Solvent-dependent conformational and fluorescence change of an N-phenylbenzohydroxamic acid derivative bearing two pyrene moieties

Article abstract of DOI:10.1016/j.tet.2012.02.012

The conformation of N-phenylbenzohydroxamic acid has been reported to change depending on the solvent properties. Here, we newly synthesized N-phenylbenzohydroxamic acid derivative, which contains two pyrene moieties separated from the phenyl rings by ethylene linkers. It showed solvent-dependent conformational change, and its fluorescence was also solvent-dependent, that is, only monomer fluorescence of pyrene was observed in DMSO or DMF, whereas the excimer fluorescence was observed in CH₂Cl₂ or CHCl ₃. Thus, the structural characteristics could be converted to fluorescence change as output, which would be a good candidate as a fluorescent sensor.

Full text of DOI:10.1016/j.tet.2012.02.012

Tetrahedron 68 (2012) 2778e2783
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Solvent-dependent conformational and fluorescence change of an
N-phenylbenzohydroxamic acid derivative bearing two pyrene moieties
,
c
d
b
a,
*
Misae Kanai a, Tomoya Hirano b , Isao Azumaya , Iwao Okamoto , Hiroyuki Kagechika , Aya Tanatani
*
a Department of Chemistry, Faculty of Science, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan
b Institute of Biomaterials and Bioengineering, Graduate School of Biomedical Science, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku,
Tokyo 101-0062, Japan
c Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan
d Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194-8543, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 15 January 2012
Received in revised form 5 February 2012
Accepted 6 February 2012
Available online 11 February 2012
The conformation of N-phenylbenzohydroxamic acid has been reported to change depending on the
solvent properties. Here, we newly synthesized N-phenylbenzohydroxamic acid derivative, which con-
tains two pyrene moieties separated from the phenyl rings by ethylene linkers. It showed solvent-
dependent conformational change, and its fluorescence was also solvent-dependent, that is, only
monomer fluorescence of pyrene was observed in DMSO or DMF, whereas the excimer fluorescence was
observed in CH2Cl2 or CHCl3. Thus, the structural characteristics could be converted to fluorescence
change as output, which would be a good candidate as a fluorescent sensor.
Keywords:
Fluorescence spectroscopy
Pyrene
Ó 2012 Elsevier Ltd. All rights reserved.
Aromatic amide
Conformational alteration
1. Introduction
while N-methylbenzanilide (2a) exists in cis form in the crystal and
predominantly in cis form (98.3% in CD2Cl2 at 198 K) in solution
A molecular switch is a molecular system that can be reversibly
interconverted between two or more stable states when exposed to
a stimulus, such as light, electrical potential or chemical reaction.1 A
number of polymers or supramolecules that change their three-
dimensional structures and functions in response to external
stimuli have been developed.2 There are also various switching
systems based on structural change of small molecules, such as
cyclization of 1,2-diarylethenes and isomerization of azobenzenes.3
Generally, the energy barriers between the two different structures
are sufficiently high that the structures can be clearly distinguished,
though in some cases, interconversion between conformers with
a rather small energy barrier has been used. When the in-
terconversion between the conformers occurs in response to some
chemical interaction or change of environmental conditions, and
results in a change of the measurable properties, the molecule has
potential utility as a sensor molecule.
(Fig. 1).4 The cis conformational preference is general for various N-
methylated amides, and also for N-methylated thioamides, ami-
dines, ureas, thioureas, and guanidines, and can be applied to the
We have previously reported the conformational alteration of
aromatic amides caused by N-methylation. Thus, benzanilide (1a)
exists in trans form both in the crystal and in various solvents,
* Corresponding authors. Tel.: þ81 3 5280 8128; fax: þ81 3 5280 8127 (T.H.); tel./
fax: þ81 3 5978 2716 (A.T.); e-mail addresses: hiraomc@tmd.ac.jp (T. Hirano), ta-
natani.aya@ocha.ac.jp (A. Tanatani).
