WO1997044304A1

WO1997044304A1 - Process for the catalytic hydrogenation of terpenoids

Info

Publication number: WO1997044304A1
Application number: PCT/EP1997/002525
Authority: WO
Inventors: Ernst Bayer; Wilhelm Schumann; Sebastian Erber; Klaus-Peter Stengele
Original assignee: Nigu Chemie Gmbh
Priority date: 1996-05-20
Filing date: 1997-05-16
Publication date: 1997-11-27
Also published as: AU2956797A; EP0901455A1; DE19620171A1

Abstract

The description relates to a process for the catalytic hydrogenation of terpenoids with water in the presence of a transition metal catalyst, in which the hydrogenation is performed in the homogenous phase in the presence of a catalyst consisting of a reaction product of transition metals of the eighth sub-group and polymer compounds selected from the group polyvinyl pyrrolidone (PVP), polyethylene imine (PEI) derivatives or starch derivatives. It is possible in this way pratically quantitatively to hydrogenate the terpenoids in a careful manner.

Description

Process for the catalytic hydrogenation of terpenoids

description

The present invention relates to a process for the catalytic hydrogenation of terpenoids in the presence of a transition metal catalyst in a homogeneous phase.

Due to their natural occurrence and the associated physiological harmlessness, terpenoid compounds play an increasingly important role, for example in the food, luxury food or cosmetics industries.

Despite the generally satisfactory properties, these substances have certain disadvantages in certain areas of application, which are attempted to be overcome by special chemical modification. Examples of this are hop ingredients such as humulones, isohumulones or lupulones, which are known to be used as condiments in brewing beer. A disadvantage here is the low lightfastness of these hop ingredients, so that special precautions are required when storing the beer so that there is no undesirable change in the smell or taste.

To prevent this disadvantage, it is possible to convert the humulones, isohumulones or lupulones by catalytic hydrogenation into the corresponding tetrahydro compounds, which have a significantly higher light resistance. For example, it is known from WO 94/15 899 to prepare the tetrahydroisohumulones or their alkali metal compounds from the corresponding unsaturated compounds by catalytic hydrogenation in the presence of a noble metal catalyst (for example palladium on carbon). A disadvantage of this known process is the fact that the catalytic hydrogenation is comparatively drastic conditions must be carried out in order to obtain satisfactory yields. In addition, the production of the catalysts is often technically complex and costly.

Another example of the chemical modification of terpenoids is the hydrogenation of squalene (2,6,10,15, 19,23-hexamethyl-2,6,10,14,18,22-tetrakosahexaene) to squalane, which on a large scale is used as an ointment base in pharmaceutical or cosmetic preparations. The hydrogenation processes known for the production of squalane also have the serious disadvantage that they are technically very complex and cause comparatively high operating and investment costs.

The present invention was therefore based on the object of developing a process for the catalytic hydrogenation of terpenoids with hydrogen in the presence of a transition metal catalyst which does not have the disadvantages of the prior art mentioned, but also extensive hydrogenation of the corresponding starting compounds with little technical outlay enables.

This object was achieved in that the hydrogenation in a homogeneous phase in the presence of a catalyst consisting of a reaction product of transition metals of the eighth subgroup or their compounds or salts and polymer compounds selected from the group polyvinylpyrrolidone (PVP), polyethyleneimine (PEI) derivatives or starch derivatives. Surprisingly, it has been shown that the terpenoids can be hydrogenated virtually quantitatively even under mild conditions with regard to pressure and temperature.

In the process according to the present invention, special catalysts are used which consist of a reaction product of transition metals of the eighth subgroup of the periodic table and special polymer compounds. Of the transition metals of the eighth subgroup, the metals are Palladium, platinum, nickel, rhodium and ruthenium and mixtures of these metals are to be regarded as particularly preferred. Mixtures of palladium and platinum, for example, have proven particularly useful.

