T -Butylphenyl-(1-Naphthyl)Phosphinothioic Acids and Their Selenium Analogs: Synthesis of the Racemic Mixtures and Attempts to Isolate the Enantiomers of t -Butyl-1-Naphthylphosphinothioic Acid

Article abstract of DOI:10.1080/10426507.2014.978328

Synthesis of racemic t-butyl-1-naphthylphosphinothio(seleno)ic acids and attempts to isolate the enantiomers of t-butyl-1-naphthylphosphinothioic acid are described.

Full text of DOI:10.1080/10426507.2014.978328

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Phosphorus, Sulfur, and Silicon and the Related
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t-Butylphenyl-(1-Naphthyl)Phosphinothioic Acids And
Their Selenium Analogs: Synthesis Of The Racemic
Mixtures And Attempts To Isolate The Enantiomers Of t-
Butyl-1-Naphthylphosphinothioic Acid
Patrycja Pokora-Sobczaka, Grażyna Mielniczaka, Dorota Krasowskaa, Jacek Chrzanowskia,
Adrian Zająca & Józef Drabowicza
a Center of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department
of Heteroorganic Chemistry, Sienkiewicza 112, 90-363 Lodz, Poland
Accepted author version posted online: 14 Nov 2014.
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To cite this article: Patrycja Pokora-Sobczak, Grażyna Mielniczak, Dorota Krasowska, Jacek Chrzanowski, Adrian Zając &
Józef Drabowicz (2014): t-Butylphenyl-(1-Naphthyl)Phosphinothioic Acids And Their Selenium Analogs: Synthesis Of The
Racemic Mixtures And Attempts To Isolate The Enantiomers Of t-Butyl-1-Naphthylphosphinothioic Acid, Phosphorus, Sulfur,
and Silicon and the Related Elements, DOI: 10.1080/10426507.2014.978328
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t-BUTYLPHENYL-(1-NAPHTHYL)PHOSPHINOTHIOIC ACIDS AND THEIR
SELENIUM ANALOGS: SYNTHESIS OF THE RACEMIC MIXTURES AND
ATTEMPTS TO ISOLATE THE ENANTIOMERS OF
t-BUTYL-1-NAPHTHYLPHOSPHINOTHIOIC ACID
Patrycja Pokora-Sobczak, Grażyna Mielniczak, Dorota Krasowska, Jacek Chrzanowski,
Adrian Zając, Józef Drabowicz*
draj@cbmm.lodz.pl
Center of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department of
Heteroorganic Chemistry, Sienkiewicza 112, 90-363 Lodz, Poland
Abstract
Synthesis of racemic t-butyl-1naphthylphosphinothio(seleno)ic acids and attempts to isolate the
enantiomers of t-butyl-1naphthylphosphinothioic acid are described.
Keywords
t-butylarylphosphinothioic acids; t-butylarylphosphinoselenoic acids; chiral solvating agents;
chirality
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INTRODUCTION
Since the pioneering paper of Harger1, optically active t-butylphenylphosphinothioic acid
1a has gained steadily increasing use as an efficient chiral solvating agent (CSA) for the
determination of the enantiomeric excesses of chiral compounds with a stereogenic carbon atom
or heteroatom.2 It might be expected that due to the presence of more extended
π- electron system in t-butyl-1-naphtylphosphinothioc acid 1b its efficiency as CSA should be
modified. It would also be interesting to compare the efficiency as CSA the corresponding
selenium analogues. To test both assumptions we need to have in hands the enantiomers of these
thio(seleno)acids. In this paper we would like to report our preliminary experiments aimed to
reach partially this goal, namely the synthesis of the racemic mixtures of the thioacid 1b and the
selenoacid 2b and attempts to isolate the enantiomers of t-butyl-1-naphtylphosphinothioic acid
1b.
