Optically active 2-(1-phenylethyl)aminoethylphosphonates

Full text of DOI:10.1134/S1070363207050283

ISSN 1070-3632, Russian Journal of General Chemistry, 2007, Vol. 77, No. 5, pp. 967 968.
Pleiades Publishing, Ltd., 2007.
Original Russian Text
S.A. Terent’eva, M.A. Pudovik, 2007, published in Zhurnal Obshchei Khimii, 2007, Vol. 77, No. 5, pp. 873 874.
LETTERS
TO THE EDITOR
Optically Active 2-(1-Phenylethyl)aminoethylphosphonates
S. A. Terent’eva and M. A. Pudovik
Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center,
Russian Academy of Sciences, ul. Akad. Arbuzova 8, Kazan, Tatarstan, 420088 Russia
fax: (8432)752253
e-mail: pudovik@iopc.knc.ru
Received January 11, 2007
DOI: 10.1134/S1070363207050283
Aminophosphonic acids are direct analogs of
natural amino acids constituting building blocks of
peptides and proteins, and they demonstrate broad and
diverse biological activity [1]. It is enough to mention
that the first amino acid found in the nature was
2-aminoethylphosphonic acid [2]. In recent years,
considerable attention has been given to the synthesis
of enantiopure organophosphorus compounds because
of their possible application as biologically active
compounds and ligands for homogeneous and hetero-
geneous catalysts [1, 3, 4]. It is known that secondary
amines smoothly add to dialkyl vinylphosphonates
to form -aminoalkylphosphonates [5]. The similar
reaction with ammonia proceeds in the presence of
sodium ethoxide only [6, 7].
IIb readily occurs at 20 C, whereas their addition to
diethyl phosphonate IIa requires a few hours to occur.
The addition of aminophosphonate IIId to phenyl
isothiocyanate results in the preparation of an enantio-
pure phosphorus-containing urea IV.
S
O
(PhO)2PCH2CH2N C NHPh.
Me *CH
IIIa + PhNCS
Ph
IV
Diethyl 2-(1-phenylethylamino)ethylphospho-
nate (IIIa). A mixture of 4.1 g of vinylphosphonate
IIa and 6.0 g of amine Ia was kept for 2 h at 100 C.
Distillation of the mixture gave 3.4 g (47%) of com-
pound IIIa, bp 138 C (0.08 mm Hg). IR spectrum
We established that racemic and R-(+)-phenylethyl-
amines Ia, Ib add to vinylphosphonates IIa, IIb in
the absence of catalyst to give 2-aminoethylphospho-
nates IIIa IIId.
1
(KBr), , cm : 1226, 1247 (P=O), 3305, 3443 (NH).
1H NMR spectrum (CDCl3), , ppm, (J, Hz): 1.27 d.t
3
4
O
(6H, CH3CH2, JHH 7.0, JHP 2.1), 1.40 d (3H, CH3,
3JHH 7.1), 1.98 m (2H, CH2P), 2.85 m (2H, CH2N),
3.82 q (1H, CHN, JHH 7.0), 4.06 m (4H, CH2O),
*
MeCHNH2 + (RO)2PCH=CH2
3
Ph
7.15 7.18 m (5H, Ph). Found, %: N 4.88; P 10.65.
C14H24NO3P. Calculated, %: N 4.91; P 10.88.
Ia, Ib
IIa, IIb
O
Diethyl R-(+)-2-(1-phenylethylamino)ethyl-
phosphonate (IIIb) was prepared similarly from
4.1 g of vinylphosphonate IIb and 6.0 g of amine Ib,
yield 3.9 g (55%), bp 143 C (0.08 mm Hg), nD20
*
(RO)2PCH2CH2NHCHMe
Ph
IIIa IIId
1.4877, [ ]2D0 +35.1 (c 0.429, CH2Cl2). IR spectrum
I, racemic (a), R-(+) (b); II, R = Et (a), Ph (b); III, R = Et
(a); Et, R-(+) (b), Ph (c), Ph, R-(+) (d).
1
(KBr), , cm : 1228, 1249 (P=O), 3305, 3443 (NH).
1H NMR spectrum (CDCl3), , ppm, (J, Hz): 1.25 d.t
3
4
(6H, CH3CH2 JHH 7.0, JHP 2.1), 1.32 d (3H, CH3,
Note that the facility of the reaction depends on
the nature of substituents at the phosphorus atom.
Thus, the addition of amines to diphenyl phosphonate
3JHH 7.0), 1.94 m (2H, CH2P), 2.08 br.s (1H, NH),
2.71 m (2H, CH2N), 3.84 q (1H, CHN, JHH 7.0),
3
967

