One-pot synthesis of N-alkyl 9H-carbazole derivatives from alcohols using 1-tosylimidazole (TsIm)

Carbazole and its derivatives are an important type of heterocyclic compounds that are widespread in nature [1]. Carbazoles especially N-alkyl derivatives are well known for their biological activities such as anti-inflammatory, anticonvulsant, antimicrobial, antiviral, antitumor, antidiabetic and analgesic activities [1]. In addition, some carbazole derivatives are useful in optoelectronic materials, conducting polymers, and synthetic dyes [2]. The N-alkylation of carbazole is usually achieved using alkyl halides, alkyl tosylates, Michael acceptors, and epoxides. Due to the advantageous and attractive strategy of the direct synthesis of carbazole derivatives from alcohols, some limited methods have been developed. Along this line, methods based on Mitsunobu conditions are widely applied [3]. However, this method is accompanied by several drawbacks including: utilizing toxic, expensive, and explosive reagents such as diethyl azodicarboxylate (DEAD) and diisopropyl azodicarboxylate (DIAD); the presence of unreacted PPh3 and formation of O=PPh3 which requires a tedious work up and cumbersome separation process. To overcome these drawbacks, we wish to report 1-tosylimidazole (TsIm) as an efficient and appropriate reagent for the one-pot synthesis of N-alkyl 9H-carbazole derivatives using alcohols in the presence of K2CO3/triethylamine mixture in anhydrous DMF at reflux condition (Scheme 1). The full optimization of the reaction condition including solvent type, base, and temperature are discussed. This method affords the corresponding N-alkyl 9H-carbazole derivatives in reasonable to good yields