CS208483B2 - Method of asymetric hydrogenation - Google Patents

Abstract

For the asymmetrical hydrogenation of prochiral ethylenically unsaturated compounds, a catalyst is proposed which is a transition metal cationic complex immobilized in or on a clay-like mineral, for example hectorite bentonite and haloysite. The transition metal of the cationic complex is preferably rhodium.

Description

(54) Asymmetric Hydrogenation Method

BACKGROUND OF THE INVENTION The present invention relates to a process for the asymmetric hydrogenation of alpha-derivatives of acetaminocoic acid and acetamino-octylic acid by hydrogen to form transition metal complexes. bound in clay minerals.

The review of the technical literature of recent years has shown considerable interest in the use of an asymmetric catalyst system for the preparation of optically active compounds by hydrogenation, hydrililylation, and hydroforming.

In the hydrogenation of α-acylcidockrylic acid, e.g. catalysed by the oral β-hydroxycyclopropylmethylphosphonium rhodium complexes, optical yields of up to 95-96% are reported, which are in fact close to those verified by enzymatic processes.

The use of homogeneous catalysts is associated with a large number of seed problems, including the reaction product separation and catalyst regeneration. This is particularly difficult when traces of catalyst remain in the reaction product. To overcome these ranges, the homogeneous catalyst is converted to insoluble. The metals are not bonded to a substrate which is predominantly organic in nature.

The polymer most commonly used is polystyrene, which is crosslinked with divinylbenzene and nationalized by bonds to which the transition metal is coordinated.

Also copolymers of equally nationalized polystyrene are used.

The method of asymmetric hydrogenation of acetaminocin cinnamic acid acetacetyl acrylic alpha derivatives is characterized in that it is a derivative. at a temperature in the range of -70 to +200 ° C and a hydrogen pressure of up to 19.613 MPa with the catalyst comprising the cationic rhodium complex and the amine derivatives of phosphorus bound to silicas, and the reaction is carried out at a molar ratio of substrate to catalyst of 10- 10 000.

In the process according to the invention, clay minerals, in particular of the smectite and kaolin classes, are used as a substrate for homogeneous catalysts of asymmetric hydrogenation reactions.

Sectects are film-forming cells whose structural unit consists of a tetrahedron layer, an octahedron layer and a dc tetrahedron layer with a charge of the layer of 0.25 to 0.60 per unit unit due to isomorphic substitution which is divided into layers of tetrahedron and octahedron; this charge is compensated for by the easily replaceable meta-layer of catioots. This exchange capacity is relatively high and varies between 80 and 150 ρΙ ^ ι ^^ ι ^ ο ^ per 100 g.

In addition, some clay-type minerals in the serpentine kaolin group, such as halloysite, which contain various mioois waters and have an exchange capacity of 40 milliequivalents per 100 g, are of particular interest.

The catalysts of the present invention are obtained by a simple exchange reaction between the transition metal complex and the clay material.

This catalytic system has a considerable advantage in a simple way. and at low cost, especially when compared to conventional heterogeneous systems using modified organic polymeric malaria.

A calioot complex that is catalytically effective in asymmetric. the hydrogenation reaction may be selected from those having the formula PR ^ d ^ Ry ^ -x '.

The catalysts of the invention may be used in the form of a fine powder or granulated or may have any shape suitable for the contacting procedure.

The asymmetric reduction process is carried out at a temperature in the range of -70 to + 200 ° C, preferably in the range of 0 to 50 ° C, at a hydrogen pressure of 19.613 MPt, preferably in the range of 0.098 to 0.490 Mo, and at a molar ratio of substrate to catalyst. between 10 and 10,000.

Some operative ^ β? 810ιι18ΗΟ is described in the following examples, which illustrate the invention without limitation.

Peak la dl

In 1 g ^ Orita pulverized in anhydrous рр ^ · оЬ ос slurry exchange was carried out over rhodium to OOC ^ Sahoo rovoov ^ahy for pouHtí ^0.475 g ^{of [Rh COD} Ь] * ^с 1 ° 4 in ⁵⁰ ml methanol.

COD = cyclooctyl: L = N-N'bii (R (+) and C 1-6 alkylcellyl) -N-N'bis (difecolloophioo) cryodiamine.

Hekritrite has an intense yellow color and is thoroughly washed with anhydrous methanol and then dried. The rhodium content is 1.6% hmmt.

This compound is sized in an anhydrous slurry and hydrogenated in an autoclave at a hydrogen pressure of 1.961 MPc; A dark red product is obtained which has the characterization of a rhodium (II) hydride hydride which is used in the hydrogenation of α-acelmiodic acid.

The glass bottle is charged with 0.942 g of substrate in 25 ml of anhydrous liquid and 0.450 g of pre-hydrogenation catalyst. Bottle sweat connects oc hydrogenation device, working! under atmospheric pressure.

