Excited-state intramolecular proton transfer in 2-(2′,6′-dihydroxyphenyl)benzoxazole: effect of dual hydrogen bonding on the optical properties

Article abstract of DOI:10.1016/j.tetlet.2010.02.043

2-(2′,6′-Dihydroxyphenyl)benzoxazole (DHBO) has been synthesized by using palladium-catalyzed oxidative cyclization. The compound utilizes both O-H···N and O-H···O bonds to ensure a coplanar structure between the benzoxazole and phenol fragments. Optical comparison with the parent compound 2-(2′-hydroxyphenyl)benzoxazole (HBO) reveals that the dual hydrogen bonding in DHBO plays an essential role in raising the desirable keto emission for ESIPT and tuning the polarity sensitivity toward the molecular environment. DHBO also exhibits a higher quantum yield (φ{symbol}_fl = 0.108 in methanol) than HBO (φ{symbol}_fl = 0.0025) in the same solvent.

Full text of DOI:10.1016/j.tetlet.2010.02.043

Tetrahedron Letters 51 (2010) 1914–1918
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
0
0
Excited-state intramolecular proton transfer in 2-(2 ,6 -dihydroxyphenyl)
benzoxazole: effect of dual hydrogen bonding on the optical properties
Wei-Hua Chen, Yi Pang *
Department of Chemistry & Maurice Morton Institute of Polymer Science, The University of Akron, Akron, OH 44325, United States
a r t i c l e i n f o
a b s t r a c t
0
0
Article history:
2-(2 ,6 -Dihydroxyphenyl)benzoxazole (DHBO) has been synthesized by using palladium-catalyzed oxi-
Received 21 December 2009
Revised 4 February 2010
Accepted 7 February 2010
Available online 11 February 2010
dative cyclization. The compound utilizes both O–HꢀꢀꢀN and O–HꢀꢀꢀO bonds to ensure a coplanar structure
0
between the benzoxazole and phenol fragments. Optical comparison with the parent compound 2-(2 -
hydroxyphenyl)benzoxazole (HBO) reveals that the dual hydrogen bonding in DHBO plays an essential
role in raising the desirable keto emission for ESIPT and tuning the polarity sensitivity toward the molec-
ular environment. DHBO also exhibits a higher quantum yield (/
= 0.0025) in the same solvent.
fl
= 0.108 in methanol) than HBO
Keywords:
(/
fl
0 0
2
-(2 ,6 -Dihydroxyphenyl)benzoxazole
Ó 2010 Elsevier Ltd. All rights reserved.
Excited-state intramolecular proton transfer
Hydrogen bonding
Rotamer
Fluorescence
0
2
-(2 -Hydroxyphenyl)benzoxazole (HBO) 1 has emerged to be
rounding solvent molecules. In the extreme cases, the solvent mol-
ecules may remove the hydroxy proton to generate the anionic
species. The enol forms (1a, 1b, and 3) in solution are in equilibrium
(Scheme 2), whose actual composition is dependent on the solvent
properties. It should be noticed that only tautomer 1b undergoes
the ESIPT to generate the desirable keto emission. The effective
content of 1b, therefore, determines the optimum performance of
the HBO derivatives. Previous studies have shown that the relative
intensity of keto emission can be significantly increased by
an interesting material, due to its intrinsic property for the excited
state intramolecular proton transfer (ESIPT). A distinctive feature
for the HBO derivatives is that their fluorescence is well separated
from their absorption maxima, leading to unusually large Stokes’
shift. Utilization of this feature has resulted in various applica-
tions including chemical sensors for zinc(II) and anions, and
1
2,3
4
5
electronic devices such as organic light-emitting diodes. In recent
years, the HBO derivatives have been studied extensively to eluci-
date the ESIPT process (Scheme 1). In the ground state, the HBO
derivative exists in the enol–imine form. Upon irradiation with
photons, the HBO molecule is driven to the excited state, where
a proton is transferred from the hydroxy group to an acceptor to
generate the corresponding keto–amine tautomer. The entire pro-
cess occurs in about a picosecond, making the HBO derivative an
attractive candidate for optical switching.6
1
0
11
decreasing the temperature (e.g., at 77 K) or solvent polarity.
