Substituents modification of meso-aryl BODIPYs for tuning photophysical properties

Article abstract of DOI:10.1016/j.tet.2017.11.061

We successfully synthesized eight meso-aryl BODIPYs with 2,6-diethyl- or 1,2,6,7-tetraethyl substituents and characterized their photophysical properties. The steric hindrance resulting from the phenolic group in the meso-aryl moiety and the ethyl groups

Full text of DOI:10.1016/j.tet.2017.11.061

Accepted Manuscript
Substituents modification of meso-aryl BODIPYs for tuning photophysical properties
Sangwon Ko, Cheul Yong Kim, Kongara Damodar, Hyun Min Lim, Jin Ho Kim,
Chang-Hee Lee, Jeong Tae Lee
PII:
S0040-4020(17)31220-6
10.1016/j.tet.2017.11.061
TET 29141
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 15 March 2017
Revised Date: 20 November 2017
Accepted Date: 21 November 2017
Please cite this article as: Ko S, Kim CY, Damodar K, Lim HM, Kim JH, Lee C-H, Lee JT, Substituents
modification of meso-aryl BODIPYs for tuning photophysical properties, Tetrahedron (2017), doi:
10.1016/j.tet.2017.11.061.
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ACCEPTED MANUSCRIPT
Graphical Abstract

