Polybrominated BOPHY Dyes: Synthesis ... - ACS Publications

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Cite This: J. Org. Chem. 2018, 83, 1134−1145

Polybrominated BOPHY Dyes: Synthesis, Reactivity, and Properties Xiaokang Lv, Tingting Li, Qinghua Wu, Changjiang Yu,* Lijuan Jiao, and Erhong Hao* The Key Laboratory of Functional Molecular Solids, Ministry of Education, Anhui Laboratory of Molecule-Based Materials (State Key Laboratory Cultivation Base), School of Chemistry and Materials Science, Anhui Normal University, Wuhu 241000, China S Supporting Information *

ABSTRACT: A series of mono- to hexabrominated BOPHY dyes have been regioselectively synthesized in 41−96% yields from bromination of parent bis(difluoroboron)-1,2-bis((1H-pyrrol-2-yl)methylene)hydrazine (BOPHY), bromination of hydrazinelinked bispyrrole intermediate, or brominated 2-formylpyrrole precursors in moderate to excellent yields. The reactivities of these polybrominated BOPHY dyes were further studied via regioselective nucleophilic substitution or Suzuki/Stille cross-coupling reactions from which a series of 5- or 5,5′-substituted BOPHYs with amine, pyrrole, thiophene, and phenyl groups were obtained in moderate to high yields of 37−94%. The regioselectivities of both the bromination and nucleophilic substitution reaction, and these resultant BOPHY dyes, are confirmed by NMR, HRMS, and crystal structures. The spectroscopic properties of these resultant BOPHYs were studied, and most of them showed strong absorbance and bright fluorescence with maximum wavelengths centered at between the range of 430 and 660 nm. Their absorption and emission spectra were red-shifted for each bromine atom incorporated. The positions in which bromines or substituents are attached modulate the photophysical properties of the resulting BOPHY dyes.

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INTRODUCTION Small organic fluorescent dyes have attracted ongoing attention because of their diverse applications in biomedical, materials, and related fields.1 The development of simple and low molecular weight dyes that can be further modified is thus of great interest. Among the synthetic fluorophores studied, boron complexes of π-conjugated chelates often have very promising features, such as high quantum yields, fine-tuned absorption/ emission wavelengths, and good photostability.2,3 For example, extensive research on 4,4′-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) has been received because of its excellent photophysical properties and high photostability.4−6 Recently, a BF2-complexed hydrazine-Schiff base-linked bispyrrole, bis(difluoroboron)-1,2-bis((1H-pyrrol-2-yl)methylene)hydrazine (BOPHY, Figure 1), has been developed as a novel small organic fluorescent dye.7,8 This new fluorophore has excellent spectroscopic properties, including high quantum yields of fluorescence, high molar extinction coefficients, highly tunable absorption/emission profiles, and excellent photostability. In addition, BOPHY dyes have larger Stokes shifts and higher solid-state fluorescence than those of classical BODIPY dyes, which generally suffer from small Stokes shifts2a,6a,b and relatively weak solid-state fluorescence. Because of their excellent photophysical properties and extremely easy syntheses from 2-formylpyrrole and hydrazine, © 2018 American Chemical Society

Figure 1. Chemical structures of BOPHY and its postfunctionalized derivatives.

BOPHY dyes have quickly found applications7−17 such as energy-transfer cascades,11 cell imaging,12 photosensitizers for solar cells13 and photodynamic therapy,14,15 and fluorescence sensors16,17 in the last three years. As a result, synthetic modifications that can modulate or improve the photophysical and photochemical properties of BOPHY dyes to achieve the desired fluorophores are needed to further spread their application. Received: September 24, 2017 Published: January 9, 2018 1134

DOI: 10.1021/acs.joc.7b02415 J. Org. Chem. 2018, 83, 1134−1145

Article

The Journal of Organic Chemistry

potential and the natural population analysis (NPA) of the C2 and Ci geometries are very similar to each other. The charge distribution map indicates that the parent BOPHY chromophore is most susceptible to electrophilic attack at the 4- and 4′-positions with the highest negative charge of −0.317 (Figure 2, Tables S1 and S2). These data are consistent with the 1H NMR spectroscopy results (Figure S1) in which protons at the 4,4′-position of BOPHY showed upfield signal at 6.65 ppm (δ = 7.32, 7.74, and 8.26 ppm in CDCl3 for the protons attached at the 3,3′-, 5,5′-, and 6,6’-positions, respectively). Thus, by carefully controlling the reaction conditions, it may be possible to achieve regioselective 4-bromination of BOPHY. Syntheses of Brominated BOPHYs. To test these hypotheses, we have investigated the bromination reactions of BOPHY using different amounts of bromine over different reaction times. The products obtained in the bromination reactions are shown in Scheme 1 from which the mono-, di-,

Until now, there have not been many synthetic alterations of BOPHY dyes. Reported functionalizations of BOPHY, such as halogenation,10−12,14 Knoevenagel condensation,7c,8a,11,13 and formylation,17 have been developed (BOPHY A−C, Figure 1). In these reactions, 3,3′,5,5′-tetramethyl-substituted BOPHY was used, and no regioselectivity was involved due to the existence of blocking methyl groups. Modification from the starting pyrroles provides another strategy to achieve functionalized BOPHYs from which ring-fused, red-shifted BOPHYs and 4,4′-dihalo-substituted BOPHYs8b,9−12 were synthesized. Among those, halogenated BOPHYs are highly versatile starting materials for installing further functionalities to achieve the desired dyes. For example, further derivations of these 4,4′diiodoBOPHYs based on the Sonogashira and Suzuki coupling reactions have been explored by several groups.10,11 However, there is still no definitive research on the regioselectivity in these reactions for the parent BOPHY. Inspired by our recent work on regioselective bromination of BODIPYs and regioselective nucleophilic substitution of polybrominated BODIPYs,18 herein we report the regioselective synthesis of a series of newly brominated BOPHYs bearing 1−6 bromine atoms at different positions on the parent BOPHY (Figure 2, 1−6) and the subsequent application of

Scheme 1. Regioselective Bromination of BOPHY

tri-, tetra-, penta-, and hexabrominated derivatives were regioselectively synthesized by direct bromination of the unsubstituted BOPHY with different amounts of liquid bromine. In contrast to the bromination of BODIPY, BOPHY showed lower reactivity toward bromine. Treatment of BOPHY with 1 equiv of bromine in dichloromethane at room temperature gave the mixture of unreacted BOPHY and monobromoBOPHY 1. 1 H NMR of 1 only showed one proton signal at 6.75 ppm in d6DMSO. The calculated 1H NMR (Figures S2 and S3) are in good agreement with the experimental results, indicating the proposed regioselective 4-bromination of BOPHY. We found that 3 equiv of bromine was needed to completely consume the BOPHY and gave monobromoBOPHY 1 in 60% yield together with small amount of dibromoBOPHY. Increasing the amount of liquid bromine to 6 equiv, 4,4′-dibromoBOPHY 2a became the main product with an isolated yield of 54%. The symmetrical structure of 2a was confirmed by the three sets of proton signals in its H1 NMR spectrum, and the signal of two protons at 4,4′-positions disappeared.

