Isocyanate-, isothiocyanate-, urea-, and thiourea-substituted boron dipyrromethene dyes as fluorescent probes

Article abstract of DOI:10.1021/jo0600151

Boron dipyrromethene dyes (Bodipy) bearing a meso-phenyl substituent carrying a variety of functional groups can be prepared under mild conditions. A single-crystal X-ray structure determination for the 3,5-dinitrophenyl compound shows the phenyl ring to

Full text of DOI:10.1021/jo0600151

Isocyanate-, Isothiocyanate-, Urea-, and Thiourea-Substituted Boron
Dipyrromethene Dyes as Fluorescent Probes
Raymond Ziessel,*,† Laure Bonardi,† Pascal Retailleau,‡ and Gilles Ulrich†
Laboratoire de Chimie Mole´culaire, EÄ cole de Chimie, Polyme`res, Mate´riaux (ECPM), UniVersite´ Louis
Pasteur (ULP), 25 rue Becquerel, 67087 Strasbourg Cedex 02, France, and Laboratoire de
Cristallochimie, ICSN - CNRS, Baˆt 27 - 1 aVenue de la Terrasse, 91198 Gif-sur-YVette, Cedex, France
ziessel@chimie.u-strasbg.fr
ReceiVed January 4, 2006
Boron dipyrromethene dyes (Bodipy) bearing a meso-phenyl substituent carrying a variety of functional
groups can be prepared under mild conditions. A single-crystal X-ray structure determination for the
3,5-dinitrophenyl compound shows the phenyl ring to be almost orthogonal (dihedral angle 84°) to the
plane of the Bodipy core, with one nitro group almost coplanar with the ring and the other tilted by
∼21°. Nitro substituents at the 3-, 4-, and 5- positions of the phenyl group are readily reduced to the
corresponding amino groups and then converted to isocyanato, isothiocyanato, urea, thiourea, and some
polyimine derivatives, the last providing additional functionality (phenazine and pyridylindole units)
suitable for chelation of metal ions. All compounds are redox active, the electron-transfer processes
being assigned on the basis of comparisons with model compounds. Their fluorescence properties are
sensitive to the phenyl group substituents. The Bodipy unit excited state appears to be a strong reductant
(E° ∼ -1.4 V) and a modest oxidant (E° ∼ +1.0 V). Quenching processes in the nitro and phenazine
derivatives appear to involve intramolecular photoinduced electron transfer.
Introduction
instance is that in which photoinduced electron transfer (PET)
quenches the luminescence in the absence of the analyte. Analyte
binding may then lead to the “switching on” of the emission
by inhibition of PET, either because of a direct interaction of
the analyte with redox active centers of the sensor or because
the binding induces a conformational change which places these
centers remote from the emissive site.4,5 Aromatic amines are
good reductants and for this reason have been widely used to
provide PET quenching by covalent binding to various fluoro-
phores such as acridine, acridinium,6 anthracene,7 phenanthrene,8
The utility of fluorescence for biological and medical analyses
stimulates considerable research to improve both the sensitivity
and selectivity of appropriate fluorophores. Mapping of both
the spatial and temporal distribution of calcium within biological
systems is a typical challenge.1 We and others have previously
argued the case that rational modification of known molecules
is a field that still retains great promise.2,3 Binding of the target
analyte to a synthetic fluorophore (sensor) can result in either
amplification or quenching of the fluorescence but a common
† Universite´ Louis Pasteur.
‡ ICSN - CNRS.
(4) (a) De Silva, A. P.; Gunaratne, H. Q. N.; Gunnlaugsson, McCoy, C.
P.; T.; Maxwell, P. R. S.; Rademacher, J. T.; Rice, T. E. Pure Appl. Chem.
1996, 68, 1443. (b) De Silva, A. P.; Gunaratne, H. Q. N.; Gunnlaugsson,
T.; Huxley, A. J. M.; McCoy, C. P.; Rademacher, J. T.; Rice, T. E. Chem.
ReV. 1997, 97, 1515.
(1) Tsien, R. W.; Tsien, R. Y. Annu. ReV. Cell Biol. 1990, 6, 715.
(2) Chemosensors of Ion and Molecular Recognition; Desverne J.-P.,
Czarnik, A. W., Eds.; NATO Advanced Study Institute Series C492;
Kluwer: Dordrecht, 1997.
(3) (a) Hissler, M.; Harriman, A.; Jost, P.; Wipff, G.; Ziessel, R. Angew.
Chem., Int. Ed. 1998, 37, 3249. (b) Harriman, A.; Hissler, M.; Jost, P.;
Wipff, G.; Ziessel, R. J. Am. Chem. Soc. 1999, 121, 14.
(5) Valeur, B. In Molecular Fluorescence: Principles and Applications;
Wiley-VCH: Weinheim, 2002.
(6) Herbich, J.; Kapturkiewicz, A. J. Am. Chem. Soc. 1998, 120, 1014.
10.1021/jo0600151 CCC: $33.50 © 2006 American Chemical Society
Published on Web 03/24/2006
J. Org. Chem. 2006, 71, 3093-3102
3093

Ziessel et al.
SCHEME 1 a
pyrene,9 and Bodipy dyes.10,11 These are fluorophores where,
in some cases, charge transfer (CT) occurs upon excitation of
the fluorophore, leading to emission from a highly polarized
CT state in the weak energy domain.12 In other cases, twisted
intramolecular charge transfer (TICT) takes place, leading to
unusually long lifetimes of the charge-separated species.13
Photoinduced electron-transfer reactions are, of course, at the
core of fundamental biochemical processes such as photosyn-
thesis. In Nature, the positioning of the reactants must be such
that the electron transfer is unidirectional, facilitated by rigid
structures. Many modifications of artificial molecular sensing
systems have been engineered, but the simultaneous implemen-
tation of urea or thiourea fragments and very efficient fluoro-
phores has not been exploited to a great extent.14 Recently,
preorganized (thio)urea receptors have been designed to complex
anions in which the recognition event is driven by multi-
intramolecular hydrogen bonding.15
Difluoroboradiaza-s-indacenes, commonly named boron dipyr-
romethene dyes (F-Bodipy),16 are effective fluorescent probes/
sensors and modification of the structure provides new oppor-
tunities to vary properties and provide recognition sites for a
variety of analytes. These dyes have properties which combine
high molar extinction coefficients and high fluorescence quan-
tum yields, strong chemical and photochemical stability in
solution and in the solid state, and remarkable electron-transfer
properties. Furthermore, the optical properties are sensitive to
modifications of the pyrrole core,17 the central meso position,18
and the boron substituents.19 Their current uses include those
a Key: (i) 2,4-dimethyl-3-ethylpyrrole (2 equiv), CH2Cl2, rt, 3 days; (ii)
BF3‚Et2O (8 equiv), TEA (6 equiv), rt, 1 day; (iii) H2 (1 atm), Pd/C 5%,
EtOH/CH2Cl2, rt, 1 day.
as chromogenic probes,20 fluorescent switches,21 electro-chemi-
luminescent materials,22,23 laser dyes,24 fluorescent labels for
biomolecules,19 drug delivery agents,25 and as electron-transfer
probes for radical ion pairs generated by local electric fields.26
(7) (a) Mataga, N.; Nishikawa, S.; Asahi, T. Okada, T. J. Phys. Chem.
1988, 92, 6233. (b) Wiessner, A.; Hu¨ttmann, G.; Ku¨hnle, W.; Staerk, H. J.
Phys. Chem. 1995, 99, 14923.
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Iwai, K.; Yamamoto, M.; Ichikawa, M.; Masuhara, M.; Maus, M.; Rettig,
W. J. Am. Chem. Soc. 1996, 118, 2892.
(9) (a) Herbich, J.; Kapturkiewicz, A. Chem. Phys. 1993, 170, 221.