ACCEPTED MANUSCRIPT
Substituents modification of meso-aryl BODIPYs for tuning photophysical
properties
Sangwon Ko a, *, Cheul Yong Kimb, Kongara Damodarb, Hyun Min Limb, Jin Ho Kimb,
Chang-Hee Leec, and Jeong Tae Leeb, *
aTransportation Environmental Research Team, Korea Railroad Research Institute, Uiwang
16105, Republic of Korea
bDepartment of Chemistry and Institute of Applied Chemistry, Hallym University, Chuncheon
24252, Republic of Korea
cDepartment of Chemistry, Kangwon National University, Chuncheon 24341, Republic of
Korea
*To whom correspondence should be addressed.
E-mail: sko@krri.re.kr (S. Ko), leo900516@gmail.com (J. T. Lee)
Phone: +82-33-248-2071
Fax: +82-33-248-3333
Abstract
We successfully synthesized eight meso-aryl BODIPYs with 2,6-diethyl- or 1,2,6,7-tetraethyl
substituents and characterized their photophysical properties. The steric hindrance resulting
from the phenolic group in the meso-aryl moiety and the ethyl groups on the BODIPY core
affected the synthesis of dipyrromethanes as an intermediate as well as the UV-Vis absorption
and fluorescence emission due to the constrained rotation of the aryl ring. The potential use
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of the meso-hydroxyphenyl BODIPY as a pH sensor was also shown by the pH-dependent
fluorescence emissions.
Keywords: BODIPY, Fluorescent dye, UV/Vis spectroscopy, Fluorescence spectroscopy, pH
sensor
1. Introduction
Fluorescence dyes, typically bearing π-conjugated bonds, have widely been studied in
various areas because of fundamental interest in photo-chemical and -physical processes as
well as technological applications such as analytical sensors, photovoltaic cells, light-emitting
diodes, biomedical imaging, and biomarkers.1–4 For example, cyanine dyes are used to label
biomolecules such as proteins, antibodies, and peptides due to their fluorescence brightness,
photostability, and low nonspecific binding.5 To extend the use of fluorophores in
technologically important fields, the first step will be to understand photophysical properties
depending on the molecular structures and environmental conditions (e.g., solvent polarity
and ions). However, it is difficult to systematically investigate the structure effect of most
organic fluorophores because of limited structural modifications and poor solubility in
common organic solvents.6 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) has
recently received considerable attention due to its favorable photophysical properties, for
example, narrow absorption and emission bands, high molar extinction coefficients,
negligible triplet-state formation, and excellent photostability.7 Furthermore, its facile
structural modification8 and high solubility in organic solvents make it easy to use in various
areas such as molecular probes,2,7,9 photosensitizers,10–12 and chemical sensors.13,14 To date,
there are numerous BODIPY derivatives with different electronic and steric effects on the
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meso-position and periphery of boradiazaindacenes.15–22 For example, electron-withdrawing
substituents at the meso-position lowered the LUMO level leading to bathochromic shifts
with respect to analogues with electron donating substituents. Additionally, the steric pressure
at the 1,3,5,7-substituted BODIPY leads to the loss of its planarity resulting in increased non-
radiative deactivation rates and lower quantum yields compared to the 3,5-substituted
counterparts.14 Though there has been many literature precedents for the BODIPYs with
electron donating methyl groups in positions 3 and 5 on BODIPY core,14,23–25 diethyl
carboxylate substituents in positions 3 and 516 was employed in this work. The introduction
of the diethyl carboxylate ester groups enables BODIPYs to increase water solubility after
hydrolysis of the ester group, leading to facile biological applications. In addition, the
carboxylate group can be converted to amide functional group for further applications, e.g.
metal detection.
In particular, meso-hydroxyphenyl substituted BODIPYs have shown fluorescence on/off
switching through deprotonation and protonation processes.23–27 The emission intensity is
attributed to the photoinduced electron transfer (PET) from the phenolate to the excited-state
indacene acceptor moiety. Thus, it is important to systematically study how photophysical
properties are affected by substituents at the periphery of meso-hydroxyphenyl substituted
BODIPYs. Herein, we investigated the feasibility of synthesizing highly substituted meso-
hydroxyphenyl/phenyl BODIPYs with di- or tetra-ethyl groups on the boradiazaindacenes as
well as their photophysical properties. We successfully synthesized eight meso-aryl
BODIPYs with 2,6-diethyl- or 1,2,6,7-tetraethyl substituents and characterized their quantum
yield including the pH-dependent fluorescence emission.
2. Results and discussion
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2.1. Design and synthesis of BODIPYs
To compare its photophysical properties with BODIPYs having aryl units in the meso
position, meso-unsubstituted BODIPY 1 was synthesized. The periphery of the
dipyrromethene is substituted with different electron driving forces. The 1, 2, 6, and 7
positions are functionalized with ethyl groups, and the 3 and 5 positions are substituted with
carboxylate units. First, ethyl 3,4-diethyl-5-formyl-1H-pyrrole-2-carboxylate was synthesized
from ethyl 3,4-diethyl-1H-pyrrole-2-carboxylate with POCl3 in DMF with a known
procedure (Scheme 1). Then, the aldehyde was condensed with ethyl 3,4-diethyl-1H-pyrrole-
2-carboxylate in the presence of Et3N followed by treatment with BF3•OEt2 to yield BODIPY
dye 1.18,28–30
Scheme 1. Synthesis of meso-unsubstituted BODIPY 1. Reagents and conditions: (i) Ethyl
3,4-diethyl-1H-pyrrole-2-carboxylate, POCl3, Et3N; (ii) BF3•OEt2
After the successful synthesis of meso-unsubstituted BODIPY 1 from ethyl 3,4-diethyl-1H-
pyrrole-2-carboxylate, we then synthesized a series of meso-aryl-substituted BODIPYs 3a-d
with ethyl substituents at the 1, 2, 6, and 7 positions and carboxylate groups at the 3 and 5
positions on the boradiazaindacenes (Scheme 2). The dipyrromethanes 2a-d, which are key
intermediates, were prepared by condensation between the corresponding benzaldehyde and
ethyl 3,4-diethyl-1H-pyrrole-2-carboxylate in the presence of trifluoroacetic acid (TFA) as a
catalyst. Whereas 2a was synthesized in CH2Cl2 (DCM), 2b-2d were prepared in THF, a
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polar solvent, due to the limited solubility of the hydroxybenzaldehydes in CH2Cl2 (DCM).
Products 2a-d were further reacted with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ),
a base, and BF3•OEt2 to yield BODIPYs 3a-d. While Et3N was used in the preparation of 3a
and 3c, N,N-diisopropylethylamine (DIPEA) was used as a base for the 3b and 3d
preparation.
Scheme 2. Synthesis of meso-aryl BODIPY 3a-3d.
As shown in Scheme 2, 3-hydroxybenzaldehyde, 4-hydroxybenzaldehyde and 3,5-
dihydroxybenzaldehyde were successfully condensed with ethyl 3,4-diethyl-1H-pyrrole-2-
carboxylate. However, 2-hydroxybenzaldehyde was unable to produce dipyrromethane. It
was speculated that the steric interference between the 2-hydroxy group of benzaldehyde and
the β-substituent of pyrrole prohibited the formation of dipyrromethane. Because the steric
interference between the 2-hydroxy group of benzaldehyde and the β-substituent of pyrrole
imposes a challenge on the formation of dipyrromethane, the elimination of the steric
hindrance could facilitate the formation of dipyrromethane and BODIPY, sequentially, from
2-hydroxybenzaldehyde. In this sense, the synthesis of BODIPYs bearing ethyl substituents
on the 2 and 6 positions was tried from ethyl 3-ethyl-1H-pyrrole-2-carboxylate (Scheme 3).
Ethyl 3-ethyl-1H-pyrrole-2-carboxylate was prepared according to a previously reported
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method.24 Unfortunately, the condensation of ethyl 3-ethyl-1H-pyrrole-2-carboxylate and
benzaldehyde in the presence of TFA not only suffered from a low yield of 4a but also
produced α,β-connected dipyrromethane 5a resulting in a poor yield (Table 1, entry 1) of the
corresponding BODIPY. Though it was already reported that the yield of dipyrromethane
from the condensation between benzaldehyde and ethyl 3-ethyl-1H-pyrrole-2-carboxylate
was negligible,31 we optimized the reaction condition to improve the yield of 4a. As shown in
Table 1, the only desired product 4a was obtained using 10 or 1 equiv. of TFA (entry 2 and 3),
while the condensation with excess TFA produced 5a as a side product (entry 1). 0.5 equiv.
of methanesulfonic acid (MSA) in CH2Cl2 (DCM) could produce 4a in an optimized yield of
25% without 5a (entry 8). However, p-toluene sulfonic acid (p-TSA), trichloroacetic acid
(TCA), and BF3•OEt2 were not effective for the formation of 4a (entry 4, 5, and 6).
Scheme 3. Synthesis of dipyrromethane from ethyl 3-ethyl-1H-pyrrole-2-carboxylate and
benzaldehyde.
Table 1
Reaction condition optimization for 4a from benzaldehyde (1 equiv.) and ethyl 3-
ethylpyrrole-2-carboxylate (2 equiv.).a
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Acid
Entry
solvent
Yield of 4a (%) Yield of 5a (%)
agent
TFA
TFA
TFA
p-TSA
TCA
equiv.
40
10
1
1
20
0.4
1
2
3
4
5
6
7
8
9
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
Toluene
9
8
10
-
12
-
Trace
b N.R.
c N.A.
12
-
b N.R.
c N.A.
-
BF3·OEt2
MSA
0.25
0.5
0.75
0.5
-
MSA
MSA
MSA
25
20
28
10
5
21
a 1 equiv. of benzaldehyde and 2 equiv. of ethyl 3-ethylpyrrole-2-carboxylate were used. b
N.R.: no reaction; c N.A.: no products, the reaction produced mostly polymers.
With these optimized conditions on hand, a series of dipyrromethane 4a-d were prepared
from 2-, 3- and 4-hydroxybenzalydehyde and subsequently converted to BODIPY 6a-d using
DIPEA as a base. It is worth mentioning that the 2-hydroxyphenyl group in the meso position
of BODIPY 6d is compatible with the 2,6-diethyl units on dipyrromethene due to the
reduction of the steric interference.
The one-pot synthesis for BODIPYs32 was also tried, but we observed numerous by-
products spots on TLC, which led to extremely low yield after column separation (<5 %).
Though we do not have the general hypothesis for the relatively low yields for BODIPY 1,
3d, and 6d compared to other BODIPYs (vide infra), we suggest that the low yield is
generally attributed to the formation of quite a few byproducts and several purification
processes.
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Scheme 4. Synthesis of meso-aryl BODIPY 6a-6d.
2.2. Photophysical properties of BODIPYs
The photophysical properties of the synthesized BODIPYs were investigated in CH2Cl2
solution. As shown in Figure 1 and Table 2, BODIPY 1, 3a-d, and 6a-d have narrow
absorption bands with two absorption maxima. The main absorption at 534 - 554 nm resulted
from the 0-0 band of a strong S0-S1 transition. The 0-1 vibrational band of the same transition
generated the second maximum or shoulder at a short wavelength around 500 nm. In addition,
a considerably weak broad absorption band is found at around 400 nm for the measured
BODIPYs attributed to the S0-S2 transition. The emission spectra of the BODIPYs exhibit
mirror symmetry with the absorption and Stokes-shifted band. Compared with the absorption
spectra of 3a-d, the absorption spectra of 6a-d are red-shifted by 9 to 20 nm due to the
increased π-conjugation of the chromophore 6a-d. The blue-shifted absorption of 3a-d can be
attributed to almost perpendicular configurations between the BODIPY core and the aryl
moiety, which hinders the delocalization of the LUMO into the aryl moiety and the
contribution of the aryl ring to the electronic absorption band.33 The dihedral angle between
the 3-hydroxybenzene and BODIPY moiety is 89.5˚ in the 3c crystal structure (Figure 2)
obtained from X-ray diffraction analysis as observed in sterically hindered BODIPYs.34 The
internal steric interference resulting from the ethyl groups at the 1 and 7 positions also leads
to relatively large Stokes shifts for 3a-d (ꢀῡ = 866 - 933 cm-1) compared to 6a-d (ꢀῡ = 455 -
750 cm-1) shown in the fluorescence emission spectra.
The high absorption coefficient (
) in range of 56,300-107,100 M-1 cm-1 were observed for
ε
the synthesized BODIPYs as shown in Table 2. When compared in BODIPY 3a-3d series,
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the absorption coefficient value of 3c and 3d was lower than 3a and 3b due to steric
hindrance between hydroxyl group in meta- positions and 1,2,6,7-tetraethyl substituents. In
comparison to 3a having 1,2,6,7-tetraethyl on BODIPY core, 6a containing 2,6-diethyl
substituents showed lower absorption coefficient. In the case of BODIPYs with phenolic
group at meso-position, 6b and 6c have much higher absorption coefficients than their 3b and
3c counterparts. We also note the highest absorption coefficients of 107,100 M-1 cm-1 for 6c
among the synthesized BODIPYs.
The quantum yield value, Φf, empirically increases as the π-conjugation and the steric
hindrance between the meso-substituted aryl ring and BODIPY core increase.14,24,34,35 In a
series of BODIPY 3a-d, the larger quantum yield (Φf = 0.27) was observed in 3d bearing
the 3,5-dihydroxyaryl group at meso-position in BODIPY core compared to 3a-c (Φf = 0.16-
0.20). This attributed to reduced non-radiative energy loss due to the decreased free rotation
of dihydroxyaryl group. When compare between 3a-c and 6a-c that has phenolic or aryl
group at same position, slightly higher quantum yield was observed in 3a (Φf = 0.17) and 3c
(Φf = 0.20) than counter partners 6a (Φf = 0.16) and 6c (Φf = 0.12), though 3b (Φf =
0.16) and 6b (Φf = 0.21) showed the contrast tendency. Exceptionally, 6d containing o-
phenolic moiety had the highest quantum yield of 0.54 among 3a-d and 6a-d. The interaction
between the 2-hydroxy group and π-system in the boradiazaindacene core may hinder the free
rotation of the aryl ring, which reduces the excited energy loss via a non-radiative decay
process.33,36 In addition to meso-(2-hydroxyphenyl) BODIPY 6d, it is also worth noting that
meso-unsubstituted BODIPY 1 had the highest quantum yield of 0.54 among all the
synthesized BODIPYs.
Table 2
Photophysical Properties of BODIPY dyes 1, 3a-d, and 6a-d in CH2Cl2.
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BODIPY dyes
ε (M-1 cm-1)
56,300
78,100
71,400
62,300
64,400
68,200
95,300
107,100
65,600
λabs (nm)a
544
λem (nm)b
566
ꢀῡ (cm-1)
715
Φfc
0.54
0.17
0.16
0.20
0.27
0.16
0.21
0.12
0.54
1
534
560
869
3a
3b
3c
3d
6a
6b
6c
6d
534
562
933
534
560
869
535
561
866
548
562
455
544
558
461
549
573
763
554
578
750
a Absorption maximum. b Emission maximum. c Quantum yields (Φf) were determined with
rhodamine 6G as a standard in ethanol (Φf = 0.95) 37
Fig. 1. (a) UV-Vis absorption spectra and (b) fluorescence emission spectra of BODIPYs 1,
3a-d, and 6a-d.
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Fig. 2. Crystal structure of BODIPY 3c. The dihedral angle between the BODIPY core and 3-
hydroxybenzene (deg): 89.5. For full data of crystal 3c, see the Supplementary data.
2.3. pH dependent UV-Vis and Fluoresence studies of BODIPY 6d
Further, we investigated the pH-dependent photophysical properties of 6d, which had the
highest quantum yield among the series of meso-aryl BODIPYs. The absorption spectra of 6d
in several pH conditions are shown in Figure 3a. A hypsochromic shift of the absorption
maximum of 6d from 548 nm at pH 4.06 to 536 nm at pH 12.21 was observed by increasing
the pH. In comparison to the absorption spectra, fluorescence emission spectra of 6d in
aqueous solution show the absence of consistent pH-dependent shifts (Figure 3b). However, a
sizeable increase in fluorescence emission intensity was observed by decreasing the pH down
to 4.06, which can extend imaging applications to cancer markers. A phenolate formed by the
deprotonation of a phenol moiety generates an intramolecular charge transfer (CT) state. The
PET like quenching leads to a low fluorescence intensity in aqueous solution. On the other
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hand, the protonation of a phenoxide ion at a lower pH suppresses the formation of the CT
state and the non-radiative decay process resulting in enhanced fluorescence.25
Fig. 3. (a) Absorption spectra and (b) fluorescence emission spectra (λex = 548 nm of
BODIPY 6d in EtOH-H2O (3:1) as a function of pH.
3. Conclusion
In summary, the highly sterically hindered meso-aryl BODIPY derivatives using ethyl 3,4-
diethyl-1H-pyrrole-2-carboxylate or ethyl 3-ethyl-1H-pyrrole-2-carboxylate were synthesized
and characterized. The steric hindrance resulting from the phenolic group in the meso-
position and the ethyl groups at the 1,7 position affected the synthesis of dipyrromethanes as
an intermediate as well as the UV absorption and fluorescence emission because of the
constrained rotation of the aryl ring. The absorption spectra of 6a-d are red-shifted 9 to 20
nm due to the increased π-conjugation with respect to the absorption spectra of 3a-d. The
internal steric interference resulting from 1,7 diethyl groups of 3a-d BODIPY core also leads
to relatively large Stokes shifts (ꢀῡ = 866 - 933 cm-1) compared to 6a-d (ꢀῡ = 455 - 750 cm-1)
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as shown in the fluorescence emission spectra. Further, meso-hydroxyphenyl BODIPY 6d
showed pH-dependent fluorescence emission intensity, which can be applicable in clinical
trial applications (i.e., cancer markers).
4. Experimental
4.1. Synthesis
4.1.1. Ethyl 3,4-diethyl-5-formyl-1H-pyrrole-2-carboxylate
POCl3 (4.58 mL, 49.2 mmol) was dropped into dimethylformamide (DMF, 3.80 mL, 49.2
mmol) in a round bottom flask, and the mixture was maintained at 40 °C for 15 minutes.
After adding 1,2-dichloroethane (80 mL) to the solution at 0 °C, Ethyl 3,4-diethylpyrrole-2-
carboxylate (8.0 g, 41.0 mmol) in 1,2-dichloroethane (48 mL) was slowly added for 20
minutes. The reaction mixture was refluxed for 30 minutes and then cooled to room
temperature. Sodium acetate (18.48 g, 225.3 mmol) in distilled H2O (160 mL) was added,
and the resulting mixture was refluxed at 100 °C. After 30 minutes, the organic layer was
washed with distilled H2O (100 mL), aq. sat. Na2CO3 solution (100 mL × 2), and brine (100
mL) sequentially. The solvent was dried over Na2SO4 and evaporated in vacuo to give the
desired product ethyl 3,4-diethyl-5-formyl-1H-pyrrole-2-carboxylate as a pale brown solid
(8.28 g, 90.6 %). 1H NMR (300 MHz, CDCl3): δ 9.75 (1H, s), 9.54 (1H, br s) 4.35 (2H, q, J =
7.2 Hz), 2.75 (2H, q, J = 7.5 Hz), 2.74 (2H, q, J = 7.5 Hz), 1.38 (3H, t, J = 7.2 Hz), 1.24 (3H,
t, J = 7.5 Hz), 1.16 (3H, t, J = 7.5 Hz); 13C NMR (75 MHz, CDCl3): δ 179.16, 160.68, 136.35,
133.10, 129.57, 124.21, 61.09, 17.83, 16.97, 15.88, 14.60; mp 48-50°C; MS (EI+) m/z (%):
223 ([M]+, 100 %); HRMS m/z (M+) calcd. for C12H17NO3: 223.1208, Found: 223.1206.
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4.1.2. BODIPY 1
Ethyl 3,4-diethylpyrrole-2-carboxylate (0.46 g, 2.38 mmol) and ethyl 3,4-diethyl-5-formyl-
1H-pyrrole-2-carboxylate (0.58 g, 2.61 mmol) were dissolved in anhydrous dichloromethane
(DCM, 40 mL), and this solution was cooled to 0 °C and stirred for 10 min under nitrogen
atmosphere. POCl3 (0.24 mL, 2.61 mmol) was added slowly to the solution and stirred for 1 h
and then the mixture was warmed to room temperature where stirring continued further 4 h.
Triethylamine (3.32 mL, 23.75 mmol) was added to the mixture and stirred for 15 min.
BF3•OEt2 (2.93 mL, 23.75 mmol) was added dropwise by a syringe to the mixture and
stirring continued another 2 h. After completion of the reaction, the resulting mixture was
diluted with DCM (40 mL) and washed sequentially with aq. sat. NaHCO3 solution, H2O and
brine. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude product
was purified by column chromatography on a silica gel (EtOAC:hexane = 1:3, DCM only,
and EtOAC:hexane = 1:6 in order) to yield the BODIPY 1 (0.075 g, 7.0 %) as a red solid. 1H
NMR (300 MHz, CDCl3): δ 7.32 (1H, s), 4.43 (4H, q, J = 7.2 Hz), 2.65 (4H, q, J = 7.5 Hz),
2.56 (4H, q, J = 7.5 Hz), 1.43 (6H, t, J = 7.2 Hz), 1.21 (6H, t, J = 7.5 Hz), 1.13 (6H, t, J = 7.5
13
Hz); C NMR (75 MHz, CDCl3): δ 161.53, 146.07, 145.61, 134.74, 134.07, 125.94, 61.87,
17.89, 17.79, 17.16, 15.38, 14.00; mp 130-132 °C; MS (EI+) m/z (%): 448 ([M]+, 100 %);
HRMS m/z (M+) calcd. for C23H31BF2N2O4: 448.2345, Found: 448.2347.
4.1.3. Dipyrromethane 2a
TFA (0.374 mL, 4.87 mmol) was added to a mixture of ethyl 3,4-diethylpyrrole-2-
carboxylate (1.0 g, 5.12 mmol) and benzaldehyde (0.260 mL, 2.56 mmol) in anhydrous DCM
(10 mL) under Ar and the resulting mixture was stirred overnight. After completion of the
reaction, the reaction was neutralized with aq. sat. NaHCO3 solution and extracted with DCM
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(2 x 45 mL). The combined organic layer was washed with distilled H2O (2 x 30 mL), brine
(30 mL), dried over Na2SO4 and concentrated in vacuo. The crude product was purified by
column chromatography on a silica gel (EtOAC:hexane = 1:10) to yield the desired product
2a (1.11 g, 91.0 %) as a pale orange liquid which then turned to solid upon kept in the
refrigerator. 1H NMR (300 MHz, CDCl3): δ 8.40 (2H, br s), 7.32-7.24 (3H, m), 7.07 (2H, d, J
= 8.1 Hz), 5.55 (1H, s), 4.21 (4H, q, J = 7.2 Hz), 2.70 (4H, q, J = 7.5 Hz), 2.30 (4H, q, J = 7.5
Hz), 1.31 (6H, t, J = 7.2 Hz), 1.14 (6H, t, J = 7.5 Hz), 0.90 (6H, t, J = 7.5 Hz); 13C NMR (75
MHz, CDCl3): δ 161.52, 139.71, 134.06, 131.71, 129.13, 128.38, 127.60, 123.86, 117.64,
60.01, 40.76, 18.71, 17.44, 16.14, 15.87, 14.72; MS (EI+) m/z (%): 478 ([M]+, 100 %);
HRMS m/z (M+) calcd. for C29H38N2O4: 478.2832, Found: 478.2836.
4.1.4. BODIPY 3a
To a stirred solution of dipyrromethane 2a (0.55 g, 1.15 mmol) in anhydrous DCM (18 mL)
was added a solution of DDQ (0.31 g, 1.38 mmol, 1.2 equiv.) in anhydrous DCM (22 mL) at
room temperature under nitrogen atmosphere and stirred for 1 h. Then, Et3N (2.3 mL) and
BF3•Et2O (3.07 mL) were added sequentially and stirring was continued for overnight. After
completion of the reaction, the reaction mixture was sequentially washed with aq. sat.
NaHCO3 solution, distilled H2O and brine. The organic layer was dried over anhydrous
Na2SO4 and concentrated in vacuo. The crude was purified by column chromatography
(EtOAc:hexane = 1:5)to afford the desired BODIPY 3a (0.34 g, 56 %) as red solid. 1H NMR
(300 MHz, CDCl3): δ 7.50-7.36 (5H, m), 4.45 (4H, q, J = 7.2 Hz), 2.41 (4H, q, J = 7.2 Hz),
1.62 (4H, q, J = 7.3 Hz), 1.43 (6H, t, J = 7.2 Hz), 1.06 (6H, t, J = 7.2 Hz), 0.67 (6H, t, J =
7.3Hz); 13C NMR (75 MHz, CDCl3): δ 162.46, 148.23, 148.06, 145.64, 135.07, 134.02,
132.44, 129.84, 128.46, 128.41, 62.16, 19.01, 17.57, 16.48, 15.50, 14.25; mp 150-152 °C;
MS (EI+) m/z (%): 524 ([M]+, 100 %); HRMS m/z (M+) calcd. for C29H35BF2N2O4: 524.2658,
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Found: 524.2664.
4.1.5. Dipyrromethane 2b
TFA (2.17 mL, 28.34 mmol) was added to a solution of ethyl 3,4-diethylpyrrole-2-
carboxylate (1.0 g, 5.12 mmol) and 4-hydroxybenzaldehyde (0.156 g, 1.28 mmol) in THF (10
mL) under Ar. After the resulting mixture was stirred overnight, the reaction was quenched
with 0.2N NaOH solution. The organic layer was extracted with DCM (40 mL), washed with
distilled H2O (40 mL) and dried over Na2SO4. After evaporation of the solvent in vacuo, the
crude product was purified by column chromatography on a silica gel (DCM:EtOAc = 97:3)
to yield the desired product 2b (0.22 g, 34.9 %) as a red liquid which then turned to solid
upon kept in the refrigerator. 1H NMR (300 MHz, CDCl3): δ 8.54 (2H, br s), 7.18 (1H, br s),
6.89 (2H, d, J = 8.3 Hz), 6.72 (2H, d, J = 8.3 Hz), 4.25 (4H, q, J = 7.1 Hz), 2.70 (4H, q, J =
7.3 Hz), 2.31 (4H, q, J = 7.3 Hz), 1.30 (6H, t, J = 7.1 Hz), 1.14 (6H, t, J = 7.3 Hz), 0.91 (6H, t,
13
J = 7.3 Hz); C NMR (75 MHz, CDCl3): δ 161.82, 155.24, 134.11, 132.41, 130.82, 129.22,
123.57, 117.16, 115.84, 60.03, 39.64, 18.52, 17.18, 15.91, 15.70, 14.47; MS (EI+) m/z (%):
494 ([M]+, 100 %); HRMS m/z (M+) calcd. for C29H38N2O5: 494.2781, Found: 494.2785.
4.1.6. BODIPY 3b
DDQ (0.05 g, 0.22 mmol) was added to the solution of 2b (0.11 g, 0.22 mmol) in DCM (6
mL) under Ar. The solution was stirred for 2 hours, and then, N,N-diisopropylethylamine (0.3
mL, 2.2 mmol) was added. The resulting mixture was refluxed for 30 minutes before
BF3•Et2O (0.4 mL, 3.3 mmol) was added. After 12 hours of refluxing, the red solution was
cooled to room temperature. The reaction was quenched with 1N NaOH solution, and then,
the pH was adjusted to 5~6 with 1N HCl. The organic layer was extracted with DCM (15
mL), washed with distilled H2O (15 mL) and dried over Na2SO4. After evaporation of the
16

