Synthesis of sterically hindered antipyrines for intramolecular charge transfer facilitated sensing

Article abstract of DOI:10.1002/poc.2948

A new series of sterically hindered antipyrine derivatives have been synthesized by Schiff base condensation for potential fluorescence sensing applications. Their optical, thermal, and electrochemical properties were fully characterized. Broad absorption spectra were observed as a result of the strong intramolecular charge transfer between antipyrine and sterically hindered conjugated moiety. Reversible one electron oxidation couple was observed for most compounds, with carbazole, phenothiazine, and bithiophene functionalized derivatives exhibiting extra reversible one one-electron oxidation process at higher positive potentials. Cabazole functionalized antipyrine derivative APCZ presents good fluorescence sensing for Co²⁺ and Cu²⁺, with 3.41-fold enhancement in fluorescence intensity and 2-fold enhancement in fluorescence quantum yield observed. Copyright

Full text of DOI:10.1002/poc.2948

Research Article
Received: 16 February 2012,
Revised: 18 March 2012,
Accepted: 23 March 2012,
Published online in Wiley Online Library: 2012
(wileyonlinelibrary.com) DOI: 10.1002/poc.2948
Synthesis of sterically hindered antipyrines
for intramolecular charge transfer facilitated
sensing
Linyi Biana, Gang Sunb, Yuxi Sunb and Weihua Tanga*
A new series of sterically hindered antipyrine derivatives have been synthesized by Schiff base condensation for
potential fluorescence sensing applications. Their optical, thermal, and electrochemical properties were fully charac-
terized. Broad absorption spectra were observed as a result of the strong intramolecular charge transfer between
antipyrine and sterically hindered conjugated moiety. Reversible one electron oxidation couple was observed for
most compounds, with carbazole, phenothiazine, and bithiophene functionalized derivatives exhibiting extra
reversible one one-electron oxidation process at higher positive potentials. Cabazole functionalized antipyrine
derivative APCZ presents good fluorescence sensing for Co2+ and Cu2+, with 3.41-fold enhancement in fluorescence
intensity and 2-fold enhancement in fluorescence quantum yield observed. Copyright © 2012 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this paper
Keywords: antipyrine; Schiff base condensation; intramolecular charge transfer; chemosensor
The aforementioned fluorophores have been explored in various
INTRODUCTION
optoelectronic devices for their good charge transfer capabil-
ity.[24–29] 4-Amnioantipyrine is a versatile building block in
Selectively recognizing biologically and environmentally impor-
constructing fluorescent probes, which can covalently connect
with various fluorophore either through Schiff base bond[21]
or amine linkage.[19] Schiff base bond can present considerable
optical characteristics and electron delocalization.[30–32] For
antypyrine-based chemosensors, fluorescence detection works
owing to their chelating groups C = N and C = O exhibiting a high
affinity to transition and post-transition metal cations such as Zn2+,
on the condition that the C = N isomerization is effectively
inhibited.
By taking advantage of antipyrine’s chelating feature, we have
recently initiated a research program to develop new antipyrine-
based fluorescent probes with sterically hindered structures
(Chart 1). All together, seven compounds were prepared via schiff
base condensation between 4-aminoantipyrine and various
aromatic aldehydes. The synthesis, optical and electrochemical
characteristics, and potential as chemoseonsor of these antipyrine
derivatives were studied.
tant chemical species via fluorescent chemosensors has
attracted intensified interest by taking advantage of their high
selectivity, sensitivity, and simplicity.[1–7] The fluorescent
chemosensor is a molecular system capable of producing
detectable fluorescent signal upon interaction with the testing
chemical species. Exploration of new interaction mechanism
between recognition and signal reporting thus inspires the
design of new fluorescent chemosensors. Depending on the
testing species, several signaling mechanisms have been devel-
oped, including photoinduced electron/energy transfer,[8–10]
metal-ligand charge transfer,[10] intramolecular charge transfer
(ICT),[2–14] excimer/exciplex formation,[15–19] and excited-state
intramolecular/intermolecular proton transfer, and so on.[20]
Recently, C = N isomerization was proposed as a new signaling
mechanism for coumarin functionalized antypyrine chemosensor
in detecting metal cations.[21]
The C = N isomerization is regarded as the predominant decay
process of the excited states for compounds with free-standing
C = N bond. Hence, the suppression of this isomerization via
covalently bridged C = N structure can lead to dramatically
enhanced fluorescence.[22,23] Recently, Wang et al.[21] designed
an elegant coumarin functionalized antipyrine chemosensor,
where the C = N isomerization was effectively inhibited using
metal cation chelating with both C = N linkage and both
carbonyl groups from coumarin and antipyrine moiety. With
triple chelating with Zn2+, the fluorescence quantum yield
of the coumarin chemosensor was effectively increased (ca
200-fold).
* Correspondence to: W. Tang, Key Laboratory of Soft Chemistry and Functional
Materials (Ministry of Education of China), Nanjing University of Science and
Technology, Nanjing 210094, China.
E-mail: whtang@mail.njust.edu.cn
a L. Bian, W. Tang
Key Laboratory of Soft Chemistry and Functional Materials (Ministry of
Education of China), Nanjing University of Science and Technology, Nanjing
210094, China
Inspired by this research, we are wondering whether we can
use bulky fluorophore such as fluorene, carbazole, phenothiazine,
bithiophene, and naphthalene to inhibit the C = N isomerization
and thus harvest good florescence for metal cation detection.
b G. Sun, Y. Sun
Key Laboratory of Life-Organic Chemistry (Shandong Province), School of
Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165,
China
J. Phys. Org. Chem. (2012)
Copyright © 2012 John Wiley & Sons, Ltd.