Fig. 1. Conformational alteration of aromatic amides by N-methylation.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.02.012

M. Kanai et al. / Tetrahedron 68 (2012) 2778e2783
2779
construction of aromatic molecules with unique three-dimensional
structures.5
In addition, we also found that N-phenylbenzohydroxamic acid
(3, N-hydroxy derivative of benzanilide) changed its conformation
solvent-dependently (Fig. 2); it existed predominantly in cis form
(>98%) in CD2Cl2, while the percentage of the cis isomer decreased
to 49% in methanol-d4, and the trans conformer was predominant
(77%) in acetone-d6.6,7 Interestingly, two types of crystal structures
were obtained depending on the recrystallization solvent, and the
structure corresponded to that of the major conformer in each
solvent. These results indicated that the N-hydroxybenzanilide
structure could be used as a solvent-dependent switch. In this
paper, we studied the applicability of this structural characteristic
to the development of fluorescent sensor by introduction of fluo-
rophores to this structure.
Fig. 3. Structure of N-phenylbenzohydroxamic acid derivative 4.
phenylbenzohydroxamic acid (9) in 56% yield. After protection
(88%) of the hydroxy group of 9, Sonogashira reaction of compound
10 with 1-ethynylpyrene (7) in the presence of copper(I) iodide and
PdCl2(PPh3)2 gave the bis(pyrenyl) compound 11 in 87% yield.12
Finally, hydrogenation (52%) followed by deprotection (89%) gave
compound 4.
The conformation of compound 4 was examined in various
solvents by means of 1H NMR spectroscopy (Fig. 4). In order to
distinguish the solvent-dependent change in the ratio of the cis/
trans conformers from simple solvent effects on the chemical shifts,
the 1H NMR spectra of methyl 4-[2-(1-pyrenyl)ethyl]benzoate
(13)10 were also measured. The signals of the aromatic protons
ortho (marked by closed circle in Fig. 4gel) to the ester group of 13
were only slightly shifted (7.9e8.0 ppm) due to the solvent effect.
The 1H NMR spectra of compound 4 at 298 K showed one set of
signals in each solvent (Fig. 4aef), while there were two sets of
signals, corresponding to trans and cis conformers of 4, at 193 K in
acetone-d6 and THF-d8 and at 223 K in DMF-d7 (Fig. S1). These
signals could be assigned to individual conformers by comparison
with the reported chemical shifts of N-phenylbenzohydroxamic
acid (3). The ratio of the cis isomer is 50% in acetone-d6 (193 K), 28%
in THF-d8(193 K), and 21% in DMF-d7 (223 K) (Table 1). The 1H NMR
spectra of 4 in CD2Cl2 and CDCl3 showed only one set of signals
even at 183 K or 223 K, respectively (Fig. S1); that is, the chemical
shifts of the protons on the two phenyl groups were observed only
at higher field (7.3 ppm for the protons at the ortho position to the
carbonyl groups, marked by closed circle, and around 7.1 ppm for
others, marked by open diamond, Fig. 4a and b). Like N-phenyl-
benzohydroxamic acid (3), compound 4 existed predominantly in
cis form (>99%) in CD2Cl2 and CDCl3. In DMSO-d6, the proton sig-
nals of the phenyl rings were observed at lower field at 298 K, being
similar to those in THF-d8. Therefore, compound 4 appears to exist
mainly in trans form in these solvents.