Figure 2. Natural population analysis (NPA) charges of carbon atoms in BOPHY (C2 symmetry), electrostatic potential map (ESP) of BOPHY, and chemicals structures of brominated BOPHYs 1−6.

these resultant bromoBOPHYs for regioselective nucleophilic substitution and Palladium-catalyzed coupling reactions. The spectroscopic properties of these resultant BOPHYs were studied.

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RESULTS AND DISCUSSION Theoretical Study. To better understand the regioselectivity of the electrophilic bromination of the BOPHY, which would prefer to occur at the least positive charged positions of the BOPHY core, we first conducted density functional theory (DFT) calculations on BOPHY. DFT calculations suggested C2 symmetry (both boron atoms deviating from planarity toward one side) and Ci symmetry (boron atoms deviating from planarity toward different sides) structures are the stationary points on the potential energy surfaces.7a,19 The electrostatic 1135


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The Journal of Organic Chemistry Alternatively, because the corresponding 4-bromo-2-formylpyrrole P1 was readily available by regioselective bromination of 2-formylpyrrole, 4,4′-dibromoBOPHY 2a was efficiently synthesized by the condensation between P1 and hydrazine followed by BF2 complexation with boron trifluoride ether in the presence of triethylamine (Scheme 2).

Scheme 3. Syntheses of Brominated BOPHYs from Regioselective Bromination of HBP

Scheme 2. Syntheses of Brominated BOPHYs from Formylpyrroles

3). Bromine instead of NBS for this bromination gave similar results. Attempts to synthesize monobrominated HBP by carefully controlling the reaction temperature and amount of bromine failed. These reactions always gave mixtures of starting HBP, monobrominated HBP, and dibrominated HBP. Separation of these products was very difficult. Unlike the bromination of BOPHY, HBP is highly reactive toward bromine. The desired penta- and hexabrominated hydrazine-linked bispyrroles H5 and H6 were regioselectively obtained in 87% and 92% yields using only 10 and 20 equiv of bromine, respectively. Brominated BOPHYs 2b, 5, and 6 were synthesized after boron complexation in toluene. The structures of all the intermediates and the brominated BOPHYs were fully characterized with 1H NMR, 13C NMR, as well as highresolution mass spectroscopies. Selective Functionalization. The easily obtained polybrominated BOPHY derivatives are possible valuable synthetic precursors for selective functionalization allowing the development of a variety of symmetric and asymmetric BOPHY compounds that are difficult to obtain by alternative procedures. It is well-known that 3,5-dihalogenated BODIPY derivatives can undergo SNAr reactions by a wide range of nucleophiles. Furthermore, the reaction is stepwise, and the reaction conditions can be adjusted to obtain mono-, di-, or even tetra-substituted products. Inspired by these works on BODIPYs,20−25 we have carried out SNAr reactions of polybrominated BOPHYs with n-butylamine, 4-tert-butylaniline, diethylamine, and pyrrole. First, we studied the reactivities of polybrominated BOPHYs with n-butylamine by nucleophilic substitution reactions. 5,5′Dibrominated BOPHY 2b and 6 equiv of n-butylamine in DCE at 70 °C gave mainly monosubstituted BOPHY 7 in 86% yield (Scheme 4). Extending the reaction time, increasing the amount of n-butylamine, and increasing the reaction temperature, the disubstituted product was still not isolated in a decent amount. However, tetrabromoBOPHY 4 with different amounts of n-butylamine gave monosubstituted BOPHY 8 and disubstituted BOPHY 9 in 83 and 85% yields, respectively (Scheme 4), which indicated that tetrabromo 4 has higher reactivity than that of dibromo 2b. Similarly, hexabrominated BOPHY 6 was combined with 3 equiv of n-butylamine, affording monosubstituted BOPHY 10

Further increasing the amount of bromine to 12 equiv, the bromination reaction afforded a major product that was isolated to be tribromoBOPHY 3 in 62% yield (Scheme 1) from the 1H NMR spectrum, which showed two proton signals at 7.33−7.31 (3,3′-positions) and one at 7.67 ppm (5-position). Interestingly, 30 equiv of bromine exclusively afforded one product, which was confirmed to be 4,4′,5,5′-tetrabromoBOPHY 4 in 90% yield. The highly symmetrical structure was evident from its NMR signals in DMSO-d6. The third and fourth brominated positions in 1H NMR spectrum showed the difference with the calculated results of electrostatic potential map and NPA distributions on BOPHY, which is similar to that of BODIPY, and the regiochemistry of 4 was further confirmed by the condensation between known 4,5-dibromo-2-formylpyrrole P2 and hydrazine followed by BF2 complexation (Scheme 2). It is worth noting that the third and fourth brominated positions differed from the calculated results, where the 3- and 3′positions of the parent BOPHY chromophore have higher negative charge than those of the 5- and 5′-positions (Figure 2). However, similar inconsistency was observed during the halogenation of BODIPY dyes.18,19 The further bromination at 3,3′-positions of BOPHY 4 required a large excess amount (160 equiv) of bromine and exclusively gave pentabromoBOPHY 5 in 91% yield (Scheme 1). HexabromoBOPHY 6 was obtained in 93% yield with 300 equiv of bromine, and no further bromination product was obtained. Considering the large amount of bromine used for the direct bromination of BOPHY, especially for pentabromoBOPHY 5 and hexabromoBOPHY 6, we then investigated the bromination of hydrazine-linked bispyrrole (HBP), the synthetic precursor for BOPHY (Scheme 3). Unlike the dipyrrin for the synthesis of BODIPY, HBP is stable and suitable for functionalization. Indeed, Ziessel and co-workers recently briefly reported the synthesis of 5,5′-dibromoBOPHY 2b from HBP in THF in a one-pot reaction. In this bromination of HBP, the regioselectivity was different from the bromination of BOPHY and the bromination of 2-formylpyrrole. With slight modification, we isolated the dibrominated H2b in 89% yield using 2.1 equiv of NBS in ethyl acetate (Scheme 1136


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Scheme 4. Regioselective Nucleophilic Substitution of BromoBOPHYs with n-Butylamine in 1,2-Dichloroethane (DCE)

moBOPHY 6 at the meso-position, which may have higher activity than that of the 5-position. Further attempts to prepare di-substituted products from 6 failed. Next, a less reactive nucleophile 4-tert-butylaniline was attempted to react with these brominated BOPHYs (Scheme 5). This reaction between hexabrominated BOPHY 6 and 4tert-butylaniline gave mainly monosubstituted BOPHY 12 in 73% yield, whereas monosubstituted BOPHY 15 was obtained in 41% yield from the reaction of 2b and 4-tert-butylaniline (Scheme 5). The corresponding disubstituted products were not obtained in these reaction conditions. Similarly, hexabrominated 6 reacted with pyrrole in refluxing toluene also only gave monopyrrole-substituted BOPHY 13 in 37% yield (Scheme 5). Furthermore, unsymmetrical derivative 14 was obtained in 78% yield in one pot by first reaction with 4-tert-butylaniline and subsequent reaction with diethylamine from hexabromoBOPHY 6 (Scheme 5). The structure of 14 was confirmed by the X-ray structure (Figure 4). In this case, the high nucleophilicity of secondary amine (diethylamine) allows the second SNAr reaction. Finally, although 5,5′-dibromoBOPHY 2b has been reported to be unreactive toward metal-catalyzed reactions,11 we found

in 93% yield. However, while increasing the amount of nbutylamine, the reaction unexpectedly gave only one product 11 in 94% yield. The reaction between monosubstituted BOPHY 10 and excess n-butylamine also gave compound 11 instead of the expected disubstituted BOPHY derivative. The X-ray structure of 11 (Figure 3) indicated that the

