46258-62-2|1-(4-Bromonaphthalen-1-yl)ethanone| Ambeed

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.

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

Product Details of [ 46258-62-2 ]

CAS No. :	46258-62-2
Formula :	C₁₂H₉BrO
M.W :	249.10
SMILES Code :	CC(C1=C2C=CC=CC2=C(Br)C=C1)=O
MDL No. :	MFCD09037858
InChI Key :	CSVHMWORIJZGTJ-UHFFFAOYSA-N
Pubchem ID :	230584

Safety of [ 46258-62-2 ]

Computational Chemistry of [ 46258-62-2 ] Show Less

Physicochemical Properties

Num. heavy atoms	14
Num. arom. heavy atoms	10
Fraction Csp3	0.08
Num. rotatable bonds	1
Num. H-bond acceptors	1.0
Num. H-bond donors	0.0
Molar Refractivity	61.84
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	17.07 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.37
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	3.55
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	3.8
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	3.44
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	3.98
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	3.43

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-4.08
Solubility	0.0206 mg/ml ; 0.0000825 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-3.59
Solubility	0.0635 mg/ml ; 0.000255 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-5.27
Solubility	0.00135 mg/ml ; 0.00000542 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	Yes
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.3 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	1.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<2.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.22

Application In Synthesis of [ 46258-62-2 ]

* 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.

Downstream synthetic route of [ 46258-62-2 ]

[ 46258-62-2 ] Synthesis Path-Downstream 1~55

1
[ 20780-76-1 ]
[ 46258-62-2 ]
2-(4-bromo-[1]naphthyl)-6-iodo-quinoline-4-carboxylic acid [ No CAS ]

References: [1]Patent: DE505160,1926, .
Fortschr. Teerfarbenfabr. Verw. Industriezweige,vol. 18,p. 2751.

2
[ 90-11-9 ]
[ 75-36-5 ]
[ 46258-62-2 ]

