Synthesis of N-substituted aminomethylenediphosphonites and their derivatives

Full text of DOI:10.1134/S1070363213060340

ISSN 1070-3632, Russian Journal of General Chemistry, 2013, Vol. 83, No. 6, pp. 1175–1177. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © A.A. Prishchenko, M.V. Livantsov, O.P. Novikova, L.I. Livantsova, I.S. Ershov, V.S. Petrosyan, 2013, published in Zhurnal
Obshchei Khimii, 2013, Vol. 83, No. 6, pp. 1045–1047.
LETTERS
TO THE EDITOR
Synthesis of N-Substituted Aminomethylenediphosphonites
and Their Derivatives
A. A. Prishchenko, M. V. Livantsov, O. P. Novikova,
L. I. Livantsova, I. S. Ershov, and V. S. Petrosyan
Lomonosov Moscow State University, Vorob’ovy Gory, Moscow, 119991 Russia
e-mail: aprishchenko@yandex.ru
Received February 7, 2013
DOI: 10.1134/S1070363213060340
Substituted aminomethylenediphosphonites are of
interest as the key materials in the synthesis of
functionalized aminomethylenediphosphorus-containing
compounds, which are analogs of natural organophos-
phorus pyrophosphates and amino acids, promising
ligands and biologically active substances with diverse
properties [1]. Recently, we have prepared two types
of the compounds by reacting bis(trimethylsiloxy)
phosphine with substituted methyleneimines [2]. To
synthesize new types of N-substituted aminomethyl-
enediphosphonites we studied the direct interaction of
bis(trimethylsiloxy) phosphine A with available N-
substituted formamides. Note that the phosphine A can
be easily attached to the carbonyl groups of various
aldehydes and ketones [3], but the analogous reaction
with formamide is not described. The reaction of an
excess of bis(trimethylsiloxy)phosphine A with N-
substituted formamides proceeds readily in methylene
chloride only in the presence of a catalyst (trimethyl-
silyl trifluoromethanesulfonate) to give the inter-
mediate diphosphonites B. The latter react with bis-
(trimethylsilyl)amine under reflux in the presence of
trimethylchlorosilane to afford diphosphonites I–III
with good yields (cf. [4]).
ХО
Х2NH, ХCl
HC(O)NR2, CF3SO3Х
P
2(ХO)2PH
[(ХO)2P]2CHNR2
2CHNR2
_Х2O
_NH3
H
O
A
B
I_III
Х = Me3Si, NR2 = NHPh (I), NMe2 (II), N
O (III).
The resulting aminomethylenediphosphonites we
used for the synthesis of new types of aminomethyl-
enediphosphorus-containing compounds. Thus, the
reaction of diphosphonite I with a dilute solution of
sodium methylate in methanol results in a stable
diphosphonous acid salt IV, which is white hygro-
scopic crystals (cf. [2]).
Diphosphonite I containing a highly reactive
moiety POSi easily attaches to the carbonyl group of
aromatic aldehydes taken in excess in methylene
chloride to form the intermediate diphosphinates C.
The treatment of the reaction mixture with methanol
gives rise to new functionalized aminomethylene-
diphosphinic acids V, VI in high yields.
The NMR spectra of compounds I–VI contain the
typical signals of Р2С1HNC2H fragments, and in the
spectra of compounds V, VI there are also the signals
of РС3H(Ar)ОН moiety, parameters of which are listed
below. According to the NMR spectra, compounds V,
NaO
2MeONa, 2MeOH
P
2CHNHPh
I
_2Me3SiOMe
H
O
IV
1175

1176
PRISHCHENKO et al.
Ar(Me3SiO)CH
Me3SiO
Ar(HO)CH
HO
2ArCHO
4MeOH
_4Me3SiOMe
I
P
P
2CHNHPh
2CHNHPh
O
O
C
V, VI
Ar =
(V), 4-MeOC6H4 (VI).
N
VI containing four asymmetric atoms are a mixture of
three stereoisomers whose ratio was determined by the
1H, 31P NMR spectra. Two diastereotopic phosphoryl
groups of the predominant isomer of compounds V, VI
in the 31P NMR spectrum are observed as a typical
AB-system.