Figure 3. Top (a, c) and side (b, d) views of the X-ray structure of 10 (a) and 11 (c). C, light gray; N, blue; B, yellow; F, bright green; Br, dark yellow. All hydrogen atoms are omitted for clarity.

hexabrominated BOPHY core was broken. It might be reasoned that n-butylamine regioselectively attacked hexabro-

Scheme 5. Syntheses of BOPHYs 12−15 through Regioselective Nucleophilic Substitution of BromoBOPHYs

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Figure 4. Top (a) and side (b) views of the X-ray structure of 14. C, light gray; N, blue; B, yellow; F, bright green; Br, dark yellow. All hydrogen atoms are omitted for clarity.

Figure 5. Top (a, c) and side (b, d) views of the X-ray structure of 16 (a) and 17 (c). C, gray; N, blue; B, yellow; F, bright green; S, green. All hydrogen atoms are omitted for clarity.

2b was successful toward Suzuki and Stille reactions (Scheme 6). The usual Suzuki coupling reaction conditions23−27 were used to obtain 4-dimethylaminobenzene-substituted BOPHY 16 in 83% yield. Similarly, the Stille coupling reaction afforded thiophene-substituted BOPHY 17 in 86% yield. The structures of both 16 and 17 were confirmed by X-ray structure analysis (Figure 5). X-ray Structure Analysis. The crystals of 10, 11, 14, 16, and 17 suitable for X-ray analysis were obtained from slow diffusion of hexane into dichloromethane at room temperature. Their ortep polts are given in Figures S4 and S5. Selected geometrical parameters are summarized in Tables S3−S5. The crystal structure of amine-substituted BOPHY 10 shows the usual planar BOPHY core of two pyrrole units at the periphery and two BF2-containing six-membered rings in the center (Figure 3), whereas for extended BOPHYs 16 and 17, the additioal aryl and thiophene rings at the 5,5′-positions are also coplanar with the BOPHY core. The dihedral angles between the BOPHY core and the phenyl or thiophene ring in 16 and 17 were observed to be less than 9.0° (Figure 5). The dihedral angle between the pyrrole ring and the neighbor BF2containing six-membered ring in 11 is 2.9°, indicating an almost planar conformation of half BOPHY core (Figure 3d). These results indicate that no steric feature of the amino substituents causes structural irregularities. Extended packing forces and structural motifs that exist in the solid state can account for the small dihedral angles noted for these dyes. In contrast, 5,5′-diamino-substituted BOPHY 14 showed a highly twisted conformation of the BOPHY core in solid state (Figure 4) with dihedral angles of 33.2° between two pyrrolic rings and 26.3° between two BF2-containing six-membered rings, a serious deviation from the previously largely planar arrangements. Further analysis of 14 illustrates that this dihedral angle generates the formation of a “boat” conformation of the BOPHY core. This behavior demonstrates the significant steric hindrance introduced by the two aminosubstituted groups at the 5,5′-positions. Such significant distortion that breaks the planarity of the BOPHY core has not been observed previously. Spectroscopic Properties. UV−vis and fluorescence spectra of all of the synthesized BOPHYs were examined in dichloromethane as shown in Figures 6−8 and Figures S6−S8.

Their photophysical properties are summarized in Table 1. Similar to the absorption and emission maximum of the parent BOPHY, each dye exhibited a strong absorption band with a shoulder in the region of 430−470 nm. The emission spectra of 1−6 are also similar to those of the parent BOPHY, displaying emission maxima in the range of 484−513 nm with a relatively large Stokes shift around 50 nm (Table 1). Similar to previously reported BOPHY derivatives,7−18 most of these BOPHY dyes exhibit the double absorption and emission maxima in their absorption and emission spectra. For example, 1 exhibits the double absorption and emission maxima at 433, 451 nm and at 484, 508 nm, respectively. A similar phenomenon was observed for other dyes such as BOPHYs 2−6. The double absorption bands observed in the visible range could be attributed by HOMO to LUMO excitation, and the splitting of the strong bands belongs to a vibronic progression of the same excited state.7a Furthermore, the splitted high- and low-energy emission bands are possible 0−0 and 0−1 transitions of the same vibronic progression.10 The absorption and emission spectra of the brominated BOPHYs 1−6 were red-shifted for each bromine atom incorporated to the parent BOPHY (Figure 6) due to the electron-withdrawing effect of the electronegative bromine atom. All of these BOPHYs with bromine atoms are colorful to the eye, and most of them are brilliant upon 365 nm hand-held UV lamp irradiation conditions with fluorescence quantum yields ranging from 0.14 to 0.69. The bromination of the BOPHY core should induce a decrease in the fluorescence capacity due to the heavy atom effect, which increases the intersystem crossing probability.27 This influence is observed for the monoand dibromo derivatives 1 and 2a, respectively. Monobrominated 1 exhibited the two main absorption bands of 433 nm and a shoulder of 451 nm, which gave ∼10 nm red shifts in dichloromethane compared to those of the parent BOPHY. The fluorescence was also red-shifted with 16 nm and gave a decreased but moderate quantum yield (53%), where the parent BOPHY had a fluorescence quantum yield close to unity. Dibrominated BOPHY 2a exhibited the absorption maximum of 439 nm and a shoulder of 455 nm and the emission maximum of 488 nm with a fluorescence quantum yield of 20%. In contrast, dibrominated 2b with bromines at the

Scheme 6. Syntheses of BOPHYs 16 and 17 from 2b

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Figure 6. Overlaid absorption (a) and normalized fluorescence emission (b) spectra of BOPHYs B1−B6 and the parent BOPHY in dichloromethane at room temperature.