ACCEPTED MANUSCRIPT
solvent in vacuo, purification by column chromatography (DCM:EtOAc = 97:3) on a silica
gel yielded BODIPY 3b (0.03 g, 25.0 %) as a red solid. 1H NMR (300 MHz, CDCl3): δ 7.19
(2H, d, J = 8.1 Hz), 6.94 (2H, d, J = 8.1 Hz), 6.27 (1H, br s), 4.45 (4H, q, J = 7.2 Hz), 2.43
(4H, q, J = 7.2 Hz), 1.72 (4H, q, J = 7.3 Hz), 1.42 (6H, t, J = 7.1 Hz), 1.07 (6H, t, J = 7.3 Hz),
0.70 (6H, t, J = 7.3 Hz); 13C NMR (75 MHz, CDCl3): δ 162.49, 157.30, 148.46, 148.14,
145.43, 134.90, 132.79, 129.77, 125.84, 115.42, 62.00, 18.93, 17.41, 16.25, 15.22, 14.04; mp
154-156 °C; MS (EI+) m/z (%): 540 ([M]+, 100 %); HRMS m/z (M+) calcd. for
C29H35BF2N2O5: 540.2607, Found: 540.2609.
4.1.7. Dipyrromethane 2c
TFA (8 mL, 104 mmol) was added to a solution of ethyl 3,4-diethylpyrrole-2-carboxylate
(1.0 g, 5.12 mmol) and 3-hydroxybenzaldehyde (0.130 g, 1.06 mmol) in THF (10 mL) under
Ar. After the resulting mixture was stirred overnight, 0.2N NaOH was added. The product
layer was extracted with DCM (40 mL) and dried over Na2SO4. After evaporation of the
solvent in vacuo, the crude product was purified by column chromatography on a silica gel
(DCM:EtOAc = 97:3) to yield the desired product 2c (0.44 g, 83.7 %) as a bright red solid.
1H NMR (300 MHz, CDCl3): δ 8.81 (2H, br s), 7.07 (1H, t, J = 7.8 Hz), 6.90 (1H, br s), 6.67
(1H, d, J = 7.8 Hz), 6.57 (1H, d, J = 7.8 Hz), 6.54 (1H, br s), 5.49 (1H, s), 4.17 (4H, q, J = 7.1
Hz), 2.69 (4H, q, J = 7.3 Hz), 2.32 (4H, q, J = 7.3 Hz), 1.25 (6H, t, J = 7.1 Hz), 1.13 (6H, t, J
13
= 7.3 Hz), 0.92 (6H, t, J = 7.3 Hz); C NMR (75 MHz, CDCl3): δ 161.72, 156.36, 141.17,
133.96, 131.89, 129.75, 123.76, 119.91, 117.18, 115.06, 114.31, 59.99, 39.94, 18.50, 17.17,
15.87, 15.84, 14.37; MS (EI+) m/z (%): 494 ([M]+, 100 %); HRMS m/z (M+) calcd. for
C29H38N2O5: 494.2781, Found: 494.2781.
4.1.8. BODIPY 3c
17

