Synthesis of 2-pyridylethylphosphinates containing 2,6-di-tert-butyl-4- methylphenol fragments

Full text of DOI:10.1134/S1070363208110297

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 11, pp. 2150–2153. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © А.А. Prishchenko, М.V. Livantsov, О.P. Novikova, L.I. Livantsova, Е.R. Milyaeva, 2008, published in Zhurnal Obshchei Khimii,
2008, Vol. 78, No. 11, pp. 1914–1917.
LETTERS
TO THE EDITOR
Synthesis of 2-Pyridylethylphosphinates
Containing 2,6-Di-tert-butyl-4-methylphenol Fragments
А. А. Prishchenko, М. V. Livantsov, О. P. Novikova, L. I. Livantsova, and Е. R. Milyaeva
Moscow State University, Vorob’evy gory 1, Moscow, 119992 Russia
е-mail: aprishchenko@yandex.ru
Received April 8, 2008
DOI: 10.1134/S1070363208110297
Various functionalized hydroxyalkylphosphonic
acids and their derivatives are effective complexones
and biologically active substances [1, 2]. Pyridine-
containing derivatives of phosphonic and phosphinic
acids are of special interest in this compounds series,
and some of them are widely used in medicine [3]. In
this work the new 2-pyridylethylphosphinates and
diphosphinates were prepared that contain fragments
of bulky phenol along with hydroxymethyl groups and
pyridine fragments and are promising complexones
and antioxidants. As initial compounds we used
accessible 2-pyridylethylphosphonites А that were
successfully applied earlier to the synthesis of organo-
phosphorous analogs of amino acids, containing amino
and carboxy groups [3, 4]. Thus, phosphonites А
readily added to the carbonyl group of 3,5-di-tert-
butyl-4-hydroxybenzaldehyde in methylene chloride
medium to form phosphinates (I) in high yield.
C2H2C3H2Py
ArCHO
(Me3SiO)2PCH2CH2Py
Me3SiOP
C1H(OSiMe3)Ar
O
A
Iа, Ib
Bu-t
4
4
(a),
(b).
N
Py =
Ar =
OH;
Bu-t
N
Under the same conditions phosphonites A react
smoothly with 3,5-di-tert-butyl-4-hydroxybenzalchlo-
ride and 3,5-di-tert-butyl-4-hydroxybenzoyl chloride
to give substituted methylenebisphosphinates (II, III)
in high yield (cf. [5, 6]).
We emphasize that under mild conditions the
pyridine-containing fragments and spatially screened
phenol groups remain intact in the initial compounds
and target products and do not undergo the possible
side reactions (cf. [5, 6]). Reactions of phosphinates I
C2H2C3H2Py
C2H2C3H2Py
ArCHCl2
ArCOCl
ArC1H
Ar(Me3SiO)C1
P
P
A
−Me3SiCl
−2 Me3SiCl
OSiMe3
OSiMe3
O
O
2
2
IIа, IIb
IIIа, IIIb
Bu-t
OH;
Bu-t
4
4
(а),
(b).
N
Py =
Ar =
N
2150

SYNTHESIS OF 2-PYRIDYLETHYLPHOSPHINATES
2151
and bisphosphonates II and III with methanol excess
afford pyridine-substituted mono- and diphos-phonic
acids (IV–VI) which are white hygroscopic crystals.
(С2, 1JPС 90 Hz), 29.22 s (С3), 160.73 d (С4, 3JPС 15 Hz).
31Р NMR spectrum, δ, ppm: 41.84 s. The second
1
2
isomer, Н NMR spectrum, δ, ppm: 4.58 d (С1Н, JРН
8 Hz). 13С NMR spectrum, δ, pm: 73.93 d (С1,
1
1JPС 117 Hz), 26.17 d (С2, JPС 91 Hz), 29.46 s (С3),
2 MeOH
CH2CH2Py
159.28 d (С4, 3JPС 13 Hz). 31Р NMR spectrum, δ, ppm:
39.94 s. Found, %: С 60.98; Н 8.72. С28Н48NО4PSi2.
Calculated, %: С 61.17; Н 8.80.
Iа, Ib−2 Me SiOMe HOP
3
CH(OH)Ar
O
IVа, IVb
Compounds Ib, II, and III were prepared similarly.
