Near-infrared dyes and fluorophores based on diketopyrrolopyrroles

Article abstract of DOI:10.1002/anie.200604763

NIRly there: The chromophore of compounds with intramolecular H bonds have been rigidified by substitution of the protons of the N-H...N bridges by BR₂ groups (R = F, Ph). This stiffening and the polymethine character of the chromophores afford

Full text of DOI:10.1002/anie.200604763

Communications
DOI: 10.1002/anie.200604763
NIR dyes
Near-Infrared Dyes and Fluorophores Based on Diketopyrrolopyrroles
Georg M. Fischer, Andreas P. Ehlers, Andreas Zumbusch, and Ewald Daltrozzo*
Dedicated to Professor Friedrich Dörr on the occasion of his 85th birthday
Our research activities over the last few decades have
concerned correlations between molecular structure and
fluorescence.[1,2] A central theme of the research has been
the synthesis and spectroscopic investigations of near-infrared
(NIR) dyes[3] to get insights into what degree the obtainable
fluorescence quantum yields[4,5] are restricted by the S0$S1
energy gap.[6,7] Our results[8] on the condensation of 1,4-
phthalazinediones with heteroarylacetonitriles in POCl3
prompted us to carry out the reaction with diketopyrrolopyr-
roles (DPPs) 1.[9] Herein we report the results of the
investigations.
To date, attempts to activate the carbonyl group of DPPs
with POCl3, and to subsequently convert the intermediates
with nucleophiles, only led to monosubstitution or to ring
opening.[9,10] The reaction of 1 and 2 in refluxing toluene with
an excess of POCl3 according to Scheme 1 afforded disub-
stituted NIR dyes 3. The progress of the reaction was
controlled by recording absorption spectra and stopping the
heating as soon as the DPP was used up and/or products
absorbing at short wavelengths appeared. Purification was
Scheme 1. Reagents and conditions: a) absolute toluene/POCl3, reflux;
b) 1,2-dichlorobenzene/BF3·Et2O, reflux, diisopropylethylamine;
c) xylene/chlorodiphenylborane, reflux; DPPs 1: R1 =4-octyloxy (1a),
R1 =4-methoxy (1b), R1 =4-butyloxy (1c), R1 =4-(hex-5-enyloxy) (1d),
R1 =4-(N-methyl-N-octylamino) (1e); heteroarylacetonitriles 2: 2-(6-
tert-butylquinolin-2-yl)acetonitrile (2a), 2-(6-tert-butylbenzothiazol-2-
yl)acetonitrile (2b), 2-(quinoxalin-2-yl)acetonitrile (2c), 2-(6-methylpyr-
idin-2-yl)acetonitrile (2d). A: aromatic ring.
carried out by digesting the product in acetone and subse-
quent flash chromatography (silica gel/CHCl3 or CH2Cl2).
The NIR dyes 3a–3h (the structures and spectroscopic
data of 3b–3h can be found in the Supporting Information)
were synthesized according to this procedure (Scheme 1)
from the reaction of 1[11] and 2. The course of the reactions
was the same in all cases and side-products with strong
absorptions below 350 nm were observed. These side-prod-
ucts are most likely compounds formed by the opening of the
DPPs pentalene ring system.
Prerequisite for the reactions is a certain solubility of the
DPPs.[12] This is a feature of all of the DPPs used here with the
exception of the 4-methoxy derivative 1b. Remarkably, the 4-
(N-methyl-N-octyl amino) derivative 1e has a much better
solubility than all the other DPPs used. Only in the case of the
reaction of 1e with 2a were we able to isolate the 1:1
condensation product (13% yield).
obtained only if the solubility of both condensation partners
was improved by having longer alkyl groups (Table 1). From
these observations we draw the following conclusion con-
cerning the reaction pathway: DPP reacts with POCl3 to form
a monophosphorylated intermediate,[9] which reacts with the
Table 1: Yield and spectroscopic data of the first electronic transition
(S0!S1) of 3a–3h.[a]
The heteroarylacetonitriles 2a and 2b substituted with a
tert-butyl group were used to improve the solubility of the
condensation products 3. In general, satisfying yields were
Reactants
NIR
dyes
Yield
[%]
l00
[nm]
e00
[mꢀ1 cmꢀ1
]
f
1a
2a
2b
2c
2d
2a
2a
2a
2a
3a
3b
3c
3d
3e
3 f
33
39
7
2
4
74
41
58
731
735
743
701
730
731
731
752
118000
115000
135000
70000
111000
103000
115000
115000
0.71
0.74
0.72
0.48
0.68
0.62
0.69
0.64
1a
1a
1a
1b
1c
1d
1e
[*] G. M. Fischer, A. P. Ehlers, Prof. Dr. A. Zumbusch,
Prof. Dr. E. Daltrozzo
Fachbereich Chemie
Universität Konstanz
Universitätstrasse 10, 78464 Konstanz (Germany)
Fax : (+49)7531-883043
E-mail: ewald.daltrozzo@uni-konstanz.de
3g
3h
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
[a] In chloroform at room temperature. l00 =absorption wavelength,
e00 =molardecadic absorption coefficient, f=oscillatorstrength.
