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With isopentyl nitrite; In tetrahydrofuran; at 0℃; for 1h;
Preparation 9 2-Chloro-6-trifluoromethyl-phenyl)-hvdrazine hydrochlorideTo a 0 0C solution of <strong>[433-94-3]2-chloro-6-trifluoromethyl-phenylamine</strong> (35.7 mmol, 7.0 g) in THF (100 mL) is added 48% BF3OEt (143 mmol, 36 mL) followed by addition of isoamyl nitrite (143 mmol, 19 mL). The reaction is stirred for 1 hour and is filtered to collect the tetrafluoroborate diazonium salt (48.7 mmol, 9.0 g). The salt is dissolved in a mixture of cone. HCl (30 mL) and water (10 mL) at 0 0C. To the resulting mixture is added ascorbic acid (48.7 mmol, 8.5 g). The reaction is heated to 50 0C for 3 hours and cooled to room temperature. The solid is filtered and washed with ice water. The wet solid is dissolved in a mixture of cone. HCl (30 mL) and water (20 mL) and heated to 90 0C for 2 hours. The reaction is cooled to 0 0C and filtered to yield the title compound (5.0 g, 60%). LC-ES/MS m/e 157.0 (M+l).
With N-Bromosuccinimide; acetic acid; In acetonitrile; at 20℃; for 18h;Heating / reflux;
Step A: 4-bromo-<strong>[433-94-3]2-chloro-6-(trifluoromethyl)aniline</strong> N-bromo succinimide (910 mg, 5.1 mmol) was added to a solution of <strong>[433-94-3]2-chloro-6-(trifluoromethyl)aniline</strong> (1.0 g, 5.1 mmol) and acetic acid (3 mL) in acetonitrile (10 mL) at room temperature. The mixture was heated at reflux, with stirring, for 18 h. The reaction mixture was then filtered through Celite and concentrated to give the title compound, which was used in the next step without further purification.
Example- 1472-(2-Chloro-6-fluorophenyl)-N-[2-chloro-6-(trifluoromethyl)phenyl]-4,4-dimethyl-l ,4- dihydrochromeno[3,4-JJimidazole-7-carboxamideTo a solution of <strong>[433-94-3]2-chloro-6-(trifluoromethyl)aniline</strong> (0.1 19 g, 0.607 mmol) in THF was added sodium hydride (0.022 g, 0.607 mmol) at 10-15C. The reaction mass was stirred for 30 mins. Then added 4-hydroxyphenyl 2-(2-chloro-6-fiuorophenyl)-4,4-dimethyl-l ,4- dihydrochromeno[3,4-JJimidazole-7-carboxylate (Intermediate-64, 0.100 g, 0.202 mmol). The reaction mass was stirred at RT for 5-6 h. The reaction mass was quenched in water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate and concentrated under vacuum to afford 0.005 g of desired product. 'HNMR (DMSO d6): delta 1.58 (s,6H), 7.37-7.57 (m, 7H), 8.36 (br s, 2H), 9.02 (s, 1H), 13.13 (brs, 1H); MS [M+H]+: 549.33.
With pyridine; phosphorus trichloride; In toluene; for 12h;Inert atmosphere; Reflux;
General procedure: The salicylic acid (1.2 equiv) was added to a mixture of toluene (0.3 M), aniline (1.0 equiv), phosphorus trichloride (1.1 equiv), and pyridine (0.05 equiv) in a Radley?s Carousel reaction tube (modified from Itai et al.20). The mixture was refluxed under nitrogen for 12 h then cooled to room temperature. Aqueous sodium bicarbonate was added dropwise to attain pH 6-7. The resultant mixture was extracted with EtOAc. The organic extracts were combined, dried (MgSO4), and concentrated under vacuum. After chromatography (1:10 EtOAc:Hex) compounds were recrystallized (EtOAc/Hex).
