A new series of 2,5-bis(4-methylphenyl)-1,3,4-oxadiazole derivatives: their synthesis and fluorescence properties for anion sensors

Article abstract of DOI:10.1016/j.tetlet.2007.09.008

A new series of 2,5-bis(4-methylphenyl)-1,3,4-oxadiazole derivatives containing various substituted groups on the ortho-position to oxadiazole ring was synthesized and their fluorescent sensor properties were investigated. The fluorescent sensor molecules

Full text of DOI:10.1016/j.tetlet.2007.09.008

Tetrahedron Letters 48 (2007) 7788–7792
A new series of 2,5-bis(4-methylphenyl)-1,3,4-oxadiazole
derivatives: their synthesis and fluorescence
properties for anion sensors
Chan Kyu Kwak,a, Chi-Han Leeb, and Taek Seung Leea,*
aOrganic and Optoelectronic Materials Laboratory, Department of Advanced Organic Materials and Textile System Engineering,
Chungnam National University, Daejeon 305-764, Republic of Korea
bInstitute of Nano-Technology and Advanced Materials, Chungnam National University, Daejeon 305-764, Republic of Korea
Received 30 July 2007; revised 31 August 2007; accepted 4 September 2007
Available online 6 September 2007
Abstract—A new series of 2,5-bis(4-methylphenyl)-1,3,4-oxadiazole derivatives containing various substituted groups on the ortho-
position to oxadiazole ring was synthesized and their fluorescent sensor properties were investigated. The fluorescent sensor mole-
cules showed UV absorption shift as well as fluorescence emission shift upon exposure to fluoride anion in DMF solution, which was
considerably dependent on the substituent attached on the phenyl group. The new sensory compound, 1d can be used as a fluoride
anion sensor in terms of naked-eye detection and fluorescent sensing with high selectivity.
ꢀ 2007 Elsevier Ltd. All rights reserved.
Recently, there is a growing interest in the design and
synthesis of fluorescent organic compounds for chemical
sensors because of their potential active components in
environmental and bio-analytical fields.1 The simple
modification of the chemical structure, the solubility,
and the optical properties of these organic materials en-
ables us to demonstrate a variety of molecular struc-
tures. Among, fluorescent materials, a great deal of
attention has been received with heterocyclic ring system
due to their interesting properties closely related to opti-
cal and optoelectronic properties. The exploration of
conjugated 1,3,4-oxadiazole-containing polymers and
small molecules offers enhanced thermal and photophys-
ical stability as well as improved electron-transporting
property. Considerable research on the synthetic routes
for oxadiazole moieties was accomplished as polymer
backbone constituents2 and side-chains,3 and as small
molecules.4 Since oxadiazole groups are known as one
of the most extensively investigated class of electron-
accepting species, oxadiazole-based compounds have
been used as electron transport materials in organic light
emitting diodes (OLEDs).5 The optical and electrical
properties exhibited by such heterocyclic cores are
mainly attributed to their electron deficiency, high photo-
luminescence quantum yields, and good thermal and
chemical stability of the oxadiazole ring. It has been
reported that introduction of oxadiazole units into the
side-chain6 or main chain7 of poly(phenylenevinylene)s
(PPVs) could significantly improve their LED device
efficiency. By utilization of such heterocyclic rings, in
which the molecular symmetry of the central core is
reduced leading to a less favorable packing in the crystal
state.8 In addition, oxadiazole derivatives were reported
as sensitive sensory materials in the forms of polymeric
materials9 and of small molecular materials10 for fluo-
ride or explosive nitroaromatic compound sensing.
It has been extensively studied on the development of
fluorescent and colorimetric sensors for anions, which
are both highly sensitive at low analyte concentration
and convenient to use.11 Among chemosensors for
anions, phosphate and fluoride ion sensing are of special
interest due to their importance in a number of disease
states and environmental pollutants.12 Fluoride has
unique chemical properties, and its recognition and
detection are of growing interest because it is associated
with nerve gas, the analysis of drinking water, and the
refinement of uranium used in nuclear weapon manufac-
ture. As a result, there is a need to develop selective
methods for fluoride detection in environments that
are not easily served by conventional ion selective elec-
trodes. In a previous paper, we reported an oxadiazole
*
Corresponding author. Fax: +82 42 823 3736; e-mail: tslee@cnu.kr
Equal first authors.
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.09.008

