Synthesis of novel profluorescent nitroxides as dual luminescent-paramagnetic active probes

Article abstract of DOI:10.1039/c7nj01698k

We describe herein the synthesis of new profluorescent nitroxides based on 2,5-disubstituted-1,3,4-oxadiazoles as fluorescent moieties and the 2,2,6,6-tetramethylpiperidine-N-oxyl radical (TEMPO) as paramagnetic probes. The synthesis and optical and electronic properties of the oxadiazole-based precursors of the profluorescent nitroxides, as well as the nitroxides and their reduced forms are also described. Physical investigations (i.e. absorption and emission spectroscopy, cyclic voltammetry) indicate a different luminescence behaviour function to the oxadiazole substituent. A linear response to reducing agents, i.e. sodium ascorbate, monitored by fluorescence spectroscopy, suggests the possibility of using the synthesized compounds as potent active probes in detection of various analytes of interest.

Full text of DOI:10.1039/c7nj01698k

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Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
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Synthesis of novel profluorescent nitroxides as dual luminescent-
paramagnetic active probes
Received 00th January 20xx,
Accepted 00th January 20xx
Anca G. Coman,a Codruta C. Paraschivescu,a Anca Paun,a Andreea Diac,b Niculina D. Hadade,b
Laurent Jouffret,c Arnaud Gautier,c ,* Mihaela Matachea,* and Petre Ionitaa,d
*
DOI: 10.1039/x0xx00000x
We describe herein synthesis of new profluorescent nitroxides based on 2,5-disubstituted-1,3,4-oxadiazoles as fluorescent
moieties and 2,2,6,6-tetramethylpiperidine-N-oxyl radical (TEMPO) as paramagnetic probe. The synthesis, optical and
electronic properties of the oxadiazole-based precursors of the profluorescent nitroxides, as well as the nitroxides and
their reduced forms are also described. The physical investigations (i.e. absorption and emission spectroscopy, cyclic
voltammetry) indicate a different luminescent behaviour function to the oxadiazole substituent. A linear response to
reducing agents, i.e. sodium ascorbate, monitored by fluorescence spectroscopy, suggests the possibility to use the
synthesized compounds as potent active probes in detection of various analytes of interest.
www.rsc.org/
systems. Thus, numerous fluorophores6,8 (i.e. naphthalenyl,
coumarinyl, pyrenyl) were attached to nitroxide units in order
to obtain profluorescent probes that are able to conveniently
Introduction
2,5-Disubstituted-1,3,4-oxadiazoles have increasingly attracted
attention due to their good luminescent behaviour, thermal
properties and high electron mobility, features that made
them suitable materials for construction of Organic-Light
Emitting Diodes (OLEDs).1 The applicability of the oxadiazole
congeners was further extended to use of these derivatives as
liquid crystals,2 cations and anions sensors,3 coordination
polymers4 or highly energetic materials.5
switch between fluorescent and paramagnetic properties.
Among the nitroxides, 2,2,6,6-tetramethylpiperidine-N-oxyl
free radical (TEMPO) is one of the most encountered due to its
commercial availability, high stability and, consequently,
usefulness in a wide range of synthetic applications.9
The minimal structural requirement of
a
good
profluorescent nitroxide is to contain a fluorescent moiety that
is linked through an adequate spacer to a stable free radical,
so as to allow the electron-exchange interactions on which the
fluorescence quenching mechanism is based.6b In this context,
taking into consideration the promising luminescent properties
of the oxadiazole-based compounds and the fact that, to the
best of our knowledge, no report has considered so far
combination of the oxadiazole-based compounds with stable
free radicals, we report herein the synthesis and photophysical
investigation of 2,5-disubstituted-1,3,4-oxadiazole-TEMPO
hybrids 1a-d (Figure 1) as profluorescent nitroxide probes.
Profluorescent nitroxides combine the properties of
fluorogenic molecules with those of stable free radicals. The
luminescence is quenched by the unpaired electron and can be
restored by the nitroxide reduction to the hydroxylamine,
allowing thus two techniques (fluorescence spectroscopy and
electron paramagnetic resonance) to inspect their switching
behaviour. Therefore, these compounds found numerous
utilities in detection of various biological analytes through
redox changes or radical trapping.6
Since first reports7 of such molecules, both the fluorogenic
and the radical moieties have been investigated in an effort to
find the optimum structural particularities that are able to
provide better responses to various chemical and biochemical
O
O
N
O
N
O
N
N
•
•
O
O
N
NH
N
NH
1a
1c
1b
1d
O
N
O
O
N
O
N
N
•
•
O
N
NH
O
N
NH
Figure
1 Structures of the 2,5-disubstituted-1,3,4-oxadiazole-TEMPO hybrids 1a-d
synthesized and investigated in this work
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corresponding aldehyde 3a-d (4-formyl benzoic acid, 1-
naphthylcarbaldehyde, 9-anthracenyl carbaldehyde and 1-
pyrenylcarbaldehyde) provided the N-acylhydrazones 4a-d
(Scheme 1).
Results and discussion
Synthesis of compounds 1a-d
The strategy for the preparation of the profluorescent
nitroxides followed a three step synthesis (Scheme 1). In the
design of our compounds, we selected the amide group as the
linker between the oxadiazole moiety and the free radical
core, based on the commercial availability of 4-amino-TEMPO
free radical and the stability of the amide bond under reducing
conditions. Therefore, 2-(4-carboxyphenyl)-5 aryl-1,3,4-
oxadiazoles 5a-d were used as intermediates. Moieties that
are recognized for their ability to enhance the optical
properties of the oxadiazole unit, such as naphthalenyl,10
anthracenyl11 and pyrenyl12 were chosen as substituents.
Among the methods currently available13 for synthesis of
the 2,5-disbstituted-1,3,4-oxadiazoles, the approach starting
from N-acylhydrazones provides a considerable advantage due
to the availability of the aldehyde and hydrazide precursors, as
well as the mild conditions of the oxidative cyclisation step.
Thus, the reaction between 4-toluic benzhydrazide 2a and 4-
(hydrazinecarbonyl)benzoic acid 2b, respectively, with the
The iodine-based oxidative reagents14 have recently
increased their usefulness for ring closure of the oxadiazoles
from N-acylhydrazones, providing the possibility to
conveniently prepare non-symmetrical 2,5-disubstituted
compounds with a wide variety of functional groups. A recent
14g
method, involving I2 in DMSO/K2CO3 at 100°C attracted our
attention and provided the convenient transformation of the
N-acylhydrazones 4a-d into the carboxy-oxadiazoles 5a-d. This
affords cheap and efficient preparation of gram-scale amounts
of 2,5-disubstituted-1,3,4-oxadiazoles, which are isolated from
the reaction medium by simple acidification and filtration in
pure form. Derivatives 5a-d were further treated with 4-
amino-TEMPO, PyBOP (benzotriazol-1-yl-oxytripyrrolidino
phosphonium hexafluorophosphate) as activating reagent of
the carboxyl group and DIPEA (N,N-diisopropylethylamine) as
base, to furnish the target probes 1a-d in isolated yields
ranging between 47% and 81%.
