Red to Near-Infrared Isoindole BODIPY Fluorophores: Synthesis, Crystal Structures, and Spectroscopic and Electrochemical Properties

Article abstract of DOI:10.1021/acs.joc.6b00414

A series of high-performance fluorophores named isoindole boron dipyrromethenes (BODIPYs) containing either symmetrical or unsymmetrical alkyl substitution patterns on pyrrole rings were synthesized by an efficient process and were characterized by X-ray

Full text of DOI:10.1021/acs.joc.6b00414

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Article
Red to Near-Infrared Isoindole BODIPY Fluorophores: Synthesis,
Crystal Structures, Spectroscopic and Electrochemical Properties
Changjiang Yu, Qinghua Wu, Jun Wang, Yun Wei, Erhong Hao, and Lijuan Jiao
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00414 • Publication Date (Web): 31 Mar 2016
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Red to Near-Infrared Isoindole BODIPY
Fluorophores: Synthesis, Crystal Structures,
Spectroscopic and Electrochemical Properties
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Changjiang Yu, Qinghua Wu, Jun Wang, Yun Wei, Erhong Hao* and Lijuan Jiao*
The Key Laboratory of Functional Molecular Solids, Ministry of Education; Anhui Laboratory of
Molecule-Based Materials; School of Chemistry and Materials Science, Anhui Normal University,
Wuhu, China 241000.
*
To whom correspondence should be addressed.
E-mail: haoehong@ahnu.edu.cn, jiao421@ahnu.edu.cn
Abstract Graphic
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Abstract: A series of high-performance fluorophores named isoindole BODIPYs containing either
symmetrical or unsymmetrical alkyl substitution patterns on pyrrole rings were synthesized by an
efficient process and were characterized by X-ray diffraction, spectroscopic and electrochemical
analysis. Most of these dyes show strong sharp absorption and bright fluorescence emission in the
red to near infrared (NIR) region (up to 805 in acetonitrile). Pyrrolic alkyl substitutions lead to the
increase of the HOMO and the LUMO energy levels, and the overall decrease of the energy band
gaps of the dye. Among the tweenty-three isoindole-BODIPY dyes synthesized, solvent-dependent
fluorescence emission and life-time decay were only observed for those containing 3-methyl
substituent on the uncoordinated pyrrole ring, while few varitaion of the fluorescence intensity was
observed for the rest of the dyes upon changing the polarity of the solvent. These resultant dyes can
be further functionalized via the Knoevenagel condensation on the -methyl substituent of the
chromophore to install a variety of functionalities, including dimethylamine group demonstrated in
this work. This dimethylamine functionalized isoindole BODIPY shows weak fluorescence at 805
nm in acetonitrile and a ratiometric “turn-on” NIR fluorescence response to the decrease of pH.
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Introduction
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Bright fluorescent dyes, especially those emitting in the red to near-infrared (NIR) region, are
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valuable for applications in biological system. Great efforts have been devoted to the fine tuning of
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the photophysical and photochemical properties of many chromophores to achieve novel types of
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far-red to NIR organic fluorophores. Boron dipyrromethenes (BODIPYs, Figure 1) have received
increasing research interests in the past three decades because of their excellent optical properties
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and easy accessibility, and have been widely applied as laser dyes, fluorescence labeling agents,
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sensors, fluorescent switches, photovoltaics/optoelectronics and photosensitizers in a varity of
fields.
Figure 1. Structure of BODIPY core (A), commercialized BODIPYs 576/589 and 650/665 marketed by Invitrogen, and isoindole BODIPYs
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1a, 5a, 1d, 1f and 7a previously communicated by us. Spectroscopic data were recorded in dichloromethane.
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Classical BODIPYs generally absorb/emit at around 500 nm. Besides the fusion of aromatic
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moieties onto the pyrrolic position of the chromophore,
extending the conjugation at the
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is a common way to achieve long wavelength NIR BODIPYs as already
demonstrated by the two commercialized long wavelength BODIPYs (576/589 and 650/665, Figure
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1). However, the synthesis of these 3-pyrrole substituted BODIPYs although elegant, generally
requires lengthy synthetic steps, the preparation of highly reactive intermediates, or the use of
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expensive metal catalysts. Recently, we have communicated a one-pot synthesis of nine isoindole
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BODIPYs with symmetrical substitution patterns of pyrrole rings in good to excellent yields based
on a POCl -promoted condensation of 3-chloro-1-formylisoindole 3 with suitable pyrroles (or
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indoles) (Scheme 1, route a). These isoindole BODIPYs show strong absorption and emission
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bands centred at 570-650 nm, which can be further tuned to NIR region via classic Knoevenagel
condensation. Alberto and Simone performed theoretical calculations on the spin-orbit matrix
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elements between singlet and triplet excited state wave functions for these isoindole BODIPYs.
We have found that alkyl substitutions at both the pyrrole rings and the meso-position greatly can
affect the absorption and emission bands of these isoindole BODIPYs in dichloromethane, with a
red-shift for pyrrolic substitution(s) and a blue-shift for meso-substitution (Figure 1). Interestingly,
isoindole BODIPY 5a with unsymmetrical alkyl substitution pattern of pyrrole ring gives not only a
red-shift of the spectra but also an enhanced fluorescence quantum yield with respect to 1a (Figure
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). These interesting preliminary spectroscopic results promoted us to further synthesize a set of
isoindole BODIPYs 5 with unsymmetrical alkyl substitution pattern of pyrrole rings (Scheme 2), and
performed a detailed comparative studies on their X-ray diffraction, spectroscopic and
electrochemical properties with isoindole BODIPYs 1 possessing symmetrical substitution patterns
of pyrrole rings (Figure 2). We also report a new synthetic route to BODIPYs 1 from the direct
condensation of 3-chloro-isoindolylidene-N,N-dimethyl(m)ethanamine with suitable pyrroles or
indoles (Scheme 1, route b).
Results and Discussions
Synthesis:
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of pyrrole rings were obtained via the condensation of 3-chloro-1-formylisoindole 3a with excess
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amount of suitable pyrrole derivatives (Scheme 1, route a). In this work, we demonstrated the step to
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hydrolyze 2 to generate 3a can be skipped, by directly applying 2 for the condensation reaction
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Scheme 1, route b). This condensation requires comparatively higher temperature (80 C, in
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,2-dichloroethane), from which the desired isoindole BODIPYs 1a-h (Figure 2) were isolated with
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a comparable (20-52%) yields to our previous report . However, at room temperature, it mainly
generates the BF complexes of dipyrromethenes. It is noteworthy that electron-deficient pyrroles
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and indoles give comparatively low yield (20-24% for 1a, 1e and 1f) in comparison to those alkyl
substituted pyrroles (38-52% for 1b-d and 1g-h) for this reaction.
Scheme 1. Synthetic outes for isoindole BODIPYs 1a-h with symmetrical substitution patterns of pyrrole rings: route a, our previously communicated
method; route b, new synthetic route presented in this work.
Figure 2. The yields for isoindole BODIPYs 1a-h using route b in Scheme 1.
In order to study the scope of this reaction and structure-property relationship of these isoindole
BODIPYs, 5a-i with unsymmetrical substitution patterns of pyrrole rings were synthesized
according to Scheme 2. Key -chlorodipyrromethenes 6a-c were generated in 79-90% yields from
the condensation of 3 with alkyl substituted pyrrole in the presence of POCl . Subsequent
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nucleophilic substitution of -chlorodipyrromethenes 6 smoothly proceeded with excess amounts of
pyrrole and indole derivatives and gave isoindole BODIPYs 5a-i in 29-54% isolated yields.
