WO2000053305A1

WO2000053305A1 - Polymer enlarged catalysts

Info

Publication number: WO2000053305A1
Application number: PCT/EP2000/001319
Authority: WO
Inventors: Jürgen Allgaier; Andreas Bommarius; Olaf Burkhardt; Karlheinz Drauz; Andreas Karau; Andreas Liese; Jean-Louis Philippe; Christian Wandrey; Jens WÖLTINGER
Original assignee: Degussa Ag; Forschungszentrum Jülich GmbH
Priority date: 1999-03-11
Filing date: 2000-02-18
Publication date: 2000-09-14
Also published as: AU3423500A; DE10003110A1

Abstract

Polymer enlarged catalysts and precatalysts for catalytic organic synthesis characterized in that the polymer enlargement has polymers based on isoprene or butadiene. The invention also relates to a method for the production and to the use of said catalysts.

Description

Polymer-enlarged catalysts

The present invention is directed to homogeneous catalysts and precatalysts for organic synthesis, processes for their preparation and their use.

In particular, the catalysts according to the invention are distinguished in that they have linear or any branched, completely saturated homo- or copolymer of butadiene or isoprene.

Catalytic processes are superior to stoichiometric reactions because one of the substances involved in the reaction is not consumed - the catalyst. Even in the batch process this could be used indefinitely for the reaction under consideration, if not for the recycling or inactivation losses

Would decrease catalyst performance over time. Limiting the loss of catalyst can therefore contribute to minimizing the process costs in the catalytic synthesis carried out on an industrial scale.

Preferred over normal catalyst recycling, however, is a continuous process in which the catalyst is immobilized in a reaction vessel while only the reactants are added and the products are removed. This procedure can be achieved through the use of polymer-enlarged catalysts

Membrane reactors can be realized (andrey et al. In yearbook 1998, chemical engineering and chemical engineering, VDI p. 151ff .; Wandrey et al. In Applied Homogeneous Catalysis with Organometallic Compounds, Vol. 2, VCH 1996, p.832 ff .; Kragl et al Angew. Chem. 1996, 6, 684f.).

Polymer-enlarged catalysts have already been reported on various occasions in the prior art (Reetz et al., Angew. Chem. 1997, 109, 1559f .; Seebach et al., Helv. Chim Acta 1996, 79, 1710f .; Kragl et al., Angew. Chem. 1996, 108, 684f .; Schurig et al., Chem. Ber./Recueil 1997, 130, 879f .; Bolm et al. , Appl. Chem. 1997, 109, 773f .; Bol et al. Eur. J. Org. Chem. 1998, 21f .; Baystone et al. in Specialty Chemicals 224f .; Salvadori et al. , Tetrahedron: Asymmetry 1998, 9, 1479; Wandrey et al., Tetrahedron: Asymmetry 1997, 8, 1529f .; ibid. 1997, 8, 1975f .; Togni et al. J. Am. Chem. Soc. 1998, 120, 10274f., Salvadori et al., Tetrahedron Lett. 1996, 37, 3375f.).

In all of the publications mentioned, either dendrimers which are difficult to synthesize or polymers made from polysiloxanes, polyethylene glycols or polyacrylates are described as polymer enlargements.

WO 98/22415 mentions a process in which polystyrene or polysiloxane is enlarged

Oxazaborolidine catalysts were used in the homogeneous enantioselective reduction of ketones in a membrane reactor. The result showed that the number of cycles (the number of process cycles that a certain amount of catalyst allows without loss of performance [ttn]) can be increased considerably.

Some of the polymer-enlarged catalysts known from the prior art have the disadvantage that they are relatively difficult to synthesize with regard to use on an industrial scale and are therefore expensive, such as, for. B. polysiloxanes and dendrimers. In addition, there is still the need to provide new polymer-enlarged catalysts which ensure the highest possible number of cycles in order to complicated and costly replenishment of the catalyst

Maintaining the process in the membrane reactor and avoiding contamination of the product with the catalyst. Using simple polymeric compounds, FIG. 1 shows how important an extremely high retention capacity of a catalyst behind a membrane is in terms of its loss due to bleeding. Only from a retention of> 99.9% are polymers obtained which remain in the reactor to a sufficient extent even with longer residence times (lecture at the Dechema working committee "Catalysis", held on January 20, 1999). It has been shown that a Better retention can be achieved by increasing the molar mass of the polymer, for example polystyrene, but the higher molar mass again causes viscosity difficulties in the solvents used and higher material usage costs.

