Syntheses of four new pyridinium phenolates with caged phenolate functionalities as chromophores for quadratic optics

Article abstract of DOI:10.1016/j.tet.2011.10.115

Semi-empirical calculations as well as our preliminary studies indicate an increase of the nonlinear response of pyridinium phenolates with the raise of their interplanar angle. Unfortunately, the tendency of previously synthesized zwitterionic compounds

Full text of DOI:10.1016/j.tet.2011.10.115

Tetrahedron 68 (2012) 628e635
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Syntheses of four new pyridinium phenolates with caged phenolate
functionalities as chromophores for quadratic optics
a
a
,
b
*
ꢀ ꢁ
Emel Ay , Helene Chaumeil , Alberto Barsella
a
ꢀ
ꢀ
Laboratoire de Chimie Organique et Bio-Organique, Universite de Haute-Alsace, Ecole Nationale Superieure de Chimie de Mulhouse, 3 bis, rue Alfred Werner,
68093 Mulhouse Cedex, France
b
ꢀ
ꢀ
Institut de Physique et de Chimie des Materiaux de Strasbourg (IPCMS), Departement d’Optique Ultrarapide et de Nanophotonique (DON), CNRS-UMR 7504,
23 rue du Loess, B.P. 43, 67034 Strasbourg Cedex 2, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 14 July 2011
Received in revised form 27 October 2011
Accepted 31 October 2011
Available online 7 November 2011
Semi-empirical calculations as well as our preliminary studies indicate an increase of the nonlinear
response of pyridinium phenolates with the raise of their interplanar angle. Unfortunately, the tendency
of previously synthesized zwitterionic compounds to form aggregates prevents their use in electro-
optical devices. In order to understand the process of aggregation and to circumvent it, the syntheses
of new pyridinium phenolates bearing alkyl chains of various length, caging the phenolate functionality,
have been achieved and are described herein.
Keywords:
Cyclophanes
Zwitterions
Ó 2011 Elsevier Ltd. All rights reserved.
Nonlinear optics
Chromophores
R3 R2
1. Introduction
1a 1b 1c 1d 1e 1f 1g
R1
R2
R3
H
H
H
H
Me Et iPr
Me Me Et iPr H Me
H Me Me
H
Me
O
O
N
Pyridinium phenolates have shown to be model pushepull
molecules with large nonlinear optical properties. These are
twisted intramolecular charge-transfer molecules, that is, in other
word, tictoïds. They are characterized by a large permanent dipole
moment in the electronic ground state. Semi-empirical calcu-
lations1e4 as well as previous work,5 indicated that increasing the
interplanar angle between the two aromatic rings could enhance
their NLO properties.
H
H
H
R3 R1
R4
1a-g
2a 2b 2c 2d 2e
Me Et iPr
Me Me Et iPr
R4
R5
H
H
N
H
R5
2a-e
Since a few years our objective is the preparation of pyridinium
phenolates with various interplanar angles and bearing (or not)
protecting groups at ortho position of the phenolate functionality
(Scheme 1). The medium-term purpose of our work is the selection
of the most promising compound with respect to its high hyper-
polarisability and solubility in order to dope polymers for the de-
velopment of promising electro-optical materials.
Until now, two series of pyridinium phenolates, sterically hin-
dered at the ortho position of the intercyclic bond, have been
synthesized. Unfortunately, the low solubilities of compounds 1aee
made their NLO characterization difficult.8 Much more reliable re-
sults were obtained with compounds 2aee in which two tert-butyl
Scheme 1. Zwitterionic compounds previously synthesized.6,7
groups are anchored at the ortho positions of the phenolate ring.5
Actually, tert-butyl groups are known to notably reduce the for-
mation of aggregates. In addition, the enhancement of the molec-
ular mass led to a better solubility of the corresponding tictoïds in
organic solvents. Unfortunately, the solubilities obtained are not yet
sufficient and aggregation is still a persistent phenomenon, which
precludes a potential use in integrated optical devises. In order to
circumvent these two main drawbacks and to understand the
process of aggregation better, aliphatic chains of various lengths
were linked, via ether functions, at both ortho positions of the
phenolate ring. A restricted torsion angle was obtained by in-
troduction of two methyl groups at the meta position of the pyri-
dine ring, leading to a twist angle of about 45ꢀ as for 2c.5 The
* Corresponding author. Tel.: þ33 389336864; fax: þ33 389336875; e-mail
address: helene.chaumeil@uha.fr (H. Chaumeil).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.10.115

E. Ay et al. / Tetrahedron 68 (2012) 628e635
629
synthesis of four new betaine chromophores having these last
mentioned characteristics is described herein.
conditions, afforded the desired cyclophanes 8aed. Despite a me-
ticulous optimisation of the reaction conditions, the cyclophanes
were obtained mixed with by-products (i.e., 25% of various mon-
osubstituted anisoles and about 20% of dimer 9) (Scheme 3).
Cyclophanes 8aed were subsequently purified by flash chroma-
tography and recovered in yields ranged between 15 and 43% (Table
1). Finally, they were readily brominated into 4-bromoanisoles
10aed, using NBS.
2. Results and discussion
2.1. Syntheses of bromocyclophanes 10aed
In a first approach, 5 was readily synthesized in two steps from
the known 2-methoxyiso-phthalic acid 3.9 Compound 3 was first
converted into its dimethylester 4 by reaction with SOCl2 in anhy-
drous MeOH (Scheme 2).10 Then, reduction with LiAlH4 afforded 5
in 67% total yield from diacid 3.
2.2. Synthesis of boronic ester 12
The preparation of the boronic ester 12 from the known 4-
bromo-3,5-dimethylpyridine 117 was easily performed, in 61%
yield, via a classical bromide/lithium exchange followed by treat-
ment with tributylborate and then pinacol.
O
O
O
O
O
O
SOCl2, MeOH
HO
OH
O
O
0°C, RT, 16h
82%
3
2.3. SuzukieMiyaura coupling reactionedeprotectione
4
quaternisation
LiAlH4, THF
0°C to RT, 2h
82%
The following three steps, namely the cross-coupling reaction
followed by deprotection and quaternisation, were performed un-
der the same conditions as previously described for the syntheses
of 1aee and 2aee.6,7 The SuzukieMiyaura coupling reaction of
11aed with boronic ester 12 afforded the 4-pyridinylanisoles
13aed in good to excellent yields (from 75 to 82%), using our
usual conditions [Pd(PPh3)4 as catalyst and Cs2CO3 as base in an-
hydrous THF] (Table 1, Scheme 4). Then, the phenol functions were
deprotected, in DMF, at 100 ꢀC, using sodium ethanethiolate, pre-
O
HO
OH
5
Scheme 2. Preparation of 5.
O
O
NBS, hν
Br
Br
CCl4, 1h
56%
7
6
OH-(CH2)n-OH
n = 5, 6, 7, 8
NaH, THF reflux
(CH2)n
(CH2)n
(CH2)n
O
O
O
O
O
O
O O O
O O O
NBS, acétonitrile
RT
+
(CH2)n
Br
10a-d
8a-d
9
+ monoalkylated and polymers derivatives
Scheme 3. Preparation of 8aed and 10aed (n ¼ 5, 6, 7, 8).
A condensation between 1,5-dibromopentane and the bis(hy-
droxymethyl) compound 5 was then attempted under high-
dilution condition. Unfortunately, using t-BuOK as base, as well as
in THF and in DMF, the reaction led to a complete decay of 5. On the
contrary, in 1,4-dioxane, or in the presence of NaH in THF, no re-
action occurred and 5 was recovered quantitatively.
Table 1
Yields leading from 7 to 16aed
n
Cyclisation
Bromination
SuzukieMiyaura
coupling yield/%
We therefore decided to invert the reactive functionalities of the
two partners as described in the literature for the syntheses of 2-
methoxy-1,3-xylyl crown compounds.11e14 The known 2,6-
dimethylanisole 6 was therefore brominated using NBS under ir-
radiation, via a radical substitution, to obtain bis(bromomethyl)
anisole 7 in 56% yield.