However, the reaction time varies from 10 minutes to 12 hours depending on the electronic
properties of the nucleophile. For example, this reaction complishes within 10 minutes in case of
electron-rich 2,4-dimethyl-3-ethylpyrrole, while it requires 6-12 hours when N-alkyl substituted,
unsubstituted pyrrole or indole was used. In contrast, highly electron-deficient 2-nitropyrrole did not
react at all in this reacton.
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Scheme 2. Synthesis and yields of isoindole BODIPYs 5a-i with unsymmetrical substitution patterns of pyrrole rings.
These resultant isoindole BODIPYs can be easily further functionalized via the Knoevenagel
condensation to install a variety of functionalities, for example carboxylic ester groups (Figure 3)
which upon hydrolysis can be used as tethering group for bioimaging and labeling. Considering that
dimethylamino group is a fragment frequently used to tune the photophysical properties of
chromophores via either an intramolecular charge transfer (ICT) or a photoinduced electron transfer
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we further applied 1d for the Knoevenegal condensation with
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-(dimethylamino)benzaldehyde 8 to generate 7f in 75% yield (Scheme 3), which shows weak
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fluorescence at 805 nm in acetonitrile and a ratiometric “turn-on” NIR fluorescence upon the
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Figure 3. Structure and yields of isoindole BODIPYs 7a-e.
Scheme 3. Synthesis and yield of isoindole BODIPY 7f from Knoevenagel reaction of isoindole BODIPY 1d.
X-Ray Crystal structure analysis:
Single crystals suitable for X-ray analysis for isoindole BODIPYs 1a, 1b, 1h, 5b, 5d, 5e, 5f, 5g and
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i were obtained from the slow evaporation of their dichloromethane/hexane solutions (1a, 1b, 1h,
d, 5e and 5g) or the slow diffusion of hexane into their concentrated dichloromethane solutions (5b,
f and 5i). The ORTEP plots of these isoindole BODIPYs are given with thermal ellipsoids at 30%
probability level (Figures S1-7 in the supporting information). As shown in Figure 4, the plane
defined by F-B-F atoms is perpendicular to the C N B core as usual for these isoindole BODIPYs.
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As summarized in Table S2 (Supporting information), the B-N distance for these isoindole
BODIPYs is in the range of 1.515-1.577 Å, indicating a usual delocalization of positive charge. All
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similar to our previously reported isoindole-BODIPYs 1c and 1f. A gradual increase of the
dihedral angle between uncoordinated pyrrole and the BODIPY core was observed from 1a (11.6(2)
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to 5d (22.2(2) ), 1b (23.9(2) ), 5c (28.5(2) ), 5i (31.0(2) ), 5e (36.5(2) ) and 1h (41.0(2) ),
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respectively with the increase of alkyl substitutions onto the uncoordinated pyrrole of these isoindole
BODIPYs. A further increase of the dihedral angle was observed in the indole, 3-methylindole and
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N-methyl substituted isoindole BODIPYs 5f (46.6(2) ), 5g (48.3(2) ) and 5b (53.1(2) ).
Figure 4. Top view and side view of the X-ray structures of isoindole BODIPYs (a) 1a, (b) 1b, (c) 1h, (d) 5b, (e) 5d, (f) 5f, (g) 5g, (h) 5e and (i) 5i. C,
light gray; H, gray; N, blue; B, dark yellow; F, green.
As shown in Figure 4, various hydrogen bondings were observed between fluorine atoms and the
hydrogens from uncoordinated pyrrole and pyrrolic methyl unit due to the strong electron negativity
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of the F atom in these dyes. As summarized in Table S2, the bond distances for these hydrogen
bondings is in the range of 1.738-2.850 Å. The various intramolecular and intermolecular hydrogen
bonding between the hydrogen of pyrrolic methyl substituent and the fluorine atoms restricts the free
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rotation of the 3-pyrrole/indole substituents, enhances the rigidity of these dyes, and forms
correspoding dimers. The weak interactions between these dimers help to establish crystal packing
structures for these isoindole BODIPYs through from F atoms and hydrogen atoms on aromatic
rings and make them nearly parallel to each other in a head-to-head orientation as demonstrated by
1a, and 5b in Figure S8 and Figure S9 (Supporting information).
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Spectroscopic properties:
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Figure 5. Overlaid and normalized (a) absorption and (b) fluorescence emission spectra of 1a-d, 1f and 7a in dichloromethane.
These isoindole BODIPYs show red to blue color under ambient light and bright red fluorescence
upon irradiation by UV light at 365 nm of a hand-hold UV lamp in hexane, toluene, dichloromethane,
tetrahydrofuran, acetonitrile and methanol. As summarized in Table 1, all these isoindole BODIPYs
show significantly red shifted absorption and emission spectra with respect to the BODIPY core
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A ). Among those, isoindole BODIPYs 1 each show fairly well to excellent fluorescence quantum
yields (from 0.61 to 0.99) in dichloromethane, except 1e ( = 0.08) containing two 3-methylindole
moieties. A gradual red-shift was observed from 1a (570/599 nm) to 1b (600/624 nm), 1c (609/631
nm) and 1d (629/650 nm) with the increase of the alkyl substitutions on the pyrrole rings (Figure 5).
This red-shift observed in 1d (629/650 nm) is even greater than that of indole containing 1e (611/648
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nm). By contrast, a blue-shift (7-11 nm) was observed when the methyl substitution took place at the
meso-position, as demonstrated by 1f in Figure 5.
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A similar gradual red-shift of the absorption and emission band was also observed from 5a
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602/621 nm) to 5d (608/629 nm) and 5e (616/640 nm) with the increase of alkyl substitutions on the
uncoordinated pyrrole rings (Figure 6). By contrast, N-alkyl substitution leads to a 10-17 nm
blue-shift of the spectra with respect to 5a in dichloromethane as demonstrated by 5b in Figure 6. As
expected, 3-methylindole substituted 5e shows an around 35 nm red-shift of the spectra in
dichloromethane with respect to the less conjugated 5f.
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Figure 6. Overlaid and normalized (a) absorption and (b) fluorescence emission spectra of 5a, 5b, 5d and 5e in dichloromethane.
Isoindole BODIPYs 7a-f show a strong NIR absorption (centred at around 680-725 nm) and
emssion (centred at around 705-770 nm) in dichloromethane, which is red shifted with respect to the
commercialized BODIPY 650/665 (Figure 1). Among those, 7f showed an around 75 and 105 nm
red-shift of the absorption and emission spectra in dichloromethane.
Fluorescent decay profiles for isoindole BODIPYs 1, 5 and 7 are either a monomeric or a
bi-exponential function, with lifetimes in the range of 1.22-8.89 ns in anhydrous
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Table 1. Photophysical properties of BODIPYs 1, 5 and 7 in dichloromethane at room temperature.
