Sodium Cyanide → 4-Cyanomethyl-2-(p-methoxyphenyl)-5-methyl-imidazole

Participants

Reaction Steps

To a stirred slurry of 15.3 g (0.06 mole) of 4-hydroxymethyl-2-p-methoxyphenyl-5-methyl-imidazole hydrochloride in 200 ml of chloroform are added 15 g (0.12 mole) of thionyl chlorine in CHCl3. Vigorous evolution of gas is observed during the addition. The reaction mixture is stirred at room temperature for 5 hours, during which time the slurry dissolves to form a pale pink solution. The solvent is then removed under reduced pressure and the solid residue taken up in fresh CHCl3. The solution is then filtered, ether is added until cloudy and then chilled. White crystals of 5-chloromethyl-2-p-methoxyphenyl-4-methyl-imidazole hydrochloride are precipitated, filtered and collected (91% yield), m.p. 203°-205° C (dec.). This chloromethyl derivative is dissolved in 75 ml of warm DMSO and added to a hot solution of 15 g (0.3 mole) of sodium cyanide in DMSO. The reaction mixture is stirred at room temperature for 16 hours and warmed to 60° C for 4 hours, then allowed to cool to room temperature and poured over 1 liter of ice and stirred. A yellow solid is precipitated, filtered and air-dried. Three recrystallizations from methylene chloride-hexane give the product, 4-cyanomethyl-2-(p-methoxyphenyl)-5-methyl-imidazole, as fluffy white crystals, m.p, 158°-160° C.

Provenance & Evidence