It was therefore an object of the present invention to provide further easy-to-produce, polymer-enlarged catalysts for the homogeneous catalysis of organic reactions.

In particular, despite the reduction in the molar mass of the polymer enlargement, they should have comparable or even better retention behavior compared to an ultra or nanofiltration membrane compared to the polymeric catalysts of the prior art.

These and other unspecified tasks, which, however, result readily and in an obvious manner from the prior art, are achieved by a catalyst according to claim 1. Preferred embodiments of the catalysts according to the invention are protected in claims 2 to 5. Claim 6 protects precatalysts as intermediate compounds of the actual active catalysts, claims 7-9 suitable processes for the preparation of the catalysts or the intermediate compounds. Claims 10 and 11 are directed to preferred uses of the catalysts according to Claim 1. If the invention speaks of polyisoprenes or polybutadienes or their copolymers, the polymers obtained from the polymerization of butadiene and isoprene are regularly meant, in which the double bonds, for. B. have been saturated by hydrogenation according to the methods of the prior art, unless otherwise stated.

In the context of the invention, the catalyst is the actual polymer-enlarged but active species. These are usually not particularly stable, which is why they are made from so-called precatalysts - precursors of the actual catalyst - and used for the reaction. Precatalyst is therefore understood to mean a predecessor compound of the catalyst which is polymer-enlarged according to the invention, for. B. a storage-stable polymer-enlarged ligand or protective polymer-enlarged catalyst or the catalyst precursor, which still has double bonds in the polymer backbone. As said, the actual catalyst is first formed from these precatalysts. The unit of the polymer-enlarged catalyst is considered to be the active center, which, without a polymer bond, represents the species actually active for this reaction. By definition, however, the term “preactive center” in the precatalyst is used in the context of the invention, analogously to the catalysts.

Characterized in that the polymer enlargement of the catalyst is a linear or arbitrarily branched homo- or copolymer of butadiene and / or isoprene or a copolymer of butadiene and / or isoprene optionally with propylene and / or styrene or a block copolymer of polybutadiene and / or polyisoprene optionally with polypropylene and / or polystyrene, catalysts are improved in an unpredictable manner compared to the prior art. Polymers based on butadiene or isoprene have the advantage over polystyrene and polysiloxanes in that they have a significantly higher hydrodynamic volume in solution with a comparable molar mass. As a result, they show better retention behavior with regard to the ultra or nanofiltration membranes used in the membrane reactor (Tab. 1 / Fig. 2).

In the case of polybutadiene or polyisoprene, it is possible to initiate a 1, 2-polymer in addition to the 1, 4-polymer. In general, mixtures are formed with a bandwidth between 1,2- and 1,4-linkage (Lit. Fetters et al. M Advances m Polymer Science 56, Springer-Verlag Berlin Heidelberg 1984, pp. 51, 56). In the context of the invention, the polymer enlargement can have any linked polybutadiene or polyisoprene.

As shown, the linear representatives of the polymer enlargements according to the invention already have clear advantages over the polymer enlargements of the prior art. In addition, the gain in retention assets must be increased even further if not

Polymers at least one branch is installed. In the context of the invention, branching means the fact that at least three polymer strands branch off from one point of the polymer. This measure leads to stiffening of the polymer pressure counters, which obviously suppresses slipping through the pores of the membrane even more effectively (Tab. 2).

Any number of such branches can be built in, right down to the dendritic configurations, but the installation of a branching point is particularly preferred since the gain in retention capacity is greatest in this step in relation to the synthesis effort and increases with the branching progressively less. In principle, all those skilled in the art can be considered as branch points for this purpose Branch options are used. An overview of preferred branching units and the possibility of synthesis is provided by WO 97/06201 and Fetters et al., Macromolecules 1980, 13, 191f .; ibid. 1978, 11, 668f .; Quirk et al. Pure appl. Chem. 1994, 31, 911f. However, the installation of a branching unit from units shown in the following scheme 1 is very particularly preferred.

