Conformationally restricted aza-BODIPY: Highly fluorescent, stable near-infrared absorbing dyes

Article abstract of DOI:10.1002/chem.200600527

Novel NIR fluorescent, conformational restricted aza-dipyrromethene boron difluoride (aza-BODIPY) dyes were prepared by an efficient process. Such conformational restricted aza-BODIPY dyes possess intense absorption, strong fluorescence, high chemical and

Full text of DOI:10.1002/chem.200600527

DOI: 10.1002/chem.200600527
Conformationally Restricted Aza-BODIPY: Highly Fluorescent,
Stable Near-Infrared Absorbing Dyes
Weili Zhao and Erick M. Carreira*[a]
Abstract: Novel NIR fluorescent, conformational restricted aza-dipyrromethene
boron difluoride (aza-BODIPY) dyes were prepared by an efficient process. Such
conformational restricted aza-BODIPY dyes possess intense absorption, strong
fluorescence, high chemical and photostability. Additionally, the sharp fluores-
cence of non-amine containing aza-BODIPY dyes is insensitive to solvent polarity.
Keywords: biosensors
fluorescent probes · heterocycles
·
dyes
·
Introduction
ity, and in most cases possess low fluorescence quantum
yields.[4] To the best of our knowledge, the highest fluores-
cence quantum yield for NIR cyanine dyes was reported to
be 0.28 in water.[5] Thus, there is a pressing need for the
identification of stable and effective NIR probes. In a recent
communication, we reported a highly fluorescent, photosta-
ble, conformationally restricted aza-dipyrromethene boron
difluoride (aza-difluoroboradiaza-s-indacene, aza-BODIPY)
dye.[8] Herein we present detailed studies on synthesis and
fluorescence of a series of NIR absorbing aza-BODIPY
dyes.
Dipyrromethene boron difluoride (difluoroboradiaza-s-in-
dacene, BODIPY) dyes are well-known to be highly fluores-
cent, very stable, and exceptionally insensitive to the polari-
ty of solvents as well as to pH. BODIPY dyes are unusual
in that they are relatively non-polar and are electronically
neutral. They have found widespread applications as laser
dyes, molecular probes and sensors in the visible region.[2e,9]
Recent efforts have been focused on tuning the fluorescent
emission to the red region and even to the NIR region by
modifying the dipyrromethene core. Those modifications in-
clude: 1) attaching strongly electron-donating groups;[10] 2)
rigidifying the structure of the core of the dye;[11] and 3) ex-
tending conjugation of the system.[12,13] A BODIPY dye with
extended conjugation can absorb over 600 nm, however, fur-
ther extension of conjugation only leads to slight red-shift in
general.[13] Additionally, such modifications have led to dyes
with absorption maxima over 700 nm, however, no fluores-
cence quantum yield was reported for these, thus it is ques-
tionable whether such systems can have practical applica-
tions.[14] Moreover, these structural alterations can lead to
molecules exhibiting undesired properties; for example,
BODIPY dyes substituted with strongly electron-donating
groups such as amines display sensitivity to the polarity of
Near-infrared (NIR) dyes have many applications in the
market place such as laser optical recording, laser thermal
writing displays, infrared photography, and applications in
medicine.[1] In recent years, there has been intense interest
on the preparation and study of NIR dyes as safe, non-inva-
sive probes.[2]
The advantages of imaging in the NIR region (700–
1100 nm) have been extensively discussed.[2] The most prom-
inent of these are the absence or significant reduction of
background absorption, fluorescence, and light scattering.[3,4]
The wide availability of low-cost diode lasers as sources of
irradiation is also a plus.[2] NIR fluorescent probes enable
researchers to detect particular components of complex bio-
molecular systems with good sensitivity and selectivity. Sev-
eral NIR absorbing dyes such as cyanines, oxazines, squar-
ines have been developed for imaging purposes.[1,2] Howev-
er, it is very difficult to design NIR fluorophores to fulfil all
the requirements for an ideal NIR probe such as: peak fluo-
rescence at 700–900 nm, high fluorescence quantum yield,
narrow excitation/emission, high chemical and photo-stabili-
ty, low toxicity, and excellent biocompatibility.[2] Problems
such as aggregation,[5] photobleaching,[6] and low fluores-
cence quantum yields[6,7] are frequently encountered for
NIR dyes. For example, NIR absorbing cyanine dyes are
most frequently used for labeling bioactive molecules, how-
ever, all NIR absorbing cyanine dyes have poor photostabil-
[a]Dr. W. Zhao, Prof. Dr. E. M. Carreira
Laboratorium für Organische Chemie
ETH Zürich, HCI H335, 8093 Zürich (Switzerland)
Fax : (+41)1-632-1328
E-mail: carreira@org.chem.ethz.ch
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Please note: Minor changes have been made to this manuscript since its publication in Chemistry - A European Journal Early View. The Editor.

FULL PAPER
solvents, leading to low F in polar solvents as a consequence
of intramolecular electron transfer.[12b] A general phenomen-
on observed in NIR dyes is that decreased fluorescence
quantum yield was often observed in a highly extended con-
jugating system due to increased internal conversion accord-
ing to the energy gap law that states that the non-radiative
deactivation probability of S0–S1 increases as the energy gap
of S0–S1 decreases.[15]
In contrast to the well-known BODIPY dyes, aza-dipyrro-
methene dyes have not been extensively studied.[16] Recent-
ly, OꢁSheaꢁs group reported that aza-BODIPY dyes carrying
heavy atoms absorb up to 688 nm, and act as efficient pho-
todynamic therapy (PDT) agents.[16] We selected the previ-
ously unknown structurally rigidified aza-dipyrromethene
dyes as our targets for synthesis. We speculated that the ri-
gidified aza-BODIPY core would offer a number of advan-
tages including: 1) inherent
Scheme 1. Series 1: R = Ph; series 2: R = p-MeOPh; series 3: R = phe-
nylethyl.
and the combined yields over four steps are shown in
Figure 1. In the developed four-step procedure, purification
was only required at the last step, and the pyrroles synthe-
sized were found to be crystalline.
bathochromic shift of the ab-
sorption maxima in compari-
son to the carbon analogue; 2)
high extinction coefficient, and
high fluorescence quantum
yield; and 3) better conjuga-
tion in the system, which per-
mits absorption of the dye at
longer wavelength. However,
the required synthesis of aza-
BODIPY dyes comprises a ni-
trosopyrrole
intermediate,
which requires 2,4-diaryl sub-
stituted pyrrole substrate in
the reported synthesis due to
the inherent problem of nitro-
sation in pyrroles.[17] To the
best of our knowledge, no syn-
theses of rigidified pyrroles
possessing 2,4-diaryl substitu-
ents have been reported. The
Figure 1. Pyrroles prepared according to Scheme 1 with combined yields over four steps shown. [a]For 1d and
3 modified conditions were employed in order to obtain good yields of the pyrroles.
known synthesis of a rigidified pyrrole with 2-aryl-4-methyl
substituents is a low yielding process.[11] We took note of a
report in the 1960s for the synthesis of 2,4-diphenyl pyrrole
in moderate yield, wherein azirine was used as the key inter-
mediate.[18] Herein, we prepare both rigidified and non-ri-
gidified 5-aryl pyrroles in a practical manner and use these
in the synthesis of novel symmetric and non-symmetric aza-
BODIPY dyes.
Conformationally restricted 2,5-diaryl pyrroles (1a/1b)
and 3,4-diaryl pyrrole (1c) were obtained in good combined
yields over four steps. However, 1c is more sensitive to oxi-
dation by oxygen compared with 1b, and is more difficult to
crystallize. The four-step synthetic pathway was also applied
to the syntheses of 2,4-diaryl pyrroles. 2,4-Diaryl pyrroles
were prepared in good combined yields in most cases. How-
ever, when the 2-aryl substituent becomes sterically hin-
dered (1h), the yield was diminished. Severe limitations are
found for pyrrole 1d incorporating a heterocyclic ring and
pyrrole 3 with a 4-arylalkyl substituent, with which low
yields were obtained. These limitations could be overcome
by using LDA/THF at À788C instead of NaH/DMSO at
room temperature. With such modifications, compound 1d
and 3 could be obtained in 72 and 43% yield, respectively.
Results and Discussion
Synthesis of 2-aryl substituted pyrroles: Our first goal was
to develop an efficient way to construct restricted 2,4-diaryl
pyrroles. The synthesis of rigidified pyrroles commences
with a four-step sequence from alkene and includes addition
of iodo azide,[19] dehydro-halogenation,[19] pyrrolysis (azirine
formation),[20] and carbanion induced pyrrole formation,[18]
as shown in Scheme 1. The examples of pyrroles synthesized
Synthesis of aza-BODIPY dyes: We next put our efforts on
the development of a convenient synthesis of the desired
conformationally restricted aza-BODIPY dyes. The typical
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E. M. Carreira and W. Zhao
process reported for prepara-
tion of aza-BODIPY dyes con-
stitutes reaction of a pyrrole
with a nitrosopyrrole, which
requires preparation in a sepa-
rate step.[21] We developed a
two-step sequence wherein the
dipyrromethene intermediates
were prepared from nitroso-
pyrroles, which were generated
in situ. The complexation of
dipyrromethene dyes were ef-
fected with BF3·Et2O in the
presence of a base in non-
polar solvent (see Scheme 2).
