EP1708986A1

EP1708986A1 - Method for the catalytic reduction of amides

Info

Publication number: EP1708986A1
Application number: EP04701131A
Authority: EP
Inventors: Alan Arthur Smith; Paulo Dani; Paul David Higginson; Alan John Pettman
Original assignee: Avantium International BV
Current assignee: Avantium International BV
Priority date: 2004-01-09
Filing date: 2004-01-09
Publication date: 2006-10-11
Also published as: WO2005066112A1

Abstract

Described is a method for the catalytic reduction of an amide for the preparation of an amine at a temperature of below 200° C and a pressure of below 50 bar, the catalyst being chosen from bimetallic and trimetallic catalysts of the group consisting of ABC, AB, AC and BC, wherein: A is a metal, chosen from the group, consisting of Co, Fe, Ir, Pt, Rh and Ru, B is a metal, chosen from the group, consisting of Cr, Mo, Re and V, and, C is a metal, chosen from the group, consisting of Cu, In and Zn. Further, novel catalysts and a selection method for such catalysts is disclosed.

Description

Title: Method for the catalytic reduction of amides.

The invention relates to a novel method for the catalytic reduction of amides at mild reaction conditions, using novel bimetallic and trimetallic catalysts, active in the reduction of amines and to a method for the selection of such catalysts. Amines constitute an important class of compounds with extensive use as medicines or basic raw materials for the preparation of pharmaceuticals. Therefore, economically viable and green methods of synthesising amines are important. A simple and direct approach would be catalytic reduction of amides, and, indeed, there are numerous reports claiming the reduction of amides either by using hydrogen gas or by means of hydride containing reagents. However, known processes for the reduction of amides into the related amines using metal catalysts and hydrogen gas, require high temperatures and pressures, therewith compromising the presence of any other reducible functional groups, thermolabile groups and precluding the available methods for many practical applications. In the art, temperatures and pressures above 200°C and