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
max
max
d
e
f
g
λ
abs
ε
λ
em
Stokes shifts
 
K
f
K
nr
c
dyes
Φ
a
-1 -1
b
-1
9
-1
9
-1
(
nm)
(cm M )
(nm)
(cm )
(ns)
(× 10 s
)
(× 10 s
)
h
A
503
570
600
609
629
611
563
599
619
602
585
584
608
616
581
608
616
605
680
675
608
676
585
725
-
512
599
624
631
650
648
592
625
645
621
611
611
629
640
606
631
634
629
705
714
687
733
631
770
0.90
0.80
0.79
0.61
0.73
0.08
0.91
0.80
0.72
0.87
0.99
0.99
0.89
0.86
0.98
0.85
0.66
0.92
0.75
0.68
0.014
0.012
0.003
0.13
349
849
641
573
514
935
870
694
651
508
727
757
549
609
710
600
461
631
521
809
1891
1150
1246
806
-
-
-
1
1
a
4.65
4.46
4.87
4.91
4.99
4.88
4.96
5.07
4.93
4.83
4.72
4.79
4.95
4.89
4.90
4.45
4.85
4.94
4.76
3.92
5.16
4.63
4.80
6.66
8.11
6.40
6.30
1.22
6.71
7.30
6.21
7.28
6.91
8.89
6.65
4.93
6.42
3.27
6.41
5.75
5.14
4.63
3.07
4.82
7.58
2.30
0.12
0.10
0.10
0.12
0.07
0.14
0.11
0.12
0.12
0.14
0.11
0.13
0.19
0.15
0.26
0.10
0.16
0.15
0.15
0.01
0.03
0.03
0.06
0.04
0.75
0.01
0.03
0.05
0.02
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
b
1
c
1
d
1
e
1
f
1
g
1h
5
5
a
b
0.001
0.001
0.02
0.01
0.003
0.05
0.05
0.01
0.05
0.07
0.32
0.21
0.13
0.38
5c
5
d
5
e
5f
5
5
g
h
5i
7
7
a
b
7c
7
d
0.003
0.0004
0.06
7
e
7f
[
a]
c]
[b]
All of values correspond to the strongest absorption peaks. Molar absorption coefficients are in the maximum of the highest peak.
Fluorescence quantum yields (were calculated using Cresyl violet perchlorate (= 0.54 in methanol) as the reference for 1a-h, 5, 7c, and 7e, and
,7-diphenyl-3,5-di(p-methoxyphenyl)-azadipyrromethene ( = 0.36 in chloroform) for 7a, 7b and 7d. Standard errors are less than 10%.
[
1
[
d]
[e]
Stokes-shifts for all dyes refer to the difference between the absorption and the emission maximum. Fluorescence lifetime; standard
[
f]
[g]
[h]
24
deviations are less than 0.1 ns.
f
K =  Knr= (1- Data taken from the reference .
dichloromethane (Table 1, Figures S33-75 in the supporting information). The fluorescence
lifetimes for most of 1 and 5 in dichloromethane are at around 5-8.89 ns, similar to most highly
1
1d
fluorescent BODIPYs apeared in the literature. The comparatively larger non-radiative decay
8
-1
8
-1
8 -1
rate constants were observed for 1e and 7c-e (7.5  10 s , 3.2  10 s , 2.1  10 s , and 1.3 
8
-1
1
0 s , respectively, Table 1) in dichloromethane, which may partially explain the comparatively
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1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
low fluorescence quantum yields observed in these dyes. These large non-radiative decay rate
constants for 7c-e may be associated with the free rotation of the phenyl moieties in the
17c-d,25
meso-styryl units
, while it is not clear for the large one observed in 1e.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Solvatochromic effect:
The solvatochromic effects on these isoindole BODIPYs in hexane, toluene, dichloromethane,
tetrahydrofuran, acetonitrile and methanol were summarized in Table S1 and Figure S10-32
(
Supporting information). For most of these isoindole BODIPYs, increasing the polarity of the
solvent only leads to a slight blue-shift of the absorption and emission band. By contrast, it
brings a gradual decrease of the fluorescence quantum yields and dramatic solvent-dependent
life-time decay for those containing 3-methyl substituent on the uncoordinated pyrrole ring (1c-e,
1g-h, 5e, 5g, and 7a-g). For example, the fluorescence quantum yield for 1c was gradually decreased
from 0.85 (hexane) to 0.81 (toluene), 0.61 (dichloromethane), 0.06 (tetrahydrofuran), 0.03 (methanol)
and 0.02 (acetonitrile) with the increase of the polarity of the solvent (Table 2). In addition, the
fluorescence life-time decay for 1c (Figure S78, Supporting information) was changed from a
monomeric exponential decay to biexponential decay with a great decrease of the excited-state
lifetime: hexane (7.17 ns), toluene (6.14 ns), dichloromethane (6.40 ns), THF ( 0.80 ns,

 3.75 ns), acetonitrile ( 0.56 ns,  4.34 ns) and MeOH ( 0.43 ns,  4.98 ns).





Similar results were observed for 5e (Table 2 and Figure S79), while for 5a and 5d, their
fluorescence quantum yields (0.78-0.90 for 5a and 0.82-0.91 for 5d) and fluorescence lifetimes
(6.82-7.93 ns for 5a and 6.17-7.31 ns for 5d, Figures S76 and S77) only have slight variations in
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different solvents. Thus, these isoindole BODIPY dyes may have potential application as red to
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
2
6
NIR environmental sensitive fluorescence probes.
Table 2. Fluorescence quantum yields and lifetimes of 5a, 5d, 1c and 5e in hexane, toluene, dichloromethane, tetrahydrofuran, acetonitrile and
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
methanol at room temperature.
a
b
Φ () 
dyes
hexane
toluene
dichloromethane
0.87 (7.28)
tetrahydrofuran
0.80 (7.36)
acetronitrile
0.85 (7.41)
methanol
0.90 (7.47)
5
5
a
0.87 (7.93)
0.91 (7.31)
0.85 (7.17)
0.99 (7.03)
0.78 (6.82)
0.83 (6.17)
0.81 (6.14)
d
0.89 (6.65)
0.82 (6.54)
0.84 (6.32)
0.83 (6.50)
c
c
c
c
c
c
1c
0.61 (6.40)
0.06 (0.80, 3.75)
0.07 (0.42, 4.41)
0.02 (0.56, 4.34)
0.12 (0.26, 5.55)
0.03 (0.43, 4.98)
0.14 (0.28, 5.60)
5
e
0.99 (5.90)
0.96 (4.93)
[a]
[b]
[c]
Fluorescence quantum yield ( monomeric exponential decay fluorescence lifetime (); biexponential decay fluorescence lifetime (



).
pH-Dependent absorption and fluorescence emission of 7f:
a)
b)
6
5
4
3
2
1
000
000
000
000
000
000
0
0.25
0.20
0.15
0.10
0.05
0.00
3
00
400
500
600
700
800
650
700
750
800
850
Wavelength (nm)
Wavelength (nm)
-6
Figure 7. (a) Absorption and (b) fluorescence titration spectra of isoindole BODIPY 7f in acetontrile (5.78 × 10 M) with the addition of TFA (6.73 ×
-2
1
0
M) from 0-230 equivalents. Excited at 610 nm.
Isoindole BODIPY 7f, containing a dimethylamine (NMe ) moiety, shows strong absorption and
2
weak fluorescence emission in the NIR region in polar solvents, like acetonitrile (713/805 nm,  =
0
.05, Table S1, Supporting information) due to the strong intramolecular charge transfer (ICT)
2
7,28
-2
process.
With the addition of trifluoroacetic acid (TFA, 6.73 × 10 M), a stepwise disappearance
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2
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5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
of the absorption bands at 713 nm and 415 nm with the appearance of two new bands at 671 nm and
354 nm was observed for 7f (Figure 7a). The sharp isosbestic point at 680 nm and 382 nm indicates
+
the formation of a mono-protonated species (7f-H ). In addition, the addition of TFA also causes a
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
blue-shift of the emission band from 805 nm to 702 nm with an isosbestic point at 774 nm (Figure
7b). This reveals that 7f may be a potential ratiometric “turn-on” NIR fluorescent pH sensor.
