ISSN 1070-4272, Russian Journal of Applied Chemistry, 2007, Vol. 80, No. 7, pp. 1151!1153. + Pleiades Publishing, Ltd., 2007.
Original Russian Text + E.V. Novikova, V.M. Smychenko, A.A. Iozep, 2007, published in Zhurnal Prikladnoi Khimii, 2007, Vol. 80, No. 7, pp. 1181!
AND POLYMERIC MATERIALS
Sulfation of Dextran with Chlorosulfonic Acid
in Organic Solvents
E. V. Novikova, V. M. Smychenko, and A. A. Iozep
St. Petersburg State Academy of Pharmaceutical Chemistry, St. Petersburg, Russia
Received November 7, 2006; in final form, March 2007
Abstract-Solutions of chlorosulfonic acid in dichloroethane and formamide are suggested for incorporation
of sulfo groups into macromolecules of polysaccharides. The influence of temperature, reaction duration, and
reactant ratio on the yield of sulfated dextran and also the influence of the reaction conditions on hydrolytic
stability of the polymer were studied.
Polysaccharides containing sulfo groups are widely
used in medicine. Among the existing procedures of
production of these valuable polymers, the best known
procedure is sulfation of polysaccharides with solu-
tions of sulfuric anhydride in organic solvents or its
complexes with tertiary amines, pyridine, and other
related bases . However, SO
should either be pre-
pared from sulfurous anhydride or desorbed from
oleum, which complicates the process equipment and
makes the process hazardous. In this connection,
chlorosulfonic acid produced on the industrial scale
and widely used in synthesis of various drugs (saccha-
rin, thrombovar, sulfanilamides, etc.) is of great inter-
est. Chlorosulfonic acid found application for produc-
tion of dextran sulfate . However, that study in-
volved the use of toxic pyridine [maximum permissi-
ble concentration (MPC) 5 mg m
], whose exhaustive
removal from the target product presents difficulties.
The aim of this study was to develop a procedure
of sulfation of polysaccharides with chlorosulfonic
acid in the medium of less toxic (MPC 10 mg m
and readily removable 1,2-dichloroethane (DCE) in
the presence of formamide (FA).
Chemical modification of polysaccharides was per-
formed by the scheme
n ! k
n ! k
where M is Na or K.
Sulfation of polysaccharides was studied by the
example of the reaction of dextran with chlorosulfonic
A suspension of polysaccharide in a mixture of
DCE and FA was stirred for 1 h at room temperature;
then, a solution of chlorosulfonic acid in DCE was
added, and the mixture was heated at 35365oC for
134 h. After the reaction completion, the mixture was
neutralized with a solution of potassium hydroxide
and dialyzed against water to remove low-molecular-
weight impurities. The dialyzate was concentrated
in a vacuum, and the product was precipitated with
ethanol. The precipitate was washed with ethanol and
dried in a vacuum.
The reaction product was a white amorphous
powder soluble in water and insoluble in ethanol.
In the IR spectrum of dextran sulfate, the absorp-
tion bands at 1250 cm
can be assigned to stretching
modes of sulfo group n
The degree of sulfation C
(number of sulfo groups
per monosaccharide unit) was evaluated from the
results of conductometric titration and acid hydrolysis
of sulfo groups .
An attempt of dextran sulfation with chlorosulfonic
acid in DCE without FA at 335oC by the procedure
developed previously for sulfuric anhydride 
resulted in tarring of the reaction mixture. A decrease
in temperature of the reaction mixture to 35oC al-
lowed us to avoid polymer blackening, but C
peared to be 3 times lower than that after the reaction