Tris-phosphorylated esters of symmetrical and unsymmetrical triols

Article abstract of DOI:10.1134/S1070363208050083

By reaction of a series of triols and monosaccharides with 5,5-dimethyl-2-chloro-1,3,2-dioxaphosphorinane their tris-phosphorylated derivatives were synthesized, and the simplest chemical transformations of the latter were studied. Structures of the obtained P(V) derivatives were confirmed by ¹H, ¹³C and ³¹P NMR spectroscopy and by the MALDI TOF mass spectrometry and X-ray structural analysis.

Full text of DOI:10.1134/S1070363208050083

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 5, pp. 883–891. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © N.M. Pugashova, A.M. Koroteev, I.S. Bushmarinov, K.A. Lysenko, E.N. Andriutse, M.P. Koroteev , E.E. Nifant’ev, 2008, published
in Zhurnal Obshchei Khimii, 2008, Vol. 78, No. 5, pp. 741–749.
Tris-Phosphorylated Esters of Symmetrical
and Unsymmetrical Triols
N. M. Pugashovaa, A. M. Koroteeva, I. S. Bushmarinovb, K. A. Lysenkob,
E. N. Andriutsea, M. P. Koroteev a, and E. E. Nifant’eva
a Moscow Pedagogical State University
Nesvizhskii per., 3, Moscow119021, Russia
е-mail: mpkoroteev@mail.ru
b Institute of Organoelemental Compounds, Russian Academy of Sciences, Moscow, Russia
Received January 25, 2008
Abstract—By reaction of a series of triols and monosaccharides with 5,5-dimethyl-2-chloro-1,3,2-
dioxaphosphorinane their tris-phosphorylated derivatives were synthesized, and the simplest chemical trans-
formations of the latter were studied. Structures of the obtained Р(V) derivatives were confirmed by 1Н, 13С
and 31Р NMR spectroscopy and by the MALDI TOF mass spectrometry and X-ray structural analysis.
DOI: 10.1134/S1070363208050083
Up till now bis-phosphorylated polyol systems
including two phosphorus atoms are well studied [1–3]
while the systems with three and more phosphoric
nodes are poorly documented. Investigation of trends
in the synthesis and reactivity features of such
compounds may provide promising ligands for
designing new types of catalysts, extraction agents and
tetrachloride or dioxane was used. Choice of these
solvents was governed by the difference in solubility
of the parent triols. Reaction progress was monitored
by TLC and 31Р NMR spectroscopy. We found that the
completion of triols phosphorylation occurred in 1.5 h
after mixing the initial reagents. In the 31Р NMR
spectra of the reaction mixtures after reaction comple-
tion were registered singlet signals in the regions of
122 or 121 ppm for the compounds IV or V,
other
practically
important
products.
This
communication describes the results of studying
exhaustive phosphorylation of a series of triols.
Scheme 1.
In the first step of this investigation simplest 1,1,1-
trimethylolalkanes, metriol (I) and etriol (II), were
chosen as a matrix for the polyphosphorylation. Due to
the presence of symmetrically located primary hydroxy
groups these triols are promising substrates for
obtaining sterically loaded systems. There are no steric
hindrances to their phosphorylation, therefore these
syntheses should proceed effectively under mild
conditions and with a high yield.
CH2OH
O
C
CH2OH + 3 Cl
R
P
O
CH2OH
Ι−II
III
O
P
O
CH2O
CH2O
CH2O
O
3 Et3N
We prepared tris-phosphorylated
1,1,1-trime-
C
R
P
−3 Et3N HCl
O
O
thylolalkane esters I, II by reaction of the
corresponding triol with three-fold equivalent amount
P
of
5,5-dimethyl-2-chloro-1,3,2-dioxaphosphorinane
O
(“neopentylchlorophosphite”) in the presence of
triethylamine at room temperature. As a solvent for the
synthesis of tris-phosphites IV and V carbon
ΙV−V
R = CH3 (I, IV); C2H5 (II, V).
883

884
PUGASHOVA et al.
respectively, that corresponded to the phosphates
based on neopentylene glycol [4]. Existence of a single
signal in each case reveals the high symmetry of the
system that leads to magnetic equivalence of all
phosphorus nuclei.
tions and the monitoring of the reaction process are
analogous to those in preceding experiments. In the 31Р
NMR spectrum of the reaction mixture were registered
three singlet signals of equal intensities with chemical
shifts 123.4, 124.0 and 124.3 ppm that confirmed
indirectly nonequivalence of hydroxy groups in the
parent triol.
Yield of tris-phosphite VII by the data of 31Р NMR
spectroscopy was only 58%, probably die to steric
hindrances for the phosphorylation at the secondary
hydroxy group of trihydroxybutane.
Yield of tris-phosphite from metriol IV was 92%,
from etriol derivative V, 93%, judging from the
31
integral intensities in the Р NMR spectra. Phosphites
IV and V after removing from the reaction mixture
triethylamine hydrochloride and solvent were
characterized by 13С NMR spectroscopy (see Experi-
mental).