Harriman, A.; Hissler, M.; Ziessel, R. Phys. Chem. Chem. Phys. 1999, 1,
4203. (b) Hissler, M.; Harriman, A.; Khatyr, A.; Ziessel, R. Chem. Eur. J.
1999, 5, 3366. (c) Shen, Z.; Procha´zka, R.; Daub, J.; Fritz, N.; Acar, N.;
Schneider, S. Phys. Chem. Chem. Phys. 2003, 5, 3257.
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J. Phys. Chem. 1998, 102, 10211. (b) Wan, C.-W.; Burghart, A.; Chen, J.;
Bergstro¨m, F.; Johanson, L. B.-A.; Wolford, M. F.; Kim, T. G.; Topp, M.
R.; Hochstrasser, R. M.; Burgess K. Chem. Eur. J. 2003, 9, 4430.
(11) (a) Ulrich, G.; Ziessel, R. Synlett 2004, 439. (b) Ulrich, G.; Ziessel,
R. J. Org. Chem. 2004, 69, 2070. (c) Ulrich, G.; Ziessel, R. Tetrahedron
Lett. 2004, 45, 1949.
(12) Rurack, K.; Kollmannsberger, M.; Resch-Genger, U.; Daub, J. J.
Am. Chem. Soc. 2000, 122, 968.
(13) (a) Grabowski, Z. R.; Rotkiewicz, K.; Siemiarczuk, A.; Cowley,
D. J.; Baumann, W. NouV. J. Chim. 1979, 3, 443. (b) Rettig, W. Angew.
Chem., Int. Ed. Engl. 1986, 25, 971.
(14) (a) Vazquez, M.; Fabbrizzi, L.; Taglietti, A.; Pedrido, R. M.;
Gonzalez_Noya, A. M.; Bermejo, M. R. Angew. Chem., Int. Ed. 2004, 43,
1962. (b) Esteban-Gomez, D.; Fabbrizzi, L.; Licchelli, M. J. Org. Chem.
2005, 70, 5717.
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Tetrahedron Lett. 2005, 46, 5343.
Results and Discussion
In the present account, we describe the relatively facile
syntheses of nitro- and dinitrophenyl derivatives of 4,4-difluoro-
4-bora-3a,4a-diaza-s-indacene which can be reduced to the
corresponding amines and then converted to a range of new
isocyanate, isothiocyanate, urea, thiourea, indole, and dipyrido-
[3,2-a:2′,3′-c]phenazine (dppz) derivatives. “Kryptopyrrole”
(2,4-dimethyl-3-ethylpyrrole) was used as the starting material
for the three-step synthesis of the desired amino compounds
outlined in Scheme 1 because of the known high quantum yield
of the resulting Bodipy core.27 The condensation of kryptopy-
(20) (a) Wagner, R. W.; Lindsey, J. S. Pure Appl. Chem. 1996, 68, 1373.
(b) Beer, G.; Rurack, K.; Daub, J. Chem. Commun. 2001, 1138. (c) Turfan,
B; Akkaya, E. U. Org. Lett. 2002, 4, 2857. (d) Beer, G.; Niederalt, C.;
Grimme, S.; Daub, J. Angew. Chem., Int. Ed. 2000, 39, 3252. (e)
Kollmannsberger, M.; Rurack, K.; Resch-Genger, U.; Rettig, W.; Daub, J.
Chem. Phys. Lett. 2000, 329, 363. (f) Sancenon, F.; Martinez-Manez, R.;
Soto, J. Angew. Chem., Int. Ed. 2002 , 41, 1416.
(21) Golovkova, T. A.; Kozlov, D. V.; Neckers, D. C. J. Org. Chem.
2005, 70, 5545.
(22) Lai, R. Y.; Bard, A. J. J. Phys. Chem. B 2003, 107, 5036.
(23) (a) Brom J. M., Jr.; Langer, J. L. J. Alloys Cmpds. 2002, 338, 112.
(b) Hepp, A.; Ulrich, G.; Schmechel, R.; von Seggern, H.; Ziessel R. Synth.
Met. 2004, 146, 11.
(16) Haugland, R. P. in Handbook of Molecular Probes and Research
Products, 9th ed.; Molecular Probes, Inc.: Eugene, OR, 2002.
(17) (a) Haugland, R. P.; Kang H. C. US Patent US 4,774,339, 1998.
(b) Thoresen, L. H.; Kim, H.; Welch, M. B.; Burghart, A.; Burgess, K.
Synlett 1998, 1276.
(18) Goze, C.; Ulrich, G.; Charbonnie`re, L.; Ziessel, R. Chem. Eur. J.
2003, 9, 3748.
(24) (a) Chen, T.; Boyer, J. H.; Trudell, M. L. Heteroatom Chem. 1997,
8, 51. (b) Sathyamoorthi, G.; Wolford, L. T.; Haag, A. M.; Boyer, J. H.
Heteroatom Chem. 1994, 5, 245.
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274, 584.
(19) Ulrich, G.; Goze, C.; Guardigli, M.; Roda, A.; Ziessel, R. Angew.
Chem., Int. Ed. 2005, 44, 3694.
(27) Burghart, A.; Kim, H.; Wech, M. B.; Thorensen, L. H.; Reibenspies,
J.; Burgess, K. J. Org. Chem. 1999, 64, 7813.
3094 J. Org. Chem., Vol. 71, No. 8, 2006

Substituted Boron Dipyrromethene Dyes as Fluorescent Probes
a
SCHEME 2
a Key: (i) trichloromethyl chloroformate (0.5 equiv), THF, 60 °C, quant; (ii) amine (1 equiv), THF, reflux, 12 h (76%); (iii) thiophosgene, CH2Cl2, rt;
(iv) tolylamine (1 equiv).
rrole with an acid chloride is straightforward,28 and the relatively
stable dipyrromethene salt can be isolated or directly converted
to the desired F-Bodipy core without extensive purification. The
second step requires treatment with boron trifluoride etherate
in the presence of triethylamine. The nitro substituents were
readily reduced to the desired amino groups by catalytic
hydrogenation.
The advantages of these procedures lie in the relatively good
yields of each step, the use of inexpensive reagents, and the
short reaction times required. Highly reactive intermediates
causing side reactions appear not to be involved. The overall
yields of the amines 5 to 8 lie in the 32-39% range. Similar
nitro-functionalized Bodipy dyes derived from knorrpyrrole (2,4-
dimethylpyrrole) have been prepared from the corresponding
aldehydes, and reduction to the amino group was performed
either under acidic conditions with SnCl2‚2H2O29 or with Pd
(10%) on charcoal and hydrazine hydrate30a or using molecular
hydrogen under atmospheric pressure with a palladium-sup-
ported catalyst.30b
the IR spectra exhibiting strong νNdCdO and νNdCdS stretching
vibrations at 2256 and 2095 cm-1, respectively.33a Test reactions
of these materials with primary amines provided urea com-
pounds 10 and 11 and the thiourea 13 in good yields. For 11,
glycinethylester hydrochloride was used and the neutral amino
acid was produced in situ by addition of 2 equiv of TEA. These
urea and thiourea derivatives show characteristic carbonyl
stretching vibrations near 1660 and 1540 cm-1, respectively.
The stability of the Bodipy unit under these reaction conditions
was demonstrated by the lack of any evidence for displacement
of the possibly sensitive BF2 fragment.
In contrast, all attempts to convert the diamino compound 7
to its diisocyanate failed, and even IR spectroscopy on the
reaction mixture in solution provided no evidence for its
presence. Addition of primary amines in the hope of trapping
the possibly transient diisocyanate provided only intractable
mixtures, with some components being highly polar. A simple
and effective way of obtaining the desired bis(urea) and bis-
(thiourea) compounds, however, proved to be the conduct of
the reaction in the reverse sense, viz., by reacting the diamine
with commercially available isocyanates and isothiocyanates,
a procedure which also worked well with the monoamine. Thus,
reactions with phenyl isocyanate and phenyl isothiocyanate
(Scheme 3) proceed smoothly and in good yield in anhydrous
dichloromethane. As expected, all these single and doubly
substituted F-Bodipy (thio)urea derivatives are fairly stable in
common solvents, even in the light.
