Synthesis and properties of novel extended BODIPYs with rigid skeletons

Article abstract of DOI:10.1016/j.tetlet.2019.01.046

Novel extended BODIPYs fused with bicyclo rings were synthesized from bicyclopyrroles by combining Knoevenagel condensation, Suzuki coupling, and O-chelation. The absorption maxima of the BODIPYs ranged from the visible to near-infrared region and the compounds showed good solubility in organic solvents. The solubility of the bicycloBODIPY with 2-naphthyl groups at the α-position of the pyrrole units was particularly high. Heating converted distyrylBODIPY with bicyclo[2.2.2]octene to benzoBODIPY with absorption (748.5 nm) and fluorescence (775.0 nm) in the near-infrared region.

Full text of DOI:10.1016/j.tetlet.2019.01.046

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Tetrahedron Letters 60 (2019) 707–712
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis and properties of novel extended BODIPYs with rigid skeletons
a
a
a
Yuki Kawamata a, Satoshi Ito a, , Masaru Furuya , Kai Takahashi , Katsuya Namai ,
⇑
Saori Hashimoto a, Makoto Roppongi b, Toru Oba a
a Department of Applied Chemistry, Faculty of Engineering, Utsunomiya University, 7-1-2 Yoto, Utsunomiya, Tochigi 321-8585, Japan
b Advanced Instrumental Analysis Department, Center for Industry-University Innovation Support, Utsunomiya University, 7-1-2 Yoto, Utsunomiya, Tochigi 321-8585, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Novel extended BODIPYs fused with bicyclo rings were synthesized from bicyclopyrroles by combining
Knoevenagel condensation, Suzuki coupling, and O-chelation. The absorption maxima of the BODIPYs
ranged from the visible to near-infrared region and the compounds showed good solubility in organic sol-
Received 6 October 2018
Revised 12 January 2019
Accepted 18 January 2019
Available online 5 February 2019
vents. The solubility of the bicycloBODIPY with 2-naphthyl groups at the a-position of the pyrrole units
was particularly high. Heating converted distyrylBODIPY with bicyclo[2.2.2]octene to benzoBODIPY with
absorption (748.5 nm) and fluorescence (775.0 nm) in the near-infrared region.
Ó 2019 Elsevier Ltd. All rights reserved.
Keywords:
BODIPY
Fluorescent dyes
Knoevenagel condensation
Suzuki coupling
retro-Diels–Alder reaction
Introduction
synthesized BODIPYs with various bicyclic rings from bicyclopy-
rroles via Knoevenagel condensation, Suzuki coupling, O-chelation,
Boron-dipyrromethene (BODIPY) dyes exhibit excellent proper-
ties, such as high photostability, high fluorescence quantum yields,
narrow emission bandwidths, and relatively high absorption coef-
ficients [1]. Therefore, these compounds have been used as laser
dyes [2], fluorescence switching materials [3], and chemical sen-
sors [4]. The absorption characteristics of BODIPY dyes can be
modulated by introducing various substituents [1a]. Although
synthetic methods have been reported that allow access to
conjugated extended BODIPY dyes, these derivatives tend to be
poorly soluble in organic solvents [5]. In general, conjugated BOD-
IPY dyes require bulky substituents, such as mesityl or tert-butyl
groups, to increase their solubility. However, this type of sub-
stituent often distorts the skeleton of the functional molecule
due to steric hindrance. We synthesized novel BODIPY fused bicyc-
lic rings from 1-ethoxycarbonyl bicyclopyrroles 1a–c [6]. BODIPYs
fused with bicyclic rings are expected to have good solubility in
organic solvents because the fused bicyclic skeletons inhibit inter-
and the retro-Diels–Alder reaction.
Results and discussion
Extended BODIPYs 4–6 were obtained as shown in Scheme 1
[9]. The ethoxycarbonyl group of bicyclopyrroles 1a–c was reduced
by refluxing with excess LiAlH4 in THF for 2 h. Resulting 2-methyl
bicyclopyrroles 2a–c were converted to the corresponding dipyrro-
methanes with benzaldehyde in the presence of TFA. The crude
dipyrromethanes were oxidized with DDQ, and then reacted with
boron trifluoride to afford BODIPYs 3a–c. BODIPYs 3a–c exhibited
good solubility in organic solvents, such dichloromethane and
chloroform. The absorption maxima of 3a, 3b, and 3c were deter-
mined as 527, 531.5, and 540 nm, respectively (Fig. 1). The absorp-
tion shifts of BODIPYs 3 were ascribed to the differences in the
fused-ring skeletons, and were influenced by the
r–p hyperconju-
molecular
[7]. Steric hindrance of the bicyclo rings in the lateral direction is
small, so the steric effect on the -conjugated unit could be
reduced by introducing substituents, which should tune the
absorption wavelength by hyperconjugation between the
p-p interactions, similar to normal bulky substituents
gation via the bicyclo[2.2.2]octane units. BODIPY 3c showed the
longest wavelength shift because the phenyl group at the
crosslinking site showed electron withdrawing properties. This
explanation was also supported by the first oxidation potential of
BODIPY 3c being higher than that of BODIPY 3b.
Next, Knoevenagel condensation of 3a–c was performed [6].
The Knoevenagel condensation reaction between 3a and benzalde-
hyde in a mixture of benzene, acetic acid, and piperidine afforded
distyrylBODIPY 4a in 50% yield alongside a trace amount of monos-
p
r-p
BODIPY unit and the condensed bicyclo rings [8]. Therefore, we
⇑
Corresponding author.
E-mail address: s-ito@cc.utsunomiya-u.ac.jp (S. Ito).
https://doi.org/10.1016/j.tetlet.2019.01.046
0040-4039/Ó 2019 Elsevier Ltd. All rights reserved.

