* 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.
Reference：
[1] Journal of Fluorine Chemistry, 1989, vol. 43, p. 35 - 52
[2] Journal of the Chemical Society, 1948, p. 1231,1233
[3] Journal fuer Praktische Chemie (Leipzig), 1889, vol. <2> 39, p. 486
2
[ 42872-73-1 ]
[ 131002-03-4 ]
[ 7697-27-0 ]
Reference：
[1] Journal of the Chemical Society, 1956, p. 776
3
[ 42872-73-1 ]
[ 824-54-4 ]
Reference：
[1] Angewandte Chemie - International Edition, 2017, vol. 56, # 9, p. 2473 - 2477[2] Angew. Chem., 2017, vol. 129, p. 2513 - 2517,5
4
[ 42872-73-1 ]
[ 93012-36-3 ]
Reference：
[1] Journal of the Chemical Society, 1948, p. 1231,1233
5
[ 131002-03-4 ]
[ 42872-73-1 ]
Yield
Reaction Conditions
Operation in experiment
98%
With phosphorus pentoxide In chloroform for 12 h; Reflux
Example 10 2-Bromo-4-methylbenzonitrile To a suspension of 2-bromo-4-methylbenzamide (14.8 g, 69.1 mmol) in CHCl3 was added phosphorous pentoxide (24.5 g, 172.8 mmol) and the mixture keep refluxing for 12 h. The reaction was allowed to cool to room temperature, and put into the ice water under the condition of stirring. The organic layer was separated and the aqueous layer was extracted with CHCl3 (150 mL*2). The combined organic phase was washed with brine, and dried over Na2SO4. Evaporation of the solvent afforded the title compound, 2-bromo-4-methylbenzonitrile (13.3 g, 98percent). 1H NMR (400 MHz, CDCl3) δ 2.41 (s, 3H), 7.20 (d, J=8.0 Hz, 1H), 7.51-7.54 (m, 2H).
98%
With phosphorus pentoxide In chloroform for 12 h; Reflux
Example 10 2-Bromo-4-methylbenzonitrile To a suspension of 2-bromo-4-methylbenzamide (14.8 g, 69.1 mmol) in CHCl3 was added phosphorous pentoxide (24.5 g, 172.8 mmol) and the mixture keep refluxing for 12 h. The reaction was allowed to cool to room temperature, and put into the ice water under the condition of stirring. The organic layer was separated and the aqueous layer was extracted with CHCl3 (150 mL*2). The combined organic phase was washed with brine, and dried over Na2SO4. Evaporation of the solvent afforded the title compound, 2-bromo-4-methylbenzonitrile (13.3 g, 98percent). 1H NMR (400 MHz, CDCl3) δ 2.41 (s, 3H), 7.20 (d, J=8.0 Hz, 1H), 7.51-7.54 (m, 2H).
98%
With phosphorus pentoxide In chloroform for 12 h; Reflux
Example 13 2-Bromo-4-methylbenzonitrile To a suspension of 2-bromo-4-methylbenzamide (14.8 g, 69.1 mmol) in CHCl3 was added phosphorous pentoxide (24.5 g, 172.8 mmol) and the mixture keep refluxing for 12 h. The reaction was allowed to cool to room temperature, and put into the ice water under the condition of stirring. The organic layer was separated and the aqueous layer was extracted with CHCl3 (150 mL*2). The combined organic phase was washed with brine, and dried over Na2SO4. Evaporation of the solvent afforded the title compound, 2-bromo-4-methylbenzonitrile (13.3 g, 98percent). 1H NMR (400 MHz, CDCl3): δ 2.41 (s, 3H), 7.20 (d, J=8.0 Hz, 1H), 7.51-7.54 (m, 2H).
98%
With phosphorus pentoxide In chloroform for 12 h; Reflux
Example 10 2-Bromo-4-methylbenzonitrileTo a suspension of 2-bromo-4-methylbenzamide (14.8 g, 69.1 mmol) in CHCI3 was added phosphorous pentoxide (24.5 g, 172.8 mmol) and the mixture keep refluxing for 12 h. The reaction was allowed to cool to room temperature, and put into the ice water under the condition of stirring.The organic layer was separated and the aqueous layer was extracted with CHCI3 (150 mL x 2).The combined organic phase was washed with brine, and dried over Na2SOzI. Evaporation of the solvent afforded the title compound, 2-bromo-4-methylbenzonitrile (13.3 g, 98percent). 1H NMR (400MHz, CDCl3) δ 2.41 (s, 3 H), 7.20 (d, J=8.0 Hz, 1 H), 7.51-7.54 (m, 2 H).
