A new procedure for the synthesis of optically active t-butylphenylphosphinothioic acid

Article abstract of DOI:10.1002/hc.21206

A new procedure for the synthesis of optically active t-butylophenylphosphinothioic acid as an enantiomerically pure dextrorotatory enantiomer having the absolute configuration (R), by a reaction of the racemate of secondary t-butylphenylphosphine oxide with elemental sulfur in the presence of a molar equivalent of the levorotatory enantiomer of enantiomerically pure (S)-α-phenylethylamine, is reported. It is obvious that with the use of the dextrorotatory enantiomer of α-phenylethylamine, the levorotatory enantiomer of this thioacid will be isolated.

Full text of DOI:10.1002/hc.21206

Heteroatom Chemistry
Volume 25, Number 6, 2014
A
New Procedure for the Synthesis of Optically
Active t-Butylphenylphosphinothioic Acid
1,2
1
1
J o´ zef Drabowicz, Patrycja Pokora-Sobczak, Adrian Zaja˛c,
1
and Paulina Wach-Panfiłow
1
Department of Heteroorganic Chemistry, Center of Molecular and Macromolecular Studies Polish
Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland
2Institute of Chemistry, Environmental Protection and Biotechnology, Jan Dlugosz University in
Czestochowa, 42-201 Czestochowa, Poland
Received 30 January 2014; revised 5 June 2014
the need for rapid and accurate determination of
ABSTRACT: A new procedure for the synthesis of
this parameter. Among the techniques used for this
optically active t-butylophenylphosphinothioic acid as
purpose, the NMR measurements have found so far
an enantiomerically pure dextrorotatory enantiomer
the widest application [1]. The most advantageous
having the absolute configuration (R), by a reaction
and simple experiments are based on the use of chi-
of the racemate of secondary t-butylphenylphosphine
ral solvating agents (CSAs).
oxide with elemental sulfur in the presence of a mo-
They form with an enantiomeric pair di-
lar equivalent of the levorotatory enantiomer of enan-
astereoisomeric solvation complexes, which are in
tiomerically pure (S)-α-phenylethylamine, is reported.
dynamic equilibrium and should show in princi-
It is obvious that with the use of the dextrorotatory
ple nonequivalent spectra. At present, more than 50
enantiomer of α-phenylethylamine, the levorotatory
compounds have been used to determine the enan-
tiomeric excess values for a variety of organic deriva-
tives with a stereogenic carbon or heteroatom such
as sulfur or phosphorus. Most of them are applied for
the determination in a particular group of organic
compounds and only a few have wider application
scope. Among CSAs reported in the literature, (–)-
enantiomer of this thioacid will be isolated. ꢀC 2014
Wiley Periodicals, Inc. Heteroatom Chem. 25:674–
677, 2014; View this article online at wileyonlineli-
brary.com. DOI 10.1002/hc.21206
(
1
S)- and (+)-(R)-t-butylphenylphosphinothioic acid
INTRODUCTION
(which exists in only one tautomeric structure
In recent years, determining the enantiomeric ex-
cesses of chiral compounds has become a very im-
portant research topic [1]. This result is mainly based
on the recent advances in the stereoselective (espe-
cially in enantioselective) synthesis [2] that induce
and one conformation in CCl4 solution [3] [Eq. (1)])
turned out to have the widest application for NMR
analysis of many classes of chiral organic com-
pounds. They are listed in the recent minireview pre-
pared in our group [4].
Correspondence to: J o´ zef Drabowicz; e-mail: draj@cbmm.
lodz.pl.
Contract grant sponsor: National Science Center.
Contract grant number: UMO-2011/01/B/ST5/06664.
Dedicated to the 77th birthday of Professor Okazaki.
(1)
ꢀC
2014 Wiley Periodicals, Inc.
674

New Procedure for the Synthesis of Optically Active t-Butylphenylphosphinothioic Acid 675
figuration (R) with (S)-α-phenylethylamine 2 is fil-
tered and crystallized, and converted to the opti-
cally active dextrorotatory enantiomer of thioacid
1
of the absolute configuration (R) by an aque-
ous basic-acidic work-up. The optically active lev-
orotatory thioacid 1 of configuration (S) was iso-
lated by a similar work-up of the mother liquor,
which contains a better soluble salt of the opti-
cally active levorotatory thioacid 1 of configura-
tion (S) with (S)-α-phenylethylamine 2. Obviously
with the use of the dextrorotatory enantiomer of
α-phenylethylamine 2, the levorotatory enantiomer
of this thioacid 1 will be isolated from the harder
soluble salt.
SCHEME 1
SCHEME 2
EXPERIMENTAL
General
RESULTS AND DISCUSSION
All the reagents and solvents were commercially
available and were used without further purifica-
tion. Thin-layer chromatography was carried out on
glass plates coated with silica gel (Merck (Darmstadt,
Germany), Kiesegel 60F254, precoated 0.25 mm).
The NMR spectra were obtained on a Bruker spec-
trometer Avance AV 200 (Bruker, Karlsruhe, Ger-
many) (200.16 MHz (1H), 50.30 MHz ( C NMR)
in CDCl3). Mass spectral data were collected on a
MAT95–Finnigan spectrometer (Finnigan MAT, Bre-
men, Germany). Optical rotation was determined on
a 241 MC–Perkin Elmer polarimeter (Perkin Elmer,
Vienna, Austria) at room temperature. Melting point
was determined on a Betius apparatus (PHMK VEB
Analytik, Dresden, Germany) and is uncorrected. Di-
ethyl ether was dried and distilled over metal sodium
with the addition of benzophenone in dry argon. The
reactions were carried out under dry argon. Racemic
t-butylphenylphosphine oxide 3 was obtained by the
modified Hoffmann and Schellenbeck method [16].
The
resolution
of
racemic
t-
butylphenylphosphinothioic acid 1 via the di-
asteromeric quinine salt was mentioned (without
giving any details) as early as in 1971 [5]. A few
years later, it was reported [6–9] that this thioacid
readily forms crystalline salts with enantiomers of
α-phenylethylamine 2, both of which have been
used to effect a resolution of the thioacid. Optically
active thioacid 1 was also prepared directly by
the addition of elemental sulfur to optically active
t-butylphenylphosphine oxide 3 [10–12] for which
the (R) absolute configuration was assigned by
chemical correlation (Scheme 1) [10–12] and using
vibrational circular dichroism [13].
1
3
Moreover, the levorotatory phosphine oxide (–)-
(
S)-3 and thione 4 gave also the dextrorotatory enan-
tiomer of t-butylphenylphosphinothioic acid (+)-
R)-1 with full retention of configuration at the stere-
(
ogenic phosphorus atom (Scheme 2) [14].
Here, we would like to report details of a re-
cently patented, new protocol for the synthesis of an
optically active t-butylophenylphosphinothioic acid
Optically Active t-Butylphenylphosphinothioic
Acid
1
in the form of the enantiomerically pure dex-
trorotatory enantiomer having the absolute config-
uration (R), by the reaction of the racemate of a
secondary t-butylphenylphosphine oxide 3 with el-
emental sulfur in the presence of enantiomerically
pure (S)-α-phenylethylamine 2 [15]. A new proce-
dure shown in Scheme 3 consists in that a mo-
lar equivalent of elemental sulfur is added to a
solution of racemic oxide 3 and molar equivalent
of the levorotatory enantiomer of enantiomerically
pure (S)-α-phenylethylamine 2 in a mixture of ether
and chloroform, after which the formed and pre-
cipitated from solution, harder soluble salt of the
optically active dextrorotatory thioacid 1 of con-
To a magnetically stirred solution of racemic
t-butylphenylphosphine oxide
3
(5.52 g, 30
mmol) and the enantiomerically pure (–)-(S)-α-
phenylethylamine 2 (3.63 g, 30 mmol) in a mixture
of diethyl ether (40 mL) and chloroform (30 mL),
elemental sulfur (0.96 g, 30 mmol) was added in two
portions at 0°C. After the addition of a second por-
tion of the sulfur, the reaction mixture was kept at a
temperature below 15°C for 1 h. After this time, the
formed crystalline salt was filtered (3.389 g, 34.5%).
It is characterized by the following spectroscopic
and analytical data:
Heteroatom Chemistry DOI 10.1002/hc

676 Drabowicz et al.
SCHEME 3
[
α]589 = + 28.2 (c = 1.46,CHCl3), mp = 182–
92°C; H NMR (CDCl3) δ = 0.96 and δ = 1.06 (d,
J = 16.26 Hz, 9H) (the composition of δ = 0.96/δ =
.06 = 3/21), δ = 1.47 (d, J = 6.85 Hz, 3H), δ = 4.19
ether (3 × 15 mL). The aqueous layer was acidified
with aqueous 3.5 molar HCl until strongly acidic,
and the precipitate was transferred to the organic
layer by shaking the water layer with chloroform (3
× 15 mL). The chloroform extract was dried over
anhydrous magnesium sulfate. The concentration of
the organic solution initially at a pressure of 15 mm
Hg and then at 1 mm Hg at room temperature pro-
vided a chemically pure (+)-(R)-1 (1.86 g, 29.0%). It
is characterized by the following spectroscopic and
analytical data:
1
1
1
(
q, J = 6.85 Hz, 1H), δ = 6.63 (very broad singlet,
3
H), δ = 7.22 – 7.39 (m 8H), δ = 7.69 – 7.79 (m, 2H);
P NMR (CDCl3) δ = 80.65 (s) and δ = 80.98 (s) the
3
1
composition of δ = 80.65/δ = 80.98 = 52.67/5.17. The
isolated salt was crystallized by dissolving in reflux-
ing CHCl3 (20 mL) and adding diethyl ether (25 mL).
The resulting crystals (2.7 g, 27.4%) were character-
ized by the following spectroscopic and analytical
data:
[α]589 = 28.7 (c = 1.24, MeOH); mp = 97–99°C
[lit. for the racemate mp = 124–125°C; for (+)-(R)
enantiomer mp = 103–106°C (softens at 96°C [6a].
[
α]589 = +32.8 (c = 1.49, CHCl3), mp = 189–
1
1
1
92°C; H NMR (CDCl3) δ = 1.00 (d, J = 16.25 Hz,
H NMR (CDCl3) δ = 1.14 (d, J = 17.61 Hz, 9H), δ =
3
1
9
H), δ = 1.47 (d, J = 6.85 Hz, 3H), δ = 4.21 (q, J = 6.85
7.27 – 7.46 (m, 4H), δ = 7.67 – 7.77 (m, 2H), P NMR
(CDCl3); δ = 98.39 (s), MS (CI/isobutane): m/z 215.1
[M + 1]. The remaining solution after filtration of the
crystalline salt (3.389 g, 34.5%) was concentrated to
give an oily residue, which was slowly crystallized
(7.125g, 65.5%). It is characterized by the following
spectroscopic and analytical data: [α] 589 = – 21.0
Hz, 1H), δ = 7.21 – 7.38 (m, 11H), δ = 7.67–7.77 (m,
3
1
2
H); P NMR (CDCl3) δ = 80.39 (s) and δ = 80.88 (s)
the composition of δ = 80.39 / δ = 80.88 = 8.34/0.31.
These crystals were dissolved in water (30 mL) and
solid sodium hydroxide (4 g) was added to this so-
lution. The resulting slurry was extracted with ethyl
Heteroatom Chemistry DOI 10.1002/hc

New Procedure for the Synthesis of Optically Active t-Butylphenylphosphinothioic Acid 677
1
[
[
3] Drabowicz, J.; Pokora-Sobczak, P.; Krasowska, D.;
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c = 1.4, CHCl3), mp = 90–101°C; H NMR (CDCl3)
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δ = 1.47 (d, J = 6.85 Hz, 3H), δ = 4.19 (q, J = 6.85
Hz, 1H), δ = 6.63 (broad singlet, 3H), δ = 7.22 – 7.39
(
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3
1
[
[
(
m, 8H), δ = 7.69 – 7.79 (m, 2H). P NMR (CDCl3)
δ = 80.84 (s) and δ = 80.93 (s) the composition of
δ = 0.80.84/δ = 80.93 = 21.88/39.48. The levorota-
tory enantiomer (–)-(S)-1 (3.21 g, 50.0%) was iso-
lated from the diastereomeric salt by following the
procedure described above for the diastereomeric
salt comprising (+)-(R)-enantiomer of the thioacid 1.
It is characterized by spectroscopic data analogous
to those described for the dextrorotatory isomer (+)-
3
1
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[7] Skrzypczynski, Z.; Michalski, J. J Org Chem 1988, 53,
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[
(
R)-1 and the specific rotation [α]589 = –14.7 (c = 1.4,
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[
[
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Heteroatom Chemistry DOI 10.1002/hc