Formation of phosphorus-containing cage structures in the reaction of 2-ethoxyvinylphosphonic acid dichloroanhydride with resorcinol and its derivatives

Article abstract of DOI:10.1002/hc.21022

The scheme of formation of bicyclic phosphonates 3 synthesized on the basis of resorcinol and its derivatives was suggested based on the model reactions of dichloroanhydride 1 with 3-methoxyphenol 7 in the presence of triethylamine with a variable ratio of reagents. Composition and structure of the products obtained were confirmed according to ¹H and ³¹P NMR, IR spectroscopy, elemental analysis, and X-ray analysis.

Full text of DOI:10.1002/hc.21022

Heteroatom Chemistry
Volume 00, Number 0, 2012
Formation of Phosphorus-Containing Cage
Structures in the Reaction of
2-Ethoxyvinylphosphonic Acid
Dichloroanhydride with Resorcinol and Its
Derivatives
Yulia M. Sadykova,1 Natalia V. Dalmatova,2 Yulia K. Voronina,1
Alexander R. Burilov,1 Michael A. Pudovik,1 and Oleg G. Sinyashin1
1A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian
Academy of Sciences, Kazan 420088, Russia
2Kazan National Research Technological University, Kazan 420015, Russia
Received 2 December 2011
There is a large number of published data, which
ABSTRACT: The scheme of formation of bicyclic
are devoted to the development of the methods of
phosphonates 3 synthesized on the basis of resor-
synthesis and study of properties of phosphorus-
cinol and its derivatives was suggested based on
containing carcass structures, the framework of
the model reactions of dichloroanhydride 1 with 3-
which is formed from three endocyclic P O [1–7],
methoxyphenol 7 in the presence of triethylamine with
P N [8, 9], or P C [10] bonds. At the same time,
a variable ratio of reagents. Composition and structure
there are almost no data on the synthesis of frame-
of the products obtained were confirmed according to
work compounds formed with the simultaneous par-
1H and 31P NMR, IR spectroscopy, elemental analy-
ticipation of endocyclic P O and P C bonds. The
ꢀ
C
sis, and X-ray analysis.
2012 Wiley Periodicals, Inc.
only mention of the synthesis of phosphonates con-
taining P O and P C bonds simultaneously is in
the works of Kobayashi, which are devoted to the
chemistry of carbophosphatranes [11–14]. However,
a method of their synthesis is sufficiently labor con-
suming, involves several steps, and is accompanied
by the low yield of final products.
We devised a convenient single-step method
of synthesis of new carcass compound 3a of a
phosphonate structure according to the reaction of
2-ethoxyvinylphosphonic acid dichloroanhydride 1
with resorcinol 2 in the presence of trifluoroacetic
acid [15] (Scheme 1).
Heteroatom Chem 00:1–5, 2012; View this article online at
wileyonlinelibrary.com. DOI 10.1002/hc.21022
INTRODUCTION
Recently, in organic chemistry, there is an in-
creased interest toward the study of the complex sub-
stances, among which special attention is devoted to
phosphorus-containing framework compounds.
Correspondence to: Yulia M. Sadykova; e-mail: jsadykova@
Formation of the phosphorus-containing frame-
work derivative 3a in this reaction was not com-
pletely understood; for this reason, we attempted
this detailed study.
mail.ru.
Contract grant sponsor: Russian Foundation for Basic Re-
search.
Contract grant number: 11-03-00416-a.
2012 Wiley Periodicals, Inc.
c
ꢀ
1