84%
Stage #1: for 4 h; Heating / reflux Stage #2: at 0℃; for 0.166667 h;
2-Bromo-4-methylbenzonitriIe (TJA02020) C8H6BrN MW 196.04. Phosphorus oxychloride (22.6 mL, 243 mmol), TJA02017 (4.00 g, 18.7 mmol) and sodium chloride (2.40 g, 41.1 mmol) were loaded to a 100 mL r.b. flask and set to reflux with stirring for 4 h. The mixture was allowed to cool and excess phosphorus oxychloride was removed via a rotary evaporator. The resultant brown residues were poured into iced water with stirring and left for 10 min. A brown ppt. had formed and was collected via filtration, washed thoroughly with distilled H2O and dried under vacuum at 70 °C.Recrystallisation (hexane) yielded the title compound as a white crystalline solid (3.07 g,84 percent), mp 49.9-51.9 0C;1H NMR (270 MHz, CDCl3) δ 2.40 (3H, s, ArH), 7.18-7.22 (IH, d, J= 8.6 Hz, ArH) and7.49-7.54 (2H, m, AJγH);13C NMR (67.9 MHz, CDCl3) δ 21.7 (CH3), 112.8 (C), 117.5 (C), 125.2 (C), 128.6 (CH),133.8 (CH), 134.1 (CH) and 145.5 (C); HPLC (70 percent CH3CN in H2O) tτ =4.917 (99.75 percent);LCMS (APCI)5 m/z 198.07 (81BrM+ + H, 100 percent), 196.07 (79BrM+ + H, 98 percent).
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 4h;Reflux;
Example 11 2-Bromo-4-(bromomethyl)benzonitrile A mixture of <strong>[42872-73-1]2-bromo-4-methylbenzonitrile</strong> (13.3 g, 81.4 mmol), NBS (14.4 g, 84.4 mmol) and BPO (0.20 g) in CCl4 (150 mL) was heated for 4 h at reflux. The reaction mixture was cooled to room temperature and filtered. Then the solid was washed with CCl4 (20 mL*2) and the combined filtrates were washed successively with saturated sodium bicarbonate (50 mL), water (2*100 mL) and sodium thiosulfate (50 mL). The organic phase was dried over NaSO4 and concentrated in vacuum afforded the titled compound, 2-bromo-4-(bromomethyl)benzonitrile (18.7 g, 100%).
100%
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 4h;Reflux;
Example 11 2-Bromo-4-(bromomethyl)benzonitrile A mixture of <strong>[42872-73-1]2-bromo-4-methylbenzonitrile</strong> (13.3 g, 81.4 mmol), NBS (14.4 g, 84.4 mmol) and BPO (0.20 g) in CCl4 (150 mL) was heated for 4 h at reflux. The reaction mixture was cooled to room temperature and filtered. Then the solid was washed with CCl4 (20 mL*2) and the combined filtrates were washed successively with saturated sodium bicarbonate (50 mL), water (2*100 mL) and sodium thiosulfate (50 mL). The organic phase was dried over NaSO4 and concentrated in vacuum afforded the titled compound, 2-bromo-4-(bromomethyl)benzonitrile (18.7 g, 100%).
100%
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 4h;Heating; Reflux;
Example 14 2-Bromo-4-(bromomethyl)benzonitrile A mixture of <strong>[42872-73-1]2-bromo-4-methylbenzonitrile</strong> (13.3 g, 81.4 mmol), NBS (14.4 g, 84.4 mmol) and BPO (0.20 g) in CCl4 (150 mL) was heated for 4 h at reflux. The reaction mixture was cooled to room temperature and filtered. Then the solid was washed with CCl4 (20 mL*2) and the combined filtrate was washed successively with saturated sodium bicarbonate (50 mL), water (2*100 mL) and sodium thiosulfate (50 mL). The organic phase was dried over Na2SO4 and concentrated in vacuum afforded the titled compound, 2-bromo-4-(bromomethyl)benzonitrile (18.7 g, 100%).
