Reagents were obtained from Sigma-Aldrich Brasil Ltd. (São Paulo, SP—Brazil) and were readily used in the synthetic procedures. Solvents were obtained from local suppliers and treated according to established purification protocols. The structures of the BODIPYs synthesized herein were determined by 75 MHz 13C-NMR and 300 MHz 1H-NMR using a Bruker Ultrashield 300-MHz NMR system from Bruker Daltonics® (Billerica, MA, USA), and a high-resolution electrospray mass spectrometer (HRMS-ESI) using the ultrOTOFQ—ESI-TOF system from Bruker Daltonics ® (Billerica, MA, USA).
5,5-difluoro-10-(2-nitrophenyl)-5H-4λ4,5λ4-dipyrrolo[1,2-c:2',1'-f][1, 3, 2]diazaborinine 1.
2-Nitrobenzaldehyde (2.0 g, 13.2 mmol, 1.0 eq.) Was dissolved in distilled pyrrole (23 mL, 331 mmol, 25.0 eq.). TFA (100 µL, 1.3 mmol, 0.1 eq.) Was added and the mixture was stirred at room temperature for 10 minutes. The reaction was stopped by adding 0.1 M NaOH (45 ml). The organic phase was extracted with ethyl acetate (50 ml) and washed with distilled water (3 x 100 ml), dried over magnesium sulfate and concentrated under reduced pressure. 5- (2-nitrophenyl) XXXipyrromethene (3.21 g, 12 mmol, 1.0 eq.) Was dissolved in dichloromethane (150 ml). A solution of DDQ (2.73 g, 13 mmol, 1.0 eq.) in dichloromethane (100 mL) was added and the mixture was stirred at room temperature for 30 minutes. Triethylamine (10 mL, 72 mmol, 6.0 eq.) was added to the mixture and the reaction medium was kept under stirring for 1 hour. Boron trifluoride ether (13.3 mL, 108 mmol, 9.0 eq.) was added dropwise and the reaction medium stirred for an additional 2 hours. The reactional misture as washed with water (4x), saturated NaCl solution (1x), dried with sodium sulfate, filtered and evaporate the solvent. The product was purified over flash chromatographic column DCM / Hex 50–70%. 1H NMR (300 MHz, CDCl3) δ 8.25–8.19 (m, 1H), 7.95 (s, 2H), 7.82–7.71 (m, 2H), 7.57 (dd, J = 6.9, 2.0 Hz, 1H), 6.67 (d, J = 4.1 Hz, 2H), 6.51 (d, J = 3.9 Hz, 2H). HRME (ESI) calculated for C15H10BF2N3O2 [M + Na] +: 336.0726, obtained: 336.0740 (S1).
4,4-difluoro-4,7-dihydro-3a,4aλ4,7-triaza-4λ4-boracyclopenta[a]acephenanthrylene 2.
(313 mg 1 mmol) of Bodipy-nitro was dissolved in a vial containing 2 ml of DMA. Then PPh3 (2.5 mmol, 2.5 eq., 655.25 mg) was added and the reaction medium was placed under constant stirring and at elevated temperature at 165 ° C for 1 hour, when the total consumption was verified of the starting product and formation of the new product by thin layer chromatography. The reaction medium was poured into water, the product extracted using chloroform (3x) and the chloroform washed with distilled water (3X). The organic phase was dried using magnesium sulfate, filtered, and the product purified using a classic chromatographic column (eluent DCM / EtOAc 4: 1). 1H NMR (300 MHz, Acetone) δ 8.92 (d, J = 8.6 Hz, 1H), 8.11 (s, 1H), 8.01–7.91 (m, 1H), 7.79 (t, J = 7.7 Hz, 1H), 7.60 (dd, J = 9.2, 6.2 Hz, 2H), 7.47 (s, 1H), 6.58 (d, J = 2.5 Hz, 1H), 6.46 (s, 1H). 13C NMR (75 MHz, Acetone) δ 142.44, 139.01, 137.62, 131.73, 131.47, 127.81, 125.38, 120.31, 119.16, 119.14, 117.86, 114.07, 114.01, 96.36, 96.33. HRMS (ESI): Calculated for C15H10BF2N3, [M + K]+: 319.0495, obtained: 319.0647 (S2).