L. BIAN ET AL.
S
N
Ar =
N
O
APCZ
APPT
APFL
N
N
Ar
N
S
S
N
OCH3
APBT
APNL
APMNL
APDANL
either by recrystallization or flush column chromatography with
satisfactory yields (ca. >85%).
RESULTS AND DISCUSSION
The thermal stability and crystallization behavior of as-
prepared antipyrine derivatives were examined by thermogra-
vimetric analysis (TGA) and differential scanning calorimetry,
respectively. The thermograms of antipyrine derivatives were
shown in Supporting Information (Fig. S1). The thermal
decomposition temperatures (Td) for all compounds are summa-
rized in Table 1. All sterically hindered antipyrine derivatives
demonstrated high thermal stability in inert gas atmosphere
(ca N2), with Td over 330ꢀC except for APFL and APBT.
Fluorene and 2,2’-bithiophene containing APFL and APBT
displayed lower thermal decomposition temperature when
compared with those naphthalene-containing, and carbazole-
containing compounds. It is noted that phenothiazine-containing
APPT is even more thermal stabile than those naphthalene-based
compounds although phenothiazine shares similar structure
as fluorene moiety.
The synthesis of key intermediates: aldehydes of fluorene (1d),
phenothiazine (2c), cabazole (3b), and bithiophene were carried
out with modified procedure.[33] As shown, 9,9-diethylfluorene-3-
carbaldehyde (1d) was prepared with a three-step protocol,
including a first alkylation with bromoethane under basic condition,
further bromination with bromine in the presence of ferric chloride
catalyst, and a final formylation with N, N-Dimethylformamide
(DMF) with the aid of n-BuLi (detail in Experimental section).
10-ethylphenothiazine-3-carbaldehyde (2c) was prepared by a first
alkylation of phenothiazine and further Vilsmeier–Haack formylation
with DMF with the aid of POCl3. Similar reaction approach was
employed to prepare 9-ethylcarbazole-3-carbaldehyde (3b) and
2,2’-bithiophene-5-carbaldehyde (4b) (Scheme 1).
With aromatic aldehydes at hand, the Schiff base condensa-
tion was employed by refluxing reaction mixture in ethanol
overnight. The targeted antipyrine compounds were obtained
O
Br
i
CHO
ii
iii
iv
N
N
N
1a
1b
1c
1d
S
O
S
S
CHO
O
i
iv
N
v
APFL
N
N
S
N
H
2a
N
N
N
N
2b
2c
APPT
CHO
v
iv
N
N
N
N
N
3b
APCZ
3a
O
S
v
S
S
iv
S
N
CHO
N
S
S
N
APBT
4b
4a
CHO
O
iv
R=H
R=OCH3
APNL
APMNL
N
N
R=N(CH3)2 APDANL
R
N
R
Scheme 1. Synthesis of the antipyrines. Reaction conditions: (i) CH2Br2, DMSO, NaOH, rt; (ii) Br2, CHCl3; (iii) n-BuLi, DMF, THF, À78 ꢀC; (iv) antipyrine,
CH3CH2OH, 80 ꢀC; (v) DMF, POCl3, CHCl3, 100 ꢀC
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J. Phys. Org. Chem. (2012)

ANTIPYRINE SENSOR
À
Á
À
Á
max
max
Table 1. Observed longest-wavelength absorption l
, longest wavelength of fluorescence emission l
, HOMO and LUMO
abs
PL
ꢀ
ꢁ
energy levels, optical bandgap Egopt , and decomposition (Td) and melting temperature (Tm) of antipyrine derivatives
max
max
PL
Compd
l
(nm)a
l
(nm)b
Φf (%)c Eox (V) HOMO (eV)d Egopt (eV)e LOMO (eV)f Td (ꢀC) Tm (ꢀC)
abs
APFL
APPT
APCZ
APBT
APNL
APMNL
APDANL
224 (358)
243 (321, 384)
240 (290, 432) 393 (309, 611)
392, 257
245 (358)
382, 256
307 (400, 610)
526
0.28
0.72
0.75
0.37
0.40
0.21
0.85
0.86
0.61
0.74
0.80
0.68
0.59
0.65
À5.26
À5.01
À5.14
À5.20
À5.08
À4.99
À5.05
3.02
2.64
2.38
2.68
2.92
2.75
2.92
À2.24
À2.37
À2.76
À2.52
À2.16
À2.24
À2.13
278
482
334
291
455
454
376
225
206
>280
193
200
153
306 (421, 607)
307 (409, 607)
344 (662)
243 (366)
310 (410, 611)
198
a1 Â 10À5 M in anhydrous CH2Cl2, the data in parentheses assigned for the wavelength of shoulder peak.
b1 Â 10À5 M in CH3CN, lex = 290 nm.
cFluorescence quantum yield (fluorescein in 0.1 M NaOH as reference, Φf = 0.85).[12]
dDerived from the oxidation potential using EHOMO = À(4.4 + Eox).
eOptical band gap was obtained from the empirical formula Egopt = 1240/ledge eV.[26]
fDeduced using the formula ELUMO = EHOMO-Egopt
.