Any environmental changes, which affect the equilibrium among
1a, 1b, and 3, can ultimately influence the population of excited
states and photophysical characteristics of HBO. The presence of
several ground-states, in addition to their unpredictable composi-
tion in equilibrium, dilutes the effective concentration of rotamer
1b, thereby lowering the intensity of the desirable keto emission
and hampering a broader application of HBO. For example, the
The HBO molecule is known to exist in the intramolecular
hydrogen-bonded rotamers 1a and 1b. X-ray diffraction reveals
that the two rotamers 1a and 1b exist in about 1:1 ratio in the crys-
1
0
12
HBO 1 in ethanol and methanol solutions gives both enol
(kem ꢁ 370 nm) and keto (kem ꢁ 500 nm) emission in about equal
intensity at room temperature, while the keto emission is nearly
exclusive in a nonpolar solvent such as 3-methylpentane.10
It remains a challenging task to effectively direct the equilib-
rium toward the useful rotamer 1b. Decreasing temperature and
using nonpolar solvents are either impractical or can only be ap-
plied to very limited situations. The known intermolecular hydro-
7
talline state, with the hydroxyl group pointing to either N- or O-
atom side of the oxazole ring. It has been demonstrated that only
rotamer 1b undergoes ESIPT process,8 which leads to the keto tau-
tomer 2 to give the emission with large Stokes shift. The rotamer
a is likely the one responsible for the enol emission.
In the solution state, HBO can also exist as the enol 3, especially
,9
1
1
3
when the solute molecule has strong interaction with the sur-
gen bond strength for O–HꢀꢀꢀN (
from phenol/pyridine) is only slightly stronger than that for O–
HꢀꢀꢀO bond ( H = ꢂ5.0 kcal/mol, measured from phenol/ether).
The small energetic difference between the O–HꢀꢀꢀN and O–HꢀꢀꢀO
D
H = ꢂ6.5 kcal/mol, measured
D
*
Corresponding author.
E-mail address: yp5@uakron.edu (Y. Pang).
0
040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.02.043

W.-H. Chen, Y. Pang / Tetrahedron Letters 51 (2010) 1914–1918
1915
H
O
N
O
N
O
O
N
O
H
O
H
1
a
1b
2
O
N
n
S (n>1)
HO
S
1
ESIPT
O
TS* of
N
H
O
Absorption
Stokes-shifted
low energy
fluorescence
O
O
N
TS of
S
0
N
H
O
HO
2
keto tautomer
enol tautomer
Scheme 1. Schematic illustration for ESIPT of HBO 1.
solvent
H
H
H
O
1
H
O
O
2
O
O
N
O
N
O
N
N
6
H
O
O
1a
3
1b
closed cis-enol
4
closed trans-enol
opened trans-enol
Scheme 2. Enol isomers of HBO in the ground state.
bonds only renders a limited control to minimize the amount of
the tautomer 1a, which is incapable of undergoing ESIPT to give
keto emission. A rational design to maximize the ESIPT signal de-
mands new strategies to minimize the content of 1a and 3, while
preserving the valuable optical characteristics of HBO. Herein, we
0
0
report the synthesis of 2-(2 ,6 -dihydroxyphenyl)benzoxazole
(DHBO) 4, in which the second hydroxy group is introduced at
the 6-position of the phenol segment. The dual hydrogen bondings
OH
OH
OH
O
OH
PPA
+
200 o
C
NH2
O
HO
O
OH
6
5
79%
7
O
O
HO
Toluene
reflux
N
+
O
2
H N
O
OH
90%
O
8
6
9
OH
O
O
O
N
N
Pd(OAc)
DMF, 80 0
1%
2
(5%), O
2
Cs
2
CO
3
BBr3
CH Cl , rt
C
2
2
O
70%
OH
8
10
4
Scheme 3. Synthesis of compound 4.