Scheme 1 Synthesis of the targeted 2,5-disubstituted-1,3,4-oxadiazole-TEMPO hybrids 1: a) CHCl3/DMF, TFA, reflux 4h, 12h at rt; b) I2, K2CO3, DMSO, 100oC, 12 h, conc. HCl till pH
5.5; c) 4-amino-TEMPO, PyBOP, DIPEA, CH2Cl2, 12h.
5a
5a
Absorption and emission properties of compounds 5a-d
350
300
250
200
150
100
50
I/a.u.
5b
5b
The carboxy-derivatives 5a-d were investigated for their
absorption and emission properties in solution and solid state.
The results obtained are summarized in Table 1. Figure 2
shows the excitation and emission spectra recorded in 15%
DMSO in HEPES 0.01 M pH=7.51, at a concentration of 5 x 10-7
M, as well as the emission spectra of compounds 5a-d
recorded in solid state.
5c
5c
5d
5d
Quinine
Quinine
0
λ
(nm)
220
270
320
370
420
470
520
570
620
670
Table 1 Absorption and emission data of compounds 5a-d in solution and solid state
Solution(a)
Solid state
λem
I/a.u.
120
100
80
60
40
20
0
5a
5b
5c
5d
Cmpn.
λex (nm,
ε(a) x 104)
294 (3.2)
323 (1.7)
370 (0.77)
360 (1.35)
λem
(nm)
376
410
496
440
Stokes
λex
(nm)
295
318
370
360
Stokes
(nm)
98
φ(b)
(nm)
82
(nm)
393
5a
5b
5c
5d
0.04
0.33
0.11
0.48
87
428
110
126
80
505
135
556
196
(a)The molar extinction coefficients were calculated from the UV-Vis spectra at
the indicated excitation wavelength. Measurements were performed on different
dilutions using 15% DMSO in HEPES 0.01 M pH=7.51 from stock solutions of
compounds dissolved in DMSO 10-3 M and the extinction coefficients were
λ
(nm)
300
350
400
450
500
550
600
650
700
Figure 2 Top: Excitation (dotted lines) and emission (plain lines) spectra of compounds
5a-d and quinine recorded at 5x10-7 M in 15% DMSO in HEPES 0.01 M pH=7.51, Bottom:
Emission spectra of compounds 5a-d recorded in solid state using λex=295 nm for 5a,
λex=318 nm for 5b, λex=370 nm for 5c, λex=360 nm for 5d.
(b)
calculated as an average of the individual values resulted for each sample.
Calculated according to ref. 15 using quinine sulphate as standard.
2 | J. Name., 2012, 00, 1-3
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0.004
0.020
0.015
0.010
0.005
0.000
-0.005
-0.010
-0.015
The absorption spectra recorded in solution display bands
corresponding both to the oxadiazole unit and its substituents.
However, while the spectra of compounds 5a (λmax=294 nm)
and 5b (λmax=323 nm) show maxima that can be assigned to
the π–π* transitions of the oxadiazole,16 the spectra profiles of
1a
1b
0.003
0.002
0.001
0.000
-0.001
-0.002
-0.003
compounds 5c (λmax=370 nm)
and 5d (λmax=360) are
dominated by the transitions corresponding to the
anthracene11c and pyrene12 cores. One can note the higher
absorption intensities of compounds 5b-d compared to 5a. The
emission maxima in solution cover blue to near-green region
(from λem=376 nm for 5a to λem=496 for 5c), all compounds
exhibiting large Stokes shifts of over 80 nm (Table 1) as well as
good quantum yields for the pyrenyl (φ=0.48) and
naphthalenyl (φ=0.33) derived compounds.
0.0
0.2
0.4
E /
0.6
vs SCE
0.8
1.0
0.0
1c
0.1
0.2
0.3
0.4
0.5
0.6
0.7
V
E /
V vs SCE
0.010
0.008
0.006
0.004
0.002
0.000
-0.002
-0.004
-0.006
-0.008
0.015
0.010
0.005
0.000
-0.005
-0.010
1d
The solid state fluorescent spectra indicate a significant red
shift of the emission maxima for all compounds, while
excitation is mostly unchanged, thus leading to very large
Stokes shifts. The anthracenyl and pyrenyl derivatives emit in
the green region, at λem=505 nm and λem=556 nm, with Stokes
shifts of 135 nm and 196 nm, respectively. In addition, the
emission intensity of compound 5a is the highest in solid state,
the low intensities for the other three compounds most
probably being due to aggregation-induced quenching
effects.17
0.0
0.2
0.4
0.6
0.8
0.0
0.2
0.4
V vs SCE
0.6
0.8
E /
V
vs SCE
E /
Figure 4 Cyclic voltammograms of compounds 1a-d.
Comparison of the cyclic voltammetry data for compounds
1a-d shows that the presence of a naphthyl group adjacent to
the oxadiazole core produces a positive shift of the anodic
peak potential (Epa), indicating a decrease of the HOMO level
in case of derivative 1b. In the negative potential region (not
shown), the CV of all compounds displays an irreversible
reduction process with cathodic peak potential (Epc) in the -
0.55 V to -0.92 V region, indicative of unstable anion radical
(see ESI).
Properties of compounds 1a-d
EPR spectroscopy
The energy levels of the frontier orbitals have been
estimated from the oxidation potentials and the optical data
(Table 2).18
The EPR spectra of all newly synthesized TEMPO-derivatives
were recorded in degassed dichloromethane, at room
temperature, at 10-4 M concentrations and showed the
expected triplet (Figure 3), due to the interaction of the free
electron with the 14N nucleus of the TEMPO moiety. Notably,
the intensities of the EPR lines are not equal, decreasing from
low to high field, probably due to the anisotropic motion of the
nitroxide in solution. This can be regarded as a supplementary
proof of the attachment of the nitroxide moiety to the
oxadiazole molecules. The hyperfine coupling constants are
aN=1.65 mT, identical for all samples.
Table
2 UV-Vis and cyclic voltammetry data of compounds 1a-d (in 0.1 M
Bu4NPF6/CH2Cl2, scan rate 100 mV s-1, Pt electrodes, ref. SCE).
EHOMO
ELUMO
Cmpn.
