Detection and identification of alkylating agents by using a bioinspired "chemical nose"

Article abstract of DOI:10.1002/chem.200901617

Alkylating agents are simple and reactive molecules that are commonly used in many and diverse fields such as organic synthesis, medicine, and agriculture. Some highly reactive alkylating species are also being used as blister chemical-warfare agents. The

Full text of DOI:10.1002/chem.200901617

DOI: 10.1002/chem.200901617
Detection and Identification of Alkylating Agents by Using a Bioinspired
“Chemical Nose”
Carmit Hertzog-Ronen,[a] Elena Borzin,[a] Yulia Gerchikov,[a] Nir Tessler,[b] and
Yoav Eichen*[a]
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Chem. Eur. J. 2009, 15, 10380 – 10386

FULL PAPER
Abstract: Alkylating agents are simple
and reactive molecules that are com-
monly used in many and diverse fields
such as organic synthesis, medicine,
and agriculture. Some highly reactive
alkylating species are also being used
as blister chemical-warfare agents. The
detection and identification of alkylat-
ing agents is not a trivial issue because
of their high reactivity and simple
structure. Herein, we report on a new
multispot
luminescence-based
ap-
a solid support and exposed to vapors
of alkylators 8–15. The alkylation-in-
duced color-shift patterns of the seven-
spot array allow clear discrimination of
the different alkylators. The spots are
sensitive to minute concentrations of
alkylators and, because the detection is
based on the formation of new cova-
lent bonds, these spots saturate at
about 50 ppb.
proach to the detection and identifica-
tion of alkylating agents. In order to
demonstrate the potential of the ap-
proach, seven p-conjugated oligomers
and polymers bearing nucleophilic pyr-
idine groups, 1–7, were adsorbed onto
Keywords: alkylation
cence · pi conjugation · sensors
·
lumines-
Introduction
and despite the high sensitivity attained by this approach,
the ability to identify the presence of specific alkylating
agents is still missing, because most alkylators yield a very
similar spectral response with PET systems. This originates
from the fact that the amine group that undergoes quaterni-
zation is not p conjugated to the luminophore and because,
in most cases, the reaction of this amine with the alkylating
Alkylating agents such as dimethylsulfate, dichloromethane,
and methyl iodide are commonly used in organic synthesis
as reagents and solvents. Similar alkylating agents are used
as soil sterilizers,[1] as anticancer drugs,[2] and unfortunately
also as chemical-warfare agents.[3] Owing to their ability to
react with many nucleophiles in our body, most of these ma-
terials are toxic, carcinogenic, and/or mutagenic.[4,5]
If the extensive use and high toxicity of alkylating agents
and their potential applications as terror-warfare agents are
considered, there is a clear need for simple, sensitive, and in-
formative tools for the detection and identification of alkyl-
À
agent yields very similar new C N bonds. Therefore, the
effect of the binding of the alkylator to the amine is expect-
ed to be very similar in all cases.
One approach to overcome this limitation is to electroni-
cally couple the nucleophile that reacts with the alkylating
agent to the p skeleton of the luminophore/chromophore so
that its electronic properties are affected by the nature of
the alkylating group as well as its counterion, if one is
formed as a result of the alkylation process. Furthermore, as
most alkylators are very similar in nature, the identification
method should rely on reactions with an array of sensing
spots for the same alkylator, to seek for specific reaction
patterns that are unique to specific alkylators.
Herein, we report on the preparation and characterization
of a seven-spot “chemical nose” that is capable of detecting
and identifying different alkylating agents in the gas phase.
The seven sensing spots are based on seven p-conjugated
oligomers and polymers that change their optical properties
upon reaction with alkylating agents.
ACHTUNGTRENNUNG
such small and reactive molecules seems to be an inefficient
approach, previous attempts either gave up selectivity and
detected all alkylating agents in a nonspecific way by relying
on the color change of a nucleophile upon reaction with an
alkylating agent[6–8] or they focused on a limited family of al-
kylators by detecting a specific mass or the presence of a
specific atom contained in the alkylators (for example, the
sulfur in mustard gas).[9]
In recent years, we and other groups[10] have reported on
the photoinduced electron transfer (PET) based detection
of alkylating agents based on the quaternization of a Lewis
base nucleophile, usually a tertiary amine group, which
serves also as a quencher to the luminophore.[11,12] Neverthe-
less, owing to the very simple structure of these alkylators
With this simple seven-spot “chemical nose” array, we
demonstrate the ability to identify a captured species from
the response pattern of the array rather than from the rec-
ognition process of a highly selective binding site, which is
very difficult if not impossible to achieve when dealing with
small, reactive, and simple molecules.