100%
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 4h;Reflux;
Example 11 2-Bromo-4-(bromomethyl)benzonitrileA mixture of <strong>[42872-73-1]2-bromo-4-methylbenzonitrile</strong> (13.3 g, 81.4 mmol), NBS (14.4 g, 84.4 mmol) and BPO (0.20 g) in CCl4 (150 mL) was heated for 4 h at reflux. The reaction mixture was cooled to room temperature and filtered. Then the solid was washed with CCl4 (20 mL x 2) and the combined filtrates were washed successively with saturated sodium bicarbonate (50 mL), water (2 x 100 mL) and sodium thiosulfate (50 mL). The organic phase was dried over NaSO4 and <n="124"/>concentrated in vacuum afforded the titled compound, 2-bromo-4-(bromomethyl)benzonitrile (18.7 g, 100%).
94%
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 4h;Heating / reflux;
2-Bromo-4-(bromomethyI)benzonitriIe (TJA02023) C8H5Br2N MW 274.94. TJA02020 (2.50 g, 12.8 mmol), N-bromosuccinimde (2.73 g, 14.4 mmol), benzyl peroxide (0.100 g, 0.410 mmol) and carbon tetrachloride (50 mL) were loaded to a 100 mL r.b. flask and set to reflux with stirring for 4 h. Allowed to cool. The succinimide was filtered off and carbon tetrachloride removed via a dry ice-acetone cooled rotary evaporator. The residues were dissolved in dichloromethane (50 mL) and washed with distilled H2O (50 mL x 3) and brine (50 mL x 2). Dried over MgSO4 and solvent removed in vacuo to leave yellow residues. Column chromatography (hexane/dichloromethane 60:40) eluted the title compound as a white crystalline solid (3.31 g, 94 %) of which (by HPLC) 23.39 % is TJA02020 and 1.32 % is 2-bromo-4-(dibromomethyl)benzonitrile.HPLC (70 % CH3CN in H2O) ttau= 4.150 (75.29 %); LCMS (APCI)5 m/z 276.06 (M+ + H, 40 %).
77%
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In 1,2-dichloro-ethane; for 5h;Reflux; Inert atmosphere;
After dissolving <strong>[42872-73-1]2-bromo-4-methylbenzonitrile</strong> (compound 12, Aldrich) (3.0 g, 15.3 mmol) in 1,2-dichloroethane (100 mL), N- bromosuccinimide (3.0 g, 16 , Azobisisobutyronitrile (1.0 g, 6.12 mmol), and the mixture was refluxed under heating in an argon atmosphere for 5 hours. After completion of the reaction, the reaction solution was concentrated under reduced pressure, and the obtained crude product was purified by silica gel column chromatography (eluent: n-hexane / dichloromethane = 2/1) to obtain Compound 13 (3.23 g, 11 .7 mmol, yield 77%).
60%
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; at 85℃; for 4h;
A solution of <strong>[42872-73-1]2-bromo-4-methylbenzonitrile</strong> (29 g, 151 mmol), benzoyl peroxide (2.2 g, 9.2 mmol), and N-bromosuccinimide (NBS) (34 g, 151 mmol) in CCI4 (500 mL) was stirred at 85C for 4 hours. The reaction mixture was cooled to 23C, filtered, and concentrated under reduced pressure. The residue was recrystallized form Petroleum Ether:EtOAc (10: 1 ) to afford 2-bromo- 4-(bromomethyl)benzonitrile as a white solid (25 g, 60%). MS (ESI) m/z: 274 [M+H]+.
With N-Bromosuccinimide; dibenzoyl peroxide; In benzene; at 80℃;
Description 42; 2-Bromo-4-(bromomethyl)benzonitrile (D42); NBS (9.57g, 0.054mol), and benzoylperoxide (130mg, 0.54mmol), were added to a solution of 4-methyl-2-bromo benzonitrile (9.Og, 0.046mol), in benzene (300ml). The reaction mixture was heated at 8O0C for 2hours. The reaction mixture was left to stand over night, heating at 8O0C was resumed for 8 hours. The reaction mixture was diluted with ethyl acetate (-20OmI) and water (~200ml), the layers were partitioned and the organic was passed through a phase separating cartridge and concentrated in vacuo. The residue was triturated with ether and the solid filtered to yield the title compound (6.48g, 0.024mol). deltaH (DMSO, 400 MHz): 8.00 (1 H, d), 7.96 (1 H, d), 7.67, (1 H, dd), 4.75, (2H, s).
4-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
62%
With potassium acetate;tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine; In 1,4-dioxane; at 80℃; for 12h;
Preparation of an Authentic Sample of 4-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaboryl)-benzonitrile; In a glove box, a 100 mL schlenk flask, equipped with a magnetic stirring bar, was charged with Pd2(dba)3 (13.8 mg, 0.015 mmol, 3 mol % Pd) and tricyclohexylphosphine (PCy3, 20.2 mg, 0.072 mmol, 7.2 mol %). Dioxane (6 mL) was added and the resulting mixture was stirred for 30 minutes at room temperature. B2Pin2 (280 mg, 1.1 mmol), KOAc (147 mg, 1.5 mmol), and <strong>[42872-73-1]2-bromo-4-methylbenzonitrile</strong> (196 mg, 1 mmol) were added successively. The schlenk flask was brought to a schlenk line. A condenser was attached, and the flask was flushed with nitrogen. The reaction mixture was stirred at 80 C. for 12 h. The mixture was treated with water (5 mL), and the product was extracted with ether, washed with brine, and dried over MgSO4. Kugelrohr distillation furnished the desired product (151 mg, 62%) as a colorless oil. Its spectral data matched the major isomer obtained from the catalytic borylation of 4-methylbenzonitrile described earlier.
In tetrahydrofuran; water; ethyl acetate; mineral oil;
Part 1 Preparation of tert-butyl ((tert-butoxycarbonyl)(4-cyanobenzyl)amino) methanoate: To a stirred suspension of sodium hydride (2.2 g, 56 mmol; 60% dispension in mineral oil) in THF (100 mL) was added <strong>[42872-73-1]2-bromo-p-tolunitrile</strong> (10 g, 51 mmol). To this mixture was slowly added a solution of di-t-butyl iminodicarboxylate (12.2 g, 56 mmol). After stirring for 20 hrs, the reaction mixture was diluted with a mixture of EtOAc (300 mL) and water (150 mL). The organic phase was dried over Na2SO4, and solvent evaporated to give the title compound as a solid (100% yield).
With phosphorus pentoxide; In chloroform; for 12h;Reflux;
Example 10 2-Bromo-4-methylbenzonitrile To a suspension of 2-bromo-4-methylbenzamide (14.8 g, 69.1 mmol) in CHCl3 was added phosphorous pentoxide (24.5 g, 172.8 mmol) and the mixture keep refluxing for 12 h. The reaction was allowed to cool to room temperature, and put into the ice water under the condition of stirring. The organic layer was separated and the aqueous layer was extracted with CHCl3 (150 mL*2). The combined organic phase was washed with brine, and dried over Na2SO4. Evaporation of the solvent afforded the title compound, 2-bromo-4-methylbenzonitrile (13.3 g, 98%). 1H NMR (400 MHz, CDCl3) delta 2.41 (s, 3H), 7.20 (d, J=8.0 Hz, 1H), 7.51-7.54 (m, 2H).
98%
With phosphorus pentoxide; In chloroform; for 12h;Reflux;
Example 10 2-Bromo-4-methylbenzonitrile To a suspension of 2-bromo-4-methylbenzamide (14.8 g, 69.1 mmol) in CHCl3 was added phosphorous pentoxide (24.5 g, 172.8 mmol) and the mixture keep refluxing for 12 h. The reaction was allowed to cool to room temperature, and put into the ice water under the condition of stirring. The organic layer was separated and the aqueous layer was extracted with CHCl3 (150 mL*2). The combined organic phase was washed with brine, and dried over Na2SO4. Evaporation of the solvent afforded the title compound, 2-bromo-4-methylbenzonitrile (13.3 g, 98%). 1H NMR (400 MHz, CDCl3) delta 2.41 (s, 3H), 7.20 (d, J=8.0 Hz, 1H), 7.51-7.54 (m, 2H).
98%
With phosphorus pentoxide; In chloroform; for 12h;Reflux;
Example 13 2-Bromo-4-methylbenzonitrile To a suspension of 2-bromo-4-methylbenzamide (14.8 g, 69.1 mmol) in CHCl3 was added phosphorous pentoxide (24.5 g, 172.8 mmol) and the mixture keep refluxing for 12 h. The reaction was allowed to cool to room temperature, and put into the ice water under the condition of stirring. The organic layer was separated and the aqueous layer was extracted with CHCl3 (150 mL*2). The combined organic phase was washed with brine, and dried over Na2SO4. Evaporation of the solvent afforded the title compound, 2-bromo-4-methylbenzonitrile (13.3 g, 98%). 1H NMR (400 MHz, CDCl3): delta 2.41 (s, 3H), 7.20 (d, J=8.0 Hz, 1H), 7.51-7.54 (m, 2H).
