Syntheses of N-phenylaminomethylenediphosphonic and -diphosphinic acids and their derivatives

Full text of DOI:10.1134/S1070363209090230

ISSN 1070-3632, Russian Journal of General Chemistry, 2009, Vol. 79, No. 9, pp. 1936–1938. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © А.А. Prishchenko, М.V. Livantsov, О.P. Novikova, L.I. Livantsova, 2009, published in Zhurnal Obshchei Khimii, 2009, Vol. 79,
No. 9, pp. 1580–1582.
LETTERS
TO THE EDITOR
Syntheses of N-Phenylaminomethylenediphosphonic
and -Diphosphinic Acids and Their Derivatives
А. А. Prishchenko, М. V. Livantsov, О. P. Novikova, and L. I. Livantsova
Moscow State University, Vorob’evy gory 1, Moscow, 119992 Russia
е-mail: aprishchenko@yandex.ru
Received February 19, 2009
DOI: 10.1134/S1070363209090230
(XO)2POSiMe3,
Substituted aminomethylene diphosphorus-containing
(XO)2P CHNHPh
(XO)2P(O)H
_EtOSiMe3
compounds are of interest as prmising ligands and
biologically active substances [1]. Some of compounds
of this type can be obtained by suitable methods using
dialkylformamide dialkylacetals [2]. Aiming to
synthesize new N-aminomethylenediphosphorus com-
pounds we examined a reaction of some of trimethyl-
silyl phosphites and hypophosphites taken in excess
with the corresponding ethoxymethyleneimine I and
formamidine IV obtained similarly to the earlier
described procedures [3]. Thus, ethoxymethylene-
imine I reacts with a mixture of diethyl(trimethylsilyl)-
phosphate and diethylphosphite and also with a mix-
ture of tris(trimethylsilyl)phosphate and bis(tri-
methylsilyl)phosphate at 140–160ºС to form diphos-
phonates II and III. In the zinc chloride catalyst is
required for the preparation of compound III (cf. [4]).
EtOCH NPh
O
2
I
II, III
X = Et (II), Me3Si (III).
Formamidine IV reacts with bis(trimethylsiloxy)phos-
phine excess under similar conditions to give diphospho-
nite V. At reflux of the latter with bis(trimethylsilyl)-
amine diphosphonite VI was produced in a high yield
(see Scheme 1).
The treatment of diphosphonite VI with a
diluted solution of sodium methylate in methanol
yields diphosphonite VII. Reaction of diphosphinate
III with excess methanol gives rise to diphosphonic
acid VIII. The compounds obtained are white hygro-
scopic crystals (see Scheme 2).
Scheme 1.
NHPh
XO
1/2 X2NH
_NH3
PCHP(OX)2
[(XO)2P]2CHNHPh
2 (XO)2PH + PhNHCH
NPh
_PhNHX
H
O
IV
V
VI
X = Me3Si.
Scheme 2.
NaO
2 MeONa, 2 MeOH
VI
4 MeOH
_4 Me3SiOMe
[(HO)2P]2CHNHPh
P CHNHPh
III
_2 Me3SiOMe
H
O
O
2
VIII
VII
1936

SYNTHESES OF N-PHENYLAMINOMETHYLENEDIPHOSPHONIC
1937
1
The NMR spectra of I–VIII contain characteristic
signals of A fragments, description of which is
presented below.
NMR spectrum, δ, ppm: 51.40 t (С1, JPС 154 Hz),
146.13 (С2), 129.08, 118.15 and 112.96 (С3, С4, С5),
0.74 and 0.86 s (СН3). 31Р NMR spectrum, δ, ppm:
–1.31. Found, %: С 40.94; Н 7.74. С19Н43NО6P2Si4.
Calculated, %: С 41.06; Н 7.80.
We point to the overlapping of the signals of
fragment С1HNH of compound II in СDCl3 with the
multiplet signal of СН2О groups. However, when one
equivalent of 85% HCOOH is added to the solution,
these signals are shifted downfield and are also
simplified due to the fast exchange of NH protons.
Similar simplification of the signals of these fragments
is observed also for acids VII and VIII. According to
the NMR spectra, compound V is a mixture of two
stereoisomers, the ratio of which was determined by
31Р NMR spectroscopy; below the data for the
prevailing isomer are first given. Elemental analysis
for easily oxidized compounds V and VI was carried
out using salt VII as their stable derivative.
N,N'-Diphenylformamidine (IV) was obtained by
method [3]. Yield 89%, mp 139ºС. 1H NMR spectrum,
δ, ppm: 8.31 s (С1H), 7.10 d (4С3H, JНH 8 Hz), 7.36 t
3
(4С4H, 3JНH 8 Hz), 7.14 t (2С5H, 3JНH 8 Hz), 10.05 br.s
(NН). 13С NMR spectrum, δ, ppm: 150.25 (С1), 145.43
(С2), 129.45, 123.39 and 119.27 (С3, С4, С5).