λmax (nm)
ΔE (eV)
Epa (V)
(eV) [a]
(eV) [b]
1a
1b
1c
1d
295
319
372
370
4.20
3.88
3.33
3.35
0.50
0.88
0.58
0.65
-5.38
-5.70
-5.44
-5.49
-1.18
-1.82
-2.11
-2.14
2000
1500
1000
500
2000
1500
1000
500
2000
1500
1000
500
2000
1500
1000
500
2000
1500
1000
500
1a
1b
1c
1d
4-amino-TEMPO
[a]
using E0 with an offset of -4.99 eV for SCE vs the vacuum level.18
ox
[b]determined by EHOMO-ΔE.
0
0
0
0
0
-500
-1000
-1500
-2000
-500
-1000
-1500
-2000
-500
-1000
-1500
-2000
-500
-1000
-1500
-2000
-500
-1000
-1500
-2000
Absorption and emission properties of compounds 1a-d and
10 mT
investigation of the fluorescent-paramagnetic switching behaviour
Figure 3 EPR spectra of compounds 1a-d and 4-amino-TEMPO for comparison reasons
The absorption properties of the nitroxides 1a-d were
investigated (in 15% DMSO in HEPES 0.01 M pH=7.51) and the
results are summarized in Table 3. No significant changes in
the absorption maxima could be observed compared to their
carboxy-precursors 5a-d (Figure 2 and Table 1).
Cyclic voltammetry
The electrochemical properties of the compounds were
analyzed by cyclic voltammetry (CV) in methylene chloride, in
presence of 0.1 M tetrabutylammonium hexafluorophosphate
as supporting electrolyte. Figure 4 shows the CV recorded at a
scan rate of 100 mVs-1, using a Pt electrode. The cyclic
voltammetry of compounds 1a-d shows a reversible oxidation
process corresponding to the formation of stable
oxoammonium cations with anodic peak potential (Epa) varying
from 0.50 V to 0.88 V (Table 2).
The attachment of the free radical moiety led to
fluorescence quenching,6b as inferred from the emission
spectra of the nitroxides both in solution and solid state
(Figure 5 and ESI). The emission maxima are red shifted
compared to the carboxy precursors with about 20 nm for
compounds 1b and 1d, 12 nm for compound 1a, while the
anthracenyl derivative 1c does not change its emission
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wavelength. The quantum yields measured for solutions of the the nitroxide in 30 minutes (see ESI). Consequently, sodium
nitroxides in 15% DMSO in HEPES 0.01 M pH=7.51, drastically ascorbate was selected as preferred reducing agent.
decreased in all cases (Table 3).
Further, fluorescence measurements of the nitroxides in
presence of sodium ascorbate indicated variable
a
Table
3 Absorption and emission data of nitroxides 1a-d and their correponding
enhancement of the luminescence intensity (Figure 6 and ESI):
approximately 5 times increase for 1a, 4 times for 1b, almost
twice for 1c, while 1d did not significantly show an increase in
the fluorescence. The quantum yields of the corresponding
hydroxylamines, calculated in reference to quinine sulphate in
0.5 M sulfuric acid, are shown in Table 3. We observed an
enhancement of the quantum yield for the reduced form of 1a
hydroxylamines in solution
λex (nm,
ε(a) x 104)
λem
Stokes
(nm)
(b)
(c)
φ0
φ1
φ1/ φ0
(nm)
1a
1b
1c
1d
296 (2.8)
319 (1.65)
372 (0.87)
370 (2.05)
388
436
496
461
92
117
124
91
0.006
0.017
0.042
0.002
0.039
0.067
0.077
0.0036
6.44
3.84
1.85
1.56
more than 6 times higher and almost 4 times higher for 1b
.
(a)The molar extinction coefficients were calculated from the UV-Vis spectra at
the indicated excitation wavelength. Measurements were performed on different
dilutions using 15% DMSO in HEPES 0.01 M pH=7.51 from stock solutions of
compounds dissolved in DMSO 10-3 M and the extinction coefficients were
1000
t=45 min
t=30 min
I/a.u.
800
600
400
200
0
t = 45 min
t = 30 min
t = 0 min
t=15 min
t=0 min
(b)
calculated as an average of the individual values resulted for each sample.
(c)
Calculated according to ref. 15 using quinine sulphate as standard. Calculated
according to ref. 15 using quinine sulphate as standard, after incubation with
sodium ascorbate in a 1:1 molar ratio for the time indicated by EPR experiments
for complete reduction of the nitroxides.
λ
(nm)
10 mT
320
370
420
470
520
570
Figure 6 Left: EPR spectra of compound 1a after treatment with sodium ascorbate, at
different reaction times. Right: Emission spectra of compound 1a after treatment with
sodium ascorbate, at different reaction times. Experiments were conducted in 15%
DMSO in HEPES 0.01 M pH=7.51, at a concentration of 5 x 10-5 M.
However, while in the case of compounds 1c and 1d
,
containing the anthracenyl and the pyrenyl moieties, the
fluorescence is completely quenched, we could observe a
residual fluorescence for compounds 1a and 1b (Figure 5 and
ESI). This behaviour may be justified considering the
fluorescence quenching mechanism of the profluorescent
nitroxides6b and the cyclic voltammetry data, which indicate
lower band gaps for compounds 1c and 1d (ΔE=3.33 eV and
ΔE=3.35 eV, respectively) as compared to 1a and 1b (ΔE=4.20
eV and ΔE=3.88 eV, respectively).
Intrigued by the results obtained for compound 1d (Table
3), we studied the effect of the solvent over the absorption
and emission properties. Thus, we performed emission spectra
of the nitroxide 1d (5 x 10-5 M) and the corresponding reduced
form (after incubation for 30 minutes with 10 equivalents of
phenylhydrazine) in DMSO, MeOH, MeCN and CHCl3 (Figure
7). The absorption spectra profiles did not change significantly
from polar to non-polar pure solvents (Table 4). The quantum
yields are considerably low in all solvents (Table 4 and Figure
7), but the fluorescence is not completely quenched as for
DMSO/water (15% DMSO). The fluorescence could be
enhanced in all cases upon reduction, except for DMSO/water.
A possible explanation for this behaviour is the water-induced
hydrophobic interactions in aqueous media that can result in
the intermolecular fluorescence quenching.
350
300
250
200
150
100
50
I/a.u.
I/a.u.
5a
5b
5c
5d
1a
1b
1c
1d
5a
5b
5c
5d
1a
1b
1c
1d
120
100
80
60
40
20
0
λ
(nm)
700
λ
(nm)
0
300
400
500
600
300
400
500
600
700
Figure 5 Left: Solution emission spectra of the nitroxides 1a-d (plain lines) compared to
their precursor carboxy-derivatives 5a-d (dotted lines) recorded in 15% DMSO in HEPES
0.01 M pH=7.51, at a concentration of 5x10-7 M, using λex=296 nm for 1a, λex=319 nm
for 1b, λex=372 nm for 1c, λex=370 nm for 1d.; Right: Solid state emission spectra of the
nitroxides 1a-d (plain lines) compared to their precursor carboxy-derivatives 5a-d
(dotted lines) recorded using λex=295 nm for 1a, λex=318 nm for 1b, λex=370 nm for 1c,
λex=360 nm for 1d.