Scheme 1:

In the context of the invention it is preferred to provide catalysts in which a spacer is installed between the polymer enlargement and the active center. The

Spacer serves to build up a distance between the active center and the polymer in order to reduce mutual interactions that are disadvantageous for the reaction or turn off. In principle, all spacers suitable for the person skilled in the art for this purpose can be used. The following scheme 2 provides a suitable overview.

Scheme 2:

CH ₃ CH. CH-CH, H-Si-HH-Si-O-Si-H

CH,

CH, CH, CH-

n = 1-2

The selection is based on the possibility of being able to couple the spacers well to the preactive center on the one hand and to the polymer on the other. However, spacers such as e.g. B. 1,4'-biphenyl, 1,2-ethylene, 1, 3-propylene, PEG- (2-10), α, ω-siloxanylene or 1,4-phenylene and α, ω-l, 4-bisethylenebenzene . Spacers which start from siloxanes of the general formula I are particularly preferred

R: Me, Et n = 0-10

are available. Under hydrosilylation conditions (overview of the hydrosilylation reaction of 0j i a in The Chemistry of Organic Silicon Compounds, 1989 John Wiley & Sons Ltd., 1480-1526) these can easily be bound to the double bonds in the polymers and suitable functional groups of the preactive centers.

As an active center in the polymer-enlarged

Any low-molecular catalyst familiar to a person skilled in the art in the field of organic synthesis is suitable for catalysts. A suitable overview is provided here by Noyori in Asymmetry Catalysis In Organic Synthesis, Wiley-Interscience Publication 1994, Chapter 2,4,5, Ojima in

Catalytic Asymmetry Synthesis, Wiley-VCH, 1993, Bolm and Beller in Transition Metalls for Organic Synthesis, Vol. II, Chap. 1 and 2, VCH, 1998.

However, catalysts from the group of catalysts for transfer hydrogenation and hydrogenation with elemental hydrogen are preferred, as are catalysts for the aldol reaction and Mukaijama-aldol reaction, dialkyl addition to carbonyl groups, Jacobsen epoxidation, Sharpless dihydroxylation, Diels-Alder and hetero -Diels-Alder reaction, the enantioselective anhydride opening, the reduction of ketones with hydrides and the Heck reaction.

Catalysts are particularly preferred for the reduction of ketones with hydrides via taddol ligands (Seebach, Helv. Chim. Acta, 1996, 79, 1710f.), For the epoxidation of double bonds with chiral salen complexes (Salvadori, Tetrahedron Lett., 37, 1996, 3375f.), Sharpless epoxidation with dihydroquinidines (Bolm, Angew. Chem., 1997, 773f.), For dialkylzinc addition using 1, 2-diamino alcohols (Wandrey, Tetrahedron: Asymmetry, 1997, 8, 1529f.) And for catalytic hydrogenation using chiral 1, 2-diphosphine ligands such as DIOP, DIPAMP; BPPFA, BPPM, CHIRAPHOS, PROPHOS, NORPHOS, BINAP, CYCPHOS, SKEWPHOS (BDPP), DEGPHOS, DuPHOS and PNNP.

Catalysts which are mentioned in EP 305180 are very particularly preferred.

Is extremely preferred

2- (hydroxydiphenylmethyl) pyrrolidm-4-ol as the active center.

The invention also relates to a polymer-enlarged precatalyst which, as polymer enlargement, comprises a linear or randomly branched homo- or copolymer of butadiene and / or isoprene or a copolymer of butadiene and / or isoprene, optionally with propylene and / or styrene or a block copolymer of polybutadiene and / or polyisoprene optionally with polypropylene and / or polystyrene. The term precatalyst also includes the polymer-enlarged catalysts which still have double bonds in the polymer component.

The invention also relates to a process for the preparation of polymer-enlarged catalysts. These can be prepared from the precatalysts according to the invention by methods familiar to the person skilled in the art.

A method is particularly preferred in which the actual catalyst is produced in situ from a precatalyst according to the invention and without prior Isolation can be used for the actual reaction.

In turn, the precatalysts can be prepared by methods familiar to the person skilled in the art. It can preferably be carried out according to two different procedures. On the one hand, there is the possibility of connecting the preactive centers to those of the invention

To bind polymer enlargement or, if necessary, to copolymerize / polymerize monomers which already have the preactive center with methods known to the skilled worker with other monomers according to the invention.

It is particularly preferred to choose a method in which the polymer enlargement is connected to the preactive centers via a spacer (see example in Scheme 3).

Another object of the invention is a use of the catalysts of the invention in organic synthesis.

In a preferred embodiment, a chiral enantiomerically enriched catalyst of this invention is used in syntheses to produce enantiomerically enriched organic compounds.

The use of the catalyst according to the invention is very particularly preferred in syntheses in which the catalyst is enclosed in a reactor while low molecular weight substances are fed to the reactor or can leave it.

In an extremely preferred embodiment, this reactor is a membrane reactor.

The pre- and catalysts according to the invention can be prepared by methods familiar to the person skilled in the art. For example, the polymer enlargements with or without branches according to WO 97/06201 and Fetters et al., Macromolecules 1980, 13, 191f .; ibid. 1978, 11, 668f .; Quirk et al. Pure appl. Chem. 1994, 31, 911f. produce. These are then bound to the active center or to the spacer containing the active center. This can also be done according to the methods familiar to the person skilled in the art. The double bonds of the unsaturated polymer offer various possibilities of attachment by addition reactions (radical, ionic, concerted) or addition reactions followed by substitution reactions, depending on whether the group available for attachment at the active center is immediately suitable for introduction into the polymer or not. Hydration, epoxidation, hydroxylation, hydrosilylation, hydroboration, coupling reactions, which can be catalyzed by Pd or Ni, or the like, can preferably be used. Organikum, VEB Deutscher Verlag der Wissenschaften, Berlin 1986, pp. 244f. Offers suitable overviews of possible double bond reactions; Carruthers, Some modern methods of organic synthesis, third ed., Cambridge University Press, pp. 63f .; Carey,

Sundberg in Organic Chemistry, VCH Weinheim 1995, pp.329f.

The following scheme 3 is shown for clarification:

Scheme 3

Hydrosilylation

Precatalyst

1. Deprotection

2. NaBHJTHF

catalyst

An additional advantage of the invention

Catalysts are that they can be constructed very variably, since a wide range of spacers and active centers are available for attachment to the double bonds of the polymer. Within the scope of the invention and the technical knowledge, the polymer, the spacer and the active center can be variably adapted to the reaction to be catalyzed. The advantage of the polymers according to the invention can be seen from retention measurements of individual polymers.

Tab. 1 shows the retention behavior of linear polybutadiene in comparison to linear polystyrene for an MPS-U20-S membrane ^® from Koch (exclusion limit 20,000 g / mol).

Tab. 1: Retention of polystyrene vs polybutadiene

It can be seen (cf. also FIG. 2) that a correspondingly good restraint is achieved in the case of polybutadiene even with a significantly lower molar mass of the polymers. This effect is due to the lower molar mass of butadiene compared to styrene. If one calculates the difference in size of the polymers due to the difference in molecular weight of a factor of 2, the retention of polybutadiene compared to polystyrene is comparable. It is nevertheless surprising, but no less advantageous, that the hydrodynamic volume of both polymers obviously coincides with a comparable chain length. Through this In fact, however, one saves raw material costs for the generation of the polymers, since the material costs are paid for by weight.

From Table 1 it can be seen that the retention capacity of polystyrene can be increased if its molar mass is increased. However, this results in

Viscosity problems. Because of the equally good retention of polybutadiene compared to polystyrene at about half the molecular weight, these disadvantages only occur with a given retention at twice the molecular weight. At a certain retention rate, a higher dosage with catalyst is possible, which means a better space / time yield.

If branched polybutadienes are used, the retention behavior is even better compared to the linear configuration (Table 2).