In the second step of this investigation we studied
synthesis of tris-phosphites based on heavier triols,
partially protected monosaccharides, 1,2-О-alkylidene-
glucofuranose and methyl β-D-xylopyranoside. We
found that tris-phosphites from these compounds were
formed in the reaction of the parent triol with 5,5-
dimethyl-2-chloro-1,3,2-dioxaphosphorinane in the 1 : 3
ratio. The syntheses were carried out at stirring and
cooling to 5°С of the reaction mixtures with dioxane as
solvent. As an acceptor of hydrogen chloride were
used either pyridine or triethylamine. After charging
neopentylenechlorophosphite the mixture was addi-
tionally stirred for 1 h at room temperature, because in
these cases reaction proceeded slower than in the
syntheses of tris-phosphites IV, V, and VII.
Besides, we carried out complete phosphorylation
of unsymmetrical 1,2,4-butanetriol. Reaction condi-
Scheme 2.
O
O
O
C
P
P
H2
OH
OH
H2C
O
O
H
C
H
C
3 Et3N
O
+ III
−3 Et3N HCl
H2C
H2C
H2C
O
O
O
P
H2C OH
VI
VII
Scheme 3.
H
H
O
H
H
H
H
O
O
H
P
3 Py
HCl
O
HO
O
OMe
OMe
+ III
H
−3 Py
O
HO
O
OH
P
O
H
H
H
H
O
P
O
O
VIII
IX
O
H
H
P
H
H
O
O
O
HO
O
O
3 Et3N
−3 Et3N
HO
O
H
HO
H
+ III
P
HCl
O
H
O
H
O
O
O
O
H
H
P
O
O
X
XI
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TRIS-PHOSPHORYLATED ESTERS OF SYMMETRICAL AND UNSYMMETRICAL TRIOLS
885
The reaction progress was monitored by TLC and
31Р NMR spectroscopy. In the 31Р NMR spectra of
reaction mixtures after reaction completion, in both
cases were registered three singlet signals in the region
of 121–123 ppm. Yields of compounds IX and XI
were 72 and 76%, respectively. Similarly, at the
treatment of thе methyl-β-D-xylopyranoside with 2-
chloro-1,3,2-dioxaphosphorinane (“propylenechloro-
phosphite”) we obtained tris-phosphite (XIII). The
phosphorus nuclei in the latter resonated at δР 127.7,
128.1, and 129.5 ppm.
were absent but singlet signals were registered in the
region of –8 ppm characteristic of this kind phosphates
[4].
Sulfuration and selenation of compounds IV and V
was achieved by keeping the mixture of reacting
substances for 1.5–2 h at room temperature. As a
solvent for sulfuration was used benzene, for
selenation, dioxane. After completing the process, in
the 31Р NMR spectra of reaction mixtures singlet
signals in the region 60–61 ppm were observed
characteristic of thiophosphates and, respectively, in
the region 64–65 ppm characteristic of selenophos-
phates [4].
Scheme 4.
O
VIII +
Cl
P
Scheme 5.
O
XII
O
X
H
H
P
X
O
O
O
CH2O
O
H
[X]
P
O
IV, V
C
CH2O
CH2O
R
P
O
OMe
H
H
O
O
3 Py
−3 Py
O
O
HCl
P
O
P
H
H
X
O
P
O
O
O
XIV–XIX
XIII
R = CH3, X = O (XIV); S (XV); Se (XVI); R = C2H5, X = O
(XVII); S (XVIII); Se (XIX).
Yield of the phosphite by the data of 31Р NMR
spectroscopy was 69%. Thus, we can conclude that the
selected triols based on the partially protected
carbohydrates VIII and X afford the corresponding
tris-phosphites IX, XI and XIII fairly readily. Despite
the steric hindrances, this reaction proceeds under mild
conditions. However, we have to note that the
synthesized phosphites are not stable enough under the
conditions of their isolation (chromatography,
crystallization). Therefore they were transformed into
compounds with pentavalent phosphorus atom.
Under the reaction conditions the target derivatives
with pentavalent phosphorus precipitated from the
reaction mixtures, and their isolation was thus
simplified. Tris-phosphates XIV and XVII, tris-
thionophosphates XV and XVIII, and tris-selenophos-
phates XVI and XIX were isolated in high yields and
were characterized. They are white powders with high
melting points (see Table 1 and Experimental)
To obtain stable derivative of tris-phosphorylated
polyol VII excess sulfur was added to this compound,
and the mixture was left overnight. After completion
of the process in the 31Р NMR spectrum a signal
characteristic of neopentylene glycol thionophosphate
was observed in the region of δР 61 ppm.
For instance, phosphorylated esters IV and V were
isolated and characterized as the corresponding
phosphates, thionophosphates, and selenophosphates.
These compounds are stable crystalline substances.
Oxidation of tris-phosphorylated esters IV and V
with urea-hydrogen peroxide adduct was carried out at
room temperature in methylene chloride with two-fold
excess of the oxidizer. Reaction process was monitored
by 31Р NMR spectroscopy.
To the reaction completion in the 31Р NMR spectra
of reaction mixture the signals of parent phosphites
Obtained compound XX was isolated by column
chromatography on silica gel in 36% yield. Structures
of the synthesized compounds XIV–XX were also
confirmed by elemental analysis and 1Н and 13С NMR
spectra. The spectra contained signals of all proton
groups with appropriate intensity and the expected sets
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 5 2008

886
PUGASHOVA et al.
