New phosphorus-containing macroheterocyclic cavitands

Article abstract of DOI:10.1134/S1070363206080056

Previously unknown phosphorus-containing macroheterocycles were prepared from an accessible symmetrical dipentaerythritol derivative and trivalent phosphorus compounds. The difference in the properties of the phosphocycles containing one and two phosphori

Full text of DOI:10.1134/S1070363206080056

ISSN 1070-3632, Russian Journal of General Chemistry, 2006, Vol. 76, No. 8, pp. 1205 1209.
Pleiades Publishing, Inc., 2006.
Original Russian Text
pp. 1254 1259.
D.A. Predvoditelev, M.A. Malenkovskaya, E.E. Nifant’ev, 2006, published in Zhurnal Obshchei Khimii, 2006, Vol. 76, No. 8,
New Phosphorus-Containing Macroheterocyclic Cavitands
D. A. Predvoditelev, M. A. Malenkovskaya, and E. E. Nifant’ev
Moscow Pedagogical State University,
Nesvizhskii per. 3, Moscow, 119021 Russia
e-mail: chemdept@mtu-net.ru
Received January 31, 2006
Abstract Previously unknown phosphorus-containing macroheterocycles were prepared from an accessible
symmetrical dipentaerythritol derivative and trivalent phosphorus compounds. The difference in the properties
of the phosphocycles containing one and two phosphoric functions was revealed.
DOI: 10.1134/S1070363206080056
Phosphorus-containing macroheterocycles show
promise for the modern supramolecular chemistry.
Their significant advantage is the possibility of
combining cavities of different configurations with
the phosphorus-containing functional groups differing
in the phosphorus valence and arrangement of sub-
stituents. Unfortunately, the design of such macro-
heterocycles is developed mainly in the direction of
using them as common building blocks, and, therefore,
the ranges of the examined molecular cavities remains
limited [1 4]. Therefore, our goal was to expand the
range of phosphorus-containing macroheterocycles by
using as the starting compound dipentaerythritol,
which was seldom used previously in fine organic
synthesis. A specific structural feature of this com-
pound is the presence of two quarternary carbon
atoms. When incorporated in a macroheterocycle,
these atoms can enclose a part of the space in the
cavity.
Recently we showed that dipentaerythritol can be
efficiently converted into symmetrical 1,3;1 ,3 -di-
benzylidene derivatives I which show promise in the
design of novel lipid systems [5]. Here we report on
the cyclophosphorylation of this compound. The first
part of the study deals with direct binding of two
hydroxy groups of diol I by the phosphoric function.
For such binding, we tested various derivatives of
phosphorous acid, among which tetraethylphosphoro-
diamidous chloride II proved to be the most effective.
First we studied the reaction of equimolar amounts of
diol I with compound II in dioxane.
NEt2
ClP
NEt2
OCH2
OCH2
CH2O
O
O
II
C6H5CH
CCH2OCH2C
(1)
HCC6H5
R
PNEt2
CH2O
CH2OH
HOCH2
I
III
OCH2
CH2O
Here and hereinafter R = C6H5CH
CCH2OCH2C
HCC6H5.
OCH2
H2C
CH2O
CH2
We found that the starting compound I in the
presence of pyridine even at +5 C undergoes deep
cyclophosphorylation within 2 h, involving the re-
placement of the chlorine atom and one diethylamino
group at the phosphorus atom by the alkoxy group of
diol I. In the course of the reaction, we observed in
the 31P NMR spectrum of the reaction mixture the
disappearance of the signal of phosphorodiamidous
1205