Disodium salt of N-anilinomethylenediphospho-
nous acid (IV). To a solution of 0.93 g of sodium
methylate in 30 ml of methanol under cooling to 10°C
and stirring was added 4.5 g of diphosphonite I in
20 ml of diethyl ether. Then the solvent was distilled
off, and the white crystals were kept in a vacuum of
1 mm Hg for 1 h. Yield 2.3 g (95%). 1H NMR, δ, ppm:
2
3
3.64 t (С1H, JРН 16.0 Hz), 6.77 d (2С1HPh, JHН
O,O,O,O-Tetra(trimethylsilyl) N-anilinomethyl-
enediphosphonite (I). To a solution of 18 g of bis-
(trimethylsiloxy)phosphine and 2.4 g of formanilide in
10 ml of methylene chloride was added with stirring 1
ml of trimethylsilyl trifluoromethanesulfonate. The
mixture was heated at 20° C for 4 h. Then the solvent
was distilled off, and to the residue was added 20 g of
bis(trimethylsilyl)amine and 2 ml of trimethyl-
chlorosilane. The mixture was refluxed for 1 h, then
3
8.0 Hz), 7.16 t (2СHPh, JН1Н 8.0 Hz), 6.70 t (С1HPh,
3JHН 8.0 Hz), 7.04 d (2РН, JРН 532.0 Hz). 13С NMR
spectrum, δС, ppm: 56.24 t (С1, 1JРС 85.7 Hz), 147.80 s
(С2), 129.52, 118.13 and 113.72 (СPh). 31Р NMR
spectrum: δР 20.10 ppm. Found, %: С 29.90; Н 3.26.
С7Н9NNa2О4P2. Calculated, %: С 30.13; Н 3.25.
N-Anilinomethylenebis[hydroxy(pyrid-3-yl)-
methylphosphinic] acid (V). To a solution of 3.5 g of
diphosphonite I in 10 ml of methylene chloride under
cooling to 10°C and stirring was added a solution of
1.6 g of 3-pyridinecarbaldehyde in 10 ml of methylene
chloride. Then the solvent was distilled off, and to the
residue was added a mixture of 10 ml of methanol and
20 ml of diethyl ether. The mixture was heated to
boiling and cooled. The precipitated crystals were
filtered off, washed with diethyl ether, and kept in a
vacuum of 1 mm Hg for 1h. Yield 2.7 g (89%), mp >
150°C (decomp.). First isomer, content 50%. 1H NMR
1
distilled. Yield 7.7 g (74%), bp 152°C (1 mm Hg). H
NMR spectrum, δ, ppm: 3.2–3.3 m (С1H), 4.44 d (NH,
3
3JHH 8.0 Hz), 6.68 d (2СНPh, JHH 8.0 Hz), 7.07 t
(2СНPh, 3JHH 8.0 Hz), 6.60 t (2СНPh, 3JHH 8.0 Hz), 0.1–
0.2 m (12 СН3). 13С NMR spectrum, δС, ppm: 71.78 t
1
(С1, JPС 38.5 Hz), 151.03 (С2), 128.53, 115.67 and
112.56 (СPh), 1.31 (CH3). 31Р NMR spectrum: δР
155.78 ppm.
Diphosphonites II, III were obtained similarly.
O,O,O,O-Tetra(trimethylsilyl) dimethylamino-
methylenediphosphonite (II). Yield 52%, bp 119°С
2
spectrum, δ, ppm: 4.14 t (С1H, JPH 16.4 Hz), 4.95 d
2
(С3H, JPH 12.4 Hz). 13С NMR spectrum, δС, ppm:
1
(1 mm Hg). H NMR spectrum, δ, ppm: 2.11 t (С1H,
50.24 t (С1, 1JPС 84.8 Hz), 69.74 d (С3, 1JPС 104.2 Hz).
2JРH 5.6 Hz), 2.67 s (2С2H3N), 0.15 с (4Me3Si). 13С
31Р NMR spectrum, δР, ppm: 29.98 d and 31.19 d (2JPР
1
NMR spectrum, δС, ppm: 82.37 t (С1, JPС 41.6 Hz),
1
3
45.19 t (С2, JPС 7.2 Hz), 1.39 s (Me3Si). 31Р NMR
20.3 Hz). Second isomer, content 30%. H NMR, δ,
2
2
ppm: 4.31 t (С1H, JPH 16.0 Hz), 4.97 d (С3H, JPH
spectrum: δР 166.82 ppm.
