calix structure with four benzene rings
bonded at the lower side for the triphenylmethyl carbon
with a small molecular structure similar to that of an
acetone included.
T a b l e 3 . S y n t h e s i s o f 3 in the presence of catalytic amount of
p-TsOH·H2O in a refluxing toluene.
p-TsOH·H2O
(equiv.)
C o nc e nt r a t i o n
( m M)
T i m e
( m i n)
Y i e l d
( % )
R u n
1
2
3
0 . 1 5
0 . 3 0
0 . 5 0
5 00
5 00
5 00
1 0
5
5
3 5
4 0
3 0
2.2 Conformation analysis
T h e F A B - M S a nd e l e m e n t a l a n a l y s i s o f t h e f o u r p r o d u c t s
( 3a–3d) gave 1025 (M þ H)þ and C60H48O16. Each
1H NMR spectrum showed characteristic chemical shifts
(Figure S1 of the Supporting Information, available via the
article webpage) as follows: from one to four singlet peaks
for the four acetyl–methyl groups at ca. 2.6 ppm, from one
to three singlet peaks for the four triphenylmethanes at
ca. 6.5 ppm and as each from one to four singlet peaks for
the three phenolic hydroxyls at 9.6, 10 and 16 ppm. They
were elucidated to be a cyclic tetramer where four
phloroacetophenones and four benzaldehydes were alter-
natively condensed. The four isomers of the cyclic
tetramer were expected, as ordered from high to low, in the
following Rf-values of the silica gel thin layer chroma-
tography (TLC) [toluene:AcOEt:AcOH ¼ 5:2:0.5, Rf-
value: 0.70 (3a), 0.25 (3b), 0.18 (3c) and 0.10 (3d)], to
be cone (3a), partial cone (3b), 1,3-alternate (3c) and 1,2-
alternate (3d) (see Figure 2), as with a p-tert-butylcalix[4]
arene (7). In isomer 3a, all peaks, with the exception of the
phenyl-aromatic protons derived from benzaldehyde, were
observed as a singlet peak: at 2.6 ppm derived from four C-
acetyl groups; at 6.5 ppm derived from triphenylmethanes;
at 9.7 and 10 ppm derived from eight phenolic hydroxyls
and at 16 ppm derived from four phenolic hydroxyls
F i n a l l y , a c h a n g e i n t h e U V – v i s s p e c t r a r e s u l t i n g f ro m
a c h a n g e i n t h e s o l u t i o n p H ( 7 – 1 3 ) o f p h l o r o g l u c i n ol a nd a
m a j o r i s o m e r 3b was measured (Figures S6 and S7 of the
Supporting Information, available via the article web-
page). The UV–vis spectra of cyclic compound 1, in
which phloroglucinol and p-tert-butylphenol had bonded
alternatively, were changed together with a change in
pH, as was phloroglucinol (6a). However, the UV–vis
spectra of 3b did not change until pH 13 was reached due
to the strong intramolecular hydrogen bonding, whereas
that of phloroacetophenone was changed with any change
in pH.
1
chelated to carbonyl groups. In the H NMR spectrum of
3c, two singlet peaks for four chelated hydroxyls, two
singlet peaks for the four upper hydroxyls and one singlet
peak for four lower hydroxyls and two singlet peaks for
four acetyl–methyl residues were observed, respectively.
Therefore, 3c was assumed from their symmetry to have
taken a 1,3-alternative conformation. In the 1H NMR
T a b l e 4 . S y n t h e s i s o f 3 in some concentrations of phloroace-
tophenone and benzaldehyde in refluxing toluene in the presence
of p-TsOH·H2O.
F o u r i s o m e r s w e r e u n s t a b le u n d e r b a s i c c o n d i t io n s t o
g i v e s o m e n o n - c y c l i c p r o d u c t s . T h e y w e r e p a r ty c le a ve d
a n d a f f o r d e d s o m e d e g r a d a t i o n p r o d u c t s e v e n u nd er
r e fl u x in g i n x y l e n e s .
p-TsOH·H2O
(equiv.)
C o nc e n t r a t i o n
( m M)
Y i e l d
( % )
R u n
T i m e
T h e r e a r e w e l l - k n o w n r e p o r t s o f v a r io u s s p e c i e s f ro m a
n e u tr a l s m a l l m o l e c u le s u c h a s o r g a n i c s o l v e n t s ( 8) to metal
ions (9) and a large molecule such as C60 (10) that were
included as guests, and, recently, an alcohol that was
included selectively under competitive conditions (11). A
study on selective inclusion using 3a is now in progress.
