Method for electrochemical hydrogenation

Abstract

The invention relates to a method for electrochemically hydrogenating organic or inorganic carbon compounds or inorganic nitrogen compounds in an electrochemical cell comprising a cathode, an anode and an electrolyte, wherein the electrolyte comprises bismuth in dissolved form. The invention also relates to the use of bismuth in dissolved form as a catalyst for the electrochemical hydrogenation of organic or inorganic carbon compounds or inorganic nitrogen compounds.

Description

[0001] Düsseldorf, December 8, 2025

[0002] RWTH Aachen

[0003] Our reference number: RD 42851 / AL

[0004] Processes for electrochemical hydrogenation

[0005] The invention relates to a process for the electrochemical hydrogenation of organic or inorganic carbon compounds as well as inorganic nitrogen compounds.

[0006] Many pharmaceuticals contain a nitrogen (N) functionality. These compounds are produced, among other things, from carbonyl compounds and amines via reductive amination. Reductive amination is based on the conversion of carbonyl compounds (RC=O) with primary amines (R-NH₂) to the corresponding imine (R-C=NR). In aqueous media, imines are not stable but exist in equilibrium with their substrates. To fix the nitrogen in the new molecular structure, imines are reduced to the corresponding amine using hydrogenating agents. Currently, hydrogenations are carried out either with the aid of molecular reducing agents such as NaBH₄ or with hydrogen in the presence of a catalyst at high temperatures and / or high pressures. However, molecular reducing agents generate waste in stoichiometric amounts and exhibit reduced atomic efficiency.Furthermore, the use of hydrogen is currently not sustainable, as the hydrogen produced is mostly derived from fossil raw materials.

[0007] An atomically efficient and sustainable hydrogenation process can be achieved using electrochemistry. In electrochemical hydrogenation (e-hydrogenation), electrons are used as reducing agents. For reductions at the negative electrode, the cathode, materials with a high overpotential against hydrogen are required. Therefore, heavy metals such as lead or tin are used. The problem of cathodic corrosion has long been known in this context. H.W. Salzberg, J. Electrochem. Soc. 1953, 100, 146, already described the cathodic corrosion of lead cathodes and the formation of PbH₂ at the cathode. E. Denkhaus et al., Fresenius J. Anal. Chem. 2001, 370, 735-743, describe the electrocatalytic and electrochemical mechanisms of hydride formation and their dependence on the hydrogen overpotential, and assume that the formation of metal hydrides is based on reduction and protonation reactions. FWS Lucas et al., Green Chem.In 2021, 23, 9154, [authors' names] describe the electrochemical reduction of levulinic acid to 4-hydroxyvaleric acid at a lead cathode and spectroscopic signals indicating the formation of PbH₂. A possible involvement of the hydride in the substrate reduction is proposed, and it is postulated that levulinic acid is reduced by PbH₂ in solution.

[0008] Mürtz et al., Green Chem. 2021, 23, 8428-8433, describe the reductive amination of acetone with methylamine in an aqueous alkaline medium and highlight copper and silver as promising cathode materials instead of lead for the electrochemical hydrogenation of imines. J. Kümper et al., Angew. Chem. Int. Ed. 2024, 63, e202411532, describe a catalytic effect of trace amounts of lead in the electrolyte during the reductive amination and reduction of acetone.

[0009] Besides lead and precious metals, other cathode materials are known for hydrogenation reactions. MN Dell'Anna et al., Green Chem. 2021, 23, 6456-6468, describe the use of bismuth electrodes or bismuth-modified electrode materials for the reduction of cis,cis-muconic acid to trans-β-hydromuconic acid. B. Avila-Bolivar et al., Electrochim. Acta 2019, 298, 580-586, describe the electrochemical reduction of CO2 to formate on nanoparticulate bismuth-tin-antimony electrodes. Y.-C. Hao et al., Nature Catalysis 2019, 2, 448-456, describe the reduction of nitrogen to ammonia using bismuth nanocrystals and potassium cations in water. M. Dortsiou et al., J. Electroanal. Chem. 2009, 630, 69-74, describe an electrochemical reduction of nitrate at bismuth cathodes to various inorganic reduction products. However, bismuth is a brittle metal, which makes the production of pure bismuth electrodes difficult and expensive.The production of bismuth-modified electrode materials remains complex and time-consuming, as the catalyst must first be manufactured and then fixed to the electrode material. Therefore, there is a need for alternative catalysts for electrochemical hydrogenation processes.

[0010] The present invention was based on the objective of providing a process for electrochemical hydrogenation that overcomes at least one of the aforementioned disadvantages of the prior art.

[0011] This problem is solved by a process for the electrochemical hydrogenation of organic or inorganic carbon compounds or inorganic nitrogen compounds in an electrochemical cell comprising a cathode, an anode and an electrolyte, wherein the electrolyte comprises bismuth in dissolved form.

[0012] Surprisingly, it was found that bismuth in dissolved form can be used as a catalyst in electrochemical hydrogenation, particularly reductive amination. Specifically, it was found that efficient electrochemical hydrogenation is possible even with bismuth concentrations in the ppm range in solution. It was demonstrated that the presence of dissolved bismuth in these small amounts enables efficient electrochemical hydrogenation at various electrodes. For example, in the presence of only 5 ppm (5 mg L 1Bismuth N-methylpropan-2-amine was prepared by reductive amination of volatile acetone in a yield of 60%. The use of bismuth in dissolved form simplifies the reaction process, as only a small amount of bismuth solution is added to the substrate solution, eliminating the need for complex electrode material modifications or lengthy electrolysis preparation.

[0013] It is particularly advantageous that bismuth exhibits only low toxicity. Pharmaceuticals based on bismuth(III) oxide are commercially available. Accordingly, drugs based on compounds produced by electrolysis in the presence of ppm amounts of bismuth should not pose a health risk. The applicability of electrochemical hydrogenation with ppm amounts of bismuth is not limited to the production of compounds used in the pharmaceutical industry through the hydrogenation of imines, but is equally suitable for the production of other compounds typically prepared by hydrogenation from organic compounds such as ketones, alkenes, or aldehydes.

[0014] According to the described process, electrochemical hydrogenation is carried out in an electrochemical cell comprising an anode, a cathode, and an electrolyte. The cathode is electrically connected to the electrolyte, which contains bismuth in solution. For the purposes of this application, the term "electrochemical cell" refers to arrangements used in electrochemistry or based on electrochemical processes. The electrochemical hydrogenation of the compound takes place at the cathode, while an oxidation reaction occurs at the anode. Electrolysis in a divided cell is accordingly based on electrochemical hydrogenation, with the catholyte containing bismuth in solution.

[0015] The provided electrochemical hydrogenation process is based on the addition of bismuth in dissolved form as a cation to the electrolyte. In embodiments, the electrolyte, in particular the catholyte, comprises a bismuth(III) salt. In preferred embodiments, the electrolyte, in particular the catholyte, comprises a bismuth(III) salt selected from the group consisting of bismuth(III) nitrate, bismuth(III) chloride, bismuth(III) phosphate, bismuth(III) sulfate, bismuth(III) carbonate, bismuth(III) hydroxide, bismuth(III) oxalate, bismuth(III) oxide, bismuth(III) oxy nitrate, bismuth(III) subnitrate, bismuth(III) tribromide, bismuth(III) sulfide, bismuth(III) oxy iodide, bismuth(III) oxy chloride, bismuth(III) oxy bromide, bismuth(III) citrate, and bismuth(III) iodide. Bismuth(III) salts selected from the group comprising bismuth(III) chloride, bismuth(III) phosphate, and bismuth(III) sulfate are preferred for use in aqueous electrolytes, as they are particularly soluble in acidic solution.Bismuth(III) salts selected from the group comprising bismuth(III) carbonate, bismuth(III) hydroxide, bismuth(III) oxalate, bismuth(III) oxide, bismuth(III) oxynitrate, bismuth(III) subnitrate, bismuth(III) tribromide, bismuth(III) sulfide, bismuth(III) oxyiodide, bismuth(III) oxychloride, and bismuth(III) oxybromide are particularly soluble in acidic solution and are also preferred for use in aqueous electrolytes. Preferably, the bismuth salts are dissolved in an acid, for example nitric acid, or a strongly acidic aqueous solution and then added to the electrolyte or reaction solution. Bismuth(III) citrate and bismuth(III) iodide are soluble in ethanol or aqueous-ethanolic mixtures and are particularly preferred for use in aqueous-ethanolic electrolytes. Bismuth(III) nitrate pentahydrate is soluble in acetone and is particularly suitable for use in mixtures of water and acetone.