98%
With phosphorus pentoxide; In chloroform; for 12h;Reflux;
Example 10 2-Bromo-4-methylbenzonitrileTo a suspension of 2-bromo-4-methylbenzamide (14.8 g, 69.1 mmol) in CHCI3 was added phosphorous pentoxide (24.5 g, 172.8 mmol) and the mixture keep refluxing for 12 h. The reaction was allowed to cool to room temperature, and put into the ice water under the condition of stirring.The organic layer was separated and the aqueous layer was extracted with CHCI3 (150 mL x 2).The combined organic phase was washed with brine, and dried over Na2SOzI. Evaporation of the solvent afforded the title compound, 2-bromo-4-methylbenzonitrile (13.3 g, 98%). 1H NMR (400MHz, CDCl3) delta 2.41 (s, 3 H), 7.20 (d, J=8.0 Hz, 1 H), 7.51-7.54 (m, 2 H).
84%
2-Bromo-4-methylbenzonitriIe (TJA02020) C8H6BrN MW 196.04. Phosphorus oxychloride (22.6 mL, 243 mmol), TJA02017 (4.00 g, 18.7 mmol) and sodium chloride (2.40 g, 41.1 mmol) were loaded to a 100 mL r.b. flask and set to reflux with stirring for 4 h. The mixture was allowed to cool and excess phosphorus oxychloride was removed via a rotary evaporator. The resultant brown residues were poured into iced water with stirring and left for 10 min. A brown ppt. had formed and was collected via filtration, washed thoroughly with distilled H2O and dried under vacuum at 70 C.Recrystallisation (hexane) yielded the title compound as a white crystalline solid (3.07 g,84 %), mp 49.9-51.9 0C;1H NMR (270 MHz, CDCl3) delta 2.40 (3H, s, ArH), 7.18-7.22 (IH, d, J= 8.6 Hz, ArH) and7.49-7.54 (2H, m, AJgammaH);13C NMR (67.9 MHz, CDCl3) delta 21.7 (CH3), 112.8 (C), 117.5 (C), 125.2 (C), 128.6 (CH),133.8 (CH), 134.1 (CH) and 145.5 (C); HPLC (70 % CH3CN in H2O) ttau =4.917 (99.75 %);LCMS (APCI)5 m/z 198.07 (81BrM+ + H, 100 %), 196.07 (79BrM+ + H, 98 %).
With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; for 6h;Inert atmosphere; Reflux;
Example7.1 tert-butyl [4-(2-amino[1 ,2,4]triazolo[1 ,5-a]pyridin-6-yl)phenyl]carbamateTo a stirred solution of Int4.1 (500 mg) in toluene (7.5 ml) was added 2- bromo-4-methylbenzonitrile (1 .2 g), Pd2dba3 (140 mg) and rac-BINAP (191 mg). The flask was twice degased and backfilled with argon. The mixture was stirred at r.t. for 5 minutes. Caesium carbonate (2.5 g) was added, the flask was twice degased and backfilled with argon and the mixture was heated to reflux for 4h. Further Pd2dba3 (140 mg) and rac-BINAP (191 mg) was added, the flask was twice degased and backfilled with argon and the mixture was heated to reflux for 2h. Water was added and the reaction mixture was extracted with a mixture of dichloromethane and methanol (10: 1 ). The combined organic phases were washed with saturated sodium chloride solution, dried (sodium sulfate) and the solvent was removed in vacuum. Silica gel chromatography gave 205 mg of the title compound.1 H-NMR (400MHz, DMSO-d6): delta [ppm]= 1 .46 (s, 9H), 2.35 (s, 3H), 6.96 (dd, 1 H), 7.54 (d, 2H), 7.57 - 7.63 (m, 2H), 7.66 (d, 2H), 7.79 (s, 1 H), 7.87 (dd, 1 H), 9.04 (dd, 1 H), 9.34 (s, 1 H), 9.47 (s, 1 H).