Yield	Reaction Conditions	Operation in experiment
91%	With aluminum (III) chloride; In 1,2-dichloro-ethane; at 0 - 20℃; for 24h;	A solution of 1-Bromo-naphthalene (10 g, 48.3 mmol) and acetyl chloride (4.2 ml, 58 mmol) in 1,2-dichloroethane (100 ml) was cooled to 0C and aluminum chloride (14.4 g, 108 mmol) was added portion wise. The mixture was stirred at RT for 24 hours. The reaction mixture was poured into ice-water (100 ml). The two layers were separated and the water layer was extracted with diethyl ether (3 x 150 ml). The combined organic layers were dried over magnesium sulfate, filtered and the solvent was removed under reduced pressure to give an orange colored oil. The 1- (4-bromo-naphtalen-1-yl)-ethanone was purified by flash chromatography (cyclohexane/ethylacetate: 95/5), yielding an yellow oil (91% yield). The 1- (4-bromo-naphtalen-1-yl)-ethanone oxime was prepared according to the procedure described for Compound 22, yielding a white powder (98% yield). Activated zinc dust (24.7 g, 379 mmol) was added portion wise to a suspension of the oxime (10.0 g, 37.9 mmol) in acetic acid (40 ml). The mixture was stirred at RT for 2 hours. The zinc dust was removed by filtration and acetic acid was removed under reduced pressure. Water (100 ml) was added and the pH was adjusted to pH = 13 with 1N NaOH. The water layer was extracted with EtOAc (3 x 100 ml). The combined organic layers were dried over MgS04, filtered and the solvent was removed under reduced pressure, yielding a yellow oil (70% yield). Boc20 (7.1 g, 31.8 mmol) was added to a solution of the amine (6.6 g, 26.5 mmol) in 1,4-dioxane (50 ml). The reaction mixture was stirred at RT for 2 hours. The solvent was removed under reduced pressure and the product was purified by flash chromatography (cyclohexane/EtOAc: 95/5), yielding a yellow powder (75% yield). The bromide (350 mg, 1 mmol) was dissolved in THF (13 ml) /water (2 ml). Potassium acetate (100 mg, 1 mmol), 1,3-bis-diphenylphosphinopropane (9.0 mg, 0.02 mmol) and palladium- (11)-acetate (9.0 mg, 0.04 mmol) were added. The mixture was stirred at 50 atm CO pressure and 150C for 3 hours. The reaction mixture was filtered, the filtrate dried over MgS04 and the solvent was removed under reduced pressure to give a yellow- greenish oil (300 mg). The 4- (l-tert-butoxycarbonylamino-ethyl)-naphthalene-l- carboxylic acid was purified by flash chromatography (DCM/MeOH : 90/10), yielding a white powder (14% yield). The title product was prepared according to the procedure of Compound 31, starting from 4- (1-tert-butoxycarbonylamino-ethyl)-naphthalene-1-carboxylic acid (44 mg) and 4-amino-pyridine (67% yield).'H NMR (300 MHz, , DMSO-d6): 1.64 ppm (d, 3H, J = 6.6 Hz); 5.3 ppm (q, 1H, J = 6.5 Hz), 7.71 ppm (m, 1H), 8.00 ppm (d, 1H, J = 7.7 Hz), 8.32 ppm (m, 1H), 8. 35 ppm (d, 1H, J = 7.3 Hz), 8.81 ppm (d, 2H, J = 7.2 Hz), 12.2 ppm (s, 1H).
91%	aluminum (III) chloride; In 1,2-dichloro-ethane; at 0 - 20℃; for 24h;	Section IExample I-IPreparation of Compound 301 and 302General Procedure I-AA solution of 1-Bromo-naphthalene (I-Ia; 2 g, 9.6 mmol) and acetyl chloride (0.84 mL, 11.6 mmol) in 1,2-dichloroethane (30 mL) was cooled to 0 C. and aluminum chloride (2.88 g, 21.6 mmol) was added portion wise. The mixture was stirred at r.t. for 24 hours. The reaction mixture was poured into ice-water (100 mL). The two layers were separated and the aqueous layer was extracted with EtOAc (150 mL×3). The combined organic layers were dried over magnesium sulfate, filtered and the solvent was removed under reduced pressure to give compound I-Ib as an orange oil (2.16 g, yield 91%). 1H NMR (400 MHz, CDCl3) delta 8.6 (m, 1H), 8.3 (m, 1H), 7.8 (d, J=8.0 Hz, 1H), 7.66 (d, J=7.6 Hz, 1H), 7.58 (m, 2H), 2.63 (s, 3H). MS (ESI) m/z (M+H)+ 250.
62%	With aluminum (III) chloride; In carbon disulfide; at 0 - 20℃; for 120h;Inert atmosphere;	To a stirred solution of 1.00 g (4.8 mmol) of 1-bromonaphthalene in 15 mL of carbon disulfide at 0 C in a flame-dried flask under N2 was added 0.42 g (5.3 mmol) of acetyl chloride. This solution was stirred at 0 C for 10 min and 0.84 g (6.3 mmol) of AlCl3 was added. The reaction was stirred at 0 C for 3 days followed by 2 days of stirring at ambient temperature. The reaction mixture was poured over ice and concentrated HCl, extracted with ether, washed with NaHCO3 and brine. After drying (MgSO4) the solution was concentrated in vacuo and purified by chromatography (petroleum ether/ether, 95:5) to give 0.75 g (62%) of 1-acetyl-4-bromonaphthalene as a brown oil: 1H NMR (300 MHz, CDCl3) delta 2.74 (s, 3H), 7.65-7.69 (m, 2H), 7.74 (d, J = 6 Hz, 1H), 7.83 (d, J = 6 Hz, 1H), 8.32-8.35 (m, 1H), 8.72-8.75 (m, 1H); 13C NMR (75.5 MHz, CDCl3) delta 30.1, 126.4, 127.5, 127.8, 128.2, 128.4, 128.7, 128.7, 131.2, 132.3, 135.2, 201.0; GC/MS (EI) m/z (rel intensity) 248 (46), 233 (100), 205 (44). The data agree in all respects with those reported previously.

References: [1]Patent: WO2005/82367,2005,A1 .Location in patent: Page/Page column 64-65.
[2]Patent: US2011/152246,2011,A1 .Location in patent: Page/Page column 110; 111.
[3]Canadian Journal of Chemistry,1981,vol. 59,p. 2629 - 2641.
[4]Canadian Journal of Chemistry,1995,vol. 73,p. 885 - 895.
[5]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 2067 - 2081.
[6]Chemische Berichte,1891,vol. 24,p. 550.
[7]Journal of Organic Chemistry,1946,vol. 11,p. 27,30.
[8]Journal of Organic Chemistry,2005,vol. 70,p. 9036 - 9039.
[9]Angewandte Chemie - International Edition,2019,vol. 58,p. 302 - 306.
Angew. Chem.,2019,vol. 131,p. 308 - 312,5.

3
[ 90-11-9 ]
[ 108-24-7 ]
[ 46258-62-2 ]

References: [1]Israel Journal of Chemistry,1963,vol. 1,p. 1 - 11.

4
[ 544-92-3 ]
[ 46258-62-2 ]
[ 29139-00-2 ]

References: [1]Canadian Journal of Chemistry,1995,vol. 73,p. 885 - 895.
[2]Bulletin of the Chemical Society of Japan,1975,vol. 48,p. 3347 - 3355.
[3]Magnetic Resonance in Chemistry,1990,vol. 28,p. 257 - 260.