The fluorescence spectra of compound 4 in various solvents
were examined (Fig. 5 and Table 1). Compound 4 emitted some
fluorescence in every solvent examined, and the spectral shape
varied depending on the solvent. In DMSO and DMF, compound 4
showed similar spectra to those of the control compound 13, which
has one pyrene moiety (Fig. S2); that is, vibrational fluorescence at
370e390 nm, which could correspond to the monomer fluores-
cence of pyrene, was strong, while little excimer fluorescence at
around 480 nm was observed (Fig. 5a and b). Excimer fluorescence
appeared weakly in THF, was a little increased in acetone, and be-
came stronger intensity in CH2Cl2 and CHCl3 (Fig. 5cef). The ratio of
the fluorescence intensity at 470 nm to that at 398 nm was 0.05,
0.05, 0.07, 0.15, 0.22, and 0.27 for DMSO, DMF, THF, acetone, CHCl3,
and CH2Cl2, respectively (Table 1). The spectral shape in each sol-
vent examined did not change in the concentration range from
Fig. 2. Solvent-dependent conformational change of N-phenylbenzohydroxamic acid 3.
2. Results
Pyrene is a polycyclic aromatic molecule with fluorescence at
370e390 nm; however, when the excimer is formed, it exhibits
fluorescence with longer wavelength (ca. 480 nm).8,9 In our pre-
vious work, we showed that the conformational difference be-
tween aromatic secondary and tertiary amides could be visualized
by the introduction of two pyrene units, at the para position to the
amide group on each aryl ring, via an ethylene linker; that is,
monomer fluorescence of pyrene was observed in the extended
trans-form of the benzanilide moiety (1b), while the folded cis-
form of N-methylbenzanilide (2b) showed excimer fluorescence
(Fig. 1).10 Based on that work, we designed compound 4 as a can-
didate molecule with solvent-dependent fluorescence, in which the
excimer fluorescence is expected to be observed only when the
compound exists in cis conformation, like N-methylbenzanilide
(2b), while monomer fluorescence would be major in the trans
conformation (Fig. 3).
The synthesis of compound 4 is illustrated in Scheme 1. 1-
Bromopyrene (5) was reacted with trimethylsilylacetylene by
means of the Sonogashira coupling reaction (99%), followed by
deprotection (57%) with potassium fluoride to give 1-
ethynylpyrene (7).11 4-Iodobenzoic acid (8) was converted to the
acid chloride, which was reacted with N-(4-iodophenyl)hydroxyl-
amine in the presence of pyridine to afford 4,40-diiodo-N-
1.25
mM to 5.0 mM, and therefore intermolecular interaction would
not be significant under these conditions.

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M. Kanai et al. / Tetrahedron 68 (2012) 2778e2783
Scheme 1. Synthesis of compound 4.
Fig. 4. 1H NMR spectra (aromatic region, 6.9e8.6 ppm) of compound 4 (aef) and methyl 4-[2-(1-pyrenyl)ethyl]benzoate (13, gel) in various solvents at 298 K. The marked signals
are due to protons ortho to the amide carbonyl group (closed circle) or nitrogen atom (open diamond).

M. Kanai et al. / Tetrahedron 68 (2012) 2778e2783
2781
Table 1
These data suggested that compound
4
shows solvent-
Fluorescence properties of compound 4 in various solvents
dependent fluorescence, i.e., the ratio of the excimer fluorescence
was increased in less polar solvents such as CH2Cl2 and CHCl3,
whereas monomer fluorescence was observed almost exclusively in
polar solvents, such as DMSO and DMF. These characteristics are
presumably derived from the solvent-dependent cis/trans struc-
tural alteration deduced from the NMR study (Fig. 4, Table 1).
Solvent
Ratio of cis/transa
Ratio of excimer/monomer
fluorescence intensityc
DMSO
DMF
THF
Acetone
CHCl3
CH2Cl2
(Trans major)b
Cis 21%
Cis 28%
Cis 50%
Cis only
0.05
0.05
0.07
0.15
0.22
0.27
Cis only
3. Discussion
a
The ratio was determined by means of 1H NMR spectroscopy in deuterated
solvents. Temperature was 183 K for CD2Cl2, 193 K for acetone-d6 and THF-d8, and
223 K for DMF-d7 and CDCl3.
N-Phenylbenzohydroxamic acid (3) shows solvent-dependent
conformational change, and exists as the cis conformer in CD2Cl2,
while the ratio of the cis conformer is decreased in more polar
solvents, such as acetone-d6 and methanol-d4. Compound 4, de-
veloped in this study, showed similar structural property to com-
pound 3 (Table 1). In fluorescence spectra, compound 4 emitted
little excimer fluorescence in polar solvents such as DMF and THF,
b
The trans conformer is major, although the cis/trans ratio could not be
determined.
c
Ratio of fluorescence intensities at 470 nm/398 nm for 5 mM of compound 4 (lex:
345 nm).