1
916
W.-H. Chen, Y. Pang / Tetrahedron Letters 51 (2010) 1914–1918
in 4, which are connected to both O- and N-atoms in benzoxazole
fragment, not only provides additional structural stability but also
eliminates the possibility of rotamer 1a, thereby increasing the
ESIPT output.
solvent
solvent
H
O
O
H
O
ESIPT
O
N
O
N
Initial attempt to condense 2,6-dihydroxybenzoic acid 5 with 2-
aminophenol 6 failed to produce 4, but gave 1,6-dihydroxyxanthe-
1
4,15
none 7 in high yield.
The synthesis of compound 4 is
H
H
O
accomplished by using an alternative method (Scheme 3). Thus,
condensation of 2,6-dimethoxybenzaldehyde 8 with 2-aminophe-
nol 6 affords the Schiff base 9 in 90% yield upon refluxing in tolu-
ene. Conversion of the Schiff base to benzoxazole 8 is accomplished
in 81% yield by using the palladium(II)-catalyzed oxidative cycliza-
tion under a relatively milder condition.16 Subsequent deprotec-
enol
keto tautomer
4
11
5
5
5
5
5
5
5
5
8
x10
DMF
Hexane
MeOH
MeCN
Water
OH
OH
O
7x10
4,17
N
tion with boron tribromide in dichloromethane
desirable product.
gave the
1
8
6x10
Filtered solution
UV–vis of 4 revealed an absorption band at 306 nm and a shoul-
der at 322 nm in polar solvents such as methanol, acetonitrile, and
DMF (Fig. 1). An additional absorption band was observed in hex-
anes at about 350 nm, which could be attributed to the aggregate
formation as polar molecule 4 is less soluble in the nonpolar sol-
vent. Upon the addition of NaOH, a new absorption band was ob-
served at 365 nm, attributed to the formation of phenoxide anion
5x10
4x10
3x10
2x10
x10
1
0
a
1.0
350
400
450
500
550
600
650
3
06
Hexane
Wavelength (nm)
MeOH
DMF
MeOH+NaOH
MeCN
Water
0
0
0
0
0
.8
.6
.4
.2
.0
Figure 2. Fluorescence spectra of
wavelength kex = 322 nm). The ‘filtered solution’ indicates that the aqueous solution
4
in various solvents at 25 °C (excitation
is filtered by using a 0.02 m alumina membrane filter.
l
3
22 nm
Filtered solution
–
OH
O
from 4, Ph–OH?Ph–O . The absorption properties of 4 were com-
pared with that of 1 under the identical conditions. In contrast to 4,
the HBO 1 in hexanes did not show the aggregation band, as the
additional hydroxy group in the former makes it less soluble in
the nonpolar solvent (aggregation easier to occur). Interestingly,
the methanol solution of 1 revealed a broad band at ꢃ365 nm.
When water (a more polar solvent) was used, the absorption band
became higher in 1, accompanied with the new band at 345 nm.
Both absorption bands at 345 nm and 365 nm are attributed to
N
OH
3
65 nm
2
50
275
300
325
350
375
400
425
450
1
9
aggregate formation, as they are absent after the aqueous solu-
Wavelength (nm)
b 0.8
Hexane
MeOH
DMF
6
1
1
1
.4x10
.2x10
.0x10
O
N
MeCN
Water
Filtered solution
MeOH+NaOH
0
0
0
0
.6
.4
.2
.0
321
6
6
5
5
5
5
Hexane
MeOH
DMF
MeCN
Water
HO
334
O
345
8.0x10
N
6
4
2
.0x10
.0x10
.0x10
HO
365 nm
0.0
2
50
275
300
325
350
375
400
425
450
3
50
400
450
500
550
600
Wavelength (nm)
Wavelength (nm)
Figure 1. UV–vis of 4 (top) and 1 (bottom) in different solvents. The ‘filtered
solution’ indicates that the aqueous solution is filtered by using a 0.02
membrane filter.
lm alumina
Figure 3. Normalized emission of HBO 1 in different solvents (excitation wave-
length kex = 331 nm).