ACCEPTED MANUSCRIPT
DDQ (0.087 g, 0.38 mmol) was added to the solution of 2c (0.19 g, 0.38 mmol) in DCM
(10 mL) under Ar. The solution was stirred for 2 hours, and then, triethylamine (0.535 mL,
3.83 mmol) was added. The reaction mixture was refluxed for 30 minutes before BF3•Et2O
(0.711 mL, 5.76 mmol) was added. After 12 hours of refluxing, the red solution was cooled to
room temperature. The reaction was quenched with 1N NaOH solution, and then, the pH was
adjusted to 5~6 with 1N HCl. The organic layer was extracted with DCM (20 mL), washed
with distilled H2O (20 mL) and dried over Na2SO4. After evaporation of the solvent in vacuo,
purification by column chromatography (DCM:EtOAc = 99:1 → 9:1) on a silica gel yielded
BODIPY 3c (0.034 g, 16.2 %) as a red solid. 1H NMR (300 MHz, CDCl3): δ 7.30 (1H, t, J =
7.8 Hz), 7.02 (1H, d, J = 6.8 Hz), 6.88 (1H, d, J = 7.8 Hz), 6.83 (1H, s), 6.32 (1H, br s), 4.44
(4H, q, J = 7.0 Hz), 2.41 (4H, q, J = 7.3 Hz), 1.70 (4H, m), 1.42 (6H, t, J = 7.4 Hz), 1.05 (6H,
t, J = 7.4 Hz), 0.71 (6H, t, J = 7.3 Hz); 13C NMR (75 MHz, CDCl3): δ 162.60, 156.05, 148.39,
147.74, 145.08, 135.30, 135.15, 132.36, 129.89, 120.78, 116.97, 115.80, 62.19, 19.06, 17.60,
16.36, 15.39, 14.24; mp 171-173 °C; MS (EI+) m/z (%): 540 ([M]+, 100 %); HRMS m/z (M+)
calcd. for C29H35BF2N2O5: 540.2607, Found: 540.2609.
4.1.9. Dipyrromethane 2d
TFA (9.8 mL, 128 mmol) was added to a solution of ethyl 3,4-diethylpyrrole-2-carboxylate
(0.50 g, 2.56 mmol) and 3,5-dihydroxybenzaldehyde (0.18 g, 1.28 mmol) in THF (5 mL) at
room temperature under nitrogen atmosphere and the resulting mixture was stirred for
overnight. After completion of the reaction, the reaction mixture was neutralized with aq. sat.
NaHCO3 solution and extracted with DCM (2 x 40 mL). The combined organic layer was
washed with distilled H2O (2 x 25 mL), brine (25 mL), dried over anhydrous Na2SO4 and
concentrated in vacuo. The crude was purified by column chromatography (EtOAc:hexane =
1:3 – 1:2) to afford the desired dipyrromethane 2d (0.50 g, 77%) as a pale brown liquid
18

