Boron-dipyrromethene based specific chemodosimeter for fluoride ion

Article abstract of DOI:10.1016/j.tet.2009.12.039

3,5-Bis(trimethylsilylethynyl)-4,4-difluoro-8-(4-tolyl)-4-bora-3a,4a-diaza-s-indacene [BODIPY(CCTMS)₂] has been synthesized by coupling of 3,5-dibromo-4,4-difluoro-8-(4-tolyl)-4-bora-3a,4a-diaza-s-indacene with trimethylsilylacetylene under pd(

Full text of DOI:10.1016/j.tet.2009.12.039

Tetrahedron 66 (2010) 1728–1734
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Boron–dipyrromethene based specific chemodosimeter for fluoride ion
*
M. Rajeswara Rao, Shaikh M. Mobin, M. Ravikanth
Department of Chemistry, Indian Institute of Technology, Bombay, Powai, Mumbai 400 076, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 13 October 2009
Received in revised form 15 December 2009
Accepted 17 December 2009
Available online 23 December 2009
3,5-Bis(trimethylsilylethynyl)-4,4-difluoro-8-(4-tolyl)-4-bora-3a,4a-diaza-s-indacene [BODIPY(CCTMS)2]
has been synthesized by coupling of 3,5-dibromo-4,4-difluoro-8-(4-tolyl)-4-bora-3a,4a-diaza-s-indacene
with trimethylsilylacetylene under pd(0) coupling conditions. The BODIPY(CCTMS)2 was used as a selective
colourimetric and fluorescent chemodosimeter for fluoride ion, following the Fꢀ ion induced cleavage of
trimethylsilyl group, the protecting group of ethyne functionality by monitoring the changes in UV–vis and
fluorescence properties. The dosimeter BODIPY(CCTMS)2 display clear changes in colour, absorption and
Keywords:
Chemodosimeter
BODIPY
emission bands selectively for Fꢀ ion over other anions such as Clꢀ, Brꢀ, Iꢀ, ClO4ꢀ and HPO24ꢀ
.
Ó 2010 Elsevier Ltd. All rights reserved.
Fluoride ion sensor
Colourimetric sensor
1. Introduction
colour and the spectroscopic characteristics of the solution allows
the determination of the anion. The underlying idea of these irre-
versible systems is to take the advantage of the selective reactivity
that certain anions may display. Recently there are some reports on
chromogenic and fluorescent chemodoimeters for fluoride anion.7
Interestingly, boron–dipyrromethene dyes (BODIPY), which are
used extensively as labelling reagents, fluorescent switches, che-
mosensors8 etc., due to their excellent photophysical properties, to
the best of our knowledge, there is only one report on BODIPY
based chemodosimeter sensor for Fꢀ ion. Hudnall and Gabba¨ı
reported9 a BODIPY boronium cation, which can act as chemo-
dosimeter sensor for fluoride ion (Scheme 1).
Anion recognition and sensing via artificial receptors are of
current interest in supramolecular chemistry because of their im-
portance in chemical and biological systems.1 Among the anions,
fluoride, the smallest anion, is of particular interest because of its
role in preventing dental caries,2 and treatment of osteoporosis.3
However, an excess fluoride anion can lead to fluorosis, which is
a type of fluoride toxicity.4 The diversity of function, both beneficial
and detrimental, necessitates the development of systems capable
of detecting the fluoride anion. The available fluoride ion sensors in
literature are mainly based on the approach of a binding site-sig-
nalling sub-unit (chemosensors).5 Although considerable progress
has been made in sensing of fluoride anion using various chemo-
sensors, the chemodosimeter approach,6 which involves the use of
specific chemical reactions induced by the presence of target an-
ions, has received much less attention comparatively. The chemo-
dosimetric approach usually shows high selectivity and is based on
the changes in the electronic properties of the fluorophore. It in-
volves the use of specific chemical reactions, which are usually ir-
reversible induced by the presence of target anions that are coupled
to a colour, absorption or emission variation. In chemodosimetric
approach, either the anion reacts with the chemodosimeter and
remains covalently bonded to the product or it simply catalyzes
a chemical reaction. In this approach, since the final compound is
chemically different from the original one, the changes in the
Non-fluorescent
Fluorescent
Me
Me
Me
Me
Me
Me
F-
+
+
B
N
F
N
N
F
N
-
-
B
Me
Me
I-
Me
Me
+
N
F
NMe2
Scheme 1. The reported chemodosimeter for fluoride ion.9
They used p-dimethylaminopyridine adduct of 1,3,5,7,8-pen-
tamethylpyrromethene–boron fluoride, the non-fluorescent com-
pound, which on reaction with Fꢀ ion turn to brightly fluorescent
difluoride complex. In this paper, we developed another example of
boron–dipyrromethene based chemodosimeter for fluoride anion,
* Corresponding author.