The progress of the reaction is checked by a conventional pressure recording method. After 8 hours, the reaction is stopped, the catalyst is filtered off and the solution is evaporated to dryness. The product characterized by meagetic resonance spectrography was R R - ^ + J J JEEEEEEEE R R R R R;;;

^[a] p = ^{0 21,} 5 ^(c = 1 ^b EZV. ethanol).

Examples 2-6

The hydrogenation of the aliaacetamino cinnamic acid is carried out with the shielded catalyst as in the previous example; the data obtained are given in Table 1.

The catalyst was recovered after each cycle by filtration of the reaction mixture, washed with anhydrous ethanol, and reused under the same conditions.

Table 1

Cycles M s ^ t ^ add% Reaction time h M 1% dec. ethanol % e 1 4.4 2 +0,170 37 2 4.4 20 May +0,218 47 3 4.3 20 May +0,230 50 4 4.3 4 +0,144 31 5 4,5 20 May +0,184 40

Catalyst: Hectorite (Rh COD L) g = 0.510

Substrate: alpha-acetimine squaric acid

Pressure: 1,961 MPa Hg

Temperature: ° C at 23 ° C

Ronporbtoo: anhydrous canol

Examples 7-12

The HeCtorit was treated with an acetone acid solution to dilute the direct carbonate and then washed thoroughly with water until the wash water was depleted. The catalyst was prepared as described in the previous example.

Table 2 shows the data obtained in the subsequent reduction of .alpha.-acetacaoinracrylic acid.

Table 2

Cycles H s ^ t ^ s ^ shrink% Editorial time h ‘ W c = 1, HgO % e «e. 1 1.9 1,1 / 2 -0.355 53 2 2,0 1, 1/4 -0.425 64 3 2,0 1.0 -0430 65 4 2,0 1,3 / 4 -0.440 66 5 2.1 1, 1/4 -0.437 66 6 2,0 2.1 / 2 ..... -0.41 2  62

208483 4

Alpha-acetminoacrylic acid ogenation

Catalyst: Hektooite (Rh COD. L) g 0.550

Room temperature: 23 ° C

Pressure: 0.098 MPa H ₂

Solvent: anhydrous ethanol

Example- 13

Using the catalyst prepared in Example 7, 0.725 g of 3-acetoxy, 4-methoxy, .alpha.-acetaminotrimic acid dissolved in 25 ml of anhydrous metrool was reduced. The reaction is carried out in a glass autoclave at a room temperature and a hydrogen pressure of 20 psig. 3-Acetoxy, 4-methoxyl, N-aaethylphenylalanine is obtained in an optical yield of 58%.

^{Mp 2} = ⁺¹ 2.8 (c = ¹ , acetone);

[ "] ^{P 2 (c} = ^1> aceten) enanttemei ^ tcetax pure ^3-yl, 4-methoxy- N -acetyl ^f enyltlaninu to 22.

Hiles 14-18

The following examples show the data obtained. (Table 3) in asymmetric hydrogenation assays using a catalyst obtained by binding rhodium cation complex to bentonite. The catalyst was prepared as described in Example 1. Reduction cycles were performed as in Example 2.

Table 3

Cycles Subst "substrate% Reaction time h []] C = 1, H ₂ 0 % e. e. 1 1.95 3 -0.272 41 2 1.95 6 -0.348 52 3 1.95 8 -0.375 56 4 2,0 10 -0.352 53 5 2,0 24 -0.416 62

Hrdrogenation of alpha-acetinacryloyl acid

Caaayzator: Bmtonite (Rh COD L) g 0.450

23 ° C

Pressure: 0.1 MPa

Diluent: anhydrous ethanol

Examples 19-21

The data collected in the reduction reactions using the catalyst obtained by binding the rhodium cation complex to the haite site is given here. The catalyst was prepared as described in Example 1. Reduction cycles were performed as described in Example 2.

Table 4

CyikLy [c], substrate% Resak & other time h []] C = 1, H ₂ O % e. e. 1 1,8 3 -0.495 74 2 2,0 3 -0.515 77 3 2,0 24 -0,500 75

Hydrogenation of alpha-acetminoacrylic acid

Catalyst: Haioyelt (Rh COD L) g 0.500

Local temperature: 23

Hydrogen pressure: 0.098 MPa

Ro-surfactant: anhydrous ethanol

Claims (1)

SUBJECT OF THE INVENTION A process for the asymmetric hydrogenation of acetamino cinnamic acid and acetaminoacrylic acid α-alpha derivatives by contacting the derivative at a temperature between -70 to +200 ° C and a hydrogen pressure of up to 19.613 MPa with a rhodium cationic complex catalyst with amine derivatives of phosphorus bound to and the reaction is carried out at a molar ratio of substrate to catalyst of between 10 and 10,000.