PROCESS FOR ELECTROCHEMICAL HYDROGENATION

Description

The invention relates to a process comprising electrochemically hydrogenating organic or inorganic carbon compounds and inorganic nitrogen compounds.

Many pharmaceuticals contain a nitrogen (N) functionality. These compounds are produced, among other things, from carbonyl compounds and amines by 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═N—R). Imines are not stable in aqueous media, but are in equilibrium with their substrates. To fix the nitrogen in the new molecular structure, imines are reduced with hydrogenation agents to the corresponding amine. Currently, hydrogenations are carried out either with the help 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 produce waste in stoichiometric quantities and have a reduced atom efficiency. Furthermore, the use of hydrogen is currently not sustainable, since hydrogen is mostly obtained from fossil raw materials.

Atom-efficient and sustainable hydrogenation can be achieved with the help of electrochemistry. In electrochemical hydrogenation (e-hydrogenation), electrons are used as a reducing agent. For reductions at the negative electrode, the cathode, materials are needed that have a high overvoltage against hydrogen. Therefore, heavy metals such as lead or tin are used. The problem of cathodic corrosion has been known for a long time. H. W. Salzberg, J. Electrochem. Soc. 1953, 100, 146, describes 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 its dependence on the hydrogen overvoltage and assume that the formation of metal hydrides is based on reduction and protonation reactions. F. W. S. Lucas et al., Green Chem., 2021, 23, 9154, describe the electrochemical reduction of levulinic acid to 4-hydroxyvaleric acid at a lead cathode and spectroscopic signals that indicate 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.

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 for the electrochemical hydrogenation of imines, instead of lead. J. Kümper et al., Angew. Chem. Int. Ed. 2024, 63, e202411532, describe a catalytic effect of trace amounts of lead in the electrolyte during reductive amination or reduction of acetone.

In addition to lead and noble metals, other cathode materials are known for hydrogenation reactions. M. N. 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 an electrochemical reduction of CO₂ to formate at nanoparticulate bismuth-tin-antimony electrodes. Y.-C. Hao et al., Nature Catalysis 2019, 2, 448-456, describe a reduction of nitrogen to ammonia with 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 costly. The production of bismuth-modified electrode materials is also expensive and time-consuming, since the catalyst must first be produced and then fixed on the electrode material. There is therefore a need for alternative catalysts for electrochemical hydrogenation processes.

The underlying objective of the present invention was to provide a process for the electrochemical hydrogenation that overcomes at least one of the aforementioned drawbacks of the prior art.

This problem is solved by a process comprising electrochemically hydrogenating organic or inorganic carbon compounds and inorganic nitrogen compounds in an electrochemical cell comprising a cathode, an anode and an electrolyte, wherein the electrolyte comprises a metal selected from the group consisting of lead, bismuth and thallium in dissolved form.

Surprisingly, it was found that a metal selected from lead, bismuth and thallium in solution form can be used as a catalyst in electrochemical hydrogenation, particularly in reductive amination. In particular, it was found that efficient electrochemical hydrogenation is possible even with concentrations of lead, bismuth and thallium in the ppm range in solution. In particular, it was shown that the presence of dissolved lead, bismuth and thallium in these small amounts enables efficient electrochemical hydrogenation at various electrodes. For example, in the presence of only 1 ppm (1 mg L⁻¹) lead or 5 ppm (5 mg L⁻¹) bismuth, N-methylpropan-2-amine was produced by reductive amination of volatile acetone in a yield of 60%. The use of lead, bismuth and thallium in solution form allows for easy handling of the reaction control, since only a small amount of the metal in dissolved form is added to the substrate solution, and neither extensive modifications of the electrode material nor a long preparation phase for electrolysis are necessary.

According to the method described, the electrochemical hydrogenation is carried out in an electrochemical cell comprising an anode, a cathode, and an electrolyte. In this process, the cathode is in electrical contact with the electrolyte containing a metal selected from lead, bismuth and thallium in dissolved form. For the purposes of this application, the term ‘electrochemical cell’ refers to arrangements that are used in electrochemistry or are based on electrochemical processes. In this case, electrochemical hydrogenation takes place at the cathode, while the oxidation reaction takes place at the anode. A corresponding electrolysis in a divided cell is based on electrochemical hydrogenation, with the catholyte containing the metal selected from lead, bismuth and thallium in dissolved form.

The process provided for electrochemical hydrogenation relies on the metal selected from lead, bismuth and thallium being added to the electrolyte in dissolved form as a cation.

In embodiments, the electrolyte, in particular the catholyte, comprises a lead (II) salt. In embodiments, the electrolyte, in particular the catholyte, comprises a lead (II) salt selected from the group of lead (II) nitrate, lead (II) acetate, lead (II) citrate, lead (II) fluoroborate, lead (II) hexafluorosilicate, lead (II) lactate, lead (II) butanoate, lead (II) carbonate, lead (II) hydroxide, lead (II) oxide hydrate, lead (II) oxide and lead (II) thiosulfate.

Lead (II) salts selected from the group of lead (II) nitrate, lead (II) acetate, lead (II) citrate, lead (II) fluoroborate, lead (II) hexafluorosilicate and lead (II) lactate are preferred for use in aqueous electrolytes as these salts are water soluble. Lead (II) salts selected from the group consisting of lead (II) butanoate, lead (II) carbonate, lead (II) hydroxide, lead (II) oxide hydrate, lead (II) oxide and lead (II) thiosulfate are particularly soluble in acidic solutions and are also preferred for use in aqueous electrolytes. The lead (II) salts are preferably dissolved in an acid, for example nitric acid, or a strongly acidic aqueous solution and then added to the electrolyte or reaction solution.