5,5-difluoro-10-(2-nitrophenyl)-3,7-bis(4-(trifluoromethyl)phenyl)-5H-4λ4,5λ4-dipyrrolo[1,2-c:2',1'-f][1, 3, 2]diazaborinine 5.
0.64 mmol (200 mg) of nitro bodipy was dissolved in 6 ml of acetone and then (2.5 eq.; 1.6 mmol; 645 mg) of the corresponding phenyldiazonium tetrafluorborate salt was added. A solution of (60 mg, 0.32 mmol) of ferrocene in 1.28 ml of acetone was added to the reaction medium dropwise (64 microliters every 5 minutes) over the course of 100 min. The reaction medium was kept under constant stirring for 30 min. At the end of the reaction period, the reaction medium was poured into 100 ml of ethyl ether, washed with distilled water 3 times, dried over sodium sulfate, filtered and evaporated. The reaction mixture was purified on a flash chromatographic column with a concentration gradient of 30–50% DCM in Hexane to isolate the diarylate product in 32% yield. 1H NMR (300 MHz, Acetone-d6) δ 8.39 (s, 2H), 8.17 (d, J = 7.1 Hz, 2H), 7.99 (ddt, J = 21.6, 14.0, 7.4 Hz, 3H), 7.81 (d, J = 7.3 Hz, 2H), 7.71 (t, J = 7.8 Hz, 2H), 6.96 (s, 3H). 13C NMR (75 MHz, Acetone) δ 157.44, 149.16, 141.79, 136.42, 133.77, 133.16, 133.04, 132.86, 131.70, 130.35, 129.98, 129.30, 127.97, 126.32, 125.24, 122.41, 121.79. HRME (ESI) calculated for C29H16BF8N3O2 [M + Na]+: 624,1100, obtained: 624,1133 (S3).
5,5-difluoro-3,7-bis(4-fluorophenyl)-10-(2-nitrophenyl)-5H-4λ4,5λ4-dipyrrolo[1,2-c:2',1'-f][1, 3, 2]diazaborinine 6.
0.64 mmol (200 mg) of nitro bodipy was dissolved in 6 ml of acetone and then (2.5 eq.; 1.6 mmol; 336 mg) of the corresponding phenyldiazonium tetrafluorborate salt was added. A solution of (60 mg, 0.32 mmol) of ferrocene in 1.28 ml of acetone was added to the reaction medium dropwise (64 µl every 5 minutes) over the course of 100 min. The reaction medium was kept under constant stirring for 30 min. At the end of the reaction period, the reaction medium was poured into 100 ml of ethyl ether, washed with distilled water 3 times, dried over sodium sulfate, filtered and evaporated. The reaction mixture was purified on a flash chromatographic column with a concentration gradient of 30–50% DCM in Hexane to isolate the diarylate product in 24% yield. 1H NMR (300 MHz, Acetone-d6) δ 8.37 (dd, J = 7.9, 1.5 Hz, 1H), 8.04–7.95 (m, 6H), 7.90 (dd, J = 7.3, 1.7 Hz, 1H), 7.27 (t, J = 8.9 Hz, 2H), 6.89 (d, J = 4.3 Hz, 2H), 6.82 (d, J = 4.4 Hz, 2H). 13C NMR (75 MHz, Acetone) δ 165.26, 161.97, 158.08, 149.29, 140.31, 136.00, 133.64, 132.89, 131.94, 131.51, 129.69, 128.78, 128.18, 125.11, 121.47, 115.35, 115.06. HRME (ESI) calculated for C27H16BF4N3O2 [M + Na]+: 524,1164, obtained: 524,1187 (S4).
4,4-difluoro-3,5-bis(4-(trifluoromethyl)phenyl)-4,7-dihydro-3a,4aλ4,7-triaza-4λ4-boracyclopenta[a]acephenanthrylene 7.
