Optically active phosphine oxide carboxylic acid and method...

Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acids and salts thereof

Reexamination Certificate

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C562S512000, C562S553000, C562S579000

Reexamination Certificate

active

06177591

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to an optically active phosphine oxide carboxylic acid and the method of producing the same. The phosphine oxide having its asymmetric center at a phosphorus atom is a compound especially useful as a precursor of an optically active phosphine compound which may be used as a ligand of an asymmetric synthesis catalyst.
2. Description of the Prior Art
The oldest known method of producing an optically active phosphine oxide is by reacting an &agr;-bromocamphor sulfonic acid to a methyl ethyl phenyl phosphine oxide, the produced salt being separated and crystallized, and then treated by ammonia to obtain an optically active phosphine oxide. (J. Meisenheimer, L. Lichtenstadt, Ber., 44, 356 (1911)).
The above-mentioned method utilizes the difference in the solubility of a diastereomer generated by the acidic of the camphor sulfonic acid and the basic of the phosphine oxide. However, since a camphor sulfonic acid (camphor) which is a natural product is used as the separating agent, there is a drawback that camphor with sufficient purity may not be obtained when isolating the same from natural products.
Therefore, another known method of obtaining an optically active phosphine oxide comprises the following steps. A thionyl chloride and an optically active 1-menthol is reacted under the existence of a triethylamine to a phosphinic acid of a different alkyl group such as a methylphenyl phosphinic acid, so as to obtain a diastereomer salt of a menthyl methyl phenyl phosphinate. The salt is separated and crystallized, and treated by base to obtain an optically active menthyl methyl phenyl phosphinate. Moreover, an optically active phosphine oxide is also known to be obtained by reacting a Grignard reagent. (Homogeneous Catalysis II, Adv. Chem. Ser., No. 132,274 (1974)).
This method utilizes an equivalent stoichiometric amount of 1-menthol which is an asymmetric source, and introduces the same by a covalent bond to a phosphinic acid which is a reaction substrate. However, this method uses a large amount of expensive asymmetric source, and moreover, the portion of the asymmetric source introduced by the covalent bond after the reaction must be removed and collected by a chemical process of some kind. Therefore, such asymmetric reaction may be used for a compound having high additional values such as a prostaglandin, but is not practical as a general industrial process.
SUMMARY OF THE INVENTION
Upon careful study of the conventional problems, the present inventors discovered and completed a most reasonable method to obtain an optically active compound having various compositions, which is an optical resolution method utilizing the solubility of the diastereomer salt. The present invention utilizes an optically active amine which may be easily obtained and is not expensive, such as 1-phenylethylamine, and uses a phosphine oxide carboxylic acid of a racemic modification, in order to obtain an optically active phosphine oxide carboxylic acid easily.
The optically active phosphine oxide carboxylic acid according to the present invention is a novel compound, and the method of producing such compound is also novel.
The object of the present invention is to utilize a reagant for optical resolution which may be easily obtained and is not so expensive, in order to provide a novel optically active phosphine oxide and the method of producing the same through a simple procedure.
The present invention provides the following:
An optically active phosphine oxide carboxylic acid shown by the following general formula (1):
(in the formula, R
1
and R
2
represent a linear or branched alkyl group, hydroxyalkyl group or aminoalkyl group with 1-18 carbons, or a substituted or non-substituted phenyl group, wherein R
1
and R
2
differ from one another, and A represents a linear or branched alkylene group).
Moreover, the present invention provides the following:
A method of producing an optically active phosphine oxide carboxylic acid, wherein an optically active 1-phenylethylamine is reacted to a phosphine oxide carboxylic acid of a racemic modification shown by the following general formula (2):
(in the formula, R
1
, R
2
and A represent what are defined above), and a produced diastereomeric salt is separated using the difference in solubility against a solvent which is subsequently decomposed by acid, so as to free and separate an optically active phosphine oxide carboxylic acid.


REFERENCES:
patent: 3770513 (1973-11-01), Wystrach
patent: 4983756 (1991-01-01), Lukas et al.
CA:122:10116 Tetrahedron Lett by Kielbasinski 35(38) pp. 7081-7084, 1994.
CA:103:196510 Tetrahedron Lett by Imamoto 26(6) pp. 783-786, 1985.
Chemistry Letters by Sugiya No. 6 pp. 479-480, 1998.
CA:82:43518 Zh Obshch Khim 44(10) pp. 2125-2129 by Aleksandrova, 1974.

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