CS219981B1 - Process for isolating rhodium compounds from the reaction mixture after hydrogenation - Google Patents

Abstract

The invention relates to a method for isolating rhodium compounds from a reaction mixture after hydrogenation of substituted alpha-acylaminoacrylic acids, in which it is contained in the form of a complex with organic phosphines, the essence of which lies in the fact that the hydrogenation product dissolved in the reaction mixture is converted with ammonia into an ammonium salt, which is separated and the remaining solution of rhodium compounds in an organic solvent is evaporated to dryness and rhodium is obtained from the residue in a known manner.

Description

The present invention relates to a process for the isolation of rhodium compounds from a reaction mixture after hydrogenation of substituted alpha-acylaminoacrylic acids, in which it is present in the form of a complex with organic phosphines, characterized in that the hydrogenation product dissolved in the reaction mixture is converted into ammonia by ammonia. The resulting solution of rhodium compounds in an organic solvent is evaporated to dryness and rhodium is obtained in a known manner.

219931

Modern and highly efficient methods of preparing optically active α-amino acids include the asymmetric hydrogenation of substituted α-acylaminoacrylic acids on chiral 8-group transition metal complexes, particularly rhodium, with organic phosphines (Valentine D., Jr., Scott John W., Synthesis, 1978, 329 j.

However, this homogeneous catalysis presents a problem of how to isolate the used rhodium for further use.

The present invention relates to a process for the isolation of rhodium compounds from a reaction mixture after hydrogenation of substituted α-acylaminoacrylic acids of the general formula I

NHCOR "

RCH = CCOOH, (I) wherein R is H, alkyl of 1 to 4 carbon atoms, phenyl, hydroxyphenyl, dihydroxyphenyl, O-methylenedihydroxyphenyl, 3-indolyl, R 'is methyl or phenyl, on complexes of rhodium with organic phosphines of general formula Π, ř?

/ ° Y ^CH A ^R (II) wherein X is isopropylidene, cyclopentylidene or cyclohexylidene, and R is phenyl, o-, m- or p-tolyl, carried out in an alcohol having 1 to 3 carbon atoms, tetrahydrofuran or a mixture thereof with benzene or toluene.

The previously described method for removing catalyst from the product was to evaporate the reaction mixture to dryness, converting the acylated amino acid into an aqueous solution (for the low soluble amino acids in the form of their sodium salt), and isolating the undissolved rhodium complex by filtration (Kagan H., Dang T .: J. Amer Chem. Soc., 94, 6429 [1972]] However, it has been found that this isolation method is not quantitative because some of the rhodium is in a water-soluble form.

Another method for isolating the rhodium compounds is to dilute the reaction mixture with water and extract the rhodium compounds into toluene or benzene, wherein the portion of the rhodium that has passed into the aqueous layer is obtained by trapping on activated carbon or washing the sparingly soluble residue with water.

It is an object of the present invention to utilize the low solubility of the ammonium salts of α-acylamino acids in a solvent in which hydrogenation has been carried out, or even to reduce this solubility by adding another solvent. This makes it possible to remove the hydrogenation product from the reaction mixture, while all the rhodium compounds remain in solution and can be obtained by evaporating the solvent.

In the process according to the invention, the hydrogenation product is converted, for example, by introducing ammonia gas into an ammonium salt which is separated from the solution. After separation and washing, if necessary, the filtrate can be concentrated and the further precipitated salt can be isolated, or it can be separated by addition of other solvents, for example benzene, toluene, ether. Evaporate the solvent from mat. The lye is then obtained practically quantitatively with rhodium compounds.

A disadvantage of the previously described methods for the isolation of rhodium compounds from the reaction mixture after hydrogenation was, inter alia, that some of the rhodium was transferred to an aqueous layer from which it had to be isolated, for example, by trapping on activated carbon.

An advantage of the process according to the invention is that the rhodium compounds still remain in solution obtained by evaporating it in practically 100% yield.

In the following, the invention is illustrated by the following non-limiting examples.

Examples

Example 1 kg of α-acetylamino-cinnamic acid was hydrogenated in a mixture of 5 L of toluene and 10 L of ethanol with the addition of 3.5 g of [Rh (C ₂ H 4 Cl ₂ ) ₂ and 9.0 g of DIOP [1,4-bis (diphenylphosphino) -1]. 4-didesoxy-2,3-O-isopropylidene-D-threitol] 2.9 kg (57%) of optically pure N-acetyl-L-phenylalanine was obtained by aspiration.

K 10 ml mat. with stirring, ammonia gas was introduced in excess. The thick slurry formed was diluted with 5 ml of toluene, the precipitated ammonium salt was filtered off with suction, washed with 5 ml of toluene and dried. 0.886 g of ammonium salt of N-acetylphenylalanine was obtained.

The filtrate was combined with the wash solution and evaporated to dryness. 0.129 g of a yellow syrup was obtained in which 100 percent Rh contained in the original mat was found by atomic absorption flame spectroscopy. louzích.

Example 2

To 50 ml. mat. The caustic liquor of Example 1 heated to 50 ° C was treated with excess ammonia gas with slow stirring. The mixture was then left overnight in a (-) - 1 ° C refrigerator. The precipitated ammonium salt was filtered off with suction, washed with 10 ml of toluene and dried. 4.02 g of the ammonium salt of N-acetylphenylalanine was obtained.

The filtrate was combined with the wash solution and evaporated to dryness. 0.7 g of a yellow semi-crystalline residue was obtained, in which 100% of the Rh contained in the original mat was found by atomic absorption flame spectroscopy. louzích.

Example 3 g of the amino acid ammonium salt was refluxed with 10 ml of ethanol for 1 hour. After cooling, the mixture was set to 5

Ammonium salt by weight per hour to the refrigerator (-j -1 ° C). After rapid aspiration of the crystals, the amount of solute was determined by solvent evaporation and weighing, and the following solubility values were found:

g / 100 ml of solution

N-acetyl-phenylalanine * J

N-acetyl-L-alanine

N-acetyl-L-leucine * 1 The ammonium salt isolated in Example 2 was used

Example 4

Analogously to Example 3, the solubility of the ammonium salt of N-acetylphenylalanine in methanol was determined. The following values were found:

4 g / 100 ml solution.

Ammonium salt

0,9 0,7

2,2 1,8

3,2 2,6

Example 5

To a saturated solution of the amino acid ammonium salt in ethanol obtained according to Example 3, half the volume of benzene was added and the mixture was left in the refrigerator (+ 1 ° C) for 5 hours. The crystals were collected and the amount of solute was determined by evaporation and weighing in the solution. The following solubility values were found:

g / 100 ml of solution

N-acetyl-L-alanine 1.3 L

N-acetyl-L-leucine 1.5 1.2

Example 1 a d 6

Analogously to Example 5, the solubility in methanol-benzene 2: 1 (v / v) was determined:

Ammonium salt% by weight g / 100 ml solution

N-acetyl-phenylalanine Example 7

0.5 g of ammonium salt of N-acetyl-L-alanine was dissolved in 5 ml of methanol, the solution was diluted with 2.5 ml of ether and left overnight

2.7

2.2 in the fridge. A sample of liquid was taken from the precipitated crystals and the amount of solute was determined. The following values were found: 4 wt%, 3.3 g / 100 ml solution.

Claims (1)

Subject Process for the isolation of rhodium compounds from the reaction mixture after hydrogenation of the substituted .alpha.-acylaminoacrylic acids of the general formula I NHCOR ¹ RCH = CCOOH, (I) wherein R is H, alkyl of 1 to 4 carbon atoms, phenyl, hydroxyphenyl, dihydroxyphenyl, O-methylenedihydroxyphenyl, 3-indolyl, R 'is methyl or phenyl, on chloride complexes with organic phosphines of formula II OF THE INVENTION wherein X is isopropylidene, cyclopentylidene or cyclohexylidene, and R is phenyl, o-, m- or p-tolyl, carried out in an alcohol having a carbon number of 1 to 3, in tetrahydrofuran, or in a mixture thereof with benzene or toluene, The process of claim 1 wherein the hydrogenation product dissolved in the reaction mixture is converted with ammonia to the ammonium salt, after separation of the precipitated salt, a solution of the rhodium compounds in an organic solvent is obtained.