* 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.
With lithium hexamethyldisilazane In tetrahydrofuran; hexane at 5 - 20℃; for 1 h; Green chemistry
General procedure: To a solution of o-aminophenol (400 mg, 3.67 mmol) and NCTS (998 mg, 3.67 mmol) in THF (6 mL), 1 M LiHMDS in hexane (3.67 mL, 3.67 mmol) was added and stirred at 5 °C to r.t. for 1h. Then the reaction mixture was poured in ice water and stirred for 15 min. Then extracted with EtOAc, the organic layer was separated. The organic layer was washed with brine solution.Then organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtained pure 2-aminobenzaxozole in 90percent yield (471 mg).
With lithium hexamethyldisilazane In tetrahydrofuran; hexane at 5 - 20℃; for 1 h; Green chemistry
General procedure: To a solution of o-aminophenol (400 mg, 3.67 mmol) and NCTS (998 mg, 3.67 mmol) in THF (6 mL), 1 M LiHMDS in hexane (3.67 mL, 3.67 mmol) was added and stirred at 5 °C to r.t. for 1h. Then the reaction mixture was poured in ice water and stirred for 15 min. Then extracted with EtOAc, the organic layer was separated. The organic layer was washed with brine solution.Then organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtained pure 2-aminobenzaxozole in 90percent yield (471 mg).
Reference：
[1] Chemistry - A European Journal, 2011, vol. 17, # 15, p. 4217 - 4222
4
[ 55305-43-6 ]
[ 38191-34-3 ]
[ 52112-66-0 ]
Yield
Reaction Conditions
Operation in experiment
94%
With lithium hexamethyldisilazane In tetrahydrofuran; hexane at 5 - 20℃; for 1 h; Green chemistry
General procedure: To a solution of o-aminophenol (400 mg, 3.67 mmol) and NCTS (998 mg, 3.67 mmol) in THF (6 mL), 1 M LiHMDS in hexane (3.67 mL, 3.67 mmol) was added and stirred at 5 °C to r.t. for 1h. Then the reaction mixture was poured in ice water and stirred for 15 min. Then extracted with EtOAc, the organic layer was separated. The organic layer was washed with brine solution.Then organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtained pure 2-aminobenzaxozole in 90percent yield (471 mg).
Reference：
[1] Journal of Organic Chemistry, 2017, vol. 82, # 7, p. 3530 - 3537
6
[ 55305-43-6 ]
[ 192182-54-0 ]
[ 19179-31-8 ]
Reference：
[1] Angewandte Chemie - International Edition, 2011, vol. 50, # 2, p. 519 - 522
7
[ 5798-75-4 ]
[ 55305-43-6 ]
[ 7153-22-2 ]
Yield
Reaction Conditions
Operation in experiment
49%
With palladium dichloride; silver(l) oxide In ethanol at 70℃; for 24 h;
General procedure: b.Cyanation of aryl bromides. To a solution of arylbromide (0.5 mmol) in EtOH (5.0 mL) was added NCTS (272 mg, 1.0 mmol), PdCl2 (13.3 mg, 0.075 mmol), and Ag2O (57.75 mg, 0.5 mmol). The mixture was stirred at 70 for 24 hunder air atmosphere. Then the reaction mixture was cooled to room temperature and filtered through a pad of celite (1.0 g) and rinsed with CH2Cl2 (10.0 mL). The resulting organic solution was concentrated under reduced pressure and further purified by flash chromatography (SiO2,petroleum ether/EtOAc gradient), yielding the corresponding aryl nitriles.
Reference：
[1] Tetrahedron Letters, 2016, vol. 57, # 11, p. 1205 - 1209
[2] Advanced Synthesis and Catalysis, 2015, vol. 357, # 16-17, p. 3419 - 3423
8
[ 51934-41-9 ]
[ 55305-43-6 ]
[ 7153-22-2 ]
Yield
Reaction Conditions
Operation in experiment
36%
With palladium dichloride; silver(l) oxide In ethanol at 70℃; for 24 h;
General procedure: a.Cyanation of aryl iodides.To a solution of aryl iodide (0.5 mmol) in EtOH (5.0 mL) was added NCTS (272 mg, 1.0 mmol), PdCl2 (13.3mg, 0.075 mmol), and Ag2O (57.75 mg, 0.5 mmol). The mixture was stirred at 70 for 24 h under air atmosphere. Then the reaction mixture was cooled to room temperature and filtered through a pad of celite (1.0 g) and rinsed with CH2Cl2 (10.0 mL). The resulting organic solution was concentrated under reduced pressure and further purified by flash chromatography (SiO2, petroleum ether/EtOAc gradient), yielding the corresponding aryl nitriles.
Stage #1: at 20℃; Schlenk technique Stage #2: for 0.416667 h; Schlenk technique
Dry 250 ml Schlenk flask was a solution of phenylurea (10.9 g, 8 mmol) in pyridine (54 mL). The flask was stirred in room temperature water bath. p-Toluenesulfonyl chloride (52.8 g, 27.7 mmol) was added potion wise over 5 minutes. The reaction mixture was stirred for another additional 20 minutes and poured into to ice-cooled water (400 mL) with mechanical stirring. Precipitate formed during mechanical stirring was filtered and then washed with water. The crude product was treated with 50 ml of ethanol and precipitated from the same solvent. The precipitate was purified with column chromatography using heptane:EtOAc (15:1) as eluent to yield N-cyano-N-phenyl-p-methylbenzenesulfonamide as colorless solid (16.5 g, 76percent).
65%
at 20℃; for 0.5 h; Inert atmosphere
The synthesis was performed under nitrogenatmosphere. N‐Phenylurea (5.46 g, 40.1 mmol) was dissolved in anhydrous pyridine (30 mL) andp‐toluenesulfonyl chloride (26.4 g, 139 mmol) was added successively. The mixture was stirred for30 min at room temperature, poured into ice water and stirred for 5 min. The precipitate wasoff and washed with water. Recrystallization from ethanol yielded colourless crystals (7.06 g, 65percent).m.p.: 83‐85 °C (lit.: 85‐87 °C [7]); IR (KBr): λmax 2233 cm‐1 (C≡N); 1H‐NMR (DMSO‐d6, 400.4 MHz): δ(ppm) = 2.45 (s, 3H, CH3), 7.19 – 7.31 (m, 2H, Ar‐H), 7.43 – 7.61 (m, 5H, Ar‐H), 7.62 – 7.72 (m, 2H,Ar‐H); 13C‐NMR (DMSO‐d6, 100.7 MHz): δ (ppm) = 21.2 (CH3), 126.3 (2C), 128.1 (2C), 130.3 (2C),130.5, 130.7 (2C) (CH), 108.3, 131.2, 133.7, 147.3 (C); C14H12N2O2S (272.32).
