Absorption and fluorescence properties of chalcones having pyrrole or indole moiety

Article abstract of DOI:10.3987/COM-16-S(S)62

2′-Hydroxychalcone derivatives having pyrrole ring have been synthesized and their absorption and fluorescence properties have been examined in connection to intramolecular hydrogen bonding.

Full text of DOI:10.3987/COM-16-S(S)62

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HETEROCYCLES, Vol. 95, No. 2, 2017
HETEROCYCLES, Vol. 95, No. 2, 2017, pp. 972-979. © 2017 The Japan Institute of Heterocyclic Chemistry
Received, 2nd September, 2016, Accepted, 25th November, 2016, Published online, 17th February, 2017
DOI: 10.3987/COM-16-S(S)62
ABSORPTION AND FLUORESCENCE PROPERTIES OF CHALCONES
HAVING PYRROLE OR INDOLE MOIETY
Yukino Shinozaki and Tatsuo Arai*
Graduate School of Pure and Applied Science, University of Tsukuba, Tennoudai,
Tsukuba, Ibaraki 305-8571, Japan; E-mail: arai@chem.tsukuba.ac.jp
Abstract – 2'-Hydroxychalcone derivatives having pyrrole ring have been
synthesized and their absorption and fluorescence properties have been examined
in connection to intramolecular hydrogen bonding.
INTRODUCTION
The chalcone derivatives with pyrrole ring have been studied from the view points of having a wide
of biological activities such as antioxidant and anticarcinogenic activities.1-3 We have been studying the
photochemical and photophysical properties of various kinds of chalcone derivatives.4-14 Although
some of the compounds having chalcone skeleton and pyrrole or indole substituent have been synthesized,
spectroscopic properties of these compounds have not been reported so far.15-22 Furthermore, for some
compound, singlet oxygen production on excitation of chalcone derivatives have been reported.1 In
some compounds, the excited state deactivates quite rapidly by way of intramolecular hydrogen atom
transfer reaction in the excited singlet state.5,6 Therefore, it seems important to study the deactivation
processes from the excited state by studying spectroscopic properties to explore the importance of
chalcone derivatives having pyrrole or indole moiety for biological activities. We also aimed to find a
way to increase the quantum yield of fluorescence emission of 2’-hydroxychalcone derivatives by
introducing proper substituents and/or changing molecular structure. In this respect, we have studied the
spectroscopic properties of chalcone derivatives 1-3 having pyrrole or indole instead of benzene ring.
Figure 1. Structures of 2’-hydroxychalcone derivatives examined in this work

HETEROCYCLES, Vol. 95, No. 2, 2017
973
Figure 2. Structures of 2’-hydroxychalcone derivatives examined in previous work
RESULTS AND DISCUSSION
Chalcone derivatives 1-3 were synthesized by condensation of corresponding aldehyde and ketones as
described in Experimental section. Compounds 1-3 form O-H:O intramolecular hydrogen bonding as
1
revealed by observation of OH proton at considerably low field in H-NMR spectroscopy at 13.2, 12.7
and 15.2 ppm for compound 1, 2, and 3, respectively. The absorption spectra of 1-3 in benzene are
shown in Figure 3. The absorption maxima at longer wavelength region together with extinction
coefficient are summarized in Table 1. The observation of absorption maximum at 390-400 nm should
be ascribable to the existence of intramolecular hydrogen bonding to extend the conjugation of the whole
molecules. The maximum wavelength of 3 appeared at slightly shorter wavelength compared to that of
1
probably due to the change of conjugation by indole group instead of pyrrole group.
Figure 3. Absorption spectra of 1-3 in benzene
Fluorescence spectra of 1-3 were studied in various solvents. Typical examples observed in benzene are
shown in Figure 4. Compounds 1 and 3 exhibited considerably weak fluorescence at longer wavelength
-5
-5
region peaking at ca. 640 nm with the quantum yield ()
f
) of ca. 10 for 1 and 3.8x10 for 3 at 298 K
(
Table 1). These values are comparable to those of related chalcones having pyridine 4 or quinoline 5.15
We could not observe the fluorescence from 2 by our instrument of fluorescence spectroscopy and
therefore the quantum yield of fluorescence emission from 2 is beyond our detection limit and much
-5
lower than 10 . In the case of hydrogen bonded compounds such as 6 having pyrrole and pyridine at

