Monosaccharide phenylphosphonites

Article abstract of DOI:10.1134/S1070363206020058

Synthesis and chemical properties of the first carbohydrate phenylphosphonites are described. Pleiades Publishing, Inc., 2006.

Full text of DOI:10.1134/S1070363206020058

ISSN 1070-3632, Russian Journal of General Chemistry, 2006, Vol. 76, No. 2, pp. 198 201.
Pleiades Publishing, Inc., 2006.
Original Russian Text
No. 2, pp. 211 214.
D.V. Khodarev, T.S. Kukhareva, E.V. Lipovtsin, E.E. Nifant’ev, 2006, published in Zhurnal Obshchei Khimii, 2006, Vol. 76,
Monosaccharide Phenylphosphonites
D. V. Khodarev, T. S. Kukhareva, E. V. Lipovtsin, and E. E. Nifant’ev
Moscow Pedagogical State University, per. Nesvizhskii 2, Moscow, 119021 Russia
e-mail: chemdept@mtu-net.ru
Received April 18, 2005
Abstract Synthesis and chemical properties of the first carbohydrate phenylphosphonites are described.
DOI: 10.1134/S1070363206020058
Previously in our laboratory we obtained and
studied hydrophosphoryl derivatives of protected
monosaccharides containing P C [1, 2] and P OAlk
[3 5] bonds. With alkyl phosphites as examples, we
showed that these compounds readily form complexes
with some of transition metals. Proceeding with these
studies, we prepared the first monosaccharide phenyl-
phosphonites and examined their chemical properties.
The desired compounds were prepared by a two-
step procedure involving in the first step the reaction
of a carbohydrate with an equimolar amount of phenyl-
phosphonous dichloride. As a carbohydrate matrix we
used 1,2:5,6-di-O-isopropylidene- -D-glucofuranose I,
1,2:4,5-di-O-cyclohexylidene- -D-fructopyranose II,
and
1-O-methyl-2,3-O-isopropylidene- -L-rhamno-
pyranozide (III):
Cl
Cl
dioxane, Py
Sug O P
SugOH + Ph P
12 C
Cl
Ph
I III
IV VI
OCH3
HO
O
H
CH2O
O
.
O
.
O
H
O
.
O\
HO
(II, V),
(III, VI).
(I, IV),
Sug =
O
H
.
HO
O
.
.
.
O
.
.
.
.
.
H
O
.
.
H
. .
.
.
.
O
O
.
.
To perform this reaction, a solution of 1 equiv of
monosaccharide and 2.5 equiv of pyridine in dioxane
was added to 1.1 equiv of phenylphosphonous dichlo-
ride. The rate of dropwise addition of the carbohydrate
to the phosphorylating agent is very significant. To
avoid formation of by-products and to increase the
phosphonous monochloride yield, the addition should
be performed over a period of 20 to 30 min. The re-
action progress was monitored by 31P NMR spec-
troscopy. The 31P spectrum of the reaction mixture
contained singlets at 168 174 ppm corresponding to
monochlorides IV VI. In the second step, mono-
chlorides IV VI obtained, which are extremely labile,
were hydrolyzed without additional purification to
the corresponding hydrophosphoryl compounds
VII IX:
OH
Ph
Py
*
IV VI + H2O
Sug O P
12 C
O
H
Sug O*P
1
2
3
4
VII IX
Their 31P NMR spectra contained doublets with
1
chemical shifts of 25 26 ppm, JPH 570 600 Hz. It
198

MONOSACCHARIDE PHENYLPHOSPHONITES
199
should be noted that phosphorylation with phenyl-
phosphonous dichloride gives rise to chirality of the
P atom, and therefore the final synthesis products
VII IX were obtained as mixtures of two diastereo-
mers. The structures of VII IX were proved by 13C
and 31P NMR spectroscopy.
eter (32.4 MHz, external reference 85% orthophos-
phoric acid). Column chromatography was performed
with silica gel L 100/160. TLC analysis was per-
formed on Silufol UV-254 plates using the following
systems: benzene dioxane 7:1 (A), hexane dioxane
3:1 (B), hexane dioxane 5:1 (C), hexane dioxane
5:2 (D), hexane dioxane 10:1 (E), and hexane di-
oxane triethylamine 28:2:1 (F). The chromatograms
were developed with iodine vapor or by calcination.
Phenylphosphonites VII and IX were brought into
electrophilic Kabachnik Fields and Abramov reac-
tions, and previously unknown carbohydrate-substi-
tuted phosphinates were prepared. In the Kabachnik
Fields reaction we used bis(diethylamino)methane as
an electrophilic reagent:
In all the syntheses we used anhydrous solvents
and performed the reactions under dry oxygen-free
argon.