Table 1. Photophysical Properties of BOPHYs 1−17 in Dichloromethane at Room Temperature BOPHY BOPHY 1 2a 2b 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

b

λmax(nm) 423, 433, 439, 444, 450, 455, 462, 465, 487 497 510, 508 522(sh), 518 557 545 499 573 516,

442(sh) 451(sh) 455 467 467(sh) 477(sh) 485(sh) 488(sh)

540 552

538

λem(nm) 468, 484, 488, 492, 498, 505, 511, 513, 546, 558, 564, 568, 580 608 630 590 574 657 572,

495(sh) 508(sh) 515(sh) 522(sh) 530(sh) 537(sh) 541(sh) 546(sh) 576(sh) 587(sh) 594(sh) 601(sh)

613(sh)

lgε

Stokes shift (nm)

Φa

4.09 4.39 4.58 4.49 4.37 4.30 4.69 4.64 4.36 4.66 4.70 4.48 3.79 4.53 4.67 4.75 4.43 4.43 4.65

2273 2434 2287 2197 2142 2176 2076 2012 2219 2200 1877 2079 1916 2858 2080 1399 2618 2231 1928

1.00 0.53 0.20 0.59 0.51 0.61 0.65 0.69 0.02 0.01 0.33 0.02 0.24 0.004 0.05 0.14 0.03 0.17 0.57

The relative fluorescence quantum yields (Φ) in dichloromethane were calculated using the parent BOPHY (Φ = 1.0 in dichloromethane) as the standard for 1, 2a, and 2b (excitation at 430 nm), Fluorescein (Φ = 0.9 in 0.1 M NaOH) as reference for 3−15 (excitation at 450 nm for 3−6, 470 nm for 7−15), Cresyl Violet perchlorate (Φ = 0.54 in methanol) for 16 (excitation at 550 nm), and Rhodamine B (Φ = 0.49 in ethanol) for 17 (excitation at 500 nm). The standard errors are less than 10%. bPhotophysical properties of BOPHY were obtained from the literature of ref 8a. a

Figure 7. Overlaid absorption (a) and normalized fluorescence emission (b) spectra of BOPHYs 4, 8, 9, and 14 in dichloromethane at room temperature.

Surprisingly, further addition of bromine atoms to 2a leads to an increase in the fluorescence emission. The fluorescence quantum yields for polybrominated BOPHYs 3−6 are 0.51,

5,5′-positions gave the absorption maximum of 444 nm and a shoulder of 467 nm and the emission maximums of 491 nm with a much higher fluorescence quantum yield of 59%. 1139


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Figure 8. Overlaid absorption (a) and normalized fluorescence emission (b) spectra of the parent BOPHY, 13, 16, and 17 in dichloromethane at room temperature.

Figure 9. Absorption (a) and fluorescence (b) titration spectra of 16 (4.5 μM) in toluene with the addition of TFA excited at 470 nm.

methane, as shown in Table 1 and Figure 8. Similarly, thiophene-substituted 17 in dichloromethane shows a red shift of 120 nm of the absorption wavelength maximum and 98 nm in the emission wavelength maximum compared to the parent BOPHY. Both of these two dyes showed a gradual decrease of the fluorescence quantum yields with the increase in the polarity of the solvents (Figures S9 and S10). As summarized in Table S6, the fluorescence quantum yield for 16 was 0.39 in hexane, which was gradually reduced to 0.12 (in toluene), 0.09 (in dichloromethane), and 0.04 (in tetrahydrofuran). With the titration of trifluoroacetic acid (TFA, Figure 9) in toluene, a stepwise disappearance of the absorption bands at 590 nm with the simultaneous appearance of a new band at 495 nm was observed for 16 in toluene (Figure 9a). The sharp isosbestic point at 510 nm indicates the formation of a diprotonated species (16-2H+), which was confirmed by the NMR spectrum of 16 in the presence of an excess amount of TFA (Supporting Information). Similarly, a blue-shift of the emission band was also observed from 634 to 530 nm, and the fluorescence intensity was increased 8-fold (Figure 9b) due to inhibition of the intramolecular charge transfer (ICT) process from the dimethylamine (NMe2) moiety to the BOPHY chromophore. Very similar results were observed in acetonitrile/water solution of different pH values (Figure S12). It shows very low fluorescence in low acidic conditions, whereas it is highly fluorescent in acidic conditions. In particular, a change in the pH value from 4.0 to strongly acidic conditions of 2.0 results in a significant increase in fluorescence intensity. This result indicates that 16 could be used as a potential ratiometric “turn-on” pH probe pending further modification.

0.61, 0.65, and 0.69, respectively, much higher than the value of 0.20 for 2a (Table 1). In comparison with the unsubstituted BOPHY, the functionalized BOPHYs 7−15 exhibited obvious red shifts up to 134 and 162 nm in their absorption and emission spectra, respectively (Table 1). The gradual red-shift of the absorption and emission has been observed with the different numbers and kinds of amine substituents. As shown in Figure 7, monoaminesubstituted 8 absorbs/emits at 497/558 nm; diaminesubstituted 9 absorbs/emits at 540/565 nm, and 14 with the two different amine substitutions absorbs/emits at 545/590 nm. Among the dyes of 7−15, monopyrrole-substituted 13 gave the longest absorption and emission wavelength, exhibiting the absorption and emission maxima in dichloromethane centered at 557 and 630 nm (Figure 8), respectively. All the monoamine-substituted BOPHYs 7−8, 10, and 12 exhibited very weak fluorescence with fluorescence quantum yields in the range of 0.004−0.02. A similar phenomenon was observed for monopyrrole-substituted 13 with the fluorescence quantum yield of 0.04 in dichloromethane, which may be due to efficient intramolecular charge transfer due to the participation of amine or pyrrole. However, diamine-substituted BOPHYs 9 and 14 still give relatively bright red fluorescence with fluorescence quantum yields of 0.33 and 0.14, respectively. To our surprise, the unexpected broken compound 11 exhibited an emission wavelength maximum at 580 nm and fluorescence quantum yield of 0.24 in dichloromethane. As expected, after the installation of electron-donating substituents (NMe 2) at the p-phenyl position of the chromophore, obvious 150 and 189 nm bathochromic shifts were observed in the absorption and emission maximum of 16 with respect to those of the parent BOPHY in dichloro1140


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CONCLUSIONS We have demonstrated that it is possible to control the degree of bromination in the BOPHY core, which allows the synthesis of various mono-, di-, and polybrominated derivatives in moderate to excellent yields. Three different synthetic methods for brominated BOPHY derivatives have been developed, including regioselective bromination of parent BOPHY, regioselective bromination of af hydrazine-linked bispyrrole intermediate, or condensation of brominated 2-formylpyrrole precursors. These are the first examples of this type of dye with more than two halogen atoms in the BOPHY core. These polyhalogenated compounds can be valuable synthetic precursors for the selective incorporation of the desired functional groups in a specific position of the BOPHY and, in this study, were applied for further functionalization via nucleophilic substitution and metal-catalyzed coupling reactions from which a series of BOPHYs 7−17 were obtained in 37−94% yields. Nucleophilic substitutions occurred first at the 5,5′-positions, whereas the 4,4′-bromo sites were unreactive under these conditions. The regioselectivities of both the bromination and nucleophilic substitution reactions were confirmed by X-ray crystallography. Moreover, the position in which bromine or substituent is attached modulates the photophysical properties of the resulting BOPHY. Bromine atoms at 4- or 4′-positions lead to an important reduction of the fluorescence quantum yield owing to the heavy atom effect, which activates the intersystem crossing processes. Functionalized BOPHYs 7−17 with substituents at the 5,5′-positions exhibited obvious red-shifted spectra (up to 134 and 162 nm in their absorption and emission spectra, respectively). This regioselective stepwise bromination and its application for the regioselectively nucleophilic substitution reaction presented in this work provide another dimension for the regioselective functionalization of BOPHY derivatives.

