Benzene-fused bis(acenaphthoBODIPY)s, stable near-infrared-selective dyes

Benzene-fused bis(acenaphthoBODIPY)s prepared by retro-Diels–Alder reaction of bicyclo[2.2.2]octadiene-fused precursors showed strong absorption bands in the near-infrared region and very weak absorptions in the visible region.


Introduction
Biological and clinical applications of near-infrared (NIR) dyes is an area of great interest because the development of lasergenerating techniques enables us to use light of a certain wavelength more easily than before. In the medical elds, NIR light in the so-called optical window region plays a key role in photodynamic therapy for cancer treatment 1 and imaging of mammalian living cells in deep tissue 2 due to its permeability. In industry, organic NIR dyes are a key material for improving the efficiency of organic solar cells; 3 fair mounts of solar energy reach the earth's surface as NIR light. Inorganic NIR dyes are used as cutoff lters for detectors and as ink for NIR-reading machines. 4 NIR dyes that have no or little absorption in the visible region can be used as invisible NIR ink for humans, whereas panchromatic NIR dyes are ideal for solar-cell application. Many kinds of organic compounds that are used as NIR dyes usually have large p chromophores such as linear cyanine, 5 cyclic oligopyrroles including porphyrin and phthalocyanine, 6 squaraine, 7 rhodamine 8 and boron dipyrromethene (BODIPY); 9 however, absorption maxima of their pristine chromophores, except for cyclo[n]pyrroles, 10 do not reach the NIR region. Expansion of the core chromophores or efficient introduction of substituents is therefore essential for dyes with NIR absorption. We have approached this subject by fusion and expansion of chromophores. We reported that p-expanded porphyrins, 11 p-expanded BODIPYs, 12 p-fused oligoporphyrins 13 and benzene-fused bisBODIPYs 14 have strong absorption maxima in the far-red-to-NIR region. Especially in the case of benzenefused bis(benzoBODIPY)s 1 (Fig. 1), only the absorption maxima with the lowest energy occurred in the NIR region (775 to 903 nm), depending on the substituents. Both panchromatic BODIPYs for solar-cell application 15 and NIR-selective BODIPYs for bio-imaging application 9 have attracted much attention. Our fusion method for the BODIPY chromophore in the proper direction was proven to be effective for the elongation of absorption maxima into the NIR region with keeping transparency in the visible region. Similar to the p-expanded porphyrins 11 and BODIPYs, 12 however, bis(benzoBODIPY)s 1a and 1b without electron-withdrawing groups was proven to be unstable. Although introduction of electron-withdrawing groups such as ethoxycarbonyl and cyano groups stabilized the benzene-fused bis(benzoBODIPY) chromophore, the absorption maxima also tended to shi bathochromically. In order to tune absorption maxima of the NIR dyes, stable NIR p systems based on the BODIPY chromophore are necessary. Lash and coworkers reported that the absorption maxima of porphyrin Q bands are remarkably bathochromically shied in the NIR region by fusion of acenaphtho moieties to b positions of porphyrins. 16 We have also reported the effective elongation of absorption maxima in the case of BODIPYs 17 and cyclo [n]pyrroles. 18 This acenaphtho-fusion method was successfully applied to the preparation of bisBODIPYs with stable NIR chromophores.

Results and discussion
Our strategy for the preparation of acenaphtho-fused bisBODI-PYs (bisANBODIPYs) was based on the retro-Diels-Alder protocol, 19 which was successfully used in the preparation of highly at, insoluble compounds. This protocol enabled us to treat the intermediary compounds in the synthetic scheme without worrying about their solubility, and it was quite successful when the nal targeted compounds did not need to be characterized. In most cases, the solubility of the targeted compounds was required for their full characterization. In order to increase the solubility of the target acenaphtho derivatives in common organic solvents, two tert-butyl groups were introduced into acenaphthylene, and the resulting compound was converted to ethylacenaphtho [1,2-c]pyrrole-1-carboxylate 2. 18 Formylation of 2 with the Vilsmeier reagent gave a-formylated compound 3a in 98% yield (Scheme 1). The formyl group of 3a was converted to an acetoxymethyl group by reduction with NaBH 4 followed by acetylation with Ac 2 O and 4-dimethylaminopyridine (DMAP). Compound 4a was obtained in 92% yield in two steps.
