Functional P-substituted hydrophosphoryl compounds and α- Aminoalkylphosphonates

Full text of DOI:10.1007/s11176-008-1029-7

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 1, pp. 153 154.
Pleiades Publishing, Ltd., 2008.
Original Russian Text
M.A. Pudovik, L.K. Kibardina, 2008, published in Zhurnal Obshchei Khimii, 2008, Vol. 78, No. 1, pp. 161 162.
LETTERS
TO THE EDITOR
Functional P-Substituted Hydrophosphoryl Compounds
and -Aminoalkylphosphonates
M. A. Pudovik and L. K. Kibardina
Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center,
Russian Academy of Sciences, ul. Akad. Arbuzova 8, Kazan, Tatarstan, 420088 Russia
e-mail: pudovik@iopc.knc.ru
Received July 17, 2007
DOI: 10.1134/S1070363208010295
Aminophosphonic acids, being direct analogs of
natural aminocarboxylic acids building blocks of
peptides and proteins, exhibit a broad-range biological
activity [1]. In this connection -aminoalkylphos-
phonate derivatives with structural fragments contain-
ing amino groups on the phosphorus atom present
indubitable interest. The presence of two amino
groups in such compounds opens up new possibilities
for their modification and for preparation of various
linear and cyclic compounds including the amino-
phosphonate fragment.
-Aminoalkylphosphonates
with the phosphorus atom bearing functional sub-
stituents can be synthesized via addition of the cor-
responding P-substituted phosphorous acids to imines.
We have developed a method for synthesis of
mixed phosphorous acids involving the aminoalkyl
fragment, using the example of the reaction of cyclic
silyl phosphoramidites [2] with phenols. The reaction
involves ring cleavage and liberation of phenoxy-
silane.
Ph
N
O
PhNH(CH2)2O
+ 2ArOH
P H + ArOSiMe3
POSiMe3
ArO
O
I
IIa, IIb
II, Ar = Ph (a); Ar = 4-MeOC6H4 (b).
Acid IIa readily adds to imine III to form P-func-
tional aminoalkylphosphonate IV.
trum and one doublet proton signal of the PCH group
in the H NMR spectrum. Bubbling dry HCl through
a solution of compound IV provides salt V.
1
O
PhNH(CH2)2O
+
O
P CH NHPh
IIa IId + ArCH=NPh
PhNH2(CH2)2O
+
ArO
2HCl
P CH NH2Ph, 2Cl
IV
Ph
ArO
III
IV
Ph
V
The addition reaction forms the second chiral
center, and, as a result, compound IV is a mixture of
diastereomers in a ratio of 76:24. The prevailing dia-
stereomer was isolated from the mixture by fractional
crystallization; its individuality was confirmed by the
observation of a single signal in the 31P NMR spec-
Phenyl 2-(phenylamino)ethyl phosphonate (IIa).
A mixture of 3.82 g of silyl phosphite I and 2.82 g of
phenol was heated at 60 C for 2 h, after which 1.92 g
(77%) of phenoxytrimethylsilane was distilled off in
a vacuum, bp 67 C (11 mm Hg), n2D0 1.4738 [3].
153

154
PUDOVIK, KIBARDINA
From the residue, 3.11 g (75%) of compound IIa was
Through a solution of 2.29 g of phosphonate IV in
30 ml of benzene, gaseous HCl was bubbled. The
precipitate formed was filtered off and washed with
two portions of benzene to obtain 76% (2.0 g) of
compound V, mp 113 115 C. 31P NMR spectrum,
P, ppm: 12.87. Found, %: C 61.49; H 5.73; Cl 13.33;
N 5.27; P 5.79. C27H29Cl2N2O3P. Calculated, %:
C 61.01, H 5.46; Cl 13.37; N 5.27; P 5.83.
1
isolated, mp 44 45 C. IR spectrum (KBr), , cm
2418 (P H), 3430 (NH). 31P NMR spectrum, P, ppm:
4.22, JPH 720 Hz. Found, %: C 60.51; H 6.11; N
4.92; P 11.12. C14H16NO3P. Calculated, %: C 60.64;
H 5.77; N 5.05; P 11.29.
4-Methoxyphenyl 2-(phenylamino)ethyl phos-
phonate (IIb) was prepared by the same procedure as
compound IIa from 2.55 g of silyl phosphite I and
2.48 g of 4-methoxyphenol. Yield 2.42 g (79%),
The IR spectra were recorded on a UR-20 spec-
1
trometer in the range of 400 3600 cm in mineral
1
1
viscous liquid. IR spectrum (KBr), , cm : 2415
oil. The H NMR spectra were registered on a Bruker
(P H). 31P NMR spectrum, P, ppm: 4.25, JPH
720 Hz. Found, %: C 58.52; H 5.97; N 4.64; P 9.87.
C15H18NO4P. Calculated, %: C 58.63; H 5.86; N 4.56;
P 10.09.
WM-250 instrument at 250.132 HMz, internal re-
ference TMS. The 31P NMR spectra were measured
on a Bruker MSL-400 NMR Fourier spectrometer at
162.0 MHz.
Phenyl 2-(phenylamino)ethyl [phenyl(phenyl-
amino)metyl]phosphonate (IV). A mixture of 2.77 g
of compound IIa, 1.81 g of benzalaniline, and a ca-
talytic quantity of sodium phenolate in 20 ml of ben-
zene was heated at 60 C for 4 h to obtain a crystalline
product VI, yield 80%, mp 138 142 C, as a mixture
of two diastereomers ( 19.72 and 19.52 ppm). Frac-
tional crystallization fProm acetonitrile gave 1.8 g
(39%) of a diastereomerically individual compound
IV, mp 147 C. 31P NMR spectrum, P, ppm: 19.48.
1H NMR spectrum (CDCl3), , ppm (J, Hz): 3.35 m
(2H, CH2N), 4.32 m (2H, CH2O), 5.04 d (1H, PCH,
2JHP 15.0), 7.32 m (25H, Ph). Found, %: C 70.78; H
5.97; N 6.14; P 6.61. C27H27N2O3P. Calculated, %:
C 70.74; H 5.89; N 6.11; P 6.76.
ACKNOWLEDGMENTS
This work was financially supported by the Rus-
sian Foundation for Basic Research (project no. 06-
03-32085).
REFERENCES
1. Kukhar, V.P. and Hudson, H.R., Aminophosphonic and
Aminophosphinic Acids: Chemistry and Biological
Activity, New York: Wiley, 2000, p. 634.
2. Pudovik, M.A., Kibardina, L.K., Medvedeva, M.D.,
Anoshina, N.P., and Pudovik, A.N., Zh. Obshch. Khim.,
1978, vol. 48, no. 12, p. 2648.
Phenyl 2-(phenylammonio)ethyl [phenyl(phenyl-
ammonio)methyl]phosphonate dichloride (V).
3. Speier, J.L., J. Am. Chem. Soc., 1952, vol. 74, no. 5,
p. 1003.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 1 2008