Fig. 5. Fluorescence spectra of compound 4 [5 (black line), 2.5 (blue dashed line), and 1.25 (red dashed line) mM] in various solvents at 293 K (lex: 345 nm).

2782
M. Kanai et al. / Tetrahedron 68 (2012) 2778e2783
in which its major conformer was determined to be the trans form
by NMR study. On the other hand, compound 4 emitted excimer
fluorescence in less polar CH2Cl2 and CHCl3, in which it existed
predominantly as the cis conformer. Excimer fluorescence was
observed at an intermediate level in acetone, in which the ratio of
cis to trans conformer was 1:1 as determined from NMR study.
Thus, excimer fluorescence of compound 4 was increased under
conditions of cis conformational preference, which indicates that
the introduction of the two pyrene units makes it possible to sense
the solvent-dependent conformational change of N-phenyl-
benzohydroxamic acid in terms of fluorescence change.
The solvent-dependent fluorescence property of compound 4
resulted from the change of the ratio of cis and trans conformers in
equilibrium. The energy barrier between the two conformers was
10.7 kcal/mol in acetone-d6, as determined by temperature-
dependent 1H NMR study. Typical molecular switches must have
a sufficiently high energy barrier to allow two switchable states to
be distinguished, but the present model shows that an equilibrium
change with a relatively low energy barrier can be employed for
switching in an appropriate scaffold.
0.064 mmol), and triethylamine (30 ml) was heated at 70 ꢀC in
a sealed tube under argon for 23 h. After evaporation, the residue
was purified by silica gel column chromatography (eluent: n-hex-
ane) to afford 6 (316 mg, 1.06 mmol, 99%). 1H NMR (CDCl3,
400 MHz)
d
8.57 (1H, d, J¼8.8 Hz), 8.12 (8H, m), 0.39 (9H, s).
5.2. Synthesis of compound 7
Potassium fluoride (74 mg, 1.27 mmol) was added to a solution
of 6 (102 mg, 0.34 mmol) in THF (23 ml) and methanol (23 ml). The
reaction mixture was stirred at room temperature for 65 h. After
evaporation, the residue was purified by silica gel column chro-
matography (eluent: n-hexane/ethyl acetate¼8:1) to afford 7
(44 mg, 0.19 mmol, 57%) as brown powder. 1H NMR (CDCl3,
600 MHz)
d
8.58 (1H, d, J¼9.1 Hz), 8.21 (1H, d, J¼7.6 Hz), 8.18 (1H, d,
J¼8.6 Hz), 8.17 (1H, d, J¼8.0 Hz), 8.16 (1H, d, J¼9.1 Hz), 8.08 (1H, d,
J¼7.9 Hz), 8.08 (1H, d, J¼8.9 Hz), 8.02 (1H, t, J¼7.6 Hz), 8.01 (1H, d,
J¼8.9 Hz) , 3.65 (1H, s); 13C NMR (CDCl3, 150 MHz)
d 132.6, 131.7,
131.3, 131.1, 130.3, 128.7, 128.5, 127.3, 126.4, 125.8, 125.8, 125.4,
124.5, 124.4, 124.3, 116.6, 82.9, 82.7.
