High-throughput electrochemical oxidation process

Abstract

The invention relates to a process for the electrochemical production of alkylene dicarboxylic acids, preferably adipic acid and alkylated derivatives thereof, preferably 3-ethyl adipic acid, by ring-opening oxidation.

Description

[0001] Electrochemical high-throughput oxidation process

[0002] The invention relates to a process for the electrochemical preparation of alkylenedicarboxylic acids, preferably adipic acid and alkylated derivatives thereof, preferably 3-ethyladipic acid, by ring-opening oxidation.

[0003] The production of adipic acid emits millions of tons of climate-damaging and toxic gases annually. The usual production process is the nitric acid oxidation of cyclohexanone / cyclohexanol mixtures (KA-ÖI) from fossil sources. This process produces approximately 300 kg of N2O per synthesized ton of adipic acid – a greenhouse gas with a 100-year greenhouse gas potential 298 times higher than CO2. Adipic acid is primarily used as a monomer in the polycondensation reaction with hexamethylenediamine to produce nylon 6.6. With a market volume of over 3 million tons per year, the reaction is accompanied by a concurrent high production of N2O. While producers agreed to reduce these toxic emissions as early as 1995, new approaches to replace the conventional process, the feedstock used, or even to replace adipic acid remain highly desirable. 25 years ago, Noyori et al.made a significant contribution to enabling the synthesis of adipic acid via a more climate- and environmentally friendly route (Sato, K. A “Green” Route to Adipic Acid: Direct Oxidation of Cyclohexenes with 30 Percent Hydrogen Peroxide. Science 1998, 281 (5383), 1646-1647). They oxidized cyclohexene in an aqueous hydrogen peroxide solution at 75-90 °C to adipic acid. They used Na2WÜ4 and quaternary ammonium bisulfate as a phase-transfer catalyst (1 mol% each). The resulting epoxide intermediates undergo ring cleavage in an acidic medium. This enabled an adipic acid yield of 90%. However, the starting material for this reaction was not biogenic. In particular, the required hydrogen peroxide is energetically rather critical, expensive, and requires considerable safety precautions. Tungsten and the phase transfer catalyst can be reused once, with significant losses, and remain as waste thereafter.In addition, chemical research aims to transition from fossil to renewable resources. One possible approach is the use of biogenic raw materials such as lignin, which is used primarily for energy purposes in the pulp industry. It is the world's largest aromatic raw material, does not compete with food, and is renewable.

[0004] Recently, an approach for the synthesis of adipic acid from lignocellulose through bacterial transformation followed by catalytic hydrogenation was developed. Other bacterial routes for the production of adipic acid from bio-based platform molecules such as 5-hydroxymethylfufural, glucose, γ-valerolactone, and phenolic compounds have been investigated by Li et al. (Lang, M.; Li, H. Sustainable Routes for the Synthesis of Renewable Adipic Acid from Biomass Derivatives. ChemSusChem 2022, 15 (1)). However, the scalability of such biotechnological processes for industrial purposes remains a challenge. The combination of biotransformation followed by electrosynthesis has shown that sugars can be selectively converted into 3-dehydroadipic acid. Easier-to-scale routes include the electrochemical oxidation of cyclohexanol in flow reactors.

[0005] Electrochemistry is a powerful, ecologically and economically sustainable method for organic reactions due to its cost and atom efficiency. However, several crucial parameters for electrosynthesis must be controlled and optimized. The versatility of electrochemical reactions in undivided arrangements enables promising scale-up of many transformations. This is especially true for flow electrolyzers. Flow electrolyzers have many advantages over batch electrolysis cells: A close electrode spacing enables lower ohmic resistance and better heat dissipation. Furthermore, the surface-to-volume ratio is better than in batch cells, which also leads to better mass transport. Larger electrode surface areas further improve these properties when the electrode spacing remains constant.This increased geometric anode surface area typically increases the production rate of the target compound linearly. A scaled flow electrolyzer can also be equipped with cooling devices. This is generally achieved by channels for the tempering fluid behind the electrodes. The design of a flow electrolyzer is usually a prerequisite for a continuous production process and represents an important aspect of scale-up.

[0006] Previous alcohol oxidation protocols rely on the use of Ni(O)OH electrodes. In the 1970s, the enhanced electrooxidation power of the heterogeneous mediator nickel oxide hydroxide for the oxidation of aliphatic alcohols was discovered. The importance of stable, complete, and regular activation of the nickel electrodes was recently highlighted by Canti Ho et al. (Jud, W.; Salazar, CA; Imbrogno, J.; Verghese, J.; Guinness, SM; Desrosiers, J.-N.; Kappe, CO; Cantillo, D. Electrochemical Oxidation of Alcohols Using Nickel Oxide Hydroxide as Heterogeneous Electrocatalyst in Batch and Continuous Flow. Org. Proc. Res. Dev. 2022, 26 (5), 1486–1495).

[0007] The following processes are also known from the state of the art: Johannes Kaulen and Hans-Jürgen Schäfer (Tetrahedron 1982, 38(22), 3299-3308) disclose the conversion of unsubstituted cyclohexanol to unsubstituted adipic acid at a Ni(O)OH electrode. This electrode was designed as a plate electrode. The products were never actually isolated. Hans-Jürgen Schäfer (Top. Curr. Chem., 1987, 142, 101-129) also obtained similar results.

[0008] Johannes Kaulen ("Oxidation of diols and secondary alcohols at the nickel hydroxide electrode. Application to the selective oxidation of hydroxysteroids," dissertation, University of Münster, 1981) discloses investigations into the electrochemical oxidation of cyclohexanol. He achieved significant conversions at nickel hydroxide electrodes at elevated temperatures, sometimes with ring-cleaving formation of adipic acid. B.V. Lyalin and V.A. Petrosyan (Russian J. Electrochem., 2010, 46(11), 1199-1214) disclose the preparation of unsubstituted adipic acid and the oxidation of carbohydrates.

[0009] The same authors disclose the ring-cleaving electrochemical oxidation of cyclohexanol to adipic acid using nickel hydroxide electrodes in "Electrosynthesis of adipic acid by undivided cell electrolysis" (Russian Chem. Bull., International Edition, Vol. 53 No. 3 pp. 688-692, March, 2004). The publication reports a maximum yield of adipic acid of 46.7% with a simultaneous current efficiency of 11.5%. Byproducts of the reaction are succinic acid and glutaric acid, which are formed in yields of 6.3% and 11.5%, respectively. These components are formed by the oxidative loss of CH2 groups from the Ce parent compound of cyclohexanol.