ACCEPTED MANUSCRIPT
which turned to solid upon kept in the refrigerator. 1H NMR (300 MHz, CDCl3): δ 8.76 (2H,
br s), 7.02 (2H, br s), 6.17 (1H, s), 6.08 (2H, s), 5.34 (1H, s), 4.21 (4H, q, J = 7.0 Hz), 2.67
(4H, q, J = 7.2 Hz), 2.30 (4H, q, J = 7.2 Hz), 1.28 (6H, t, J = 7.0 Hz), 1.12 (6H, t, J = 7.2 Hz),
0.92 (6H, t, J = 7.2 Hz); 13C NMR (75 MHz, CDCl3): δ 162.50, 157.58, 141.99, 134.43,
132.44, 124.10, 117.37, 107.92, 102.50, 60.48, 40.36, 18.79, 17.39, 16.13, 16.00, 14.62; MS
(EI+) m/z (%): 510 ([M]+, 100 %); HRMS m/z (M+) calcd. for C29H38N2O6: 510.2730, Found:
510.2730.
4.1.10. BODIPY 3d
To a stirred solution of dipyrromethane 2d (0.54 g, 1.05 mmol) in anhydrous DCM (18 mL)
was added a solution of DDQ (0.29 g, 1.26 mmol, 1.2 equiv.) in anhydrous DCM (22 mL) at
room temperature under nitrogen atmosphere and stirred for 1 h. Then, Et3N (2.11 mL) and
BF3•Et2O (3.31 mL) were added sequentially and stirring was continued for overnight. After
completion of the reaction, the reaction mixture was sequentially washed with aq. sat.
NaHCO3 solution, distilled H2O and brine. The organic layer was dried over anhydrous
Na2SO4 and concentrated in vacuo. The crude was purified by column chromatography
(EtOAc:hexane = 1:1 and EtOAc:DCM = 3:20 in order) to afford the desired BODIPY 3d
(0.04 g, 6.3 %) as a red solid. 1H NMR (300 MHz, Methanol-d4): δ 6.42 (1H, t, J = 2.1 Hz),
6.34 (2H, d, J = 2.1 Hz), 4.39 (4H, q, J = 7.2 Hz), 2.47 (4H, q, J = 7.5 Hz), 1.96 (4H, q, J =
7.5 Hz), 1.39 (6H, t, J = 7.2 Hz), 1.08 (6H, t, J = 7.5 Hz), 0.88 (6H, t, J = 7.5 Hz); 13C NMR
(75 MHz, Methanol-d4): δ 163.99, 160.26, 150.63, 149.99, 146.65, 136.15, 133.16, 108.05,
104.78, 63.29, 19.95, 18.34, 16.98, 15.94, 14.61; mp 210-212 °C; MS (EI+) m/z (%): 556
([M]+, 100 %); HRMS m/z (M+) calcd. for C29H35BF2N2O6: 556.2556, Found: 556.2558.
4.1.11. Dipyrromethane 4a
19