2 MeOH
CH2CH2Py
Тrimethylsilyl [2-(pyrid-4-yl)ethyl][3,5-di-tert-
butyl-4-hydroxyphenyl(trimethylsiloxy)methyl]phos-
phinate (Ib). Yield 91%, viscous oily liquid. The first
P
IIа, IIb
ArCH
−2 Me3SiOMe
OH
O
2
1
isomer content 55%. Н NMR spectrum, δ, ppm: 4.85
Vа, Vb
2
13
d (С1Н, JРН 5 Hz). С NMR spectrum, δ, ppm: 74.78
d (С1, JPС 120 Hz), 27.71 d (С2, JPС 90 Hz), 27.39 d
1
1
3 MeOH
CH2CH2Py
(С3, JPС 3 Hz), 150.72 d (С4, JPС 14 Hz). 31Р NMR
1
3
P
Ar(HO)C
IIIа, IIIb
1
−3 Me3SiOMe
OH
spectrum, δ, ppm: 40.80 s. The second isomer, Н
NMR spectrum, δ, ppm: 4.66 d (С1Н, JРН 8 Hz). 13С
2
O
2
NMR spectrum, δ, ppm: 74.10 d (С1, JPС 118 Hz),
1
VIа, VIb
27.22 d (С2, JPС 89 Hz), 27.21 d (С3, JPС 3 Hz),
1
1
Bu-t
150.78 d (С4, JPС 15 Hz). 31Р NMR spectrum, d, pm:
3
38.90 s. Found, %: С 60.95; Н 8.69. С28Н48NО4PSi2.
Calculated, %: С 61.17; Н 8.80.
(a),
(b).
Py =
N
Ar =
OH;
Bu-t
N
Bis(trimethylsilyl) (3,5-di-tert-butyl-4-hydroxy-
phenyl)methylenebis[2-(pyrid-2-ylethyl)phosphinate]
(IIа). Yield 90%, bp 82°С. The first isomer (content
In the NMR spectra of compounds I–IV character-
istic signals of РС1Н(ОХ) fragments, methylene-
diphosphorous-containing PC1Р fragments, and also
signals of substituted aromatic fragments were ob-
served. These signals are partially superimposed in the
1H and 13С NMR spectra and appear as multiplets.
According to the NMR spectra compounds I–III are
mixtures of two stereoisomers whose ratio was
determined from 31Р NMR. Data on the prevailing
isomer are given first.
1
2
75%): Н NMR spectrum, δ, ppm: 3.42 t (С1Н, JРН
16 Hz). 13С NMR spectrum, δ, ppm: 49.80 t (С1,
1JPС 81 Hz), 27.47 d (С2, JPС 97 Hz), 29.18 s (С3),
1
160.31 d (С4, 3JPС 18 Hz). 31Р NMR spectrum, δ, ppm:
1
37.94 s. The second isomer, Н NMR spectrum, δ,
ppm: 3.38 t (С1Н, JРН 18 Hz). 13С NMR spectrum, δ,
2
1
ppm: 52.34
t
(С1, JPС 80 Hz), 29.25
d
(С2,
1JPС 106 Hz), 29.14 s (С3), 160.35 d (С4, JPС 18 Hz).
31Р NMR spectrum, δ, ppm: 39.23 s. Found, %: С
59.74; Н 7.96. С35Н56N2О5P2Si2. Calculated, %: С
59.80; Н 8.03.
3
Trimethylsilyl [2-(pyrid-2-yl)ethyl][3,5-di-tert-
butyl-4-hydroxyphenyl(trimethylsiloxy)-methyl]phos-
phinate (Iа). To a solution of 4 g of bis(trimethylsilyl)
2-(pyrid-2-yl)ethylphosphonite in 20 ml of methylene
chloride was added a solution of 2.4 g of 3,5-di-tert-
butyl-4-hydroxybenzaldehyde in 15 ml of methylene
chloride at the cooling to 0°С while stirring. The
mixture was stirred for 0.5 h and then was heated to
boiling. The solvent was removed and 5 ml of hexane
was added to the residue. After cooling the mixture to
0°С hexane was decanted and residue was kept under a
vacuum (0.5 mm Hg) for 1 h. Yield 5 g (89%), viscous
Bis(trimethylsilyl) (3,5-di-tert-butyl-4-hydroxy-
phenyl)methylenebis[2-(pyrid-4-ylethyl)phosphinate]
(IIb). Yield 88%, bp 102°С. The first isomer content
1
2
75%, Н NMR spectrum, δ, ppm: 3.41 t (С1Н, JРН
17 Hz). 13С NMR spectrum, δ, ppm: 49.82 t (С1,
1JPС 80 Hz), 28.42 d (С2, JPС 84 Hz), 28.88 s (С3),
1
147.00 d (С4, 3JPС 17 Hz). 31Р NMR spectrum, δ, ppm:
1
36.32 s. The second isomer, Н NMR spectrum, δ,
ppm: 3.26 t (С1Н, JРН 18 Hz). 13С NMR spectrum, δ,
2
ppm: 52.40 t (С1, 1JPС 78 Hz), 28.91 d (С2, 1JPС 82 Hz),
28.00 s (С3), 147.22 d (С4, JPС 16 Hz). 31Р NMR
3
1
oily liquid. The first isomer content 55%. Н NMR
spectrum, δ, ppm: 4.78 d (С1Н, JРН 5 Hz). 13С NMR
2
spectrum, δ, ppm: 36.56 s. Found, %: С 59.66; Н 7.91.