E-mail address: ravikanth@chem.iitb.ac.in (M. Ravikanth).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.12.039

M.R. Rao et al. / Tetrahedron 66 (2010) 1728–1734
1729
which exhibited drastic changes in colour, absorption and fluo-
rescence properties selectively for Fꢀ ion over other anions. We
used the BODIPY dye BODIPY(CCTMS)2 1 containing trimethylsily-
lethynyl groups at 3,5-positons (Chart 1) to act as chromogenic and
fluorescent sensor for fluoride anion (TBAþ, Kþ salts) by adopting
simple chemodosimetric approach. We hypothesized that the
electron-rich trimethylsilyl protective group10 could be removed by
Fꢀ ion to reveal the electron-deficient ethyne group. This trans-
formation of electron-rich trimethylsilylethyne group to electron-
deficient ethyne group alter the electronic properties of the dye and
should lead to changes in the colour and shifts in absorption and
emission maxima and downfield shifts of certain protons in 1H
NMR spectrum. Furthermore, to show that the position of trime-
thylsilylethyne group(s) on BODIPY dye play any important role in
designing chemodosimeter for fluoride ion, we synthesized an al-
ternate BODIPY dye 2 in which the trimethylsilylethyne group is
placed at the para-position of meso-phenyl group11 (Chart 1).
3 by treating it with two equivalents of NBS at ꢀ78 ꢁC in THF for 1 h,
which was then followed by oxidation with DDQ at room temper-
ature for 10 min. The solvent was removed on rotary evaporator in
high vacuo and quickly flash chromatographed on silica. The re-
sultant compound was dissolved in CH2Cl2 and treated with
BF3$Et2O for 1 h.
CH3
CH3
Method I
THF / NBS
NH HN
-78 oC / 1 hr
NH HN
Br
Br
4
3
1. CH2Cl2 / DDQ / 1 hr.
2. Et3N / BF3 Et2O / 1hr.
THF / NBS
-78 oC / 1 hr
DDQ
Method II
CH3
CH3
CH3
CH3
CH3
Si
H3C
CH2Cl2
N
F
N
Et3N / BF3 Et2O / 1hr.
NH
N
B
7
1
Br
Br
F
Br
Br
6
5
2
N
F
N
4
B
5
3
Toluene/ Et3N
F
Me3Si-C
CH
Pd(PPh3)2Cl2/ CuI
CH3
CH3
N
N
H3C
CH3
Si
Si
B
H3C
F
F
CH3
CH3
1
2
Chart 1.
N
N
B
2. Results and discussion
F
F
H3C
H3C
CH3
CH3
Si
Si
H3C
The BODIPY dye 2 was prepared by following the literature
procedure.11 The BODIPY dye 1 was prepared in three steps starting
from meso-phenyl dipyrromethane 3 as shown in Scheme 2. The
meso-(p-tolyl) dipyrromethane 3 was prepared as reported in lit-
erature12 by treating one equivalent of benzaldehyde with 25 equiv
of pyrrole in the presence of catalytic amount of BF3$OEt2 at room
temperature followed by work-up and column chromatographic
purification. The meso-(p-tolyl)-3,5-dibromodipyrromethane 4 was
prepared by treating 3 with two equivalents of N-bromosuccini-
mide at ꢀ78 ꢁC for 1 h. The crude compound was subjected to flash
column chromatography using CH2Cl2 and isolated compound 4 in
75% yield. The compound 4 was confirmed by 1H NMR, mass and
elemental analysis (Supplementary data). The BF2 complex 5 was
prepared in subsequent step by adopting two-steps in one pot re-
action methodology (Method I).13 In the first step, the compound 4
was oxidized with one equivalent of DDQ in CH2Cl2 for 1 h at room
temperature to afford dipyrromethene. Without isolating the
dipyrromethene, in the second step, the reaction mixture was first
neutralized with triethylamine and then reacted with BF3$Et2O at
room temperature for 1 h. The dark fluorescent crude reaction
mixture was subjected to column chromatographic purification and
afforded clean fluorescent BF2 complex 5 in 25% yield. During the
course of our synthesis, we realized that the compound 4 is not
very stable hence we attempted to synthesize compound 5 in one
step starting from compound 3 without isolating compound 4
(Method II). According to method II, we first brominated compound
CH3
1
Scheme 2. Synthesis of chemodosimeter 1.