Reference：
[1] Angewandte Chemie - International Edition, 2011, vol. 50, # 2, p. 519 - 522
[2] Chemistry - A European Journal, 2011, vol. 17, # 15, p. 4217 - 4222
[3] Advanced Synthesis and Catalysis, 2015, vol. 357, # 16-17, p. 3419 - 3423
[4] Tetrahedron Letters, 2016, vol. 57, # 11, p. 1205 - 1209
[5] Organic Letters, 2016, vol. 18, # 5, p. 1100 - 1103
[6] Organic Letters, 2017, vol. 19, # 14, p. 3835 - 3838
[7] Organic Letters, 2018, vol. 20, # 17, p. 5282 - 5285
[8] Molecules, 2018, vol. 23, # 2,
[9] Journal of the Chemical Society, 1949, p. 1034,1036
11
[ 64-10-8 ]
[ 98-09-9 ]
[ 55305-43-6 ]
Reference：
[1] Journal of the American Chemical Society, 2013, vol. 135, # 29, p. 10630 - 10633
[2] Chemical Communications, 2015, vol. 51, # 59, p. 11848 - 11851
12
[ 98-59-9 ]
[ 622-34-4 ]
[ 55305-43-6 ]
Reference：
[1] Journal of the Chemical Society, 1949, p. 1034,1036
13
[ 98-59-9 ]
[ 103-85-5 ]
[ 55305-43-6 ]
Reference：
[1] Journal of the Chemical Society, 1950, p. 3269,3273
Reference：
[1] Chemistry - A European Journal, 2011, vol. 17, # 15, p. 4217 - 4222
21
[ 1422-53-3 ]
[ 55305-43-6 ]
[ 77532-79-7 ]
Reference：
[1] Chemistry - A European Journal, 2011, vol. 17, # 15, p. 4217 - 4222
22
[ 452-63-1 ]
[ 55305-43-6 ]
[ 147754-12-9 ]
Reference：
[1] Advanced Synthesis and Catalysis, 2015, vol. 357, # 16-17, p. 3419 - 3423
23
[ 55305-43-6 ]
[ 1575-37-7 ]
[ 791595-74-9 ]
Yield
Reaction Conditions
Operation in experiment
60%
With lithium hexamethyldisilazane In tetrahydrofuran; hexane at 5 - 20℃; for 1 h; Green chemistry
General procedure: To a solution of o-aminophenol (400 mg, 3.67 mmol) and NCTS (998 mg, 3.67 mmol) in THF (6 mL), 1 M LiHMDS in hexane (3.67 mL, 3.67 mmol) was added and stirred at 5 °C to r.t. for 1h. Then the reaction mixture was poured in ice water and stirred for 15 min. Then extracted with EtOAc, the organic layer was separated. The organic layer was washed with brine solution.Then organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtained pure 2-aminobenzaxozole in 90percent yield (471 mg).
Stage #1: phenyl carbamate With pyridine at 20℃; Schlenk technique;
Stage #2: p-toluenesulfonyl chloride for 0.416667h; Schlenk technique;
(II) General synthesis of N-cyano-N-phenyl-p-methylbenzenesulfonamide (NCTS): (see reference 2)
Dry 250 ml Schlenk flask was a solution of phenylurea (10.9 g, 8 mmol) in pyridine (54 mL). The flask was stirred in room temperature water bath. p-Toluenesulfonyl chloride (52.8 g, 27.7 mmol) was added potion wise over 5 minutes. The reaction mixture was stirred for another additional 20 minutes and poured into to ice-cooled water (400 mL) with mechanical stirring. Precipitate formed during mechanical stirring was filtered and then washed with water. The crude product was treated with 50 ml of ethanol and precipitated from the same solvent. The precipitate was purified with column chromatography using heptane:EtOAc (15:1) as eluent to yield N-cyano-N-phenyl-p-methylbenzenesulfonamide as colorless solid (16.5 g, 76%).
74%
With pyridine at 20℃; for 0.25h;
74%
With pyridine at 25℃; for 0.25h; Sealed tube; Inert atmosphere;
74%
With pyridine at 25℃; for 0.333333h; Sealed tube; Inert atmosphere;
65%
With pyridine at 20℃; for 0.5h; Inert atmosphere;
N-Cyano-N-phenyl-p-toluenesulfonamide (12)
The synthesis was performed under nitrogenatmosphere. N-Phenylurea (5.46 g, 40.1 mmol) was dissolved in anhydrous pyridine (30 mL) andp-toluenesulfonyl chloride (26.4 g, 139 mmol) was added successively. The mixture was stirred for30 min at room temperature, poured into ice water and stirred for 5 min. The precipitate wasoff and washed with water. Recrystallization from ethanol yielded colourless crystals (7.06 g, 65%).m.p.: 83-85 °C (lit.: 85-87 °C [7]); IR (KBr): λmax 2233 cm-1 (C≡N); 1H-NMR (DMSO-d6, 400.4 MHz): δ(ppm) = 2.45 (s, 3H, CH3), 7.19 - 7.31 (m, 2H, Ar-H), 7.43 - 7.61 (m, 5H, Ar-H), 7.62 - 7.72 (m, 2H,Ar-H); 13C-NMR (DMSO-d6, 100.7 MHz): δ (ppm) = 21.2 (CH3), 126.3 (2C), 128.1 (2C), 130.3 (2C),130.5, 130.7 (2C) (CH), 108.3, 131.2, 133.7, 147.3 (C); C14H12N2O2S (272.32).
40%
With pyridine at 20℃; for 0.25h;
25 COMPOUND 29
To a solution of phenylurea (1Y) (1 g, 7.3 mmol, 1 eq.) in pyridine (5 mL) was added dropwise toluenesulfonyl chloride (4.90 g, 25.7 mmol, 3.71 mL, 3.5 eq.) at 20 °C. After addition, the mixture was stirred at 20 °C for 15 min. The reaction progress was monitored by TLC (PE:EA=1 : 1). Upon completion, the reaction was quenched by addition of ice-cooled water (30 mL) at 20 °C. The precipitate formed during stirring was filtered and washed with water. The solid was collected by filtration to give a crude product. The crude product was triturated with EtOH (5mL) at 20 °C for 30 min and then filtered to give 2Y (800 mg, 2.9 mmol, 40 % yield) as a white solid. NMR (400 MHz, CDCb) d: 7.64 (d, =8.3 Hz, 2 H), 7.33-7.45 (m, 5 H), 7.20 (d, =7.5 Hz, 2 H), 2.48 (s, 3 H).
