Facile cyclization of terphenyl to triphenylene: A new chemodosimeter for fluoride ions

Article abstract of DOI:10.1021/ol902861b

[Chemical equation presented] Terphenyl derivatives 3 and 4 having OTBS groups have been synthesized via a Suzuki-Miyura coupling reaction. These compounds undergo unprecedented irreversible cyclization to symmetrically/ unsymmetrically substituted triphenylenes while carrying out the deprotection of OTBS groups using tetrabutylammonium fluoride. Terphenyl 3 also serves as a new chemodosimeter for fluoride Ions.

Full text of DOI:10.1021/ol902861b

ORGANIC
LETTERS
2
010
Vol. 12, No. 3
28-631
Facile Cyclization of Terphenyl to
Triphenylene: A New Chemodosimeter
for Fluoride Ions
6
Vandana Bhalla,* Hardev Singh, and Manoj Kumar*
Department of Chemistry, UGC Sponsored-Centre for AdVance Studies-I, Guru Nanak
DeV UniVersity, Amritsar-143005, Punjab, India
Vanmanan@yahoo.co.in; mksharmaa@yahoo.co.in
Received December 11, 2009
ABSTRACT
Terphenyl derivatives 3 and 4 having OTBS groups have been synthesized via a Suzuki-Miyura coupling reaction. These compounds undergo
unprecedented irreversible cyclization to symmetrically/unsymmetrically substituted triphenylenes while carrying out the deprotection of OTBS
groups using tetrabutylammonium fluoride. Terphenyl 3 also serves as a new chemodosimeter for fluoride ions.
Terphenyls have attracted a lot of attention due to a wide
range of significant biological activities, for example, potent
immunosuppressant, neuroprotective, antithrombotic, anti-
coagulant, specific 5-lipoxygenase inhibitory, and cytotoxic
ubstituted derivatives as peripheral substitution on triph-
1
0
enylene core has a large effect on the thermal behavior of
liquid crystalline materials. However, the only existing
rational routes for the synthesis of symmetrically/unsym-
metrically hexasubstituted triphenylene involve the iodine
1
activities. Besides, terphenyls can also be converted to
11
12
triphenylenes, which have great potential in supramolecular
and material chemistry owing to their role as liquid crystal-
promoted photocyclisation or iron(III) chloride promoted
cyclization of ortho-terphenyl which are prepared by Ullman
coupling reaction or by palladium catalyzed cross coupling
reactions involving aryl boronic acids. Iron(III) chloride and
2
3-5
line materials, molecular scale devices,
and molecular
6
–8
receptors. They are potential components for organic and
optoelectronic devices. Particularily appealing are hexas-
9
(
6) Waldvogel, S. R.; Wartini, A. R.; Rasmussen, P. H.; Rebek, J.
(
(
1) Liu, J. K. Chem. ReV. 2006, 106, 2209.
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K. In Electronic Materials: The Oligomer Approach; M u¨ llen, K., Wegner,
G., Eds.; Wiley-VCH: New York, 1998; p 1. (c) Kumar, S. Liq. Cryst.
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K. J. Mater. Chem. 2004, 14, 494.
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Stoddart, J. F.; Williams, D. J. Chem.sEur. J. 2003, 9, 5348
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721.
(
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(12) Naarman, H.; Hanack, M.; Mattmer, R. Synthesis 1994, 477.
10.1021/ol902861b  2010 American Chemical Society
Published on Web 12/31/2009