968
TERENT’EVA, PUDOVIK
4.03 m (4H, CH2O), 7.19 7.28 m (5H, Ph). 31P NMR
spectrum, P, ppm: 30.41.
H 5.68; N 5.76; P 6.20; S 6.26. C22H24NO3P. Calcu-
lated, %: C 67.44; H 5.62; N 5.43; P 6.01; S 6.20.
Diphenyl 2-(1-phenylethylamino)ethylphospho-
nate (IIIc). A mixture of 5.2 g of phosphonate IIb
and 4.8 g of amine Ia was kept for 48 h at 20 C. Ex-
cess amine was then removed in a vacuum, and the
residue was distilled in a vacuum to obtain 4.8 g
The IR spectrum was registered on a UR-20 spec-
1
trometer within the range 400 3600 cm in Vaseline.
1
The H NMR spectra were obtained on a Bruker WM-
250 instrument (250.132 MHz) against internal TMS.
The 31P NMR spectra were recorded on a Bruker
MSL-400 NMR Fourier spectrometer operated at
100.62 MHz.
(63%) of compound IIIc, bp 180 185 C (0.1 mm Hg).
1H NMR spectrum (CDCl3), , ppm, (J, Hz): 1.39 d
(3H, CH3, 3JHH 7.0), 2.31 m (2H, CH2P), 2.97 m (2H,
3
ACKNOWLEDGMENTS
CH2N), 3.83 q (1H, CHN, JHH 7.0), 7.17 m (5H, Ph),
7.38 m (10H, Ph). 31P NMR spectrum, P, ppm: 23.99.
Found, %: N 3.61; P 7.97. C22H24NO3P. Calculated,
%: N 3.67; P 8.14.
This work was financially supported by the Rus-
sian Foundation for Basic Research (project no. 06-
03-32085).
Diphenyl R-(+)-2-(1-phenylethylamino)ethyl-
phosphonate (IIId) was prepared similarly from
2.0 g of phosphonate IIb and 1.8 g of amine Ib, yield
REFERENCES
1.7 g (61%), bp 183 188 C (0.1 mm Hg), [ ]2D0 +21.3
1. Kukhar, V.P. and Hudson, H.R., Aminophosphonic and
Aminophosphinic Acids: Chemistry and Biological
Activity, New York: Wiley, 2000.
1
(c 0.939, CH2Cl2). H NMR spectrum (CDCl3),
,
ppm, (J, Hz): 1.39 d (3H, CH3, 3JHH 7.0), 2.31 m (2H,
CH2P), 2.97 m (2H, CH2N), 3.82 q (1H, CHN, JHH
3
2. Horiguchi, M. and Kandatsu, M., Nature, 1959,
7.0), 7.17 m (5H, Ph), 7.38 m (10H, Ph). 31P NMR
spectrum, P, ppm: 22.25. Found, %: N 3.59; P 8.19.
C22H24NO3P. Calculated, %: N 3.67; P 8.14.
vol. 184, no. 5, p. 901.
3. Kafarski, P. and Lejczak, B., Phosph., Sulfur, Relat.
Elem., 1991, vol. 63, no. 2, p. 193.
N-(Diphenoxyphosphinoylethyl)-N-(1-phenyl-
4. Kolodiazhnyi, O.I., Tetrahedron: Asymmetry, 1998,
ethyl)-N1-phenylthiourea (IV). A mixture of 0.30 g
of phosphonate IIId and 0.11 g of phenyl isothio-
cyanate was kept for 20 days at 20 C. Crystals formed
and were separated, repeatedly washed with ether, and
dried in a vacuum to obtain 0.22 g (53.6%) of com-
vol. 9, no. 6, p. 1279.
5. Gubnitskaya, E.S., Peresypkina, L.P., and Sama-
raib, L.I., Usp. Khim., 1990, vol. 59, no. 6, p. 1386.
6. Pudovik, A.N. and Denisova, G.M., Zh. Obshch. Khim.,
pound IV, mp 120 123 C, [ ]2D0 +65.0 (c 0.185,
1953, vol. 23, no. 2, p. 263.
1
CH2Cl2). IR spectrum (KBr), , cm : 3327 (NH). 31P
7. Kato, M., Nishino, S., and Ohno, M., Bioorg. Med.
Chem. Lett., 1996, vol. 6, no. 1, p. 33.
NMR spectrum, P, ppm: 30.41. Found, %: C 67.96;
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 5 2007