Synthesis of substituted hydroxymethylene diphosphonic acids and their derivatives containing unsaturated fragments

Full text of DOI:10.1134/S1070363211080263

ISSN 1070-3632, Russian Journal of General Chemistry, 2011, Vol. 81, No. 8, pp. 1730–1731. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © A.A. Prishchenko, M.V. Livantsov, O.P. Novikova, L. I. Livantsova, 2011, published in Zhurnal Obshchei Khimii, 2011, Vol. 81,
No. 8, pp. 1386–1388.
LETTERS
TO THE EDITOR
Synthesis of Substituted Hydroxymethylene Diphosphonic Acids
and Their Derivatives Containing Unsaturated Fragments
A. A. Prishchenko, M. V. Livantsov, O. P. Novikova, and L. I. Livantsova
Lomonosov Moscow State University, Vorob’evy gory, Moscow, 119991 Russia
e-mail: aprishchenko@yandex.ru
Received April 5, 2011
DOI: 10.1134/S1070363211080263
A variety of substituted hydroxymethylene diphos-
phonic acids derivatives comprises good complexones
and the substances widely used in medicine [1].
Compounds containing hydrolytically stable hydroxy-
methylene diphosphonic fragment PCP are of interest
as an unusual organophosphorus analogs of natural
pyrophosphates [2]. We found that the reaction of
trimethylsilyl esters of trivalent phosphorus with the
readily accessible chlorides of unsaturated carboxylic
acids affords new hydroxymethylene diphosphonic
compounds containing unsaturated fragments. They
may be of interest as promising complexones and anti-
oxidants.
An excess of alkylsilylphosphite in methylene
chloride solution reacts readily with unsaturated
carboxylic acids chlorides to form diphosphonates I–
IV in a high yield [3].
2(Me3SiO)3P
2(EtO)2POSiMe3
[(EtO)2P]2CR
RCOCl
[(Me3SiO)2P]2CR
_2Me3SiCl
_2Me3SiCl
O
OSiMe3
O
I, II
OSiMe3
III_V
(CH2)7
H
(CH2)7CH3
H
(II, V).
R = (CH=CH)2Me (I, IV), CH=CHPh (III),
C
C
The reaction of diphosphonates III–V with an
excess of methanol gives rise to the substituted
hydroxymethylenediphosphonic acids VI–VIII, which
are thick oils. Note that the mild conditions of the
methanolysis of trimethylsilyl esters III–V allow
retaining unchanged the methylenediphosphonic frag-
ments in the acids VI–VIII [3].
of diethyl(trimethylsilyl)phosphite in 20 ml of me-
thylene chloride with stirring and cooling to 10°C was
added a solution of 6 g of sorbinoyl chloride in 10 ml
of methylene chloride. The mixture was stirred for
0.5 h and then heated to boiling. The solvent was
distilled off in a vacuum; the residue was kept in a
vacuum (0.5 mm Hg) for 1 h at 30°C. Yeld 19.5 g,
1
96%, oil. Н NMR spectrum, δН, ppm: 0.16 s (Ме3Si),
5MeOH
III_V
[(HO)2P]2CR
3
0.9–1.1 m (4МеСН2ОР), 1.37 d (С6Н3, JНН 5.6 Hz),
_5Me3SiOMe
3.6–3.8 m (4СН2ОР), 5.2–6.1 m (СН=СН). 13С NMR
O
OH
1
spectrum, δС, ppm: 78.53 t (С1, JРС 155.9 Hz), 132.63
VI_VIII
2
3
t (С2, JРС 10.1 Hz), 124.26 t (С3, JРС 5.9 Hz), 130.36
(С4, С5), 17.37 (С6). 31Р NMR spectrum: δР 15.59 ppm.
Found, %: С 45.96; Н 8.11. С17Н36О7P2Si. Calculated,
%: С 46.14; Н 8.20.