The concentration of lead can be in the range of ≥0.1 mg/L to ≤38.5 mg/L, particularly in aqueous electrolytes. In embodiments, the concentration of lead in the electrolyte is in a range of ≥0.1 mg/L to ≤3 mg/L. In embodiments, the concentration of lead in the electrolyte is in a range of ≥0.25 mg/L to ≤2 mg/L. In embodiments, the concentration of lead in the electrolyte is in a range of ≥0.5 mg/L to ≤1 mg/L. These concentrations refer to the metal or metal cation. Using concentrations of lead in these ranges, good yields were obtained in the reductive amination of acetone in the presence of methylamine. In particular, good yields of N-methylpropan-2-amine were obtained in the range from 0.5 ppm to 2 ppm lead, with the best yields obtained in the range from 1 ppm to 2 ppm. Since lead acts as a catalyst, it is not consumed, so the concentration remains unchanged or at least substantially unchanged during the course of the electrochemical hydrogenation.

Advantageously, good current efficiency was observed when using a lead salt as a catalyst for the reductive amination of acetone. An efficiency of about 60% was observed when using a Faraday equivalent (F_eq) for the reductive amination of the highly volatile acetone.

In embodiments, the electrolyte, in particular the catholyte, comprises a bismuth (III) salt. It is of particular advantage that bismuth is only slightly toxic. Thus, 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 be harmful to health. The applicability of electrochemical hydrogenation with ppm quantities of bismuth is not limited to the production of compounds used in the pharmaceutical industry by hydrogenation of imines, but is also suitable for the production of other compounds usually produced by hydrogenation from organic compounds such as ketones, alkenes or aldehydes.

In 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) 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.

Bismuth (III) salts selected from the group consisting of bismuth (III) chloride, bismuth (III) phosphate, and bismuth (III) sulfate are preferred for use in aqueous electrolytes because they are particularly water soluble in acidic solution. Bismuth (III) salts selected from the group consisting of 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 solutions and are also preferred for use in aqueous electrolytes. The bismuth salts are preferably 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 suitable 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.

In high dilution or low concentration, the bismuth (III) salts can also remain dissolved in alkaline solution. The concentration of bismuth can be in the range of ≥1 mg/L to ≤35 mg/L, particularly in aqueous electrolytes. In aqueous electrolytes containing 0.5 M KH₂PO₄ (pH 8.3), no cloudiness was observed up to a bismuth concentration of 35 ppm. At a bismuth concentration of 37.5 ppm, cloudiness was observed, indicating a reduced solubility. In non-aqueous electrolytes, higher solubilities may well be present. In embodiments, the concentration of bismuth in the electrolyte is in the range of ≥1 mg/L to ≤7 mg/L. In embodiments, the concentration of bismuth in the electrolyte is in the range of ≥3 mg/L to ≤7 mg/L. In embodiments, the concentration of bismuth in the electrolyte is in the range of ≥5 mg/L to ≤7 mg/L. These concentrations refer to the metal or metal cation. Using concentrations of bismuth in these ranges, good yields were obtained in the reductive amination of acetone in the presence of methylamine. In particular, good yields of N-methylpropan-2-amine were obtained in the range from 3 ppm to 7 ppm bismuth, with the best yields obtained in the range from 5 ppm to 7 ppm bismuth. Since bismuth acts as a catalyst, it is not consumed, so the concentration remains unchanged or at least substantially unchanged during the course of the electrochemical hydrogenation.

Advantageously, good current efficiency was observed when using bismuth salt as a catalyst for the reductive amination of acetone. Thus, an efficiency of about 60% was observed when using a Faraday equivalent (F_eq) for the reductive amination of the highly volatile acetone. This corresponded to that of the material yield. For the electrochemical reductive amination of acetone, 1≤F_eq≤2 is preferred. The Faraday efficiency (or current utilisation efficiency) is the quotient of the charge consumed in the desired reaction and the total charge transferred.

When using 1 F_eq and the Faraday efficiency is 100%, the substrate would be completely converted to the desired product. In practice, the theoretical conversion is not achieved due to an equivalent of the charge theoretically required for this (Faraday equivalent) due to side reactions, such as the decomposition of the solvent. It was shown that with increasing bismuth concentration, the yield of amine and the conversion of acetone increased and side reactions (solvent decomposition) were suppressed. This shows that the bismuth salt used was a good catalyst for reductive amination.

In embodiments, the electrolyte, in particular the catholyte, comprises a thallium (I) salt or a thallium (III) salt. In embodiments, the electrolyte, in particular the catholyte, comprises a thallium (I) salt or thallium (III) salt selected from the group of thallium (I) acetate, thallium (I) formate, thallium (I) nitrite, thallium (I) oxide, thallium (I) nitrate, thallium (I) sulfide, thallium (III) chloride and thallium (III) bromide. For use in aqueous electrolytes thallium (I) salts and thallium (III) salts selected from the group of thallium (I) acetate, thallium (I) formate, thallium (I) nitrite, thallium (I) oxide, thallium (I) nitrate, thallium (III) chloride and thallium (III) bromide are preferred as these salts are water soluble. Thallium (I) sulfide is particularly soluble in acidic solutions and is also preferred for use in aqueous electrolytes. The thallium (I) salts and thallium (III) salts are preferably dissolved in an acid, for example nitric acid, or a strongly acidic aqueous solution and then added to the electrolyte or reaction solution. The concentration of thallium can be in the range of ≥0.1 mg/L to ≤10 mg/L, particularly in aqueous electrolytes. In embodiments, the concentration of thallium in the electrolyte is in a range of ≥1 mg/L to ≤3 mg/L, preferably in a range of ≥2 mg/L to ≤3 mg/L. These concentrations refer to the metal or metal cation. Using 1 ppm of thallium, good yields were obtained in the reductive amination of acetone in the presence of methylamine.