Table 1. Characteristic parameters of compounds XIV–
Scheme 7.
XXIII
H
R
S
O
H
Compound
XIV
X
О
S
Yield, %
81
mp, °С
202–204
202–203
δР, ppm
–7.4
O
R
P
H
O
O
OMe
H
S
S
O
IX,
XIII
O
71
60.8
XV
S
O
P
O
H
H
P
Se
О
S
65
166–168 65.1 (JРSe 987 Hz)
XVI
O
O
75
208–210
202–204
–8.5
61.1
XVII
XVIII
XIX
R
R
R
94
R
Se
S
65
168–170 64.4 (JРSe 987 Hz)
125–126 60.7, 61.1, 61.4
158–160 61.5, 62.8, 63.1
152–153 63.2, 64.5, 65.1
139–140 59.7, 60.1, 60.4
XXI, XXII
R = H (XXI); R = Me (XXII).
36
XX
S
31
XXI
S
27
XXII
XXIII
In the spectrum of tris-thionophosphate from
glucose XXIII were observed three signals in the
region of 60–61 ppm of equal intensity, evidencing
formation of this product.
S
32
Scheme 6.
S
Scheme 8.
O
O
O
H2C
P
O
O
O
P
S
H
C
P
S
H
O
S
O
O
H
O
VII
O
O
O
S
H2C
S
H
O
S
XI
P
O
O
O
H
C
H2
O
P
S
O
H
P
O
O
XX
of the signals of carbon nuclei. Composition of tris-
phosphorylated butanetriol derivative XX was also
proved by the MALDI TOF method. In the mass
spectrum thus obtained a well expressed peak is
observed with mass number 621 corresponding to
molecular ion [М + Na+] (see Experimental), and
fragmentation peaks of this compound.
XXIII
Thiophosphates XXI–XXIII were isolated in
individual state by column chromatography on silica
gel. The obtained compounds are white solid
substances with high melting points. Their structures
13
were confirmed by 1Н and С NMR spectroscopy and
We found that the tris-phosphites derived from
carbohydrates (IX, XI and XIII) add sulfur under more
rigid conditions, therefore to these tris-phosphites was
added crystalline sulfur in excess at short heating and
then reaction mixtures were left overnight. After
completion of the process, in the 31Р NMR spectra
signals characteristic of thionophosphates were
registered: from thionophosphate XXI appeared a
group of signals in the region of 63–65 ppm, and from
phosphate XXII were observed three signals with
chemical shifts 61.5, 62.8 and 63.0 ppm.
elemental analysis. By the MALDI TOF method was
measured the molecular mass of compound XXII. The
mass of molecular ion was m/z = 678 [М + + Na+]+.
Unambiguous evidence of the structure of tris-
thiophosphate XXI was obtained by X-ray diffraction
analysis. The general view of molecule XXI is shown
in the figure, the principal bond lengths and bond
angles are listed in Table 2. In crystal of compound
XXI methyl-β-D-xylopyranoside fragment of the
4
molecule is in the chair С1 conformation with devia-
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TRIS-PHOSPHORYLATED ESTERS OF SYMMETRICAL AND UNSYMMETRICAL TRIOLS
887
tion of O5 and C3 atoms 0.702(3) and –0.606(4) Å,
respectively, from the plane formed by the atoms
C1C2C4C5 (average deviation 0.01 Å).
bonds are in antiperiplanar position that promotes
charge transfer lpO
→σ*(P42–O41), lpO →σ*(P42–O43)
4
4
(pseudo-torsion angles lpO4P42O41 and lpO4P42O43 are
170.2 and 176.1°, respectively), while for two other
dioxathionophosphate substituents such interaction is
either impossible, or is much weaker because the
respective pseudotorsion angles lpOPO are 140° only
or less. Existence of these stereoelectronic interactions
involving lone electron pairs of oxygen atom О4 fol-
lows from contraction of P42–O4 bond length [1.573(2) Å]
by 0.026 Å as compared to the bonds P32–O3 [1.599(2) Å]
and P22–O2 [1.599(2) Å], and some elongation of
bonds Р42–О in the rings (see Table 2.). Difference in
the orientation of dioxathionophosphate fragments
probably is defined by the scope of weak van der
Waals interactions in the crystal.
All three dioxathionophosphate fragments of the
molecule are characterized by the same conformation
of screwed chair with deviation of phosphorus and Сn5
atoms (С25, С35 and С45, see the figure) from the planes
of remaining atoms of the ring (average deviation
varies in the range 0.005–0.02 Å) by 0.60–0.72 Å.
Phosphorus atoms in the structure are characterized
by slightly distorted tetrahedral configuration with
bond angles in the range 101.1(1)°–117.1(1)° with
systematic decrease in endocyclic ОРО angles and
increase in exocyclic ОРS angles. The bond lengths
and bond angles in dioxathionophosphate rings are
close by value and correspond to published data for
such systems [5]. Noteworthy that the mutual positions
of dioxathionophosphate rings and central pyranose
ring for three independent fragments are different.