200 bar are often necessary. For example, methods are known using a bimetallic copper chromium catalyst at temperatures between 200 and 260°C and pressures of 100-400 bar, see e.g. ojcik, B.; Adkins, H. J. Am. Chem . Soc. 1934, 56, 2419-2425; Paden, J.H.; Adkins, K. J. Am. Chem. Soc. 1936, 58, 2487-2499; Sauer, J.C.; Adkins, H. J. Am. Chem. Soc. 1938, 60, 402-406 and US-A-2, 143, 751. Regarding the above, several attempts have been made to obtain amines by catalytic reduction of amides at mild reaction conditions. Hiroshawa et al (Hirosawa, C; Wakasa, N.; Takamasa, F. Tetrahedron Lett . 1996, 37, 6749-6752) describe such catalytic reduction using the bimetallic catalysts RhRe, Rh , RhMo, RuRe and RuMo. Primary, secondary and tertiary amides were reduced to the corresponding amines, although the reaction conditions where still moderately harsh (100 bar at 160°C) . The present inventors have now found a novel method for the catalytic reduction of amides for the preparation of amines at mild reaction conditions to obviate the above drawbacks, i.e. at a temperature of below 200°C and a pressure of below 50 bar, by performing the said reduction reaction at the above mild reaction conditions with numerous bimetallic and trimetallic catalysts. Said experiments were performed by high-throughput experimentation, as e.g is described in EP 1001846. It was found that a catalyst, chosen from bimetallic and trimetallic catalysts of the group, consisting of ABC, AB, AC and BC, wherein: A is a metal, chosen from the group, consisting of Co, Fe, Ir, Pt, Rh and Ru, B is a metal, chosen from the group, consisting of Cr, Mo, Re and V, and, C is a metal, chosen from the group, consisting of Cu, In and Zn, were surprisingly suitable for the reduction of amides at mild reaction conditions. The reduction process is preferably performed with a heterogeneous catalyst. However, it is not necessary for the metals of the catalyst to be bound on the same support. E.g., one of the metals can be present on a carbon support, whereas another metal of the said catalyst can be present on e.g. a silica, titania or carbon support. The skilled person is aware of suitable supports for the envisaged catalysts. It is also possible to provide a metal of the catalyst on different supports. It is however preferred to provide the bimetallic and/or trimetallic catalyst on similar support material, although the different metals do not necessary have to be present on the very same support particles . Preferably, the support is chosen from carbon, titania, amorphous silica-alumina and silica or a combination thereof. It has been found that, using the catalysts as identified above, the catalytic reduction can even be performed at pressures of 30 bar or less, even at 15 bar or less. As will be explained below, the method according to the invention can also successfully be performed at a pressure of 10 bar, preferably between 5-10 bar, more preferably between 6-10 bar. In a preferred embodiment, the reduction is performed in a continuous flow mode. Although according to the invention such a continuous flow mode can be performed in a liquid phase, it is preferably performed in gaseous phase, i.e. wherein one or more, preferably all of the reactants are passed in gaseous phase over the catalyst at the above-mentioned reaction conditions . It is also been found that the above method according to the invention can successfully be performed at a temperature of 160°C or less, even at a temperature of 130°C or less. Also, it has been found that the method can be suitably performed at a temperature between 70-100°C, preferably around 80°C. "About" means that a deviation of 5°C is allowed. However, in another preferred embodiment, the method of the invention is performed at batch mode reactions, e.g. wherein at least one but preferably all of the reactants are in a liquid phase, e.g. in solution, and contacted with the catalyst. At batch mode reaction conditions, the amide substrate is dissolved in an appropriate solvent, such as an acid, an ether, an ester or an alcohol, preferably an acid, preferably a Bronsted acid, more preferably an organic acid. The term "Bronsted acid" is well known in the art. Carboxylic acid is a preferred organic acid; most preferably, the organic acid comprises acetic acid. The solvent preferably has a pKa value of 5 or less, more preferably between 3 and 5. The preferred concentration of the acid, preferably organic acid, more preferably carboxylic acid and most preferably acetic ^"acid is up to 1.0 M, preferably between 0.2 and 0.8 M, more preferably between 0.4 and 0.5 M. An internal standard, such as n-decane can be co-added to the reaction mixture for quantitative gas-chromatography analysis. In batch mode reactions according to the invention, the addition of an additive may be favoured. The additive preferably comprises an acid, more preferably a Lewis acid, most preferably a boron-containing compound. The term "Lewis acid" is well known in the art. The substrate: additive ratio in the reaction mixture is preferably 4 or less, more preferably 2 or less, and most preferably between 0.9-1.1. During the reaction, the reaction mixture is preferably subjected to hydrogen pressures between 1 and 17 bar, more preferably between 5 and 10 bar. The reaction temperature is preferably between 90 and 140 °C, more preferably between 100 and 130°C. According to a preferred embodiment of the method of the invention, both for flow and batch mode reactions, the catalyst is chosen from the group, consisting of:

CoCu IrMoCu Fein IrReCu FeRe IrReZn IrMo IrVZn IrRe PtMoCu IrV PtMoIn Moln PtMoZn PtMo PtReCu PtRe PtReln PtV PtReZn Rein PtVIn RhCu PtVZn Rhln RhMoCu RhMo RhMoIn RhRe RhMoZn RhV RhReCu RuRe RhReIn CoMoZn RhReZn CoReCu RhMoZn CoReln RhVIn CoVIn RuReCu FeCrln RuReZn FeReCu FeReln FeReZn

Preferably, the catalyst is chosen from the group consisting of PtRe, IrMo, IrRe, PtRe, PtV, RhRe, RhV, FeReln, PtReCu, PtReln, PtReZn, RhMoCu, RuReZn, PtMo, RhMo, RuRe, IrReZn and PtMoCu, most preferably more preferably from the group consisting of PtRe, PtReCu, PtReln, FeReln, PtMo, PtV, RhMo, PtMoCu, RhMoCu, and RuRe, even more preferably from the group, consisting of PtReCu, PtReln, FeReln, PtMo, PtV, RhMo, PtMoCu, RhMoCu, PtRe and RuRe, and most preferably from the group consisting of PtReCu, PtRe, PtMo IrReZn, PtMoCu and PtReln. As will be shown in the Examples, the above-identified catalysts can effectively be used at the mild reaction conditions according to the invention. In a further aspect, the invention relates to novel bi- or trimetallic catalysts for the reduction of amides to amines, chosen from the group, consisting of:

