Synthesis and structure of bis-phosphorylated 1,4:3,6-dianhydro-D-mannitol derivatives

Article abstract of DOI:10.1023/A:1026348701071

A number of bis-phosphorylated 1,4:3,6-dianhydro-D-mannitol derivatives were synthesized. The increased steric loading of the phosphorus-containing residues in the compounds prepared gives rise to complicated ¹H and ³¹P NMR spectra a

Full text of DOI:10.1023/A:1026348701071

Russian Journal of General Chemistry, Vol. 73, No. 6, 2003, pp. 903 908. Translated from Zhurnal Obshchei Khimii, Vol. 73, No. 6, 2003,
pp. 955 960.
Original Russian Text Copyright
2003 by Grachev, Soboleva, Kurochkina, Vasyanina, Bel’skii, Nifant’ev.
Synthesis and Structure of Bis-phosphorylated
1,4:3,6-Dianhydro-D-mannitol Derivatives
M. K. Grachev, N. O. Soboleva, G. I. Kurochkina, L. K. Vasyanina,
V. K. Bel’skii, and E. E. Nifant’ev
Moscow State Pedagogical University, Moscow, Russia
Received June 26, 2001
Abstract A number of bis-phosphorylated 1,4:3,6-dianhydro-D-mannitol derivatives were synthesized.
The increased steric loading of the phosphorus-containing residues in the compounds prepared gives rise to
complicated 1H and 31P NMR spectra and magnetic nonequivalence of structurally similar molecular fragments.
We previously reported on the synthesis of new
phosphorus-containing cyclic systems on the basis of
1,4:3,6-dianhydro-D-mannitol (I) and phosphorous
amides. We found that the formation of such complex
molecular structures is possible only when fine details
of spatial compatibility of the initial amides and
ring-closing reagents is taken into account [1, 2].
Furthermore, the compounds thus obtained were used
for design of new chelating ligands; transition metal
complexes derived from these ligands are promising
stereoselective catalysts in homogeneous reactions
(see structure A, where X is an unshared electron pair
[3, 4]).
action between the phosphorus-containing fragments
should exist. This interaction should lead to dephos-
phorylation (see [3]) and change of usual spectral
1
parameters, e.g., complication of H NMR spectra and
nonequivalence of phosphorus nuclei in 31P NMR
spectra [1, 2].
We have started our study with the synthesis of
phosphorous amides II VII from diol I and examina-
tion of their spectral parameters. Compounds II VII
can be regarded as a series of type A derivatives
with successively increasing steric loading of the
phosphorus-containing moieties. Compounds II and
III were obtained in 35 and 50% yield, respectively,
by heating of diol I with 2 equiv. of the corresponding
phosphorous triamide at 80 C under a weak stream of
nitrogen with continuous removal (by distillation) of
the released dialkylamine. Compounds II and III
readily take up sulfur to give phosphinothioyl deriva-
tives IV and V. On the other hand, we succeeded in
synthesizing analogous P-phenyl derivative VI and
the corresponding phosphine sulfide VII only by
treatment of diol I with chloro(diethylamino)phenyl-
phosphine in benzene at 20 C in the presence of
triethylamine as hydrogen chloride acceptor. The
progress of formation of P(III) derivative VI was
monitored by 31P NMR spectroscopy. When the reac-
tion was complete, product VI was converted into
bis-sulfide VII without isolation from the reaction
mixture (see Experimental). Our attempts to syn-
thesize bis(tetrapiperidino)phosphine under analogous
conditions resulted in formation of a mixture of prod-
ucts which were difficult to separate.
X
R
P
OH
O
O
R
H6d
H6c
H1b
H1a
H6d
H6c
O
O
H3
H4
H3
H4
H2
H5
H2
H5
H1b
H1a
O
O
R
R
OH
P
X
I
A
With the above in mind, we have continued studies
in the field of synthesis of new bis-phosphorylated
derivatives of diol I, which attract interest from the
viewpoint of creation of molecular cavities and other
3D structures. As a separate problem, we examined
the effect of steric loading of the phosphorus atom
on the steric structure of the products. It should be
noted that the C2 O and C5 O bonds in phos-
phorylated derivatives like A are oriented inside the
fused bicyclic system; therefore, a certain steric inter-
Compounds II, III, and IV were described pre-
viously. They are characterized by symmetric arrange-
ment of the phosphorus-containing fragments with
respect to the dianhydro-D-mannitol cavity, which
1070-3632/03/7306-0903$25.00 2003 MAIK Nauka/Interperiodica

904
GRACHEV et al.
S1
O1
C1
C3
C10
P1
C14
C6
C2
N2
N1
O4
C5
N4
O3
C9
C8
P2
C7
C11
N3
O2
C4
C13
S2
C12
Structure of compound IV according to the X-ray diffraction data.
1
gives rise to the corresponding H NMR spectra and
similar signals from two equivalent phosphorus nuclei
in the 31P NMR spectra [3]. However, the spectral
pattern becomes more complicated on addition of
sulfur (compound V) or introduction of bulkier sub-
stituents (compounds VI and VII).
mobilities, and we failed to separate them completely
by column chromatography. Therefore, the assignment
of their H NMR signals given in Experimental was
based on analysis of the spectra of the corresponding
chromatographic fractions.
1
It should be noted that, according to the TLC and
NMR (1H and 31P) data, the previously reported com-
pound III possessing two tetraethyldiaminophosphino
groups is an individual substance [3]. More sterically
loaded phosphorus(III) derivative VI is also an in-
dividual substance, but the phosphorus-containing
moieties therein are nonequivalent: Two signals are
X
R
P
R
O
O
O
PR3 (PR3)
observed in the 31P NMR spectrum at
132.9 and
I
ClP(Ph)NEt2
135.2 ppm. Like compound V, phosphoruPs(V) deriva-
tive VII exists as two conformers at a ratio of about
1:1. According to the 1H and 31P NMR spectra,
isomers VIIa and VIIb are, respectively, symmetric
and unsymmetric products (cf. Va and Vb). We
succeeded in isolating by column chromatography
only symmetric isomer VIIa; the spectra of isomer
VIIb were analyzed using its mixture with VIIa.
Presumably, the lack of symmetry in structures Vb
and VIIb results from restricted rotation of the phos-
phorus-containing groups about the O P bonds which
are extensions of the endo-oriented C2 O and C5 O
bonds.
O
R
P
R
X
II VII
II, IV, R = R = NMe2; III, V, R = R = NEt2; VI, VII,
R = NEt2, R = Ph; II, III, VI, X = unshared electron pair;
IV, V, VII, X = S.
According to the TLC data, compound V is a mix-
ture of two isomers Va and Vb at a ratio of 2:1.
Isomer Va is a symmetric product; it shows in the 31P
NMR spectrum a singlet at
80 ppm, and the
Phosphorus(V) derivative IV was isolated as in-
dividual crystalline substance, and its structure was
determined by X-ray analysis (see figure). The fura-
nose rings in the bicyclic framework have a nearly
planar structure: Only the oxygen atoms deviate from
the plane by 0.35 . Essential differences are ob-
served for the endo- and exo-substituents on C1, C2,
C5, and C6. The C2 O and C5 O bonds, which
connect the anhydromannitol skeleton with phos-
phorus-containing fragments, are oriented endo, and
P
1-H/6-H, 2-H/5-H, and 3-H/4-H protons of the di-
anhydro-D-mannitol skeleton are equivalent in pairs.
Unsymmetrical isomer Vb gives two equal-intensity
singlets in the 31P NMR spectrum,
79.9 and
P
1
80 ppm, and the H NMR spectral pattern is more
complicated due to nonequivalence of the above listed
dianhydro-D-mannitol protons and phosphorus-con-
taining moieties (see Experimental). Isomers Va and
Vb are characterized by similar chromatographic
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 6 2003

SYNTHESIS AND STRUCTURE OF BIS-PHOSPHORYLATED
905
they form angles of 111.5 and 113.8 , respectively,
with the furanose planes. The bond angles at the
oxygen atoms are 109.7 and 111.0 (see table),
indicating their sp3 hybridization. The phosphorus
atoms are tetrahedral: The average bond angle is
109.2 . The larger bond angles involving sulfur atom
(SPO, SPN) suggest repulsion between electrons of
the P=S bond (which is characterized by increased
electron density), on the one hand, and P O and two
P N bonds, on the other. Therefore, the angles
between the latter are on the average 103.3 .
Bond lengths (d, ) and bond angles ( , deg) in the mole-
cule of compounds IV
Bond
d
Bond
d
S1 P1
S2 P2
P1 O3
P1 N2
P1 N1
P2 O4
P2 N3
P2 N4
O1 C1
O1 C4
O2 C6
O2 C3
O3 C2
O4 C5
1.912(3)
1.930(3)
1.577(5)
1.621(8)
1.655(8)
1.592(6)
1.612(8)
1.654(7)
1.422(13)
1.435(12)
1.420(10)
1.431(10)
1.419(10)
1.434(9)
N1 C8
N1 C7
N2 C9
N3 C11
N3 C12
N4 C14
N4 C13
C1 C2
C2 C3
C3 C4
C6 C5
C5 C4
N2 C10
1.421(14)
1.446(14)
1.427(13)
1.45(2)
1.463(13)
1.455(13)
1.460(14)
1.513(14)
1.551(14)
1.513(12)
1.507(13)
1.509(12)
1.414(13)
By reaction of diol I with phosphoryl chloride and
thiophosphoryl chloride we synthesized P(V) deriva-
tives VIII XI. The reactions were carried out in
dioxane at 20 C in the presence of excess diethyl-
amine (compound VIII), diisopropylamine (IX), or
triethylamine (X, XI) as hydrogen chloride acceptor.
The progress of the reactions was monitored by 31P
NMR spectroscopy.
X
P(NR2)2
O
O
Angle
Angle
1) P(X)Cl3;
2) NHR2 or NR3
O3P1N2
O3P1N1
108.6(4)
97.9(4)
C10N2P1
C11N3C12
125.9(8)
I
113.8(12)
O
N2P1N1
O3P1S1
N2P1S1
N1P1S1
O4P2N3
O4P2N4
N3P2N4
O4P2S2
N3P2S2
N4P2S2
C1O1C4
C6O2C3
C2O3P1
C5O4P2
C8N1C7
C8N1P1
C7N1P1
C9N2C10
C9N2P1
103.8(4)
114.3(3)
112.3(3)
118.5(3)
106.1(4)
97.4(3)
105.8(4)
114.4(2)
113.1(3)
118.3(3)
111.0(7)
109.7(7)
121.6(5)
119.8(5)
115.6(12)
112.0(8)
114.3(8)
112.8(10)
121.1(7)
C11N3P2
C12N3P2
C14N4C13
C14N4R2
C13N4P2
O1C1C2
O3C2C1
O3S2S3
S1S2S3
121.8(9)
124.3(9)
111.6(10)
117.9(7)
114.6(7)
105.8(10)
110.8(9)
112.2(8)
102.6(9)
106.7(7)
109.0(8)
103.8(9)
103.3(7)
115.7(7)
111.9(7)
102.4(8)
112.3(8)
107.0(9)
102.3(7)
O
P(NR2)2
X
VIII XI
VIII, R = Et; IX, R = i-Pr; X, XI, R2N = piperidino;
VIII, IX, X, X = O; XI, X = S.
Compounds VIII XI were isolated in 65 85% by
reprecipitation (VIII, X) or by column chromatog-
raphy (IX, XI). They are viscous, difficultly crystal-
lizable oily substances. According to the TLC and
NMR (1H and 31P) data, compounds VIII, X, and
XI exist as a single isomer, whereas sterically loaded
bis(tetraisopropyldiamidophosphate) IX is a mixture
of two isomers (TLC data) with very close chromato-
graphic mobilities (we failed to separate them by
column chromatography). Compound IX showed
double sets of signals in the 1H and 31P NMR spectra.
O2S3S4
O2S3S2
S4S3S2
O2S6S5
O4S5S6
O4S5S4
S6S5C4
O1C4C5
O1C4C3
C5C4C3
The reaction of dianhydro-D-mannitol I with thio-
phosphoryl chloride was not complete under the given
conditions. Separation of the reaction mixture by
column chromatography, apart from the expected
product XI (yield 50%), gave 25% of mono(dipiperi-
didophosphate) XII. This is a specific feature of phos-
phorylation of diol I with phosphorus(V) chlorides.
The reaction with P(III) derivatives (both chlorides
and amides) involves both hydroxy groups of I
simultaneously even at an equimolar reactant ratio [3].
Thus the structure of bis-phosphorylated 1,4:3,6-di-
anhydro-D-mannitol derivatives strongly depends on
the nature and steric loading of the phosphorus-con-
taining moieties.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 6 2003

906
GRACHEV et al.
(2H, 3-H, 4-H), 4.84 4.98 m (2H, 2-H, 5-H). 31P
EXPERIMENTAL
NMR spectrum (C6H6): 80 ppm. Found, %:
P
1
The H NMR spectra were recorded on a Bruker
C 47.38; H 8.79; P 10.87. C22H48N4O4P2S2. Calcu-
lated, %: C 47.29; H 8.65; P 11.08.
WP-250 spectrometer at 250 MHz, and the 31P {1H}
NMR spectra were obtained on a Bruker WP-80
instrument operating at 32.4 MHz, respectively. The
chemical shifts were measured relative to tetramethyl-
silane (1H, internal reference) and 85% phosphoric
acid (31P, external reference).
1
Isomer Vb. Yield 0.19 g (35%), Rf 0.77 (B). H
NMR spectrum (CDCl3), , ppm (J, Hz): 1.03 1.13 m
(24H, NCH2CH3); 2.95 3.19 m (16H, NCH2CH3);
3.55 d.d, 3.67 d.d, 3.94 d.d, 4.08 d.d (4H, 1-Ha, 6-Hc,
2
2
1-Hb, 6-Hd, Ja, b = 9.5, Jc, d = 8.3); 4.21 4.31 m,
4.48 4.54 m (2H, 3-H, 4-H); 4.41 4.47 m, 4.87
5.01 m (2H, 2-H, 5-H). 31P NMR spectrum (C6H6),
P, ppm: 79.9, 80.0 (intensity ratio 1:1). Found, %:
C 48.16; H 8.57; P 10.98. C22H48N4O4P2S2. Calcu-
lated, %: C 47.29; H 8.65; P 11.08.
Thin-layer chromatography was performed on
Silufol UV-366 plates using the following solvent
systems as eluent: benzene dioxane, 5:1 (A); ben-
zene dioxane, 3:1 (B); acetone ethanol, 3:1 (C);
chloroform ethanol, 3:1 (D); acetone ethanol, 10:1
(E); dioxane ethanol, 10:1 (F); chloroform ethanol,
3:2 (G); hexane dioxane, 1:1 (H).
1,4:3,6-Anhydro-D-mannitol 2,5-bis(N,N-di-
ethyl-P-phenylphosphonamidothioate) (VIIa/VIIb).
A solution of 8.75 g of diethylamine and 13.3 g of
triethylamine in 50 ml of hexane was added over
a period of 1.5 h while stirring at 0 C to a solution
of 21.4 g of dichlorophenylphosphine in 200 ml of
hexane. The mixture was stirred for 20 h at 20 C,
filtered from triethylamine hydrochloride, and
evaporated under reduced pressure. The residue was
distilled in a vacuum. Yield of chloro(diethylamino)-
phenylphosphine 20.6 g (80%), bp 96 98 C (1 mm).
X-Ray diffraction study of a single crystal of com-
pound IV was performed on a CAD-4 diffractometer
(MoK radiation,
= 0.71073 ). Crystals suitable
for the analysis were obtained by slowly cooling
a saturated solution of IV in hexane. Orthorhombic
crystals with the following unit cell parameters: a =
7.2790(1), b = 12.307(2), c = 25.257(5) ; Z = 4;
space group P212121. Total of 2371 reflections were
measured, 817 of which were unique [R(int) =
0.0170]. The structure was solved by the direct
method and was refined by the full-matrix least-
squares procedure in anisotropic approximation for
non-hydrogen atoms to R = 0.024. The positions of
hydrogen atoms were determined from the difference
synthesis and were partially included in the refine-
ment. The bond lengths and bond angles are given in
table. The X-ray diffraction study was performed with
participation of K.L. Anfilov.
31P NMR spectrum (C6H6):
140 ppm.
P
Diol I, 0.20 g, was added with stirring at 20 C
to a solution of 0.6 g chloro(diethylamino)phenyl-
phosphine (prepared as described above) and 0.31 g
of triethylamine in 15 ml of benzene. The mixture
was stirred for 20 h at 20 C and filtered from triethyl-
amine hydrochloride; Rf 0.8 (B). 31P NMR spectrum
of the reaction mixture (compound VI), P, ppm:
132.9 and 135.2 (intensity ratio 1:2).
All syntheses were carried out under dry nitrogen
in anhydrous solvents. The procedures for preparation
of compounds II IV were described by us previously
[3].
Finely powdered sulfur, 0.17 g, was added to the
mixture obtained as described above. The resulting
mixture was stirred for 1 h at 80 C, filtered from
excess sulfur, and evaporated under reduced pressure.
The residue (compound VII) was purified by column
chromatography on aluminum oxide (activity grade II)
using solvent system B as eluent.
1,4:3,6-Dianhydro-D-mannitol 2,5-bis(tetraethyl-
diamidophosphorothioate) (Va/Vb). Finely powder-
ed sulfur, 0.064 g, was added to a mixture of 0.5 g of
compound III and 5 ml of benzene. The mixture was
stirred for 40 min at 60 65 C, filtered from excess
sulfur, and evaporated under reduced pressure. The
residue was subjected to column chromatography on
aluminum oxide (activity grade II) using solvent
system B as eluent.
Isomer VIIa. Yield 0.1 g (22%), light yellow thick
oily substance, Rf 0.7 (A). 1H NMR spectrum
(CDCl3), , ppm (J, Hz): 1.01 1.10 m (12H,
3
NCH2CH3, JHH = 6.9), 3.12 3.32 m (8H, NCH2CH3,
2
2
3JPH = 12.4), 3.87 d.d (2H, 1-Ha, 6-Hc, Ja, b = Jc, d
=
8.5), 4.12 d.d (2H, 1-Hb, 6-Hd), 4.59 d.d (2H, 3-H,
1
3
Isomer Va. Yield 0.29 g (52%), Rf 0.8 (B). H
4-H, J3, 4 = 4.7), 4.96 5.16 m (2H, 2-H, 5-H), 7.44 s
NMR spectrum (CDCl3), , ppm (J, Hz): 1.05 1.15 m
(24H, NCH2CH3), 3.09 3.11 m (16H, NCH2CH3),
(6H, Harom), 7.74 7.92 m (4H, Harom). 31P NMR
spectrum (C6H6):
82 ppm. Found, %: C 54.99;
P
2
2
3.68 d.d (2H, 1-Ha, 6-Hc, Ja, b = Jc, d = 8.8), 4.07 d.d
H 6.76; P 10.98. C26H38N2O4P2S2. Calculated, %:
C 54.91; H 6.74; P 10.89.
2
2
(2H, 1-Hb, 6-Hd, Ja, b = Jc, d = 8.8), 4.52 4.58 m
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 6 2003

SYNTHESIS AND STRUCTURE OF BIS-PHOSPHORYLATED
907
Isomer mixture VIIa/VIIb. Yield 0.22 g (51%),
light yellow thick oily substance, Rf 0.7, 0.5 (A).
1H NMR spectrum (CDCl3), , ppm: 1.02 1.10 m
(NCH2CH3), 3.12 3.34 m (NCH2CH3), 3.74 4.00 m
(1-Ha, 6-Hc), 4.02 4.22 m (1-Hb, 6-Hd), 4.48 4.68 m
(3-H, 4-H), 4.97 5.16 m (2-H, 5-H), 7.44 br.s (Harom),
1.32 m [48H, NCH(CH3)2], 3.50 3.78 m [8H,
2
NCH(CH3)2], 3.80 3.92 m (2H, 1-Ha, 6-Hc, Ja, b
=
3
2Jc, d = 8.3, Ja, 2 = 8.3), 4.13 d.d (2H, 1-Hb, 6-Hd,
2
3
2Ja, b = Jc, d = 8.3, Jb, 2 = 6.2), 4.59 4.71 m (2H,
3-H, 4-H), 4.86 5.02 m (2H, 2-H, 5-H). 31P NMR
spectrum (CHCl3), P, ppm: 13.3, 13.9. Found, %:
C 56.49; H 10.39; P 9.63. C30H64N4O6P2. Calculated,
%: C 56.41; H 10.10; P 9.70.
7.75 7.94 m (Harom). 31P NMR spectrum (C6H6),
,
P
ppm: 81, 82 (intensity ratio 1:2). Found, %: C 55.12;
H 6.95; P 10.78. C26H38N2O4P2S2. Calculated, %:
C 54.91; H 6.74; P 10.89.
1,4:3,6-Dianhydro-D-mannitol 2,5-bis(dipiperi-
didophosphate) (X). A mixture of 1 g of diol I and
1.54 g of triethylamine in 10 ml of dioxane was added
with stirring at 10 C to a solution of 2.10 g of phos-
phiryl chloride in 10 ml of dioxane. The mixture was
stirred for 20 h at 20 C and filtered from triethyl-
amine hydrochloride. 31P NMR spectrum of the mix-
1,4:3,6-Dianhydro-D-mannitol 2,5-bis(tetraethyl-
diamidophosphate) (VIII). A mixture of 1.46 g diol
I and 2.23 g of triethylamine in 25 ml of dioxane
was added with stirring at 10 C to a solution of 3.06 g
of phosphoryl chloride in 20 ml of dioxane. The mix-
ture was stirred for 20 h at 20 C and filtered from
triethylamine hydrochloride. 31P NMR spectrum of
ture:
7 ppm.
P
the reaction mixture:
7 ppm.
A solution of 2.32 g of piperidine and 3.03 g of
triethylamine in 20 ml of dioxane was added over
a period of 1 h to the mixture prepared as described
above while stirring at 10 C. The mixture was stirred
for 20 h at 20 C, filtered from triethylamine hydro-
chloride, and evaporated under reduced pressure. The
residue was dissolved in 10 ml of dioxane, 5 ml of
diethyl ether was added, and oily product X was
separated. Yield 3.20 g (82%), Rf 0.4 (D), 0.5 (G).