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

In embodiments, the electrolyte comprises an aqueous solution of phosphoric acid, sulfuric acid, hydrochloric acid, perchloric acid, mono- or di-hydrogen phosphate, their salts or their mixtures. Salts of perchloric acid may be perchlorates selected from LiClO₄, KClO₄ and NaClO₄. 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.

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.

The aqueous electrolyte may comprise a mixture of water with one or more organic solvents selected, for example, from the group comprising alcohols, ethers, dioxanes, acetonitrile, furan, tetrahydrofuran, dioxolane, dimethyl sulfoxide, dimethyl formamide, sulfolane, 3-sulfolene, N-methyl-2-pyrrolidone or mixtures thereof. In embodiments, the aqueous electrolyte comprises mixtures of water and alcohol, for example water and ethanol, and mixtures of water and acetone.

The term ‘alcohols’ includes monohydric and polyhydric alcohols, in particular dihydric alcohols. In embodiments, the alcohol is selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol, tert-butanol and ethylene glycol. In embodiments, the alcohol is selected from the group comprising methanol, ethanol, tert-butanol and ethylene glycol. The term ‘dioxane’ includes 1,3-dioxane and 1,4-dioxane. The term ‘dioxolane’ includes 1,2-dioxolane and 1,3-dioxolane.

When using methylamine as the nitrogen source for reductive amination, it 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. An alkaline 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, on the other hand, an acidic pH is preferred. When hydroxylamine is used as the nitrogen source, aqueous mixtures with sulfuric acid or phosphoric acid or hydrochloric acid as the electrolyte can also be used for the reductive amination.

The organic or inorganic carbon compounds or inorganic nitrogen compounds are 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, may comprise the organic or inorganic carbon compound or inorganic nitrogen compound to be hydrogenated and at least one further organic compound, for example, in the case of reductive amination, an organic compound serving as a nitrogen source. For example, in the case of reductive amination of a ketone such as acetone, the electrolyte, in particular the catholyte, may comprise a mixture of acetone and methylamine or another nitrogen-containing compound that can react in a condensation reaction.

The compound contains at least one multiple bond that can be hydrogenated by the described method. Such compounds are preferably organic compounds. Inorganic carbon compounds such as carbon monoxide and carbon dioxide have electrochemically hydrogenatable multiple bonds that can also be hydrogenated by means of the described method and are included herein. Inorganic nitrogen compounds such as nitrates, nitrites and nitrogen (N₂) also have electrochemically hydrogenatable multiple bonds that can be hydrogenated using the method described and are included herein.

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

In embodiments, the inorganic carbon compound has at least one or two carbon-oxygen double bond(s) or a carbon-oxygen triple bond. In embodiments, the inorganic carbon compound is selected from the group consisting of carbon dioxide and carbon monoxide.

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

The organic or inorganic carbon compound or inorganic nitrogen compound is preferably liquid under process conditions, in particular at ambient temperature. The organic or inorganic carbon compound or inorganic nitrogen compound may also be partially gaseous, in particular in the case of carbon dioxide, carbon monoxide or nitrogen. The compound can also be present as a solid, provided that at least a part of it goes into solution or is present in dissolved form and is available as a starting material. In particular, low-molecular-weight compounds that can be readily dissolved in the electrolyte are suitable for electrochemical hydrogenation.

The process may, for example, be 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 one embodiment, the method is, for example, a method for electrochemically aminating a ketone such as acetone or an aldehyde in the presence of methylamine or another nitrogen source. In other embodiments, the method is a reductive hydrogenation. In one embodiment, the method is, for example, a method for electrochemically hydrogenating a ketone such as acetone or an aldehyde. The process can also be a process for the electrochemical reduction of nitrogen to ammonia.

The electrochemical hydrogenation can be carried out in various temperature ranges. In embodiments, the electrochemical hydrogenation is carried out at a temperature in the range of ≥5° C. to ≤95° C., or in the range of ≥20° C. to ≤60° C., or in the range of ≥15° C. to ≤25° C. Electrochemical hydrogenation can be carried out under cooling, for example, provided that the solvent/electrolyte system can be maintained in the liquid phase. For example, an increase in pressure can enable a working temperature above the actual boiling point of the solvents. It is advantageous to carry out electrochemical hydrogenation at normal pressure and ambient temperatures, which can improve the energy balance of the hydrogenation.

For the reductive amination of acetone in the presence of methylamine, good yields of N-methylpropan-2-amine were obtained at temperatures ranging from ≥5° C. to ≤45° C., especially in the range from ≥15° C. to ≤25° C. and from ≥15° C. to ≤20° C. The reductive amination of acetone can thus be carried out with a good yield at ambient temperature.

In processes for the reductive amination of acetone in the presence of methylamine, current densities of −30 mA/cm² at 5° C. and −110 mA/cm² at 45° C. were achieved with a concentration of 6 ppm bismuth and a constant potential of −2.94 V vs. RHE (standard hydrogen electrode). High current densities are advantageous from an economic point of view.

