Phosphorylation of chitin with tris(dimethylamino)phosphine

Full text of DOI:10.1134/S001250080808003X

ISSN 0012-5008, Doklady Chemistry, 2008, Vol. 421, Part 2, pp. 179–181. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © I.Yu. Kudryavtsev, E.I. Matrosov, E.E. Nifant’ev, 2008, published in Doklady Akademii Nauk, 2008, Vol. 421, No. 5, pp. 638–640.
CHEMISTRY
Phosphorylation of Chitin
with Tris(dimethylamino)phosphine
I. Yu. Kudryavtsev, E. I. Matrosov, and Corresponding Member of the RAS E. E. Nifant’ev
Received March 3, 2008
DOI: 10.1134/S001250080808003X
Chitin is a natural biodegradable polymer available
In this work, we have suggested for the first time a
from renewable natural resources and has the structure new simple method for chitin phosphorylation with the
poly[β-(1 → 4)-N-acetyl-D-glucosamine]. It is present use of tris(dimethylamino)phosphine as a phosphory-
in fungi, yeast, and exoskeletons of insects and marine lating reagent showing high reactivity and previously
invertebrates; chitin is the second most abundant used for the phosphorylation of different hydroxy com-
polysaccharide in nature after cellulose. At the same pounds [13]. The reaction was carried out in the pres-
time, chitin is little utilized as compared with cellulose ence of anhydrous dimethylamine hydrochloride as a
on account of poor solubility in common solvents. Its catalyst upon heating at reflux in dry acetonitrile under
use is confined to its conversion into chitosan by a nitrogen atmosphere.
deacetylation in an alkaline medium [1].
The reaction of chitin with (Me N) P (taken in a
2
3
ratio of 2–4 mol of the phosphorylating reagent per
monomer unit of the polysaccharide) in the presence of
At the same time, the chemical modification of
chitin [1–3] can expand substantially the range of new
advanced products. Chemically modified chitins are of
interest for obtaining biomedical preparations owing to
a lack of toxicity and easy biodegradation in the human
body [3]. These compounds can be used as sorbents for
waste water treatment [4] or as a biopolymer support
for preparing immobilized catalysts [5].
1
0 mol % Me NH Cl (with respect to the phosphorylat-
2 2
ing reagent) leads to a product containing 8.5–8.6% N
and 5.8–5.9% P and an atomic ratio N : P = 3.3–3.1,
which corresponds to the phosphorylation of approxi-
mately half of the glucosamine units (table, entries 1
and 2). The twofold increase in the excess of the phos-
phorylating reagent has little effect on the degree of
substitution (see the table, entry 2).
The relatively low phosphorus content in the poly-
mer is likely to be explained by the hampered diffusion
of the reagent in the biopolymer because of the dense
packing of chitin macromolecules, resulting from an
extended network of hydrogen bonds between polymer
chains. We have studied the possibility of loosening the
polymer structure by introduction into the reaction sys-
tem of additional agents capable of forming competi-
tive hydrogen bonds with hydroxy and amide groups of
the polysaccharide. This would facilitate the access of
the phosphorylating reagent to the reactive groups of
the biopolymer.
Phosphorus-containing derivatives of chitin are a
matter of considerable interest; among them is chitin
phosphate, which was obtained by the reaction of chitin
with phosphoric acid and urea in DMF [6] or phospho-
ric anhydride in methanesulfonic acid [7]. Moreover, it
was reported that the reaction of chitin with P4S10
resulted in phosphorylation products containing 2–22%
S and 1–10% P [8]. Chitin phosphates can be used to
prepare substrates accelerating hydroxyapatite growth
[
9], create biocompatible tissues [10], adsorb alkaline-
earth and transition metals [6] and uranium [11], and
design ion-exchange membranes for fuel cells [12].
As a whole, the known examples of chitin phospho-
rylation are confined to the synthesis of pentavalent
phosphorus compounds, whereas trivalent phosphorus
derivatives are unknown. Nonetheless, the latter should
be highly reactive and therefore able to undergo various
transformations. Furthermore, they could be used as
chiral polymeric ligands for metal-complex catalysts.
For this purpose, we have studied the effect of dim-
ethylamine hydrochloride as such a loosening agent. It
was found that phosphorus content can be increased by
increasing the amount of Me NH Cl in the reaction sys-
2
2
tem. When a mixture of the reagents was heated under
reflux in acetonitrile for 36 h at the molar ratio (per
monomer unit of the polysaccharide) chitin : (Me N) P :
2
3
Me NH Cl = 1 : 4 : 4, a polymer was obtained with the
2
2
degree of substitution (DS) 70% (the value in the poly-
mer containing one phosphorus atom per glucosamine
unit is taken as 100%) (see the table, entry 3). A further
Nesmeyanov Institute of Organoelement Compounds,
Russian Academy of Sciences,
ul. Vavilova 28, Moscow, 119991 Russia
1
79

1
80
KUDRYAVTSEV et al.