[42]
All of the compounds are amorphous in nature, as no
exothermic crystallization peaks observed during cooling trace
differential scanning calorimetry. The melting points (Tm) are
summarized in Table 1. Except for APMNL, all Schiff base
compounds showed high Tm above 190ꢀC, especially APCZ
demonstrating a Tm over 280ꢀC. The relatively high decomposition
and melting temperatures of organic conjugated materials are
beneficial for their application in optoelectronic devices such
as organic solar cells, light-emitting diodes, and chemosen-
sors.[2,21,24–29]
The absorption spectra of seven Schiff base compounds
(~1 Â 10À5 M) were measured in dichloromethane, with the
maximum peak wavelengths summarized in Table 1. Broad
absorption spectra (Fig. 1) of all compounds showed their first
absorption maxima in 220–310-nm region and second maxima
of lower energy around 400 nm. The first absorption maxima
can be attributed to the p-p* transition in antipyrine moiety
and second maxima (~400 nm) attributed to p-p* transition in
sterically hindered aromatic ring. The subsequent broad band
expanding between two major absorption maxima can be
assigned to the ICT transitions between antipyrine and
corresponding aromatic units, owing to the occurring of certain
electron delocalization between them. The spectra of APFL,
APBT, APNL, APMNL, and APDANL show an intense absorption
maximum peaking at 358 to 392 nm, whereas additional peaks
(269 and 321 nm, respectively) and broader ICT band were
observed for APPT and APCZ, as a result of varied conjugation
length in phenothizaine and carbazole moieties. The electronic
spectra of the parent compound APFL possess two bands: one
max
arising from the p-p*(l
= 224 nm) of the antipyrine unit and
abs
max
another from ICT (l
= 358 nm) transitions. Similar behavior
abs
was observed for APBT, which showed more red-shifted
max
abs
maximum absorptions (l
= 243, 392 nm) caused by longer
effective conjugation length and lower energy p-p* transition.
It should note that naphthalene-containing APNL, APMNL, and
APDANL presented red-shifted maximum peaks when the naph-
thalene moiety was substituted with electron-withdrawing
group (ca. -N(CH3)2 and -OCH3), that is, APMNL (lambasx = 382 nm)
max
and APDANL (l
= 366 nm) possessed more bathomic peaks
abs
max
than APNL (l
= 358 nm).
abs
The fluorescence spectra of all antipyrine of derivatives
(~1 Â 10À5 M) were obtained in acetonitrile solutions by exciting
at 290 nm except for APPT, which was excited at 395 nm owing
to its different maximum absorption. As clearly observed from
Fig. 2, APPT presented single much red-shifted maximum
1.0
0.8
0.6
0.4
0.2
0.0
APFL
APPT
APCZ
APBT
APNL
APMNL
APDANL
APMNL
APPT
1.0
0.8
0.6
0.4
0.2
0.0
APCZ
APDANL
APFL
APBT
200
250
300
350
400
450
500
Wavelength (nm)
300
400
500
600
700
Wavelength (nm)
Figure 1. Normalized absorption spectra of seven antipyrines in CH2Cl2
solution
Figure 2. Emission spectra for antipyrines in acetonitrile solution
J. Phys. Org. Chem. (2012)
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L. BIAN ET AL.
emission at 526 nm (Table 1), whereas a maximum emission
~310 nm was observed for APFL, APBT, APNL, and APDANL.
The only emission maxima of APPT can be attributed to the
existence of unique conjugated structure of phenothiazine.
Interestingly, the maximum emission of APMNL and APCZ was
further red-shifted to 344 and 393 nm, respectively, probably
because of their longer effective conjugation length. A close look
at the fluorescence spectra of naphthalene-containing deriva-
tives APNL, APMNL, and APDANL, much red-shifted emission
maxima (~344 nm) and shoulder peak (662 nm) were clearly
observed for APMNL. All antipyrine derivatives display a quantum
yield ranging from 0.21 to 0.85 in solution, which is even higher
than that of coumarin derivative.[21] As shown in Table 1, APPT,
APCZ, and APDANL showed relatively higher quantum yield,
which should be attributed to the high fluorescencent conjugated
moiety including phenothiazine, carbazole, and 4-dimethylamino-
1-naphthyl ring.
pathway together with antipyrine ring and its -N-N- bond. Similar
oxidation behavior was also observed for antipyrine derivative at
E = 1.2–1.3 V.[43]
Interestingly, APPT, APCZ, and APMNL displayed one-
electron quasi-reversible oxidation couple at the relatively
low oxidation potentials (0.6–0.8 V), which is more positive
than that observed for ferrocene. This low oxidation potential
can be attributed to the oxidation of its peripheral amine or
ether moiety.
The highest occupied molecular orbital (HOMO) energy levels
of all antipyrine derivatives (Table 1) were calculated accordingly
using the first oxidation potential (Eox) in reference to ferrocene
(4.8 eV).[42] The HOMO energy levels of all compounds range
from À4.99 to À5.26 eV. The lowest unoccupied molecular or-
bital (LUMO) levels were estimated from the values of HOMO
ꢀ
ꢁ
[42]
and the optical band gap Egopt
.
The band gaps of the com-
pounds were estimated from the onset value of absorption
spectrum in long wavelength range.[24–29] Except APCZ, all
compounds possessed a Egopt ranging from 2.64 to 3.02 eV,
The electrochemical behavior of antipyine derivatives (Table 1)
was investigated by cyclic voltammetry in acetonitrile solution
with 0.1 M tetrabutylammonium hexafluorophosphate CH3CN
solution in a three-electrode assembly. And the oxidation cyclic
voltammograms are displayed in Fig. 3.
whereas APCZ showed the narrowest Egopt of 2.38 eV. Accord-
ingly, APCZ presented a lowest LUMO of À2.76 eV, whereas a
higher LUMO value of À2.13 ~ À2.52 eV was observed for the
rest of antipyrine derivatives.