[a] Dr. C. Hertzog-Ronen, E. Borzin, Y. Gerchikov, Prof. Y. Eichen
Schulich Department of Chemistry
Technion-Israel Institute of Technology
Technion City, 32000, Haifa (Israel)
Fax : (+972)4-829-5703
Results and Discussion
E-mail: chryoav@techunix.technion.ac.il
In films or when adsorbed onto high-surface paper, materi-
als 1–7[13] react at room temperature with vapors of various
alkylating agents, such as 1-chloro-2-ethylsulfanyl-ethane (8,
a close analogue of sulfur mustard gas), chloromethoxy-
ethane (9), iodomethane (10), and even dichloromethane
(11), according to Scheme 1.
[b] Prof. N. Tessler
Nanoelectronics Center, Department of Electrical Engineering
Technion-Israel Institute of Technology
Technion City, 32000, Haifa (Israel)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200901617.
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Y. Eichen et al.
system do not suffice for the
clear identification of an al-
AHCTUNGTRENNUNG
the electronic energy calcula-
tions clearly demonstrate that
the nature of the counterions
and lone-pair electrons of het-
eroatoms on the alkyl group
are involved in determining
the position of the HOMOs
and LUMOs and, hence, the
band gap of alkylated 1,
mainly through what seem to
be charge-transfer interactions.
The reaction is performed be-
tween a film and molecules in
the gas phase, so the ion pairs
that are formed are not labile
and cannot be easily ex-
changed with the environment.
Scheme 1. Generalized reaction between 1–7 and alkylating agents. LG:
Leaving group.
For example, Figure 1 depicts the absorption and emission
spectra of thin films of oligomer 5 and polymer 6 before and
after alkylation with vapors of 8. In both cases, the films of
the nucleophiles readily react with vapors of the alkylator.
Both the absorption and emission spectra of the nucleo-
philes are affected by the reaction with the alkylating
agents. The alkylator is covalently bound to the film in the
product, so the change in the optical characteristics does not
revert when the concentration of alkylator is lowered.
Table 1 depicts the position of the HOMO and LUMO or-
bitals and the band gaps for 1–7 and their derivatives with
alkylators 8–10, as calculated from their cyclic voltammo-
grams and optical spectra.[14]
The alkylation-induced spectral shifts depend not only on
the nature of the p-conjugated nucleophile but also on the
nature of the alkylating agent, despite the fact that their het-
eroatoms and aromatic rings are not electronically conjugat-
ed to the p-conjugated nucleophile.
The origin of the differences in the specific positions of
the HOMOs and LUMOs is revealed by electronic energy
calculations[15] performed on model system 1 and on some
of its alkylated derivatives bearing different counter-ions
and lone-pair electrons (Table 2). These types of charge-
transfer interactions between nonbonding electrons and
counterions and the p system of the nucleophile could be
harnessed to provide information on the exact nature of the
alkylator that was trapped. Nevertheless, the small differen-
ces that are observed upon alkylation of a single-nucleophile
Figure 1. Absorption and emission spectra of 5 (thick lines) and 6 (thin
lines) of thin films on quartz before (continuous lines) and after (dashed
lines) exposure to 8.
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Detection and Identification of Alkylating Agents
FULL PAPER
Inspired by the olfactory system,[16] several groups have
developed artificial olfactory-like sensing arrays[17] for de-
tecting ions,[18,19] volatile substances,[20] amines,[21] amino
acids,[22] proteins,[23] and carbohydrates;[24] in these arrays,
the identity of the target is defined by the response pattern
of an array of low-selectivity sensors. We have harnessed a
similar approach for the detection and identification of al-
Table 1. Highest occupied molecular orbital (HOMO) and lowest unoc-
cupied molecular orbital (LUMO) energy values and band gaps for 1–7
and their derivatives with alkylators 8–10.
