Highly efficient process of imidazole synthesis by Radziszewski reaction was explored in a continuous-flow microreactor. Process variables of residence time

reaction temperature

molar ratio of formaldehyde to glyoxal

molar ratio of ammonium acetate to glyoxal

glyoxal concentration

and different ammonia sources on imidazole yield were studied to obtain optimized condition for imidazole synthesis in the continuous-flow microreactor. Under the optimal operating conditions of ammonium acetate as ammonia source

pressure 1.7 MPa

reaction temperature 140℃

glyoxal concentration 0.25 mol/L

molar ratio of formaldehyde to glyoxal 1.4

molar ratio of ammonium acetate to glyoxal 2.0

and residence time 159.4 s

yield of imidazole could be reached to 81.6%. Besides

the continuous-flow microreactor was tentatively investigated for preparation of 2-methylimidazole

2-ethylimidazole

2-isopropylimidazole and challenges appeared in the process were discussed.