Magneto-catalysis for low pressure hydrogenation

Abstract

The present invention is directed towards catalysts comprising magnetic particles and metal particles on a support, as well as methods of hydrogenating substrates utilising such catalysts. In particular, a method employing such catalysts to hydrogenate amides is claimed. The catalysts and methods of the present invention improve upon the disadvantages associated with literature hydrogenation reactions and in particular, allow hydrogenation reactions under mild conditions.

Description

[0001] 274 792

[0002] Title of Invention

[0003] Magneto-Catalysis for Low Pressure Hydrogenation

[0004] Field of the Invention

[0005] The present invention is directed towards methods of hydrogenating at low pressures, particularly hydrogenating amides at low pressures. The present invention is further directed towards a catalyst and its use in hydrogenation reactions, particularly hydrogenation reactions of amides.

[0006] Background of the Invention

[0007] The reduction of amides to amines is a key transformation for the chemical industry as it produces pivotal building blocks used for the preparation of agrochemicals, polymers, dyes, and pharmaceuticals. Traditional methods rely on the use of (over)stoichiometric reductants such as LiAlH4, DIBAL, Red- Al, hydrosilanes and hydroboranes under mild conditions, making them economically and ecologically unfavourable.

[0008] The catalytic hydrogenation of amides using molecular hydrogen (H2) could be considered a promising alternative to produce amines in a sustainable manner. However, the C=0 bond in amides is the most difficult to hydrogenate among carbonyl functionalities, hindering the development of this approach.

[0009] Previously, homogeneous catalysts based on molecular organometallic catalysts with specific ligand frameworks and appropriate additives were reported to hydrogenate amides to amines (C-0 bond cleavage) or to alcohols (C-N bond cleavage) at elevated temperatures and H2pressures (100-200 °C, 10-80 bar H2). Solid heterogeneous catalysts have been reported for amide hydrogenation, including the development of bimetallic catalysts. For example, Kaneda et al. ("Mild Hydrogenation of Amides to Amines over a Platinum-Vanadium Bimetallic Catalyst" Angew. Chem. Int. Ed. 2017, 56, 9381-9385), report on a hydrogenation reaction of amides using a Pt-V bimetallic catalyst. However, reaction conditions remain demanding (VO- SOO °C, 20-900 bar H2) and / or are associated with limited catalytic activity and stability, making the development of new sustainable and practical catalytic technologies that enable efficient amide hydrogenation with H2under mild conditions, greatly desirable. An overview of hydrogenation reactions of amides to amines by heterogeneous catalysis is provided by H. Yang, H. Garcia and C. Hu ("Hydrogenation of amides to amines by heterogeneous catalysis: a review" Green Chem. 2024, 26, 2341-2364).

[0010] Hydrogenation reactions of aromatic ketones under milder reaction conditions have been described. For example, Bordet et al. describe a magnetically induced hydrogenation of aromatic ketones utilising a bulk catalyst decorated with iron carbide nanoparticles ("Commercial Cu2Cr20s Decorated with Iron Carbide Nanoparticles as a Multifunctional Catalyst for Magnetically Induced Continuous-Flow Hydrogenation of Aromatic Ketones" Angew. Chem. Int. Ed. 2021, 60, 26639- 26646). However, such hydrogenation reactions have a limited substrate scope, and the catalyst is not suitable for the hydrogenation of challenging functionalities (e.g., amides, acids, and esters).

[0011] In summary, traditional methods of amide hydrogenation reactions are coupled with significant drawbacks, including the need for high pressure and / or temperature, narrow range of functional group tolerance, and catalysts are not recyclable . To avoid the disadvantages associated with past methods, the present inventors have developed a catalyst and a method to access amines through the selective hydrogenation of amides, using magnetically induced catalysis.

[0012] It is an object of the present invention to hydrogenate amides to access the corresponding amines and to improve upon the disadvantages associated with conventional methods. In particular, the present invention allows for the production of amines from amides with good yields, good selectivity and good substrate scope, whilst the catalyst according to the present invention is stable and recyclable. Furthermore, the hydrogenation reaction according to the present invention proceeds under mild reaction conditions (low pressures and temperatures, including ambient pressures), is efficient, is sustainable and has a high turnover frequency. The herein described method also provides for a potential adaptivity of the catalytic process to intermittent power supply.

[0013] In addition, the catalysts described herein allow for rapid, localised and energy efficient heating due to magnetically induced catalysis. This contributes to the potential adaptivity of the catalytic process to intermittent power supply, to sustainability, to mild reaction conditions (e.g., <5 bar H2), and to efficiency of the reactions.

[0014] The presently claimed invention also allows for the hydrogenation of substrates, in particular amide substrates, with H2pressures below 5 bar (mild conditions). This is also greatly beneficial from a practical and safety point of view and avoids the need for specialised high-pressure technologies on laboratory or production scale. Summary of the Invention

[0015] The above object is solved by a method of hydrogenating a substrate, the method comprising bringing a substrate and hydrogen into contact with a catalyst and applying an alternating current magnetic field, as defined in claims 1. It is also solved by a catalyst comprising metal particles on a support and magnetic particles, and the use of such catalysts in hydrogenation reactions, as defined in claims 10 and 15. Preferred embodiments are the subject of the dependent claims.

[0016] By employing the methods and / or catalyst according to the present invention, the inventors have improved upon the drawbacks associated with traditional methods of hydrogenation reactions, particularly amide hydrogenation reactions.

[0017] Brief Description of the Drawings

[0018] Figure 1: Synthesis and characterization of ICNPs-Pt / Al2O3. a) Synthetic procedure for the ICNPs-Pt / Al2O3 catalyst, and b-g) characterization of ICNPs-Pt / Al2O3 by electron microscopy, b-c) SEM images at different magnifications, d) STEM-HAADF, and e-g) SEM-EDX elemental mapping, e) Fe, f) Pt, and g) Al using Fe Ka, Pt La and Al Ka.

[0019] Figure 2: Powder XRD diffractogram of ICNPs-Pt / Al2O3. References: y-Al2O3(dot), fee Pt(0) (triangle) and ICNPs (square).

[0020] Figure 3: Superconducting quantum interference device (SQUID) measurement at 300 K. The saturation magnetization (Ms) of per unit weight of Fe is 168.5 A m2kg-1. Figure 4: Characterization of ICNPs-Pt / Al2O3 by a) Fe K-edge XANES (normalized), b)57Fe zero-field Mdssbauer measurement at 80 K, c) Pt L3-edge XANES (normalized) and d) Fourier transform magnitudes of Pt L3-edge k2-weighted EXAFS data and corresponding fits in R-space (without phase correction).

[0021] Figure 5: Reaction time profiles of the hydrogenation of 1 using ICNPs-Pt / Al2O3heated by magnetic induction, a) Time profile; b) time profile recorded while regularly switching ON and OFF the power supply of the magnetic induction generator (light grey area = power ON and dark grey area = power OFF). Reaction conditions: 1 (12.9 mg, 0.10 mmol), ICNPs-Pt / Al2O3(35.0 mg, 1.26 pmol Pt), decalin (0.5 mL), H2(3 bar), magnetic field (poHmax= 72 mT, 350 kHz). The product selectivity is >99%. Product yields determined by GC-FID using tetradecane as the internal standard. Data point are average values of three experiments, and error bars represent standard deviations.

[0022] Figure 6: Study of the stability of ICNPs-Pt / Al2O3through recycling experiments, a) Conversion and yield of la over 5 cycles. Reaction conditions: 1 (12.9 mg, 0.10 mmol), ICNPs- Pt / Al2O3(35.0 mg, 1.26 pmol Pt), decalin (0.5 mL), H2(3 bar), 0.5 h, magnetic field (poHmax= 72 mT, 350 kHz). Products yields determined by GC-FID using tetradecane as the internal standard. The product selectivity to la is >99%. Data point are average values of three experiments, and error bars represent standard deviations, b-g) Characterization of the catalyst by electron microscopy, b-c) SEM images at different magnifications, d) STEM-HAADF, and e-g) SEM-EDX elemental mapping, e) Fe, f) Pt, and g) Al using Fe Ka, Pt La and Al K .

[0023] Figure 7: Superconducting quantum interference device (SQUID) measurement after catalysis at 300 K. Figure 8: The XANES and EXAFS measurement, a) Fe K-edge XANES spectra (normalized), b) Pt L3-edge XANES spectra (normalized), c) Fourier transform magnitudes of Pt L3-edge k2-weighted EXAFS spectra in R-space and d) Pt L3-edge k2- weighted EXAFS in k-space.

[0024] Figure 9: Hydrogenation of l-acetyl-3-methyl piperidine (1)2H NMR (400 MHz, CDC13) 5 (ppm): 5 = 11.77 (br, 1H), 3.53 (d, 2H), 3.38 (d, 2H), 3.04 (br, 2H), 2.49-2.14 (m, 4H), 1.91- 1.82 (t, 2H), 1.46-1.43 (t, 3H), 1.09-1.04 (m, 1H), 1.01 (t, 3H).13C NMR (100 MHz, CDC13) 5 = 58.46, 52.65, 52.26, 22.60, 18.98, 9.19.

[0025] Figure 10: Hydrogenation of l-methyl-2-piperidone (6)

[0026] 2H NMR (400 MHz, CDC13) 5 (ppm): 5 = 11.68 (br, 1H), 3.43 (d, 2H), 2.73 (d, 3H), 2.70-2.66 (m, 2H), 2.19-2.14 (m, 2H),

[0027] 1.90-1.79 (m, 3H), 1.41-1.33 (m, 1H).13C NMR (100 MHz, CDC13) 5 = 55.06, 43.96, 22.80, 21.43.

[0028] Figure 11: The global temperature of the reactor surface resulting from the heat dissipated by the ICNPs-Pt / Al2O3was measured using an infrared camera under standard conditions (72 mT, 350 kHz).

[0029] Figure 12: Simplified overview of a method according to the present invention.

[0030] Detailed Description

[0031] Embodiments according to the present invention will now be described in more detail.

[0032] As used herein, the term "support" refers to a typical support material for catalysis. The support is a solid material on which the components of the catalyst could be immobilised. The support is preferably a particulate support.

[0033] A "support" according to the present invention does not include bulk metal material, such as Cu2Cr2O5, which can be used directly as a heterogeneous catalyst.

[0034] Examples of a support according to the present invention include, but are not limited to, alumina (AI2O3), SiCy, CeCy, TiCh, further metal oxides, and carbon supports (such as activated carbon, graphene, graphite, and carbon nanotubes). For example, alumina is an excellent support material for the present invention, due to its large surface area, excellent thermal, mechanical and chemical stability, as well as having no catalytic activity. According to a preferred embodiment of the invention, the support is alumina.

[0035] As used herein, the term "particles" refers to ensembles of atoms that can possess various shapes and structures, which generally have a size of 1 nm - 1 pm for metal particles, and 1 nm - 10 pm for magnetic particles. In a preferred embodiment of the invention, the particles are nanoparticles. Metal nanoparticles according to a preferred embodiment can have a size of 1-20 nm, more preferably 1-10 nm. Magnetic nanoparticles according to a preferred embodiment can have a size of 5-50 nm .

[0036] As used herein, the term "magnetic particles" refers to particles that heat upon exposure to external alternating current magnetic fields. Examples of such magnetic particles include iron carbide particles, metallic iron particles, iron oxide particles, cobalt particles, nickel particles, and bimetallic or multimetallic combinations thereof. A method of preparing iron carbide nanoparticles is outlined in US 2020 / 0047166 Al.

[0037] As used herein, the term "neat conditions" refers to a reaction that is carried out without the presence of any additional solvents.

[0038] As used herein, the term "alternating current magnetic field" refers to the magnetic field produced by an alternating current .

[0039] As used herein, the term "monometallic particle" refers to particles comprised of one metal. The term "bimetallic particles" refers to particles comprised of two different metals. The term "multimetallic particles" refers to particles comprised of more than two different metals.

[0040] As used herein, the term "3d transition metal" refers to metals from the first transition series or 3d series, including Sc, Ti, V, Or, Mn, Fe, Co, Ni, Cu and Zn.

[0041] As used herein, the term "4d transition metal" refers to metals from the second transition series or 4d series, including Y, Zr, Nb, Mo, Tc, Ru, Rh, Pd, Ag and Cd.

[0042] As used herein, the term "5d transition metal" refers to metals from the third transition series or 5d series, including La, Hf, Ta, W, Re, Os, Ir, Pt, Au and Hg.

[0043] As used herein, the term "ICNPs-Pt / A^Oa" refers to iron carbide nanoparticles (ICNPs) immobilised on the support AI2O3 that contains Pt (nano)particles. A preferred method of immobilising the nanoparticles on the support is outlined in the examples of the present invention. As used herein, the "viscosity" of the solvent can be measured on a capillary viscometer at 20 °C.

[0044] As used herein, "low pressures" generally refer to pressures of 4 bar or less.

[0045] As used herein, "low temperatures" generally refer to temperatures of 170 °C or less.

[0046] Method according to the invention

[0047] According to an embodiment of the present invention, a method of hydrogenating a substrate comprises: bringing a substrate and hydrogen into contact with a catalyst; and applying an alternating current magnetic field (ACMF) with a frequency and field amplitude sufficient to effect the hydrogenation reaction, wherein the catalyst comprises: a)metal particles on a support, and b)magnetic particles.

[0048] It is preferred that the metal particles and the magnetic particles are immobilised to the support. This has the advantage that leaching of the particles is prevented. Furthermore, without wishing to be bound by theory, functionalising the support with magnetic particles is thought to allow for localised and rapid heating, resulting in the activation of neighbouring metal particle sites by thermal energy transfer. This further promotes the methods according to the present invention to be operated at low (including ambient) hydrogen pressures. The various aspects of the method according to the present invention will be described in more detail in the following sections .

[0049] Hydrogenation reaction

[0050] The method of the present invention is particularly suitable for a hydrogenation reaction.

[0051] According to a preferred embodiment, the hydrogenation reaction is a hydrogenation reaction of an amide substrate.

[0052] The method and the catalyst according to the present invention, allow the selective hydrogenation of an amide substrate to its corresponding amine. It is thus preferred, that the hydrogenation reaction is a hydrogenation reaction of an amide to an amine. The method according to an embodiment of the present invention can thus be summarised as follows : o

[0053] RU MagneticallyinducedcatalysisR

[0054] ^R3+ 2H2 ,SNZXR3+ H2O

[0055] The definition of each of Ri, R2and R3 is not particularly limited and can include, for example, H, a substituted or unsubstituted carbocyclic ring, a substituted or unsubstituted heterocyclic ring, or a linear or branched substituted or unsubstituted C1-C30 alkyl group, wherein the linear or branched alkyl group is optionally substituted. Ri and R2can also form a ring system.

[0056] Substrate

[0057] The substrates according to the present invention are not particularly limited, except that the substrate should include a moiety that can be hydrogenated. Examples of suitable substrates include but are not limited to aldehydes, ketones, amides, alkenes, alkynes, nitro, esters, carboxylic acids and nitriles.

[0058] According to a preferred embodiment, the substrate is an amide substrate. This can include primary, secondary, and tertiary amides.

[0059] According to a more preferred embodiment, the substrate is a secondary or tertiary amide. It is more preferred, that the amide is a heterocyclic secondary amide or a heterocyclic tertiary amide.

[0060] In a preferred embodiment of the presently claimed method, the amide substrate is hydrogenated to an amine.

[0061] In an embodiment of the present invention, the substrate is:

[0062]

[0063] Hydrogen

[0064] According to a preferred embodiment of the present invention, the pressure of the hydrogen is 1-100 bar, preferably 1-20 bar, more preferably 1-10 bar, even more preferably 1-5 bar, most preferably 2-4 bar.

[0065] Magnetic field

[0066] The method of hydrogenating a substrate includes the application of a magnetic field. It is preferred that an alternating current magnetic field (ACMF) is applied.

[0067] The magnetic field has a frequency and field amplitude sufficient to effect the hydrogenation reaction.

[0068] According to a preferred embodiment, the magnetic field heats the magnetic particles to a temperature of 100-450 °C, preferably 150-400 °C, more preferably 250-350 °C.

[0069] It is preferred that the applied magnetic field has a field amplitude of 1 - 200 mT, preferably 15 - 150 mT, more preferably 30 - 80 mT, most preferably 45 - 80 mT.

[0070] It is also preferred that the applied magnetic field has a frequency of 50 - 600 kHz, preferably 150 - 400 kHz.

[0071] According to a preferred embodiment, an alternating current magnetic field with a frequency of 150 - 400 kHz and a field amplitude of 30 - 80 mT, preferably 45 - 80 mT, is applied. The advantage of applying such a magnetic field is achieving good selectivity and yields in the hydrogenation reaction, while providing localised, rapid and energy efficient heating of the catalyst. A further advantage is that the reaction can proceed at low pressure and low temperature.

[0072] Catalyst components

[0073] Metal particles

[0074] It is preferred that the metal particles on the support are catalytically active metals. Preferably, the metal particles on the support are a hydrogenation active metal.

[0075] According to a preferred embodiment, the metal particles on the support are nanoparticles.

[0076] According to a more preferred embodiment, the metal particles have a size of 1-100 nm, more preferably 1-20 nm, most preferably 1-10 nm.

[0077] The content of the metal particles in the catalyst is not particularly limited. In a preferred embodiment, the content of the metal particles in the catalyst is 0.1-10 weight-%, more preferably 1-5 weight-%.

[0078] In an embodiment of the present invention, the metal particles on the support are monometallic, bimetallic or multimetallic particles. It is preferred that the metal particles on the support are monometallic, bimetallic or multimetallic nanoparticles.

[0079] According to an embodiment of the invention, the metal particles on the support are selected from 3d, 4d and / or 5d transition metals. When the metal particles on the support are monometallic particles, the metal particles are preferably selected from a 4d or 5d transition metal.

[0080] According to a preferred embodiment, the metal particles on the support are selected from one or more 4d or 5d transition metals. More preferably, the metal particles on the support are selected from one or more of platinum, palladium, rhodium, or ruthenium.

[0081] According to a preferred embodiment, the metal particles are immobilised on the support.

[0082] In a more preferred embodiment, the metal particles on the support are platinum particles. According to a most preferred embodiment, the metal particles on the support are platinum nanoparticles .

[0083] Support

[0084] According to a preferred embodiment, the support is a particulate support.

[0085] Preferred examples of a support according to the present invention include, but are not limited to, alumina (AI2O3), Sieg, CeC>2, H O2, further metal oxides, and carbon supports (such as activated carbon, graphene, graphite, and carbon nanotubes) . For example, alumina is an excellent support material for the present invention, due to its large surface area, excellent thermal, mechanical and chemical stability, as well as having no catalytic activity.

[0086] A support according to the present invention does not include bulk metal material, such as Cu2Cr2O5.

[0087] According to a most preferred embodiment of the invention the support is alumina. An advantage of a support according to the present invention is that the support can serve to support both the metal particles, as well as the magnetic particles. This allows for a very versatile approach, in which a variety of metal particles and / or magnetic particles can be immobilised on typical catalytic support materials such as metal oxides, Sieg, alumina, etc.

[0088] One advantage of the metal particles and / or magnetic particles being immobilised on the support, is that leaching and coalescence of the particles is prevented.

[0089] Furthermore, functionalising the support with magnetic particles allows for localised and rapid heating, resulting in the activation of neighbouring metal particle sites by thermal energy transfer. This allows the methods according to the present invention to be operated at low (including ambient) hydrogen pressures.

[0090] Magnetic particles

[0091] It is preferred that the magnetic particles are magnetic nanoparticles. This has the advantage that the nanoparticles provide a more localised and efficient heating.

[0092] The nanoparticles can be spread individually across the support or can be agglomerated. Preferably the nanoparticles are not agglomerated.

[0093] According to a more preferred embodiment, the magnetic particles have a size of 5-50 nm, most preferably 10-20 nm.

[0094] According to a further preferred embodiment, the content of the magnetic particles in the catalyst is 3-50 weight-%, preferably 10-40 weight-%, more preferably 20-35 weight-%. According to a preferred embodiment, the magnetic particles are immobilised on the support. The magnetic particles can be immobilised on the support, for example, by using a magnetic induction treatment. The immobilisation of the magnetic particles on the support has the advantage that leaching of the particles is prevented. This allows for an improved catalyst recyclability and reusability.

[0095] It is further preferred that the magnetic particles comprise one or more of iron, cobalt or nickel, or any combination thereof. It is particularly preferred that the magnetic particles comprise iron. For example, the magnetic particles can comprise Fe(0), FeNi or FeCo.

[0096] According to a preferred embodiment, the magnetic particles further comprise carbon, nitrogen, phosphorous, boron or sulphur .

[0097] It is preferred that the magnetic particles comprise one or more of iron, cobalt or nickel, or any combination thereof, and that they are present as a carbide, boride, nitride, phosphide or sulphide.

[0098] For example, the magnetic particles according to the present invention can be iron carbide particles, iron-cobalt particles, iron nickel particles, cobalt-nickel particles, iron-phosphide particles, iron-boride, and iron nitride particles .

[0099] It is preferred that the magnetic particles are different from the metal particles. It is preferred that the magnetic particles and the metal particles are of a different material .

[0100] According to a more preferred embodiment, the magnetic particles are iron carbide nanoparticles. It is preferred that the iron carbide nanoparticles have a size of 5-50 nm, more preferably 10-20 nm. It is also preferred that the content of the iron carbide nanoparticles in the catalyst is 3-50 weight-%, preferably 10-40 weight-%, more preferably 20- 35 weight-%.

[0101] According to an embodiment of the invention, when the magnetic particles are iron carbide nanoparticles, it is preferred that 40-100% of the iron atoms that the iron carbide nanoparticle comprises are present in an Fe2.2C crystalline structure. More preferably, in the iron carbide nanoparticle, 70-90% of the iron atoms that it comprises are present in an Fe2.2C crystalline structure. The remainder of the iron atoms can be present as FesC2, Fe(0), FeOx, and any combination thereof.

[0102] According to a most preferred embodiment, the magnetic particles are iron carbide nanoparticles and the iron carbide nanoparticles are immobilised on the support.

[0103] General

[0104] According to an embodiment of the present invention, the hydrogenation reaction is carried out under neat conditions. This can be particularly useful when the substrate is a liquid.

[0105] According to another embodiment of the present invention, the reaction is carried out in a solvent. It is preferred that the solvent has a boiling point of 100-350 °C, more preferably 120-300 °C, most preferably 180-260 °C. Working within these ranges has the advantage that the activity of the reaction is improved.

[0106] Without wishing to be bound by theory, boiling points that are too low can be problematic due to the Leidenfrost effect. The solvent can heavily boil around the catalyst, building an isolating gaseous layer and decreasing the activity. It is thus advantageous to work within the above-mentioned temperature ranges.

[0107] It is further preferred that the solvent has a viscosity of 0.1-5 mPa-s, preferably 0.5-3 mPa-s. Working within these ranges has the advantage that the reaction rate is improved. Working within these ranges can further prevent mass transfer limitations from the substrate to the catalytically active sites. If the solvent is too viscous, the reaction rate can decrease because the substrate molecules take longer to diffuse and reach the catalyst.

[0108] It is particularly preferred that the solvent has a boiling point of 180 - 260 °C and a viscosity of 0.5-3 mPa-s.

[0109] Examples of suitable solvents include but are not limited to decalin, propylene carbonate, tetradecane, dodecane, propylene carbonate, diethyl succinate, diethyl sulfate, diethyl malonate, 2-ethylhexyl acetate, D-limonene, mesitylene, diglyme, anisole, cumene, p-xylene, diethyl carbonate, and dioxane.

[0110] It is preferable that the solvent is dioxane, tetradecane, hexadecane, decalin or propylene carbonate.

[0111] If a solvent is used, the substrate and / or the catalyst can be dispersed in the solvent.

[0112] Advantages of the catalysts described in the sections above, include their recyclability and re-usability.

[0113] Overall, according to a most preferred embodiment, the invention is directed towards a method of hydrogenating an amide substrate, wherein the method comprises: bringing an amide substrate and hydrogen into contact with a catalyst; and applying an alternating current magnetic field with a frequency and field amplitude sufficient to effect the hydrogenation reaction, wherein the catalyst comprises: a) Pt nanoparticles on alumina (AI2O3), and b) iron carbide nanoparticles, wherein the iron carbide nanoparticles are immobilised on the alumina and wherein the reaction is carried out in a solvent, wherein the solvent has a boiling point of 180 - 260 °C and a viscosity of 0.5-3 mPa-s, preferably wherein the solvent is decalin.

[0114] Preferably, 40-100% of the iron atoms that the iron carbide nanoparticle comprises are present in an Fe2.2C crystalline structure, more preferably 70-90%; and / or the content of the iron carbide nanoparticles in the catalyst is 3-50 weight-%, preferably 10-40 weight-%, more preferably 20-35 weight-%.

[0115] Utilising platinum particles as the metal particles and alumina as the support, has the advantage that Pt / Al2O3 is commercially available. Furthermore, functionalising Pt / Al2O3 with iron carbide nanoparticles allows for localised and rapid heating, resulting in the activation of neighbouring Pt sites by thermal energy transfer. This allows the methods according to the present invention to be operated at low hydrogen pressures.

[0116] Such a method is furthermore particularly advantageous in providing the production of amines from amides with good yields, good selectivity and good substrate scope, whilst the catalyst is stable and recyclable. Furthermore, the hydrogenation reaction proceeds under mild reaction conditions (low pressures and temperatures), is efficient and sustainable. The method also provides for a potential adaptivity of the catalytic process to intermittent power supply.

[0117] Catalyst according to the invention

[0118] According to an embodiment of the present invention, the catalyst comprises: i)metal particles on a support, and ii) magnetic particles, preferably magnetic nanoparticles, preferably wherein the magnetic particles are immobilised on the support.

[0119] The components of the catalyst (such as the metal particles, the support, and the magnetic particles) are as outlined in the method section above.

[0120] For example, it is preferred that the magnetic particles comprise one or more of iron, cobalt or nickel, or any combination thereof, preferably wherein the magnetic particles comprise iron. Most preferably the magnetic particles are iron carbide nanoparticles.

[0121] It is particularly preferred that the catalyst according to the present invention comprises: i) platinum nanoparticles on alumina, and ii) iron carbide nanoparticles, wherein the iron carbide nanoparticles are immobilised on the alumina.

[0122] It is preferred that the iron carbide nanoparticles have a size of 5-50 nm, more preferably 10-20 nm. It is also preferred that the content of the iron carbide nanoparticles in the catalyst is 3-50 weight-%, preferably 10-40 weight-%, more preferably 20-35 weight-%.

[0123] It is further preferred that 40-100% of the iron atoms that the iron carbide nanoparticle comprises are present in an Fe2.2C crystalline structure. More preferably, in the iron carbide nanoparticle, 70-90% of the iron atoms that it comprises are present in an Fe2.2C crystalline structure. The remainder of the iron atoms can be present as FesC2, Fe(0), FeOx, and any combination thereof.

[0124] The present invention further includes the use of the abovedescribed catalysts in a hydrogenation reaction. It is preferred that the hydrogenation reaction is a hydrogenation reaction of an amide. It is further preferred that the hydrogenation reaction is a hydrogenation reaction of an amide to an amine.

[0125] Such catalysts are advantageous in for example hydrogenation reactions. Particularly in the production of amines from amides with good yields, good selectivity and good substrate scope, whilst the catalyst is stable and recyclable. Furthermore, the hydrogenation reaction proceeds under mild reaction conditions (low pressures and temperatures), is efficient and sustainable.

[0126] Overall, the present invention allows for the low-pressure (<5 bar) hydrogenation of amides using magnetically induced catalysis with a catalyst composed of magnetically-responsive particles on a support. Using an alternating current magnetic field, the catalyst provides excellent activity, selectivity and stability in the hydrogenation of various substrates. The invention includes:

[0127] Item 1

[0128] Method of hydrogenating a substrate, wherein the method comprises : bringing a substrate and hydrogen into contact with a catalyst; and applying an alternating current magnetic field with a frequency and field amplitude sufficient to effect the hydrogenation reaction, wherein the catalyst comprises: c)metal particles on a support, and d)magnetic particles.

[0129] Itern 2

[0130] Method according to item 1, wherein the magnetic field heats the magnetic particles to a temperature of 100-450 °C, preferably 250-350 °C.

[0131] Itern 3

[0132] Method according to any preceding item, wherein the magnetic particles are magnetic nanoparticles.

[0133] Itern 4

[0134] Method according to any preceding item, wherein the magnetic particles comprise any one of iron, cobalt or nickel, or a combination thereof, preferably wherein the magnetic particles comprise iron.

[0135] Itern 5 Method according to item 4, wherein the magnetic particles further comprise carbon, nitrogen, phosphorous, boron or sulphur .

[0136] Itern 6

[0137] Method according to item 4 or item 5, wherein the iron, cobalt, or nickel, or combinations thereof, is present as a carbide, nitride, phosphide, boride or sulphide.

[0138] Itern 7

[0139] Method according to any preceding item, wherein the magnetic particles are iron carbide nanoparticles.

[0140] Itern 8

[0141] Method according to any preceding item, wherein the magnetic particles are immobilised on the support.

[0142] Itern 9

[0143] Method according to any preceding item, wherein the metal particles on the support: i) are monometallic, bimetallic or multimetallic particles; and / or ii) are nanoparticles; and / or iii) are different from the magnetic particles.

[0144] Item 10

[0145] Method according to any preceding item, wherein the metal particles on the support are selected from: i) one or more 3d, 4d or 5d transition metals; ii) one or more 4d or 5d transition metals; or iii) one or more of platinum, palladium, rhodium, or ruthenium; preferably wherein the metal particles on the support are platinum. Item 11

[0146] Method according to any preceding item, wherein the support is a particulate support.

[0147] Item 12

[0148] Method according to any preceding item, wherein the support is selected from A12O3, TiO2, SiO2, CeO2, activated carbon, graphene, graphite, or carbon nanotubes, preferably wherein the support is A12O3.

[0149] Item 13

[0150] Method according to any preceding item, wherein the content of magnetic particles in the catalyst is 3-50 weight-%, preferably 10-40 weight-%, more preferably 20-35 weight-%.

[0151] Item 14

[0152] Method according to any preceding item, wherein an alternating current magnetic field with a field amplitude of 1 - 200 mT, preferably 15 - 150 mT, more preferably 30 - 80 mT, most preferably 45-80 mT is applied.

[0153] Item 15

[0154] Method according to any preceding item, wherein an alternating current magnetic field with a frequency of 50 - 600 kHz, preferably 150 - 400 kHz is applied.

[0155] Item 16

[0156] Method according to any preceding item, wherein an alternating current magnetic field with a frequency of 150 - 400 kHz and a field amplitude of 30 - 80 mT is applied.

[0157] Item 17

[0158] Method according to any preceding item, wherein the substrate is an amide substrate, preferably wherein the substrate is a secondary or tertiary amide, more preferably wherein the substrate is a heterocyclic amide, most preferably wherein the amide substrate is a secondary or tertiary heterocyclic amide.

[0159] Item 18

[0160] Method according to item 17, wherein the amide substrate is hydrogenated to an amine.

[0161] Item 19

[0162] Method according to any preceding item, wherein the hydrogen is pressurised at 1-100 bar, preferably 1-20 bar, more preferably 1-10 bar, even more preferably 1-5 bar, most preferably 2-4 bar.

[0163] Item 20

[0164] Method according to any preceding item, wherein the reaction is carried out: i) under neat conditions; or ii) in a solvent, wherein the solvent has a boiling point of 100-350 °C, preferably 120-300 °C, more preferably 180-260 °C.

[0165] Item 21

[0166] Method according to item 20, wherein the solvent has a viscosity of 0.1-5 mPa-s, preferably 0.5-3 mPa-s.

[0167] Item 22

[0168] Method according to item 20 or item 21, wherein the solvent has a boiling point of 180 - 260 °C and a viscosity of 0.5-3 mPa •s.

[0169] Item 23

[0170] Method according to any one of items 20-22, wherein the solvent is decalin, propylene carbonate, tetradecane, dodecane, propylene carbonate, diethyl succinate, diethyl sulphate, diethyl malonate, 2-ethylhexyl acetate, D-limonene, mesitylene, diglyme, anisole, cumene, p-xylene, diethyl carbonate, and dioxane, preferably wherein the solvent is tetradecane, decalin or propylene carbonate.

[0171] Item 24

[0172] Catalyst comprising: i) metal particles on a support, and ii) magnetic particles, preferably magnetic nanoparticles .

[0173] Item 25

[0174] Catalyst according to item 24, wherein the magnetic particles comprise any one of iron, cobalt or nickel, or a combination thereof, preferably wherein the magnetic particles comprise iron.

[0175] Item 26

[0176] Catalyst according to item 24 or item 25, wherein the magnetic particles further comprise carbon, nitrogen, phosphorous, boron or sulphur.

[0177] Item 27

[0178] Catalyst according to item 25 or item 26, wherein the iron, cobalt, or nickel, or combinations thereof, is present as a carbide, nitride, phosphide, boride or sulphide.

[0179] Item 28 Catalyst according to any one of items 24-27, wherein the magnetic particles are iron carbide nanoparticles.

[0180] Item 29 Catalyst according to any one of items 24-28, wherein the magnetic particles are immobilised on the support.

[0181] Item 30 Catalyst according to any one of items 24-29, wherein the content of magnetic particles in the catalyst is 3-50 weight- %, preferably 10-40 weight-%, more preferably 20-35 weight-%.

[0182] Item 31

[0183] Catalyst according to any one of items 24-30, wherein the metal particles on the support are selected from one or more 4d or 5d transition metals, preferably wherein the metal particles on the support are selected from one or more of platinum, palladium, rhodium, or ruthenium, more preferably wherein the metal particles on the support are platinum.

[0184] Item 32

[0185] Catalyst according to any one of items 24-31, wherein the metal particles on the support: i) are monometallic, bimetallic or multimetallic particles; and / or ii) are nanoparticles; and / or iii) are different from the magnetic particles.

[0186] Item 33

[0187] Catalyst according to any one of items 24-32, wherein the support is a particulate support, preferably wherein the support is selected from A12O3, TiO2, SiO2, CeO2, activated carbon, graphene, graphite, or carbon nanotubes, more preferably wherein the support is A12O2.

[0188] Item 34

[0189] Catalyst according to any one of items 24-33, wherein the catalyst comprises: i) platinum on alumina, preferably platinum nanoparticles on alumina, and ii) iron carbide nanoparticles, wherein the iron carbide nanoparticles are immobilised on the alumina. Item 35

[0190] Use of a catalyst according to any one of items 24-34 in a hydrogenation reaction.

[0191] Item 36

[0192] Use according to item 35, wherein the hydrogenation reaction is a hydrogenation reaction of an amide, preferably wherein the hydrogenation reaction is a hydrogenation reaction of an amide to an amine.

[0193] Examples

[0194] Examples according to the present invention will be presented.

[0195] General:

[0196] Unless stated otherwise, the syntheses were performed under argon either by using Schlenk techniques or in a glove box. Solvents were purified through a solvent purification system (MBraun-SPS-7) or dried over activated 4 A molecular sieves then degassed and preserved under an argon atmosphere before use. Hexadecylamine (HDA, 99%), palmitic acid (PA, 99%) and platinum on alumina material (Pt / AlaOa) were purchased from Sigma-Aldrich. Amides are purchased from the local suppliers and used without further purification.

[0197] Characterisation techniques:

[0198] • SEM and EDX measurements were carried out using a Hitachi S-5500.

[0199] • XRD measurements were performed on a PANalytical Empyrean diffractometer using Co Ka radiation (X = 0.1789 nm) at 45 kV and 40 mA.

[0200] •57Fe Mossbauer spectra were collected on a spectrometer with conventional constant acceleration of the y source (57Co source in Rh matrix, 1.8 GBq). The sample temperature was kept constant using a Cryogen-Free Magnet (CFM) with integrated variable temperature insert

[0201] (VTI) for zero-field measurements. The minimum experimental linewidth was 0.24 mm-sA Isomer shifts are quoted relative to a-iron at 300 K. The57Fe Mossbauer spectra were simulated and fitted with MX program written by Dr. Eckhard Bill.

[0202] • Superconducting quantum interference device (SQUID) data were collected on a Quantum Design MPMS-3 SQUID magnetometer. DC susceptibility was recorded at 300 K with an applied DC field of 1 T, if not stated otherwise. The SQUID data analysis was conducted with JulX2 program written by Dr. Eckhard Bill.

[0203] • Fe K-edge data was collected using an easyXES-100 spectrometer in transmission mode (E. P. Jahrman, W. M. Holden, A. S. Ditter, D. R. Mortensen, G. T. Seidler, T. T. Eister, S. A. Kozimor, L. F. J. Piper, J. Rana, N. C. Hyatt, M. C. Stennett, Rev. Sci. Instrum. 2019, 90,

[0204] 024106). An X-ray tube with a W anode set to 25 kV and 2 mA, a 1 mm wide entrance slit, a Ge (310) crystal in second diffraction order and a silicon drift detector were used to this end. The samples were enclosed in an in-house designed anaerobic sample cell sealed with Kapton films that served as entrance and exit windows for the X-rays. The X-ray transmission of the Kapton films was included in the reference measurement without sample. The offset on the energy scale of the spectrometer was determined using an Fe foil with a thickness of 4 pm. The energy scan was repeated 60 times with an integration time of Is per position in each scan. The Pt L3-edge XAFS spectra for the fresh and spent catalysts were collected at the P65 beamline of PETRA III (P65 applied X-ray absorption spectroscopy) in fluorescence mode due to the low relative Pt concentration (E. Welter, R. Chernikov, M. Herrmann, R. Nemausat, AIR Conf. Proc. 2019, 2054, 040002.). At the P65 beamline, synchrotron radiation from the 3rd harmonic radiation of an 11-period undulator and monochromatized by a Si(111) double crystal monochromator (DCM) was used. The DCM was operated in QEXAFS mode, and the undulator energy offset to the DCM was calibrated to have the maximum photon flux. Rh coated mirrors were used for focusing and collimation. The beam size at the sample position was approx. 0.5 x 1.0 mm2(V x H) and the photon flux was ~1011photons / s (without attenuation). The incident beam intensity was monitored by an ionization chamber (4 cm length, filled with 680 mbar N2and 370 mbar Ar(g)) and the fluorescence signal was detected by a 4-element silicon drift detector (SDD). A 3 gm thick V foil was mounted in front of the fluorescence detector in order to avoid excessively high dead time due to significant Fe Ka and Kp fluorescence from the sample. The sample pellets were prepared inside a glovebox and mounted into in-house designed fluorescence sample cells to prevent exposure to air or moisture. The measurements were performed at room temperature. The XAFS of each sample was measured 5 times and merged to improve the signal-noise ratio. A Pt foil was measured separately as the reference for energy calibration. The energy of the incident beam was calibrated by assigning the energy of the first inflection in the first derivative XANES of Pt foil to 11564 eV.

[0205] • The Pt L3-edge XAFS spectra were analyzed using the

[0206] Demeter software package (including Athena and Artemis programs, version 0.9.26) (B. Ravel, M. Newville, J.

[0207] Synchrotron Radiat. 2005, 12, 537-541) . Pre-edge background subtraction and post-edge normalization of the XAFS data were performed using the Athena program. A linear regression background in the range of 11481 eV to 11497 eV was determined, and a quadratic polynomial regression for post-edge normalization in the range of 11598 to 12306 eV was applied. The fitting of EXAFS spectra (R range: 1.2 to 3.2 A, k-range: 3.0 to 12.3 A-x) was performed using the Artemis program based on scattering paths generated from FEFF6. The amplitude reduction factor So2is determined to be 0.785 by fitting of k2-weighted R-space EXAFS of the Pt foil based on the standard crystal parameters of platinum metal (retrieved from Crystal Open Database, entry ID: 9008480), and was used as fixed parameter in the EXAFS fitting model for the catalysts.

[0208] • High resolution aberration-corrected BF-STEM and HAADF- STEM images were acquired using a probe-corrected (CEOS) JEOL ARM300CF electron microscope (instrument E02) in the electron Physical Science Imaging Center (ePSIC) at Diamond Light Source (DLS, UK). The acceleration voltage was 80 kV and the probe size was set to 8C (spot 8) with a 30 pm probe-forming aperture (CL aperture) selected, resulting in a probe convergence semi-angle of 24.8 mrad and a beam current of 28.3 pA. The STEM camera length was set to 9.0 cm, which allowed the ADE detector to integrate the scattered electron intensity between 73.7 ± 1.8 and 155.4 ± 1.8 mrad. In addition, a 3 mm aperture was inserted for the BE imaging, corresponding to a semi-angle of 14.8 ± 1.2 mrad (outer angle) for the BE detector. For each sample, a small amount of dry powder was sprinkled on a 200-mesh Cu grid with lacey carbon support film. Each sample was exposed to an intense electron beam for 10-15 minutes ('beam shower') to eliminate the accumulation of carbon contamination during the STEM imaging. Gatan Microscopy Suite software was used for image data acquisition.

[0209] Product analysis:

[0210] Product analysis was done by GC-FID (gas chromatography coupled with flame ionization detection) on a Shimadzu GC 2030 equipped with a CP-WAX-52CB column and further by GC-MS (gas chromatography coupled with mass spectrometry) on a Shimadzu QP 2020 instrument. Product quantification was done by referencing the product peak area to the peak area of the added tetradecane standard, following internal GC calibration with the isolated products. For identification of unknown products and trace compounds GC-MS was used with its internal compound library for product identification. NMR spectra were recorded on Bruker AV-400 spectrometer. The coupling constants (J) are given in Hertz (Hz), and the chemical shifts (5) expressed in ppm are calibrated using deuterated solvent (CDCI3 at 7.26 ppm forXH NMR, and 77.2 ppm for13C NMR). The peak patterns are indicated as follows: s = singlet; d = doublet; t = triplet; m = multiplet. Catalytic experiments:

[0211] As an example, the procedure for a catalysis reaction with magnetic induction heating, a catalysis reaction with conventional heating and a recycling experiment is described. The overall procedure stays the same, exchanging the reaction conditions (e.g., substrate, solvent, magnetic field, etc.) as outlined for the individual experiments.

[0212] Catalysis with magnetic induction heating

[0213] In a typical experiment, ICNPs-Pt / Al2O3 (35.0 mg, 1.26 pmol Pt), solvent (0.5 mL), and the substrate (0.10 mmol) were placed in a Fisher-Porter bottle. The Fisher-Porter bottle was degassed, and pressurized with the desired pressure of hydrogen (3 bar). The reaction mixture was placed at the center of a copper coil at the desired magnetic field amplitude and fixed frequency of 350 kHz. Once the reaction was finished, the reactor was cooled and vented. After filtration, the reaction mixture was analyzed by GC-FID using tetradecane as the internal standard.

[0214] Catalysis with conventional heating

[0215] In a typical experiment, catalyst, solvent (0.5 mL), and the substrate (0.10 mmol) were placed in a Fisher-Porter bottle or high-pressure autoclave. The Fisher-Porter bottle or autoclave was degassed, and pressurized with the desired pressure of hydrogen (3 or 50 bar). The reaction mixture was placed in an aluminum heating block and the reaction performed at the desired temperature. Once the reaction was finished, the reactor was cooled and vented. After filtration, the reaction mixture was analyzed by GC-FID using tetradecane as the internal standard.

[0216] Recycling experiments

[0217] In a typical experiment, ICNPs-Pt / Al2O3 (35.0 mg, 1.26 pmol Pt), decalin (0.5 mL), and l-acetyl-3-methylpiperidine (12.9 mg, 0.10 mmol) were placed in a Fisher-Porter bottle. The Fisher-Porter bottle was degassed, and pressurized with the desired pressure of hydrogen (3 bar). The reaction mixture was placed at the center of a copper coil at 72 mT and 350 kHz for 0.5 hours. Once the reaction was finished, the reactor was cooled and vented. After filtration, the reaction mixture was analyzed by GC-FID using tetradecane as the internal standard. For the next cycle, fresh portions of the substrate (0.10 mmol) and decalin (0.5 mL) were added and the reaction mixture was performed again. This procedure was repeated for each catalyst cycle by pressurizing the Fisher- Porter bottle with 3 bar of hydrogen.

[0218] Isolated yield:

[0219] General procedure: ICNPs-Pt / Al2O3 (35.0 mg) and substrate (0.40 mmol) were dispersed in decalin (0.5 mL) in a Fischer- Porter bottle inside the glovebox, then sealed and pressurized with H2(3 bar). The Fischer-Porter bottle was placed in the coil under an alternating magnetic field for selected amount of the time. After the reaction, the catalyst was removed by magnetic separation and filtration and 1.0 M HC1 in diethyl ether was added to the resulting solution, immediately producing the precipitant. The hydrochloride salt was then filtered and dried. The desired product was isolated as a solid.

[0220] Example 1: Synthesis of iron carbide nanoparticles (ICNPs), their immobilisation on Pt / A12Os, and catalyst characterisation (Figure la)

[0221] Iron carbide nanoparticles immobilised on Pt / Al2O3 is denoted as ICNPs-Pt / A12O3.

[0222] Synthesis of bis [bis(trimethylsilyl)amido]iron ( )

[0223] ([[Fe[N (SiMe3)2J2]2]2):

[0224] Bis [bis(trimethylsilyl)amido]iron (II) ([[Fe[N (SiMe3)2J2J2J2) was prepared following a procedure published by D. L. J. Broere, I. Coric, A. Brosnahan, and P. L. Holland in Inorg. Chem. 2017, 56, 3140-3143:

[0225] Inside an argon-filled glovebox, anhydrous FeC12 (1.9 g, 15.0 mmol) and diethyl ether (60.0 mL) were introduced in a Schlenk flask. The suspension was cooled to 0 °C in an ice bath. Subsequently, a solution of LiN(SiMe3)3(5.0 g, 30.0 mmol) in diethyl ether (90.0 mL) was added dropwise (at a rate of approximately 3 drops per second). While continuously stirring under argon, the resulting suspension was allowed to slowly warm up to room temperature over the course of the night. To remove volatile components, the mixture was concentrated under vacuum, resulting in the formation of a dark green oil. Following this, the Schlenk flask was connected to a distillation setup and the product was distilled under reduced pressure (preferably below 0.05 mbar; cooling water is not necessary). The temperature of the oil bath was gradually raised from 40 °C to eliminate most of the solvent and then it was eventually maintained at 105-110 °C to start the distillation process.

[0226] Synthesis of Fe (0) nanoparticles from bis [bis(trimethylsilyl)amido]iron ( ) ([[Fe[N (SiMe3)2J2J2J2):

[0227] Fe(0) nanoparticles were prepared following a procedure published by Bordet et al. in Angew. Chem. Int. Ed. 2016, 55 (51), 15894-15898:

[0228] In a typical experiment, in a glovebox, [[Fe[N (SiMe3)2J2]2]2 (1.0 mmol, 753.0 mg) was dissolved in mesitylene (8.0 mL) and introduced in a Fischer-Porter bottle (225 mL). To this solution, solutions of 1.30 mmol of PA (666.4 mg) in 16.0 mL mesitylene and 1.0 mmol of HDA (483.0 mg) in 16.0 mL mesitylene were added. The Fischer Porter bottle was pressurized with 3 bar of hydrogen and placed in an oil bath set at 150 °C. Under vigorous magnetic stirring, the reaction proceeded for 48 hours. After 48 hours, the nanoparticles (NPs) were recovered using magnet-assisted decantation. The NPs were washed with toluene (3 * 10.0 mL) and THF (3 * 10.0 mL). Subsequently, the NPs were dried under vacuum to remove residual solvents, and stored under argon in a glovebox.

[0229] Synthesis of iron carbide nanoparticles (ICNPs) from Fe(0) nanoparticles :

[0230] ICNPs were prepared following a procedure published by Bordet et al. in Angew. Chem. Int. Ed. 2016, 55 (51), 15894-15898:

[0231] In a typical experiment, in a glovebox, 12.5 nm Fe(0) nanoparticles (100.0 mg) were dispersed in mesitylene (8.0 mL). The resulting suspension was pressurized with CO / H2(3 bar total pressure, 1:1 ratio) and stirred at 150 °C for 5 days. Upon completion of the reaction, the NPs were recovered by magnet-assisted decantation. Subsequently, the NPs were washed with toluene (3 * 5.0 mL). Finally, the NPs were dried under vacuum to remove residual solvents, and stored under Ar(g) in a glovebox.

[0232] These ICNPs had excellent heating power under ACMF (specific absorption rate SAR of ca. 3000 W g-1at 100 kHz and 47 mT; measured by calorimetry).

[0233] Immobilising of iron carbide nanoparticles (ICNPs) on Pt / Al2O3(denoted as ICNPs-Pt / Al2O3):

[0234] In a typical experiment, ICNPs (ca. 15.0 nm; 10.0 mg) and Pt / Al2O3 (25.0 mg) were dispersed in THF (1.0 mL) in a Fischer-Porter bottle. ICNPs were dispersed in THF and the resulting colloidal solution was used to impregnate commercial Pt / Al2O3 (1.0 wt% Pt) with a target loading of 28.5 wt% ICNPs, corresponding to a Fe loading of ca. 20 wt%. The bottle was then sealed under an argon atmosphere and subjected to sonication for 1 minute. At the end of the impregnation step, a black precipitate and a clear supernatant were observed. To finish, the magnetic powder was dried under vacuum and treated using magnetic induction (]aoHmax = 45mT, 350 kHz) for 1hour to anchor / anneal the ICNPs to the AI2O3 surface and prevent leaching.

[0235] Characterisation of the iron carbide nanoparticles (ICNPs) immobilised on Pt / Al2O3 (denoted as ICNPs-Pt / Al2O3):

[0236] The resulting ICNPs-Pt / Al2O3 material was characterized by nitrogen adsorption experiments, giving a Brunauer-Emmett- Teller (BET) specific surface area of 92.6 m2g-1(measured utilising a commercial device - Quantachrome, QuadraSorb Station 1). This value is lower than that of starting Pt / Al2O3 material (155.4 m2g-1), as expected due to the decoration of the material with ICNPs. Powder X-ray diffraction analysis (XRD) of ICNPs-Pt / Al2O3 (Figure 2) revealed diffraction patterns characteristic of A12O3 and Pt (fee Pt(0)). Diffraction peaks associated with ICNPs were also visible, although some of them overlapped with A12O3 and Pt signals. Elemental analysis by inductively coupled plasma optical emission spectroscopy (ICP-OES) revealed the distribution Pt = 0.59 wt%, Fe = 17.52 wt% and Al = 30.17 wt%, well in agreement with theoretical expectations (Table 1)•

[0237] Table 1. Elemental analysis of ICNPs-Pt / Al2O3by inductively coupled plasma optical emission spectroscopy (ICP-OES).

[0238] Pt (wt%) Fe (wt%) Al (wt%)

[0239] Theoretical content 0.7 20.0 37.8 Experimental 0 .6 17.5 30.2 content

[0240] Scanning electron microscopy (SEM) showed clearly ICNPs of expected size (ca. 15 nm) attached to the surface of quite regular spherical catalyst particles (Figure Ib-c). Scanning transmission electron microscopy in high angle annular dark field (STEM-HAADF) at high resolution demonstrated that the ICNPs are located near Pt nanoparticles that are responsible for hydrogen activation and transfer (Figure Id). SEM with energy dispersive X-ray spectroscopy (EDX) showed a fairly uniform dispersion of ICNPs and Pt across the AI2O3 support (Figure le-g).

[0241] The magnetic properties of ICNPs-Pt / Al2O3 were determined using a superconducting quantum interference device (SQUID) at 300 K, showing a saturation magnetization (Ms) of 23.6 A m2kg-1and a coercive field (Hc) of 9.4 mT (Figure 3). The electronic structure of the ICNPs-Pt / Al2O3 material was investigated through X-ray absorption fine structure (XAFS) analysis, focusing on the near-edge regions of the Fe K and Pt L3ionization thresholds (X-ray absorption near edge spectroscopy, XANES, Figure 4). The Fe K-edge measurement showed no noticeable shift in the near-edge area as compared to a reference iron foil (7111.2 eV), and only a +0.8 eV shift in the inflection point of the rising edge (Figure 4a).

[0242] These results indicate the absence of oxidized iron and align with previous literature indicating the prevalence of an iron carbide phase. This is consistent with57Fe zero-field Mdssbauer spectroscopy at 80 K, which revealed the existence of two iron carbide phases (Fe2.2C and FesCQ in an expected 7:3 ratio) without any oxidized iron, in agreement with previous reports (Figure 4b). The inflection point of the rising edge of the Pt L3-edge XANES of ICNPs-Pt / Al2O3is slightly shifted by +0.8 eV as compared to reference Pt foil (11567.2 eV), but is 1.0 eV lower than that of PtO2(11568.2 eV), pointing toward metallic Pt nanoparticles with a slightly oxidized surface (Figure 4c). Pt L3-edge EXAFS spectra and fittings show two scattering paths in the first coordination shell: Pt-0 with a coordination number (C.N.) of 1.0 ± 0.2 at 1.96 ± 0.01 A, and Pt-Pt with a C.N. of 8.2 ±

[0243] 0.7 at 2.75 ± 0.01 A, consistent with XANES findings of metallic Pt nanoparticles with surface oxidation (Figure 4d and Table 2). The relatively small Pt-Pt C.N. and large

[0244] Debye-Waller factor (0.0060) as compared to metallic Pt

[0245] (fee structure) confirms the nanosized nature of the Pt components in ICNPs-Pt / Al2O3.

[0246] Table 2. Summary of the coordination numbers (C.N.), path distances (R, in A), and Debye-Waller factor (ct2) of Pt-Pt and Pt-0 in fresh / spent

[0247] ICNPs-Pt / Al2O3catalysts in comparison with Pt foil, determined by EXAFS fitting.

[0248] Sample Path C.N. R (A) o2(A2)Eo (eV)

[0249] 12 2.76± 0.004 11571.5

[0250] Pt foil Pt—Pt

[0251] (fixed) 0.01 ±0.0002 ± 0.3

[0252] 8.2± 2.78± 0.006 11570.3

[0253] 0.7 0.01 ±0.0005 ± 0.7

[0254] ICNPs-Pt / A12O31.0± 1.96± 0.006 11570.3

[0255] Pt—0

[0256] 0.2 0.01 ±0.0005 ± 0.7

[0257] 7.3± 2.74± 0.006 11570.3

[0258] ICNPs-Pt / A12O30.7 0.01 ±0.0006 ± 0.9 after 4 cycles 1.4+ 1.96± 0.006 11570.3

[0259] Pt—0 0.2 0.01 ±0.0006 ± 0.9

[0260] Example 2: Catalytic study using 1-acetyl-3-methylpiperidine (1) as a model substrate

[0261] The amide l-acetyl-3-methylpiperidine (1) was selected as a model substrate to investigate the reactivity of the ICNPs- Pt / Al203 catalyst. Its hydrogenation to l-ethyl-3-methyl- piperidine (la) is important for the preparation of antitumor agents.

[0262] Reactions were performed in thick-walled borosilicate glassware (Fischer-Porter bottles) under 3 bar of H2(pressure at room temperature) for 4 h with decalin as a solvent, using either conventional heating in an oil bath or magnetic induction with a commercial copper coil (f = 350 Hz, tunable field amplitude p0Hmax). Reactions at pressures >3 bar and / or temperatures >200 °C were conducted in stainless-steel autoclaves fitted with glass inlets.

[0263] Table 3. Hydrogenation of l-acetyl-3-methylpiperidine (1) using various catalytic systems and conditions.

[0264] Catalyst H2O

[0265] Decalin,4h

[0266] Conventionalheating or

[0267] Magneticinductionheating Catalyst

[0268] (bar)- (mT) (°C) (%) (%) Pt / Al2O350 200 43 43 Pt / Al2O33 200 2 2 ICNPs-Pt / Al2O33 200 7 7 ICNPs-Pt / Al2O33 300 60 60cICNPs-Pt / Al2O33 36 110d7 7 ICNPs-Pt / Al2O33 54 130d57 57 ICNPs-Pt / Al2O33 72 156d>99 >99 ICNPs-Pt / Al2O31 72 156d>99 >99 ICNPs-Pt / Al2O33 72 - 31 31 ICNPs-Pt / Al2O33 72 - 11 11

[0269] 11 Pt / Al2O33 72 r.t. 0 0 ICNPs +

[0270] 12 3 72 - 55 55

[0271] Pt / Al2O3

[0272] Reaction conditions: 1 (12.9 mg, 0.10 mmol), catalyst, decalin (0.5 mL), H2(3 bar), 4 h in a Fisher-Porter bottle. Product yields determined by GC-FID using tetradecane as the internal standard.a)Pressure at room temperature. Increase of pressure at reaction temperature below 0.5 bar for reactions using magnetic induction heating.b)The reaction was performed in an autoclave (autoclave reactor in a heating bag).c)Mass balance not closed.d)Determined using an infrared camera.e)40 h.f)16 wt% of ICNPs. 7 wt% of ICNPs. |u.0Hmax(mT) = magnetic field amplitude. T = temperature. Conv. = conversion. Yia= yield of la.

[0273] Using conventional heating, Pt / Al2O3 was found active at 200 °C and 50 bar H2giving l-ethyl-3-methyl-piperidine (la, 43%) as the only detected product (Table 3, Entry 1). Lowering the H2pressure to 3 bar resulted in low activity for Pt / Al2O3 and ICNPs-Pt / Al2O3 at 200 °C (Table 3, Entries 2-3). A moderate conversion yield of 60% la could be observed when raising the temperature to 300 °C, although the system pressure increased up to 10 bar and unidentified side products resulted in a not fully closed mass balance at this extreme condition.

[0274] Using ICNPs-Pt / Al2O3 under magnetic induction at a field amplitude of 36 mT, 7% conversion to la was observed (Table 3, Entry 5). A temperature of 110 °C resulting from the heat dissipated by the ICNPs was determined at the surface of the Fischer-Porter bottle by an infrared camera. Increasing the field strength to 54 mT resulted in higher conversion and yield of la (57%) at a reactor temperature of 130 °C (Table 3, Entry 6). Full conversion and quantitative yield of la were observed at a moderate magnetic field amplitude of 72 mT (Table 3, Entry 7), corresponding to a global reactor temperature of 156 °C (Figure 11) and a pressure at reaction temperature below 4 bar. Under these conditions, the local temperature at the catalyst surface was estimated to reach between 287 °C and 327 °C by placing ICNPs-Pt / Al2O3 in solvents of known boiling points and monitoring bubble formation upon ACME exposure (Table 4). Quantitative yield of la was also observed at ambient H2pressure, although the reaction was slower (Table 3, Entry 8). Decreasing the ICNPs loading on Pt / Al2O3from 28 wt% to 16 wt% and 7 wt% resulted in reduced catalytic activity with la yields of >99%, 31% and 11%, respectively (Table 3, Entries 7, 9 and 10), as can be expected from a decrease in the amount of heating agents. Pt / Al2O3did not heat upon exposure to the ACME and was found inactive under previously optimized conditions (Table 3, Entry 11). A physical mixture of ICNPs and Pt / Al2O3gave good yields of la (55%, Table 3, Entry 12).

[0275] Overall, these results demonstrate that the selective heating of ICNPs-Pt / Al2O3by magnetic induction enables excellent amide hydrogenation activity and selectivity under mild reaction conditions (1-3 bar H2, TReactor ~ 150 °C). Such performances are strikingly out of reach for Pt / Al2O3or ICNPs-Pt / Al2O3catalysts heated in a conventional manner. In addition, reference experiments confirm that ICNPs heated by magnetic induction generate localized hot spots on the surface of the Pt / Al2O3catalyst. Achieving intimate contact between ICNPs and Pt / Al2O3active sites was found beneficial for unlocking high catalytic activity under these conditions.

[0276] Example 3: Investigation into solvents used in the catalytic reaction

[0277] Experiments were completed to investigate different solvents in the catalytic reaction. The results showed that when the catalytic reactions are performed using magnetic induction, activity levels increased with increasing solvent boiling point (Table 4). This observation could be attributed to the Leidenfrost effect, which describes the rapid vaporization of liquids at hot surfaces way above their boiling points, building an insulating vapor layer that can potentially affect mass transfer and lead to reduced reaction rates in catalysis.

[0278] Table 4. Experimental estimation of the surface temperature of ICNPs-

[0279] Pt / Al2O3heated by magnetic induction.

[0280] Dimethoxyethane 85 Yes 85 0 0

[0281] Heptane 98 Yes 90 0 0

[0282] Dioxane 101 Yes 95 2 2

[0283] Decalin 186 Yes 160 77 77

[0284] Dodecane 216 Yes - - -

[0285] Tetradecane 254 Yes - - -

[0286] Hexadecane 287 Yes - - -

[0287] Tetraethylene

[0288] , , 327 No - - - glycol

[0289] Local temperature at solvent / ICNPs-Pt / Al203 interface estimated from local boiling / gas bubble formation of respective solvent. Experimental conditions: ICNPs-Pt / Al2O3(35.0 mg), solvent (0.5 mL), Ar(g), magnetic field (|u.0Hmax= 72 mT, 350 kHz), 5 min. For catalysis: amide 1 (12.9 mg, 0.1 mmol), ICNPs-Pt / Al2O3(35.0 mg, 1.26 pmol Pt), magnetic field (|u.0Hmax= 72 mT, 350 kHz), solvent (0.5 mL), H2(3 bar), 1 h. Products yields determined by GC-FID using tetradecane as the internal standard.a

[0290] Determined using an infrared camera. T. = temperature. Conv. = conversion. Yia= yield of la.

[0291] Example 4 : Further investigations into the reaction A time profile recorded for the conversion of amide 1 using ICNPs-Pt / Al2O3 under conditions of 3 bar H2, 72 mT, 350 kHz, revealed an apparent 1storder reaction, with compound la as the only product detected over the course of the reaction (Figure 5a). Quantitative yield of compound la was reached after two hours, and no further reaction or degradation of the product was observed even at prolonged reaction time. Notably, C-N cleavage was not detected, highlighting the excellent selectivity of the ICNPs-Pt / Al2O3catalyst for this substrate .

[0292] Notably, turning the ACMF generator's electricity supply ON and OFF while recording a time profile resulted in the perfectly concomittent START and STOP of the catalytic reaction (Figure 5b). For example, after 30 minutes the ACMF was turned OFF and no further conversion occurred. The reaction started immediately with a similar rate upon restart of the ACMF. This highlights the remarkably fast and selective heating of ICNPs-Pt / Al2O3provided by magnetic induction, which are crucial features to access adaptivity to intermittent energy supply.

[0293] Example 5: Study of reusability and recyclability of ICNPs- Pt / Al2O3

[0294] The possibility to reuse and recycle the ICNPs-Pt / Al2O3catalyst was investigated using the hydrogenation of amide 1. For this purpose, reaction conditions were adapted and set at 72 mT and 0.5 h to ensure an incomplete conversion of amide 1 to compound la allowing to monitor any change in catalytic performance. Catalytic activity and selectivity were conserved for a minimum of four cycles (Figure 6a), with only little variations lying within experimental error. After four cycles, the BET surface area of ICNPs-Pt / Al2O3increased slightly from 92.6 to 102.5 m2g-1, possibly due to minor leaching of ICNPs. A ICNPs-Pt / Al2O3catalyst prepared without heat treatment under magnetic induction to anchor the ICNPs to the Pt / Al2O3surface was found poorly recyclable (Table 5) presumably due to more severe ICNPs leaching.

[0295] Table 5. Recycling experiments with ICNPs-Pt / Al2O3prepared without heat treatment to anchor the ICNPs.

[0296] Entry Cycle Conversion (%) Yield la (%)

[0297] 1 1 95 95

[0298] 2 2 97 97

[0299] 3 3 65 65

[0300] Reaction condition: 1 (12.9 mg, 0.1 mmol), ICNPs-Pt / Al2O3without heat treatment (35.0 mg, 1.26 mol Pt), magnetic field (|u.0Hmax= 72 mT, 350 kHz), decalin (0.5 mL), H2(3 bar), 2 h. Products yield determined by GC- FID using tetradecane as the internal standard.