[0010] EP 2 907 898 A1 (US 2015 / 0225861 A1) discloses the use of nickel foam at reaction temperatures of 80°C for the oxidative ring cleavage of 3,3,5-trimethylcyclohexanol. The reaction was carried out in highly dilute solution with low yields.

[0011] Schmitt et al. (Beilstein J. Org. Chem., 2015, 11, 473-480) report the cleavage of lignin into various oxo-substituted aromatics using different electrodes. Oxidation to the corresponding acids was unsuccessful.

[0012] WO 2021 / 249775 (A1) discloses a process for the electrochemical production of alkylenedicarboxylic acids by ring-opening oxidation using a doped Ni(O)OH foam electrode. The process is carried out in an aqueous alkaline solution. Preferred cosolvents can be alcohols or DMSO.

[0013] CN 111 229 267 A discloses foam electrodes, but not the preparation of alkanedicarboxylic acids by ring-opening oxidation.

[0014] The known processes are not entirely satisfactory. In particular, reactions at very small electrode areas have the disadvantage that, at low space-time yields, they often do not exhibit effects that occur under scaled reaction conditions. Furthermore, a ninefold increase in the electrode area did not achieve a comparable yield of the main product. Furthermore, only mixing processes with a conventional magnetic stirring system or chemical additives have been reported so far (AL Rauen, F. Weinelt, SR Waldvogel, Green Chem. 2020, 22, 5956-5960; and H.-J. Schäfer, Electrochem I, Top. Curr. Chem. 1987, 142, 101-129).

[0015] It is therefore an object of the present invention to provide methods which have advantages over the known methods.

[0016] This object is achieved by the subject matter of the patent claims and the description. The present invention relates, in a first aspect, to a process for the electrochemical preparation of alkanedicarboxylic acids (b) by ring-opening oxidation in an emulsion of at least one cyclic reactant (a) in an electrolysis cell according to scheme (I).

[0017] Scheme (I), wo b ei ejne represents a single or double bond and R is present or absent accordingly, where R is hydrogen or an acyl radical and the acyl radical is the radical of an aliphatic monocarboxylic acid having 2 to 8 carbon atoms,

[0018] A is a hydrocarbon having 3 to 30 carbon atoms and all ring carbons of A in the cyclic reactant (a) of scheme (I) carry at least one hydrogen substituent and / or at least one alkyl substituent, wherein the oxidation is carried out on a metal electrode which consists at least partly of nickel and / or cobalt and wherein a continuous feed of the cyclic reactant (a) into the electrolysis cell takes place

[0019] It was surprisingly found that by carrying out the process on the basis of an emulsion of the cyclic reactant (a), the current efficiency of the reaction and the yield are significantly increased.

[0020] The process according to the invention enables, in particular, the efficient electrochemical synthesis of adipic acid derivatives, especially in the flow-through electrolysis process. The cyclic reactants (a) used can be obtained in part from lignocellulose as a renewable raw material source, such as 4-alkylcyclohexanols. This has an important economic impact on a large scale. The process according to the invention is highly relevant for the industrial implementation of the electrochemical synthesis of such adipic acid derivatives, especially in a continuous reaction process.

[0021] The process claimed according to the invention enables efficient oxidation of cyclic reactants of the general formula (a), in particular of 4-alkylcyclohexanols to 3-alkyladipic acids on a larger scale in a flow as well as an increase in the product yield by continuous feed of the cyclic reactant of the general formula (a) and thus an improved continuous reaction control.

[0022] A further advantage of the process according to the invention compared to chemical oxidation processes is the avoidance of the use of chemical oxidizing agents such as nitric acid.

[0023] Figure 1 illustrates a flow electrolysis cell for carrying out the process according to the invention.

[0024] Figure 2 shows a graphical evaluation of the parameter results with a plot corresponding to the qNMR yields of 3-ethyladipic acid after the electrochemical oxidation of 4-ethylcyclohexanol.

[0025] Figures 3 and 4 illustrate the qNMR yield change of 3-propyladipic acid without and with addition of 4-propylcyclohexanone over the course of the applied charge

[0026] Preferably, the cyclic reactant (a) is continuously fed into the electrolysis cell.

[0027] The process according to the invention is carried out in particular in such a way that oxidation takes place with the following parameters, ie with: a reaction temperature of 10 to 60°C, preferably 10 to 50°C, more preferably 10 to 30°C, particularly preferably 20 to 28°C, very particularly preferably 24 to 26°C and / or a flow rate of the reaction medium of 20 to 100 mL mim 1 , preferably 20 to 80 mL mim 1 , particularly preferably 40 to 60 mL mim 1 most preferably 45 to 55 mL mim 1; and / or a concentration of the cyclic reactant (a) of 0.1 to 1 M, preferably 0.1 to 0.7 M, more preferably 0.1 to 0.5 M, particularly preferably 0.17 to 0.23 M, most preferably 0.18 to 0.22 M and / or an applied current density of 1 to 10 mA cm' 2 , preferably 2 to 8 mA cm' 2 , particularly preferably 3 to 7 mA cm 2 , most preferably 4 to 6 mA cm 2 , where the area refers to the geometric anode surface without taking into account the inner surface of the foam, preferably with the following parameters: a reaction temperature of 25 ± 2.5 °C and / or a flow rate of the reaction medium of 50 ± 5 mL mim 1 and / or a concentration of the reactant (a) 0.2 ± 0.02 M and / or an applied current density of 5.0 ± 0.5 mA crm 2Wherein the area specification refers in each case to the geometric anode surface without taking into account the inner surface of the foam. The process according to the invention is preferably carried out in such a way that the emulsion of the cyclic reactant (a) is present in water.

[0028] The emulsion for use in the process according to the invention preferably comprises at least one base, preferably at least one inorganic base or one organic base.