We have reported that the fusion geometry of two BODIPY chromophores is very important for the elongation of absorption maxima with the lowest energy: fusion of the chromophores in the anti manner was found to be more effective than the was syn manner. 14 Therefore, we chose bicyclo [2.2.2] octadiene-fused (BCOD-fused) dipyrroles 5 (ref. 20) as the starting material. Double condensation of 4a with 5 under acidic conditions gave BCOD-fused bis(dipyrromethene)s 6a in 66% yield (Scheme 2). Four ester groups of 6a were transformed to four methyl groups by rigorous reduction with LiAlH 4 in reuxing THF in 37% yield. The rather unstable tetramethyl derivative was then converted to BCOD-fused bis(boron acenaphthodipyrromethene) (BCOD-bisANBODIPY) 7a in 27% yield by treatment with 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), (i-Pr) 2 EtN and BF 3 $OEt 2 . The thermogravimetric experiment on precursor 7a showed that evolution of ethylene gas started from ca. 200 C and ceased at 250 C (temperature increase rate of 10 C min À1 ). The starting reddish purple color of 7a turned black. Thus, the bulk thermal conversion of 7a was performed at 200 C for 2 h in vacuo. The obtained material was poorly soluble and no purication was possible, although the ultraviolet-visible-NIR (UV-vis-NIR) spectrum and matrixassisted laser-ionization time-of-ight (MALDI-TOF) MS of the material indicated the formation of benzene-fused bisANBO-DIPY (B-bisANBODIPY) 10a (Scheme 2).
We next examined the use of solubilizing substituents such as 3,5-di-tert-butylphenyl and 4-hexyloxyphenyl groups in order to characterize the B-bisANBODIPYs. Thus, acetoxy(aryl)methyl derivatives 4b and 4c were prepared (Scheme 1). Friedel-Cras acylation of 2 by the mixed anhydrides of 3,5-di-tert-butylbenzoic acid and 4-hexyloxybenzoic acid with triuoroacetic anhydride (TFAA) and triuoroacetic acid (TFA) afforded a-acylated compounds 3b and 3c in respective yields of 80 and 96%. 21 Reduction of the acyl groups of 3 with NaBH 4 followed by acetylation with Ac 2 O gave a-acetoxymethyl derivatives 4b and 4c in 69% and 65% yields, respectively. Treatment of 4b with 5 under acidic conditions afforded a diastereomeric mixture of BCOD-fused bis(dipyrromethane) 6b in 58% yield (Scheme 2). Bis(dipyrromethane) 6b was transformed into three types of BCOD-bisANBODIPYs: rst, bis(dipyrromethane) 6b was directly converted to BCOD-bisANBODIPY 8b with four ester groups in 70% yield by treatment with DDQ, N,N-diisopropylethylamine and BF 3 $OEt 2 . Second, four ester groups of 6b were transformed to four methyl groups by rigorous reduction with LiAlH 4 in reuxing THF. The rather unstable tetramethyl derivative was then converted to BCOD-bisANBODIPY 7b in 35% yield by treatment with DDQ, N,N-diisopropylethylamine and BF 3 $OEt 2 . Third, the four ester groups of 6b were removed by treatment with NaOH in ethylene glycol at 170 C. The unstable a-free derivative obtained was cyanated with chlorosulfonyl isocyanate (CSI) 22 and then transformed to BCOD-bisANBODIPY 9b with four cyano groups in 5% overall yield from 6b. Bis(dipyrromethane) 6c with two hexyloxyphenyl groups obtained from the reaction of 4c with 5 (75% yield) was converted to BCOD-bisANBODIPY 8c with four ester groups at 80% yield. The thermal treatment of 7b, 8b, 8c and 9b at 200 C for 2 h or at 250 C for 30 min in vacuo produced almost quantitative yields of B-bisANBODIPYs 10b, 11b, 11c and 12b, respectively (Scheme 2). Both thermal conditions gave similar results.