Condensation of 2,6-bis(bromomethyl)anisole with alkanes-1,n-
diols (n¼5e8) of various lengths, conducted in the presence of
sodium hydride in anhydrous THF at reflux and under high-dilution
Time/h
Yield/%
Time/h
Yield/%
8a
8b
8c
8d
5
6
7
8
96
96
48
48
15
25
38
43
10a
8
8
1
1
85
95
88
90
13a
13b
13c
13d
85
75
80
85
10b
10c
10d
Deprotection yield/%
Quaternisation yield/%
Deprotonation yield/%
14a
14b
66
65
15a
15b
70
80
16a
16b
60
65

630
E. Ay et al. / Tetrahedron 68 (2012) 628e635
pared in situ by deprotonation of ethanethiol. The four corre-
sponding free phenols 14aed were recovered in yields ranging
from 65 to 83%. The quaternisation of pyridines 14aed with iodo-
methane was also performed very easily to give the corresponding
4-pyridinio phenol iodide salts 15aed.
three representative solvents of different polarity (Fig. 1). In order
to avoid the protonation of phenolate oxygen, all measurements
were conducted in the presence of an excess of tetramethylguani-
dine as base. As for 4-[N-methyl-4-pyridinio]phenolate, POMP, the
absorption bands are moderately large and structureless.15 The nmax
~
(CH2)n
(CH2)n
O
(CH2)n
Br
O
O
O
O
O OH O
O
Br
1) BuLi, THF
2) B(OBu)3
O
O
EtSH, NaH
B
10a-d
N
11
Pd(PPh3)4, Cs2CO3
THF, reflux
3) Pinacol, tamis 4 Å
61%
DMF, 100°C
16h
N
N
13a-d
N
14a-d
12
(CH2)n
(CH2)n
MeI, CH3CN
reflux, 4h
O
O
O
O OH O
Ag2O, MeOH
N
N
I
16a-d
15a-d
Scheme 4. Preparation of 16aed (n¼5, 6, 7, 8).
2.4. Deprotonation
values undergo a severe blue shift (negative solvatochromism)
from THF to MeOH ðDnmax ¼ 5000 cmꢁ1Þ, which indicates that the
~
Deprotonation of 15aed has to afford the tictoïds 16aed free
from traces of salts. Previously, we used a small excess of
Bu4NþHOꢁ.6,7 The zwitterions 1aee and 2aee were weakly solu-
ble and were therefore easily purified by making use of their
differences in solubility with tetra-n-butylammonium iodide in
solvent mixtures such as CH2Cl2/Et2O or CH2Cl2/cyclohexane. One
advantage of this method was the possibility to detect traces of
Bu4NþIꢁ by NMR spectroscopy using duroquinone in CD3OD as an
internal reference. Analogous attempts with our new tictoïds have
proved to be negative because of their far better solubilities in
organic solvents as compared to that of the zwitterions of the first
two series, i.e., compounds 1aeg and 2aee. This property admit-
tedly confronted us with a synthetic problem but, in other re-
spects, bodes well for a future incorporation in organic NLO
devices.
dipole moment of 16d decreases largely upon excitation. This result
is in agreement with the charge-transfer nature of the electron
transition from the phenolate to the pyridinium ring, experimen-
tally observed using femtosecond spectroscopy in the case of the
related compounds 2aec and 2d.16
Therefore, we have elaborated an alternative procedure using
Ag2O as an efficient reagent, knowing that Ag2O and AgI are in-
soluble in organic solvents and precipitate in them. After treatment
with Ag2O for a few minutes, all new tictoïds were recovered, after
a meticulous centrifugation, free from any inorganic salts. In order
to definitively validate this new deprotonation method, we com-
pared the EFISHG responses of two batches of compound 2b. One
batch was obtained, as previously, using Bu4NþHOꢁ, and the second
one, using our new method, namely Ag2O. In both cases similar
results were obtained. The small differences lay in the range of
measurement errors.
Fig. 1. UV/visible absorption spectra of 16d measured in three solvents of different
polarity
2.6. Preliminary EFISHG results
2.5. UV/visible absorption spectra of 16d
Compounds 16aed and 2c possess equivalent interplanar an-
gles. Moreover, the phenolate function of each derivative is con-
gested at the ortho positions by the presence of alkyl groups:
a saturated chain with 7e10 methylene groups or tert-butyl groups
Logically, the chain length should not significantly influence the
UV/visible absorption spectra. So, we only recorded those of 16d in

E. Ay et al. / Tetrahedron 68 (2012) 628e635
631
at each ortho position. As a consequence, the NLO response for
16aed was expected to be of the same magnitude as that pre-
viously obtained for 2c.5 Preliminary EFISHG experiments have
been performed with tictoïds 16bed under the conditions de-
silicagel (cyclohexane/AcOEt) afforded the pure cyclophanes 8aed
and dimer 9.
4.2.2. Procedure B: bromination of cyclophanes. Under an atmo-
sphere of Ar, to a solution of cyclophanes 8aed (1 equiv) in MeCN
(8 mL per mmol of 8aed) was added NBS (1.4 equiv). The reaction
mixture was stirred at room temperature overnight. The solvent
was then evaporated under reduced pressure. Cyclohexane was
added to the crude residue. Insoluble solids were filtered off and
rinsed with another portion of cyclohexane. The filtrate was
evaporated under reduced pressure. Purification by chromatogra-
phy on silicagel (cyclohexane/AcOEt) afforded the pure bromo
cyclophanes 10aed.
scribed in the literature5 in order to determine the magnitude of
m,
the permanent dipole moment. While the measurements with 2a
led to a value of
m
equal to ꢁ950ꢂ10ꢁ48 esu, for 16b, 16c, and 16d
we obtained values of ꢁ750, ꢁ930, and ꢁ1400ꢂ10ꢁ48 esu, re-
spectively, as was to be expected.
3. Conclusion
In summary, four new tictoïds of the pyridinium phenolate type
have been readily synthesized. Their solubilities are notably im-
proved. However, the ortho alkyl chains at the phenolate ring seem
not to be bulky enough to protect the phenolate function against
protonation both in acidic and in neutral media as it was reported
in literature for related pyridinium phenolates betaine dyes.5,8,17 To
hinder protonation, the chain substitution at the ortho position of
the phenolate ring at is now considered. Nevertheless, no signifi-
cant aggregation has been highlighted, allowing preliminary
EFISGH measurements.
4.2.3. Procedure C: SuzukieMiyaura coupling reaction. Under an
atmosphere of Ar, Cs2CO3 (1.2 equiv), the boronic ester 12
(1.2 equiv), and Pd(PPh3)4 (0.08 equiv) were successively added to
a solution of 10aed (1 equiv) in anhydrous THF (10 mL per mmol of
10aed). The reaction mixture was stirred overnight. The suspen-
sion was then filtered through Celite with CH2Cl2. The reaction
mixture was concentrated under reduced pressure and the residue
was purified by chromatography on silicagel (cyclohexane/AcOEt)
to afford pure 13aed.
4. Experimental section
4.1. General points
4.2.4. Procedure D: deprotection of phenols. Under an atmosphere
of Ar, EtSH (7 equiv) was added dropwise to NaH (8 equiv) sus-
pended in DMF (14 mL per mmol of 13aed). On completion of H2
emission, 13aed (1 equiv) was introduced in the reaction mixture.
After an overnight stirring at 100 ꢀC, H2O (2.5 mL per mmol of
13aed), aqueous HCl (1 M, 8 mL per mmol of 13aed), and a phos-
phate buffer (0.5 M, pH¼2) were successively added. The aqueous
layer was extracted three times with Et2O. The combined organic
layers were extracted twice with H2O and dried with MgSO4. The
solution was concentrated under reduced pressure and the residue
was purified by chromatography on silicagel (cyclohexane/AcOEt)
to afford pure 14aed.
Reagents were purchased from commercial suppliers and used
without further purification. THF, diethyl ether, and toluene were
freshly distilled from sodium/benzophenone, MeOH from Mg/I2.
A freshly opened DMF bottle was used and DMF was dried over
ꢂ
3 A molecular sieves. All melting points were taken on a Kofler
bench. IR spectra (cmꢁ1) were recorded on either a Bruker Vertex
70 or an Equinox 55 spectrometer. 1H NMR (400 MHz) and 13C
NMR (100.6 MHz) spectra were measured with a Bruker Avance
(Serie 400) at 295 K. Microanalyses were performed by the an-
alytical service of the Service de Microanalyse du CNRS in Ver-
naison and high resolution MS were measured with an Agilent
Technologies 6510 (Q-TOF) Spectrometer using a dual ESI source.
Irradiations were performed using a Hanau mercury vapour lamp
HPK 125.
4.2.5. Procedure E: alkylation reaction. Under an atmosphere of Ar,
to a suspension of the biaryl compounds 14aed (1 equiv) in acetone
(16 mL per mmol of 14aed), iodomethane (4 equiv) was added
dropwise. The reaction mixture was refluxed for 4 h. The solvent
was then removed under reduced pressure. The residue was
washed first with Et2O then with AcOEt. The crude iodides 15aed
were not further purified and only characterized by NMR
spectroscopy.
UV/visible spectra were carried out with an Agilent 8453 spec-
trometer. Acetonitrile, MeOH, and CH3CN employed were of spec-
troscopic grade. The absorption of all solvents was subtracted from
the sample spectra. In order to maintain exclusively the zwitter-
ionic form, an excess of tetramethylguanidine was added to each
sample.