W.-H. Chen, Y. Pang / Tetrahedron Letters 51 (2010) 1914–1918
1917
0
0
1
.0
0.8
.6
0.4
In summary, we have synthesized 2-(2 ,6 -dihydroxy-
phenyl)benzoxazole (DHBO). In comparison with the parent HBO
system, the additional hydrogen bonding in DHBO effectively re-
moves the rotamer formation, thereby increasing the desirable
ESIPT signals. As a result, the DHBO exhibits higher fluorescence
quantum yield, larger Stokes’ shift (due to red-shifted fluores-
cence) and improved sensitivity to solvent polarity and pH. These
improved optical characteristics are expected to find applications
in relevant fields, where ESIPT are desirable.
0
1
2
µL
µL
µL
5
6
5
4
3
2
1
x10
0
5
5 µL
x10
1
1
0µL
5µL
0
0
.2
.0
5
20µL
x10
0
4
8
12
16
20
2
3
5µL
0µL
Equiv. of NaoH Added
5
x10
35µL
4
5
0µL
0µL
5
x10
60µL
Acknowledgments
7
1
2
0µL
00µL
00µL
5
x10
Financial support has been provided by The University of Akron
and Coleman endowment. We also wish to thank The National Sci-
ence Foundation (CHE-9977144 and MRI-0821313) for funds used
to purchase the NMR instrument and high resolution ESI mass
spectrometer used in this work. We are grateful for a reviewer’s
helpful suggestions.
0
350
400
450
500
550
600
Wavelength (nm)
ꢂ6
Figure 4. Changes in fluorescence of 4 (2 mL of 5 ꢄ 10 M in MeOH/H
2
O; 10:1)
ꢂ3
Supplementary data
upon successive additions of NaOH (1.0ꢄ10 M aqueous). Excitation wavelength
k
ex = 322 nm. The inset shows the dependence of fluorescence on the equivalent
base added.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.02.043.
tion is filtered by using a 0.02 lm alumina membrane. Addition of
NaOH to the methanol solution induced a new absorption band
References and notes
(k
max = 365 nm), as the consequence of phenoxide anion formation.
The fluorescence of 4 in DMF reveals a major band at 544 nm
1
2
.
.
Williams, D. L.; Heller, A. J. Phys. Chem. 1970, 74, 4473–4480.
Taki, M.; Wolford, J. L.; O’Halloran, T. V. J. Am. Chem. Soc. 2004, 126, 712–713.
and a minor band at 366 nm (Fig. 2), attributing to the keto and
enol emissions, respectively. In methanol solution, the enol emis-
sion from 4 is negligible, in sharp contrast to that from 1 (Fig. 3)
where the enol emission consists of ꢃ30–40% of total fluorescence
3. Ohshima, A.; Momotake, A.; Arai, T. Tetrahedron Lett. 2004, 45, 9377–9381.
4
5
.
.
Chu, Q.; Medvetz, D. A.; Pang, Y. Chem. Mater. 2007, 19, 6421–6429.
Vazquez, S. R.; Rodriguez, M. C. R.; Mosquera, M.; Rodriguez-Prieto, F. J. Phys.
Chem. A 2007, 111, 1814–1826.
6. Zhang, G.; Wang, H.; Yu, Y.; Xiong, F.; Tang, G.; Chen, W. Appl. Phys. B Lasers and
Optics 2003, 76, 677–681.
signals. In addition, the quantum yield of 4 (/
fl
= 0.108 in metha-
7.
8.
9.
Tong, Y. P. Acta Crystallogr., Sect. E 2005, 61, o3076–o3078.
Woolfe, G. J.; Melzig, M.; Schneider, S.; Doerr, F. Chem. Phys. 1983, 72, 213–221.
Das, K.; Sarkar, N.; Majumdar, D.; Bhattacharyya, K. Chem. Phys. Lett. 1992, 198,
443–448.
nol) is significantly higher than that of 1 (/
fl
= 0.0025 in CH OH)
3
under the same conditions,20 attributing to the increased molecu-
lar rigidity and the presence of an additional hydroxy group in the
former. While the keto emission of 1 varies within 480–505 nm,
the keto emission of 4 changes between 478 nm and 557 nm in re-
sponse to solvent polarity. The larger optical response observed in
1
1
1
1
0. Das, K.; Sarkar, N.; Ghosh, A. K.; Majumdar, D.; Nath, D. N.; Bhattacharyya, K. J.
Phys. Chem. 1994, 98, 9126–9132.