Actually, the values of torsion angles S2P22O2C2,
S3P32O3C3, and S4P42O4C4 are 26.6(2), –5.4(2) and
172.91(18)°, respectively. Therewith, the difference in
torsion angles leads to change in character of possible
stereoelectronic interactions of oxygen atoms О2, О3
and О4. Thus, in the case of dioxathionophosphate
fragment in the 4th position of pyranose ring the lone
electron pairs (lp) of the atom О4 and endocyclic Р–О
Thus, we first synthesized a series of earlier unknown
esters containing three phosphorus atoms, investigated
their structure and showed that cyclic phosphites of
triols and monosaccharides show high reactivity in
oxidation and sulfuration.
EXPERIMENTAL
All experiments with trivalent phosphorus com-
pounds were carried out under nitrogen atmosphere
using carefully dried solvents. The 31Р NMR spectra
C11
O5
C24
O23
C25
O1
O2
C1
C5
O4
C2
C4
S4
O41
C26
C3
P42
P22
S3
C46
C45
O21
O3
P32
O43
S2
C44
O33
C34
O31
C36
C35
General view of 2,3,4-Tris-(2'-thio-5',5'-dimethyl-1',3',2'-dioxaphosphorinane)methyl-β-D-xylopyranoside (XXII) .
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 5 2008

888
PUGASHOVA et al.
Table 2. Selected values of bond length (d, Å) and bond
angles (ω, deg) of compound XXI
NMR spectra of compounds V and XV and XIX were
additionally registered on a Bruker АVANCE-400
instrument with operating frequencies 161.98 (31Р),
100.61 (13С) and 400.13 MHz (1Н). For elemental
analysis was used automatic analyzer Perkin-Elmer-
2400. Measuring of monoisotopic (12С) molecular
masses was realized on a Bruker UltraFlex (Bruker
Daltomics, Germany) instrument.
Bond
d
Bond
P42–O41
P42–O43
O1–C1
O1–C11
O2–C2
O3–C3
O4–C4
O5–C5
O5–C1
d
S2–P22
1.9061(11)
1.9125(10)
1.9127(11)
1.573(2)
1.579(2)
1.599(2)
1.573(2)
1.577(2)
1.594(2)
1.584(2)
1.589(2)
1.376(3)
1.427(4)
1.435(3)
1.446(3)
1.448(3)
1.427(3)
1.432(3)
S3–P32
S4–P42
P22–O21
P22–O23
P22–O2
Colorless crystals of compound XXI have been
grown from benzene. At100 K the crystals of XXI are
rhombic, space group P212121, a 8.1904(7), b 12.827(1),
c 22.951(2) Å, V 2411.4(4) Å3, Z 4 (Z' 1), dcalc. 1.577 g
cm−3, μ(MoKα) 0.559 cm–1, F(000) 1192. Intensities of
16 999 reflexes were measured at the tem-perature 100
K on a Bruker SMART APEX II CCD diffractometer
[λ(MoKα) 0.71073 Å, ω-scan, 2θ < 60°], 6836
independent reflexes (Rint 0.0527) were used for
further refinement. Structure was solved by the direct
method and consecutive syntheses of electron density.
Positions of hydrogen atoms were determined from
difference Fourier syntheses. Refinement was carried
out on F2hkl in anisotropic approximation for
nonhydrogen atoms and isotropically for hydrogen
atoms. Positions of hydrogen atoms were refined using
rider model.
P32–O31
P32–O33
P32–O3
P42–O4
1.573(2)
ω
ω
Angle
Angle
O21P22O23
O21P22O2
O23P22O2
O21P22S2
O23P22S2
O2P22S2
O31P32O33
O31P32O3
O33P32O3
O31P32S3
O33P32S3
O3P32S3
O4P42O41
O4P42O43
O41P42O43
O4P42S4
105.30(12)
101.12(11)
104.20(11)
114.57(9)
113.47(9)
116.68(8)
105.08(12)
102.51(11)
103.41(12)
114.05(9)
113.27(9)
117.08(8)
102.74(11)
104.01(12)
103.45(11)
112.21(9)
O41P42S4
O43P42S4
C1O1C11
C2O2P22
C3O3P32
C4O4P42
C5O5C1
116.57(9)
116.21(9)
113.4(2)
125.63(17)
125.59(17)
122.98(17)
110.6(2)
Absolute configuration of crystal XXI is confirmed
on the basis of the Flack parameter that had value of
0.03(7). Final values of reliability factors for XXI are:
R1 0.0458 [calculated from Fhkl for 5590 reflexes with
I > 2σ(I)], wR2 0.0906 (calculated from F2hkl for all
6836 reflexes), the number of refined parameters 290,
GOF 1.011. Calculations were carried out using
program package SHELXTL 5.10. [6].
C26O21P22
C24O23P22
C36O31P32
C34O33P32
C46O41P42C
C44O43P42
O1C1O5
118.56(18)
116.83(18)
117.79(19)
118.16(18)
115.79(18)
114.87(19)
109.1(2)
For thin layer chromatography were used plates
Silufol UV-254. Eluents benzene–dioxane, 3 : 1 (A)
and benzene–dioxane, 5 : 1 (B).
5,5-Dimethyl-2-chloro-1,3,2-dioxaphosphorinane,
2-chloro-1,3,2-dioxaphosphorinane [7] and 1,2-О-
alkylideneglucofuranose [8] were synthesized along
the known procedures. Methyl-β-D-xylopyranoside
from Sigma and 2,2-dimethyl-1,3-propanediol from Fluka
Chemie were used without additional purification.