In our previous studies on an N-methylbenzanilide derivative
with two pyrene units (2b), the ratio of excimer fluorescence (at
470 nm) to monomer fluorescence (at 398 nm) in CH2Cl2 was 0.74. A
much higher ratio (3.67) was observed with the (cis,cis) folded N,N0-
dimethyl-N,N0-diphenylurea structure bearing two pyrenes at the
para position on each aryl ring via ethylene linkers.10 Compared with
these N-methylated amide and urea compounds, the excimer fluo-
rescence of compound 4 was not so marked, and its monomer fluo-
rescence was still moderate even in CH2Cl2 and CHCl3, in which only
the cis conformer was detected by NMR study. The difference pre-
sumably arises from the folded structure of the cis conformers. In the
crystal structures, the dihedral angle between the two phenyl rings is
70ꢀ for the conformer of N-phenylbenzohydroxamic acid (3), while it
is 60ꢀ for N-methylbenzanilide (2a), and 35ꢀ for N,N0-dimethyl-N,N0-
diphenylurea.13 Thus, a smaller dihedral angle between the two
phenyl rings permits better orientation of the two pyrene moieties
for intramolecular excimer formation. By optimization of the linker
group between N-phenylbenzohydroxamic acid and the two pyrene
units, and those substituent sites, it may be possible to develop
fluorescent derivatives of N-phenylbenzohydroxamic acid with
larger solvent-dependent fluorescence change, and such molecule
could be a good candidate as a fluorescent sensor of solvent property.
5.3. Synthesis of compound 9
One drop of DMF was added to a solution of 4-iodobenzoic acid
(8, 228 mg, 0.92 mmol) in thionyl chloride (4 ml). The reaction
mixture was stirred at room temperature for 3.5 h, then evapo-
rated. The residue was taken up in anhydrous toluene (10 ml) and
again evaporated. The resultant residue was dissolved in anhydrous
pyridine (3 ml). A solution of 4-iodophenylhydroxylamine (184 mg,
0.78 mmol) in anhydrous toluene (7 ml) was added to the above
solution, and the reaction mixture was stirred at room temperature
for 12 h. Methanol and water were added, and the whole was
extracted with ethyl acetate. The organic layer was washed with
2 M hydrochloric acid, and brine, dried over MgSO4, and evapo-
rated. The residue was suspended in CH2Cl2 and collected by fil-
tration to give 9 (204 mg, 0.44 mmol, 56%). Pale brown plates
(AcOEt); mp 197.8e200.9 ꢀC (dec); 1H NMR (THF-d8, 600 MHz)
d
9.72 (1H, s), 7.77 (2H, d, J¼8.4 Hz), 7.67 (2H, d, J¼8.9 Hz), 7.49 (2H,
d, J¼8.7 Hz), 7.46 (2H, d, J¼8.3 Hz); 13C NMR (THF-d8, 150 MHz)
d
168.1, 143.2, 138.5, 138.0, 136.2, 131.6, 123.6, 97.8, 89.5; HRMS
(ESIþ) calcd for C13H10I2NO2 (MþHþ): 465.8795; found: 465.8804;
IR 3161.7, 1606.4, 1583.3 cmꢁ1
.
4. Conclusion
5.4. Synthesis of compound 10
In conclusion, we designed and synthesized the N-phenyl-
benzohydroxamic acid derivative (4), bearing two pyrene mole-
cules on the phenyl rings via ethylene linkers, and showed that the
solvent-dependent conformational alteration of the N-phenyl-
benzohydroxamic acid moiety is reflected in a moderate change of
the fluorescence properties. These results demonstrate that the
structural characteristics of N-hydroxybenzanilide can be applied
as a core structure of fluorescent sensor for solvent property. To
date, several types of aromatic amides, which exhibit conforma-
tional change in response to various types of environmental change
such as pH and redox state, have been reported.14 By utilizing the
similar strategy shown in this paper, they could be transformed to
fluorescent sensors for various environmental conditions, and such
work is in progress.
