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Bashar, Noorul ; Kundu, Bidyut Kumar ; Pozdeev, Anton S ; Jiang, De-en ; Sun, Yujie ;
Abstract: Aryl radicals serve as essential intermediates in contemporary organic synthesis, facilitating diverse carbon−carbon and carbon-heteroatom bond-forming reactions under mild conditions. Aryl halides, widely available and frequently employed as precursors for photocatalytic aryl radical generation, typically require photocatalysts with strong reducing capabilities to overcome their high reduction potentials. Herein, we report an innovative approach for the photocatalytic generation of aryl radicals using an organic photocatalyst 5,5′-bis((4-methoxyphenyl)ethynyl)-2,2′-bibenzo[d]thiazole (dBAP) that leverages the proton-coupled electron transfer (PCET) mechanism. This strategy allows the selective generation of aryl radicals at the ortho and para positions of aryl halides bearing PCET handles, despite dBAP’s intrinsic reducing power being insufficient for direct electron transfer to the aryl halides, in contrast to the prevalent approaches. Mechanistic investigations highlight the role of PCET in lowering the activation barrier for aryl radical formation, enabling efficient C−H, C−C, and C−B bond-forming reactions with high regioselectivity and functional group tolerance. This work underscores the potential of PCET-driven photocatalysis using organic photocatalysts as a sustainable and versatile platform for expanding the synthetic utility of aryl radicals under ambient conditions.
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Purchased from AmBeed: 42348-86-7 ; 34598-50-0 ; 46258-62-2 ; 3988-03-2 ; 2001-29-8 ; 214701-49-2 ; 16184-89-7 ; 2142-63-4 ; 99-90-1 ; 10342-83-3 ; 2142-69-0 ; 99-91-2
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CAS No. : | 2142-69-0 |
Formula : | C8H7BrO |
M.W : | 199.04 |
SMILES Code : | C1=CC=CC(=C1C(C)=O)Br |
MDL No. : | MFCD00000067 |
InChI Key : | PIMNFNXBTGPCIL-UHFFFAOYSA-N |
Pubchem ID : | 75060 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With pyridine; selenium(IV) oxide; at 100℃; for 2h; | 8.3 g (75 mmoles) of selenium dioxide were added to 10 g (50 mmoles) of 2'- bromoacetophenone dissolved in 20 ml of pyridine; the mixture was left under magnetic stirring at 100C for 2 hours. After control in TLC and LC-MS, the mixture was filtered to eliminate the selenium and the pyridine was removed at reduced pressure. The residue was acidified with diluted HCl and extracted with ethyl acetate; the phases were then separated; the aqueous phase was re- extracted twice with ethyl acetate. The organic phases were joined and washed with water and a saturated solution of NaCl. After anhydrification on sodium sulfate, filtration and evaporation of the solvent at reduced pressure, 11.4 g of the desired product (50 mmoles) were obtained, as a cream-coloured solid. The raw product thus obtained was used for the subsequent reaction. Quantitative yield. LC-MS [M+H] = 229. |
87% | With pyridine; selenium(IV) oxide; at 120℃; for 18h;Inert atmosphere; | Into a 250-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of l-(2-bromophenyl)ethan-l-one (10 g, 50.24 mmol, 1.00 equiv) in pyridine (80 mL). This was followed by the addition of Se02 (22 g, 198.27 mmol, 3.95 equiv). The resulting solution was stirred for 18 h at 120 C in an oil bath. The reaction mixture was cooled to room temperature. The solids were filtered out. The resulting mixture was concentrated under vacuum. The residue was dissolved in 100 mL of water. The resulting mixture was washed with 2x50 mL of ethyl acetate. The pH value of the aqueous layer was adjusted to 1-2 with hydrogen chloride (4 mol/L). The resulting solution was extracted with 3x80 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate. The solids were filtered out. The resulting mixture was concentrated under vacuum. This resulted in 10 g (87%) of 2-(2- bromophenyl)-2-oxoacetic acid as yellow oil. MS (ESI) m/z 230 ([M + H]+) |