2
Sadykova et al.
O
P
O
P
O
O
O
O
OCH3
H3CO
H3CO
OH
+
HO
2
+
OH
CF3COOH
OH
HO
C2H5OCH=CHP(O)Cl2
1
2 Et3N
C6H6
2
1
2
3 a
OEt
8
7
SCHEME 1
SCHEME 4
O
Cl
O
OH
P
O
P
+ 2
1 + 2
3a
HC
– HCl
O
Cl
CH
H3CO
(C2H5)3N
OC2H5
4
1 + 7
9
OC2H5
SCHEME 2
SCHEME 5
RESULTS AND DISCUSSION
It could be suggested that the first step of the
reaction involves phosphorylation of the hydroxyl
group of resorcinol with the intermediate forma-
tion of chlorophosphonate 4, which undergoes fur-
ther transformation to bicyclic phosphonate 3a
(Scheme 2).
An alternative route involves primary protona-
tion of dichloroanhydride 1 with the formation of
carbocation 5 and further electrophilic substitution
in an aromatic ring, resulting in phosphonate 6. Its
reaction with the second resorcinol molecule is ac-
companied by the formation of the carcass structure
3a (Scheme 3).
uct 8 in toluene in the presence of trifluoroacetic
acid is not accompanied by the formation of the
carcass structure and a hardly separable mixture of
phosphorus-containing products is formed. During
the reaction of equimolar amounts of phenol 7 with
dichlorophosphonate 1 in benzene in the presence
of triethylamine, only product 9 was synthesized,
which has a chemical shift of a phosphorus nucleus
δP 26.40 ppm (Scheme 5).
Heating of chloride 9 in toluene in the presence
of trifluoroacetic acid results in oxaphosphorinine
11 formed from chlorophosphorinine 10, which is
intrinsic to the chemical shift δP 10.28 ppm in the 31
P
We managed to make a choice between two al-
ternative possibilities given above with the use of
a series of model reactions of dichloroanhydride 1
with 3-methoxyphenol 7 in the presence of triethy-
lamine with a varying ratio of reagents. When using
compounds 1, 2 in 1:2 ratio, phosphonate 8 was syn-
thesized as an oily liquid with almost quantitative
yield (Scheme 4).
Structure and composition of the product syn-
thesized was confirmed according to 1H and 31P
NMR, IR spectroscopy, and elemental analysis. In
the 31P NMR spectrum of compound 8, there is
one signal δP 15.90 ppm. Further heating of prod-
NMR spectrum of the reaction mixture. Compounds
of this type described in the published data have the
chemical shift values in the range of 10 ppm [16]
(Scheme 6).
In the 1H NMR spectrum of compound 11, there
are signals of the methoxy group (3.79 ppm), pro-
tons at a double bond as a doublet of doublets (6.12
ppm and 7.34), and protons at meta- (6.76 ppm) and
ortho- (7.37 ppm) positions of the aromatic ring as
doublets. The chemical shift of the phosphorus nu-
cleus has the value of 7.07 ppm for compound 11.
The structure of product 11 was confirmed ac-
cording to X-ray analysis (Fig. 1).
HO
OH
O
O
O
HO
P Cl
OH
+ 2
Cl
+H
Cl2PCH = CH - OC2H5
1
Cl2PCH2 - CH - OC2H5
5
3a
- H
CH
OC2H5
6
SCHEME 3
Heteroatom Chemistry DOI 10.1002/hc

Formation of Phosphorus-Containing Cage Structures
3
O
P
O
Cl
O
O
O
O
H3CO
H3CO
H3CO
P
P
CF3COOH
Cl
OH
OC2H5
9
11
10
SCHEME 6
FIGURE 1 Molecular structures of compound 11.
Bond lengths, valence, and torsion angles have
values that are in the range intrinsic to each type of
bond. A bicyclic system is a plane in the range of
NMR, it is characterized by the signal with the chem-
ical shift δP 15.0 ppm. In the H NMR spectrum of
1
compound 12, there are signals of methylene groups
bonded to the phosphorus atom as a doublet of dou-
blets (2.69 ppm), methoxy groups (3.69 ppm), me-
thine groups as a doublet of triplets (4.67-4.75 ppm),
and protons at meta- (6.66 ppm) and ortho- (7.38
ppm) positions of the aromatic ring as doublets and
ortho- (6.64 ppm) protons as a singlet. Thus, it can
be concluded that the formation of bicyclic phos-
phonates synthesized on the basis of resorcinol and
its derivatives takes place according to Scheme 8.
At the first step of the reaction, phosphorylation
of one hydroxyl group of resorcinol or its derivative
takes place with the formation of chlorophospho-
nate 4, which transforms to phosphacyclane 13 upon
protonation. The latter undergoes elimination of the
alcohol molecule in acidic medium with the genera-
tion of carbocation 14. Its further reaction with the
second molecule of resorcinol or its derivative gives
2
˚
0.016(2) A; a phosphorus atom P deviates from this
13 14
˚
plane by 0.252(3) A. A bond O C is masked by the
C6C7 bond. Configuration of the phosphorus atom
is tetrahedral, and the O1P2O12 angle corresponds
to 111.08(1)◦. The presence of phosphoryl and hy-
droxyl groups results in the formation of a classical
hydrogen bond between neighboring molecules in a
crystal; the distance from the hydrogen atom of the
hydroxyl group of one molecule to the oxygen atom
of the phosphoryl group of another one corresponds
12 12
to 1.56 A and angle O H · · · O1, 169◦.
˚
Bicyclic phosphonate 12 was synthesized ac-
cording to the reaction of chloride 9 with an equimo-
lar amount of phenol 7 in the presence of trifluo-
roacetic acid in toluene (Scheme 7).
Product 12 represents a white crystal substance
soluble in DMSO and acetone–water mixture. In 31
P
O
P
O
O
O
O
P
Cl
H3CO
H3CO
+
OH
CF3COOH
OCH3
H3CO
OC2H5
9
7
12
SCHEME 7
Heteroatom Chemistry DOI 10.1002/hc