C. K. Kwak et al. / Tetrahedron Letters 48 (2007) 7788–7792
Table 1. UV–vis and photoluminescence data of 1a–ea in DMF
7789
analogue with ortho-hydroxyphenyl group acting as a
fluoride-selective sensor.10b Addition of fluoride anion
into the sensory compound caused a color change as
well as blue shift of emission, which was explained by
intramolecular hydrogen bond alteration. Herein, we
are reporting synthesis of new p-conjugated oxadiazole
compounds 1a–e containing blocked ortho-hydroxyphe-
nyl units, and this class of compounds was found to ex-
hibit strong fluorescence in their solutions. Moreover,
one of these analogues 1d showed anion recognition
event even though the intramolecular hydrogen bond
was forbidden.
Compound
Before addition of FÀ
After addition of FÀb
kmax (nm)
kem (nm)c
kmax (nm)
kem (nm)c
1a
1b
1c
1d
1e
274, 312
274, 314
273, 315
286
366
365
369
359
368
274, 312
274, 314
273, 315
382
366
365
369
448
368
274, 312
274, 312
a [1] = 1.0 · 10À5 M.
b [FÀ] = 1.0 · 10À3 M.
c Excited at 324 nm.
the number of absorption bands depends on the substi-
tuent on the hydroxyl group and solvent used.9c It is pre-
sumed that the conjugated resonance structure of ester
bond with benzene ring in 1d played a major role in
the single absorption.
Compound 3, 2,5-bis(2-hydroxy-4-methylphenyl)-1,3,4-
oxadiazole was synthesized in a single step by a reaction
with 4-methylsalicylic acid and aminourea in polyphos-
phoric acid (PPA) at 130 ꢁC according to the reported
method (Scheme 1).13 Compounds 1a–c were synthe-
sized by Williamson ether synthesis with the correspond-
ing halides and 3 with good yields. Compound 1d was
obtained by reaction with 3 and acetic anhydride in
methylene chloride in the presence of triethylamine.
Compound 1e was obtained by hydrolysis of 1c using
concentrated hydrochloric acid. All the compounds are
readily soluble in organic solvents such as tetrahydrofu-
ran (THF), chloroform, and dichloromethane, and were
Compounds 1a–e exhibited the fluorescence emis-
sion maxima ranging from 359 to 368 nm as shown in
Table 1. Since the hydroxyl groups in 1 were blocked
with various substituents, the long wavelength emission
from keto tautomer was not observed, which was fre-
quently seen in the free hydroxyl group-containing
oxadiazole with the excited state intramolecular proton
transfer (ESIPT) as reported earlier.9c,10b Absorption
and fluorescence spectra of 1d in DMF after addition
of fluoride anion (as its tetrabutylammonium counter-
ion) are shown in Figures 1 and 2, respectively, and the
related spectra maxima of other compounds are summa-
rized in Table 1. In the cases of 1a–c and 1e, the absorp-
tion and emission spectral maxima remain virtually
unchanged. Figure 1 shows absorption changes of 1d
upon addition of FÀ, AcOÀ, BrÀ, ClÀ, and IÀ. Only
the fluoride anion induces a red shift of the absorption
from 286 nm to 382 nm with a color change from color-
less to yellow. The color change of 1d upon exposure to
1
characterized by H NMR spectroscopy and elemental
analysis.14 The spectroscopic results were consistent
with the proposed molecular structures. Compounds
1a–e are stable such that they can be stored at ambient
temperature for a long period more than three months.
Optical characteristics of 1a–e were investigated in
DMF solution. Their absorption and fluorescence emis-
sion data in DMF are summarized in Table 1. Com-
pounds 1a–c and 1e show well-resolved vibronic
structures with two distinct absorption maxima around
270 and 310 nm, while a single absorption at 286 nm
was exhibited by 1d. It has already been reported that
OH
COOH
OR
OH
RO
HO
N
N
N
N
ii
i
H3C
O
O
H3C
H3C
CH3
CH3
3
2
1a, 1b, 1c
iii
OAc
AcO
N
N
O
H3C
CH3
1d
OX
XO
N
N
iv
X : (CH2)6COOH
1c
O
H3C
CH3
1e
Scheme 1. Synthesis of 2,5-bis(4-methylphenyl)-1,3,4-oxadiazole derivatives. Reagents and conditions: (i) aminourea hydrochloride, PPA, 130 ꢁC;
(ii) NaH, DMF, 130 ꢁC (1a: R = CH3, 1b: R = 2-hydroxy(2-ethoxy)ethoxy, 1c: R = 6-cyanohexyl); (iii) (CH3CO)2, Et3N, CH2Cl2, room
temperature; (iv) concentrated HCl, 90 ꢁC.