1. Ohshima, A.; Lkegami, M.; Shinohara, Y.; Momotake, A.; Arai, T. Bull. Chem. Soc.
Jpn. 2007, 80, 561–566.
2. Wang, H.; Zhang, H.; Abou-Zied, O. K.; Yu, C.; Romesberg, F. E.; Glassbeek, M.
Chem. Phys. Lett. 2003, 367, 599–608.
3. (a) Selected hydrogen bond strength can be found in E.V. Anslyn, D.A.
Dougherty, Modern Physical Organic Chemistry, University Science Books,
4
can be rationalized by considering its keto tautomer 11. The hy-
droxy group in 11, along with its electronic connection with the
carbonyl group, effectively transmits the solvent interaction to
the optical response. In summary, the presence of the second hy-
droxy group in 4 plays several useful functions: suppressing the
enol emission, increasing the quantum yield, and enhancing the
solvent responses.
2006, pp 171–180.; (b) Joesten, M. D.; Schaad, L. J. Hydrogen Bonding; Marcel
Dekker: New York, 1974.
1
4. Synthesis of 7. 2,6-Dihydroxybenzoic acid (1.5 g, 10 mmol) and 2-
aminophenol(1.1 g, 10 mmol) were added into 30 mL preheated
polyphosphoric acid to give a stirrable paste. The mixture was then heated
slowly to 200 °C, and the resulting solution was stirred at this temperature for
ꢂ
The fluorescence of DHBO 4 is also responsive to the OH con-
4
h. The reaction mixture was cooled to about 100 °C, and poured in 300 mL of
centration (Fig. 4). Upon increasing pH from neutral to basic condi-
tions, the fluorescence intensity is gradually decreased, and nearly
completely quenched when ꢃ4 equiv NaOH is added (correspond-
water. The acidic aqueous solution was neutralized with solid K CO , extracted
2
3
with EtOAc (100 mL ꢄ 4), and dried over Na
was concentrated to give a dark crude product which was purified by column
chromatography on silica gel using CH Cl as an eluent to provide pure product
as a white solid (1.8 g, 79%). The NMR spectrum of 7 was identical with the
2 4
SO . After filtration, the solution
2
2
ꢂ
ꢂ5
ing to hydroxide concentration [OH ] = 2 ꢄ 10 M), attributing to
the formation of anionic species as a consequence of deprotona-
tion. The result indicates that anionic 12 is weakly fluorescent.
And the gradual change in fluorescence intensity shows that the
DHBO 4 can be used as a pH sensor.
7
data reported in Refs: (a) Liu, Y.; Zou, L.; Ma, L.; Chen, W.-H.; Wang, B.; Xu, Z.-L.
Bioorg. Med. Chem. 2006, 14, 5683–5690; (b) Fatel, G. F.; Trivedi, K. N. Synth.
Commun. 1989, 19, 1641–1647. This reaction appears to be an improved
method to synthesis xanthone derivatives such as 7, since the current
literature examples typically give low yield and by-products.
HO
HO
O
O
O
N
H2O
O
N
H O
2
+
O
N
+
+
H O
3
2 H O
+
3
HO
O
12
13
4

1
1
918
W.-H. Chen, Y. Pang / Tetrahedron Letters 51 (2010) 1914–1918
5. The proposed mechanism for 7 is following:
O
H
H
O
O
O
O
O
O
O
O
O
HO
O
O
O
H
tautomerization
-H O
2
H+
HO
HO
HO
HO
HO
OH
OH
OH2
HO
O
O
OH
O
OH2
O
O
O
OH
OH
OH
O
O
-H+
-
H O
2
HO
HO
HO
HO
O
O
O
O
O
O
OH
O
O
OH
O
OH
1
,3-H shift
-CO2
O
HO
O
7
H
O
Synthesis of 4. Boron tribromide (0.6 mL of 1 M BBr
added to a stirring mixture of 10 (50 mg, 0.2 mmol) in anhydrous CH
3
in hexanes, 0.6 mmol) was
Cl
1
1
6. Chen, W.-H.; Pang, Y. Tetrahedron Lett. 2009, 50, 6680–6683.
7. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis; John Wiley
Sons: New York, 1999.