4
Sadykova et al.
R
R
O
P
Cl
O
HO
OH
+ H
O
OH
+ H
+
Cl2PCH = CH - OC2H5
HC
- HCl
1
CH
O
4
OC2H5
R
R
R
HO
OH
O
P
O
P
OH
O
O
Cl
OH
Cl
- C2H5OH
CH
OC2H5
- H
CH
14
13
O
P
O
P
Cl
OH
R
R
R
R
O
O
OH
OH
HO
HO
CH
15
- HCl
3
R=H (a), CH3 (b), OH (c)
SCHEME 8
rise to the intermediate formation of chlorophos-
phonate 15 and then a final product 3. This mech-
anism is confirmed by the fact that condensation of
dichloroanhydride 1 with resorcinol and its deriva-
tives in water-alcohol medium in the presence of
hydrochloric acid, which proceeds according to the
electrophilic substitution, gives a different synthetic
result, namely, formation of phosphorus-containing
calix [4] resorcinols bearing phosphoryl groups on
the lower rim of a molecule [17].
(3-Methoxy-phenyl) 2-Ethoxyethinylphospho-
nium Chloride (9)
To a mixture of 7 (0.66 g, 5.3 mmol, 1 equiv) and
triethylamine (0.54 g, 5.3 mmol, 1 equiv) in 5 mL
benzene, the solution of 1 (1 g, 5.3 mmol, 1 equiv)
was added dropwise in 25 mL benzene in the argon
flow and upon cooling in water bath. The reaction
mixture was taken to room temperature upon stir-
ring. Triethylamine hydrochloride precipitated was
filtered, and the filtrate was distilled in vacuum.
1
There is an oily product in residue. Yield 94%; H
EXPERIMENTAL
NMR (600 MHz CDCl3): δ = 1.35 (t, 3H), 3.78 (s, 6H),
3.97 (q, 2H), 5.14 (dd, J = 13.32 Hz, J = 15.86 Hz,
1H), 6.76 (d, J = 8.25 Hz, 2H), 6.78 (s, 2H), 6.84 (d,
J = 7.93 Hz, 2H), 7.24 (t, J = 8.25 Hz, 2H), 7.43 (dd,
J = 13.32 Hz, 1H) 31P NMR (CDCl3, 100.62 MHz):
δ = 26.4. Anal. Calcd for C11H14O4PCl: C, 47.74; H,
5.06; P, 11.21; Cl, 12.84.Found: C, 48.01; H, 5.16; P,
11.49; Cl, 12.77.
(2-Ethoxyethenyl)-phosphonic Acid
Bis-(3-methoxy-phenyl) Ester (8)
To 7 (1.32 g, 10.6 mmol, 2 equiv) in a mixture of ben-
zene (25 mL) and triethylamine (1.07 g, 10.6 mmol,
2 equiv), the solution of 1 (1.0 g, 5,3 mmol, 1 equiv)
was added dropwise in 5 mL benzene in an argon
flow and upon cooling in water bath. The reaction
mixture was taken to room temperature upon stir-
ring. Triethylamine hydrochloride precipitated was
filtered, and the filtrate was distilled in vacuum.
There is an oily product in the residue. Yield 95%; IR
2-Hydroxy-2-oxa-7-methoxy-benzo[e]-1,2-oxa-
phospharinine (11)
1
1266, 1490, 1606 cm−1. H NMR (600 MHz CDCl3):
A solution of 9 (1.37 g, 5.0 mmol, 1 equiv) in
10 mL dioxane in the presence of trifluoroacetic acid
(0.57 g, 5.0 mmol, 1 equiv) was refluxed for 10 h. The
reaction mixture was taken to room temperature,
white crystal precipitate was filtered, washed with
ethyl alcohol, and dried up to a constant weight.
Yield 87%; mp = 158–159◦C. IR 1230, 1553, 1606,
δ = 1.29 (t, 3H), 3.75 (s, 6H), 3.88 (q, 2H), 4.91 (dd,
J = 11.11 Hz, J = 13.64 Hz, 1H), 6.71 (d, J = 8.25 Hz,
2H), 6.79 (s, 2H), 6.84 (d, J = 7.93 Hz, 2H), 7.20 (t,
J = 8.25 Hz, 2H), 7.35 (dd, J = 11.42 Hz, 1H). 31P
NMR (CDCl3, 100.62 MHz): δ = 15.9. Anal. Calcd
for C18H21O6P: C, 59.34; H, 5.77; P, 8.52. Found: C,
60.11; H, 5.93; P, 8.49.
1
2301 cm−1. H NMR (600 MHz DMSO): δ = 3.79
Heteroatom Chemistry DOI 10.1002/hc