In processes for the reductive amination of acetone in the presence of methylamine, with a concentration of 1 ppm lead at 10° C. current densities of −9 mA/cm² were achieved at a potential of −1.34 V vs. RHE and current densities of −54 mA/cm² at a potential of −3.34 V vs. RHE.

In general, cathode materials that exhibit a high overvoltage against hydrogen are preferred. In embodiments, the cathode material is selected from the group consisting of lead, silver, tin, indium, niobium, aluminium, bismuth, cobalt, iron, copper, alloys of the aforementioned metals in particular steel, silver alloys, iron alloys, graphite, carbon in particular glass-like carbon and boron-doped diamond. In embodiments, the anode material is selected from the group consisting of lead, silver, gold, palladium, iridium, ruthenium, rhodium and platinum.

In embodiments, the material has a high hydrogen evolution overpotential, such as lead, silver, copper, glassy carbon and boron-doped diamond. For the reductive amination of acetone in the presence of methylamine, good results have been obtained with lead/lead, silver/lead, glassy carbon/platinum, boron-doped diamond/platinum, and silver/platinum cells.

Overall, electrochemical hydrogenation using a dissolved metal selected from lead, bismuth and thallium provides a promising method that allows atom-efficient and sustainable hydrogenation. In particular, when using dissolved bismuth an electrochemical hydrogenation of compounds suitable for applications in the pharmaceutical industry can be provided.

Unless otherwise stated, the technical and scientific terms used have the meanings commonly understood by a person skilled in the art to which the invention belongs.

Examples serving to illustrate the present invention are given below.

Chemicals:

Substance/Material	Manufacture	Purity
Acetone	Chemsolute	99.50%
Antimony standard solution for	Alfa	—
ICP (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 of starting
(1000 ppm Bi in HNO3 (3%))		material 99.991%
Lead(II)nitrate	Roth	≥99%
Dimethylsulfoxide-d6	Deutero	99.80%
1,4-Dioxane	Emsure	99.50%
Indium(III) chloride tetrahydrate	Aldrich/Merck KGaA	99.999%
Monopotassium phosphate	Fluka	99%
Potassium hydroxide	Chemsolute	85%
Methylamine	Merck	40%
MicroPolish Alumina 1.0 μm	Buehler
Nafion N-324 (0.15 mm, Teflon	Thermo scientific
fabric reinforced)
Nafion N-424	Ion Power
Phosphoric acid	Merck	85%
Platinum	Evochem	99.95%
Selenium standard solution for	Fluka Chemie AG	1000 ppm ± 0.3%
ICP (1000 ppm Se in HNO3
(~0.5M))
Silver	Chempure	99.90%
Tin standard solution for ICP	Merck KGaA
(1000 ppm Sn in HCl (7%))
Tellurium standard solution for	Roth	Purity of starting
ICP (1000 ppm Te in HNO3		material 99.96%
(2%))
Thallium(I)nitrate	Sigma-Aldrich/Merck KGaA	99.999%
1,3,5-Trioxane	Aldrich	99%
Boron-doped diamond (Mo-basis)	Diachem
Glassy carbon (GC) (Sigradur G)	HTW Hochtemperatur-
	Werkstoffe GmbH
Copper	Aldrich	99.98%

Methods:

Nuclear Magnetic Resonance Spectroscopy (NMR):

The yields (Y), conversions (X) and carbon balances (C.B.) were determined by quantitative ¹H-NMR spectroscopy using a Bruker Avance spectrometer (400 MHz) at room temperature (16 scans, d1 time: 10 s). DMSO-d₆ (2.50 ppm) was used as the solvent. 1,3,5-trioxane (δH: 5.07 ppm) and 1,4-dioxane (δH: 3.52 ppm) were used as internal standards for the cathode and anode solutions, respectively.

EXAMPLE 1

Reductive Amination of Acetone in the Presence of Various Metallic or Semi-Metallic Additives

A reductive amination of acetone with methylamine as the nitrogen source was carried out electrochemically in the presence of various metallic or semi-metallic additives (c_additive=1 ppm).

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 assembly consisting of a cathode (silver, 5×5 cm), an anode (platinum, 5×5 cm) and a reference electrode (Hg/HgO electrode (1 M KOH), ZH514 RE-61AP, BASi) was used for the electrolysis. The silver electrode used had a mirror-like surface obtained by polishing with a 1 μm alumina suspension (MicroPolish Alumina 1.0 μm; Buehler). The silver electrode was freshly polished before each electrolysis. Metrohm potentiostats (PGSTAT302N/PGSTAT204) were used to carry out the electrolysis.

The reaction mixture of the cathode compartment 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 metal or metalloid (0.02 mL of an aqueous 100 ppm solution of the metal/metalloid). 0.5 M KH₂PO₄ (pH 8.3) was used as the reaction mixture solvent, the volume of which was adjusted so that the final volume of the reaction solution was 2 mL. The 100 ppm solutions of the metals and semi-metals (the ‘100 ppm’ concentration refers to the (semi-) metal and possible counterions are not taken into account) were prepared by dilution with deionised water. The starting materials for the aqueous 100 ppm solutions of In, Tl and Pb were InCl₃×4H₂O, TlNO₃ and Pb(NO₃)₂. The 100 ppm solutions of As, Se, Sn, Sb, Te and Bi were obtained by dilution with deionised water from the respective ICP standard solutions (1000 ppm).

2 mL of 25% H₃PO₄ was added to the anode compartment. After filling the half-cells, the reaction mixture was cooled to 10° C. within 18 min while stirring at 250 rpm. At 10° C., the pH of the reaction mixture was 12.9. After 18 min, stirring was stopped and cyclic voltammetry measurements were carried out at a scan rate of 50 mV s⁻¹ between −1.12 V and 0.06 V vs. RHE. Subsequent potentiostatic electrolysis was carried out at −2.94 V vs. RHE and terminated when 1 Faradaic equivalent (F_eq) of current had passed (−926.3 C).

Table 1 shows the yields of the intermediate (N-methylpropan-2-imine, Y_Imine), the desired product (N-methylpropan-2-amine, Y_Amine), and the byproduct (isopropanol, Y_Alcohol) as a function of the additive. In addition, the conversion (X) and carbon balance (C.B.) are given.

TABLE 1
Influence of various metals/half-metals on the electrochemical reductive
amination of acetone with methylamine. The final concentration of the
metal/half-metal in the reaction solution was 1 ppm. Reaction conditions:
Ag∥Pt, E = −2.94 V vs RHE; Feq = 1; solvent: 0.5M KH2PO4
(pH 8.3); substrates: acetone: 2.4M, methylamine: 2.9M; T = 10° C.;
pH at 10° C.: 12.9; anolyte: 25% H3PO4.

Additive	YImin (%)	YAmin (%)	YAlcohol (%)	X (%)	C.B. (%)
As	35.2	1.5	0.0	66.1	71.1
Se	38.7	1.3	0.7	68.7	71.7
In	36.8	1.1	0.5	68.4	70.1
Sn	35.0	3.0	0.9	68.0	69.6
Sb	35.3	2.2	0.6	70.5	66.4
Te	35.8	3.0	0.2	67.3	71.5
Tl	6.5 (±0.1)	54.3 (±1.0)	0.7 (±0.1)	86.7 (±0.1)	72.7 (±1.1)
Pb	3.4 (±0.9)	60.8 (±1.2)	2.0 (±0.7)	90.4 (±1.2)	74.5 (±1.4)
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, which are known as electrode materials for electrochemical hydrogenations, showed only extremely slight hydrogenation reactions. Thallium and lead showed good yields of the electrochemical hydrogenation of the imine to the amine. Bismuth also showed good yields of the electrochemical hydrogenation of the imine to the amine, and, compared to lead, a lower conversion to the alcohol. Bismuth is further suitable as catalyst for the hydrogenation of compounds that are to be used as pharmaceuticals.

EXAMPLE 2

Determination of Reductive Amination of Acetone in the Presence of Different Lead Concentrations

The electrochemically initiated reductive amination of acetone with methylamine was investigated as a function of the lead concentration in the ppm range. The final reaction volume of 2 mL contained 2.4 M acetone (0.36 mL, 1 eq.) and 2.9 M methylamine (1.2 eq., 40% methylamine solution: 0.50 mL). Acetone and methylamine were added to an aqueous 0.5 M KH₂PO₄-solution (pH 8.3) that was used as solvent. The volume of the solvent was adjusted to yield a final reaction volume of 2 mL. Final Pb concentrations between 0.25 ppm and 2 ppm were obtained by using aqueous standard solutions of 10 ppm or 100 ppm Pb(NO₃)₂, with the 10 ppm standard solution being used only for the final concentration of 0.25 ppm. For the anode compartment, 2 mL 25% H₃PO₄ were used. A Nafion N-324 membrane was used in this example.

After transferring the solutions into the respective half-cell compartment, the reaction solution was cooled to 10° C. within 18 min while stirring at 250 rpm. At 10° C., the prepared reaction solution had a pH value of 12.9. The stirrer was turned off after 18 min of cooldown and cyclic voltammetry measurements were carried out with a scan rate of 50 mV s⁻¹ between −1.12 V and 0.06 V vs RHE. In the subsequent galvanostatic electrolysis experiments a current density of −40 mA cm² was applied. The electrolysis's were stopped after 1 F_eq was passed (−926.3 C).

Table 2 shows the yields of the intermediate (N-methylpropan-2-imine, Y_Imine), the desired product (N-methylpropan-2-amine, Y_Amine) and the by-product (isopropanol, Y_Alcohol) as a function of the Pb concentration. The conversion (X), carbon balance (C.B.) and turn over number (TON) are also given.

TABLE 2
Impact of different Pb concentrations on the reductive
amination of acetone with methylamine by electrolysis.

cPb	YImine	YAmine	YAlcohol	X	C.B.	TON
[ppm]	[%]	[%]	[%]	[%]	[%]	[ ]

0.25	38.4	3.4	0.7	66.4	75.6	69336
	(±1.0)	(±0.9)	(±0.0)	(±0.6)	(±1.0)	(±17433)
0.5	18	37	0.5	77	77	375948
	(±3)	(±10)	(±0.0)	(±4)	(±2)	(±97937)
1	3.7	62.9	1.7	89.6	76.8	319068
	(±0.1)	(±1.6)	(±0.0)	(±1.0)	(±1.2)	(±9088)
2	1.9	62	5.2	92.7	75	158218
	(±0.0)	(±2)	(±0.4)	(±0.5)	(±3)	(±5420)
Conditions: Ag || Pt; j = −40 mA cm−2; Feq = 1; solvent: 0.5M KH2PO4 (pH 8.3); substrates: acetone: 2.4M, methylamine: 2.9M; T = 10° C.; pH at 10° C.: 12.9; anolyte: 25% H3PO4; a N-324 membrane; and a Pb free cell.