3,4-Dihydro-2H-pyran (0.09 ml) was added to a mixture of p-
toluenesulfonic acid monohydrate (8 mg, 0.04 mmol) and
9
(204 mg, 0.44 mmol) in CH2Cl2 (40 ml) under an Ar atmosphere,
and the mixture was stirred for 4 h at room temperature. The
mixture was diluted with CH2Cl2, washed with water, dried over
MgSO4, and evaporated. The residue was purified by silica gel col-
umn chromatography (eluent: acetone/methylene chloride¼1:40)
to afford 10 (211 mg, 0.38 mmol, 88%). Colorless needles (AcOEt);
mp 157.2e157.9 ꢀC; 1H NMR (CDCl3, 600 MHz)
d 7.66 (4H, m), 7.30
(2H, d, J¼8.3 Hz), 7.18 (2H, d, J¼8.6 Hz), 5.10 (1H, s), 3.39 (2H, m),
1.70 (3H, m), 1.54 (2H, m), 1.46 (1H, m); 13C NMR (CDCl3, 150 MHz)
d
167.8, 140.9, 138.3, 137.4, 133.9, 130.6, 128.0, 102.6, 97.7, 92.9, 62.7,
28.4, 24.9, 18.5; HRMS (ESIþ) calcd for C18H17I2NNaO3 (MþNaþ):
571.9190; found: 571.9180; IR 1681.6, 1582.3 cmꢁ1
.
5. Experimental section
5.5. Synthesis of compound 11
5.1. Synthesis of compound 6
A solution of 7 (117 mg, 0.52 mmol) in triethylamine (4.5 ml)
and THF (2 ml) was added to a mixture of 10 (94 mg, 0.17 mmol),
PdCl2(PPh3)2 (25 mg, 0.036 mmol), and CuI (14 mg, 0.072 mmol) in
triethylamine (2 ml) and THF (2.5 ml) at 65 ꢀC under an Ar
A mixture of 1-bromopyrene (5, 301 mg, 1.07 mmol), trime-
thylsilylacetylene (1.4 ml, 2.0 mmol), PdCl2(PPh3)2 (45 mg,

M. Kanai et al. / Tetrahedron 68 (2012) 2778e2783
2783
atmosphere. The reaction mixture was stirred at 65 ꢀC for 3 h. After
evaporation, the residue was purified by silica gel column chro-
matography (eluent: methylene chloride) to afford 11 (112 mg,
J¼7.8 Hz), 3.11 (4H, m); 13C NMR (THF-d8, 150 MHz)
d
167.9, 145.5,
141.7, 140.4, 137.1, 137.0, 134.4, 132.8, 132.3, 131.4, 131.3, 130.3, 129.9,
129.6, 128.9, 128.6, 128.6, 128.5, 128.5, 128.4, 127.8, 127.7, 126.9,
126.9, 126.3, 126.3, 126.3, 126.0, 126.0, 125.9, 125.9, 125.9, 125.8,
124.4, 124.4, 123.6, 39.0, 38.7, 36.6, 36.3; HRMS (ESIþ) calcd for
C49H35NNaO2 (MþNaþ): 692.2560; found: 692.2587; IR: 3131.8,
0.15 mmol, 87%) as brownish oil. 1H NMR (CDCl3, 600 MHz)
d 8.64
(1H, d, J¼9.1 Hz), 8.63 (1H, d, J¼9.1 Hz), 8.22 (2H, d, J¼7.6 Hz), 8.20
(2H, d, J¼7.9 Hz), 8.19 (2H, d, J¼8.0 Hz), 8.18 (2H, d, J¼9.1 Hz), 8.13
(2H, dd, J¼7.9, 1.3 Hz), 8.10 (2H, dd, J¼8.9, 1.3 Hz), 8.05 (2H, d,
J¼8.1 Hz), 8.03 (2H, t, J¼7.5 Hz), 7.72 (2H, d, J¼8.5 Hz), 7.70 (4H, d,
J¼9.1 Hz), 7.55 (2H, d, J¼8.4 Hz), 5.29 (1H, br), 3.58 (1H, m), 3.48
(1H, m), 1.89 (1H, m), 1.80 (2H, m),1.63 (1H, m), 1.55 (2H, m); 13C
3046.0, 1603.5, 1588.1, 1565.0 cmꢁ1
.