Stage #1: 5-bromo-1-methyl-H-indole With magnesium; lithium chloride In tetrahydrofuran at 20℃; Inert atmosphere;
Stage #2: N-cyano-N-phenyl-p-toluenesulfonamide In tetrahydrofuran at 0 - 20℃; Inert atmosphere;
Stage #1: 1,2-(methylenedioxy)-4-bromobenzene With magnesium; lithium chloride In tetrahydrofuran at 20℃; Inert atmosphere;
Stage #2: N-cyano-N-phenyl-p-toluenesulfonamide In tetrahydrofuran at 0 - 20℃; Inert atmosphere;
0.291 g
Stage #1: 1,2-(methylenedioxy)-4-bromobenzene With 3-chloroprop-1-ene; trifluoroacetic acid; cobalt(II) bromide; zinc In acetonitrile at 20℃;
Stage #2: N-cyano-N-phenyl-p-toluenesulfonamide With zinc In acetonitrile at 0 - 50℃; Inert atmosphere;
With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; sodium acetate; silver(I) triflimide In 1,2-dichloro-ethane at 130℃; for 24h; Green chemistry;
3-(pyridin-2-yl)thiophene-2-carbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
With bromopentacarbonylmanganese(I); N-cyclohexyl-cyclohexanamine; zinc(II) chloride In 1,4-dioxane at 100℃; for 16h; Schlenk technique; Inert atmosphere;
85%
With silver hexafluoroantimonate; carbonyl(pentamethylcyclopentadienyl)cobalt diiodide; sodium acetate In 1,2-dichloro-ethane at 110℃; for 12h; Schlenk technique; Inert atmosphere; Sealed tube; regioselective reaction;
3-(pyridin-2-yl)thiophene-2-carbonitrile[ No CAS ]
3-(pyridin-2-yl)thiophene-2,4-dicarbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
1: 77%
2: 21%
With silver hexafluoroantimonate; carbonyl(η-5-cyclopentadienyl)diiodocobalt(III); potassium acetate In 1,2-dichloro-ethane at 120℃; for 16h; Inert atmosphere; Schlenk technique; chemoselective reaction;
With lithium hexamethyldisilazane; In tetrahydrofuran; hexane; at 5 - 20℃; for 1h;Green chemistry;
To a solution of o-aminophenol (400 mg, 3.67 mmol) and NCTS (998 mg, 3.67 mmol) in THF (6 mL), 1 M LiHMDS in hexane (3.67 mL, 3.67 mmol) was added and stirred at 5 °C to r.t. for 1h. Then the reaction mixture was poured in ice water and stirred for 15 min. Then extracted with EtOAc, the organic layer was separated. The organic layer was washed with brine solution.Then organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtained pure 2-aminobenzaxozole in 90percent yield (471 mg).
With lithium hexamethyldisilazane; In tetrahydrofuran; hexane; at 5 - 20℃; for 1.0h;Green chemistry;
General procedure: To a solution of o-aminophenol (400 mg, 3.67 mmol) and NCTS (998 mg, 3.67 mmol) in THF (6 mL), 1 M LiHMDS in hexane (3.67 mL, 3.67 mmol) was added and stirred at 5 C to r.t. for 1h. Then the reaction mixture was poured in ice water and stirred for 15 min. Then extracted with EtOAc, the organic layer was separated. The organic layer was washed with brine solution.Then organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtained pure 2-aminobenzaxozole in 90% yield (471 mg).
With lithium hexamethyldisilazane; In tetrahydrofuran; hexane; at 5 - 20℃; for 1h;Green chemistry;
General procedure: To a solution of o-aminophenol (400 mg, 3.67 mmol) and NCTS (998 mg, 3.67 mmol) in THF (6 mL), 1 M LiHMDS in hexane (3.67 mL, 3.67 mmol) was added and stirred at 5 C to r.t. for 1h. Then the reaction mixture was poured in ice water and stirred for 15 min. Then extracted with EtOAc, the organic layer was separated. The organic layer was washed with brine solution.Then organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtained pure 2-aminobenzaxozole in 90% yield (471 mg).
With lithium hexamethyldisilazane In tetrahydrofuran; hexane at 5 - 20℃; for 1h; Green chemistry;
Typical Experimental Procedure for the Synthesis of 2-Aminobenzaxozole from o-Aminophenol
General procedure: To a solution of o-aminophenol (400 mg, 3.67 mmol) and NCTS (998 mg, 3.67 mmol) in THF (6 mL), 1 M LiHMDS in hexane (3.67 mL, 3.67 mmol) was added and stirred at 5 °C to r.t. for 1h. Then the reaction mixture was poured in ice water and stirred for 15 min. Then extracted with EtOAc, the organic layer was separated. The organic layer was washed with brine solution.Then organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtained pure 2-aminobenzaxozole in 90% yield (471 mg).
With lithium hexamethyldisilazane; In tetrahydrofuran; hexane; at 5 - 20℃; for 1h;Green chemistry;
General procedure: To a solution of o-aminophenol (400 mg, 3.67 mmol) and NCTS (998 mg, 3.67 mmol) in THF (6 mL), 1 M LiHMDS in hexane (3.67 mL, 3.67 mmol) was added and stirred at 5 C to r.t. for 1h. Then the reaction mixture was poured in ice water and stirred for 15 min. Then extracted with EtOAc, the organic layer was separated. The organic layer was washed with brine solution.Then organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtained pure 2-aminobenzaxozole in 90% yield (471 mg).
With lithium hexamethyldisilazane In tetrahydrofuran; hexane at 5 - 20℃; for 1h; Green chemistry;
Typical Experimental Procedure for the Synthesis of 2-Aminobenzaxozole from o-Aminophenol
General procedure: To a solution of o-aminophenol (400 mg, 3.67 mmol) and NCTS (998 mg, 3.67 mmol) in THF (6 mL), 1 M LiHMDS in hexane (3.67 mL, 3.67 mmol) was added and stirred at 5 °C to r.t. for 1h. Then the reaction mixture was poured in ice water and stirred for 15 min. Then extracted with EtOAc, the organic layer was separated. The organic layer was washed with brine solution.Then organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtained pure 2-aminobenzaxozole in 90% yield (471 mg).
With lithium hexamethyldisilazane; In tetrahydrofuran; hexane; at 5 - 20℃; for 1.0h;Green chemistry;
General procedure: To a solution of o-aminophenol (400 mg, 3.67 mmol) and NCTS (998 mg, 3.67 mmol) in THF (6 mL), 1 M LiHMDS in hexane (3.67 mL, 3.67 mmol) was added and stirred at 5 C to r.t. for 1h. Then the reaction mixture was poured in ice water and stirred for 15 min. Then extracted with EtOAc, the organic layer was separated. The organic layer was washed with brine solution.Then organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtained pure 2-aminobenzaxozole in 90% yield (471 mg).
With lithium hexamethyldisilazane; In tetrahydrofuran; hexane; at 5 - 20℃; for 1h;Green chemistry;
General procedure: To a solution of o-aminophenol (400 mg, 3.67 mmol) and NCTS (998 mg, 3.67 mmol) in THF (6 mL), 1 M LiHMDS in hexane (3.67 mL, 3.67 mmol) was added and stirred at 5 °C to r.t. for 1h. Then the reaction mixture was poured in ice water and stirred for 15 min. Then extracted with EtOAc, the organic layer was separated. The organic layer was washed with brine solution.Then organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtained pure 2-aminobenzaxozole in 90percent yield (471 mg).