7000
6000
5000
4000
3000
2000
1000
0
I/a.u.
Cloroform
Acetonitrile
Methanol
DMSO
Cloroform
Acetonitrile
Methanol
DMSO
DMSO/water
DMSO/water
In order to check the reduction of the nitroxide to the
hydroxylamine, EPR experiments were performed in presence
of sodium ascorbate19 or phenylhydrazine,20 using different
ratios between the nitroxides and the reducing agents. The
experiments were conducted in degassed 15% DMSO in HEPES
0.01 M pH=7.51, at a concentration of 5 x 10-5 M, indicating
(Figure 6 and ESI) that the reaction with sodium ascorbate
leads to complete disappearance of the radical in 45 minutes
for 1a and 1d and 120 minutes for 1b and 1c in a 1:1 molar
ratio. When phenylhydrazine was used instead, a higher
amount (10 equivalents) was required to completely reduce
λ
(nm)
370
420
470
520
570
Figure 7 Emission spectra of 1d in various solvents (5 x 10-5 M): dotted lines: spectra of
the nitroxide; plain lines: spectra of the nitroxides after reduction
In order to support this assumption, NMR recordings in CDCl3
and DMSO-d6, in presence of an excess of phenylhydrazine,
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were performed. Increasing the polarity of the deuterated Solid state structure of compound 1d
solvent we noticed changes of the chemical shifts of all
Slow diffusion of compound 1d in CH2Cl2/ petroleum ether
afforded colourless, suitable single crystal for X-Ray
Diffraction.
protons on the pyrene core (see ESI). Indeed, interactions
between the pyrene unit from one molecule with phenyl and
oxadiazole rings from another molecule could be observed in
the solid state (vide infra).
The analysis (Figure 8) revealed that the aromatic rings and
the amide group are almost coplanar with dihedral angles
between the planes of the pyrene and oxadiazole, phenyl and
oxadiazole and phenyl and amide of: 3.22°, 8.07° and 14.46°,
respectively. The elementary cell contains two molecules that
are oriented head-to-tail (see ESI).
Table
4 Absorption and emission data of nitroxide 1d and the corresponding
hydroxylamine in various polar and non-polar solvents
λex (nm, ε(a)
104)
x
λem
(b)
(c)
Solvent
φ0
φ1
φ1/ φ0
(nm)
DMSO
MeOH
MeCN
CHCl3
370 (2.66)
367 (2.75)
366 (2.48)
370 (2.39)
428
429
427
426
0.092
0.06
0.248
0.19
2.67
3.12
2.74
2.33
0.078
0.056
0.213
0.13
(a)
The molar extinction coefficients were calculated from the UV-Vis spectra at
the indicated excitation wavelength. Measurements were performed on different
dilutions from stock solutions of compounds dissolved in DMSO/MeOH/MeCN 2 x
10-4 M and in CHCl3 10-3 M and the extinction coefficients were calculated as an
average of the individual values resulted for each sample. (b) Calculated according
Figure 8 Structure of compound 1d revealed by single crystal X-Ray Diffraction
(c)
to ref. 15 using quinine sulphate as standard. Calculated according to ref. 15
using quinine sulphate as standard after incubation with phenylhydrazine in a
1:10 molar ratio for the time indicated by EPR experiments for complete
reduction of the nitroxide.
Figure 9 Crystal packing of compound 1d revealed by single crystal X-Ray Diffraction - view along z axis
The crystal packing, viewed along z axis (Figure 9), consists
of supramolecular layers in which the molecules have a head
to tail arrangement and are held together by interactions
between the pyrenyl core of one molecule with the phenyl and
oxadiazole rings of a neighbour molecule in almost parallel
planes at a distance between the planes of about 3.536 Å.
Each molecule in a layer interacts with a molecule in an
adjacent layer through short contacts N-O...H-C (d=2.701 Å
between the oxygen in the nitroxide group and hydrogen of a
methyl group of another molecule), thus establishing two
short contacts between two head to head oriented molecules
in each layer (Figure 9).
In addition, molecules within the same layer, viewed along
x axis (Figure 10), are held together by C-H(Me)---O(amide)
interactions (d=2.511 Å) and C-H(pyrene)---O(nitroxide)
interactions (d=2.406 Å).
Figure 10 Crystal packing of compound 1d revealed by single crystal X-Ray Diffraction -
view along x axis
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ARTICLE
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eq.) were dissolved in a mixture of CHCl3/DMF (10:1 volumetric ratio to a
0,01 M concentration) and a few drops of trifluoroacetic acid were added. The
Linear response to sodium ascorbate
Since compound 1a had the most significant increase of
reaction mixture was refluxed for
4 hours and then stirred at room
fluorescence upon reduction and due to its convenient and temperature overnight (12 h). The solvent was evaporated to half volume and
the resulted solid was filtered, washed with diethylether and dried.
inexpensive synthetic procedure compared to the other potent
candidates, we checked the response to various amounts of 4-((2-(4-methylbenzoyl)hydrazono)methyl)benzoic acid 4a. White solid.
Yield 97 % (1.87 g). m.p. 309-311°C. Rf =0.18 (silica, EtOAc). 1H NMR (500
sodium ascorbate, as a target for quantitative determinations
MHz, DMSO-d6): δ= 11.93 (s, 1H, NH), 8.50 (s, 1H, CHN), 8.00 (d, 2H, 3J=7.8 Hz,
in biological systems.
H
Ar), 7.83 (overlapped peaks, 4H, HAr), 7.34 (d, 2H, 3J=7.8 Hz, HAr), 2.38 (s, 3H,
CH3) ppm. 13C NMR (125 MHz, DMSO-d6): δ= 166.8; 163.0; 146.2; 141.9;
138.4; 131.5; 130.3; 129.7; 129.0; 127.6; 126.9; 20.9. HRMS (APCI, +,
Orbitrap) m/z: calc. for C16H15N2O3 [M+H]+283.1077; found 283.1075.
800
700
600
500
400
300
200
100
0
I/a.u.
4-(2-(naphthalen-1-ylmethylene)hydrazinecarbonyl)benzoic acid 4b.
White solid. Yield 70% (242 mg) m.p. 298-300°C. Rf=0.36 (silica, EtOAc). 1H
NMR (500 MHz, DMSO-d6): δ= 12.08 (s, 1H, NH), 9.12 (s, 1H, CHN), 8.87 (d, 1H,
3J=8.5 Hz, ), 8.11-8.02 (overlapped peaks, 6H, HAr), 7.95 (d, 1H, 3J=7.1 Hz, HAr),
I/a.u.