Previously reported procedures were used to prepare 1,3-
dimethylanisole 6, 2-methoxyiso-phthalic acid 3,9 and 4-bromo-
3,5-dimethylpyridine 11.7
4.2.6. Procedure F: deprotonation. Ag2O (2 equiv) was added to
a solution of 15aed in MeOH (11 mL per mmol of 15aed). After
10 min of reaction an excess of both Ag2O and AgI precipitated. The
suspension was then centrifugated. The supernatant organic phase
was centrifugated once more and was then evaporated under re-
duced pressure to afford the pure tictoïds 16aed.
Pd(PPh3)4 was prepared according to Ref. 18 and used directly or
within three months at longest while stored under N2 at ꢁ30 ꢀC.
4.2. General procedures
4.3. Synthesis of derivatives
4.2.1. Procedure A: synthesis of cyclophanes 8aed. Under an atmo-
sphere of Ar, to NaH (13 equiv), suspended in anhydrous THF
(500 mL per mmol of 7) at reflux was added dropwise a solution of
7 (1 equiv) and alkane-1,n-diol (1.1 equiv) in THF (120 mL per mmol
of 7). The reaction mixture was stirred under reflux until comple-
tion of the reaction, which was monitored by NMR spectroscopy. An
aqueous solution of NH4Cl (10%) was then added at 0 ꢀC until
neutralization. THF was evaporated under reduced pressure. The
crude residue was dissolved in Et2O. This organic layer was then
extracted twice with water, dried with MgSO4, and evaporated
under reduced pressure. Purification by chromatography on
4.3.1. 2-Methoxy-1,3-benzenedicarboxylic acid dimethyl ester
4. Under an atmosphere of Ar, SOCl2 (0.4 mL, 5.5 mmol) was added
dropwise at 0 ꢀC to 2-methoxyiso-phthalic acid
3 (500 mg,
2.5 mmol) in anhydrous methanol (4 mL). The reaction mixture
was then allowed to reach room temperature. After stirring over-
night, the reaction mixture was evaporated under reduced pres-
sure. The crude residue was then dissolved in AcOEt. This organic
layer was successively washed with a saturated aqueous solution of
NaHCO3 and water. After drying with MgSO4, the solvent was
evaporated under reduced pressure to afford 4 (468 mg, 82%),

632
E. Ay et al. / Tetrahedron 68 (2012) 628e635
which was used in the next step without further purification. Mp
oil from bis(bromomethyl)anisole 7 (1 g, 3.4 mmol) by using pro-
cedure
with 48 h at reflux. 1H NMR (400 MHz, CDCl3):
and 1H NMR were in agreement with the literature values.9,19
A
d
¼0.53e0.72 (m, 2H), 1.00e1.15 (m, 2H), 1.15e1.26 (m, 2H),
4.3.2. 2,6-Bis(hydroxymethyl)anisole 5. Under an atmosphere of Ar,
at 0 ꢀC, a solution of 4 (116 mg, 0.52 mmol) in anhydrous THF
(2.5 mL per mmol of 4, 1.3 mL) was added dropwise to a suspension
of LiAlH4 (49 mg,1.26 mmol) in anhydrous THF (2.5 mL per mmol of
4, 1.3 mL). The reaction mixture was stirred overnight at room
temperature. AcOEt was then carefully added at 0 ꢀC in order to
neutralize LiAlH4 in excess. Na2SO4, 10ꢂH2O (152 mg) and an
aqueous solution of NaOH (0.25 M, 0.2 mL) were then added. The
solution was filtered through Celite with AcOEt. The aqueous so-
lution was separated and extracted twice with AcOEt. The com-
bined organic layers were dried with MgSO4, and evaporated under
reduced pressure to afford 5 (71 mg, 82%), which was used in the
next step without further purification. Mp and 1H NMR were in
agreement with literature values.20
1.26e1.40 (m, 2H), 1.60e1.75 (m, 2H), 3.13e3.18 (m, 2H), 3.31e3.32
2
(m, 2H), 3.39(s, 3H), 4.14 (d, JH,H¼12.2 Hz, 2H), 5.04 (t,
2JH,H¼12.2 Hz, 2H), 7.02 (d, JH,H¼7.3 Hz, 1H), 7.22 (d, JH,H¼7.3 Hz,
2
2
2H) ppm. 13C NMR (100.6 MHz, CDCl3):
d
¼24.9, 25.1 (2C), 28.7 (2C),
61.8, 65.4 (2C), 69.3 (2C), 122.8, 131.4 (2C), 133.2 (2C), 159.6 ppm. IR
~
(KBr):
n
¼ 666; 716, 770, 833, 879, 942, 1013, 1047, 1094, 1131, 1171,
1232, 1280, 1364, 1428, 1472, 1593, 1728, 2855, 2935 cmꢁ1. HRMS
(ESI-Q-Tof): calcd for C32H52NO6 [2MþNH4]ꢃþ 546.7743; found
546.3780.
4.3.7. 3,12-Dioxa-1[2,6]-(11-methoxy)benzenacyclotridecaphane
8d and 11,141-dimethoxy-1,14(2,6)-dibenzena-3,12,16,25-
tetraoxacyclohexacosane 9. After purification by chromatography
on silicagel (cyclohexane/AcOEt, 9:1), compounds 8d (610 mg, 43%)
and 9 (284 mg, 20%) were obtained as from bis(bromomethyl)ani-
sole 7 (1.5 g, 5.1 mmol) by using procedure A with 48 h at reflux.
Compound 8d: colourless oil. 1H NMR (400 MHz, CDCl3):
4.3.3. 2,6-Bis(bromomethyl)anisole 7. Under an atmosphere of Ar,
1,6-dimethylanisole 6 (488 mg, 3.59 mmol) was added dropwise to
a suspension of NBS (1.278 mg, 7.18 mmol) in CCl4 (25 mL). After
stirring for 60 min under irradiation (125 nm), the reaction mixture
was filtered and evaporated under reduced pressure. The crude
residue was dissolved in CH2Cl2 and extracted twice with an
aqueous solution of NH4Cl (10%). The organic layer was then dried
with MgSO4 and evaporated under reduced pressure to afford 7
(590 mg, 56%), which was used in the next step without further
purification (7 is a lachrymator). Mp was in agreement with the
literature values.11
d
¼0.81e0.94 (m, 2H), 0.94e1.02 (m, 2H), 1.02e1.10 (m, 2H),
1.10e1.18 (m, 2H), 1.18e1.29 (m, 2H), 1.44e1.63 (m, 2H), 3.35e3.45
2
(m, 4H), 3.83 (s, 3H), 4.25 (d, JH,H¼12.2 Hz, 2H), 4.88 (d,
2JH,H¼12.2 Hz, 2H), 7.09 (t, JH,H¼7.6 Hz, 1H), 7.31 (d, JH,H¼7.6 Hz,
2
2
2H) ppm. 13C NMR (100.6 MHz, CDCl3):
d¼24.3 (2C), 26.6 (2C), 28.4
(2C), 62.8, 67.6 (2C), 67.72 (2C), 123.5, 131.6 (2C), 132.1 (2C),
~
158.4 ppm. IR (KBr):
n
¼ 664; 770, 1012, 1092, 1171, 1221, 1268,
1361, 1430, 1471, 1594, 2856, 2930 cmꢁ1. HRMS (ESI-Q-Tof): calcd
for C17H27O3 [MþH]ꢃþ 279.1955; found 279.1943.
Compound 9: colourless crystals. Mp 84 ꢀC. 1H NMR (400 MHz,
4.3.4. 3,9-Dioxa-1[2,6]-(11-methoxy)benzenacyclodecaphane
8a. After purification by chromatography on silicagel (cyclohex-
ane/AcOEt, 7:3), compound 8a (60.5 mg, 15%) was obtained as
CDCl3):
d
¼1.20e1.40 (m, 16H), 1.59 (quint, 3JH,H¼6.3 Hz, 8H), 3.48 (t,
3JH,H¼6.3 Hz, 8H), 3.81 (s, 6H), 4.53 (s, 8H), 7.08 (t, 2JH,H¼7.6 Hz, 2H),
7.33 (d, 2JH,H¼7.6 Hz, 4H) ppm. 13C NMR (100.6 MHz, CDCl3):
¼25.8
d
colourless crystals from bis(bromomethyl)anisole
1.7 mmol) by using procedure A (96 h at reflux). Mp 82 ꢀC. 1H NMR
(400 MHz, CDCl3):
7
(500 mg,
(4C), 28.9 (4C), 29.6 (4C), 62.6 (2C), 67.6 (4C), 70.3 (4C), 124.1 (2C),
~
129.6 (4C), 131.6 (4C), 156.7 (2C) ppm. IR (KBr):
n
¼ 494; 531, 589,
d
¼0.38e0.51 (m, 2H), 0.89e1.10 (m, 1H),
604, 717, 773, 787, 817, 865, 902, 979, 1013, 1050, 1070, 1098, 1113,
1173, 1212, 1228, 1267, 1280, 1295, 1351, 1393, 1430, 1468, 1594,
1727, 2855, 2926 cmꢁ1. HRMS (ESI-Q-Tof): calcd for C34H56NO6
[MþNH4]ꢃþ 574.4108; found 574.4112.