Electrochemical properties
The electronic structures of BODIPYs 1a, 5a, 1c, 1d and 7f were investigated by cyclic
voltammetry (CV) in deoxygenated dichloromethane containing 0.1 M tetrabutylammonium
hexafluorophosphate (TBAPF ) as the supporting electrolyte (Figure 8 and Table 3). Among those,
6
1
a exhibits an irreversible reduction wave (E at -0.91 V) and an irreversible oxidation wave (Epa at
pc
0.96 V) relative to the saturated calomel electrode (SCE). Similarly, 5a shows one reversible
reduction wave (with half-wave potential at -1.13 V) and one reversible oxidation wave (with
half-wave potential at 0.72 V). By contrast, 1c, 1d and 7f each exhibits two or three reversible waves
with half-wave potential values at -1.20/0.65 V, -1.24/0.54 V and -1.14/0.29/0.52 V, respectively.
Epc = -0.91 V
1a
E
= -1.13 V
= -1.20 V
1/2
Epa = +0.96 V
= +0.72 V
1/2
5a
1c
E
E
1/2
E
= +0.65 V1
E
E
= -1.24 V
= -1.14 V
1
/2
1/2
d
E
= +0.54 V
1
/2
1/2
7
f
E
= +0.29 V
1/2
E
= +0.52 V
1/2
1.0
0.5
0.0
-0.5
-1.0
-1.5
Potential vs SCE (V)
6
Figure 8. Cyclic voltammograms of 1a, 5a, 1c, 1d and 7f recoreded in dichloromethane containing 0.1 M TBAPF at room temperature.
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6
Based on the onset potential of their first oxidation and reduction waves, the HOMO/LUMO
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
energy levels for 1a, 5a, 1c, 1d and 7f were estimated to be at -5.28/-3.59, -5.06/-3.36, -4.96/-3.31,
-
4.86/-3.13 and -4.65/-3.31 eV, respectively. In comparison with 1d, 7f showed an increased HOMO
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
from -4.86 to -4.65 eV) and a decreased LUMO energy level (from -3.13 to -3.31 eV) with an overall
1.34 eV derease of the band gap. A gradual increase of the HOMO/LUMO energies and a gradual
decrease of the energy band gaps were observed for these isoindole BODIPYs with the increase of
the alkyl substitutions on the pyrrole rings. Among those, alkyl substitutions on the coordinated
pyrrole unit is more efficient in decreasing the HOMO and LUMO energy levels for these dyes.
Table 3. Electrochemical data acquired and HOMO-LUMO band gaps determined from spectroscopy of 1a, 5a, 1c, 1d and 7f.
1
2
onset
onset
dyes
E
(
ox
E
ox
E
(V)
red
E
(V)
red
E
ox
LUMO
(eV)
HOMO
(eV)
Eg
(eV)
V)
(V)
(V)
0.96
1
5
1
1
7
a
a
c
d
f
-
-0.91
-0.81
-1.04
-1.09
-1.13
-1.09
0.88
-3.59
-3.36
-3.31
-3.13
-3.31
-5.28
-5.06
-4.96
-4.86
-4.65
1.69
1.66
1.65
1.59
1.34
0
0
0
0
.78
.70
.58
.35
-
-1.19
-1.23
-1.27
-1.19
0.62
0.56
0.46
0.25
1.17
1.09
0.57
1
2
E
ox = the first oxidation peak potential; Eox = the second oxidation peak potential; Ered = the
onset
onset
onset
reduction peak potential; Ered
= the onset reduction potential; ELUMO = -e(Ered
+ 4.4); Eox
onset
=
the onset oxidation potential; EHOMO = -e(Eox
+ 4.4); Eg = ELUMO - EHOMO.
DFT calculations:
Figure 9. The relative energies of the frontier molecular orbitals (MOs) of 1a, 1c, 5a, 5e and 5h. Calculations are based on ground state geometry by
DFT at the B3LYP/6-31G* level.
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9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
For a better understanding of the photophysical properties of these dyes, DFT calculation was
performed at the B3LYP/6-31G(d) level. As shown in Figure 9, the HOMO and the LUMO were
localized over the BODIPY core and the uncoordinated pyrrole ring for 1 and 5. Increasing alkyl
substitutions on pyrrole rings leads to a gradual increase of the HOMO/LUMO energy levels from
1a (-5.07/-2.55 eV) to 5a (-4.86/-2.42), 5h (-4.81/-2.39), 1c (-4.76/-2.36) and 5e (-4.73/-2.34 eV).
These results of our calculation are in good agreement with electrochemical experimetal results.
We further performed time-dependent DFT calculations (TD-DFT) on these dyes in
dichloromethane (Table S3, supporting information). The calculated absorption maximum (524-562
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
9
nm) is blue shifted with respect to the experimental spectra, similar to the recently reported results .
The lowest energy absorption band for these dyes is mainly contributed by HOMO → LUMO
transition with high oscillator strength above 0.7, which correspondes to the electronic transition
from the ground to the first excited states (S0→S1).
Conclusion
In conclusion, we have synthesized a series of isoindole BODIPYs based on either the one-pot
condensation of 3-halogenated isoindolylidene with pyrrole/indole derivatives or a two-step reaction
between 3-chloro-1-formylisoindole and pyrroles. These dyes show strong absorption and
fluorescence emission tunable from far red to NIR region (up to 805 nm in acetonitrile) via the
simple variation of substituents. Most of these dyes show high fluorescence quantum yields (up to
0
.99). Solvent-dependent fluorescence emissions were observed for those possessing 3-methyl
substituent on the uncoordinated pyrrole unit. X-ray diffraction analysis shows that alkyl and
styryl substitution(s) on the pyrrole rings greatly enhanced the dihedral angle between
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uncoordinated pyrrole and the BODIPY core. Cyclic voltammetry and DFT calculation results
indicate that alkyl substitutions on the pyrrole rings increases the HOMO and the LUMO energy
levels and brings an overall decrease of the energy band gaps. These isoindole BODIPYs can be
further functionalization with a variety of functionalities via Knoevenegal condensation, as
dimethylamine demonstrated in this work. This dimethylamine functionalized dye shows weak
fluorescence in polar solvents, and show great potential to be a ratiometric “turn-on” NIR
fluorescent pH sensor.
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Experimental Section
General. Reagents and solvents were used as received from commercial suppliers unless noted
otherwise. All reactions were performed in oven-dried or flame-dried glassware unless otherwise
stated, and were monitored by TLC using 0.25 mm silica gel plates with UV indicator (HSGF 254)
for thin-layer chromatography (TLC). Flash column chromatography was performed using silica gel
1
13
(
200−400 mesh). H NMR (300 MHz) and C NMR (75 MHz) spectra were recorded at 300 MHz
NMR spectrometer in CDCl . Chemical shifts (δ) are given in ppm relative to CDCl (7.26 ppm for
3
3
1
13
H and 77 ppm for C) or to internal TMS (δ = 0 ppm) as internal standard. Data are reported as
follows: chemical shift, multiplicity, coupling constants and integration. High-resolution mass
spectra (HRMS) were obtained using APCI (or ESI or EI)-TOF in positive mode. BODIPYs 5a and
2
0
7
a-e were synthesized using the procedures described in our previous communication.
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0
Compounds 2a and 2b were synthesized using a modified literature method.
o
2
a: To a solution of POCl (3.2 mL, 30 mmol) in anhydrous dichloromethane (7 mL) at 0 C was
3
added dropwisely N,N-dimethylformamide (DMF, 2.6 mL, 30 mmol) in anhydrous dichloromethane
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(
15 mL). The reaction mixture was stirred for 30 min at room temperature. To the reaction mixture
was slowly added 1H-isoindolinone 1 (2 g, 15 mmol) in 80 mL dichloromethane. It was heated at
refluxing for 4.5 h, neutralized with ice-cold aqueous solution of Na CO (2 M), extracted with
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dichloromethane, filtered and dried over anhydrous Na SO . Solvent was removed under vacuum.