Our initial approach toward the synthesis of urea and thiourea
derivatives was based upon reactions of the amines 5-8.
Conventional procedures31,32 (Scheme 2) provided satisfactory
yields of the isocyanate 9 and the isothiocyanate 12 from 5,
(28) Fischer, H.; Halbig, P.; Walach, B. Ann. Chem. 1927, 452, 268.
(29) Gabe, Y.; Urano, Y.; Kikuchi, K.; Kojima, H.; Nagano, T. J. Am.
Chem. Soc. 2004, 126, 3357.
(30) (a) Li. M.; Wang, H.; Zhang, X.; Zhang, H.-S. Spectrochim. Acta
A 2004, 60, 987. (b) Azov, V. A.; Diederich, F.; Lill, Y.; Hecht, B. HelV.
Chim. Acta 2003, 86, 2149.
(31) (a) Grubert, L.; Jacobi D.; Buck K.; Abraham W.; Mugge C.; Krause
E. Eur. J. Org. Chem. 2001, 20, 3921. (b) Krantz, A.; Spencer, R. W.;
Tam, T. F.; Liak, T. J.; Copp, L. J.; Thomas, E. M.; Rafferty, S. P. J. Med.
Chem. 1990, 33, 464.
(32) Kym P. R.; Carlson K. E.; Katzenellenbogen J. A. J. Med. Chem.
1993, 36, 1111.
Further investigations of the reactivity of the diamine 8
involved its reactions with 1,10-phenanthroline-5,6-dione34 and
(33) (a)Silverstein, R. M.; Bassler, G. C. Identification Spectrome´triques
des Compose´s Organiques; Gauthier-Villars: Paris, 1968. (b) Nakanishi,
K. Infrared Absorption Spectroscopy-practical; Holden Day: San-Francisco,
1964.
J. Org. Chem, Vol. 71, No. 8, 2006 3095

Ziessel et al.
a
SCHEME 3
a Key: (i) phenyl isocyanate (1 equiv per amino group), CH2Cl2, reflux; (ii) phenyl isothiocyanate (1 equiv per amino group), CH2Cl2, reflux.
a
SCHEME 4
FIGURE 1. Molecular structure of compound 3 with the atom-labeling
scheme. Thermal ellipsoids are plotted at the 30% level.
formation of a triazole Bodipy derivative by reaction with nitric
oxide, the enhanced fluorescence of the product making the
reaction useful for the detection of trace amounts of NO.37
X-ray Structure of Compound 3. The X-ray crystal structure
a Key: (i) 1,10-phenanthroline-5,6-dione (1 equiv), EtOH, reflux, 15 h;
(ii) 6-methylpyridine-2-carboxaldehyde (1 equiv), EtOH, p-TsOH (cat.), air,
reflux.
of the dinitro compound 3 has been solved (Figure 1). The
molecule adopts approximate but not exact 2-fold rotational
symmetry. The central six-membered ring lies coplanar with
the adjacent five-membered ring [the maximum deviation from
the least-squares mean plane for the 12 atoms of the Bodipy
group being -0.041(2) Å]. The Bodipy core including the two
pyrrole rings, the four methyl groups and the two methylene
carbons is planar [the maximum deviation from the least-squares
mean plane for the 19 atoms of the Bodipy group (B, N1, N2,
C1A > C1C, C1 > C14) being -0.033(2) Å], while the
dinitrobenzene subunit is almost orthogonal, with a dihedral
angle of 83.6°. Moreover, the phenyl ring containing the
functional reactive amino groups is deviated from planarity of
the dipyrromethene core engender the loss of extended conjuga-
tion in the synthesized structures. The average B-N and B-F
bond lengths are, respectively, around 1.542(3) and 1.384(3)
6-formyl-2-methylpyridine35 to give the potential metal che-
lates36 22 and 23. Good yields were obtained by condensation
in hot ethanol (Scheme 4). Reaction with the phenanthroline
derivative is relatively slow (15 h reaction time) compared to
that with the formylpyridine (<1 h), although isolated yields
of the products were acceptable (79% for 22; 83% for 23). The
reactions are analogous to a recently reported method for the
(34) Amouyal, E.; Homsi, A.; Chambron, J.-C.; Sauvage, J.-P. J. Chem.
Soc, Dalton Trans. 1990, 1841.
(35) Furukawa S.; Kuroiwa Y. Pharm. Bull. Jpn. 1995, 3, 232.
(36) (a) Piguet, C.; Bu¨nzli, J.-C. G.; Bernardinelli, G.; Hopfgartner, G.;
Willimas, A. F. J. Am. Chem. Soc. 1993, 115, 8197. (b) Shavaleev, N. M.;
Bell, Z. R.; Easun, T. L.; Rutkaite, R.; Swanson, L.; Ward, M. D. J. Chem.
Soc., Dalton Trans. 2004, 3678. (c) Jenkins, Y.; Friedman, A. E.; Turro,
N. J.; Barton, J. K. Biochemistry 1992, 31, 10809. (d) Holmlin, R. E.; Barton,
J. K. Inorg. Chem. 1995, 34, 7.
(37) Gabe, Y.; Urano, Y.; Kikuchi, K.; Kojima, H.; Nagano, T. J. Am.
Chem. Soc. 2004, 126, 3357.
3096 J. Org. Chem., Vol. 71, No. 8, 2006

Substituted Boron Dipyrromethene Dyes as Fluorescent Probes
TABLE 1. Solution Electrochemical Properties of the
Bodipy-Grafted Nitro-, Amino-, Urea-, Thiourea-, and
Dipyridinophenazine and Indole Compoundsa
CHART 1
compd
E′°ox, V (∆E, mV)
E′°red, V (∆E, mV)
-1.26 (70)
A
1
2
3
4
B
C
5
6
+1.11 (60)
+1.05 (60)
+1.05 (60)
+1.13 (80)
+1.10 (60)
-1.09 (110); -1.33 (60)
-1.10 (110); -1.43 (80)
-0.85 (90); -1.27 (90); -1.49 (90)
-0.77 (90); -1.16 (90)
-1.02 (90); -1.60 (irrev)
-0.93 (110); -1.44 (irrev)
-1.44 (80)
+0.95 (60)
+0.96 (60)
+0.98 (irrev.)
+0.99 (90)
+0.94 (60)
+0.93 (60)
+0.99 (60)
+0.94 (60)
+0.94 (60)
+0.93 (60)
+0.93 (60)
+0.99 (60)
+0.99 (70)
+0.97 (60)
+0.98 (60)
+1.04 (60)
+1.04 (60)
+1.02 (60)
amino-, urea-, and thiourea-substituted Bodipy’s than in the
toluyl reference compound A or the dipyridinophenazine 22 or
indole 23 derivatives. This probably reflects the fact that the
amino-, urea-, thiourea substituents are better electron-donating
groups compared to the nitro or the other derivatives. The
oxidation of the Bodipy is facilitated by 60 mV in the urea
compounds 14-17 compared to the thiourea compounds 18-
21. There is no indication of oxidation to the (Bodipy2+) dication
within the given electrochemical window as previously observed
for pyridine linked Bodipy’s.11
-1.41 (70)
7
8
-1.42 (70)
-1.45 (60)
10
11
13
14
15
16
17
18
19
20
21
22b
22c
23b
-1.40 (60)
-1.41 (60)
-1.32 (70)
-1.36 (60)
-1.35 (60)
-1.36 (60)
-1.37 (60)
-1.31 (60)
-1.30 (60)
Without nitro substituents, the reduction of the Bodipy
fragment to the radical anion (Bodipy•-) was in all cases
reversible and more cathodic compared to the toluyl compound
A (Chart 1). For the amino derivatives 5-8, this reduction is
more difficult by at least 140 mV, by 100 mV for the urea, and
50 mV for the thiourea compounds compared to A. For
compounds 5-8 protonation of the amino group obtained by
progressive addition of trifluoroacetic acid to the solution does
not significantly perturb the redox potentials of the Bodipy
fragments. Given the well-known redox activity of nitro
groups,40 it was anticipated that the reduction of the Bodipy to
the radical anion would be significantly perturbed. For com-
pounds 1-4, the first reduction is assigned to the nitro group
reduction (Figure 2).