Electronic spectra of BODIPYs in CH 2 Cl 2 were recorded. Fig. 2 shows the UV-vis-NIR and uorescence spectra of BCOD-bisANBODIPY 7b and B-bisANBODIPY 10b as representative cases. The spectral shapes of other bisANBODIPYs are almost the same as those of 7b and 10b (see ESI †). The results are listed in Table 1. In the spectra of BCOD-bisANBODIPYs 7a, 7b, 8b and 8c, strong absorption bands with the lowest energy can be observed at ca. 625 nm, irrespective of substituent difference between tetramethyl and tetra(ethoxycarbonyl). On the other hand, the absorption band was shied by ca. 20 nm to 646 nm by substitution of four cyano groups. In the case of B-bisANBODIPYs, the absorption bands with the lowest energy shied by ca. 200 nm relative to those of the corresponding BCOD-bisANBODIPYs. The absorption maxima of 10a, 10b, 11b, 11c and 12b were observed at 828, 824, 835, 836 and 900 nm, respectively. In all cases, these large peaks were accompanied by smaller peaks with shorter wavelengths. In the acenaphtho series, differences in absorption maxima with the lowest energy between tetramethyl 10b, tetra(ethoxycarbonyl) 11b and tetracyano 12b were ca. 11 and 64 nm. Therefore, the spectrum of tetra(ethoxycarbonyl) 11b resembled that of tetramethyl 10b rather resembling that of tetracyano 14. In the benzo series 1a, 1b and 1c, the opposite tendency was reported. 14 The spectrum of tetra(ethoxycarbonyl) 1b resembled that of tetracyano 1c. The differences of the absorption maxima between 1a, 1b and 1c were 62 and 10 nm.
Next, we studied the structure of bisANBODIPYs. Fortunately, single crystals of BCOD-and B-bisANBODIPYs 7b, 8b, 10b, 11b, 11c and 12b were obtained by the solvent-vapor diffusion method: bisANBODIPYs were dissolved in chloroform or dichloromethane and placed under an atmosphere of a poor solvent such as methanol or acetonitrile. In the case of 11b and 12b were dry solvent sets used in order to avoid hydrolysis of a BF 2 unit (vide infra). The crystals obtained were subjected to Xray analysis. Ortep drawings of 8b and 11b are respectively illustrated in Fig. 5 and 6 as representative, and others are provided in the ESI. † All crystals except for those from 11c were proven to involve co-crystallized solvent molecules in a disordered fashion. B-bisANBODIPY 11c, however, underwent partial hydrolysis during recrystallization from an undried solvent system. The crystal was proven to consist of mono-BF 2 -removed 17 and 11c (17/11c ratio of ca. 3 : 1; Fig. 7 and S7 in ESI †). There might be fully-hydrolyzed bisdipyrrin 18 in the crystal. We could not determine the possibility by the X-ray analysis. When the solvent molecules were not properly modeled, the rest of the molecules were rened by the Platon Squeeze technique.
In the crystal structure of BCOD-bisANBODIPY 8b, one of the ester parts was disordered. Another ester carbonyl group was directed toward the BF 2 moiety of BODIPY, even though this conformation was thought to be disadvantageous because of the dipole-dipole interaction. Both ester groups were disordered in one BODIPY part of B-bisANBODIPYs 11c and 17. On the other hand, no disordered ester group was observed in the other BODIPY part, which consisted of 75% dipyrrin and 25% BODIPY. BCOD-bisANBODIPY 8b adopted the gable shape because of the BCOD skeleton and the dihedral angle between    This journal is © The Royal Society of Chemistry 2018 the mean planes of twelve BODIPY atoms (121.1(1) ; Table 3). Contrary to almost at structures of 10b and 12b (see Fig. S6 and S8 †), the mixtures of 11c and 17 adopted slightly waved conformation. The dihedral angle between the BODIPY mean planes was 9.64 (4) , and those between the mean planes and benzene moiety were 6.47(8) and 3.44 (7) . Dihedral angles between the ester and BODIPY planes are also listed in Table 3.