As can be taken from Table 2, an increase in lead concentration resulted in an increased yield of amine. Good yields were obtained at concentrations of 0.5 to 2 ppm of lead, with the best yields obtained at 1 to 2 ppm of lead, where the increase in concentration from 1 to 2 ppm of lead did not result in an increased yield of amine, but of alcohol.

EXAMPLE 3

Transition from Galvanostatic to Potentiostatic Conditions and Determination of the Impact of Applied Potential on Electrochemical Hydrogenation of N-Methylpropan-2-Imine.

The electrochemically initiated reductive amination of acetone with methylamine in the presence of 1 ppm Pb as a function of the applied potential was determined. The experiments were carried out in the cell system as described in example 2, except that a Nafion N-424 membrane was utilized. The electrodes used were also identical.

The final reaction volume of 2 mL contained 2.4 M acetone (0.36 mL, 1 eq.) and 2.9 M methylamine (1.2 eq., 40% methylamine solution: 0.50 mL). Acetone and methylamine were added to an aqueous 0.5 M KH₂PO₄-solution (pH 8.3) that was used as solvent. The volume of the solvent was adjusted to yield a final reaction volume of 2 mL. The final Pb concentration of 1 ppm in the substrate solution was obtained by using the aqueous 100 ppm Pb solution based on Pb(NO₃)₂. For the anode compartment, 2 mL 25% H₃PO₄ were used.

After transferring the solutions into the respective half-cell compartment, the reaction solution was cooled to 10° C. within 18 min while stirring at 250 rpm. At 10° C., the prepared reaction solution had a pH value of 12.9. The stirrer was turned off after 18 min of cooldown and cyclic voltammetry measurements were carried out with a scan rate of 50 mV s⁻¹ between −1.12 V and 0.06 V vs RHE. In galvanostatic electrolysis experiments a current density of −40 mA cm 2 was used. In potentiostatic electrolysis experiments, potentials of −3.34 V, −2.94 V, −2.54 V, −2.14 V, −1.74 V and −1.34 V vs RHE were applied. The electrolysis's were stopped after 1 F_eq was passed (−926.3 C). The current density of −40 mA cm⁻² is equal to a potential of −2.94 V vs RHE.

Table 3A shows the yields of the intermediate (N-methylpropan-2-imine, Y_Imine), the desired product (N-methylpropan-2-amine, Y_Amine) and the by-product (isopropanol, Y_Alcohol) after potentiostatic and/or galvanostatic electrolysis in presence of 1 ppm Pb. Table 3B shows the conversion (X), carbon balance (C.B.) and duration of electrolysis (telectrolysis).

Table 3A and 3B: Transition from galvanostatic to potentiostatic conditions and studying the impact of applied potential on e-hydrogenation of N-methylpropan-2-imine. Conditions: Ag∥Pt; 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; a N-424 membrane; and 1 ppm Pb in the final substrate solution (added in form of an aqueous Pb(NO₃)₂ solution). (*: are equivalent)

	E [V] vs RHE
Example	or j [mA cm−2]	YImine [%]	YAmine [%]	YAlcohol [%]

2.1	−3.34	V	4.3 (±0.3)	60.5 (±1.4)	3.6 (±0.5)
2.2	−40	mA cm−2(*)	2.5 (±0.7)	60.7 (±1.9)	1.7 (±0.1)
2.3	−2.94	V(*)	3.4 (±0.9)	60.8 (±1.2)	2.0 (±0.7)
2.4	−2.54	V	2.3 (±0.3)	63 (±4)	1.6 (±0.2)
2.5	−2.14	V	1.8 (±0.0)	62.9 (±0.6)	1.2 (±0.2)
2.6	−1.74	V	1.0 (±0.7)	59.8 (±0.8)	0.9 (±0.0)
2.7	−1.34	V	0.7 (±0.1)	57.8 (±0.7)	0.0 (±0.0)

Table 3B:

Example	X [%]	C.B. [%]	telectrolysis [h]

2.1	91.4 (±0.0)	75.4	(±0.4)	2.1	(±0.1)
2.2	90.5 (±0.2)	71.3	(±2.1)	2.9	(±0.0)
2.3	90.4 (±1.2)	74.5	(±1.4)	2.9	(±0.1)
2.4	90.3 (±1.2)	74.2	(±1.8)	3.5	(±0.1)
2.5	91.4 (±0.7)	72.3	(±1.2)	4.8	(±0.3)
2.6	90.6 (±0.9)	69	(±2)	7.1	(±0.3)
2.7	87.2 (±0.0)	66.0	(±1.2)	12.8	(±0.2)

As can be taken from Table 3, the results show a successful change from galvanostatic to potentiostatic conditions.

EXAMPLE 4

Determination of the Impact of Cathode Material on the Reductive Amination of Acetone with Methylamine as Nitrogen Source in Presence of 1 ppm Pb

Determined was the electrochemically initiated reductive amination of acetone with methylamine in the presence of 1 ppm Pb as a function of the utilized cathode material. The investigated cathode materials differ in their hydrogen evolution reaction overpotential. The experiments were carried out in the cell system as described in example 2 except that a Nafion N-424 membrane was utilized and potentiostatic conditions were applied.