500
400
300
200
100
0
R² = 0.994
7.69 (m, 1H,HAr), 7.64-7.61 (overlapped peaks, 2H, HAr)
ppm. 13C NMR (125
MHz, DMSO-d6): δ=166.9; 162.5; 148.4; 137.2; 133.7; 130.9; 130.3; 129.6;
129.5; 128.9; 128.1; 128.0; 127.5; 126.4; 125.7; 124.3. HRMS (APCI, +,
Orbitrap) m/z: calc. for C19H15N2O3 [M+H]+319.1077; found 319.1072.
No. of eq.
0.4 0.5
4-(2-(anthracen-9-ylmethylene)hydrazinecarbonyl)benzoic acid 4c.
Yellow solid. Yield 67 % (275 mg). m.p. 309-310°C. Rf=0.5 (silica, EtOAc). 1H
NMR (500 MHz, DMSO-d6): δ= 13.31 (s, 1H, COOH), 12.24 (s, 1H, NH), 9.69 (s,
1H, CHN), 8.77-8.75 (overlapped peaks, 3H, HAr), 8.17 (d, 2H, 3J=8.4 Hz, HAr),
8.14 (s, 4H, HAr), 7.66 (overlapped peaks, 2H,HAr), 7.60 (overlapped peaks,
2H,HAr) ppm. 13C NMR (125 MHz, DMSO-d6): δ=166.7; 162.3; 147.6; 137.0;
133.5; 130.8; 129.7; 129.6; 129.4; 129.0; 127.9; 127.2; 125.5; 124.9; 124.8.
HRMS (APCI, +, Orbitrap) m/z: calc. for C23H17N2O3 [M+H]+369.1234; found
369.1231.
0
0.1
0.2
0.3
No. of eq.
0
0.5
1
1.5
2
2.5
Figure 11 Response of 1a to increasing amounts of sodium ascorbate (number of
equivalents on x axis) followed by fluorescence emission (y axis) after 30 minutes
incubation time
Treatment of 1a solutions (5 x 10-5 M in 15% DMSO in
HEPES 0.01 M pH=7.51) with increasing amounts of sodium
ascorbate (between 0 and 2 equivalents) and measurement of
the fluorescence emission at λem=388 nm (λex=295 nm) after 30
and 45 minutes incubation time showed a linear response
(R2=0.995 and 0.992, respectively) up to the stoichiometric
amount of the reducing agent (0.5 equivalents). The
experiments (Figure 11) indicated that 1a may be useful as a
sensitive redox probe for measurement of ascorbate.
4-(2-((3,8-dihydropyren-1-yl)methylene)hydrazinecarbonyl)
benzoic
acid 4d. Yellow solid. Yield 78 %. (169 mg) m.p. 310-312°C. Rf=0.42 (silica,
EtOAc). 1H NMR (500 MHz, DMSO-d6): δ= 13.30 (s, 1H, COOH), 12.20 (s, 1H,
NH), 9.54 (s, 1H, CHN), 8.83 (d, 1H, 3J=9.4 Hz, HAr), 8.59 (d, 1H, 3J=8.2 Hz,
HAr), 8.40-8.37 (overlapped peaks, 5H, HAr), 8.28 (d, 1H, 3J=8.9 Hz, HAr), 8.24
(d, 1H, 3J=8.9 Hz, HAr), 8.15-8.10 (overlapped peaks, 6H, HAr) ppm. 13C NMR
(125 MHz, DMSO- d6): δ=166.3; 161.9; 146.8; 136.8; 133.2; 131.7; 130.5;
129.7; 129.1; 128.5; 128.3; 128.1; 127.5; 127.0; 126.4; 126.3; 125.8;
125.5;124.9; 124.7;123.8; 123.4; 121.9 ppm. HRMS (APCI, +, Orbitrap) m/z:
calc. for C25H17N2O3 [M+H]+393.1234; found 393.1226.
General experimental procedure for the synthesis of 1,3,4-oxadiazoles
5a-d. The corresponding N-acylhydrazone (1 eq.) was dissolved in DMSO (4-
10 mL) and K2CO3 (1,5 eq.), followed by I2 (1.2 eq.) were added. The mixture
was allowed to stir overnight at 100°C and the resulted solid salt was filtered
and then dissolved in the minimum amount of water. The pH was adjusted to
5.5 using concentrated HCl and the precipitated product was filtered, washed
with water and dried. No other purifications were necessary.
Experimental
General experimental information. All solvents and reagents were
purchased from commercial suppliers and used without further purification.
Thin layer chromatography (TLC) was performed on silica gel 60 coated
aluminium F254 plates with visualisation by UV irradiation at 254 nm.
Preparative column chromatography was carried out using Merck silica gel
60, 0.040-0.063 mm. The NMR spectra were recorded on Bruker Advance
Ultrashield Plus spectrometer operating at 500 MHz for 1H and 125 MHz for
13C. Chemical shifts (δ) are reported in parts per million (ppm) using residual
solvent peak as internal reference. High resolution mass spectra were
recorded on a Thermo Scientific (LTQ XL Orbitrap) spectrometer, in positive
ion mode, using APCI technique. Melting points were determined in open
capillary tubes using a STUART SMP3 electric melting point apparatus and
are uncorrected. Electron paramagnetic resonance (EPR) spectra were
recorded on a Jeol Jes FA 100 apparatus. The UV-Vis spectra were recorded
on a UV-3100 spectrophotometer and a JASCO Jasco V-630 spectrophotometer
using 10 mm quartz cell. The solution fluorescence spectra were performed
on a Cary Eclipse fluorimeter or a Thermo Scientific Varioskan Flash spectral
scanning multimode reader. The solid state fluorescence spectra were
recorded using a JASCO FP 8300 spectrofluorometer. Cyclic voltammograms
were obtained using a Biologic SP-150 potentiostat. The single crystal X-Ray
Diffraction was performed on a ApexII, Brucker.
4-(5-p-tolyl-1,3,4-oxadiazol-2-yl)benzoic acid 5a. White solid. Yield 72%
(158 mg). m.p.>312°C. Rf=0.3 (silica, EtOAc). 1H NMR (500 MHz, DMSO-d6): δ=
3
3
3
8.24 (d, 2H, J=8.2 Hz, HAr), 8.15 (d, 2H, J=8.2 Hz, HAr), 8.03 (d, 2H, J=8.0 Hz,
HAr), 7.45 (d, 2H, 3J=8.0 Hz, HAr), 2.41 (s, 3H, CH3) ppm. 13C NMR (125 MHz,
DMSO-d6): δ= 166.6; 164.6; 163.3; 142.6; 133.6; 130.3; 130.1; 127.1; 126.9;
126.8; 120.5; 21.3. HRMS (APCI, +, Orbitrap) m/z: calc. for C16H13N2O3
[M+H]+281.0921; found 281.0923.