Acknowledgements
NMR (CDCl3, 150 MHz) d 168.0, 141.2, 134.3, 132.5, 132.2, 132.1, 131.7,
The work described in this paper was partially supported by
Grants-in-Aid for Scientific Research from The Ministry of Educa-
tion, Science, Sports and Culture, Japan (#22790106 to T.H.). A.T.
also thanks The Asahi Glass Foundation for financial support. T.H.
also thanks the Astellas Foundation and Takeda Science
Foundation.
131.6, 131.4, 131.2, 131.2, 129.9, 129.8, 129.3, 128.7, 128.6, 128.5,
128.5, 127.4, 126.5, 126.4, 126.3, 126.2, 125.9, 125.9, 125.8, 125.6,
125.5, 124.7, 124.7, 124.6, 124.5, 124.4, 122.9, 117.5, 117.3, 102.7, 94.5,
94.5, 91.0, 90.0, 62.8, 28.5, 25.1, 18.6; HRMS (ESIþ) calcd for
C54H36NO3 (MþHþ): 746.2690; found: 746.2696; IR: 1654.6, 1623.8,
1601.6, 1583.3 cmꢁ1
.
Supplementary data
5.6. Synthesis of compound 12
Temperature-dependent 1H NMR spectra of compound 4 in
various solvents, The fluorescence spectra of compound 13 in var-
ious solvents, and 1H and 13C NMR data of synthetic intermediates.
Supplementary data related to this article can be found in the
online version, at doi:10.1016/j.tet.2012.02.012.
Palladiumhydroxideoncarbon(88 mg)wasaddedtoa solutionof
11 (204 mg, 0.27 mmol) in ethyl acetate (22 ml) at room temperature
under an Ar atmosphere. The reaction mixture was stirred for 3 h
under a hydrogen atmosphere. After filtration, the residue was dis-
solved with CH2Cl2 and water. The organic layer was washed with
brine, driedwith MgSO4, andevaporated. The residuewas purified by
silica gel column chromatography (eluent: methylene chloride, then
n-hexane/ethyl acetate¼5:2) to afford 12 (106 mg, 0.14 mmol, 52%).
References and notes
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(2H, d, J¼9.3 Hz), 8.16 (2H, d, J¼7.9 Hz), 8.15 (2H, d, J¼8.0 Hz), 8.09
(2H, d, J¼9.2 Hz), 8.03 (1H, d, J¼7.7 Hz), 8.03 (1H, d, J¼7.7 Hz), 8.00
(4H, m), 7.98 (2H, t, J¼7.6 Hz), 7.69 (2H, d, J¼7.7 Hz), 7.47 (2H, d,
J¼8.0 Hz), 7.29 (2H, d, J¼8.2 Hz), 7.10 (2H, d, J¼7.6 Hz), 7.09 (2H, d,
J¼7.7 Hz), 5.26 (1H, s), 3.59 (4H, m), 3.56 (1H, m), 3.40 (1H, m), 3.12
(4H, m),1.84 (1H, m),1.75 (2H, m),1.58 (2H, m),1.45 (1H, m); 13C NMR
(CDCl3,150 MHz) d 168.6,144.5,141.4,139.8,135.5,135.4,132.5,131.5,
131.0, 131.0, 130.1, 130.1, 129.3, 129.3, 129.2, 129.2, 128.7, 128.7, 128.4,
128.2, 127.6, 127.6, 127.6, 127.5, 127.5, 127.3, 126.9, 126.0, 125.2, 125.1,
124.9,124.8,124.8,123.2,123.2,102.0, 62.4, 37.9, 37.6, 35.3, 35.3, 28.5,
25.2, 18.5; HRMS (ESIþ) calcd for C54H43NNaO3 (MþNaþ): 776.3135;
5. Tanatani, A.; Yamaguchi, K.; Azumaya, I.; Fukutomi, R.; Shudo, K.; Kagechika, H.
J. Am. Chem. Soc. 1998, 120, 6433 and references therein.
6. Yamasaki, R.; Tanatani, A.; Azumaya, I.; Masu, H.; Yamaguchi, K.; Kagechika, H.
Cryst. Growth Des. 2006, 6, 2007.
