A short synthesis of highly soluble chemoselective chitosan derivatives via "click chemistry"

A short synthesis of chemoselective chitosan derivatives was achieved by copper-catalyzed Huisgen cycloaddition, which is an ideal reaction for click chemistry, by using N-(4-azidophthaloyl)-chitosan. N-(4-azidophthaloyl)-chitosan was prepared through chemoselective N-bromophthaloylation of chitosan in acidic water and subsequent azidation. The obtained N-(4-bromopthaloyl)-chitosan had higher solubility in common solvents than conventional phthaloyl chitosan. N-(4-azidophthaloyl)-chitosan was successfully converted with ethynyl derivatives having functional groups (hydroxymethyl, phenyl, and methyl ester) in the presence of copper(II) sulfate, sodium ascorbate and/or trimethylamine. FT-IR spectra, elemental analyses, and (1)H and (13)C NMR spectra supported that the desired chitosan derivatives were chemoselectively transferred by these groups with a 1,4-triazole linker.