3
1.09e1.22 (m, 2H), 1.78e1.93 (m, 1H), 3.15 (ddd, JH,H¼4.0 Hz,
3JH,H¼8.0 Hz, 2JH,H¼12.0 Hz, 2H), 3.51 (ddd, 3JH,H¼4.0 Hz,
3JH,H¼8.0 Hz, 2JH,H¼12.0 Hz, 2H), 3.93 (s, 3H), 4.08 (d, 2JH,H¼12.4 Hz,
2
2
2H), 5.18 (d, JH,H¼12.4 Hz, 2H), 7.00 (t, JH,H¼7.4 Hz, 1H), 7.20 (d,
2JH,H¼7.4 Hz, 2H) ppm. 13C NMR (100.6 MHz, CDCl3):
d
¼19.6, 28.2
4.3.8. 14-Bromo-3,9-dioxa-1(2,6)-(11-methoxy)benzenacyclodeca-
phane 10a. After purification by chromatography on silicagel (cy-
clohexane/AcOEt, 7:3), compound 10a (155 mg, 85%) was obtained
as colourless crystals from cyclophane 8a (136 mg, 0.58 mmol) by
using procedure B with 8 h of stirring. Mp 119.5 ꢀC. 1H NMR
(2C), 61.1, 66.6 (2C), 70.6 (2C), 122.2, 132.1(2C), 132.4 (2C),
~
160.7 ppm. IR (KBr):
n
¼ 651; 728, 780, 834, 854, 885, 951, 991,
1017, 1046, 1079, 1129, 1183, 1219, 1263, 1287, 1360,1427,1472,1592,
2857, 2920 cmꢁ1. HRMS (ESI-Q-Tof): calcd for C14H21O3Na [MþH]ꢃþ
237.1485; found 237.1485.
(400 MHz, CDCl3):
1.11e1.26 (m, 2H), 1.75e1.90 (m, 1H), 3.11e3.20 (m, 2H), 3.48e3.56
d
¼0.45e0.60 (m, 2H), 0.90e1.02 (m, 1H),
4.3.5. 3,10-Dioxa-1[2,6]-(11-methoxy)benzenacycloundecaphane
8b. After purification by chromatography on silicagel (cyclohex-
ane/AcOEt, 8:2), compound 8b (12.8 mg, 18%) was obtained as
colourless oil from bis(bromomethyl)anisole 7 (84.5 mg, 2.8 mmol)
by using procedure A (96 h at reflux). 1H NMR (400 MHz, CDCl3):
(m, 2H), 3.91 (s, 3H), 4.00 (d, JH,H¼12.6 Hz, 2H), 5.11 (d,
2
2JH,H¼12.6 Hz, 2H), 7.31 (s, 2H) ppm. 13C NMR (100.6 MHz, CDCl3):
d
¼19.5, 28.2 (2C), 61.0, 67.0 (2C), 70.2 (2C), 114.3, 134.2 (2C), 134.5
~
(2C), 159.8 ppm. IR (KBr):
n
¼ 612; 656, 690, 777, 845, 868, 999,
1048, 1079, 1129, 1182, 1228, 1264, 1359, 1425, 1470, 1692, 2856,
2922 cmꢁ1. HRMS (ESI-Q-Tof): calcd for C14H19BrNaO3 [MþNa]ꢃþ
337.0409; found 237.0413.
d
¼0.62e0.74 (m, 2H), 1.00e1.12 (m, 2H), 1.15e1.26 (m, 2H), 1.2e1.39
3 3 2
(m, 2H), 3.43 (ddd, JH,H¼4.0 Hz, JH,H¼7.2 Hz, JH,H¼10.5 Hz, 2H),
3
3
3
3.61 (ddd, JH,H¼4.0 Hz, JH,H¼7.2 Hz, JH,H¼10.5 Hz, 2H), 3.62 (s,
3H), 4.22 (d, 2JH,H¼12.4 Hz, 2H), 4.95 (d, 2JH,H¼12.4 Hz, 2H), 7.09 (t,
4.3.9. 14-Bromo-3,10-dioxa-1(2,6)-(11-methoxy)benzenacyclounde-
caphane 10b. After purification by chromatography on silicagel
(cyclohexane/AcOEt, 8:2), compound 10a (678 mg, 95%) was ob-
tained as colourless oil from cyclophane 8b (542 mg, 2.17 mmol) by
using procedure B with 8 h of stirring. 1H NMR (400 MHz, CDCl3):
0.65e0.82 (m, 2H), 1.08e1.19 (m, 2H), 1.19e1.29 (m, 2H), 1.32e1.43
2JH,H¼7.6 Hz, 1H), 7.27 (d, JH,H¼7.6 Hz, 2H) ppm. 13C NMR
2
(100.6 MHz, CDCl3):
d
¼23.3 (2C), 29.7 (2C), 62.3, 67.7 (2C), 69.1
~
(2C), 123.8, 132.5 (4C), 158.6 ppm. IR (KBr):
n
¼ 651; 771, 828, 917,
1014, 1064, 1090, 1124, 1175, 1219, 1274, 1369, 1429, 1470, 1593,
2857, 2929 cmꢁ1
. HRMS (ESI-Q-Tof): calcd for C15H22NaO3
[MþNa]ꢃþ 273.1461; found 273.1463.
(m, 2H), 3.42 (ddd, JH,H¼4.0 Hz, JH,H¼7.6 Hz, JH,H¼11.2 Hz, 2H),
3
3
2
3
3
2
3.60 (ddd, JH,H¼4.0 Hz, JH,H¼7.6 Hz, JH,H¼11.2 Hz, 2H), 3.82 (s,
4.3.6. 3,11-Dioxa-1[2,6]-(11-methoxy)benzenacyclododecaphane
8c. After purification by chromatography on silicagel (cyclohexane/
AcOEt, 9:1), compound 8c (341 mg, 38%) was obtained as colourless
3H), 4.17 (d, 2JH,H¼12.4 Hz, 2H), 4.89 (d, 2JH,H¼12.4 Hz, 2H), 7.40 (s,
2H) ppm. 13C NMR (100.6 MHz, CDCl3):
d
¼23.4 (2C), 29.6 (2C), 62.2,
67.9 (2C), 68.6 (2C),116.0,134.7 (2C),134.8 (2C),157.7 ppm. IR (KBr):

E. Ay et al. / Tetrahedron 68 (2012) 628e635
633
~
n
¼ 573; 614, 654, 692, 878, 1013, 1091, 1172, 1217, 1469, 2858,
3.16e3.25 (m, 2H), 3.52e3.62 (m, 2H), 4.03 (s, 3H), 4.07 (d,
2JH,H¼12.5 Hz, 2H), 5.24 (d, 2JH,H¼12.5 Hz, 2H), 6.97 (s, 2H), 8.34 (s,
2929 cmꢁ1. HRMS (ESI-Q-Tof): calcd for C15H21BrNaO3 [MþNa]ꢃþ
351.0566; found 251.0554.
1H), 8.38 (s, 1H) ppm. 13C NMR (100.6 MHz, CDCl3):
d
¼17.3, 17.5,
19.5, 28.3 (2C), 61.1, 66.7 (2C), 70.7 (2C), 130.7, 131.0, 131.7, 131.9
4.3.10. 14-Bromo-3,11-dioxa-1(2,6)-(11-methoxy)benzenacyclodode-
caphane 10c. After purification by chromatography on silicagel
(cyclohexane/AcOEt, 9:1), compound 10c (286 mg, 88%) was ob-
tained as colourless crystals from cyclophane 8b (238 mg,
(2C), 132.4 (2C), 145.8, 148.2, 148.5, 160.2 ppm. IR (KBr):
n
¼ 539;
~
661, 697, 722, 852, 885,1003, 1019,1047, 1078,1100,1121, 1129,1161,
1194, 1229, 1259, 1282, 1358, 1375, 1439, 1467, 1584, 2853, 2922,
2956 cmꢁ1
.
HRMS (ESI-Q-Tof): calcd for C21H28NO3 [MþH]ꢃþ
0.9 mmol) by using procedure
B
with 1 h of stirring. Mp
342.2064; found 242.2064.