7. (a) Kakkar, R.; Grover, R.; Chadha, P. Org. Biomol. Chem. 2003, 1, 2200; (b) García,
B.; Ibeas, S.; Munoz, A.; Leal, M.; Ghinami, C.; Secco, F.; Venturini, M. Inorg.
Chem. 2003, 42, 5434.
found: 776.3164; IR: 1646.0, 1603.5 cmꢁ1
.
8. Birks, J. B. Photophysics of Aromatic Molecules; Wiley-InterScience: London,
1970.
5.7. Synthesis of compound 4
9. Winnik, F. M. Chem. Rev. 1993, 93, 587.
10. Hirano, T.; Osaki, T.; Fujii, S.; Komatsu, D.; Azumaya, I.; Tanatani, A.; Kagechika,
H. Tetrahedron Lett. 2009, 50, 488.
11. Hissler, M.; Harriman, A.; Khatyr, A.; Ziessel, R. Chem.dEur. J. 1999, 5, 3366.
12. Maeda, H.; Maeda, T.; Mizuno, K.; Fujimoto, K.; Shimizu, H.; Inouye, M. Chem.
dEur. J. 2006, 12, 824.
13. (a) Yamaguchi, K.; Matsumura, G.; Kagechika, H.; Azumaya, I.; Ito, Y.; Itai, A.;
Shudo, K. J. Am. Chem. Soc. 1991, 113, 5474; (b) Azumaya, I.; Kagechika, H.; Ya-
maguchi, K.; Shudo, K. Tetrahedron 1995, 51, 5277.
A mixture of 12 (54 mg, 0.07 mmol) and p-toluenesulfonic acid
monohydrate (38 mg, 0.20 mmol) in methanol (5 ml) and methy-
lene chloride (5 ml) was stirred for 5 h at room temperature. After
evaporation, the residue was suspended with methanol and filtered
to give 4 (42 mg, 0.062 mmol, 89%). Yellow plates (acetone); mp
210.3e211.2 ꢀC; 1H NMR (CDCl3, 600 MHz)
d 9.10 (1H, s), 8.23 (1H,
d, J¼9.2 Hz), 8.20 (1H, d, J¼9.2 Hz), 8.17 (1H, d, J¼7.5 Hz), 8.16 (1H,
d, J¼7.4 Hz), 8.13 (2H, d, J¼7.6 Hz), 8.09 (1H, d, J¼9.2 Hz), 8.07 (1H,
d, J¼9.2 Hz), 8.04 (2H, d, J¼7.8 Hz), 8.00 (4H, m), 7.97 (2H, t,
J¼7.6 Hz), 7.68 (2H, d, J¼7.8 Hz), 7.29 (2H, d, J¼8.2 Hz), 7.05 (2H, d,
J¼8.5 Hz), 7.01 (2H, d, J¼8.3 Hz), 7.00 (2H, d, J¼8.2 Hz), 3.58 (4H, t,
14. (a) Yamasaki, R.; Tanatani, A.; Azumaya, I.; Saito, S.; Yamaguchi, K.; Kagechika,
H. Org. Lett. 2003, 5, 1265; (b) Okamoto, I.; Nabeta, M.; Hayakawa, Y.; Morita, N.;
Takeya, T.; Masu, H.; Azumaya, I.; Tamura, O. J. Am. Chem. Soc. 2007, 129, 1892;
(c) Okamoto, I.; Yamasaki, R.; Sawamura, M.; Kato, T.; Nagayama, N.; Takeya, T.;
Tamura, O.; Masu, H.; Azumaya, I.; Yamaguchi, K.; Kagechika, H.; Tanatani, A.
Org. Lett. 2007, 9, 5545.