Both symmetric and non-sym-
metric conformationally re-
stricted aza-BODIPY dyes
shown in Figure 2 were synthe-
sized using this method. The
aza-BODIPY dyes are highly
crystalline and could be easily
purified. The symmetric aza-
BODIPY dyes restricted with
carbocyclic rings were pre-
pared in high yields. Substitu-
tion at the 4-position in pyr-
roles has little effect on the
yield of aza-BODIPY dyes
(see compounds 4–6). The
symmetric aza-BODIPY dye
restricted with a heterocyclic
ring 7 was produced in accept-
able yield. The 2-aryl substitu-
ent in the pyrrole is essential
Figure 2. Aza-BODIPY dyes prepared according to Scheme 2 with yields shown.
for the formation of aza-
BODIPY dyes. For example, when 2,4-dimethylpyrrole was
used to react with nitrosated 1a, no trace of the expected
aza-BODIPY dye was detected. When pyrrole 1c was used
with nitrosated 1a, only dehydrogenated aza-BODIPY 9
was isolated in low yield. When the 2-aryl substituent be-
comes more sterically congested, lower yield of the desired
dye was obtained (compare compounds 10–15). In the case
where pyrrole 1h carries a very hindered 2-methoxy-1-naph-
thyl group, low yield of the desired non-symmetric dye 15
was generated. The known reference dye 17 was also pre-
pared in excellent yield with our methodology.
Spectroscopic properties of aza-BODIPY dyes: The spectral
characteristics of the conformationally restricted dyes 4–16
were then examined and compared with the known dye
17.[16] Spectroscopic data for 4–17 are collected in Table 1.
All aza-BODIPY dyes prepared absorb over 650 nm in
CHCl3. The most notable features of aza-BODIPY dyes 4–6
with both sides restricted with carbocyclic rings are their in-
tense, narrow absorption bands at long absorption maxima
and high extinction coefficients (Table 1, entries 1–3). The
best example is compound 4, which has the longest absorp-
tion maximum (labs =740 nm) with e up to 159000mÀ1 cmÀ1
and full-width at half-maximum (fwhm) of 30.4 nm (Table 1,
entry 1). In comparison, non-restricted reference 17 has labs
688 nm with e
(Table 1, entry 14). Thus, restriction of the aromatic ring re-
=
78500mÀ1 cmÀ1 and fwhm of 57 nm
Scheme 2.
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Near-Infrared Absorbing Dyes
FULL PAPER
Table 1. Spectroscopic data of aza-BODIPY dyes in chloroform at room
temperature.
entries 7–13 and entry 1). The labs of such dyes is also short-
er except in dye 16 with a very electron-rich amine substitu-
ent. The quantum yields of non-symmetric aza-BODIPY
dyes are highly dependent on the substituents on the aro-
matic ring. In the absence of substitution or with a single
methoxy substituent at the para-position of the phenyl ring
(dye 10 and 11), higher quantum yield is observed, however
with shorter labs, which indicates that the phenyl ring is
twisted (compare Table 1, entries 7, 8 and entries 1, 5).
When a single methoxy is present in the ortho-position of
the phenyl ring (dye 12), short labs, low e, and broad absorp-
tion peak (low fwhm) were observed (compare Table 1, en-
tries 9 and 8). The quantum yield of 12 is much lower than
that of dye 10 without a substituent on the phenyl ring
(compare Table 1, entries 9 and 7). These features indicate
that the phenyl ring in 12 is twisted and electron transfer
might take place. When two methoxy substituents are pres-
ent in the phenyl ring (dye 13 and 14), the labs was unex-
pectedly shorter than that of the mono-methoxy substituted
dye (compare Table 1, entries 10, 11 and 8). The absorption
peaks become even broader (low e, low fwhm) than those of
the monosubstituted species, and quantum yields are lower.
Such facts suggest electron transfer does take place in both
13 and 14. Electron transfer is more obvious in dye 16 with
the very electron rich para-piperidino substituent. Dye 16
displays very long labs, very broad absorption peak, and pos-
sesses much lower fluorescence quantum yield (compare
Table 1, entries 13 and 7). In a special case (dye 15) wherein
a 2-methoxy-1-naphthyl substituent is present, the labs is the
shortest among all the synthesized dyes (compare Table 1,
entries 12 and 7–11). The sharp absorption (surprisingly
higher e than other mono-restricted dyes, and smaller
fwhm), and the high quantum yield of 15 suggest that naph-
thyl ring is distorted so that electron transfer is suppressed.
It was reported that in a BODIPY dye substituted with
naphthalene at the para-position of a phenyl group, the tor-
sion angle between the naphthyl and the BODIPY core is
as great as 558.[11a]
Compound labs/lem [nm] e [mÀ1 cmÀ1]fwhm [nm]
F
Stokes
shift [nm]
4
5
6
7
8
9
10
11
12
13
14
15
16
17
740/752
736/748
721/732
706/730
723/734
715/730
688/710
708/732
678/713
681/728
707/735
668/692
774/815
688/715
159000
157000
162000
115000
157000
141000
108000
96200
83900
66500
78000
113000
70300
30.4
29.5
27.1
38.6
27.8
36.1
45.3
51.4
59.2
71.0
74.5
34.3
93.0
52.0
0.28
0.29
0.31
0.11
0.32
0.11
0.44
0.38
0.38
0.24
0.18
0.46
0.05
0.36
12
12
11
24
11
15
22
24
35
47
28
24
41
27
78500
sults in a bathochromic shift of up to 52 nm (cf. 17) and a
concomitant halving of the fwhm.
The emission of 4 occurs in the near infrared with lem
=
754 nm. Dye 4 possesses high fluorescence quantum yield
(F=0.28 relative to 17 with F=0.36 in CHCl3), which
matches the best value of fluorescence quantum yield re-
ported to date for the widely used NIR cyanine dyes.[5] The
Stokes shift of dye 4 is 12 nm which is smaller than refer-
ence compound 17 (27 nm).
Substitution at the b position of the pyrrole in aza-
BODIPY dyes does not affect the e value of the dye (com-
pare 4–6, Table 1, entries 1–3); however, electron-rich aryl
substituents lead to a slight hypsochromic shift of the ab-
sorption maximum, and slightly higher fluorescent quantum
yield (compare Table 1, entries 2 and 1). It should be noted
that the solubility of dye 5 is much lower than that of 4. Ar-
ylalkyl substituent results in a large hypsochromic shift of
the labs, and higher fluorescent quantum yield (compare
Table 1, entries 3 and 1).
Heterocyclic restriction (see dye 7, Table 1, entry 4) leads
to many deleterious effects such as shorter labs, lower e,
broader absorption (larger fwhm), and lower fluorescent
quantum yield (compare Table 1, entry 4 and entries 1–3).
The low fluorescence quantum yield (F=0.11) in 7 may be
due to the heavy atom effect. Dye 7 has slightly better solu-
bility than dye 5, however much lower solubility than 4 and
6.
The non-symmetric aza-BODIPY 8 with both sides re-
stricted displays slightly higher F than the symmetric dye 4,
however, with shorter labs because of the lack of an elec-
tron-donating methoxy substituent on one side (compare
Table 1, entries 5 and 1). In non-symmetric dye 9, lower
quantum yield was observed (compare Table 1, entries 6 and
5), which is consistent with the observation in the parent
BODIPY system that oxidation of the carbocyclic restricted
ring decreases the rigidity of the molecule, leading to a di-
minished fluorescence quantum yield.[11c]
Thus dye 4 is the best concerning solubility, extinction co-
efficient, absorption maximum, and fluorescence quantum
yield. Both the absorption and emission behavior of 4 are
insensitive to solvent polarity. The spectroscopic data of 4 in
various solvents are given in Table 2. Both the maxima of
absorption and emission are slightly blue-shifted with in-
creased polarity of solvents. The fluorescence quantum yield
is also slightly decreased in polar solvents compared to non-
polar solvents.
The novel aza-BODIPY dyes synthesized have excellent
stability. Solutions of 4–17 in CHCl3 remain unchanged over
Table 2. Absorption maxima and fluorescence quantum yields of com-
pound 4 in various solvent at 298 K.
CHCl3
Toluene
EtOAc
0.23
CH3CN
0.23
EtOH
0.22
labs [nm]740
lem [nm]754
F[a]
740
752
732
745
732
746
731
747
0.28
0.28
Aza-BODIPY dyes with only one side restricted have
much lower extinction coefficients than 4 (compare Table 1,
[a]Relative to reference compound 17.
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E. M. Carreira and W. Zhao
months in the dark, indicating excellent chemical stability.
The photostabilities for dye 4–17 are also very good. For ex-
ample, compound 4 was compared with 17 in toluene as
well as against the well-known indocyanine green dye (ICG,
2-[7-[1,3-dihydro-1,1-dimethyl-3-(4-sulfobutyl)-2H-benz[e]in-
dol-2-ylidene]-1,3,5-heptatrienyl]-1,1-dimethyl-3-(4-sulfobu-
tyl)-1H-benz[e]indolium inner salt) which is widely used and
was approved by the FDA as a NIR fluorochrome (F=0.11
in DMSO).[2b] Compound 4 retains 97.7% of the initial in-
tensity of the fluorescence after 1 h strong excitation, which
is similar to that observed for 17 (98.0%); by comparison
ICG loses 75% of the initial intensity after 1 h exposure to
light.
In summary, we have developed novel fluorescent aza-di-
pyrromethene dyes with exceptional stabilities. With appro-
priate substitution and restriction, the novel aza-BODIPY
dyes possess: 1) peak fluorescence at 700–900 nm; 2) high
quantum yield; 3) narrow excitation/emission; and 4) high
chemical and photostability. Moreover, the convenient syn-
theses allow the generation of useful quantities. Additional-
ly, the sharp fluorescent peaks are insensitive to the polarity
of solvents. Efforts are currently underway to develop non-
symmetrically substituted, water soluble versions to allow
conjugation for biosensing experiments.
