Near‐Infrared Dyes and Fluorophores Based on Diketopyrrolopyrroles (2007)

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 affords dyes with intense fluorescence at room temperature and high NIR absorption, but virtually no absorption in the visible range (see the picture for an example, —: absorption, ••••: fluorescence). 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) dyes3 to get insights into what degree the obtainable fluorescence quantum yields4, 5 are restricted by the S0↔S1 energy gap.6, 7 Our results8 on the condensation of 1,4-phthalazinediones with heteroarylacetonitriles in POCl3 prompted us to carry out the reaction with diketopyrrolopyrroles (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 disubstituted 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 carried out by digesting the product in acetone and subsequent flash chromatography (silica gel/CHCl3 or CH2Cl2). 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 (1 a), R1=4-methoxy (1 b), R1=4-butyloxy (1 c), R1=4-(hex-5-enyloxy) (1 d), R1=4-(N-methyl-N-octylamino) (1 e); heteroarylacetonitriles 2: 2-(6-tert-butylquinolin-2-yl)acetonitrile (2 a), 2-(6-tert-butylbenzothiazol-2-yl)acetonitrile (2 b), 2-(quinoxalin-2-yl)acetonitrile (2 c), 2-(6-methylpyridin-2-yl)acetonitrile (2 d). A: aromatic ring. The NIR dyes 3 a–3 h (the structures and spectroscopic data of 3 b–3 h can be found in the Supporting Information) were synthesized according to this procedure (Scheme 1) from the reaction of 111 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-products 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 1 b. Remarkably, the 4-(N-methyl-N-octyl amino) derivative 1 e has a much better solubility than all the other DPPs used. Only in the case of the reaction of 1 e with 2 a were we able to isolate the 1:1 condensation product (13 % yield). The heteroarylacetonitriles 2 a and 2 b substituted with a tert-butyl group were used to improve the solubility of the condensation products 3. In general, satisfying yields were 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 concerning the reaction pathway: DPP reacts with POCl3 to form a monophosphorylated intermediate,9 which reacts with the 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. Reactants NIR dyes Yield [%] λ00 [nm] ε00 [M−1 cm−1] f 1 a 2 a 3 a 33 731 118 000 0.71 1 a 2 b 3 b 39 735 115 000 0.74 1 a 2 c 3 c 7 743 135 000 0.72 1 a 2 d 3 d 2 701 70 000 0.48 1 b 2 a 3 e 4 730 111 000 0.68 1 c 2 a 3 f 74 731 103 000 0.62 1 d 2 a 3 g 41 731 115 000 0.69 1 e 2 a 3 h 58 752 115 000 0.64 The NIR dyes 3 a, 3 e, 3 f, and 3 g 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 (λ00, ε00, and oscillatory strength f) is summarized in Table 1. Figure 1 shows the first electronic absorption of the dyes obtained from 1 a and 2 a–2 d. Whereas the absorption of 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. Absorption of the NIR dyes 3 a (—), 3 b (- - - -), 3 c (••••), and 3 d (•–•–) with the DPP core 1 a in chloroform at room temperature. The large intramolecular mobility (high amplitude torsional 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 both NH⋅⋅⋅N bridges 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 Hünig's base in refluxing 1,2-dichlorobenzene—for example, 4 a was obtained in 61 % yield from 3 a. Compound 4 a is stable in dichloromethane: the absorption does not change upon illumination for several hours at 366 nm. Analogous results were obtained for 3 e and 3 f. To our surprise, the difluoroboryl derivate of the benzothiazole dye 3 b could not be isolated because of its lability. Heating 3 a in xylene and addition of chlorobiphenylborane afforded the diphenylboryl chelate 4 a′ in a yield of 56 %. As expected, all chelates 4 show intense NIR fluorescence at room temperature. Table 2 gives the characterization data of the first electronic transition and the fluorescence for the boron chelates 4 a and 4 a′. A comparison of the long-wavelength absorptions of 3 a, 4 a, and 4 a′ (Figure 2) clearly demonstrates the effects of chromophore stiffening: a) sharpening of the vibronic bands (Δ1/2≈750 cm−1 for 3 a versus Δ1/2≈500 cm−1 for 4 a and Δ1/2≈400 cm−1 for 4 a′), b) increase in the ε00 and f(S0→S1) values, c) shift of the Franck–Condon factors in favor of the 00 transition. Absorption of 3 a, X=H (- - - -), 4 a (X=BF2, ••••), and 4 a′ (X=BPh2, —) in chloroform at room temperature. 