2
4
The residue was purified from silica gel chromatograph (petroleum/ ethylacetate = 4/1, v/v) to give
1
2
a as white crystals in 47 % yield (1.45 g). H NMR (300 MHz, CDCl ):  7.62 (d, J = 7.8 Hz, 1H),
3
7
.57 (d, J = 7.8 Hz, 1H), 7.30 (t, J = 7.8 Hz, 1H), 7.24-7.17 (m, 2H), 3.58 (s, 3H), 3.33 (s, 3H).
2b was obtained in 45% yield (1.49 g) as a white solid from dimethylacetamide (2.8 mL, 30 mmol)
1
using the above procedure for 2a. H NMR (300 MHz, CDCl ):  7.66-7.64 (m, 2H), 7.32 (t, J = 4.5
3
Hz, 1H), 7.20 (t, J = 7.5 Hz, 2H), 3.46 (s, 6H), 2.69 (s, 3H).
3
0
Compounds 3a and 3b were synthesized using a modified literature procedure.
3
a: To 2a (1.03 g, 5 mmol) in 100 mL ethanol was added NaOH (4 M, 6 mL). The reaction mixture
was refluxed for 3 h, cooled to room temperature, concentrated. Then the solution was neutralized
with HCl (3 M) to tune pH to 7, extracted with dichloromethane (3 × 80 mL), filtered, and dried over
anhydrous Na SO . Solvent was removed under vacuum. The residue was recrystallized from
2
4
1
MeOH/H O (1:3) to give 3a as white crystals in 85% yield (760 mg). H NMR (300 MHz, CDCl ): 
2
3
9.73 (s, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.43 (t, J = 7.8 Hz, 1H), 7.26 (t, J =
7
.5 Hz, 1H).
3
b was obtained as a white solid in 80% yield of (702 mg) from 2b (1.0 g, 4.5 mmol) using the
1
above procedure for 3a and was purified via recrystallized in MeOH/H O (v/v = 1:3) . H NMR (300
2
MHz, CDCl ):  7.86 (d, J = 8.7 Hz, 1H), 7.66 (d, J = 7.8 Hz, 1H), 7.38 (t, J = 7.2 Hz, 1H), 7.18 (t, J
3
=
7.8 Hz, 1H), 2.72 (s, 3H).
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General procedure for the preparation of isoindole BODIPYs 1.
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To the mixture of compound 2a (0.5 mmol) and pyrrole derivatives (10 mmol) in 60 mL
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,2-dichloroethane (or the mixture of 1,2-dichloroethane and toluene, v/v = 1/1) was added POCl3
(0.47 mL, 5 mmol) at ice-cold condition under argon. The reaction mixture was stirred under
refluxing condition and was monitored by TLC. Upon the completion of the reaction, Et N (1.5 mL)
3
was added to the reaction mixture under ice-cold condition, and the mixture was left stirring for
additional 10 min before adding BF ·OEt (2.5 mL) under ice-cold condition through syringe. The
3
2
reaction mixture was left stirring overnight, poured into water and extracted with CH Cl (3 × 60
2
2
mL). Organic layers were combined, and solvent was removed under vacuum. The crude product
was purified from silica gel chromatograph (petroleum/CH Cl = 2/1, v/v) to afford the desired
2
2
compound as a bluish (or reddish, or greenish) powder.
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0
1a was obtained as a reddish powder in 24% yield (37 mg) from 2a (103 mg, 0.5 mmol) and
pyrrole (0.69 mL, 10 mmol) in a mixture solvents of 1,2-dichloroethane and toluene (v/v = 1/1) at
1
1
10℃ for 10 h . H NMR (300 MHz, CDCl ):  10.11 (s, 1H), 7.95 (d, J = 7.2 Hz, 1H), 7.75 (d, J =
3
7.2 Hz, 1H), 7.41-7.31 (m, 2H), 7.14 (s, 1H), 7.02 (s, 1H), 6.90 (s, 1H), 6.80 (s, 1H), 6.50 (s, 1H),
.31 (s, 1H), 6.14 (s, 1H).
6
20
1b was obtained as bluish powder in 38% yield (64 mg) from 2a (103 mg, 0.5 mmol) and
1
2
-methylpyrrole (0.42 mL, 5 mmol) in 1,2-dichloroethane for 40 min. H NMR (300 MHz, CDCl ):
3

10.59 (s, 1H), 8.12 (d, J = 7.8 Hz, 1H), 7.78 (d, J = 7.5 Hz, 1H), 7.54 (t, J = 7.5 Hz, 1H), 7.40 (t, J
= 7.8, 1H), 7.19 (s, 1H), 6.64 (s, 1H), 6.24 (s, 1H), 6.13 (s, 1H), 2.59 (s, 3H), 2.50 (s, 3H).
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c was obtained as a bluish powder in 52% yield (94 mg) from 2a (103 mg, 0.5 mmol) and 2,
1
4-dimethylpyrrole (0.5 mL, 5 mmol) in 1,2-dichloroethane for 40 min. H NMR (300 MHz, CDCl ):
3

9.70 (s, 1H), 7.83-7.77 (m, 2H), 7.49 (d, J = 7.2 Hz, 1H), 7.34-7.28 (m, 2H), 6.03 (s, 1H), 5.99 (s,
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H), 2.50 (s, 3H), 2.40 (s, 3H), 2.30 (s, 3H), 2.29 (s, 3H).
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0
1
d was obtained as a greenish powder in 47% yield (99 mg) from the 2a (103 mg, 0.5 mmol) and
1
2
,4-dimethyl-3-ethylpyrrole (0.65 mL, 5 mmol) in 1,2-dichloroethane for 40 min. H NMR (300
MHz, CDCl ):  9.64 (s, 1H), 7.81-7.74 (m, 2H), 7.46 (d, J = 7.2 Hz, 1H), 7.31-7.13 (m, 2H),
3
2
.53-2.37 (m, 7H), 2.35 (s, 3H), 2.25 (s, 3H), 2.22 (s, 3H), 1.16 (t, J = 7.5 Hz, 3H), 1.09 (t, J = 7.5
Hz, 3H).
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0
1
e
was obtained as a brown powder in 20% yield (44 mg) from 2a (103 mg, 0.5 mmol) and
3
-methylindole ( 1.2 g, 9.2 mmol) in a mixture solvents of ClCH CH Cl and toluene (v/v = 1/1) at
2
2
1
110℃ for 10 h. H NMR (300 MHz, CDCl ):  10.06 (s, 1H), 8.00 (d, J = 4.2 Hz, 1H), 7.89 (d, J =
3
7
7
.2 Hz, 1H), 7.72-7.66 (m, 4H), 7.54-7.53 (m, 2H), 7.42-7.37 (t, J = 6.6 Hz, 1H), 7.29-7.21 (m, 3H),
.06 (s, 1H), 2.61-2.59 (m, 6H).
20
1
f was obtained as a reddish powder in 22% yield (35 mg) from 2b (110 mg, 0.5 mmol) and
pyrrole (0.69 mL, 10 mmol) in a mixture of ClCH CH Cl and toluene (v/v = 1/1) at 110℃ for 10 h.
2
2
1
H NMR (300 MHz, CDCl ):  10.80 (s, 1H), 8.19 (d, J = 7.8 Hz, 1H), 8.00 (d, J = 7.8 Hz, 1H), 7.59
3
(
t, J = 7.5 Hz, 1H), 7.48-7.41 (m, 2H), 7.34-7.30 (m, 2H), 6.90 (s, 1H), 6.51(s, 1H), 6.43 (s, 1H),
2
.76 (s, 3H).
