Pyrrolidylsubstituted azadipyrromethene with fully chelated boron atom

Article abstract of DOI:10.1080/00397910903219542

A difluorosubstituted aza-boron-dipyrromethene derivative with fully chelated boron atom was synthesized by the reaction of BF₃Et ₂O with 3,3,5,5-tetraarylazadipyrromethene, which was easily prepared from 1,3-diaryl-4-nitro-butan-1-one and ammonium acetate. One fluorine atom of the dye was substituted by pyrrolidine residue. This resulted in a significant bathochromic effect. Ultraviolet absorption and fluorescence emission spectra were recorded, and quantum yields of the obtained compounds were calculated.

Full text of DOI:10.1080/00397910903219542

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Pyrrolidylsubstituted
Azadipyrromethene with Fully Chelated
Boron Atom
Viktor P. Yakubovskyi a , Mykola P. Shandura a & Yuriy P. Kovtun a
a Institute of Organic Chemistry, National Academy of Sciences of
Ukraine , Kyiv, Ukraine
Published online: 04 Mar 2010.
To cite this article: Viktor P. Yakubovskyi , Mykola P. Shandura & Yuriy P. Kovtun (2010)
Pyrrolidylsubstituted Azadipyrromethene with Fully Chelated Boron Atom, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 40:7, 944-950, DOI:
10.1080/00397910903219542
To link to this article: http://dx.doi.org/10.1080/00397910903219542
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Synthetic Communications1, 40: 944–950, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903219542
PYRROLIDYLSUBSTITUTED AZADIPYRROMETHENE
WITH FULLY CHELATED BORON ATOM
Viktor P. Yakubovskyi, Mykola P. Shandura, and
Yuriy P. Kovtun
Institute of Organic Chemistry, National Academy of Sciences of Ukraine,
Kyiv, Ukraine
A difluorosubstituted aza-boron–dipyrromethene derivative with fully chelated boron atom
was synthesized by the reaction of BF3 ꢀ Et2O with 3,3,5,5-tetraarylazadipyrromethene,
which was easily prepared from 1,3-diaryl-4-nitro-butan-1-one and ammonium acetate.
One fluorine atom of the dye was substituted by pyrrolidine residue. This resulted in a
significant bathochromic effect. Ultraviolet absorption and fluorescence emission spectra
were recorded, and quantum yields of the obtained compounds were calculated.
Keywords: BODIPY; boradiaza-s-indacene; long-wavelength dye
The popularity of boron–dipyrromethene dyes (4,4-difluoro-4-bora-3a,4a-diaza-s-
indacenes, BODIPY, BDP) has steadily increased over the past two decades. Their
excellent thermal, chemical, and photochemical stability, high molar absorptivity,
fluorescence quantum yields, insensitivity to solvent polarity and pH, relatively long
excited-state lifetimes, a large two-photon cross-section for multiphoton excitation,
lack of ionic charge, and good solubility all have added to the general attractiveness
of these materials.[1] Recently, special attention has been paid to long-wave com-
pounds of this type[2] caused by practical applications of near infrared (NIR) dyes.[3]
There are a number of approaches to shift BODIPY absorption bands to
longer wavelengths. For example, the substitution of a carbon at the meso position
of dipyrromethene by the nitrogen atom results in a bathochromic shift of an
absorption band (compound of A type aza-BODIPY).[4] Modification of this basic
core by electron-donating groups at the para position of 5-aryl substituents leads
to a further red shift. The introduction of dialkylamino groups has been observed
to cause especially high bathochromic effect (structures of B type, 150 nm shift).[5]
Finally, the complete chelation of boron atoms not only induces a red shift of
80 nm and increases the fluorescence but also produces the spiral chirality
(compounds of C type).[6] Our goal was to combine all three factors in a target
structure, E.
Received May 7, 2009.
Address correspondence to Yuriy P. Kovtun, Institute of Organic Chemistry, National Academy of
Sciences of Ukraine, Murmanska Str., 5, 02660, Kyiv, Ukraine. E-mail: kovtun@ioch.kiev.ua
944