O1C1C2
108.2(2)
O5C1C2
108.9(2)
General procedure for the synthesis of tris-
phosphorylated esters of 1,1,1-trimethylolalkanes
(IV, V). To a mixture of an appropriate triol with
triethylamine in equimolar amounts dissolved in 5–10-
fold excess of a solvent and cooled to 5–10°С was
slowly added dropwise at stirring 10–15% solution of
were registered on a Bruker WP-80 SY instrument
with operating frequency 32.4 MHz, relatively to 85%
1
orthophosphoric acid. The 13С and Н NMR spectra
were registered on a Bruker АС-200 instrument with
operating frequencies 50.32 and 200 MHz. respectively,
1
relatively to tetramethylsilane. The Н, 13С and 31Р
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889
three-fold molar excess of 5,5-dimethyl-2-chloro-
1,3,2-dioxaphosphorinane. As a solvent was taken car-
bon tetrachloride or 1,4-dioxane. The reaction progress
was monitored by 31Р NMR spectroscopy and TLC.
The mixture was stirred at room temperature for 1.5 h.
The triethylamine hydrochloride precipitate was
filtered off, the filtrate was concentrated in a vacuum
(20 mm Hg.). The product was extracted with benzene,
the solvent was removed, and residue was dried in a
vacuum (1 mm Hg) at 50°С to a constant weght.
(СН3а), 31.4 [C(СН3)2, 3JCP 6.3], 45.5 (СН3С, 3JCP 8.5),
2
2
68.3 (СН2ОР, JCP 4.9), 77.7 [СН2C(СН3)2, JCP 6.6].
1Н NMR spectrum (СD3СN), δ, ppm: 0.82 s (9Н,
СН3е), 1.05 s (9Н, СН3а), 1.23 s (3Н, СН3), 3.72 m (6Н,
ОСН2е), 3.96 m (6Н, СН2ОР), 4.16 m (6Н, ОСН2а).
Found, %: С 42.51; Н 6.85; Р 16.42; С20Н39О12Р3.
Calculated, %: С 42.55; Н 6.91; Р 16.49.
1,1,1-Tris-hydroxymetylene-(2'-oxo-5',5'-dime-
thyl-1',3',2'-dioxaphosphorinane)propane (ХVII). From
1.26 g of ester V and 1.34 g of hydrogen peroxide
adduct with urea was obtained phosphate XVII. Yield
1.03 g, white crystalline substance. 13С NMR spectrum
[(CD3)2СO], δ, ppm (J, Hz): 7.6 (СН3СН2), 20.7
(СН3е), 21.5 (СН3СН2), 21.8 (СН3 а), 32.2 [C(СН3)2,
1,1,1-Tris-hydroxymetylene-(5',5'-dimethyl-
1',3',2'-dioxaphosphorinane)ethane (IV). From 0.31 g
of 1,1,1-trimethylolethane (I), 0.79 g of triethylamine
and 1.32 g of 5,5-dimethyl-2-chloro-1,3,2-dioxaphos-
phorinane was obtained ester IV. Yield 1.23 g, syrup-
3
2
3JCP 6,3], 43.2 (С2Н5С, JCP 8,9), 65.5 (СН2ОР, JCP
4.5), 78.4 [СН2C(СН3)2, 2JCP 5.33]. 1Н NMR spectrum
[(CD3)2СO], δ, ppm: 0.83 s (9Н, СН3е), 0.85 t (3Н,
СН3), 0.89 s (9Н, СН3а), 1.38 q (2Н, СН2), 3.54 m (6Н,
ОСН2е), 4.57 m (6Н, СН2ОР), 4.61 m (6Н, ОСН2а).
Found, %: С 43.55; Н 7.05; Р 16.03; С21Н41О12Р3.
Calculated, %: С 43.60; Н 7.09; Р 16.09.
13
like liquid, Rf 0.81 (А). С NMR spectrum (СD3СN),
δ, ppm (J, Hz): 7.9 (СН3), 19.5 (СН3е3), 20.5 (СН3а),
3
31.8 [C(СН3)2, JCP 6.7], 45.7 (СН3С, JCP 8.9), 68.5
2
(СН2ОР, 2JCP 5.1), 77.6 [СН2C(СН3)2, JCP 6.7].
1,1,1-Tris-hydroxymetylene-(5',5'-dimethyl-
1',3',2'-dioxaphosphorinane)propane (V). From 0.27 g
of 1,1,1-trimethylolpropane (II), 0.61 g of triethyl-
amine and 1.01 g of 5,5-dimethyl-2-chloro-1,3,2-dioxa-
phosphorinane was obtained ester V. Yield 0.98 g, syrup-
like liquid, Rf 0.9 (А). 13С NMR spectrum [(CD3)2SO],
δ, ppm (J, Hz): 7.9 (СН3СН2), 20.3 (СН3е), 20.7
General procedure for the synthesis of 1,1,1-
tris-hydroxymethylene-(2'-thio-5',5'-dimethyl-1',3',2'-
dioxaphosphorinane)alkanes (ХV, XVIII) and 1,1,1-
tris-hydroxymethylene-(2'-seleno-5',5'-dimethyl-
1',3',2'-dioxaphosphorinane)alkanes (ХVI, XIX). To
a solution of the respective tris-phosphorylated ester
in 10-fold excess of benzene was added sulfur or
selenium in equivalent amount, and the mixture was
stirred at 20°С. Reactions duration: of sulfuration, 1 h,
of selenation, 5 h. The precipitate formed was filtered
off and washed with the same solvent (2 × 15 ml).
