Optically active 2-(1-Phenylethyl)aminoethylphosphonates

Full text of DOI:10.1134/S1070363207060321

ISSN 1070-3632, Russian Journal of General Chemistry, 2007, Vol. 77, No. 6, pp. 1136 1137.
Pleiades Publishing, Ltd., 2007.
Original Russian Text S.A. Terent’eva, M.A. Pudovik, 2007, published in Zhurnal Obshchei Khimii, 2007, Vol. 77, No. 6, pp. 1050 1051.
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
e-mail: arbuzov@iopc.knc.ru
Received February 27, 2007
DOI: 10.1134/S1070363207060321
Amino phosphonic acids, which are direct analogs
of natural amino acids, show a wide spectrum of
biological activity [1]. Suffice it to say, the first
amino phosphonic acid found in the nature was
their addition to diethyl phosphonate IIa requires
heating for several hours. As a result of addition of
amino phosphonate IIId to phenyl isothiocyanate,
enantiomerically pure phosphorus-containing urea IV
was prepared:
2-aminoethanephosphonic acid [2]. Recently there has
been a great deal of interest in the synthesis of the
enantiomerically pure organophosphorus compounds
because of their possible application as biological
active compounds and ligands for preparation of
homogeneous and heterogeneous catalysts [1, 3, 4]. It
is known that dialkyl vinylphosphonates readily add
secondary amines to form -aminoalkylphosphonates
O
O
IIId + PhNCS
(PhO) PCH CH N C NHPh.
2
2
2
*CH Me
Ph
IV
[
5]. The related reaction with ammonia occurs only in
Diethyl
2-(1-phenylethyl)aminoethylphospho-
the presence of sodium ethoxide [6, 7].
nate (IIIa). A mixture of 4.1 g of vinylphosphonate
IIa and 6.0 g of amine Ia was kept at 100 C for 2 h.
Then the reaction mixture was distilled, and com-
pound IIIa in 3.4 g (47%) yield was obtained, bp
38 C (0.08 mm Hg). IR spectrum (KBr), , cm :
We found that racemic amine Ia and R-(+)-phenyl-
ethylamines Ib undergo addition to vinylphosphonates
IIa and IIb in the absence of any catalyst with the
formation of 2-aminoethylphosphonates IIIa IIId:
1
1
1
O
1226, 1247 (P=O), 3305, 3443 (NH). H NMR spec-
trum (CDCl ), , ppm (J, Hz): 1.27 d.t (6H, CH CH ,
*
3
3
2
MeCHNH + (RO) PCH=CH
2
2
2
3
4
3
JHH 7.0, J
2.1), 1.40 d (3H, CH , J 7.1),
HP
3
HH
Ph
1
.98 m (2H, CH P), 2.85 m (2H, CH N), 3.82 q (1H,
2 2
3
CHN, J
7.0), 4.06 m (4H, CH O), 7.15 7.18 m
2
Ia, Ib
IIa, IIb
HH
(
5H, Ph). Found, %: N 4.88; P 10.65. C H NO P.
14 24 3
O
Calculated, %: N 4.91; P 10.88.
*
(
RO) PCH CH NHCHMe,
2
2
2
Diethyl R-(+)-2-(1-phenylethyl)aminoethylphos-
phonate (IIIb) was prepared similarly to IIIa from
Ph
IIIa IIId
4
.1 g of vinylphosphonate IIb and 6.0 g of amine Ib
2
0
in 55% (3.9 g) yield, bp 143 C (0.08 mm Hg), n
D
I, racemic (a), R-(+) (b); II, R = Et (a), Ph (b); III, R = Et
a); Et R-(+) (b), Ph (c), Ph R-(+) (d).
20
1
.4877, [ ]D +35.1 (c 0.429, CH Cl ). IR spectrum
2
2
(
1
(
KBr), , cm : 1228, 1249 (P=O), 3305, 3443 (NH).
1
H NMR spectrum (CDCl ), , ppm (J, Hz): 1.25 d.t
3
It should be noted that the ease of the reaction is
significantly affected by the nature of substituents at
the phosphorus atom. Whereas the addition of amines
to diphenyl phosphonate IIb readily occurs at 20 C,
3
4
(
6H, CH CH , J 7.0, J 2.1), 1.32 d (3H, CH3,
JHH 7.0), 1.94 m (2H, CH P), 2.08 br.s (1H, NH),
3 2 HH HP
3
2
3
2.71 m (2H, CH N), 3.84 q (1H, CHN, J
7.0),
2
HH
1136