R = CH=CHPh (VI), (CH=CH)2Me (VII),
(CH2)7
H
(CH2)7CH3
(VIII).
C
C
Compounds II–V were obtained similarly.
H
Tetraethyl (1,3-pentadien-1-yl)trimethylsiloxy-
methylene diphosphonate (I). To a solution of 21 g
Tetraethyl (8-heptadecen-1-yl)trimethylsiloxy-
methylene diphosphonate (II). Yield 97%, oil. Н
1
1730

SYNTHESIS OF SUBSTITUTED HYDROXYMETHYLENE DIPHOSPHONIC ACIDS
1731
3
3
4
NMR spectrum, δН, ppm: –0.06 s (Ме3Si), 0.9–1.1 m
(5СН3, 11СН2), 1.25–1.40 m (С2Н2), 1.7–1.8 m
(2СН2С=), 3.8–4.0 m (4СН2ОР), 5.0–5.1 m (СН=СН).
15.4, JРН 4.8 Hz), 6.67 d t (С3Н, JНН 15.4, JРН <
1 Hz), 7.2–7.5 m (С6Н5). 13С NMR spectrum, δС, ppm:
75.79 t (С1, JРС 149.2 Hz), 130.96 t (С2, JРС 10 Hz),
1
2
13С NMR spectrum, δС, ppm: 78.66 t (С1, JРС 155.9
123.47 t (С3, JРС < 1 Hz), 136.57 (С4), 126.45 and
1
3
Hz), 23.33 t (С2, JРС 5 Hz), 31.58 and 35.03
128.50 (С5, С6), 127.69 (С7). 31Р NMR spectrum: δР
16.12 ppm. Found, %: С 36.64; Н 4.07. С9Н12О7P2.
Calculated, %: С 36.75; Н 4.11.
2
(2СН2СН=), 129.46 (СН=СН). 31Р NMR spectrum: δР
19.16 ppm. Found, %: С 56.68; Н 10.12. С29Н62·
О7P2Si. Calculated, %: С 56.84; Н 10.20.
Compound VII, VIII were obtained similarly.
Tetra(trimethylsilyl) (2-phenylethyl-1-yl)tri-
(1,3-Pentadien-1-yl)hydroxymethylene diphos-
phonic acid (VII). Yield 97%, oil. 1Н NMR spectrum,
δН, ppm: 5.5–6.6 m (СН=СН), 1.75 (С6Н3). 13С NMR
spectrum, δС, ppm: 75.25 t (С1, 1JPС 149.6 Hz), 131.35
methylsiloxymethylene diphosphonate (III). Yield
1
96%, oil. Н NMR spectrum, δН, ppm: 0.5–1.0 m
4
4
(Ме3Si), 6.19 d. t (С3Н, JНН 15.8, JРН 6.2 Hz), 6.47 d.
t (С2Н, JНН 15.8, JРН 5.2 Hz), 6.8–7.1 m (С6Н5). 13С
2
3
3
4
t (С2, JPС < 1 Hz), 129.58 t (С3, JPС < 1 Hz), 131.07
(С4), 124.27 (С5), 17.41 (С6). 31Р NMR spectrum: δР
16.27 ppm. Found, %: С 27.78; Н 4.59. С6Н12О7P2.
Calculated, %: С 27.92; Н 4.68.
NMR spectrum, δС, ppm: 79.03 t (С1, JРС 162.6 Hz),
1
130.37 t (С2, JРС 10 Hz), 126.34 t (С3, JРС 5.8 Hz),
2
3
136.22 t (С4, JРС < 1 Hz), 128.43 and 126.04 (С5, С6),
4
127.32 (С7), 2.46 (Me3SiOC), 0.95 d (Me3SiОР,
3JPС 5.9 Hz). 31Р NMR spectrum 31Р: δР –2.58 ppm.
Found, %: С 43.89; Н 7.91. С24Н52О7P2Si5. Calculated,
%: С 44.01; Н 8.00.