Thionophosphates were precipitated from the reaction
mixture by adding methyl-tert-butyl ether, selenono-
phosphates, by hexane. The products were
recrystallized from hot toluene and dried in a vacuum
(1 mm Hg) at 70°С to a constant weight.
3
(СН3СН2), 20.9 (СН3а), 32.0 [C(СН3)2, JCP 6.7], 45.8
(СН3С, 3JCP 9.1), 71.3 (СН2ОР, 2JCP 5.4), 76.3 [СН2C·
2
(СН3)2, JCP 8.3].
General procedure for the synthesis of 1,1,1-tris-
hydroxymethylene-(5',5'-dimethyl-1',3',2'-dioxaphos-
phorinane)alkanes (ХIV, XVII). To a solution of an
appropriate tris-phosphorylated ester in 5-fold excess
of carbon tetrachloride was added two-fold excess of
hydrogen peroxide adduct with urea, and the mixture
was stirred for 4 h at 20°С. The precipitate formed
was filtered off, washed with the same solvent, then
the solvent was removed in a vacuum, the residue was
extracted with hot benzene (2 × 15 ml). Benzene was
removed in a vacuum (20 mm Hg) to the beginning of
product crystallization, crystals formed were filtered
off and tris-phosphates obtained were dried in a
vacuum (1 mm Hg) at 90°С to a constant weight.
1,1,1-Tris-hydroxymetylene-(2'-thio-5',5'-dime-
thyl-1',3',2'-dioxaphosphorinane)ethane (ХV). From
0.51 g of ester IV and 0.09 g of sulfur was obtained
thionophosphate XV. Yield 0.42 g, white crystalline
substance. 13С NMR spectrum (СD3СN), δ, ppm (J,
Hz): 7.9 (СН3), 19.5 (СН3е), 20.6 (СН3а), 31.9 [C(СН3)2,
3
2
3JCP 6.3], 45.7 (СН3С, JCP 8.9), 68.5 (СН2ОР, JCP
2
1
1,1,1-Tris-hydroxymetylene-(2'-oxo-5',5'-dime-
thyl-1',3',2'-dioxaphosphorinane)ethane (ХIV). From
1.29 g of ester IV and 1.41 g of hydrogen peroxide
adduct with urea was obtained phosphate XIV. Yield
1.14 g, white crystalline substance. 13С NMR spectrum
(СD3СN), δ, ppm (J, Hz): 7.8 (СН3), 19.4 (СН3е), 20.5
4.9), 77.9 [СН2C(СН3)2, JCP 6.6]. Н NMR spectrum
(СD3СN), δ, ppm: 0.94 s (9Н, СН3е), 1.12 s (9Н, СН3а),
1.25 s (3Н, СН3), 3.97 m (6Н, ОСН2е), 4.08 m (6Н,
СН2ОР), 4.21 m (6Н, ОСН2а). Found, %: С 39.17; Н
6.31; Р 15.16; С20Н39О9Р3S3. Calculated, %: С 39.22;
Н 6.37; Р 15.20.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 5 2008

890
PUGASHOVA et al.
reaction was completed, the mixture was stirred for 1 h
1,1,1-Tris-hydroxymetylene-(2'-thio-5',5'-dime-
at room temperature, then filtered, and the solvent was
removed in a vacuum. The residue was dissolved in
benzene, sulfur in 10% excess was added, the mixture
was stirred for 2 h and left overnight. If the reaction
was not completed, then the mixture was heated to
100°С for 30 min. Solvent was removed in a vacuum,
the residue was subjected to column chromatography
eluting consecutively with benzene and system B.
Isolated products were dried in a vacuum.
thyl-1',3',2'-dioxaphosphorinane)propane (ХVIII).
From 1.05 g of ester V and 0.18 g of sulfur was
obtained thionophosphate ХVIII. Yield 1.1 g, white
crystalline substance. 13С NMR spectrum (CDCl3), δ,
ppm (J, Hz): 7.2 (СН3СН2), 20.8 (СН3е), 21.5
3
(СН3СН2), 21.8 (СН3а), 32.4 [C(СН3)2, JCP 6,3], 43.3
(С2Н5С, 3JCP 8.9), 65.6 (СН2ОР, 2JCP 4.5), 77.7 [СН2C·
2
(СН3)2, JCP 7.4]. 1Н NMR spectrum (CD3СN), δ,
ppm: 0.94 s (9Н, СН3е), 0.98 s (9Н, СН3а), 1.10 t (3Н,
СН3), 1.51 q (2Н, СН2), 3.87 m (6Н, СН2ОР), 3.98 m
(6Н, ОСН2е), 4.06 m (6Н, ОСН2а). Found, %: С 40.21;
Н 6.48; Р 14.84; С21Н41О9Р3S3. Calculated, %: С
40.26; Н 6.55; Р 14.86.