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C. K. Kwak et al. / Tetrahedron Letters 48 (2007) 7788–7792
hydrogen bonding, it is believed that the electron-with-
0.8
0.6
0.4
0.2
0.0
drawing effect was facilitated by acetyl group and this
leaded to higher anion binding affinities.15 New emission
maximum can be observed upon addition of excess fluo-
ride anion to 1d as shown in Figure 2. Initially, upon
exposure to fluoride anion, original emission band at
359 nm decreased dramatically with appearance of small
emission band at 530 nm. As the concentration of fluo-
ride anion increased more than 40 equiv, a new and
broad emission band at 448 nm was newly formed and
the fluorescence intensity was gradually enhanced, of
which the new emission maximum appeared at the
wavelength of the absorption band edge of fluoride-
added solution. Demonstration of dual fluorescence col-
ors depending on the analyte concentration is rare in the
sensory system. Though the long wavelength emission
appeared by addition of anion, it did not result from
the ESIPT tautomer, because long wavelength emission
(keto form emission) generally centered above 500 nm as
reported earlier.16 The 1H NMR FÀ titration experiment
in 1d did not exhibit a formation of new peak, especially
free hydroxyl group at 9–10 ppm, responsible for cleav-
age of acetyl group from 1d (Fig. 3). However it is
clearly seen the considerable up-field shifts of three ben-
zene protons. For the up-field shifts in NMR spectra,
strong electron-donating effect through anion to ben-
zene ring is responsible for the spectral changes, which
affects the electron distribution of benzene group.17
Thus it is presumed that the structural variation by addi-
tion of fluoride anion was not expected for the new emis-
sion at 448 nm, presumed that significant electron or
energy transfer occurred in the presence of fluoride an-
ion. Fluorescence emission shift as well as absorption
changes upon addition of fluoride originate from the en-
hanced electron density on oxygen atom, which
strengthens the intramolecular charge transfer (ICT)
effect between the electron-withdrawing oxadiazole and
electron-donating fluoride anion.18
1d
F-
AcO-
Br-
Cl-
I-
300
400
500
600
Wavelength (nm)
Figure 1. UV–vis absorption spectra of 1d (1 · 10À5 M) in DMF upon
titration with tetrabutylammonium fluoride (TBAF, 100 equiv).
6000
1d
1d + F- (10 equiv)
5000
1d + F- (20 equiv)
1d + F- (40 equiv)
1d + F- (80 equiv)
1d + F- (100 equiv)
4000
3000
2000
1000
0
400
500
600
Wavelength (nm)
Figure 2. Emission spectra of 1d (1 · 10À5 M) in DMF upon titration
with TBAF.
fluoride anion can be used for naked-eye detection of
FÀ. Similar results on the possible naked-eye detection
with oxadiazole analogues with adjacent hydroxyl group
were drawn by precedent experiments accomplished by
Wang et al. and by our group, which resulted from the
strong intramolecular charge transfer effect.10a,b Though
1d has acetyl-protected hydroxyl groups adjacent to
oxadiazole ring, that is, in the absence of intramolecular
As a concluding remark, we have presented a facile
synthetic procedure for the preparation of 2,5-bis(4-
methylphenyl)-1,3,4-oxadiazole derivatives with various
substituents in the ortho-position to oxadiazole ring.
These compounds are highly blue-luminescent and,
1
3
O
O
O
O
N N
O
3
2
1
2
(a)
(b)
3
1
2
Figure 3. Partial 1H NMR spectra of 1d in DMSO-d6 in the absence (a) and in the presence (b) of 100 equiv of TBAF.

C. K. Kwak et al. / Tetrahedron Letters 48 (2007) 7788–7792
7791
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Acknowledgement
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Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2007.09.008.
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Typical procedure for product 1a: To a mixture of
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added 2,5-bis[2-hydroxy-4-methylphenyl]-1,3,4-oxadiazole
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