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Φx = Φr ×

Fx n2 1 − 10−A r (λex ) × × x2 A ( ) − λ Fr nr 1 − 10 x ex

(1)

where the subscripts x and r refer respectively to our sample x and reference (standard) fluorophore r with known quantum yield Ar in a specific solvent, F stands for the spectrally corrected, integrated fluorescence spectra, A(λex) denotes the absorbance at the used excitation wavelength λex, and n represents the refractive index of the solvent (in principle at the average emission wavelength). Crystals of 10, 11, 14, 16, and 17 suitable for X-ray analysis were obtained by slow diffusion of hexane into their dichloromethane solutions. Diffraction was performed on a Bruker SMART APEXII CCD area detector diffractometer using graphite-monochromated Mo Kα radiation (λ = 0.71073 Å) at 293(2) K with φ and ω scan techniques. An empirical absorption correction was applied with the SADABS program.32 Using Olex2,33 the structures were solved by direct methods using the ShelXS structure solution program, and nonhydrogen atoms were anisotropically refined by full-matrix leastsquares calculations based on F2 using the ShelXL program.34 The hydrogen atom coordinates were calculated with SHELXTL using an appropriate riding model with varied thermal parameters. The residual electron densities were of no chemical significance. Crystals of 10 (CCDC 1565803), 11 (CCDC 1565803), 14 (CCDC 1565806), 16 (CCDC 1565805), and 17 (CCDC 1565801) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. Syntheses and Characterizations of Compounds. General Procedure for the Direct Bromination of BOPHY. To BOPHY (50 mg, 0.18 mmol) in 40 mL of dry CH2Cl2 was slowly added liquid bromine in dry CH2Cl2 (10 mL) over a period of 1 h. This reaction was tracked by TLC. The reaction mixture was washed with an aqueous solution of sodium thiosulfate and then with water. Organic layers were dried over Na2SO4 and evaporated to dryness under a vacuum. The crude residue was purified by column chromatography on silica gel using the mixture of petroleum ether and CH2Cl2 as eluent and was recrystallized in the mixture of hexane and CH2Cl2 to give the brominated BOPHY as a yellow or red powder. BOPHY 1 was obtained from BOPHY (50 mg, 0.18 mmol) and liquid bromine (0.028 mL, 0.54 mmol) in 60% yield (38 mg) as a yellow powder. Mp 141.5−143.1 °C; 1H NMR (300 MHz, DMSO-d6) δ 8.98 (s, 2H), 8.13 (s, 1H), 8.05 (s, 1H), 7.58−7.61 (m, 2H), 6.75 (s, 1H); 13C NMR (75 MHz, DMSO-d6) δ 146.5, 143.4, 143.2, 139.1, 136.3, 131.3, 129.1, 126.6, 125.2, 118.3. HRMS (ESI) calcd for C10H7BBrF2N4 [M − BF2]−: 310.9915, found 310.9905. BOPHY 2a was obtained from BOPHY (50 mg, 0.18 mmol) and liquid bromine (0.056 mL, 1.06 mmol) in 54% yield (43 mg) as a yellow powder. Mp 222.1−224.3 °C; 1H NMR (300 MHz, CDCl3) δ 8.21 (s, 2H), 7.67 (s, 2H), 7.30 (s, 2H); 13C NMR (125 MHz, CDCl3) δ 140.8, 137.6, 128.7, 124.5, 105.6. HRMS (APCI) calcd for C10H6B2Br2F3N4 [M − F]+: 418.9097, found 418.9091. BOPHY 3 was obtained from BOPHY (50 mg, 0.18 mmol) and liquid bromine (0.11 mL, 2.12 mmol) in 62% yield (56 mg) as a yellow powder. Mp 252.7−254.1 °C; 1H NMR (300 MHz, CDCl3) δ 8.22 (d, J = 2.4 Hz, 1H), 8.11 (d, J = 3.6 Hz, 1H), 7.67 (s, 1H), 7.33− 7.31 (m, 2H); 13C NMR (75 MHz, DMSO-d6) δ142.1, 132.5, 131.7, 130.2, 126.4, 125.9, 121.6, 121.2, 119.7, 116.0. HRMS (MALDI) calcd for C10H5B2Br3F4N4 [M]−: 517.8166, found 517.8179. BOPHY 4 was obtained from BOPHY (50 mg, 0.18 mmol) and liquid bromine (0.28 mL, 5.3 mmol) in 85% yield (89 mg) as a yellow powder. Mp 283.5−288.3 °C; 1H NMR (300 MHz, DMSO-d6) δ 8.97 (s, 2H), 7.74 (s, 2H); 13C NMR (125 MHz, DMSO-d6) δ 142.0, 130.3, 125.4, 124.8, 108.0. HRMS (APCI) calcd for C10H4B2Br4F3N4 [M − F]+: 574.7308, found 574.7286. BOPHY 5 was obtained from BOPHY (50 mg, 0.18 mmol) and liquid bromine (1.44 mL, 28.3 mmol) in 91% yield (108 mg) as a red powder. Mp 277.2−279.7 °C; 1H NMR (300 MHz, CDCl3) δ 8.19 (s, 1H), 8.10 (s, 1H), 7.36 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 138.8, 138.1, 129.7, 128.1, 126.5, 125.1, 124.5, 120.2, 112.9, 110.2.

EXPERIMENTAL SECTION

General Methods. Reagents and solvents were used as received from commercial suppliers unless otherwise noted. All reactions were performed in flame-dried or oven-dried glassware and were monitored by thin layer chromatography (TLC). Flash column chromatography was performed using silica gel (300−400 mesh). 1H NMR and 13C NMR spectra were recorded on a 300 or 500 MHz NMR spectrometer in CDCl3 or DMSO-d6. Chemical shifts (δ) are given in ppm relative to CDCl3 (7.26 ppm for 1H and 77 ppm for 13C) or internal TMS (δ = 0 ppm) as internal standard. Data are reported as follows: chemical shift, multiplicity, coupling constants, and integration. High-resolution mass spectra (HRMS) of all new compounds except 1 and 3 were obtained using APCI-TOF or ESI-TOF in positive mode. HRMS was obtained using ESI-TOF for 1 and MALDI for 3 in negative mode. UV−vis absorption spectra and fluorescence emission spectra were recorded on commercial spectrophotometers (190−900 nm scan range) with a quartz cuvette (path length = 1 cm). The relative fluorescence quantum yields (Φ) in dichloromethane were calculated by comparing the areas under the corrected emission spectrum using the parent BOPHY (Φ = 1.0 in dichloromethane)8a as the standard for BOPHYs 1, 2a, and 2b (excitation at 430 nm), Fluorescein (Φ = 0.9 in 0.1 M NaOH)28 as reference for BOPHYs 3−15 (excitation at 450 nm for 3−6, 470 nm for 7−15), Cresyl Violet perchlorate (Φ = 0.54 in methanol)29 for 16 (excitation at 550 nm), and Rhodamine B (Φ = 0.49 in methanol)30 for 17 (excitation at 500 nm). Nondegassed spectroscopic-grade solvents and a 10 mm quartz cuvette were used. Dilute solutions (0.01 < A < 0.05) were used to minimize the reabsorption effects. Quantum yields were determined using eq 1.31 1141