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Y. Kawamata et al. / Tetrahedron Letters 60 (2019) 707–712
Scheme 1. Synthesis of extended BODIPYs 4–6.
4, 5, and 6 were redshifted by the introduction of the styryl groups
compared with the precursors 3 (Fig. 2). DistyrylBODIPY 6a, syn-
thesized via the reaction of 3a with methyl 4-formylbenzoate
and 4-nitrobenzoate, was obtained in a low yield compared with
the other distyryl analogues, and an unexpected black powder
was formed. The low yield was attributed to the formation of a
charge-transfer complex between BODIPY 3a and the aldehyde.
The black powder was dissolved in chloroform and the UV absorp-
tion was measured. The solution had a broad absorption in the vis-
ible region specific to the CT complex (Figs. 3 and 4). The 1H NMR
spectrum of the black powder contained a broad signal indicating
the presence of unpaired electrons. In contrast, for BODIPY 3c, the
CT complex was not formed during the same reaction. The steric
hindrance of the benzene ring protruding above and below BODIPY
3c probably prevented the formation of the CT complex.
BicycloBODIPYs 4a, 5a, and 6a were converted to benzoBODIPYs
7a–c by heating at 200 °C for 30 min (Scheme 2), which resulted in
a dramatic redshift in the position of the absorption maximum
(Fig. 5). The absorption and fluorescence maxima of benzoBODIPYs
7a–c were in the near-infrared region. Introducing a methoxy
group (5a) or ethoxycarbonyl group (6a) to the terminal benzene
ring of the styrylBODIPYs resulted in a redshift in the maximum
absorption wavelength of about 15 nm compared with unsubsti-
tuted styrylBODIPY 4a. (UV: 731.5, 745.5, 748.5 nm; FL: 747.0,
761.0, 775.0 nm).
Fig. 1. UV–vis absorption spectra of BODIPYs 3a (red), 3b (blue), and 3c (orange) in
CHCl3. (For interpretation of the references to colour in this figure legend, the reader
is referred to the web version of this article.)
tyrylBODIPY. Upon changing the solvent from benzene to acetoni-
trile, the yield of 4a was improved considerably (73%). This is
because the acidity of the allyl protons was increased by using
an aprotic polar solvent. BicycloBODIPYs 3b and 3c were con-
densed with benzaldehyde in acetonitrile under similar conditions
to afford distyrylBODIPYs 4b and 4c. We also synthesized substi-
tuted distyrylBODIPYs 5 and 6 from 3. The absorption maxima of
BODIPYs 11a–c were synthesized using Suzuki coupling to
introduce the aryl group at the
a-position of the pyrrole
(Scheme 3). First, 2-bromobicyclopyrrole 8 was prepared by treat-
ing pyrrole 1c with N-bromosuccinimide. 2-Arylpyrroles 9a–c
were prepared by Suzuki cross-coupling reactions of 2-bromobicy-
clopyrrole 8 with arylboronic acids. Removal of the ester groups of
pyrroles 9a–c using NaOH afforded compounds 10a–c. Subsequent
condensation of 10a–c with benzaldehyde followed by oxidation
with DDQ and complexation afforded 11a–c.
The UV–vis absorption spectra of 10a–c are shown in Fig. 6. The
absorption maximum of 2-naphthyl derivative 11b occurred at a
longer wavelength than that of 1-naphthyl derivative 11a. It has
Fig. 2. UV–vis absorption spectra of distyrylBODIPY derivatives 4a (red), 4b (blue),
4c (orange), 5a (black solid line), and 6a (black dotted line) in CHCl3. (For
interpretation of the references to colour in this figure legend, the reader is referred
to the web version of this article.)
Fig. 3. Formation of a charge-transfer complex between BODIPY derivative 3a and
methyl benzoate with EWG.