RESULTS AND DISCUSSION
Racemic t-butyl-1-naphthylphosphinothioic acid 1b was obtained by the modification of
the original Hoffmann and Schellenbeek3 protocol in which racemic secondary
t-butylnaphthylphosphine oxide 3b is a key intermediate. Racemic thioacid 1b was synthesized
by an oxidative addition of elemental sulfur to racemic t-butyl-1-naphthyl-phosphine oxide 3b,
which was prepared according to the reactions presented in Scheme 1. Similar experiments were
conducted to obtain t-butyl-1-naphthylphosphinoselenoic acid 2b.
We began our attempts at the resolution of racemic t-butyl-1-naphthylphosphinothioic
acid 1b into enantiomers by a modification of the published procedure which is commonly
applied for the optical resolution of racemic t-butylphenylphosphinothioic acid 1a with the use of
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both enantiomers of α-methylbenzylamine 52,3 (Scheme 2). As it is evident from
Table 1, all experiments in which various solvent systems were used for the formation and/or
recrystallization of the diastereomeric salts gave always a mixture in which the ratio of
diasteromers was very close to 50:50 (based on the analysis of the 31P NMR spectra in which two
singlet absorptions at 82.8; 82.4 ppm could be observed) both for samples prepared from the
precipitated oil (which turned out to a solid upon evaporation of the remaining solvent) and from
a mother liquid. Next we attempted without success to extend the list of optically active base by
the use of optically pure mono and bis amines containing a sterogenic carbon atom or alkaloids.
Table 1 lists the amines used in these experiments and the solvent systems applied. Now we are
going to check whether optically active t-butyl-1-naphthyl-phosphinothioic acid 1b could be
obtained by a modification of the recently published procedure used for the isolation of the
enantiomers of t-butylphenylphosphinothioic acid 1a based on the addition of elemental sulfur to
racemic t-butylphenylphosphine oxide in the presence of enantiomers of α-methylbenzylamine
54.( Scheme 3)
EXPERIMENTAL
The NMR spectra were recorded on a Bruker spectrometer Avance AV 200 (Bruker, Karlsruhe,
Germany) (200.16 MHz (1H), 50.30 MHz (13C), 81,03 MHz (31P)) in CDCl3. Mass spectral data
were collected on MAT95-Finnigan spectrometer (Finnigan MAT, Bremen, Germany). Optical
rotation was determined on 241 MC-Perkin Elmer polarimeter (Perkin Elmer, Vienna, Austria) at
room temperature. Melting point was determined on Betius apparatus (PHMKVEB Analytik,
Dresden, Germany) and was uncorrected. Column chromatography was performed on Merk
Silica Gel (F254 60, 270–400 mesh). Merk Silica F254 plates were used for thin layer
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chromatography and visualization was effected with UV light (254 nm). Elemental analyses
were performed in the Microanalytical Laboratory of the Centre of Molecular and Macro
molecular Studies PAS. Reactions were performed under a blanket of dry nitrogen.
Starting Materials. t-butyldichlorophosphine was synthesized by a known method5.
Preparation of racemic t-butyl-1-naphthylphosphine oxide 3b:
A
solution of
1-naphthylmagnesiumbromide was prepared by slow adding 1-naphthylbromide (52.9mL, 0.378
mol) to a suspension of magnesium chips (9.06 g, 0.378 mol) and a few crystal of iodine in
diethyl ether (300 mL) at room temperatur followed by 4 hours reflux of the reaction mixture.
The solution was cooled to -10ºC and stirred while t-butyl-dichlorophosphine (20 g, 0.126 mol))
in diethyl ether (100 ml) was added dropwise. The mixture was allowed to warm up to 0ºC. The
solution was acidified (10% HC1, 250 mL). The organic layer was separated, and aqueous layer
was extracted with chloroform (3 x 250 mL). The organic layers were combined and dried over
magnesium sulfate, filtered and evaporated under vacuum to yield a crude product which was
purified by chromatography on silica gel using diethyl ether/hexane 1:1 as eluent to give t-butyl-
1
1-naphthylphosphine oxide 3b (21.8g, 9.40 mol, 75%). Mp= 130-132ºC. H NMR (200 MHz,
CDCl3) δ: 1.19 (d, J=16.6 Hz ,9H), 7.46 (d, J=456.6 Hz, 1H), 7.49-8.06 (m, 6H), 8.69-8.73 (m,
31
13
1H),. P NMR (81 MHz, CDCl3) δ: 52.81. C NMR (125 MHz, CDCl3) δ: 24.4, 24.4,. 34.18,
34.8, 124.3, 126.6, 126.7, 127.3, 128.7, 131.6, 131.9, 133.1, 133.2. MS (CI): m/z= 223 [M+H]+.
MS (EI): m/z= 232 [M]+. Anal. Calcd. for C14H17OP: C, 72.40; H, 7.38. Found: C, 72.05; H,
7.48.
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Preparation of racemic t-butylnaphthylphosphinothioic acid 1b: A mixture of racemic
t-butylnaphthylphosphine oxide 3b (1.5g, 6.5 mmol), triethylamine (0.906mL, 6.5 mmol) and
sulfur (0,208 g, 6.5 mmol) in anhydrous benzene was heated at 60 ºC under nitrogen for 2h. The
reaction mixture was cooled to room temperature and then an aqueous sodium hydroxide
solution (10%, 20 mL) was added and the organic layer was separated. The aqueous layer was
extracted with chloroform (3 x 20 mL) and acidified with an aqueous hydrochloric acid solution
(10%) to pH 1 and extracted with chloroform (3 x 20 mL). The combined chloroform extracts
were dried over magnesium sulfate, filtered and concentrated to give a crude product as
yellowish crystals. Its crystallization from a hexane: CH2Cl2 mixture (5:1) gave pure thiacid 1b
as
white
crystals
(1.673g,
6.3
mmol,
98%).
Mp=
188-190ºC.
1H NMR (200 MHz, CDCl3) δ: 1.16 (d, J=17.86 Hz, 9H), 7.30-7.39 (m, 1H), 7.46-7.51(m, 2H),
31
7.78-7.89 (m, 2H), 8.11-8.22 (m, 1H), 9.05-9.10 (m, 1H). P NMR (81 MHz, CDCl3) δ: 99.4.
13C NMR (125 MHz, CDCl3) δ: 24.9, 37.9, 38.4, 123.9, 124.0, 125.9, 126.5, 127.2, 127.9, 128.8,
133.2, 133.3, 133.4, 133.5, 133.5, 133.8, 133.9. MS (EI): m/z= 264 [M+]. HRMS: 264.07418.
Anal.
Calcd.
for
C14H17OPS:
C,
63.62;
H,
6.48;
S,
12.13.
Found:
C, 63.78; H, 7.43; S, 12.27.
Preparation of racemic t-butyl-1-naphthylphosphinoselenoic acid 2b: A mixture of racemic
t-butylnaphtylphosphine oxide 3b (0.5 g, 2.16 mmol), triethylamine (0.30 mL, 2.16 mmol) and
selenium (0.17 g, 2.16 mmol) in anhydrous benzene was heated at 60 ºC under nitrogen for 8 h.
The reaction mixture was cooled to room temperature and an aqueous sodium hydroxide solution
(10%, 10 mL) was added. The organic layer was separated and the aqueous layer was extracted
with chloroform (3 x 10 mL) and then acidified with an aqueous hydrochloric acid solution
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(10%)
to
pH
1
and
extracted
with
chloroform
(3
x
15
mL).
The combined chloroform extracts were dried over magnesium sulfate, filtered and concentrated
to give pure t-butyl-1-naphthylphosphinoselenoic acid 2b as white solid. (0.641g, 2.05 mmol,
1
98%). Mp=168-170ºC. H NMR (200 MHz, CDCl3) δ: 1.17 (d, J=18.4 Hz, 9H), 4.9 (s, 1H),
7.15-7.54 (m, 3H), 7.81-7.98 (m, 2H), 8.17-8.29 (m, 1H), 9.12-9.15 (m, 1H). 31P. NMR (81
13
MHz, CDCl3) δ: 98.13. C NMR (125 MHz, CDCl3) δ: 25.3, 38.6, 39.8, 123.5, 123.8, 125.8,
126.5, 128.1, 128.4, 132.4, 133.3, 133.52, 133.6, 133.8, 135.6, 135.9.