1H NMR spectrum (CDCl3), , ppm (J, Hz): 1.34
1.68 m [24H, N(CH2)2(CH2)33], 2.86 3.24 m [16H,
P
A solution of 6.44 g of diethylamine in 40 ml of
dioxane was added to the above mixture over a period
of 1 h while stirring at 20 C. The mixture was stirred
for 2 h at 75 C, filtered from diethylamine hydro-
chloride, and evaporated under reduced pressure. The
residue was dissolved in 20 ml of benzene, 10 ml of
hexane was added, the mixture was stirred, and oily
product VIII was separated. Yield 4.48 g (85%),
1
Rf 0.8 (C), 0.4 (D). H NMR spectrum (CDCl3), ,
3
ppm (J, Hz): 0.92 0.98 m (24H, NCH2CH3, JHH
7.3), 2.88 2.98 m (16H, NCH2CH3, JPH = 11.1),
=
3
N(CH2)2(CH2)3, JPH = 8.9, JPH = 7.3], 3.71 d.d
3
2
2
3
(2H, 1-Ha, 6-Hc, Ja, b = Jc, d = 8.5, Ja, 2 = 8.5),
2
2
3
3.57 d.d (2H, 1-Ha, 6-Hc, Ja, b = Jc, d = 8.5, Ja, 2
=
2
2
4.07 d.d (2H, 1-Hb, 6-Hd, Ja, b = Jc, d = 8.5), 4.52 d
2
2
8.5), 3.90 d.d (2H, 1-Hb, 6-Hd, Ja, b = Jc, d = 8.5,
(2H, 3-H, 4-H), 4.68 4.80 m (2H, 2-H, 5-H). 31P
3Jb, 2 = 6.4), 4.39 d.d (2H, 3-H, 4-H, J3, 4 = 3.8,
3
NMR spectrum (C6H6):
15 ppm. Found, %:
3J3, 2 = 1.3), 4.55 4.61 m (2H, 2-H, 5-H, JHP = 6.3).
3
C 54.59; H 8.39; P 10.51. C2P6H48N4O6P2. Calculated,
%: C 54.34; H 8.42; P 10.78.
31P NMR spectrum (CHCl3):
18 ppm. Found, %:
P
C 50.49; H 9.39; P 11.61. C22H48N4O6P2. Calculated,
%: C 50.18; H 9.19; P 11.76.
1,4:3,6-Dianhydro-D-mannitol 2,5-bis(dipiperi-
didophosphorothioate) (XI) and 1,4:3,6-dianhydro-
D-mannitol 2-dipiperididophosphorothioate (XII).
Diol I, 0.73 g, and a solution of 1.11 g of triethyl-
amine in 10 ml of dioxane were added with stirring
at 20 C to a solution of 1.69 g of thiophosphoryl
chloride in 10 ml of dioxane. The mixture was stirred
for 20 h at 20 C and filtered from triethylamine
1,4:3,6-Dianhydro-D-mannitol 2,5-bis(tetraiso-
propyldiamidophosphate) (IX). A mixture of 1 g of
diol I and 1.54 g of triethylamine in 10 ml of dioxane
was added with stirring at 10 C to a solution of 2.1 g
of phosphoryl chloride in 10 ml of dioxane. The mix-
ture was stirred for 20 h at 20 C and filtered from
triethylamine hydrochloride. 31P NMR spectrum of
hydrochloride. 31P NMR spectrum of the mixture,
,
P
the mixture:
7 ppm.
P
ppm: 59 (product), 33 (unreacted thiophosphoryl
chloride); intensity ratio 2:1.
A solution of 6.05 g of diisopropylamine in 20 ml
of dioxane was added over a period of 1 h to the
above mixture while stirring at 20 C. The mixture
was stirred for 20 h at 20 C and filtered from diiso-
propylamine hydrochloride. Product IX was purified
by column chromatography on aluminum oxide
(activity grade II) using solvent system E as eluent.
Yield 2.70 g (65%), Rf 0.9, 0.8 (E), 0.6, 0.5 (F).