[0301] SEM and SEM-EDX revealed no significant changes in the ICNPs size nor in their distribution on the Pt / Al2O3 surface (Figure 6b-g). SQUID measurement at 300 K showed a Msof 29.8 A m2kg-1and a Hcof 9.5 mT (Figure 7), very similar to that of the fresh catalyst. Fe K-edge XANES measurements of ICNPs- Pt / Al2O3were found similar before and after catalysis, with only a tiny alteration (+0.2 eV as compared to the metallic Fe) in the rising edge region for the used catalyst (Figure 8a). This can be attributed to a trace amount of iron carbide being reduced, as can be expected under reduced conditions. Pt L3-edge XANES spectra are nearly identical for fresh and used catalysts (Figure 8b), and EXAFS analysis in the first coordination shell showed no change in the coordination number for the ICNPs-Pt / Al2O3catalyst before and after recycling (Figure 8c-d and Table 2).

[0302] Example 4: Catalytic study using a scope of amides The magnetically induced catalysis for low-pressure hydrogenation was explored for a scope of amides, using the ICNPs-Pt / Al2O3 catalyst under the following reaction conditions :

[0303] Compound substrate (0.10 mmol), ICNPs-Pt / A12O3(35.0 mg, 1.26 pmol Pt), decalin (0.5 mL), H2(3 bar). GC Products yields were determined relative to an internal standard of tetradecane and isolated yields are given in parentheses.

[0304] Table 6. Catalytic study of further amide substrates with ICNPs-Pt / Al2O3.

[0305]

[0306] Reaction conditions: substrate (0.10 mmol), ICNPs-Pt / Al2O3 (35.0 mg), decalin (0.5 mL), H2(3 bar). Products yield determined by GC-FID using tetradecane as the internal standard. For substrate 12: mixture of dioxane and decalin as solvent to ensure good substrate solubility. Magneto-catalysis for low-pressure hydrogenation was explored for a scope of amides, using the ICNPs-Pt / Al2O3 catalyst under previously optimized conditions (Table 6).

[0307] Satisfyingly, the hydrogenation of tertiary heterocyclic amides (1-10) proceeded smoothly, producing the corresponding amine products in good to excellent yields (50-99%). Notably, la (l-ethyl-3-methyl-piperidine), 2a (1-ethylpiperidine), and 6a (1-methylpiperidine) serve as building blocks for the synthesis of bicyclic amines that act as core intermediates in the synthesis of anti-tumor agents. Notably, the catalysts could be separated from the reaction mixtures very easily by magnetic separation greatly facilitating work-up and product isolation. Following this protocol, products la and 5a were isolated in excellent yields (95% and 89%, respectively) demonstrating the practicability of this approach (Figures 9 and 10 respectively). For substrate 3, the amide reduction gave a 1:1 mixture of the tertiary and secondary amine. Notably, quantitative hydrodeoxygenation of the alcohol side group also occurred. Hydrogenation of N-methyl pyrrolidone (7) gave a mixture of the expected 1-methylpyrrolidine (7a) along with partly (7b) and fully dehydrogenated products (7c, 1-methylpyrrole) . Interestingly, amide functionalities in substrates 9-14 were hydrogenated selectively without reduction of aromatic rings.

[0308] In the case of substrate 9, even the heterocyclic C=C bond was conserved, giving products 9a-9c as valuable building blocks used for the preparation of pharmaceuticals (e.g., non-steroidal aromatase inhibitors). 5-acetyl-10,11-dihydro- 5H-dibenz [b,f]azepine (10) was converted selectively to 5- ethyl-10,1l-dihydro-5H-dibenz [b,f]azepine (10a), an important intermediate entering in the synthesis of dyes. The ringopening activity through C-N bond cleavage observed in the conversion of indolin-2-one (11) may originate from the presence of acid sites on the AI2O3 support. Hydrogenation of 303 benzylamide (12) occurred smoothly without any aromatic hydrogenation. Benzylamine was never observed as primary product, but rapidly converted to toluene (12a) by debenzylation. Full reduction to toluene (12a) was also observed for substrates 13 and 14, indicating protecting group cleavage as another potential application of this technique.

Claims

ClaimsClaim 1Method of hydrogenating a substrate, wherein the method comprises : bringing a substrate and hydrogen into contact with a catalyst; and applying an alternating current magnetic field with a frequency and field amplitude sufficient to effect the hydrogenation reaction, wherein the catalyst comprises: a)metal particles on a support, and b)magnetic particles.Claim 2Method according to claim 1, wherein the magnetic field heats the magnetic particles to a temperature of 100-450 °C, preferably 250-350 °C.Claim 3Method according to claim 1 or 2, wherein the magnetic particles : i) are magnetic nanoparticles; and / or ii) comprise any one of iron, cobalt or nickel, or a combination thereof, preferably iron, wherein preferably: a.the magnetic particles further comprise carbon, nitrogen, phosphorous, boron or sulphur; and / or b. the iron, cobalt, or nickel, or combinations thereof, is present as a carbide, nitride, phosphide, boride or sulphide;and / or iii) are immobilised on the support; preferably wherein the magnetic particles are iron carbide nanoparticles immobilised on the support.Claim 4Method according to any preceding claim, wherein the metal particles on the support: i) are monometallic, bimetallic or multimetallic particles; and / or ii) are nanoparticles; and / or iii) are selected from: a. one or more 3d, 4d or 5d transition metals; b. one or more 4d or 5d transition metals; or c. one or more of platinum, palladium, rhodium, or ruthenium; preferably wherein the metal particles on the support are platinum.Claim 5Method according to any preceding claim, wherein the support: i) is a particulate support; and / or ii) is selected from A12O3, TiO2, SiO2, CeO2, activated carbon, graphene, graphite, or carbon nanotubes, preferably wherein the support is A12O2.Claim 6Method according to any preceding claim, wherein the content of magnetic particles in the catalyst is 3-50 weight-%, preferably 10-40 weight-%, more preferably 20-35 weight-%.Claim 7Method according to any preceding claim, wherein:i) an alternating current magnetic field with a field amplitude of 1 - 200 mT, preferably 15 - 150 mT, more preferably 30 - 80 mT, most preferably 45 - 80 mT is applied; and / or ii) an alternating current magnetic field with a frequency of 50 - 600 kHz, preferably 150 - 400 kHz is applied; and / or iii) an alternating current magnetic field with a frequency of 150 - 400 kHz and a field amplitude of 30 - 80 mT, preferably 45 - 80 mT, is applied; and / or iv) the hydrogen is pressurised at 1-100 bar, preferably 1-20 bar, more preferably 1-10 bar, even more preferably 1-5 bar, most preferably 2-4 bar.Claim 8Method according to any preceding claim, wherein the reaction is carried out: i) under neat conditions; or ii) in a solvent, wherein the solvent has a boiling point of 100-350 °C, preferably 120-300 °C, more preferably 180-260 °C.Claim 9Method according to any preceding claim, wherein the solvent: i) has a viscosity of 0.1-5 mPa-s, preferably 0.5-3 mPa •s; and / or ii) has a boiling point of 180 - 260 °C and a viscosity of 0.5-3 mPa-s; and / or iii) is decalin, propylene carbonate, tetradecane, dodecane, propylene carbonate, diethyl succinate, diethyl sulphate, diethyl malonate, 2-ethylhexyl acetate, D-limonene, mesitylene, diglyme, anisole, cumene, p-xylene, diethyl carbonate, and dioxane,preferably wherein the solvent is tetradecane, decalin or propylene carbonate.Claim 10Catalyst comprising: a)metal particles on a support, and b) magnetic particles, preferably magnetic nanoparticles.Claim 11Catalyst according to claim 10, wherein: i) the magnetic particles are magnetic nanoparticles; and / or ii) the magnetic particles comprise any one of iron, cobalt or nickel, or a combination thereof, preferably iron, wherein preferably: a.the magnetic particles further comprise carbon, nitrogen, phosphorous, boron or sulphur; and / or b. the iron, cobalt, or nickel, or combinations thereof, is present as a carbide, nitride, phosphide, boride or sulphide; and / or iii) the magnetic particles are immobilised on the support; and / or iv) the content of magnetic particles in the catalyst is 3-50 weight-%, preferably 10-40 weight-%, more preferably 20-35 weight-%; preferably wherein the magnetic particles are iron carbide nanoparticles immobilised on the support and wherein the content of the iron carbide nanoparticles in the catalyst is 3-50 weight-%, preferably 10-40 weight-%, more preferably 20-35 weight-%.Claim 12Catalyst according to claim 10 or 11, wherein the metal particles on the support: i) are selected from one or more 4d or 5d transition metals, preferably wherein the metal particles on the support are selected from one or more of platinum, palladium, rhodium, or ruthenium, more preferably wherein the metal particles on the support are platinum; and / or ii) are monometallic, bimetallic or multimetallic particles; and / or iii) are nanoparticles.Claim 13Catalyst according to any one of claims 10-12, wherein the support is a particulate support, preferably wherein the support is selected from A12O3, TiO2, SiO2, CeO2, activated carbon, graphene, graphite, or carbon nanotubes, more preferably wherein the support is A12O2.Claim 14Catalyst according to any one of claims 10-13, wherein the catalyst comprises: a) platinum nanoparticles on alumina, and b) iron carbide nanoparticles, wherein the iron carbide nanoparticles are immobilised on the alumina.Claim 15Use of a catalyst according to any one of claims 10-14 in a hydrogenation reaction; preferably wherein the hydrogenation reaction is a hydrogenation reaction of an amide, more preferably wherein the hydrogenation reaction is a hydrogenation reaction of an amide to an amine.

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