The polymer component of the catalyst used according to the invention consists of polyvinylpyrrolidone (PVP), polyethyleneimine (PEI) derivatives or starch derivatives. Polyvinylpyrrolidones with a relatively low molecular weight of approximately 10,000 to 50,000 are preferably used here. Polyethyleneimine derivatives include both polyethyleneimines with a preferred molecular weight of 1,000 to 50,000 or derivatized compounds

Find use. The derivatization can be carried out with the appropriate alkylating agents (such as methyl iodide or dimethyl sulfate), acylating agents (such as acetic anhydride) or epoxidation reagents (such as ethylene oxide, propylene oxide etc.).

The degree of derivatization of the polyethyleneimines is relatively unproblematic, i. H. The primary and secondary amino groups of the polyethyleneimine can, if desired, be derivatized in whole or in part.

The usual starch types based on wheat, corn and potato are suitable as starch derivatives for the polymer compounds used according to the invention. According to a preferred embodiment, a carboxymethylated starch with a degree of substitution of 0.5 to 3.0 is used as the starch derivative.

The ratio of transition metal to polymer compound can be varied within wide limits within the scope of the present invention, but it has proven to be particularly advantageous to set the quantitative ratio of transition metal to polymer compound to 1:20 to 1:50.

It is to be regarded as essential to the invention that the catalytic hydrogenation reaction takes place in a homogeneous phase, because only in this way can rapid hydrogenation also take place under mild conditions. The hydrogenation reaction will preferably carried out in water or in alkaline aqueous solution, provided that the corresponding Teφenoide dissolve in these media. In the case of the humulon or isohumulone, it is preferred to work in alkaline solution at a pH of 7.0 to 10.0. Instead of water, alcohols with 1 to 4 carbon atoms can also be used as solvents, where in the case of

Hop ingredients ethanol and in the case of squalene n-butanol have proven their worth.

The reaction temperature in the process according to the invention can also be varied within certain limits and depends essentially on the

Temperature sensitivity of the starting compounds or the products. The preferred temperature range is between 10 and 80 ° C. The reaction pressure is also relatively uncritical, i.e. it can be carried out either at normal pressure or to accelerate the reaction rate at an overpressure which, depending on the autoclaves available, can be up to 50 bar.

The preparation of the catalysts used according to the invention is technically relatively easy to carry out and is described, for example, in US Pat. No. 4,419,490. Usually a salt of the transition metal used is placed in a suitable solvent, then the polymer compound is optionally also added in dissolved form and finally the catalyst with a reducing agent such as e.g. Sodium borohydride (NaBH4) or hydrogen, reduced.

Subsequently, the corresponding terpenoid can be added to the catalyst solution without prior isolation of the catalyst and the hydrogenation can be carried out under the respective reaction conditions, the hydrogen being preferably used in excess. As Teφenoide within the scope of the present invention, hop ingredients such as. As humulon, isohumulon or lupulon, or squalene can be used. Following the hydrogenation, which is usually complete after 3 to 12 hours, the catalyst is separated off by customary methods, for example by ultrafiltration, and can easily be used again for hydrogenation reactions. The separated filtrate with the dissolved product can, if necessary, be isolated by removing the solvent or can be analyzed, for example, by HPLC or GC. As these analytical studies show, the teipenoids used according to the invention are practically quantitatively hydrogenated, and neither the corresponding starting compounds nor any partially hydrogenated intermediates can be found.

The following examples are intended to explain the invention in more detail.

Examples

General:

The HPLC chromatograms according to Examples 1 to 5 were recorded under the following conditions:

Column: Grom-Sil ODS-O AB (25 cm x 4.6 mm) with silica gel (5 μm) Solvent: acetonitrile / water (+ 0.05% H3PO4) 60/40 (isochratic) UV detection: 275 nm

Sample: Dilute 1 ml product with approx. 3 ml methanol; Injection quantity: 5 μl flow: 0.8 ml / min. Pressure: approx. 75 bar

example 1

0.3 ml of a methanolic Li2PdCl4 solution (palladium content: 3 mg) is diluted with 20 ml of ethanol, mixed with 5 ml of a 2% by weight aqueous PVP solution (K value: 25) and then with 5 mg sodium borohydride reduced at room temperature (duration: 15 minutes). Then 400 mg of isohumulone dissolved in 10 ml of ethanol are added to the catalyst solution and hydrogenated at room temperature and 1 bar within 3 hours (hydrogen absorption: 45 ml). The catalyst is then largely separated by ultrafiltration and the filtrate is analyzed by HPLC. The evaluation of the corresponding chromatogram shows that an almost quantitative hydrogenation of the exocyclic double bonds has occurred since neither the starting compound nor the dihydro compound was found.

Example 2

0.3 ml of a methanolic LΪ2PdCl4 solution (palladium content: 3 mg) is diluted with 20 ml of ethanol, with 5 ml of a 2% by weight aqueous solution of acetylated PEI (degree of acetylation approx. 25%; MW approx. 50 000) and then reduced with excess hydrogen at room temperature (duration: 30 minutes). 400 mg of isohumulone in 10 ml of ethanol are then added to the catalyst solution and the mixture is hydrogenated at room temperature and 1 bar for 3.5 hours (hydrogen absorption: 45 ml). The subsequent analysis by HPLC shows an almost quantitative hydrogenation of the exocyclic double bonds.

Example 3

0.3 ml of an aqueous Na2PdC.4 solution (palladium content: 3 mg) is diluted with 20 ml of water, mixed with 5 ml of a 2% by weight aqueous PVP solution (K value: 25) and then reduced with excess hydrogen at room temperature (duration: 30 minutes). After the reduction, 4 ml of a 10.5% strength aqueous isohumulone solution are added to the catalyst solution and hydrogenated at room temperature and 1 bar for about 10 hours (hydrogen absorption: 45 ml). The subsequent analysis by HPLC shows an almost quantitative hydrogenation of the exocyclic double bonds. Example 4

2 ml of an aqueous Na2PdCl4 solution (palladium content: 20 mg) are diluted with 50 ml of water, mixed with 30 ml of a 2% by weight aqueous PVP solution (K value: 25) and with excess hydrogen at room temperature reduced (duration: 30 minutes). Then 100 ml of a 10% aqueous isohumulone solution are added and the reaction mixture is hydrogenated at 50 ° C. and 5 bar for about 12 hours (hydrogen absorption: 1300 ml). The subsequent analysis by HPLC shows a practically quantitative hydrogenation of the exocyclic double bonds.

Example 5

1 ml of an aqueous Na2PdCl4 solution (palladium content: 10 mg) is diluted in 30 ml of water with 20 ml of a 2% by weight aqueous solution of acetylated PEI (degree of acetylation approx. 25%; MW approx. 50,000 ) and then reduced with excess hydrogen at room temperature (duration: 30 minutes). After the reduction has taken place, 40 ml of a 10% strength by weight aqueous isohumulone solution are added to the catalyst solution and hydrogenated at a temperature of 50 ° C. and normal pressure for about 8 hours (hydrogen absorption: 450 ml). The catalyst is separated from the hydrogenated isohumulone by means of ultrafiltration using a UV membrane with an exclusion limit of approximately 10,000 daltons. After redissolving, the catalyst can be used again for the hydrogenation. Analysis by HPLC shows a practically quantitative hydrogenation of the exocyclic double bonds.

Example 6

0.3 ml of a methanolic Li2PdCl4 solution (palladium content: 3 mg) is diluted with 20 ml of ethanol, mixed with 5 ml of a 2% by weight ethanolic PVP solution (K value: 25) and the solution with Reduced hydrogen. To If the reduction has taken about 30 minutes, 300 mg of humulon, dissolved in 10 ml of ethanol, are added and the mixture is hydrogenated at room temperature and 1 bar of hydrogen pressure for 1 hour (hydrogen uptake: 30 ml). The soluble polymeric hydrogenation catalyst is separated by means of ultrafiltration (membrane with exclusion limit of 10,000 daltons), and the filtrate is analyzed by means of HPLC. The spectrum shows that the humulon used was almost completely hydrogenated to tetrahydrohumulon.

Example 7

0.3 ml of a methanolic Li2PdCl4 solution (palladium content: 3 mg) is diluted with 20 ml of n-butanol, mixed with 2 ml of a 2% by weight aqueous solution of alkylated PEI (degree of alkylation approx. 50%) and then reduced with 5 mg sodium borohydride at room temperature (duration: 15 minutes). Then 2 g of squalene are added and the hydrogenation is carried out at 50 ° C. and 1 bar for a period of 3 hours (hydrogen uptake: 600 ml). The catalyst is then separated off by ultrafiltration and the filtrate is spun in. The yield is 1.92 g of squalane (yield: 93.7%) with a gas chromatographic purity of over 99%.

Example 8

1 ml of a methanolic Li2PdCl4 solution is diluted with 30 ml of n-butanol, mixed with 10 ml of a 2% by weight PVP solution in butanol (K value: 25) and then reduced with 10 mg of sodium borohydride at room temperature

(Duration: 15 minutes). Then 20 g of squalene are added to the catalyst solution and hydrogenated at 60 ° C. and 5 bar for about 12 hours (hydrogen uptake: about 6,000 ml). After the hydrogenation has taken place, the catalyst is separated off by ultrafiltration and the filtrate is spun in, 19.1 g of squalane (yield: 93.2%) having a gas chromatographic purity of over 99% being obtained.

Claims

claims

1. A process for the catalytic hydrogenation of Teφenoiden with hydrogen in the presence of a transition metal catalyst, characterized in that the hydrogenation in a homogeneous phase in the presence of a catalyst consisting of a reaction product of transition metals of the eighth subgroup or their compounds or salts and polymer compounds selected from the group polyvinylpyrrolidone (PVP), polyethyleneimine (PEI) derivatives or starch derivatives.

2. The method according to claim 1, characterized in that the transition metal consists of a metal selected from the group consisting of palladium, platinum, nickel, rhodium or ruthenium.

3. Process according to claims 1 and 2, characterized in that the polyethyleneimine compound has been derivatized by alkylation, acylation or epoxidation.

4. Process according to claims 1 to 3, characterized in that a carboxymethylated starch with a degree of substitution of 0.5 to 3.0 is used as the starch derivative.

5. Process according to claims 1 to 4, characterized in that the quantitative ratio of transition metal to polymer compound is 1:20 to 1 50.

6. The method according to claims 1 to 5, characterized in that one carries out the catalytic hydrogenation in aqueous solution.

7. The method according to claims 1 to 6, characterized in that the

Reaction takes place in an alkaline medium at a pH between 7.0 and 10.0.

8. The method according to claims 1 to 5, characterized in that one carries out the hydrogenation in an alcohol having 1 to 4 carbon atoms.

9. The method according to claims 1 to 8, characterized in that the hydrogenation is carried out at a temperature of 10 to 80 ° C.

10. The method according to claims 1 to 9, characterized in that the hydrogenation takes place at a pressure between 1 and 50 bar.

1 1. Process according to claims 1 to 10, characterized in that a catalyst is used which has been prepared by reacting a transition metal salt with the corresponding polymer compound in the presence of a reducing agent.

12. The method according to claim 1 1, characterized in that sodium borohydride (NaBH4) or hydrogen has been used as the reducing agent.

13. The method according to claims 1 to 12, characterized in that one uses a hop ingredient selected from the group Humulon, Isohumulon or Lupulon as Teφenoid.

14. The method according to claims 1 to 12, characterized in that squalene is used as Teφenoid.