Simple molecule-based fluorescent sensors for vapor detection of TNT

Article abstract of DOI:10.1021/ol801030u

(Chemical Equation Presented) 1,4-Diarylpentiptycenes (1a-e) were synthesized from 1,4-dichloro- or 1,4-difluoro-2,5-diarylbenzene derivatives by double base-promoted dehydrohalogenation to give corresponding arynes, which in the presence of anthracene un

Full text of DOI:10.1021/ol801030u

ORGANIC
LETTERS
2008
Vol. 10, No. 17
3681-3684
Simple Molecule-Based Fluorescent
Sensors for Vapor Detection of TNT
Grigory V. Zyryanov, Manuel A. Palacios, and Pavel Anzenbacher, Jr.*
Center for Photochemical Sciences and Department of Chemistry, Bowling Green State
UniVersity, Bowling Green, Ohio 43403
paVel@bgsu.edu
Received June 7, 2008
ABSTRACT
1,4-Diarylpentiptycenes (1a-e) were synthesized from 1,4-dichloro- or 1,4-difluoro-2,5-diarylbenzene derivatives by double base-promoted
dehydrohalogenation to give corresponding arynes, which in the presence of anthracene undergo cycloaddition providing 1,4-diarylpentiptycenes
in moderate overall yields. The resulting 1,4-diarylpentiptycenes show fluorescence modulated by the 1,4-aryl residues. The fluorescence is
quenched in the presence of vapors of nitroaromatic compounds suggesting potential application in sensing of explosives.
Host materials that form inclusion complexes with small
molecules are the subject of considerable interest owing
to potential applications in the preparation of sensors and
materials for selective sequestration of substrates of
interest. Growing attention is currently devoted to studying
supramolecular complexes of a wide variety of lipophilic
hosts for electroneutral species that include calixarenes1
and related macrocycles, cyclodextrins,2 cyclovera-
trylenes,3 cryptophanes,4 cucurbiturils,5 and their deriva-
tives.
used in landmines and improvised explosive devices.7 The
materials successfully used for detection of nitroaromates
are fluorescent polymers with the ability to form com-
plexes with nitroaromates while changing their emission.
Examples are polyphenyleneethynylenes with integrated
pentiptycene receptors,8a polyphenylenebutadiynylenes,8b
polyacetylenes,8c and polymetalloles8d such as polysiloles.8e
As a part of our work on polythiophene conductivity-based
sensors9 we decided to investigate electropolymerizable
pentiptycene receptors carrying thiophene moieties to be
deposited as electrochemical sensors for TNT.
The interest in pentiptycene receptors was sparked by
the discovery that iptycenes bind nitroaromate explosives6
Pentiptycene derivatives are most frequently synthesized
by the Clar synthesis, which involves double Diels-Alder
(1) Calixarenes 2001; Asfari, Z., Bohmer, V., Harrowfield, J., Vicens,
J, Eds.; Kluwer Academic Publishers: Dordrecht, 2001.
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J. E., MacNicol, D. D., Vo¨gtle, F., Reinhoudt, D. N., Lehn, J.-M., Eds.;
Volume 3: Cyclodextrins; Szejtl, J., Osa, T., Volume Eds.; Pergamon-
Elsevier Science: Oxford, 1996.
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100, 2537. (b) Zhao, D.; Swager, T. M. Macromolecules 2005, 38, 9377.
(c) Liu, Y.; Mills, R. C.; Boncella, J. M.; Schanze, K. S. Langmuir 2001,
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10.1021/ol801030u CCC: $40.75
Published on Web 07/26/2008
2008 American Chemical Society

