Synthesis of N,N-difluoroboryl complexes of 3,3′-diarylazadiisoindolylmethenes

Article abstract of DOI:10.1016/j.tetlet.2008.08.026

N,N-Difluoroboryl complexes of 3,3′-diarylazadiisoindolylmethenes were synthesized by the reaction of BF₃·OEt₂ and 3,3′-diarylazadiisoindolylmethenes, which were easily prepared from a reaction between phthalonitrile and aryl Grignard reagents. These novel dyes exhibit strong absorption in the visible region and intense fluorescence in the vis/NIR region. Their synthesis, characterization, and optical properties are reported in this Letter.

Full text of DOI:10.1016/j.tetlet.2008.08.026

Tetrahedron Letters 49 (2008) 6152–6154
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Tetrahedron Letters
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Synthesis of N,N-difluoroboryl complexes of 3,30-diarylazadiisoindolylmethenes
a,
Valentina F. Donyagina a, Soji Shimizu b, Nagao Kobayashi b, , Evgeny A. Lukyanets
*
*
a Organic Intermediates and Dyes Institute, B. Sadovaya 1/4, Moscow 123995, Russia
b Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan
a r t i c l e i n f o
a b s t r a c t
N,N-Difluoroboryl complexes of 3,30-diarylazadiisoindolylmethenes were synthesized by the reaction of
BF3ꢀOEt2 and 3,30-diarylazadiisoindolylmethenes, which were easily prepared from a reaction between
phthalonitrile and aryl Grignard reagents. These novel dyes exhibit strong absorption in the visible region
and intense fluorescence in the vis/NIR region. Their synthesis, characterization, and optical properties
are reported in this Letter.
Article history:
Received 18 June 2008
Revised 6 August 2008
Accepted 7 August 2008
Available online 27 August 2008
Ó 2008 Elsevier Ltd. All rights reserved.
In recent years, vis/NIR (visible/near infrared) absorbing dyes
with intense fluorescence have been the focus of considerable
research interest because their optical properties make them suit-
able for a variety of applications such as use as dyes in recording
devices and in molecular labeling in biological research.1 Among
them, BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene, Fig.
1)2 dyes have been the subject of intense investigation due to their
high extinction coefficients, intense fluorescence, high stability,
and insensitivity to the polarity of solvents as well as to pH.3 Cur-
rently, one of the key goals in this field of research is to develop
methods for shifting the major absorption to the vis/NIR region
by modifying the BODIPY core, which includes attachment of elec-
tron-donating groups at the periphery, creation of a rigid structure,
Figure 1. BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene, left) and aza-BOD-
IPY (right).
Reaction of phthalonitrile with arylmagnesium bromides in
dry benzene at room temperature for 1 h provided 3,30-diaryl-
and extension of the p
-conjugation system.4 Recently, O’Shea and
azadiisoindolylmethenes
(N-(3-phenyl-2H-isoindol-1-yl)-N-(3-
co-workers reported that the replacement of the methine carbon
atom at the meso-position with a nitrogen atom can also cause a
sizable red-shift of the absorption without lowering the extinction
coefficients and fluorescence intensity. The resulting aza-BODIPY
dyes can be utilized as an efficient sensitizer for photodynamic
therapy (PDT).5,6 During the course of our research on the synthesis
phenyl-1H-isoindol-1-ylidene)amine (1) and N-[3-(4-tert-butyl-
phenyl)-2H-isoindol-1-yl]-N-[3-(4-tert-butylphenyl)-1H-isoindol-
1-ylidene]amine (2)) in moderate yields (28% for 1 and 27% for 2,
Scheme 1). Compounds 1 and 2 were fully characterized by high
resolution electrospray FT-ICR (HR-ESI-FT-ICR) mass and 1H and
13C NMR spectroscopy.8,9 Treatment of 1 and 2 with BF3ꢀOEt2 in
the presence of diisopropylamine in refluxing benzene resulted
in the formation of 3 and 4 in 70% and 73% yields, respectively.10,11
The HR-ESI-FT-ICR mass spectra of 3 and 4 firstly characterized
them as difluoroboryl complexes of 3,30-diarylazadiisoindolyl-
methenes (3: m/z: 468.1452 [M++Na], calcd for C28H18BF2N3Na,
468.1454 and 4: 580.2704 [M++Na], calcd for C36H34BF2N3Na,
580.2706).