With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; for 6h;Reflux; Inert atmosphere;
Intermediate Example Int7.1tert-butyl [4-(2-amino[1 ,2,4]triazolo[1 ,5-a]pyridin-6-yl)phenyl]carbamate To a stirred solution of Int4.1 (500 mg) in toluene (7.5 ml) was added <strong>[42872-73-1]2-bromo-4-methylbenzonitrile</strong> (1.2 g), Pd2dba3 (140 mg) and rac-BINAP (191 mg). The flask was twice degased and backfilled with argon. The mixture was stirred at r.t. for 5 minutes. Caesium carbonate (2.5 g) was added, the flask was twice degased and backfilled with argon and the mixture was heated to reflux for 4h. Further Pd2dba3 (140 mg) and rac-BINAP (191 mg) was added, the flask was twice degased and backfilled with argon and the mixture was heated to reflux for 2h. Water was added and the reaction mixture was extracted with a mixture of dichloromethane and methanol (10:1 ). The combined organic phases were washed with saturated sodium chloride solution, dried (sodium sulfate) and the solvent was removed in vacuum. Silica gel chromatography gave 205 mg of the title compound.1H-NMR (400MHz, DMSO-d6): delta [ppm]= 1.46 (s, 9H), 2.35 (s, 3H), 6.96 (dd, 1H), 7.54 (d, 2H), 7.57 - 7.63 (m, 2H), 7.66 (d, 2H), 7.79 (s, 1H), 7.87 (dd, 1 H), 9.04 (dd, 1H), 9.34 (s, 1 H), 9.47 (s, 1 H).
To a stirred solution of Int4.1 (500 mg) in toluene (7.5 ml) was added <strong>[42872-73-1]2-bromo-4-methylbenzonitrile</strong> (1.2 g), Pd2dba3 (140 mg) and rac-BINAP (191 mg). The flask was twice degased and backfilled with argon. The mixture was stirred at r.t. for 5 minutes. Caesium carbonate (2.5 g) was added, the flask was twice degased and backfilled with argon and the mixture was heated to reflux for 4h. Further Pd2dba3 (140 mg) and rac-BINAP (191 mg) was added, the flask was twice degased and backfilled with argon and the mixture was heated to reflux for 2h. Water was added and the reaction mixture was extracted with a mixture of dichloromethane and methanol (10:1). The combined organic phases were washed with saturated sodium chloride solution, dried (sodium sulfate) and the solvent was removed in vacuum. Silica gel chromatography gave 205 mg of the title compound. 1H-NMR (400MHz, DMSO-d6): delta [ppm]= 1.46 (s, 9H), 2.35 (s, 3H), 6.96 (dd, 1H), 7.54 (d, 2H), 7.57 - 7.63 (m, 2H), 7.66 (d, 2H), 7.79 (s, 1 H), 7.87 (dd, 1 H), 9.04 (dd, 1 H), 9.34 (s, 1 H), 9.47 (s, 1H).
With caesium carbonate;tris(dibenzylideneacetone)dipalladium(0) chloroform complex; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; for 6h;Inert atmosphere; Reflux;
To a stirred solution of lnt4.1 (500 mg) in toluene (7.5 ml) was added <strong>[42872-73-1]2-bromo-4-methylbenzonitrile</strong> (1.2 g), Pd2dba3 (140 mg) and rac-BlNAP (191 mg). The flask was twice degased and backfilled with argon. The mixture was stirred at r.t. for 5 minutes. Caesium carbonate (2.5 g) was added, the flask was twice degased and backfilled with argon and the mixture was heated to reflux for 4h. Further Pd2dba3 (140 mg) and rac-BINAP (191 mg) was added, the flask was twice degased and backfilled with argon and the mixture was heated to reflux for 2h. Water was added and the reaction mixture was extracted with a mixture of dichloromethane and methanol (10:1). The combined organic phases were washed with saturated sodium chloride solution, dried (sodium sulfate) and the solvent was removed in vacuum. Silica gel chromatography gave 205 mg of the title compound. 1H-NMR (400MHz, DMSO-d6): delta [ppm]= 1.46 (s, 9H), 2.35 (s, 3H), 6.96 (dd, 1 H), 7.54 (d, 2H), 7.57 - 7.63 (m, 2H), 7.66 (d, 2H), 7.79 (s, 1H), 7.87 (dd, 1H), 9.04 (dd, 1 H), 9.34 (s, 1 H), 9.47 (s, 1 H).