[0029] In principle, all customary bases known to the person skilled in the art for use in electrochemical reactions are suitable as inorganic or organic bases. Preferably, in the process according to the invention, one or more bases, in particular one base, are used in the emulsion, which are independently selected from the group consisting of N(R A )4OH with R Aeach independently of one another is H or C 1-4 -alkyl I, linear or branched, NaOH, KOH, LiOH, Na2CO3, K2CO3, and U2CO3, preferably selected from the group consisting of NaOH and KOH. The use of NaOH as a base in the emulsion is particularly preferred.

[0030] The concentration of the base in the emulsion, preferably in the oil-in-water emulsion, is preferably 0.5 to 2 mol / l, particularly preferably 0.8 to 1.5 mol / l and most preferably 1 ± 0.1 mol / l.

[0031] The process according to the invention is also characterized by the fact that no addition of surfactants is required to stabilize the emulsion. Depending on the type of cyclic reactant (a) used and the resulting alkanedicarboxylic acid, the latter itself, particularly in the presence of a base, may exhibit surface-active properties, which may have a beneficial effect on emulsion stabilization.

[0032] After its formation, the emulsion is preferably stable at least until the ring-opening oxidation of the at least one cyclic reactant (a) in the undivided electrolysis cell. The emulsion is preferably maintained during and / or after its formation at a temperature of 10 to 50°C, particularly preferably 10 to 30°C, very particularly preferably 20 to 28°C, and even more preferably 24 to 26°C.

[0033] The emulsion typically has a visually cloudy appearance. The emulsion droplets preferably have a size in the range >100 nm.

[0034] Electrodes based on nickel, cobalt, and optionally iron are preferably used as metal electrodes in the process according to the invention, wherein the metal electrode preferably contains 0 to 100% by weight of nickel and 100 to 0% by weight of cobalt, based in each case on the total content of nickel and cobalt in the electrode, or 10 to 100% by weight of nickel and 0 to 90% by weight of iron, based in each case on the total content of nickel and iron in the electrode. The content of other metals in the metal electrode is preferably equal to or less than 10% by weight, more preferably equal to or less than 5% by weight, most preferably equal to or less than 2% by weight, and even more preferably equal to or less than 1% by weight, based in each case on the total metal content.

[0035] The metal electrode preferably contains at most up to 1 wt.% each, particularly preferably at most up to 0.1 wt.% each and even more preferably at most 0.01 wt.% each of V, Wo and Mo. It should be noted that these metals are subject to corrosion, particularly in alkaline-aqueous emulsions.

[0036] Particularly preferred metal electrodes in the process according to the invention are those which contain at least 80% by weight, preferably at least 90% by weight, particularly preferably at least 95% by weight, of nickel, in each case based on the total weight of the metals in the electrode.

[0037] The metals nickel and / or cobalt and optionally iron can be present in the metal electrode on a substrate, wherein the substrate is in particular at least one material selected from the group consisting of steel, copper and titanium, carbon, preferably graphite.

[0038] The metal electrode can preferably be doped with at least one element of the 5th and / or 6th main group, particularly preferably with one or more elements, preferably an element which is / are selected from the group consisting of phosphorus, arsenic, selenium and sulfur.

[0039] The doping content information refers to the elemental state of the doping relative to the mass of the metal of the electrode.

[0040] If the metal electrode is doped with phosphorus, it can preferably contain 2 to 10 wt.% phosphorus, particularly preferably 3 to 9 wt.% and very particularly preferably 4 to 9 wt.%, wherein phosphorus is considered as an element in each case and is related to the metal mass of the electrode.

[0041] The determination of the phosphorus doping content can preferably be carried out according to DIN EN ISO 5427, Annex D.1.

[0042] Preferably, the metal electrode has a thickness of several millimeters, more preferably more than 3 mm, further more preferably more than 5 mm and particularly preferably equal to or thicker than 6 mm.

[0043] In the process according to the invention, a Ni(O)OH foam electrode is preferably used as the metal electrode, which preferably contains at least 80 wt.%, particularly preferably at least 85, 90, 95, 98, or 99 wt.%, very particularly preferably at least 99.9, and even more preferably at least 99.99 wt.% nickel, in each case based on the metal content of the Ni(O)OH foam electrode. The metal electrode is preferably pretreated before carrying out the oxidation by bringing it into contact with a base, preferably at least one inorganic base and / or at least one organic base.

[0044] Suitable for use in the contacting step are customary inorganic and organic bases known to those skilled in the art. Preferably, one or more bases, preferably one base, are independently selected from the group consisting of N(R A )4OH, N(R A )4acetate, with R A each independently of one another H or Ci-4-alkyl, linear or branched, NaOH, sodium acetate, KOH, potassium acetate, LiOH, lithium acetate, Na2CO3, K2CO3 and U2CO3 are used, particularly preferably selected from the group consisting of NaOH and KOH.

[0045] The base is preferably used in aqueous solution in the contacting step, the concentration of the base preferably being 10 mM to 10 M, particularly preferably 0.2 to 5 M, very particularly preferably 0.5 to 1.5 M and even more preferably 1 ± 0.1 M.

[0046] Bringing the metal electrode into contact with the base can be done by spraying, immersing, in a jet or in a flow.

[0047] The metal electrode and the base can be brought into contact with each other over a wide temperature range. Contacting the metal electrode with the base preferably takes place at a temperature of 10 to 40°C, particularly preferably at 18 to 27°C.

[0048] Before carrying out the oxidation according to the process according to the invention, an electrochemical activation of the metal electrode can advantageously be carried out, preferably an activation without polarity reversal, one or more salts of nickel and / or cobalt and optionally iron being particularly suitable for this step.

[0049] If nickel or cobalt salts are used, the salts selected from the group consisting of Ni2SO4 and CoSO4 are particularly suitable.

[0050] For electrochemical activation of the metal electrode, the salt or salts may preferably be present in aqueous basic solution, preferably in a concentration of 0.05 to 0.15 M.

[0051] In this case, customary bases known to the person skilled in the art are suitable. Preferably, one or more bases, in particular one base, are used which are independently selected from the group consisting of N(R A )4OH, N(R A )4acetate, with R A each independently of one another is H or C 1-4 -alkyl, linear or branched, NaOH, sodium acetate, KOH, potassium acetate, LiOH, lithium acetate, Na2CO3, K2CO3 and U2CO3, particularly preferably selected from the group consisting of NaOH and KOH. The concentration of the base during the activation of the metal electrode is preferably 10 mM to 10 M, preferably 0.2 to 5 M, particularly preferably 0.5 to 1.5 M, most preferably 1 ± 0.1 M.

