Organic compounds -- part of the class 532-570 series – Organic compounds – Phosphorus containing
Reexamination Certificate
2001-01-12
2003-10-14
Vollano, Jean F. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Phosphorus containing
C556S012000
Reexamination Certificate
active
06632969
ABSTRACT:
The present invention relates to a process for separating the (d/l) and (meso) diasteroisomers of bis-[1-phospha-2,3-diphenyl-4,5-dimethyinorbornadiene].
The invention also relates to a preparation process for optically active diphosphines of bis-[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene].
The preparation of a mixture of diasteroisomers of bis-[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene] has been described by F. Mathey et al, in Bull. Soc. Chim. Fr. 129, pp. 1-8 (1992).
The starting product of the synthesis of this is 1-phenyl-3,4-dimethylphosphole (II) described by F. Mathey et al, in Synthesis, 1993, pp.983.
The operation starts by preparing 3,3′,4,4′-tetrarethyl-1,1′-diphosphole-(IV). To that end 1-phenyl-3,4-dimethylphosphole (II) in THF is reacted with lithium metal according to the following reaction:
At the end of the reaction aluminium chloride is introduced to trap the phenyllithium produced during the reaction.
In a following stage, the dimerization of (II) is carried out by the action of diiodine I
2
in THF. For further details on the preparation of (IV) the article by F. Mathey et al, Organometallics, 1983, 2, 1234 can be referred to.
By heating at about 140° C., compound (IV) rearranges to (V) which reacts with diphenylacetylene according to Diels-Adler, in order to produce bis-[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene].
A practical embodiment is given on page 6 of the publication by F. Mathey et al, in Bull. Soc. Chim. Fr. 129, pp. 1-8 (1992).
However, as mentioned on page 3, right-hand column, lines 7 and 8, the authors obtained a mixture of two diasteroisomers, subsequently identified by the Applicant as being a meso (Im)—RS,SR—and a racemic (Ir)—RR,SS—called (13b) and (13a) respectively in the article.
The publication mentions the separation of the two diastereoisomers by the formation of a palladium (II) chelateo. In order to do this, the separation of the mixture of diastereoisomers obtained is described, by reaction with PdCl
2
(PhCN)
2
in dichloroethane leading to (VIm) and (VIr), separation by chromatography on silica gel followed by elution, then decomplexation carried out with NaCN.
Therefore, the two diastereoisomers are recovered separately, on the one hand meso (Im) and on the other hand the racemic (Ir).
The process described above allows separation of the diastereoisomers but it is currently difficult to use on an industrial scale as the palladium complex is expensive.
The purpose of the present invention is to make available a more economical process for the separation of the diastereoisomers.
It has been found that the (d/l) and (meso) diastereoisomers of bis-[1-phospha-2,3-diphenyl-4,5-dimethyinorbomadiene] can be separated according to a process which consists of converting the mixture of diastereoisomers of bis-[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene] to a mixture of diastereoisomers of the corresponding diphosphine dioxide or disulphide, then separating the two diastereoisomers in the form of the dioxide or disulphide.
According to a first variant of the invention, the separation of the diastereoisomers of the bis-[1-phospha-2,3-diphenyl-4,5-dimethylnorbomadiene]dioxide obtained is carried out by subjecting the mixture of diastereoisomers of bis-[1-phospha-2,3diphenyl-4,5-dimethylnorbornadiene] to an oxidation reaction thus convert them to bis-[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene]dioxide.
Another variant of the invention consists of carrying out the separation of the diastereoisomers of the bis-[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene]dioxide obtained by reacting the mixture of diastereoisomers of bis-[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene] with sulphur leading to a mixture of diastereoisomers of the bis-[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene]disulphide.
Dioxides of Diphosphines in Meso or Racemic Form
Another object of the invention is the dioxides of bis-[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene] in meso or racemic form as well as the process for obtaining them.
According to a first operation, the diastereoisomers are converted into oxide form.
They can be symbolized by the following formula:
The oxides of diphosphines of formula (IX) are obtained by oxidation of the two diastereoisomers of formula (Im) amd (Ir) using an oxidizing agent.
Although any type of oxidizing agent can be used, a chemical oxidizing agent, for example potassium permanganate or molecular oxygen or a gas containing it, it is preferable to use hydrogen peroxide, preferably, in the form of an aqueous solution.
The concentration of the hydrogen peroxide solution is advantageously comprised between 10% and 35% by weight.
The quantity of oxidizing agent used can vary widely from the stoichiometric quantity up to an excess representing for example 20 times the stoichiometry.
An organic solvent can be used which solubilizes all the reagents. The solvent can be chosen from aliphatic, cyclo aliphatic or aromatic hydrocarbons, preferably aromatic hydrocarbons. Examples are given below.
Among all these solvents, toluene and the xylenes are preferred.
The concentration of diphosphine in the reaction solvent is preferably between 0.05 and 1 mole/litre and yet more particularly between 0.05 and 0.2 mole/litre.
Thus the diastereoisomers which are generally dissolved in a suitable solvent are brought into contact with the oxidizing agent.
The reaction is advantageously carried out between 50° C. and 100° C.
The duration of the reaction is generally between 30 minutes and 4 hours.
The oxides of diphosphine are recovered from the organic phase.
The aqueous and organic phases are separated.
A standard treatment of the phases is carried out.
Thus the aqueous phase is washed several times (from 1 to 3) with an organic solvent for extraction of the diphosphine oxides, for example ethyl ether.
All the organic phases are collected and they are washed with salt water (saturated solution of sodium chloride) then a usual drying operation is preferably carried out, over a desiccating agent for example sodium or magnesium sulphate.
In a following stage, the oxides of the two diastereoisomers are separated.
The solvent is concentrated by evaporation, then the separation is carried out in a known manner [A. Bertheillier—Dunod Paris (1972)] by liquid chromatography on a column, preferably with a silica support.
The column is eluted with a mixture of suitable solvents.
The solvents suitable for the separation are determined, by simple execution operations for a person skilled in the art which consist of carrying out a chromatography on a silica plate.
The solvents are generally chosen from ethyl acetate, methanol, ethyl ether or their mixtures.
Therefore, depending on the case, the diphosphine dioxide is meso form (IXm) and the diphosphine dioxide in racemic form (IXr) are recovered in a variable order, in the elution solvents.
Disulphides of Diphosphines in Recemic or Meso Form
Another object of the invention is the disulphides of bis-[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene] in meso or racemic form as well as the process for obtaining them.
It has also been found that the diastereoisomers can be separated according to a process which consists of reacting the mixture of diastereoisomers (Im) and (Ir) with sulphur, thus converting them to diphosphine disulphide (IX′m) and (IX′r), then separating the two diastereoisomers of the diphosphine disulphides.
According to a first operation, the diastereoisomers are converted into sulphide form.
They can be symbolized by the following formula:
Therefore, sulphur (S
8
) is reacted with the mixture of the two diastereoisomers in meso form (Im) and in racemic form (Ir) leading to a mixture of the disulphides of diphosphines, in meso or racemic form.
Generally, the quantity of sulphur used defined relative to each phosphorus atom varies from the stoichiometric quantity up to a slight e
Mathey Francois
Mercier Francois
Robin Frederic
Spagnol Michel
Rhodia Chimie
Vollano Jean F.
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