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Y. Kawamata et al. / Tetrahedron Letters 60 (2019) 707–712
709
Fig. 4. UV spectrum of CT complex of BIDOPY 3a and 4-nitrobenzaldehyde in CHCl3.
The synthesis of O-chelate BODIPY 13 was carried out with ref-
erence to a reported method [11], as presented in Scheme 4. A
1.0 M solution of boron tribromide in methylene chloride was
added dropwise to 11c and the resulting mixture was purified by
column chromatography to afford O-chelate BODIPY 13. The
absorption maximum of 13 was redshifted by 73 nm relative to
its precursor, 11c, which was ascribed to the extended conjugation
due to the aromatic ring being fixed on the same plane as the BOD-
IPY skeleton (Fig. 7).
The X-ray crystal structure analysis of 13 is presented in Fig. 8
[12–14]. The O–B–O and N–B–N bond angles were determined as
108.2(1)° and 106.5(1)°, respectively. The bond distances of the
two N–B bonds were found to be 1.513(2) and 1.505(3) Å, whereas
those of the two O–B bonds were found to be 1.466(2) and 1.484(2)
Å. BODIPY derivative 13 and reported bicyclo[2.2.2]octane BODIPY
have similar structures [11]. These results demonstrated that the
fused skeleton has little influence on the structure of the BODIPY
skeleton. In contrast, the maximum absorption wavelength of
BODIPY 13 was redshifted by 13 nm compared with the previously
Scheme 2. Synthesis of benzoBODIPYs 7a–c.
been reported by Schmidt et al. that the 2-naphthyl group leads to
less steric hindrance than the 1-naphthyl group and can contribute
efficiently to conjugated systems [10]. However, the difference in
the absorption maximum depending on the substitution position
was 35 nm for reported BODIPY derivatives, whereas it was as
small as 17 nm for bicycloBODIPY 11b. This smaller difference is
due to the rotation of the naphthyl group being more restricted
for BODIPY 11b as a result of the steric hindrance of the fused-ring
skeleton.
reported BODIPY [11] due to the
r-p hyperconjugation with the
condensed benzene ring through the bicyclo rings.
Fig. 5. Absorption (solid line) and emission (dotted line) spectra of BODIPYs 4a (blue) and 7a (green) in CHCl3. (For interpretation of the references to colour in this figure
legend, the reader is referred to the web version of this article.)

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Y. Kawamata et al. / Tetrahedron Letters 60 (2019) 707–712
Scheme 3. Synthesis of BODIPYs 11a–c.
Fig. 6. UV–vis absorption spectra of BODIPYs 11a (green), 11b (blue), and 11c (red) in CHCl3. (For interpretation of the references to colour in this figure legend, the reader is
referred to the web version of this article.)
truding above and below the plane preventing the intermolecular
interaction of the dye moiety [12]. The fluorescence life-time of
BODIPY 7a-c was very short (<4 ns), but two systems determining
the fluorescence lifetimes were observed.
Because distyrylbenzoBODIPYs 7a,b and 2-naphthylBODIPY 11b
have conjugated extended structures, a second oxidation potential
was observed for these compounds. The oxidation potential of 2-
naphthylBODIPY 11b was much lower than that of 1-naph-
thylBODIPY 11a, suggesting that the
p-conjugation expanded in
Scheme 4. Synthesis of O-chelate BODIPY 13.
2-naphthylBODIPY 11b, which is consistent with the UV measure-
ments. The synthesized BODIPYs showed good solubilities in
organic solvent. The solubility of 2-naphthylBODIPY 11b was par-
ticularly high, and was about 10 times that of 1-naphthylBODIPY
11a. However, the solubility of other extended ring BODIPYs
12a–c (Fig. 9) was greatly reduced by the introduction of 2-naph-
The fluorescence quantum yields (/) of the BODIPYs were not
high for this kind of compound, probably because of
between molecules or self-quenching due to intramolecular energy
transfer. However, the fluorescence lifetimes ( ) of the extended
p-p stacking
s
thyl groups because of increased intermolecular
p-p stacking.
BODIPYs were about 6 ns, which is typical for BODIPYs. O-Chelate
BODIPY 13 had a longer life span than previously reported analogs,
which may be due to the steric hindrance of the benzene rings pro-
Although benzoBODIPY 7a was expected have lower solubility
owing to
(Table 1).
p-p stacking, it showed good solubility in chloroform