ACCEPTED MANUSCRIPT
MSA (0.04 mL, 0.60 mmol) was added to a solution of ethyl 3-ethylpyrrole-2-carboxylate
(0.40 g, 2.40 mmol) and benzaldehyde (0.12 mL, 1.20 mmol) in DCM (20 mL) at room
temperature under nitrogen atmosphere and the resulting mixture was stirred for overnight.
After completion of the reaction, aq. sat. NaHCO3 solution was added to the mixture to
quench MSA and then extracted with DCM (2 x 30 mL). The combined organic layer was
washed with distilled H2O (2 x 30 mL), brine (30 mL), dried over anhydrous Na2SO4 and
concentrated in vacuo. The crude product was purified by column chromatography
(EtOAc:hexane = 1:7 – 1:6) to yield the desired product 4a (0.13 g, 25 %) as a pale yellow
liquid. 1H NMR (300 MHz, CDCl3): δ 9.40 (2H, br s), 7.33-7.20 (5H, m), 5.77 (2H, d, J = 3.0
Hz), 5.35 (1H, s), 4.18 (4H, q, J = 7.2 Hz), 2.71 (4H, qd, J = 7.5 and 1.5 Hz), 1.30 (6H, t, J =
13
7.2 Hz), 1.14 (6H, t, J = 7.5 Hz); C NMR (75 MHz, CDCl3): δ = 161.94, 140.56, 136.18,
135.16, 128.90, 128.57, 127.49, 118.30, 110.54, 60.19, 44.64, 20.69, 15.06, 14.73; MS (EI+)
m/z (%): 422 ([M]+, 100 %); HRMS m/z (M+) calcd. for C25H30N2O4: 422.2206, Found:
422.2206.
4.1.12. BODIPY 6a
To a stirred solution of dipyrromethane 4a (0.12 g, 0.291 mmol) in anhydrous DCM (4 mL)
was added a solution of DDQ (0.08 g, 0.35 mmol, 1.2 equiv.) in anhydrous DCM (6 mL) at
room temperature under nitrogen atmosphere and stirred for 1 h. Then, Et3N (0.58 mL) and
BF3•Et2O (0.78 mL) were added sequentially and stirring was continued for overnight. After
completion of the reaction, the reaction mixture was diluted with DCM (15 mL) and
sequentially washed with aq. sat. NaHCO3 solution, H2O and brine. The organic layer was
dried over anhydrous Na2SO4 and concentrated in vacuo. The crude was purified by column
chromatography (EtOAc:hexane = 1:5) to afford the desired BODIPY 6a (0.06 g, 47 %) as a
sticky merlot color solid. 1H NMR (300 MHz, CDCl3): δ 7.53 (5H, m), 6.65 (2H, s), 4.46 (4H,
20