-1.32 (60)
-1.31 (60)
-1.16 (60); -1.31 (irrev)*
-0.94 (60); -1.18 (60)
-1.32 (60)
a Potentials determined by cyclic voltammetry in deoxygenated CH2Cl2
solutions, containing 0.1 M TBAPF6, at a solute concentration of 1.5 ×
10-3 M, at 20 °C. Potentials were standardized using ferrocene (Fc) as
internal reference and converted to SCE assuming that E1/2 (Fc/Fc+) )
+0.38 V (∆Ep ) 70 mV) vs SCE. Error in half-wave potentials is (10
mV. Scan rate 100-200 mV/s. When the redox process is irreversible, the
peak potentials (Eap or Ecp) are quoted. All waves are monoelectronic unless
otherwise specified. *This process corresponds to the exchange of about
two electrons. b Measured in a mixture of anhydrous CH3CN and CH2Cl2
(1/1, v/v). c Obtained after addition of 1 equiv of anhydrous Zn(CF3SO3)2
as an acetonitrile solution under argon.
There are significant differences in the second reduction
potentials depending on the substitution position of the nitro
group, and the situation is more complicated when two nitro
groups are present. The reference compounds B and C were
used to help the potential assignments. They display two
quasireversible cathodic waves likely corresponding to the
successive reduction of each nitro group (Figure 3). The
presence of a Bodipy fragment in place of the ethyl ester
facilitates the reduction of the nitro groups, highlighting the
electron-withdrawing effect of the Bodipy moiety.
The second reduction likely corresponds to the reduction of
the Bodipy unit to the radical anion. The reduction of the second
nitro group is only observed in compound 3, and the potential
at -1.49 V is in keeping with the one determined for C.
Interestingly, the position of the nitro on the phenyl ring has
also a major influence on the reduction potential of the Bodipy.
In the 4-position (compd 1), the reduction of the Bodipy is easier
by 100 mV than it is when in the 3-position (compd 2), whereas
the nitro group reduction potentials are similar. With two nitro
groups, reduction of both the nitro and Bodipy centers is
facilitated: 3,4-disubstitution (compound 4) decreases the
reduction potential by 110 mV compared to 3,5-disubstitution
(compound 5), and reduction of one of the nitro groups is easier
by 80 mV.
Å, and the N1-B-N2, F1-B-F2, N1-B-F2, and N2-B-
F1 angles are, respectively, 107.4(2), 110.0(2), 109.8(2), and
109.9(2)°. These observations are in line with previous molec-
ular structures.38 A point of interest is the pronounced double-
bond character for the C4-N1 and C5-N2 bonds [1.349(3)
Å], which contrasts with the longer C1-N1 and C8-N2 bond
lengths [1.398(2) Å]. Such an observation has also been
previously made for similar compounds.39 One of the two nitro
groups is basically coplanar with the phenyl ring (the dihedral
angle between the mean planes of the phenyl ring and the nitro
group O1-N1A-O2 is 0.91°) whereas the second one is slightly
twisted versus the phenyl ring (with a dihedral angle of 20.86°).
The lattice shows no significant intermolecular contacts below
4 Å except for short nitro oxygen interactions with carbons
(e2.88 Å).
Electrochemical Properties. The electrochemical properties
of the new molecules were determined by cyclic voltammetry
in dichloromethane solution. Table 1 lists the potentials (relative
to the SCE reference electrode) for the waves that were observed
in the +1.6 to -2.0 V window. First, for all of the compounds
(except 7), a single reversible anodic wave was observed in the
region between +1.11 and +0.93 V that is due to the (Bodipy/
Bodipy+.) couple. Note that this wave is less anodic in the
Finally, the urea derivatives 10, 11, and 14-17 are easier to
oxidize (∆Eox ≈ 50 mV) than the thiourea compounds 13 and
(38) Ziessel, R.; Goze, C.; Ulrich, G.; Ce´sario, M.; Retailleau, P.;
Harriman, A.; Roston, J. P. Chem. Eur. J. 2005, 11, 7366.
(39) Shen, Z.; Ro¨hr, H.; Rurack, K.; Uno, H.; Spieles, M.; Schulz, B.;
Reck, G.; Ono, N. Chem. Eur. J. 2004, 10, 4853.
(40) Chan-Leonor, C.; Martin, S. L.; Smith, D. K. J. Org. Chem. 2005,
70, 10817.
J. Org. Chem, Vol. 71, No. 8, 2006 3097

Ziessel et al.
n
FIGURE 2. Cyclic voltammetry of compounds 2 (blue) and 3 (red) in CH2Cl2 at rt using 0.1 M Bu4PF6 as supporting electrolyte at a scan rate
of 200 mV/s. Ferrocene is used as internal reference at +0.38 V.
n
FIGURE 3. Cyclic voltammetry of compounds B (blue) and C (red) in CH2Cl2 at rt using 0.1 M Bu4PF6 as supporting electrolyte at a scan rate
of 100 mV/s. Ferrocene is used as internal reference at +0.38 V.
18-21, whereas the latter are easier to reduce (∆Eox ≈ 60 mV).
Note that the LUMO-HOMO gap (at about 2.30 eV) remains
similar in both series, as reflected by the constancy of the
emission wavelength (vide infra). Changing the substitution
position or increasing the number of urea fragments does not
significantly change the redox potentials of the concerned
fragments (Figure 4).
For 22, the anodic envelope around -1.24 V involves an
overlap of two reduction processes, as would be expected from
the presence of the two redox-active dipyridinophenazine and
Bodipy sites. The overlapping could be fortuitous, but no
splitting of the wave is observed using anhydrous DMF or CH2-
Cl2 as solvent. The use of a mixture of acetonitrile and
dichloromethane enables partial resolution of both signals
(Figure 5). By progressive addition of anhydrous Zn(CF3SO3)2
or [Cu(CH3CN)4](PF6)2, a new reversible anodic system at
-0.94 V grows at the expense of the redox system appearing
as a shoulder at -1.16 V. This new wave is attributed to the
dipyridinophenazine fragment complexed to the metal. Signifi-
cantly, on the addition of either Zn(II) or Cu(I) the color of the
solution turned deep-red while the oxidation process remained
unaffected. Visual observations of metal ion complexation by
These observations reflect the different electronic environ-
ments of Bodipy and nitro groups and indicate that significant
electronic interaction are effective despite the quasi-orthogonal-
ity of the Bodipy and phenyl fragments (see the X-ray structure
of compound 3 in Figure 1). These results clearly reflect the
combined effects of electron withdrawal and charge delocal-
ization and are in keeping with previous observations on related
molecules.38
3098 J. Org. Chem., Vol. 71, No. 8, 2006

Substituted Boron Dipyrromethene Dyes as Fluorescent Probes
FIGURE 4. Cyclic voltammetry of compounds 15 (blue) and 17 (red) in CH2Cl2 at rt using 0.1 M nBu4PF6 as supporting electrolyte at a scan rate
of 200 mV/s. Ferrocene is used as internal reference at +0.38 V.
n
FIGURE 5. Cyclic voltammetry of compounds 22 (blue) and 22/Zn (red) (stoichiometric amounts) in CH2Cl2 at rt using 0.1 M Bu4PF6 as
supporting electrolyte at a scan rate of 200 mV/s. Ferrocene is used as internal reference at +0.38 V.
similar molecules have been previously applied to the detection
of trace environmental levels of transition metals.18 Another
effect of the metal ion binding is to shift the Bodipy reduction
wave anodically by 130 mV and render it reversible. Such
effects are as expected on the basis of previous observations of
polypyridine complexes.18
Bodipy fluorophores,16,17,27,41,42 and prototypical examples are
given in Figure S1 (Supporting Information). In solution, the
absorption spectrum shows a strong S0 f S1 (π-π*) transition
located around 526 nm with extinction coefficients (between
55000 and 87000 M-1 cm-1) almost independent of the number
and nature of the substituents.