With lithium hexamethyldisilazane; In tetrahydrofuran; hexane; at 5 - 20℃; for 1.0h;Green chemistry;
General procedure: To a solution of o-aminophenol (400 mg, 3.67 mmol) and NCTS (998 mg, 3.67 mmol) in THF (6 mL), 1 M LiHMDS in hexane (3.67 mL, 3.67 mmol) was added and stirred at 5 °C to r.t. for 1h. Then the reaction mixture was poured in ice water and stirred for 15 min. Then extracted with EtOAc, the organic layer was separated. The organic layer was washed with brine solution.Then organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtained pure 2-aminobenzaxozole in 90percent yield (471 mg).
With lithium hexamethyldisilazane; In tetrahydrofuran; hexane; at 5 - 20℃; for 1h;Green chemistry;
General procedure: To a solution of o-aminophenol (400 mg, 3.67 mmol) and NCTS (998 mg, 3.67 mmol) in THF (6 mL), 1 M LiHMDS in hexane (3.67 mL, 3.67 mmol) was added and stirred at 5 C to r.t. for 1h. Then the reaction mixture was poured in ice water and stirred for 15 min. Then extracted with EtOAc, the organic layer was separated. The organic layer was washed with brine solution.Then organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtained pure 2-aminobenzaxozole in 90% yield (471 mg).
With lithium hexamethyldisilazane; In tetrahydrofuran; hexane; at 5 - 20℃; for 1h;Green chemistry;
General procedure: To a solution of o-aminophenol (400 mg, 3.67 mmol) and NCTS (998 mg, 3.67 mmol) in THF (6 mL), 1 M LiHMDS in hexane (3.67 mL, 3.67 mmol) was added and stirred at 5 °C to r.t. for 1h. Then the reaction mixture was poured in ice water and stirred for 15 min. Then extracted with EtOAc, the organic layer was separated. The organic layer was washed with brine solution.Then organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtained pure 2-aminobenzaxozole in 90percent yield (471 mg).
With lithium hexamethyldisilazane In 1,4-dioxane at 90 - 100℃; Inert atmosphere;
Generalprocess for the synthesis 2-amino 3- substituted quinazolinone derivatives (10a-10s):
General procedure: To the solution of isatoic anhydride (1.0eq) in 1,4 dioxane (4.0 ml), Amine ( 1.0eq) was added and then reaction mass temperature was raised to 90-100°C and maintained for 3-4 hrs, LiHMDS solution (3.0 eq) followed by N-cyano-4-methyl-N-phenylbenzenesulfonamide (NCTS) (1.0 eq) was added and reaction mass was further maintained for 10-12hrs at same temperature, reaction progress was monitored by TLC. After completion of the reaction, 20% aqueous ammonium chloride solution (5.0 ml) was added and reaction mass was diluted with ethyl acetate (10.0 ml). Ogranic layer was separated and aqueous layer extracted with ethyl acetate (4.0 ml). Combined organic layer was washed with water (4.0 ml) followed by 10% sodium chloride solution (4.0 ml). Solvent was evaporated under vacuum and crude material was purified by column chromatography in Ethyl acetate / hexane (3:7).
2-amino-3-cyclopropylquinazolin-4(3H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With lithium hexamethyldisilazane In 1,4-dioxane at 90 - 100℃; Inert atmosphere;
Generalprocess for the synthesis 2-amino 3- substituted quinazolinone derivatives (10a-10s):
General procedure: To the solution of isatoic anhydride (1.0eq) in 1,4 dioxane (4.0 ml), Amine ( 1.0eq) was added and then reaction mass temperature was raised to 90-100°C and maintained for 3-4 hrs, LiHMDS solution (3.0 eq) followed by N-cyano-4-methyl-N-phenylbenzenesulfonamide (NCTS) (1.0 eq) was added and reaction mass was further maintained for 10-12hrs at same temperature, reaction progress was monitored by TLC. After completion of the reaction, 20% aqueous ammonium chloride solution (5.0 ml) was added and reaction mass was diluted with ethyl acetate (10.0 ml). Ogranic layer was separated and aqueous layer extracted with ethyl acetate (4.0 ml). Combined organic layer was washed with water (4.0 ml) followed by 10% sodium chloride solution (4.0 ml). Solvent was evaporated under vacuum and crude material was purified by column chromatography in Ethyl acetate / hexane (3:7).
2-amino-3-(naphthalen-1-yl)quinazolin-4(3H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With lithium hexamethyldisilazane In 1,4-dioxane at 90 - 100℃; Inert atmosphere;
Generalprocess for the synthesis 2-amino 3- substituted quinazolinone derivatives (10a-10s):
General procedure: To the solution of isatoic anhydride (1.0eq) in 1,4 dioxane (4.0 ml), Amine ( 1.0eq) was added and then reaction mass temperature was raised to 90-100°C and maintained for 3-4 hrs, LiHMDS solution (3.0 eq) followed by N-cyano-4-methyl-N-phenylbenzenesulfonamide (NCTS) (1.0 eq) was added and reaction mass was further maintained for 10-12hrs at same temperature, reaction progress was monitored by TLC. After completion of the reaction, 20% aqueous ammonium chloride solution (5.0 ml) was added and reaction mass was diluted with ethyl acetate (10.0 ml). Ogranic layer was separated and aqueous layer extracted with ethyl acetate (4.0 ml). Combined organic layer was washed with water (4.0 ml) followed by 10% sodium chloride solution (4.0 ml). Solvent was evaporated under vacuum and crude material was purified by column chromatography in Ethyl acetate / hexane (3:7).
With silver hexafluoroantimonate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; water In acetone at 120℃; for 24h; Sealed tube; Inert atmosphere;
With silver hexafluoroantimonate; bis(1,5-cyclooctadiene)iridium(I) tetrafluoroborate; ammonium cerium (IV) nitrate; lanthanum(lll) triflate; XPhos at 80℃; for 12h;
1 Example 1
At room temperature,To a suitable amount of organic solvent PEG-200,100 mmol of the compound of formula (I) above,150 mmol of the compound of the above formula (II)20 mmol of catalyst (5 mmolAnd bis (1,5-cyclooctadiene) iridium tetrafluoroborate15 mM AgSbF6mixture),20 mmol of ligand Ll and 15 mmol of adjuvant (7.5 mmolLanthanum trifluoromethanesulfonate7.5mmolCeric ammonium nitrate) was added, and then the temperature was raised to 80 ° C and the reaction was stirred at that temperature for 12 hours;After completion of the reaction, the reaction system was filtered while hot, and an equal volume of a saturated aqueous solution of sodium carbonate was added to the filtrate.And then extracted with ethyl acetate for 2-3 times. The organic phases were combined, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography300-400 mesh silica gel column chromatography, the volume ratio of 1: 2 acetone and petroleum ether mixture of elution, resulting in the upperThe compound of formula (III) was obtained in 95.3% yield.
69%
With palladium dichloride; silver(l) oxide In ethanol at 70℃; for 24h;
(IV) General synthesis of aryl nitriles from the corresponding arylhalides.
General procedure: b.Cyanation of aryl bromides. To a solution of arylbromide (0.5 mmol) in EtOH (5.0 mL) was added NCTS (272 mg, 1.0 mmol), PdCl2 (13.3 mg, 0.075 mmol), and Ag2O (57.75 mg, 0.5 mmol). The mixture was stirred at 70 for 24 hunder air atmosphere. Then the reaction mixture was cooled to room temperature and filtered through a pad of celite (1.0 g) and rinsed with CH2Cl2 (10.0 mL). The resulting organic solution was concentrated under reduced pressure and further purified by flash chromatography (SiO2,petroleum ether/EtOAc gradient), yielding the corresponding aryl nitriles.
0.336 g
Stage #1: 1-bromo-4-methoxy-benzene With 3-chloroprop-1-ene; trifluoroacetic acid; cobalt(II) bromide; zinc In acetonitrile at 20℃;
Stage #2: N-cyano-N-phenyl-p-toluenesulfonamide With zinc In acetonitrile at 0 - 50℃; Inert atmosphere;
Stage #1: 4-Ethoxyaniline With tetrafluoroboric acid; sodium nitrite In water at 0℃;
Stage #2: N-cyano-N-phenyl-p-toluenesulfonamide With palladium diacetate; silver carbonate In ethanol at 58℃; for 15h;
(I) General synthesis of arenediazonium tetrafluoroborates: (see reference1)
General procedure: In an Erlenmeyer flask, the aniline (10.0 mmol) was dissolved in an aqueous solution of H4BF4 (50%, 5.0 mL,40.0 mmol) and a saturated solution of sodium nitrite (760 mg, 11.0 mmol) was added dropwise at 0 °C. The excess oxidant was removed by the addition of urea. Then, the precipitated diazonium salt was filtered off and dissolved in a small amount of acetone. Diethyl ether was added to the clear solution, causing the precipitation of the arenediazonium tetrafluoroborate, which was filtered off and washed with diethyl ether (3×10.0 mL). The arenediazonium tetrafluoroborate was dried in vacuo (10-3 mbar) for 10 minutes and was then directly used without further purification. (II) General synthesis of N-cyano-N-phenyl-p-methylbenzenesulfonamide(NCTS): (see reference 2) Dry 250 ml Schlenk flask was a solution of phenylurea (10.9 g, 8 mmol) in pyridine (54 mL). The flask was stirred in room temperature water bath. p-Toluenesulfonylchloride (52.8 g, 27.7 mmol) was added potion wise over 5 minutes. The reaction mixture was stirred for another additional 20 minutes and poured into to ice-cooled water (400 mL) with mechanical stirring. Precipitate formed during mechanical stirring was filtered and then washed with water. The crude product was treated with 50 ml of ethanol and precipitated from the same solvent. The precipitate was purified with column chromatography using heptane:EtOAc (15:1) as eluent to yield N-cyano-N-phenyl-p-methylbenzenesulfonamide as colorless solid (16.5 g, 76%). (III) General synthesis of aryl nitriles from the corresponding arenediazonium salts. To a solution of arenediazonium tetrafluoroborate (0.5 mmol) in EtOH (3.0 mL) was added NCTS (272 mg, 1.0 mmol), Pd(OAc)2 (16.8 mg, 0.075 mmol), Ag2CO3 (68.7mg, 0.25 mmol). The mixture was stirred at 58 for 15 h under air atmosphere. Then the reaction mixture was cooled to room temperature and filtered through a pad of celite (1.0 g) and rinsed with CH2Cl2 (10.0 mL). The resulting organic solution was concentrated under reduced pressure and further purified by flash chromatography (SiO2, petroleum ether/EtOAc gradient), yielding the corresponding aryl nitriles.
Stage #1: 3,4-dimethoxyaniline With tetrafluoroboric acid; sodium nitrite In water at 0℃;
Stage #2: N-cyano-N-phenyl-p-toluenesulfonamide With palladium diacetate; silver carbonate In ethanol at 58℃; for 15h;
(I) General synthesis of arenediazonium tetrafluoroborates: (see reference1)
General procedure: In an Erlenmeyer flask, the aniline (10.0 mmol) was dissolved in an aqueous solution of H4BF4 (50%, 5.0 mL,40.0 mmol) and a saturated solution of sodium nitrite (760 mg, 11.0 mmol) was added dropwise at 0 °C. The excess oxidant was removed by the addition of urea. Then, the precipitated diazonium salt was filtered off and dissolved in a small amount of acetone. Diethyl ether was added to the clear solution, causing the precipitation of the arenediazonium tetrafluoroborate, which was filtered off and washed with diethyl ether (3×10.0 mL). The arenediazonium tetrafluoroborate was dried in vacuo (10-3 mbar) for 10 minutes and was then directly used without further purification. (II) General synthesis of N-cyano-N-phenyl-p-methylbenzenesulfonamide(NCTS): (see reference 2) Dry 250 ml Schlenk flask was a solution of phenylurea (10.9 g, 8 mmol) in pyridine (54 mL). The flask was stirred in room temperature water bath. p-Toluenesulfonylchloride (52.8 g, 27.7 mmol) was added potion wise over 5 minutes. The reaction mixture was stirred for another additional 20 minutes and poured into to ice-cooled water (400 mL) with mechanical stirring. Precipitate formed during mechanical stirring was filtered and then washed with water. The crude product was treated with 50 ml of ethanol and precipitated from the same solvent. The precipitate was purified with column chromatography using heptane:EtOAc (15:1) as eluent to yield N-cyano-N-phenyl-p-methylbenzenesulfonamide as colorless solid (16.5 g, 76%). (III) General synthesis of aryl nitriles from the corresponding arenediazonium salts. To a solution of arenediazonium tetrafluoroborate (0.5 mmol) in EtOH (3.0 mL) was added NCTS (272 mg, 1.0 mmol), Pd(OAc)2 (16.8 mg, 0.075 mmol), Ag2CO3 (68.7mg, 0.25 mmol). The mixture was stirred at 58 for 15 h under air atmosphere. Then the reaction mixture was cooled to room temperature and filtered through a pad of celite (1.0 g) and rinsed with CH2Cl2 (10.0 mL). The resulting organic solution was concentrated under reduced pressure and further purified by flash chromatography (SiO2, petroleum ether/EtOAc gradient), yielding the corresponding aryl nitriles.