ACCEPTED MANUSCRIPT
q, J = 7.1 Hz), 2.61 (4H, q, J = 7.5 Hz), 1.45 (6H, t, J = 7.1 Hz), 1.14 (6H, t, J = 7.5 Hz); 13C
NMR (75 MHz, CDCl3): δ 161.33, 148.42, 145.28, 138.77, 135.23, 133.72, 130.76, 130.38,
129.43, 128.34, 61.94, 19.84, 14.26, 14.06; MS (EI+) m/z (%): 468 ([M]+, 100 %), HRMS m/z
(M+) calcd. for C25H27BF2N2O4: 468.2032, Found: 468.2035.
4.1.13. Dipyrromethane 4b
MSA (0.09 mL, 1.18 mmol) was added to a solution of ethyl 3-ethylpyrrole-2-carboxylate
(0.2 g, 1.20 mmol) and 4-hydroxybenzaldehyde (0.07 mL, 0.60 mmol) in DCM (2 mL) under
Ar. After the resulting mixture was stirred overnight, the reaction was quenched with 0.2N
NaOH solution. The organic layer was extracted with DCM (20 mL), washed with distilled
H2O (20 mL) and dried over Na2SO4. After evaporation of the solvent in vacuo, the crude
product was purified by column chromatography on a silica gel (EtOAc:hexane = 1:6) to
1
yield the desired product 4b (0.136 g, 52.2 %) as a reddish liquid. H NMR (300 MHz,
CDCl3): δ 9.14 (2H, br s), 7.01 (2H, d, J = 8.4 Hz), 6.72 (2H, d, J = 8.4 Hz), 6.39, (1H, br s),
5.81 (2H, d, J = 2.4 Hz), 5.27 (1H, s), 4.22 (4H, q, J = 7.0 Hz), 2.72 (4H, q, J = 7.5 Hz), 1.30
13
(6H, t, J = 7.0 Hz), 1.15 (6H, t, J = 7.5 Hz); C NMR (75 MHz, CDCl3): δ 162.24, 155.27,
136.74, 135.54, 132.06, 129.62, 118.09, 115.86, 110.42, 60.38, 43.73, 20.72, 15.06, 14.72;
MS (EI+) m/z (%): 438 ([M]+, 100 %), HRMS m/z (M+) calcd. for C25H30N2O4: 438.2155,
Found: 438.2152.
4.1.14. BODIPY 6b
To a stirred solution of dipyrromethane 4b (0.19 g, 0.43 mmol) in anhydrous DCM (7 mL)
was added a solution of DDQ (0.12 g, 0.51 mmol, 1.2 equiv.) in anhydrous DCM (13 mL) at
room temperature under nitrogen atmosphere and stirred for 1 h. Then, Et3N (0.85 mL) was
added and after 5 min stirring, BF3•Et2O (1.14 mL) was added dropwise. The resulting
21

ACCEPTED MANUSCRIPT
mixture was stirred for overnight. After completion of the reaction, the reaction mixture was
diluted with DCM (35 mL) and washed sequentially with aq. sat. NaHCO3 solution, H2O and
brine. The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo. The
crude was purified by column chromatography (EtOAc:hexane = 1:2 and DCM:MeOH =
98:2 in order) to afford the desired BODIPY 6b (0.11 g, 54 %) as a sticky merlot color solid.
1H NMR (300 MHz, CDCl3): δ 7.34 (2H, d, J = 8.7 Hz), 7.09 (1H, br s), 7.01 (2H, d, J = 8.7
Hz), 6.69 (2H, s), 4.46 (4H, q, J = 7.2 Hz), 2.61 (4H, q, J = 7.5 Hz), 1.44 (6H, t, J = 7.2 Hz),
1.14 (6H, t, J = 7.5 Hz); 13C NMR (75 MHz, CDCl3): δ 162.02, 159.71, 149.34, 144.45,
138.81, 135.38, 132.87, 129.73, 125.91, 116.02, 62.31, 20.10, 14.50, 14.30; MS (EI+) m/z (%):
484 ([M]+, 100 %), HRMS m/z (M+) calcd. for C25H27BF2N2O5: 484.1981, Found: 484.1981.
4.1.15. Dipyrromethane 4c
MSA (0.19 mL, 2.92 mmol) was added to a solution of ethyl 3-ethylpyrrole-2-carboxylate
(0.40 g, 2.40 mmol) and 3-hydroxybenzaldehyde (0.15 g, 1.20 mmol) in DCM (5 mL) at
room temperature under nitrogen atmosphere and the resulting mixture was stirred for
overnight. After completion of the reaction, aq. sat. NaHCO3 solution was added to the
mixture to quench MSA and extracted with DCM (2 x 35 mL). The combined organic layer
was washed with distilled H2O (2 x 30 mL), brine (30 mL), dried over anhydrous Na2SO4 and
concentrated in vacuo. The crude product was purified by column chromatography
(EtOAc:hexane = 1:4) to afford the desired product 4c (0.31 g, 60 %) as a pale brown oil. 1H
NMR (300 MHz, CDCl3): δ 9.45 (2H, br s), 7.13 (1H, t, J = 7.8 Hz), 6.77-6.68 (3H, m), 6.14
(1H, br s), 5.78 (2H, d, J = 2.4 Hz), 5.26 (1H, s), 4.18 (4H, q, J = 7.0 Hz), 2.70 (4H, q, J = 7.5
Hz), 1.29 (6H, t, J = 7.0 Hz), 1.13 (6H, t, J = 7.5 Hz); 13C NMR (75 MHz, CDCl3): δ 162.22,
156.25, 142.09, 136.20, 135.38, 130.01, 120.70, 118.19, 115.48, 114.60, 110.58, 60.36, 44.40,
20.71, 15.01, 14.69; MS (EI+) m/z (%): 438 ([M]+, 100 %), HRMS m/z (M+) calcd. for
22