Except APMNL, all antipyrine derivatives displayed irrevers-
ible oxidation couple at the relatively low oxidation potentials
(ca <1.0 V). The oxidation potential of the studied antipyrines
increases in the following order: APMNL < APPT < APDANL <
APNL < APCZ < APBT < APFL. Among fluorene, carbazole,
thiophene, and phenothiazine containing derivatives, the oxi-
dation potential assumes the following order: APFL > APBT >
APCZ > APPT. Thiophene[34] and fluorene-containing aryla-
mines[35–41] have been reported to exhibit facile oxidation
owing to the electron richness of the thiophene and fluorene
moieties. It is generally known that the more electron-rich
and more conjugated moiety, the easier to be oxidized.
Although phenothiazine unit possesses shorter conjugation
length than bithiophene and fluorene moieties, APPT presents
lower oxidation potential (0.61 V) than APFL (0.86 V) and APBT
(0.80 V), owing to the existence of amine structure.[42] It should
note that APCZ presents an oxidation potential of 0.74 V, which
is higher than APPT and attributable to its longer conjugation
length of carbazole unit in comparison to phenothiazine unit.
An additional one-electron oxidation at the high positive
potential (1.0–1.4 V) is also observed for APPT, APCZ, and APBT,
probably originating from oxidation of aromatic conjugation
The Schiff base bonded 4-aminoantipyrine and coumarin de-
rivative was explored as fluorescent probe for metal cations.[21]
A significant fluorescence enhancement to zinc cation was
observed with the chelating of Zn2+ with C = N bond and both
carbonyl groups from coumarin and antipyrine moieties to
suppress the C = N isomerization in the excited states.[22] Such
fluorescence enhancement could not be achieved with analo-
gous coumarin derivative when carbonyl group was absent. This
behavior was explained with the quenching of fluorescence by
C = N isomerization.[21]
In order to explore the potential of sterically hindered antipy-
rine derivatives, the cation sensing study was performed with all
as-prepared antipyrine derivatives.[21] The variations of fluores-
cence spectra of APCZ upon addition of different metal cations
including Al3+, Co2+, Cu2+, Fe3+, Ni2+, Pd2+, and Zn2+ in CH3CN
was depicted in Fig. 4. The fluorescence sensing of metal
cations using other derivatives were also measured, with
sensing capabilities either comparable with or inferior to that
of APCZ. Fluorescence sensing capabilities of APBT and APPT
were described in Supporting Information (Fig. S2, S3). So the
Figure 3. Oxidation CV of antipyrines in acetonitrile solution
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ANTIPYRINE SENSOR
1000
800
600
400
200
spectra were collected from Finnigan/MAT TSQ 7000. The UV–Vis
absorption and photoluminescence spectra were recorded on a Shimadzu
UV 3101 spectrophotometer and on a Perkin-Elmer LS-50B luminescence
spectrometer, respectively. TGA was performed at a heating rate of
20ꢀC/min under N2 atmosphere with DuPont TGA 2050. Cyclic voltamme-
try measurements were performed on CHI660D work station with 0.10 M
tetrabutylammonium hexafluorophosphate acetonitrile solution (scan rate,
100 mV sÀ1) as electrolyte. Three electrodes including a platinum plate
working electrode, a copper counter electrode, and a Ag/AgCl in 3 M KCl
reference electrode were used.
APCZ+10 eq. Co2+
APCZ+10 eq. Cu2+
APCZ only
APCZ+10 eq. Ni2+, orAl3+, Pd2+, Zn2+, Fe3+
0
Synthesis of 9,9-diethylfluorene 1b
Fluorene (5 g, 30 mmol) was added to a suspension of sodium hydroxide
(6 g, 0.15 mol) in 70 ml of dimethyl sulfoxide, which was prepared by
vigorous stirring for 0.5 h under nitrogen atmosphere. After stirring for
1 h, Bromoethane (4.7 ml, 63 mmol) was added. Then the reaction was
carried out at 80 ꢀC for overnight. The following procedure was similar
as for 1. 4.67 g of product 1b was afforded as colorless solid with a yield
of 70%. 1 H NMR (500 MHz, CDCl3) d 7.74–7.69 (m, 2 H), 7.29–7.36 (m, 6 H),
2.03 (p, 4 H, J =7.5 Hz), 0.33(t, 6 H, J = 7.5 Hz).
350
400
450
500
550
600
wavelength (nm)
Figure 4. Fluorescence spectra of APCZ (1 Â 10À5 M) in CH3CN upon
addition of 10 equivalent of Al3+, Co2+, Cu2+, Fe3+, Ni2+, Pd2+, and Zn2+
discussion was focused on the fluorescence sensing of APCZ.
The emission of APCZ, peaked at 416 nm, was very weak
(fluorescence quantum yield is 0.75%)[44] and quenched 10 to
Synthesis of 3-bromo-9,9-diethylfluorene 1c
45% upon addition of 10 equiv Ni2+, Al3+, Pd2+, Zn2+, and Fe3+
.