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The Journal of Organic Chemistry HRMS (APCI) calcd for C10H3B2Br5F3N4 [M − F]+: 656.6372, found 656.6365. BOPHY 6 was obtained from BOPHY (50 mg, 0.18 mmol) and liquid bromine (2.67 mL, 53.1 mmol) in 93% yield (123 mg) as a red powder. Mp >300 °C; 1H NMR (300 MHz, CDCl3) δ 8.16 (s, 2H); 13 C NMR (125 MHz, CDCl3) δ 183.0, 127.1, 124.6, 120.6, 113.2. HRMS (APCI) calcd for C10H2B2Br6F3N4 [M − F]+: 734.5477, found 734.5460. Synthesis of Brominated HBPs from Brominated Formylpyrroles. Synthesis of Hydrazine-Linked Bispyrrole H2a. To 4bromo-2-formylpyrrole P1 (173 mg, 1 mmol) in 50 mL of ethanol in a 100 mL round-bottom flask were added 80% hydrazine hydrate (30 μL, 0.5 mmol) and a few drops of acetic acid (100 μL). The reaction mixture was stirred for 1 h at room temperature, and TLC was used to follow the reaction. Upon completion of the reaction, 50 mL of cold water was poured. The yellow precipitate was filtered, and the filter cake was washed with water and dried under a vacuum to give H2a as a yellow powder in 85% yield (145 mg). 1H NMR (300 MHz, CDCl3) δ 9.29 (s, 2H), 8.28 (s, 2H), 6.96 (s, 2H), 6.62 (s, 2H); 13C NMR (75 MHz, CDCl3) δ 150.5, 128.0, 122.9, 115.7, 96.3. HRMS (APCI) calcd for C10H9Br2N4 [M + H]+: 344.9173, found 344.9177. Hydrazine-linked bispyrrole H4 was obtained as a yellow powder in 83% yield (207 mg) from 4,5-dibromo-2-formylpyrrole P2 (252 mg, 1 mmol) and 80% hydrazine hydrate (30 μL, 0.5 mmol) using the above procedure of H2a. 1H NMR (300 MHz, CDCl3) δ 12.83 (s, 2H), 8.28 (s, 2H), 6.82 (s, 2H); 13C NMR (75 MHz, CDCl3) δ 150.8, 129.9, 117.5, 107.4, 100.0. HRMS (APCI) calcd for C10H7Br4N4 [M + H]+: 502.7363, found 502.7351. Synthesis of Brominated Hydrazine-Linked Bispyrroles from Direct Bromination of HBP. Hydrazine-Linked Bispyrrole H2b. To HBP (186 mg, 1 mmol) was added dry ethyl acetate (20 mL), and the mixture was stirred until completely dissolved. NBS (374 mg, 2.1 mmol) was added in portions to the above solution at room temperature. The mixture was stirred at room temperature for 1 h under protection of light, and TLC was used to track the reaction. Petroleum ether (50 mL) was then poured into the reaction mixture, which was stirred for 5 min. The reaction mixture was then filtered, and the filter cake was washed with petroleum ether and dried under a vacuum to afford H2b (304 mg) as a yellow powder in 89% yield. 1H NMR (300 MHz, CDCl3) δ 9.38 (s, 2H), 8.25 (s, 2H), 6.52 (d, J = 3.6 Hz, 2H), 6.25 (d, J = 3.6 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 149.9, 129.0, 117.4, 112.8, 105.0. HRMS (APCI) calcd for C10H9Br2N4 [M + H]+: 342.9194, found 342.9185. Hydrazine-Linked Bispyrrole H5. To HBP (0.2 mmol, 37 mg) in 20 mL of dry CH2Cl2 was slowly added liquid bromine (0.12 mL, 2.4 mmol) in dry CH2Cl2 (10 mL) over a period of 1 h. This reaction was stirred for 12 h and tracked by TLC. The reaction mixture was washed with an aqueous solution of sodium thiosulfate and then with water. Organic layers were dried over Na2SO4 and evaporated to dryness under a vacuum. The solvents were evaporated to dryness under a vacuum to give H5 (101 mg) as a yellow powder in 87% yield. 1H NMR (300 MHz, CDCl3) δ 11.63 (s, 1H), 12.02 (s, 1H), 8.33 (s, 1H), 8.28 (s, 1H), 7.65(s, 1H). 13C NMR was not available due to its poor solubility. HRMS (ESI) calcd for C10H6Br5N4 [M + H]+: 580.6468, found 580.6458. Hydrazine-linked bispyrrole H6 was obtained as a yellow powder in 92% yield (120 mg) from HBP (37 mg, 0.2 mmol) and liquid bromine (0.2 mL, 4.0 mmol) using the above procedure for H5. 1H NMR (300 MHz, CDCl3) δ 13.37 (s, 2H), 8.34 (s, 2H); 13C NMR (125 MHz, CDCl3) δ 149.7, 127.03, 108.9, 106.5, 103.2. HRMS (ESI) calcd for C10H5Br6N4 [M + H]+: 660.5553, found 660.5542. General Procedure for the Brominated BOPHYs from Brominated Hydrazine-Linked Bispyrroles. To brominated hydrazine-linked bispyrroles (1 mmol) in 50 mL of toluene was added triethylamine (2 mL) and boron trifluoride ethyl ether complex (3 mL). The reaction was heated at 100 °C for 8 h. The reaction mixture was then poured into water (100 mL) and extracted with CH2Cl2 (60 × 3 mL). Organic layers were dried over Na2SO4 and evaporated to dryness under a vacuum. The residue was purified by silica gel column