The TLC analysis of crude reaction mixture showed three spots
corresponding to monobromo, dibromo and tribromo compounds.
Column chromatography on silica gave pure 5 as second band in
64% yield. Although both methods work efficiently, we found that it
is convenient to synthesize the compound 5 by following method II.
The compound 5 was characterized by mass, NMR, absorption and
fluorescence spectroscopic techniques. The Mþ ion peak at 421
confirmed the formation of BF2 complex 5. In 1H NMR spectrum of
5, the pyrrole protons appeared as two sets of doublets at 6.53 and
6.82 ppm, which shifted to downfield as compared to those in 4.
The absorption spectrum of 5 showed one sharp band at 520 nm,
which was red shifted by 18 nm compared to 2 due to presence of
two bromine atoms at 3, 5-position (Supplementary data). In the
last step, the compound 5 was treated with trimethylsilylacetylene
in toluene/triethylamine in the presence of Pd(PPh3)2Cl2/CuI at
40 ꢁC for 3 h (Scheme 2). The crude compound was subjected to
column chromatographic purification and afforded the target
compound 1 as blue crystals in 60% yield. The compound 1 was
characterized by mass, NMR, absorption, fluorescence and single
crystal X-ray analysis. In 1H NMR spectrum, the methyl protons of
trimethylsilyl group appeared as singlet at 0.31 ppm and four

1730
M.R. Rao et al. / Tetrahedron 66 (2010) 1728–1734
pyrrole protons appeared as sets of two doublets at 6.68 and
6.92 ppm (Table 1). The absorption spectrum of 1 showed one
strong sharp band at 571 nm, which was red shifted by w50 nm
compared to compound 5. The single crystal of compound 1 was
obtained from n-hexane/dichloromethane on slow evaporation
over a period of one week. The single crystal X-ray diffraction
(CCDC 728412) study of 1 revealed that the two pyrrole rings and
the central six-membered ring containing the boron ring are planar
(Fig. 1). The dihedral angle between the meso-aryl ring and the
plane defining various dipyrrin atoms in compound 1 is almost
same (53ꢁ) as that of reported unsubstituted N,N0-difluoroboryl-5-
phenyldipyrrin complex11 (w60ꢁ). However, there are slight vari-
ations in some bond lengths, such as pyrrole ‘N’–B and B–F bonds in
compound 1 as compared to N,N0-difluoroboryl-5-phenyldipyrrin11
complex, which is attributed to alteration of electronic properties of
boron–dipyrromethene due to the presence of electron releasing
trimethylsilylethynyl substituents at 3,5-positions in 1 (Supple-
mentary data).
functional groups would alter the electronic properties of the dye,
which in turn expected to result in changes in spectroscopic
properties. Because of the high affinity of fluoride for silicon, the
trimethylsilyl groups present at the 3,5-positions of 1 can be easily
cleaved by fluoride ion but not by other anions to afford the BODIPY
dye containing two ethynyl functional groups, thus 1 can act as
specific chemodosimeter for fluoride ion (Scheme 3). This irre-
versible reaction can be monitored by following changes in NMR,
absorption, and fluorescence spectroscopic features and also by
following changes in the colour under naked eye and UV light
conditions.