Note that for the nitro compounds 1-4, clear bathochromic
shifts in the absorption and emission spectra were observed
compared to the other derivatives, likely related to the significant
decrease of the LUMO energy level and in line with the
electrochemical data. A second weak and broad S0 f S2 (π-
In contrast, for the indole derivative 23 the reversible
formation of the Bodipy•+ and Bodipy•- are observed at the
expected potential range but the addition of metal cations has
little effect, indicating that compound 23 is not a good ligand
for ZnII or CuI.
(41) Chen, T.; Boyer, J. H.; Trudell, M. L. Heteroatom Chem. 1997, 8,
51.
(42) Sathyamoorthi, G.; Wolford, L. T.; Haag, A. M.; Boyer, J. H.
Heteroatom Chem. 1994, 5, 245.
Optical Properties. Spectroscopic data relevant to the present
discussion are collected in Table 2. All compounds exhibit
absorption patterns that might be considered characteristic of
J. Org. Chem, Vol. 71, No. 8, 2006 3099

Ziessel et al.
TABLE 2. Spectroscopic Data in Dichloromethane Solution at 298 K
c
λabs
(nm)
ꢀ
λ F
(nm)
τF
(ns)
∆GES
(eV)
E° B*/B•+ d
E° B•-/B* e
(eV)
a
compd
(M-1 cm-1
)
ΦF
krb (108 s-1
)
knrb (108 s-1
)
(eV)
1
2
3
4
5
6
7
8
10
11
13
14
15
16
17
18
19
20
21
22
23
533
536
536
536
526
524
524
523
524
524
525
525
525
526
526
526
526
527
526
529
524
70000
72000
67000
55000
71000
85000
70000
84000
87000
74000
85000
88000
77000
81000
78000
83000
62500
74000
84000
71500
68000
540
544
541
543
536
538
539
531
540
540
542
541
540
540
541
542
542
544
540
542
540
0.02
0.01
0.01
0.005
0.18
0.42
0.20
0.01
0.85
0.83
0.71
0.86
0.86
0.84
0.86
0.73
0.69
0.84
0.65
0.01
0.72
<1
<1
<1
<1
9.3
12.4
1.1
<1
4.5
4.3
5.6
6.4
6.2
5.5
7.3
5.3
11
0.19
0.34
0.09
0.88
0.47
9
2.40
2.41
2.38
-1.45
-1.45
-1.40
0.96
1.00
0.96
1.80
1.93
1.27
1.34
1.39
1.52
1.18
1.58
0.63
1.50
1.48
0.08
0.68
0.33
0.39
0.52
0.22
0.22
0.29
0.19
0.51
0.28
0.28
0.79
7.6
2.41
2.41
2.38
2.39
2.40
2.40
2.38
2.38
2.39
2.38
2.39
-1.47
-1.48
-1.39
-1.45
-1.46
-1.47
-1.45
-1.39
-1.40
-1.41
-1.42
1.01
1.00
1.06
1.03
1.05
1.04
1.01
1.07
1.09
1.06
1.08
5.6
4.4
1.3
10.6
0.26
2.40
-1.39
1.08
a At a concentration of 5 × 10-7 M using Rhodamine 6G, as reference Φ ) 0.78 in water, λexc ) 488 nm.46 All ΦF are corrected for changes in refractive
index. b Calculated using the following equations: kr ) ΦF /τF, knr ) (1 - ΦF)/τF, assuming that the emitting state is produced with unit quantum efficiency.
c Excited-state energies were estimated ((5%) by drawing a tangent on the high energy side of the emission. d Calculated excited-state oxidation potential
vs SCE, E°(B+/B*) ) E°(B+/B) - ∆GES. B ) Bodipy. e Calculated excited-state reduction potential vs SCE, E°(B*/B•-) ) E°(B/B•-) + ∆GES
.
π*) transition located at ca. 380 nm was also clearly evident
for most of the new species.43 On the basis of literature data,
the peak appearing in the high energy region around 250 nm
may be assigned to spin-allowed π-π* transitions centered on
the phenyl ring of the dye.44 For the derivatives 22 and 23, the
additional absorption bands around 270 and 370 nm for 22 and
around 320 nm for 23 are tentatively assigned to π-π* and
n-π* transitions involving the dipyridinophenazine and indole
sites, respectively (Figure S2. Supporting Information).45 Finally,
no long wavelength charge transfer (CT) absorption bands are
observed for these neutral compounds.12
With the exception of all nitro, one diamino, and the
phenazine compounds, these molecules exhibit strong fluores-
cence with quantum yields being measured using Rhodamine
6G.46 The highest quantum yields were found for derivatives
14-17, which have the highest oscillator strength for the
corresponding absorption, likely induced by the substitution of
the phenyl ring by urea functions. No marked difference in the
quantum yield was found by changing the substitution patterns
on the phenyl ring (e.g., compare 14 and 15). The slight decrease
in φlum observed for the thiourea derivatives is possibly due to
the increase of the rate of nonradiative decay induced by the
bulky and electron-rich sulfur atom. The weak Stokes shifts of
about 500 cm-1 for the series of Bodipy fluorophores are in
keeping with a singlet emitting state. Excitation spectra per-
formed under similar conditions perfectly match the absorption
spectra (Figures S1 and S2), allowing the conclusion that the
emitted light originates from a single excited state with almost
no contribution of a possible CT transition, despite the fact that
these molecules contain both electron-donating groups such as
Bodipy and electron-accepting fragments such as the urea or
thiourea fragments. The absence of any significant dynamic
quenching of the luminescence by molecular oxygen excludes
the presence of an emissive triplet excited state.
Furthermore, the fluorescence decay profiles could be de-
scribed by a single-exponential fit, with fluorescence lifetimes
in the range of 1-12 ns, in accordance with a singlet excited
state. In fact, most of the radiative rate constants of 1 × 10-8
s-1 are the same within experimental error (Table 2). However,
the nonradiative rate constants are significantly higher for
compounds 7 and 22 compared to the others, mostly because
of the short excited-state lifetime, which may be attributed to
the interaction of the emitting state with an energetically low-
lying localized state. At this stage of our investigation, we do
not have any evidence for the formation of a triplet excited state
possibly able to readily quench the fluorescence. In the case of
the nitro derivative, an electron-transfer process is likely
responsible for the absence of emission. In addition, no
significant solvatochromic effect was observed in the absorption
and fluorescence spectra, confirming weak polarization of the
ground and excited states. More importantly, the fluorescence
spectrum shows good mirror symmetry with the lowest energy
absorption transition, confirming that these transitions are due
to the same state. These photophysical data are in keeping with
related functionalized boron dipyrromethene dyes.10,47
The weak fluorescence observed for the four nitro compounds
and for the dipyridinophenazine derivative could be explained
within the framework of a photoinduced electron transfer from
the Bodipy excited state toward the nitro or phenazine fragments.
In these cases, the Bodipy excited state is a good reductant,
with E′0 (Bodipy*/Bodipy•+) around -1.48 V (Table 2). The
easy reduction of the nitro groups (Table 1) at reduction
potentials around or lower than -1.0 V enables us to make an
estimation of the photoinduced electron-transfer driving force
(-480 mV < ∆G° > -710 mV). For compound 23, this driving
force is decreased to -160 mV but still efficient quenching is
(43) Karolin, J.; Johansson, L. B.-A.; Strandberg, L.; Ny, T. J. Am. Chem.