1
3
MoCl
5
have been shown to promote the cyclotrimerization
ran, we observed an unprecedented irreversible cyclization
of intermediate terphenyls 3 and 4 to triphenylenes 6a and
6b along with significant color changes. Thus, in the present
manuscript, we report terphenyls having OTBS groups which
are easily converted to hexasubstituted triphenylenes during
the deprotection of terphenyl using TBAF. We also inves-
tigated the sensing behavior of terphenyl 3 toward fluoride
ions using UV-vis and fluorescence spectroscopy. To the
best of our knowledge, this is the first report where
cyclization of terphenyl to triphenylene has been carried out
in absence of any oxidizing reagent.
of 1,2-dialkoxybenzene derivatives and also to allow a
selective coupling of a 3,3′,4,4′-tetraalkoxybiphenyl and a
,2-dialkoxybenzene. All of these reagents, iron(III) chlo-
14
1
ride, and molybdenum chloride are insoluble in common
organic solvents, and therefore, the synthesis of triphenylenes
from terphenyls on a large scale using conventional oxidizing
agents is inconvenient. Keeping in view the importance of
triphenylenes, the development of new methods which allow
the preparation of triphenylenes on large scale without using
conventional oxidizing reagents will be very beneficial.
Our research work on molecular recognition and sensing
is focused on the development of novel artificial receptors
Palladium catalyzed Suzuki-Miyura cross coupling of
boronic ester 2 with dibromide 1a and 1b furnished terphe-
nyls 3 and 4 in 86 and 79% yields, respectively (S4 and S7
Supporting Information). The structures of compounds 3 and
1
5
for the selective sensing of soft metal ions and inorganic
16
anions of clinical interest. We recently reported “Turn On”
fluorescent sensors for mercury ion based on terphenyls
appended with pyrene and quinoline moieties which exhibit
4
were confirmed from their spectroscopic and analytical data
(
Scheme 1).
1
7
high binding affinity for mercury.
1
The H NMR spectrum of compound 3 showed six singlets
(
(
18H, 12H) for TBS group, two singlets and two doublets
2H each) for aromatic protons of terphenyl moiety. The FAB
+
Scheme 1
mass spectrum showed a parent ion peak at 1011 (M )
corresponding to coupled product 3. These spectroscopic data
corroborates the structure 3 for this compound. Now that
the terphenyl 3 was in hand in substantial quantities, its
deprotection to corresponding hexahydroxy terphenyl 5a was
examined using tetrabutylammonium fluoride. Interestingly,
the treatment of terphenyl 3 with tetrabutylammonium
fluoride furnished hexahydroxy triphenylene 6a along with
drastic color changes. The reaction, which was complete in
five minutes, probably involves two steps. The first step is
-
cleavage of Si-O bond in the presence of F ion follwed
by cyclization and both steps are very fast and irreversible.
The structure of compound 6a was confirmed from its
1
spectroscopic data. The H NMR spectrum of compound 6a
showed one singlet (6H) for protons of triphenylene core
and one broad signal for OH groups. Similarly, deprotection
1
of 4 with TBAF yielded compound 6b. H NMR of 6b in
THF showed one singlet (6H) due to methoxy protons, three
singlets (2H, each) due to aromatic protons and two singlets
(2H, each) for OH groups. Compound 6a and 6b were further
confirmed by their conversion to their triflate derivatives 7
and 8 (S5 and S8 Supporting Information).
As part of our ongoing research on terphenyl-based
materials, we were interested in synthesis of symmetrically/
unsymmetrically hexasubstituted terphenyls. For this mul-
tistep synthesis, we employed hydroxyl group protection/
deprotection strategy for selective reaction on a particular
site. However, while carrying out unmasking of silyl ether
with tetrabutylammonium fluoride (TBAF) in tetrahydrofu-
To gain deeper insight into mechanism of the reaction Viz
a Viz number of OTBS moieties, its topology, we also
prepared terphenyl derivatives 9a (S10 Supporting Informa-
tion) 9b-9c (S13 Supporting Information) and carried out
their deprotection using TBAF. However, no aryl-aryl bond
formation was observed in 9a-9c derivatives (Scheme 2).
Although we were not surprised that 9a having two OTBS
groups on the central aryl ring and 9b having OTBS groups
meta to the ring closing site did not undergo cyclization, we
were amazed that 9c having OTBS groups para to ring
closing site did not lead to the formation of triphenylene
either, during deprotection reaction. On the basis of these
results, we may conclude that increased negative charge on
phenolate oxygens after deprotection of OTBS groups in
terphenyls 3 and 4 provide an optimal amount of directing
ability and electron density to complete cyclization. The
(
13) (a) Kumar, S.; Manikman, M. Chem. Commun. 1997, 1615. (b)
Allen, M. T.; Diele, S.; Harris, K. D. M.; Hegmann, T.; Kariuki, B. M.;
Lose, D.; Preece, J. A.; Tschierske, C. J. Mater. Chem. 2001, 11, 302.
(
14) Boden, N.; Bushby, R. J.; Cammidge, A. N. J. Chem. Soc., Chem.
Commun. 1994, 465.
(
15) (a) Dhir, A.; Bhalla, V.; Kumar, M. Org. Lett. 2008, 10, 4891. (b)
Kumar, M.; Dhir, A.; Bhalla, V. Org. Lett. 2009, 11, 2567. (c) Kumar, M.;
Kumar, R.; Bhalla, V. Chem. Commun. 2009, 7384.
(16) (a) Babu, J. N.; Bhalla, V.; Kumar, M.; Puri, R. K.; Mahajan, R. K.
New. J. Chem. 2009, 675. (b) Kumar, M.; Kumar, R.; Bhalla, V. Tetrahedron
009, 65, 4340.
17) (a) Bhalla, V.; Tejpal, R.; Kumar, M.; Puri, R. K.; Mahajan, R. K.
2
(
Tetrahedron Lett. 2009, 50, 2649. (b) Bhalla, V.; Tejpal, R.; Kumar, M.;
Sethi, A. Inorg. Chem. 2009, 11677.
Org. Lett., Vol. 12, No. 3, 2010
629