С35Н56N2О5P2Si2. Calculated, %: С 59.80; Н 8.03.
spectrum, δ, ppm: 74.64 d (С1, JPС 120 Hz), 26.22 d
1
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 11 2008

2152
PRISHCHENKO et al.
Bis(trimethylsilyl) (3,5-di-tert-butyl-4-hydroxy-
phenyl)trimethylsiloxymethylenebis[2-(pyrid-2-yl)-
(3,5-Di-tert-butyl-4-hydroxyphenyl)methylenebis
[2-(pyrid-2-yl)ethylphosphinic] acid (Vа). Yield
1
phosphinate] (IIIa). Yield 91%, bp 75°С. The first
96%, bp 105°С. Н NMR spectrum, δ, ppm: 3.77 t
1
isomer content 70%. Н NMR spectrum, δ, ppm: 5.28
(С1Н, 2JРН 19 Hz). 13С NMR spectrum, δ, ppm: 50.99 t
(С1, 1JPС 77 Hz), 29.50 d (С2, 1JPС 93 Hz), 27.49 s (С3),
158.62 d (С4, 3JPС 15 Hz). 31Р NMR spectrum, δ, ppm:
37.62 s. Found, %: С 62.12; Н 7.26. С29Н40N2О5P2.
Calculated, %: С 62.36; Н 7.22.
br.s (ОН). 13С NMR spectrum, δ, ppm: 82.91 t (С1,
1
1JPС 98 Hz), 27.30 d (С2, JPС 101 Hz), 28.87 s (С3),
160.37 d (С4, 3JPС 16 Hz). 31Р NMR spectrum, δ, ppm:
1
39.46 s. The second isomer, Н NMR spectrum, δ,
ppm: 4.74 br.s (ОН). 13С NMR spectrum, δ, ppm:
(3,5-Di-tert-butyl-4-hydroxyphenyl)methylenebis
[2-(pyrid-4-yl)ethylphosphinic] acid (Vb). Yield
1
1
83.12 t (С1, JPС 96 Hz), 27.39 d (С2, JPС 103 Hz),
29.10 s (С3), 160.28 d (С4, JPС 18 Hz). 31Р NMR
3
1
97%, bp 110°С. Н NMR spectrum, δ, ppm: 3.84 t
spectrum, δ, ppm: 39.17 s. Found, %: С 57.52; Н 8.12.
С38Н64N2О6P2Si3. Calculated, %: С 57.69; Н 8.15.
(С1Н, 2JРН 18 Hz). 13С NMR spectrum, δ, ppm: 50.03 t
(С1, 1JPС 78 Hz), 28.37 d (С2, 1JPС 74 Hz), 28.64 s (С3),
162.68 d (С4, 3JPС 15 Hz). 31Р NMR spectrum, δ, ppm:
39.10 s. Found, %: С 62.23; Н 7.28. С29Н40N2О5P2.
Calculated, %: С 62.36; Н 7.22.
Bis(trimethylsilyl) (3,5-di-tert-butyl-4-hydroxy-
phenyl)trimethylsiloxymethylenebis[2-(pyrid-4-yl)-
phosphinate] (IIIb). Yield 93%, bp 85°С. The first
1
isomer content 70%. Н NMR spectrum, δ, ppm: 5.88
(3,5-Di-tert-butyl-4-hydroxyphenyl)hydroxyme-
thylenebis[2-(pyrid-2-yl)ethylphosphinic] acid (VIа).
