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With ammonium chloride; sodium methylate; In methanol; diethyl ether;
4-(Trifluoromethyl)benzamidine Hydrochloride A solution of 4-(trifluoromethyl)benzonitrile (Avocado 14514, 15 g) in anhydrous methanol (90 ml) was treated with sodium methoxide (0.50 g) and the resulting solution stirred for 4 d at ambient temperature. After this time, ammonium chloride (4.7 g) was added and the mixture stirred for a further day. The mixture was subsequently evaporated and the residual white solid triturated in diethyl ether, filtered and dried to afford of 4-(trifluoromethyl)benzamidine hydrochloride as a white solid (14.2 g, 72%). Mass spectrum 188 [M]+.
With hydrogenchloride; NaNH2; In ethanol; ethyl acetate; toluene;
EXAMPLE 1 Preparation of p-(Trifluoromethyl)benzamidine Hydrochloride STR13 A stirred solution of p-(trifluoromethyl)-benzonitrile (100 g, 0.585 mol)in toluene is treated with NaNH2 (38 g, 0.878 mol. 90% pure) and dibenzo-18-crown-6 (1.5 g), heated at reflux temperatures for 4 hours, cooled to 10 C. and treated slowly with 175 ml of concentrated HCl over a 30 minute period. The resultant reaction mixture is filtered and the filtercake is washed with toluene and dried to give a powdery yellowish solid. The solid is dissolved in ethanol and filtered. The filtrate is concentrated in vacuo to give a yellow solid residue. The residue is slurried in ethyl acetate and filtered. The filtercake is washed with ether and dried to give the title product as a yellow solid, 132.3 g (quantitative yield), identified by 1 H-NMR, 13 C-NMR and 19 FNMR analyses.
4-(trifluoromethyl)benzimidamide hydrochloride To a 3-neck flask equipped with a reflux condenser was added 4-(trifluoromethyl)benzonitrile (80 g, 0.468 mol), NaNH2 (27.4 g, 0.701 mol), 18-Crown-6 (1.2 g) and toluene (350 mL). The solution was heated to reflux for 4 h. The mixture was cooled to 0 C. and concentrated aqueous HCl (140 mL) was added slowly. The precipitated solid was collected by filtration and washed with 1:2 methanol:dichloromethane (1:2, 250 mL) to provide 4-(trifluoromethyl)benzimidamide hydrochloride (53 g) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) delta 9.83 (s, 2H), 9.62 (s, 2H), 8.09 (d, J=8.0 Hz, 2H), 7.90 (d, J=8.0 Hz, 2H).
General procedure: A 100 mL flask was charged with 30 mL of anhydrous MeOH, 10 mmol of the arylnitrile, and 1.0 mmol of sodium methoxide. The complex was protected from moisture and stirred for 48 h. Then, 10 mmol of NH4Cl was added and stirring was continued for 24 h. Unreacted NH4Cl was filtered, and methanol was stripped from the filtrate to afford the product aryl amidine hydrochlorides, which was dissolved in 2.5 mL 8M sodium hydroxide aqueous solution and stirred for 1 h. Then chloroform (20 ml x 3) and H2O (20 ml x 3) were added successively to extract the product, and the combined organic layer was dried with anhydrous MgSO4 and then evaporated under vacuum to remove the organic solvent to give the desired arylamidine.
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