of phthalocyanine analogs, we have noticed that the
p-extended
3,30-diarylazadiisoindolylmethenes were obtained in moderate
yields from the reaction of phthalonitrile with arylmagnesium bro-
mide, which turned out to be a revisit of an old literature.7 Their
difluoroboryl complexes are of considerable interest as novel vis/
NIR dyes, since a significant red-shift can be expected due to the
combined effects of introducing a nitrogen atom at the meso-posi-
tion and extension of the p-conjugation system. In this Letter, their
synthesis and optical properties are reported in detail.
The 1H NMR spectrum of 3 shows signals at 8.07 (
(ortho), 7.61 ( -benzo), 7.53–7.50 (meta, para, and b-benzo), and
7.32 (b-benzo) ppm, while that of 4 exhibits signals at 8.10 ( -ben-
zo), 7.85 (ortho), 7.67 ( -benzo), 7.53 (meta), 7.49 (b-benzo), and
a-benzo), 7.82
a
a
a
* Corresponding authors. Tel./fax: +81 (0)22 795 7719 (N.K.); tel./fax: +7 495 254
1200 (E.A.L.).
E-mail addresses: nagaok@mail.tains.tohoku.ac.jp (N. Kobayashi), rmeluk@
niopik.ru (E. A. Lukyanets).
7.29 (b-benzo) ppm, and a peak due to the t-butyl groups is
observed at 1.37 ppm. These results are consistent with C2v
symmetry and free rotation of aryl groups at 3 and 30 positions.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.08.026

V. F. Donyagina et al. / Tetrahedron Letters 49 (2008) 6152–6154
6153
Scheme 1. Synthesis of difluoroboryl complexes of 3,30-diarylazadiisoindolylmethenes. Reagents and conditions: (i) dry benzene, rt, 1 h; (ii) BF3ꢀOEt2, diisopropylamine,
benzene, reflux.
Further evidence for this is provided, in the case of 3, by the NOE
correlation between the peaks at 7.82 and 7.61 ppm.
Finally, the structure of 3 was revealed by single crystal X-ray
analysis as shown in Figure 2.12 3 takes a near C2v symmetric con-
formation, in which the isoindole moieties are arranged in a co-
planar manner, and the boron atom is coordinated in a tetrahedral
fashion by two nitrogen atoms with B–N distances of 1.573(2) and
1.579(2) Å and by two fluorine atoms with B–F distances of
1.372(2) and 1.380(2) Å. The coordination geometry around the
boron atom is quite similar to those of the other aza-BODIPY dyes
reported previously. In the crystal structure, columnar p–p stack-
ing with intermolecular distance of 3.27–3.65 Å is observed with
neighboring molecules aligned in opposite directions.
The absorption spectra of 1 and 2 contain intense bands at
653 nm and 658 nm, respectively, which exhibit a red-shift similar
to that observed previously in the spectra of azadipyrromethenes
with extended p
-conjugation systems.4,5 The fluorescence spectra
of 1 and 2 exhibit emission at 701 and 705 nm with UF = 9.6 ꢁ 10ꢂ3
and 9.7 ꢁ 10ꢂ3, respectively, upon excitation at 630 nm (Table 1).13
Complexation of a difluoroboryl unit further caused a red-shift of
absorption (715 nm for 3 and 724 nm for 4, Fig. 3 and Table 1). 3
and 4 exhibit intense emission at 736 nm (UF = 0.15) and 749 nm
(UF = 0.11), respectively, whose decays are found to obey a single
exponential function with F = 2.1 ns for 3 and 2.0 ns for 4.
s
The transition energies and oscillator strength were calculated
using TDDFT methods to derive a further insight into the electronic
structure of difluoroboryl complex of 3,30-diarylazadiisoindolyl-
methene. A geometry optimization was carried out for 3 using
the B3LYP hybrid functional with 6-31G(d) basis sets. TDDFT calcu-
lations were also carried out for a model compound consisting of
the carbon counterpart of 3 (5). In both the calculations, the red-
shifted absorption band mainly arises from a transition from
HOMO to LUMO. The energies of the HOMO and LUMO of 3 are
both stabilized relative to those of 5, but the stabilization of the
LUMO of 3 is greater than that of HOMO (Fig. 4). Since the LUMO
is delocalized over the meso-position, this can readily be accounted
for in terms of the comparatively stronger electron-withdrawing
nature of a nitrogen atom. The HOMO–LUMO gap of 3 is, therefore,
smaller than that of 5, resulting in the observed red-shift of the
absorption of 3.4d
Figure 2. Crystal structure of 3; (a) top view, (b) side view, and (c) packing diagram.
