Chitosan Derivatives - Chitosan Based Hydrogels: Functions and Applications - page 45

OH
O

OH

OH

OH

CH 3 l

NaBH 4 O

O RCHO O

O

HO

O

O -

O

HO NaOH

Nal

+

HO

N(CH 3 ) 2

HO l

NH

NH 2

N

RH 2 C

RH 2 C

RHC

R = Methyl, Butyl, Octyl, and Dodecyl groups

Figure 2.7
Synthesis of quaternized N -alkyl chitosan derivatives using iodomethane as a quaternizing agent.

and Choi [25] and Kim et al. [26] prepared quaternized N -alkyl chitosan derivatives con-
taining alkyl substituents of different chain lengths. The reaction was carried out in two
steps: N-alkylation and quaternization. In the first step, chitosan reacted with formalde-
hyde, butyraldehyde, n -octylaldehyde, and n -dodecylaldehyde. Then the resulting Schiff
bases were reduced with NaBH 4 . In the last step, the N -alkyl chitosan derivatives were quat-
ernized with iodomethane in the presence of sodium hydroxide as base and NMP (Figure
2.7). The trimethylated and triethylated 6-NH 2 -6-deoxy chitosans were synthesized by
Sadeghi et al. [27]. The 6-NH 2 -6-deoxy chitosan was prepared in four steps: phthaloylation,
tosylation, amination, and deprotection of the phthaloyl group. Then methylation and ethy-
lation were carried out at both C-2 and C-6 of 6-NH 2 -6-deoxy chitosan using iodomethane
and iodoethane in the presence of sodium hydroxide and NMP, respectively. The DQs of
trimethylated and triethylated 6-NH 2 -6-deoxy chitosans were 65% and 51%, respectively.
Holappa et al. [28] synthesized chitosan N -betainates with various DSs. An efficient five-
step synthetic route (N-phthaloylation, 6-O-triphenylmethylation, removal of the
N -phthalimido moiety, addition of the N -betainate, and chitosan N -betainates) was devel-
oped for the full N-substitution of chitosan ( Figure 2.8). Previously, N-acylation of chitosan
with betaine was performed in aqueous acidic solutions, but it did not yield sufficient sub-
stitution degrees. To overcome this problem, an organo-soluble 6- O -triphenylmethyl
chitosan intermediate was used as the starting material for N-acylation reactions to enable
reactions in homogeneous reaction mixtures in organic solvents.
Furthermore, novel quaternary ammonium chitosan derivatives were synthesized by
the same group [29]. N -Chloroacyl-6- O -triphenylmethylchitosan was used as the starting
material for the synthesis of quaternary ammonium chitosan derivatives through reaction
with four tertiary amines: pyridine, N -methylpyrrolidone, triethylamine, and tributylam-
ine ( cf. Figure 2.9).
The quaternary piperazine derivatives of chitosan were synthesized in two ways [30].
First, 1,4-dimethylpiperazine reacted with N -chloroacyl-6- O -triphenylmethylchitosan in
the presence of potassium iodide and NMP under argon at 60°C for 72 h ( Figure 2.10a) .
Second, 4-carboxymethyl-1,1-dimethylpiperazinium iodide or 1-carboxymethyl-1,4,4-trim-
ethylpiperazi-1,4-dium diiodide reacted with 6- O -triphenylmethylchitosan using a cou-
pling agent (Figure 2.10b). They found that the quaternary ammonium moiety can be
selectively inserted into either one or both of the piperazine nitrogens, yielding structur-
ally uniform chitosan derivative structures.
Sajomsang et al. [31,32] synthesized quaternary ammonium chitosan containing aro-
matic moieties, particularly aromatics bearing N , N -dimethylaminobenzyl and N , N -
dimethylaminocinnamyl groups, based on the method of Curiti et al. [14]. In addition,
quaternized N -(4-pyridylmethyl)chitosan was also synthesized. Quaternization occurred
among N , N -dimethylaminobenzyl, N , N -dimethylcinnamylamino, and N -pyri-dylmethyl
groups and the primary amino groups of chitosan (Figure 2.11). The total DQ of each