General procedure: In an Erlenmeyer flask, the aniline (10.0 mmol) was dissolved in an aqueous solution of H4BF4 (50%, 5.0 mL,40.0 mmol) and a saturated solution of sodium nitrite (760 mg, 11.0 mmol) was added dropwise at 0 C. The excess oxidant was removed by the addition of urea. Then, the precipitated diazonium salt was filtered off and dissolved in a small amount of acetone. Diethyl ether was added to the clear solution, causing the precipitation of the arenediazonium tetrafluoroborate, which was filtered off and washed with diethyl ether (3×10.0 mL). The arenediazonium tetrafluoroborate was dried in vacuo (10-3 mbar) for 10 minutes and was then directly used without further purification. (II) General synthesis of N-cyano-N-phenyl-p-methylbenzenesulfonamide(NCTS): (see reference 2) Dry 250 ml Schlenk flask was a solution of phenylurea (10.9 g, 8 mmol) in pyridine (54 mL). The flask was stirred in room temperature water bath. p-Toluenesulfonylchloride (52.8 g, 27.7 mmol) was added potion wise over 5 minutes. The reaction mixture was stirred for another additional 20 minutes and poured into to ice-cooled water (400 mL) with mechanical stirring. Precipitate formed during mechanical stirring was filtered and then washed with water. The crude product was treated with 50 ml of ethanol and precipitated from the same solvent. The precipitate was purified with column chromatography using heptane:EtOAc (15:1) as eluent to yield N-cyano-N-phenyl-p-methylbenzenesulfonamide as colorless solid (16.5 g, 76%). (III) General synthesis of aryl nitriles from the corresponding arenediazonium salts. To a solution of arenediazonium tetrafluoroborate (0.5 mmol) in EtOH (3.0 mL) was added NCTS (272 mg, 1.0 mmol), Pd(OAc)2 (16.8 mg, 0.075 mmol), Ag2CO3 (68.7mg, 0.25 mmol). The mixture was stirred at 58 for 15 h under air atmosphere. Then the reaction mixture was cooled to room temperature and filtered through a pad of celite (1.0 g) and rinsed with CH2Cl2 (10.0 mL). The resulting organic solution was concentrated under reduced pressure and further purified by flash chromatography (SiO2, petroleum ether/EtOAc gradient), yielding the corresponding aryl nitriles.
General procedure: In an Erlenmeyer flask, the aniline (10.0 mmol) was dissolved in an aqueous solution of H4BF4 (50%, 5.0 mL,40.0 mmol) and a saturated solution of sodium nitrite (760 mg, 11.0 mmol) was added dropwise at 0 C. The excess oxidant was removed by the addition of urea. Then, the precipitated diazonium salt was filtered off and dissolved in a small amount of acetone. Diethyl ether was added to the clear solution, causing the precipitation of the arenediazonium tetrafluoroborate, which was filtered off and washed with diethyl ether (3×10.0 mL). The arenediazonium tetrafluoroborate was dried in vacuo (10-3 mbar) for 10 minutes and was then directly used without further purification. (II) General synthesis of N-cyano-N-phenyl-p-methylbenzenesulfonamide(NCTS): (see reference 2) Dry 250 ml Schlenk flask was a solution of phenylurea (10.9 g, 8 mmol) in pyridine (54 mL). The flask was stirred in room temperature water bath. p-Toluenesulfonylchloride (52.8 g, 27.7 mmol) was added potion wise over 5 minutes. The reaction mixture was stirred for another additional 20 minutes and poured into to ice-cooled water (400 mL) with mechanical stirring. Precipitate formed during mechanical stirring was filtered and then washed with water. The crude product was treated with 50 ml of ethanol and precipitated from the same solvent. The precipitate was purified with column chromatography using heptane:EtOAc (15:1) as eluent to yield N-cyano-N-phenyl-p-methylbenzenesulfonamide as colorless solid (16.5 g, 76%). (III) General synthesis of aryl nitriles from the corresponding arenediazonium salts. To a solution of arenediazonium tetrafluoroborate (0.5 mmol) in EtOH (3.0 mL) was added NCTS (272 mg, 1.0 mmol), Pd(OAc)2 (16.8 mg, 0.075 mmol), Ag2CO3 (68.7mg, 0.25 mmol). The mixture was stirred at 58 for 15 h under air atmosphere. Then the reaction mixture was cooled to room temperature and filtered through a pad of celite (1.0 g) and rinsed with CH2Cl2 (10.0 mL). The resulting organic solution was concentrated under reduced pressure and further purified by flash chromatography (SiO2, petroleum ether/EtOAc gradient), yielding the corresponding aryl nitriles.
General procedure: In an Erlenmeyer flask, the aniline (10.0 mmol) was dissolved in an aqueous solution of H4BF4 (50percent, 5.0 mL,40.0 mmol) and a saturated solution of sodium nitrite (760 mg, 11.0 mmol) was added dropwise at 0 °C. The excess oxidant was removed by the addition of urea. Then, the precipitated diazonium salt was filtered off and dissolved in a small amount of acetone. Diethyl ether was added to the clear solution, causing the precipitation of the arenediazonium tetrafluoroborate, which was filtered off and washed with diethyl ether (3×10.0 mL). The arenediazonium tetrafluoroborate was dried in vacuo (10-3 mbar) for 10 minutes and was then directly used without further purification. (II) General synthesis of N-cyano-N-phenyl-p-methylbenzenesulfonamide(NCTS): (see reference 2) Dry 250 ml Schlenk flask was a solution of phenylurea (10.9 g, 8 mmol) in pyridine (54 mL). The flask was stirred in room temperature water bath. p-Toluenesulfonylchloride (52.8 g, 27.7 mmol) was added potion wise over 5 minutes. The reaction mixture was stirred for another additional 20 minutes and poured into to ice-cooled water (400 mL) with mechanical stirring. Precipitate formed during mechanical stirring was filtered and then washed with water. The crude product was treated with 50 ml of ethanol and precipitated from the same solvent. The precipitate was purified with column chromatography using heptane:EtOAc (15:1) as eluent to yield N-cyano-N-phenyl-p-methylbenzenesulfonamide as colorless solid (16.5 g, 76percent). (III) General synthesis of aryl nitriles from the corresponding arenediazonium salts. To a solution of arenediazonium tetrafluoroborate (0.5 mmol) in EtOH (3.0 mL) was added NCTS (272 mg, 1.0 mmol), Pd(OAc)2 (16.8 mg, 0.075 mmol), Ag2CO3 (68.7mg, 0.25 mmol). The mixture was stirred at 58 for 15 h under air atmosphere. Then the reaction mixture was cooled to room temperature and filtered through a pad of celite (1.0 g) and rinsed with CH2Cl2 (10.0 mL). The resulting organic solution was concentrated under reduced pressure and further purified by flash chromatography (SiO2, petroleum ether/EtOAc gradient), yielding the corresponding aryl nitriles.