2
0
1
g was obtained as a bluish powder in 43% yield (81 mg) from 2b (110 mg, 0.5 mmol) and
1
2
,4-dimethylpyrrole (0.5 mL, 5 mmol) in 1,2-dichloroethane for 40 min. H NMR (300 MHz,
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CDCl ):  9.52 (s, 1H), 8.00 (d, J = 8.1 Hz, 1H), 7.78 (d, J = 8.1 Hz, 1H), 7.49 (t, J = 7.5 Hz, 1H),
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7.30 (t, J = 7.5 Hz, 1H), 6.01-5.98 (m, 2H), 2.85 (s, 3H), 2.48 (s, 3H), 2.46 (s, 3H), 2.38 (s, 3H), 2.23
(s, 3H).
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1h was obtained as a greenish powder in 42% yield (91 mg) from 2b (110 mg, 0.5 mmol) and 2,
1
4
-dimethy-3-ethyllpyrrole (0.65 mL, 5 mmol) in 1,2-dichloroethane for 40 min. H NMR (300 MHz,
CDCl ):  9.46 (s, 1H), 8.00 (d, J = 8.4 Hz, 1H), 7.76 (d, J = 8.1 Hz, 1H), 7.46 (t, J = 7.8 Hz, 1H),
3
7.30-7.26 (t, J = 7.8 Hz, 1H), 2.88 (s, 3H), 2.53-2.40 (m, 10H), 2.34 (s, 3H), 2.18 (s, 3H), 1.17 (t, J =
7
.2 Hz, 3H), 1.06 (t, J = 7.2 Hz, 3H).
6a was used as an example to show the general procedure for the preparation of dipyrromethene 6:
To compound 3a (179 mg, 1 mmol) in 60 mL dichloromethane were added 2,4-dimethylpyrrole (103

L, 1 mmol) in 1 mL CH Cl , and POCl (94 L, 1 mmol) in 1 mL CH Cl at ice-cold condition
2
2
3
2
2
under argon. The reaction mixture was stirred in ice-cold condition for 30 min, and was followed by
TLC. Upon completion of the reaction, the reaction mixture was quenched by triethylamine (1.2 mL),
poured into water and extracted with dichloromethane (3 × 80 mL). Organic layers were combined,
and dried over anhydrous Na SO Solvent was removed under vacuum. The crude product was
2
4.
purified from silica gel chromatograph (petroleum/dichloromethane = 2/1, v/v) to afford the desired
1
compound 6a as reddish powder in 90% yield (230 mg). H NMR (300 MHz, CDCl ):  10.78 (s,
3
1H), 7.73 (d, J = 6.0 Hz, 1H), 7.59 (d, J = 6.0 Hz, 1H), 7.41 (t, J = 6.0 Hz, 1H), 7.30 (t, J = 6.0 Hz,
1
3
1
1
H), 7.07 (s, 1H), 5.85 (s, 1H), 2.35 (s, 3H), 2.25 (s, 3H). C NMR (75 MHz, CDCl ):  152.8,
3
40.3, 138.4, 137.6, 133.1, 130.8, 128.5, 127.2, 125.9, 120.5, 118.7, 114.8, 111.6, 13.9, 11.4. HRMS
+
(EI) calcd for C H N Cl [M] : 256.0767, found 256.0774.
1
5
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b was obtained as a reddish powder in 83% yield (212 mg) from 3a (179 mg, 1 mmol) and
1
2,4-dimethyl-3-ethylpyrrole (135 L, 1 mmol). H NMR (300 MHz, CDCl ):  10.67 (s, 1H), 7.67 (d,
3
J = 6.0 Hz, 1H), 7.53 (d, J = 6.0 Hz, 1H), 7.33 (t, J = 6.0 Hz, 1H), 7.23 (t, J = 6.0 Hz, 1H), 7.01 (s,
0
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3
1
H), 2.35 (q, J = 6.0 Hz, 2H), 2.25 (s, 3H), 2.14 (s, 3H), 1.00 (t, J = 6.0 Hz, 3H). C NMR (75 MHz,
CDCl ):  152.0, 140.3, 138.0, 135.1, 132.8, 128.9, 128.3, 126.2, 125.6, 124.6, 120.4, 118.6, 114.8,
3
+
1
7.4, 15.3, 12.0, 9.5. HRMS (EI) calcd for C H N Cl [M] : 284.1080 , found 284.1079.
1
7
17
2
6c was obtained as a reddish powder in 79% yield (235 mg) from 3b (193 mg, 1 mmol) and
1
2
,4-dimethyl-3-ethylpyrrole (135 L, 1 mmol). H NMR (300 MHz, CDCl ):  12.23 (s, 1H), 7.91 (d,
3
J = 6.0 Hz, 1H), 7.64 (d, J = 6.0 Hz, 1H), 7.41 (t, J = 6.0 Hz, 1H), 7.30 (t, J = 6.0 Hz, 1H), 2.81 (s,
1
3
3H), 2.45-2.32 (m, 8H), 1.06 (t, J = 6.0 Hz, 3H). C NMR (75 MHz, CDCl ):  149.0, 139.4, 137.9,
3
1
35.6, 133.4, 133.3, 128.3, 127.8, 127.7, 125.5, 125.0, 122.8, 120.9, 18.5, 17.3, 15.5, 13.6, 12.0.
+
HRMS (EI) calcd for C H N Cl [M] : 298.1237 , found 298.1245.
1
8
19
2
General procedure for the preparation of isoindole BODIPYs 5: To compound 6 (0.5 mmol) in
0 mL 1,2-dichloroethane were added suitable pyrrole or indole derivatives (10 mmol) in 1 mL
6
1,2-dichloroethane, and POCl (0.47 mL, 5 mmol) in 1 mL 1,2-dichloroethane at ice-cold condition
3
o
under argon. The reaction mixture was stirred at varying temperature (from 35 C to refluxing
temperature) depending on the reactivity of the pyrrole or indole derivatives, and was followed by
TLC. Upon the completion of the reaction, triethylamine (1.5 mL) was added into the reaction
mixture under ice-cold condition. The reaction mixture was further stirred for additional 10 min
before adding BF ·OEt (2.5 mL) under ice-cold condition through syringe. The reaction mixture
3
2
was left stirring for 2 h, poured into water and extracted with dichloromethane (3 × 80 mL). Organic
2
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layers were combined, and solvent was removed under vacuum. The crude product was purified
from silica gel chromatograph (petroleum/CH Cl = 2/1, v/v) to afford the desired compound as a
5
6
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2
reddish or greenish powder.
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5b was obtained as a reddish powder in 30% yield (52 mg) from 6a (128 mg, 0.5 mmol) and
1
N-methylpyrrole (0.94 mL, 10 mmol) at refluxing condition for 10 h. H NMR (300 MHz, CDCl ): 
3
7
.85 (d, J = 4.5 Hz, 1H), 7.53-7.45 (m, 2H), 7.41 (s, 1H), 7.29 (t, J = 6.0 Hz, 1H), 6.94 (s, 1H), 6.83
1
3
(s, 1H), 6.39 (s, 1H), 6.01 (s, 1H), 3.58 (s, 3H), 2.49 (s, 3H), 2.30 (s, 3H). C NMR (75 MHz,
CDCl ):  153.6, 146.1, 138.3, 134.9, 132.3, 131.7, 129.6, 128.9, 126.6, 125.7, 123.8, 123.3, 119.0,
3
+
1
17.9, 116.7, 115.8, 109.3, 35.6, 14.6, 11.3. HRMS (APCI) Calcd. for C H N BF [M + H] :
20
19
3
2
350.1636, found 350.1635.