1
2
3
4
5
0 . 1 5
0 . 1 5
0 . 1 5
0 . 1 5
0 . 1 5
5 00
1 00 0
1 00
3 4
1 0 m i n
1 0 m i n
4 h
4 h
4 h
3 5
2 4
4 2
6 3
6 4
3 . 4

Supramolecular Chemistry
5
1
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Ac
OH
OH
Ac
OH
Ac
HO
Ac
HO
OH
OH
Ph
HO
OH
HO
OH
HO
OH
HO
OH OH
HO
OH
HO
HO
OH
OH
OH
OH
HO
HO
OH
O
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
OH
OH
OH
Ph
Ph
OH
OH
HO
Ph
OH
HO
Ph
OH
Ph
Ph
Ph
OH
HO
OH
Ac
OH
HO
OH
Ac
HO
HO
OH
Ac
Ac
HO OH
Ac
Cone
Partial-cone
1,3-alternate
1,2-alternate
F i g u r e 2 . T h e f o u r p os s i b l e c o n fo r m e r s f o r 3.
3. Conclusion
r ec or de d o n a Fou ri er t ra ns fo rm i nf rared s pe ctr op ho to me te r
u si ng a K Br d is k. Th e NM R s pe ct ra were rec ord ed on a
5 0 0 - M Hz s p e c t r o m e t e r us i n g M e S i a s t h e i n t e r n a l
T h e fi r s t s y n t h es i s o f p h l o r o a c e t o p h e n o n [ 4 ]a r e n e ( 3) was
accomplished via the Bronsted-catalysed one-pot conden-
sation of phloroacetophenone and benzaldehyde, and it
consisted of four isomers. One of the four isomers, 3a,
adopted a characteristic structure with a calyx structure on
the upper side and a small calix structure on the lower side
where a small molecule can be included, as shown by the
X-ray crystal structure. Phloroacetophenon[4]arene (3)
showed no change in the structure that had taken a keto-
form, such as a phloroacetophenone in an alkaline solution
as shown by the UV–vis spectra.
4
s ta nd ard . Fast- at om b omb ardm en t m as s s pe ctr al d at a w er e
m ea su re d u si ng 3 -n it ro be nz yl a lc oh ol o r g ly cerol a s a
m at ri x o n a FA B- MS i nstr um en t. E le me nt al analy se s w er e
p er fo rm ed o n a n e le me nt al a na ly si s i ns tr ume nt.
5. Synthesis (typical procedure for the synthesis of 3)
To a s ti rred s ol ut io n o f p hl or oa ce to ph en on e ( 67 2 m g,
4 m mol) a nd p-TsOH·H2O (114mg, 0.15equiv.) in dried
toluene (5ml), benzaldehyde [406ml (424mg), 4 mmol] in
toluene (3.5 ml) was added, and the resultant mixture was
refluxed in an oil bath at 1408C for 15min. The colour of the
reaction mixture was changed from yellow to red. After
cooling at room temperature, the reaction mixture was
poured into a 0.5N-HCl solution (ca. 30ml). The mixture
was extracted twice with AcOEt. The organic extract was
washed with water and brine and dried over anhydrous
Na2SO4. After evaporation, the residue was purified by
silica gel column chromatography (CHCl3) to give 3
(410mg, Y: 40%) as a pale yellow powder. Separation of
four isomers of 3 was conducted using preparative silica gel
TLC (solvent system: toluene–AcOEt–AcOH ¼ 5:2:0.5)
or silica gel column chromatography (solvent system:
CHCl3–EtOH, or/and toluene–AcOEt–AcOH).
4. Experimental section
T he s ol ve nt s u sed i n th is s tu dy w er e p ur ifi ed b y d istil la ti on .