CH3
CH3
TBAF/ CH2 Cl2
N
F
N
B
F
N
F
N
Table 1
CH3
1H NMR and Photophysical data of compounds 1, 2, 6 and 7
B
CH3
Si
CH3
Si
H3C
F
CH3
H3C
Compound
1H NMR (
1,7-py
d
in ppm)
2,6-py
Absorption
lnm
Emission
lnm
6
H
H
1
(
)
(
)
1
6
2
7
6.92
6.98
6.56
6.56
6.68
6.76
5.88
5.88
571
551
497
497
584
564
516
516
CH3
CH3
H3C Si
H
TBAF/ CH 2Cl2
N
F
N
N
F
N
B
B
F
F
7
2
Scheme 3. Fluoride sensing chemodosimetric reaction.
The fluoride ion induced transformation of protected 1 to
deprotected 6 can be systematically followed by 1H NMR spec-
troscopy. The changes in the selected protons of dosimeter 1 on
addition of increasing amounts of KF in CD3OD are shown in
Figure 2. We used maximum two equivalents of KF, which is re-
quired to cleave the two trimethylsilyl groups of 1. As it is clear from
Figure 1. ORTEP diagram of compound 1.
The compound 1 is freely soluble in all common organic sol-
vents. The compound 1 exhibits one fluorescence band at 584 nm
with a quantum yield of 0.29 and singlet state lifetime of 5.6 ns. The
compound 1 can be used as fluorescent and as well as chromogenic
chemodosimeter for fluoride ion detection based on selective
fluoride ion catalyzed deprotection of ethyne functional groups
present at the 3- and 5-positions of the dye. It is established that if
functional group is in close proximity to a fluorophore, the change
in electronic properties of the functional group due to protection/
deprotection may influence the photophysical properties of the
dye, which should lead to an observable change in the absorption/
emission profile of the dye. Since the trimethylsilyl groups, the
protective groups for ethyne functional groups, are electron do-
nating groups and removal of trimethylsilyl groups from ethyne
Figure 2. 1H NMR spectra of 1 (in CD3OD, 31 mM) in the presence of different con-
centrations of Fꢀ ions. The final mole ratio of [Fꢀ] to [1] is 0, 0.5, 1.0, 1.5 and 2.0,
respectively.

M.R. Rao et al. / Tetrahedron 66 (2010) 1728–1734
1731
Figure 2, on sequential addition of KF, the trimethylsilyl groups,
0.5
0.4
0.3
0.2
0.1
0.0
0.5
0.4
0.3
0.2
0.1
0.0
which appear at 0.31 ppm slowly start disappearing and upon
complete addition of two equivalents, the signal corresponding to
trimethylsilyl groups completely disappeared supporting the for-
mation of 6. The systematic changes were also observed with
pyrrole and aryl protons of 1 on sequential addition of increasing
amounts of KF to 1. For e.g., the 1,7 and 2,6-pyrrole protons, which
appears at 6.92 and 6.68 ppm, respectively, in 1, upon addition of
two equivalents of KF, the protons experience slight downfield
shifts and appears at 6.98 and 6.76 ppm, respectively, supporting
the formation of 6 (Table 1).
0
5
10
15
20
25
Concentration ( M)
However, on addition of one equivalent of Fꢀ to 1, the signals
corresponding to the mixture of compounds, such as 1, 6 and
the intermediate compound containing one protected and one
deprotected ethynyl functional groups are present. Thus, on
complete addition of two equivalents of Fꢀ, the pyrrole and aryl
proton signals corresponding to 1 disappeared completely and
the signals corresponding to 6 appeared. Although, the changes
in chemical shifts are relatively small, it is enough to follow the
progress of the reaction by 1H NMR. Under same conditions, the
other anions, such as Brꢀ, Clꢀ, Iꢀ, HPO42ꢀ and ClOꢀ4 did not affect
the changes in the pyrrole and aryl protons of 1 even after the
addition of three equivalents of each anion. Similarly, the 1H
NMR studies were also carried out with compound 2 in which
the trimethylsilylethyne group is present at the para–position
of meso-phenyl group. The addition of Fꢀ ion to compound 2
results in the deprotection of ethyne group and forms com-
pound 7 (Scheme 3). The comparison of 1H NMR spectra of
compound 2 and compound 7 is shown in Figure 3. Although
some negligible changes were noticed in the chemical shifts of
aryl protons, no changes were observed in the chemical shifts
of pyrrole protons on formation of compound 7 (Table 1). Thus,
1H NMR study reveals that compound 1 can be used as che-
modosimeter for fluoride ion, whereas compound 2 cannot be
used.