With sulfuric acid; dihydrogen peroxide; iron(II) sulfate; In water; dimethyl sulfoxide; at 30 - 70℃; for 0.833333h;Inert atmosphere;
11075] A three-neck flask was initially charged with 30 g (0.153 mol) of <strong>[433-94-3]2-chloro-6-trifluoromethylaniline</strong> (commercially available) in 765 ml of dimethyl sulphoxide (DMSO),and then 68.1 g (0.23 mol) of 2-iodoheptafluoropropane, 46ml of a 1 molar aqueous iron(II) sulphate solution and 15.4g of 98% sulphuric acid were added. The mixture was degassed with argon and then a syringe pump was used to add 34.8 g of 30% aqueous hydrogen peroxide solution dropwise within 30 minutes. In the course of this, the temperature rose to 70 C. The mixture was stirred for a further 20 minutes, in the course of which the temperature fell to 30 C. The reaction mixture was then poured onto saturated aqueous sodium hydrogencarbonate solution and extracted with ethyl acetate. The combined extracts were washed first with water, then with saturated aqueous bisulphite solution and saturated aqueous sodium chloride solution, dried with sodium sulphate and concentrated on a rotary evaporator under reduced pressure. For purification, chromatography was effected using a cartridge containing 330 g of silica gel and a gradient proceeding from pure cyclohexane to 90:10 (v/v) cyclohexane/ethyl acetate. 46.1 g of 2-chloro-4-heptafluoroisopropyl-6-trifluoromethylani- line were obtained.
46.1 g
With sulfuric acid; dihydrogen peroxide; iron(II) sulfate; In water; dimethyl sulfoxide; at 70℃; for 0.833333h;Inert atmosphere;
First, 30 g (0.153 mol) <strong>[433-94-3]2-chloro-6-trifluoromethylaniline</strong> (commercially available)765 ml of dimethyl sub-grind (DMSO)Followed by the addition of 68.1 g (0.23 mol) of 2-iodoheptafluoropropane,46 ml 1 molar aqueous solution of iron (II) sulfate with 15.4 g 98% strength sulfuric acid.The mixture was then degassed with argon,And using a syringe pump,Then 34.8 g of a 30% strength aqueous hydrogen peroxide solution was added dropwise over 30 minutes.During the addition,The temperature rose to 70 C.The mixture was allowed to stir for another 20 minutes,During that period,The temperature dropped to 30 C.The reaction mixture was then poured onto a saturated aqueous solution of sodium hydrogencarbonate,And extracted with ethyl acetate.The combined extracts were washed with water,Followed by washing with a saturated aqueous solution of sodium hydrogen sulfate and a saturated aqueous solution of sodium chloride,Dried over sodium sulfate,And concentrated on a rotary evaporator under reduced pressure. In terms of purification,The residue was placed in cassettes containing 330 g of silica gel,Gradient chromatography using pure cyclohexane to 90:10 (v / v) cyclohexyl acetate / ethyl acetate. This gave 46.1 g of 2-chloro-4-heptafluoroisopropyl-6-trifluoromethylaniline.
46.1 g
With sulfuric acid; dihydrogen peroxide; iron(II) sulfate; In water; dimethyl sulfoxide; at 30 - 70℃; for 0.833333h;
Analogously, 2-chloro-4-heptafluoroisopropyl-6-trifluoromethylaniline was also obtained proceeding from <strong>[433-94-3]2-chloro-6-trifluoromethylaniline</strong> and 2 -iodoheptafluoropropane: A three-neck flask was initially charged with 30 g (0.153 mol) of 2 -chloro-6-trifluoromethylaniline (commercially available) in 765 ml of dimethyl sulphoxide (DMSO), and then 68.1 g (0.23 mol) of 2- iodoheptafluoropropane, 46 ml of a 1 molar aqueous iron(II) sulphate solution and 15.4 g of 98% sulphuric acid were added. The mixture was degassed with argon and then a syringe pump was used to add 34.8 g of 30% aqueous hydrogen peroxide solution dropwise within 30 minutes. In the course of this, the temperature rose to 70C. The mixture was stirred for a further 20 minutes, in the course of which the temperature fell to 30C. The reaction mixture was then poured onto saturated aqueous s odium hydrogencarbonate solution and extracted with ethyl acetate. The combined extracts were washed first with water, then with saturated aqueous bisulphite solution and saturated aqueous sodium chloride solution, dried with sodium sulphate and concentrated on a rotary evaporator under reduced pressure. For purification, chromatography was effected using a cartridge containing 330 g of silica gel and a gradient proceeding from pure cyclohexane to 90: 10 (v/v) eye lohexane/ethyl acetate. 46.1 g of 2- chloro-4-heptafluoroisopropyl-6-trifluoromethylaniline were obtained.