MS (CI): m/z= 313 [M+H]+. Anal. Calcd. for C14H17OPSe: C, 54.03; H, 5.51. Found:
C, 54.21; H, 5.79.
Attempts at optical resolution of racemic t-butyl-1-naphthylphosphinothioic acid 1b with (-
)-(S)-α-methylbenzylamine
A portion of racemic t-butyl-1-naphthylphosphinothioic acid 1b (2.301 g, 8.7 mol) was dissolved
in anhydrous diethyl ether (8 mL) at room temperature under nitrogen and a solution of (-)-(S)-α-
methylbenzylamine (1.1 mL, 8.7 mmol) in diethyl ether (2 mL) was added. Then hexane (10
mL) was added and the resulting homogenic solution was left overnight for crystallization. The
precipitated oil was removed from a mother liquor (it turned out to a solid upon evaporation of
the remaining solvent). The salt which precipitated consisted of ca. 50 % of the diastereoisomer
1
having δ31p = 82.8 and ca 50% of the diastereoisomer having δ31p = 82.4 and the following H
NMR
spectrum
recorded
at
200 MHz in a CDCl3 solution: δ: 1.01 (d, J=16,4 Hz, 4.5 H), 1.04 (d, J=16.4Hz, 4.5 H), 1.32 (d,
J=6.8 Hz, 3H), 3.96 (q, J= 6.8 Hz, 1H), 6.81 (s, 3H), 7.05-7.21 (m, 5H), 7.40-7.47 (m, 3H), 7.80-
7.90 (m, 2H), 8.31-8.48 (m, 1H), 9.37-9.42 (m, 1H). The salt isolated from the mother liquor
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contained also an equimolar amount of the both diastereoisomers. All attempts to change this
ratio by fractional crystallizations from the solvent system given in Table 1 were unsuccessful
until now.
ACKNOWLEDGEMENTS
This project was financially supported by the National Science Center fund award based on the
decision UMO- 2011/01/B/ST5/06664 (to JD). Authors would like to thank Professor Piotr
Kiełbasiński for helpful discussions during preparation of the manuscript.
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REFERENCES:
[1] Harger, M. J. P. J. Chem. Soc. Perkin II 1978, 326-331
[2] Drabowicz, J.; Pokora-Sobczak, P.; Krasowska, D.; Czarnocki, Z. Phosphours, Sulfur Silicon
and Related Elements 2014, 189,977-991
[3] Hoffmann H., Schellenbeck P., Chem. Ber. 1966, 99, 1134
[4] a) Drabowicz, J.; Pokora-Sobczak, P.; Zajac, A.; Wach-Panfilow, P. Polish patent pending
P.405141; b) Drabowicz, J.; Pokora-Sobczak, P.; Zajac, A.; Wach-Panfilow, P. Heteroatom
Chemistry (2014, after proof reading)
[5] Karaghiosoff K. and Eckste K. in: Synthetic Methods of Organometallic and Inorganic
Chemistry: Phosphorus, Arsenic, Antimony, and Bismoth, Herrmann W.A. Ed., Vol. 3,Thieme,
1996, pp. 54-56.
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Scheme 1
Scheme 2
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Scheme 3
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Table 1
31P NMR
Solvent for
[ppm]
Base [B]
crystallization
CDCl3
C6D6
Et2O ; Et2O:Hex;
CH2Cl2:Hex;
CHCl3:Hex;
Acetone:Hex;
Et2O:C6H6
(-)-(S)-α-methylbenzylamine
82.8; 82.4
-
Et2O; Et2O:Hex;
CH2Cl2:Hex
CDCl3; C6D6
CDCl3; C6D6
CDCl3; C6D6
C6H6 : CDCl3;
CH2Cl2
(-)-(S)-1-(1-naphthyl)ethylamine
82.0
82.5
(-)-1-(2-pyridil)ethylamine
(1R, 2R)-(-)-cyclohexanediamine
(-)-ephedrine
85.6; 85.4
83.8; 83.3
84.0
85.0
84.3; 83.5
83.9
(-)-quinine
87.3
86.9
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