General procedure: A solution of 5-chloro-2-fluoro-benzonitrile (3.60 g, 23.1 mmol) in DMF (46 ml) was cooled to 0C. Potassium carbonate (9.60 g, 69.4 mmol) was added thereto under nitrogen atmosphere, and the mixture was stirred at room temperature for five minutes. Ethanethiol (2.05 ml, 27.8 mmol) was added thereto, and the mixture was stirred at room temperature for three hours. Ethyl acetate was added to the reaction mixture. After washing with brine, the organic layer was dried over anhydrous magnesium sulfate. The drying agent was removed by filtration, and the residue obtained after concentration under reduced pressure was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (4.57 g, quant.) as a colorless solid. The title compound was synthesized from <strong>[42872-73-1]2-bromo-4-methyl-benzonitrile</strong> under the same conditions as for Compound 1. However, the reaction was performed at 90C instead of room temperature.
With copper(l) iodide; potassium carbonate; In toluene; at 120℃; for 12h;Schlenk technique; Inert atmosphere;
4-methyl-2-bromophenyl-carbonitrile (97.5mg, 0.5mmol), copper iodide (18.9mg, 0.1mmol), potassium carbonate (60.0mg, 1.5mmol), methyl phenyl ketone (90.0mg, after 0.75 mmol) were added to a Schlenk reaction flask, vacuum, purged with nitrogen three times, in a nitrogen atmosphere, toluene was added 4.0mL, 120C for 12 hours. after completion of the reaction, the solvent was removed under reduced pressure, column chromatography (elution off with petroleum ether: ethyl acetate = 20: 1, V: V ), to give the product as a white solid 0.116g, 98% yield.
2-(dibromofluoromethyl)-4-methylbenzonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
30%
General procedure: To a stirred mixture of Ar-X (1, 1.0 mmol) and lithium bromide (208 mg, 2.4 mmol) in THF (3.5mL) was added dropwise a solution of i-PrMgBr in THF (2.0 M, 0.53 mL, 1.06 mmol) at -40C under Ar and the resulting mixture was stirred at -40C for 10 min and at room temperature for 3 h. To a stirred solution of dibromodifluoromethane (CF2Br2) in THF (4.90 M, 0.49 mL and 2.4 mmol) was added dropwise the prepared solution of ArMgBr 2 in THF via cannula at between room temperature and 35C over 1 min. and the resulting solution was stirred for 1 h. The reaction was quenched with saturated aqueous NH4Cl (10 mL) and extracted with EtOAc (10 mL×3). The combined extracts were dried over Na2SO4. Concentration of the solvent in vacuo afforded a residue, which was purified by silica gel column chromatography (hexane/EtOAc=10/1) and recycle GPC to give alpha,alpha-dibromo-alpha-fluorotoluene derivative 8.
15%
4-iodobenzonitrile (229.0mg, 1.0mmol) and a lithium bromide (208.4 mg, 2.4mmol) were added to THF (3.5ml) under argon atmosphere, and it cooled at -40 degrees C. The THF solution(0.7M, 1.5 ml, 1.05mmol) of isopropylmagnesium bromide was added to theobtained mixed solution, and it stirred for 20 minutes. Then, stirring was performed for the reaction solution at -40 degree C for 3 hours, and the THF solution of 4-cyanophenyl magnesium bromide was prepared. The prepared THF solution of 4-cyanophenyl magnesium bromide was dropped at the THF solution(2.46M, 980microl, 2.4mmol) of dibromodifluoromethane at 20 degrees C, andstirring was performed for 30 minutes at 20 degrees C. The reaction liquid saturated ammonium chloride solution (2. 0 ml) is added, extracted with ethyl acetate. The organic layer, washed with saturated sodium chloride solution and water, after drying, somas concd. is depressurized. The crude product is silica gel column chromatography (ethyl acetate normalhexane) by recycling and purifying a GPC (chloroform), 4-(dibromonitro fluoromethylnucleoside) trifluoromethylbenzonitrile (101. 9 mg, 41%)obtained as a white solid. The THF solution of 2-cyano5-methylphenyl magnesium bromide was prepared under lithium bromide (208.4-mg,2.4mmol) existence like working-example-14 using 2-bromo 4-methylbenzonitrile(196.0 mg, 1.0mmol). The THF solution and dibromodifluoromethane of 2-cyano-5-methylphenyl magnesium bromide which were prepared were made to react, and 2-(dibromofluoromethyl)-4-methylbenzonitrile
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