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17 EXAMPLE 17
EXAMPLE 17 The method of Example 16 was repeated with 2-methylaniline replaced by 10 g of 4-methylaniline, and 2-methylpyridine replaced by 10 ml of 2,6-dimethylpyridine. After 3 hours' reaction, 4.9 g (0.028 mole) of 4-methyl-2-trifluoromethylaniline were obtained (30% yield). B.p.: 41°/0.5 mm Hg deltaF: -63 ppm deltaH: 6.7 ppm (1H); 7.03 ppm (1H); J:8.5 Hz, 7.3 ppm (1H).
7 EXAMPLE 7
EXAMPLE 7 100 g of iron fillings are heated to 95° C. in 300 ml of water, 5 ml of hydrochloric acid and 5 ml of dioxane in a stirred vessel, and 57 g of 2-nitro-5-methylbenzotrifluoride are added dropwise in the course of about 1 hour. The mixture is stirred for a further 2 hours, and a distillation is then carried out using steam. The organic material extracted with dichloromethane and re-distilled. 42 g (boiling point: 92°-95° C./20 mbar) of 2-trifluoromethyl-4-methylaniline are obtained.
With fluorescein In water; N,N-dimethyl-formamide at 20℃; for 2h; Irradiation;
1-4
Add 21.4mg (0.2mmol) of 4-methylaniline to 2ml of a mixed solvent of DMF and water (the volume ratio of DMF to water is 1:4),Add 75.8mg (0.24mmol) to it 1-(trifluoromethyl)-1,2-benziodoxol-3(1H)-one, 1.33mg (0.004mmol) of fluorescein, reacted for 2 hours under 9W blue LED light at room temperature,After the reaction, the extraction operation is carried out: 1.Sequentially add saturated NaCl aqueous solution and ethyl acetate to the reaction solution for extraction twice, 2. Add 50 mL of saturated NaCl aqueous solution and 25 mL of ethyl acetate for the first time for extraction.3. After the primary extraction is completed, collect the organic layer, take the aqueous phase layer and add 25ml of ethyl acetate for secondary extraction. After the extraction is completed, take the organic layer and dry it with anhydrous sodium sulfate, filter,Take the filtrate and evaporate to dryness under reduced pressure at room temperature to obtain the crude compound.The crude compound was subjected to silica gel column chromatography, using a solution with a volume ratio of ethyl acetate and petroleum ether of 1:15 as the mobile phase.TLC tracked collection of the eluent with Rf value of 0.5, and the collected eluent was subjected to rotary evaporation and reduced pressure at room temperature to remove the solvent, and then dried.31.2 mg of pure compound represented by formula 2a was obtained, and the reaction yield was 89%.
80%
With potassium carbonate In acetonitrile at 75℃; for 6h; Schlenk technique; Inert atmosphere;
3. General procedure for the reaction
General procedure: Experimental Procedure: A dried 25 mL Schlenk tube equipped with a magnetic stir bar was charged with Togni’s Reagent 2 (0.25 mmol, 1.0 equiv), free anilines 1 (0.75 mmol, 3.0 equiv), K2CO3 (0.375 mmol, 1.5 equiv) and CH3CN (1.5 mL). The reaction mixture was then stirred at 75 °C for 6 h under an argon atmosphere. The reaction progress was monitored by TLC. After cooling to room temperature, the mixture was washed with water and extracted with CH2Cl2 three times, then washed with saturated NaCl solution. The combined organic layer was dried with anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel (Elutent: petroleum ether-EtOAc) to give the pure product. The products were characterized by 1H NMR, 13C NMR, 19F NMR, GC -MS.
60%
With potassium carbonate; nickel(II) hydroxide In dimethyl sulfoxide at 35℃; for 2h; Inert atmosphere;
60%
With potassium carbonate; nickel(II) hydroxide In dimethyl sulfoxide at 35℃; for 2h;
29
In the preparation method of the trifluoromethyl aromatic amine of the present embodiment, the aromatic amine is p-methylaniline, and other reactions and post- treatment processes are the same as in the embodiment 28. The preparation method of the trifluoromethyl aromatic amine of the present embodiment, the aromatic amine is aniline, and the nickel compound is nickel hydroxide.The base is potassium carbonate, and the reaction process parameters are: 1-trifluoromethyl-1,2-phenyliodo-3(H)-one (0.5 mmol, 1.0 eq).Aromatic amine (1.5 mmol, 3.0 eq), nickel hydroxide 10 mol%, potassium carbonate (1.5 mmol, 3.0 eq),DMSO (2 mL) was reacted at 35 ° C for 2 h, and the other reactions and workup procedures were the same as in Example 1.
2-methoxy-N-(4-methyl-2-(trifluoromethyl)phenyl)benzamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
100 mg
In 5,5-dimethyl-1,3-cyclohexadiene at 140℃; for 16h;
10 Example 10. 2-methoxy-N-(4-methyl-2-(trifluoromethyl)phenyl)benzamide (29)
A mixture of 2-methoxybenzoyl chloride 2 (200 mg, 1.17 mmol) and 4-m ethyl-2- (trifluoromethyl)aniline 28 (350 mg, 1.53 mmol) in xylene (2 mL) was stirred at 140 °C for 16 hours. The mixture was concentrated in vacuo and purified by flash chromatography over silica gel eluting over a gradient of 30: 1 to 20: 1 petroleum ether/ethyl acetate to afford 2- methoxy-N-(4-methyl-2-(trifluoromethyl)phenyl)benzamide 29 (100 mg). LCMS analysis of 29: [M+H]+= 310
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