To a solution of 9,9-diethylfluorene 1b (3.5 g, 15.7 mmol) in CHCl3 (15 mL)
at 0 ꢀC was added dropwise the solution of bromine (0.85 mL, 16.5 mmol
) in CHCl3 (10 mL). Then, 30 mg (0.18 mmol) of ferric chloride was added.
The solution was warmed to room temperature and stirred for 3 h. It is
important that the reaction proceeds in the dark to avoid any bromina-
tion of the aliphatic chain of the molecule. The resulting mixture was
poured into water and washed with sodium thiosulfate until the red color
disappeared. The aqueous layer was extracted with dichloromethane, and
the combined organic layers were dried over anhydrous magnesium
sulfate to afford the title product (4.7g, 99% yield) as a pale-brown solid.
1 H NMR (500 MHz, CDCl3) d 7.69–7.65 (m, 1 H), 7.58–7.51 (m, 1 H), 7.44–7.48
(m, 2 H), 7.35–7.31 (m, 3 H), 2.05–1.97 (m, 4 H), 0.32 (t, 6 H, J=7.5Hz)
It can be found that Co2+ gives rise to the largest fluorescence
enhancement among all selected metal cations, with a 2-fold
enhancement in quantum yield and 3.4-fold enhancement in
fluorescence intensity achieved. It should note that Cu2+ also
induce significant fluorescence enhancement for APCZ, as
indicated by enhancement of fluorescence quantum yield by
1.4-fold and fluorescence intensity by 2.4-fold. In addition, the
nearly 10-nm red-shift emission is valuable for APCZ as fluores-
cent probes.
CONCLUSIONS
Synthesis of 9,9-diethylfluorene-3-carbaldehyde 1d
To a stirred solution of 3-bromo-9,9-diethylfluorene 1c (2.5 g, 8.2 mmol)
in freshly dried THF (40 mL) was added n-BuLi (4.5 mL, 2.0 M in hexane
9 mmol) at À78 ꢀC under nitrogen. The mixture was first stirred for
1.5 h at this temperature before DMF (0.96 mL, 12.4 mmol) was added.
The solution was stirred for another 1.5 h and allowed to warm to room
temperature gradually. The solution was stirred overnight. Hydrochloric
(2 M, 50 mL) was added and stirred for 2 h. The organic layer was
separated, the aqueous layer extracted with dichloromethane for three
times, the combined organic layer dried over anhydrous magnesium
sulfate, and evaporated to dryness. Chromatography on silica gel using
petroleum ether and ethyl acetate (20:1) as eluent, the title compound
1d (0.93 g, 45% yield) was obtained as pale-brown solid. 1 H NMR
(500 MHz, CDCl3) d 10.06 (s, 1 H), 7.88–7.84 (m, 3 H) 7.80–7.77(m, 1 H),
7.42–7.35 (m, 3 H), 2.12–2.02 (m, 4 H), 0.303 (t, 6 H, J = 7.5 Hz).
In summary, a series of sterically hindered antipyrine derivatives
have been synthesized with Schiff base condensation in good
yields, with their photophysical, electrochemical, and thermal
properties thoroughly characterized, and potential in fluorescence
probe application explored. All these antipyrine derivatives
are amorphous in nature and display good thermal stability
(Td >278 ꢀC) for optoelectronic applications. The ICT effect
induced broad UV–Vis absorption bands were observed to
expand between two major absorption maxima attributed to a
p-p* transition in antipyrine moiety (~250 nm) and sterically
hindered aromatic rings (~400 nm).
APCZ presents good fluorescence sensing for Co2+ and Cu2+
,
that is, 3.41-fold and 2.39-fold enhancement in fluorescence
intensity as well as 2-fold and 1.4-fold enhancement in fluores-
cence quantum yield were observed, respectively, upon addition
of 10 equiv Co2+ and Cu2 in CH3CN solution.
Synthesis of N-ethylphenothiazine 2b
To a suspension of sodium hydroxide (6 g, 0.15 mol) in dimethyl sulfoxide
(50 mL) was added with phenothiazine (5 g, 25 mmol). After stirring for
1 h, bromoethane (4.1 mL, 55 mmol) was added. The reaction was carried
out for 3 h at room temperature. The reaction mixture was filtered to
remove sodium hydroxide and then washed with water. The organic
layer was extracted using petroleum ether for several times and dried
over anhydrous magnesium sulfate. The crude product was concentrated
and purified by silica gel column using petroleum ether as eluent. After
evaporation of the eluent solvent, the title compound 2b (2.87 g, 50%
yield) was obtained as colorless solid.
EXPERIMENTAL
General
All reagents were purchased from Sigma–Aldrich Chemical Co. and used
without further purification. Tetrahydrofuran (THF) was distilled from
sodium benzophenone prior to use. N, N-Dimethylformamide and aceto-
nitrile were dried and distilled from CaH2. All reactions were performed
under N2 atmosphere unless otherwise stated. 1 H NMR and 13 C NMR
spectra were recorded on a Bruker AVANCE 500 spectrometer. The mass
1 H NMR (500 MHz, CDCl3): d7.18–7.12 (m, 4 H), 6.95–6.85 (m, 4 H), 3.93
(q, 2 H, J = 6.5 Hz), 1.43(t, 3 H, J = 6.5 Hz).
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L. BIAN ET AL.