Tris(trimethylsilyl) N-aminomethylene diphos-
phonite (V). A mixture of 4 g of formamidine IV and
13 g of bis(trimethylsiloxy)phosphine in 15 ml of
methylene chloride was refluxed at 140–150ºС,
evaporating a solvent, for 1 h and then distilled. Yield
7.6 g (83%), bp 157ºС (1 mm Hg). The first isomer
1
(content 60%): H NMR spectrum, δ, ppm: 3.45–3.55
N-Phenylethoxymethylene imine (I) was obtained
m (С1H), 4.29 d.d (NН, JНH 8 Hz, JНH 2 Hz), 7.04 d
3
4
1
by method [3]. Yield 84%, bp 91ºС (10 Hg mm). Н
1
NMR spectrum, δ, ppm: 7.75 s (С1Н), 7.03 d (2 С3Н,
(РН, JРH 560 Hz), 6.60–7.10 m (С6Н5), 0.05–0.20 m
(Ме). 13С NMR spectrum, δ, ppm: 61.86 d.d (С1,
3
3JНН 8 Hz), 7.36 t (2 С4Н, JНН 8 Hz), 7.18 t (С5Н,
1JPС 93 and JPС 39 Hz), 147.66 d (С2), 128.62, 118.17
1
3
3JНН 8 Hz), 4.38 q (СН2О, JНН 8 Hz), 1.43 t (СН3,
and 113.82 (С3, С4, С5), 1.27 s (Me). 31Р NMR
3JНН 8 Hz). 13С NMR spectrum, δ, ppm: 155.17 (С1),
148.20 (С2), 129.13, 124.31 and 121.49 (С3, С4, С5),
62.39 (СН2О), 14.27 (СН3).
spectrum, δ, ppm: 19.45 d and 147.08 d (2JPР 43.7 Hz).
1
The second isomer: H NMR spectrum, δ, ppm: 3.45–
3.55 m (С1H), 4.22 d (NН, JНH 10 Hz), 7.02 d (РН,
3
1JРH 560 Hz), 6.60–7.10 m (С6Н5), 0.05–0.20 m (Ме).
Tetraethyl N-phenylaminomethylenediphosphonate
(II). A mixture of 4.5 g of imine I, 6.5 g of diethyl-
phosphite, 9.5 g of diethyl(trimethylsilyl)phosphate
was heated at 140ºС with distilling off trimethyl
(ethoxy)silane for 1 h and then the product was
distilled. Yield 6.8 (59%), bp 182ºС (1 Hg mm), mp
13С NMR spectrum, δ, ppm: 62.12 d.d (С1, JPС 101
1
and JPС 45 Hz), 148.00 (С2), 129.04, 118.29 and
1
113.64 (С3, С4, С5), 1.14 (Me). 31Р NMR spectrum, δ,
ppm: 22.58 d and 147.27 d (2JPР 48.6 Hz).
1
2
74ºС. H NMR spectrum, δ, ppm: 4.24 t (С1H, JPH
24 Hz), 4.89 br.s (NН), 6.52 d (2С3H, 3JНH 8 Hz), 6.88
t (2С4H, 3JНH 8 Hz), 6.46 t (С5H, 3JНH 8 Hz), 3.75–3.95
By the NMR data, diphosphonite V contains 15%
of diphosphonite VI admixture.
Tetra(trimethylsilyl) N-phenylaminomethylene-
diphosphonite (VI). A mixture of 13.7 g of diphos-
phonite V and 31 g of bis(trimethylsilyl)amine was
refluxed for 1 h and then distilled. Yield 12.5 g (78%),
m (4СН2О), 0.91 t and 0.99 t (4 СH3, JНH 8 Hz). 13С
3
NMR spectrum, δ, ppm: 50.35 t (С1, JPС 147 Hz),
1
146.15 (С2), 129.17, 118.94 and 113.70 (С3, С4, С5),
63.22 and 63.64 (СН2О), 16.27 and 16.34 (СН3). 31Р
NMR spectrum, δ, ppm: 17.30. Found, %: С 47.29; Н
7.08. С15Н27NО6P2. Calculated, %: С 47.50; Н 7.17.