Thermal ellipsoids were scaled to 50% probability level.
Table 1
Absorption and fluorescence properties of 1–4
Compound
kmax (nm)
e
(Mꢂ1 cmꢂ1
)
fwhm (nm)
kem (nm)
UF
sF (ns)
Stokes shift (nm)
1
2
3
4
653
658
715
724
47,900
46,800
87,100
85,100
82.3
83.0
46.7
49.7
701
705
736
749
9.6 ꢁ 10ꢂ3
9.7 ꢁ 10ꢂ3
0.15
0.1
0.1
2.1
2.0
48
47
21
25
0.11

6154
V. F. Donyagina et al. / Tetrahedron Letters 49 (2008) 6152–6154
3. (a) McGrath, J. C.; Daly, C. J. Br. J. Pharmacol. 2003, 139, 187; (b) Reents, R.;
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H.; Calzaferri, G. Angew. Chem., Int. Ed. 2002, 41, 2284; (e) Burghart, A.;
Thoresen, L. H.; Chen, J.; Burgess, K.; Bergströn, F.; Johansson, L. B.-Å. Chem.
Commun. 2000, 2203; (f) Beer, G.; Niederalt, C.; Grimme, S.; Daub, J. Angew.
Chem., Int. Ed. 2000, 39, 3252; (g) Haugland, R. P. Handbook of Fluorescent Probes
and Research Chemicals, 6th ed.; Molecular Probes: Eugene, OR, 1996.
4. (a) Rurack, K.; Kollmannsberger, M.; Daub, J. New J. Chem. 2001, 25, 289; (b)
Rurack, K.; Kollmannsberger, M.; Daub, J. Angew. Chem., Int. Ed. 2001, 40, 385;
(c) Wada, M.; Ito, S.; Uno, H.; Murashima, T.; Ono, N.; Urano, T.; Urano, Y.
Tetrahedron Lett. 2001, 42, 6711; (d) Chen, J.; Burghart, A.; Derecskei-Kovacs, A.;
Burgess, K. J. Org. Chem. 2000, 65, 2900.
5. (a) Killoran, J.; Allen, L.; Gallagher, J. F.; Gallagher, W. M.; O’Shea, D. F. Chem.
Commun. 2002, 1862; (b) Gorman, A.; Killoran, J.; O’Shea, C.; Kenna, T.;
Gallagher, W. M.; O’Shea, D. F. J. Am. Chem. Soc. 2004, 126, 10619; (c)
McDonnell, S. O.; Hall, M. J.; Allen, L. T.; Byrne, A.; Gallagher, W. M.; O’Shea, D.
F. J. Am. Chem. Soc. 2005, 127, 16360; (d) McDonnell, S. O.; O’Shea, D. F. Org. Lett.
2006, 8, 3493; (e) Hall, M. J.; Allen, L. T.; O’Shea, D. F. Org. Biomol. Chem. 2006, 4,
776; (f) Killoran, J.; McDonnell, S. O.; Gallagher, J. F.; O’Shea, D. F. New J. Chem.
2008, 32, 483.
Figure 3. UV–vis absorption spectra of 3 and 4 in CHCl3. Dotted lines indicate their
fluorescence spectra in CHCl3.
6. (a) Zhao, W.; Carreira, E. M. Angew. Chem., Int. Ed. 2005, 44, 1677; (b) Zhao, W.;
Carreira, E. M. Chem. Eur. J. 2006, 12, 7254.