1,2,4-Tris-(2'-thio-5',5'-dimethyl-1',3',2'-dioxa-
phosphorinane)butanetriol (XX). From 1.0 g of
1,2,4-butanetriol, 4.8 g of neopentylenechlorophos-
phite and 0.9 g of sulfur was obtained 0.64 g of
product XX. White crystalline substance. Rf 0.51 (B).
1Н NMR spectrum (CDCl3, δ, ppm): 0.95 s, 1.22 s
1,1,1-Tris-hydroxymetylene-(2'-seleno-5',5'-di-
methyl-1',3',2'-dioxaphosphorinane)ethane (XVI).
From 0.52 g of ester IV and 0.27 g of selenium was
obtained selenonophosphate XVI. Yield 0.48 g, white
crystalline substance. 13С NMR spectrum (СD3СN), δ,
ppm (J, Hz): 7.9 (СН3), 19.6 (СН3е), 20.6 (СН3а), 31.9
2
(18Н, ОСН2(СН3)2СН2О), 2.15 d (2Н, JНН 6.05 Hz),
2
3.92 m (6Не, ОСН2С(СН3)2, JНН 11.9 Hz), 3.94 m
(2Н, 2JНН 6.5 Hz, 3JНР 10.5 Hz), 4.10 m (6На, ОСН2С·
(СН3)2, J 6.2 Hz, 2JН Н
а
е
10.9 Hz), 4.28 d (2Н, 2J Н Н
1
2
4.3 Hz,
3
3
3
[C(СН3)2, JCP 6.4], 45.7 (СН3С, JCP 8.9), 68.6
JН Н
а
е
3.4 Hz), 4.38 m (1Н, J Н Н
2
3
10.4 Hz). Found, %:
(СН2ОР, JCP 4.9), 77.9 [СН2C(СН3)2, JCP 6.7]. 1Н
NMR spectrum (СD3СN), δ, ppm: 0.95 s (9Н, СН3е),
1.12 s (9Н, СН3а), 1.29 s (3Н, СН3), 3.99 m (6Н,
ОСН2е), 4.11 m (6Н, СН2ОР), 4.25 m (6Н, ОСН2а).
Found, %: С 31.81; Н 5.14; Р 12.33; С20Н39О9Р3Sе3.
Calculated, %: С 31.87; Н 5.18; Р 12.35.
С 38.15; Н 6.26; Р 15.49; С19Н37О9Р3S3. Calculated,
%: С 38.12; Н 6.23; Р 15.52. М 598.62. Found,
М (12С): 598.86. Calculated, М (12С): 598.43.
2
2
2,3,4-Tris-(2'-thio-1',3',2'-dioxaphosphorinane)-
methyl-β-D-xylopyranoside (XXI). From 1.0 g of
methyl-β-D-xylopyranoside, 2.5 g of propylenechloro-
phosphite and 0.5 g of sulfur was obtained 1.02 g of
product XXI. White crystalline substance. Rf 0.6 (B).
1Н NMR spectrum (CDCl3, δ, ppm): 1.72, 1.73, 1.77 m
1,1,1-Tris-hydroxymetylene-(2'-seleno-5',5'-di-
methyl-1',3',2'-dioxaphosphorinane)propane (XIX).
From 1.26 g of ester V and 0.56 g of selenium was
obtained selenonophosphate XIX. Yield 1.17 g, white
crystalline substance. 13С NMR spectrum [(CD3)2SO],
δ, ppm (J, Hz): 8.7 (СН3СН2), 20.3 (СН3е), 20.8
2
(3Не, ОСН2СН2, JНН 10.8 Hz), 2.27, 2.32, 2.35 m
(3На, ОСН2СН2, 2J 6.1 Hz, 2JН Н
10.7 Hz), 3.52 s (3Н,
а
е
2
3
ОСН3), 3.92 m (2Н, JНН 6.4 Hz, JНР 10.2 Hz), 4.31,
4.36, 4.50 m (6Не, ОСН2СН2), 4.26 d (2Н, 2J Н Н
4.1 Hz),
10.3 Hz), 4.60 d (1Н, J 3.4 Hz),
3
(СН3СН2), 20.9 (СН3а), 32.0 [C(СН3)2, JCP 6.3], 45.7
1 2
3
3
(С2Н5С, 3JCP 8.9), 71.7 (СН2ОР, 2JCP 5.6), 76.7 [СН2C·
4.36 m (1Н, J Н Н
4.58, 4.64, 4.70 m (6На, ОСН2СН2, JН Н
4.97 d (1Н, 3J3Н Н
3.4 Hz). Found, %: С 31.51; Н 4.80;
2 3
2
2
(СН3)2, JCP 8.7]. 1Н NMR spectrum [(CD3)2SO], δ,
а
е
10.5 Hz),
ppm: 0.88 t (3Н, СН3), 0.99 s (9Н, СН3е), 1.13 s (9Н,
СН3а), 1.41 q (2Н, СН2), 3.56 m (6Н, СН2ОР), 3.85 m
(6Н, ОСН2е), 4.19 m (6Н, ОСН2а). Found, %: С 32.81;
Н 5.31; Р 11.95; С21Н41О9Р3Sе3. Calculated, %: С
32.86; Н 5.35; Р 12.10.
4
Р 16.28; С15Н27О11Р3S3. Calculated, %: С 31.47; Н
4.75; Р 16.23.