[0052] The activation of the metal electrode preferably takes place at a charge of 2 to 10 coulombs, preferably 5 to 7 coulombs.

[0053] The metal electrode can be activated over a wide temperature range. Preferably, the metal electrode is activated at a temperature of 10 to 40°C, particularly preferably at 18 to 27°C.

[0054] In a preferred embodiment of the process according to the invention, cyclic reactants of the general formula (a) according to scheme (I) are used, wherein R represents a single bond, R is hydrogen or an acyl radical, wherein the acyl radical is the radical of an aliphatic monocarboxylic acid having 2 to 6 carbon atoms and wherein A is a hydrocarbon having 3 to 10 carbon atoms, wherein all ring carbons of A in the cyclic reactant (a) of scheme (I) carry at least one hydrogen substituent and / or at least one alkyl substituent.

[0055] In a particularly preferred embodiment of the process according to the invention, cyclic reactants of the general formula (a) according to Scheme (I) are used, in which '“ '" rw '' represents a single bond, R represents -H and A represents -CH2-CH2-CH2-, -CH2-C(H)(CH3)-CH2-, -CH2- C(H)(CH2CH3)-CH2- or -CH2-C(H)(CH2CH2CH3)-CH2-.

[0056] In a further particularly preferred embodiment of the process according to the invention, cyclic reactants of the general formula (a) according to Scheme (I) are used, in which a

[0057] single bond, R is hydrogen and the concentration of the cyclic reactant (a) is 0.1 to 1 M, preferably 0.1 to 0.7 M, more preferably 0.1 to 0.5 M, particularly preferably 0.17 to 0.23 M, most preferably 0.18 to 0.22 M.

[0058] Also preferred is an embodiment of the process according to the invention according to Scheme (II)

[0059] (away)

[0060] Scheme (II) where

[0061] R 1 , R 2 and R 3 are the same or different, represent hydrogen or an alkyl radical having 1 to 8 carbon atoms, preferably 1 to 5 carbon atoms, linear or branched, and wherein preferably at least one of the radicals R 1 , R 2 and R 3 is such an alkyl radical; preferably only one of the radicals R 1 , R 2 and R 3 an alkyl radical having 1 to 4 carbon atoms, linear or branched, and particularly preferred are the radicals R 1 and R 3 Hydrogen and R 2 is an alkyl radical having 1 to 4 carbon atoms, linear or branched; preferred.

[0062] In a further particularly preferred embodiment of the process according to the invention, cyclic reactant (a) is 4-methylcyclohexanol, 4-ethylcyclohexanol or 4-propylcyclohexanol, in particular 4-methylcyclohexanol, 4-ethylcyclohexanol or 4-n-propylcyclohexanol.

[0063] Advantageously, the process according to the invention can be carried out in an undivided electrolysis cell.

[0064] The cathode material for use in the process according to the invention may preferably be stainless steel, platinum or nickel or a mixture thereof, particularly preferably stainless steel.

[0065] The following examples further illustrate the present invention but are not to be construed as limiting the scope of the invention. Examples:

[0066] General information and methods

[0067] Analytical-grade chemicals were purchased and used from common suppliers (such as TCI, Aldrich, Rotisolv, Fisher Chemical, VWR, Thermos Scientific, and Acros). Solvents were purified by standard methods such as distillation or demineralization.

[0068] Unless otherwise stated, ambient pressure and ambient temperature were used as reaction conditions.

[0069] The electrodes applied for the reactions were commercially available and contain small channels on the inlet and outlet sides: stainless steel (1.4571) and Recemat™ nickel foam. They are compatible with the setup of the IKA ElectraSyn flow 6-18. For activation, a separate sheet electrode (6 x 18 cm²) made of stainless steel (1.4571) was cut by the university workshop. A TDK Lambda Genesys 750 W / 1500 W power supply was used as the galvanostat. The reaction mixture was pumped through Ismapren tubing (size 16) using a Regio Digital Masterflex™ peristaltic pump (model no. 78018-42) from Ismatec. A heating circuit was installed and connected to an IKA WICO CBC 5 C refrigeration and circulation thermostat (model RN41).

[0070] Melting point determination: Melting points were measured using an M-565 device (Büchi, Essen, Germany). The heating rate was 1 °C per minute.

[0071] NMR spectroscopy: A Bruker Avance III 600 (Bruker, probe head: 5 mm TCI-CryoProbe head with z-gradient and ATM) NMR spectrometer was used to measure 1 H (600 MHz) and 13 C (151 MHz) inverse gated spectra at 25°C. Chemical shifts (δ) are given in parts per million (ppm). Quantification was performed by integrating the respective signals in the 13 C inverse-gated spectrum against 1,3,5-trimethoxybenzene as internal standard (δ = (55.4±0.02) ppm). The DMSO-d6 signal was chosen as reference (δ = 39.52 ppm).