R ea ct io ns were m on it ore d b y TLC o n 0 .2 5- mm S il ica Ge l
F2 54 p la te s u sin g UV l ig ht a nd eithe r a 5 % e th an oli c
s ol ut io n o f f er ri c c hl or id e o r a 7 % e th an ol ic s ol ut io n o f
p ho sp ho mo ly bd ic a cid wit h h ea t a s a c ol ou ra tio n a ge nt. Fo r
s ep ar ati on a nd p urific at io n, flas h c ol um n c hr om atog ra ph y
w as p erfo rm ed o n s il ic a g el ( 40 – 5 0 mm ). IR s pect ra w er e
C o m p o u n d 3a: Pale yellow powder. m.p. ¼ .2508C
(dec.). IRn 3255, 3058, 3027, 2935, 1604, 1494, 1446,
1365, 1299 cm21. UV–vis (CHCl3) l (log 1): 391 (3.03),
330 (3.97), 282 (4.71), 241 (4.62) nm. 1H NMR (CDCl3) d
2.78 (s, 12H, CH3 £ 4), 6.34 (s, 4H, . CHZ £ 4), 7.13
(d, 8H, J ¼ 7.5, ArH), 7.19–7.22 (m, 12H, ArH), 9.52 (s,
4H, OH £ 4), 9.88 (s, 4H, OH £ 4), 16.43 (s, 4H, OH
£ 4). 13C NMR (CDCl3) d 33.5 ( £ 4), 34.3 ( £ 4), 107.1
( £ 4), 108.2 ( £ 4), 109.5 ( £ 4), 126.7 ( £ 4), 127.0
( £ 8), 128.1 ( £ 8), 136.5 ( £ 4), 157.8 ( £ 4), 160.2
( £ 4), 162.1 ( £ 4), 206.2 ( £ 4). FAB-MS (m/z) 1025
(M þ H)þ. Anal. calcd for C60H48O16·H2O: C69.09,
H4.83; found: C69.20, H4.73.
C o m p o u n d 3b: Pale yellow powder. m.p. ¼ .2508C
(dec.). IRn 3226, 3058, 3027, 2933, 1604, 1494, 1446,
1365, 1301 cm21. UV–vis (CHCl3) l (log 1): 391 (3.12),
F i g u r e 3 . ( C o l o u r o nl i n e ) X - r a y s t r u c t ur e o f 3a. Dotted lines
represent the intra- and intermolecular hydrogen bonds.

5
2
A. Yashiro et al.
330 (4.04), 282 (4.73), 241 (4.72) nm. 1H NMR (CDCl3) d
2.66, 2.73, 2.79 and 2.80 (each s, 3H, CH3 £ 4), 5.90
(s, 1H, . CHZ), 6.36 (s, 2H, . CHZ £ 2), 6.40 (br s, 1H,
. CHZ), 7.17–7.38 (m, 20H, ArH £ 20), 9.48, 9.52, 9.56
and 9.59 (each s, 1H, OH £ 4), 9.81 (br s, 4H, OH £ 4),
16.11, 16.41, 16.45 and 16.47 (each s, 1H, OH £ 4). 13C
NMR (CDCl3) d 33.4, 33.4 ( £ 2), 33.6, 34.2, 34.3, 34.4,
35.1, 107.0, 107.1, 107.1, 107.2, 107.3, 107.9, 108.0,
108.2, 108.3, 108.9, 109.2, 109.4, 126.8 ( £ 2), 126.9
( £ 2), 126.9 ( £ 6), 127.1 ( £ 2), 128.1 ( £ 2), 128.2
( £ 2), 128.3 ( £ 2), 128.3 ( £ 2), 136.2, 136.4, 136.5,
136.7, 157.7, 157.8, 157.9, 157.9, 159.7, 160.1 (x2), 160.2,
161.3, 161.8, 162.1 ( £ 2), 206.1, 206.1, 206.2 ( £ 2).
FAB-MS (m/z) 1025 (M þ H)þ. Anal. calcd for
C60H48O16: C70.30, H4.72; found: C69.91, H4.75.
O16·C3H6O, Mw ¼ 1083.06] suitable for X-ray analysis
were grown by slowly cooling a hot chloroform/acetone
(5 ml/5 ml) solutionof 3a(5.0 mg) toambient temperature,
and a pale yellow crystal with dimensions 0.20 mm
£ 0.20 mm £ 0.05 mm was selected for intensity measure-
ments. The unit cell was monoclinic with the space
groupP21/c. LatticeconstantswithZ ¼ 4,Dcalcd ¼ 1.376 -
g cm23
,
m ¼ 0.890 mm21
,
F(000) ¼ 2272 and
2umax ¼ 136.58 were a ¼ 12.2930(3), b ¼ 25.1174(8),
˚
c ¼ 17.6902(5) A, a ¼ 908, b ¼ 105.4385(14)8, g ¼ 908
3
˚
and V ¼ 5265.1(3) A . In total, 58,369 reflections were
collected, of which 9484 reflections were independent
(Rint ¼ 0.1305). The structure was refined to final
R1 ¼ 0.1698for6910data[I . 2s(I)]with725parameters
and wR2 ¼ 0.3949 for all data, goodness-of-fit on
F 2 ¼ 1.060 and residual electron density max/
C o m po u n d 3c: Pale yellow powder. m.p. ¼ .2508C
(dec.). IRn 3247, 3058, 3027, 2931, 1602, 1494, 1446,
1365, 1301 cm21. 1H NMR (CDCl3) d 2.67, 2.74 (each s,
6H, CH3 £ 4), 6.02 and 6.38 (each s, 2H, . CHZ £ 4),
7.22–7.40 (m, 20H, ArH £ 20), 9.42 and 9.53 (each s, 2H,
OH £ 4), 9.61 (br s, 4H, OH £ 4), 16.11 and 16.40 (each
s, 2H, OH £ 4). 13C NMR (CDCl3) d 33.5 ( £ 2), 33.7
( £ 2), 34.7 ( £ 2), 35.2 ( £ 2), 107.0 ( £ 2), 107.3 ( £ 2),
107.4 ( £ 2), 108.1 ( £ 2), 108.3 ( £ 2), 109.0 ( £ 2), 126.6
( £ 2), 127.1 ( £ 2), 127.2 ( £ 4), 127.3 ( £ 4), 128.4
( £ 4), 128.7 ( £ 4), 136.4 ( £ 2), 136.7 ( £ 2), 157.9
( £ 2), 158.4 ( £ 2), 159.9 ( £ 2), 160.2 ( £ 2), 161.5
( £ 2), 161.9 ( £ 2), 206.3 ( £ 4). FAB-MS (m/z) 1025
(M þ H)þ. Anal. calcd for C60H48O16: C70.30, H4.72;
found: C70.27, H5.04.