CoCu IrMoCu Fein IrReCu FeRe IrReZn IrMo IrVZn IrRe PtMoCu IrV PtMoIn Moln PtMoZn PtMo PtReCu PtRe PtReln PtV PtReZn Rein PtVIn RhCu PtVZn Rhln RhMoCu RhV RhMoIn CoMoZn RhMoZn CoReCu RhReCu CoReln RhReIn CoVIn RhReZn FeCrln RhMoZn FeReCu RhVIn FeReln RuReCu FeReZn RuReZn

more preferably from the group, consisting of IrMo, IrRe, PtRe, PtV, RhV, FeReln, PtReCu, PtReln, PtReZn, RhMoCu, RuReZn, PtMo, IrReZn and PtMoCu, preferably chosen from the group, consisting of FeReln, PtReCu, IrReZn, PtMoCu, PtRe and PtReln, and most preferably chosen from the group, consisting of PtReCu, PtRe, PtMo IrReZn, PtMoCu and PtReln The catalyst is preferably supported on a carrier, as outlined above . In a further aspect, the invention relates to a method for the selection of at least one bi- or trimetallic catalyst, active in the reduction of amides into amines from a collection of bi- and/or trimetallic catalysts, comprising the steps of A) preparing the catalysts on separate carriers, B) loading the catalysts prepared in step A) in separate reactor vessels, the vessels having a parallel arrangement, C) feeding and incubating the reactor vessels with an amide and hydrogen at identical conditions regarding at least one of the quantities, chosen from reaction time, temperature and pressure, D) measuring the conversion of amides into amines in each reactor vessel, E) selecting one or more of the catalysts, based on the measured conversion in step D) . This method allows the rapid identification and selection of active catalysts for the reduction of amides; a large range of different catalysts, having a different metal composition or ratio between the metals can be tested in the hydrogenation reaction, wherein the reaction conditions can be controlled and ^' optimised. Thereto, the different catalysts are prepared on separate carriers, according to methods, known in the art. Preferably, in step A) the catalysts are prepared in parallel. The carriers can be the same for the catalysts to be tested, but may also be different in order to test and select an optimal catalyst-carrier combination. Then the prepared catalysts on a carrier are loaded in reactor vessels arranged in parallel , so that the reactions to be performed with the catalysts can be done simultaneously. Preferably, after feeding of the reactants, which is preferably performed in parallel in the reactor vessels; the reaction conditions, such as reaction time, temperature and pressure are identical for the catalysts to be tested. This way, the reactions are performed at identical conditions, so that relevant selections of active catalysts can be made. Once selected, the said catalyst can be further tested at reaction conditions that differ from the first selection process to identify one or more catalysts that are optimally suitable for the envisaged reaction conditions. Further, the selection method, that is preferably performed in a gaseous phase in flow mode, can be extrapolated to batch mode reaction for industrial processes for the preparation of amines at suitably mild reaction conditions. The invention will now be further illustrated by way of non- limiting Examples and Figures. Figures 1 to 5 refer to the results of amide reduction in flow mode. Figure 1 shows a gas chromatogram of a reduction reaction of 1-acetylpyrrolidine with the catalyst RhReCu on a carbon carrier at a temperature of 160°C and a pressure of 10 bar. The metal molar ratio of the catalyst was 1:1:1. Figure 2 and Figure 3 show the performance of silica and carbon supported catalysts, respectively, in the reduction of 1-acetylpyrrolidine at several different temperatures. In these examples, the metal molar ratio of the catalysts is 1:1 or 1:1:1 for bimetallic or trimetallic catalysts, respectively. Figure 4 shows the amine (in this case, 1-ethylpyrrolidine) formation profile at 100°C and 130°C as a function of the catalyst composition (bi- and trimetallic catalysts from groups A and B-C) . The grey intensity of the squares shows the amine yield. Only yields higher than 35% were plotted. Figure 5, like Figure 4, shows 1-ethylpyrrolidine formation profile at 100°C and 130°C as a function of the catalyst composition but for the case of bimetallic catalysts from groups B and C. The grey intensity of the squares shows the amine yield. For clarity, only yields higher than 35% were plotted. Figures 6-10 refer to results of amide reduction in batch mode, wherein figures 6-7 show the performance of trimetallic catalysts without and with the presence of BF₃ as additive, respectively, and wherein figures 8-9 show the performance of bimetallic catalysts without and with the presence of BF₃ as additive, respectively. Figure 10 shows the performance of physical-mixture and pre-made catalysts, as well as the importance of having more than one metal element in the catalyst composition.