OPTICALLY ACTIVE 2-(1-PHENYLETHYL)AMINOETHYLPHOSPHONATES
1137
4
.03 m (4H, CH O), 7.19 7.28 m (5H, Ph). 31P NMR
Found, %: C 67.96; H 5.68; N 5.76; P 6.20; S 6.26.
C H NO P. Calculated, %: C 67.44; H 5.62; N 5.43;
2
spectrum, P, ppm: 30.41.
22
24
3
P 6.01; S 6.20.
Diphenyl 2-(1-phenylethyl)aminoethylphos-
phonate (IIIc). A mixture of 5.2 g of phosphonate
IIb and 4.8 g of amine Ia was allowed to stand at
The IR spectra were recorded on a UR-20 instru-
1
ment within the range 400 3600 cm in mineral oil.
1
2
0 C for 48 h. Excess amine was removed in a va-
The H NMR spectra were measured on a Bruker
cuum, and the residue was distilled in a vacuum to
WM-250 spectrometer (250.132 MHz), internal
reference TMS. The 31P NMR spectra were recorded
on a Bruker MSL-400 NMR Fourier spectrometer
operating at 100.62 MHz.
obtain 4.8 g (63%) of compound IIIc, bp 180 185 C
1
(
0.1 mm Hg). H NMR spectrum (CDCl ), , ppm (J,
3
3
Hz): 1.39 d (3H, CH , J 7.0), 2.31 m (2H, CH P),
.97 m (2H, CH N), 3.83 q (1H, CHN, J
.17 m (5H, Ph), 7.38 m (10H, Ph). P NMR spec-
3
HH
2
3
2
7
7.0),
2
HH
3
1
ACKNOWLEDGMENTS
trum, P, ppm: 23.99. Found, %: N 3.61; P 7.97.
C H NO P. Calculated, %: N 3.67; P 8.14.
This study was financially supported by the Rus-
sian Foundation for Basic Research (project no. 06-
2
2
24
3
Diphenyl R-(+)-2-(1-phenylethylamino)ethyl-
03-32085).
phosphonate (IIId) was prepared similarly to IIIc
from 2.0 g of phosphonate IIb and 1.8 g of amine Ib;
REFERENCES
2
0
yield 1.7 g (61%), bp 183 188 C (0.1 mm Hg), [ ]
D
1
+
21.3 (c 0.939, CH Cl ). H NMR spectrum (CDCl ),
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2
2
3
3
,
ppm (J, Hz): 1.39 d (3H, CH , J 7.0), 2.31 m
3 HH
(
2H, CH P), 2.97 m (2H, CH N), 3.82 q (1H, CHN,
2 2
3
31
JHH 7.0), 7.17 m (5H, Ph), 7.38 m (10H, Ph).
NMR spectrum, P, ppm: 22.25. Found, %: N 3.59; P
.19. C H NO P. Calculated, %: N 3.67; P 8.14.
P
2. Horiguchi, M. and Kandatsu, M., Nature, 1959,
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8
2
2
24
3
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1
ethyl)-N -phenylthiourea (IV). A mixture of 0.30 g
of phosphonate IIId and 0.11 g of phenyl isothio-
cyanate was allowed to stand at 20 C for 20 days. The
crystals formed were separated, repeatedly washed
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5
6
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(
+
3
53.6%) of compound IV, mp 120 123 C, [ ]2
0
D
1953, vol. 23, no. 2, p. 263.
1
65.0 (c 0.185, CH Cl ). IR spectrum (KBr), , cm :
2 2
7. Kato, M., Nishino, S., and Ohno, M., Bioorg. Med.
Chem. Lett., 1996, vol. 6, no. 1, p. 33.
3
1
327 (NH). P NMR spectrum, P, ppm: 30.41.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 6 2007