Stage #1: 4-bromo-2,6-dimethylphenylamine With tetrafluoroboric acid; sodium nitrite In water at 0℃;
Stage #2: N-cyano-N-phenyl-p-toluenesulfonamide With palladium diacetate; silver carbonate In ethanol at 58℃; for 15h;
(I) General synthesis of arenediazonium tetrafluoroborates: (see reference1)
General procedure: In an Erlenmeyer flask, the aniline (10.0 mmol) was dissolved in an aqueous solution of H4BF4 (50%, 5.0 mL,40.0 mmol) and a saturated solution of sodium nitrite (760 mg, 11.0 mmol) was added dropwise at 0 °C. The excess oxidant was removed by the addition of urea. Then, the precipitated diazonium salt was filtered off and dissolved in a small amount of acetone. Diethyl ether was added to the clear solution, causing the precipitation of the arenediazonium tetrafluoroborate, which was filtered off and washed with diethyl ether (3×10.0 mL). The arenediazonium tetrafluoroborate was dried in vacuo (10-3 mbar) for 10 minutes and was then directly used without further purification. (II) General synthesis of N-cyano-N-phenyl-p-methylbenzenesulfonamide(NCTS): (see reference 2) Dry 250 ml Schlenk flask was a solution of phenylurea (10.9 g, 8 mmol) in pyridine (54 mL). The flask was stirred in room temperature water bath. p-Toluenesulfonylchloride (52.8 g, 27.7 mmol) was added potion wise over 5 minutes. The reaction mixture was stirred for another additional 20 minutes and poured into to ice-cooled water (400 mL) with mechanical stirring. Precipitate formed during mechanical stirring was filtered and then washed with water. The crude product was treated with 50 ml of ethanol and precipitated from the same solvent. The precipitate was purified with column chromatography using heptane:EtOAc (15:1) as eluent to yield N-cyano-N-phenyl-p-methylbenzenesulfonamide as colorless solid (16.5 g, 76%). (III) General synthesis of aryl nitriles from the corresponding arenediazonium salts. To a solution of arenediazonium tetrafluoroborate (0.5 mmol) in EtOH (3.0 mL) was added NCTS (272 mg, 1.0 mmol), Pd(OAc)2 (16.8 mg, 0.075 mmol), Ag2CO3 (68.7mg, 0.25 mmol). The mixture was stirred at 58 for 15 h under air atmosphere. Then the reaction mixture was cooled to room temperature and filtered through a pad of celite (1.0 g) and rinsed with CH2Cl2 (10.0 mL). The resulting organic solution was concentrated under reduced pressure and further purified by flash chromatography (SiO2, petroleum ether/EtOAc gradient), yielding the corresponding aryl nitriles.
With palladium dichloride; silver(l) oxide; In ethanol; at 70℃; for 24h;
General procedure: a.Cyanation of aryl iodides.To a solution of aryl iodide (0.5 mmol) in EtOH (5.0 mL) was added NCTS (272 mg, 1.0 mmol), PdCl2 (13.3mg, 0.075 mmol), and Ag2O (57.75 mg, 0.5 mmol). The mixture was stirred at 70 for 24 h under air atmosphere. Then the reaction mixture was cooled to room temperature and filtered through a pad of celite (1.0 g) and rinsed with CH2Cl2 (10.0 mL). The resulting organic solution was concentrated under reduced pressure and further purified by flash chromatography (SiO2, petroleum ether/EtOAc gradient), yielding the corresponding aryl nitriles.
With palladium dichloride; silver(l) oxide; In ethanol; at 70℃; for 24h;
General procedure: b.Cyanation of aryl bromides. To a solution of arylbromide (0.5 mmol) in EtOH (5.0 mL) was added NCTS (272 mg, 1.0 mmol), PdCl2 (13.3 mg, 0.075 mmol), and Ag2O (57.75 mg, 0.5 mmol). The mixture was stirred at 70 for 24 hunder air atmosphere. Then the reaction mixture was cooled to room temperature and filtered through a pad of celite (1.0 g) and rinsed with CH2Cl2 (10.0 mL). The resulting organic solution was concentrated under reduced pressure and further purified by flash chromatography (SiO2,petroleum ether/EtOAc gradient), yielding the corresponding aryl nitriles.
With palladium dichloride; silver(l) oxide; In ethanol; at 70℃; for 24h;
General procedure: b.Cyanation of aryl bromides. To a solution of arylbromide (0.5 mmol) in EtOH (5.0 mL) was added NCTS (272 mg, 1.0 mmol), PdCl2 (13.3 mg, 0.075 mmol), and Ag2O (57.75 mg, 0.5 mmol). The mixture was stirred at 70 for 24 hunder air atmosphere. Then the reaction mixture was cooled to room temperature and filtered through a pad of celite (1.0 g) and rinsed with CH2Cl2 (10.0 mL). The resulting organic solution was concentrated under reduced pressure and further purified by flash chromatography (SiO2,petroleum ether/EtOAc gradient), yielding the corresponding aryl nitriles.
With silver hexafluoroantimonate; ammonium cerium (IV) nitrate; [Ir(COD)2]BF4; 1-butyl-methylpyrrolidinium bis(trifluoromethylsulfonyl)amide; lanthanum(lll) triflate; XPhos at 100℃; for 8h;
2 Example 2
At room temperature, to the right amount of organic solvent PEG - 200 in, adding 100mmol formula (I) compound, 250mmol formula (II) compound, 10mmol catalyst (for 2mmol double (1, 5 - cyclooctadiene) four fluoboric acid iridium with8mmol AgSbF6mixture), 30mmol ligand L1, 8mmol adjuvant (for 4mmol trifluro sulfonic acid lanthanum with 4mmol mixture of ammonium nitrate) and 20mmol activator N - butyl - N - methyl pyrrolidine double (trifluoromethane sulfonyl) iminium salts, then heating up to 100 °C, and at this temperature the stirring reaction 8 hours;After the reaction, the reaction system is still hot filtering, is added into the filtrate volume such as saturated sodium carbonate aqueous solution, full oscillation, adding ethyl acetate extraction 2 - 3 time, combined with the organic phase, dried anhydrous magnesium sulfate, concentrated under reduced pressure, the residue by 300 - 400 mesh silica gel column chromatographic separation, in order to volume ratio 1:2 of acetone and petroleum ether elution of the mixed solution, thereby obtaining states the type (III) compound, and the yield is 89.5%.
64.3%
With silver hexafluoroantimonate; bis(1,5-cyclooctadiene)iridium(I) tetrafluoroborate; ammonium cerium (IV) nitrate; lanthanum(lll) triflate; XPhos at 90℃; for 10h;
4 Example 4
To a suitable amount of organic solvent PEG-200 at room temperature,100 mmol of the compound of the above formula (I), 200 mmol of the above formula was added(II), 15 mmol of catalyst (a mixture of 3.5 mmol of iridium (1,5-cyclooctadiene) tetrafluoroborate and 11.5 mmol of AgSbF6), 25 mmol of ligand L1 and 12 mmol of auxiliaries (6 mmol of trifluoromethanesulfonic acid Lanthanum with 6 mmol cerium ammonium nitrate), And then the temperature was raised to 90 ° C, and the reaction was stirred at that temperature for 10 hours;After completion of the reaction, the reaction system was filtered while hot, and an equal volume of a saturated aqueous solution of sodium carbonate was added to the filtrate.And then extracted with ethyl acetate for 2-3 times. The organic phases were combined, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography300-400 mesh silica gel column chromatography, the volume ratio of 1: 2 acetone and petroleum ether mixture of elution, resulting in the upperThe compound of formula (III) was obtained in 64.3% yield.