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HETEROCYCLES, Vol. 95, No. 2, 2017
both end of C=C double bond, hydrogen atom transfer took place to produce the tautomer in the excited
-3
singlet state. The fluorescence quantum yield of the tautomer of 6 is as low as 10 , but is increased to
.1 by introduction of CHO group at pyrrole ring such as 7.16 The reason why we synthesized and
0
studied the compound 2 is that we may increase the quantum yield of fluorescence emission from the
tautomer of 2. But in these chalcone derivatives CHO group did not increase the fluorescence emission
from the tautomer. Together with the previous reports for chalcone derivatives,10,14 substitution of
electron donating group or electron accepting group in benzene ring somewhat changed the quantum
yield of fluorescence emission of the tautomer produced by intramolecular hydrogen atom transfer, but
-4
the effect is small and the quantum yield is at most in the range of 10 . Among the compounds studied,
heteroaromatic ring such as pyrrole, indole, pyridine and quinoline are ineffective to increase the
fluorescence emission and the non-radiative deactivation seems to be dominant in these chalcones.
Therefore, 2’-hydroxychalcone derivatives are rather stable on photoirradiation and only undergo
intramolecular hydrogen atom transfer reaction in the excited state and finally go back to the stating
material by reverse hydrogen atom transfer in the ground state. The observed fluorescence at ca. 640 nm
can be assigned to the tautomer produced by intramolecular hydrogen atom transfer in the excited singlet
state as shown in Figure 4. As to the photostability of the compounds 1-3, the absorption spectra of 1-3
did not change on irradiation with 395 nm light and is highly stable on photoirradiation.
(a)
(b)
Figure 4. Fluorescence and fluorescence excitation spectra of 1 (a) and 3 (b) in benzene
Table 1. Parameters of absorption and fluorescence spectra of 1-3 in benzene
4
-1
-1
3
Compound Oabs/nm H(OAbs)/10 mol cm dm
O
FL/nm 'Ess/cm
)
FL
-
5
1
2
3
397
385,399
393
2.94
2.88
2.82
642
-
9500
-
≦10
-
636
9400
3.8×10-5

HETEROCYCLES, Vol. 95, No. 2, 2017
975
As described in the part of introduction, chalcones, especially pyrrole or indole derivatives have been
studied as biologically important compounds and are sometimes discussed to produce singlet oxygen by
energy transfer from the excited triplet state chalcone or to produce superoxide anion radical by electron
transfer reaction. We have tried to directly observe the important step of energy transfer to observe the
triplet state of chalcones 1-3, but we could not observe the triplet state of the corresponding chalcones by
laser flash photolysis. Although we could not exclude the small contribution of the involvement of
triplet state chalcones, one could comment that the direct observation of the precursor species should be
essential in discussing the photochemical and photophysical properties of molecules.
From the experimental results, we will propose the potential energy surfaces of deactivation from the
excited singlet state after photoexcitation of 1-3 including the possibility of deactivation through
intramolecular hydrogen bonding and the intersystem crossing to the triplet state (Figure 5). In
conclusion, the compounds studied here did not enhance the quantum yield of fluorescence emission from
neither normal form nor tautomer form and the main deactivation process should be non-radiative
deactivation through intramolecular hydrogen bonding.
Figure 5. Potential energy surfaces of photoinduced hydrogen atom transfer and subsequent processes
EXPERIMENTAL
(
2E)-1-(2-Hydroxyphenyl)-3-(1H-pyrrol-2-yl)-2-propen-1-one (1)22

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To a mixture of pyrrole-2-carboxaldehyde (0.40 g, 4.2 mmol) and 2’-hydroxyacetophenone (0.58 mL, 4.2
mmol) in Et O (5.0 mL) was added a solution of 1 M NaOH (7.5 mL). The solution was stirred for 7 h
2
at 50 °C and then a solution of 1M HCl was added to make neutralized. The resulting mixture was
extracted with EtOAc. The combined organic phases were washed with brine, and then dried over
MgSO , filtered and the solvent was removed under reduced pressure. The orange solid was collected
4
by filtration followed by purification by silica gel column chromatography [eluent: EtOAc / hexane (1:3)].
The solid was recrystallized from EtOH for two times to give the compound 1 (102 mg, 11%) as a yellow
1
needle crystal; H NMR (270 MHz, CDCl
3
): δ = 13.20 (s, 1H, OH), 11.20 (br, 1H), 8.07 (d, J = 7.0 Hz,
1
H), 7.85 (d, J = 15.2 Hz, 1H), 7.68 (d, J = 15.2 Hz, 1H), 7.51 (t, J = 7.0 Hz, 1H), 7.17 (s, 1H), 6.92-6.97
(m, 2H), 6.83 (s, 1H), 6.29 (s, 1H).
5-[3-(2-Hydroxyphenyl)-3-oxo-1-propen-1-yl]-1H-pyrrole-2-carboxaldehyde (2)
To a mixture of 2,5-diformylpyrrole (0.49 g, 4.0 mmol) and 2’-hydroxyacetophenone (4.8 mL, 4.0 mmol)
in THF (4.7 mL) was added a solution of 1 M NaOH (7.0 mL). The solution was stirred for 7 h at 70 °C
and then a solution of 1M HCl was added to make neutralized. The resulting mixture was extracted with
EtOAc. The combined organic phases were washed with brine, and then dried over MgSO4, filtered and
the solvent was removed under reduced pressure. The orange solid was collected by filtration followed
by purification by silica gel column chromatography [eluent: EtOAc / hexane (1:2)]. The solid was
recrystallized from EtOH for two times to give the compound 1 (240 mg, 6%) as an orange needle crystal;
1H NMR (270 MHz, CDCl3): δ = 12.7 (s, 1H, OH), 9.68 (s, br, 1H), 9.62 (s, br, 1H), 7.90 (d, 1H, J = 8.1
Hz), 7.77 (d, J = 16.2 Hz, 1H), 7.56 (d, J = 16.2 Hz, 1H), 7.52 (t, J = 8.1 Hz, 1H), 7.02-7.05 (m, 2H), 6.97
(
t, J = 8.1 Hz, 1H), 6.77-6.78 (m, 1H). Anal. Calcd for C14
H
11NO : C, 69.70; H, 4.60; N, 5.81. Found:
3
C, 69.90; H, 4.64; N, 5.82.

HETEROCYCLES, Vol. 95, No. 2, 2017
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2
,5-Diformylpyrrole23
Step 1
To a solution of benzimidazole (5.9 g, 50 mmol) in acetic anhydride (24 mL) at 100 °C was added
dropwise pyrrole (2.2 mL, 25 mmol) as a solution in acetic anhydride (15 mL) under atmosphere of
nitrogen. The solution was stirred for 7 h at 130 °C, cooled to room temperature, and added hexane (50
mL). The white powder (8.0 g, 68 %) was collected by filtration followed by washing with EtOAc.
Step 2
To a solution of Step 1 product (8.0 g, 17 mmol) in 50 % EtOH (200 mL) at 100 °C was added dropwise
3
M NaOH (30 mL) under atmosphere of nitrogen and the solution was stirred at 100 °C for 3 h. The
resulting mixture was extracted with CHCl and then a solution of 1 M HCl was added to the combined
aqueous phases to make neutralized. The aqueous phase was extracted with EtOAc. The combined
organic phases were washed with brine, and then dried over MgSO , filtered and the solvent was removed
3
4
under reduced pressure. The resulting solid purified by silica gel column chromatography [eluent:
1
CH
2
Cl
2
/ EtOAc (3:1)] to give the desired 2,5-diformylpyrrole as white powder; H NMR (270 MHz,
CDCl
3
): δ = 9.53 (s, 2H), 6.98 (d, J = 2.7 Hz, 2H).
(
2E)-1-(2-Hydroxyphenyl)-3-(1H-indol-3-yl)-2-propen-1-one(3)3

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HETEROCYCLES, Vol. 95, No. 2, 2017
To a mixture of indole-3-carboxaldehyde (0.16 g, 1.1 mmol) and 2’-hydroxyacetophenone (0.12 mL, 1.0
mmol) in EtOH (1.0 mL) was added piperidine (0.10 mL, 1.0 mmol). The solution was stirred for 5 h at
80 °C and the solvent was removed under reduced pressure. The residue was purified by silica gel
column chromatography [eluent: EtOAc / hexane (1:2)]. The solid was recrystallized from EtOH for
1
two times to give the compound 4 (30.4 mg, 12%) as a yellow needle crystal; H NMR(400 MHz,
CDCl
3
): δ = 13.20 (s, 1H, OH), 8.61 (br, 1H), 8.22 (d, J = 15.3 Hz, 1H), 8.03 (dd, J = 6.2 Hz, 4.1 Hz, 1H),
7
7
1
.98 (dd, J = 8.0 Hz, 1.6 Hz, 1H), 7.71 (d, J = 15.3 Hz, 1H), 7.66 (d, J = 2.7 Hz, 1H), 7.50-7.56 (m, 1H),
.47-7.49 (m, 2H), 7.47-7.45 (m, 1H), 7.03 (dd, J = 8.4 Hz, 0.95 Hz, 1H), 6.97 (ddd, J = 8.0 Hz, 7.1 Hz,
.2 Hz, 1H).
MEASUREMENTS
Absorption and fluorescence spectra were measured on a Shimadzu UV-1600 and on a Hitachi F-4500
fluorescence spectrometer, respectively. All solvents of spectral grade for spectroscopy were purchased
and used without further purification. All measurements were carried out at 298 K under Ar. The
concentration of solution for spectroscopy was adjusted so that the absorption maximum at the excitation
wavelength was less than 0.1 for each sample. Fluorescence quantum yields were determined relative to
anthracene ()
f
= 0.27 in ethanol). 1H NMR spectra in CDCl
with TMS as an internal standard were
3
measured on 270 MHz or 400 MHz NMR spectrometer.
REFERENCES
1
.
Y. S. Pandian, K. Venkatesan, R. Gandhidasan, and R. Murugesan, J. Photochem. Photobiol., B,
011, 102, 200.
2
2
.
R. Gaur, D. K. Yadav, S. Kumar, M. P. Darokar, F. Khan, and R. S. Bhakuni, Curr. Top. Med.
Chem., 2015, 15, 1003.
3
4
5
6
7
8
.
.
.
.
.
.
S. Sumathi, P. Tharmaraj, C. D. Sheela, and R. Ebenezer, J. Coord. Chem., 2011, 64, 1707.
T. Arai, M. Moriyama, and K. Tokumaru, J. Am. Chem. Soc., 1994, 116, 3171.
T. Arai and Y. Norikane, Chem. Lett., 1997, 339.
T. Arai and Y. Hozumi, Chem. Lett., 1998, 1153.
Y. Norikane and T. Arai, Chem. Lett., 1999, 909.
Y. Norikane, H. Itoh, and T. Arai, J. Phys. Chem. A, 2002, 106, 2766; Y. Norikane,ꢀN. Nakayama, N.
Tamaoki, T. Arai, and U. Nagashima, J. Phys. Chem. A, 2003, 107, 8659.
S. Tasaki, A. Momotake, Y. Kanna, and T. Arai, Res. Chem. Intermed., 2013, 39, 61.
9
1
1
.
0. K. Kaneda and T. Arai, Photochem. Photobiol. Sci., 2003, 2, 402.
1. K. Kaneda and T. Arai, Org. Biomol. Chem., 2003, 1, 2041.

HETEROCYCLES, Vol. 95, No. 2, 2017
979
1
1
1
1
1
1
1
1
2
2. K. Kaneda, S. Sato, H. Hamaguchi, and T. Arai, Bull. Chem. Soc. Jpn., 2004, 77, 1529.
3. T. Teshima, M. Takeishi, and T. Arai, New J. Chem., 2009, 33, 1393.
4. F. Aizawa, Y. Shinozaki, Y. Ishida, and T. Arai, Heterocycles, 2016, 93, 572.
5. P. Venturella, A. Bellino, and F. Piozzi, Farmaco. Ed. Sci., 1971, 26, 591.
6. D. T. Nguyen and M. T. Nguyen, Tap. Chi. Hoa. Hoc., 1999, 37, 20.
7. Y. U. Mikhail, S. M. Vladimir, and Y. S. Vyacheslav, Chem. Heterocycl. Compd., 2015, 51, 858.
8. P. O. Patil and S. B. Bari, J. Chem., 2013, 637205 (DOI: 10.1155/2013/637205).
9. F. Z. Zhao, Z. D. Qing-Jie, Y.-S. Jin, and W. Zhang, Asian J. Chem., 2011, 23, 5339.
0. F. Mannaa, F. Chimentia, A. Bolascoa, B. Bizzarria, W. Filippellib, A. Filippellib, and L. Gagliardic,
Eur. J. Med. Chem., 1999, 34, 245.
2
2
2
1. A. Ullah, F. L. Ansari, Ihsan-ul-Haq, S. Nazir, and B. Mirza, Chem. Biodivers., 2007, 4, 203.
2. A. K. Mallik, S. P. Dey, F. P. Chattopadhyay, and A. Patra, Tetrahedron. Lett., 2002, 43, 1295.
3. J. Bergman, Tetrahedran Lett., 1972, 46, 4723.