ASYMMETIC SYNTHESIS OF A PHOSPHORUS ANALOG
1511
optical rotation of our synthesized phosphocarnitine
IV was higher than that of the earlier described com-
pound obtained as an uncrystallizable oil. The struc-
ture of compounds I IV was also confirmed by ele-
mental analysis and NMR spectroscopy.
thylene chloride was successively treated with 2 mol
of bromotrimethylsilane and 60% aqueous ethanol.
Yield 98%, oil. H NMR spectrum (C6D6), , ppm
1
(J, Hz): 1.6 1.9
(2H, CH2Cl), 4.8 m (1H, CHO), 4.9 br (OH). 31P
NMR spectrum (CD3OD): 25.5 ppm.
m
(2H, PCH2), 3.2 3.4
m
P
Diethyl (3-chloro-2-oxopropyl)phosphonate (I).
To a solution of butyllithium (1.7 N, 0.07 mol) at
78 C we successively added 50 ml of THF, a solu-
tion of 0.07 mol of diethyl methylphosphonate in
25 ml of THF, and, after 20 min, 0.077 mol of
Cu2Br2. The mixture was stirred for 1.5 h at 60 to
40 C, and 0.073 mol of chloroacetyl chloride in
30 ml of ether was then added. After 1.5-h stirring at
40 to 30 C, the mixture was left overnight at this
temperature and then treated with 65 ml of water. The
precipitate was separated, and the solution was ex-
tracted with chloroform (2 40 ml). The extract was
washed with a solution of sodium carbonate and dried
over Na2SO4. The solvent was evaporated, and the
residue was distilled in a vacuum. Yield 60%, color-
less oil, bp 97 99 C (0.04 mm Hg). 31P NMR spec-
(R)-(+)-[2-Hydroxy-3-(trimethylammono)-
propyl]phosphonic acid [(R)-(+)-phosphocarnitine].
Excess 29% aqueous trimethylamine was added to
acid III. The mixture was kept for 48 h at 40 C and
then evaporated to leave an oily residue which was
purified by column chromatography on silica gel,
eluent methanol water. Yield 80%, colorless crystals,
mp >250 C (decomp.), [ ]2D0 +17.85 (c 1.26, H2O). 1H
NMR spectrum (CD3OD), , ppm (J, Hz): 1.85 br
(2H, PCH2), 3.2 s (9H, CH3N), 3.35 3.55 m (CH2N),
4.5 m (1H, CHOH), 4.9 5.0 br (OH). 31P NMR spec-
trum (CD3OD), P, ppm: 18.7. Found, %: P 15.62.
C5H16NO4P. Calculated, %: P 15.63.
The NMR spectra were taken on a Varian-300
instrument, internal references TMS (1H) and 85%
H3PO4 in D2O (31P). The optical rotations were
measured on a Polax-2L polarimeter (Japan).
trum (C6D6):
value [5]).
18.8 ppm (coincides with published
P
Diethyl (S)-( )-(3-chloro-2-hydroxypropyl)-
phosphonate (II) was prepared by an earlier des-
cribed procedure from NaBH4, (R,R)-(+)-tartaric acid,
and oxophosphonate I. Yield 92%, [ ]2D0 12.42
(c 3.22, CHCl3). 1H NMR spectrum (CD3OD), , ppm
REFERENCES
1. Nesterov, V.V. and Kolodyazhnyi, O.I., Zh. Obshch.
Khim., 2005, vol. 75, no. 7, p. 1225.
2. Nesterov, V.V. and Kolodiazhnyi, O.I., Proc. XIV Int.
Conf. on Chemistry of Phosphorus Compounds, Kazan,
2005, p. 99.
3
(J, Hz): 1.35 t (6H, JHH 7.2, CH3CH2), 1.8 m (1H,
PCaH2), 2.15 m (1H, PCbH2), 3.35 d.d (3JHH 6,
3JHP 12, 1H, CaHCl), 3.53 m (1H, CbHCl), 3.56 m
(2H, CHOH), 4.05 m (4H, CH2O), 4.7 m (1H, OH).
3. Kielbasinski, P., Luczak, J., and Mikolajczyk, M.,
31P NMR spectrum (CD3OD): P 29.4 ppm. Found, %:
Cl 14.43; P 13.50. C7H16ClO4P. Calculated, %: Cl
15.37; P 13.43.
J. Org. Chem., 2002, vol. 67, no. 22, p. 7872.
4. Wang, K., Zhang, Y., and Yuan, C., Org. Biomol.
Chem., 2003, vol. 1, no. 20, p. 3564.
(S)-(3-Chloro-2-hydroxypropyl)phosphonic acid
(III). A solution of hydroxyphosphonate II in me-
5. Yuan, C., Wang, K., and Li, Z., Heteroatom. Chem.,
2001, vol. 12, no. 6, p. 551.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 9 2006