[0016] In high dilution or low concentration, bismuth(III) salts can remain dissolved even in alkaline solutions. The bismuth concentration, particularly in aqueous electrolytes, can range from > 1 mg / L to < 35 mg / L. In aqueous electrolytes containing 0.5 M KH₂PO₄ (pH 8.3), no turbidity was observed up to a bismuth concentration of 35 ppm. At a bismuth concentration of 37.5 ppm, turbidity was observed, indicating reduced solubility. Higher solubilities may well exist in non-aqueous electrolytes. In certain embodiments, the bismuth concentration in the electrolyte ranges from > 1 mg / L to < 7 mg / L, preferably from > 3 mg / L to < 7 mg / L, and more preferably from > 5 mg / L to < 7 mg / L. These concentration values ​​refer to the metal or the bismuth cation.Using bismuth concentrations within these ranges, good yields were obtained in the reductive amination of acetone in the presence of methylamine. Particularly good yields of µ-methylpropan-2-amine were obtained in the range of 3 ppm to 7 ppm bismuth, with the best yields in the range of 5 ppm to 7 ppm bismuth. Since bismuth acts as a catalyst, it is not consumed, so the concentration preferably remains unchanged, or at least substantially unchanged, during the electrochemical hydrogenation.

[0017] Advantageously, good current utilization efficiency was observed when using bismuth salt as a catalyst for the reductive amination of acetone. For example, when using a Faraday equivalent (F eqFor the reductive amination of the volatile acetone, an efficiency of approximately 60% was observed. This corresponded to the mass yield. For the electrochemical reductive amination of acetone, 1 < F is preferred. eq < 2. Faraday efficiency (or current utilization efficiency) is the quotient of the charge consumed in the desired reaction and the total charge transferred. When using 1 F eqWhen the Faraday efficiency reaches 100%, the substrate is completely converted into the desired product. In practice, the theoretical conversion is not achieved by one equivalent of the theoretically required charge (Faraday equivalent) due to side reactions such as solvent decomposition. It was demonstrated that with increasing bismuth concentration, the yield of amine and the conversion of acetone increased, while side reactions (solvent decomposition) were suppressed. This shows that the bismuth salt used was a good catalyst for the reductive amination.

[0018] In some embodiments, the electrolyte is an aqueous solution. Water can serve as a proton source for the hydrogenation. Electrochemical hydrogenation does not require the addition of hydrogen gas. Alternatively, electrochemical hydrogenation, particularly of imines, can be carried out in non-aqueous, aprotic solvents such as tetrahydrofuran (THF) or dimethylformamide (DMF), provided a proton source, for example benzoic acid, is added.

[0019] In embodiments, the electrolyte comprises an aqueous solution of phosphoric acid, sulfuric acid, hydrochloric acid, perchloric acid, mono- or dihydrogen phosphate, their salts, or mixtures thereof. Salts of perchloric acid can be perchlorates selected from LiCl₂C₆, KCl₄, and NaCl₂Ch₄. Salts of phosphoric acid, sulfuric acid, hydrochloric acid, perchloric acid, mono- or dihydrogen phosphate are preferably alkali metal salts, in particular their sodium or potassium salts.

[0020] In embodiments, in particular a reductive amination of acetone in the presence of methylamine or a reductive hydrogenation of acetone, the catholyte is an aqueous solution of KH2PO4, for example in a concentration in the range of > 0.1 M to < 1 M, preferably in the range of > 0.2 M to < 0.5 M, and / or the anolyte is an aqueous solution of H3PO4, for example a 25% to 50% aqueous solution of orthophosphoric acid.

[0021] In further embodiments, in particular a reductive amination of acetone in the presence of methylamine, the catholyte is an aqueous solution of NaClO4, for example in a concentration in the range of > 0.1 M to < 1 M, preferably in the range of > 0.2 M to < 0.5 M, and / or the anolyte is an aqueous solution of H3PO4 or HClO4, for example a 25% to 50% aqueous solution of orthophosphoric acid or aqueous solution of HClO4 of a concentration in the range of > 0.1 M to < 1 M, preferably in the range of > 0.2 M to < 0.5 M.

[0022] The aqueous electrolyte can comprise a mixture of water with one or more organic solvents, for example, selected from the group consisting of alcohols, ethers, dioxanes, acetonitrile, furan, tetrahydrofuran, dioxolanes, dimethyl sulfoxide, dimethylformamide, sulfolane, 3-sulfolene, N-methyl-2-pyrrolidone, or mixtures thereof. Mixtures of water and alcohol, for example, water and ethanol, as well as mixtures of water and acetone, are particularly preferred.

[0023] The term "alcohols" here includes monohydric and polyhydric alcohols, in particular dihydric alcohols. Preferably, the alcohol is selected from the group comprising methanol, ethanol, propanol, isopropanol, butanol, tert-butanol, and / or ethylene glycol. The term "dioxanes" here includes 1,3-dioxane and 1,4-dioxane. The term "dioxolanes" here includes 1,2-dioxolane and 1,3-dioxolane.

[0024] In embodiments, the electrolyte comprises a mixture of an aqueous solution of phosphoric acid, sulfuric acid, hydrochloric acid, perchloric acid, mono- or dihydrogen phosphate, or their salts, and an alcohol, in particular ethanol. The mixing ratio of aqueous solution and alcohol can vary, with an excess or a higher proportion of aqueous solution, particularly an aqueous solution of phosphoric acid, sulfuric acid, perchloric acid, or their salts, being preferred. The ratio of aqueous solution, for example, an aqueous solution of phosphoric acid, sulfuric acid, perchloric acid, or their salts, to alcohol, particularly ethanol, can be in the range of 2:1 to 5:1, for example, 3:1. It has been found that the addition of ethanol has no negative effect on the yield. The addition of an alcohol such as ethanol can improve the solubility of poorly water-soluble substrates.

[0025] When using methylamine as the nitrogen source for reductive amination, this is preferably carried out in basic electrolytes. The catholyte can have a pH value in the range of > pH 8 to < pH 13 at a temperature in the range of > 10 °C to < 25 °C. When using ethylamine or serinol as the nitrogen source for reductive amination, this is also preferably carried out in basic electrolytes. The catholyte can have a pH value in the range of > pH 8 to < pH 13 at a temperature in the range of > 10 °C to < 25 °C.

[0026] A basic pH is particularly advantageous when the reductive amination is carried out in situ in an aqueous environment and the nitrogen source is not hydroxylamine. For embodiments in which hydroxylamine is used as the nitrogen source, an acidic pH is preferred. When using hydroxylamine as the nitrogen source, aqueous mixtures with sulfuric acid, phosphoric acid, or hydrochloric acid as the electrolyte are also suitable for the reductive amination.

[0027] In embodiments where hydroxylamine is used as the nitrogen source, an acidic pH is preferred. When using hydroxylamine as the nitrogen source, sulfuric acid, phosphoric acid, or hydrochloric acid and their aqueous mixtures can be used as the electrolyte for the reductive amination.

[0028] In embodiments, particularly the reductive amination of levulinic acid with hydroxylamine as the nitrogen source, good results were obtained in acidic electrolytes, especially sulfuric acid or phosphoric acid, or their aqueous solutions. Aqueous solutions of sulfuric acid or phosphoric acid are particularly preferred. The acidic catholyte can have a pH value in the range of > pH 0 to < pH 7 at a temperature in the range of > 10 °C to < 25 °C. It was found that higher yields could be achieved at lower pH values ​​of the solution.

[0029] In embodiments where the electrolyte comprises an acidic aqueous solution, for example an aqueous solution of phosphoric acid or sulfuric acid, particularly an aqueous solution of phosphoric acid, the concentration of bismuth in the electrolyte can be lower, for example in the range of > 0.5 mg / L to < 7 mg / L, preferably in the range of > 1 mg / L to < 4 mg / L. Good yields have already been achieved using bismuth concentrations of 0.5 mg / L in the reductive amination of levulinic acid in aqueous phosphoric acid solution.