cycloaddition of an acene to benzoquinone.10 The resulting
pentiptycene quinone 211 may then be reacted with organo-
metallic reagents such as lithium acetylides to yield 1,4-
substituted derivatives 3 according to Scheme 1, which was
as the Stille,18 Suzuki-Miyaura,16 and Negishi19 couplings
(Scheme 2). The reduction of quinone 2 to the corresponding
Scheme 2.
Alternative Synthesis of 1,4-Diaryl Pentiptycenesa
Scheme 1. Synthesis of 1,4-Substituted Pentiptycenes
utilized by Swager to generate poly-(phenyleneethynylene)s
comprising pentiptycene moieties.6 Unfortunately, there is
no literature describing a similar approach using aryllithiums
or arylmagnesium halides.
This pattern of limited reactivity of both iptycene-
benzoquinone carbonyls was also observed by Yang et
al.,12,13 who synthesized pentiptycenes with middle ring
substituents (described here as 1,4-positions based on the
p-benzoquinone).14 Yang et al. successfully attached a variety
of substituents to 1,4-positions, however, carbon substituents
proved difficult to introduce to both 1,4-positions. Notable
exceptions are the acetylene derivatives introduced following
the outline in Scheme 1.
Originally, we believed the lack of a direct coupling
method to be due to the limited availability of the 1,4-dihalo
derivatives.12,15,16 However, Yang et al.12,13 were able to
successfully perform a Suzuki-Miyaura17 coupling on
1-alkoxy-4-iodopentiptycene in 72% yield. In an effort to
circumvent the problem of limited availability of 1,4-dihalo
derivatives, we synthesized the corresponding 1,4-triflate 4,
which we hoped would react in Pd0-catalyzed reactions such
aX-ray ORTEP representation of 4 (displacement ellipsoids are scaled
to the 50% probability level).
hydroquinone form20 followed by reaction with triflic
anhydride in pyridine at 0 °C gave the corresponding bis-
triflate 4 in a quantitative yield (>99%). Triflate 4 is a stable
crystalline compound that can be prepared at a multigram
scale. The coupling procedures, however, failed to yield 1,4-
diarylpentiptycenes 1 in yields exceeding 9%. The starting
material 4 was recovered regardless of the coupling method
or reaction conditions.
Simultaneously with the above approach, we attempted
to construct the 1,4-diarylpentiptycene using the aryne-
anthracene [4 + 2] cycloaddition approach.21 Toward this
end we considered several strategies to generate a 1,4-diaryl
bisaryne precursor 5 to be reacted with anthracene.
Numerous methods of generating benzyne are known from
the literature,22 starting, for example, from haloaromates
using sodium amide or other strong bases, 1,2-dihaloarenes,23
from arenediazonium ions derived from anthranilic acid,24
2-(trimethylsilyl)phenyl triflates, aminotriazoles,25,26 and
aryl[2-(trimethylsilyl)phenyl]iodonium triflates,27 etc. Com-
pared to the double dehydrohalogenation, these methods of
generating aryne are often carried out using mild conditions
and furnish moderate to high yields of corresponding arynes.
However, the preparation of the hexasubstituted benzene
precursors requires multiple-steps syntheses that with excep-
tion of tetrahalo-1,2-diarylbenzenes in our hands did not
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(16) Rare Sonogashira coupling of 1,4-diiodopentiptycene was reported
by: Williams, V. E.; Yang, J. S.; Lugmair, C. G.; Miao, Y. J.; Swager,
T. M. Proc. SPIE 1999, 3710 (Pt. 1), 402
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Meijere, A., Diederich, F., Eds.; Wiley-VCH: Weinheim, 2004; p 125.
(19) Negishi, E.-I.; Dumond, Y. In Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E.-I., Ed.; Wiley: New York,
2002; Vol. 1, p 229.
(22) Pellisier, H.; Santenelli, M. Tetrahedron 2003, 59, 701.
(23) Shahlai, K.; Acquaah, S. O.; Hart, H. Organic Syntheses 2004, 10,
678; Organic Syntheses 1998, 75, 678.
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J.-M. J. Org. Chem. 2000, 65, 871.
(24) Buxton, P. C.; Heaney, H. J. Chem. Soc., Chem. Commun. 1973,
545.
(21) (a) Hoffman, R. W. Dehydrobenzene and Cycloalkynes; Academic
Press: New York, 1967. (b) Gilchrist, T. L. In The Chemistry of Functional
Groups; Supplement C, Chapter 11; Patai, S.; Rappoport, Z.; Eds.; Wiley,
Chichester, 1983. (c) Hart, H. In The Chemistry of Triple-Bonded Functional
Groups; Supplement C2, Chapter 18; Patai, S. ; Ed.; Wiley, Chichester,
1994.
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Kitamura, T.; Yamane, M. J. Chem. Soc. Chem. Commun. 1995, 9, 983.
3682
Org. Lett., Vol. 10, No. 17, 2008