(8-Heptadecen-1-yl)hydroxymethylene diphos-
phonic acid (VIII). Yield 96%, oil. Н NMR spec-
1
trum, δН, ppm: 5.5–6.6 m (СН=СН), 2.0–2.2 m
(2СН2С=), 1.6–1.8 m (С2Н2), 1.1–1.4 m (11 СН2),
Tetra(trimethylsilyl) (1,3-pentadien-1-yl)tri-
0.89 t (СН3, JНН 6.2 Hz). 13С NMR spectrum, δС,
3
methylsiloxymethylene diphosphonate (IV). Yield
ppm: 73.18 t (С1, JPС 147.1 Hz), 23.30 t (С2, JPС
<
1
2
1
96%, oil. Н NMR spectrum, δН, ppm: –0.2–0.3 m
1 Hz), 129.39 and 129.60 (СН=СН), 30.39 and 31.84
(2СН2СН=), 22.53–29.65 m (11СН2), 13.62 (СН3). 31Р
NMR spectrum: δР 20.35 ppm. Found, %: С 50.26; Н
8.86. С18Н38О7P2. Calculated, %: С 50.46; Н 8.94.
3
(Me3Si), 1.22 d (С6Н3, JНН 6 Hz), 5.1–5.8 m
(СН=СН). 13С NMR spectrum, δС, ppm: 78.30 t (С1,
2
1JРС 162.6 Hz), 131.01 t (С2, JРС 10.9 Hz), 126.69 t
3
3
(С3, JРС 5.9 Hz), 130.28 t (С4, JРС < 1 Hz), 129.13
(С5), 17.55 (С6), 2.12 (Me3SiOC), 0.64 d (Me3SiОР,
3JPС 5.8 Hz). 31Р NMR spectrum: δР –2.46 ppm. Found,
%: С 40.61; Н 8.40. С21Н52О7P2Si5. Calculated, %: С
40.75; Н 8.47.
The NMR spectra were recorded on a Bruker
Avance-400 spectrometer in CDCl3 (I–V) and СD3OD
(VI–VIII), internal reference TMS (1H, 13C) and
external reference 85% phosphoric acid solution in
D2O (31Р).
Tetra(trimethylsilyl) (8-heptadecen-1-yl)tri-
methylsiloxymethylene diphosphonate (V). Yield
ACKNOWLEDGMENTS
1
97%, oil. Н NMR spectrum, δН, ppm: –0.1–0.0 s
This work was financially supported by the Russian
Foundation for Basic Research (grant no. 11-03-
00402).
(Me3Si), 0.97 t (СН3, 3JНН 6.4 Hz), 1.4–1.5 m (11СН2),
1.62–1.72 m (С2Н2), 2.05–2.15 m (2СН2С=), 5.35–
13
5.45 m (СН=СН). С NMR spectrum, δС, ppm: 77.89
1
2
t (С1, JPС 164.6 Hz), 23.37 t (С2, JPС 5.9 Hz), 129.29
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22.31–29.91
m
(11СН2), 13.73 (СН3), 2.45
(Me3SiОС), 0.96 d (Me3SiОР, 3JPС 5.1 Hz),). 31Р NMR
spectrum: δР 1.80 ppm. Found, %: С 50.03; Н 9.88.
С33Н78О7P2Si5. Calculated, %: С 50.21; Н 9.96.
(2-Phenylethyl-1-yl)hydroxymethylene diphos-
phonic acid (VI). To 30 ml of methanol at 10°C under
stirring was added a solution of 11 g of diphosphonate
III in 10 ml of diethyl ether. The mixture was heated
to boiling, the solvent was distilled off, the residue was
kept in a vacuum (1 mm Hg) for 1 h. Yield 4.8 g, 98%,
1
3
oil. Н NMR spectrum, δН, ppm: 6.95 d.t (С2Н, JНН
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 8 2011