HOMO [eV]
LUMO [eV]
Band gap [eV]
1
5.76
5.98
5.51
5.78
4.95
5.25
4.77
5.40
4.72
4.64
4.50
4.93
5.03
5.10
5.12
5.04
1.87
2.97
2.08
3.14
2.40
3.27
2.33
3.12
2.44
2.40
3.54
2.93
2.47
2.65
2.92
2.57
3.89
3.01
3.43
2.64
2.55
1.98
2.44
2.18
2.28
2.24
1.96
2.00
2.56
2.19
2.20
2.47
1+10
2
2+10
3
3+10
5
5+8
6
6+8
6+9
6+10
7
7+8
7+9
7+10
AHCTUNGTREGkNNNU ylating agents by using a highly reactive and nonspecific
multispot sensor system that relies on the optical detection
of luminescence spectral shifts for the identification step.
For that purpose, compounds 1–7 were adsorbed onto
high-surface filter paper squares (Whatman grade 50, low
ash) and assembled into a seven-spot sensor array. Figure 2
depicts luminescence (lmax =365 nm) pictures of the sensor
array before (first row) and after (subsequent rows) expo-
sure to vapors of alkylating agents 8–15. The identity of the
alkylating agent that the sensor array was exposed to can be
clearly deduced from the color pattern that is developed.[25]
For example, dichloromethane (11) and diethyl carbonate
(15) produce a very similar luminescence-shift response
upon reaction with 1, 2, and 4–7. Nevertheless, with 3, the
luminescence color shifts from RGB=164,84,38 to
169,135,35 and 140,152,53, with 11 and 15, respectively. This
color difference is easily noticeable by using a colorimeter
and is even clear to the naked eye. Structurally similar 8 and
9 generate a very different luminescence shift with all the
spots.
Table 2. Calculated HOMO and LUMO energies and band gaps for 1
with alkylators 8 and 16–19.[a]
HOMO [eV]
LUMO [eV]
Band gap [eV]
1
6.69
5.66
5.66
5.55
7.67
4.38
5.39
1.57
2.58
2.50
2.37
3.23
2.23
2.64
5.12
3.08
3.16
3.18
4.44
2.15
2.75
1+8 (ClÀ)
1+16 (ClÀ)
1+17 (ClÀ)
1+18 (CNÀ)
1+19 (MeOÀ)
1+20 (acetate)
The array responds to even minute amounts of alkylating
agents because the alkylation process yields a new and
[a] Calculations performed at the B3LYP 6-311+G(d) level.
Figure 2. A seven-spot sensor array of 1–7, adsorbed on high-surface filter paper, before (first row) and after (lower rows) exposure to alkylating agents
8–15. The figures on the right side of each square denote the red/green/blue (RGB) value of the spot when exposed to UV exciting light (lmax =365 nm).
Chem. Eur. J. 2009, 15, 10380 – 10386
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Y. Eichen et al.
(Whatman grade 50, low ash). These filter papers were dried in air and
exposed to vapors of alkylating agent in a closed glass vessel until the
spectra stabilized (several hours). The fluorescence colors were measured
under UV excitation (lmax =365 nm).
stable covalent bond. Figure 3 depicts a titration curve of a
film of 7 in an atmosphere of chloromethoxyethane (9). As
can be seen from the graph, even without forcing the atmos-
phere through the sensing filter paper, the system responds
to concentrations as low as a few ppb and saturates at con-
centrations that are lower than 50 ppb.
Characterization of the saturation curve: A film of 7 (spin coated on a
quartz window) was mounted on
a previously described detection
system.[8,26] The film was exposed to different concentrations of vapor of
9. Data were recorded after stabilization of the system.
Materials: 5,5’-Bis(tri-n-butylstannyl)-2,2’-bithiophene,[27] 2,7-diformyl-
9,9-di-n-octylfluorene,[28] poly[9,9’-dioctylfluoren-2,7-ylenevinylene-co-alt-
5,5’-(2,2’-bipyridylenevinylene)][29] (7), 4-(2-bromo-thiophen-3-yl)-pyri-
dine,[30] 1,4-di(2’-ethylhexyloxy)benzene,[31] 2,5-di(bromomethyl)-1,4-di(2’-
ethylhexyloxy)benzene,[18] 1,4-di(2’-ethylhexyloxy)-2,5-bis(triphenylphos-
phino)methylbenzene dibromide,[18] 2-bromo-9,9-dioctylfluorene,[32] 2-al-
dehyde-9,9-dioctylfluorene,[33] and 2,2’-bipyridinyl-5,5’-dicarbaldehyde[34]
were prepared according to previously reported procedures.