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Chemie
Table 2: Spectroscopic data of the first electronic transition (S0$S1) of
the difluoroboryl chelate 4a and diphenylboryl chelate 4a’.[a]
heteroarylacetonitrile to give the 1:1 condensation product.
Since the solubility of this product is higher than that of the
DPP, it reacts faster with an additional equivalent of POCl3
and heteroarylacetonitrile to yield 3.
4
lA00
lF00
Dn˜A-F
[cmꢀ1
e00
[mꢀ1 cmꢀ1
]
f
FF
[nm]
[nm]
]
The NIR dyes 3a, 3e, 3 f, and 3g differ only in the length
of the alkyl groups on the alkoxy substituent. Consequently
they show identical absorption spectra at room temperature.
The effect of DPP substituents and of the nature of the
heteroarylacetonitrile on both the yield and first electronic
transition (l00, e00, and oscillatory strength f) is summarized in
Table 1. Figure 1 shows the first electronic absorption of the
dyes obtained from 1a and 2a–2d. Whereas the absorption of
4a
4a’
754
819
773
831
320
180
205000
256000
0.83
0.76
0.59
0.53
[a] In chloroform at room temperature. lA00/l0F0 =absorption/emission
wavelength, Dn˜A-F =Stokes shift, e00 =molardecadic absoprtion coef-
ficient, f=oscillatorstrength, FF =fluorescence quantum yield.
chelates 4a and 4a’. A comparison of the long-wavelength
absorptions of 3a, 4a, and 4a’ (Figure 2) clearly demonstrates
the effects of chromophore stiffening: a) sharpening of the
vibronic bands (Dn˜1/2 ꢁ 750 cmꢀ1 for 3a versus Dn˜1/2
ꢁ 500 cmꢀ1 for 4a and Dn˜1/2 ꢁ 400 cmꢀ1 for 4a’), b) increase
in the e00 and f(S0!S1) values, c) shift of the Franck–Condon
factors in favor of the 00 transition.
Figure 1. Absorption of the NIR dyes 3a (c), 3b (a), 3c (g),
and 3d (d) with the DPP core 1a in chloroform at room temper-
ature.
the quinoline, benzothiazole, and quinoxaline derivative
differ only slightly, the absorption of the pyridine derivate is
hypsochromically and hypochromically shifted, which agrees
with theoretical predictions.
Figure 2. Absorption of 3a, X=H (a), 4a (X=BF2, g), and 4a’
(X=BPh2, c) in chloroform at room temperature.
The large intramolecular mobility (high amplitude tor-
sional vibrations of the heteroaromatic terminal groups) of
the NIR dyes 3 in solution results in no fluorescence being
observed at room temperature. Substitution of the protons in
Compound 4a has a rigid planar chromophore, whereas
4a’ is somewhat twisted as a result of the steric requirements
of the phenyl rings of the BPh2 group. This finding explains
the lower S0!S1 transition moment (f = 0.76 for 4a’ versus f =
0.83 for 4a). The smaller half-width of the 00 band[13]
indicates that the asymmetrical torsional potential for 4a’
on the side of the small torsional angle is steeper than the
symmetrical torsional potential of 4a. The bathochromic shift
of 4a to 4a’ is the expected consequence of the different s-
inductive effects of BF2 and BPh2 on the chromophoric
system.
ꢀ
both N H···Nbridges in 3 by a BF2 or BPh2 group proved to
be the most convenient method to rigidize the chromophore
and thus eliminate efficient torsions by radiationless S1
decay.[2] The desired difluoroboryl chelates 4 were obtained
by the reaction of 3 with boron trifluoride etherate and
Hünigꢀs base in refluxing 1,2-dichlorobenzene—for example,
4a was obtained in 61% yield from 3a. Compound 4a is
stable in dichloromethane: the absorption does not change
upon illumination for several hours at 366 nm. Analogous
results were obtained for 3e and 3 f. To our surprise, the
difluoroboryl derivate of the benzothiazole dye 3b could not
be isolated because of its lability. Heating 3a in xylene and
addition of chlorobiphenylborane afforded the diphenylboryl
chelate 4a’ in a yield of 56%. As expected, all chelates 4 show
intense NIR fluorescence at room temperature.