[0030] For example, compounds selected from methylamine, ethylamine, hydroxylamine, or serinol can be preferred as nitrogen sources for reductive amination. Hydroxylamine proved to be well-suited as a nitrogen source for reductive amination in acidic electrolytes and mixtures of aqueous acidic solutions with ethanol, while the primary amines methylamine, ethylamine, and serinol proved to be well-suited for reductive amination in aqueous basic electrolytes.

[0031] The organic or inorganic carbon compound or inorganic nitrogen compound is hydrogenated in the cathode compartment. Accordingly, the electrolyte, in particular the reaction mixture of the cathode compartment or the catholyte, of the electrochemical cell contains the organic or inorganic carbon compound or inorganic nitrogen compound. In embodiments, the electrolyte, in particular the catholyte, can contain the organic or inorganic carbon compound to be hydrogenated and at least one other organic compound, for example, in the case of reductive amination, an organic compound that serves as a nitrogen source. For example, in the case of reductive amination of a ketone such as acetone, the electrolyte, in particular the catholyte, can comprise a mixture of acetone and methylamine or another nitrogen-containing compound that can react in a condensation reaction.

[0032] The compound contains at least one multiple bond that can be hydrogenated by the described process. Such compounds are preferably organic compounds. Inorganic carbon compounds such as carbon monoxide and carbon dioxide exhibit electrochemically hydrogenable multiple bonds, which can also be hydrogenated by the described process and are included herein. Inorganic nitrogen compounds such as nitrates, nitrites, and nitrogen (N₂) also exhibit electrochemically hydrogenable multiple bonds, which can be hydrogenated by the described process and are included herein.

[0033] In embodiments, the organic compound has at least one multiple bond. In embodiments, the organic compound has at least one nitrogen-carbon multiple bond, one carbon-oxygen double bond, one nitrogen-nitrogen multiple bond, one carbon-carbon multiple bond, or comprises a nitro group and / or is an aromatic or heteroaromatic compound. The organic compound may have combinations of multiple bonds. The organic compound may be an unsaturated compound, for example, an alkene or alkyne. The organic compound may be a reducible or hydrogenable compound containing a carbon-oxygen double bond or a nitrogen-carbon multiple bond, in particular a nitrogen-carbon double bond. In embodiments, the organic compound is selected from the group comprising imines, oximes, ketones, aldehydes, and alkenes.In preferred embodiments, the organic compound is selected from the group comprising imines, ketones, aldehydes and alkenes.

[0034] In embodiments, the inorganic carbon compound has at least one or two carbon-oxygen double bonds or one carbon-oxygen triple bond. In embodiments, the inorganic carbon compound is selected from the group comprising carbon dioxide and carbon monoxide.

[0035] In embodiments, the inorganic nitrogen compound is selected from the group comprising nitrates, nitrites, and nitrogen (N₂). The countercation of the nitrates can be, for example, potassium, sodium, or another soluble, preferably monovalent, metal cation. Nitrates are generally readily soluble in water. Nitrites are preferably selected from ammonium nitrite, barium nitrite (in particular, barium nitrite monohydrate), calcium nitrite (in particular, calcium nitrite monohydrate), cesium nitrite, lithium nitrite (in particular, lithium nitrite monohydrate), magnesium nitrite (in particular, magnesium trinitrite tetrahydrate), potassium nitrite, sodium nitrite, and strontium nitrite. Preferred substrates for reduction exhibit good water solubility.

[0036] The organic or inorganic carbon compound and the inorganic nitrogen compound are preferably liquid under process conditions, particularly at ambient temperature. The organic or inorganic carbon compound or inorganic nitrogen compound may also be partially gaseous, especially in the case of carbon dioxide, carbon monoxide, or nitrogen. The compound may also be solid, provided that at least a portion has dissolved or is present in dissolved form and is available as a reactant. Low-molecular-weight compounds that dissolve well in the electrolyte are particularly suitable for electrochemical hydrogenation.

[0037] The process can be, for example, a process for the electrochemical reduction of an amide to an amine, a nitrile to an amine, or an acid to an alcohol. In embodiments, the process is a reductive amination. In embodiments, the process is, for example, a process for the electrochemical amination of a ketone such as acetone or an aldehyde in the presence of methylamine or another nitrogen source. In other embodiments, the process is a reductive hydrogenation. In embodiments, the process is, for example, a process for the electrochemical hydrogenation of a ketone such as acetone or an aldehyde. In further embodiments, the process is, for example, a process for the electrochemical hydrogenation of 2-butanone. The process can also be a process for the electrochemical reduction of nitrogen to ammonia.

[0038] Electrochemical hydrogenation can be carried out in a wider temperature range. In some embodiments, the electrochemical hydrogenation is performed at a temperature in the range of > 5 °C to < 95 °C, preferably in the range of > 20 °C to < 60 °C, and more preferably in the range of > 15 °C to < 25 °C. The electrochemical hydrogenation can, for example, be carried out under cooling, provided the solvent / electrolyte system can be maintained in the liquid phase. For example, increasing the pressure can enable a working temperature above the actual boiling point of the solvents. Advantageously, electrochemical hydrogenation can be carried out at normal pressure and ambient temperatures, which can improve the energy efficiency of the hydrogenation process.For processes involving the reductive amination of acetone in the presence of methylamine, good yields of μ-methylpropan-2-amine were obtained at temperatures ranging from > 5 °C to < 45 °C, particularly in the ranges of > 15 °C to < 25 °C and > 15 °C to < 20 °C. The reductive amination of acetone can therefore be carried out with good yield at ambient temperature. It has also been shown that the reductive amination of 2-butanone can be performed with good yield at ambient temperature.

[0039] In the context of processes for the reductive amination of acetone in the presence of methylamine, current densities of -30 mA / cm² were achieved at a bismuth concentration of 6 ppm and a constant potential of -2.94 V vs. RHE (normal hydrogen electrode) at 5°C. 2 and at 45°C from -110 mA / cm 2 High current densities can be achieved. High current densities are advantageous from an economic point of view.

[0040] In general, cathode materials exhibiting a high overpotential against hydrogen are preferred. In embodiments, the cathode material is selected from the group comprising lead, silver, tin, indium, niobium, aluminum, bismuth, cobalt, iron, copper, alloys of the aforementioned metals, in particular steel, iron alloys and silver alloys, carbon, in particular graphite, glassy carbon and boron-doped diamond and / or the anode material is selected from the group comprising lead, silver, gold, palladium, iridium, ruthenium, rhodium and platinum.

[0041] Preferably, the material exhibits a high hydrogen evolution overpotential, such as lead, silver, copper, glassy carbon, and boron-doped diamond. Good results have been achieved with lead / lead, silver / lead, glassy carbon / platinum, boron-doped diamond / platinum, and silver / platinum cells for processes involving the reductive amination of acetone in the presence of methylamine and the reductive amination of acetone. A further aspect of the invention relates to the use of bismuth in dissolved form as a catalyst for the electrochemical hydrogenation of organic or inorganic carbon compounds or inorganic nitrogen compounds. For a description of the electrochemical hydrogenation, bismuth, and the compounds, reference is made to the preceding description.

[0042] It was found that bismuth, when used as a catalyst in dissolved form, possesses the property of selectively reducing or hydrogenating organic compounds. Furthermore, it was found that high Faraday efficiencies could be achieved using bismuth in dissolved form as a catalyst for electrochemical hydrogenation.