118.5e120.5 ꢀC. 1H NMR (400 MHz, CDCl3): 0.55e079 (m, 2H),
1.04e1.16 (m, 2H), 1.16e1.27 (m, 2H), 1.27e1.41 (m, 2H), 1.62e1.76
(m, 2H), 3.13e3.21 (m, 2H), 3.28e3.35 (m, 2H), 3.88 (s, 3H), 4.08 (d,
4.3.14. 4-[(3,5-Dimethyl)pyridin-4-yl]-2,6-[(2,9-dioxa)decan-1,10-
diyle]-1-methoxybenzene 13b. After purification by chromatogra-
phy on silicagel (cyclohexane/AcOEt, 5:5), compound 13b (497 mg,
75%) was obtained as colourless crystals from bromocyclophane
10b (608 mg, 1.84 mmol) by using procedure C. Mp 119 ꢀC. 1H NMR
2JH,H¼12.4 Hz, 2H), 4.99 (d, 2JH,H¼12.4 Hz, 2H), 7.34 (s, 2H) ppm. 13
C
NMR (100.6 MHz, CDCl3):
d
¼24.5, 24.7 (2C), 28.2 (2C), 61.2, 65.3
~
(2C), 68.6 (2C), 114.6, 133.1 (2C), 135.0 (2C), 158.3 ppm. IR (KBr):
n
¼
626; 685, 716, 852, 916, 943, 1015, 1051, 1094, 1134, 1223, 1284,
1362, 1426, 1453, 1470, 2852, 2932 cmꢁ1. HRMS (ESI-Q-Tof): calcd
for C16H24BrO3 [MþH]ꢃþ 343.0909; found 343.0894.
(400 MHz, CDCl3):
d
¼0.69e0.80 (m, 2H), 1.05e1.17 (m, 2H),
1.17e1.40 (m, 4H), 2.00 (s, 3H), 2.10 (s, 3H), 3.42e3.51 (m, 2H),
3.61e3.69 (m, 2H), 3.90 (s, 3H), 4.21 (d, 2JH,H¼12.4 Hz, 2H), 4.99 (d,
2JH,H¼12.4 Hz, 2H), 7.04 (s, 2H), 8.33 (s, 1H), 8.35 (s, 1H) ppm. 13C
4.3.11. 14-Bromo-3,12-dioxa-1(2,6)-(11-methoxy)benzenacyclo-
tridecaphane 10d. After purification by chromatography on silica-
gel (cyclohexane/AcOEt, 9:1), compound 10d (647 mg, 90%) was
obtained as colourless crystals from cyclophane 8d (560 mg,
2 mmol) by using procedure B with 1 h of stirring. Mp 62 ꢀC. 1H
NMR (100.6 MHz, CDCl3):
d
¼17.3, 17.6, 23.4 (2C), 29.7 (2C), 62.4,
67.9 (2C), 69.1 (2C), 130.8, 130.9, 132.2 (2C), 133.1 (2C), 133.6, 148.3,
~
n
148.4, 148.5, 158.0 ppm. IR (KBr): ¼ 538; 651, 673, 693, 723, 877,
904, 920, 1015, 1040, 1065, 1094, 1125, 1160, 1196, 1233, 1272, 1358,
1468, 1587, 2733, 2759, 2858, 2921, 2956, 2995 cmꢁ1. HRMS (ESI-Q-
Tof): calcd for C22H30NO3 [MþH]ꢃþ 356.2220; found 356.2212.
NMR (400 MHz, CDCl3):
1.07e1.23 (m, 4H), 1.25e1.35 (m, 2H), 1.45e1.60 (m, 2H), 3.35e3.48
d
¼0.80e0.95 (m, 2H), 0.95e1.07 (m, 2H),
2
(m, 4H), 3.82 (s, 3H), 4.20 (d, JH,H¼12.0 Hz, 2H), 4.82 (d,
4.3.15. 4-[(3,5-Dimethyl)pyridin-4-yl]-2,6-[(2,10-dioxa)undecan-
1,11-diyle]-1-methoxybenzene 13c. After purification by chroma-
tography on silicagel (cyclohexane/AcOEt, 5.5:4.5), compound 10c
(126 mg, 80%) was obtained as colourless crystals from bromocy-
clophane 8c (146 mg, 0.42 mmol) by using procedure C. Mp
2JH,H¼12.0 Hz, 2H), 7.44 (s, 2H) ppm. 13C NMR (100.6 MHz, CDCl3):
d
¼24.4 (2C), 26.8 (2C), 28.4 (2C), 62.8, 67.3 (2C), 68.2 (2C), 116.1,
~
134.0 (2C), 134.6 (2C), 157.5 ppm. IR (KBr):
n
¼ 793; 854, 882, 1008,
1047, 1088, 1171, 1220, 1426, 1470, 2861, 2923, 2954 cmꢁ1. HRMS
(ESI-Q-Tof): calcd for C17H25BrNaO3 [MþNa]ꢃþ379.0893; found
379.0877.
151e153 ꢀC. 1H NMR (400 MHz, CDCl3):
d
¼0.61e0.74 (m, 2H),
1.04e1.15 (m, 2H),1.17e1.40 (m, 6H), 1.60e1.75 (m, 2H), 2.01 (s, 3H),
2.07 (s, 3H), 3.18e3.30 (m, 2H), 3.32e3.42 (m, 2H), 3.96 (m, 3H),
4.14 (d, 2JH,H¼12.3 Hz, 2H), 5.07 (d, 2JH,H¼12.3 Hz, 2H), 7.00 (s, 2H),
4.3.12. 3,5-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2yl)-
pyridine 12. Under an atmosphere of Ar, at ꢁ78 ꢀC, a solution of n-
BuLi (2.5 M in cyclohexane, 0.53 mL, 1.29 mmol) was added drop-
8.33 (s, 1H), 8.34 (s, 1H) ppm. 13C NMR (100.6 MHz, CDCl3):
d
¼17.3,
17.4, 24.5, 24.6 (2C), 28.3 (2C), 61.9, 65.2 (2C), 68.6 (2C), 130.8, 130.9,
wise to
a
stirred solution of 4-bromopyridine 11 (200 mg,
131.5 (2C), 132.2, 132.4 (2C), 148.3, 148.4 (2C), 158.4 ppm. IR (KBr):
~
1.07 mmol) in anhydrous Et2O (8 mL). Fifteen minutes later,
B(OBu)3 (0.35 mL, 1.29 mmol) was added dropwise. The reaction
mixture was then warmed up to room temperature. Acetic acid
n
¼ 526; 670, 718, 877, 899, 940, 1015, 1048, 1093, 1131, 1161, 1195,
1248, 1278, 1360, 1376, 1430, 1477, 1584, 2697, 2728, 2757, 2853,
2896, 2935, 3018 cmꢁ1. HRMS (ESI-Q-Tof): calcd for C23H32NO3
[MþH]ꢃþ 370.2382; found 370.2374.
(65 mL, 1 mmol) was added. The suspension was filtered and the
solid was removed with anhydrous Et2O. The combined solvents
were evaporated under reduced pressure and 1-butanol was taken
off via azeotropic distillation with toluene. The crude residue was
then dissolved in anhydrous toluene (5 mL), MgSO4 (1 g) and
pinacol (153 mg, 1.29 mmol) were successively added. This reaction
mixture was stirred at reflux for 2 h. The obtained suspension was
filtered and the solvent was evaporated under reduced pressure.
The crude material was purified by chromatography on silicagel
(cyclohexane/AcOEt, 3:7) to afford pure 12 as a colourless solid
(153 mg, 61%), which can be sublimated (100 ꢀC, 1 mmHg). Mp
4.3.16. 4-[(3,5-Dimethyl)pyridin-4-yl]-2,6-[(2,11-dioxa)dodecan-
1,12-diyle]-1-methoxybenzene 13d. After purification by chroma-
tography on silicagel (cyclohexane/AcOEt, 5.5:4.5), compound 13d
(596 mg, 85%) was obtained as colourless crystals from bromocy-
clophane 10d (654 mg, 1.83 mmol) by using procedure C. Mp 88 ꢀC.