With pyridine; selenium(IV) oxide; at 90 - 110℃; for 5h; | General procedure: The substituted alpha-keto acids were prepared from oxidation of corresponding methyl ketones with SeO2 (Scheme 1). Methyl ketones (5 mmol), SeO2 (6 mmol), 20 mL of pyridine were added in a 50 mL round-bottom flask. The reaction mixture was stirred at 110 oC for 1 h, and under 90 oC for another 4 h. The desired products were isolated by silica-gel column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17% | With di-tert-butyl peroxide; copper(l) chloride; at 120℃; for 6.0h; | General procedure: 2'-Bromoacetophenone (1a) (100.0 mg, 0.5mmol), benzyl alcohol (5a) (325.0mg,1.5mmol), CuCl (5.0mg, 0.05mmol), DTBP (365.0mg, 1.25 mmol), and 25% aqueous ammonia (0.5 mL) were placed in a thick-walled Pyrex screw-captube(25mL), and the tube was capped and the mixture heated in an oil bath at 120 C with stirring for 6 h. After the reaction mixture was cooled to room temperature, the workup and isolation of the products were essentially similar to the procedure above-mentioned. Compound 3a was obtained as white solid in 65% (71.5 mg, 0.33 mmol), and the GC analysis of the reaction mixture disclosed the formation of 3a in 66% GC yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With ammonia; copper(l) chloride; In 1-methyl-pyrrolidin-2-one; water; at 80℃; for 12.0h;Sealed tube; | General procedure: 2'-Bromoacetophenone (1a) (100.0 mg, 0.5 mmol), benzaldehyde (2a) (58.0 mg, 0.55 mmol), CuCl (5.0 mg, 0.05 mmol), 25% aqueous ammonia (0.5 mL), and NMP (0.5 mL) were placed in a thick-walled Pyrex screw-cap tube (25 mL) under air atmosphere, and the tube was capped and the mixture was heated in an oil bath at 80 C with stirring for 12 h. After the reaction mixturewas cooled to room temperature, the crude reaction mixture was extracted with EtOAc for three times (3.0 mL 3). After removal of volatiles under a reduced pressure, the residue was diluted with CH2Cl2 (4.0 mL) and then n-docosane (62.1 mg, 0.2 mmol) was added as an internal standard for GC analysis. After GC and GCeMS analyses of the reaction mixture, volatiles were removed under a reduced pressure, and the residue was then subjected to silica gel column chromatography [eluting with petroleum ether and then with a mixture of petroleum ether and ethyl acetate (100:1e50:1)] to afford 4-methyl-2-phenylquinazoline (3a) (69.6 mg, 0.32 mmol, 63%) as white solid. The GC analysis of the reaction mixture disclosed the formation of 3a in 65% GC yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With potassium tert-butylate; palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In toluene; at 80℃; for 2h;Schlenk technique; Inert atmosphere; | Compound 1 was mixed with with aryliodide 2c (132.0 mg, 0.50 mmol), ortho-bromoacetophenone 1a (109.4 mg, 0.55 mmol), Pd(OAc)2 (2.2 mg, 2 mol%), xantphos (11.6 mg, 4 mol%), tBuOK (72.9 mg, 0.65 mmol), and dry toluene (4 mL)at 80 C for 45 min. Silica-gel column chromatography (20g, petroleum ether/ethyl acetate, 85:15 to 80:20) furnished the title compound 3ac (155 mg, 92%) as yellow solid, recrystallized the solid with dichloromethane/hexane, mp 74-76 C [TLCc ontrol (petroleum ether/ethyl acetate 90:10), Rf(1a)0.55, Rf(2c)0.45, and Rf(3ac) 0.20, UV detection]. IR (MIR-ATR, 4000-600 cm1): νmax2956, 2923,2852, 1697, 1587, 1512, 1463, 1422, 1259, 1154, 1140, 1025, 791, 757, 678 cm1. 1HNMR (CDCl3, 400 MHz): d7.57 (d, 1H, J7.8 Hz, Ar-H), 7.35-7.15 (m, 3H,Ar-H), 6.78 (d, 1H, J8.7 Hz, Ar-H), 6.76 (dd, 1H, J8.7 and 1.9 Hz, Ar-H),6.74 (d, 1H. J1.9 Hz, Ar-H), 4.15 (s, 2H, ArCOCH2), 3.83 (s, 3H, ArOCH3),3.82 (s, 3H, ArOCH3) ppm. 13C NMR (CDCl3, 100 MHz): 201.8 (s, Ar-C=O),148.9 (s, Ar-C), 148.1 (s, Ar-C), 141.4 (s, Ar-C), 133.5 (d, Ar-CH), 131.4 (d, Ar-CH),128.6 (d, Ar-CH), 127.2 (d, Ar-CH), 125.8 (s, Ar-C), 121.9 (d, Ar-CH), 118.6(s, Ar-C), 112.7 (d, Ar-CH), 111.2 (d, Ar-CH), 55.8 (q, 2C, 2ArOCH3), 49.0 (t, Ar-COCH2) ppm. HR-MS (ESI) m=z calculated for [C16H7916 BrO3][MH]:335.0277; found 335.0294. [C16H8116 BrO3][MH]: 337.0259; found 337.0274. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69.3% | In ethanol;Reflux; | General procedure: solutionof acid hydrazide (0.01 mol) and appropriate benzaldehyde/acetophenone (0.01 mol) in ethanol was refluxed for 5-6 h. The precipitated title compounds were then filtered off, washed with water and recrystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine; In toluene; at 110℃; for 24h;Schlenk technique; Inert atmosphere; Molecular sieve;Catalytic behavior; | General procedure: The following compounds were synthesized based upon reported literatureprocedure2 under our optimized cross-coupling conditions. An oven-dried round-bottom flaskwith a Teflon stir bar was charged with amide (2.0 equiv, 1.00 mmol), CuI (20 mol%, 0.10mmol), base (2 equiv, 1.00 mmol), and 200 mg activated 4 Å molecular sieves. The roundbottomflask was sealed with a rubber septum, evacuated and refilled with nitrogen (thissequence was performed three times). Under nitrogen, 2’-bromoacetophenone (1.0 equiv, 0.50 mmol), N, N’- dimethylethylenediamine (40 mol%, 0.2 mmol), and toluene (3 mL) were eachadded via syringe. The round-bottom flask was then placed in a preheated oil bath at 110 C. Thereaction was heated with stirring for 24 h until TLC showed completion of the reaction. Thecrude of reaction obtained was cooled to room temperature. Toluene was removed under vacuothen water (5 mL) was added to the reaction mixture. The biphasic mixture was extracted withethyl acetate (3x15 mL). The organic extracts were collected, dried over anhydrous sodiumsulfate, filtered, and concentrated in vacuo to remove solvent. The product was purified bycolumn chromatography on silica gel (100-200 mesh) with EtOAc/hexane system, to afford thecorresponding N-ketoarylamides. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | O-bromoacetophenone 1a (119.4 mg, 0.12 mmol) was sequentially added to a 25 mL round bottom flask as described in Example 1,0.6 mmol), dimethylsulfoxide (3 mL) and iodine (152 mg, 0.6 mmol) were added and the mixture was stirred under heating at 110 ° C for 3 h, then cooledBut to room temperature, 2d (68.2 mg, 0.4 mmol), CuBr (11.5 mg, 0.08 mmol) and K2CO3 (221 mg, 1.6 mmol)The reaction was stirred at room temperature for 5h, then heated and stirred at 100 for 3h. After the reaction was completed, saturated chlorination was added to the reaction vesselThe reaction was quenched with ammonium chloride and extracted with dichloromethane. The combined organic phases were washed with deionized water and saturated sodium chloride solution,Sodium drying. Filtration, spin-drying, separation through a silica gel column (petroleum ether / ethyl acetate = 2/1, v / v)3-Chloroindole [2,1-b] quinazoline-6,12-dione 3k (61 mg, 54percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | In ethanol; at 20℃; for 16h; | A solution of 2-bromoacetophenone (1.99 g, 10 mmol) and tert-butyl (2-amino 2-thioxoethyl)carbamate (1.90 g, 10 mmol) in EtOH (50 mL) was stirred at room temperature for 16 h. The solution was evaporated and the resulting residue diluted in water (25 mL) and extracted with EtOAc (2 x 25 mL). The combined extracts were dried and evaporated affording a pale yellow solid. Recrystallisation from MeCN (13 mL) led to colourless solid (2.03 g, 70%). M/z 235 (M+H-tBu)+. |