1
bp 154ºС (1 mm Hg). H NMR spectrum, δ, ppm:
3.20–3.25 m (С1H), 4.44 d (NН, JНH 8 Hz), 6.68 d
3
(2С3Н, JНH 8 Hz), 7.07 t (2С4Н, JНH 8 Hz), 6.60 t
3
3
(С5Н, JНH 8 Hz), 0.12–0.18 m (12СН3). 13С NMR
3
Tetra(trimethylsilyl) N-phenylaminomethylene-
diphosphonate (III). A mixture of 3.3 g of imine I,
7.5 g of bis(trimethylsilyl)phosphite, 10 g of tris
(trimethylsilyl)phosphate and 0.1 g of zinc chloride
was refluxed at 150–160ºС for 1 h and then distilled.
spectrum, δ, ppm: 71.09 t (С1, JPС 38 Hz), 149.33
1
(С2), 128.25, 116.34 and 113.47 (С3, С4, С5), 0.88
(СН3). 31Р NMR spectrum, δ, ppm: 153.77.
Disodium salt of N-phenylaminomethylenedi-
phosphonous acid (VII). To a solution of 0.62 g of
sodium methoxide in 20 ml of methanol was added 3 g
of diposphonite VI in 20 ml of diethyl ether under
cooling to 10ºС and stirring. Then the solvent was
1
Yield 10.6 g (86%), bp 157ºС (0.5 mm Hg). H NMR
spectrum, δ, ppm: 3.70–3.85 m (С1H, NH), 6.41 d
3
3
(2С3H, JНH 8 Hz), 6.96 t (2С4H, JНH 8 Hz), 6.51 t
3
(2С4H, JНH 8 Hz), 0.04 s and 0.06 s (12СН3). 13С
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 9 2009

1938
PRISHCHENKO et al.
evaporated. The obtained white crystals were kept
under a vacuum (1 mm Hg) for 1 h. Yield 1.5 g (94%).
(VII) or CD3OD (VIII) as solvents, TMS as internal
reference (1H, 13C) and 85% H3PO4 in D2O as external
reference (31Р).
2
1H NMR spectrum, δ, ppm: 3.64 t (С1H, JPH 16 Hz),
3
3
6.77 d (2С3H, JНH 8 Hz), 7.16 t (2С4H, JНH 8 Hz),
6.70 t (С5H, 3JНH 8 Hz), 7.04 d (2РН, 1JPH 532 Hz). 13С
ACKNOWLEDGMENTS
NMR spectrum, δ, ppm: 56.24 t (С1, JPС 85 Hz),
1
147.80 (С2), 129.52, 118.13 and 113.72 (С3, С4, С5).
31Р NMR spectrum, δ, ppm: 20.06. Found, %: С 30.03;
Н 3.28. С7Н9NNa2О4P2. Calculated, %: С 30.13; Н
3.25.
This work was financially supported by the Russian
Foundation for Basic Research (grant no. 08-03-
00282).
N-Phenylaminomethylene diphosphonic acid
(VIII). To 30 ml of methanol was added 10.6 g of
diphosphonate III under cooling to 10ºС and stirring.
This mixture was heated to boiling. After the solvent
removal the white crystals were kept under a vacuum
REFERENCES
1. Ebetino, F.H., Phosphorus, Sulfur, and Silicon, 1999,
vols. 144–146, p. 9; Widler, L., Jaeggi, K.A., and
Green, J.R., Phosphorus, Sulfur, and Silicon, 1999,
vols. 144–146, p. 5.
1
(1 mm Hg) for 1 h. Yield 5 g (97%), mp 182ºС. H
NMR spectrum, δ, ppm: 4.20 t (С1H, 2JPH 22 Hz), 6.81
2. Prishchenko, А.А., Livantsov, M.V., and Petrosyan, V.S.,
Zh. Obshch. Khim., 1994, vol. 64, no. 8, p. 1316.
3
3
d (2С3H, JНH 8 Hz), 7.15 t (2С4H, JНH 8 Hz), 6.69 t
(С5H, JНH 8 Hz). 13С NMR spectrum, δ, ppm: 50.95 t
3
3. Weigand-Hilgetag, Eksperimental’nye metody v organi-
cheskoi khimii, Moscow: Khimiya, 1968, p. 944.
Translated under the title Organischchemische Experi-
mentierkunst, Leipzig, 1964.
(С1, JPС 142 Hz), 147.03 (С2), 128.63, 117.75 and
1
113.41 (С3, С4, С5). 31Р NMR spectrum, δ, ppm: 16.99.
Found, %: С 31.37; Н 4.19. С7Н11NО6P2. Calculated,
%: С 31.48; Н 4.15.
4. Krutikov, V.I., Erkin, A.V., Pautov, P.A., and
Zolotukhina, М.М., Zh. Obshch. Khim., 2003, vol. 73,
no. 2, p. 205.
The NMR spectra were registered on a Bruker
Avance-400 spectrometer using CDCl3 (I–VI), D2O
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 9 2009