1206
PREDVODITELEV et al.
chloride II ( 157.3 ppm) and growth of a signal in
glet of the methine proton of the CHC6H5 group (
5.41 ppm), and also signals of two aromatic rings:
two signals at 7.27 and 7.29 ppm and a broadened
P
the range typical of monoamidocyclophosphites (
P
147.6 ppm, br.s). We also studied the reaction of I
with II in 1:2 molar ratio and found that the expected
bisphosphorylation did not occur. Instead, macrocycle
III was formed, and a half of chloride II remained
unchanged. This result shows that diol I preferentially
undergoes cyclophosphorylation. Cycloamidophos-
phite III without isolation was easily converted into
the corresponding 10-membered cyclophosphoramido-
thioate IV by treatment with sulfur at room tempera-
ture (25 C).
singlet at
7.48 ppm (m-, p-, and o-protons).
Note that the broadening of the signals of the
CHC6H5 methine protons of the two 1,3-dioxane rings
of IV can be due to their slight magnetic nonequiv-
alence. Molecular modeling performed for the most
favorable conformation of compound IV1 showed that
one of the 1,3-dioxane rings has a boat conformation
and hence the meso proton of the ring is deshielded
and its signal is shifted downfield, whereas the other
1,3-dioxane ring has a chair form, the related proton
is shielded, and its signal is shifted upfield. This,
O
[S]
(2)
III
R
PNEt2.
S
1
O
broadening of these signals in the H NMR spectra
can be assigned to magnetic anisotropy of the aro-
matic rings (Fig. 1).
IV
Phosphorothioate IV was isolated by chromatog-
raphy on a column with silica gel. Its overall yield in
the two steps was 65%. The product is an oily sub-
stance stable in storage at room temperature. Its purity
and structure were proved by elemental analysis, TLC,
Another novel 20-membered cyclobis(phosphor-
amidothioate) VIII prepared from dibenzylidene
pentaerythritol I but containing two phosphorothioic
residues was synthesized by the method of molecular
assembling using a new phosphorylating agent. Di-
meric phosphocyclane VIII was synthesized in three
steps: preparation of bisphosphorylated diol VI, cyclo-
phosphorylation of the second molecule of diol I with
VI, and addition of sulfur to the resulting cyclobis-
phosphite VII.
1
and H and 31P NMR spectroscopy. The molecular
weight of cyclophosphoramidothioate IV was con-
firmed by the MALDI-TOF mass spectrum.
The 31P NMR spectrum of IV contains a broadened
1
signal at
76.2 ppm. The H NMR spectrum, along
P
P(NEt2)3
V
with the resonance of the N-ethyl protons as typical
triplet and quartet at 1.14 and 3.17 ppm, respec-
tively, contains signals of methylene protons of the
molecular core ( 3.80 4.59 ppm), a broadened sin-
OP(NEt2)2
OH
OH
R
R
2HNEt3
OP(NEt2)2
I
VI
O R O
I
Et2NP
PNEt2
2HNEt3
O R O
VII
O R O
2[S]
(3)
Et2NP
S
PNEt2
S
O R O
VIII
The reaction of diol I and phosphorous triamide V
was performed at their molar ratio of 1:2 in dioxane
at room temperature (25 C) without special removal
of diethylamine formed in the process. In the course
of bisphosphorylation (10 h), the signal of V (
117 ppm) disappears from the 31P NMR spectrum oPf
the reaction mixture, whereas the signal of phos-
phorodiamidous ester VI at P 134.8 ppm (br.s) grows.
In this case, the reaction result depends mainly on the
1
Here and hereinafter, the molecular modeling of the com-
pounds was performed for gas phase by the MM2 procedure
in Chem 3D Ultra 7.0 package [6].
Fig. 1. Optimal conformation of the molecule of IV.
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NEW PHOSPHORUS-CONTAINING MACROHETEROCYCLIC CAVITANDS
1207
Fig. 2. Optimal conformation of the molecule of VIII.
duration of complete bisphosphorylation of diol I. The
optimal time was elucidated using the results of
monitoring the reaction mixture by 31P NMR spec-
troscopy. After the reaction of I with V was complete,
an additional 1 equiv of diol I was added, and the
mixture was stirred at 65 C for 50 h. In the 31P NMR
protons of one water molecule. We failed to remove
water, which is incorporated in the composition of
phosphocycle VIII in the course of its chromatographic
isolation, even by heating for 5 h at 80 C in a vacuum
(1 mm Hg).
The possibility of inclusion of a water molecule
into VIII is confirmed by molecular modeling (Fig. 2).
An essential feature of the steric structure of the
10-membered phosphocyclane IV and 20-membered
diphosphocyclane VIII (calculated using van der
Waals atomic radii) is the practical absence of a free
internal cavity in the molecule of IV. The difference
in the molecular geometries of IV and VIII (Figs. 1,
2) can be illustrated by the calculated distances
between the atoms taken as the reference [6]. In IV,
the distance between the quarternary carbon atoms is
as short as 4.69 , while in the molecule of VIII the
distance between the opposite phosphorus atoms
reaches 7.39 , and the inclusion of a water molecule
in the cavity of VIII is sterically possible.
spectrum,
a
broadened signal appeared at
P
147.6 ppm. Its chemical shift corresponds to the
above-described monophosphocyclic compound III.
Phosphorothioate VIII was isolated by column
chromatography; overall yield in three steps 60%.
Compound VIII is an oily substance stable in storage.
Its purity was confirmed by TLC and MALDI-TOF
mass spectrometry. Its structure was proved by
elemental analysis and 31P NMR spectroscopy. The
31P NMR spectrum of VIII contained a broadened
1
singlet at
76.5 ppm, and the H NMR spectrum
contained siPgnals from all proton groups expected for
VIII. The spectrum of VIII closely resembles that of
IV; the main difference is the existence of a
broadened singlet at 1.70 ppm in the spectrum of
VIII with the integral intensity corresponding to
The steric structure and geometric parameters of
the molecules of 20-membered phosphocyclanes VII
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 8 2006

1208
PREDVODITELEV et al.
Fig. 3. Optimal conformation of the molecule of VII.
and VIII containing, respectively, tri- and pentavalent
phosphorus atoms were examined in more detail. We
compared the bond angles, interatomic distances, and
potential energies of these phosphocycles. In VII, the
OPO angles at the frontal endocyclic phosphorus
atoms differ significanly from each other (166.08 and
96.30 ). This difference in angles correlates with the
difference in the distance between the carbon atoms of
CH2OCH2 groups at the opposite sides of the cyclic
molecules: 7.37 and 6.58 . One of the 1,3-dioxane
rings is in chair conformation, while another has the
conformation of a strongly twisted boat. These con-
formations alternate and the whole molecule of VII
has a folded structure (Fig. 3). On the contrary, the
molecule of VIII, due to a change in the delocaliza-
tion of the electron density as compared to VII, has a
rather regular geometry with alternating chair boat
conformations of the 1,3-dioxane rings. The OPO
bond angles are close to each other (100.79 and
93.82 ), and the distances between the carbon atoms
in the CH2OCH2 groups at the opposite sides of the
molecule differ insignificantly (7.84 and 7.28 ).
apparently originates from the rigidity of P(V) deriva-
tive VIII compared to P(III) derivative VII which is
conformationally labile.
To conclude, we demonstrated the possibility of
preparing novel macroheterocycles based on dipenta-
erythritol derivatives. By choosing specific phospho-
rylating agents and reaction conditions, it is possible
to obtain ring systems of different types.
EXPERIMENTAL
1
The H NMR spectra were recorded on a Bruker
WM-250 instrument (250 MHz); the chemical shifts
are given relative to internal HNDS; the proton
signals were assigned using double magnetic res-
onance experiments. The 31P {1H} NMR spectra
were taken on a Bruker WP-80SY spectrometer,
operating frequency 32.4 MHz, external reference
85% phosphoric acid. The monoisotopic (12C) molec-
ular weights were measured on a Bruker UltraFlex
(Bruker Daltomics, Germany) instrument. Adsorption
chromatography was performed on a colum 15 mm in
diameter, packed with silica gel L 100 250 m. The
Rf values were measured on Silufol UV-254 plates in
Our experimental results show that phosphocy-
clanes VII and VIII are stable under ordinary condi-
tions. However, they differ significantly in the steric
energy: 86.6 and 134.92 eV, respectively. This fact
the systems benzene dioxane, 3:1 (A) and hexane
dioxane, 3:1 (B).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 8 2006