4-Thiophen-3-yl-pyridine (1): 4-Bromopyridine hydrochloride (1.23 g,
6.32 mmol), PdACHTUNGTRENGN(U PPh3)4 (0.35 g, 3.12 mmol), Ba(OH)2·8H2O (4.98 g,
9.49 mmol), and thiophene-2-boronic acid (0.89 g, 6.97 mmol) were dis-
solved in a mixture of 1,2-dimethoxyethane (DME) (82 mL) and H2O
(22 mL) under an inert atmosphere, and the mixture was stirred over-
night at 858C. After being cooled to room temperature, the reaction mix-
ture was extracted with three portions of dichloromethane. The com-
bined organic layers were washed with water and brine, then dried over
sodium sulfate. The solvents were evaporated. The crude product was pu-
rified by using column chromatography (silica; methanol/dichlorometh-
AHCTUNGERTGaNNUN ne, 1:99) to afford 4-thiophen-3-yl-pyridine (1) as a white solid (1.7 g,
Figure 3. Dependence of the fluorescence peak maximum of a film of 7
(thickness of 12 mm) on the concentration of 9 in its ambient atmosphere
(carrier gas N2, V=2 L, lex =355 nm).
75%); m.p. 1388C; 1H NMR (300 MHz, CDCl3, tetramethylsilane
(TMS), 258C): d=7.43 (d, 2H), 7.45 (d, 2H), 7.64 (dd, 1H), 8.69 ppm (d,
2H); 13C NMR (125 MHz, CDCl3, 258C): d=120.73, 123.05, 125.63,
127.06, 139.41, 142.54, 150.34 ppm; MS (CI): m/z: 162 [M+H+], 161
[M+].
3,3’-Bis(4-pyridyl)-2,2’-bithiophene (2): A solution of anhydrous NiCl2
(0.65 g, 5 mmol) and triphenylphosphine (5.24 g, 20 mmol) in N,N-di-
Conclusions
AHCTUNGTREGNmNUN ethylformamide (DMF) (25 mL) was stirred at 808C under N2 until a
In conclusion, the application of a p-conjugated nucleo-
phile-based chemosensing concept for the efficient and in-
formative detection of alkylating agents has been demon-
strated. Compounds 1–7 were found to be highly effective in
reacting with even low concentrations of alkylating agents,
with saturation at about 50 ppb. In a similar manner to the
olfactory system, the different p-conjugated nucleophiles re-
spond with different spectral shifts upon reaction with differ-
ent alkylating agents; this allows clear identification of the
specific alkylator in the atmosphere by using a multispot
sensor array.
homogenous blue solution was formed. Zinc powder (0.32 g, 5 mmol)
was then added, and the mixture was stirred at 808C for approximately
1 h until the mixture turned red. 4-(2-Bromo-thiophen-3-yl)-pyridine
(0.96 g, 4 mmol) was added, and the mixture was stirred overnight at
808C. The resulting mixture was added to an aqueous ammonia solution
and was extracted with three portions of dichloromethane. The combined
organic layers were dried over sodium sulfate, filtered, and concentrated
under reduced pressure. The crude residue was purified by using column
chromatography (alumina; hexane/ethyl acetate, 50:50) to afford 3,3’-
bis(4-pyridyl)-2,2’-bithiophene (2) as a yellowish solid (0.77 g, 60%);
1H NMR (300 MHz, CDCl3, 258C, TMS): d=6.72 (dd, 4H), 7.07 (d, 2H),
7.45 (d, 2H), 8.27 ppm (dd, 4H); 13C NMR (125 Hz, CDCl3, 258C): d=
122.58, 127.29, 128.73, 138.43, 143.11, 160.88 ppm; MS (DCI+): m/z:
321.4 [M+H+], 320.4 [M+].
3,3’’’-Bis(4-pyridyl)-2,2’;5’,2’’;5’’,2’’’-quaterthiophene (3): 4-(2-Bromothio-
phen-3-yl)pyridine (0.2 g, 0.8 mmol), 5,5’-bis(tributyltin)-2,2’-bithiophene
(0.24 g, 0.32 mmol), and PdACHTUNRGTNEUNG(PPh3)4 (0.03 g, 0.03 mmol) were dissolved in
Experimental Section
dry toluene (20 mL) and the mixture was refluxed under nitrogen for
48 h. The mixture was then cooled to room temperature and concentrat-
ed. The crude was purified by using column chromatography (alumina;
methanol/dichloromethane, 0.5:99.5) to afford 3,3’’’-bis(4-pyridyl)-
2,2’;5’,2’’;5’’,2’’’-quaterthiophene (3) as an orange solid (0.12 g, 77%);
m.p. 197.58C; 1H NMR (300 MHz, CDCl3, 258C, TMS): d=6.77 (d, 2H),
6.90 (d, 2H), 7.06 (d, 2H), 7.40 (d, 2H), 8.56 ppm (d, 2H); 13C NMR
(125 MHz, CDCl3, 258C): d=90.07, 93.78, 123.79, 124.26, 125.51, 128.08,
129.78, 143.82, 150.08, 162.77 ppm; MS (MALDI-TOF): m/z: 484.0 [M+].
Apparatus: Absorption spectra were recorded on a Shimadzu UV-1601
spectrometer and fluorescence spectra were recorded on a Perkin–Elmer
LS 50 luminescence spectrometer. All of the optical measurements were
performed in analytical-grade solvents or in the solid state. NMR spectra
were recorded on Bruker AV-300 and Bruker AV-500 spectrometers.
Mass spectra were recorded on MALDI micro MX (MICROMASS),
ESI-MS, and TSQ-70B (FINNIGAN MAT) spectrometers. GPC analysis
of the polymers was performed at Waters Corp., Milford, MA, USA,
with tetrahydrofuran (THF) as the eluent and polystyrene standards for
reference. Cyclic voltammograms were recorded by using a PGSTAT12
(Autolab) system. The three-electrode electrochemical cell included a
Ag/AgNO3 (10À2 m in acetonitrile) reference electrode, a Pt (F=3 mm)
working electrode, and a Pt counter electrode.
3-Bromo-5-(1,3-dioxolan-2-yl)pyridine: 5-Bromopyridine-3-carbaldehyde
(1.5 g, 8 mmol), ethylene glycol (0.6 mL, 10 mmol), and
a catalytic
amount of camphorsulphonic acid were dissolved in benzene (50 mL) in
a Dean–Stark apparatus and heated to reflux overnight. The mixture was
then cooled, washed with a basic aqueous solution, dried over sodium
sulfate, and concentrated under reduced pressure to result in 3-bromo-5-
(1,3-dioxolan-2-yl)pyridine in the form of a colorless oil (1.84 g, quantita-
Preparation of the multispot array: Each of the oligomers and polymers
(5 mg) was dissolved in THF (2 mL) and then adsorbed onto filter papers
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Detection and Identification of Alkylating Agents
FULL PAPER
1
tive yield). The material was used as obtained for the next step; H NMR
(300 MHz, CDCl3, 258C, TMS): d=4.01 (m, 4H), 5.77 (s, 1H), 7.88 (s,
1H), 8.54 (d, 1H), 8.6 ppm (d, 1H); 13C NMR (75 MHz, CDCl3, 258C):
d=65.13, 100.64, 120.31, 135.25, 136.43, 146.10, 151.10 ppm; MS
(MALDI-TOF): m/z: 230.6 [M+].
white solid (0.28 g, 80%); m.p. >2008C; 1H NMR (300 MHz, CDCl3,
258C, TMS): d=0.68 (m, 4H), 0.68–0.72 (t, 6H), 0.82 (m, 8H), 0.97–1.1
(m, 12H), 1.7 (m, 2H), 1.75 (m, 2H), 5.19 (d, 2H), 6.83–6.84 (d, 1H), 6.9
(dd,1H), 7.18–7.19 (m, 2H), 7.53–7.59 (m, 12H), 7.66–7.69 ppm (m, 3H);
13C NMR (75 MHz, CDCl3, 258C): d=14.10, 22.88, 24.50, 29.49, 29.70,
30.36, 31.93, 41.72, 43.98, 45.21, 126.82, 127.66, 128.29, 128.35, 128.45,
128.85, 128.89, 130.63, 138.01, 141.01, 147.87 ppm; MS (MALDI-TOF):
m/z: 664.97 [MÀ2H+].
5,5-Bis[2-(9,9-dioctyl-9H-fluoren-2-yl)vinyl]-3,3’-bipyridinyl (4): Sodium
ethoxide (0.005 g, 0.23 mmol) in ethanol (5 mL) was added dropwise with
stirring to a solution of 2-(9,9-dioctyl-9H-fluorenyl)methyltriphenylphos-
phonium chloride (0.25 g, 0.35 mmol) and [3,3’]bipyridinyl-5,5’-dicarbal-
dehyde (0.046 g, 0.01 mmol) in dichloromethane (10 mL) under nitrogen.
After 2 h of stirring at room temperature, the solvents were evaporated
under reduced pressure and the crude residue was purified by using
column chromatography (alumina; ethyl acetate/hexane, 20:80) to yield
5,5-bis[2-(9,9-dioctyl-9H-fluoren-2-yl)vinyl]-3,3’-bipyridinyl (4) in the
form of a yellow powder (0.28 g, 50%); 1H NMR (300 MHz, CDCl3,
258C, TMS): d=0.72–0.76 (m , 8H), 0.8–0.84 (m, 12H), 1.08–1.12 (m,
20H), 1.17–1.20 (m, 4H), 1.91–1.97 (m, 8H), 6.65 (s, 1H), 6.85 (m, 3H),
7.27–7.31 (m, 8H), 7.48–7.51 (m, 4H), 7.64–7.67 (m, 4H), 8.03 (dd, 2H),
8.7–8.71 (dd, 2H), 8.77 ppm (dd, 2H); 13C NMR (75 MHz, CDCl3, 258C):
d=15.9, 24.4, 25.5, 31.0, 31.5, 33.5, 42.2, 56.9, 121.7, 121.8, 124.7, 125.2,
127.7, 128.7, 129.2, 132.8, 134.2, 135.3, 137.1, 142.3, 143.7, 148.5, 149.8,
152.9, 153.2 ppm; MS (MALDI-TOF): m/z: 985.54 [M+].
5,5-Bis(1,3-dioxolan-2-yl)-3,3’-bipyridinyl: A solution of anhydrous NiCl2
(1.3 g, 10 mmol) and triphenylphosphine (10.48 g, 40 mmol) in DMF
(50 mL) was stirred at 808C under N2 until a homogenous blue solution
was formed. Zinc powder (0.64 g, 10 mmol) was then added, and the mix-
ture was stirred at 808C for approximately 1 h until the mixture turned
red. 3-Bromo-5-(1,3-dioxolan-2-yl)-pyridine (2.3 g, 10 mmol) was added,
and the mixture was stirred overnight at 808C The resulting mixture was
added to an aqueous ammonia solution and was extracted with three por-
tions of dichloromethane. The combined organic layers were dried over
sodium sulfate, filtered, and concentrated under reduced pressure. The
crude residue was purified by using column chromatography (alumina;
hexane/ethyl acetate, 20:80) to afford 5,5-bis(1,3-dioxolan-2-yl)-3,3’-bipyr-
idinyl in the form of a white solid (1.8 g, 60%); m.p. 1308C; 1H NMR
(300 MHz, CDCl3, 258C, TMS): d=4.01 (m, 8H), 5.80 (s, 2H), 7.89 (s,
1H), 8.54 (d, 1H), 8.70 (d, 2H), 8.79 ppm (d, 2H); 13C NMR (75 MHz,
CDCl3, 258C): d= 65.51, 101.72, 116.73, 132.69, 134.01, 145.93,
147.98 ppm; MS (MALDI-TOF): m/z: 301 [M+H+].
3,3’-Bipyridinyl-5,5’-dicarbaldehyde: HCl (10 mL, 7m) was gradually
added to a solution of 5,5-bis(1,3-dioxolan-2-yl)-3,3’-bipyridinyl (0.8 g,
2.6 mmol) in CHCl3 (20 mL). The mixture was stirred at room tempera-
ture for 24 h. The organic layer was separated, washed with a saturated
solution of potassium carbonate, and dried over sodium sulfate. It was
concentrated to afford 3,3’-bipyridinyl-5,5’-dicarbaldehyde in the form of
a white solid (0.55 g, quantitative); m.p. >2008C; 1H NMR (300 MHz,
CDCl3, 258C, TMS): d=8.36 (s, 2H), 9.08 (d, 4H), 10.18 ppm (s, 2H);
13C NMR (75 MHz, CDCl3, 258C): d=133.84, 152.04, 152.91, 189.94 ppm;
MS (MALDI-TOF): m/z: 230 [M+NH4+].