500
550
600
650
Wav el ength ( nm)
Figure 4. The absorption spectra of 1 in the presence of Fꢀ in CH2Cl2 (8
concentration is 0, 2.4, 4.8, 7.2, 9.6, 12.0, 14.4 and 16.8 M, respectively. The inset shows
m
M). The Fꢀ
m
the plot of changes in absorbance (A) at 571 nm (solid line) and 551 nm (dotted line).
Furthermore, the time dependence of the conversion of 1 to 6 at
551 nm in the presence of two equivalents Fꢀ ion was monitored by
means of absorption spectroscopy (Supplementary data). The re-
sults indicate that the reaction completes within 5 min duration
(Supplementary data). Similar observations were made with fluo-
rescence studies. The addition of fluoride ions to a solution of 1 in
CH2Cl2 also results in clear ratiometric changes in fluorescence
spectra, which reflected in the decrease of the intensity of emission
band at 584 nm corresponding to dosimeter 1 and increase in in-
tensity of new band at 564 nm corresponding to 6 (Fig. 5).
420
350
280
210
140
70
0
500
550
600
650
Wavelength (nm)
Figure 5. Fluorescence emission changes (ex 425 nm) of dosimeter 1 (2
addition of Fꢀ in CH2Cl2. The Fꢀ concentration is (equiv) 0, 2.5, 5, 7.5, 10, 12.5, 15, 17.5,
20 and 22.5 M.
mM) upon the
Figure 3. 1H NMR spectra of 2 (in CDCl3) in the presence of two different concentra-
tions of Fꢀ ions. The final mole ratio of [Fꢀ] to [2] is 0 and 2.0, respectively.
m
There are no changes in absorption and fluorescence bands of 1
on addition of any other anions, such as Brꢀ, Clꢀ, Iꢀ, HPO42ꢀ and ClOꢀ4
as shown in Figure 6. Thus, these results support that the com-
pound 1 can be used as chromogenic and fluorescent chemo-
dosimter for fluoride anion. To show that only 1 can be used
exclusively as chemodosimeter for fluoride ion, the absorption and
fluorescence studies were carried out with compound 2 in which
the trimethylsilylethynyl group is present on meso-phenyl group.
The absorption and emission spectra of compound 2 on addition of
excess amount of Fꢀ ion are shown in Figure 7. The addition of Fꢀ
ion to 2 results in cleavage of trimethylsilyl group present at the
para-position of meso-phenyl group, but there are no significant
changes in absorption and fluorescence bands observed suggesting
The boron–dipyrromethene dyes, in general possess in-
teresting absorption and fluorescence properties8 and it is con-
venient to follow the changes in absorption and fluorescence peak
maxima of 1 on addition of Fꢀ ions. The systematic changes in
absorption spectra of dosimeter 1 on increasing the concentration
of TBAF in CH2Cl2 are shown in Figure 4. The addition of Fꢀ ions to
a dichloromethane solution of 1 showed nice ratiometric changes,
which reflected in the decrease of the intensity of the absorption
band at 571 nm corresponding to 1 and appearance of new band
at 551 nm corresponding to 6. This is also clearly evident in the
plot, which shows the changes in the absorbance of band at 571
and 551 nm (A) versus the concentration of Fꢀ (Fig. 4 inset).

