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

Martin Hulla; Sami M A Chamam; Gabor Laurenczy; Shoubhik Das; Paul J Dyson

doi:10.1002/anie.201705438

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

Angew Chem Int Ed Engl. 2017 Aug 21;56(35):10559-10563. doi: 10.1002/anie.201705438. Epub 2017 Jul 26.

Authors

Martin Hulla¹, Sami M A Chamam¹, Gabor Laurenczy¹, Shoubhik Das², Paul J Dyson¹

Affiliations

¹ Institut des Sciences et Ingénierie Chimiques, École Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland.
² Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Göttingen, Germany.

PMID: 28678430
DOI: 10.1002/anie.201705438

Abstract

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.

Keywords: base catalysis; carbon dioxide; ionic liquids; organocatalysis; sustainable chemistry.

Publication types

Research Support, Non-U.S. Gov't