[strat_cat_11]

Does anyone know the mechanism of the reaction of urea with a secondary amine and what are the reaction conditions? I believe this is a carbamate with ammonia byproduct?

[o alquimista]

A while ago I synthesized Dulcin from Paracetamol in which the final reaction step is the reaction of a primary amine with urea (mechanism for secondary amine should be the same). Reaction conditions for the urea reaction were: dissolved in water, added a few drops of glacial acetic acid, 4 equivalents urea, 1 1/2 h reflux.

[strat_cat_11]

Thanks for the reply. I guess this would be your typical nucleophilic substitution reaction? Do you think the water solvent is needed? I intend to quaternize with dimethylsulfate after the urea reaction and would like to avoid the water. Would acetic acid as the solvent prevent the carbamate formation? This would eliminate the need to remove the ammonia gas; I would rather filter off ammonium acetate.

[o alquimista]

The reason it was dissolved in water was because I started from phenacetin R-NH-CO-CH3 which was dissolved in diluted HCl (and later neutralised). By adding the urea to the water I didn't have to isolate the R-NH2 in between.