4-(5-(naphthalen-1-yl)-1,3,4-oxadiazol-2-yl)benzoic acid 5b. Yellow
solid. Yield 94 % (915 mg). m.p. 269-271°C. Rf=0.5 (silica, EtOAc). 1H NMR
(500 MHz, DMSO-d6): δ= 13.4 (br, 1H, COOH), 9.19 (d, 1H, 3J=8.6 Hz, HAr), 8.43
(d, 1H, 3J=7.3 Hz, HAr), 8.31 (d, 2H, 3J=8.2 Hz, HAr), 8.26 (d, 1H, 3J=8.2 Hz, HAr),
8.18 (d, 2H, 3J=8.2 Hz, HAr), 8.12 (d, 1H, 3J=8.2 Hz, HAr), 7.80-7-71 (overlapped
peaks, 2H, HAr), 7.71-7.68 (m, 1H, HAr) ppm. 13C NMR (125 MHz, DMSO-d6): δ=
166.3; 164.2; 162.8; 133.4; 133.2; 132.7; 130.0; 129.0; 128.8; 128.7; 128.1;
126.8; 126.7; 126.6; 125.2; 125.2; 119.3 ppm. HRMS (APCI, +, Orbitrap) m/z:
calc. for C19H13N2O3 [M+H]+317.0921; found 317.0917.
4-(5-(anthracen-9-yl)-1,3,4-oxadiazol-2-yl)benzoic acid 5c. Yellow solid.
Yield 68 % (67 mg). m.p. 302-304°C. Rf=0.6 (silica, EtOAc). 1H NMR (500 MHz,
General experimental procedure for the synthesis of N-acylhydrazones
4a-d. A mixture of the aldehyde (1 eq.) and the corresponding hydrazide (1
6 | J. Name., 2012, 00, 1-3
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ARTICLE
DMSO-d6): δ= 9.01 (s, 1H, HAr), 8.28-8.26 (overlapped peaks, 2H, HAr), 8.05-
8.01 (overlapped peaks, 6H, HAr), 7.67-7.63 (overlapped peaks, 4H, HAr) ppm.
13C NMR (125 MHz, DMSO-d6): δ=166.8; 165.3; 161.6; 144.7; 131.2; 130.3;
130.1; 129.4; 128.4; 127.8; 125.6; 124.4; 124.3; 122.5; 116.4. HRMS (APCI, +,
Orbitrap) m/z: calc. for C23H15N2O3 [M+H]+367.1077; found 367.1078.
Conclusions
In conclusion, new 1,3,4-oxadiazole-based compounds bearing
p-tolyl, naphthyl, anthracenyl and pyrenyl moieties were
efficiently synthesized by oxidative cyclisation of N-
acylhydrazones. These compounds were characterised for
their electronic and optical properties and the pyrenyl and
naphthyl substituted derivatives were found to display high
quantum yields (0.33 and 0.48, respectively) and large Stokes
4-(5-(3,8-dihydropyren-1-yl)-1,3,4-oxadiazol-2-yl)benzoic
acid
5d.
Orange solid. Yield 70 % (69 mg). m.p.>312°C. Rf=0.36 (silica, EtOAc). 1H NMR
(500 MHz, DMSO-d6): δ= 13.38 (s, 1H, COOH), 9.49 (d, 1H, 3J=9.3 Hz HAr), 8.83
(d, 1H, 3J=8.1 Hz, HAr ), 8.50-8.48 (overlapped peaks, 2H, HAr), 8.46-8.43
(overlapped peaks, 2H, HAr), 8.38-8.29 (overlapped peaks, 4H, HAr), 8.20-8.17
(overlapped peaks, 3H, HAr) ppm. 13C NMR (125 MHz, DMSO-d6): δ=166.5; shifts (124 nm and 91 nm, respectively). In addition,
164.9; 163.1; 133.5; 133.2; 130.6; 130.2; 129.9; 129.8; 129.6; 128.5; 127.1;
127.0; 126.93; 126.92; 126.90; 126.8; 126.5; 125.1; 124.4; 123.9; 123.3;
116.0. HRMS (APCI, +, Orbitrap) m/z: calc. for C25H15N2O3 [M+H]+391.1077;
found 391.1081.
profluorescent probes obtained in conjunction with stable free
radical TEMPO were further prepared and characterised by
EPR, cyclic voltammetry and XRD (for the pyrenyl-derived
nitroxide). The fluorescence of these probes could be turned
on by reaction with a reducing agent. In addition, we assessed
the usefulness of the synthesized compounds for detection of
sodium ascorbate in the low micromolar range. Our results
indicate that fine tuning of the structure could bring an
improvement of the profluorescent nitroxides behaviour in
order to enhance their properties and extend scope.
General experimental procedure for the synthesis of profluorescent
nitroxides 1a-d. The corresponding 1,3,4-oxadiazole (1 eq.) was dissolved in
dichloromethane (2-5 mL). To this solution were sequentially added PyBop
(1.1 eq.), DIPEA (3 eq.) and 4-amino-TEMPO (0.9 eq.). The reaction mixture
was allowed to stir at room temperature for 12 hours and then the solvent
was evaporated in vacuo. The residue was diluted with water and extracted
with ethyl acetate (3 x 20 mL). The organic layer was washed with saturated
solution of sodium bicarbonate (3 x 5 mL), brine and dried over anhydrous
magnesium sulphate. Purification of each product was performed by column
chromatography. The NMR spectra were performed on the reduced
compounds with phenylhydrazine. The mass spectra were performed on
reduced solutions of the samples using trifluoroacetic acid.
Acknowledgements
This work was supported by a grant of the Romanian National
Authority for Scientific Research and Innovation, CNCS-
UEFISCDI, project number PN-II-RU-TE-2014-4-0808. We thank
Dr. Gabriela Ionita and Dr. Iulia Matei for EPR measurements.
A.D. acknowledges Babes-Bolyai University for financial
N-(1-oxy-2,2,6,6-tetramethylpiperidin-4-yl)-4-(5-(p-tolyl)-1,3,4-
oxadiazol-2-yl)benzamide 1a. White solid. Yield 85% (67 mg). m.p. 174-
177°C. Rf=0.4 (silica, EtOAc). 1H NMR reduced with PhNHNH2 (500 MHz,
3
CDCl3): δ= 8.20 (d, 2H, J=8.4 Hz, HAr), 8.03 (d, 2H, 3J=8.3 Hz, HAr), 7.94 (d, 2H,
3J=8.4 Hz, HAr), 7.34 (d, 2H, 3J=8.3 Hz, HAr), 4.57-4.54 (m, 1H, CHTEMPO), 2.45 (s,
3H, CH3), 2.10-2.05 (overlapped peaks, 4H, CH2-TEMPO), 1.50 (s, 6H, CH3-TEMPO ), support through GTC 31787/23.03.2016.