12.4 Hz). 13С NMR spectrum, δС, ppm: 48.51 t (С1,
1JPС 86.9 Hz), 69.97 d (С3, JPС 106.4 Hz). 31Р NMR
1
O,O,O,O-Tetra(trimethylsilyl) N-morpholinome-
thylenediposphonite (III). Yield 72%, bp 144°С
spectrum: δР 30.22 ppm. Third isomer, content 20%.
1
(1 mm Hg). H NMR spectrum, δ, ppm: 2.08 t (С1H,
2
1H NMR, δ, ppm: 3.92 t (С1H, JPH 16.3 Hz), 5.05 d
2JРH 6.2 Hz), 3.0–3.1 m (2С2H2), 3.4–3.5 m (2СH2О),
0.17 s (4Me3Si). 13С NMR spectrum, δС, ppm: 82.34 t
2
(С3H, JPH 12.4 Hz). 13С NMR spectrum, δС, ppm:
1
1
51.89 t (С1, JPС 87.6 Hz), 69.13 d (С3, JPС 97.8 Hz).
31Р NMR spectrum: δР 30.67 ppm. The signals of
aromatic fragments of isomers in the 1H and 13С NMR
spectra are in the typical ranges and overlapped.
1
3
(С1, JPС 42.8 Hz), 53.11 t (С2, JPС 6.8 Hz), 67.73 s
(СН2О), 1.35 s (Me3Si). 31Р NMR spectrum: δР
165.33 ppm.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 6 2013

SYNTHESIS OF N-SUBSTITUTED AMINOMETHYLENEDIPHOSPHONITES
1177
Found, %: С 50.57; Н 4.78. С19Н21N3О6P2. Calculated,
%: С 50.79; Н 4.71.
(IV–VI), internal rference TMS (1H, 13C), external
reference 85% H3PO4 in D2O (31P) .
Acid VI was obtained similarly.
ACKNOWLEDGMENTS
N-Anilinomethylenebis[hydroxy(anisyl)methyl-
phosphinic] acid (VI). Yield 87%, mp > 150°C
This work was supported by the Russian Founda-
tion for Basic Research (grant no. 11-03-00402, 12-03-
00003).
1
(decomp.). First isomer, content 50%. H NMR spec-
trum, δ, ppm: 4.71 t (С1H, 2JPH 16.2 Hz), 4.89 d (С3H,
2JPH 16.1 Hz). 13С NMR spectrum, δС, ppm: 48.39 t
REFERENCES
1
1
(С1, JPС 78.7 Hz), 70.27 d (С3, JPС 103.3 Hz). 31Р
NMR spectrum, δР, ppm: 38.17 d, 39.07 d (2JPР
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1
24.3 Hz). Second isomer, content 30%. H NMR
spectrum, δ, ppm: 4.78 t (С1H, JPH 16.0 Hz), 4.89 d
2
(С3H, JPH 16.1 Hz). 13С NMR spectrum, δС, ppm:
2
48.59 t (С1, 1JPС 81.2 Hz), 70.96 d (С3, 1JPС 105.2 Hz).
31Р NMR spectrum: δР 39.80 ppm. Third isomer,
content 20%. H NMR spectrum, δ, ppm: 4.41 t (С1H,
1
2JPH 16.2 Hz), 4.89 d (С3H, JPH1 16.1 Hz). 13С NMR
2
spectrum, δС, ppm: 49.64 t (С1, JPС 79.8 Hz), 69.20 d
(С3, 1JPС 106.4 Hz). 31Р NMR spectrum: δР 39.08 ppm.
The signals of methoxy and aromatic fragments of
isomers in the H and 13С NMR spectra are in the
1
typical ranges and overlapped. Found, %: С 54.26; Н
5.28. С23Н27NО8P2. Calculated, %: С 54.44; Н 5.36.
The NMR spectra were obtained on a Bruker
Avance 400 spectrometer in CDCl3 (I–III) or D2O
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 6 2013