[0043] The use of bismuth in dissolved form is achieved, in particular, by adding it to the electrolytes in the form of bismuth(III) cations. In various embodiments, bismuth(III) salts can be used, especially those selected from the group comprising bismuth(III) nitrate, bismuth(III) chloride, bismuth(III) phosphate, bismuth(III) sulfate, bismuth(III) carbonate, bismuth(III) hydroxide, bismuth(III) oxalate, bismuth(III) oxide, bismuth(III) oxynitrate, bismuth(III) subnitrate, bismuth(III) tribromide, bismuth(III) sulfide, bismuth(III) oxyiodide, bismuth(III) oxychloride, bismuth(III) oxybromide, bismuth(III) citrate, and bismuth(III) iodide. For example, bismuth concentrations in the range of > 1 mg / L to < 35 mg / L are suitable. In embodiments, the usable concentration of bismuth is in the range of > 1 mg / L to < 7 mg / L, preferably in the range of > 3 mg / L to < 7 mg / L, preferably in the range of > 5 mg / L to < 7 mg / L.In embodiments, particularly in acidic electrolytes such as sulfuric acid or phosphoric acid or their aqueous solutions, the usable concentration of bismuth can be in the range of > 0.5 mg / L to < 7 mg / L.

[0044] In embodiments, the organic compound has at least one multiple bond. In embodiments, the organic compound has at least one nitrogen-carbon multiple bond, one carbon-oxygen double bond, one nitrogen-nitrogen multiple bond, one carbon-carbon multiple bond, or comprises a nitro group and / or is an aromatic or heteroaromatic compound. The organic compound may have combinations of multiple bonds. The organic compound may be an unsaturated compound, for example, an alkene or alkyne. The organic compound may be a reducible or hydrogenable compound containing a carbon-oxygen double bond or a nitrogen-carbon multiple bond, in particular a nitrogen-carbon double bond. In preferred embodiments, the organic compound is selected from the group comprising imines, ketones, aldehydes, and alkenes.

[0045] In embodiments, the inorganic carbon compound has at least one or two carbon-oxygen double bonds or one carbon-oxygen triple bond. In embodiments, the inorganic carbon compound is selected from the group comprising carbon dioxide and carbon monoxide.

[0046] In embodiments, the inorganic nitrogen compound is selected from the group comprising nitrates, nitrites, and nitrogen (N₂). The countercation of the nitrates can be, for example, potassium, sodium, or another soluble, preferably monovalent, metal cation. Nitrates are generally readily soluble in water. Nitrites are preferably selected from ammonium nitrite, barium nitrite (in particular, barium nitrite monohydrate), calcium nitrite (in particular, calcium nitrite monohydrate), cesium nitrite, lithium nitrite (in particular, lithium nitrite monohydrate), magnesium nitrite (in particular, magnesium trinitrite tetrahydrate), potassium nitrite, sodium nitrite, and strontium nitrite. Preferred substrates for reduction exhibit good water solubility.

[0047] In preferred embodiments, bismuth in dissolved form can be used as a catalyst for reductive amination or reductive hydrogenation.

[0048] Overall, electrochemical hydrogenation using bismuth in dissolved form provides a promising method that allows for atom-efficient and sustainable hydrogenation, for example reductive amination, especially of compounds that are suitable for applications in the pharmaceutical industry.

[0049] Unless otherwise stated, the technical and scientific terms used have the meanings that would be commonly understood by a person skilled in the art in the field to which this invention relates.

[0050] Examples that serve to illustrate the present invention are given below.

[0051] Chemicals used:

[0052] Chemical manufacturer purity

[0053] Acetone Chemsolute 99.50%

[0054] Antimony standard solution for ICP Alfa (1000 ppm Sb in 20% HCl) Arsenic standard solution for ICP Fluka Chemie AG 1000 ppm ±0.3% (1000 ppm As in HNO3) Bismuth standard solution for ICP Roth purity starting material (1000 ppm Bi in HNO3 (3%)) 99.991% Lead(II) nitrate Roth > 99% 2-Butanone Sigma-Aldrich > 99.5% 1,4-Dioxane Em acid 99.50%

[0055] Ethanol Sigma-Aldrich > 99.9%

[0056] Ethylamine Sigma-Aldrich 65%

[0057] Hydroxylamine Sigma-Aldrich 50%

[0058] Indium(III) chloride tetrahydrate Aldrich / Merck KGaA 99.999% Potassium dihydrogen phosphate Fluka 99% Potassium hydroxide Chemsolute 85%

[0059] Levulinic acid Sigma-Aldrich 98%

[0060] Methylamine Merck 40%

[0061] MicroPolish Alumina 1.0 pm Buehler Nafion N-424 Ion Power

[0062] Sodium perchlorate monohydrate Merck KGaA 85-90% Perchloric acid Fulka 70-72% Phosphoric acid Merck 85% Phosphoric acid Chemsolute 85% Platinum Evochem 99.95%

[0063] Sulfuric acid Chemsolute 98%

[0064] Selenium standard solution for ICP Fluka Chemie AG 1000 ppm ±0.3% (1000 ppm Se in HN03 (~0.5 M)) Serinol Fluorochem 96%

[0065] Silver Chempure 99.90%

[0066] Tin standard solution for ICP Merck KGaA (1000 ppm Sn in HCl (7%)) Tellurium standard solution for ICP Roth purity starting material (1000 ppm Te in HNO3 (2%)) 99.96% Thallium(I) nitrate Sigma-Aldrich / Merck KGaA 99.999% 1,3,5-Trioxane Aldrich 99%

[0067] Methods:

[0068] Nuclear magnetic resonance spectroscopy (NMR): The yields (F), conversions (X) and carbon balances (CB) for examples 1 to 3 were determined by quantitative analysis. 1The yields (F), conversions (X), and carbon balances (CB) for Examples 4 to 9 were determined by quantitative ¹H NMR spectroscopy using a Bruker Avance III HD spectrometer (600 MHz) at room temperature (16 scans, dl time: 10 s). DMSO-de (2.50 ppm) was used as the solvent. 1,3,5-Trioxane (5H: 5.07 ppm) and 1,4-dioxane (5H: 3.52 ppm) were used as internal standards for the cathode and anode solutions, respectively.

[0069] Example 1 Reductive amination of acetone in the presence of various metallic or semi-metallic additives A reductive amination of acetone with methylamine as a nitrogen source by electrochemistry was carried out in the presence of various metallic or semi-metallic additives (c additive = 1 ppm).

[0070] The reactions were carried out in an electrochemical cell with cylindrical reaction chambers (r = 1 cm, h = 1 cm). The anode and cathode compartments were separated by a Nafion membrane (N-424, Ion Power). The cathode compartment was cooled to 10 °C from the back of the cathode using a cryostat (Julabo CORIO CD-200F). A three-electrode array consisting of a cathode (silver, 5 x 5 cm), an anode (platinum, 5 x 5 cm), and a reference electrode (Hg / HgO electrode (1 M KOH), ZH514 RE-61AP, BASi)) was used for the electrolyses. The silver electrode was characterized by a mirror-like surface, which was obtained by polishing with a 1 m³ alumina suspension (MicroPolish Alumina 1.0 m³; Buehler). The silver electrode was freshly polished before each electrolysis. Potentiostats from Metrohm (PGSTAT302N / PGSTAT204) were used to perform the electrolyses.

[0071] The cathode compartment reaction mixture contained 2.4 M acetone (0.36 mL, 1 eq), 2.9 M methylamine (1.2 eq, 40% methylamine solution: 0.50 mL), and 1 ppm of metal or semimetal (0.02 mL of an aqueous 100 ppm solution of the metal / semimetal). 0.5 M KH₂PO₄ (pH 8.3) was used as the solvent for the reaction mixture, the volume of which was adjusted to ensure a final volume of 2 mL for the reaction solution. The 100 ppm solutions of the metals and semimetals (the concentration "100 ppm" refers to the (semi)metal and does not include any counterions) were prepared by dilution with deionized water. The starting materials for the aqueous 100 ppm solutions of In, TI, and Pb were InChx4H₂O, TINO₃, and Pb(NC>3)₂. The 100 ppm solutions of As, Se, Sn, Sb, Te, and Bi were obtained from the respective ICP standard solutions (1000 ppm) by dilution with deionized water. Two mL of 25% H3PO4 solution were placed in the anode compartment.After filling the half-cells, the reaction mixture was cooled to 10 °C within 18 minutes while stirring at 250 rpm. At 10 °C, the pH of the reaction solution was 12.9. After 18 minutes, stirring was stopped and cyclic voltammetry measurements were taken at sampling rates of 50 mV s. 1 The electrolysis was performed between -1.12 V and 0.06 V vs. RHE. Subsequent potentiostatic electrolysis was performed at -2.94 V vs. RHE, and the electrolysis was terminated as soon as 1 Faraday equivalent (F) was reached. eq ) had flowed (-926.3 C).

