From Chitin to Chitosan - Chitosan Based Hydrogels: Functions and Applications - page 18

butyryl through the following steps: mixing 2.1 g of chitosan powder with 11 mL of meth-
anesulfonic acid, stirring the mixture at 0°C for 30 min until the solution is homogeneous,
dripping 125 mmol of butyric anhydride into the liquid, stirring at 0−5°C for 2 h, placing
the mixture at −20°C overnight, pouring the mixture into 300 mL of acetone the next day for
depositing, filtering, and extracting deposits by acetone for 18 h, and drying the deposits.
On replacing butyric anhydride with 20 mmol of benzoyl chloride, the product is fully
benzoylated chitosan.
N-acylation of chitosan is useful. The same steps as the preparation method of fully
acylated chitin with less acetic anhydride will form N-acylated chitosan, namely, chitin.
Corresponding acylates can be formed when acetic anhydride is replaced with propionic
anhydride, butyric anhydride, or caproic anhydride. Amido acid derivatives of chitosan can
be formed if the acylating agent is diacid anhydride (succinic anhydride, maleic anhydride,
or phthalic anhydride). The derivatives are soluble in water, dilute acid, dilute alkali, or
some organic solvents and have good hygroscopicity and water-retaining property [66,67].
1.5.2 esterification using inorganic Oxygen Acids
Hydroxyls of chitin and chitosan, especially C6 hydroxyls, can be esterified by using inor-
ganic oxygen acids or their anhydrides. Such reactions are similar to cellulose reactions.
Aminos of chitosan can be esterified as well.
Sulfates of chitin and chitosan are the focus of esterification using inorganic oxygen
acids. Studies on this subject have not subsided since 1953 because these esters are like
heparin in structure and also have anticoagulation function. However, heparin is hard to
extract and produce and is expensive, and may increase plasma fatty acid concentration. A
cheap substitute for heparin with better anticoagulation function and no side effects can
be formed by designing chitosan sulfate of a certain structure and molecular weight.
The esterifying agents for chitin and chitosan are concentrated sulfuric acid, a mixture
of sulfur dioxide and sulfur trioxide, chlorosulfonic acid, and so on. Reactions are usually
heterogeneous reactions. Chitosan 6- O -sulfate is prepared by the following steps [68]:
cooling 40 mL of 95% H 2 SO 4 and 20 mL of 98% HCl-SO 3 at 0-4°C, adding 1 g of chitosan to
the solution, slowly heating the mixture to room temperature during stirring, stirring for
1 h, pouring the mixture into 250 mL of cold ether, filtering the mixture, washing the filter
cake with cold ether, dissolving the deposit in water, neutralizing the solution with
0.5 mol/L NaHCO 3 , dialyzing it with water, filtering and drying the product by freezing;
or forming a formic acid solution of chitosan, keeping the pH at 2-7, slowly dripping
1 mol/L CuSO 4 solution into the solution until chitosan-Cu chelate appears, stirring for
16 h, filtering, grinding wet deposits, washing them with dry DMF, mixing them with
30 mL of anhydrous DMF, cooling the mixture to 0-2°C, dripping anhydrous DMF solu-
tion of pyridine-sulfur trioxide that is six times the chelate in mol, heating to 25°C, stirring
for 16 h, ending the reaction by using saturated NaHCO 3 , filtering, dialyzing the filter cake
with water and drying the product by freezing. Chitosan 6- O -sulfate can also be formed
by a mixture of 95% H 2 SO 4 and 98% HClO 4 .
Chitosan 6- O -sulfate is a polyampholyte and is soluble in water. It has stable conforma-
tion in solution because sulfate groups form strong hydrogen bonds with aminos, C3
hydroxyls, and the oxygen bridge of pyranose (Figure 1.10).
Chitosan 6- O -sulfate and chitosan 3- O -sulfate can be formed by changing chitosan into
formate, acetate, perchlorate, nitrate, hydrochloride, or hydrobromide, dissolving it in
DMF, adding cold chlorosulfonic acid to the solution, and stirring. Besides esterification,