7. Bredereck, H.; Vollmann, H. W. Chem. Ber. 1972, 105, 2271.
8. Experimental procedure for the synthesis of N-(3-phenyl-2H-isoindol-1-yl)-N-(3-
phenyl-1H-isoindol-1-ylidene)amine (1): To a vigorously stirred dry benzene
solution (60 ml) of phthalonitrile (12.8 g, 0.1 mol), a diethyl ether solution
(60 ml) of phenylmagnesium bromide prepared from 6.1 g of magnesium and
26 ml of bromobenzene was added at room temperature, and the resultant
mixture was stirred for a further 1 h. The flask was then cooled to 0–5 °C, and
the excess of Grignard reagent was decomposed carefully with 20% ammonium
chloride. The solvents were removed by evaporator, and the residue was
distilled with water steam. The residue was ground into a fine powder, and was
recrystallized from a mixture of pyridine and methanol to give 1 as violet
powder (5.5 g, 0.014 mol, 28%). 1H NMR (594.17 MHz, CDCl3, 297 K): d = 8.15
(d, J = 4.10 Hz, 2H;
a-benzo), 8.04 (m, 4H; ortho), 7.97 (d, J = 4.01 Hz, 2H; a-
benzo), 7.58 (m, 4H; meta), 7.49 (m, 2H; para), 7.43 (dd, J1 = 7.31 Hz,
J2 = 7.22 Hz, 2H; b-benzo), and 7.34 (dd, J1 = 7.13 Hz, J2 = 7.13 Hz, 2H; b-benzo)
ppm; 13C NMR (149.40 MHz, CDCl3, 297 K): d = 148.6 (
a
-pyrrole), 143.9 (
pyrrole), 135.4 (b-pyrrole), 133.2 (ipso), 129.9 (b-pyrrole), 129.4 (para), 129.2
(meta), 127.7 (ortho), 127.6 (b-benzo), 126.3 (b-benzo), 122.1 ( -benzo), and
121.3 ( -benzo) ppm; UV–vis (CHCl3): kmax [nm] ( ) = 653 (47,900); HR-ESI-
a-
a
a
e
MS: m/z (% intensity): 398.1651 (100) [M++H]; calcd for C28H20N3, 398.1652.
9. Experimental procedure for the synthesis of N-[3-(4-tert-butylphenyl)-2H-isoindol-
1-yl]-N-[3-(4-tert-butylphenyl)-1H-isoindol-1-ylidene]amine (2): 2 was prepared
under similar reaction conditions in 27% yield from phthalonitrile and tert-
butylphenylmagnesium bromide. 1H NMR (500.16 MHz, CDCl3, 297 K): d = 8.13
(d, J = 4.05 Hz, 2H; a-benzo), 7.99–7.95 (m, ortho (4H), a-benzo (2H)), 7.60 (m,
4H; meta), 7.40 (dd, J1 = 7.70 Hz, J2 = 7.48 Hz, 2H; b-benzo), 7.31 (dd,
J1 = 8.10 Hz, J2 = 7.48 Hz, 2H; b-benzo), and 1.42 (s, 18 H; t-butyl) ppm; UV–
Figure 4. Calcualted MO diagrams of 3 (right) and 5 (left).
vis (CHCl3): kmax [nm] (e) = 658 (46,800); HR-ESI-MS: m/z (% intensity):
Difluoroboryl complexes of 3,30-diarylazadiisoindolylmethenes
were synthesized for the first time, and were characterized based
on the analysis of the NMR spectral data and the single crystal
structure. These dyes exhibit sizable red-shifts in both the absorp-
tion and emission spectra relative to what is observed for normal
BODIPY dyes. Since other arylmagnesium bromides can also poten-
tially be utilized, further modification of the properties should be
relatively straightforward. It should be noted that 3,30-diarylazadi-
isoindolylmethene can also be used as a planar bidentate ligand.14
We are currently carrying out additional experiments to explore
these possibilities.
510.2903 (100) [M++H]; calcd for C36H36N3, 510.2904.