20
-
sis. Furthermore, F ions are also associated with anesthet-
ics, hypnotics, psychiatric drugs, nerve gases, in the analysis
of drinking water, and in the refinement of uranium used in
nuclear weapon manufacture. Thus, due to diversity of its
functions, the development of optical sensors for naked eye
detection of fluoride ion becomes important.
Scheme 2
2
1
The UV-vis experiments were carried out in THF at 5.0
10 M concentration of dosimeter 3. In the absence of
anions, the absorption spectrum of receptor 3 is characterized
by the presence of one absorption maximum peak at 295
nm (Figure 1). It was found that the UV-vis absorption band
-
5
×
cyclization is also enthalpically favored by the greater
conjugation of planar triphenylene relative to terphenyl. A
feasible mechanism for this cyclization involves a common
phenolate anion intermediate obtained via fluoride-mediated
desilylation, followed by cyclization to triphenylene through
oxidative dehydrogenation as shown in Scheme 3.
Scheme 3
.
Proposed Mechanism for Cyclization of Terphenyl 3
and 4 to Triphenylene
-
5
Figure 1
.
UV-vis spectrum of 3 (5 × 10 M) in the presence of
-
different anions (210 µM) in THF. A ) Free ligand, B d F , C )
Cl , D ) Br , E ) I , F ) CN , G ) HSO
-
-
-
-
-
-
4
2 4
, H ) H PO , I )
-
-
NO , J ) OAc .
3
of receptor 3 is red-shifted to 342 nm (∆λ 47 nm) and at
63 nm (∆λ 368 nm) as fluoride ions come in contact with
6
solution of receptor 3 and most importantly, at such a low
concentration these changes were clearly visible to the naked
eye where the solution changes from colorless to violet
(Figure 1, inset). However, there was absolutely no change
in the absorption spectrum of receptor 3 or color of the
solution in the presence of chloride, bromide, iodide, nitrate,
acetate, cyanide, hydrogen phosphate and hydrogen sulfate
ions, as their tetrabutylammonium salts, respectively at this
particular concentration (Figure 1, inset).
Since the cyclization of terphenyl 3 in the presence of
fluoride ions was accompanied by drastic color changes, we
examined the behavior of terphenyl 3 toward different anions
by UV-vis and fluorescence spectroscopy as the selective
recognition and sensing of anions by artificial optical
receptors has emerged as a key research theme within the
-
Thus, upon the addition of 0.0-4.2 equiv of F , the
UV-vis absorption band centered at 294 disappeared
completely and new bands centered at 342 and 663 nm
appeared (Figure 2a). On further addition of fluoride ions,
the band at 663 nm decreased and three new bands centered
at 879, 526, and 287 nm appeared with isosbestic points at
1
8
host guest chemistry. Among the biologically important
anions, fluoride is of particular interest owing to its role in
19
preventing dental caries and in the treatment for osteoporo-
716, 582, and 315 nm, respectively (Figure 2b) and the color
(
18) (a) Sessler, J. L.; Davis, J. M. Acc. Chem. Res. 2001, 34, 989. (b)
of solution turned violet (Figure 3). The band at 287 nm is
characteristic band for the triphenylene moiety. Thus, we
Gale, P. A. Coord. Chem. ReV. 2000, 199, 181. (c) Beer, P. D.; Gale, P. A.
Angew. Chem., Int. Ed. 2001, 40, 486. (d) Gale, P. A. Coord. Chem. ReV.
2
001, 213, 79. (e) Suksai, C.; Tuntulani, T. Chem. Soc. ReV. 2003, 32,
1
92. (f) Martinez-Manez1, R.; Sanceno′n, F. J. Fluoresc. 2005, 15, 267.
(20) (a) Riggs, B. L. Bone and Mineral Research; Annual 2; Elseiver:
Amsterdam, 1984; p 366. (b) Kleerekoper, M. Endocrinol. Metab. Clin.
North Am. 1998, 27, 441.
(
g) Gunnlaugsson, T.; Glynn, M.; Tocci, G. M.; Kruger, P. E.; Pfeffer, F. M.
Coord. Chem. ReV. 2006, 250, 3094.
19) Kirk, K. L. Biochemistry of the Halogen and Inorganic Halides;
Plenum Press: New York, 1991; p 58.
(
(21) Wiseman, A. Handbook of Experimental Pharmacol-ogy XX/2;
Springer-Verlag: Berlin, 1970; Part 2, p 48.
630
Org. Lett., Vol. 12, No. 3, 2010