1H NMR (400 MHz, CDCl3):
d
¼0.86e0.98 (m, 2H), 0.98e1.15 (m,
4H), 1.15e1.31 (m, 4H), 1.44e1.58 (m, 2H), 2.01 (s, 3H), 2.08 (s, 3H),
3.43e3.48 (m, 4H), 3.92 (s, 3H), 4.24 (d, 2JH,H¼12.4 Hz, 2H), 4.95 (d,
2JH,H¼12.4 Hz, 2H), 7.08 (s, 2H), 8.33 (ls, 2H) ppm. 13C NMR
133 ꢀC. 1H NMR (400 MHz, CDCl3):
(s, 2H) ppm. 13C NMR (CDCl3):
¼19.0 (2C), 25.0 (4C), 84.4 (2C),
136.0 (3C), 147.3 (2C) ppm. IR (KBr):
d
¼1.39 (s, 12H), 2.35 (s, 6H), 8.20
(100.6 MHz, CDCl3):
d
¼17.3, 17.5, 24.3 (2C), 26.7 (2C), 28.6 (2C),
d
63.2, 67.7 (2C), 67.9 (2C), 130.8, 130.9, 131.8 (2C), 132.3 (2C), 133.2,
~
~
n
n
¼ 680; 856, 1085, 1145, 1168,
148.3, 148.4, 148.5, 157.8 ppm. IR (KBr):
¼ 518; 675, 857, 875,
1273,1314,1338,1371,1380,1391,1411,1456, 2975 cmꢁ1. Anal. Calcd
for C13H20BNO2 (233.12) C, 66.98; H, 8.65; B, 4.64; N, 6.01. Found: C,
66.84; H, 8.68; B, 4.66; N, 5.88.
1008, 1045, 1086, 1162, 1198, 1235, 1268, 1314, 1378, 1472, 1584,
2860, 2931 cmꢁ1. HRMS (ESI-Q-Tof): calcd for C24H34NO3 [MþH]ꢃþ
384.2533; found 384.2530.
4.3.13. 4-[(3,5-Dimethyl)pyridin-4-yl]-2,6-[(2,8-dioxa)nonan-1,9-
diyle]-1-methoxybenzene 13a. After purification by chromatogra-
phy on silicagel (cyclohexane/AcOEt, 7:3), compound 13a (126 mg,
85%) was obtained as colourless crystals from bromocyclophane
10a (137 mg, 0.43 mmol) by using procedure C. Mp 128 ꢀC. 1H NMR
4.3.17. 4-[(3,5-Dimethyl)pyridin-4-yl]-2,6-[(2,8-dioxa)nonan-1,9-
diyle]phenol 14a. After purification by chromatography on silicagel
(cyclohexane/AcOEt, 8:2), compound 14a (66 mg, 66%) was ob-
tained as colourless crystals from biaryl 13a (116 mg, 0.34 mmol) by
using procedure D. Mp 118.5 ꢀC. 1H NMR (400 MHz, CDCl3):
(400 MHz, CDCl3):
1.15e1.29 (m, 2H), 1.82e2.20 (m, 1H), 2.00 (s, 3H), 2.16 (s, 3H),
d
¼0.50e0.65 (m, 2H), 0.95e1.09 (m, 1H),
d
¼0.75e0.90 (m, 2H), 1.10e1.25 (m, 1H), 1.25e1.39 (m, 2H),
1.91e2.06 (m, 2H), 2.01 (s, 3H), 2.14 (s, 3H), 3.24e3.34 (m, 2H),

634
E. Ay et al. / Tetrahedron 68 (2012) 628e635
2
3.63e3.71 (m, 2H), 4.14 (d, JH,H¼13.0 Hz, 2H), 5.32 (d,
1384, 1434, 1479, 1603, 1634, 2853, 2899, 2951, 3202 cmꢁ1. HRMS
(ESI-Q-Tof): calcd for C21H28NO3 [M]ꢃþ 342.2063; found 342.2064.
2JH,H¼13.0 Hz, 2H), 6.88 (s, 2H), 8.37 (br s, 2H) ppm. 13C NMR
(100.6 MHz, CDCl3):
d
¼17.3, 17.5, 20.4, 27.9 (2C), 68.0 (2C), 71.0 (2C),
128.0 (2C), 129.0, 130.0 (2C), 131.9, 131.95, 147.7, 147.8, 149.1,
4.3.22. 4-{4-[3,10-Dioxa-1(2,6)-(11-hydroxy)benzenacycloundeca-
phanyl]-1,3,5-trimethylpyridinium iodide 15b. Compound 15b
(174 mg, 80%) was obtained as colourless crystals from pyr-
idinylphenol 14b (154 mg, 0.45 mmol) by using procedure E. Mp
~
155.6 ppm. IR (KBr):
n
¼ 542; 668, 695, 721, 991, 1029, 1044, 1077,
1097,1120,1129,1160,1195,1222,1236,1281,1319,1338,1438,1455,
1474, 1496, 1590, 2852, 2907, 2948, 3034 cmꢁ1. HRMS (ESI-Q-Tof):
calcd for C20H26O3N [MþH]ꢃþ 328.1907; found 328.1904.
270 ꢀC. 1H NMR (400 MHz, CD3OD):
d
¼0.80e1.01 (m, 2H),1.20e1.41
(m, 4H), 1.41e1.56 (m, 2H), 2.22 (s, 3H), 2.34 (s, 3H), 3.40e3.54 (m,
2H), 3.68e3.83 (m, 2H), 4.26 (d, 2JH,H¼12.8 Hz, 2H), 4.36 (s, 3H), 5.15
4.3.18. 4-[(3,5-Dimethyl)pyridin-4-yl]-2,6-[(2,9-dioxa)decan-1,10-
diyle]phenol 14b. After purification by chromatography on silicagel
(cyclohexane/AcOEt, 5:5), compound 14b (268 mg, 65%) was ob-
tained as colourless crystals from biaryl 13b (429 mg, 1.2 mmol) by
using procedure D. Mp 163 ꢀC. 1H NMR (400 MHz, CDCl3):
(d, 2JH,H¼12.8 Hz, 2H), 7.10 (s, 2H), 8.68 (s, 1H), 8.69 (s, 1H) ppm. 13
C
NMR (100.6 MHz, CD3OD):
69.6 (2C), 70.0 (2C), 126.5, 128.7 (2C), 131.3 (2C), 138.9, 139.0, 144.0
(2C), 157.0, 159.6 ppm. IR (KBr):
979, 1012, 1050, 1122, 1178, 1224, 1285, 1307, 1357, 1379, 1432, 1482,
1595, 1613, 1638, 1834, 2880, 2899, 2918, 2987, 3257 cmꢁ1. HRMS
(ESI-Q-Tof): calcd for C22H30NO3 [M]ꢃþ 356.2220; found 356.2214.
d
¼18.0, 18.3, 25.2 (2C), 30.7 (2C), 48.2,
~
n
¼ 658; 786, 862, 899, 928, 966,
d
¼0.93e1.05 (m, 2H), 1.29e1.43 (m, 4H), 1.46e1.57 (m, 2H), 1.99 (s,
3H), 2.08 (s, 3H), 3.40e3.49 (m, 2H), 3.72e3.80 (m, 2H), 4.19 (d,
2JH,H¼12.8 Hz, 2H), 5.16 (d, 2JH,H¼12.8 Hz, 2H), 6.86 (s, 2H), 7.90 (s,
1H), 8.31 (s, 1H), 8.33 (s, 1H) ppm. 13C NMR (100.6 MHz, CDCl3):
d
¼17.3, 17.4, 24.3 (2C), 29.3 (2C), 69.0 (2C), 70.0 (2C), 126.6 (2C),
4.3.23. 4-{4-[3,11-Dioxa-1(2,6)-(11-hydroxy)benzenacyclododeca-
phanyl]-1,3,5-trimethylpyridinium iodide 15c. Compound 15c
(81 mg, 96%) was obtained as colourless crystals from pyr-
idinylphenol 14c (60 mg, 0.17 mmol) by using procedure E. Mp
129.2, 129.9 (2C), 131.0, 131.1, 148.3 (2C), 148.6, 154.2 ppm. IR (KBr):
~
n
¼ 514; 535, 658, 673, 787, 863, 881, 900, 969, 1012, 1031, 1053,
1082, 1123, 1161, 1193, 1221, 1282, 1312, 1339, 1468, 1496, 1585,
2867, 2882, 2925, 3016, 3288 cmꢁ1. HRMS (ESI-Q-Tof): calcd for
C21H28NO3 [MþH]ꢃþ 342.2063; found 342.2056.