(0.51 g, 85% yield) as a pale yellow solid. 13 C NMR (125 MHz, CDCl3)
d 161.25, 158.54, 151.46, 141.50, 140.43, 135.08, 129.35, 129.09,
126.61, 125.90, 125.84, 124.16, 123.22, 123.17, 120.68, 119.47,
119.33, 108.66, 108.42, 37.71, 36.13, 13.81, 10.23; ESI-MS (m/z): for
Synthesis of 10-ethylphenothiazine-3-carbaldehyde 2c
To an ice-cooled solution of dimethylformamide (0.51 ml, 5.5 mmol) was
added with phosphorus oxychloride (0.46 ml, 5 mmol). After 1 h stirring at
ice bath, N-ethylphenothiazine 2b (1.14 g, 5 mmol) solution in CHCl3
(15 mL) was added dropwise. The resulting mixture was slowly warmed
to room temperature and then stirred at 100 ꢀC overnight. The solution
was cooled to room temperature before pouring into a saturated sodium
acetate aqueous solution (30 ml) and stirred for 6 h to complete the
hydrolysis. The mixture solution was extracted four times with dichloro-
methane. The combined dichloromethane organic layer was dried over
anhydrous magnesium sulfate and then concentrated by distillation
under reduced pressure. After purification by silica gel column chroma-
tography using n-hexane and ethyl acetate (8:1) as eluent, the title
compound 2c (0.81 g, 63% yield) was obtained as viscous yellow solid.
1 H NMR (500 MHz, CDCl3) d 9.78 (s,1 H), 7.63 (dd, 1 H, J = 2.0 Hz,
J = 8.5 Hz), 7.57 (d, 1 H, J = 2.0 Hz), 7.16 (m,1 H, J = 1.5 Hz, J = 8.5 Hz), 7.09
(dd, 1 H, J = 1.5 Hz, J = 7.5 Hz), 6.96 (m, 1 H), 6.89 (m, 2 H), 3.98 (q, 2 H,
J = 7 Hz), 1.47 (t, 3 H, J = 7 Hz).
C
26H26N4O [M]+ 410.21, found 410.11.
Synthesis of 4-(2,2’-bithiophen-5-ylmethyleneamino)-1,5-dimethyl-
2- phenyl-1 H-pyrazol-3(2 H)-one (APBT)
By employing the similar procedure as for APFL, 2,2’-bithiophene-5-
carbaldehyde(4b) (0.29 g, 5 mmol) was used. However, the title prod-
uct did not precipitate from solution. A column chromatography of
the concentrated residue with petroleum ether and ethyl acetate
(5/1, v/v) afforded the title compound (0.47 g, 84%) as a yellow solid.
13 C NMR (125 MHz, CDCl3) d 160.81, 151.49, 150.33, 143.79, 140.00,
137.55, 134.75, 131.08, 129.15, 127.93, 126.89, 125.04, 124.38,
124.29, 124.10, 118.48, 35.79, 10.06; ESI-MS (m/z): calcd. for
C20H17N3OS2 [M]+ 379.08, found 378.98.
Synthesis of 1,5-dimethyl-4-(naphthalen-1-ylmethyleneamino)-2-
phenyl- 1 H-pyrazol-3(2 H)-one (APNL)
Synthesis of 9-ethylcarbazole-3-carbaldehyde 3b
By following similar procedure as for 2c, the title compound 3 (0.63 g,
56% yield) was prepared using N-ethylcarbazole (0.98 g, 5 mmol) to
afford as yellow solid. 1 H NMR (500 MHz, CDCl3) d 10.10 (s, 1 H), 8.62
(d, 1H, J= 1.5Hz) 8.17 (d, 1 H, J = 8.5Hz), 8.02 (dd, 1 H, J= 1.5Hz,
J = 8.5Hz), 7.54 (m, 1 H), 7.48 (t, 2H, J = 8.5Hz), 7.33 (m, 1 H), 4.42 (q, 2 H,
J = 7.5Hz), 1.48 (t, 3 H, J = 7.5 Hz).
A similar synthetic approach was employed using naphthalene-1-
carbaldehyde to afford the title compound APNL (81% yield) as a
yellow solid. 13 C NMR (125 MHz, CDCl 3d(ppm):160.96, 156.16, 152.04,
134.81, 133.88, 133.15, 131.71, 130.55, 129.19, 128.50, 126.93, 126.71,
126.35, 125.81, 125.37, 124.43, 124.09, 119.29, 35.82,10.23; ESI-MS
(m/z): calcd. for C22H19N3O [M]+ 341.15, found 341.10.
Synthesis of 2,2’-bithiophene-5-carbaldehyde (4b)
Synthesis of 4-((4-methoxynaphthalen-1-yl)methyleneamino)-1,5-
dimethyl- 2-phenyl-1 H-pyrazol-3(2 H)-one (APMNL)
By following similar procedure as for 2c, 2,2’-bithiophene (0.83 g, 5 mmol)
was used to afford 4b as a dark brown solid with a yield of 61% (0.59 g).
1 H NMR (500 MHz CDCl3) d 9.86 (s, 1 H), 7.67 (d, 1 H, J = 4 Hz), 7.36 (d, 2 H,
J = 4.5 Hz), 7.25 (d, 1 H, J = 4 Hz), 7.08 (t, 1 H, J = 4.5 Hz).
4-Methoxynaphthalene-1-carbaldehyde was employed to afford the title
compound APMNL as a brown solid (80% yield). 13 C NMR (125 MHz,
CDCl3): d 161.13, 157.43, 156.90, 151.58, 135.35,134.92,132.64, 129.17,
126.81, 125.89, 125.84, 125.62, 125.28, 124.32, 124.18, 122.86, 119.57,
103.75, 55.65, 37.81, 35.97, 10.29, 10.17; ESI-MS (m/z): calcd. for
C23H21N3O2 [M]+ 371.16, found 371.06.