PYRROLIDYLSUBSTITUTED AZADIPYRROMETHENE
945
Partially, this task has been already realized. Recently, we reported the syn-
thesis of azadipyrromethene dye with fully chelated boron atom (structure D).[7]
As expected, this dye is a quite intensive long-wave luminophore. Almost simul-
taneously, the dye and its close analogs were obtained by joint efforts of the groups
of Burgess and O’Shea.[8] However, their attempt to obtain the dye of E type failed,
presumably because of the instability of the latter. Independently, we performed our
own investigations and obtained some promising results, although we could not
reach the goal of synthesizing compound E as well.
We used a well-known approach[4b,7–9] for the synthesis (Scheme 1). By starting
from 2-hydroxy-4-diethylaminoacetophenone[10] and anisaldehyde chalcone, it was
obtained, although in a quite poor yield (25–35%). The next step, addition of nitro-
methane, also proceeded with considerable difficulties because of the cleavage of the
nitromethane molecule from nitrobutanone under basic conditions (retro-Michael
reaction). Apparently, for the same reason, the attempts to obtain the desired azadi-
pyrromethene were not successful (elimination of nitromethane from nitrobutanone
in the presence of ammonium acetate is faster than its cyclization).
We therefore decided to use another approach starting from 2-hydroxy-4-
fluoroacetophenone,[11] with the aim of substituting fluorine atoms with dialkyla-
mino groups. As expected, in this case we faced no special difficulties in the synthesis
of the corresponding azadipyrromethene. Chalcone and 1,3-diaryl-4-nitrobutan-
1-one (1) were prepared with yields of 80% and 65%, respectively (reactions were per-
formed just as shown in Scheme 1[4,7–9]). The cyclization of compound 1 (Scheme 2)
led to the desirable azadipyrromethene (2) (27% yield, which is quite good for this
reaction).
Azadipyrromethene then reacted with an excess of BF3 ꢀ Et2O in the presence of
diisopropylethylamine (DIEA) in toluene under short reflux to form the expected
complex (3) with 63% yield. However, when pyrrolidine was used as a base under
the same conditions, the substitution of one of the fluorine atoms by amine occurred
simultaneously with chelating to give the complex (4) with 61% yield. The same
Scheme 1. Approach to the synthesis of diethylamino-substituted azadipyrromethene.

946
V. P. YAKUBOVSKYI, M. P. SHANDURA, AND Y. P. KOVTUN
Scheme 2. Synthesis of NIR dyes 3 and 4.
complex can be also obtained by refluxing compound (3) with pyrrolidine in the
presence of BF3 etherate, though the first method seems to be more attractive for
the preparative synthesis. Nevertheless, only mono-pyrrolidine substituted complex
(4) was formed in the latter case as well. Also, numerous efforts to substitute the
second fluorine atom to obtain the dye (5) failed. A variety of attempts to employ
less basic amines such as morpholine and diethylamine in the reaction were not
successful.
The spectral properties of difluorosubstituted dye (3) are very similar to those
of nonsubstituted analog D, which has a narrow and quite intensive absorption band
(Table 1, Fig. 1). When going from 3 to compound 4, the expected bathochromic
shift (69 nm) was observed with some intensity decrease and broadening of the
absorption band. Changing CH2Cl2 for DMF resulted in minor bathochromic shifts
of 4 and 2 nm for 4 and 3, respectively.
Fluorescent properties of the dyes are shown in Table 1. The small Stokes shift
(17 nm) is observed for 3; its fluorescent quantum yield is 0.2 and is not affected by
the solvent polarity. Unlike that dye, compound 4 has a significantly greater Stokes
shift (56 nm). Its fluorescence quantum yield is only 0.02 because of PET as in the
cases described in Refs. 2a, 2e, and 5. In contrast to their close analogs, the BF2
complexes,[5] dye 4 cannot be fully protonated. The reason for this is the strong
Table 1. Optical properties of compounds 2, 3, and 4
CH2Cl2
DMF
k
max, nm
kem
fwhm
k
max, nm
kem
fwhm
Dye (e ꢀ 10ꢁ3, Mꢁ1 ꢀ cmꢁ1
)
(nm) (cmꢁ1
)
Uf
(e ꢀ 10ꢁ3, Mꢁ1 ꢀ cmꢁ1
)
(nm) (cmꢁ1
)
Uf
2
3
4
621 (41)
725 (67)
794 (55)
—
2062
689
—
0.204
0.02
629 (50)
727 (67)
798 (52)
—
2181
705
—
0.20
0.025
742
850
743
854
1034
1173

