Chitosan Derivatives - Chitosan Based Hydrogels: Functions and Applications - page 43

sufficiently in order to keep the O-methylation down. They found that DQ was in the
range of 0-74% depending on the reaction conditions accompanying N-monomethylation,
N,N-dimethylation, and O-methylation. Based on this solvent system, they also recently
claimed to achieve a high DQ ranging from 81% to 88% by the “one-pot” synthesis proce-
dure. They suggested a protection group strategy for more selective N-quaternization
(sequence of N-phthaloylation, O-tritylation, N-deprotection, N-methylation, and
O-deprotection) [17]. Recently, Verheul et al. [18] synthesized TMC without O-methylation
using two steps (Figure 2.3). In the first step, a formic acid-formaldehyde methylation
(Eschweiler-Clarke) was used to synthesize the N , N -dimethylated chitosan (DMC).
Quaternization of DMC was performed by using iodomethane in NMP without the assis-
tance of a catalyst for the last step. Moreover, they found that the molecular weight of
TMC slightly increased with increasing DQ, implying that no chain scission occurred
during synthesis.

2.3.2 Quaternization of Chitosan using glycidyl Trimethylammonium Chloride

Glycidyl trimethylammonium chloride (GTMAC) was selected as a quarternizing agent
because it has a quaternary ammonium group itself. When a primary amino group at C-2
of chitosan reacted with GTMAC, the chain of the quaternary ammonium group obtained
was longer than that of TMC. Loubaki et al. [19] synthesized and characterized GTMAC-
modified chitosan by reacting chitosan with GTMAC ( cf. Figure 2.4). The reaction was
performed in water at 60°C for 15 h. The complete DQ was obtained by using the molar
ratio of GTMAC:GlcN of chitosan as 6:1. They found that N-monoalkylation was obtained
under this condition.
Daly and Manuszak-Guerrini [20] developed a method for the synthesis of N-(2-hydroxy)
propyl-3-trimethylammonium chitosan chloride (HPTC) using commercially available
Quat-188 salt, 3-chloro-2-hydroxypropyl trimethylammonium chloride, under the basic
condition. This product was called chitosan Quat-188. Under this condition, Quat-188 read-
ily generated the corresponding epoxide, which reacted in both the primary amino groups
and hydroxyl groups of chitosan via a nucleophilic substitution pathway to introduce the
quaternary ammonium substituent ( cf. Figure 2.5). It is important to note that sodium
hydroxide concentration affects the generation of the epoxide form of Quat-188. If a high
sodium hydroxide concentration is used, it will not only activate the polysaccharide but
will also hydrolyze Quat-188 and produce large amounts of the diol [21,22].
Recently, Sajomsang et al. [23] quaternized N -aryl chitosan derivatives, which contained
different electron-donating and electron-withdrawing substituents, using Quat-188 (cf.
Figure 2.6). Iodine was used as a catalyst and the pH of the reaction condition was main-
tained at 8 at room temperature for 48 h. To obtain complete quaternization, the reaction
was heated up to 50°C for 24 h. Even when the reaction was performed at room tempera-
ture and the pH was adjusted to 8, O-alkylation could occur in this condition.

OH

OH

+

O

-

O +

N(CH 3 ) 3 O

Cl

O HO

HO

O NH

+

NH 2

-

CH 2 CH

OH

CH 2 N(CH 3 ) 3 Cl

Figure 2.4
Reaction of chitosan with GTMAC.