4-difluoromethyl-1,2,3-thiadiazole-5-carboxylic acid chloride[ No CAS ]
C11H5ClF5N3OS[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
23%
With sodium hydride; In tetrahydrofuran; mineral oil; at 20℃; for 2h;
The reaction flask was charged with <strong>[433-94-3]2-chloro-6-trifluoromethylaniline</strong> (460 mg, 2.36 mmol)Sodium hydride (130 mg,60%, 3.25 mmol) and 10 ml of tetrahydrofuran,Stirring at room temperature was added dropwise 4-difluoromethyl-1,2,3-thiadiazole-5-carboxylic acid chloride (470 mg, 2.36 mmol) in 10 ml tetrahydrofuran.Drop finished, reaction at room temperature,2 hours after the reaction is completed.The reaction solution was poured into 30 ml of water,Take the organic layer,The organic layer was washed successively with saturated aqueous sodium bicarbonate,Saturated brine washing,Dried over anhydrous magnesium sulfate,Heat the solvent under reduced pressure.The residue was purified by column chromatography (eluent: ethyl acetate: petroleum ether = 1: 8)To give 190 mg of compound 79 in 23% yield.
A) 15 g of hydrochloric acid (0.15 mol) are added to the reaction apparatus,After cooling, 9.2 g (0.047 mol) of <strong>[433-94-3]2-chloro-6-trifluoromethylaniline</strong> was dropwise added to the system,Dropping added insulation reaction 60min,Then sodium nitrite solution 13.5g (0.09mol) was added dropwise to the system,Process temperature 3 ,Dropping added insulation reaction 2h; B) 32 g (0.32 mol) of hydrochloric acid was added to the above system,1.6 g (0.01 mol) of copper sulfate,Stirring until dissolved,Then 33.84 g (0.141 mol) of sodium bisulfite solution was added dropwise,After the addition was complete, the temperature was raised to 60 C. and incubated for 1.5 hours.The reaction is completed and extracted with methylene chloride, separated, the organic phase is dried, filtered, and the solvent is removed to give 2-chloro-6-trifluoromethylbenzenesulfonyl chloride;
With phosphorus trichloride In chlorobenzene at 100 - 130℃; for 0.75h; Microwave irradiation;
General Procedure for the Synthesis of N-(Disubstituted phenyl)-3-hydroxynaphthalene-2-carboxamides 1-24
General procedure: 3-Hydroxynaphthalene-2-carboxylic acid (0.5 g, 2.65 mM) was suspended in drychlorobenzene (20 mL) at ambient temperature and phosphorus trichloride (0.12 mL,1.35 mM), and the corresponding substituted aniline (2.65 mM) was added dropwise.The reaction mixture was transferred to the microwave reactor, where the synthesis wasperformed (1st phase: 10 min, 100 C; 2nd phase: 15 min, 120 C; 3rd phase: 20 min, 130 C;max 500 W). The mixture was then cooled to 60 C, and the solvent was removed underreduced pressure. The residue was washed sequentially with hydrochloric acid and water,and the crude product was recrystallized from EtOH. All the compounds are presented inTable 1.