1,2:5,6-Di-O-isopropylidene- -D-glucofuranose
3-O-phenylphosphonite VII. A solution of 1.06 g of
monosaccharide I and 0.81 g of pyridine in 5 ml of
dioxane was slowly (over a period of 20 30 min)
added dropwise with cooling (bath temperature 12 C)
to a solution of 0.80 g of phenylphosphonous dichlo-
ride in 3 ml of dioxane. The mixture was stirred for
30 min at room temperature, then again cooled, and
0.08 g of water dissolved in 3 ml of dioxane was
slowly added. The mixture was then stirred for 30 min
at room temperature, the pyridinium chloride preci-
pitate was filtered off, the filtrate was evaporated, and
the residue was passed through a column packed with
silica gel (elution with system A). Yield 0.67 g (43%);
white powder-like substance, mp 115 117 C, Rf 0.51
NEt2
VII, IX + H2C
NEt2
O
CH2 NEt2
CHCl3
Sug O*P
+ NHEt2
46 48 C
Ph
X, XI
Bis(diethylamino)methane was taken in an excess
(2.5 equiv per 1 equiv of the sugar) at a glycerol bath
temperature of 46 47 C. Compounds X and XI were
formed each as two diastereomers in approximately
equal amounts. In the Abramov reaction we used
chloral. The reaction occurred more readily than the
Kabachnik Fields aminomethylation:
(E). 13C NMR spectrum (CDCl3), , ppm: 24.9 26.5
O
all s [C(CH3)2], 67.0, 67.4 both s (C6), 72.4 s (C5),
74.0, 74.6 both s (C3), 81.1, 83.4 s (C4), 83.5, 84.9
both s (C2), 104.8, 105.0 both s (C1), 108.9,
111.3 and 109.2, 112.2 all s [C(CH3)2], 128.4, 128.7
both s (C3 ), 130.6 s (C2 ), 131.3 s (C4 ), 131.9 d (C1 ,
1JPC 153.0 Hz). 31P NMR spectrum (CHCl3), P, ppm:
28.2 d (1JPH 578.0 Hz), 26.5 d (1JPH 577.3 Hz).
Found, %: C 56.15; H 6.66; P 7.98. C18H25O7P.
Calculated, %: C 56.25; H 6.56; P 8.06.
VII, IX + Cl3C C
H
OH
O
*
CH CCl3
CHCl3
Sug O*P
Ph
XII, XIII
The reaction was performed at equimolar reactant
ratio with slight cooling (15 C in the bath). Com-
pounds XII and XIII were formed each as four iso-
mers. It is interesting that in the reaction with rham-
nose virtually a single diastereomer of XIII was ob-
tained. Thus, it is principally possible to prepare in a
satisfactory yield monosaccharide hydrophosphoryl
derivatives which can be used in reactions with elec-
trophiles. This result opens prospects for the design
of complicated carbohydrate phosphorus structures
which are interesting as bioregulators and the ligands
for coordination catalysts.
1,2:4,5-Di-O-cyclohexylidene- -D-fructopyra-
nose 3-O-phenylphosphonite VIII. A solution of
0.71 g of monosaccharide II and 0.41 g of pyridine
in 5 ml of dioxane was slowly (over a period of 20
30 min) added dropwise with cooling (bath tempera-
ture 12 C) to a solution of 0.41 g of phenylphos-
phonous dichloride in 3 ml of dioxane. Then the mix-
ture was stirred for 30 min at room temperature,
cooled again, and 0.04 g of water dissolved in 2 ml of
dioxane was added. Then the mixture was stirred for
30 min and left overnight. The resulting mixture was
filtered to remove pyridinium chloride precipitate and
evaporated; by-products were removed by precipita-
tion with hexane. The solution in hexane was left for
12 h for complete precipitation of the by-products.
The solvent was then evaporated and the residue was
EXPERIMENTAL
The 13C NMR spectra were recorded on a Bruker
AC-200 instrument (50.32 MHz). The 31P NMR spec-
tra were measured on a Bruker WP-80SY spectrom-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 2 2006

200
KHODAREV et al.