1.42 (s, 6H, CH3-TEMPO ) ppm. HRMS reduced with TFA (APCI, +, Orbitrap) m/z:
calc. for C25H31N4O3 [M+H]+435.2391; found 435.2386.
Notes and references
N-(1-oxy-2,2,6,6-tetramethylpiperidin-4-yl)-4-(5-(naphthalen-1-yl)-
1,3,4-oxadiazol-2-yl)benzamide 1b. Yellow solid. Yield 60% (29 mg). m.p.
†
Electronic Supplementary Information (ESI) contains
211-214°C (dec.). Rf=0.63 (silica, EtOAc: petroleum ether= 1:2). 1H NMR
experimental procedures and electron paramagnetic spectra,
fluorescence spectra, crystalographic parameters and NMR
spectra
3
reduced with PhNHNH2 (500 MHz, CDCl3): δ= 9.27 (d, 1H, J=8.7 Hz, HAr HAr),
8.28-8.26 (overlapped peaks, 3H,HAr), 8.05 (d, 1H, 3J=8.3 Hz, HAr), 8.00 (d, 2H,
3J=8.3 Hz, HAr), 7.94 (d, 1H, 3J=8.1 Hz, HAr), 7.71 (t, 1H, 3J=7.8 Hz,HAr), 7.62-
7.59 (overlapped peaks, 2H, HAr), 4.68-4.65 (m, 1H, CHTEMPO), 2.50 (m, 2H,
CH2-TEMPO), 2.18-2.15 (m, 2H, CH2-TEMPO), 1.68 (s, 6H, CH3-TEMPO ), 1.54 (s, 6H,
CH3-TEMPO ) ppm. HRMS reduced with TFA (APCI, +, Orbitrap) m/z: calc. for
C28H31N4O3 [M+H]+471.2391;found 471.2381
1
For reviews regarding the use of substitiuted-1,3,4-
oxadiazoles in construction of OLEDs see: a) A. Paun, N.D.
Hadade, C.C. Paraschivescu and M. Matache, J. Mater. Chem.
C, 2016,
Chem. C, 2015,
4
, 8596; b) X. Yang, X. Xu and G. Zhou, J. Mater.
, 913; c) Y. Tao, C. Yang and J. Qin, Chem.
3
4-(5-(anthracen-9-yl)-1,3,4-oxadiazol-2-yl)-N-(1-oxy-2,2,6,6-tetra
methylpiperidin-4-yl)benzamide 1c. Brown solid. Yield 47%, (27 mg). m.p.
254-257°C. Rf=0.53 (silica, EtOAc: petroleum ether= 1:1). 1H NMR reduced
with PhNHNH2 (500 MHz, CDCl3): δ= 8.70 (s, 1H, HAr ), 8.24 (d, 2H, 3J=8.2 Hz,
HAr), 8.10 (d, 2H, 3J=7.6 Hz, HAr), 8.03 (d, 2H, 3J=8.2 Hz, HAr), 7.96 (d, 2H, 3J=7.6
Hz, HAr), 7.56 (overlapped peaks, 4H, HAr), 4.55-4.52 (m, 1H, CHTEMPO), 2.11-
2.04 (m, 4H, CH2-TEMPO), 1.48 (m, 6H, CH3-TEMPO ), 1.40 (m, 6H, CH3-TEMPO ) ppm.
HRMS reduced with TFA (APCI, +, Orbitrap) m/z: calc. for C32H33N4O3 [M+H]+
521.2547; found 521.2535.
Soc. Rev., 2011, 40, 2943; d) G. Hughes and M.R. Bryce, J.
Mater. Chem., 2005, 15, 94; e) A.P. Kulkarni, C.J. Tonzola, A.
Babel and S.A. Jenekhe, Chem. Mater., 2004, 16, 4556.
2
3
For a review see: J. Han, J. Mater. Chem. C, 2013, 1, 7779.
See selected examples for: cations: a) L. Tang, Z. Zheng, Z.
Huang, K. Zhong, Y. Bian, and R. Nandhakumar, RSC Adv.,
2015, 5, 10505. b) C. Köhler and E. Rentschler, Eur. J. Inorg.
Chem., 2016, 1955. anions: c) J. Ma, Z. Li, Y. Zong, Y. Men and
G. Xing, Tetrahedron Lett., 2013, 54, 1348. d) L. Tang, Z.
N-(1-oxy-2,2,6,6-tetramethylpiperidin-4-yl)-4-(5-(pyren-1-yl)-1,3,4-
oxadiazol-2-yl)benzamide 1d. Orange solid. Yield 81% (22 mg). m.p. 249-
251°C (dec.). Rf= 0.78 (silica, EtOAc). 1H NMR reduced with PhNHNH2 (500
MHz, CDCl3): δ= 9.55 (d, 1H, 3J=9.5 Hz, HAr), 8.66 (d, 2H, 3J=8.5 Hz, HAr), 8.31-
8.27 (overlapped peaks, 4H, HAr), 8.23 (t, 2H, 3J=8.5 Hz, HAr), 8.16 (d, 1H,
3J=8.5 Hz, HAr), 8.08-8.05 (overlapped peaks, 2H, HAr), 7.99 (d, 2H, 3J=8.5 Hz,
HAr), 4.59-4.56 (m, 1H, CHTEMPO), 2.15-2.13 (m, 2H, CH2-TEMPO), 2.06-2.04 (m,
2H, CH2-TEMPO), 1.48 (s, 6H, CH3-TEMPO ), 1.44 (s, 6H, CH3-TEMPO ) ppm. HRMS
reduced with TFA (APCI, +, Orbitrap) m/z: calc. for C34H33N4O3 [M+H]+
545.2547; found 545.2535.
Zheng, K. Zhong and Y. Bian, Tetrahedron Lett., 2016, 57
1361.
,
4
5
For selected examples, see: a) Y.-B. Dong, J.-P. Ma, R.-Q.
Huang, M.D. Smith and H.-C. zur Loye, Inorg. Chem., 2003,
42, 294; b) Y.-B. Dong, H.-Y. Wang, J.-P. Ma, D.-Z. Shen and
R.-Q. Huang, Inorg. Chem., 2005, 44, 4679; c) C. Anghel, M.
Matache, C.C. Paraschivescu, A. M. Madalan and M Andruh,
Inorg. Chem. Commun., 2017, 76, 22.
a) Z. Wang, H. Zhang, B.J. Killian, F. Jabeen, G.G. Pillai, H.M.
Berman, M. Mathelier, A.J. Sibble, J. Yeung, W. Zhou, P.J.