58%
With palladium dichloride; silver(l) oxide In ethanol at 70℃; for 24h;
(IV) General synthesis of aryl nitriles from the corresponding arylhalides.
General procedure: b.Cyanation of aryl bromides. To a solution of arylbromide (0.5 mmol) in EtOH (5.0 mL) was added NCTS (272 mg, 1.0 mmol), PdCl2 (13.3 mg, 0.075 mmol), and Ag2O (57.75 mg, 0.5 mmol). The mixture was stirred at 70 for 24 hunder air atmosphere. Then the reaction mixture was cooled to room temperature and filtered through a pad of celite (1.0 g) and rinsed with CH2Cl2 (10.0 mL). The resulting organic solution was concentrated under reduced pressure and further purified by flash chromatography (SiO2,petroleum ether/EtOAc gradient), yielding the corresponding aryl nitriles.
2-(7-methylimidazo[1,2-α]pyridin-2-yl)isophthalonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
With silver hexafluoroantimonate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; sodium hydrogencarbonate In 1,2-dichloro-ethane at 120℃; for 24h; Sealed tube;
80%
With silver hexafluoroantimonate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; sodium hydrogencarbonate In 1,2-dichloro-ethane at 120℃; for 24h; High pressure;
6 Example 6
Preparation method: in the air environment,To a 35 mL high pressure tube was added 0.1 mmol of 2-phenyl-7-methylimidazol[1,2-α] pyridine compound, 0.25 mmol of N-cyano-N-phenyl-p-toluenesulfonamide, 0.05 mmol of dichloroCyclopentadienyl) rhodium (III) dimer, 0.4 mmol of silver hexafluoroantimonate, 0.5 mmol of sodium bicarbonate, 1 mL of 1,2-Dichloroethane, 120 oC reaction 24 hours. After the reaction was completed, the residue was chromatographed (silica gel 200-300 mesh, eluent: ethyl acetate /Petroleum ether gradient elution, the ratio from 0/100 to 100/0), dried to give a pale yellow solid, yield 80%
2-(pyridin-2-yl)thiophene-3-carbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
With bis[dichloro(pentamethylcyclopentadienyl)ruthenium(III)]; silver(I) acetate; 1-butyl-3-methylimidazolium trifluoromethanesulfonimide; silver(I) triflimide; at 20℃; for 24h;
(1) 2-thiophenepyridine (50 mg, 0.311 mmol) was added sequentially to a clean reactor.N-cyano-N-phenyl-p-toluenesulfonamide (169.2 mg, 0.622 mmol), dichloro(pentamethylcyclopentadienyl) ruthenium (III) dimer (9.96 mg, 0.016 mmol),Silver bistrifluoromethanesulfonimide (36.0 mg, 0.093 mmol),Silver acetate (52.0 mg, 0.311 mmol) and 1-butyl-3-methylimidazolium bistrifluoromethanesulfonimide salt (0.5 mL),Stir at room temperature for 24 hours. (2) After the reaction is completed, cyclohexane extraction (3 × 3 mL) is added.The cyclohexane layer was collected, and the solvent was removed under reduced pressure.The residue was purified by silica gel column chromatography ( petroleum ether / methylene chloride / acetone = 100 / 1 / 1, v / v).The target product was obtained 53.1 mg, white solid, yield 92%.
With dicobalt octacarbonyl; In 1,2-dichloro-ethane; at 110℃; for 24h;
Synthesis of N-p-toluenesulfonyl-<strong>[621-72-7]2-benzylbenzimidazole</strong> by reaction of N-cyano-N-phenyl-p-toluenesulfonamide with p-toluenesulfonylation reagent and <strong>[621-72-7]2-benzylbenzimidazole</strong> And detecting the effect of the amount of octacarbonyldicobalt on the reaction (taking the compound of the formula III-1 represented by the formula as an example); <strong>[621-72-7]2-benzylbenzimidazole</strong> (0.2 mmol), octacarbonyldicobalt (2 mol%, 5 mol%, 10 mol%), 1,2-dichloroethane (2 mL) were added to a 10 mL reaction tube. And N-cyano-N-phenyl p-toluenesulfonamide (0.24 mmol) was reacted at 110 C for 24 h. The mixture was extracted with ethyl acetate and water, and the organic phase was dried over anhydrous sodium sulfate. The title compound was isolated by silica gel column chromatography, and the isolated yield was calculated as shown in Table 1, wherein the amount of octacarbonyl bis-cobalt was 10 mol%. The yield of the target product of formula III-1 was 66%, and the optimum catalyst amount was determined to be 10 mol%.
Stage #1: N-cyano-N-phenyl-p-toluenesulfonamide; 3,5-Dimethylphenol With aluminum (III) chloride; boron trifluoride diethyl etherate In acetonitrile at 80℃; for 24h;
Stage #2: With sodium hydroxide In water at 20℃; for 5h; Reflux;
1-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85%
Stage #1: 5,6,7,8-Tetrahydronaphthalen-1-ol; N-cyano-N-phenyl-p-toluenesulfonamide With aluminum (III) chloride; boron trifluoride diethyl etherate In acetonitrile at 80℃; for 24h;
Stage #2: With sodium hydroxide In water at 20℃; for 5h; Reflux;
Stage #1: N-cyano-N-phenyl-p-toluenesulfonamide; 4-methoxy-phenol With aluminum (III) chloride; boron trifluoride diethyl etherate In acetonitrile at 80℃; for 24h;
Stage #2: With sodium hydroxide In water at 20℃; for 5h; Reflux;
3-benzyl-2-imino-1-phenylimidazolidin-4-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
99%
With 18-crown-6 ether; cesium fluoride In acetonitrile at 0℃; for 4h;
16 The synthesis method of 3-benzyl-1-phenyl-2-iminohydantoin, the steps are as follows:
Take a 25 mL reaction flask and add 46 mg of N-benzyl-2-bromoacetamide, 71 mg of N-phenyl-N-cyano-p-toluenesulfonamide, 84 mg of cesium fluoride, and 145 mg of 18-crown ether-6 , Acetonitrile 2mL, stirring at 0°C for 4 hours.After the reaction was completed, 10 mL of water was added to quench the reaction, acetic acid was added for extraction 3 times, the organic phases were combined, and column chromatography was separated to obtain 52 mg of pure 3-benzyl-1-phenyl-2-iminohydantoin. The yield is 99%.
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