The room-temperature fluorescence quantum yields of
0.59 and 0.53 for 4a and 4a’, respectively (with an error of less
than 10%), in chloroform at emission wavelengths (lF00) of
773 nm and 831 nm, respectively, are, to our knowledge, far
higher than for any other known fluorophore.
In contrast to the naphthalenediimides[14] and the rylene-
diimides,[15] there are only small changes in the molecular
geometry resulting from the first electronic excitation in our
systems, that is, the potential surfaces of S0 and S1 are very
Table 2 gives the characterization data of the first
electronic transition and the fluorescence for the boron
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3751

Communications
solid was separated by filtration, washed with acetone, and purified by
column chromatography.
similar. Thus, the intensities of the vibrational transitions are
strongly shifted towards the 00 transition. This effect com-
bined with the appearance of the 00 band above 800 nm in the
spectrum results in 4a’ coming close to being an ideal
selective NIR absorber (intense absorption in the near-
infrared range, but extremely low absorptions in the visible
range from 700 to 380 nm), as is shown by the absorption of
4a’ in methylcyclohexane (Figure 3). Selective NIR absorbers
are of technical interest for NIR laser welding of transparent
polymers.[16]
3a: Column chromatography (silica gel/CHCl3) afforded 3a as a
green crystalline powder in 33% yield. 1H NMR (400 MHz, CDCl3):
d = 14.78 (brs, 2H; N-H), 7.96 (d, 3J = 8.8 Hz, 2H; H-4’), 7.77 (m, 8H;
3
AA’, H-7’, H-8’), 7.65 (d, J = 8.8 Hz, 2H; H-3’), 7.63 (s, 2H; H-5’),
7.14 (m, 4H; XX’), 4.10 (t, 3J = 6.6 Hz, 4H; OCH2), 1.86 (m, 4H;
OCH2CH2), 1.6–1.3 (m, 38H; alkyl, tert-butyl), 0.92 ppm (t, 3J =
6,8 Hz, 6H; CH3). MALDI-MS: m/z calcd: 957.6 [M+H]+, 979.6
[M+Na]+, 995.5 [M+K]+; found: 956.8, 978.8, 995.7; UV/Vis/NIR
(CHCl3): n00 = 13700 cmꢀ1 (l00 = 731 nm); e00 = 118000mꢀ1 cmꢀ1, f =
0.71. Elemental analysis calcd (%) for C64H72N6O2 [M =
957.30 gmolꢀ1]: C 80.30, H 7.58, N8.78; found: C 80.36, H 7.67, N
8.37.
4a: BF3·Et2O (0.98 mL, 1.77 g, 7.38 mmol) was added to a
solution of 3a (500 mg, 0.52 mmol) in ortho-dichlorobenzene
(15 mL) at reflux in a nitrogen atmosphere. After 10 min, Hünigꢀs
base (0.22 mL, 169 mg, 1.31 mmol) was added and the mixture heated
at reflux for a further 10 min. The reaction was then stopped. After
removal of the solvent and excess BF3·Et2O, the crude product was
dissolved in methanol in an ultrasonic bath and separated by
filtration. Column chromatography (silica gel/CH2Cl2) afforded 4a
in 76% yield (420 mg, 0.40 mmol) as a green powder. 1H N MR
(400 MHz, C2D2Cl4): d = 8.42 (m, 2H; H-8’), 8.14 (d, 3J = 9.3 Hz, 2H;
H-4’), 7.74 (dd, 3J = 9.5 Hz, 4J = 2.2 Hz, 2H; H-7’), 7.72 (d, 4H; AA’),
3
7.66 (m, 4H; H-3’,H-5’), 7.06 (m, 4H; XX’), 4.08 (t, J = 6.6 Hz, 4H;
OCH2), 1.85 (m, 4H; OCH2CH2), 1.53 (m, 4H; O(CH2)2CH2), 1.45–
1.2 (brs, 16H; alkyl), 1.36 (s, 18H; tert-butyl), 0.91 ppm (t, 6H; CH3).