264 ꢀC. 1H NMR (400 MHz, CD3OD):
d
¼0.60e1.00 (br m, 2H),
1.25e1.85 (m, 8H), 2.27 (s, 6H), 4.00e5.5 (br m, 8H), 4.36 (s, 4H),
7.12 (s, 2H), 8.71 (s, 2H) ppm. 13C NMR (100.6 MHz, CD3OD):
d¼18.1
4.3.19. 4-[(3,5-Dimethyl)pyridin-4-yl]-2,6-[(2,10-dioxa)undecane-
1,11-diyle]phenol 14c. After purification by chromatography on sil-
icagel (cyclohexane/AcOEt, 5.5:4.5), compound 14c (89 mg, 79%)
was obtained as colourless crystals from biaryl 13c (117 mg,
0.32 mmol) by using procedure D. Mp 187e189 ꢀC. 1H NMR
(2C), 24.6, 26.0 (2C), 29.2 (2C), 48.2, 65.6 (2C), 70.1 (2C), 125.6, 126.9
(2C), 132.0 (2C), 138.9 (2C), 144.1 (2C), 157.9, 159.5 ppm. IR (KBr):
~
n
¼ 589; 617, 671, 687, 760, 889, 921, 932, 1038, 1087, 1099, 1130,
1176, 1208, 1243, 1289, 1317, 1362, 1384, 1434, 1475, 1602, 1634,
1838, 2856, 2913, 2844, 2981, 3414 cmꢁ1. HRMS (ESI-Q-Tof): calcd
for C23H32NO3 [M]ꢃþ 370.2377; found 370.2372.
(400 MHz, CDCl3):
d
¼0.70e1.00 (m, 2H), 1.36e1.50 (m, 4H),
3
1.50e1.70 (m, 4H), 2.04 (s, 6H), 3.32 (t, JH,H¼5.5, 4H), 4.80 (br m,
4H), 6.86 (s, 2H), 7.52 (s, 1H), 8.34 (ls, 2H) ppm. 13C NMR
4.3.24. 4-{4-[3,12-Dioxa-1(2,6)-(11-hydroxy)benzenacyclo-
tridecaphanyl]-1,3,5-trimethylpyridinium iodide 15d. Compound
15d (235 mg, 75%) was obtained as colourless crystals from pyr-
idinylphenol 14d (226 mg, 0.61 mmol) by using procedure E. Mp
(100.6 MHz, CDCl3):
d
¼17.3 (2C), 23.2, 24.8 (2C), 27.9 (2C), 65.0 (2C),
70.1 (2C), 124.9 (2C), 128.7, 130.5 (2C), 131.1 (2C), 148.4 (2C), 148.5,
~
154.9 ppm. IR (KBr):
n
¼ 679; 704, 877, 896, 909, 939, 960, 986,
1045, 1091, 1129, 1160, 1195, 1223, 1278, 1317, 1346, 1378, 1456, 1474,
1496, 1592, 1615, 2850, 2927, 2941, 3129 cmꢁ1. HRMS (ESI-Q-Tof):
calcd for C22H30NO3 [MþH]ꢃþ356.2226; found 356.2237.
254 ꢀC. 1H NMR (400 MHz, CD3OD):
d
¼1.15e1.20 (m, 4H), 1.22e1.35
(m, 4H), 1.47 (quint, 3JH,H¼6 Hz, 4H), 2.27 (s, 6H), 3.55 (t, 3JH,H¼6 Hz,
4H), 4.37 (s, 3H), 4.85 (s, 4H), 7.13 (s, 2H), 8.71 (s, 2H) ppm. 13C NMR
(100.6 MHz, CD3OD):
48.2, 69.7 (2C), 69.9 (2C), 126.2, 127.4 (2C), 131.4 (2C), 138.9 (2C),
144.1 (2C), 157.5, 159.6 ppm. IR (KBr):
d
¼18.2 (2C), 25.7 (2C), 28.2 (2C), 30.0 (2C),
4.3.20. 4-[(3,5-Dimethyl)pyridin-4-yl]-2,6-[(2,11-dioxa)dodecane-
1,12-diyle]phenol 14d. After purification by chromatography on sil-
icagel (cyclohexane/AcOEt, 5.5:4.5), compound 14d (300 mg, 83%)
was obtained as colourless crystals from biaryl 13d (374 mg,
0.98 mmol) by using procedure D. Mp 135 ꢀC. 1H NMR (400 MHz,
~
n
¼ 664; 863, 913,1015, 1038,
1074, 1179, 1218, 1289, 1363, 1479, 1613, 1643, 2853, 2834, 2996,
3285 cmꢁ1
384.2533; found 384.2527.
.
HRMS (ESI-Q-Tof): calcd for C24H34NO3 [MþH]ꢃþ
CDCl3):
d
¼1.10e1.20 (m, 4H),1.23e1.35 (m, 4H),1.51 (q, 3JH,H¼6.0 Hz,
4H), 2.03 (s, 6H), 3.52 (t, 3JH,H¼6.0 Hz, 4H), 4.65 (s, 4H), 6.87 (s, 2H),
4.3.25. 4-[(1,3,5-Trimethyl)-4-pyridinio]-2,6-[2,8-dioxanonan-1,9-
diyle]phenolate 16a. Compound 16b (13 mg, 60%) was obtained as
red crystals from iodide 15b (30 mg, 0.06 mmol) by using pro-
7.78 (br s,1H), 8.32 (s, 2H) ppm.13C NMR (100.6 MHz, CDCl3):
d¼17.3
(2C), 24.6 (2C), 26.9 (2C), 28.7 (2C), 69.0 (2C), 69.9 (2C), 125.0 (2C),
128.9, 130.0 (2C), 131.1 (2C), 148.4 (2C), 148.6, 154.6 ppm. IR (KBr):
cedure F. Mp (dec) 84 ꢀC. 1H NMR (400 MHz, CD3OD):
d
¼0.73e0.87
~
n
¼ 481; 669, 714, 886,1016,1047,1079,1157,1215,1274,1340,1476,
(m, 2H), 0.87e1.00 (m, 1H), 1.20e1.35 (m, 2H), 1.83e1.98 (m, 1H),
2.36 (s, 6H), 3.26e3.38 (m, 2H), 3.47e3.58 (m, 2H), 3.94 (d,
1592,1614, 2851, 2934 cmꢁ1. HRMS (ESI-Q-Tof): calcd for C23H32N O3
[MþH]ꢃþ 370.2376; found 370.2375.
2JH,H¼11.7 Hz, 2H), 4.28 (s, 3H), 5.35 (d, JH,H¼11.7 Hz, 2H), 6.92 (s,
2
2H), 8.55 (s, 2H) ppm. 13C NMR (100.6 MHz, CD3OD):
d
¼18.6 (2C),
4.3.21. 4-{4-[3,9-Dioxa-1(2,6)-(11-hydroxy)benzenacyclodeca-
phanyl]-1,3,5-trimethylpyridinium iodide 15a. Compound 15a
(80 mg, 70%) was obtained as colourless crystals from pyr-
idinylphenol 14a (80 mg, 0.24 mmol) by using procedure E. Mp
22.2, 29.5 (2C), 47.5, 67.1 (2C), 71.3 (2C), 117.5, 129.0 (2C), 132.8 (2C),
~
138.3 (2C), 143.5 (2C), 161.1, 169.8 ppm. IR (KBr):
n
¼ 651; 665, 752,
1066, 1128, 1097, 1306, 1355, 1594, 1416, 1642, 2845, 2921, 2954,
3042, 3415 cmꢁ1. HRMS (ESI-Q-Tof): calcd for C21H28NO3 [MþH]ꢃþ
342.2064; found 342.2061.
240 ꢀC. 1H NMR (400 MHz, CD3OD):
d
¼0.66e079 (m, 2H), 0.98e1.10
(m, 1H), 1.16e1.28 (m, 2H), 2.01e2.16 (m, 1H), 2.20 (s, 3H), 2.39 (s,
2
3H), 3.24e3.35 (m, 2H), 3.55e3.63 (m, 2H), 4.14 (d, JH,H¼12.6 Hz,
4.3.26. 4-[(1,3,5-Trimethyl)-4-pyridinio]-2,6-[2,9-dioxadecan-1,10-
diyle]phenolate 16b. Compound 16b (19 mg, 65%) was obtained as
red crystals from iodide 15b (40 mg, 0.08 mmol) by using pro-
2H), 4.36 (s, 3H), 5.29 (d, 2JH,H¼12.6 Hz, 2H), 7.10 (s, 2H), 8.59 (s,1H),
8.73 (s, 1H) ppm. 13C NMR (100.6 MHz, CD3OD):
d¼18.0, 18.4, 21.0
(2C), 29.4 (2C), 48.1, 67.9 (2C), 71.0 (2C), 125.6, 129.1 (2C), 131.6 (2C),
138.8, 139.1, 144.0, 144.1, 158.9, 159.5 ppm. IR (KBr):
676, 731, 775, 845, 918, 935, 984, 1061, 1128, 1178, 1226, 1292, 1319,
cedure F. Mp (dec) 94 ꢀC. 1H NMR (400 MHz, CD3OD):
d
¼0.84e0.97
~
n
¼ 548; 660,
(m, 2H), 1.15e1.26 (m, 2H), 1.26e1.45(m, 4H), 2.36 (br s, 6H),
2
3.49e3.3.57 (m, 2H), 3.72e3.8 (m, 2H), 4.03 (d, JH,H¼11.6 Hz, 2H),

E. Ay et al. / Tetrahedron 68 (2012) 628e635
635
2
4.29 (s, 3H), 5.26 (d, JH,H¼11.6 Hz, 2H), 6.94 (s, 2H), 8.55 (s, 2H)
Ay We are also indebted to the Centre National de la Recherche
Scientifique for financial support. We would like also to gratefully
acknowledge Dr. Albert Defoin for his valuable help in guiding this
research work and for numerous fruitful comments. Finally, the
ppm. 13C NMR (100.6 MHz, CD3OD):
(2C), 47.5, 68.9 (2C), 70.5 (2C), 117.7, 129.7 (2C), 132.8 (2C), 138.4
(2C), 143.5 (2C), 161.4, 169.3 ppm. IR (KBr):
1053, 1083, 1122, 1178, 1220, 1305, 1334, 1417, 1466, 1595, 1645,
2341, 2361, 2851, 2927, 3333 cmꢁ1. HRMS (ESI-Q-Tof): calcd for
C22H30NO3 [MþH]ꢃþ 356.2220; found 356.2211.