[0072] Table 1 shows the yields of the intermediate (WMethylpropan-2-imine, Fimin), the desired target product (Ä-methylpropan-2-amine, and the by-product)

[0073] (Isopropanol, lAikohoi) depending on the additive. In addition, conversion (X) and carbon balance (CB) are given.

[0074] Table 1: Influence of various metals / semimetals on the electrochemical reductive amination of acetone with methylamine. The final concentration of

[0075] The metal / semimetal concentration in the reaction solution was 1 ppm. Reaction conditions: Ag||Pt, E = -2.94 V vs RHE; F eq = 1; Solvent: 0.5 M KH2PO4 (pH 8.3); Substrates: Acetone: 2.4 M, Methylamine: 2.9 M; T = 10 °C; pH at 10 °C: 12.9; Anolyte: 25 % H3PO4.

[0076] Additive Fimin (%) FAmin (%) F A alcohol (%) X (%) CB (%)

[0077] As 35.2 1.5 0.0 66.1 71.1

[0078] Se 38.7 1.3 0.7 68.7 71.7

[0079] In 36.8 1.1 0.5 68.4 70.1

[0080] Sn 35.0 3.0 0.9 68.0 69.6

[0081] Sb 35.3 2.2 0.6 70.5 66.4

[0082] Te 35.8 3.0 0.2 67.3 71.5

[0083] TI 6.5 (±0.1) 54.3 (±1.0) 0.7 (±0.1) 86.7 (±0.1) 72.7 (±1.1)

[0084] Pb 3.4 (±0.9) 60.8 (±1.2) 2.0 (±0.7) 90.4 (±1.2) 74.5 (±1.4)

[0085] Bi 12.1 (±1.6) 36.9 (±1.4) 0.7 (±0.1) 78.0 (±0.2) 69.6 (±1.1) As can be seen from Table 1, arsenic, selenium, indium, and tellurium, as well as the heavy metals tin and antimony, known as electrode materials for electrochemical hydrogenations, showed only extremely minor hydrogenation reactions. Thallium and lead showed good yields in the electrochemical hydrogenation of the imine to the amine; however, thallium and lead are toxic and therefore not very suitable as catalysts, especially for the production of compounds intended for use in pharmaceuticals. Bismuth showed good yields in the electrochemical hydrogenation of the imine to the amine, and, compared to lead, a lower conversion to the alcohol.

[0086] Example 2

[0087] Determination of the influence of bismuth concentration on the reductive amination of acetone with methylamine

[0088] The electrochemically initiated reductive amination of acetone with methylamine was investigated as a function of the bismuth concentration in the ppm range. The experiments were carried out in the same cell system and with the same electrodes as shown in Example 1.

[0089] The reaction mixture in the cathode compartment contained 2.4 M acetone (0.36 mL, 1 eq) and 2.9 M methylamine (1.2 eq, 40% methylamine solution: 0.50 mL), as well as bismuth concentrations between 1 and 7 ppm, with a reaction mixture volume of 2 mL. The bismuth was added to the acetone-methylamine mixture in dissolved form. Solutions with bismuth concentrations of 100 ppm, 400 ppm, and 700 ppm were prepared from a 1000 ppm bismuth standard solution by dilution with deionized water. The 100 ppm bismuth solution was used for experiments with final bismuth concentrations of 1 and 2 ppm. The 400 ppm bismuth solution was used for experiments with 3, 4, 5, and 6 ppm bismuth. The 700 ppm Bi solution served as the starting point for the experiments, with a final Bi concentration of 7 ppm. A 0.5 M KH₂PO₄ solvent (pH 8.3) was used, the volume of which was adjusted to achieve a final reaction solution volume of 2 mL. The anode compartment was filled with 2 mL of 25% H₃PO₄.After filling the half-cells, the reaction mixture was cooled to 10 °C within 18 minutes while stirring at 250 rpm. At 10 °C, the pH of the reaction solution was 12.9. After 18 minutes, stirring was stopped and cyclic voltammetry measurements were taken at sampling rates of 50 mV s. 1 The electrolysis was performed between -1.12 V and 0.06 V vs. RHE. Subsequent potentiostatic electrolysis was performed at -2.94 V vs. RHE, and the electrolysis was terminated as soon as 1 Faraday equivalent (F) was reached. eq ) had flowed (-926.3 C).

[0090] Table 2 below shows the yields of the intermediate (A-methylpropan-2-imine, Timin), the desired target product (A-methylpropan-2-amine, TAmin), and the by-product (isopropanol, Tukohoi) as a function of the bi concentration. Conversion (X) and carbon balance (CB) are also given.

[0091] Table 2: Influence of different bismuth concentrations on the reductive amination of acetone with methylamine as the nitrogen source. Bismuth was added in dissolved form to the acetone-methylamine mixture. Reaction conditions: Ag||Pt, E = -2.94 V vs RHE;

[0092] F eq = 1; Solvent: 0.5 M KH2PO4 (pH 8.3); Substrates: Acetone: 2.4 M, Methylamine:

[0093] 2.9M; T = 10°C; pH at 10 °C: 12.9; Anolyte: 25% H3PO4.

[0094] C Bi (ppm) Timin (%) TAmin (%) T A alcohol (%) X (%) CB (%)

[0095] 1 12.1 (±1.6) 36.9 (±1.4) 0.7 (±0.1) 78.0 (±0.2) 69.6 (±1.1)

[0096] 2 12.9 (±2.3) 43.6 (±1.2) 0.7 (±0.2) 82.0 (±1.0) 73.6 (±2.8)

[0097] 3 8.8 (±0.9) 49.9 (±1.0) 0.9 (±0.0) 84.8 (±0.2) 73.7 (±0.1)

[0098] 4 7.9 (±2.5) 53.1 (±4.1) 1.1 (±0.3) 85.6 (±2.2) 75.2 (±4.0)

[0099] 5 5.2 (±1.9) 58.5 (±4.3) 1.0 (±0.1) 89.3 (±1.8) 73.9 (±2.9)

[0100] 6 4.6 (±1.0) 59.7 (±1.4) 0.9 (±0.2) 90.5 (±0.6) 73.5 (±0.3)

[0101] 7 4.2 (±0.3) 59.5 (±0.8) 1.1 (±0.1) 90.5 (±0.5) 72.5 (±1.9) As can be seen from Table 2, an increase in bismuth concentration showed an increased yield of amine. Good yields were obtained at 3 ppm to 7 ppm bismuth, best yields at 5 ppm to 7 ppm bismuth, whereby the increase in concentration from 5 ppm to 7 ppm bismuth had hardly any effect on the yield of amine.

[0102] Example 3

[0103] Determination of the influence of temperature on the electrochemically initiated reductive amination of acetone with methylamine with bismuth

[0104] The electrochemically initiated reductive amination of acetone with methylamine was investigated as a function of temperature in the presence of 6 ppm bismuth. The experiments were carried out in the same cell system and with the same electrodes as shown in Example 1.

[0105] The cathode compartment reaction mixture contained 2.4 M acetone (0.36 mL, 1 eq), 2.9 M methylamine (1.2 eq, 40% methylamine solution: 0.50 mL), and 6 ppm bismuth (400 ppm bismuth solution: 0.03 mL). The bismuth was added in dissolved form to the acetone-methylamine mixture. The 400 ppm bismuth solution was prepared from a 1000 ppm bismuth standard solution by dilution with deionized water. A 0.5 M potassium hydroxide solution (KH₂PO₄, pH 8.3) was used as the solvent for the reaction mixture, the volume of which was adjusted to achieve a final volume of 2 mL of the reaction solution.

[0106] Two mL of 25% H3PO4 solution were placed in the anode compartment. After filling the half-cells, the reaction mixture was cooled / heated to the appropriate temperature between 5 and 45 °C over 18 minutes while stirring at 250 rpm. 45 °C was defined as the upper limit due to the substrate, as the boiling point of a 40% methylamine solution is 49 °C. After 18 minutes, stirring was stopped and cyclic voltammetry measurements were taken at sampling rates of 50 mV / s. 1 The electrolysis was performed between -1.12 V and 0.06 V vs RHE. The subsequent potentiostatic electrolysis was performed at -2.94 V vs RHE and the electrolysis was terminated as soon as 1 Faraday equivalent ( eq ) had flowed (-926.3 C).

