Synthesis of α-aminophosphine oxides with chiral phosphorus and carbon atoms

Article abstract of DOI:10.1080/10426507.2010.524181

Lipophilic α-aminophosphine oxides are good extractants for liquid and membrane extraction. Optically active α-aminophosphine oxides, containing chiral centers in their structure, can provide selective means for transfer of stereoisomers through supported liquid membranes. We have developed a method for synthesis of such carrier compounds based on a three-component Kabachnik-Fields reaction. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426507.2010.524181

This article was downloaded by: [McGill University Library]
On: 27 November 2012, At: 04:01
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the
Related Elements
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gpss20
Synthesis of α-Aminophosphine Oxides
with Chiral Phosphorus and Carbon
Atoms
Rafael A. Cherkasov a , Airat R. Garifzyanov a & Sergey A. Koshkin a
a A. M. Butlerov Chemical Institute, Kazan University, Kazan, Russia
Version of record first published: 25 Apr 2011.
To cite this article: Rafael A. Cherkasov, Airat R. Garifzyanov & Sergey A. Koshkin (2011): Synthesis of
α-Aminophosphine Oxides with Chiral Phosphorus and Carbon Atoms, Phosphorus, Sulfur, and Silicon
and the Related Elements, 186:4, 782-784
To link to this article: http://dx.doi.org/10.1080/10426507.2010.524181
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Phosphorus, Sulfur, and Silicon, 186:782–784, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.524181
SYNTHESIS OF α-AMINOPHOSPHINE OXIDES WITH
CHIRAL PHOSPHORUS AND CARBON ATOMS
Rafael A. Cherkasov, Airat R. Garifzyanov,
and Sergey A. Koshkin
A. M. Butlerov Chemical Institute, Kazan University, Kazan, Russia
Lipophilic α-aminophosphine oxides are good extractants for liquid and membrane extraction.
Optically active α-aminophosphine oxides, containing chiral centers in their structure, can
provide selective means for transfer of stereoisomers through supported liquid membranes. We
have developed a method for synthesis of such carrier compounds based on a three-component
Kabachnik–Fields reaction.
Keywords α-Aminophosphine oxide; chiral phosphorus atom; Kabachnik–Fields reaction;
membrane extraction; stereoselective membrane transport
INTRODUCTION
The increased interest in α-aminophosphine oxides is caused by their well-defined
complexation abilities. These properties and hydrolytic stability of α-aminophosphine
oxides allow them to be used in the processes of liquid and membrane extraction of
both inorganic and organic substrates. Supported liquid membranes containing chiral
α-aminophosphine oxides can provide stereoselective transport of optically active organic
substrates.
RESULTS AND DISCUSSION
We have developed a technique for synthesizing of α-aminophosphine oxides and
derivatives containing chiral phosphorus and carbon atoms, based on the three-component
Kabachnik–Fields reaction of formaldehyde, phosphinic acids, and amines or amino acids
(Scheme 1). Formaldehyde was used in excess of 5%.
The introduction of chiral centers in the resulting α-aminophosphine oxides was
achieved by application of reagents that contained asymmetric phosphorus and carbon
atoms: (R)-, (S)-1-phenylethylamines, (S)-alanine, and racemic phenyldecylphosphinic acid
(only for compounds 5 and 6) in the Kabachnik–Fields reaction.
Syntheses were performed in suitable solvents (toluene for amines and acetonitrile for
the amino acid) under reflux and were catalyzed by p-toluenesulfonic acid. These conditions
Received 7 July 2010; accepted 9 September 2010.
Address correspondence to Rafael A. Cherkasov, A. M. Butlerov Chemistry Institute, Kremlevskaya 18,
Kazan 420008, Russian Federation. E-mail: Rafael.Cherkasov@ksu.ru
782

SYNTHESIS OF α-AMINOPHOSPHINE OXIDES
783
O
P
R2
H
H
NH2
R4
O
H
H
cat.
N
R4
O
P
*
+
+
*
R1
- H2O
*
R3
*
R1 R2
R3
R1
R2
R3
R4
Ph
1
Me
2
3
4
n-C10H21
n-C8H17
n-C10H21
n-C8H17
Me
Me
Ph
Ph
COOH
Me
5
6
n-C10H21
n-C10H21
Ph
Ph
COOH
Me
N
CHR3R4 =
Scheme 1
allowed us to obtain α-aminophosphine oxides in high yield. The structure of the products
was confirmed by 1H and 31P NMR spectroscopy. The yield and selected physicochemical
data of final α-aminophosphine oxides are presented in Table 1.
Separationofanenantiomerof P-phenyl-P-decyl-N-2-pyridineaminometylphosphine
oxide (compound 6) was performed by crystallization of its diastereoisomeric salt with
D-tartaric acid. As the result, laevorotatory scalemic aminophosphine oxide 6 was obtained.
Table 1 Yields and properties of α-aminophosphine oxides
b
+c
pKBH
Compound
Yield [%]
31P NMR [ppm] δa
Mp [◦C]
Rf
(R)-1
(S)-1
(R)-2
(S)-2
(S)-3
(S)-4
(S)-5
(−)-6
93
92
94
95
95
51
64
88
50.9 (chloroform)
50.8 (chloroform)
43.9 (toluene)
43.9 (toluene)
49.1 (toluene)
52.4 (acetonitrile)
32.1 (metanol)
40.5 (chloroform)
99
99
47
47
—
172
—
—
0.46
0.47
0.64
0.65
0.58
0.26
0.41
0.47
4.35
4.35
4.13
4.13
4.65
aExternal reference 85% H3PO4.
bEluent chloroform/acetone/methanol (3.6:3.7:0.7), Silufol UV-254.
cрKBH+ was determined in the propanol-2 water system (1:1).

784
R. A. CHERKASOV ET AL.
Membrane extraction of tartaric acids through supported liquid membranes (teflon
porous matrix with a pore diameter of 0.6 mkm saturated, 0.1 M solution of car-
rier α-aminophosphine oxide in phenylcyclohexane) was studied for (R)-didecyl-N-1-
phenylethylaminometylphosphine oxide (compound (R)-2). The difference between flow
rate transfer of L-tartaric acid (40.40 × 106 mol/min × m2) versus the D-form (13.95 ×
106 mol/min × m2) through the membrane demonstrates the stereoselectivity of transport.
Such stereoselectivity is probably a consequence of formation of diastereomeric complexes
of α-aminophosphine oxide with substrates of different stability. The results indicate that
(R)-didecyl-N-1-phenylethylaminometylphosphine oxide can be used for stereo enrichment
of tartaric acid.