1
passed through a column packed with silica gel (elu-
tion with system E). For better purification, the
product was dissolved in a small amount of hexane
(ca. 2 ml) and left for 12 h, then the solution was
filtered and evaporated. Yield 0.31 g (32%); colorless
oily substance, Rf 0.15 (E). 13C NMR spectrum
(CDCl3), , ppm: 23.35 23.77, 34.93 37.75 (cyclo-
hexylidene protecting group); 60.6, 60.7 both s (C6),
1JPC 115.6, JPC 122.0 Hz), 66.8, 67.0 both s (C6),
71.4, 71,6 both s (C5), 71.9, 72.3 both s (C3), 80.1,
80.3 both d (C4, JPC 7.5, JPC 5.5 Hz), 83.1 d (C2,
3JPC 8.2 Hz), 104.4, 104.5 both s (C1), 108.6, 111.4
and 108.6, 111.5 all s [C(CH3)2], 127.7, 127.9 both d
3
3
(C2 , JPC 11.4, JPC 12.4 Hz), 128.9, 129.0 both s
2
2
(C3 ), 131.4, 131.6 both d (C1 , JPC 72.5, JPC
1
1
72.4 Hz), 131.5, 131.8 both s (C4 ). 31P NMR spec-
trum (CHCl3), P, ppm: 40.2, 42.7 both s. Found, %:
C 58.96; H 7.59; P 6.74. C23H36NO7P. Calculated, %:
C 58.84; H 7.73; P 6.60.
71.5, 71.7 both s (C1), 72.9 d (C4, 3JPC 5.2 Hz), 73.9,
2
74.0 both s (C5), 74.7 d (C3, JPC < 2.0 Hz), 103.0,
3
103.1 both d (C2, 3JPC 5.5, JPC 4.7 Hz), 110.0, 112.7,
and 110.5, 112.8 all s (Cquat), 128.3, 128.5 both d
2,3-O-Isopropylidene- -L-methylrhamnopyra-
noside 4-O-[(diethylaminomethyl)phenylphosphi-
nate] XI. A solution of 0.60 g of bis(diethylamino)-
methane in 2 ml of chloroform was added dropwise
to 0.55 g of IX in 3 ml of chloroform. The mixture
was heated for 5 h at a glycerol bath temperature of
44 46 C. Then the solvent was evaporated and the
mixture was separated on a column using system F.
Yield 0.34 g (49%); colorless oily substance, Rf 0.26
(F). 13C NMR spectrum (C6D6), , ppm: 12.3, 12.4
2
(C2 , JPC 6.0 Hz); 130.3 s (C3 ), 130.5, 130.8 both s
1
(C4 ), 132.0 d (C1 , JPC 92.6 Hz). 31P NMR spectrum
(CHCl3), P, ppm: 27.2, 27.6 d (1JPH 598.5 Hz).
Found, %: C 62.17; H 7.03; P 6.54. C24H33O7P.
Calculated, %: C 62.06; H 7.16; P 6.67.
2,3-O-Isopropylidene- -L-methylrhamnopyra-
noside 4-O-phenylphosphonite (IX). A solution of
0.65 g of monosaccharide III and 0.59 g of pyridine
in 5 ml of dioxane was slowly (over a period of 20
30 min) added dropwise with cooling (bath tempera-
ture 12 C) to a solution of 0.59 g of phenylphospho-
nous dichloride in 3 ml of dioxane. The mixture was
stirred for 30 ml at room temperature and cooled
again, and 0.06 g of water dissolved in 2 ml of di-
oxane was added. The stirring was continued for
30 min, and the mixture was left overnight. Pyridi-
nium chloride was filtered off, and the residue was
separated on a column (system B). Yield 0.28 g
(27%); colorless oily substance, Rf 0.32 (C). 13C NMR
spectrum (CDCl3), , ppm: 18.2 s (C6), 26.5 28.7 all s
[C(CH3)2], 54.8 s (OCH3), 63.9, 64.0 both s (C5),
75.9, 76.0 both s (C2), 78.3, 78.6 both s (C3), 79.1 d
both s (NCH2CH3), 18.6 s (C6), 49.1, 49.3 both d
3
3
(NCH2CH3, JPC 9.3, JPC 8.9 Hz), 53.7 d (P CH2,
1JPC 113.7 Hz), 55.0 s (OCH3), 65.3, 65.6 both d (C5,
3JPC 3.4, JPC 2.9 Hz), 77.1, 77.2 both s (C2), 77.6,
3
77.7 both s (C3), 86.8 s (C4), 98.7 s (C1), 98.7, 109.8
and 98.7, 110.3 all s [C(CH3)2], 128.2, 128.8 both s
(C2 ), 132.3, 132.5 both s (C3 ), 133.6, 133.9 both s
1
(C4 ), 133.8 d (C1 , JPC 71.9 Hz). 31P NMR spectrum
(CHCl3), P, ppm: 40.15 s. Found, %: C 59.10; H
8.09; P 7.11. C21H34NO6P. Calculated, %: C 59.00;
H 8.02; P 7.25.