chromatography using the mixture of petroleum ether and CH2Cl2 as eluent. BOPHY 2a was prepared from H2a (342 mg, 1 mmol) as an orange powder in 56% yield (245 mg). Mp 222.1−224.3 °C; 1H NMR (300 MHz, CDCl3) δ 8.21 (s, 2H), 7.67 (s, 2H), 7.30 (s, 2H); 13C NMR (125 MHz, CDCl3) δ 140.8, 137.6, 128.7, 124.5, 105.6. HRMS (APCI) calcd for C10H6B2Br2F3N4 [M − F]+: 420.9077, found 420.9063. BOPHY 2b9a was prepared from H2b (171 mg, 0.5 mmol) as an orange powder in 85% yield (186 mg). Mp 244.5−245.2 °C; 1H NMR (300 MHz, CDCl3) δ 8.01 (s, 2H), 7.31 (d, J = 7.5 Hz, 2H), 6.82 (d, J = 7.5 Hz, 2H). HRMS (ESI) calcd for C10H6B2Br2F4N4Na [M + Na]+: 460.8974, found 460.8997. BOPHY 4 was obtained from H4 (502 mg, 1 mmol) as an orange powder in 43% yield (255 mg). Mp 286.5−288.3 °C; 1H NMR (300 MHz, DMSO-d6) δ 8.97 (s, 2H), 7.74 (s, 2H); 13C NMR (125 MHz, DMSO-d6) δ 142.0, 130.3, 125.4, 124.8, 108.0. HRMS (APCI) calcd for C10H4B2Br4F3N4 [M − F]+: 574.7308, found 574.7293. BOPHY 5 was obtained from H5 (100 mg, 0.17 mmol) as a red powder in 52% yield (60 mg). Mp 278.2−279.7 °C; 1H NMR (300 MHz, CDCl3) δ 8.19 (s, 1H), 8.10 (s, 1H), 7.36 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 138.8, 138.1, 129.7, 128.1, 126.5, 125.1, 124.5, 120.2, 112.9, 110.2. HRMS (APCI) calcd for C10H3B2Br5F3N4 [M − F]+: 656.6372, found 656.6365. BOPHY 6 was obtained from H6 (100 mg, 0.15 mmol) as a red powder in 48% yield (55 mg). Mp >300 °C; 1H NMR (300 MHz, CDCl3) δ 8.16 (s, 2H); 13C NMR (125 MHz, CDCl3) δ 183.0, 127.1, 124.6, 120.6, 113.2. HRMS (APCI) calcd for C10H2B2Br6F3N4 [M − F]+: 734.5477, found 734.5460. Synthesis of BOPHY 7. To BOPHY 2b (50 mg, 0.11 mmol) in 12 mL of DCE was added butylamine (38.8 mg, 0.531 mmol). The reaction mixture was stirred at 70 °C for 75 min, poured into water, and extracted with CH2Cl2 (3 × 60 mL). Organic layers were dried over Na2SO4 and evaporated to dryness under a vacuum. The crude product was purified by silica gel column chromatography (petroleum ether/dichloromethane = 4/1, v/v) to give a dark orange powder in 86% yield (66 mg). Mp 186.3−187.2 °C; 1H NMR (300 MHz, CDCl3) δ 7.87 (s, 1H), 7.50 (s, 1H), 7.21 (d, J = 4.5 Hz, 1H), 7.02 (d, J = 3.6 Hz, 1H), 6.54 (d, J = 3.9 Hz, 1H), 6.05 (d, J = 4.5 Hz, 1H), 5.57 (s, 1H), 3.37−3.35 (m, 2H), 1.72−1.63 (m, 2H), 1.44 (q, J = 7.2 Hz, 2H), 0.98 (t, J = 7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 157.9, 134.0, 133.9, 129.2, 125.3, 124.6, 121.0, 119.1, 118.7, 105.7, 44.4, 32.0, 19.8, 13.7. HRMS (APCI) calcd for C14H16B2BrF3N5 [M − F]+: 412.0727, found 412.0728. Synthesis of BOPHY 8. Compound 8 was obtained from 4 (50 mg, 0.08 mmol) and butylamine (38.9 mg, 0.53 mmol) at 70 °C using the above procedure for 7 as a red powder in 85% yield (88 mg). Mp 188.5−188.9 °C; 1H NMR (500 MHz, DMSO-d6) δ 7.76 (s, 1H), 7.46 (s, 1H), 6.73 (d, J = 7.0 Hz, 1H), 3.59 (q, J = 7.0 Hz, 3H), 1.59−1.53 (m, 2H), 1.35−1.28 (m, 2H), 0.89 (t, J = 7.5 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 151.1, 131.9, 129.7, 119.0, 92.6, 43.6, 33.0, 19.6, 14.1. HRMS (APCI) calcd for C14H14B2Br3F3N5 [M − F]+: 569.8917, found 569.8914. Synthesis of BOPHY 9. Compound 9 was obtained from 4 (200 mg, 0.337 mmol) in 35 mL of ClCH2CH2Cl and butylamine (147.6 mg, 2.042 mmol) at 70 °C using the above procedure for 7 as a red powder in 83% yield (162 mg). Mp 193.2−194.7 °C; 1H NMR (500 MHz, DMSO-d6) δ 7.76 (s, 1H), 7.46 (s, 1H), 6.73 (d, J = 7.0 Hz, 1H), 3.59 (q, J = 7.0 Hz, 3H), 1.59−1.53 (m, 2H), 1.35−1.28 (m, 2H), 0.89 (t, J = 7.5 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 151.1, 131.9, 129.7, 119.0, 92.6, 43.6, 33.0, 19.6, 14.1. HRMS (APCI) calcd for C18H24B2Br2F3N6 [M − F]+: 563.0547, found 563.0547. Synthesis of BOPHY 10. Compound 10 was obtained from 6 (50 mg, 0.067 mmol) and butylamine (14.67 mg, 0.20 mmol) at 40 °C for 25 min using the above procedure for 7 as a dark orange powder in 93% yield (46 mg). Mp 209.7−210.9 °C; 1H NMR (300 MHz, CDCl3) δ 7.94 (s, 1H), 7.57 (s, 1H), 5.51 (s, 1H), 3.80 (q, J = 6.6 Hz, 2H), 1.76−1.66 (m, 2H), 1.51−1.44 (m, 3H), 1.00 (t, J = 7.2 Hz, 2H). 13 C NMR (75 MHz, CDCl3) δ 151.7, 150.5, 132.7, 129.2, 127.4, 121.4, 1142


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>300 °C; 1H NMR (300 MHz, CDCl3) δ 8.02 (s, 2H), 7.80 (d, J = 8.7 Hz, 4H), 7.22 (d, J = 4.2 Hz, 2H), 6.79 (d, J = 8.1 Hz, 4H), 6.74 (d, J = 4.2 Hz, 2H), 3.06 (s, 12H). 13C NMR (125 MHz, CDCl3) δ 153.3, 151.8, 137.9, 131.0, 130.5, 126.5, 118.6, 118.5, 112.4, 58.8, 55.7. HRMS (APCI) calcd for C26H27B2F4N6 [M + H]+: 521.2419, found 521.2420. Synthesis of BOPHY 17. To a dry Schlenk tube (10 mL) loaded with BOPHY 2b (55 mg, 0.126 mmol), 2-(tributylstannyl)thiophene (197 mg, 0.52 mmol), and Pd(PPh3)4 (7 mg, 6.3 μmol) was added toluene (2 mL) through a syringe into the mixture. The freeze− pump−thaw cycle was carried out three times. After that, the mixture was warmed to 90 °C under argon and stirred for 5 h. After cooling to room temperature, the reaction mixture was extracted with ethyl acetate and dried over anhydrous Na2SO4. The organic layers were combined, dried over Na2SO4, and evaporated to dryness under a vacuum. The crude product was purified by silica gel column chromatography to give purple powder 17 in 86% yield (48 mg). Mp 235.5−236.7 °C; 1H NMR (500 MHz, CDCl3) δ 8.14 (s, 2H), 7.91 (d, J = 4.0 Hz, 2H), 7.50 (d, J = 5.0 Hz, 2H), 7.29 (d, J = 4.5 Hz, 2H), 7.20 (t, J = 4.0 Hz, 2H), 6.88 (t, J = 4.0 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ 144.4, 139.4, 132.4, 130.6, 130.2, 129.6, 128.6, 125.9, 118.3. HRMS (ESI) calcd for C18H13B2F4N4S2 [M + H]+: 447.0704, found 447.0699. DFT Calculations. The ground state geometry was optimized using the DFT method at the B3LYP/6-31G (d,p) level. The same method was used for vibrational analysis to verify that the optimized structures correspond to local minima on the energy surface. Natural population analysis (NPA) was used based on the optimized ground state geometry at the same level to be calculated. All of the calculations were carried out by the methods implemented in the Gaussian 09 package.35