min ¼ 0.713/20.467 eA23. Data collection, cell refine-
˚
ment and data reduction were conducted using the
CrystalStructure (12) crystallographic software package.
The structure was solved by direct methods using the
program SHELXS-97 (13) and refined by full-matrix least
squares methods on F 2 using SHELXL-97 (13). All non-
hydrogenatoms were refinedanisotropicallyexcept for the
solventmolecule.Thepositionsofallhydrogenatomswere
calculated geometrically and refined as a riding model.
Crystallographic data are deposited at the Cambridge
Crystallographic Data Centre (CCDC; No. 943290). The
data can be obtained free of charge from the CCDC via
http://www.ccdc.cam.ac.uk/data_request/cif.
C o m po u n d 3d: Pale yellow powder. m.p. ¼ .2508C
(dec.). IRn 3232, 3060, 3027, 2929, 1602, 1494, 1446,
1365, 1301 cm21. 1H NMR (CDCl3) d 2.61, 2.67, 2.75 and
2.81 (each s, 3H, CH3 £ 4), 5.98 and 6.00 (each s, 1H,
. CHZ £ 2), 6.42 (br s, 1H, . CHZ), 7.26–7.37 (m,
20H, ArH £ 20), 9.54, 9.56, 9.60 and 9.66 (each s, 1H,
OH £ 4), 9.98 (br s, 4H, OH £ 4), 16.13, 16.15, 16.48 and
16.53 (each s, 1H, OH £ 4). 13C NMR (CDCl3) d 33.36,
33.39, 33.48, 33.56, 34.33, 34.48, 35.67, 35.72, 107.08,
107.21, 107.28, 107.36, 107.39, 107.49, 107.83, 108.22,
108.24, 108.37, 108.96, 109.30, 126.46, 126.49, 126.75,
126.78, 126.97 ( £ 4), 127.02 ( £ 4), 128.15 ( £ 2), 128.19
( £ 2), 128.34 ( £ 2), 128.39 ( £ 2), 136.25, 136.40,
136.63, 136.73, 157.69, 157.72, 158.09 ( £ 2), 159.66,
159.81, 160.16, 160.19, 161.30, 161.35, 161.89, 162.21,
206.09, 206.22, 206.27, 206.32. FAB-MS (m/z) 1025
(M þ H)þ. Anal. calcd for C60H48O16·H2O: C69.09,
H4.83; found: C69.26, H4.87.
Supporting Information
1
1 3
H a n d C N M R a n d U V – v i s s p e c t r a d a t a : a v a i l ab l e o n
t h e a r t i c l e w e b p a g e .
References
( 1 ) R e v i e w s : ( a ) G u t s c h e , C . D . , E d . Calixarenes; The Royal
Society of Chemistry: Cambridge, 1989; (b) Mandolini, L.,
Ungaro, R., Eds. Calixarenes in Action; Imperial College
Press: London, 2000; (c) Gregg J.L., Robin D.R.,
Aravamudan S.G., Eds. Calixarenes for Separations; ACS
Symposium Series, Vol. 757, American Chemical Society,
Oxford University Press: Washington, DC, 2000; (d) Asfai,
¨
Z., Bohmer, V., Harrowfield, J.M., Vicens, J., Eds.
Calixarenes 2001; Kluwer Academic Publishers: Dor-
drecht, 2001.
