Uses
3'',4'',5''-Trifluoro-[1,1''-biphenyl]-2-amine is a building block used in various chemical synthesis.
Synthesis
In a 1 liter reactor, zinc chloride (20 g, 0.147 mol) was mixed with THF (29 g) and heated to a suitable temperature. Subsequently, a THF solution (1.15 mmol/g solution) of 3,4,5-trifluorophenylmagnesium bromide (0.133 mol) was added. After stirring for 10 min, (1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)(3-chloropyridyl)-palladium(II) dichloride (462 mg) was added at 25 °C. After 5 min, N-methylpyrrolidone (30 g) was added. after 10 min, phenylmethylideneamino-2-chlorobenzene, 99% pure, was added to the reaction mixture (29 g, 0.133 moles). Subsequently, the mixture was heated to 50 °C and stirred at this temperature for 6 hours. The post-treatment step consisted of adding 3.4 g of activated carbon, stirring the suspension for 1 hour and then filtering through diatomaceous earth. The filter cake was washed with THF (200 g) and the filtrate was subsequently concentrated. Concentration was carried out using a rotary evaporator at 50 °C and a vacuum below 5 mbar. Water (200 g) and concentrated sulfuric acid (28 g) were added to the residue. The mixture was stirred at 80 °C for 3 h while the generated benzaldehyde was removed by azeotropic distillation. Afterwards, the pH was adjusted to 2.8 with sodium hydroxide solution and toluene (200 g) was added. After separation of the organic phase, the aqueous phase was re-extracted with toluene (200 g) and the combined organic phases were washed with water (100 g) and concentrated. Concentration at 80 °C and 5 mbar using a rotary evaporator yielded a dark colored oil (26.7 g), which crystallized after standing. Quantitative HPLC analysis showed 86.4% by weight of 3,4,5-trifluoro-2'-aminobiphenyl in the oily substance, corresponding to 78% yield.
