In this study, we explored a new method for preparing C6 quaternary ammonium chitosan (CTS) derivatives. The C2NH2 of CTS was first protected by benzaldehyde. The C6OH of CTS was then transformed into a sulfonyl ester, which was then reacted with NaN3 through nucleophilic substitution to introduce the N3 group at the CTS C6 position. This intermediate was reacted in a click chemistry reaction with a terminal alkynyl quaternary ammonium salt; this was followed by the deprotection of C2NH2 with acid to furnish the C6 quaternary ammonium CTS derivative. The structures and properties of synthesized products in the reactions were characterized by Fourier transform infrared spectroscopy, NMR, X-ray diffraction, and thermogravimetric analysis, respectively. The effects of the reaction conditions on the degree of Schiff-base CTS quaternization were evaluated by elemental analysis. The largest inhibition zone test and the minimum inhibitory concentration test showed that compared with CTS, the prepared CTS derivative had significantly improved antibacterial activity toward Staphylococcus aureus and Escherichia coli. (c) 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013