1732
M.R. Rao et al. / Tetrahedron 66 (2010) 1728–1734
(a)
(a)
0.5
0.4
0.3
0.2
0.1
2
-
-
1+F
0.5
2+F
0.4
0.3
0.2
0.1
0.0
450
500
550
600
500
550
600
Wavelength (nm)
Wavelength (nm)
600
400
200
0
(b)
2
2+F
(b)
500
400
300
200
100
0
-
-
1+F
500
550
600
650
Wavelength (nm)
m
m) with excess of Fꢀ (b) Emission spectra of 2
500
550
600
650
Figure 7. (a) Absorption spectra of 2 (8
(2
m) with excess of Fꢀ.
m
Wavelength (nm)
Figure 6. (a) Absorption spectra of 1 (8
m
m) with Fꢀ (excess equivalents), Clꢀ, Brꢀ, Iꢀ
,
clear colour change, where as the addition of other anions does not
bring any noticeable colour change to the dye. Thus, compound 1
can be used exclusively as colourimetric and chemodosimeter
sensor for fluoride ion.
ClOꢀ4 and HPO24ꢀ (excess equivalents) (b) Emission spectra of 1 (2 M) with Fꢀ (excess
m
equivalents), Clꢀ, Brꢀ, Iꢀ, ClO4ꢀ and HPO24ꢀ (excess equivalents).
that compound 2 cannot be used as chemodosimeter for Fꢀ ion
(Table 1).
This study also indicates that the location of functional group,
such as trimethylsilylethynyl functional group on BODIPY plays
a very important role in designing the chemodosimetric sensor. If
the functional group is closer to the fluorophore as in 1, the changes
in the functional group alter the electronic properties of the dye
resulting in significant changes in the spectroscopic properties.
However, if the functional group is away from the fluorophore as in
2, the changes in the functional groups do not reflect clearly in the
spectroscopic properties. Apart from the shifts in absorption and
fluorescent bands of compound 1 on addition of Fꢀ ion, there is also
visible colour change to naked eye as well as under UV light on
addition of Fꢀ ion to compound 1 as shown in Figure 8. This sup-
ports that 1 can also be used as colourimetric sensor (Fig. 8). The
bright pink fluorescencent colour of compound 1 was turned to
violet on addition of Fꢀ ion, whereas compound 2 did not show any
such changes in colour.
Similarly, under UV light, the bright orange fluorescence of 1
was changed to fluorescent green on addition of fluoride ion. The
comparison of colour changes on addition of various anions, such as
Brꢀ, Clꢀ, Iꢀ, HPO42ꢀ, ClOꢀ4 and Fꢀ to compound 1 is shown in Figure 9.
As clear from Figure 9 that addition of only Fꢀ ion to 1 results in
Figure 8. (a) Naked eye colour changes in compound 1 with (right) and without (left)
Fꢀ ion. (b) Under UV lamp colour changes in compound 1 with (right) and without
(left) Fꢀ ion.

M.R. Rao et al. / Tetrahedron 66 (2010) 1728–1734
1733
and afforded 4 as a red solid (1.27 g, 75%); mp 118–119 ꢁC; 1H NMR
(400 MHz, CDCl3, d inppm): 2.34 (s, 3H; –CH3), 5.29 (s,1H; –CH), 5.82
(m, 2H; Py), 6.06 (m, 2H; Py), 7.06 (d, 3J (H, H)¼7.8 Hz, 2H; Ar), 7.13 (d,
3J (H, H)¼7.8 Hz, 2H; Ar); ES–MS: (C16H14Br2N2). 394.2 [Mþ], CHN
calcd: C-48.76, H-3.58, N-7.11, Obsd, C-48.36, H-3.79, N-7.30.
4.2.2. 3,5-Dibromo-4,4-difluoro-8-(4-tolyl)-4-bora-3a,4a-diaza-s-
indacene (5).
4.2.2.1. Method I. Compound 4 (500 mg, 1.31 mmol) was taken
in CH2Cl2 (30 mL) and oxidized with DDQ (300 mg, 1.31 mmol) at
room temperature. The reaction was allowed to stir for 1 h at
room temperature. Triethylamine (6.38 mL, 46.0 mmol) followed
by BF3$Et2O (8.20 mL, 65.8 mmol) was added, and continued
stirring at room temperature for additional 1 h. The reaction
mixture was washed with 0.1 M NaOH solution and water thor-
oughly. The combined organic layers were dried over Na2SO4,
filtered, and evaporated. The crude product was purified by silica
gel column chromatography using of petroleum ether/dichloro-
methane (75:25) to afford compound 5 as a purple powder
(208 mg, 25%); Rf (pet. ether/25% CH2Cl2) 0.70; mp 210–211 ꢁC; IR
(KBr, cmꢀ1) 737, 777, 827, 980, 1083, 1110, 1182, 1255, 1313, 1386,
Figure 9. Under UV lamp colour changes in compound 1 on addition of two equiva-
lents of various anions.
