Catalytic application of room temperature ionic liquids: [bmim][MeSO₄] as a recyclable catalyst for synthesis of bis(indolyl)methanes. Ion-fishing by MALDI-TOF-TOF MS and MS/MS studies to probe the proposed mechanistic model of catalysis

Abstract

The catalytic application of room temperature ionic liquids (RTILs) has been explored to catalyse the reaction of indole with aldehydes to afford bis(indolyl)methanes. The catalytic efficiency of the RTILs derived from butylmethylimidazolium (bmim) cation is influenced by the structure of the imidazolium moiety and the counter anion following the order: [bmim][MeSO₄] > [bmim][HSO₄] ≈ [bmim][MeSO₃] ≫ [bmim][BF₄] > [bmim][Br] > [bmim][NTf₂] ≈ [bmim][PF₆] > [bmim][N(CN)₂] ≈ [bmim][ClO₄] ≈ [bmim][HCO₂] > [bmim][N₃] > [bmim][OAc]. Substitution of the C-2 hydrogen in [bmim][MeSO₄] decreased the catalytic efficiency. In the 1-methyl-3-alkylimidazolium methyl sulfates, the best results are obtained with the 3-butyl derivative and the catalytic property was retained with ethyl, n-propyl, and n-pentyl groups at N-3 although to a lesser extent with respect to the 3-butyl analogue. However, much reduction of the catalytic effect is observed with n-hexyl at N-3. The method is simple, environment friendly, compatible with various functional groups such as halogen, alkoxy, nitrile and O-t-Boc and gives excellent yields in short times. The catalyst is recyclable upto three consecutive uses. A mechanism has been proposed invoking ambiphilic dual activation role of the IL through the formation of intermediates involving hydrogen bond formation between the oxygen atom of the aldehyde carbonyl (or the transiently formed indolyl methanol in the subsequent step) and the C-2 hydrogen atom of the bmim cation, electrostatic intercation between the quarternary nitrogen atom of the bmim cation with the nitrogen lone pair of electrons of the indole and enforced hydrogen bond formation between the indole N–H hydrogen atom and the anion of the IL. The transient indolyl methanol and intermediate non-covalent clusters were “fished” by MALDI-TOF-TOF MS and MS/MS studies and served as ‘proof-of-concept’ to the mechanistic model.