4 [nm] [nm] ΔA-F [cm−1] ε00 [M−1 cm−1] f ΦF 4 a 754 773 320 205 000 0.83 0.59 4 a′ 819 831 180 256 000 0.76 0.53 Compound 4 a has a rigid planar chromophore, whereas 4 a′ 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 4 a′ versus f=0.83 for 4 a). The smaller half-width of the 00 band13 indicates that the asymmetrical torsional potential for 4 a′ on the side of the small torsional angle is steeper than the symmetrical torsional potential of 4 a. The bathochromic shift of 4 a to 4 a′ is the expected consequence of the different σ-inductive effects of BF2 and BPh2 on the chromophoric system. The room-temperature fluorescence quantum yields of 0.59 and 0.53 for 4 a and 4 a′, respectively (with an error of less than 10 %), in chloroform at emission wavelengths () of 773 nm and 831 nm, respectively, are, to our knowledge, far higher than for any other known fluorophore. In contrast to the naphthalenediimides14 and the rylenediimides,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 similar. Thus, the intensities of the vibrational transitions are strongly shifted towards the 00 transition. This effect combined with the appearance of the 00 band above 800 nm in the spectrum results in 4 a′ 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 4 a′ in methylcyclohexane (Figure 3). Selective NIR absorbers are of technical interest for NIR laser welding of transparent polymers.16 Absorption (—) and fluorescence (••••) of 4 a′ in methylcyclohexane at room temperature. 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. The fluorescence quantum yields were determined on diluted solutions (c<2×10−6 M) with a home-made spectrometer.7 A 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 (ΦF=0.60 in CH2Cl2).17 General procedure for the synthesis of NIR dyes 3: POCl3 (8 mmol) was added to a mixture of DPP 1 (1 mmol) and heteroarylacetonitrile 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 solid was separated by filtration, washed with acetone, and purified by column chromatography. 3 a: Column chromatography (silica gel/CHCl3) afforded 3 a as a green crystalline powder in 33 % yield. 1H NMR (400 MHz, CDCl3): δ=14.78 (br s, 2 H; N-H), 7.96 (d, 3J=8.8 Hz, 2 H; H-4′), 7.77 (m, 8 H; AA′, H-7′, H-8′), 7.65 (d, 3J=8.8 Hz, 2 H; H-3′), 7.63 (s, 2 H; H-5′), 7.14 (m, 4 H; XX′), 4.10 (t, 3J=6.6 Hz, 4 H; OCH2), 1.86 (m, 4 H; OCH2CH2), 1.6–1.3 (m, 38 H; alkyl, tert-butyl), 0.92 ppm (t, 3J=6,8 Hz, 6 H; 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): ν00=13 700 cm−1 (λ00=731 nm); ε00=118 000 M−1 cm−1, f=0.71. Elemental analysis calcd (%) for C64H72N6O2 [M=957.30 g mol−1]: C 80.30, H 7.58, N 8.78; found: C 80.36, H 7.67, N 8.37. 4 a: BF3⋅Et2O (0.98 mL, 1.77 g, 7.38 mmol) was added to a solution of 3 a (500 mg, 0.52 mmol) in ortho-dichlorobenzene (15 mL) at reflux in a nitrogen atmosphere. After 10 min, Hünig's 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 4 a in 76 % yield (420 mg, 0.40 mmol) as a green powder. 1H NMR (400 MHz, C2D2Cl4): δ=8.42 (m, 2 H; H-8′), 8.14 (d, 3J=9.3 Hz, 2 H; H-4′), 7.74 (dd, 3J=9.5 Hz, 4J=2.2 Hz, 2 H; H-7′), 7.72 (d, 4 H; AA′), 7.66 (m, 4 H; H-3′,H-5′), 7.06 (m, 4 H; XX′), 4.08 (t, 3J=6.6 Hz, 4 H; OCH2), 1.85 (m, 4 H; OCH2CH2), 1.53 (m, 4 H; O(CH2)2CH2), 1.45–1.2 (br s, 16 H; alkyl), 1.36 (s, 18 H; tert-butyl), 0.91 ppm (t, 6 H; CH3). MALDI-MS: m/z calcd: 1053.6 [M+H]+, 1075.6 [M+Na]+; found: 1053.1, 1076.1; UV/Vis/NIR (CHCl3): =13 260 cm−1 (=754 nm), ε00=205 000 M−1 cm−1, f=0.83; =12 940 cm−1 (=773 nm), ΦF=0.59. Elemental analysis calcd (%) for C64H70B2F4N6O2 [M=1052.90 g mol−1]: C 73.01, H 6.70, N 7.98; found: C 72.51, H 6.95, N 7.83. 4 a′: A mixture of 3 a (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 4 a′ as a yellow solid in 56 % yield (189 mg, 0.147 mmol). 1H NMR (400 MHz, C2D2Cl4): δ=8.18 (d, 3J=9.5 Hz, 2 H; H-8′), 7.83 (d, 3J=9.3 Hz, 2 H; H-4′), 7.58 (d, 3J=9.3 Hz, 2 H; H-3′), 7.34 (m, 10 H; H-5′, m-phenyl), 7.15 (dd, 3J=9.5 Hz, 4J=2.2 Hz, 2 H; H-7′), 7.10 (m, 12 H; o- ,p-phenyl), 6.52 (d, 4 H; AA′), 6.06 (m, 4 H; XX′), 4.02 (t, J=6.6 Hz, 4 H; OCH2), 1.86 (m, 4 H; OCH2CH2), 1.53 (m, 4 H; O(CH2)2CH2), 1.48–1.25 (br s, 16 H; alkyl), 1.16 (s, 18 H; tert-butyl), 0.93 ppm (m, 6 H; CH3). MALDI-MS: m/z calcd: 1285.7 [M+H], found: 1285.5; UV/Vis/NIR (CHCl3): =12 210 cm−1 (=821 nm), ε00=256 000 M−1 cm−1, f=0.76; νλ=12 030 cm−1 (=831 nm), ΦF=0.53. Elemental analysis calcd (%) for C88H90B2N6O2 [M=1285.32 g mol−1]: C 82.23, H 7.06, N 6.54; found: C 81.59, H 7.11, N 6.49. Dedicated to Professor Friedrich Dörr on the occasion of his 85th birthday Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z604763_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.