Pt, Ni, Cu, Ag, glassy carbon (GC) and boron-doped diamond (BDD) were tested as cathode materials. Ag, Ni and Cu were characterized by a mirror-like surface, obtained by intensive polishing of the rolled metal material with a 1 μm alumina suspension (MicroPolish Alumina 1.0 μm from Buehler). These electrodes were freshly polished with sandpaper or with the 1 μm alumina suspension before each electrolysis, unless otherwise stated. Pt, GC and BDD were used as received.

The final reaction volume of 2 mL contained 2.4 M acetone (0.36 mL, 1 eq.) and 2.9 M methylamine (1.2 eq., 40% methylamine solution: 0.50 mL). Acetone and methylamine were added to an aqueous 0.5 M KH₂PO₄-solution (pH 8.3) that was used as solvent. The volume of the solvent was adjusted to yield a final reaction volume of 2 mL. The final Pb concentration of 1 ppm in the substrate solution was obtained by using the aqueous 100 ppm Pb solution based on Pb(NO₃)₂. For the anode compartment, 2 mL 25% H₃PO₄ were used.

After transferring the solutions into the respective half-cell compartment, the reaction solution was cooled to 10° C. within 18 min while stirring at 250 rpm. At 10° C., the prepared reaction solution had a pH value of 12.9. The stirrer was turned off after 18 min of cooldown and cyclic voltammetry measurements were carried out with a scan rate of 50 mV s⁻¹ between −1.12 V and 0.06 V vs RHE. The potentiostatic electrolysis experiments were performed using −2.94 V vs RHE. The electrolysis's were stopped after 1 F_eq was passed (−926.3 C).

Table 4 shows the yields of the intermediate (N-methylpropan-2-imine, Y_Imine), the desired product (N-methylpropan-2-amine, Y_Amine) and the by-product (isopropanol, Y_Alcohol) after electrolysis at −2.94 V vs RHE in presence of 1 ppm Pb using different cathode materials. The conversion (X) and carbon balance (C.B.) are also given.

TABLE 4
Impact of the cathode material on the reductive amination of acetone with
methylamine in presence of 1 ppm Pb. Conditions: Ag ∥ Pt; E = −2.94 V vs
RHE; Feq = 1; solvent: 0.5M KH2PO4 (pH 8.3); substrates: acetone: 2.4M,
methylamine: 2.9M; T = 10° C.; pH at 10° C.: 12.9; anolyte: 25% H3PO4;
a N-424 membrane; and 1 ppm Pb in the final substrate solution
(added in form of an aqueous Pb(NO3)2 solution).

Cathode material

(from low to high

HER overpotential)	YImine [%]	YAmine [%]	YAlcohol [%]	X [%]	C.B. [%]

Pt	37.4	(±1.7)	3.2	(±0.1)	1.4 (±0.1)	67.1	(±1.1)	74.0 (±0.5)
Ni	33.5	(±0.3)	3.1	(±0.7)	1.7 (±0.3)	66.8	(±1.1)	70.9 (±0.1)
Cu	27	(±3)	9	(±2)	6.6 (±0.6)	70.9	(±0.4)	69.8 (±1.5)
Ag	3.4	(±0.9)	60.8	(±1.2)	2.0 (±0.7)	90.4	(±1.2)	74.5 (±1.4)
GC	3.1	(±0.9)	62.2	(±1.3)	3.7 (±0.7)	92.4	(±1.3)	76.0 (±1.1)
BDD	3.5	(±0.6)	62.2	(±1.9)	2.5 (±0.6)	90	(±2)	76.7 (±0.7)

As can be taken from Table 4, cathode materials with high HER overpotential such as silver, glassy carbon (GC) and boron-doped diamond (BDD) were suitable for reductive amination of acetone with methylamine in presence of 1 ppm Pb.

EXAMPLE 5

Determining the Influence of the Bismuth Concentration on the Reductive Amination of Acetone with Methylamine

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 cell system and with the electrodes as described in example 1.

The reaction mixture of 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, whereby the volume of the reaction mixture was 2 mL. The bismuth was added in dissolved form to the acetone-methylamine mixture. To do this, solutions with bismuth concentrations of 100 ppm, 400 ppm and 700 ppm were prepared from a 1000 ppm Bi standard solution by dilution with deionised water. The 100 ppm Bi solution was used for the experiments with a final Bi concentration of 1 and 2 ppm. The 400 ppm Bi solution was used for the experiments with 3, 4, 5 and 6 ppm Bi. The 700 ppm Bi solution served as the starting point for the experiments with a final Bi concentration of 7 ppm. 0.5 M KH₂PO₄ (pH 8.3) was used as the solvent, the volume of which was adjusted so that the final volume of the reaction solution was 2 mL.

2 mL of 25% H₃PO₄ was added to the anode compartment. After filling the half-cells, the reaction mixture was cooled to 10° C. within 18 min while stirring at 250 rpm. At 10° C., the pH of the reaction mixture was 12.9. After 18 min, stirring was stopped and cyclic voltammetry measurements were carried out at a scan rate of 50 mV s⁻¹ between −1.12 V and 0.06 V vs. RHE. Subsequent potentiostatic electrolysis was carried out at −2.94 V vs. RHE and terminated when 1 Faradaic equivalent (F_eq) of current had passed (−926.3 C).

The following Table 5 shows the yields of the intermediate (N-methylpropan-2-imine, Y_Imine), the desired product (N-methylpropan-2-amine, Y_Amine), and the by-product (isopropanol, Y Alcohol) as a function of the bismuth concentration. In addition, the conversion (X) and carbon balance (C.B.) are given.