ACCEPTED MANUSCRIPT
C25H30N2O5: 438.2155, Found: 438.2153.
4.1.16. BODIPY 6c
To a stirred solution of dipyrromethane 4c (0.4 g, 0.91 mmol) in anhydrous DCM (10 mL)
was added a solution of DDQ (0.25 g, 1.09 mmol, 1.2 equiv.) in anhydrous DCM (25 mL) at
room temperature under nitrogen atmosphere and stirred for 1 h. Then, Et3N (1.83 mL) was
added and after 5 min stirring, BF3•Et2O (2.43 mL) was added dropwise. The resulting
mixture was stirred for overnight. After completion of the reaction, the reaction mixture was
diluted with DCM (50 mL) and washed sequentially with aq. sat. NaHCO3 solution, H2O and
brine. The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo. The
crude was purified by column chromatography (EtOAc:hexane = 1:2 and DCM:MeOH =
98:2 in order) to afford the desired BODIPY 6c (0.17 g, 38 %) as sticky merlot color solid.
1H NMR (300 MHz, CDCl3): δ 7.34 (1H, t, J = 8.1 Hz), 7.09 (1H, dt, J = 8.1, 1.2 Hz), 6.99-
6.97 (2H, m), 6.70 (2H, s), 6.35 (1H, br s), 4.43 (4H, q, J = 7.0 Hz), 2.57 (4H, q, J = 7.5 Hz),
13
1.42 (6H, t, J = 7.0 Hz), 1.11 (6H, t, J = 7.5 Hz); C NMR (75 MHz, CDCl3): δ 161.72,
156.11, 148.53, 145.36, 139.00, 135.43, 135.02, 129.90, 129.78, 122.90, 118.34, 117.60,
62.29, 20.09, 14.46, 14.27; MS (EI+) m/z (%): 484 ([M]+, 100 %); HRMS m/z (M+) calcd. for
C25H27BF2N2O5: 484.1981, Found: 484.1983.
4.1.17. Dipyrromethane 4d
MSA (0.04 mL, 0.60 mmol) was added to a solution of ethyl 3-ethylpyrrole-2-carboxylate
(0.40 g, 2.40 mmol) and 2-hydroxybenzaldehyde (0.13 mL, 1.20 mmol) in DCM (5 mL) at
room temperature under nitrogen atmosphere and the resulting mixture was stirred for
overnight. After completion of the reaction, aq. sat. NaHCO3 solution was added to the
mixture to quench MSA and extracted with DCM (2 x 30 mL). The combined organic layer
23

ACCEPTED MANUSCRIPT
was washed with distilled H2O (2 x 30 mL), brine (30 mL), dried over anhydrous Na2SO4 and
concentrated in vacuo. The crude product was purified by column chromatography
(EtOAc:hexane = 1:3) to afford the desired product 4d (0.26 g, 49 %) as a pale brown liquid.
1H NMR (300 MHz, CDCl3): δ 9.26 (2H, br s), 7.13-7.04 (2H, m), 6.87-6.78 (2H, m), 6.64
(1H, br s), 5.86 (2H, d, J = 2.7 Hz), 5.56 (1H, s), 4.22 (4H, q, J = 7.2 Hz), 2.72 (4H, q, J = 7.5
Hz), 1.29 (6H, t, J = 7.2 Hz), 1.15 (6H, t, J = 7.5 Hz); 13C NMR (75 MHz, CDCl3): δ 162.09,
153.36, 135.84, 135.48, 130.11, 128.96, 126.88, 121.29, 118.06, 116.60, 110.25, 60.32, 39.72,
20.70, 15.07, 14.72; MS (EI+) m/z (%): 438 ([M]+, 100 %); HRMS m/z (M+) calcd. for
C25H30N2O5: 438.2155, Found: 438.2151.
4.1.18. BODIPY 6d
To a stirred solution of dipyrromethane 4d (0.38 g, 0.88 mmol) in anhydrous DCM (13 mL)
was added a solution of DDQ (0.24 g, 1.05 mmol, 1.2 equiv.) in anhydrous DCM (17 mL) at
room temperature under nitrogen atmosphere and stirred for 1 h. Then, Et3N (1.76 mL) and
BF3•Et2O (2.34 mL) were added sequentially and stirring was continued for overnight. After
completion of the reaction, the reaction mixture was diluted with DCM (30 mL) and
sequentially washed with aq. sat. NaHCO3 solution, H2O and brine. The organic layer was
dried over anhydrous Na2SO4 and concentrated in vacuo. The crude was purified by column
chromatography (EtOAc:hexane = 1:3 and EtOAc:DCM = 1:20 in order) to afford the desired
1
BODIPY 6d (0.05 g, 12 %) as a sticky merlot color solid. H NMR (300 MHz, CDCl3): δ
7.40 (1H, t, J = 7.5 Hz), 7.18 (1H, d, J = 7.8 Hz), 7.05-7.00 (2H, m), 6.62 (2H, s), 5.78 (1H,
br s), 4.46 (4H, q, J = 7.0 Hz), 2.59 (4H, q, J = 7.3 Hz), 1.43 (6H, t, J = 7.0 Hz), 1.11 (6H, t, J
13
= 7.3 Hz); C NMR (75 MHz, CDCl3): δ 161.53, 153.54, 145.88, 144.52, 139.22, 135.75,
132.18, 131.60, 129.33, 120.42, 120.32, 117.06, 62.27, 20.06, 14.36, 14.28; MS (EI+) m/z (%):
484 ([M]+, 100 %); HRMS m/z (M+) calcd. for C29H35BF2N2O4: 484.1981, Found: 484.1984.
24

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4.2. Measurements and Characterization
1
NMR spectra were recorded on the Varian Gemini 300 FT-NMR 300 MHz for H and 75
MHz for 13C with the chemical shifts (δ) reported in parts per million (ppm) relative to TMS
and the coupling constants (J) quoted in Hz. CDCl3, DMSO-d6, and CD3OD were used as
solvents with TMS as an internal standard. UV absorptions were measured on the Shimadzu
UV-1800 spectrometer, and fluorescence emissions and quantum yield were recorded on the
Perkin Elmer LS-55B fluorescence spectrometer and Agilent Cary Eclipse Fluorescence
Spectrophotometer, respectively. Rhodamine 6G was used as the reference for the quantum
yield. The Origin 8 program was used to analyze the spectra. Single crystal X-ray diffraction
data were collected on a Bruker D8 Venture diffractometer, with Mo Kα radiation (λ =
0.71073 Å). Mass spectra were acquired on the Jeol JMS-700 in the central laboratory at
Kangwon National University.
Acknowledgments
This study was supported by the Basic Science Research Program through the National
Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and
Technology (2012R1A1A1013930 and 2017R1D1A1A02018831, Prof. Jeong Tae Lee) and
(2015R1A2A1A10052586, Prof. Chang-Hee Lee). S. Ko acknowledges financial support
from the R&D Program of the Korea Railroad Research Institute, Republic of Korea. We
thank Philjae Kang for solving X-ray crystal structure of 3c.
25

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Supplementary data
Supplementary data related to this article can be found at http://dx.doi.org/(will be filled).
CCDC-1539238 (3c) contains the supplementary crystallographic data for this paper. These
data can be obtained free of charge via http://ccdc.cam.ac.uk/conts/retrieving.html (or from
the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033; e-mail:
deposit@ccdc.cam.ac.uk).
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