result in overall yields exceeding 40% of the precursor for
the preparation of diaryl bisaryne 5. Because we are targeting
low-cost precursors for the sensor polymers, we decided to
focus on a more straightforward method that would utilize
few synthetic steps and would be easy to scaleup.
bromide or iodide, the preparation of the starting 1,4-diaryl-
2,5-dichlorobenzenes 9a-e in photonic purity30 using appropri-
ate arylboronic acid16 or aryl-tin derivative17 to give the
corresponding dichloro-derivatives 9a-e was easier. In the case
of 1,4-diaryl-2,5-dibromobenzenes prepared from 1,4-dibromo-
2,5-diiodobenzene using Pd0 coupling procedures, the presence
of 1-5% of difficult to separate side-products was observed.31
Following the arylation of 1,4-dibromo-2,5-dichlorobenzene 8
the 1,4-diaryl-2,5-dichlorobenzenes 9a-e were subjected to
double t-BuOK-promoted dehydrohalogenation/cycloaddition
to anthracene present in excess (∼5 equiv) in the reaction
mixture. Pentiptycenes 1a-e were purified by column chro-
matography and the pure products were obtained in respectable
yields of 20-56%. Similarly, sodium amide also furnished
expected pentiptycenes, albeit in a lower amount. The synthesis
of 1,4-diarylpentiptycenes 1a-e is shown in Scheme 4.
For this reason, we decided to investigate the simple
dehydrohalogenation/Diels-Alder cycloaddition of an in situ
generated aryne to anthracene. There are literature precedents,
albeit not for diarylpentiptycenes, suggesting that this reaction
would proceed. For example, Hart28 described a Bu-Li
promoted reaction of 3,6-substituted 1,2,4,5-tetrabromoben-
zene derivatives in the presence of anthracene to yield
pentiptycene, 1,4-dimethylpentiptycene, and 1,4-dimethoxy-
pentiptycene in 26, 14, and 21% yield, respectively. An
earlier report by Cadogan29 describes the reaction of sterically
crowded 1,4-dibromo-2,5-di-t-butylbenzene and tBuOK as
a base in the presence of anthracene, which yielded t-butyl
aryl ethers as well as a pentiptycene side-product, albeit in
∼2% yield.
Scheme 4. Synthesis of 1,4-Diaryl Pentiptycenes
First, we explored the reaction conditions described by
Cadogan28 using 3-halo-1,4-bis(thien-2-yl)benzene and po-
tassium t-butoxide in the presence of anthracene (Scheme
3). Reaction condition tuning allowed to generate the
Scheme 3. Base-Promoted Reaction of
3-Halo-1,4-bis(thien-2-yl)benzene (X ) Br, Cl)a
Thus far, we have prepared 1,4-diarylpentiptycenes 1a-e,
and it seems that the reaction is fairly general: both arenes
and heteroarenes may be used.
Additionally, we explored the flexibility of this synthetic
protocol. The regioselectivity in the coupling step is deter-
mined by the preferential oxidative addition (C-I > Br >
Cl) of the haloarene to the Pd0-catalyst. The combination of
I and Br substituents gave the expected 1,4-diaryl-2,5-
dibromobenzene, which underwent dehydrohalogenation-
cycloaddition smoothly to give 1 in slightly higher (∼5-10%)
yields compared to the dichloro-compound 8. Following the
recently described double dehydrofluorination of 1,4-dif-
luoro-2,5-dimethoxybenzene, which was also utilized in the
Diels-Alder reaction32 we also tested the difluoro-analogs
of 9. Here too, the 1,4-diaryl-2,5-difluorobenzenes underwent
dehydrohalogenation-cycloaddition, with only slightly di-
minished yields compared to the chloro-congeners. A step-
wise dehydrohalogenation using BuLi at -78 °C as described
in the literature31 resulted in only small (<5%) improvement.
It seems that the sterical demands of the 1,4-aryl substituents
aX-ray ORTEP representation of 7 (displacement ellipsoids are scaled
to the 50% probability level).
corresponding di(thien-2-yl)triptycene 7 in up to 87% yield.
The identity of 7 was confirmed by spectroscopic methods
as well as X-ray crystallography.
Similar conditions were then used to synthesize 1,4-diaryl
pentiptycenes 1a-e. While the previous reaction was carried
out using 3-bromo- or 3-iodo-1,4-bis(thien-2-yl)benzene, for the
synthesis of 1a-e we decided to use the 3,6-dichloro congener.
While the chloride is certainly not as good a leaving group as
(28) Hart, H.; Shamouilian, S.; Takehira, Y. J. Org. Chem. 1981, 46,
4427.
(31) These side-products were observed even when the reaction was
carried out at low temperature (30-45° C). According to MS spectra these
minor products originated from deiodination and coupling to m-position
(i.e., result of C-Br oxidative addition).
(29) Cadogan, J. I. G.; Harger, M. J. P.; Sharp, J. T. J. Chem. Soc. 1971,
602.
(30) Photonic materials were purified to obtain satisfactory results using
MS/NMR/elemental analyses, but also single-exponential luminescence lifetime
decays. Even small amounts (<1%) of brigthly fluorescent terphenyl-type
impurities would invalidate the later spectroscopic measurements.
(32) Morton, G. E.; Barrett, A. G. M. J. Org. Chem. 2005, 70, 3525.
(34) Zhao, D.; Swager, T. M. Macromolecules 2005, 9377.
(33) Thomas, S. W.; Amara, J. P.; Bjork, R. E.; Swager, T. M. Chem.
Commun. 2005, 4572.
Org. Lett., Vol. 10, No. 17, 2008
3683