PYRROLIDYLSUBSTITUTED AZADIPYRROMETHENE
947
Figure 1. Absorption spectra of the dyes 3 (dotted line) and 4 (solid line) in CH2Cl2.
conjugation between the terminal nitrogen atom and p-system of BODIPY, owing to
a rigid molecular structure.
EXPERIMENTAL
General
Absorption spectra were recorded on a Shimadzu UV-3100 spectrophot-
1
ometer. H NMR [300 MHz, 25 ꢂC, tetramethylsilane (TMS) as internal standard]
spectra were obtained on a Varian VXR-300 instrument. Liquid chromatography=
mass spectral (LC=MS) measurements were performed with an LC=MS system
consisting of an Agilent 1100 Series HPLC instrument equipped with a diode matrix
detector and Agilent LC=MSD SL mass-selective detector. Atmospheric pressure
chemical ionization (APCI) with detection of positive ions was used. Fluorescence
spectra were recorded on a Solar CM 2203 fluorescence spectrophotometer. Fluor-
escence quantum yields (/) for compounds were determined relative to pentamethine
dioxaborinate (/ ¼ 0.57, CH2Cl2).[12]
Synthesis
1-(4-Fluoro-2-hydroxypenyl)-3-(4-methoxyphenyl)-4-nitrobutan-1-one
(1). A mixture of 1-(4-fluoro-2-hydroxpenyl)-3-(4-methoxyphenyl)-propenone
(5.44 g, 0.02 mol), nitromethane (12.2 g, 0.2 mol), dry KF (0.23 g, 0.004 mol), and
18-crown-6 (0.264 g, 0.001 mol) in dry acetonytrile was heated under reflux for 2 h.
The acetonitrile was removed, and the resulting oil was portioned between CH2Cl2
(50 mL) and water (100 mL). The aqueous layer was extracted with CH2Cl2
(2 ꢃ 25 mL), and the combined organic fractions were dried over sodium sulfate.
The solvent was removed, and the resulting material was recrystallized from a mix-
1
ture of i-PrOH-hexane in a 1:1 ratio (4.5 g, 67%), mp 93–95 ꢂC. H NMR (CDCl3,