5
c was obtained as grey powder in 38% yield (92 mg) from 6a (128 mg, 0.5 mmol) and
1
N-undecylpyrrole (2.21 g, 10 mmol) at refluxing condition for 10 h. H NMR (300 MHz, CDCl ): 
3
7
.85 (d, J = 4.5 Hz, 1H), 7.54-7.46 (m, 2H), 7.40 (s, 1H), 7.31 (d, J = 4.5 Hz, 1H), 7.00 (s, 1H), 6.84
(s, 1H), 6.39 (t, J = 3.0 Hz, 1H), 6.02 (s, 1H), 3.98-9.84 (m, 2H), 2.49 (s, 3H), 2.31 (s, 3H),
1
3
1.33-1.05 (m, 18H), 0.86 (t, J = 6.0 Hz, 3H). C NMR (75 MHz, CDCl ):  153.3, 146.7, 137.9,
3
1
3
35.0, 132.1, 131.6, 129.6, 129.0, 125.7, 125.5, 123.9, 122.8, 119.0, 117.7, 116.5, 116.1, 109.4, 48.8,
1.9, 31.6, 29.5, 29.3, 28.9, 26.3, 22.6, 14.7, 14.1, 11.3. HRMS (APCI) Calcd. for C H N BF [M
3
0
39
3
2
+
+ H] : 490.3200, found 490.3190.
5
d was obtained as bluish powder in 47% yield (82 mg) from 6a (128 mg, 0.5 mmol) and distilled
o
1
2-methylpyrrole (0.81 g, 10 mmol) at 35 C for 1 h. H NMR (300 MHz, CDCl ):  10.52 (s, 1H),
3
8
.11 (d, J = 4.5 Hz, 1H), 7.81 (d, J = 4.5 Hz, 1H), 7.51 (t, J = 6.0 Hz, 1H), 7.39-7.29 (m, 2H), 7.21
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6
1
3
(
s, 1H), 6.21 (s, 1H), 5.98 (s, 1H), 2.54 (s, 3H), 2.49 (s, 3H), 2.27 (s, 3H). C NMR (75 MHz,
CDCl ):  147.4, 146.2, 137.3, 136.1, 132.9, 130.8, 130.6, 130.4, 129.9, 126.4, 124.6, 121.5, 120.0,
3
+
1
3
19.1, 116.1, 112.1, 111.0, 14.3, 13.8, 11.1. HRMS (APCI) Calcd. for C H N BF [M + H] :
2
0
19
3
2
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6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
50.1635, found 350.1634.
5
e was obtained as a greenish powder in 54% yield (105 mg) from 6a (128 mg, 0.5 mmol) and
o
1
3
-ethyl-2,4-dimethylpyrrole (0.65 mL, 5 mmol) at 35 C for 10 min. H NMR (300 MHz, CDCl ): 
3
9.69 (s, 1H), 7.80 (t, J = 6.0 Hz, 2H), 7.49 (t, J = 6.0 Hz, 1H), 7.32 (t, J = 6.0 Hz, 1H), 7.25 (s, 1H),
1
3
5
.98 (s, 1H), 2.53-2.45 (m, 5H), 2.36 (s, 3H), 2.28 (s, 3H), 2.26 (s, 3H), 1.16 (t, J = 6.0 Hz, 3H). C
NMR (75 MHz, CDCl ):  148.5, 147.9, 136.1, 133.8, 131.7, 131.2, 130.7, 130.6, 129.9, 125.9,
3
125.5, 125.4, 118.9, 117.7, 116.3, 112.9, 17.8, 15.1, 14.3, 12.9, 11.9, 11.2. HRMS (APCI) Calcd. for
+
C H N BF [M + H] : 392.2104, found 392.2098.
2
3
25
3
2
5f was obtained as greenish powder in 29% yield (55 mg) from 6a (128 mg, 0.5 mmol) and indole
1
(
1.17 g, 10 mmol) at refluxing condition for 12 h. H NMR (300 MHz, CDCl ):  8.81 (s, 1H), 8.24
3
(
s, 1H), 7.87 (d, J = 9.0 Hz, 2H), 7.69 (d, J = 4.5 Hz, 1H), 7.53 (t, J = 9.0 Hz, 1H), 7.43-7.27 (m,
13
2H), 7.25-7.14 (m, 3H), 6.00 (s, 1H), 2.49 (s, 3H), 2.31 (s, 3H). C NMR (75 MHz, CDCl ): 
3
1
1
51.9, 150.4, 136.2, 136.0, 135.8, 131.8, 131.2, 130.1, 130.0, 129.6, 129.4, 129.3, 126.5, 125.4,
23.0, 120.9, 119.0, 116.9, 115.1, 111.8, 107.4, 14.5, 11.3. HRMS (APCI) Calcd. for C H N BF
2
2
3
19
3
+
[M + H] : 386.1635, found 386.1631.
5
g was obtained as a bluish powder in 40% yield (79 mg) from 6a (128 mg, 0.5 mmol) and
1
3-methylindole (1.31 g, 10 mmol) at refluxing condition for 12 h. H NMR (300 MHz, CDCl ): 
3
9
.61 (s, 1H), 7.88 (d, J = 4.5 Hz, 1H), 7.75 (d, J = 3.0 Hz, 1H), 7.69 (d, J = 3.0 Hz, 1H), 7.52 (t, J =
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.0 Hz, 2H), 7.43 (s, 1H), 7.38-7.30 (m, 2H), 7.18 (s, 1H), 6.06 (s, 1H), 2.51 (s, 6H), 2.33 (s, 3H).
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
3
C NMR (75 MHz, CDCl ):  162.7, 153.5, 145.6, 138.4, 137.3, 135.4, 132.3, 131.1, 129.8, 129.1,
3
1
25.8, 125.1, 124.4, 124.2, 119.8, 119.0, 118.1, 116.5, 116.2, 111.8, 14.6, 11.7, 11.4. HRMS (ESI)
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
Calcd. for C H N BF [M + H] : 400.1791, found 400.1788.
2
4
21
3
2
5
h was obtained as a reddish powder in 43% yield (78 mg) from 6b (142 mg, 0.5 mmol) and pyrrole
o
1
(0.69 mL, 10 mmol) at 35 C for 8 h. H NMR (300 MHz, CDCl ):  10.71 (s, 1H), 8.12 (d, J = 3.0
3
Hz, 1H), 7.82 (d, J = 3.0 Hz, 1H), 7.49 (d, J = 3.0 Hz, 1H), 7.38-7.30 (m, 4H), 6.49 (s, 1H),
1
3
2
1
.52-2.41 (m, 5H), 2.23 (s, 3H), 1.10 (t, J = 6.0 Hz, 3H). C NMR (75 MHz, CDCl ):  147.7, 145.1,
3
41.5, 135.8, 132.4, 130.4, 130.3, 129.9, 129.7, 126.1, 124.9, 124.5, 122.7, 119.0, 117.5, 113.3,
+
111.4, 17.4, 14.9, 12.2, 9.5. HRMS (EI) Calcd. for C H N BF [M] : 363.1718, found 363.1723.