Phosphorylation of chitin with tris(dimethylamino)phosphine under reflux for 36 h
Amounts of reagents (mmol) at
Found, %
Additive,
mmol
Oxidizing
agent
N : P atomic
ratio
the chitin : (Me N) P : Me NH Cl
Solvent
2
3
2
2
ratio
N
P
2
2
2
2
2
2
2
: 4 : 0.4
: 8 : 0.8
: 8 : 8
–
MeCN
–
–
8.50
8.63
7.95
7.84
6.37
7.25
7.31
5.92
5.76
7.81
6.08
6.45
6.51
6.47
3.14
3.31
2.24
2.85
2.18
2.48
2.52
–
"
–
–
"
–
: 8 : 16
: 8 : 0.8
: 8 : 0.8
: 8 : 0.8
"
–
LiCl, 8
–
"
Pyridine
"
–
NO2
NO2
LiCl, 8
increase in the amount of Me NH Cl up to the molar lent phosphorus derivative in these experiments was
2
2
ratio chitin : (Me N) P : Me NH Cl = 1 : 4 : 8 slightly oxidized with nitrogen dioxide. Thus, the refluxing of
2
3
2
2
decreases the DS (down to 54%) and the phosphorus chitin with a twofold excess of (Me N) P in pyridine in
2
3
content in the product (see the table, entry 4).
the presence of catalytic amounts of Me NH Cl for
2 2
3
6 h (the ratio chitin : (Me N) P : Me NH Cl = 1 : 4 :
2 3 2 2
We also studied anhydrous LiCl as a loosening
agent that breaks down hydrogen bonds. At the ratio
chitin : (Me N) P : Me NH Cl : LiCl = 1 : 4 : 0.4 : 4
0
.4) followed by treatment with NO afforded a poly-
2
mer with DS = 61% (see the table, entry 6). The addi-
tion of anhydrous LiCl as a loosening agent to this sys-
tem had a negligible effect on the composition of the
phosphorylated biopolymer and the degree of substitu-
tion (see the table, entry 7).
2
3
2
2
(
refluxing in MeCN for 36 h), we obtained a polysac-
charide with DS = 57% (see the table, entry 5).
The IR spectra of the phosphorylated polymers
–
1
show an absorption band at 1660 cm typical of C=O
groups of both phosphorylated polymer and initial
The IR spectra of the phosphorylated biopolymers
–1
chitin; additional bands also appear at 900 cm , which
corresponds to P–N vibrations of the amide fragment
obtained by the reaction of chitin with (Me N) P in a
2
3
pyridine medium followed by oxidation with NO
–1
2
[
14], and at 860 cm , typical for vibrations of P–O
bonds [15].
We also explored the possibility of using pyridine as
–1
show, in addition to the bands at 1660 cm (C=O),
–1
–1
bands at 1230 cm (P=O), 900 cm (P–N), and
–1
8
60 cm (P–O).
a solvent capable of destroying hydrogen bonds
between chitin macromolecules. To facilitate and sim-
The phosphorylation seems to proceed at the most
plify the process of isolation and purification of phos- reactive hydroxy group at the 6-position. As a whole,
phorylated biopolymer and to increase its stability the phosphorylation of chitin can be represented by the
toward washing with water, the initially formed triva- following general scheme:
OH
O
+
(Me N) P
2
3
O
HO
NHAc
n
O
O
OP(NMe2)2
OH
PNMe2
O
O
O
O
O
HO
O
HO
NHAc
NHAc
x
NHAc
Scheme 1.
y
z
It should be noted that many experiments lead to N : P < 3, which can point to the presence of intramo-
phosphorylated polysaccharides with an atomic ratio lecular cyclization or intermolecular crosslinking of
DOKLADY CHEMISTRY Vol. 421 Part 2 2008

PHOSPHORYLATION OF CHITIN WITH TRIS(DIMETHYLAMINO)PHOSPHINE
181
polymer chains of intermediate polysaccharide phos- light brown powder insoluble in common organic sol-
phoramidites through their reaction with free hydroxy vents (see the table, entry 6).
groups to form dimethylamine.
Phosphorylation of chitin with tris(dimethyl-
amino)phosphine in pyridine in the presence of LiCl
followed by oxidation. A mixture of 0.406 g (2 mmol)
EXPERIMENTAL
of chitin, 1.304 g (8 mmol) of (Me N) P, 0.066 g
2
3
(
5
0.8 mmol) of Me NH Cl, 0.34 g (8 mmol) of LiCl, and
2 2
Infrared spectra were recorded on a UR-20 spectro-
photometer in KBr pellets. Chitin from crab shells
mL of anhydrous pyridine was heated for 36 h under
reflux with stirring. The resulting reaction mixture was
(
Fluka) had molecular weight 400 000. Acetonitrile and purged with NO for 2 h. The precipitate was filtered
2
methylene chloride were distilled over P O prior to off, washed with water (7 × 5 mL) and ether (3 × 5 mL),
2
5
and dried in vacuum to give 0.54 g of a product as a
light brown powder insoluble in common organic sol-
vents (see the table, entry 7).
use. Ether was dried and distilled over sodium metal.
Pyridine was dried and distilled over solid KOH.