119.3, 117.5, 95.8, 93.6, 43.7, 32.9, 19.6, 14.1. HRMS (APCI) calcd for C14H12B2Br5F3N5 [M − F]+: 727.7107, found 727.7114. Synthesis of BOPHY 11. Compund 11 was obtained from 6 (50 mg, 0.067 mmol) and butylamine (48.9 mg, 0.67 mmol) at 40 °C for 1 h using the above procedure for 7 as a dark orange powder in 94% yield (30 mg). Mp 166.1−166.7 °C; 1H NMR (300 MHz, CDCl3) δ 7.94 (s, 1H), 7.57 (s, 1H), 5.51 (s, 1H), 3.80 (q, J = 6.6 Hz, 2H), 1.76−1.66 (m, 2H), 1.51−1.44 (m, 3H), 1.00 (t, J = 7.2 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 197.3, 150.2, 128.6, 121.9, 117.9, 95.3, 44.1, 32.9, 19.6, 13.7. HRMS (APCI) calcd for C10H12BBr2ClFN4 [M − F + Cl − Br]+: 412.9174, found 412.9189. Synthesis of BOPHY 12. Compound 12 was obtained from 6 (20 mg, 0.027 mmol) in 15 mL of toluene and 4-tert-butylaniline (40 mg, 0.27 mmol) at 80 °C using the above procedure for 7 to give a dark orange powder in 73% yield (16 mg). Mp 245.4−246.7 °C; 1H NMR (300 MHz, CDCl3) δ 7.96 (s, 1H), 7.77 (s, 1H), 7.42 (d, J = 7.8 Hz, 2H), 7.13 (d, J = 8.1 Hz, 2H), 1.35 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 150.7, 150.3, 134.2, 133.1, 130.9, 126.9, 126.2, 125.0, 124.2, 121.8, 119.7, 115.9, 111.2, 34.7, 31.4. HRMS (APCI) calcd for C20H16B2Br5F3N5 [M − F]+: 803.7420, found 803.7438. Synthesis of BOPHY 13. To 6 (55 mg, 0.126 mmol) in a 25 mL Schlenk tube was added toluene (1.0 mL) and pyrrole (1.0 mL). The reaction mixture was heated at 110 °C for 12 h under Ar. The cooled reaction mixture was concentrated under a vacuum, and the residue was purified by silica gel column chromatography to give 13 in 37% yield (34 mg) as a red powder. Mp 273.5−274.2 °C; 1H NMR (300 MHz, CDCl3) δ 9.90 (brs, 1H), 8.12 (s, 1H), 8.06 (s, 1H), 7.59 (brs, 1H), 7.18 (brs, 1H), 6.47 (brs, 1H); 13C NMR (125 MHz, CDCl3) δ 142.9, 136.1, 135.1, 125.0, 124.5, 124.4, 123.3, 120.3, 119.0, 118.4, 118.0, 112.4, 111.5, 109.6. HRMS (APCI) calcd for C14H7B2Br5F4N5 [M + H]+: 741.6700, found 741.6697. Synthesis of BOPHY 14. To BOPHY 4 (200 mg, 0.337 mmol) in 15 mL of ClCH2CH2Cl was added 4-tert-butylaniline (151 mg, 1.01 mmol). The reaction mixture was stirred at 80 °C. After the starting material was consumed completely, diethylamine (37 mg, 0.51 mmol) was added to the reaction mixture, and the mixture was stirred for 4 h. The mixture was poured into water (100 mL) and then extracted with CH2Cl2 (3 × 60 mL). Organic layers were combined, dried over Na2SO4, and evaporated to dryness under a vacuum. The crude product was purified by silica gel column chromatography (petroleum ether/dichloromethane = 2/1, v/v) to give dark orange powder 14 in 78% yield (172 mg). Mp 168.2−186.4 °C; 1H NMR (300 MHz, CDCl3) δ 9.90 (s, 1H), 8.12 (s, 1H), 8.06 (s, 1H), 7.59 (s, 1H), 7.18 (s, 1H), 6.47 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 142.9, 136.1, 135.1, 125.0, 124.5, 124.4, 123.3, 120.3, 119.0, 118.4, 118.0, 112.4, 111.5, 109.6. HRMS (APCI) calcd for C24H29B2Br2F4N6 [M + H]+: 659.0922, found 659.0921. Synthesis of BOPHY 15. Compound 15 was obtained from 2b (25 mg, 0.057 mmol) in 15 mL of toluene and 4-tert-butylaniline (85 mg, 0.57 mmol) at 85 °C using the above procedure for 7 to give red powder A9 in 41% yield (12 mg). Mp 272.4−273.6 °C; 1H NMR (300 MHz, CDCl3) δ 7.95 (s, 1H), 7.64 (s, 1H), 7.43 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 4.8 Hz, 1H), 7.18 (d, J = 8.4 Hz, 2H), 7.07 (d, J = 3.6 Hz, 1H), 6.57 (d, J = 3.9 Hz, 1H), 6.34 (d, J = 4.5 Hz, 1H), 1.34 (s, 9H); 13 C NMR (125 MHz, CDCl3) δ 154.5, 149.1, 135.1, 134.8, 133.3, 130.9, 126.7, 125.4, 121.8, 120.9, 119.8, 119.5, 107.1, 98.9, 34.6, 31.3. HRMS (APCI) calcd for C20H20B2BrF3N5 [M − F]+: 488.1040, found 488.1048. Synthesis of BOPHY 16. To a dry a dry Schlenk tube (10 mL) loaded with BOPHY 2b (30 mg, 0.068 mmol), 4-dimethylaminobenzene boronic acid (34 mg, 0.204 mmol), Pd(PPh3)4 (9 mg, 7.8 μmol), and Na2CO3 (30 mg, 0.286 mmol) were added toluene (2 mL) and H2O (0.2 mL) through a syringe into the mixture. The freeze− pump−thaw cycle was carried out three times. After that, the mixture was warmed to 90 °C under argon and stirred for 10 h. After cooling to room temperature, the reaction mixture was extracted with ethyl acetate and dried over anhydrous Na2SO4. Organic layers were combined, dried over Na2SO4, and evaporated to dryness under a vacuum. The crude product was purified by silica gel column chromatography to give violet powder 16 in 83% yield (29 mg). Mp

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ASSOCIATED CONTENT

S Supporting Information *

could be available free of charge via the Internet at The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b02415. Photophysical data and spectra, copies of NMR spectra, high-resolution mass spectra, and additional computational data for all new compounds (PDF) Crystal structure data for dyes 10, 11, 14, 16, and 17 (CIF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Changjiang Yu: 0000-0002-9509-7778 Lijuan Jiao: 0000-0002-3895-9642 Erhong Hao: 0000-0001-7234-4994 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work is financially supported by the National Nature Science Foundation of China (Grants 21672006, 21402001, and 21372011), the Nature Science Foundation of Anhui Province (Grants No. 1508085J07), and the Doctoral up Starting Foundation of Anhui Normal University (Grants No. 2017XJJ28). The numerical calculations in this paper have been performed on the supercomputing system in the Supercomputing Center of The University of Science and Technology of China. 1143


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