948
V. P. YAKUBOVSKYI, M. P. SHANDURA, AND Y. P. KOVTUN
300 MHz): d 3.41 (dd, J ¼ 5.1 CH2), 3.79 (s, 3H, CH3), 4.12–4.21 (m, 1H, CH),
4.62–4.81 (m, 2H, CH2), 6.57–6.68 (m, 2H, ArH), 6.89 (d, J ¼ 9 Hz, 2H, ArH),
7.20 (d, J ¼ 8.7 Hz, 2H, ArH), 7.74 (dd, J ¼ 6.3, 6.0 Hz, 1H, ArH), 12.31 (s, 1H,
OH). LC-MS: m=z 334 ([M þ H]þ). Elemental analysis: calcd. for C17H16FNO5: C,
61.26; H, 4.80; N, 4.20. Found: C, 61.41; H, 4.71; N, 4.29.
[5-(4-Fluoro-2-hydroxyphenyl)-3-(4-methoxyphenyl)-1H-pyrrol-2-yl]-
[5-(4-fluoro-2-hydroxyphenyl)-3-(4-methoxyphenyl)-pyrrol-2-ylidene]
amine (2). AcONH4 (19 g, 0.245 mol) was added to 1-(4-fluoro-2-hydroxpenyl)-3-
(4-methoxyphenyl)-4-nitrobutan-1-one 1 (2.1 g, 6.3 mmol) in AcOH (20 mL), and the
reaction mixture was heated at 110 ꢂC for 5 h. After cooling, the mixture was kept
overnight at room temperature. Crude product 2 was filtered off and washed with
1
AcOH. Yield 0.5 g, 27%, mp > 250 ꢂC. H NMR (DMSO-d6, 300 MHz): d 3.87 (s,
6H, CH3), 6.77–6.83 (m, 4H, ArH), 7.03 (d, J ¼ 8.1, 4H, ArH), 7.56 (s, 2H, pyrrole
H), 7.99 (d, J ¼ 8.4, 4H, ArH), 8.12 (dd, J ¼ 7.2, 2H, ArH). LC-MS: decomposition.
Elemental analysis: calcd. for C34H25F2N3O4: C, 70.71; H, 4.33; N, 7.28. Found: C,
70.52; H, 4.49; N, 7.43.
Boron chelated [5-(4-fluoro-2-hydroxyphenyl)-3-(4-methoxyphenyl)-1H-
pyrrol-2-yl]-[5-(4-fluoro-2-hydroxyphenyl)-3-(4-methoxyphenyl)-pyrrol-2-yli-
dene]amine (3). The mixture of compound 2 (0.173 g, 0.3 mmol), BF3 ꢀ Et2O
(0.64 g, 4.5 mmol), and DIEA (0.39 g, 3 mmol) in dry toluene (30 mL) was stirred
under reflux for 1 h. After cooling, the reaction mixture was washed with water
(4 ꢃ 50 mL), and the organic layer was separated, dried over Na2SO4, and evapo-
rated to dryness. The residue was chromatographed on Al2O3 (eluent CCl4–EtOAc
98:2). Yield 0.11 g, 63%, mp > 250 ꢂC. 1H NMR (CDCl3): d 3.84 (s, 6H, CH3),
6.65 (dd, J ¼ 10.5, J ¼ 2.1, 2H, ARH), 6.78 (ddd, J ¼ 10.5, J ¼ 6.6, J ¼ 2.1, 2H,
ArH), 6.93 (d, J ¼ 8.4, 4H, ArH), 7.00 (s, 2H, pyrroleH), 7.73 (dd, J ¼ 6.6, J ¼ 2.1,
2H, ArH), 8.03 (d, J ¼ 8.4, 4H ArH). LC-MS: m=z ¼ 587 ([M þ H]þ). Elemental
analysis: calcd. for C34H23BF2N3O4: C, 69.64; H, 3.95; N, 7.17. Found: C, 69.82;
H, 4.19; N, 7.05.
Boron chelated [5-(4-pyrolidyl-2-hydroxyphenyl)-3-(4-methoxyphenyl)-
1H-pyrrol-2-yl]-[5-(4-fluoro-2-hydroxyphenyl)-3-(4-methoxyphenyl)-pyrrol-
2-ylidene]amine (4).
Method A. The mixture of compound 2 (0.12 g, 0.2 mmol), BF3 ꢀ Et2O (0.57 g,
4 mmol), and pyrrolidine (0.15 g, 2 mmol) in dry toluene (10 mL) was stirred for 1 h
at 110 ꢂC. Pyrrolidine (0.5 mL) was added to this mixture, and stirring continued for
30 min. Then the mixture was evaporated to dryness, and the residue was diluted
with CH2Cl2. The mixture was washed with water (4 ꢃ 50 ml), and organic layer
was separated and dried over Na2SO4. The dye 4 was isolated by flash-column
chromatography on silica gel (eluent CH2Cl2). Yield 0.08 g, 61%.
Method B. The mixture of compound 3 (0.12 g, 0.2 mmol), BF3 ꢀ Et2O (0.57 g,
4 mmol), and pyrrolidine (0.45 g, 6 mmol) in dry toluene (15 mL) was stirred under
reflux for 30 min. After cooling, the reaction mixture was washed with water
(4 ꢃ 25 mL), and organic layer was separated, dried over Na2SO4 and evaporated

PYRROLIDYLSUBSTITUTED AZADIPYRROMETHENE
949
to dryness. The residue was chromatographed on silica gel (eluent CH2Cl2) to give
pure dye 4. Yield 0.1 g, 75%.
1
Mp 204–206 ꢂC. H NMR (CDCl3): d 2.01 (q, 4H, pyrrolidineH), 3.37 (q, 4H,
pyrrolidineH), 3.87 (s, 3H, CH3), 3.88 (s, 3H, CH3), 6.12 (d, J ¼ 2.1, 1H), 6.38 (dd,
J ¼ 7, J ¼ 2.1, 1H, ArH), 6.65–6.78 (m, 2H, ArH), 6.88 (s, 1H, pyrroleH), 6.96 (d,
J ¼ 4.2, 2H, ArH), 6.99 (d, J ¼ 4.2, 2H, ArH), 7.09 (s, 1H, pyrroleH), 7.58 (d,
J ¼ 9, 1H, ArH), 7.69 (dd, J ¼ 6.6, J ¼ 1.5, 1H, ArH), 8.05 (d, J ¼ 8.7, 2H, ArH),
8.12 (d, J ¼ 8.7, 2H, ArH). LC-MS: m=z ¼ 638 ([M þ H]þ). Elemental analysis: calcd.
for C38H31BFN4O4: C, 71.60; H, 4.90; N, 8.79. Found: C, 71.82; H, 4.79; N, 8.95.
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