Density functional theory study on the reaction mechanism of synthesizing 1,3-dimethyl-2-imidazolidinone by urea method.

We report a first-principles density functional theory investigation on tailoring the fundamental reaction mechanism of synthesizing 1,3-dimethyl-2-imidazolidinone (DMI) through the urea method with water serving as both solvent and catalyst. The nucleophilic cyclization reaction is implemented by two ammonia removal steps. One -NH group of dimethylethylenediamine (DMEDA) first attacks the carbon atom of urea, eliminating one -NH3 group and forming an intermediate state CH3NHC2H4N(CH3)CONH2 (IMI). IMI subsequently undergoes the cyclization process through a secondary ammonia removal via similar manner. Without water, the two ammonia removal steps are both slightly exothermic with high activation barriers (~50 kcal mol(-1)). As water participated in the reaction, the kinetics of the two steps can be significantly improved, respectively. The role that water plays, beside as solvent, more importantly, is to serve as a proton exchange bridge. Due to the spatial configuration, the direct proton migration from the N atoms of ethylenediamine to urea is difficult to occur. The water bridge facilitates the proton migration by shortening the migration distance. As a consequence, the activation barriers are considerably lowered down to ~30 kcal mol(-1), indicating a strong catalytic effect from water. In contrast, the three possible side reactions of IM(I), even catalyzed by water, have higher activation barriers due to strong steric inhibitive effect and consequently become difficult to occur at the same condition. The current computational understanding on the prototypical reaction to DMI can be extended to guide developing more efficient routes to synthesize imidazolidinone derivatives through the urea method.