2
2
(5 mL), and the reaction was stirred at room temperature under a nitrogen
atmosphere. After 48 h, the reaction was quenched with MeOH (2 mL), and the
&
1
8. Synthesis of 10. To a 10 mL round-bottomed flask equipped with a sidearm,
magnetic stirring bar, and connecting tube were added the Schiff base 9
reaction mixture was extracted with EtOAc (20 mL) and washed with H
(2 ꢄ 10 mL) and brine (10 mL). The organics were then filtered, dried over
Na SO , and concentrated on a rotatory evaporator. Purification over a silica
column with (4:1 hexanes/EtOAc) afforded 2-(2 ,6 -dihydroxyphenyl)benz-
oxazole (4) as a white solid (32 mg, 70%). The obtained pure product was
2
O
(
100 mg, 0.4 mmol), Pd(OAc)
2
(4.6 mg, 0.02 mmol), Cs
.8 mmol), and 15 mL DMF. The mixture was stirred at room temperature for
min then warmed to 80 °C, while the oxygen gas was bubbled into the flask
2
CO
3
(260 mg,
2
4
0
0
0
5
below the surface of the liquid. The progress of the reaction was monitored by
recrystallized from hexane/EtOAc to give white needle-like crystals (mp 191–
1
1
H
NMR spectroscopy, which revealed the disappearance of the imine
192 °C). H NMR (CDCl
7.45 (m, 2H), 7.33 (t, J = 8.4 Hz, 1H), 6.66 (d, 2H, J = 8.4 Hz). C NMR (CDCl ,
3
3
300 MHz) d 9.79 (br, 2H), 7.78 (m, 1H), 7.67 (m, 1H),
13
resonance signal at around d 9.1 ppm when the reaction was complete. Upon
completion of the reaction, the mixture was poured into 30 mL of water. The
precipitate was collected by vacuum filtration and washed with 20 mL of
water. The solid was redissolved in 30 mL of dichloromethane, washed with 1%
EDTA aqueous solution (to remove the palladium catalyst), then washed with
75 MHz) d 162.2, 158.2, 147.9, 138.3, 134.5, 126.0, 125.9, 119.5, 110.7, 118.7,
ꢂ1
99. IR (KBr)
m
max (cm ): 3485 (s), 1637 (s), 1581 (m), 1533 (w), 1478 (w), 1452
(m), 1412(w), 1250(m), 1157(m), 1041(w), 1017(w), 817(w), 788(w), 744(w),
+
701(w). HRMS (m/z): [M+H] calcd for C13
H
10NO
3
, 228.0661, found, 228.0677;
+
water. The organic layer was dried over anhydrous Na
2
SO
4
. Removal of solvent
[M+Na] calcd for C13H NNaO , 250.0480, found 250.0484.
9 3
afforded the crude product which was purified by column chromatography on
19. Huang, J.; Peng, A.; Fu, H.; Ma, Y.; Zhai, T.; Yao, J. J. Phys. Chem. A 2006, 110,
9079–9083.
20. The fluorescence quantum yields were measured by using quinine sulfate in
silica gel using a mixed eluent of hexane and EtOAc (10:1) to provide pure
1
product as white solid (84 mg, 81%). H NMR (CDCl
3
300 MHz) d 7.82 (m, 1H),
7
6
.60 (m, 1H), 7.45 (t, 1H, J = 8.4 Hz), 7.36 (m, 2H), 6.67(d, 2H, J = 8.4 Hz), 3.81(s,
H).
1 N H
2 4
SO as the standard (quantum yield = 0.53, at 366 nm). Lakowicz, J. R.
Principles of Fluorescence Spectroscopy; Kluwer Academic: New York, 1999.