EXAMPLES

Equipment and Conditions Flow Reactions

The Nanoflow Equipment The catalyst screening in flow mode was carried out in reactors, arranged in parallel, the Avantium' s Nanoflow 2b (Avantium Technologies B.V., Netherlands), designed to allow gas and liquid feeds in trickle flow mode performed for this application. The equipment consists of 64 parallel reactors divided into four blocks of 16 reactors. Each reactor can be loaded with up to 200 mg of catalyst. Temperature can be varied independently on each block. The maximum temperature of the unit is 450-500°C, and the maximum pressure is 40 bar. An evaporator is placed up-stream of each reactor, so that controlled evaporation of liquid can take place. Typical Run Conditions in Flow Mode After an equipment-commissioning phase, and regarding the low vapour pressure of the chosen amide, the catalyst screening was carried out in an effective manner at temperatures higher than 70 ^CC. Thus, the experiments were performed at temperatures of 70, 100, 130, and 160^CC and at 10 bar of H₂. 1-Acetylpyrrolidine (substrate) and n- nonane (internal standard) were dissolved in diisopropyl ether forming a solution containing 0.25 wt% and 0.12 wt% of each component respectively. This solution was pumped through the 64 Nanoflow reactors at a rate of 0.8 ml/min, causing the amide (mass) flow to be equal to 0.0015 g/min. Under these conditions, the estimated vapour residence time in the catalyst bed (on each reactor, and per temperature) is shown in Table 1.

Table 1. Estimated 1-acetylpyrrolidine vapour residence time (RT) used during the screening for temperatures above 90°C. T(°C) R_τ (s) 90 0.87 100 0.81 130 0.75 160 0.70

Analysis of the reactor effluent was done using an on-line gas- chromatograph.

Batch Reactions

The QS Equipment The catalyst screening in batch mode was carried out in 96 pressure reactors, arranged in parallel: the Avantium QS Equipment (Avantium Technologies B.V., Netherlands). This equipment is divided into eight blocks of 12 reactors that operate in the so-called gas- on-demand system. This means that gas is added as soon as it is consumed by reaction, but no gas leaves the reactor at the exit. The maximum volume of each reactor is 7 ml; the maximum operating pressure for the blocks is 17 bar, and the maximum temperature is 140°C. Stirring is provided via magnetic stirring.

Typical Run Conditions in Batch Mode

A solution of 1-acetylpiperidine in acetic acid (2 ml, 0.8 mmol) containing n-decane (0.2 mmol) was added to a reactor containing 1 mol% of reduced PtV/titania. After purging, the hydrogen pressure was brought to 10 bar and the temperature to 130 °C. GC analysis of the reaction mixture after 16 h showed formation of 1-ethylpiperidine as the sole product, having a yield of 20%.

Reaction Quantification

Amine quantification was performed via on-line and off-line GC for flow and batch reactions, respectively. In both cases, a suitable internal standard was added to the reaction mixture to allow quantification of amide consumption and product formation. The gas- chromatograph was mounted with a COT fused silica 10 m x 0.32 mm column (coating: CP-Volamine) .

Catalyst Preparation and Handling The two or three metals forming the catalysts were deposited onto the carrier using the techniques known by the skilled person, and preferably by incipient wetness impregnation directly from aqueous solutions containing a mixture of all desired metal salts. The total metal loading was kept between 2 and 5 wt% for the catalysts.

Catalyst reduction can be attained by several reductants, like, and not limited to, NaBH, hydrazine, and hydrogen gas. Reduction by hydrogen gas was the preferred method, mainly in case of the reactions in flow mode. Catalyst reduction can be carried out in situ (immediately before addition of the reaction mixture) or beforehand.

In the latter situation, it is recommended to store and handle the reduced catalyst under an oxygen free environment (e.g. a glove box under an atmosphere of nitrogen) , to prevent metal oxidation. It is recommended, but not essential, to have the support particle size between 50 and 1000 μm, preferably between 100 and 700 μm, and most preferably between 200 and 400 μm.

RESULTS

Catalyst Performance and Best Catalysts

Table 2 shows those catalysts that formed the amine in yields higher than 35% and at temperatures lower than 160 °C. An alternative and more comprehensive visualisation of these data are presented in Figure 4 and Figure 5. Figure 4 shows that many of the active species result from combinations of Pt, Rh or Ir (Group A metals) with Re (followed by Mo and V from Group B) . Figure 5 shows the amine yield obtained with catalysts containing only metals from groups B and C. As can be seen, only combinations of Re and Mo with In formed 1-ethylpyrrolidine in yields higher than 35%, and at temperature of 130°C. This result bears the important message that the presence of a metal from Group A is important in the formation of active catalytic species. Figure 4 and Figure 5 also show that the support may also affect the catalyst activity. Table 2. List of silica- and carbon-supported catalysts that formed amine in yields equal or higher than 35%. Values lower than 35% were left blank. The table is divided into bi- and trimetallic catalysts, and within each division the content is sorted by catalyst alphabetical order. Support: Silica Support: Carbon Amine (%) Amine (%) Type Catalyst 100°C 130°C Type Catalyst irjrj°C 130°C CoCu 72 Fein 66 FeRe 40 IrMo 62 IrMo 35 53 IrRe 40 IrRe 48 70 IrV 52 = PtRe 45 44 Moln 55 "S PtV 36 49 o PtMo 69 46 ε to Rein 61 ra PtRe 58 ω RhRe 77 36 E PtV 67 71 RhV 42 51 m Rein 54 Ruin 37 RhCu 40 RuRe 44 63 Rhln 76 CoMoZn 59 RhMo 68 77 CoReCU 41 RhRe 38 83 CoReln 77 RuRe 48 69 FeCrln 48 CoVIn 54 FeReln 68 76 FeReCu 71 IrMoCu 39 FeReln 73 IrReCu 65 FeReZn 35 IrReln 59 IrReZn 57 84 IrReZn 66 IrVZn 38 o PtMoCu 74 PtMoCU 64 85 nj PtReCu 79 76 o PtMoIn 35 "ffi PtReln 76 86 ra PtMoZn 63 E E PtReZn 37 81 PtVIn 37 .1 PtReln 86 X— PtReZn 35 PtVZn 74 RhMoCu 36 73 RhMoCu 60 85 RhMoln 37 RhMoln 54 RhMoZn 77 RhReCu 51 RhReCu 83 RhRelπ 56 RhReZn 37 RhReZn 47 RuMoZn 58 RhVIn 46 RuReZn 41 58 RuReCu 48 RuReZn 39 75

Performance of Related Bi- and Trimetallic Catalysts In a number of situations, trimetallic catalysts performed better than related bimetallic species. This synergistic effect has been noticed with carbon and silica supports, and Table 3 gives two examples of such situation (both with silica supported catalysts) . Thus, in case of PtReln/Silica and PtReCu/Silica, none of the related bimetallic species performed as well as the trimetallic ones. Conversely, the catalyst IrRe/Silica gave higher yields of amine than any other trimetallic species containing Ir and Re (i.e., IrReCu, IrReln and IrReZn on silica, Table 6) .

Table 3. Examples of the performance of bi- and trimetallic catalysts . Amine (%) catalyst '- 100°C 130°C PtReln 76 86 PtRe 45 44 Ptln 10 67 Rein 60 70 PtReCu 79 76 PtRe 45 44 PtCu >10 >10 ReCu >10 27 IrReCu 26 65 IrReln 15 59 IrReZn 24 66 IrRe 48 70 a) Support: silica.

Amide reduction in Batch Mode

Figures 6 to 9 show the performance of several bi- and trimetallic catalysts in the reduction of 1-acetylpiperidine at 10 bar and 130°C having acetic acid as solvent. The amount of catalyst on each reaction was kept constant at 5 mol% (calculated considering the total number of moles of metals on each catalyst) . The ratio in front of each catalyst name refers to the molar fraction of each metal in the catalyst composition. The code for the first metal element is related to the type of salt used during the catalyst preparation:

FeNH : Ammonium iron (III) citrate

FeN03: Fe (N0₃) ₃.9H₂0

IrCl4: IrCl₄.H₂0 IrNH4: NH₄IrCl₆

PtNH3: (NH₃)₄Pt (N0₃)₂

PtN03: Pt (N0₃)₂(H₂0)₂

RhNH4: (NH₄)₃RhCl₆

RhN03: Rh(N0₃)₃ RuCl3: RuCl₃.H₂0

RuNO: Ru(NO) (N0₃)_x. (H₂0) _y

Testing of physical mixtures

It is mentioned in the available literature, that the physical mixture Rh/C + Re/C constitutes one of the most active catalytic systems, capable to form 1-ethylpiperidine from 1-acetylpiperidine in 98% yield in a reaction carried out in 1,2-DME at 100 bar, 170°C, for 16 h and using 1 mol% of catalyst (Hirosawa, C; akasa, N.; Takamasa, F. Tetrahedron Lett. 1996, 37, 6749-6752) . The authors also claim that the performance of the physical mixture is equivalent to the pre-made Rh-Re/C catalyst. We decided to test these aspects under our reaction conditions (i.e. reduction of 1-acetylpiperidine for 16 h in batch mode at 10 bar, 130°C, 5 mol% of metal, and acetic acid as solvent). A similar test was carried out with catalyst 0.5:0.5 Pt (N03) Re/Ti; we tested the performance of the physical mixture 0.5 Pt/Ti + 0.5 Re/C, and also the situation in which rhenium was not present. The results are shown in Figure 10. As can be seen, unlike the case of 0.5:0.5 Pt(N03) Re/Ti, the amine is formed in yields lower than 10%, showing the superiority of the catalyst system explored in the course of this work. Moreover, the described experiment points out the importance of having platinum and rhenium intimately mixed for the generation of a catalytic active system able to reduce the amide substrate under the applied mild reaction conditions.

Claims

C L A I M S

1. Method for the catalytic reduction of an amide for the preparation of an amine at a temperature of below 200°C and a pressure of below 50 bar, the catalyst being chosen from bimetallic and trimetallic catalysts of the group consisting of ABC, AB, AC and BC, wherein:

A is a metal, chosen from the group, consisting of Co, Fe, Ir, Pt, Rh and Ru,

B is a metal, chosen from the group, consisting of Cr, Mo, Re and V, and,

C is a metal, chosen from the group, consisting of Cu, In and Zn.

2. Method according to claim 1, wherein the catalyst is a heterogeneous catalyst on a support.

3. Method according to claim 2, wherein the support is chosen from carbon, silica, titania, silica-alumina or a combination thereof.

4. Method according to any of the preceding claims, wherein the pressure is 30 bar or less, preferably 15 bar or less.

5. Method according to claim 4, wherein the pressure is between 1- 17 bar, preferably between 5-10 bar, most preferably between 6-10 bar.

6. Method according to any of the preceding claims, wherein the reduction is performed in continuous flow mode, preferably in a gaseous phase.

7. Method according to any of the preceding claims, wherein the temperature is 160° or less.

8. Method according to claim 7, wherein the temperature is 130°C or less .

9. Method according to claim 8, wherein the temperature is between 70°C-100°C, preferably around 80°C.

10. Method according to any of the claims 1-5, wherein the reduction is performed in batch mode, preferably in liquid phase.

11. Method according to claim 10, wherein the amide is dissolved in a Bronsted-acid.

12. Method according to claim 11, wherein the acid is an organic acid.

13. Method according to claim 12, wherein the organic acid is a carboxylic acid.

14. Method according to claim 13, wherein the carboxylic acid comprises acetic acid.

15. Method according to any of the claims 11-14, the acid having a pKa value of 5 or less, preferably between 3 and 5.

16. Method according to any of the preceding claims, the concentration of the acid being 1.0 M or less, preferably between 0.2 and 0.8 M, more preferably between 0.4 and 0.5 M.

17. Method according to any of the claims 10-16, the liquid phase comprising an additive comprising a Lewis acid.

18. Method according to claim 17, wherein the Lewis acid comprises a Boron compound.

19. Method according to claim 17 or 18, wherein the ratio amide : additive is 4 or less, preferably 2 or less, most preferably between 0.9 and 1.1.

20. Method according to any of the claims claim 10-19, wherein the temperature is between 90-140^cC, preferably 100-130°C.

21. Method according to any of the preceding claims, wherein the catalyst is chosen from the group, consisting of:

CoCu IrMoCu Fein IrReCu FeRe IrReZn IrMo IrVZn IrRe PtMoCu IrV PtMoIn Moln PtMoZn PtMo PtReCu PtRe PtReln PtrV PtReZn Rein PtVIn RhCu PtVZn Rhln RhMoCu RhM RhMoln RhRe RhMoZn RhV RhReCu RuRe RhReIn CoMoZn RhReZn CoReCu RhMoZn CoReln RhVIn CoVIn RuReCu FeCrln RuReZn FeReCu FeReln FeReZn

22. Method according to claim 21, wherein the catalyst is chosen from the group, consisting of IrMo, IrRe, PtRe, PtV, RhRe, RhV, FeReln, PtReCu, PtReln, PtReZn, RhMoCu, RuReZn, PtMo, RhMo, RuRe, IrReZn and PtMoCu.

23. Method according to claim 22, wherein the catalyst is chosen from the group, consisting of IrReZn, PtReCu, PtReln, FeReln, PtMo, PtV, RhMo, PtMoCu, RhMoCu, PtRe, and RuRe.

24. Method according to claim 23, wherein the catalyst is chosen from the group, consisting of PtReCu, PtRe, PtMo IrReZn, PtMoCu and PtReln.

25. Bi- or trimetallic catalysts for the reduction of amides to amines, chosen from the group, consisting of: CoCu IrMoCu Fein IrReCu FeRe IrReZn IrMo IrVZn IrRe PtMoCu IrV PtMoIn Moln PtMoZn PtMo PtReCu PtRe PtReln PtrV PtReZn Rein PtVIn RhCu PtVZn Rhln RhMoCu RhV RhMoln CoMoZn RhMoZn CoReCu RhReCu CoReln RhReIn CoVIn RhReZn FeCrln RhMoZn FeReCu RhVIn FeReln RuReCu FeReZn RuReZn

26. Bi- or trimetallic catalyst according to claim 25, the catalyst being chosen from the group, consisting of IrMo, IrRe, PtRe, PtV,

RhV, FeReln, PtReCu, PtReln, PtReZn, RhMoCu, RuReZn, PtMo, IrReZn and PtMoCu.

27. Catalyst according to claim 26, chosen from the group, consisting of PtReCu, PtRe, PtMo IrReZn, PtMoCu and PtReln.

28. Method for the selection of at least one bi- or trimetallic catalyst, active in the reduction of amides into amines, from a collection of bi- and/or trimetallic catalysts comprising the steps of: A) preparing the catalysts on separate carriers, B) loading the catalysts prepared in step A) in separate reactor vessels, the vessels having a parallel arrangement, C) feeding and incubating the reactor vessels with an amide and hydrogen at identical conditions regarding at least one of the quantities, chosen from reaction time, temperature and pressure, D) measuring the conversion of amides into amines in each reactor vessel, E) selecting one or more of the catalysts, based on the measured conversion in step D) .

29. Method according to claim 28, wherein in step C) the reaction time, temperature and pressure in the reactor vessel are similar for each reactor vessel.

^•30. Method according to any of the claims 28-29, wherein in step A) the catalysts are prepared on separate carriers in parallel.

31. Method according to any of the claims 28-30, wherein in step C) the reaction vessels are fed in parallel.