The values are rather large probably because of the steric effect of the acenaphtho moiety. This may be the reason for the differences in absorption mentioned earlier. Conjugation of the ester groups to the B-bisANBODIPY chromophore was thought to be poor. Thus, the HOMO and LUMO energy levels were not close enough. We monitored the UV-vis-NIR spectra of B-bisANBODIPYs 10a, 10b, 11b, 11c and 12b in order to test their stability (Fig. 8, S9 and S10 †). We reported a smooth decomposition pattern showing new strong absorption (614 nm) and emission (619 nm) peaks in the case of tetramethyl B-bis(benzoBODIPY) 1a (see Fig. S11 and S12 †). 14 The spectral feature was thought to be due to two benzoBODIPY chromophores, because strength of the absorption was similar to that of 1a. Moreover, the decomposition was suppressed by protection either from oxygen or light. Taking these facts into an account, singlet oxygen was thought to attack the center benzene moiety forming an endo-peroxide species, although decomposition of a BODIPY chromophore by singlet oxygen was reported to proceed by initial attack at its C 8 -C 8a bond forming a dioxetane species. 23 Contrary to the B-bis(benzoBODIPY)s 1, 14 tetracyano derivative 12b was revealed to decompose faster than the other derivatives. As Fig. 8c shows, the absorption spectra of tetracyano derivative 12b only decreased in intensity and no obvious other peak emerged. On the other hand, a new absorption peak slowly appeared at 650 nm in the case of tetramethyl derivative 10a, similarly to the case of B-bis(benzoBODIPY). In the cases of tetra(ethoxycarbonyl) derivatives 11b and 11c, the peaks at 745 nm accompanying with the longest-wavelength absorption maxima (835 and 836 nm) increased (Fig. 8a) and then decreased. Aer 84 days, the longest-wavelength absorptions completely disappeared and the new large absorptions   appeared at 666 and 620 nm (Fig. 8b). The absorption maxima at 745 and 666 nm were determined to be due to mono-BF 2 derivative 17 and bisdipyrrin 18, respectively, by diagnosis of the X-ray analysis (vide ante) and mass spectroscopies (Fig. S14 †). This decomposition pattern of tetra(ethoxycarbonyl) derivatives was hydrolysis and was different from that of tetramethyl derivatives. As the single crystals of 12b were obtained from the anhydrous solvent system (vide ante), the rst decomposition step of 12b was also thought to be hydrolysis. Substitution of electron-withdrawing groups such as cyano and ethoxycarbonyl groups at 3-and 5-positions of 4-bora-3a,4adiaza-s-indacene skeleton made the BODIPY chromophore labile toward hydrolysis, although the pristine diuoro BODIPY was robust toward hydrolysis under neutral conditions. 24 Alkyl and/or aryl substituted BODIPYs was only hydrolyzed to dipyrrins under strongly acidic or basic conditions. 25 Next, B-bisANBODIPYs 10a, 10b, 11b, 11c and 12b were subjected to a cyclic voltammetry experiment (results are summarized in Table 4). In all cases, one reversible oxidation and two reversible reduction peaks were observed. The oxidation half-wave potentials (E 1/2 ) of 10b, 11b, 11c and 12b were 0.472, 0.922, 0.944 and 1.273 V, respectively. These values were sufficiently high for resisting oxidation by air. Therefore, the smooth decomposition observed with tetra(ethoxycarbonyl) and tetracyano derivatives could not be ascribed to oxidation. In the case of tetra(ethoxycarbonyl) derivatives 11b and 11c, the decomposition could be due to hydrolysis of the diuorodiazaboridine to dipyrrin moieties by moisture in the spectroscopic-grade dichloromethane. The spectrum aer four days was similar to that of the mother liquor obtained in the   case of single-crystal synthesis of 11c, and the amounts of 11b and 11c almost did not decrease in the dehydrated solvents. Moreover, mass peaks due to the corresponding monohydrolyzed products were observed in the MS spectra of 11b, 11c and 12b. Although the decomposition pathway of 12b was ambiguous at that time, we believed that the rst stage of decomposition was hydrolysis.

