4-Bromo-2-(trifluoromethyl)aniline

Clear yellow liquid

In the preparation method of the trifluoromethyl aromatic amine of the present embodiment, the aromatic amine is p-bromoaniline, and other reactions and post-treatment processes are the same as in the embodiment 28. Under nitrogen or argon, 4-bromo-aniline 0.4 mmol, 0.2mmol, Ir (ppy) 3 (2 mg) and DMF (1 ml) were added to the reaction flask and then irradiated with a blue LED band (7W) at room temperature until complete conversion of the trivalent iodine reagent was complete. 10 ml of a saturated aqueous Na2C03 solution was added thereto, and the mixture was extracted three times with ethyl acetate. The organic layer was washed once with saturated brine, and the organic layer was dried over anhydrous Na2S04. Column chromatography [200-300 mesh chromatography silica (the same below), eluent: petroleum ether 60-90: ethyl acetate = 20: 1-10: 1], to give yield 61percent (NMR 86percent Yield).General procedure: Into a reaction glass vial fitted with a magnetic stirring bar anda septum cap penetrated with a syringe needle was added theCo3O4/NGrC-catalyst (2 molpercent, 3 wtpercent Co-phenanthroline oncarbon, 20 mg) followed by the nitro arene (0.5 mmol), theinternal standard (hexadecane, 100 μL), THF (2 mL), and H2O(200 μL). The reaction vial was then placed into a 300 mL autoclave.The autoclave was flushed twice with nitrogen, pressurized with CO at 30 bar pressure. Finally, the autoclave was usedat 60 bar by adding nitrogen and placed into an aluminiumblock, which was preheated at 125 °C. After 24 h the autoclavewas placed into a water bath and cooled to r.t. Finally, theremaining gas was discharged, and the samples were removedfrom the autoclave, diluted with EtOAc and analyzed by GC. Todetermine the yield of isolated products, the general procedurewas scaled up by the factor of two, and no internal standard wasadded. After the reaction was completed, the catalyst was filteredoff, and the filtrate was concentrated and purified by silicagel column chromatography (n-heptane–EtOAc mixtures) togive the corresponding anilines.The procedure was adapted from Lemair, M. et.al . Tetrahedron, 2011 67, 1971 1976. To the solution of 2-(trifluoromethyl)aniline (1.5 g, 9.31 mmol) inacetic acid (15 mL) was added KBr (1.307 g, 10.99 mmol) and sodium perborate monohydrate (0.929 g, 9.31 mmol) and the mixture was stirred for 5 mm. To this mixture was added ammonium molybdate tetrahydrate (11.51 g, 9.31 mmol) and the reaction mixture was stirred at room temperature for 3 h. After completion of the reaction as determined by TLC, water was added and the pH was adjusted to 8 usingaq. saturated sodium bicarbonate solution. The reaction mixture was extracted with ethyl acetate (3 x 5 mL). The combined organic extracts were washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure to afford 4-bromo-2-(trifluoromethyl)aniline (800 mg, 36percent yield) as a yellow solid. The analytical data was consistent with the literature reference cited above.General procedure: A 25 mL of Schlenk tube equipped with a magnetic stir bar were charged with aniline (1.2 mmol, 3.0 equiv) or heterocycles (0.8 mmol, 2.0 equiv), K2CO3 (0.8 mmol, 2.0 equiv) and fac-Ir(ppy)3 (2.6 mg, 0.004 mmol, 1 mol percent), under air. The vessel was evacuated and backfilled with Ar (3 times), CF3I stock solution (0.56 mL, 0.71 mmol/mL in 1, 2-chloroethane or 0.36 mL, 1.11 mmol/mL in DMSO, 1.0 equiv), anhydrous 1, 2-dichloroethane (3 mL) were then added. The tube was screw capped and stirred at room temperature under irradiation of blue LEDs (12 W) for 24 hours. The reaction mixture was filtered through a pad of Celite and washed with ethyl acetate (3×5 mL). The filtrate was concentrated. The residue was subjected to column chromatography on silica gel to afford the pure product.General procedure: Add magnetic particles to a dry 50 mL three-neck reaction flask at room temperature, then add 20 mL of anhydrous B.The nitrile was added to the dry acetonitrile with stirring, then trifluoromethyltrimethylsilane (213 mg, 1.5 mmol) was added, then anhydrous potassium acetate (147 mg, 1.5 mmol) was added. Then, the reaction liquid was heated to 80 C, aniline (93 mg, 1.0 mmol) was dissolved in 5 mL of anhydrous acetonitrile, and then the aniline solution was slowly added dropwise to the above-mentioned 80 C reaction solution by a constant pressure dropping funnel. Approx. 1 hour. After the dropwise addition was completed, the reaction was carried out at 80 C for 12 hours. The reaction solution was cooled to room temperature, and the solid was filtered off, and then the reaction mixture was evaporated to dryness to afford the desired product.General procedure: Dried pressure tube was charged with magnetic stir bar and50 mg of PdSiO2 catalysts (1 mol% with respect to amine). Then, 1.0 mL o-xylene was added, followed by the addition of 0.5 mmolof amine and 1 mmol of benzyl alcohol. The pressure tube wasflushed with argon was closed with screw cap. Then it was placedin the preheated aluminum block and reaction was allowed to progressfor 30 h at 150 C. After completion of the reaction, pressuretube was removed from aluminum block and cooled down to roomtemperature. The catalyst was filtered out by ciliate and reactionproducts were analyzed by GC-MS and the corresponding amineswere purified by column chromatography. The yields of selectedamines were determined by GC analysis using n-hexadecane asstandard. For this purpose, after completion of the reaction, nhexadecane(100 mL) as standard was added to the reaction pressuretube and the reaction products were diluted with ethyl acetate followed by filtration using plug of silica and then subjected GCanalysis.To a mixture of 4-bromo-2-(trifluoromethyl)aniline (960 mg, 4 mmol), isobutylboronic acid (612 mg, 6 mmol), caesium carbonate (612 mg, 6 mmol) and toluene/water (10:1, 10 mL) in a microwave tube was added Pd(dppf)Cl2 (146 mg, 5% eq) under argon atmosphere. The reaction mixture was heated to react at 120' for 1 hour under microwave. After completion of the reaction, the mixture was filtered through Celite and washed with dichloromethane. The filtrate was concentrated in vacuo to remove the solvent, and the residue was purified by a silica gel column to give a product 4-isobutyl-2-(trifluoromethyl)aniline (583.9 mg), with a yield of 67.2%. MS (ESI) m/z: 218 (M+1).

Used as medicine and pesticide intermediate

Molecular Weight:240.02
XLogP3:2.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Exact Mass:238.95575
Monoisotopic Mass:238.95575
Topological Polar Surface Area:26
Heavy Atom Count:12
Complexity:159
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes