Convenient method for determination of optical purity of chiral alcohols and amines [3]

Full text of DOI:10.1007/s11176-005-0124-2

Russian Journal of General Chemistry, Vol. 74, No. 12, 2004, pp. 1947 1948. Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 12, 2004,
pp. 2060 2061.
Original Russian Text Copyright
2004 by Nesterov, Grishkun, Kolodyazhnyi.
LETTERS
TO THE EDITOR
Convenient Method for Determination of Optical Purity
of Chiral Alcohols and Amines
V. V. Nesterov, E. V. Grishkun, and O. I. Kolodyazhnyi
Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine
Received March 31, 2004
Chemical transformation of chiral compounds
serves as an important method of determination of
their optical purity, and it has been widely explored
over the past years [1 5].
prepared by the reaction of phosphorus trichloride
with (1R,2S,5R)-menthol and triethylamine in toluene
at 20 C and purified by vacuum distillation. Phos-
phorochloridite I should not be distilled and isolated
pure to be used in analysis of alcohols and amines.
The analysis can be accomplished in one step by
We found that di-(1R,2S,5R)-menthyl phosphoro-
chloridite (I) is a convenient reagent for the determina- successively treating phosphorus trichloride with
tion of optical purity of chiral alcohols and amines by
menthol, triethylamine, and the corresponding alcohol
or amine.
31P NMR spectroscopy. Phosphorochloridite I is
OH
O
O
*
RR C HXH
Et3N
PCl
PXC*HRR
+ PCl3
2
2
I
II, III
X = O (II), NH (III).
Diastereomers of compounds II and III feature
quite different 31P NMR shifts, which allows rather
accurate integration of the corresponding signals and
thus accurate determination of diastereomeric ratios.
Evidence for the high accuracy of the determination
was obtained by analysis of model enantiomeric
mixtures.
Di-(1R,2S,5R)-menthyl phosphorochloridite (I).
A solution of 6.2 g of thoroughly dried (1R,2S,5R)-
menthol and 8 ml of triethylamine in 15 ml of ab-
solute toluene at 20 C to 2.7 g of freshly prepared
phosphorus trichloride in 25 ml of absolute toluene.
The mixture was stirred for 2 h at 20 C, triethylamine
hydrochloride was filtered off, the solvent was
removed, and the residue was vacuum-distilled. Yield
50%, bp 135 C (0.01 mm Hg), [ ]2D0 83 (c 3,
The starting materials, particularly menthol and the
solvent, should be thoroughly purified, and the reac-
tion should be performed in moisture-proof conditions,
since compound I is readily hydrolyzed to di-(1R,2S,-
5R)-menthyl phosphite [6]. The latter can be removed
by vacuum distillation, while its presence in the reac-
tion mixture does not interfere with subsequent
determination of alcohols and amines, since the sig-
nals of di-(1R,2S,5R)-menthyl phosphite is far from
toluene). 31P NMR spectrum (CHCl3):
165 ppm.
Found, %: Cl 9.41; P 8.22. C20H38ClO2P.PCalculated,
%: Cl 9.62; P 8.01
Determination of optical purity of chiral al-
cohols and amines. a. A solution of 0.38 g of di-
menthyl phosphorochloridite I in 2.5 ml of toluene
was added with cooling to 70 C to a solution of
0.001 mol of triethylamine and the corresponding
alcohol (or amine) in 2.5 ml of toluene. The reaction
those of transformed compounds II and III (
P
140 145 ppm).
1070-3632/04/7412-1947 2004 MAIK Nauka/Interperiodica

1948
NESTEROV et al.
mixture was heated to room temperature. After 1 h,
the precipitate was separated, and the solution was
placed into an NMR ampule, a few drops of deutero-
benzene were added, and the 31P NMR spectrum was
taken.
The chemically transformed P(III) derivatives II
and III were isolated individual and subjected to
certain chemical transformations for structural asses-
sment. These compounds, as well as a detailed proce-
dure will be described in the following publication.
b. A solution of 0.5 g of menthol and 0.45 ml of
triethylamine in 5 ml of toluene was added to a solu-
tion of 0.14 ml of phosphorus trichloride in 6 ml of
toluene at 20 C. The reaction mixture was heated to
room temperature and, after 1-h standing, cooled
again to ca. 20 C, and a solution of 0.0015 mol of
the corresponding alcohol (or amine) and 0.002 mol
of triethylamine in 2 ml of toluene was added. The
mixture was stirred, heated to 20 C, and let to stand
at 30 60 min, after which its 31P NMR spectrum was
taken.
The NMR spectra were measured on a Varian-300
instrument, internal references TMS (1H and 13C) and
85% H3PO4 in D2O (31P). The optical rotations were
measured on a Polax-2L polarimeter.
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p. 267.
Below we give the chemical shifs ( , ppm) of
certain alcohols and amines whose opticalPpurity was
determined by the proposed method: (S/R)-
Ph(Me)CHOH 143.0, 143.75; (S/R)-Et(Me)CHOH
142.23, 142.50; (S/R)-Et2NCH(Me)CH2OH 140.54,
140.88; (S/R)-Et2NCH(Et)CH2OH 142.4, 141.9; (S/R)-
(EtO)2P(O)CH(Ph)OH 142.83, 143.37; (1R,2S,5R)/
(1S,2R,5S)-menthol 143.17, 143.44; (S/R)-Ph(Me)
CHNH2 142.3, 143.1; (S/R)-Pr(Me)CHNH2 143.8,
144.0.
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 12 2004