21
20
3
2
5
i was obtained as reddish powder in 42% yield (79 mg) from 6c (150 mg, 0.5 mmol) and pyrrole
o
1
(0.69 mL, 10 mmol) at 35 C for 8 h. H NMR (300 MHz, CDCl ):  10.60 (s, 1H), 8.15 (d, J = 4.5
3
Hz, 1H), 7.99 (d, J = 3.0 Hz, 1H), 7.48 (m, 1H), 7.32-7.25 (m, 1H), 7.20-7.16 (m, 2H), 6.47 (s, 1H),
13
2
.85 (s, 3H), 2.50-2.39 (m, 8H), 1.07 (t, J = 6.0 Hz, 3H). C NMR (75 MHz, CDCl ):  146.2,
3
143.7, 135.2, 134.4, 132.6, 130.9, 130.0, 129.8, 128.3, 125.1, 125.0, 123.8, 122.4, 122.1, 116.8,
+
1
3
10.8, 17.2, 16.9, 15.2, 13.8, 12.1. HRMS (EI) Calcd. for C H N BF [M] : 377.1875, found
2
2
22
3
2
77.1883.
7
f : To 4-(dimethylamino)benzaldehyde 8 (90 mg, 0.6 mol) and 1d (126 mg, 0.33 mmol) in 20 mL
toluene were added piperidine (1.5 mL) through syringe, and a crystal of p-TsOH. The reaction
o
mixture was left heated at 140 C for 14 h. Water was removed with a Soxhlet extractor containing
anhydrous CaCl . The reaction was monitored by TLC. Upon the disappearence of 1d, the reaction
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mixture was cooled down to room temperature, poured into water and extracted with
dichloromethane (3 × 50 mL). Organic layers were combined and dried over anhydrous Na SO .
2
4
Solvent was removed under vacuum. The crude product was purified from chromatograph
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
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9
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6
7
8
9
0
(
petroleum/dichloromethane = 1/1, v/v), and was washed with CH OH to afford 7f as a grey power
3
1
in 30% yield (54 mg). H NMR (300 MHz, CDCl ):  9.74 (s, 1H), 7.76-7.74 (m, 2H), 7.44-7.39 (m,
3
4
6
H), 7.27-7.17 (m, 3H), 6.70 (d, J = 3.0 Hz, 1H), 2.99 (m, 5H), 2.68-2.21 (m, 13H), 1.23-1.17 (m,
1
3
H). C NMR (75 MHz, CDCl ):  150.3, 146.1, 135.1, 133.2, 130.8, 129.2, 128.2, 126.4, 125.6,
3
125.2, 124.6, 119.1, 118.0, 115.9, 112.3, 40.4, 18.8, 17.8, 15.2, 14.2, 12.8, 11.9, 9.1. HRMS (APCI)
+
Calcd. for C H N BF [M + H] : 551.3158, found 551.3154.
3
4
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4
2
Photophysical Measurements. UV-visible absorption and fluorescence emission spectra were
recorded on commercial spectrophotometers (190-870 nm scan range) at room temperature (10 mm
quartz cuvette). Relative fluorescence quantum efficiencies of BODIPY derivatives were obtained by
comparing the areas under the corrected emission spectrum of the test sample in various organic
3
1
solvents with Cresyl violet perchlorate (= 0.54 in anhydrous methanol)
and
3
2
1
,7-diphenyl-3,5-di(p-methoxyphenyl)-azadipyrromethene (= 0.36 in chloroform) . Non-degassed,
spectroscopic grade solvents and a 10 mm quartz cuvette were used. Dilute solutions (0.01<A<0.05)
were used to minimize the reabsorption effects. Quantum yields were determined using the
3
3
following equation :

A (
)
)
2
r
ex
ex
Fx 110
nx
   


x
r
A (
2
x
Fr
nr
110
Where the subscripts x and r refer respectively to our sample x and reference (standard) fluorophore
r with known quantum yield  in a specific solvent, F stands for the spectrally corrected, integrated
r
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fluorescence spectra, A( ) denotes the absorbance at the used excitation wavelength  , and n
ex
ex
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8
9
1
1
1
1
1
1
1
1
1
1
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2
2
2
2
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3
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3
3
3
3
3
3
4
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4
4
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5
5
5
5
5
5
5
5
5
6
represents the refractive index of the solvent (in principle at the average emission wavelength).
0
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Fluorescence lifetimes (τ) of S1 state was measured by time-correlated single photon counting
method on a commercial steady-state lifetime fluorescence spectrometer with cossesponding
excitation and emission was monitored at the peak maximum. The fluorescence lifetime values were
obtained from deconvolution and distribution lifetime analysis. When the fluorescence decays were
single exponential, the rate constants of radiative (k ) and non-radiative (k ) deactivation were
f
nr
calculated from the measured fluorescence quantum yield and fluorescence lifetime in
dichloromethane using the following equation: k = /τ and k = (1- )/τ.
f
nr
Crystallography. Crystal diffraction of BODIPYs 1a, 1b, 1h, 5b, 5d, 5e, 5f, 5g and 5i suitable for
X-ray analysis was performed on a CCD diffractometer using graphite-monochromated Mo-Kα
radiation (λ = 0.71073 Å) at 293(2) K, with φ and ω scan techniques. An empirical absorption
3
4
correction was applied using the SADABS program. All structures were solved by direct methods,
completed by subsequent difference Fourier syntheses, and refined anisotropically for all
2
non-hydrogen atoms by full-matrix least-squares calculations based on F using the SHELXTL
3
5
program package. The hydrogen atom coordinates were calculated with SHELXTL by using an
appropriate riding model with varied thermal parameters. The residual electron densities were of no
chemical significance. Crystals of BODIPYs 1a (CCDC 978648), 1b (CCDC 1055531), 1h (CCDC
1
055368), 5b (CCDC 1003315), 5d (CCDC 979479), 5e (CCDC 978647), 5f (CCDC 978651), 5g
(CCDC 978650) and 5i (CCDC 978674), contain the supplementary crystallographic data for this
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paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
0
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Electrochemistry. Electrochemical cells used for cyclic voltammetry experiment consist of a
three-electrode setup including a glassy carbon as working electrode, platinum wire as counter
electrode, and saturated calomel electrode (SCE) as pseudo reference electrode. Experiments were
-1
run at 20 mV s scan rates in degassed dichloromethane solutions of the analytes (~1 mM) and
supporting electrolyte (0.1 M tetrabutylammonium hexafluorophosphate) at room temperature.
Cyclic voltammograms were referenced against an external standard (~1 mM potassium ferricyanide)
and corrected for external cell resistance.
Computational details. All of the calculations were carried out by the methods implemented in
3
6
Gaussian 09 package . The ground state geometry was optimized by using DFT method at
B3LYP/6-31G (d) level. The same method was used for vibrational analysis to verify that the
optimized structures correspond to local minima on the energy surface. TD-DFT computations were
used to obtain the vertical excitation energies and oscillator strengths at the optimized ground state
equilibrium geometries under the B3LYP/6-31+G (d) theoretical level. TD-DFT calculated
molecules in dichloromethane were done using the Self-Consistent Reaction Field (SCRF) method
and Polarizable Continuum Model (PCM).
Supplementary Information (SI) available: Crystal structure data and CIF files, additional
photophysical data and spectra, copies of NMR spectra and high resolution mass spectra for all new
compounds, calculated frontier orbitals and absorption spectra. This material is available free of
charge via the Internet at http://pubs.acs.org.
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Acknowledgements
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We thank the National Nature Science Foundation of China (Grants Nos. 21372011, 21402001
and 21472002), Nature Science Foundation of Anhui Province (Grants No 1508085J07) and
Graduate student research innovation project of Anhui Normal University (Grants No 2014yks071zd)
for supportting this work. We thank the Supercomputing Center of The University of Science and
Technology of China for the numerical calculations in this paper.
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