Uses
2-Phenylacetimidamide Hydrochloride is useful for the preparation of trifluoromethyl pyrimido[1,3]diazepine compounds.
Synthesis
The general procedure for the synthesis of 2-phenylacetamidine hydrochloride from phenylacetonitrile is as follows: ammonium chloride (2.9 g, 54 mmol) was suspended in 20 mL of anhydrous toluene, stirred under argon protection and cooled to 0 °C. To this suspension 25 mL (50 mmol) of 2 M trimethylaluminum in toluene was slowly added. After the reaction system was gradually warmed to room temperature, stirring was continued until the release of methane gas ceased (about 1 hour). Subsequently, 3.46 mL (30 mmol) of benzeneacetonitrile dissolved in 10 mL of anhydrous toluene was added and the reaction mixture was heated to 80°C and maintained for 18 hours. After completion of the reaction, it was cooled to room temperature and slowly poured into a slurry consisting of 15 g of silica gel with 50 mL of chloroform and stirred for 5 minutes. The silica gel was removed by filtration and washed with methanol. The filtrate was combined with the wash solution, concentrated to about 15 mL and filtered again. To the filtrate was added 18 mL (54 mmol) of 3 N methanolic hydrochloric acid solution followed by 400 mL of diethyl ether. After stirring for 16 hours at room temperature, the resulting white precipitate was collected by filtration. The crude product was dissolved in 150 mL of a solvent mixture of isopropanol and acetone (4:1, v/v) and stirred for 16 hours at room temperature. Undissolved ammonium chloride was removed by filtration and the filtrate was concentrated to about 15 mL. 300 mL of diethyl ether was added and stirred for 1 h. The white precipitate was obtained by filtration and 3.7 g (72% yield) of 2-benzeneethanimidamide hydrochloride was obtained after drying. Mass spectrum (ESI, positive ion mode) m/z: 157.9 (M+23). 1H NMR (500 MHz, DMSO-d6) δ (ppm): 9.06 (broad peak, 3H), 7.49 (double peak, 2H), 7.36 (triple peak, 2H), 7.31 (triple peak, 1H), 3.74 (single peak, 2H).
References
[1] Patent: US2009/286815, 2009, A1. Location in patent: Page/Page column 6-7
[2] Patent: US2009/286810, 2009, A1. Location in patent: Page/Page column 6
[3] Tetrahedron, 1984, vol. 40, # 5, p. 887 - 892
[4] Patent: US2008/146625, 2008, A1. Location in patent: Page/Page column 18
