| 42% |
Stage #1: 2,4-dimethyl pyrrole; 4-iodobenzoic acid chloride In dichloromethane at 20℃; Inert atmosphere;
Stage #2: boron trifluoride diethyl ether complex With triethylamine In dichloromethane at 0℃; for 12h; Inert atmosphere; |
|
| 41% |
Stage #1: 2,4-dimethyl pyrrole; 4-iodobenzoic acid chloride In dichloromethane for 3h; Reflux; Inert atmosphere;
Stage #2: boron trifluoride diethyl ether complex With triethylamine In dichloromethane at 20℃; Reflux; Inert atmosphere; |
5 8-iodophenyl-l,3,5,7-tetramethyl BP:
A 500 mL 3 neck Morton flask with high efficiency condenser was charged with a stir bar, 250 mL degassed dichloro methane, 5.33 g 4-iodobenzoyl chloride, and 3.85 g 2,4-dimethylpyrrole then refluxed 3 hours. Initially the reaction was a white-yellow suspension that became clear red while refluxing. The hot water bath was removed with the argon flow increased, and the reflux stopped. Room temperature water was added to the bath. 14 mL trimethylamine was added via syringe and needle through a septum over 2 minutes. After the addition the reaction was stirred 5 minutes then 17.5 mL boron trifluoride diethyletherate was added dropwise over 5 minutes via addition funnel. The reaction was refluxed for 1 hour in a 50°C water bath from 5 pm to 6 pm then water bath drained and the reaction allowed to stir at room temperature overnight. TLC shows a BP dye. 100 mL water was carefully added and stirred vigorously 10 minutes. The organic layer was pushed out and dried over anhydrous sodium sulfate, decanted, rinsed with 5x50 mL dichloromethane, stripped, then run on a silica column in 1: 1 hexane/DCM. The material was dissolved in 100 mL DCM, washed with 100 mL water, separated and the organic layer absorbed onto 25 g silica. Chromatography was done on a 40 gram column, and a gradient from 100% hexanes to 1: 1 hexanes DCM, the pure dye collected (verified by TLC), stripped on rotavap then high vacuum overnight (0.15 torr), 3.7 grams (41% yield). |
| 36% |
With triethylamine In dichloromethane; toluene 1.) CH2Cl2, 50°C, 2 h, 2.) toluene/CH2Cl2, BF3*OEt2, 50°C,1.5 h; |
|
| 30.6% |
With triethylamine In dichloromethane at 20℃; for 96h; Inert atmosphere; |
1 Example 1 Synthesis of para-iodophenyl-BODIPY (p-BD-1)
2,4-Dimethylpyrrole (0.70 mL, 6.71 mmol) was added dropwise to a solution of p-iodobenzoyl chloride (0.70 g, 2.62 mmol) in anhydrous dichloromethane (150 mL) Under argon atmosphere for 72h at room temperature; Triethylamine (2.2 mL, 15.75 mmol) and boron trifluoride diethyl ether (2.68 mL, 21 mmol) were successively added, Argon under stirring at room temperature for 24h; After stopping the reaction, The reaction mixture solution was washed with saturated sodium bicarbonate solution (60 mL x 3) three times, After extracting with dichloromethane, the organic layer was collected and then dried over anhydrous sodium sulfate; Rotate the rotary evaporator to remove the organic solvent, The crude solid was isolated and purified by silica gel column chromatography (mobile phase: cyclohexane / ethyl acetate = 4/1) to give para-iodophenyl-BODIPY (361.2 mg, 30.6%). |
| 30.6% |
With triethylamine In dichloromethane at 20℃; for 96h; Inert atmosphere; |
1 Example 1 Synthesis of para-iodophenyl-BODIPY (p-BD-1)
2,4-Dimethylpyrrole (0.70 mL, 6.71 mmol) was added dropwise to a solution of p-iodobenzoyl chloride (0.70 g, 2.62 mmol) in anhydrous dichloromethane (150 mL) Under argon atmosphere for 72h at room temperature; Triethylamine (2.2 mL, 15.75 mmol) and boron trifluoride diethyl ether (2.68 mL, 21 mmol) were successively added, Argon under stirring at room temperature for 24h; After stopping the reaction, The reaction mixture solution was washed with saturated sodium bicarbonate solution (60 mL x 3) three times, After extracting with dichloromethane, the organic layer was collected and then dried over anhydrous sodium sulfate; Rotate the rotary evaporator to remove the organic solvent, The crude solid was isolated and purified by silica gel column chromatography (mobile phase: cyclohexane / ethyl acetate = 4/1) to give para-iodophenyl-BODIPY (361.2 mg, 30.6%). |