extended conjugation leads to the red shift and enhancement
-
of fluorescence emission. On further addition of F ions,
fluorescene emission intensity was decreased (Figure 4B).
This decrease in emission intensity may be ascribed to an
electron transfer from phenolate oxygen to triphenylene
-6
moiety. It was found that 3 has a detection limit of 2 × 10
-5
Figure 2
TBAF in THF.
.
UV-vis spectrum of 3 (5 × 10 M) in the presence of
propose that the spectral changes in Figure 2 are due to the
formation of triphenylene moiety. To test the practical
-
applicability of compound 3 as F selective sensor, competi-
-
-6
tive experiments were carried out in the presence of F at
Figure 4
of TBAF in THF.
.
Fluorescence spectrum of 3 (5 × 10 M) in the presence
-
-
-
-
-
-
2
H
10 µM mixed with Cl , Br , I , OAc , HSO
2 4
4
, NO
3
,
-
-
PO , CN at 500 µM, no significant variation in
mol L- for F which is sufficiently low for the detection of
1
-
-
submillimolar concentration range of F ions found in many
chemical systems. The other anions (Cl , Br , I , HSO ,
4
OAc , H PO , NO , and CN ) did not cause any change
2 4 3
-
-
-
-
-
-
-
-
in fluorescence spectra (S42-S45 Supporting Information).
Thus, these UV-vis and fluorescence changes indicate that
protected terphenyl 3 can also be exploited for the develop-
ment of fluoride sensor. In conclusion, we synthesized
terphenyl based derivatives 3 and 4 responsible for the
fluoride ion induced cyclization to symmetrically/unsym-
metrically substituted triphenylenes in absence of any oxidiz-
ing reagent. Terphenyl derivative 3 is also found to be highly
selective for fluoride ions over the other anions tested.
-
5
Figure 3
.
Change in color intensity of 3 (5 × 10 M) upon the
-
addition of F ion (from left to right, free ligand, 1, 2, and 6 equiv)
in THF.
absorption behavior was observed by comparison with or
without the other anions besides F . This means that
compound 3 has high selectivity for F ion over other anions
-
-
Acknowledgment. V.B. is thankful to DST (New Delhi,
India) for financial support (Project. No. SR/FT/CS/10-2006).
We are also thankful to UGC (New Delhi, India) for financial
support (Project No. 33-276/2007(SR)), DST (New Delhi)
for FIST programme, UGC for SAP programme and Guru
Nanak Dev University for laboratory facilities.
studied (S41 Supporting Information).
We also used fluorescence spectroscopy to investigate the
behavior of terphenyl 3 in the presence of fluoride ions.
Hexasubstituted terphenyl 3 exhibited a fluorescence emis-
sion at 393 nm when excited at λmax 294 nm. Upon addition
of F ions, a red-shifted band appeared at 425 nm (a shift
of 32 nm) with 32% enhancement of fluorescence emission
-
Supporting Information Available: Experimental pro-
1
13
cedure, characterization data including mp, H, C and mass
spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
(
Figure 4A). The presence of fluoride ions results in cleavage
of Si-O bond which increases negative charge on the
phenolate oxygen followed by cyclization to triphenylene
as a result of which the conjugation is extended. This
OL902861B
Org. Lett., Vol. 12, No. 3, 2010
631