Real-time Raman monitoring of dry media heterogeneous alkylation of imidazole with acidic and basic catalysts

The N-substitution of heterocycles, e.g., imidazole, is a key route to prepare important bactericidal compounds and new drugs; these are also precursors for the synthesis of ionic liquids, which are very promising as an alternative to conventional organic solvents. Controlling alkylation of imidazoles to a monoalkylation is challenging due to the tendency of bis-alkylation leading to the formation of ionic liquids (ILs; imidazolium salts). Raman spectroscopy provides a real-time non-invasive insight during reaction in the presence of acidic or basic catalysts. 2-Methylimidazole is first alkylated to 1-butyl-2-methylimidazole, but alkylation reaction continues with either catalyst; 2-methylimidazole to N-alkyl-2-methylimidazole, N-alkyl-2-bromo-2-methyl-2,3-dihydro-1H-imidazole, N-alkyl-2-methylimidazolium bromide and 1,3-dialkyl-2-methylimidazolium bromide following different alkylation mechanism. We report here the use of in situ Raman during dry media N-alkylation of 2-methylimidazole with 1-bromobutane in the presence of both acid and basic heterogeneous catalysts. Real-time Raman spectroscopy allows determining when monoalkylation is completed and suggesting different reaction pathways for bis-alkylation towards the ILs formation. This feature underlines the great potential of Raman spectroscopy for reaction investigation and process monitoring.