| 29% |
Stage #1: 2,4-dimethyl pyrrole; 4-iodobenzoic acid chloride In dichloromethane at 20℃; for 24h; Inert atmosphere;
Stage #2: boron trifluoride diethyl ether complex With triethylamine In dichloromethane at 20℃; for 4h; Inert atmosphere; |
8.1 Step (1): Preparation of Intermediate (4)
A 500 ml round bottom flask under a nitrogen atmosphere charged with 2,4-dimethyl-pyrrole 7.1g (75 mmol), 4-iodobenzoyl chloride 10.1 g (38 mmol) and dichloromethane (DCM) 250 ml were added and stirred at room temperature for 24 hours. Then, triethylamine (TEA) 26 ml, boron trifluoride diethyl ether (BF3OEt2) 26 ml was added and stirred for 4 hours at room temperature. Subsequently, by introducing water and the layers were separated and the organic layer was concentrated and then a mixed solvent of dichloromethane and hexane (1: 2 (v / v)) by performing column chromatography to give a orange solid of intermediate (4) 5.0 g (yield: 29%). |
| 29% |
Stage #1: 2,4-dimethyl pyrrole; 4-iodobenzoic acid chloride In 1,2-dichloro-ethane for 13h; Inert atmosphere; Reflux;
Stage #2: With triethylamine In 1,2-dichloro-ethane for 0.166667h; Inert atmosphere;
Stage #3: boron trifluoride diethyl ether complex In 1,2-dichloro-ethane for 2h; Inert atmosphere; Reflux; |
|
|
Stage #1: 2,4-dimethyl pyrrole; 4-iodobenzoic acid chloride at 20℃; for 24h;
Stage #2: boron trifluoride diethyl ether complex With triethylamine |
18
EXAMPLE 18Preparation of Compound 18Compound 18 is prepared according to the following reaction pattern The 4,4-difluoro-1,3,5,7-tetramethyl-8-(p-iodophenyl)-4-bora-3a,4a-diaza-s-indacene 4' was prepared according to the following mode of operation. 1.17 g of p-iodo-benzoyle chloride and 1 ml of 2,4-dimethyl-pyrrole were stirred for one day at ambient temperature. 3.7 ml of triethylamine and 4.5 ml of BF3Et2O were subsequently added. The mixture was stirred overnight, and the organic phase was subsequently washed with water. Chromatography over alumina (hexane/dichloromethane, 7:3) and recrystallisation in a hexane/dichloromethane mixture yielded 0.9 g of compound 4'.A solution of n-butyllithium 1.27 M in hexane (0.304 ml) was added to a solution of 1-ethynylpyrene (100 mg, 0.44 mmol) in anhydrous THF (10 ml) under argon at -78° C. The mixture was stirred for 1 hour at -78° C., then at ambient temperature for 30 minutes. The solution thus obtained was transferred by cannula into a solution of 4,4-difluoro-1,3,5,7-tetramethyl-8-(p-iodophenyl)-4-bora-3a,4a-diaza-s-indacene (80 mg, 0.176 mmol) in anhydrous THF (10 ml). The solution was stirred for 15 minutes at ambient temperature until the starting material had disappeared (monitored by TLC), then water was added (10 ml). Said solution was extracted with dichloromethane (20 ml). After evaporation, the organic residue was purified by chromatography on a column of alumina (CH2Cl2/cyclohexane, with a gradient of from 90:10 to 70:30), and was then recrystallised in a CH2Cl2/cyclohexane mixture in order to obtain compound 7 in the form of orange crystals (76 mg, 50%).Characterisation of Compound 201H NMR (CDCl3 400 MHz): δ=8.79 (d, 2H, 3J=9.3 Hz), 8.18-7.99 (m, 16H), 7.89 (d, 2H3J=8.5 Hz), 7.21 (d, 2H, 3J=8.2 Hz), 6.20 (s, 2H), 3.17 (s, 6H), 1.53 (s, 6H)13C NMR (CDCl3, 100 MHz): 156.3, 141.6, 140.7, 138.6, 135.6, 132.5, 131.7, 131.6, 130.9, 130.7, 130.1, 128.3, 127.9, 127.7, 126.6, 126.4, 125.5, 125.0, 124.9, 124.8, 122.4, 120.7, 95.4, 94.9, 17.0, 15.4;11B NMR (CDCl3, 128 MHz); -8.87 (s);UV-Vis (CH2Cl2) λnm (ε, M-1 cm-1)=501 (70000) 471sh (6200), 369 (89000), 349 (69700), 285 (94000) |
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Stage #1: 2,4-dimethyl pyrrole; 4-iodobenzoic acid chloride In dichloromethane at 50℃; for 3h;
Stage #2: boron trifluoride diethyl ether complex With triethylamine In dichloromethane; toluene at 50℃; for 1.5h; |
|
|
Stage #1: 2,4-dimethyl pyrrole; 4-iodobenzoic acid chloride In dichloromethane for 3h; Inert atmosphere; Reflux;
Stage #2: boron trifluoride diethyl ether complex With triethylamine at 20℃; for 16h; |
|
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