1,2:5,6-Di-O-isopropylidene- -D-glucofuranose
3-O-[(1 -hydroxy-2 ,2 ,2 -trichloroethyl)phenylphos-
phinate] XII. A solution of 0.31 g of freshly distilled
chloral in 2 ml of chloroform was added dropwise at
15 C (water bath) to 0.73 g of VII in 3 ml of chloro-
form. The mixture was stirred for 1 h, after which the
solvent was evaporated and the system was separated
on a column using system A. Yield 0.38 g (38%);
colorless amorphous substance, mp 73 76 C, Rf 0.20
2
(C4, JPC 7.2 Hz), 97.7 s (C1), 109.5, 110.0 both s
2
2
[C(CH3)2], 128.5, 128.8 both d (C2 , JPC 7.1, JPC
7.0 Hz), 130.5, 130.8 both s (C3 ), 131.0, 131.3 both
s (C4 ), 132.2 d (C1 , JPC 93.4 Hz). 31P NMR spec-
1
1
trum (CHCl3), P, ppm: 26.6, 27.1 both d, JPH
572.3 Hz. Found, %: C 56.25; P 8.93. C16H23O6P.
Calculated, %: C 56.14; P 9.05.
1,2:5,6-O-Diisopropylidene- -D-glucofuranose
3-O-[(diethylaminomethyl)phenylphosphinate] X.
A solution of 0.72 g of bis(diethylamino)methane in
2 ml of chloroform was added dropwise to 0.75 g of
VII in 3 ml of chloroform. The reaction mixture was
heated for 5 h at a glycerol bath temperature of 45
47 C. Then the solvent was evaporated and the mix-
ture was separated on a column using system C. Yield
0.39 g (42%); oily substance, Rf 0.15 (C). 13C NMR
spectrum (CDCl3), , ppm: 12.9 c (NCH2CH3), 24.5
26.3 all s [C(CH3)2], 47.8, 47.9 both d (NCH2CH3,
(A). 13C NMR spectrum (CDCl3), , ppm: 25.0 26.6
[C(CH3)2], 66.8 67.8 (C6), 71.8 72.8 (C5), 78.4 79.8
(CHOH), 80.3 81.1 (C4), 83.5 85.0 (C2), 97.5 97.8
(CCl3), 105.0 105.1 (C1), 109.1 112.4 [C(CH3)2],
125.3 133.8 (Ph). 31P NMR spectrum (CHCl3),
,
P
ppm: 37.0, 34.5, 35.1, 32.6 all s. Found, %: C 45.25;
H 5.03; P 5.65. C20H26Cl3O8P. Calculated, %: C
45.17; H 4.93; P 5.82.
2,3-O-Isopropylidene- -L-methylrhamnopyra-
noside 4-O-[(1 -hydroxy-2 ,2 ,2 -trichloroethyl)-
phenylphosphinate] XIII. A solution of 0.29 g of
3
3JPC 12.8, JPC 13.0 Hz), 51.2, 51.6 both d (P CH2,
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MONOSACCHARIDE PHENYLPHOSPHONITES
freshly distilled chloral in 2 ml of chloroform was
201
REFERENCES
added dropwise at 15 C (water bath) to 0.62 g of IX
in 3 ml of chloroform. The mixture was stirred for
1 h. The solvent was evaporated, and the mixture was
separated on a column using system D. Yield 0.46 g
(52%); colorless amorphous substance, mp 149
150 C, Rf 0.35 (D). 13C NMR spectrum (CDCl3), ,
1. Nifantyev, E.E., Kukhareva, T.S., Khodarev, D.V.,
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ppm: 18.2 s (C6), 26.5 28.7 all s [C(CH3)2], 54.8 s
3
(OCH3), 64.1 d (C5, JPC 3.2 Hz), 78.8 s (C3), 80.0 s
1
(C4), 81.6 d (CHOH, JPC 113.2 Hz), 97.4 s (C1),
3. Nifant’ev, E.E. and Kukhareva, T.S., Zh. Obshch. Khim.,
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4. Nifant’ev, E.E., Kukhareva, T.S., Koroteev, M.P.,
Klabunovskii, E.I., and Pavlov, V.A., Dokl. Akad. Nauk
SSSR, 1980, vol. 253, no. 6, p. 1389.
2
97.8 d (CCl3, JPC 7.3 Hz), 109.1, 110.1 both s
2
[C(CH3)2], 127.6 d (C2 , JPC 13.8 Hz), 132.6 s (C3 ),
1
133.3 d (C1 , JPC 46.8 Hz), 133.5 s (C4 ). 31P NMR
spectrum (CHCl3), P, ppm: 33.0, 34.0 all s. Found,
%: C 44.02; H 5.00; P 6.20. C18H24Cl3O7P. Calcu-
lated, %: C 44.15; H 4.94; P 6.32.
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SSSR, 1980, vol. 250, no. 6, p. 1395.
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