NEW PHOSPHORUS-CONTAINING MACROHETEROCYCLIC CAVITANDS
1209
All syntheses involving trivalent phosphorus com-
pounds were performed in an atmosphere of dry argon.
Tetraethylphosphorodiamidous chloride II and hexa-
ethylphosphorous triamide V were prepared as de-
scribed in [7], and 1,3;1 ,3 -dibenzylidene pentaery-
thritol I, as in [6]; their constants coincided with the
published data.
and the mixture was heated for 1 h at 50 C. Excess
sulfur was filtered off, and dioxane was removed in a
vacuum. Compound VIII was purified by chromato-
graphy on a column packed with silica gell (5 g) and
filled with benzene; the product was eluted with 30
ml of benzene. After removing the solvent in a
vacuum, the residue was heated for 5 h at 80 C
(1 mm Hg). Yield of VIII 0.48 g (60%), n2D0 1.5738,
1
10-Membered cyclophosphoramidothioate IV. A
solution of 0.15 g of acid chloride II in 5 ml of an-
hydrous dioxane was added dropwise with cooling to
5 C and stirring to a solution of 0.2 g of diol I and
0.5 g of pyridine in 10 ml of the same solvent. Then
the mixture was warmed to 25 C and kept at this
temperature for 2 h. The formation of cyclophosphite
III was monitored by the 31P NMR spectoscopy [
147.6 ppm, br.s (dioxane)]. Then 0.1 g of sulfur waPs
added, and the reaction mixture was kept at room
temperature for 3 h. Excess sulfur was filtered off, and
the solvent was removed in a vacuum. Cyclophos-
phoramidothioate IV was purified by chromatography
on a column packed with silica gel (5 g) and filled
with hexane. Compound IV was eluted with 20 ml of
a hexane dioxane (5:1) mixture. The solvents were
removed in a vacuum, and the residue was kept for
2 h at 80 C (1 mm Hg). Yield 0.17 g (65%), nD20
Rf 0.75 (A), 0.45 (B). H NMR spectrum (CDCl3), ,
3
ppm: 1.16 t and 1.26 t (12H, NCH2CH3, JHH
6.72 Hz), 1.69 br.s (2H, H2O), 3.29 q (8H, NCH2CH3,
3JHP 11.16 Hz), 3.60 s, 3.70 s, 3.77 s (8H, CH2OCH2),
2
3.90 m (8He) and 4.60 m (8Ha) [CH2OCH, J(HaHe)
3
11.70 Hz], 4.14 m (8H, CH2OP, JHP 10.50 Hz),
5.42 s and 5.43 s (4H, CHC6H5), 7.36 br.s (12H, m,
p) and 7.47 br.s (8H, o) (C6H5). 31P NMR spectrum
(dioxane), P, ppm: 76.52 br.s. Found, %: C 58.82; H
6.73; P 5.38. C56H76N2O14P2S2 H2O. Calculated, %:
C 58.70; H 6.69; P 5.41. M 1145.29. Found, M (12C):
1126.38. C56H76N2O14P2S2. Calculated, M (12C):
1127.67.
ACKNOWLEDGMENTS
Thus study was financially supported by the Pre-
sident of the Russian Federation (program for support
of leading scientific schools of the Russian Federation,
grant NSh-5515.2006.3).
1
1.5663, Rf 0.83 (A), 0.55 (B). H NMR spectrum
3
(CDCl3), , ppm: 1.14 t (6H, NCH2CH3, JHH
3
7.01 Hz), 3.17 q (4H, NCH2CH3, JHP 13.73 Hz),
3.70 s (4H, CH2OCH2), 3.80 m (4He) and 4.55 m
2
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(4Ha) (CH2OCH, J(HaHe) 11.82 Hz), 4.18 m (4H,
3
CH2OP, JHP 9.94 Hz), 5.41 br.s (2H, CHC6H5), 7.36
br.s (6H, m, p) and 7.46 br.s (4H, o) (C6H5). 31P NMR
spectrum (dioxane), P, ppm: 76.17 br.s. Found, %: C
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P
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