The excellent stabilities of 4–17 are also reflected in the
changes of absorbance (Figure 3). The normalized absorb-
ance of 4 versus ICG is shown in Figure 3a. After 1 h of
strong illumination with visible light, 99.7% of dye 4 re-
mained. By contrast, only 39.9% of ICG remained under
same condition.
Even amine-containing dye 16 displays excellent photosta-
bility, the absorbance remained almost constant over the
period of 1 h under strong irradiation as shown in Figure 3b.
Dye 16 possessed 99.8% of the initial absorbance after 1 h
of strong illumination with visible light.
Experimental Section
General: All solvents used for UV and fluorescence measurements were
either spectroscopic grade or HPLC grade, and were purchased from
Acros, Aldrich, or Fluka. 1-Acetyl-2-methoxynaphthalene, 2,5-dimethoxy-
acetophenone, 2,4-dimethoxyacetophenone were prepared by literature
procedures.[22] Other ketones were obtained from commercial sources.
Indocyanine green dye (ICG) was purchased from Aldrich. CH2Cl2 and
THF were dried by passing through two 4”36 inch columns of anhydrous
neutral A-2 alumina (8”14 mesh; Macherey und Nagel; activated under
a flow of N2 at 3008C over night) to remove water. 1,2-Dichloroethane
was dried over molecular sieves 3 Š. Other commercial available chemi-
cals were purchased from Aldrich and Fluka, and used as such. Melting
points were not corrected.
Chromatographic purification was performed as flash chromatography
using Brunschwig silica (32–63, 60 Š), or MN-aluminiumoxide (neutral,
deactivated with water to activity III prior to use) with 0.3–0.5 bar pres-
sure, and technical grade solvents were used, which were distilled prior
to use.
1H NMR spectra were recorded on a VARIAN Mercury 300 MHz spec-
trometer in CDCl3, all signals are reported in ppm with the internal
chloroform signal at d 7.26 ppm as standard. The data are being reported
as (s=singlet, d=doublet, t=triplet, m=multiplet or unresolved, cou-
pling constant(s) in Hz, and integration).
1
13C NMR spectra were recorded with H decoupling on a VARIAN Mer-
cury 75 MHz spectrometer in CDCl3, all signals are reported in ppm with
the internal chloroform signal at d 77.0 ppm as standard.
Infrared spectra were recorded on a Perkin-Elmer Spectrum RX-I FT-IR
spectrophotometer and are reported as cmÀ1
.
Mass spectrometric measurements were performed by the mass spec-
trometry service of the LOC at the ETHZ on an IONSPEC Ultima ESI-
FT-ICR spectrometer.
Combustion analysis was performed by the Mikroelementaranalytisches
Laboratorium at ETHZ.
UV/Vis spectra were recorded on Varian Cary 50 UV/Vis spectrometer
at room temperature. Florescence measurements were performed on Flu-
orolog-3 fluorometer (Model FL-3-22, equipped with a R928P photomul-
tiplier tube which is sensitive up to ꢀ850 nm). To obtain accurate excita-
tion spectra, excitation monochromator was calibrated by a Xenon lamp
scan. The emission monochromator was calibrated using a mercury lamp.
The response of the detector was calibrated with a standard tungsten-hal-
ogen lamp. Fluorescence quantum yield determination was performed
following the method recommended by Varian, see: (www.jobinyvon.
com/usadivisions/Fluorescence/applications/quantumyieldstrad.pdf), and
was compared with the method reported by Fery-Forgues and Lavabre.[23]
Compound 17 was used as a standard, and the measurements were per-
formed under identical conditions with 4–16. Non-degassed, spectroscop-
ic grade chloroform and a 10 mm quartz cuvette were used for fluores-
cence measurements, and very dilute solutions (A=0.010) were used to
minimize reabsorption effect. The optical densities of solutions of aza-
BODIPY dyes and 17 were adjusted to 0.200 at 650 nm or 670 nm, and
Figure 3. Absorbance change of aza-BODIPY dyes (5.0”10À6 molLÀ1
)
under continuous irradiation with light >540 nm (the intensity of the
light was 70.5 mWcmÀ2). a) Normalized absorbance change of compound
4 in non-degassed toluene and ICG in aerated water. b) Dye 4 and 16 in
non-degassed toluene.
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Near-Infrared Absorbing Dyes
FULL PAPER
these solutions were diluted by factors 20, 40, 60, 80, and 100. Excitation
wavelength was 650 nm or 670 nm, and a 510 nm cut-off optical filter was
placed between the excitation monochromator and sample cuvette to
eliminate UV (335 nm) excitation.
ed, purified by chromatography on silica gel (CH2Cl2/hexane as eluent)
and recrystallization gave more solid product.
4,5-Dihydro-7-methoxy-3-phenylbenzo[g]indole (1a): The general proce-
dure was followed and 6-methoxy-1-tetralone was used as starting materi-
al. Yield: 336 mg, 61.0% (4 steps). M.p. 147–1488C; 1H NMR (300 MHz,
CDCl3): d=8.30 (brs, 1H), 7.49–7.34 (m, 4H), 7.26–7.20 (m, 1H), 7.13
(d, J=8.4 Hz, 1H), 6.93 (d, J=2.5 Hz, 1H), 6.83 (d, J=2.5 Hz, 1H), 6.76
(dd, J=8.1, 2.5 Hz, 1H), 3.82 (s, 3H), 2.98–2.90 (m, 4H); 13C NMR
(75 MHz, CDCl3): d=157.4, 136.7, 135.8, 128.5, 128.4, 127.0, 125.5, 123.8,
122.5, 119.3, 116.1, 115.1, 114.5, 111.3, 55.3, 30.6, 21.3 ppm; IR (CHCl3):
n˜ =3473, 3003, 2939, 2837, 1603, 1590, 1510, 1480, 1462, 1440, 1302, 1280,
1246, 1150, 1039, 935 cmÀ1; MS (EI): m/z: 275.1307 [M +].
Photostability measurements were conducted in a thermostated cuvette
in toluene at 298 K under continuous illumination from xenon lamp in
fluorometer with 16 nm slit width at the corresponding absorption
maxima with identical optical density (0.10). Temperature was controlled
with RM6 LAUDA thermo-cryostat. After 5 min of continuous illumina-
tion, emission intensity data were collected with 2 nm slit width at the
emission maxima of individual samples.
Photostability evaluation was also conducted in aerated toluene in a ther-
mostated cuvette connected to Cary 50 UV/Vis spectrometer at 298 K
under magnetic stirring. The temperature was controlled with RM6
LAUDA thermo-cryostat. A cut-off OC 13 optical filter was used to
obtain light > 540 nm from a 200 W Xenon lamp as irradiation source.
The intensity of the light was measured with EPM-1000 powermeter to
be 70.5 mWcmÀ2. The beam of illumination was at 908 angle to the moni-
toring beam of Cary 50.
4,5-Dihydro-3-phenylbenzo[g]indole (1b): The general procedure was
followed and 1-tetralone was used as starting material. Yield: 314 mg,
63.9% (4 steps). M.p. 150–1518C; 1H NMR (300 MHz, CDCl3): d=8.39
(brs, 1H), 7.50–7.34 (m, 4H), 7.28–7.17 (m, 4H), 7.15–7.05 (m, 1H), 6.98
(d, J=2.8 Hz, 1H), 3.04–2.88 ppm (m, 4H); 13C NMR (75 MHz, CDCl3):
d=135.7, 134.8, 129.0, 128.4, 127.1, 126.4, 125.5, 125.2, 123.9, 118.2, 117.8,
116.0, 30.1, 21.2 ppm; IR (CHCl3): n˜ =3472, 3062, 3009, 2938, 2840, 1604,
1506, 1481, 1455, 1446, 1396, 1107, 1076, 934 cmÀ1
; MS (EI): m/z:
245.1201 [M +]; elemental analysis calcd (%) for C18H15N: C 88.13, H
General procedure for preparation of pyrroles
i) 1-Azido-2-iodoethylbenzene:[19] Iodine monochloride (5.02 g,
30.3 mmol) was added dropwise to a stirred suspension of sodium azide
(2.26 g, 33.0 mmol) in dry MeCN (55 mL) over 4 min at 08C and then
stirred for 20 min. Styrene (3.16 g, 30 mmol) was added dropwise over
15 min, the reaction mixture was stirred for 0.5 h and was allowed to
warm to room temperature and stirred for 2 h. The reaction mixture was
poured into water (20 mL) and extracted with Et2O (3”20 mL). The
combined extracts were washed with 5% aqueous Na2S2O3 (20 mL) fol-
lowed by water (20 mL), then dried over anhydrous Na2SO4. Solvent was
removed in vacuo, The residue was evacuated at 40 mbar/238C to afford
a mixture of 1-chloro-2-iodoethylbenzene and the desired 1-azido-2-io-
doethylbenzene (about 1:10). This mixture was direct used for the next
step without further purification. 1H NMR (300 MHz, CDCl3): d=7.46–
7.36 (m, 3H), 7.35–7.30 (m, 2H), 4.72 (t, J=7.2 Hz, 1H), 3.39 ppm (d,
J=7.2 Hz, 2H).
ii) (1-Azidovinyl)benzene:[19] The mixture from step i) was dissolved in
dry Et2O (55 mL). tBuOK (4.04 g, 36 mmol) was added in portions at
08C with vigorous stirring, then the mixture was stirred for 40 min,
quenched with cold water (50 mL), and was extracted with Et2O. The sol-
ution was washed with brine (10 mL), dried over anhydrous Na2SO4 and
concentrated in vacuo to give a brown oil, which was dissolved in
CH2Cl2, filtered through a pad of silica gel and was washed with CH2Cl2.
