CS225428B1 - Preparation of 1,4-bis(diarylphosphine)-2,3-0-isopropylidene-2,3-dihydroxybutane - Google Patents

Description

The present invention relates to a process for the preparation of 1,4-bis (diarylphosphino) -2,3-O-isopropylidene-2,3-dihydroxybutane of the general formula:

Wherein Ar is phenyl or tolyl.

Phosphine complexes of this type of threo configuration with a transition group of the 8th group, especially rhodium, are very efficient catalysts for asymmetric hydrogenation of substituted (.alpha.-acylaminoacrylic acids, providing optically pure amino acids. Valentine D., Jr., Scott John W. Synthesis 1978, 329

The methods of preparation of the compound I so far described are based on the substitution reaction of the p-toluenesulfonate of the corresponding tetritol derivative with the appropriate alkaline diaryl phosphide prepared in situ, and differ in the method for preparing the phosphide and the environment in which the reaction is carried out. Following the procedure of Kagan and Danga / Kagan H., Dang T .: J.Amer.Chem.Soc. 94. 6429 ZL972 // Prepare 1,4-bis (diphenylphosphino) - (2R, 3R) -2,3-O-isopropylidene-2,3-dihydroxybutane by reacting diphenylchlorophosphine with finely divided sodium in boiling dioxane to prepare a sodium diphenylphosphide suspension which, after addition of tetrahydrofuran, is reacted with 1,4-di-O-tosyl-2,3-O-isopropylidene-L-threitol dissolved in tetrahydrofuran to increase its solubility. Similarly, the opposite antipod is prepared by Czech authors / Červinka 0., Pábryová A., Gajewski K., Lukáč J .: čsl. aut. osv. 201352 /. Murrer et al. / Murrer B.A. et al., Synthesis 1979. 350) prepare potassium diphenylphosphide by the reaction of triphenylphosphine

A solution of 1,4-di-O-tosyl-2,3-O-isopropylidene-L-threitol in toluene is then added to the slurry of sodium and potassium in dioxane and to its suspension.

A disadvantage of the above processes is that they use an excess of alkali metal / or to prepare the alkali diphenylphosphide. its alloy), which after reaction remains in the reaction mixture in the form of a fine suspension and is removed together with salts by filtration or centrifugation. This poses a significant risk in terms of occupational safety. The reaction mixture is usually poorly filterable and a fine alkali metal suspension together with a solvent that is; is a serious fire hazard. In the small-scale preparation, it is also possible to carry out inert filtration, and the disposal of the alkali metal in the filter cake will also not cause great difficulty, but on the scale; the risk is too great without the use of a special apparatus.

The above disadvantage has no process according to the invention. It is based on the fact that upon completion of the reaction, the excess alkali metal is removed by conversion to the alcoholate by addition of alcohol.

The process according to the invention brings a considerable increase in the safety of work and facilitates the technological implementation of the synthesis, since it allows work on conventional equipment. It does not adversely affect either the yield or the quality of the product.

The process according to the invention is such that when the synthesis is carried out in water-soluble solvents (dioxane, tetrahydrofuran), the reaction mixture is evaporated after dissolution of the metal by addition of an alcohol to dryness, the product is converted into a water-miscible solvent such as benzene or toluene. , and salts and alkalis are removed by washing with water. When the reaction is carried out in an aromatic solvent, after the alkali metal has been dissolved by addition of alcohol, water is added directly to the reaction mixture, and after stirring and phase separation, the organic layer is separated and washed with water until neutral. The solutions are then dried, concentrated and the product recrystallized.

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In the following, the invention is illustrated in more detail by way of example without being limited thereto.

Example 1

A mixture of 150 ml of dioxane, 26.4 g of diphenylchlorophosphine and 11.5 g of sodium was refluxed under vigorous stirring for 7 hours after cooling vigorously. Anhydrous tetrahydrofuran (100 mL) was added, a solution of 1,4-di-O-tosyl-2,3-O-isopropylidene-D-threitol (21.1 g) in tetrahydrofuran (5.0 mL) was added dropwise with stirring, and the mixture was stirred for 2 hours. Then 70 ml of methanol was added dropwise to the mixture. When the sodium dissolved, the mixture was concentrated and the slurry was shaken with 200 mL benzene and 80 mL water. The separated benzene layer was then washed with portions of 80 ml of water until the aqueous phase had no alkaline reaction. The benzene solution was dried over sodium sulfate, evaporated, and the residue recrystallized from ethanol. 13.9 g (62%) of 1,4-bis (diphenylphosphino) (2S, 3S) -2,3-0-isopropylidene-2,3-dihydroxybutane, m.p. Mp 86-88 ° C. Pour. indicates for the antipod m.p. 88-89 ° C / Kagan H., Dang T .: J.Amer.Chem. Soc. 94, 6429 (1972)].

Example 2

The reaction was carried out under nitrogen. To a mixture of 1050 ml of toluene and 81 g of sodium heated to boiling, a solution of 187.5 g of diphenylchlorophosphine in 300 ml of dry toluene was added dropwise with vigorous stirring. The reaction mixture was then heated to reflux for 6 hours with stirring. After cooling, a solution of 150 g of 1,4-di-O-tosyl-2,3-O-isopropylidene-D-threitol in 1050 ml of toluene was added dropwise with stirring so that the temperature did not exceed 30 ° C. After the addition, the mixture was stirred for a further 2 hours and then 300 ml of methanol was added dropwise so that the temperature did not exceed 30 ° C. When sodium dissolved and the evolution of hydrogen ceased, 750 ml of water was added in portions, stirring was discontinued, the toluene layer was separated and washed 3 times with 750 ml of water. After drying over sodium sulfate, evaporation and crystallization, 112 g (70%) of 1,4-bis (diphenylphosphino) - (2S, 3S) -2,3-O-isopropylidene-2,5-dihydroxybutane of m.p. Mp 86-88 ° C

-4 Example 5

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The same procedure as in the example. 2, only to decompose the reaction mixture, ethanol was used instead of methanol. The yield and product quality remained unchanged.

Claims (3)

1. A process for preparing l, 4-bis. / Diarylfosfino / -2,3-0-isopropylidene-2,3-dihydroxybutanedioic formula I, ch ₅ and _C-5 CK ₂ PAr ₂ CH ₂ PAr ₂ A), wherein Ar is phenyl or tolyl, by reacting the corresponding phosphine with an excess of an alkali metal to form the corresponding diarylphosphide of formula Ar ₂ PMe, wherein Ar is as defined above and Me is a sodium or potassium atom which upon reaction with a sulfonate of formula II GH ₅ CH ₂ X / 11 /. Wherein X is a group of GglI4SO4 or CH2Cl2H4SO4 to give a compound of formula I, wherein the resulting reaction mixture containing an excess of alkali metal is treated with an alcohol having a carbon number of 1 to 3. 2. Process according to claim 1, characterized in that after the reaction of the diaryl phosphide with the sulfonate of the general formula (II) carried out in an aromatic solvent medium, the reaction mixture is shaken with water after addition of alcohol and the two layers are separated. 3. A process according to claim 1, characterized in that after the reaction of the diaryl phosphide with a sulfonate of the general formula II taking place in an environment of water-immiscible solvents, the reaction mixture is concentrated after addition of alcohol and the residue is evaporated between water and benzene or toluene.