[0107] The following Table 3 shows the yields of the intermediate (M-methylpropane-2-imine, fimin), the desired target product (7V-methylpropane-2-amine), and the By-product (isopropanol, Eukohoi) as a function of temperature in the presence of 6 ppm Bi. In addition, conversion (A), carbon balance (CB) and the pH value of the substrate solution at the corresponding temperature (pH?) are given.

[0108] Table 3: Influence of temperature on the electrochemical reductive amination of acetone with methylamine as a nitrogen source in the presence of 6 ppm Bi. Bismuth was added in dissolved form to the acetone-methylamine mixture. Reaction conditions: Ag||Pt, E = -2.94 V vs RHE; F eq = 1; Solvent: 0.5 M KH2PO4 (pH 8.3); Substrate: Acetone:

[0109] 2.4M, methylamine: 2.9M; T = 10°C; pH at 10 °C: 12.9; Anolyte: 25% H3PO4.

[0110] T(°C) pH / der Fimin (%) lAmin (%) FAlcohol X(%) CB (%)

[0111] substrate solution

[0112] 5 13.12 6.6 (±1.2) 55.0 (±3.5) 1.2 (±0.6) 86.3 (±2.5) 76.1 (±0.0)

[0113] 10 12.88 4.6 (±1.0) 59.7 (±1.4) 0.9 (±0.2) 90.5 (±0.6) 73.5 (±0.3)

[0114] 15 12.66 3.3 (±0.3) 60.7 (±0.4) 0.5 (±0.1) 91.3 (±0.2) 71.3 (±0.5)

[0115] 20 12.42 3.3 (±0.4) 61.2 (±0.4) 0.6 (±0.0) 91.2 (±0.2) 71.8 (±0.8)

[0116] 25 12.21 2.7 (±0.0) 61.6 (±1.0) 0.7 (±0.1) 91.5 (±0.5) 71.4 (±0.0)

[0117] 35 11.97 1.7 (±0.1) 59.1 (±0.5) 0.5 (±0.1) 90.9 (±0.7) 67.9 (±0.4)

[0118] 45 11.39 1.4 (±0.1) 52.1 (±0.5) 0.5 (±0.1) 91.3 (±0.4) 59.8 (±0.5)

[0119] As can be seen from Table 3, good yields of the amine were obtained across the entire temperature range between 5°C and 45°C, with the best yields being obtained in the temperature range between 15°C and 25°C.

[0120] Example 4: Reductive amination of further carbonyl compounds

[0121] The bismuth-mediated electrochemical reductive amination of 2-butanone was investigated in comparison to acetone using methylamine as the nitrogen source. The experiments were carried out in the same cell system and with identical electrodes as described in Example 1.

[0122] The cathode compartment reaction mixture contained 2.4 M acetone (0.36 mL, 1 eq) or 2-butanone (0.43 mL (1 eq)), 2.9 M methylamine (1.2 eq, 40% methylamine solution: 0.50 mL), and 6 ppm bismuth (400 ppm bismuth solution: 0.03 mL). The bismuth was added in dissolved form to the carbonyl-methylamine mixture. The 400 ppm bismuth solution was prepared from a 1000 ppm bismuth standard solution by dilution with deionized water. 0.5 M KH₂PO₄ (pH 8.3) was used as the solvent for the reaction mixture, the volume of which was adjusted to achieve a final volume of 2 mL of the reaction solution. The pH of the reaction solution with acetone was 12.21 at 25 °C. When using 2-butanone, this value was 12.85.

[0123] The anode compartment was filled with 2 mL of 25% H3PO4. After filling the half-cells, the reaction mixture was heated to the target temperature of 25 °C within 18 min under stirring at 250 rpm. After 18 min, stirring was stopped and potentiostatic electrolysis was carried out at -2.94 V us RHE. The electrolysis was terminated as soon as 1 Faraday equivalent ( eq ) had flowed (-926.3 C).

[0124] The following Table 4 shows the yields of the intermediates (V-methylpropane-2-imine or N-methylbutane-2-imine, Fimin), the desired target products (N-methylpropane-2-amine or N-methylbutane-2-amine, and, if applicable, the by-product (isopropanol, lAikohoi) in Dependence of the carbonyl source. The byproduct 2-butanol from the reduction of 2-butanone was not observed. Furthermore, conversion (X) and carbon balance (CB) are given. Table 4: Influence of the carbonyl source on the reductive amination with methylamine as the nitrogen source in the presence of 6 ppm bismuth. Bismuth was added in solution to the carbonyl-methylamine mixture. Reaction conditions: Ag| |Pt, E = -2.94 V vs RHE; F eq = 1; Solvent: 0.5 M KH₂PO₄ (pH 8.3); Substrates: Carbonyl compound: 2.4 M, Methylamine: 2.9 M; T = 25 °C; pH at 25 °C: Acetone: 12.21, 2-Butanone: 12.85; Anolyte: 25% H₃PO₄; and 6 ppm bismuth in the final substrate solution. *CB with respect to the limiting substrate.

[0125] Carbonyl source fimin (%)

[0126] _

[0127] Acetone 2.7 (±0.0) 61.6 (±1.0) 0.7(±0.l) 91.5 (±0.5) 71.4 (±0.0)

[0128] 2-Butanone 2.3 (±0.5) 50.5 (±0.5%) - 83.3 (±1.1) 69.2 (±1.3)*

[0129] As can be seen from Table 4, good yields of the amine and good conversion were also obtained for the reductive amination of 2-butanone.

[0130] Example 5

[0131] Investigation of the usability of other nitrogen sources in the aqueous system

[0132] The bismuth-mediated electrochemical reductive amination of two different amine sources in an aqueous system with acetone as the carbonyl compound was investigated. The experiments were carried out in the same cell system and with identical electrodes as described in Example 1.

[0133] The cathode compartment reaction mixture contained 2.4 M acetone (0.36 mL, 1 eq), 2.9 M methylamine (1.2 eq, 40% methylamine solution: 0.50 mL) or ethylamine (1.2 eq, 65% ethylamine solution: 0.50 mL), and 6 ppm bismuth (400 ppm bismuth solution: 0.03 mL). The bismuth was added in dissolved form to the acetone-amine mixture. The 400 ppm bismuth solution was prepared from a 1000 ppm bismuth standard solution by dilution with deionized water. 0.5 M KH₂PO₄ (pH 8.3) was used as the solvent for the reaction mixture, the volume of which was adjusted to achieve a final volume of 2 mL of the reaction solution. The pH of the reaction solution containing methylamine was 12.21 at 25 °C. When using ethylamine, this value was 12.75.

[0134] The anode compartment was filled with 2 mL of 25% H3PO4. After filling the half-cells, the reaction mixture was heated to the target temperature of 25 °C within 18 min while stirring at 250 rpm. After 18 min, stirring was stopped and potentiostatic electrolysis was carried out at -2.94 V vs RHE. The electrolysis was stopped as soon as 1 Faraday equivalent ( eq ) had flowed (-926.3 C).

[0135] Table 5 below shows the yields of the intermediates (A-methylpropane-2-imine or A-ethylpropane-2-imine, Timin), the desired target products (A-methylpropane-2-amine or A-ethylpropane-2-amine, FAmin), and, if applicable, the by-product (isopropanol, lAikohoi), depending on the amine source. Conversion (X) and carbon balance (CB) are also given.

[0136] Table 5: Influence of the amine source on the reductive amination of acetone in the presence of 6 ppm bismuth. Bismuth was added in dissolved form to the acetone-amine mixture. Reaction conditions: Ag||Pt, E = -2.94 V vs RHE; F eq = 1; Solvent: 0.5 M KH₂PO₄ (pH 8.3); Substrates: Acetone: 2.4 M, Amine: 2.9 M; T = 25 °C; pH at 25 °C: Methylamine: 12.21, Ethylamine: 12.75; Anolyte: 25% H₃PO₄ and 6 ppm bismuth in the final substrate solution. *CB with respect to the limiting substrate.