Synthesis of 4-((9-ethyl-9 H-fluoren-3-yl)methyleneamino)-1,5-dimethyl
À2-phenyl-1 H-pyrazol-3(2 H)-one (APFL)
The as-prepared 9,9-diethylfluorene-3-carbaldehyde (1d) (0.37 g,
1.48 mmol) was dissolved in ethanol (20 mL) and followed by the
addition of 4-aminoantipyrine (0.30 g, 1.48 mmol). The mixture was
heated to reflux overnight at 70 ꢀC. The crude product precipitated from
the solution. After cooling the reaction mixture to room temperature, the
precipitate was filtered and washed with ethanol several times prior to dry-
ing in vacuo. The title compound APFL (0.56 g, 81% yield) as a yellow solid.
13 C NMR (125MHz, CDCl3) d 160.92, 157.91, 151.80, 150.59, 150.13, 143.78,
140.96, 136.85, 134.88, 129.08, 127.48, 127.42, 126.83, 126.72, 124.23,
122.89, 121.76, 119.98, 119.59, 118.99, 56.00, 35.91, 32.63, 10.17, 8.44;
ESI-MS (m/z): calcd. for C29H29N3O [M]+ 435.56, found 435.10.
Synthesis of 4-((4-(dimethylamino)naphthalen-1-yl)methyleneamino)-
1,5- dimethyl-2-phenyl-1 H-pyrazol-3(2 H)-one (APDANL)
4-Dimethlaminonaphthalene-1-carbaldehyde was employed to afford
the title compound APNL-DMA as a yellow solid (88% yield). 13 C NMR
(125 MHz, CDCl3) d 161.07, 156.76, 153.20, 151.60, 134.90, 133.00,
129.09, 128.41, 127.72, 127.51, 126.70, 126.54, 124.87, 124.69, 124.66,
124.22, 119.64, 113.29, 44.92, 35.93, 10.21; ESI-MS (m/z): calcd. for
C24H24N4O [M]+ 384.20, found 384.12.
Acknowledgements
Synthesis of 4-((10-ethyl-10 H-phenothiazin-3-yl)methyleneamino)-1,
5- dimethyl-2-phenyl-1 H-pyrazol-3(2 H)-one (APPT)
The Financial support from the National Natural Science Founda-
tion of China (Grant No. 21074055) and Doctoral Fund of Ministry
of Education of China (No. 20103219120008) was acknowledged.
The authors thank Ms Lan Yi for the help in NMR measurement.
By following similar reaction approach as for APFL, APPT was prepared
using as-prepared 10-ethyl-10 H-phenothiazine-3-carbaldehyde (2c)
(0.38 g, 1.48 mmol) and 4-aminoantipyrine. The title compound APPT
(0.56 g, 86% yield) was obtained as
a
yellow solid. 13 C NMR
(125 MHz, CDCl3) d 160.96, 155.79, 151.71, 146.48, 144.11, 134.88,
132.47, 129.16, 129.01, 128.09, 127.31, 127.22, 126.73, 125.50, 124.25,
123.79, 122.58, 118.90, 115.10, 114.54, 42.06, 35.91, 12.91, 10.08; ESI-MS
(m/z): calcd. for C26H26N4OS [M]+ 442.18, found 442.03.
REFERENCES
[1] F. P. Schmidtchen, M. Berger, Chem. Rev. 1997, 97, 1609–1646.
[2] D. P. Beer, P. A. Gale, Angew. Chem. Int. Ed. 2001, 40, 486–516.
[3] M. R. Martinez, F. Sancenon, Chem. Rev. 2003, 103, 4419–4476.
[4] P. A. Gale, Coord. Chem. Rev. 2001, 213, 79–128.
[5] S. Goswami, K. Ghosh, S. Dasgupta, J. Org. Chem. 2000, 65,
1907–1914.
Synthesis of 4-((9-ethyl-9 H-carbazol-3-yl)methyleneamino)-1,5-
dimethyl- 2-phenyl-1 H-pyrazol-3(2 H)-one (APCZ)
By employing the similar procedure as for APFL, 9-ethyl-9 H-carba-
zole-3-carbaldehyde (3b) (0.33 g, 5 mmol) was used to afford APCZ
[6] R. W. Hoffmann, F. Hettche, K. Harms, Chem. Commun. 2002,
782–783.
wileyonlinelibrary.com/journal/poc
Copyright © 2012 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. (2012)

ANTIPYRINE SENSOR
[7] L. L. Zhou, H. Sun, H. P. Li, H. Wang, X. H. Zhang, S. K. Wu, S. T. Lee,
Org. Lett. 2004, 6, 1071–1074.
[8] T. Gunnlaugsson, A. P. Davis, J. E. O’Brien, M. Glynn, Org. Lett. 2002,
4, 2449–2452.
[27] W. H. Tang, T. Lin, L. Ke, Z. K. Chen, J. Polym. Sci. Part A: Polym. Chem.
2008, 46, 7725–7738.
[28] W. H. Tang, T. Kietzke, P. Vemulamada, Z. K. Chen, J. Polym. Sci. Part
A: Polym. Chem. 2007, 45, 5266–5276.
[9] D. H. Vance, A. W. Czarnik, J. Am. Chem. Soc. 1994, 116, 9397–9398.