3. Conclusions
In summary, we have synthesized a simple boron–dipyrrome-
thene (BODIPY) based chemodosimeter in three steps and demon-
strated that it can be used as colourimetric and fluorescent
chemodosimeter for fluoride anion. The chemodosimeter, which is
basedonwellknowndesilylationreactionrevealsthatthefluorescent
chemodosimeters for specific anion can be developed by making
small alterations on the molecular structure of fluorescent dyes.
1543, 1569, 2853, 2923; 1H NMR (400 MHz, CDCl3,
d in ppm): 2.46
(s, 3H; –CH3), 6.53 (d, 3J (H, H)¼4.28 Hz, 2H; Py), 6.82 (d, 3J (H,
H)¼4.28 Hz, 2H; Py), 7.32 (d, 3J (H, H)¼7.9 Hz, 2H; Ar), 7.38 (d, 3J
(H, H)¼7.9 Hz, 2H; Ar); ES–MS: (C16H11BBr2F2N2) 421.06 [MþꢀF],
CHN calcd: C-43.69, H-2.52, N-6.37, Obsd, C-43.60, H-3.99, N-7.41.
4.2.2.2. Method II. meso-(p-Tolyl)-Dipyrromethane 3 (500 mg,
2.15 mmol) was taken in dry THF (50 mL) and cooled to ꢀ78 ꢁC
under argon. N-Bromosuccinimide (762 mg, 4.31 mmol) was
added in two portions over 1 h period. After N-bromosuccinimide
dissolved completely (w1 h), DDQ (491 mg, 2.15 mmol) in THF
was added dropwise over 10 min. The reaction mixture was
warmed to room temperature and the solvent was evaporated on
rotary evaporator under vacuum. The crude compound was sub-
jected to flash column chromatography using CH2Cl2, concen-
trated on rotary evaporator, neutralized with triethylamine
(10.49 mL, 75.4 mmol) and treated with BF3$Et2O (13.44 mL,
107.0 mmol) at room temperature for additional 1 h. The reaction
mixture was washed with 0.1 M NaOH solution and water thor-
oughly. The combined organic layers were dried over Na2SO4,
filtered, and evaporated. The TLC analysis of crude compound
showed three spots corresponding to monobromo, dibromo and
tribromo derivatives and the desired dibromo derivative was the
second spot. The crude product was subjected to silica gel column
chromatography and second was collected using of petroleum
ether/dichloromethane (75:25). The solvent was removed on ro-
tary evaporator under vacuo and afforded 5 as purple powder
(600 mg, 64% yield).
4. Experimental section
4.1. General
1H, 13C NMR (
300 spectrometer. TMS was used as an internal reference for re-
cording 1H (of residual proton; 7.26) and 13C (
77.0) signal of CDCl3.
d in ppm) spectra were recorded using Varian VXR
d
d
Absorption and steady state fluorescence spectra were obtained
with Perkin–Elmer Lambda-35 and Lambda-55 instruments, re-
spectively. The ES–MS mass spectra were recorded with a Q-Tof
micro mass spectrometer. High-resolution mass spectrum was
obtained from Q-TOF instrument by electron spray ionization (ESI)
technique. Microanalyses were performed on a Thermo Finnigan
(FLASH EA 1112) microanalyzer. THFand Chloroformweredried over
sodium benzophenone ketyl and distilled prior to use. BF3$Et2O, 2,3-
dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and trimethylsily-
lacetylene were used as obtained. All other chemicals used for the
synthesis were reagent grade unless otherwise specified. Column
chromatography was performed on silica (60–120 mesh).