[0137] F Alcohol y / Q / x

[0138] Amine source Timin (%) TAmin (%) CB (%)

[0139] (%) y ( / o)

[0140] Methylamine 2.7 (±0.0) 61.6 (±1.0) 0.7 (±0.1) 91.5(±0.5) 71.4 (±0.0) Ethylamine 1.8 (±0.1) 60 (±3) - 88.7(±0.5) 74 (±2)*

[0141] As can be seen in Table 5, good yields of the amine and good conversion were also obtained when using ethylamine as a nitrogen source. Example 6

[0142] Investigation of the influence of electrolyte composition on bismuth-mediated reductive amination

[0143] The bi-mediated electrochemical reductive amination of acetone with methylamine was investigated as a function of the electrolyte composition of the catholyte and anolyte. The experiments were carried out in the same cell system and with identical electrodes as described in Example 1.

[0144] The cathode compartment reaction mixture contained 2.4 M acetone (0.36 mL, 1 eq), 2.9 M methylamine (1.2 eq, 40% methylamine solution: 0.50 mL), and 6 ppm bismuth (400 ppm bismuth solution: 0.03 mL). The bismuth was added in dissolved form to the acetone-methylamine mixture. The 400 ppm bismuth solution was prepared from a 1000 ppm bismuth standard solution by dilution with deionized water. The solvent used was either 0.5 M KH₂PO₄ (pH 8.3), 0.5 M NaCl₂, or a 3:1 mixture of 3 M NaCl₂ and ethanol, the volume of which was adjusted to achieve a final reaction solution volume of 2 mL.

[0145] The anode compartment was filled with either 2 mL of 25% H3PO4 or 0.5 M HClIO4. After filling the half-cells, the reaction mixture was stirred in the cell for 18 min. Stirring was stopped after 18 min. The subsequent galvanostatic electrolysis was carried out at 25 °C using a current density of -66 mA cm⁻¹. 2performed and completed as soon as 1 Faraday equivalent ( eq ) had flowed (-926.3 C).

[0146] Table 6 below shows the yields of the intermediate (M-methylpropan-2-imine, Fimin), the desired target product (N-methylpropan-2-amine, lAmin), and the byproduct (isopropanol, lAikohoi) as a function of the electrolyte composition. Conversion (X) and carbon balance (CB) are also given. Table 6: Influence of electrolyte composition on the reductive amination of acetone with methylamine as a nitrogen source in the presence of 6 ppm bismuth. Bismuth was added in dissolved form to the acetone-methylamine mixture. Reaction conditions: Ag||Pt,j = -66 mA cm 2 ; F eq = 1; Substrates: Acetone: 2.4 M, Methylamine: 2.9 M; T= 25°C.

[0147] As can be seen from Table 6, comparably good yields of the amine and good conversions were obtained using aqueous solutions of KH₂PO₄ or NaClCh, as well as its ethanolic solution, as electrolytes. In particular, the addition of ethanol showed no negative effect on the yield.

[0148] Example 7

[0149] Investigation of the usability of other nitrogen sources in the water-ethanol system

[0150] The bismuth-mediated electrochemical reductive amination of acetone with two different primary amines was investigated. The experiments were carried out in the same cell system and with identical electrodes as described in Example 1.

[0151] The cathode compartment reaction mixture contained 2.4 M acetone (0.36 mL, 1 eq), 2.9 M amine (1.2 eq), and 6 ppm bismuth (400 ppm bismuth solution: 0.03 mL). The bismuth was added in dissolved form to the acetone-amine mixture. The 400 ppm bismuth solution was prepared from a 1000 ppm bismuth standard solution by dilution with deionized water. Either methylamine (40% methylamine solution: 0.50 mL) or serinol (2-amino-1,3-propanediol, 528.4 mg) was used as the amine. A 3:1 mixture of 3 M NaCl₂ and ethanol was used as the solvent, with the volume adjusted to achieve a final reaction solution volume of 2 mL.

[0152] The anode compartment was filled with 2 mL of 0.5 M HCIO4. After filling the half-cells, the reaction mixture was stirred in the cell for 18 min. After 18 min, stirring was stopped. The subsequent galvanostatic electrolysis was carried out at 25 °C using a current density of -66 mA cm⁻¹.2 carried out and terminated as soon as 1 Faraday equivalent (F eq ) had flowed (-926.3 C).

[0153] Table 7 below shows the yields of the intermediates (V-methylpropane-2-imine or (7V-(propane-1,3-diol)propane-2-imine, Fimin), the desired target products (V-methylpropane-2-amine or 7V-(propane-1,3-diol)propane-2-amine, TAmin), and the by-product (isopropanol, lAikohoi) depending on the amine source. Conversion (X) and carbon balance (CB) are also given.

[0154] Table 7: Influence of the nitrogen source on the reductive amination of acetone using electrochemistry in the presence of 6 ppm bismuth. Bismuth was added in dissolved form to the acetone-amine mixture. Reaction conditions: Ag||Pt, j = -66 mA cm 2 ; F eq = 1; Solvent: 3 M NaCKL + Ethanol (3 : 1), Substrates: Acetone: 2.4 M, Amine: 2.9 M;

[0155] T = 25 °C; Anolyte: 0.5M HC1O4.

[0156] Amine source Fimin (%) lAmin (%) Uikohoi (%) V(%) CB (%)

[0157] Methylamine 3.l(±l.0) 61.0(±0.9) 3.9(±1.5) 91.8(±1.5) 76.4(±1.5)

[0158] Serinol 3.4(±0.04) 9.2(±1.5) - 60.9(±l.3) 60(±3)

[0159] As can be seen from Table 7, the desired amine was also obtained for serinol as a nitrogen source for the reductive amination of acetone in ethanolic solution, albeit in lower yield.

[0160] Example 8: Investigation of the influence of bismuth concentration on the electrochemical reductive amination of levulinic acid with hydroxylamine

[0161] The electrochemically initiated reductive amination of levulinic acid with hydroxylamine was investigated as a function of the bismuth concentration in the ppm range, using sulfuric acid as the electrolyte for the cathode compartment, to produce primary amines under acidic conditions. The experiments were carried out in the same cell system and with identical electrodes as described in Example 1.

[0162] The reaction mixture in the cathode compartment contained 2.0 M levulinic acid (464.5 mg, 1 eq), 3.2 M hydroxylamine (1.6 eq, 50% hydroxylamine solution: 422.8 mg), and bismuth concentrations between 0 and 2 ppm. The bismuth was added to the levulinic acid-hydroxylamine mixture in dissolved form. The 100 ppm bismuth stock solution used for this purpose was prepared from a 1000 ppm bismuth standard solution by dilution with deionized water. 3.71 M H₂SO₄ was used as the solvent for the reaction mixture, the volume of which was adjusted to achieve a final volume of 2 mL of the reaction solution.

[0163] The anode compartment was filled with 2 mL of 25% H3PO4. After filling the half-cells, galvanostatic electrolysis was carried out at 25°C using a current density of -106 mA cm⁻¹. 2 The electrolysis is carried out and stopped as soon as 1.2 Faraday equivalents (F) are reached. eq ) had flowed into the electricity.

[0164] Under the chosen conditions, no free levulinic acid remained after preparation of the catholyte. This was completely reacted with the hydroxylamine to form the corresponding oxime ((4-hydroxyimino)pentanoic acid). Reduction of the oxime yielded 4-aminopentanoic acid, a primary amine. Based on the complete conversion of levulinic acid to the oxime and the fact that the reduction of the oxime yielded the amine, the conversion of oxime (Δκκκα) is given in the following table. Furthermore, Table 8 lists the yield of the desired target product (4-aminopentanoic acid, λAmin) and the byproduct (4-hydroxypentanoic acid, λκκακα) as a function of the bismuth concentration used. The carbon balance (CB) is also given.

[0165] Table 8: Influence of different bismuth concentrations on the reductive amination of levulinic acid with hydroxylamine as a nitrogen source under acidic conditions and using electrochemistry. Sulfuric acid was used as the electrolyte for the cathode compartment. Bismuth was added in dissolved form to the levulinic acid-hydroxylamine mixture. Reaction conditions: Ag||Pt,j = -106 mA cm 2 ; F eq = 1.2; Solvent: 3.71 M H2SO4; Substrates: Levulinic acid: 2.0 M, Hydroxylamine: 3.2 M; T = 25 °C; Anolyte: 25 % H3PO4.