TABLE 5
Effect 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; Feq = 1; solvent: 0.5M KH2PO4 (pH 8.3);
substrates: acetone: 2.4M, methylamine: 2.9M; T = 10° C.; pH at 10° C.:
12.9; anolyte: 25% H3PO4.

cBi (ppm)	YImine (%)	YAmine (%)	YAlcohol (%)	X (%)	C.B. (%)

1	12.1	(±1.6)	36.9 (±1.4)	0.7 (±0.1)	78.0 (±0.2)	69.6 (±1.1)
2	12.9	(±2.3)	43.6 (±1.2)	0.7 (±0.2)	82.0 (±1.0)	73.6 (±2.8)
3	8.8	(±0.9)	49.9 (±1.0)	0.9 (±0.0)	84.8 (±0.2)	73.7 (±0.1)
4	7.9	(±2.5)	53.1 (±4.1)	1.1 (±0.3)	85.6 (±2.2)	75.2 (±4.0)
5	5.2	(±1.9)	58.5 (±4.3)	1.0 (±0.1)	89.3 (±1.8)	73.9 (±2.9)
6	4.6	(±1.0)	59.7 (±1.4)	0.9 (±0.2)	90.5 (±0.6)	73.5 (±0.3)
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 5, an increase in the bismuth concentration resulted in an increased yield of amine. Good yields were obtained at 3 to 7 ppm of bismuth, with the best yields obtained at 5 to 7 ppm of bismuth, where the increase in concentration from 5 to 7 ppm of bismuth had hardly any effect on the yield of amine.

EXAMPLE 6

Determining the Influence of Temperature on the Electrochemically Initiated Reductive Amination of Acetone with Methylamine Using Bismuth

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 cell system and with the electrodes as described in example 1.

The reaction mixture of the cathode compartment 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 Bi (400 ppm Bi solution: 0.03 mL). The bismuth was added in dissolved form to the acetone-methylamine mixture. The 400 ppm bismuth solution was prepared by diluting a 1000 ppm Bismuth standard solution with deionised water. 0.5 M KH₂PO₄ (pH 8.3) was used as the reaction mixture solvent, and its volume was adjusted so that the final volume of the reaction solution was 2 mL.

2 mL of 25% H₃PO₄ was added to the anode compartment. After filling the half-cells, the reaction mixture was cooled/heated to the appropriate temperature between 5 and 45° C. within 18 min while stirring at 250 rpm. 45° C. was defined as the upper limit due to the substrate, since the boiling point of a 40% methylamine solution is 49° C. After 18 min, stirring was stopped and cyclic voltammetry measurements were performed at scan rates of 50 mV s⁻¹ between −1.12 V and 0.06 V vs RHE. Subsequent potentiostatic electrolysis was carried out at −2.94 V vs. RHE and terminated when 1 Faradaic equivalent (F_eq) of current had passed (−926.3 C).

Table 6 shows the yields of the intermediate (N-methylpropan-2-imine, Y_Imine), the desired product (N-methylpropan-2-amine, Y_Amine) and the by-product (isopropanol, Y_Alcohol) as a function of temperature in the presence of 6 ppm bismuth. In addition, the conversion (X), carbon balance (C.B.) and pH of the substrate solution at the corresponding temperature (pH_T) are given.

TABLE 6
Effect of temperature on the electrochemical reductive
amination of acetone with methylamine as the nitrogen
source in the presence of 6 ppm Bismuth. Bismuth was added
to the acetone-methylamine mixture in dissolved form.

	pHT of
T	substrate	YImine	YAmine	YAlcohol	X	C.B.
(° C.)	solution	(%)	(%)	(%)	(%)	(%)

5	13.12	6.6	55.0	1.2	86.3	76.1
		(±1.2)	(±3.5)	(±0.6)	(±2.5)	(±0.0)
10	12.88	4.6	59.7	0.9	90.5	73.5
		(±1.0)	(±1.4)	(±0.2)	(±0.6)	(±0.3)
15	12.66	3.3	60.7	0.5	91.3	71.3
		(±0.3)	(±0.4)	(±0.1)	(±0.2)	(±0.5)
20	12.42	3.3	61.2	0.6	91.2	71.8
		(±0.4)	(±0.4)	(±0.0)	(±0.2)	(±0.8)
25	12.21	2.7	61.6	0.7	91.5	71.4
		(±0.0)	(±1.0)	(±0.1)	(±0.5)	(±0.0)
35	11.97	1.7	59.1	0.5	90.9	67.9
		(±0.1)	(±0.5)	(±0.1)	(±0.7)	(±0.4)
45	11.39	1.4	52.1	0.5	91.3	59.8
		(±0.1)	(±0.5)	(±0.1)	(±0.4)	(±0.5)
Reaction conditions: Ag||Pt, E = −2.94 V vs RHE; Feq = 1; solvent: 0.5M KH2PO4 (pH 8.3); substrates: acetone: 2.4M, methylamine: 2.9M; T = 10° C.; pH at 10° C.: 12.9; anolyte: 25% H3PO4.

As can be seen from Table 6, good yields of the amine were obtained over the entire temperature range between 5° C. and 45° C., with the best yields obtained in the temperature range between 15° C. and 25° C.

In summary, the results show that electrochemical hydrogenation of organic compounds can be achieved with good selectivity using small amounts of lead, bismuth or thallium in solution.