Delineating the Mechanism of Ionic Liquids in the Synthesis of Quinazoline-2,4(1H,3H)-dione from 2-Aminobenzonitrile and CO2

Ionic liquids (ILs) are versatile solvents and catalysts for the synthesis of quinazoline-2,4-dione from 2-aminobenzonitrile and CO2. However, the role of the IL in this reaction is poorly understood. Consequently, we investigated this reaction and showed that the IL cation does not play a significant role in the activation of the substrates, and instead plays a secondary role in controlling the physical properties of the IL. A linear relationship between the pK(a) of the IL anion (conjugate acid) and the reaction rate was identified with maximum catalyst efficiency observed at a pK(a) of > 14.7 in DMSO. The base-catalyzed reaction is limited by the acidity of the quinazoline-2,4-dione product, which is deprotonated by more basic catalysts, leading to the formation of the quinazolide anion (conjugate acid pK(a) 14.7). Neutralization of the original catalyst and formation of the quinazolide anion catalyst leads to the observed reaction limit.