[0166] Cßi (ppm) Umin (%) ^Alcohol (%) Abxim (%) CB (%)

[0167] 0 4.3 (±0.1) 2.0 (±0.1) 30 (±3) 80 (±3)

[0168] 0.5 4.8 (±0.6) 18.0 (±0.5) 19.2 (±0.4) 90.7 (±0.3)

[0169] 1 18.7 (±0.7) 10.0 (±1.2) 42 (±2) 88.1 (±0.5)

[0170] 2 36 (±4) 2.2 (±0.5) 73 (±4) 82.7 (±1.5)

[0171] As can be seen from Table 8, when using sulfuric acid as the electrolyte, an increased yield of amine was obtained by increasing the bismuth concentration, with an increase in the concentration from 1 ppm to 2 ppm bismuth resulting in approximately a doubling of the yield of amine.

[0172] Example 9

[0173] Investigation of the influence of bismuth concentration on the electrochemical reductive amination of levulinic acid with hydroxylamine using phosphoric acid as solvent

[0174] The electrochemically initiated reductive amination of levulinic acid with hydroxylamine was investigated as a function of bismuth concentration using phosphoric acid as the electrolyte for the cathode compartment to produce primary amines under acidic conditions. The experiments were carried out in the same cell system and with identical electrodes as described in Example 1.

[0175] The reaction mixture in the cathode compartment contained 2.0 M levulinic acid (464.5 mg, 1 eq), 3.2 M hydroxylamine (1.6 eq, 50% hydroxylamine solution: 422.8 mg), and bismuth concentrations between 0 and 2 ppm. The bismuth was added to the levulinic acid-hydroxylamine mixture in dissolved form. The 100 ppm bismuth stock solution used for this purpose was prepared from a 1000 ppm bismuth standard solution by dilution with deionized water. 3.71 M H3PO4 was used as the solvent for the reaction mixture, the volume of which was adjusted to achieve a final volume of 2 mL of the reaction solution.

[0176] The anode compartment was filled with 2 mL of 25% H3PO4. After filling the half-cells, galvanostatic electrolysis was carried out at 25°C using a current density of -106 mA cm⁻¹. 2 The electrolysis is carried out and stopped as soon as 1.2 Faraday equivalents (F) are reached. eq ) had flowed into the electricity.

[0177] Under the chosen conditions, no free levulinic acid remained after preparation of the catholyte. This was completely reacted with the hydroxylamine to form the corresponding oxime ((4-hydroxyimino)pentanoic acid). Reduction of the oxime yields 4-aminopentanoic acid, a primary amine. Based on the complete conversion of levulinic acid to the oxime and the fact that the reduction of the oxime yielded the amine, the conversion of oxime (Φbxime) is given in Table 9 below. Furthermore, Table 9 shows the yield of the desired target product (4-aminopentanoic acid, Φmin) and the byproduct (4-hydroxypentanoic acid, Φikohoi) as a function of the bismuth concentration used. The carbon balance (CB) is also given.

[0178] Table 9: Influence of different bismuth concentrations on the reductive amination of levulinic acid with hydroxylamine as a nitrogen source under acidic conditions and using electrochemistry. Phosphoric acid was used as the electrolyte for the cathode compartment. Bismuth was added in dissolved form to the levulinic acid-hydroxylamine mixture. Reaction conditions: Ag||Pt, j = -106 mA cm 2 ;

[0179] F eq = 1.2; Solvent: 3.71 M H3PO4; Substrates: Levulinic acid: 2.0 M, Hydroxylamine: 3.2 M; T = 25 °C; Anolyte: 25 % H3PO4.

[0180] Cßi (ppm) lAmin (%) ^Alcohol (%) Abxim (%) CB (%)

[0181] 0 2.1 (±0.2) 0.8 (±0.1) 15 (±6) 87 (±6)

[0182] 0.5 69 (±2) 0.0 (±0.0) 82 (±3) 86.9 (±0.8)

[0183] 1 71 (±4) 0.0 (±0.0) 91 (±3) 80 (±5)

[0184] 2 75 (±5) 0.0 (±0.0) 90.6 (±1.1) 84 (±4)

[0185] As can be seen from Table 9, a high yield of amine was obtained using phosphoric acid as the electrolyte even at a bismuth concentration of 0.5 ppm, with an increase in concentration to 1 ppm and 2 ppm bismuth showing a further slight increase in the yield of amine.

[0186] The results show overall that electrochemical hydrogenation using small amounts of bismuth in dissolved form can be provided with good selectivity.

Claims

Patent claims 1. A process for the electrochemical hydrogenation of organic or inorganic carbon compounds or inorganic nitrogen compounds in an electrochemical cell comprising a cathode, an anode and an electrolyte, characterized in that the electrolyte comprises bismuth in dissolved form.

2. The method according to claim 1, characterized in that the electrolyte comprises a bismuth(III) salt, in particular selected from the group comprising bismuth(III) nitrate, bismuth(III) chloride, bismuth(III) phosphate, bismuth(III) sulfate, bismuth(III) carbonate, bismuth(III) hydroxide, bismuth(III) oxalate, bismuth(III) oxide, bismuth(III) oxynitrate, bismuth(III) subnitrate, bismuth(III) tribromide, bismuth(III) sulfide, bismuth(III) oxyiodide, bismuth(III) oxychloride, bismuth(III) oxybromide, bismuth(III) citrate and bismuth(III) iodide.

3. Method according to claim 1 or 2, characterized in that the concentration of bismuth in the electrolyte is in the range of > 1 mg / L to < 7 mg / L, preferably in the range of > 3 mg / L to < 7 mg / L, preferably in the range of > 5 mg / L to < 7 mg / L.

4. Method according to one of the preceding claims, characterized in that the electrolyte comprises an aqueous solution of phosphoric acid, sulfuric acid, hydrochloric acid, perchloric acid, mono- or dihydrogen phosphate, their salts or mixtures thereof.

5. Method according to one of the preceding claims, characterized in that the electrolyte comprises an aqueous solution of phosphoric acid or sulfuric acid, wherein the concentration of bismuth in the electrolyte is in the range of > 0.5 mg / L to < 7 mg / L, preferably in the range of > 1 mg / L to < 4 mg / L.

6. Method according to one of the preceding claims, characterized in that the electrolyte comprises a mixture of an aqueous solution of phosphoric acid, sulfuric acid, hydrochloric acid, perchloric acid, mono- or dihydrogen phosphate, or their salts and an alcohol, in particular ethanol.

7. A method according to any of the preceding claims, characterized in that the organic compound comprises at least one multiple bond, in particular a nitrogen-carbon multiple bond, a carbon-oxygen double bond, a nitrogen-nitrogen multiple bond, a carbon-carbon multiple bond, or a nitro group and / or is an aromatic or heteroaromatic compound.

8. Method according to one of the preceding claims, characterized in that the organic compound is selected from the group comprising imines, oximes, ketones, aldehydes and alkenes.

9. A method according to any of the preceding claims, characterized in that the inorganic carbon compound is selected from the group comprising carbon dioxide and carbon monoxide, or the inorganic nitrogen compound is selected from the group comprising nitrates, nitrites and nitrogen.

10. Method according to one of the preceding claims, characterized in that the electrochemical hydrogenation is carried out at a temperature in the range of > 5 °C to < 95 °C, preferably in the range of > 20 °C to < 60 °C, preferably in the range of > 15 °C to < 25 °C.

11. Method according to one of the preceding claims, characterized in that the cathode material is selected from the group comprising lead, silver, tin, Indium, niobium, aluminium, bismuth, cobalt, iron, copper, alloys of the aforementioned metals, in particular steel, iron alloys and silver alloys, carbon, in particular graphite, glassy carbon and boron-doped diamond and / or the anode material is selected from the group comprising lead, silver, gold, palladium, iridium, ruthenium, rhodium and platinum.

12. Use of bismuth in dissolved form as a catalyst for the electrochemical hydrogenation of organic or inorganic carbon compounds or inorganic nitrogen compounds.

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