1H NMR spectrum (CDCl3), , ppm (J, Hz): 1.24
A solution of 1.7 g of piperidine and 2.23 g of
triethylamine in 20 ml of dioxane was added over
a period of 1 h to the mixture prepared as described
above while stirring at 20 C. The mixture was stirred
for 20 h at that temperature, filtered from triethyl-
amine hydrochloride, and evaporated under reduced
pressure. Products XI and XII were separated by
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 6 2003

908
GRACHEV et al.
column chromatography on aluminum oxide (activity
grade II) using solvent system B as eluent.
1-Hb), 4.23 4.31 m (1H, 5-H), 4.45 d.d (1H, 4-H,
5J4, 5 = 4.7, 5J3, 4 = 4.7), 4.52 d.d (1H, 3-H, 5J2, 3 = 4.9,
5J3, 4 = 4.7), 4.87 5.07 m (1H, 2-H). 31P NMR spec-
Compound XI. Yield 1.52 g (50%), Rf 0.6 (B),
1
trum (C6H6):
78 ppm. Found, %: C 51.29; H 7.89;
P 8.21. C16HP29N2O4PS. Calculated, %: C 51.05;
H 7.76; P 8.23.
0.5 (H). H NMR spectrum (CDCl3), , ppm (J, Hz):
1.46 1.56 m [24H, N(CH2)2(CH2)3], 2.94 3.12 m
3
3
[16H, N(CH2)2(CH2)3, JPH = 6.8, JPH = 7.5],
2
2
3
3.69 d.d (2H, 1-Ha, 6-Hc, Ja, b = Jc, d = 8.5, Ja, 2
=
2
2
REFERENCES
8.5), 4.01 d.d (2H, 1-Hb, 6-Hd, Ja, b = Jc, d = 8.5,
3Jb, 2 6.8), 4.50 d.d (2H, 3-H, 4-H, J3, 4 = 4.5, J3, 2
1.5), 4.83 4.99 m (2H, 2-H, 5-H). 31P NMR spectrum
(C6H6): 78 ppm. Found, %: C 51.92; H 7.99;
=
3
3
1. Kurochkina, G.I., Grachev, M.K., Vasyanina, L.K.,
Piskaev, A.E., and Nifant’ev, E.E., Dokl. Ross. Akad.
Nauk, 2000, vol. 371, no. 2, p. 189.
P
P 10.17. C26H48N4O4P2S2. Calculated, %: C 51.47;
H 7.97; P 10.21.
2. Grachev, M.K., Kurochkina, G.I., Soboleva, N.O.,
Vasyanina, L.K., and Nifant’ev, E.E., Zh. Obshch.
Khem., 2002, vol. 72, no. 11, p. 1918.
Compound XII. Yield 0.47 g (25%), Rf 0.9 (B),
1
0.7 (H). H NMR spectrum (CDCl3), , ppm (J, Hz):
3. Grachev, M.K., Anfilov, K.L., Bekker, A.R., and
Nifant’ev, E.E., Zh. Obshch. Khim., 1995, vol. 65,
no. 12, p. 1946.
1.43 1.63 m [12H, N(CH2)2(CH2)3], 2.93 3.17 m
3
3
[8H, N(CH2)2(CH2)3, JPH = 6.6, JPH = 6.9], 2.61
3
2.69 br.s (1H, OH, JHH = 5.5), 3.61 d.d (1H, 6-Hc,
2Jd, c = 9.4, J5, 6 = 6.8), 3.74 d.d (1H, 1-Ha, Ja, b
=
4. Reetz, M.T. and Neugebauer, T., Angew. Chem., Int.
Ed. Engl., 1999, vol. 38, no. 1/2, p. 179.
3
2
3
8.1, Jb, 2 = 8.1), 3.95 d.d (1H, 6-Hd), 4.06 d.d (1H,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 6 2003