[10] S. K. Kim, J. Yoon, Chem. Commun. 2002, 770–771.
[11] M. J. Kim, R. Konduri, H. Ye, F. M. MacDonnell, F. Puntoriero,
S. Serroni, S. Campagna, T. Holder, G. Kinsel, K. Rajeshwar, Inorg.
Chem. 2002, 41, 2471–2476.
[12] Z. Xu, Y. Xiao, X. Qian, J. Cui, D. Cui, Org. Lett. 2005, 7, 889–892.
[13] F. Y. Wu, Y. B. Jiang, Chem. Phys. Lett. 2002, 355, 438–444.
[14] J. B. Wang, X. F. Qian, J. N. Cui, J. Org. Chem. 2006, 71, 4308–4311.
[15] S. Nishizawa, Y. Kato, N. Teramae, J. Am. Chem. Soc. 1999, 121,
9463–9464.
[29] W. H. Tang, L. Ke, Z. K. Chen, J. Phys. Chem. B 2008, 112, 3590–3596.
[30] Y. Sun, Q. Hao, Z. Yu, W. Wei, L. Lu, X. Wang, Mol. Phys. 2009, 107,
223–235.
[31] Y. Sun, R. Zhang, D. Ding, S. Liu, B. Wang, Y. Wang, Y. Lin, Struct.
Chem. 2006, 17, 655–665.
[32] Y. Sun, Q. Hao, W. Tang, Y. Wang, X. Yang, L. Lu, X. Wang, Mater.
Chem. Phys. 2011, 129, 217–222.
[33] M. Ranger, D. Rondeau, M. Leclerc, Macromolecules 1997, 30,
7686–7691.
[34] K. R. J. Thomas, J. T. Lin, Y.-T. Tao, C.-W. Ko, Chem. Mater. 2002, 14,
[16] H. Yuasa, N. Miyagawa, T. Izumi, M. Nakatani, M. Izumi, H. Hashimoto,
Org. Lett. 2004, 6, 1489–1492.
[17] B. Schazmann, N. Alhashimy, D. Diamond, J. Am. Chem. Soc. 2006,
128, 8607–8614.
1354–1361.
[35] K. Noine, Y.-J. Pu, K.-I. Nakayama, J. Kido, Org. Electron. 2010, 11,
717–723.
[36] Y. S. Kwon, K. H. Lee, K. G. Young, J. H. Seo, Y. K. Kim, S. S. Yoont, J. Nanosci.
[18] N. Chandrasekharan, L. A. Kelly, J. Am. Chem. Soc. 2001, 123, 9898–9899.
[19] J. S. Wu, J. H. Zhou, P. F. Wang, X. H. Zhang, S. K. Wu, Org. Lett. 2005,
7, 2133–2136.
Nanotechnol. 2009, 9, 7056–7060.
[37] Z. Jiang, Z. Liu, C. Yang, C. Zhong, J. Qin, G. Yu, Y. Liu, Adv. Funct.
Mater. 2009, 19, 3987–3995.
[20] X. Zhang, L. Guo, F. Y. Wu, Y. B. Jiang, Org. Lett. 2003, 5, 2667–2670.
[21] J. S. Wu, W. M. Liu, X. Q. Zhuang, F. Wang, P. F. Wang, S. L. Tao, X. H.
Zhang, S. K. Wu, S. T. Lee, Org. Lett. 2007, 9, 33–36.
[22] G. Q. Yang, F. Morlet-Savary, Z. K. Peng, S. K. Wu, J. P. Fouassier,
Chem. Phys. Lett. 1996, 256, 536–542.
[23] Z. M. Li, S. K. Wu, J. Fluorescence 1997, 7, 237–242.
[24] W. H. Tang, S. P. Singh, K. H. Ong, Z. K. Chen, J. Mater. Chem. 2010,
20, 1497–1505.
[38] M.-Y. Lai, C.-H. Chen, W.-S. Huang, J. T. Lin, T.-H. Ke, L.-Y. Chen, M.-H.
Tsai, C.-C. Wu, Angew. Chem. Int. Ed. 2008, 47, 581–585.
[39] Z. Q. Gao, Z. H. Li, P. F. Xia, M. S. Wong, K. W. Cheah, C. H. Chen, Adv.
Funct. Mater. 2007, 17, 3194–3199.
[40] Z. H. Li, M. S. Wong, Y. Tao, J. Lu, Eur. J. Chem. 2005, 11, 3285–3293.
[41] D. E. Loy, B. E. Koene, M. E. Thompson, Adv. Func. Mater. 2002, 12,
245–249.
[42] K. R. J. Thomas, P. Tyagi, J. Org. Chem. 2010, 75, 8100–81111.
[43] N. V. Bashkatova, E. I. Korotkova, Y. A. Karbainov, A. Yagovkin, A. Bakibaev,
J. Pharm. Biomed. Anal. 2005, 37, 1143–1147.
[25] W. H. Tang, L. Ke, L. Tan, T. T. Lin, T. Kietzke, Z. K. Chen, Macromolecules
2007, 40, 6164–6171.
[26] W. H. Tang, V. Chellappan, M. H. Liu, Z. K. Chen, L. Ke, ACS Appl.
Mater. Interfaces 2009, 1, 1467–1473.
[44] T. Gabe, Y. Urano, K. Kikuchi, H. Kojima, T. Nagano, J. Am. Chem. Soc.
2004, 126, 3357–3367.
J. Phys. Org. Chem. (2012)
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