rather than their electronic properties, the nature of the
leaving group or the method generating the aryne determine
the reaction yield.
The ability of 1,4-diarylpentiptycenes to act as TNT
sensors was studied in solution and in the solid state
following Swager’s procedures33,34 utilizing fluorescence as
a measure of the pentiptycene receptor-nitroaromate interac-
tion. The fluorescence quantum yields were estimated as
follows: 1a (10%, 4.03 ns), 1b (19%, ND), 1c (15%, 0.3
ns), 1d (∼25%, 0.8 ns), 1e (20%, 0.82 ns) using anthracene
as a standard. Fluorimetric titration of 1a-e by various
nitroaromates such as nitrobenzene (NB), 2,4-dinitrotoluene
(2,4-DNT), trinitrotoluene (TNT), 1-nitronaphthalene (NN),
and 2,3-dimethyl-2,3-dinitrobutane taggant (DMDNB) in
dichloromethane showed an expected decrease in fluores-
cence intensity (Figure 1). Fits of the first linear part of the
Figure 2. (Top) Photograph of the sensor slide before and after
exposure to DNT and TNT in their equilibrium vapors at 22 °C,
and finally upon recovery in the stream of clean air. (Bottom)
Integrated light output from the sensors represented as a quasi-3D
graph (X-Y-Intensity) allows for signal quantitation.
Given the difference in the LUMO-levels of the two
sensors as well as the quenchers it is not entirely surprising
that the sensor films show a different degree of quenching
for each vapor analyte. The fluorescence of the sensor films
was largely restored when the films were washed by a stream
of clean air. This suggests that these easy-to-make sensor
films may be used in differential (array-based) sensors for
nitroaromates.35
In summary, we have developed a simple method for
synthesis of 1,4-diarylpentiptycenes in two steps from 1,4-
dibromo-2,5-dichlorobenzene that involves double dehydro-
halogenation followed by aryne cycloaddition to anthracene.
The yield of the respective 1,4-diarylpentiptycenes is moder-
ate considering that four consecutive steps are involved
(20-56% overall for four steps, i.e., 60-85% per step).
Moreover, the synthesis is easy to perform from inexpensive
starting materials. Preliminary fluorescence quenching ex-
periments aimed at evaluation of 2,4-DNT and TNT interac-
tion with 1,4-diarylpentiptycenes 1d and 1e showed a high
degree of fluorescence quenching characterized by apparent
quenching constant in the range of 1000-3300 M-1 for TNT.
Solution-cast polyurethane films doped with 1d and 1e
showed similar quenching patters in the solid state. Taken
together these observations suggest that 1,4-diarylpentip-
tycenes could be of potential interest for the fabrication of
sensors for explosives. The preparation of such materials and
devices is underway.
Figure 1. (Left) Emission quenching observed with 1e (5.0 µM in
CH2Cl2) upon DNT addition. (Right) Stern-Volmer plots for 1e
and various nitroaromates. Excited at 325 nm (abs. maximum).
Stern-Volmer plots allowed estimating apparent quenching
constants to be in the range of 1000-3300 M-1 in the case
of TNT. These values of quenching constants are comparable
to the ones found for amplifying polymers.8a
To estimate the ability of 1a-e to sense nitroaromate
vapors, we used a glass slide with round wells (1.3 mm
diameter; 0.8 mm deep; 4 × 3 wells, 3 compounds in 4
replicas), and the sensors 1d and 1e were cast in the wells
as a polyurethane solution in THF. Tetraphenylporphyrin
(TPP) was used as an internal standard.
Upon illumination with black light (∼360 nm), TPP as well
as 1d and 1e showed emission in the solid state. The order of
fluorescence intensity from the slides in Figure 2, that is, before
being exposed to equilibrium vapors of DNT (0.18 ppm) or
TNT (7.70 ppb), was 1e > TPP > 1d. The glass slide and
sensor films were imaged before and after exposition to DNT
or TNT vapors. Within 30 min the sensors fluorescence was
quenched (Figure 2). Comparison of all slides shows the red
TPP fluorescence did not change, presumably because the
electron excited to the TPP LUMO level does not possess the
energy to reduce the nitroaromates.8a 1d and 1e, on the other
hand, displayed DNT and TNT-mediated fluorescence quench-
ing suggesting an interaction between 1d and 1e and DNT or
TNT.
Acknowledgment. Financial support from BGSU (TIE
grant to P.A.), the NSF (EXP-LA #0731153 to P.A.) and
McMaster Endowment to M.A.P. is acknowledged.
Supporting Information Available: Experimental pro-
cedures and spectroscopic data for 8a-e, 1a-e, X-ray data
for 3 and 6. This material is available free of charge via the
Internet at http://pubs.acs.org.
(35) Germain, M. E.; Knapp, M. J. J. Am. Chem. Soc. 2008, 130, 5422
3684
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