Soc. 1994, 116, 7801.
(44) De Armond, M. K.; Carlin, C. M. Coord. Chem. ReV. 1981, 36,
325.
(45) Klessinger, M.; Michl, J. In Excited States and Photochemitry of
Organic Molecules; VCH: Weinheim, 1994.
(46) Olmsted, J., III. J. Phys. Chem. 1979, 83, 2581.
(47) Rurack, K.; Kollmannsberger, M.; Daub, J. Angew. Chem., Int. Ed.
2001, 40, 385.
3100 J. Org. Chem., Vol. 71, No. 8, 2006

Substituted Boron Dipyrromethene Dyes as Fluorescent Probes
Et2O (2.7 mL, 21.5 mmol). Chromatography (silica gel, CH2Cl2/
cyclohexane 50:50 to 100:0). Recrystallization in CH2Cl2/hexane
afforded the desired compound as a purple powder (0.511 g, 46%),
mp 240-242 °C. 1H NMR (CDCl3, 300 MHz): δ (ppm) ) 8.39-
8.35 (m, 1H), 8.23-8.22 (m, 1H), 7.74-7.65 (m, 2H), 2.54 (s,
observed. For all the others dyes, the absence of the electron
accepting group results in efficient fluorescence of the Bodipy
fragment.
Concluding Remarks
3
3
6H), 2.3 (q, 4H, J ) 7.5 Hz), 1.25 (s, 6H), 0.98 (t, 6H, J ) 7.5
Hz). 13C NMR (CDCl3, 75 MHz): δ (ppm) ) 155.2, 148.8, 137.8,
136.4, 135.0, 133.7, 130.5, 130.4, 124.1, 124.0, 17.2, 14.7, 12.8,
We have described the synthesis and redox and optical
properties of a new class of mono- and disubstituted urea- and
thiourea-based fluorescent probes. For the first time, reactive
isocyanate and isothiocyanate F-Bodipy-based synthons have
been prepared and display a good reactivity toward primary and
aromatic amines without any degradation of the Bodipy core.
A convenient condensation of the orthodiaminophenyl derivative
with dione and formyl compounds readily allows the preparation
of dipyridinophenazine and indole ligands. A strong electronic
transition located about 530 nm is responsible for the very
efficient fluorescence emission, reaching 86% in the best cases.
For the nitro- and dipyridinophenazine compounds, the fluo-
rescence is efficiently quenched owing to an intramolecular
electron-transfer process from the F-Bodipy excited state to the
nitro electron-accepting unit. The driving force is of the order
of -710 mV in the case of compound 4. Consideration of
electrochemical and optical properties allows the conclusion that
the Bodipy excited state is a good reductant and a modest
oxidant. Coordination of zinc(II) cation to the dipyridinophena-
zine ligand results in resolution of the two cathodic processes
due to successive reduction of the complexed phenanthroline
fragment and the F-Bodipy core.
Taken together, these findings establish that these neutral and
stable materials exhibit bipolar character and might behave as
exciton carriers in optoelectronic devices. Ongoing efforts are
focused on the use of these interesting isocyanate and isothio-
cyanate compounds in materials science for the engineering of
block copolymers,48 silica nanoparticles,49 and derivatization of
macrostructures.50 The attachment of these dyes to the entry of
zeolite nanochannels for directional energy transfer is currently
in progress.
1
12.3. 11B NMR (CDCl3, 128 MHz): δ (ppm) ) 3.82 (t, J ) 32
Hz). IR (KBr, cm-1): ν ) 2963, 2928, 2872, 1594, 1537 s, 1429 s,
1347, 1321, 1189 s, 1116, 1084, 980. UV-vis (CH2Cl2) λ (nm) (ꢀ,
M-1 cm-1) ) 530 (72000), 499 (sh, 23600), 382 (8000), 262
(13000). FAB+-MS m/z (nature of peak, relative intensity): 426.2
([M + H]+, 100), 406.2 ([M - F]+, 30). Anal. Calcd for C23H26-
BF2N3O2: C, 64.96; H, 6.16; N, 9.88. Found: C, 64.74; H, 5.83; N,
9.55.
4,4-Difluoro-8-(3,4-dinitrophenyl)-1,3,5,7-tetramethyl-2,6-di-
ethyl-4-bora-3a,4a-diaza-s-indacene 4. In a flame-dried Schlenk
flask, under argon, to a stirred solution of 3,4-dinitrobenzoic acid
(1 g, 4.7 mmol) in anhydrous CH2Cl2 (30 mL) were added oxalyl
chloride (0.8 mL, 9.4 mmol) and three drops of distilled pyridine.
The colorless solution, which slowly became turbid, was stirred
overnight at room temperature. The excess oxalyl chloride and the
solvent were then evaporated under vacuum, and 30 mL of freshly
distilled CH2Cl2 was added. The solution was then tranferred via
cannula to a stirred degassed solution of 2,4-dimethyl-3-ethylpyrrole
(1.3 mL, 9.4 mmol) in 30 mL of anhydrous CH2Cl2. The reaction
mixture was stirred for 4 days at room temperature and progres-
sively turned from pale brown to deep red in color. Triethylamine
(4 mL, 28.3 mmol) was then added, and the solution turned brown.
After 10 min, BF3‚Et2O (4.8 mL, 37.7 mmol) was added and the
reaction mixture turned purple. After being stirred for 24 h at room
temperature, it was washed with three portions of saturated aqueous
NaHCO3 (3 × 40 mL). The organic layer was then dried over
MgSO4 and filtered and the solvent evaporated. The crude product
was purified by chromatography on a column packed with flash
silica gel, using CH2Cl2/cyclohexane (30:70 to 100:0) as eluent.
Recrystallization in CH2Cl2/hexane afforded the desired compound
1
as a purple powder (1.411 g, 64%), mp 228-230 °C. H NMR
(CDCl3, 300 MHz): δ (ppm) ) 8.12 (d, 1H, 3J ) 8.1 Hz), 7.90 (d,
3
3
4
1H, J ) 1.7 Hz), 7.76 (dd, 1H, J ) 8.1 Hz, J ) 1.7 Hz), 2.54
3
3
(s, 6H), 2.32 (q, 4H, J ) 7.5 Hz), 1.33 (s, 6H), 1.00 (t, 6H, J )
7.5 Hz). 13C NMR (CDCl3, 75 MHz): δ (ppm) ) 156.3, 143.7,
142.8, 142.4, 137.2, 134.3, 133.9, 133.4, 129.9, 126.0, 125.8, 17.2,
14.6, 12.8, 12.7. 11B NMR (CDCl3, 128 MHz): δ (ppm) ) 3.72 (t,
1J ) 32 Hz). IR (KBr, cm-1): ν ) 2973, 2964, 2929, 1543 s, 1473
s, 1421 s, 1190 s, 1080, 979. UV-vis (CH2Cl2) λ (nm) (ꢀ, M-1
cm-1) ) 536 (55000), 504 (sh, 21000), 386 (7500), 262 (14000).
FAB+-MS m/z (nature of peak, relative intensity): 471.2 ([M +
H]+, 100), 424.1 ([M - NO2]+, 35). Anal. Calcd for C23H25-
BF2N4O4: C, 58.74; H, 5.36; N, 11.91. Found: C, 58.51; H, 4.95;
N, 11.62.
General Procedure B for the Reduction of the Nitrobenzene-
Bodipy. To a stirred, degassed CH2Cl2/EtOH (20 mL/20 mL)
solution of nitrophenyl-Bodipy (1 equiv) was added under argon
Pd/C 5% (5% mol.). The reaction mixture was stirred under H2
(atmospheric pressure) until total consumption of the starting
material was observed by TLC (SiO2, CH2Cl2). After 24 h, the
solution was then filtered through Celite, and the solvents were
evaporated. The crude product was purified by chromatography.