Yield 97%, bp 119°С. 1Н NMR spectrum, δ, ppm: 2.1–
2.3 m (СН2Р), 3.1–3.3 m (СН2Рy). 13С NMR spec-
br.s (ОН). 13С NMR spectrum, δ, ppm: 82.65 t (С1,
1
1JPС 96 Hz), 28.08 d (С2, JPС 94 Hz), 29.56 s (С3),
150.16 d (С4, 3JPС 16 Hz). 31Р NMR spectrum, δ, ppm:
1
1
38.14 s. The second isomer, Н NMR spectrum, δ,
trum, δ, ppm: 78.72 t (С1, JPС 91 Hz), 26.67 d (С2,
ppm: 5.94 br.s (ОН). 13С NMR spectrum, δ, ppm:
1JPС 96 Hz), 27.19 s (С3), 158.37 d (С4, JPС 14 Hz).
3
1
1
82.58 t (С1, JPС 96 Hz), 28.21 d (С2, JPС 92 Hz),
31Р NMR spectrum, δ, ppm: 39.80 s. Found, %: С
60.49; Н 7.08. С29Н40N2О6P2. Calculated, %: С 60.62;
Н 7.02.
29.46 s (С3), 150.49 d (С4, JPС 18 Hz). 31Р NMR
3
spectrum, δ, ppm: 38.38 s. Found, %: С 57.55; Н 8.07.
С38Н64N2О6P2Si3. Calculated, %: С 57.69; Н 8.15.
(3,5-Di-tert-butyl-4-hydroxyphenyl)hydroxyme-
thylenebis[2-(pyrid-4-yl)ethylphosphinic] acid (VIb).
Yield 97%, bp 152°С. 1Н NMR spectrum, δ, ppm: 2.1–
2.2 m (СН2Р), 3.1-3.2 m (СН2Рy). 13С NMR spectrum,
2-(Pyrid-2-yl)ethyl[3,5-di-tert-butyl-4-hydroxyphe-
nyl(hydroxy)methyl]phosphinic acid (IVa). To 30 ml
of methanol was added 5 g of phosphinate Ia at
cooling to 10°С while stirring. The mixture was heated
to boiling, the solvent was removed, and the residue
was kept under a vacuum (1 mm Hg) for 1 h. Yield 3.6
g (98%), bp 139°С. 1Н NMR spectrum, δ, ppm: 4.70 d
1
δ, ppm: 77.02 t (С1, JPС 102 Hz), 27.40 d (С2,
3
1JPС 96 Hz), 28.36 s (С3), 159.72 d (С4, JPС 17 Hz).
31Р NMR spectrum, δ, ppm: 43.13 s. Found, %: С
60.47; Н 6.98. С29Н40N2О6P2. Calculated, %: С 60.62;
Н 7.02.
2
13
(С1Н, JРН 8 Hz). С NMR spectrum, δ, ppm: 71.86 d
(С1, JPС 112 Hz), 24.92 d (С2, JPС 85 Hz), 28.04 s
The NMR spectra were obtained on a Bruker
Avance-400 instrument using CDCl3 (I–IV) or (СD3)2SO
(V–VII) as solvents and ТМS (1H, 13C) and 85%
H3PO4 in D2O solution (31Р) as references.
1
1
(С3), 159.27 d (С4, JPС 14 Hz). 31Р NMR spectrum, δ,
3
ppm: 42.85 s. Found, %: С 64.97; Н 8.02.
С22Н32NО4P. Calculated, %: С 65.17; Н 7.95.
ACKNOWLEDGMENTS
Acids IVb, V, and VI were prepared similarly.
This work was financially supported by the Russian
Foundation for Basic Research (grant No. 08-03-
00282).
2-(Pyrid-4-yl)ethyl[3,5-di-tert-butyl-4-hydroxy-
phenyl(hydroxy)methyl]phosphinic acid (IVb). Yield
1
97%, bp 152°С. Н NMR spectrum, δ, ppm: 5.50 d
2
13
(С1Н, JРН 8 Hz). С NMR spectrum, δ, ppm: 72.66 d
(С1, JPС 110 Hz), 27.42 d (С2, JPС 78 Hz), 27.76 d
1
1
REFERENCES
(С3, JPС 3 Hz), 149.36 d (С4, JPС 14 Hz). 31Р NMR
spectrum, δ, ppm: 44.0 s. Found, %: С 64.92; Н 7.99.
С22Н32NО4P. Calculated, %: С 65.17; Н 7.95.
2
3
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SYNTHESIS OF 2-PYRIDYLETHYLPHOSPHINATES
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