[0072] Liquid chromatography: Photodiode array analysis was performed using a Shimadzu DUGA-20A3 instrument equipped with a Knauer C18 column (Eurospher II, 100-5 C18, 150 x 4 mm). The column was conditioned to 25°C, and the flow rate was set to 1 mL / min. The aqueous eluent was buffered with formic acid (0.8 mL / 2.5 L) and stabilized with acetone (5 vol%). To prepare samples, the carboxylic acid product mixture was extracted from the reaction mixture by acid-base extraction with ethyl acetate, dried over MgSO4, and the solvent evaporated. The product was filtered (VWR 13 mm syringe filter with 0.45 pm PTFE membrane), dissolved, and diluted in acetonitrile (MS grade). This organic solution was analyzed by liquid chromatography. High-resolution mass spectra were obtained using a G6545A Q-ToF (Agilent GmbH, Waldbronn, Germany) with dual AJS electrospray ion source (Dual AJS ESI).The MS parameters were as follows: mass range: 80 to 3200 m / z, scan rate: 1 spectrum s. -1, Nebulizer pressure: 25 psig, Capillary voltage: 3500 V, Fragmentor: 50 V, Skimmer: 45 V, Dry gas temperature: 275°C, Dry gas flow: 10 L min-1, Sheath gas temperature: 350°C, Sheath gas flow: 10 L min-1. Mass calibration was performed on the day of measurement using an external standard. The mass accuracy of the measurement results is better than 5 ppm. The chromatographic separation was performed on a 1260 Infinity II HPLC system (Agilent GmbH, Waldbronn, Germany) equipped with a G7111B 1260 Quaternary Pump, G7129A 1260 Vialsampler, and G7116A 1260 Multicolumn Thermostat, equipped with an Agilent EclipsePlus C18 RRHP (2.1 x 50 mm, 2.1 pm particle size) analytical column. Eluents were 98% H2O with 2% ACN and 0.05% formic acid (eluent A) and 2% H2O with 98% ACN and 0.05% formic acid (eluent B).The following gradient elution was used for separation at a flow rate of 200 pl min-1: starting at 10% B for 1 min, followed by a linear increase to 95% B at 10 min, maintaining 95% B until 30 min before proceeding back to 10% B at 33 min. The column was equilibrated at 10% B for 15 min before the next measurement. The injection volume was 2 pl. Data were acquired using Agilent MassHunter Workstation LC / MS software version 11.0, and data analysis was performed using Agilent MassHunter Workstation Qualitative Analysis software version 10.0.

[0073] MALDI-TOF MS: The Autoflex MALDI-TOF mass spectrometer from Bruker Daltonik GmbH (Fahrenheitstraße 4, 28359 Bremen, Germany) equipped with a smartbeam™ll Nd:YAG laser (355 nm) was used. The image was measured in linear mode. 2-[(2E)-3-(4-tert-butylphenyl)-2-methylprop-2-enylidene]malononitrile (DCTB) was used as the matrix.

[0074] Electrolysis cell

[0075] A flow electrolysis cell with a geometric anodic surface of 108 cm 2 used (Figure 1). The modular design of the cell further includes a self-supporting frame and a cage for the foam electrode - all with an active geometric surface area of ​​108 cm 2 - make this electrolyzer particularly interesting for scaled electrolysis in flow mode. Furthermore, the high heat dissipation is enabled by channels behind the electrodes, which allow for better temperature control than smaller commercial flow electrolyzers, where only the reservoir can be set to a specific temperature.

[0076] Figure 1 shows the reaction setup in an undivided flow electrolysis cell with a stainless steel cathode and a nickel foam anode contacted by a nickel plate electrode. The distance between the electrodes was 3 mm. The cooling circuit used water to maintain the temperature between 25 and 50 °C. The reaction mixture was emulsified using an IKA Magie lab mixing unit with a DR mixing element (IKA-Werke GmbH & Co. KG, Staufen, Germany). Activation of the nickel anode:

[0077] First, an activation solution was prepared consisting of 0.1 M NiSO4(aq), 0.1 M NaOAc(aq), and 5 mM NaOH(aq). This activation solution (420 mL) was filled into a cup-shaped cell made of polymethyl methacrylate (PMMA). A stainless steel electrode (6 x 18 cm) was immersed and connected. Before fully immersing and connecting the nickel foam anode at a distance of 10 mm, it was immersed in 1 M sodium hydroxide solution or thoroughly rinsed with it and then drained. A current density of 5.0 mA cm 2 was applied for 30 minutes. This corresponds to a charge of 9 C cm 2The activation solution was stirred at 300 rpm. The activated dark nickel foam was then rinsed with demineralized water. The stainless steel cathode was cleaned by briefly immersing it in dilute sulfuric acid (4M), then washed with water and treated with sandpaper (pore size 300) until it achieved a homogeneous optical shine. The cell was then rearranged. Although SEM images showed that the cleaning process did not fully restore the original surface morphology, the activation procedure described above could also be successfully applied to the cleaned nickel foams.

[0078] Flow cell electrolysis: The commercially available modular flow cell electrolyzer IKA ESF 6-18 was used, as described above. This was equipped with a nickel foam anode (Recemat™ RCM-Ni4753.05), connected by a nickel sheet, and a stainless steel cathode (1 .4571), each measuring 6 x 18 cm. 2 A polytetrafluoroethylene (PTFE) spacer (0.4 mm) was used. The nickel foam anode was activated as described above.

[0079] The commercially available IKA magic LAB® mixing device was connected to the IKA magic PLANT® stirred tank. The electrolyte, consisting of NaOH(aq) (1 M) and the respective cyclic reactant 4-alkylcyclohexanol (1), was emulsified in it. This mixing unit features a powerful DR mixing element and cyclically pumps the liquid into the storage tank and back again. The flow rate is 12,000 rpm (corresponding to approximately 70 L per hour). From there, a peristaltic pump feeds the upright flow cell from below. Outlet pipes are connected to the storage tank, allowing the hydrogen formed to be safely removed. A specified charge quantity and current density were applied and monitored using Python software control and the TDK Lambda Genesys galvanostat. After electrolysis, the reaction mixture was pumped out of the electrolyzer in the reverse flow direction.Then, methyl tert-butyl ether (MTBE, 80 ml) and 1 M sodium hydroxide solution (80 ml) were used to purify the cell sequentially. All fractions were combined and processed by liquid-liquid extraction in a 2L perforator.

[0080] First, non-acidic components were extracted from the basic aqueous reaction mixture using MTBE. After acidification to pH 1-2, the acids were extracted with ethyl acetate. The organic fractions were dried over MgSO4 and the solvents removed. The remaining acid fraction was weighed, and the products were quantitatively determined by 13 C analyzed by inverse gated NMR spectroscopy. 1,3,5-trimethoxybenzene (0.1 mmol) was used as an internal standard. Example 1 (comparative example):

[0081] T2'

[0082] Anodic oxidation of 4-methylcyclohexanol (1') to 3-methyladipic acid (2') was carried out in the flow cell described above.

[0083] 4-Methylcyclohexanol oxidation: 4-Methylcyclohexanol (1', 10 mmol, c = 0.1 M, isomer mixture) was mixed with sodium hydroxide solution (1 M) in a beaker (V = 100 mL). The cell was heated to 50 °C using an external IKA-HBC-5 thermostat. The reaction mixture was circulated at a flow rate of 61 mL. 1 through the electrolyzer. The applied current density was set to 5.0 mA cm -2set, and a total charge of 8.0 F was used. After the reaction, the product mixture was collected, tert-butyl methyl ether was pumped through the cell, and an acid-base extraction was performed. For this purpose, the basic reaction medium was extracted three times with tert-butyl methyl ether (100 mL each), acidified to pH 1-2 with 4.5 M sulfuric acid, and extracted four times with ethyl acetate (100 mL each). After drying over MgSO4 and subsequent solvent removal, the product mixture was analyzed by 1 H and 13 C inverse-gated NMR against 1,3,5-trimethoxybenzene as an internal standard.

[0084] Example 2:

[0085] First, 4-ethylcyclohexanol was synthesized according to the following procedure. 4-Ethylphenol (100 g, 0.82 mol) was dissolved in methanol (500 mL), ruthenium / carbon (10 g, 5% Ru on C) was added to the 1-liter autoclave, and a hydrogen atmosphere (10 bar) was applied. The autoclave was heated to 120 °C. To monitor the yield of 4-ethylcyclohexanol (1"), samples (0.1 mL of the reaction medium) were taken once daily. Product formation was monitored by gas chromatography, and the reaction was stopped when no further product formation was observed. 4-Ethylphenol was purchased from Sigma Aldrich, and ruthenium was purchased from Heraeus Chemicals. 4-Ethylcyclohexanol (1") was synthesized on a 200 g scale with isolated yields of up to 95% after vacuum distillation.

[0086] Subsequently, the electrochemical oxidation of 4-ethylcyclohexanol to 3-ethyladipic acid was carried out according to the following Scheme 1

[0087] The oxidation was subjected to a design-of-experiment screening procedure with regard to the parameters reaction temperature, flow rate, concentration of the cyclic reactant, and current density. A nickel foam anode activated as described above and a V5A stainless steel plate cathode were used. The reaction takes place in a semi-stable emulsion of the cyclic reactant with 1 M NaOH(aq), as the two liquids are immiscible under standard conditions.

[0088] To conduct the screening procedure, a Masterflex™ PharMed™ BPT, L / S 16, tube setup for long-term use was installed. A Masterflex™ Ismatec™ 78018-42 peristaltic pump was used for pumping. An IKA Magie Lab / IKA Magie Plant system with a DR mixing element (IKA-Werke GmbH & Co. KG, Staufen, Germany) was used for continuous mixing. In all experiments, the mixing system operated at 12,000 rpm (= 70 L h-1 circulation rate) to achieve an optically semi-stable emulsion for the time it was pumped through the flow-through electrolyzer and back into the mixer. A charge of 9 F was used for all reactions.

[0089] The reaction mixture was processed as follows: After each experiment, the reaction mixture was collected in a vial, and tert-butyl methyl ether (50 mL) was pumped through the electrolyzer in cycle mode for 1 minute to minimize losses. The same procedure was performed with 1 M sodium hydroxide solution (50 mL). Subsequently, an acid-base extraction was performed using a Ludwig perforator. High stirring speeds can be more easily achieved by using a small stir bar. Additionally, the solvent should be added to the main compartment. The yellow basic reaction mixture was extracted overnight with MTBE. The two phases were then separated, and the aqueous layer was acidified to pH 1-2 with 4.5 M H2SO4(aq). The neutralized crude product was then extracted in a perforator with ethyl acetate.The two organic fractions were dried over MgSO4, the solvent was removed under low pressure and the product was analyzed by 13C inverse gated NMR with 1,3,5-trimethoxybenzene as internal standard.

[0090] For isolation, the resulting carboxylic acid mixture was passed through a Vigreux column in vacuo at 10°- 10' 2mbar. The main product was distilled at 180-220°C. The remaining yellow color could be removed by recrystallization from heptane. If ethyl esters of 3-ethyladipic acid were present, the product mixture was dissolved in sodium hydroxide solution (3M), heated to 80°C, and stirred vigorously for 3 hours. The mixture was then extracted with tert-butyl methyl ether (3 x one-third of the aqueous volume) in a sufficiently large separatory funnel, acidified to pH 2-3 with H2SO4(aq) (4.5M), and extracted with ethyl acetate. The organic fraction was dried over MgSO4, and after removal of the solvent, the crystals were collected. A second recrystallization resulted in optically higher purity.

[0091] For the parameter DoE screening, four parameters were varied: the concentration of the cyclic reactant c, the reaction temperature T, the flow rate of the reaction medium <D sowie die Stromdichte j, wobei die entsprechenden Parametergrenzen in der nachstehenden Tabelle 1 wiedergegeben sind. Neben den gesetzten Parametergrenzen wurden auch Zentralpunktversuche durchgeführt. Alle Versuche wurden einmal wiederholt, um die Reproduzierbarkeit der Umsetzungen zu bestimmen, und die Reaktionsreihenfolge dieser 18 chemischen Versuche wurde randomisiert. Die Reaktion dauerte zwischen 0,9 und 2,3 Tagen. Quantitative NMR-Ausbeuten von nahezu 40 % wurden für das Zielprodukt (2") erzielt. Die maximale isolierte Ausbeute betrug 39 %. Die Nickelschaumanode wurde für alle hier berichteten Reaktionen wiederverwendet, wodurch sich der Abfallstrom verringerte.

[0092] Table 1: Parameters of the DoE screening. The geometric current density refers to the current relative to the geometric anodic surface area of ​​the anodic foam - 108 cm 2 . Reaction conditions: 1 M NaOH(aq), water, activation = 7.5 mA crm 2 (geometric current density), activation = 10 C cm -2 , 9 F. The flow rate of the reaction <D ist eine kumulierte Durchflussrate beider Röhren. Jeder Parameter hat drei Datenpunkte.

[0093] It was found that the flow rate and the concentration of the reactant have the greatest influence on the yield of the desired product. Higher flow rates, especially from 30 to 50 mL 1 and lower concentrations of the reactant, especially from 0.2 to 0.35 M, have a positive effect on the yield of 3-ethyladipic acids.

[0094] The analyzed product spectrum of the investigated oxidation of 4-ethylcyclohexanol is shown below:

[0095] Structures of 3-ethyladipic acid (2"), 3-ethylglutaric acid (3), 2-ethylglutaric acid (4) and ethylsuccinic acid (5). A graphical evaluation of the parameter results with a plot corresponding to the qNMR yields of 3-ethyladipic acid (2) is shown in Figure 2. The tested parameters are reaction temperature T (25 °C, 37.5 °C and 50 °C), flow rate of the reaction mixture <D (10 mL min-1 , 30 mL mi 1 and 50 mL mim 1 ), concentration of 4ethylcyclohexanol c(1) (0.2 m, 0.35 m and 0.5 m) and applied reaction current density j (3.0 mA cm' 2 , 4.0 mA cm -2 and 5.0 mA cm' 2 ).

[0096] The screening showed that a particular combination of the four tested parameters leads to the highest yields, namely a flow rate of 50 mL mim 1, a reaction temperature of 25 °C, a current density j of 5.0 mA cm' 2 and a reactant concentration of 0.2 mol / l. This enabled yields of the desired product (2") of well over 30% to be achieved.

[0097] With these parameters, the best quantitative NMR yields of the products were as follows: YqNMR (3-ethyladipic acid) = 38%

[0098] YqNMR (3-ethylglutaric acid) = 4%

[0099] YqNMR (2-ethylglutaric acid) = 4%, YqNMR (ethylsuccinic acid) = 1%.

[0100] After the workup procedure, 2" was isolated with a yield of 38%. This is the most efficient isolation of 2" by an electrochemical synthesis reported to date.

[0101] Characterization of 3-ethyladipic acid (2")

[0102] 2" was synthesized electrochemically from 4-ethylcyclohexanol (6.41 g, 50 mmol, 0.2 M) according to the procedure described above. The product 2" was obtained by acid-base extraction, vacuum distillation, and recrystallization from n-heptane as a light yellow crystalline solid (3.31 g, 19 mmol, 30%).

[0103] 1 H NMR (600 MHz, DMSO-d6): ö [ppm] = 12.04 (s, 2H), 2.18 (t, J = 7.9 Hz, 2H), 2.12 (d, J = 6.9 Hz, 2H), 1 .68 (hept, J = 6.5 Hz, 1 H), 1 .57 - 1 .42 (m, 2H), 1 .33 - 1 .21 (m, 2H), 0.81 (t, J = 7.5 Hz, 3H).

[0104] 13 C NMR (151 MHz, DMSO-d6): δ [ppm] = 174.75, 174.29, 38.07, 35.41, 31.20, 28.17, 25.63, 10.69. Melting point: (47.4 - 49.8) °C.

[0105] HRMS (ESI+) m / z: calculated for C8HI4O4+ H + 175.0965 [M+H + ] + , found: 175.0965.

[0106] Example 3:

[0107] Anodic oxidation of 4-propylcyclohexanol to 3-propyladipic acid was carried out in the flow cell described above, and the development of the yield of 3-propyladipic acid was analyzed over the course of the reaction. Table 2: Parameters of the DoE screening. The geometric current density refers to the current relative to the geometric anodic surface area of ​​the anodic foam - 1225 cm 2 . Reaction conditions: 1 M NaOH(aq), water, activation = 7.5 mA cm -2 (geometric current density), activation = 5 C cm -2 , 8.5 F. The flow rate of the reaction <D ist eine kumulierte Durchflussrate beider Röhren. Jeder Parameter hat drei Datenpunkte.

[0108] Figure 3 shows the qNMR yield change of 3-propyladipic acid with the applied charge. The qNMR yield was analyzed against the standard 1,3,5-trimethoxybenzene.

[0109] The formation of 3-propyladipic acid was influenced by the formation of 4-propylcyclohexanone. 1 F after the maximum available concentration of 4-propylcyclohexanone, the production rate of 3-propyladipic acid was highest. The final result was a yield of over 30%.

[0110] Subsequently, the reaction procedure was modified so that 4-propylcyclohexanone was present at the most stable concentration possible, thus keeping the production rate of 3-propyladipic acid constant. To achieve this, the reactant was added at a constant rate, adjusted to the production rate of 3-propyladipic acid.

[0111] Surprisingly, a high yield of the desired product was observed here as well. This procedure thus has a positive impact on the yield and also enables continuous reaction.

[0112] The qNMR yield change of 3-propyladipic acid upon addition of 4-propylcyclohexanone over the course of the applied charge is shown in Figure 4. List of reference symbols:

[0113] 1 flow electrolysis cell

[0114] 2 self-standing frame and cage for the electrode 3 mixer

[0115] 4 Emulsion

[0116] 5 stainless steel electrode

[0117] 6 nickel foam electrode

[0118] 7 Nickel plate electrode 8 Cooling circuit

[0119] 9 Cooling circuit

[0120] 10 Cooling circuit

[0121] 11 Pump

Claims

Patent claims: 1 . A process for the electrochemical preparation of alkanedicarboxylic acids (b) by ring-opening oxidation in an emulsion of at least one cyclic reactant (a) in an electrolysis cell according to Scheme (I) Scheme (I), w o b ei ejne egg n f ac h_ oc | er double bond and R is present or not, where R is hydrogen or an acyl radical and the acyl radical is the radical of an aliphatic monocarboxylic acid having 2 to 8 carbon atoms, A is a hydrocarbon having 3 to 30 carbon atoms and all ring carbons of A in the cyclic reactant (a) of scheme (I) carry at least one hydrogen substituent and / or at least one alkyl substituent, wherein the oxidation is carried out on a metal electrode which consists at least partly of nickel and / or cobalt and wherein a continuous feed of the cyclic reactant (a) into the electrolysis cell takes place.

2. The process according to claim 1, wherein no surface-active substances are added to stabilize the emulsion.

3. The process according to at least one of the preceding claims, wherein the oxidation is carried out with the following parameters: - a reaction temperature of 10 to 60°C, preferably 10 to 50°C, more preferably 10 to 30°C, particularly preferably 20 to 27°C, most preferably 24 to 26°C and / or - a flow rate of the reaction medium of 20 to 100 mL mi 1, preferably 20 to 80 mL mim 1 , particularly preferably 40 to 60 mL mim 1 most preferably 45 to 55 mL mim 1 ; and / or - a concentration of the cyclic reactant (a) of 0.1 to 1 M, preferably 0.1 to 0.7 M, more preferably 0.1 to 0.5 M, particularly preferably 0.17 to 0.23 M, most preferably 0.18 to 0.22 M and / or - an applied current density of 1 to 10 mA cm 2 , preferably 2 to 8 mA cm 2 , particularly preferably 3 to 7 mA cm -2 , most preferably 4 to 6 mA cm -2 , where the area specification refers to the geometric anode surface without taking into account the inner surface of the foam, preferably with the following parameters: - a reaction temperature of 25 ± 2.5 °C and / or - a flow rate of the reaction medium of 50 ± 5 mL mi 1 and / or - a concentration of the reactant (a) 0.2 ± 0.02 M and / or - an applied current density of 5.0 ± 0.5 mA crrr 2 where the area specification refers to the geometric anode surface without taking into account the inner surface of the foam.

4. The process according to at least one of the preceding claims, wherein an emulsion of the cyclic reactant (a) is present in water.

5. The process according to at least one of the preceding claims, wherein an emulsion of the cyclic reactant (a) is present in water, wherein the emulsion comprises at least one base, preferably at least one or more bases which are independently selected from the group consisting of N(R A )4OH with R A each independently of one another H or Ci-4-alkyl, linear or branched, NaOH, KOH, LiOH, Na2CO3, K2CO3 and U2CO3, preferably selected from the group consisting of NaOH and KOH.

6. The method according to at least one of the preceding claims, wherein the metal electrode contains 0 to 100 wt% nickel and 100 to 0 wt% cobalt, each based on the total content of nickel and cobalt in the electrode, or 10 to 100 wt% nickel and 0 to 90 wt% iron, each based on the total content of nickel and iron in the electrode.

7. The method according to at least one of the preceding claims, wherein the metal electrode is a Ni(O)OH foam electrode, wherein the Ni(O)OH foam electrode contains as metal in particular at least 80 wt.%, preferably at least 85, 90, 95, 98 or 99 wt.%, particularly preferably at least 99.9, especially preferably at least 99.99 wt.% nickel, in each case based on the metal content of the Ni(O)OH foam electrode.

8. The method according to at least one of the preceding claims, wherein the metal electrode is pretreated before carrying out the oxidation by bringing it into contact with a base, preferably at least one inorganic base and / or at least one organic base, wherein one or more bases are used which are independently selected from the group consisting of N(R A )4OH, N(R A )4acetate, with R A each independently of one another H or C 1-4 alkyl, linear or branched, NaOH, sodium acetate, KOH, potassium acetate, LiOH, lithium acetate, Na2CO3, K2CO3 and U2CO3, particularly preferably selected from the group consisting of NaOH and KOH.

9. The method according to claim 8, wherein the base is used in aqueous solution, in particular in a concentration of the base of 10 mM to 10 M, preferably 0.2 to 5 M, particularly preferably 0.5 to 1.5 M, very particularly preferably 1 ± 0.1 M and / or wherein the contacting of the metal electrode with the base takes place at a temperature of 10 to 40°C, preferably at 18 to 27°C.

10. The method according to at least one of the preceding claims, wherein an electrochemical activation of the metal electrode, preferably without polarity reversal, takes place before the oxidation.

11. The method according to claim 9, wherein the electrochemical activation is carried out by one or more salts of nickel and / or cobalt and optionally iron, particularly preferably by salts selected from the group consisting of Ni2SO4 and / or CoSO4, wherein the salt or salts are present in aqueous basic solution, wherein one or more bases, preferably one base, are independently selected from the group consisting of N(R A )4OH, N(R A )4acetate, with R A each independently of one another H or Ci-4-alkyl, linear or branched, NaOH, sodium acetate, KOH, potassium acetate, LiOH, lithium acetate, Na2CO3, K2CO3 and U2CO3, particularly preferably selected from the group consisting of NaOH and KOH.

12. The method according to any one of claims 10 or 11, wherein the electrochemical activation of the metal electrode takes place at a temperature of 10 to 40°C, preferably at 18 to 27°C.

13. The process according to at least one of the preceding claims, wherein in the formula (a) according to scheme (I) represents a single bond, R is hydrogen or an acyl radical, wherein the acyl radical is the radical of an aliphatic monocarboxylic acid having 2 to 6 carbon atoms and wherein A is a hydrocarbon having 3 to 10 carbon atoms, wherein all ring carbons of A in the cyclic starting material (a) of scheme (I) carry at least one hydrogen substituent and / or at least one alkyl substituent, preferably represents a single bond, R is hydrogen or an acyl radical, wherein the acyl radical is the radical of an aliphatic monocarboxylic acid having 2 to 4 carbon atoms and wherein A is a Hydrocarbon having 3 to 9 carbon atoms, wherein all ring carbons of A in the cyclic reactant (a) of Scheme (I) carry at least one hydrogen substituent and / or at least one alkyl substituent, particularly preferably represents a single bond, R represents -H and A represents -CH2-CH2-CH2-, -CH2-C(H)(CH3)-CH2-, -CH2-C(H)(CH2CH3)-CH2- or -CH2-C(H)(CH2CH2CH3)-CH2-.

14. The method according to at least one of the preceding claims, wherein one single bond, R is hydrogen and the concentration of the cyclic reactant (a) is 0.1 to 1 M, preferably 0.1 to 0.5 M, particularly preferably 0.17 to 0.23 M, most preferably 0.18 to 0.22 M.

15. The process according to at least one of the preceding claims, wherein the process is carried out according to scheme (II) (away) Scheme (II) is carried out, whereby - R 1 , R 2 and R 3 are the same or different, represent hydrogen or an alkyl radical having 1 to 8 carbon atoms, preferably 1 to 5 carbon atoms, linear or branched, and wherein preferably at least one of the radicals R 1 , R2 and R 3 is such an alkyl radical; preferably - only one of the residues R 1 , R 2 and R 3 an alkyl radical having 1 to 4 carbon atoms, linear or branched, and particularly preferred are the radicals R 1 and R 3 Hydrogen and R 2 is an alkyl radical with 1 to 4 carbon atoms, linear or branched.

16. The process according to any one of the preceding claims, wherein the cyclic reactant (a) is 4-methylcyclohexanol, 4-ethylcyclohexanol or 4-propylcyclohexanol, preferably 4-methylcyclohexanol, 4-ethylcyclohexanol or 4-n-propylcyclohexanol.

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