Conclusion
We prepared B-bisANBODIPYs with very strong NIR absorption. The strength of other absorptions in the visible region was less than 15% relative to that of the corresponding absorption maximum at the longest wavelength. Although B-bisANBODIPYs with electron-withdrawing groups were rather labile toward hydrolysis, they proved to be robust toward oxidation by air. Therefore, B-bisANBODIPYs are promising candidates for stable NIR-selective dyes in non-aqueous media such as resins.

General
Melting points were measured on a Büchi M-565 apparatus and were uncorrected. NMR spectra were obtained with an AL-400 spectrometer at ambient temperature by using CDCl 3 as a solvent and tetramethylsilane as an internal standard for 1 H and 13 C, unless otherwise indicated. IR spectra were obtained on a Thermo Scientic Nicolet iS5 FT-IR spectrometer with an iD5 ATR diamond plate. UV-vis-NIR and uorescence spectra were recorded on Jasco V-570 and Hitachi F-4500 spectrophotometers, respectively. Absolute quantum yields were measured with a Hamamatsu Photonics C 9920-03G spectrophotometer. Mass spectra were obtained either with a JEOL JMS-700 (EI, 70 eV; FAB + , p-nitrobenzyl alcohol) or with a JEOL JMS-S3000 (MALDI-TOF). Elemental analyses were performed with a Yanaco MT-5 elemental analyzer at ADRES, Ehime University. Preparative GPC using LC-911 or LC-916 with Jaigel-1H and 2H was performed by Japan Analytical Industry Ltd. Co. Dehydrated solvents were purchased from Kanto Chemical Co. and used without further purication. Commercially available materials were used without further purication.

BCOD-bisANBODIPY 7a
To a stirred solution of 6a (0.173 g, 0.157 mmol) in dry THF (10 mL), LiAlH 4 (0.179 g, 4.72 mmol) was added at rt in the dark. The mixture was then heated to reux for 3 h. Aer cooling to 0 C, the reaction was quenched by slow addition of an aqueous saturated sodium tartrate. The mixture was ltered through a Celite pad, which was washed with EtOAc. The ltrate was extracted with EtOAc. The combined organic phase was washed with water and brine, dried over anhydrous Na 2 SO 4 , and concentrated in vacuo. The residual material was ltered with CH 2 Cl 2 through a short silica-gel column, and the ltrate was concentrated in vacuo to give 0.051 g (0.0585 mmol, 37%) of tetramethyl bis(dipyrromethane), which was used without further purication. The complexation with BF 2 was performed according to the general procedure to provide 0. BCOD-bisANBODIPY with four methyl and two 3,5-di-tertbutylphenyl group 7b The reduction of 6b (0.100 g, 0.090 mmol) with LiAlH 4 (0.170 g, 4.72 mmol) was carried out according to the procedure described above to afford 0.079 g of crude bis(dipyrromethane) with four methyl and two 3,5-di-tert-butylphenyl groups, which was used without further purication. Complexation with BF 2 was performed according to the general procedure to give 0.043 g (0.032 mmol, 35%) of 7b as a reddish purple powder:  9, 151.1, 151.0, 150.9, 149.8, 149.3, 148.3, 145.2, 141.4, 137.1, 136.3, 135.1, 133.0, 131.9, 131.2, 129.2, 128.9, 128.7, 128.2, 124.9, 124