Intramolecular Cycloalkylation of Pyrrole in Ionic Liquids and Immobilized Ionic Liquids

Abstract

The formation of C-C bonds-the basic building blocks of molecules is the most significant chemical phenomena in chemistry. Friedel-Crafts alkylation is among the one in the construction of C-C bond. The alkylation of aromatic rings via Friedel-Crafts alkylation is well established. An intramolecular form of the Friedel-Crafts alkylation has become an effective method for the rapid construction of many carboand heterocyclic compounds. However, due to high reactivity the reaction in certain fused ring systems were found to be of less benefit. Also, heterocyclic rings tend to be poor substrates for the Friedel-Crafts reaction. Over a past decade, ionic liquids (ILs, Figure 1) have gained tremendous potential as a solvent over conventional organic solvents in many organic reactions including nucleophilic substitution reactions. Song et al. have recently reported metal triflate catalyzed Friedel-Crafts alkylation of aromatic compounds with alkenes and alkynes in hydrophobic ILs. Also recently, we have demonstrated that ILs enhance pyrrole C–alkylation regioselectively at C2 position via nucleophilic substitution reaction. Further, our group reported the synthesis of chromane derivatives using intramolecular Friedel-Crafts reaction in IL. In addition, immobilizing IL onto solid supports is the growing field of interest due to easier separation of the catalyst from the reaction media and its possible utilization of the catalyst in a continuous system. Further, polymer forms of ILs were found to have exceptional properties such as stability, electrochemical activity, and high ionic conductivity. Our group has designed a polystyrene supported ionic liquid (PSIL, Figure 1) that can be used for nucleophilic substitution reactions. In extension of our program on alkylations of heteroarenes in IL media, herein, we wish to report cycloalkylation of pyrrole in IL and PSIL as two ecofriendly protocols. Table 1 illustrates intramolecular pyrrole C-alkylation of 1-(4-bromobutyl)-1H-pyrrole (1a) under various reaction conditions. Our initial investigation begins with the entry 1 where the cyclization is performed at the temperature of 100 °C in aprotic organic solvent like acetonitrile without any IL. The reaction afforded 23% of 5,6,7,8-tetrahydropyrrolo[1,2-a]pyridine 2a after 24 h. Next, we have performed the same reaction in IL, [bmim][SbF6] in the absence of co-solvent. We observed dark-brown coloration within 1 h. The reaction mixture on thin-layer chromatography showed absence of starting material however, the reaction provided uncharac-