Preparation background and overview of 2-amino-4-trifluoromethylpyridine
2-Amino-substituted nitrogen-containing six-membered heterocyclic compounds have important applications in the chemical industry. In particular, 2-aminopyridine and its derivatives are one of the important structures in pharmaceutical and agricultural chemical molecules and are widely present in In the synthesis and application of natural products, drugs, luminescent materials and various fine chemicals. 2-Amino-4-trifluoromethylpyridine is a 2-amino-substituted nitrogen-containing six-membered heterocyclic compound. It is an important pharmaceutical intermediate and can be synthesized from 2-fluoro-4-trifluoromethyl-pyridine and ethanol. Preparation of amidine hydrochloride reaction.
Preparation of 2-amino-4-trifluoromethylpyridine
Preparation of 4-trifluoromethyl-2-amino-pyridine: Add 2-fluoro-4-trifluoromethyl-pyridine (1mmolg) and acetamidine hydrochloride (1.2mmol) into a 25 ml reaction tube , 113.4 mg), NaOH (2.5 mmol, 100 mg), H2O (0.5 mL) and dimethyl sulfoxide (2.5 mL). The reaction was carried out at 130°C for 24 hours. After the reaction was completed, it was cooled to room temperature. Add 10 mL of ethyl acetate to quench the reaction, add 6 mL of saturated brine to wash, separate the organic phase, and then extract the aqueous phase 3 times with ethyl acetate (the amount of ethyl acetate used is 6 mL each time). Combine the organic phases, and add anhydrous sodium sulfate. Dry, and remove the solvent, including organic solvents and inorganic solvents, by distillation under reduced pressure. The organic solvent is then separated by column chromatography to obtain the target product 4-trifluoromethyl-2-amino-pyridine with a yield of 61%. The prepared product was qualitatively analyzed by gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectrometry (NMR). Qualitative characterization data are as follows: GC-MS (EI, 70eV) m/z.162, 143, 135, 116.
1HNMR (600MHz, Acetone) δ8.17 (d, J＝4.8Hz, 1H), 6.81 (s, 1H), 6.77 (d, J＝4.8Hz, 1H), 5.94(s,2H)pyridinium tribromide;
13CNMR (150MHz, Acetone) δ 161.31 (s, 1C), 150.68 (s, 1C), 139.56 (d phenanthrene borate d, J = 65.53, 65.69Hz, 1C), 124.36 (dd, J=544.36, 544.51Hz, 1C), 108.03 (t, J=3.322Hz, 1C), 104.25 (t, J=4.228Hz, 1C).