Removal of solvent gave a brown oil which was evacuated at 40 mbar/
238C. The oil containing (1-chloro-vinyl)benzene and desired (1-azido-vi-
nyl)benzene (1:10) was not purified further and was used directly in the
next step. 1H NMR (300 MHz, CDCl3): d=7.60–7.52 (m, 2H), 7.39–7.32
(m, 3H), 5.43 (d, J=2.5 Hz, 1H), 4.96 ppm (d, J=2.5 Hz, 1H).
6.16, N 5.71; found: C 87.91, H 6.25, N 5.67.
4,5-Dihydro-3-phenyl-3H-benzo[e]indole (1c): The general procedure
was followed and 2-tetralone was used as starting material. Yield:
286 mg, 58.3% (4 steps). M.p. 110–1118C; 1H NMR (300 MHz, CDCl3):
d=8.02 (brs, 1H), 7.53–7.46 (m, 2H), 7.41–7.33 (m, 2H), 7.32–7.27 (m,
1H), 7.21–7.12 (m, 2H), 7.02–6.94 (m, 2H), 6.68 (d, J=2.5 Hz, 1H),
3.07–2.98 (m, 2H), 2.84–2.76 ppm (m, 2H); 13C NMR (75 MHz, CDCl3):
d=136.4, 133.7, 133.2, 131.2, 128.8, 128.1, 127.8, 126.1, 126.0, 124.1, 122.8,
122.7, 115.9, 30.3, 22.4 ppm; IR (CHCl3): n˜ = 3468, 3062, 3008, 2944,
2837, 1604, 1530, 1496, 1222, 1208, 1006, 947, 702 cmÀ1; MS (EI): m/z:
245.1199 [M +].
1,4-Dihydro-3-phenyl-[1]-benzothiopyran[4,3-b]pyrrole (1d)
E
i) NaH/DMSO process: The general procedure was followed and thio-
chroman-4-one was used as starting material. Yield: 12.2 mg, 2.3% (4
steps).
ii) LDA/THF process: Thiochroman-4-one (2.0 mmol) in THF (6 mL)
was cooled to À788C, LDA (Acros 2.0m, 1.01 mL, 2.02 mmol) was added
dropwise with stirring over 5 min under nitrogen. Crude phenyl azirine
(2.05 mmol) was added dropwise with stirring over 5 min. The mixture
was stirred at À788C for 2 h, and was allowed to warm up to room tem-
perature slowly. It was quenched with water, neutralized with dilute HCl
to a pH about 7. THF was removed in vacuo, the residue was extracted
with Et2O. The solvent was removed in vacuo, and the residue was dis-
solved in CH2Cl2, filtered through a short alumina column (neutral, activ-
ity III) and washed with CH2Cl2. After removal of solvent, the residue
was recrystallized from Et2O/hexane. The resulting beige solid was col-
lected by filtration. The mother liquid was concentrated and was purified
by chromatography (silica gel, CH2Cl2/hexane 2:3) and recrystallization;
yield: 389 mg, 72% (4 steps). M.p. 150.8–151.38C; 1H NMR (300 MHz,
CDCl3): d=8.43 (brs, 1H), 7.45–7.32 (m, 5H), 7.31–7.23 (m, 2H), 7.15
(td, J=7.5, 1.3 Hz, 1H), 7.07 (td, J=7.8, 1.6 Hz, 1H), 6.97 (d, J=2.8 Hz,
1H), 4.12 ppm (s, 2H); 13C NMR (75 MHz, CDCl3): d = 134.8, 130.6,
128.5, 128.1, 127.8, 127.6, 126.0, 125.7, 123.7, 119.9, 116.8, 113.2,
24.5 ppm; IR (CHCl3): n˜ =3470, 3064, 3008, 2894, 2833, 1604, 1580, 1559,
1527, 1481, 1448, 1441, 1430, 1392, 1287, 1172, 1112, 1073, 1059, 1033,
936 cmÀ1; MS (EI): m/z: 263.0768 [M +]; elemental analysis calcd (%) for
C17H17NS: C 77.53, H 4.98, N 5.32; found: C 77.32, H 5.01, N 5.27.
iii) 3-Phenyl-2H-azirine:[20] Crude (1-azidovinyl)benzene prepared above
was divided into 3 portions. Each portion was dissolved in CH2Cl2
(100 mL) and heated in an autoclave (300 mL) at 1758C for 25 min. Re-
moval of the solvent under slight vacuum followed by evacuation at
50 mbar/238C for 1.5 h in rotavap gave a brown oil (3.77 g) containing
(1-chloro-vinyl)benzene and desired 3-phenyl-2H-azirine (about 1:8.5 es-
timated by 1H NMR) which was used directly in the next step without
1
further purification. H NMR (300 MHz, CDCl3): d = 7.95–7.88 (m, 2H),
7.62–7.55 (m, 3H), 3.90 (s, 3H), 1.77 ppm (s, 2H); 13C NMR (75 MHz,
CDCl3): d=164.2, 163.1, 131.4, 118.0, 114.5, 55.6, 19.5 ppm.
iv) Pyrrole:[18] Ketone (2.0 mmol) was added in portions at room temper-
ature to a stirred suspension of NaH (purity 95%, 50.2 mg, 2.0 mmol) in
DMSO (2 mL) over 8 min, stirred for 0.5 h. Crude azirine from step iii)
(251.3 mg, about 2.0 mmol) was added dropwise under water cooling
(108C) with vigorous stirring over 5 min. The mixture was stirred at
room temperature for 1.5 h, quenched with crushed ice (15 g). The solid
collected by filtration was dissolved in CH2Cl2/hexane, filtered through a
short silica gel column, washed with CH2Cl2/hexane. Solvent was re-
moved, the residue was recrystallized from CH2Cl2/hexane, and the re-
sulted solid was collected by filtration. The mother liquid was concentrat-
2,4-Diphenylpyrrole (1e): The general procedure was followed and ace-
tophenone was used as starting material. Yield: 291 mg, 66.4% (4 steps).
M.p. 180.4–181.48C (lit. 179.5–180.58C[24]); 1H NMR (300 MHz, CDCl3):
d=8.44 (brs, 1H), 7.64–7.47 (m, 4H), 7.45–7.32 (m, 4H), 7.29–7.17 (m,
2H), 7.15 (dd, J=3.8, 1.7 Hz, 1H), 6.84 (dd, J=3.8, 1.7 Hz. 1H) ppm; IR
(CHCl3): n=3472, 3078, 3009, 1607, 1490, 1454, 1414, 1122, 1037, 932,
810 cmÀ1; MS (EI): m/z: 219.1044 [M +]; elemental analysis calcd (%) for
C16H13N: C 87.64, H 5.98, N 6.39; found: C 87.42, H 6.03, N 6.33.
Chem. Eur. J. 2006, 12, 7254 – 7263
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7259

E. M. Carreira and W. Zhao
2-(p-Methoxyphenyl)-4-phenylpyrrole (1 f): The general procedure was
1077, 928, 809 cmÀ1; MS (EI): m/z: 302.1779 [M +]; elemental analysis
calcd (%) for C21H22N2: C 83.40, H 7.33, N 9.26; found: C 83.53, H 7.34,
N 9.20.
followed and 4-methoxyacetophenone was used as starting material.
1
Yield: 331 mg, 66.3% (4 steps). M.p. 208.8–209.68C; H NMR (300 MHz,
CDCl3): d=8.34 (brs, 1H), 7.60–7.53 (m, 2H), 7.40–7.32 (m, 2H), 7.20
(tt, J=7.5, 1.2 Hz, 1H), 7.11 (dd, J=3.5, 1.9 Hz. 1H), 6.98–6.90 (m, 2H),
6.72 (dd, J=2.5, 1.9 Hz, 1H), 3.84 ppm (s, 3H); 13C NMR (75 MHz,
CDCl3): d=158.3, 135.5, 133.0, 128.5, 125.5, 125.2, 125.0, 114.7, 114.3,
102.9, 95.4, 55.4, 25.9 ppm; IR (CHCl3): n˜ = 3472, 3035, 3007, 2942, 2837,
1604, 1530, 1249, 1180, 1119, 1038, 926, 832 cmÀ1; MS (EI): m/z: 249.1150
[M +]; elemental analysis calcd (%) for C17H15NO: C 81.90, H 6.06, N
5.62; found: C 81.65, H 6.10, N 5.54.
4,5-Dihydro-7-methoxy-3-(p-methoxyphenyl)-benzo[g]indole (2): The
general procedure of step i)–iv) was followed except that p-methoxy styr-
ene was used instead of styrene. Yield: 458 mg, 74.5% (4 steps).
i)
1-Azido-2-iodoethyl-(p-methoxy)benzene:
1H NMR
(300 MHz,
CDCl3): d=7.28–7.20 (m, 2H), 6.96–6.89 (m, 2H), 4.68 (t, J=7.2 Hz,
1H), 3.83 (s, 3H), 3.37 ppm (d, J=7.2 Hz, 2H).
ii) 1-Azidovinyl(p-methoxy)benzene: 1H NMR (300 MHz, CDCl3): d=
7.52–7.46 (m, 2H), 6.90–6.84 (m, 2H), 5.32 (d, J=2.5 Hz, 1H), 4.86 (d,
2-(o-Methoxyphenyl)-4-phenylpyrrole (1g): The general procedure was
followed and 2-methoxyacetophenone was used as starting material.
Yield: 325 mg, 65.2% (4 steps). M.p. 110.7–111.38C (lit. 105–1068C[24]);
1H NMR (300 MHz, CDCl3): d=9.85 (brs, 1H), 7.73 (dd, J=7.8, 1.6 Hz,
1H), 7.63–7.55 (m, 2H), 7.40–7.32 (m, 2H), 7.23–7.13 (m, 3H), 7.04 (dd,
J=7.5, 1.3 Hz, 1H), 7.01–6.96 (m, 1H), 6.92 (dd, J=2.5, 1.6 Hz, 1H),
3.99 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): d=154.7, 135.7, 130.7,
128.5, 126.8, 126.5, 125.3, 125.2, 125.0, 121.4, 120.6, 114.6, 111.5, 103.9,
55.7 ppm; IR (CHCl3): n˜ = 3459, 3065, 3008, 2943, 2838, 1604, 1587,
1578, 1525, 1485, 1461, 1406, 1300, 1251, 1237, 1182, 1122, 1027, 936, 807,
696 cmÀ1; MS (EI): m/z: 249.1153 [M +]; elemental analysis calcd (%) for
C17H15NO: C 81.90, H 6.06, N, 5.62; found: C 81.67, H 6.16, N 5.57.
J=2.5 Hz, 1H), 3.83 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): d
=
160.3, 144.6, 126.9, 113.7, 96.1, 55.3 ppm.
iii) 3-(p-Methoxy)phenyl-2H-azirine: 1H NMR (300 MHz, CDCl3): d =
7.88–7.82 (m, 2H), 7.09–7.03 (m, 2H), 3.90 (s, 3H), 1.74 (s, 2H);
13C NMR (75 MHz, CDCl3): d = 164.2, 163.1, 131.4, 118.0, 114.5, 55.6,
19.5 ppm; IR (KBr film): n˜ = 3039, 2969, 2840, 1744, 1605, 1577, 1510,
1463, 1442, 1422, 1324, 1305, 1289, 1258, 1172, 1125, 1107, 1028, 988,
836 cmÀ1
.
iv) 4,5-Dihydro-7-methoxy-3-(p-methoxyphenyl)-benzo[g]-indole: M.p.
186–187.68C; 1H NMR (300 MHz, CDCl3): d=8.23 (brs, 1H), 7.41–7.34
(m, 2H), 7.12 (d, J=8.4 Hz, 1H), 6.97–6.91 (m, 2H), 6.86 (d, J=2.5 Hz,
1H), 6.82 (d, J=2.5 Hz, 1H), 6.85 (dd, J=8.4, 2.5 Hz, 1H), 3.84 (s, 3H),
3.82 (s, 3H), 3.00–2.84 (m, 4H); 13C NMR (75 MHz, CDCl3): d=157.6,
157.4, 136.7, 128.5, 128.3, 128.1, 123.4, 122.5, 119.2, 115.9, 114.5, 113.9,
111.2, 55.3, 55.3, 30.6, 21.2 ppm; IR (CHCl3): n˜ = 3474, 3006, 2939, 2837,
1614, 1590, 1563, 1532, 1511, 1490, 1463, 1442, 1302, 1280, 1247, 1176,
2-(2-Methoxynaphthalene-1-yl)-4-phenylpyrrole (1h): The general proce-
dure was followed and 1-acetyl-2-methoxynaphthalene was used as start-
ing material. Yield: 217 mg, 36.2% (4 steps). M.p. 129.8–130.58C;
1H NMR (300 MHz, CDCl3): d=8.80 (brs, 1H), 8.30 (d, J=8.4 Hz, 1H),
7.85 (d, J=8.7 Hz, 1H), 7.83 (d, J=8.1 Hz, 1H), 7.68–7.60 (m, 2H), 7.50–
7.29 (m, 6H), 7.24–7.16 (m, 1H), 6.82 (dd, J=2.5, 1.6 Hz, 1H), 3.93 ppm
(s, 3H); 13C NMR (75 MHz, CDCl3): d=154.0, 135.8, 133.1, 129.3, 129.2,
128.5, 127.9, 126.6, 126.3, 125.5, 125.3, 125.0, 123.8, 116.1, 114.5, 113.3,
108.9, 56.7 ppm; IR (CHCl3): n˜ = 3471, 3061, 3008, 2940, 2840, 1622,
1604, 1594, 1511, 1463, 1413, 1367, 1335, 1269, 1252, 1127, 1077, 928,
809 cmÀ1; MS (EI): m/z: 299.1306 [M +]; elemental analysis calcd (%) for
C21H17NO: C 84.25, H 5.72, N 4.68; found: C 84.01, H 5.83, N 4.62.
1037, 936, 835 cmÀ1
.
4,5-Dihydro-7-methoxy-3-phenylethylbenzo[g]indole(3)
i) NaH/DMSO process: The general procedure of step i)–iv) was followed
except that 4-phenyl-1-butene was used instead of styrene and in step (ii)
the product was isolated by chromatography on silica gel (hexane/CH2Cl2
1:6) to afford of desired intermediate in 69% combined yield (2 steps),
and final product 22 mg in 3.6% combined yield (4 steps).
2-(2,5-Dimethoxyphenyl)-4-phenylpyrrole (1i): The general procedure
was followed and 2,5-dimethoxyacetophenone was used as starting mate-
rial. 415 mg, Yield: 74.2% (4 steps). M.p. 113.5–114.28C; 1H NMR
(300 MHz, CDCl3): d=9.93 (brs, 1H), 7.64–7.57 (m, 2H), 7.42–7.33 (m,
2H), 7.28 (d, J=2.8 Hz, 1H), 7.24–7.13 (m, 2H), 6.95–6.90 (m, 1H), 6.92
(d, J=9.0 Hz, 1H), 6.74 (dd, J=2.5, 1.6 Hz. 1H), 3.93 (s, 3H), 3.85 ppm
(s, 3H); 13C NMR (75 MHz, CDCl3): d=154.0, 149.2, 135.6, 130.6, 128.5,
125.4, 125.2, 125.0, 121.4, 114.8, 112.8, 111.8, 111.7, 104.1, 56.3, 55.8 ppm;
IR (CHCl3): n˜ = 3454, 3007, 2941, 2836, 1606, 1526, 1491, 1467, 1226,
1212, 1179, 1127, 1048, 1024, 928, 808 cmÀ1; MS (EI): m/z: 279.1254 [M +
]; elemental analysis calcd (%) for C18H17NO2: C 77.40, H 6.13, N 5.01;
found: C 77.27, H 6.07, N 4.96.
(1-Azidovinyl)ethylbenzene: Yield: 69% (2 steps); 1H NMR (300 MHz,
CDCl3): d=7.38–7.16 (m, 5H), 4.67–4.63 (m, 2H), 2.84–2.76 (m, 2H),
2.42–2.33 ppm (m, 2H); 13C NMR (75 MHz, CDCl3): d=145.8, 140.6,
128.3, 128.2, 126.0, 98.5, 35.7, 33.8 ppm; IR (KBr film): n˜ =3064, 3028,
2928, 2861, 2104, 1628, 1604, 1496, 1454, 1280, 1076, 846, 748, 699 cmÀ1
.
3-Phenylethyl-2H-azirine: 1H NMR (300 MHz, CDCl3): d=7.35–7.28 (m,
2H), 7.26–7.15 (m, 3H), 3.14–3.06 (m, 4H), 1.40 ppm (s, 2H); 13C NMR
(75 MHz, CDCl3): d=169.3, 139.8, 128.5, 128.2, 126.4, 30.4, 30.4,
19.4 ppm; IR (KBr film): n˜ = 3062, 3029, 2977, 2927, 2861, 1763, 1604,
1496, 1454, 1418, 1076, 1030, 987, 750, 700 cmÀ1
4,5-Dihydro-7-methoxy-3-phenylethylbenzo[g]indole:
.
M.p.
104.3–
106.38C; 1H NMR (300 MHz, CDCl3): d=8.30 (brs, 1H), 7.49–7.34 (m,
4H), 7.26–7.20 (m, 1H), 7.13 (d, J=8.4 Hz, 1H), 6.93 (d, J=2.5 Hz, 1H),
6.83 (d, J=2.5 Hz, 1H), 6.76 (dd, J=8.1, 2.5 Hz, 1H), 3.82 (s, 3H), 2.98–
2.90 ppm (m, 4H); 13C NMR (75 MHz, CDCl3): d=157.4, 136.9, 135.8,
128.5, 128.4, 127.0, 125.5, 123.8, 122.5, 119.3, 116.1, 115.1, 114.5, 111.3,
55.3, 30.6, 21.3 ppm; IR (CHCl3): n˜ = 3477, 3064, 3029, 3006, 2936, 2837,
1615, 1590, 1566, 1517, 1496, 1462, 1442, 1426, 1300, 1281, 1247, 1221,
1209, 1151, 1062, 1037, 700 cmÀ1; MS (EI): m/z: 303.1617 [M +]; elemen-
tal analysis calcd (%) for C21H21NO: C 83.13, H 6.98, N 4.62; found: C
83.07, H 7.02, N 4.56.
2-(2,4-Dimethoxyphenyl)-4-phenylpyrrole (1j): The general procedure
was followed and 2,4-dimethoxyacetophenone was used as starting mate-
rial. Yield: 370 mg, 66.2% (4 steps). M.p. 143–1448C; 1H NMR
(300 MHz, CDCl3): d=9.66 (brs, 1H), 7.62 (d, J=8.4 Hz, 1H), 7.61–7.55
(m, 2H), 7.39–7.31 (m, 2H), 7.18 (tt, J=7.5, 1.3 Hz, 1H), 7.11 (dd, J=
2.5, 1.8 Hz, 1H), 6.79 (dd, J=2.5, 1.8 Hz, 1H), 6.61–6.6.54 (m, 2H), 3.96
(s, 3H), 3.85 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): d=158.9, 155.8,
135.8, 130.7, 128.4, 127.3, 125.3, 125.0, 114.1, 113.8, 105.5, 102.8, 99.1,
55.7, 55.5 ppm; IR (CHCl3): n˜ = 3464, 3064, 3006, 2941, 2839, 1613, 1588,
1578, 1529, 1493, 1462, 1439, 1299, 1243, 1159, 1120, 1048, 1030, 943,
838 cmÀ1; MS (EI): m/z: 279.1256 [M +]; elemental analysis calcd (%) for
C18H17NO2: C 77.40, H 6.13, N 5.01; found: C 77.16, H 6.00, N 4.99.
ii) LDA/THF process: The process of 1d was followed except 6-methoxy-
1-tetralone and 3-phenylethyl-2H-azirine were used instead of thio-chro-
man-4-one and phenyl azirine. The desired product (269 mg, 43%) was
obtained.
2-(p-Piperidinophenyl)-4-phenylpyrrole (1k): The general procedure was
followed and 4-piperidinoacetophenone was used as starting material.
Yield: 376 mg, 62.2% (4 steps). M.p. 143–1448C; 1H NMR (300 MHz,
CDCl3): d=8.34 (brs, 1H), 7.60–7.53 (m, 2H), 7.45–7.30 (m, 4H), 7.18
(tt, J=7.4, 1.3 Hz, 1H), 7.09 (dd, J=2.5, 1.8 Hz, 1H), 7.00–6.92 (m, 2H),
6.69 (dd, J=2.5, 1.8 Hz, 1H), 3.22–3.14 (m, 4H), 1.80–1.60 ppm (m, 6H);
13C NMR (75 MHz, CDCl3): d=150.5, 135.6, 133.4, 128.5, 126.2, 125.5,
124.7, 116.6, 114.5, 102.4, 50.6, 25.8, 24.3 ppm; IR (CHCl3): n˜ = 3471,
3061, 3009, 2940, 2841, 1622, 1604, 1594, 1511, 1463, 1269, 1252, 1127,
General procedure for preparation of symmetric aza-BODIPY dyes:
Sodium nitrite (6.9 mg, 0.1 mmol) was added at 58C with stirring to a sol-
ution of pyrrole derivative (0.2 mmol) in a mixture of acetic acid/acetic
anhydride (1 mL/0.4 mL). The mixture was stirred for 0.5 h, followed by
heating at 808C for 0.5 h. Crushed ice was added to the cold reaction
mixture, the resulted blue dye was filtered and washed with water. The
blue dye was dissolved in CH2Cl2, filtered through a pad of alumina (ac-
7260
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 7254 – 7263

Near-Infrared Absorbing Dyes
FULL PAPER
tivity III) and washed with CH2Cl2. Solvent was removed in vacuo, the
residue was dissolved in dry 1,2-dichloroethane, triethylamine (0.24 mL)
was added, followed by slow addition of BF3·Et2O (0.24 mL) with stirring
at room temperature. The mixture was stirred for 0.5 h, then heated in a
808C oil bath for 0.5 h, and was cooled down. The reaction was quenched
with crushed ice, extracted with CH2Cl2, filtered through a pad of alumi-
na (activity III). Solvent was removed, the residue was recrystallized
from CH2Cl2/hexane. Coppery solid was obtained. Mother liquid was pu-
rified by chromatography on alumina (activity III) or silica gel (CH2Cl2/
hexane 1:1) and recrystallization from CH2Cl2/hexane.
tracted with CH2Cl2, and was purified by chromatography on silica gel
followed by recrystallization from CH2Cl2/hexane.
Aza-BODIPY dye 8: The general procedure for non-symmetric aza-
BODIPY was followed using 1b as the second pyrrole moiety, and cop-
pery solid was obtained (39.9 mg, 68.7%). M.p. 298–2998C; 1H NMR
(300 MHz, CDCl3): d=8.82 (d, J=8.7 Hz, 1H), 8.74 (d, J=8.1 Hz, 2H),
7.76–7.66 (m, 4H), 7.50–7.26 (m, 9H), 7.04 (dd, J=9.0, 2.5 Hz, 1H), 6.85
(d, J=2.5 Hz, 1H), 3.92 (s, 3H), 2.95 (s, 4H), 2.94 ppm (s, 4H); 13C NMR
(75 MHz, CDCl3): d=162.3, 154.0, 150.2, 146.5, 145.1, 144.6, 140.9, 137.8,
136.2, 132.3, 131.8, 131.7, 130.6, 130.2, 128.2, 128.0, 127.9, 127.8, 127.5,
120.1, 114.5, 113.1, 55.5, 30.6, 30.4, 21.9, 21.8 ppm; IR (KBr): n˜ = 3043,
2937, 2837, 1599, 1512, 1464, 1450, 1391, 1304, 1292, 1275, 1252, 1236,
Aza-BODIPY dye 4: The general procedure for symmetric aza-BODIPY
was followed using 1a as starting material, and coppery solid (46.7 mg,
76.5%) was obtained. M.p. 297–2988C; 1H NMR (300 MHz, CDCl3): d=
8.76 (d, J=9.0 Hz, 2H), 7.76–7.66 (m, 4H), 7.49–7.32 (m, 6H), 7.02 (dd,
J=9.0, 2.5 Hz, 2H), 6.84 (d, J=2.5 Hz, 2H), 3.91 (s, 6H), 2.94 ppm (s,
8H); 13C NMR (75 MHz, CDCl3): d=161.6, 151.6, 145.6, 143.9, 136.6,
132.2, 131.0, 130.8, 130.7, 130.2, 127.9, 120.6, 114.4, 112.9, 55.5, 30.8,
21.9 ppm; IR (KBr): n˜ =2932, 2835, 1762, 1601, 1514, 1448, 1394, 1279,
1256, 1235, 1142, 1054, 772, 698 cmÀ1; HRMS (MALDI): m/z (%): calcd
for C38H30BF2N3O2: 609.2394; found: 609.2383 (100) [M +].
1187, 1142, 1122, 1081, 1057, 1029, 1010, 762, 698 cmÀ1
; HRMS
(MALDI): m/z (%): calcd for C37H28BF2N3O: 580.2366; found: 580.2357
(100) [M+H+].
Aza-BODIPY dye 9: The general procedure for non-symmetric aza-
BODIPY was followed using 1c as the second pyrrole moiety, and cop-
pery solid was obtained (4.4 mg, 7.6%). M.p. 304–3058C; 1H NMR
(300 MHz, CDCl3): d=8.97 (d, J=9.0 Hz, 1H), 8.19 (d, J=8.1 Hz, 1H),
7.86–7.64 (m, 7H), 7.56–7.26 (m, 8H), 7.09 (dd, J=8.7, 2.8 Hz, 1H), 6.89
(d, J=2.2 Hz, 1H), 3.96 (s, 3H), 3.08–2.92 ppm (m, 4H); 13C NMR
(75 MHz, CDCl3): d=164.1, 146.5, 134.8, 133.8, 133.8, 133.0, 131.1, 130.9,
130.4, 130.2, 129.6, 129.1, 128.9, 128.1, 128.0, 127.7, 127.0, 124.9, 124.0,
119.0, 115.7, 114.6, 113.8, 55.8, 30.4, 22.3 ppm; IR (KBr): n˜ = 3046, 3009,
2963, 2921, 2833, 1598, 1544, 1478, 1451, 1386, 1356, 1309, 1284, 1250,
1146, 1118, 1098, 1057, 1027, 818, 749, 692 cmÀ1; HRMS (MALDI): m/z
(%): calcd for C37H26BF2N3O: 578.2210; found: 578.2201 (100) [M+H+].
Aza-BODIPY dye 5: The general procedure for symmetric aza-BODIPY
was followed using 2 as starting material, and coppery solid was obtained
(53.8 mg, 80.2%). M.p. 324–3258C; 1H NMR (300 MHz, CDCl3): d=8.75
(d, J=9.3 Hz, 2H), 7.73–7.64 (m, 4H), 7.05–6.93 (m, 6H), 6.83 (d, J=
2.7 Hz, 2H), 3.91 (s, 6H), 3.87 (s, 6H), 2.92 ppm (s, 8H); 13C NMR
(75 MHz, CDCl3): d=161.4, 159.5, 151.4, 148.2, 148.2, 143.7, 136.4, 133.5,
131.5, 130.8, 129.6, 125.1, 120.8, 114.4, 113.5, 112.8, 55.5, 55.4, 30.8,
22.0 ppm; IR (KBr): n˜ = 2935, 2834, 1608, 1514, 1495, 1451, 1430, 1396,
1279, 1256, 1236, 1181, 1164, 1136, 1061, 1032, 839, 762 cmÀ1; HRMS
(MALDI): m/z (%): calcd for C40H34BF2N3O4: 670.2683; found: 670.2682
(41) [M+H+].
Aza-BODIPY dye 10: The general procedure for non-symmetric aza-
BODIPY was followed using 1e as the second pyrrole moiety, and cop-
pery solid was obtained (38.1 mg, 68.7%). M.p. 231–2328C; 1H NMR
(300 MHz, CDCl3): d=8.73 (d, J=9.0 Hz, 1H), 8.10–8.00 (m, 3H), 7.78–
7.70 (m, 2H), 7.55–7.30 (m, 9H), 6.97 (dd, J=9.0, 2.8 Hz, 1H), 6.93 (s,
1H), 6.84 (d, J=2.5 Hz, 1H), 3.90 (s, 3H), 3.04–2.90 ppm (m, 4H);
13C NMR (75 MHz, CDCl3): d=163.2, 156.8, 153.8, 147.2, 145.5, 143.9,
139.6, 139.1, 133.0, 132.7, 131.6, 130.4, 129.6, 129.3, 128.8, 128.7, 128.4,
128.4, 128.2, 119.6, 116.9, 114.6, 113.3, 55.5, 30.4, 21.8 ppm; IR (KBr): n˜
= 3058, 2920, 2833, 1601, 1533, 1512, 1500, 1485, 1468, 1451, 1384, 1285,
1251, 1229, 1191, 1131, 1092, 1049, 1028, 999, 964, 763, 691 cmÀ1; HRMS
(MALDI): m/z (%): calcd for C35H26BF2N3O: 554.2210; found: 554.2201
(100) [M+H+].