d
¼18.7 (2C), 24.7 (2C), 30.9
~
n
¼ 649; 752, 902, 966,
ꢀ
authors thank the undergraduate students Claire Sauvee and Marie
ˇ
Dejean de la Batie for her dedicated help in the syntheses.
References and notes
4.3.27. 4-[(1,3,5-Trimethyl)-4-pyridinio]-2,6-[2,10-dioxaundecan-
1,11-diyle]phenolate 16c. Compound 16c (35 mg, 65%) was obtained
as orange crystals from iodide 15c (60 mg, 0.12 mmol) by using
procedure F. Mp (dec) 99 ꢀC. 1H NMR (400 MHz, CD3OD):
ꢀ
1. Keinan, S.; Zojer, E.; Bredas, J.-L.; Ratner, M. A.; Marks, T. J. Theochem 2003, 633,
227e235.
2. Kang, H.; Fachetti, A.; Zu, P.; Jiang, H.; Yang, Y.; Cariati, E.; Righetto, S.; Ugo, R.;
Zuccaccia, C.; Macchioni, A.; Stern, C.; Lui, Z.; Ho, S.-T.; Marks, T. J. Angew. Chem.
2005, 117, 8136e8139; Angew. Chem., Int. Ed. 2005, 44, 7922e7925.
3. Brown, E. C.; Marks, T. J.; Ratner, M. A. J. Phys. Chem. B 2008, 112, 44e50.
4. Liu, L.; Xue, Y.; Wang, X.; Chu, X.; Yang, M. Int. J. Quantum Chem. 2011, doi:10.
1002/qua.23087
5. Boeglin, A.; Barsella, A.; Fort, A.; Manc¸ ois, F.; Rodriguez, V.; Diemer, V.;
Chaumeil, H.; Defoin, A.; Jacques, P.; Carre, C. Chem. Phys. Lett. 2007, 442,
289e301.
6. Diemer, V.; Chaumeil, H.; Defoin, A.; Fort, A.; Boeglin, A.; Carre, C. Eur. J. Org.
Chem. 2006, 2727e2738.
7. Diemer, V.; Chaumeil, H.; Defoin, A.; Fort, A.; Boeglin, A.; Carre, C. Eur. J. Org.
Chem. 2008, 1767e1776.
d
¼0.80e0.97 (m, 2H), 0.97e1.18 (m, 2H), 1.18e1.44 (m, 4H),
1.44e1.70 (m, 2H), 2.35 (br s, 6H), 3.40e3.6 (m, 4H), 3.88e4.14 (m,
2H), 4.28 (s, 3H), 5.11e5.37 (m, 2H), 6.93 (s, 2H), 8.54 (s, 2H) ppm.
13C NMR (100.6 MHz, CD3OD):
d¼18.6 (2C), 25.8 (2C), 26.6, 30.0
ꢀ
(2C), 47.5, 66.9 (2C), 69.7 (2C), 117.2, 128.8 (2C), 133.1 (2C), 138.4
(2C), 143.5 (2C), 161.5, 169.1 ppm. IR (KBr):
~
n
¼ 658; 750, 910, 1032,
ꢀ
1092, 1130, 1177, 1217, 1302, 1338, 1417, 1468, 1593, 1644, 2850,
2924, 3337 cmꢁ1
.
HRMS (ESI-Q-Tof): calcd for C23H32NO3
ꢀ
[MþH]ꢃþ370.2377; found 370.2370.
ꢀ
8. Diemer, V.; Chaumeil, H.; Defoin, A.; Boeglin, A.; Barsella, A.; Fort, A.; Carre, C.
Proc. Spie-Org. Optoelectron. Photonics II 2006, 6192, 559e565.
€
4.3.28. 4-[(1,3,5-Trimethyl)-4-pyridinio]-2,6-[2,11-dioxadodecan-
1,12-diyle]phenolate 16d. Compound 16d (116 mg, 86%) was ob-
tained as red crystals from iodide 15d (180 mg, 0.35 mmol) by using
9. Kuebel-Pollack, A.; Ruttimann, S.; Dunn, N.; Melich, X.; Williams, A. F.; Ber-
nardinelli, G. Helv. Chim. Acta 2006, 89, 841e853.
10. Behr, J.-B.; Defoin, A.; Pires, J.; Streith, J.; Macko, L.; Zehnder, M. Tetrahedron
1996, 52, 3283e3302.
11. Browne, C. M.; Ferguson, G.; McKervey, M. A.; Mulholland, D. L.; O’Connor, T.;
Parvez, M. J. Am. Chem. Soc. 1985, 107, 2703e2712.
procedure F. Mp (dec) 157 ꢀC. 1H NMR (400 MHz, CD3OD):
3
d
¼0.99e1.08 (m, 4H), 1.17e1.28 (m, 4H), 1.41 (q, JH,H¼6.5 Hz, 4H),
12. Koenig, K. E.; Lein, G. M.; Stuckler, P.; Kaneda, T.; Cram, D. J. J. Am. Chem. Soc.
3
2.34 (s, 6H), 3.52 (t, JH,H¼6.5 Hz, 4H), 4.28 (s, 3H), 4.62 (br s, 4H),
1979, 101, 3553e3566.
6.97 (s, 2H), 8.55 (s, 2H) ppm. 13C NMR (100.6 MHz, CD3OD):
d¼18.6
13. Skowronska-Ptasinska, M.; Aarts, V. M. L. J.; Egberink, R. J. M.; Van Eerden, J.;
Harkema, S.; Reinhoudt, D. N. J. Org. Chem. 1988, 53, 5484e5491.
14. Hirose, K.; Nishihara, K.; Harada, N.; Nakamura, Y.; Masuda, D.; Araki, M.; Tobe,
Y. Org. Lett. 2007, 9, 2969e2972.
(2C), 25.4 (2C), 27.8 (2C), 29.8 (2C), 47.5, 68.3 (2C), 69.2 (2C), 117.9,
128.8 (2C), 132.6 (2C), 138.4 (2C), 143.5 (2C), 161.5, 168.7 ppm. IR
~
(KBr):
n
¼ 656; 753, 861, 891, 1013, 1042, 1087, 1178, 1221, 1342,
ꢀ
15. Diemer, V.; Chaumeil, H.; Defoin, A.; Jacques, P.; Carre, C. Tetrahedron Lett. 2005,
1387, 1416, 1466, 1598, 1643, 2851, 2923, 3392 cmꢁ1. HRMS (ESI-Q-
46, 4737e4740.
Tof): calcd for C24H34NO3 [MþH]ꢃþ384.2533; found 384.2524.
16. Duvanel, G.; Grilj, J.; Chaumeil, H.; Jacques, P.; Vauthey, E. Photochem. Photobiol.
Sci. 2010, 9, 908e915.
17. Reichardt, C.; Asharin-Fard, S.; Schafer, G. Liebigs Ann. Chem. 1993, 23e24.
€
18. Cotton, F. A. Inorg. Synth. 1972, 13, 121e124.
19. Zhu, J.; Wang, X.-Z.; Chen, Y.-Q.; Jiang, X.-K.; Chen, X.-Z.; Li, Z.-T. J. Org. Chem.
Acknowledgements
2004, 69, 6221e6227.
20. Czech, A.; Czech, B. P.; Bartsch, R. A.; Allen Chang, C. J. Org. Chem. 1988, 53,
5e9.
ꢁ
ꢀ
We thank the Ministere de l’Enseignement Superieur et de la
Recherche for financial support of this work through a grant to Emel