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.

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► 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.