5
[ 46258-62-2 ]
[ 58149-70-5 ]

Yield	Reaction Conditions	Operation in experiment
68%	With sodium tetrahydroborate; In methanol; at 60℃; for 1.5h;	A solution of 1 -(4-bromonaphthalen- 1 -yl)ethanone (260 mg, 1.044 mmol) in methanol (5 ml) was treated with sodium borohydride (158 mg, 4.17 mmol). The mixture was allowed to heat at 60 Cfor 1.5 hr. The reaction was diluted with water and partitioned between ethyl acetate and water. Theorganic layer was collected, dried, filted and concentrated. Purification by 5i02 chromatography (0-30% EtOAC-hexanes) provided 1-(4-bromonaphthalen-1-yl)ethanol as a white solid (180 mg, 68%yield). 1H NMR (400 MHz, Chloroform-d) 8.31 (dd, J = 7.3, 2.2 Hz, 1H), 8.16 - 8.08 (m, 1H),7.84 - 7.74 (m, 1H), 7.66 - 7.50 (m, 3H), 5.71 - 5.61 (m, 1H), 1.70 - 1.63 (m, 4H).

References: [1]Patent: WO2016/11019,2016,A1 .Location in patent: Page/Page column 78.
[2]Bulletin of the Chemical Society of Japan,1975,vol. 48,p. 3347 - 3355.
[3]Israel Journal of Chemistry,1963,vol. 1,p. 1 - 11.

6
[ 141-78-6 ]
[ 46258-62-2 ]
[ 131513-65-0 ]

References: [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 124 - 135.

7
[ 46258-62-2 ]
[ 16650-55-8 ]

References: [1]Canadian Journal of Chemistry,1981,vol. 59,p. 2629 - 2641.
[2]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 2067 - 2081.

8
[ 46258-62-2 ]
[ 16650-55-8 ]
[ 32405-50-8 ]

References: [1]Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical and Analytical,1980,vol. 19,p. 646 - 649.

9
[ 3240-34-4 ]
[ 46258-62-2 ]
Acetic acid 2-(4-bromo-naphthalen-1-yl)-2-oxo-ethyl ester [ No CAS ]

References: [1]Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical and Analytical,1984,vol. 23,p. 1008 - 1010.
[2]Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical and Analytical,1984,vol. 23,p. 1008 - 1010.

10
[ 46258-62-2 ]
[ 50637-92-8 ]

12
[ 46258-62-2 ]
diluted aqueous nitric acid [ No CAS ]
[ 16650-55-8 ]

References: [1]Bulletin de l'Academie Polonaise des Sciences, Serie des Sciences Chimiques,1931,vol. <A>,p. 59,65.

14
[ 75-15-0 ]
[ 7446-70-0 ]
[ 90-11-9 ]
[ 75-36-5 ]
[ 46258-62-2 ]

References: [1]Journal of Organic Chemistry,1946,vol. 11,p. 27,30.

15
[ 74262-49-0 ]
[ 46258-62-2 ]
1-[4-(2-cyano-2-piperidinoethenyl)naphthalenyl]ethanone [ No CAS ]

References: [1]New Journal of Chemistry,2001,vol. 25,p. 1605 - 1609.

16
[ 383-63-1 ]
[ 46258-62-2 ]
[ 695176-26-2 ]

Yield	Reaction Conditions	Operation in experiment
58%		Example 6; Step 1; Synthesis of 4-bromo-1-naphthoyltrifluoroacetone: Ethyltrifluoroacetate (6.91 g, 49 mmol) was added dropwise to an ether (10 mL) solution containing sodium t-butoxide (6.7 g, 52 mmol), which formed a slurry. The <strong>[46258-62-2]4-bromo-1-acetylnaphthalene</strong> (12.2 g, 49 mmol) was added to the slurry in several large additions and the solution was allowed to stir for 18 hours. The solution was diluted with additional ether (50 mL) and was washed with 1 M hydrochloric acid (2×50 mL). The ethereal solution was dried over magnesium sulfate, filtered and the solvent removed. The 4-bromonapthoyltrifluoroacetone could was separated from the unreacted <strong>[46258-62-2]4-bromo-1-acetylnaphthalene</strong> by forming the copper bis(diketonate) from a methanolic solution of the raw beta-diketone and cupric chloride. The first band collected resulted in a yellow powder (9.8 g, 58% yield) upon solvent removal. 1H-NMR (90 MHz, 25 C., CDCl3): delta 14.15 (s, 1 H), 8.40 (m, 2 H), 7.67 (m, 4 H), 6.47 (s, 1 H). Anal.: (found/calc for C17H14O2) 81.71 (81.58), H 5.65 (5.59).

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 9036 - 9039.
[2]Patent: US2006/69288,2006,A1 .Location in patent: Page/Page column 10.

17
[ 46258-62-2 ]
[ 552-89-6 ]
(NO₂)C₆H₄CHCHC(O)C₁₀H₆Br [ No CAS ]