Additional purification is performed routinely by recrystallization
in adequate solvents.
Experimental Section
General Procedure A for the Synthesis of Nitrobenzenebo-
radiazaindacene Derivatives. To a solution of 2,4-dimethyl-3-
ethylpyrrole (2 equiv) in anhydrous dichloromethane was added
the aroyl chloride (1 equiv). The solution was stirred at room
temperature during 4 days, the color changing slowly from pale
brown to deep red. Triethylamine (6 equiv) was then added (yellow
brown solution), followed by a subsequent addition of boron
trifluoride etherate (8 equiv) (purple solution). The mixture was
stirred for 1 day at rt and then was washed 3 times with saturated
aqueous NaHCO3. The organic layer was then dried over MgSO4
and filtered and the solvent removed. Chromatography on silica
gel gave the pure compounds. Additional purification is performed
routinely by recrystallization in adequate solvents.
4,4-Difluoro-8-(3-nitrophenyl)-1,3,5,7-tetramethyl-2,6-diethyl-
4-bora-3a,4a-diaza-s-indacene 2. Prepared according to general
procedure A using 3-nitrobenzoyl chloride (0.31 mL, 2.7 mmol),
2,4-dimethyl-3-ethylpyrrole (0.73 mL, 5.39 mmol) in anhydrous
CH2Cl2 (50 mL), triethylamine (2.3 mL, 16.2 mmol), and BF3‚
4,4-Difluoro-8-(3-aminophenyl)-1,3,5,7-tetramethyl-2,6-dieth-
yl-4-bora-3a,4a-diaza-s-indacene 6. Prepared according to general
procedure B: 2 (0.400 g, 0.89 mmol), Pd/C 5% (0.100 g).
Chromatography (silica gel, CH2Cl2/cyclohexane 80:20 to 100:0).
Recrystallization in CH2Cl2/hexane gave the title compound as an
orange powder (0.317 g, 85%), mp 291-293 °C. 1H NMR (CDCl3,
300 MHz): δ (ppm) ) 7.28-7.23 (m, 1H), 6.80-6.61 (m, 3H),
(48) (a) Kim, D. U.; Tsutsui, T. J. Appl. Phys. 1996, 80, 4785. (b) Peng,
K.-Y.; Chen, S.-A.; fann, W.-S. J. Am. Chem. Soc. 2001, 123, 11388. (c)
Simas, E. R.; Akcelrud, L. J. Lum. 2003, 105, 69. (d) Akcelrud, L. Prog.
Polym. Sci. 2003, 28, 875.
(49) Montalti, M.; Prodi, L.; Zaccheroni, N.; Zattoni, A.; Reschiglian,
P.; Falini, G. Langmuir 2004, 20, 2989.
(50) Huber, S.; Calzaferri, G. Angew. Chem., Int. Ed. 2004, 43, 6738.
J. Org. Chem, Vol. 71, No. 8, 2006 3101

Ziessel et al.
3
3.78 (br s, 2H), 2.54 (s, 6H), 2.33 (q, 4H, J ) 7.5 Hz), 1.44 (s,
ν ) 3399, 2959, 2925, 2868, 1646, 1599, 1538 s, 1474 s, 1441 s,
6H), 1.01 (t, 6H, J ) 7.5 Hz). 13C NMR (CDCl3, 75 MHz): δ
1310, 1191 s, 1062, 976. UV-vis (CH2Cl2) λ (nm) (ꢀ, M-1 cm-1
)
3
(ppm) ) 153.6, 147.3, 140.7, 138.6, 136.9, 132.7, 130.8, 130.1,
) 525 (77000), 493 (sh, 24000), 376 (9000), 251 (42000). FAB+-
MS m/z (nature of peak, relative intensity): 515.1 ([M + H]+, 100),
495.1 ([M - F]+, 20). Anal. Calcd for C30H33BF2N4O: C, 70.04;
H, 6.47; N, 10.89. Found: C, 69.69; H, 6.12; N, 10.65.
118.4, 115.3, 114.7, 17.2, 14.8, 12.6, 11.7. 11B NMR (CDCl3, 128
MHz): δ (ppm) ) 3.86 (t, J ) 32 Hz). IR (KBr, cm-1): ν )
1
3370, 2965, 2924, 2871, 1601 s, 1537 s, 1450 s, 1317, 1190 s,
1062, 978. UV-Vis (CH2Cl2) λ (nm) (ꢀ, M-1 cm-1) ) 524 (85000),
491 (sh, 25000), 376 (8000), 287 (7000). FAB+-MS m/z (nature
of peak, relative intensity): 396.2 ([M + H]+, 100), 376.2 ([M -
F]+, 30). Anal. Calcd for C23H28BF2N3‚1/2H2O: C, 68.33; H, 7.23;
N, 10.39. Found: C, 68.40; H, 6.82; N, 10.38.
4,4-Difluoro-8-(dipyrido[3,2-a:2′,3′-c]phenazin-11-yl)phenyl)-
1,3,5,7-tetramethyl-2,6-diethyl-4-bora-3a,4a-diaza-s-indacene 22.
To a solution of 8 (0.05 g, 0.12 mmol) in EtOH (15 mL) was added
1,10-phenanthroline-5,6-dione (0.026 g, 0.12 mmol). The reaction
mixture was refluxed during 15 h, and after cooling, the red
precipitate was filtered and washed with three portions of EtOH (3
× 5 mL). The analytically pure compound was recovered as a red
4,4-Difluoro-8-(4-isocyanatophenyl)-1,3,5,7-tetramethyl-2,6-
diethyl-4-bora-3a,4a-diaza-s-indacene 9. In a round-bottomed
flask, under argon, trichloromethyl chloroformate (0.014 mL, 0.12
mmol) was added to a stirred solution of 5 (0.092 g, 0.23 mmol)
in anhydrous THF (10 mL). The reaction mixture was stirred at
room temperature during 45 min and then heated at 60 °C during
30 min. The solvent was then evaporated, and the resulting
isocyanate was used without further purification (0.098 g, 100%).
1H NMR (CDCl3, 200 MHz): δ (ppm) ) 7.23 (m, 4H), 2.53 (s,
6H), 2.30 (q, 4H, 3J ) 7.5 Hz), 1.31 (s, 6H), 0.98 (t, 6H, 3J ) 7.5
Hz). 13C NMR (CDCl3, 75 MHz): δ (ppm) ) 154.3, 138.9, 138.2,
134.3, 133.6, 133.2, 130.9, 130.0, 129.7, 125.6, 17.2, 14.7, 12.7,
12.0. IR (KBr, cm-1): ν ) 3410, 2957, 2927, 2864, 2256 s, 1779,
1534 s, 1471 s, 1312 s, 1184 s, 1112, 1051 s, 974 s.