AHCTUNGTRENNUNG
A
(230 mg, 0.23 mmol) and 4-methoxybenzaldehyde (31 mg, 0.23 mmol) in
dichloromethane (10 mL). The mixture was stirred at room temperature
for 1 h. Evaporation of the solvents and purification by using column
chromatography (silica; dichloromethane/methanol, 95:5) afforded {2,5-
bis(2-ethylhexyloxy)-4-[2-(4-methoxyphenyl)vinyl]benzyl}triphenylphos-
phonium bromide in the form of a yellow powder (0.13 g, 50% yield);
m.p. >2008C; 1H NMR (300 MHz, CDCl3, 258C, TMS): d=0.55 (t, 6H),
0.82 (m, 16H), 1.07–1.18 (m, 16H), 1.22 (m, 2H), 2.79 (m, 2H), 3.67 (s,
2H), 3.74 (s, 1H), 5.13–5.18 (d, 2H), 6.45 (dd, 2H), 6.61–6.67 (d, 2H),
6.82 (d, 1H), 7.06 (d, 2H), 7.33 (d, 1H), 7.66 (m, 12H), 7.69 ppm (t, 3H);
13C NMR (75 MHz, CDCl3, 258C): d=15.80, 24.8, 25.60, 30.07, 31.0, 32.1,
72.5, 115.9, 119.8, 120.4, 125.4, 129.5, 131.8, 136.1, 136.6, 152.1,
160.4 ppm; MS (MALDI-TOF): m/z: 480.33 [MÀPPh3+].
(9,9-Dioctyl-9H-fluoren-2-yl)methanol: A mixture of 9,9-dioctylfluorene-
2-aldehyde (1.2 g, 2 mmol) and sodium borohydride (0.085 g, 2.8 mmol)
in dry THF (40 mL) was stirred under nitrogen at room temperature for
24 h. The mixture was then made slightly acidic by using an aqueous HCl
solution (7m). The aqueous layer was saturated with NaCl and extracted
with three portions of dichloromethane. The organic layers were com-
bined, dried with sodium sulfate, and concentrated under reduced pres-
sure to give (9,9-dioctyl-9H-fluoren-2-yl)methanol in the form of a white
solid (1.1 g, 95%); 1H NMR (300 MHz, CDCl3, 258C, TMS): d=0.54 (t,
6H), 0.78 (t, 6H), 1.03–1.13 (m, 16H), 1.78 (m, 2H), 1.90 (t, 4H), 4.71 (s,
2H), 7.23–7.27 (m.5H), 7.63 ppm (dd, 2H); 13C NMR (75 MHz, CDCl3,
258C): d=14.54, 23.09, 24.30, 29.71, 30.53, 32.28, 40.82, 55.54, 66.30,
120.20, 122.06, 126.27, 140.29, 140.93, 151.88 ppm; MS (MALDI-TOF):
m/z: 420.35 [M+].
5,5’-Bis(2-
ACHTUNGTRENNUNG
vinyl)-3,3’-bipyridinyl (5):
A
0.23 mmol) in ethanol (5 mL) was added dropwise to a solution of {2,5-
bis(2-ethylhexyloxy)-4-[2-(4-methoxyphenyl)vinyl]benzyl}triphenylphos-
phonium bromide (120 mg, 0.15 mmol) and 3,3’-bipyridinyl-5,5’-dicarbal-
dehyde (15 mg 0.07 mmol) in CH2Cl2 (10 mL). NaOEt (0.005 g,
0.23 mmol) in ethanol (5 mL) was added dropwise with stirring. After 1 h
of stirring, the solvent was evaporated under vacuum and the residue was
passed through an alumina chromatographic column eluted with ethyl
acetate/hexane (20:80) to yield a yellow viscose solid in 80% yield;
1H NMR (300 MHz, CDCl3, 258C, TMS): d=0.88 (t, 12H), 0.93–1.19 (m,
32H), 1.27 (m, 8H), 3.71 (d, 8H), 6.51 (m, 1H), 6.84 (d, 2H), 7.10–7.12
(t, 2H), 7.28 (d, 1H), 7.40–7.43 (d, 2H), 7.60 (m, 2H), 7.50–7.61 (d, 1H),
7.96 (s, 1H), 8.66 (t, 1H), 8.74 ppm (d, 2H); 13C NMR (125 MHz, CDCl3,
258C): d=13.2, 15.9, 24.9, 26.0, 31.0, 31.1, 31.2, 31.5, 32.1, 32.7, 33.7, 41.5,
57.1, 73.2, 11.7, 112.4, 115.3, 115.9, 123.0, 125.6, 125.9, 126.6, 127.0, 128.5,
129.5, 129.9, 130.6, 132.0, 132.5, 132.9, 134.5, 135.8, 148.3, 149.6, 152.7,
153.3, 161.1 ppm; MS (TOF LD+): m/z: 1085.44 [M+].