Aza-BODIPY dye 6: The general procedure for symmetric aza-BODIPY
was followed using 3 as starting material, and coppery solid was obtained
(58.1 mg, 87.1%). M.p. 229.5–230.58C; 1H NMR (300 MHz, CDCl3): d=
8.66 (d, J=9.0 Hz, 2H), 7.32–7.15 (m, 10H), 6.96 (dd, J=8.7, 2.5 Hz,
2H), 6.78 (d, J=2.5 Hz, 2H), 3.88 (s, 6H), 2.99 (s, 8H), 2.80 (dd, J=7.5,
6.5 Hz, 4H), 2.44 ppm (t, J=7.5, 6.5 Hz, 4H); 13C NMR (75 MHz,
CDCl3): d=161.3, 151.2, 145.7, 143.8, 141.7, 138.0, 131.4, 130.6, 128.5,
128.2, 125.9, 120.7, 114.4, 112.7, 55.4, 36.9, 30.5, 26.8, 20.4 ppm; IR (KBr):
n˜ =2929, 2833, 1603, 1513, 1493, 1446, 1412, 1391, 1278, 1252, 1191, 1088,
1071, 1061, 1052, 1035, 991, 963, 698 cmÀ1; HRMS (MALDI): m/z (%):
calcd for C42H38BF2N3O2: 666.3098; found: 666.3086 (100) [M+H+].
Aza-BODIPY dye 11: The general procedure for non-symmetric aza-
BODIPY was followed using 1 f as the second pyrrole moiety, and cop-
pery solid was obtained (40.2 mg, 73.4%). M.p. 246.5–2488C; 1H NMR
(300 MHz, CDCl3): d=8.72 (d, J=9.0 Hz, 1H), 8.12–8.03 (m, 4H), 7.77–
7.70 (m, 2H), 7.54–7.30 (m, 6H), 7.08–7.01 (m, 2H), 6.97 (dd, J=9.0,
2.8 Hz, 1H), 6.96 (s, 1H), 6.84 (d, J=2.5 Hz, 1H), 3.91 (s, 3H), 3.90 (s,
3H), 3.00–2.91 ppm (m, 4H); 13C NMR (75 MHz, CDCl3): d=162.7,
161.2, 155.2, 154.7, 146.6, 145.0, 144.4, 140.3, 138.4, 132.9, 132.3, 132.1,
131.9, 131.1, 130.4, 128.9, 128.6, 128.5, 128.4, 128.1, 124.9, 120.0, 117.0,
114.5, 114.1, 113.2, 55.5, 55.4, 30.5, 21.8 ppm; IR (KBr): n˜ = 2967, 2835,
1603, 1526, 1503, 1474, 1428, 1393, 1303, 1260, 1181, 1124, 1110, 1024,
768, 682 cmÀ1; HRMS (MALDI): m/z (%): calcd for C36H28BF2N3O2:
584.2315; found: 584.2305 (42) [M+H+].
Aza-BODIPY dye 7: The general procedure for symmetric aza-BODIPY
was followed except that 1d was used as starting material and chromato-
graphic purification followed by recrystallization was adopted, dark
brown solid (17.0 mg, 29.0%) was obtained. M.p. 2508C (decomp);
1H NMR (300 MHz, CDCl3): d=8.74 (d, J=7.8 Hz, 2H), 7.66–7.56 (m,
4H), 7.51–7.29 (m, 12H), 4.00 ppm (s, 4H); 13C NMR (75 MHz, CDCl3):
d=152.8, 146.0, 138.5, 138.3, 131.1, 131.0, 130.7, 130.6, 130.4, 129.0, 128.9,
128.6, 128.3, 127.1, 126.9, 24.4 ppm; IR (KBr): n˜ = 3050, 2887, 1583,
1553, 1527, 1449, 1386, 1316, 1266, 1213, 1135, 1124, 1090, 1071, 1055,
1039, 1004, 993, 976, 768, 732, 696 cmÀ1; HRMS (MALDI): m/z (%):
calcd for C34H22BF2N3S2: 586.1389; found: 586.1381 (100) [M+H+].
General procedure for preparation of non-symmetric aza-BODIPY dyes:
Sodium nitrite (6.9 mg, 0.1 mmol) was added at 58C with stirring to a sus-
pension of 1a (27.6 mg, 0.1 mmol) in acetic acid (1 mL), and was stirred
for 10 min. The color changed from colorless to brown, then green, and
finally brown was observed. The second pyrrole moiety was added, fol-
lowed by addition of acetic anhydride (0.4 mL). The mixture turned blue
immediately. After 0.5 h stirring, the mixture was heated at 808C for
0.5 h. Crushed ice was added to the cold reaction mixture, the resulted
blue dye was filtered, washed with water. The blue dye was dissolved in
CH2Cl2, filtered through a pad of alumina (activity III) and washed with
CH2Cl2. Solvent was removed in vacuo, the residue was dissolved in dry
1,2-dichloroethane, triethylamine (0.24 mL) was added, followed by drop-
wise addition of BF3·Et2O (0.24 mL) with stirring at room temperature.
The mixture was stirred for 0.5 h, then heated in 808C oil bath for 0.5 h,
and was cooled down. The reaction was quenched with crushed ice, ex-
Aza-BODIPY dye 12: The general procedure for non-symmetric aza-
BODIPY was followed using 1g as the second pyrrole moiety, and cop-
pery solid was obtained (20.5 mg, 43.5%). M.p. 239–2408C; 1H NMR
(300 MHz, CDCl3): d=8.60 (d, J=9.0 Hz, 1H), 8.10–8.03 (m, 2H), 7.88
(dd, J=7.5, 1.3 Hz, 1H), 7.76–7.70 (m, 2H), 7.55–7.30 (m, 7H), 7.11 (td,
J=7.5, 1.9 Hz, 1H), 7.02 (d, J=8.4 Hz, 1H), 6.92 (s, 1H), 6.89 (dd, J=
9.0, 2.8 Hz, 1H), 6.81 (d, J=2.8 Hz, 1H), 3.87 (s, 3H), 3.86 (s, 3H), 3.00–
2.89 ppm (m, 4H); 13C NMR (75 MHz, CDCl3): d=162.7, 157.8, 156.2,
151.0, 145.0, 139.0, 138.8, 133.1, 132.4, 131.8, 131.7, 130.7, 130.3, 128.7,
128.5, 128.2, 128.2, 128.0, 121.9, 120.2, 119.6, 119.0, 114.4, 113.2, 111.1,
56.0, 55.5, 30.5, 21.9 ppm; IR (KBr): n˜ = 2935, 2834, 1602, 1540, 1486,
1470, 1451, 1384, 1284, 1252, 1223, 1188, 1142, 1123, 1096, 1068, 1051,
1026, 1006, 972, 768, 731, 698, 680 cmÀ1; HRMS (MALDI): m/z (%):
calcd for C36H28BF2N3O2: 584.2315; found: 584.2306 (100) [M+H+].
Chem. Eur. J. 2006, 12, 7254 – 7263
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7261

E. M. Carreira and W. Zhao
Aza-BODIPY dye 13: The general procedure for non-symmetric aza-
BODIPY was followed using 1i as the second pyrrole moiety, and cop-
pery solid was obtained (26.6 mg, 43.4%). M.p. 140–1428C; 1H NMR
(300 MHz, CDCl3): d=8.64 (d, J=9.0 Hz, 1H), 8.10–8.04 (m, 2H), 7.77–
7.70 (m, 2H), 7.57 (d, J=2.2 Hz, 1H), 7.54–7.29 (m, 6H), 6.99–6.95 (m,
3H), 6.91 (dd, J=9.0, 2.8 Hz, 1H), 6.82 (d, J=2.5 Hz, 1H), 3.88 (s, 3H),
3.86 (s, 3H), 3.82 (s, 3H), 3.01–2.88 ppm (m, 4H); 13C NMR (75 MHz,
CDCl3): d=162.8, 156.3, 152.9, 152.2, 150.5, 147.0, 145.1, 143.2, 138.9,
138.8, 133.1, 132.6, 132.4, 131.6, 130.3, 128.7, 128.5, 128.2, 128.0, 122.5,
119.6, 119.0, 116.9, 116.3, 114.4, 113.2, 112.9, 56.9, 55.8, 55.5, 30.5,
21.9 ppm; IR (KBr): n˜ = 2931, 2833, 1600, 1538, 1508, 1486, 1476, 1450,
1432, 1382, 1284, 1252, 1227, 1186, 1139, 1093, 1068, 1049, 1025, 1007,
[1]a) M. Matsuoka, Infrared Absorbing Dyes, Plenum, New York,
1990; b) Near-Infrared Dyes for high Technology Applications,
NATO Series 3, Vol. 52 (Eds.: S. Dähne, U. Resch-Genger, O. S.
Wolfbeis), Kluwer, Dordrecht, 1998; c) B. Valeur, Molecular Fluo-
rescence, Principles and Applications, Wiley-VCH, Weinheim, 2002.
[2]a) J. V. Frangioni, Curr. Opin. Chem. Biol. 2003, 7, 626–634;
b) E. M. Sevick-Muraca, J. P. Houston, M. Gurfinkel, Curr. Opin.
Chem. Biol. 2002, 6, 642–650; c) C. Sun, J. Yang, L. Li, X. Wu, Y.
Liu, S. Liu, J. Chromatogr. B 2004, 803, 173–190; d) M. Funovics, R.