4.2. X-ray diffraction studies
The intensity data collection for compound 1 have been carried
out on a Nonius MACH3 four circle diffractometer at 293 K. Struc-
ture solution for the compound 1 was obtained using direct
methods (SHELXS-97)14 and refined using full-matrix least-squares
methods on F2 using SHELXL-97.15 Other details pertaining to data
collection, structure solution and refinement are given as Table S1
Supplementary data.
4.2.3. 3,5-Bis(trimethylsilylethynyl)-4,4-difluoro-8-(4-tolyl)-4-bora-
3a,4a-diaza-s-indacene (1). Sample of 5 (50 mg, 113
dissolved in toluene/triethylamine and trimethylsilylacetylene
(38 L, 284 mol) was added under argon atmosphere the coupling
was initiated by addition of catalytic amounts of CuI (4.2 mg,
22.6 mol) and Pd(PPh3)2Cl2 (9.5 mg, 13.6 mol). After disappear-
mmol), was
m
m
m
m
ance of the starting material as judged by TLC analysis, the solvent
was evaporated under reduced pressure. The crude residue
was purified by column chromatography on silica gel, using of
petroleum ether/dichloromethane (40:60) and afforded 1 as blue
crystals (32 mg, 60% yield); Rf (pet. ether/60% CH2Cl2) 0.58; mp
184–185 ꢁC; IR (KBr, cmꢀ1) 710, 797, 874, 942, 1017, 1071, 1140, 1164,
1269, 1384, 1453, 1468, 1549, 1816, 2852, 2922; 1H NMR (400 MHz,
4.2.1. meso-(p-Tolyl)-3,5-dibromodipyrromethane (4). meso-(p-To-
lyl)-dipyrromethane 3 (1.0 g, 4.23 mmol) was taken in dry THF
(75 mL) and cooled to ꢀ78 ꢁC under argon. N-Bromosuccinimide
(1.6 g, 9.0 mmol) was added in two portions over 1 h period. After N-
bromosuccinimide dissolved completely (w1 h), the reaction mix-
ture was warmed to room temperature and the solvent evaporated
by rotary evaporator. The residue was purified by silica gel column
chromatography usingof petroleum ether/dichloromethane (85:15)
CDCl3, d in ppm): 0.31(s, 18H; –Si(CH3)3), 2.45 (s, 3H; –CH3), 6.60 (d,
3J (H, H)¼4.39 Hz, 2H; Py), 6.81 (d, 3J (H, H)¼4.39 Hz, 2H; Py), 7.30
(d, 3J (H, H)¼7.8 Hz, 2H; Ar), 7.38 (d, 3J (H, H)¼7.8 Hz, 2H; Ar); HRMS

1734
M.R. Rao et al. / Tetrahedron 66 (2010) 1728–1734
Handbook of Experimental Pharmacology XX/1, Part 1; Springer: Berlin, 1969, pp
141-172; (c) Dreisbuch, R. H. Handbook of Poisoning; Lange Medical: Los Altos,
CA, 1980.
calcd for C26H29BF2N2Si2Na 497.1828, found 497.1814; CHN calcd:
C-65.81, H-6.16, N-5.90, Obsd, C-66.20, H-5.85, N-5.80.
´
´
5. (a) Martınez, M. R.; Sancenon, F. Chem. Rev. 2003, 103, 4419–4476; (b) Hundall,
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4.3. Procedure for anion sensing
Stock solutions of the anions (2.0 mM) were prepared in
methanol and stock solution of 1 (1 mM) was prepared in CH2Cl2.
For absorption measurements, the stock solution of 1 was diluted to
8
mM with CH2Cl2. Titration experiments were performed by plac-
ing 2.5 mL of solution 1 (8 M) in a quartz cuvette of 1 cm optical
m
path length, and various amounts of anions were added in-
crementally by means of a micro-pipette. For fluorescence mea-
surements, 2 mM concentration of 1 was used. Excitation was
provided at 425 nm, and emission was collected from 500–700 nm.
Acknowledgements
M.R. thanks CSIR and DST for financial support. MRR thanks CSIR
for fellowship. We thank the DST funded National Single Crystal X-
ray Diffraction Facility for diffraction data.
Supplementary data
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M. R.; Sanceno´ n, F. Coord. Chem. Rev. 2006, 250, 3081–3093.
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Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2009.12.039.
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