( 2 ) ( a ) Z i n k e , A . ; Z i e g l e r , E . Ber. 1941, B74, 1729–1805; (b)
Zinke, A.; Ziegler, E. Ber. 1944, 77, 264–272.
( 3 ) ( a ) N i e d e r l , J . B . ; V o g e l , H . J . J. Am. Chem. Soc. 1940, 62,
2512–2514; (b) Niederl, J.B.; McCoy, J.S. J. Am. Chem.
¨
Soc. 1943, 65, 629–631; (c) Hogberg, A.G.S. J. Org. Chem.
5.1 X-ray crystallographic structure determination
¨
1980, 45, 4498–4500; (d) Hogberg, A.G.S. J. Am. Chem.
X - r a y d i f f r a c t i o n d a t a f o r 3a were collected on a Rigaku
R-axis Rapid diffractometer with Cu Ka radiation
Soc. 1980, 102, 6046–6050; (e) Reference (1c), pp 325–
340; (f) Barrett, G.M.A.; Braddock, D.C.; Henschke, J.P.;
Walker, E.R. J. Chem. Soc. Perkin Trans. 1999, 1, 873–878.
˚
(l ¼ 1.54187 A) at 93 K. Single crystals of 3a [C60H48-

Supramolecular Chemistry
5 3
( 4 ) ( a ) G e r k e n s m e i s e r , T . ; A g e na , C . ; I w a n e k, W . ; F r o l i c h , K . ;
( 7 ) ( a ) R e f e r e n c e ( 1 a ) , p 8 8 ; ( b ) R e f e r e n c e ( 1 c ) , p 1 5 ; ( c )
R e f e r e n c e ( 1 d ) , p 2.
¨
K o t i l a , S . ; N a t h e r , C . ; M a t t a y , J . Z. Naturforsch. Teil B.
2001, 56, 1063–1073; (b) Bohmer, V. Angew. Chem. Int.
( 8 ) ( a ) R e f e r e n c e ( 1 a ) , p p 1 4 9 – 1 8 1 ; ( b ) R e f e r e nc e ( 1 b ) ,
p p 3 7 – 6 1 ; ( c ) A n d r e e t t i, G . D . ; U n g a r o, R . ; P o c h i n i , A .
J. Chem. Soc. Chem. Commun. 1979, 1005–1007.
( 9 ) ( a ) R e f e r e n c e ( 1 a ) , p p 1 4 9 – 1 8 1 ; ( b ) R e f e r e nc e ( 1 b ) ,
p p 6 2 – 8 4 ; ( c ) R e f e r e n c e ( 1 c ) , p p 4 0 7 – 4 2 0 .
( 1 0 ) ( a ) R e f e r e n c e ( 1 b ) , p p 1 5 5 – 1 5 8 ; ( b ) R e f e r e n c e ( 1 d ) ,
p p 4 7 6 – 4 9 5 .
( 1 1 ) M o r oh a s h i , N . ; N o j i , S . ; N a k a y a m a , H . ; K u d o, Y . ; T a n a k a ,
S . ; K a b u t o , C . ; H a t t o r i , T . Org. Lett. 2011, 13 (13),
3292–3295.
¨
Ed. Engl. 1995, 34, 713–745; (c) Yan, C.; Chen, W.; Chen,
J.; Jiang, T.; Yao, Y. Tetrahedron 2007, 63, 9614–9620.
( 5 ) ( a ) C o m m e t t i , G . ; D a l c a n a l e , E . ; D u V o se l, A . ; L e v e l u t , A .
J. Chem. Soc. Chem. Commun. 1990, 163–165; (b) Tanaka,
Y.; Miyachi, M.; Kobuke, Y. Angew. Chem. Int. Ed. 1999,
38, 504–506; (c) Yan, C.; Chen, W.; Chen, J.; Jiang, T.;
Yao, Y. Tetrahedron 2007, 63, 9614–9620.
( 6 ) ( a ) S a t o S . ; I i j i m a H . ; H a g a N . ; O s o no K . ; M i z u g u c h i H . ;
K i j im a T .; O n o d e r a J . - I . Supramol. Chem. 2006, 18, 39–46;
(b) Sato S.; Yashiro A.; Tsushima N.; Hosaka K. Chem.
Pharm. Bull. 2008, 56, 1173–1176.
( 1 2 ) R i g a k u /M S C , CrystalStructure, version 3.6.0 Rigaku/MSC:
The Woodlands, TX, 2003;.
( 1 3 ) S h e l d r i c k, G . M . Acta. Cryst. A 2008, 64, 112–122.