Weissleder, C. H. Tung, Anal. Bioanal. Chem. 2003, 377, 956–963;
e) R. P. Haugland, Handbook of Fluorescent Probes and Research
Chemicals, Molecular Probes, Eugene, 6th ed., 1996.
972, 770, 748, 690 cmÀ1
; HRMS (MALDI): m/z (%): calcd for
C37H30BF2N3O3: 614.2421; found: 614.2411 (100) [M+H+].
[3]V. Ntziachristos, J. Ripoll, R. Weissleder, Opt. Lett. 2002, 27, 333–
335.
Aza-BODIPY dye 14: The general procedure for non-symmetric aza-
BODIPY was followed using 1j as the second pyrrole moiety, and cop-
pery solid was obtained (28.4 mg, 46.3%). M.p. 226–2278C; 1H NMR
(300 MHz, CDCl3): d=8.70 (d, J=9.0 Hz, 1H), 8.10–8.04 (m, 2H), 7.99
(d, J=8.5 Hz, 1H), 7.76–7.70 (m, 2H), 7.54–7.29 (m, 6H), 7.00 (s, 1H),
6.91 (dd, J=9.0, 2.8 Hz, 1H), 6.82 (d, J=2.8 Hz, 1H), 6.66 (dd, J=8.5,
2.5 Hz, 1H), 6.57 (d, J=2.5 Hz, 1H), 3.90 (s, 3H), 3.87 (s, 3H), 3.86 (s,
3H), 3.00–2.88 ppm (m, 4H); 13C NMR (75 MHz, CDCl3): d=162.3,
162.1, 159.3, 154.7, 152.0, 146.4, 144.6, 143.7, 139.4, 138.1, 133.0, 132.8,
131.9, 130.3, 128.8, 128.3, 128.2, 128.0, 119.9, 119.8, 114.5, 114.3, 113.1,
104.5, 98.9, 55.9, 55.5, 55.5, 30.6, 21.9 ppm; IR (KBr): n˜ = 2934, 2835,
1611, 1533, 1515, 1499, 1473, 1452, 1389, 1300, 1279, 1257, 1224, 1184,
1129, 1092, 1047, 1022, 824, 768 cmÀ1; HRMS (MALDI): m/z (%): calcd
for C37H30BF2N3O3: 614.2421; found: 614.2410 (100) [M+H+].
[4]J. Sowell, L. Strekowski, G. Patonay, J. Biomed. Opt. 2002, 7, 571–
575.
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Bioconjugate Chem. 1996, 7, 356–362; b) E. G. McRae, M. Kasha, J.
Chem. Phys. 1958, 28, 721–722.
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Behera, Chem. Rev. 2000, 100, 1973–2011; b) J. Fabian, H. Nakazu-
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[7]M. Casalboni, F. De Matteis, P. Prosposito, A. Quatela, F. Sarcinelli,
Chem. Phys. Lett. 2003, 373, 372–378.
[8]W. Zhao, E. M. Carreira, Angew. Chem. 2005, 117, 1705–1707;
Angew. Chem. Int. Ed. 2005, 44, 1677–1679; the general structure of
the parent BODIPY dye is represented by:
Aza-BODIPY dye 15: The general procedure for non-symmetric aza-
BODIPY was followed using 1h as the second pyrrole moiety, and cop-
pery solid was obtained (5.5 mg, 8.7%). M.p. 277.5–278.58C; 1H NMR
(300 MHz, CDCl3): d=8.44 (d, J=9.6 Hz, 1H), 8.17–8.09 (m, 2H), 7.98
(d, J=9.0 Hz, 1H), 7.86–7.72 (m, 3H), 7.66 (d, J=8.1 Hz, 1H), 7.58–7.30
(m, 9H), 6.80–6.71 (m, 3H), 3.96 (s, 3H), 3.80 (s, 3H), 3.00–2.84 ppm (m,
4H); 13C NMR (75 MHz, CDCl3): d=163.1, 157.7, 155.7, 149.1, 147.8,
145.4, 142.9, 139.6, 138.9, 134.0, 133.4, 133.0, 131.7, 131.0, 130.5, 128.8,
128.4, 128.3, 128.2, 127.7, 126.6, 125.6, 123.7, 119.4, 117.7, 116.4, 114.5,
113.6, 113.2, 57.0, 55.4, 30.4, 21.8 ppm; IR (KBr): n=3047, 2934, 2834,
1600, 1540, 1526, 1482, 1450, 1388, 1352, 1284, 1251, 1218, 1184, 1139,
1081, 1059, 1045, 1003, 972, 810, 768, 688 cmÀ1; HRMS (MALDI): m/z
(%): calcd for C40H30BF2N3O2: 634.2472; found: 634.2462 (100) [M+H+].
[9]a) J. C. McGrath, C. J. Daly, Br. J. Pharmacol. 2003, 139, 187–189;
b) R. Reents, M. Wagner, J. Kuhlmann, H. Waldmann, Angew.
Chem. 2004, 116, 2765–2768; Angew. Chem. Int. Ed. 2004, 43, 2711–
2714; c) S. C. Hung, R. A. Mathies, A. N. Glazer, Anal. Biochem.
1997, 252, 78–88; d) H. Maas, G. Calzaferri, Angew. Chem. 2002,
114, 2607–2608; Angew. Chem. Int. Ed. 2002, 41, 2284–2288; e) A.
Burghart, L. H. Thoresen, J. Chen, K. Burgess, F. Bergstrçm, L. B.-
Š. Johansson, Chem. Commun. 2000, 2203–2204; f) G. Ulrich, R.
Ziessel, Synlett 2004, 3, 439–444; g) F. S. Wouters, P. J. Verveer, P. I.
Bastiaens, Trends Cell Biol. 2001, 11, 203–211; h) A. Costela, I.
Garcꢂa-Moreno, C. Gꢃmez, R. Sastre, F. Amat-Guerri, M. Liras,
F. L. Arbeloa, J. B. Prieto, I. L. Arbeloa, J. Phys. Chem. A 2002, 106,
7736–7742; i) G. Beer, C. Niederalt, S. Grimme, J. Daub, Angew.
Chem. 2000, 112, 3385–3388; Angew. Chem. Int. Ed. 2000, 39, 3252–
3255.
[10]A. Burghart, H. J. Kim, M. B. Welch, L. H. Thoresen, J. Reibenspies,
K. Burgess, F. Bergstrçm, L. B.-Š. Johansson, J. Org. Chem. 1999,
64, 7813–7819.
[11]a) H. Kim, A. Burghart, M. B. Welch, J. Reibenspies, K. Burgess,
Chem. Commun. 1999, 1889–1890; b) J. Chen, J. Reibenspies, A.
Derecskei-Kovacs, K. Burgess, Chem. Commun. 1999, 2501–2502;
c) J. Chen, A. Burghart, A. Derecskei-Kovacs, K. Burgess, J. Org.
Chem. 2000, 65, 2900–2906.
Aza-BODIPY dye 16: The general procedure for non-symmetric aza-
BODIPY was followed using 1k as the second pyrrole moiety, and cop-
pery solid was obtained (43.0 mg, 67.6%). M.p. 186–1888C; 1H NMR
(300 MHz, CDCl3): d=8.71 (d, J=9.0 Hz, 1H), 8.19–8.05 (m, 4H), 7.78–
7.70 (m, 2H), 7.53–7.30 (m, 6H), 7.10 (s, 1H), 7.02–6.93 (m, 3H), 6.83 (d,
J=2.5 Hz, 1H), 3.89 (s, 3H), 3.48–3.36 (m, 4H), 2.94 (s, 4H), 1.80–
1.62 ppm (m, 6H); 13C NMR (75 MHz, CDCl3): d=161.5, 156.1, 152.4,
151.5, 145.3, 145.2, 143.8, 140.8, 136.3, 132.7, 132.3, 131.4, 130.7, 130.3,
128.8, 128.5, 128.2, 127.9, 120.6, 120.2, 117.7, 114.2, 114.0, 112.9, 55.4,
48.6, 30.7, 25.6, 24.5, 21.8 ppm; IR (KBr): n˜ =2933, 2833, 1598, 1503,
1478, 1445, 1418, 1390, 1313, 1281, 1252, 1240, 1211, 1141, 1119, 1094,
1043, 1023, 1010, 763, 679 cmÀ1; HRMS (MALDI): m/z (%): calcd for
C40H35BF2N4O: 637.2945; found: 637.2934 (61) [M+H+].
Aza-BODIPY dye 17: The general procedure for symmetric aza-
BODIPY was followed using 1 f as starting material, and coppery solid
was obtained (53.5 mg, 96.0%).
The characterization data are consistent with the data reported.[16b]
[12]a) K. Rurack, M. Kollmannsberger, J. Daub, New J. Chem. 2001, 25,
289–292; b) K. Rurack, M. Kollmannsberger, J. Daub, Angew.
Chem. 2001, 113, 396–399; Angew. Chem. Int. Ed. 2001, 40, 385–
387.
[13]H. C. Kang, R. P. Haugland, US Patent 5187288, 1993.
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nod, R. Paolesse, S. Nardis, C. D. Natale, A. D. Carlo, L. Prodi, M.
Montalti, K. M. Smith, Tetrahedron 2004, 60, 1099–1106; c) Y. Wu,
D. H. Klaubert, H. C. Kang, Y. Z. Zhang, US Patent 6005113, 1999.
Acknowledgements
We thank the ETH-Zürich for support through the INIT program.
7262
www.chemeurj.org
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Chem. Eur. J. 2006, 12, 7254 – 7263

Near-Infrared Absorbing Dyes
FULL PAPER
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Received: April 13, 2006
Published online: July 19, 2006
Chem. Eur. J. 2006, 12, 7254 – 7263
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7263