2-Chloromethyl-9,9-dimethyl-9H-fluorene: A solution of thionyl chloride
(0.1 mL, 1 mmol) and (9,9-dioctyl-9H-fluoren-2-yl)methanol (0.3 g,
0.07 mmol) in dichloromethane (5 mL) was stirred for 3 h at room tem-
perature and then washed with 3 portions of water (50 mL each). The
aqueous layer was extracted with 3 portions of dichloromethane (50 mL
each). The combined organic layers were washed with a dilute aqueous
sodium bicarbonate solution, dried over sodium sulfate, and evaporated
under reduced pressure to afford 2-chloromethyl-9,9-dimethyl-9H-fluo-
rene in the form of a white solid (0.25 g, 85%); 1H NMR (300 MHz,
CDCl3, 258C, TMS): d=0.54–0.57 (m, 4H), 0.73–0.77 (m, 6H), 1.03–1.10
(m, 16H), 1.12–1.15 (m, 4H), 1.85–1.91 (m, 4H), 4.6 (s, 2H), 7.24–7.28
(m, 3H), 7.59–7.61 (m, 1H), 7.63–7.64 ppm (m, 2H); 13C NMR (75 MHz,
CDCl3, 258C): d=14.0, 22.5, 23.60, 29.1, 29.13, 29.8, 31.7, 40.1, 46.8, 55.1,
119.9, 123.2, 127.5, 136.5, 140.7, 151.6 ppm; MS (MALDI-TOF): m/z:
665.47 [M+].
PolyACTHNUTRGNEUG[N 1,4-di-(2’-ethylhexyloxy)benzenylene vinylene-co-alt-5,5’-(2,2’-bipyr-
idylenevinylene)] (6): A solution of sodium ethoxide (0.025 g, 1.15 mmol)
in ethanol (8 mL) was added dropwise to a solution of 2,2’-bipyridinyl-
5,5’-dicarbaldehyde (0.1 g, 0.47 mmol) and 1,4-di-(2’-ethylhexyloxy)-2,5-
bis(triphenylphosphino)methyl benzene dibromide (0.49 g, 0.47 mmol) in
dichloromethane (30 mL). The mixture was stirred for three days at
room temperature. The mixture was then added to methanol (300 mL),
and the precipitate was collected by filtration. The crude residue was pu-
2-(9,9-Dioctyl-9H-fluorenyl)methyltriphenylphosphonium chloride:
A
mixture of 2-chloromethyl-9,9-dimethyl-9H-fluorene (0.2 g, 0.5 mmol)
and triphenylphosphine (0.054 g, 2 mmol) in DMF (35 mL) was stirred
for 5 h at 1008C. The mixture was then cooled to room temperature and
mixed with diethyl ether (200 mL) with stirring. The white precipitate
was collected, washed with diethyl ether and dried to afford 2-(9,9-dioc-
tyl-9H-fluorenyl)methyltriphenylphosphonium chloride in the form of a
Chem. Eur. J. 2009, 15, 10380 – 10386
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10385

Y. Eichen et al.
rified by using column chromatography (silica; dichloromethane/meth-
anol, 95:5) to afford poly[1,4-di-(2’-ethylhexyloxy)benzenylene vinylene-
red solid
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
co-alt-5,5’-(2,2’-bipyridylenevinylene)] (6) in the form of
a
(300 mg, 30%); 1H NMR (300 MHz, CDCl3, 258C, TMS): d=0.87 (br,
6H), 0.89 (br, 4H), 1–1.2 (m, 16H), 1.22 (m, 2H), 2.87 (s, 4H), 5.24 (m,
4H), 7.17 (br, Ph), 7.49–7.7 (m, vinyl H), 7.98 (pyridyl), 8.44 (pyridyl),
8.80 ppm (pyridyl); GPC: Mn =2480 gmolÀ1
.
Acknowledgements
This work was supported by the Technion Funds for Security Research.
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Received: June 13, 2009
Published online: September 11, 2009
10386
www.chemeurj.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 10380 – 10386