4,4-Difluoro-8-(4-isothiocyanatophenyl)-1,3,5,7-tetramethyl-
2,6-diethyl-4-bora-3a,4a-diaza-s-indacene 12. In a round-bot-
tomed flask, under argon, was added dropwise a solution of
thiophosgen (0.013 mL, 0.18 mmol) in distilled CH2Cl2 (5 mL) to
a solution of 5 (0.05 g, 0.13 mmol) in anhydrous CH2Cl2/NEt3 (20
mL/0.2 mL) maintained at 0 °C. As soon as total consumption of
the starting materiel was observed by TLC (one spot, about 5 min),
the reaction was quenched with water (10 mL). The organic layer
was then washed with water (3 × 20 mL), dried over anhydrous
MgSO4, and filtered, and the were solvents evaporated. The residue
was then passed through a very short pad of silica gel and the
resulting isothiocyanate used without further purification for the
following reaction (0.055 g, 100%). 1H NMR (CDCl3, 200 MHz):
1
powder (0.056 g, 79%), mp> 280 °C dec. H NMR (CDCl3, 300
MHz): δ (ppm) ) 9.71-9.62 (m, 2H), 9.31-9.28 (m, 2H), 8.53
3
4
(d, 1H, J ) 8.7 Hz), 8.37 (d, 1H, J ) 1.3 Hz), 7.88-7.79 (m,
3H), 2.57 (s, 6H), 2.29 (q, 4H, 3J ) 7.5 Hz), 1.25 (s, 6H), 0.97 (t,
6H, 3J ) 7.5 Hz). 13C NMR (CDCl3, 75 MHz): δ (ppm) ) 154.7,
153.1, 148.78, 148.76, 142.3, 142.23, 142.22, 142.1, 138.5, 138.1,
138.0, 134.1, 134.0, 133.4, 131.4, 130.7, 129.6, 127.54, 127.49,
124.44, 17.2, 14.7, 12.7, 12.3. 11B NMR (CDCl3, 128 MHz): δ
1
(ppm) ) 3.93 (t, J ) 32 Hz). IR (KBr, cm-1): ν ) 1541 s, 1475
s, 1442 s, 1404 s, 1320, 1190 s, 1115, 1071, 979. UV-vis (CH2-
Cl2) λ (nm) (ꢀ, M-1 cm-1) ) 529 (71500), 496 (sh, 24000), 384
(32000), 365 (27000), 294 (31000), 270 (74000). FAB+-MS m/z
(nature of peak, relative intensity): 585.2 ([M + H]+, 100), 565.2
([M - F]+, 35). Anal. Calcd for C35H31BF2N6: C, 71.92; H, 5.35;
N, 14.38. Found: C, 71.78; H, 5.29; N, 14.22.
4,4-Difluoro-8-(1H-benzimidazole-2-(6-methyl-2-pyridinyl)-
5-yl)-1,3,5,7-tetramethyl-2,6-diethyl-4-bora-3a,4a-diaza-s-in-
dacene 23. To a solution of 8 (0.100 g, 0.24 mmol) in EtOH (20
mL) were added 6-methylpyridine-2-carboxaldehyde (0.03 g, 0.25
mmol) and p-toluenesulfonic acid (10% mol., 0.005 g). The reaction
mixture was heated under reflux while air was bubbled through
the solution. After 1 h, total consumption of the starting material
was observed. After cooling, the solution was washed with water
(3 × 10 mL), the organic layer was dried over MgSO4 and filtered,
and the solvent was evaporated. Chromatography on silica gel (CH2-
Cl2/cyclohexane 80:20 to 100:0, then CH2Cl2/MeOH 100:0 to 98:
2), followed by recrystallization in CH2Cl2/hexane, afforded the
desired compound as a red powder (0.103 g, 83%), mp > 291 °C
3
δ (ppm) ) 7.32 (m, 4H), 2.53 (s, 6H), 2.30 (q, 4H, J ) 7.5 Hz),
1.30 (s, 6H), 0.98 (t, 6H, 3J ) 7.5 Hz). 13C NMR (CDCl3, 75 MHz):
δ (ppm) ) 154.5, 138.4, 138.1, 137.2, 135.1, 133.3, 132.3, 130.7,
130.1, 126.5, 17.2, 14.7, 12.7, 12.1. IR (KBr, cm-1): ν ) 2962,
2929, 2867, 2095 s, 1743, 1546, 1470, 1316, 1259 s 1186, 1018 s,
975, 799 s.
1
3
dec. H NMR (CD3OD, 300 MHz): δ (ppm) ) 8.14 (d, 1H, J )
8.1 Hz), 7.90-7.84 (m, 2H), 7.60 (s, br, 1H), 7.39 (d, 1H, 3J ) 7.5
Hz), 7.24 (d, 1H, 3J ) 7.9 Hz), 2.67 (s, 3H), 2.50 (s, 6H), 2.35 (q,
3
3
4H, J ) 7.5 Hz), 1.30 (s, 6H), 0.99 (t, 6H, J ) 7.5 Hz). 13C
NMR (CDCl3, 75 MHz): δ (ppm) ) 158.5, 153.8, 153.6, 152.4,
147.2, 145.1, 144.9, 138.7, 137.6, 134.1, 133.9, 132.9, 131.5, 131.4,
130.2, 124.7, 124.2, 123.2, 121.0, 120.2, 118.8, 112.1, 111.3, 24.6,
17.2, 14.8, 12.6, 11.9. 11B NMR (CDCl3, 128 MHz): δ (ppm) )
3.93 (t, 1J ) 32 Hz); IR (KBr, cm-1): ν ) 3436, 2960, 2925, 2853,
1597, 1541, 1434 s, 1320, 1191, 1115, 1082, 980. FAB+-MS m/z
(nature of peak, relative intensity): 512.2 ([M + H]+, 100). UV-
vis (CH2Cl2) λ (nm) (ꢀ, M-1 cm-1) ) 524 (68000), 494 (sh, 21600),
371 (10500), 316 (28000). Anal. Calcd for C30H31BF2N5: C, 70.46;
H, 6.31; N, 13.69. Found: C, 70.33; H, 6.28; N, 13.57.
General Procedure C: For the Synthesis of Urea or Thiourea
with Phenyl Isocyanate or Isothiocyanate. In a flame-dried
Schlenk flask, under argon, to a stirred solution of aminophenyl-
Bodipy (1 equiv) in anhydrous CH2Cl2/CH3CN (3 mL/3 mL) was
added phenyl iso(thio)cyanate (1.5 equiv per amino group). The
reaction mixture was stirred under reflux until complete consump-
tion of the starting material was observed by TLC. Water was then
added, and the solution was extracted with CH2Cl2. The organic
layer was dried on MgSO4 and filtered, and the solvents were
evaporated. Purification was performed by chromatography. Ad-
ditional purification is performed routinely by recrystallization in
adequate solvents.
Acknowledgment. We are grateful to CNRS and ULP for
financial support. L.B. thanks the French Ministe`re de la
Recherche for a fellowship. We are also indebted to Professor
Jack Harrowfield (ISIS Strasbourg) for careful reading of this
manuscript prior to publication.
4,4-Difluoro-8-(3-phenylureaphenyl)-1,3,5,7-tetramethyl-2,6-
diethyl-4-bora-3a,4a-diaza-s-indacene 15. Prepared according to
general procedure C using 6 (0.05 g, 0.13 mmol) and phenyl
isocyanate (0.19 mmol, 0.02 mL). Chromatography (silica gel, CH2-
Cl2/cyclohexane, 80:20 to 100:0). Recrystallization in CH2Cl2/
hexane afforded the desired compound as a red powder (0.045 g,
70%), mp >150 °C dec. 1H NMR (CDCl3, 300 MHz): δ (ppm) )
7.65 (m, 1H), 7.43-7.30 (m, 5H), 7.15-7.08 (m, 2H), 6.99-6.94
(m, 1H), 6.88 (s, br, 1H), 6.73 (s, br, 1H), 2.52 (s, 6H), 2.28 (q,
Supporting Information Available: General experimental
procedure, reagents, materials, and experimental details for com-
pounds 1, 3, 5, 7, 8, 10, 11, 13, 14, and 16-21. Detailed X-ray
crystal structure determination and geometrical parameters (Table
S1) for 3. This material is available free of charge via the Internet
at http://pubs.acs.org.
4H, J ) 7.5 Hz), 1.34 (s, 6H), 0.97 (t, 6H, J ) 7.5 Hz). 13C
NMR (CDCl3, 75 MHz): δ (ppm) ) 153.9, 152.9, 139.6, 139.5,
138.6, 137.9, 136.7, 133.0, 130.8, 130.1, 129.6, 129.5, 124.8, 124.7,
123.4, 121.6, 120.1, 119.5, 17.2, 14.7, 12.7, 11.9. IR (KBr, cm-1):
3
3
JO0600151
3102 J. Org. Chem., Vol. 71, No. 8, 2006