Imidazo[1,2-a]pyridines Susceptible to Excited State Intramolecular Proton Transfer: One-Pot Synthesis via an Ortoleva–King Reaction

• Published in: Journal of organic chemistry 2012-07, Vol.77 (13), p.5552-5558
• Main Authors: Stasyuk, Anton J, Banasiewicz, Marzena, Cyrański, Michał K, Gryko, Daniel T
• Format: Article
• Language: English
• Subjects: Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Molecular Structure; Noncondensed benzenic compounds; Organic chemistry; Preparations and properties; Protons; Pyridines - chemical synthesis; Pyridines - chemistry; Stereoisomerism
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo300643w

A short and efficient route to a broad range of imidazo[1,2-a]pyridines from 2-aminopyridines and acetophenones is achieved by a tandem, one-pot process starting with an Ortoleva–King reaction. Optimal conditions for the first step were established after examining various reaction parameters (solvent, reagent ratios, and temperature). The conditions identified (1st step, neat, 2.3 equiv of 2-aminopyridine, 1.20 equiv of I2, 4 h, 110 °C; 2nd step, NaOHaq, 1 h, 100 °C) resulted in the formation of imidazo[1,2-a]pyridines in 40–60% yields. The synthesis is compatible with various functionalities (OH, NMe2, Br, OMe). Products containing a 2-(2′-hydroxyphenyl) substituent undergo excited state intramolecular proton transfer (ESIPT) in nonpolar and polar-aprotic solvents. Although ESIPT-type emission in nonpolar solvents is weak, the Stokes shifts are very high (11000 cm–1). The comparison of the properties of six ESIPT-capable imidazo[1,2-a]pyridines shows the influence of various substituents on emission characteristics. All of them also display strong, solid-state emission in blue–green–yellow region. 2-Aryl-imidazo[1,2-a]pyridines not capable of ESIPT emit in the blue region, displaying high fluorescence quantum yield.