2,3,4-Tris--(2'-thio-5',5'-dimethyl-1',3',2'-dioxa-
phosphorinane)methyl-β-D-xylopyranoside (XXII).
From 1.0 g of methyl-β-D-xylopyranoside, 3.0 g of
neopentylenechlorophosphite and 0.6 g of sulfur was
obtained 0.92 g of product XXII. White crystalline
General procedure for the synthesis of tris-
phosphorylated derivatives of carbohydrates and
1,2,4-butanetriol (XX–XXIII). To the cooled to 0–5°С
mixture of an appropriate carbohydrate (or polyol)
with pyridine or triethylamine (at the ratio 1 : 3) dis-
solved in dioxane was slowly added dropwise at
strirring three-fold molar amount of phosphorylating
agent in the same solvent. The reaction progress was
monitored by 31Р NMR spectroscopy and TLC. When
1
substance. Rf 0.51 (B). Н NMR spectrum (CDCl3, δ,
ppm): 0.86 s, 1.24 s [18Н, ОСН2(СН3)2СН2О], 2.15 d
2
2
(2Н, JНН 6.05 Hz), 3.92 m [6Не, ОСН2С(СН3)2, JНН
11.9 Hz], 3.94 m (2Н, 2JНН 6.5 Hz, 3JНР 10.5 Hz), 4.10
m (6На, ОСН2С(СН3)2, J 6.2 Hz, 2JН Н
а
е
10.9 Hz), 4.28
d (2Н, 2J1Н2Н 4.3 Hz, JН Н
а
е
3.4 Hz), 4.38 m (1Н, 3J Н Н
2 3
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 5 2008

TRIS-PHOSPHORYLATED ESTERS OF SYMMETRICAL AND UNSYMMETRICAL TRIOLS
891
10.4 Hz). Found, %: С 30.43; Н 5.96; Р 14.10;
С21Н39О11Р3S3. Calculated, %: С 30.41; Н 5.99; Р
14.15. М 656.65. Found, М (12С): 655.70. Calculated,
М (12С): 656.44.
REFERENCES
1. Diéguez, M., Pamies, O., and Claver, C., Chem. Rev.,
2004, vol. 104, no. 10, p. 3189.
2. Buisman, G.J.H., Martin, M.E., Vos, E.J., Klootwijk, A.,
Kamer, P.C.J., and van Leeuwen, P.W.N.M., Tetra-
hedron Asym., 1995, vol. 6, no. 3, p. 719.
3,5,6-Tris-(2'-thio-5',5'-dimethyl-1',3',2'-dioxa-
phos-phorinane)-1,2-О-isopropylidene-D-glucof ura-
noses (XXIII). From 1.0 g of 1,2-О-isopropylidene-
glucofuranose, 2.3 g of neopentylenechlorophosphite
and 0.6 g of sulfur was obtained 1.04 g of thiophos-
phate (XXIII). White crystalline substance. Rf 0.69
(B). 1Н NMR spectrum (CDCl3, δ, ppm): 0.93 s, 1.25 s
3. Gavrilov, K.N. and Mikhel’, I.S., Koord. Khim., 1999,
vol. 25, no. 2, p. 83.
4. Nifant’ev, E.E. and Vasyanina, L.K., Spektroskopiya 31
P
YaMR (31P NMR Spectroscopy), Moscow: Izd. Mosk.
Gos. Pedagog. Inst. im. V.I. Lenina, 1986.
5. Rasadkina, E.N., Magomedova, N.S., Bel’skii, V.K., and
Nifant’ev, E.E., Zh. Obshch. Khim., 1995, vol. 65, no. 2,
p. 214.
[18Н, ОСН2(СН3)2СН2О], 3.49 s (3Н, ОСН3), 3.84
2
m [6Не, JН Н
а
е
5.1 Hz ОСН2С(СН3)СН2О], 3.91 m
9.5 Hz, 3JНР 4.1 Hz), 3.98 m (1Н, 3JНР ≤ 1 Hz),
4.24 m (1На, 3J Н Н 9.5 Hz), 4.31 d (1Н, 3J Н Н
4.6 Hz),
4.37 m [6На, 2JН Н
5.1 Hz ОСН2С(СН3)СН2О], 4.58 d
(1Н, 3J Н Н 3.6 Hz), 4.91 m (1Н, 3J Н Н4.6 Hz, 3JНР 12.8 Hz),
5.91 d (1Н, 3J Н Н
3.6 Hz). Found, %: С 40.51; Н 5.90;
6. Sheldrick, G.M., SHELXTL-97, Version 5.10, Bruker
(1Не, 3J Н Н
6 6
AXS Inc., Madison,WI-53719, USA.
6
6
4 5
7. Nifant’ev, E.E. and Zavalishina, A.I., Khimiya elemento-
organicheskikh soedinenii (Chemistry of Organoele-
ment Compounds), Moscow: Izd. Mosk. Gos. Pedagog.
Inst. im. V.I. Lenina, 1980.
а
е
1
2
4 5
1
2
Р 13.01; С24Н43О12Р3S3. Calculated, %: С 40.44; Н
6.08; Р 13.03.
8. Cramera, R.E., Park, A. and Whistler, R.L., J. Org.
Chem., 1963, vol. 28, no. 11, p. 3230.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 5 2008