Electric Literature of 654-70-6,Some common heterocyclic compound, 654-70-6, name is 4-Cyano-3-trifluoromethylaniline, molecular formula is C8H5F3N2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
The indicated aniline (0.52 g, 2.8 mmol) was added to a solution of the bromide (prepared according to the procedure of Example 5, 0.21 g, 0.56 mmol) in Toluene (3 mL), followed by Cs2CO3 (0.18 g, 0.56 mmol). The reaction mixture was heated at reflux overnight. The reaction mixture was cooled to room temperature and H2O was added. The resulting mixture was extracted with ethyl acetate (3×80 mL). The combined ethyl acetate extracts were washed with brine and dried over Na2SO4. Na2SO4 was then filtered off and solvent was evaporated in vac and the residue was chromatographed on silica gel using acetone:hexanes (20:80) 1% Et3N to give the titled compound. NaH (7.0 mg, 0.17 mmol) was added to the aniline (prepared according to the procedure of Example 19 Step 1, 41.0 mg, 0.09 mmol) in THF (1.5 mL) at -20 C. and stirred under N2 for 10 minutes. MeI (16.3 muL, 0.26 mmol) was added to the reaction mixture and the resulting mixture stirred at room temperature overnight. The residue was partitioned between ethyl acetate and H2O. The combined ethyl acetate extracts were dried over sodium sulfate and filtered. The solvent was evaporated in vac to give the titled compound. Aqueous NaOH (50, 2 mL) was added to the nitrile (prepared according to the procedure of Example 19 Step 2, 171.2 mg, 0.35 mmol) in MeOH (10 mL) and THF (4 mL). The reaction mixture was heated at reflux overnight. The reaction mixture was cooled to room temperature and neutralized with acetic acid, then extracted with ethyl acetate. The combined ethyl acetate extracts were washed with brine and dried over Na2SO4. Na2SO4 was then filtered off and solvent was evaporated in vac. The residue was chromatographed on silica gel using ethyl acetate:hexanes (20:80) 2.5% acetic acid to give the titled compound. 1H NMR (CDCl3) delta7.99 (d, 1H, J=9.0 Hz), 7.59 (d, 1H, J=9.0), 7.07 (m, 2H), 6.84 (m, 1H), 4.18 (t, 2H, J=5.5), 3.75 (t, 2H, J=7.5), 3.13 (s, 3H), 3.00 (t, 2H, J=7.5), 2.20 (m, 2H), 1.80 (m, 2H), 1.00 (t, 3H, J=7.5). MS: m/z=505 (M+H).
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4-Cyano-3-trifluoromethylaniline, its application will become more common.
Reference:
Patent; Adams, Alan D.; Huang, Shaei Y.; Szewczyk, Jason W.; US2006/178398; (2006); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts