Regioselective pivaloylation of N-phthaloylchitosan: a promising soluble intermediate for chitosan chemistry

A simple and efficient pivaloylation of primary alcohols was realized on N-phthaloylchitosan that was regioselectively and entirely protected. The selectivity of this mild esterification was demonstrated by comparison with 1H NMR chemical shifts of H-1 and H-3 of complete 3,6-O-dipivaloylated derivatives. The selective hydrazinolysis of N-phthaloyl groups in the presence of pivaloyl ester was achieved in ethanol/water. High molecular weight 6-O-pivaloylchitosan, purified by ultrafiltration, with solubility in organic solvents was obtained. The selective introduction of a phosphorus moiety in O-3 using chlorodiphenylphosphine has led to 3-O-diphenylphosphinito-N-phthaloyl-6-O-pivaloylchitosan with a ds of 0.97 from energy dispersive X-ray spectroscopy, which demonstrates the potential applications of O-6 pivaloyl protection. The pivaloylation of O-6 alcohols can enhance the solubility of some chitosan derivatives and therefore contributes to the development of applications involving chitosan through regioselective modifications of alcohol and amino groups.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Chitosan derivatives were synthesized by pivaloyl chloride and N-phthaloylchitosan. ► Pivaloylchitosan derivatives were characterized by NMR and vibrational spectroscopy. ► The introduction of pivaloyl groups enhanced the solubility in some organic solvents. ► Regioselective pivaloylation and hydrazinolysis are interesting synthetic tools.