10. Experimental procedure for the synthesis of N,N-difluoroboryl-[N-(3-phenyl-2H-
isoindol-1-yl)-N-(3-phenyl-1H-isoindol-1-ylidene)amine] (3): 1 was reacted with
BF3ꢀOEt2 in the presence of diisopropylamine in a refluxing benzene to give
difluoroboryl complex of 1 (3) in 70% yield. 1H NMR (594.17 MHz, CDCl3,
297 K): d = 8.07 (d, J = 3.98 Hz, 2 H;
J = 4.07 Hz, 2H; -benzo), 7.53–7.50 (m, meta (4H), para (2H), b-benzo (2H)),
and 7.32 (dd, J1 = 7.45 Hz, J2 = 7.53 Hz, 2H; b-benzo) ppm; 13C NMR
(149.40 MHz, CDCl3, 297 K): d = 153.7 ( -pyrrole), 139.7 ( -pyrrole), 134.0 (b-
pyrrole), 131.6 (b-pyrrole), 131.1 (b-benzo), 130.7 (para), 130.6 (ortho), 128.8
(meta), 127.6 (b-benzo), 124.5 ( -benzo), and 121.3 ( -benzo) ppm; UV–vis
a-benzo), 7.82 (m, 4H; ortho), 7.61 (d,
a
a
a
a
a
(CHCl3): kmax [nm] (e) = 715 (87,100); HR-ESI-MS: m/z (% intensity): 468.1452
(100) [M++Na]; calcd for C28H18BF2N3Na, 468.1454.
11. Experimental procedure for the synthesis of N,N-difluoroboryl-{N-[3-
(4-tert-butylphenyl)-2H-isoindol-1-yl]-N-[3-(4-tert-butylphenyl)-1H-isoindol-1-
ylidene]amine} (4): 4 was similarly obtained in 73% yield from the reaction of 2
and BF3ꢀOEt2. 1H NMR (500.16 MHz, CDCl3, 297 K): d = 8.10 (d, J = 4.05 Hz, 2H;
Acknowledgments
a
-benzo), 7.85 (m, 4H; ortho), 7.67 (d, J = 4.05 Hz, 2H; a-benzo), 7.53 (m, 4H;
meta), 7.49 (dd, J1 = 7.30 Hz, J2 = 7.48 Hz, 2H; b-benzo), 7.29 (dd, J1 = 7.70 Hz,
J2 = 7.48 Hz, 2H; b-benzo), and 1.37 (s, 18H; t-butyl); UV–vis (CHCl3): kmax [nm]
This work was partly supported by a Grant-in-Aid for Explor-
atory Research (No. 19655045) from the Japan Society for the Pro-
motion of Science (JSPS) and by the Moscow city government. S.S.
thanks the Exploratory Research Program for Young Scientists
(ERYS) from Tohoku University for the financial support.
(e
) = 724 (85,100); HR-ESI-MS: m/z (% intensity): 580.2704 (100) [M++Na];
calcd for C36H34BF2N3Na, 580.2706.
12. Crystallographic data of 3: C28H18B1N3F2, MW = 445.26, monoclinic, space group
P21/c (no. 14), a = 10.221(4), b = 8.486(3) c = 25.565(8) Å, b = 112.185(12)°,
V = 2053.2(13) Å3, Z = 4,
q
calcd = 1.440 g/cm3, T = –100 °C, 28,680 measured
reflections, 4688 unique reflections (Rint = 0.0513), R = 0.0528, Rw = 0.1260 (all
data), GOF = 1.160. CCDC 691385 contains the supplementary crystallographic
data for 3. These data can be obtained free of charge from the Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
13. Quantum yields were determined relative to magnesium complex of
phthalocyanine (UF = 0.84, upon excitation at 630 nm). Stiel, H.; Teuchner,
K.; Paul, A.; Freyer, W.; Leupold, D. J. Photochem. Photobiol. A: Chem. 1994, 80,
289.
References and notes
1. (a) Matsuoka, M. Infrared Absorbing Dyes; Plenum: New York, 1990; (b) Near-
Infrared Dyes for High Technology Applications; Dähne, S., Resch-Genger, U.,
Wolfbeis, O. S., Eds.; NATO Series 3; Kluwer: Dordrecht, 1998; Vol. 52; (c)
Valeur, B. Molecular Fluorescence, Principles and Applications; Wiley-VCH:
Weinheim, 2002.
14. Teets, T. S.; Partyka, D. V.; Updegraff, J. B., III; Gray, T. G. Inorg. Chem. 2008, 47,
2338.
2. (a) Treibs, A.; Kreuzer, F.-H. Liebigs Ann. Chem. 1968, 718, 208; (b) Loudet, A.;
Burgess, K. Chem. Rev. 2007, 107, 4891.