Synthesis of imidazo[2,1-b]thiazoles via GBB reaction

The Groebke-Blackburn-Bienaymé reaction (GBB-3CR) is a choice method for synthesizing fused heterocyclic imidazoles from readily available reagents, including aldehydes, 2-aminoazines, and isocyanides. Its broad versatility, excellent atom economy, and potential biological applications have positioned it among the most popular and efficient MCR-I reactions today.

Imidazo[2,1-b]thiazoles are a family of compounds formed by two fused five-membered heterocycles (thiazole and imidazole) that are of significant interest in the scientific community due to their potential applications as anticancer, antiviral, antibiotic, anti-inflammatory, antifungal, and phytotoxic agents. Analogs containing a phenolic residue in their structure exhibit photophysical properties arising from the Excited-State Intramolecular Proton Transfer (ESIPT) process, enabling the synthesis of fluorescent probes and chemosensors useful for the development of OLEDs, bioimaging, biomarkers, molecular switches, or lasers. Multicomponent synthesis has emerged as the most efficient strategy for generating libraries of ESIPT compounds with high atom economy, speed, and functional versatility.

The ESIPT mechanism typically involves light excitation, photoisomerization between the enol and zwitterionic forms, and the formation of intramolecular hydrogen bonds between a donor group (e.g., ─NH₂, ─OH, or ─SH) and an acceptor atom (typically ═N, ═S, or C═O). ESIPT-active luminescent materials exhibit dual-state emission and large Stokes shifts (up to 10,000 cm⁻¹). Therefore, the development of new ESIPT-active imidazo[2,1-b]thiazoles represents a promising strategy for expanding the library of functional fluorescent heterocycles.