In a vial containing 115 mg of BODIPY (1 eq.; 0.19 mmol), 253 mg of triphenylphosphine (5 eq,; 0.96 mmol) and 200 µl of dimethylacetamide were added. The atmosphere of the vial was replaced by N2 and, later, sealed. The temperature of the reaction medium was raised to 180 ° C and maintained at that temperature and constant stirring for 120 min. After checking in TLC the total consumption of the starting product, the reaction medium was poured into ethyl ether and the resulting solution was washed with deionized water (3X), dried over sodium sulfate, filtered and evaporated. The product was isolated by flash chromatographic column using DCM: hexane 8: 1 as eluent in 25% yield. 1H NMR (300 MHz, Acetone-d6) δ 9.06 (d, J = 8.5 Hz, 1H), 8.45 (s, 1H), 8.30–8.25 (m, 4H), 8.11–8.05 (m, 2H), 7.94 (t, J = 7.7 Hz, 1H), 7.82–7.61 (m, 8H), 6.97 (s, 1H), 6.78 (d, J = 3.9 Hz, 1H). 13C NMR (75 MHz, Acetone) δ 200.82, 186.55, 169.15, 155.11, 144.25, 138.04, 136.79, 136.22, 133.83, 133.28, 132.50, 132.47, 131.03, 129.17, 128.76, 128.51, 127.78, 127.06, 126.32, 126.26, 125.88, 125.58, 124.73, 123.68, 123.63, 119.35, 117.45, 116.20, 96.88. HRME (ESI) calculated for C29H16BF8N3 [M + Na]+: 592,1202, obtained: 592,1254 (S5).
4,4-difluoro-3,5-bis(4-fluorophenyl)-4,7-dihydro-3a,4aλ4,7-triaza-4λ4-boracyclopenta[a]acephenanthrylene 8.
In a vial containing 71 mg of BODIPY (1 eq.; 0.14 mmol) 176 mg of triphenylphosphine (5 eq.; 0.71 mmol) and 200 µl of dimethylacetamide were added. The atmosphere of the vial was replaced by N2 and subsequently sealed. The temperature of the reaction medium was raised to 180 ° C and maintained at that temperature and constant stirring for 120 min. After checking in TLC the total consumption of the starting product, the reaction medium was poured into ethyl ether and the resulting solution was washed with deionized water (3X), dried over sodium sulfate, filtered and evaporated. The product was isolated by flash chromatographic column using DCM / hexane 8 : 1 as eluent in 15% yield. 1H NMR (300 MHz, Acetone-d6) δ 9.02 (d, J = 8.6 Hz, 1H), 8.09–8.02 (m, 4H), 7.92–7.80 (m, 3H), 7.71 (dd, J = 15.6, 5.6 Hz, 2H), 7.24 (t, J = 8.9 Hz, 1H), 7.15 (t, J = 8.9 Hz, 1H), 6.79 (s, 1H), 6.61 (d, J = 3.9 Hz, 1H). 13C NMR (75 MHz, Acetone) δ 159.11, 159.08, 152.46, 142.23, 138.67, 137.55, 136.81, 132.96, 132.39, 131.97, 131.71, 128.04, 125.37, 124.64, 120.09, 116.49, 116.10, 115.81, 115.36, 115.08. HRME (ESI) calculated for C27H16BF4N3 [M + Na]+: 492.1266, obtained: 492.1293 (S6).
Absorption spectra were obtained on an Agilent 8453 UV-Visible spectrophotometer at room temperature in the solvents described above. Steady state fluorescence spectra were obtained on a Shimadzu RF5301PC spectrofluorimeter with a xenon arc lamp as the light source while using an excitation wavelength (λexc) of 470 nm.
Quantum yields were obtained by a comparative method [12] using fluorescein in 0.1 M NaOH(aq) as the standard (φ = 0.91, λexc = 470 nm) [13] The quantum yield of the tested compound (φx) was calculated using Eqs. (1), where φst is the quantum yield of the standard, mx and mst are the slopes for the test compound and standard compound, and ƞx and ƞst are the refractive indexes of the solvents.
(1)