MALDI-MS: m/z calcd: 1053.6 [M+H]+, 1075.6 [M+Na]+; found:
1053.1, 1076.1; UV/Vis/NIR (CHCl3): nA00 = 13260 cmꢀ1 (l0A0
=
=
754 nm), e00 = 205000mꢀ1 cmꢀ1
,
f = 0.83; nF00 = 12940 cmꢀ1 (lF00
773 nm), FF = 0.59. Elemental analysis calcd (%) for
C64H70B2F4N6O2 [M = 1052.90 gmolꢀ1]: C 73.01, H 6.70, N7.98;
found: C 72.51, H 6.95, N7.83.
Figure 3. Absorption (c) and fluorescence (g) of 4a’ in methyl-
cyclohexane at room temperature.
4a’: A mixture of 3a (250 mg, 0.26 mmol) and (321 mg, 1.6 mmol)
chlorodiphenylborane was refluxed in absolute xylene (15 mL) under
nitrogen. After 10 min at reflux, the reaction was stopped, xylene
removed, and the residue purified by column chromatography (silica
gel/CH2Cl2) to afford 4a’ as a yellow solid in 56% yield (189 mg,
In conclusion, the condensation of sufficiently soluble
diketopyrrolopyrroles with 2-heteroarylacetonitriles provides
a new approach to dyes 3 with strong NIR absorptions.
Stiffening the chromophore affords NIR fluorophores 4
which results in spectacular properties becoming available.
Future applications of the dyes as NIR labels could be
accomplished by their functionalization. The first steps
towards this goal were already achieved by the synthesis of
systems with terminal alkene groups.
1
3
0.147 mmol). H NMR (400 MHz, C2D2Cl4): d = 8.18 (d, J = 9.5 Hz,
2H; H-8’), 7.83 (d, 3J = 9.3 Hz, 2H; H-4’), 7.58 (d, 3J = 9.3 Hz, 2H; H-
3
4
3’), 7.34 (m, 10H; H-5’, m-phenyl), 7.15 (dd, J = 9.5 Hz, J = 2.2 Hz,
2H; H-7’), 7.10 (m, 12H; o- ,p-phenyl), 6.52 (d, 4H; AA’), 6.06 (m,
4H; XX’), 4.02 (t, J = 6.6 Hz, 4H; OCH2), 1.86 (m, 4H; OCH2CH2),
1.53 (m, 4H; O(CH2)2CH2), 1.48–1.25 (brs, 16H; alkyl), 1.16 (s, 18H;
tert-butyl), 0.93 ppm (m, 6H; CH3). MALDI-MS: m/z calcd: 1285.7
[M+H], found: 1285.5; UV/Vis/NIR (CHCl3): nA00 = 12210 cmꢀ1 (l0A0
=
821 nm), e00 = 256000mꢀ1 cmꢀ1
,
f = 0.76; nlF00 = 12030 cmꢀ1 (lF00
=
831 nm), FF = 0.53. Elemental analysis calcd (%) for C88H90B2N6O2
[M = 1285.32 gmolꢀ1]: C 82.23, H 7.06, N6.54; found: C 81.59, H 7.11,
N6.49.
Experimental Section
The fluorescence quantum yields were determined on diluted
solutions (c < 2 ” 10ꢀ6 m) with
a A
home-made spectrometer.[7]
Received: November 23, 2006
Revised: January 11, 2007
Published online: April 5, 2007
HeNe laser or a 804-nm diode laser were used as the excitation
sources, and a germanium diode (NORTHCOAST) used as the
detector. CZ 144 (= DY-665-X, Dyomics) was used as a reference dye
(FF = 0.60 in CH2Cl2).[17]
Keywords: chromophores · dyes/pigments · fluorophores ·
General procedure for the synthesis of NIR dyes 3: POCl3
(8 mmol) was added to a mixture of DPP 1 (1 mmol) and hetero-
arylacetonitrile 2 (2.5 mmol) in absolute toluene (20 mL) at reflux in
a nitrogen atmosphere. The reaction was monitored by UV/Vis/NIR
spectroscopy and thin-layer chromatography. As soon as the DPP was
used up or short-wavelength-absorbing by-products increased, the
reaction was stopped. After removal of the toluene and excess POCl3
by vacuum distillation, the crude product was dissolved in CH2Cl2 and
neutralized with aqueous NaHCO3 solution. The organic phase was
separated and dried with MgSO4. After removing the solvent, the
residue was dissolved in acetone in an ultrasonic bath. The remaining
.
polymerwelding · UV/Vis/NIR spectroscopy
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