Tab. 2: Retention of linear vs branched polybutadiene

: Si atom as branch point; 4 polymers with a molecular weight of 1000 g / mol branching

An advantage that polybutadienes and polyisoprenes have over polysiloxanes, polystyrenes and polyacrylates and polyethylene glycols is that after the polymerization in the polymer there is a double bond for each monomer used for potential binding of the active centers. About the ratio of

Concentrations of the reactants can be so easily set the number of active centers in the polymer strand. The reverse procedure is also possible. So you can first partially hydrogenate the double bonds, so that the degree of functionality is set by the degree of hydrogenation. All remaining double bonds are then transferred to active centers. With all other polymers which are known in the prior art, with the exception of polyacrylates, copolymerization with monomers specially modified for the attachment is necessary. Compared to polyacrylates, there is the advantage that the connection to the unsaturated polyisoprene or butadiene can be established via a stable covalent bond, whereas in the case of polyacrylates a hydrolysis-sensitive ester bond must be formed.

Polymer-enlarged catalysts for homogeneous catalysis containing polybutadiene and polyisoprene are superior to the known catalysts of the prior art. The presence of these polymers is responsible for the advantages shown with regard to their use in the membrane reactor. The result is that stable technical processes can be carried out cost-effectively in the membrane reactor.

The term homogeneous in the context of the invention denotes the exclusion of the presence of separate phases. The phases are to be regarded as separate if two or more phases are visible to the naked eye. Gels are to be considered as one phase.

The polymer enlargements according to the invention can have any tacticity.

The catalysts and precatalysts presented can be both achiral and chiral in nature and accordingly generate chiral, achiral or racemic substances. Enantiomerically enriched in the context of the invention denotes the presence of an enantiomer in excess over its optical antipode.

Examples

1. Reaction of hexamethylsiloxane with N-Z-protected 2- (hydroxydiphenylmethyl) pyrrolidin-4-yl allyl ether

1.43 mmol of N-Z-2- (hydroxydiphenylmethyl) pyrrolidin-4-yl allyl ether are dissolved in 50 ml of absolute tetrahydrofuran and 10 equivalents of hexamethyltrisiloxane are added at room temperature. 3 ml of a 10 percent solution of the Wilkinson catalyst (in tetrahydrofuran) are added. The mixture is stirred under protective gas for two hours. The solvent and the excess

Hexamethyltrisiloxane is removed on a rotary evaporator and in a high vacuum. The crude product can be used in the subsequent reaction without further purification.

2. Partial hydrogenation of a polybutadiene (1, 2)

3.3 g of a polybutadiene (1, 2) with a molecular weight of 20,000 g / mol are dissolved in 200 ml of toluene and 580 mg of Wilkinson catalyst are added. The reactor is filled with 50 bar of hydrogen and the mixture is stirred at 25 ° C. for four hours. The reaction solution is removed. You shake it

Reaction solution with 100 ml sat. NaHC0 ₃ solution and dries the organic phase after phase separation with sodium sulfate. The toluene is drawn off. The proportion of double bonds is calculated to be 21% by NMR spectroscopy.

3. Connect the polymer to the active center

100 mg of the partially hydrogenated polybutadiene shown in 2. are dissolved with the crude product from 1. in 50 ml of THF. 10 mg of the hydrosilylation catalyst Pt (COD) Cl ₂ are added. The mixture is stirred at room temperature for 43 hours. The solvent is removed. Then a 10 ml Membrane reactor prepared by a

Nanofiltration membrane (MPF-50 membrane ^® from Koch (cut-off limit 700 g / mol) is inserted. 10 ml of freshly distilled tetrahydrofuran per hour are passed through the reactor via an alternating-piston pump P-500 from Pharmacia, so that a residence time of 1 h is set The membrane is rinsed in this way with tetrahydrofuran for 24 hours, and the crude product of the reaction is flushed into the reactor by means of an interchangeable piston pump, rinsed with tetrahydrofuran for 48 hours in order to separate off the low molecular weight fraction, and the retentate is removed from the reactor via NMR spectroscopy The ratio of the aromatics signals to the signals in the range between 2.5 and 0.5 ppm is determined. The retentate is again flushed into a membrane reactor as described above. It is flushed again with tetrahydrofuran for 48 hours. The ratio is again obtained from the retentate of the signal ranges specified above. A comparison of the signal intensities results in only one Very little shift in favor of the signals in the range between 2.5 and 0.5 ppm. This means that the low molecular weight fraction is completely separated and that the aromatics signals-dependent catalyst units must be firmly bound to the polymer.

4. Retention measurement with polymers (Fig. 1)

In a 10 ml membrane reactor

Nanofiltration membrane (MPF-U50 membrane ^® from Koch (exclusion limit 700g / mol) is inserted. 10 ml of freshly distilled tetrahydrofuran per hour are passed through the reactor via a P-500 alternating piston pump from Pharmacia, so that a residence time of 1 hour is set. In this way, the membrane is rinsed with tetrahydrofuran for 24 hours, and 625.5 mg of 70,000 polystyrene standard from Fluka are then passed through the Piston pump flushed into the reactor. For a further 72 h, tetrahydrofuran is passed through the reactor at a flow of 10 ml / h. The reactor is then opened and the retentate removed. 602 mg of retentate and 15 mg of permeate are obtained. This corresponds to a retention of 99.96% for the polystyrene standard used.

5. Retention measurement with polymers with the ultrafiltration membrane (FIG. 2)

In a 10 ml membrane reactor

Ultrafiltration membrane (MPS-U20-S membrane ^® from Koch (cut-off limit 20,000 g / mol). 10 ml of freshly distilled tetrahydrofuran per hour are passed through the reactor via a P-500 alternating piston pump from Pharmacia, so that a residence time of 1 h The membrane is rinsed in this way with tetrahydrofuran for 24 hours, then 739.2 mg of Fluka polystyrene standard 100,000 from Fluka are rinsed into the reactor via the piston pump, and tetrahydrofuran is passed through the reactor at a rate of 10 ml / h for a further 71 hours the reactor is opened and the retentate removed, giving 715 mg retentate and 11.2 mg permeate, which corresponds to a retention of 99.95% for the polystyrene standard used.

Claims

Claims:

1. Polymer-enlarged catalyst for homogeneous catalysis, characterized in that it as polymer enlargement em linear or arbitrarily branched homo- or copolymer of butadiene and / or isoprene or em copolymer of butadiene and / or isoprene, optionally with propylene and / or styrene or em Has block copolymer of polybutadiene and / or polyisoprene, optionally with polypropylene and / or polystyrene.

2. Catalyst according to claim 1, characterized in that the polymer enlargement has arbitrarily linked polybutadiene or polyisoprene.

3. Catalyst according to claim 1 and / or 2, characterized in that the polymer enlargement has a branching point.

4. Catalyst according to one of the preceding claims, characterized in that em spacer is installed between the polymer enlargement and the active center.

5. Catalyst according to one of the preceding claims, characterized in that it has as the active center a catalyst selected from the group of oxazaborolidme, TADDOLE, Salene, Ch mdme, 1, 2-amino alcohols and 1, 2-Dιphosphane.

6. Polymer-enlarged precatalyst, characterized in that it consists of linear or arbitrarily branched homo- or copolymer as polymer enlargement Has butadiene and / or isoprene or a copolymer of butadiene and / or isoprene optionally with propylene and / or styrene or a block copolymer of polybutadiene and / or polyisoprene optionally with polypropylene and / or polystyrene.

7. A process for the preparation of polymer-enlarged catalysts according to claim 1, characterized in that they are generated in situ from polymer-enlarged precatalysts according to claim 6.

8. A process for the preparation of polymer-enlarged precatalysts, characterized in that the preactive centers are bound to the polymer enlargement according to claim 1 or monomers which have preactive centers are co- / polymerized.

9. The method according to claim 8, characterized in that the polymer enlargement is connected to the preactive centers via a spacer.

10. Use of the catalyst according to claim 1 in organic synthesis.

11. Use of a chiral enantiomer-enriched catalyst according to claim 1 in a synthesis for the preparation of enantiomer-enriched organic compounds.

12. Use according to claim 10 and / or 11, characterized in that one carries out the synthesis in a reactor in which the catalyst is enclosed, while low molecular weight substances are fed to the reactor or can leave it.