Formation of Phosphorus-Containing Cage Structures
5
0.0415, wR2 = 0.1394, max. Residual electron den-
(s, 3H), 6.12 (dd, J = 12.53 Hz, J = 19.75 Hz, 1H),
6.74 (s, 1H), 6.76 (d, J = 8.65 Hz, 1H), 7.34 (dd, J =
12.53 Hz, J = 42.51 Hz, 1H), 7.37 (d, J = 8.65 Hz,
1H). MHz) 31P NMR (DMSO,100.62 MHz): δ = 7.
Anal. Calcd for C9H9O4P: C, 50.94; H, 4.25; P, 14.62.
Found: C, 50.99; H, 4.14; P, 14.57.
−3
˚
sity 0.225(–0.312) eA . The positions of hydrogen
atoms were located from the Fourier electron den-
sity synthesis and were included in the refinement
in the isotropic riding model approximation. CCDC
871527.
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A solution of 7 (0.64 g, 5.1 mmol, 1 equiv) in 3 mL
toluene was added dropwise upon reflux to the so-
lution of 9 (1.43 g, 5.1 mmol, 1 equiv) in 7 mL
toluene in the presence of trifluoroacetic acid (0.59 g,
5.1 mmol, 1 equiv). The reaction mixture was re-
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3.88 Hz, J = 35.64 Hz, 1H), 6.64 (s, 2H), 6.66 (d,
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C16H15O5P: C, 60.38; H, 4.72; P, 9.75. Found: C, 60.19;
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Crystal data for 11: C9H9O4P, M = 212.13, colorless
crystal 0.1 × 0.2 × 0.3 mm, orthorhombic, space
group Pbca, Z = 8, a = 11.035(2), b = 7.9699(16),
3
˚
˚
c = 21.908(4) A,
V
= 1926.8(7) A , ρcalc
=
−3
−1
˚
1.463 g cm , μ = 0.270 mm , λ = 0.71073 A,
T = 293 K, Bruker Smart Apex II CCD diffrac-
tometer, 19,865 reflections collected ( h, k, l),
2361 independent (R 0.0611) and 1499 observed
int
reflections [I ≥ 2 σ(I)], 132 refined parameters, R =
Heteroatom Chemistry DOI 10.1002/hc