(
Me N) P was synthesized from Me NH and PCl by a
2 3 2 3
standard procedure. All manipulations with P(III)
derivatives were carried out in a dry nitrogen atmo-
sphere.
REFERENCES
1
. Ravi Kumar, M.N.V., Muzzarelli, R.A.A., Muzzarelli, C.,
Sashiwa, H., and Domb, A.J., Chem. Rev., 2004,
vol. 104, no. 12, pp. 6017–6084.
Phosphorylation of chitin with tris(dimethy-
lamino)phosphine in the presence of dimethy-
lamine hydrochloride in acetonitrile. A mixture of
2
3
4
5
6
. Kurita, K., Prog. Polym. Sci., 2001, vol. 26, no. 9,
0
.406 g (2 mmol) of finely divided chitin, appropriate
pp. 1921–1971.
amounts of (Me N) P and Me NH Cl, and 5 mL of
2
3
2
2
. Sashiwa, H. and Aiba, S., Prog. Polym. Sci., 2004,
vol. 29, no. 9, pp. 887–908.
anhydrous acetonitrile was heated for 36 h under
reflux with stirring. The precipitate was filtered off,
washed with acetonitrile (5 × 10 mL) and methylene
chloride (5 × 10 mL), and dried in vacuum to give a
product as a light brown powder insoluble in common
organic solvents. The molar amounts of the reagents
. Crini, G., Prog. Polym. Sci., 2005, vol. 30, no. 1, pp. 38–
7
0.
. Guibal, E., Prog. Polym. Sci., 2005, vol. 30, no. 1,
pp. 71–109.
. Nishi, N., Maekita,Y., Nishimura, S., Hasegawa, O., and
Tokura, S., Int. J. Biol. Macromol., 1987, vol. 9, no. 2,
pp. 109–114.
(
with respect to one glucosamine unit of chitin), the
content of N and P, and the N : P atomic ratio are pre-
sented in the table (entries 1–4).
7
. Nishi, N., Ebina, A., Nishimura, S., Tsutsumi, A., Hase-
gawa, O., and Tokura, S., Int. J. Biol. Macromol., 1986,
vol. 8, no. 5, pp. 311–317.
Phosphorylation of chitin with tris(dimethyl-
amino)phosphine in the presence of LiCl in acetoni-
trile. A mixture of 0.406 g (2 mmol) of finely divided
chitin, 1.304 g (8 mmol) of (Me N) P, 0.066 g
8
9
. Yalpani, M., Carbohydr. Res., 1992, vol. 19, no. 1,
2
3
pp. 35–39.
(
0.8 mmol) of Me NH Cl, 0.34 g (8 mmol) of LiCl, and
2 2
. Yokogawa,Y., Paz Reyes, J., Mucalo, M.R., Toriyama, M.,
Kawamoto,Y., Suzuki, T., Nishizawa, K., Nagata, F., and
Ratayama, N., J. Mater. Sci. Mater. Med., 1997, vol. 8,
no. 7, pp. 407–412.
5
mL of anhydrous acetonitrile was heated for 36 h
under reflux with stirring. The precipitate was filtered
off, washed with acetonitrile (5 × 10 mL) and ether
(
5 × 10 mL), and dried in vacuum to give 0.45 g of a
1
0. Wang, X.H., Zhu,Y., Feng, Q.L., Cui, F.Z., and Ma, J.B.,
light brown powder insoluble in common organic sol-
vents (see the table, entry 5).
J. Bioact. Compat. Polym., 2003, vol. 18, no. 2, pp. 135–
1
46.
1
1
1. Sakaguchi, T., Hirokoshi, T., and Nakajima, A., Agric.
Biol. Chem., 1981, vol. 45, no. 10, pp. 2191–2195.
Phosphorylation of chitin with tris(dimethy-
lamino)phosphine in pyridine followed by oxida-
tion. A mixture of 0.406 g (2 mmol) of chitin, 1.304 g
2. Yamada, M. and Honma, I., Fuel Cells Bull., 2006, May,
pp. 11-15.
(
8 mmol) of (Me N) P, 0.066 g (0.8 mmol) of
2 3
Me NH Cl, and 5 mL of anhydrous pyridine was 13. Nifantiev, E.E., Grachev, M.K., and Burmistrov, S.Yu.,
2
2
Chem. Rev., 2000, vol. 100, no. 10, pp. 3755–3800.
heated for 36 h under reflux with stirring. The resulting
reaction mixture was purged with NO for 2 h. The pre- 14. Chittenden, R.A. and Thomas, L.C., Spectrochim. Acta,
2
1
966, vol. 22, no. 8, pp. 1449–1463.
cipitate was filtered off; washed with methylene chlo-
ride (3 × 5 mL), water (5 × 5 mL), and ether (3 × 5 mL);
and dried in vacuum to give 0.48 g of a product as a
1
5. Van Der Veken, B.J. and Herman, M.A., Phosphorus
Sulfur, 1981, vol. 10, no. 4, pp. 357–368.
DOKLADY CHEMISTRY Vol. 421 Part 2 2008