Multidisciplinary Synthetic Approach for Rapid Combinatorial Library Synthesis of Triaza-Fluorenes

Abstract

A new multidisciplinary synthetic approach comprising polymer-support synthesis, microwave-assisted synthesis, and multicomponent condensation facilitates synthesis of triaza-fluorenes library with a set of advantages such as rapid process, simple purification, and structural diversity in one shot. Microwave-assisted multistep synthetic protocol was used to construct the benzimidazole ring on soluble polymer support using activated aryl-fluorides. The PEG anchored aryl fluoride was condensed with selective primary amines via an ipso-fluoro displacement reaction followed by reduction of nitro group. The subsequent cyclization with cyanogen bromide is used as a key step to furnish immobilized benzimidazoles. Finally multicomponent condensation of resulted polymer bound benzimidazoles with various aldehydes and 1,3-diones under microwave irradiations provides rapid access for triaza-fluorenes with high purity and excellent yields. Microwave irradiation greatly accelerates the rate of all reactions while polymer support facilitates purifications by simple precipitation technique. This strategy dramatically increases efficiency of overall multistep synthesis.

Synthetic Strategies for Preparing Bicyclic Guanidines

“…[93] The synthetic strategy was based on the use of polymer-supported 2-aminobenzimidazoles 170 as the starting materials. [93] The synthetic strategy was based on the use of polymer-supported 2-aminobenzimidazoles 170 as the starting materials.…”

Developments Towards Regioselective Synthesis of 1,2‐Disubstituted Benzimidazoles

“…Subsequent reduction of nitro group to a primary amine followed by cyclization yields the benzimidazole ring (Scheme ) 17. 21…”

“…During their work towards a triazafluorene library,21 Sun and co‐workers adopted a multidisciplinary approach in which a clear comparison between regular and microwave conditions was undertaken (Scheme ). The group adopted a classical synthetic route to solid‐phase conditions.…”

Microwave dielectric heating in modern organic synthesis and drug discovery

“…Microwave irradiation greatly accelerates the rate of all reactions while polymer support facilitates purifications by simple precipitation technique. This strategy dramatically increases the efficiency of the overall multistep synthesis (Hsiao, Y. et al, 2010).…”