Steel, C.D. Hall and A.R. Katritzky, Eur. J. Org. Chem., 2015,
This journal is © The Royal Society of Chemistry 20xx
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Journal Name
5183; b) T.M. Klapçtke and T.G. Witkowski, ChemPlusChem, 19 a) T. Yang, B. Zheng, H. Liang, Y. Wan, J. Du and D. Xiao,
2016, 81, 357.
Talanta, 2015, 132, 191; b) Y. Matsuoka, M. Yamato, T.
Yamasaki, F. Mito and K. Yamada, Free Radical Biol. Med.,
2012, 53, 2112; c) M. Shiga, Y. Miyazono, M. Ishiyama, K.
Sasamoto and K. Ueno, Anal. Commun., 1997, 34, 115.
6
a) A. Kaur, J.L. Kolanowski and E.J. New, Angew. Chem. Int.
Ed., 2016, 55, 1602; b) J.P. Blinco, K.E. Fairfull-Smith, B.
Morrow and S.E. Bottle, Aust. J. Chem., 2011, 64, 373; c) Z.
Lou, P. Li and Keli Han, Acc. Chem. Res., 2015, 48, 1358; d) X. 20 T.D. Lee and J.F.W. Keana, J. Org. Chem., 1975, 40, 3145.
Chen, F. Wang, J. Young Hyun, T. Wei, J. Qiang, X. Ren, I. Shin
and J. Yoon, Chem. Soc. Rev., 2016, 45, 2976; e) G.I.
Likhtenstein, K. Ishii and S. Nakatsuji, Photochem. Photobiol.
2007, 83, 871.
7
8
9
a) L. Stryer and H.O. Griffith, Proc. Natl. Acad. Sci. USA, 1965,
54, 1785; b) I. M. Bystryak, G. I. Likhtenshtein, A. I.
Kotelnikov, O.H. Hankovsky and K. Hideg, Russ. J. Phys.
Chem., 1986, 60, 1679.
a) C. Bueno, L. Mikelsons, L. Maretti, J.C. Scaiano and A.
Aspee, Photochem. Photobiol., 2008, 84, 1535; b) S.
Hirosawa, S. Araiband and S. Takeoka, Chem. Commun.,
2012, 48, 4845.
a) L. Tebben and A. Studer, Angew. Chem. Int. Ed., 2011, 50
,
5034; b) T Vogler and A. Studer, Synthesis, 2008, 13, 1979; c)
O.G. Mancheno and T. Stopka, Synthesis, 2013, 45, 1602.
10 See for example a) W. Lee, Y. Kang, and P.H. Lee, J. Org.
Chem., 2008, 73 4326; b) S. Hou and W.K. Chan,
Macromolecules, 2002, 35, 850.
,
11 See for example: a) A. Slodek, M. Filapek, E. Schab-Balcerzak,
M. Grucela, S. Kotowicz, H. Janeczek, K. Smolarek, S.
Mackowski, J.G. Malecki, A. Jedrzejowska, Gr. Szafraniec-
Gorol, A. Chrobok, B. Marcol, S. Krompiec and M. Matussek
Eur. J. Org. Chem., 2016, 4020; b) A. Kumar, P. Tyagi, M.A.
Reddy, G. Mallesham, K. Bhanuprakash, V.J. Rao, M.N.
Kamalasanan and R. Srivastava, RSC Adv., 2014,
Z. Zhang, W. Jiang, X. Ban, M. Yang, S. Ye, B. Huang and Y.
Sun, RSC Adv., 2015, , 29708.
4, 12206; c)
5
12 S. Chidirala, H. Ulla, A. Valaboju, M.R. Kiran, M.E. Mohanty,
M.N. Satyanarayan, G. Umesh, K. Bhanuprakash and V.J. Rao,
J. Org. Chem., 2016, 81, 603.
13 a) K.D. Patel, S.M. Prajapati S.N. Panchal and H.D. Patel,
Synth. Commun., 2014, 44, 1859; b) C. Soares de Oliveira,
B.F. Lira, J.M. Barbosa-Filho, J.G. Fernandez Lorenzo and P.
Filgueiras de Athayde-Filho, Molecules, 2012, 17, 10192; c) Z.
Jakopin and M.S. Dolenc, Curr. Org. Chem. 2008, 12, 850.
14 For cyclisation using diacetoxyiodobenzene (DBI) see for
example: a) R-.Y. Yang and L.-X. Dai, J. Org. Chem., 1993, 58
,
3301. For cyclisation using bis(trifluoroacetoxy)iodobenzene
see: b) C.C. Paraschivescu, N.D. Hădade, A.G. Coman, A.
Gautier, F. Cisnetti and M. Matache, Tetrahedron Lett. 2015,
56, 3691; c) C. Paraschivescu, M. Matache, C. Dobrotă, A.
Nicolescu, C. Maxim, C. Deleanu, I.C. Fărcășanu and N.D.
Hãdade, J. Org. Chem., 2013, 78, 2670; d) Z. Shang, Synth.
Commun., 2006, 36, 2927. For cyclisation using Dess-Martin
reagent see: e) C. Dobrota, C.C. Paraschivescu, I. Dumitru, M.
Matache, I. Baciu and L.L. Ruta, Tetrahedron Lett., 2009, 50,
1879. For cyclisation using molecular iodine see: f) G.
Majji, S.K. Rout, G. Guin, A. Gogoi and B.K. Patel, RSC
Adv., 2014,
Dong, X. Yu, Y. Li and J. Chang J. Org. Chem., 2013, 78
10337; h) S. Guin, S.K. Rout, T. Ghosh, N. Khatun B.K. Patel,
RSC Adv., 2012, , 3180.
4, 5357; g) W. Yu, G. Huang, Y. Zhang, H. Liu, L.
,
2
15 a) D.F. Eaton, Pure Appl. Chem., 1988, 60, 1107; b) A.M.
Brouwer, Pure Appl. Chem., 2011, 83, 2213.
16 S. Chen, X. Xu, Y. Liu,W. Qiu, G. Yu, X. Sun, H. Zhang, T. Qi, K.
Lu, X. Gao, Y. Liu and D. Zhu, J. Mater. Chem., 2007, 17, 3788.
17 J. Mei, N.L.C. Leung, R.T.K. Kwok, J.W.Y. Lam and B.Z. Tang,
Chem. Rev., 2015, 115, 11718.
18 D. Baran, A. Balan, S. Celebi, B. Meana Esteban, H.
Neugebauer, N.S. Sariciftci and L. Toppare, Chem. Mater.,
2010, 22, 2978.
8 | J. Name., 2012, 00, 1-3
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New Journal of Chemistry
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DOI: 10.1039/C7NJ01698K
Table of contents
Profluorescent nitroxides containing 2,5-diaryl-1,3,4-oxadiazoles as fluorophore units were
synthesized and characterized as actively-responsive probes to reducing agents.