Electrochemical oxidation of cycloalkenes to α,ω-dicarboxylic acids and ketocarboxylic acids.

Abstract

The present invention relates to a process for the preparation of unsubstituted or at least monosubstituted α,ω-dicarboxylic acids and ketocarboxylic acids by electrochemically oxidizing unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkenes in the presence of inorganic or organic nitrates in an electrolytic cell in a reaction medium in the presence of oxygen.

Description

[Technical field]

[0001] The present invention relates to a process for the preparation of unsubstituted or at least monosubstituted α,ω-dicarboxylic acids and ketocarboxylic acids by electrochemically oxidizing unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkenes in the presence of inorganic or organic nitrates in an electrolytic cell in a reaction medium in the presence of oxygen. [Background technology]

[0002] α,ω-Dicarboxylic acids and ketocarboxylic acids are important substrates in synthetic organic chemistry and monomeric components in polymer synthesis, and therefore highly relevant for industrial applications. Conventional methods to obtain these substrates from cycloalkenes are essentially transition metal catalysis and the use of chemical oxidants.

[0003] So far, only a few electrochemical processes for the synthesis of dicarboxylic acids from cycloalkenes by direct C=C bond cleavage have been described. Known processes are usually mediated and also use expensive transition metal catalysts. They usually require additional oxidants that are electrochemically regenerated (CN 101092705; U.-St.Baumer, HJ Schafer, J.Appl.Electrochem. 2005, 35, 1283-1292). In addition, toxic transition metals and their oxides are commonly used as electrode materials (S.Torii, T.Inokuchi, R.Oi, J.Org.Chem. 1982, 47, 47-52; D.D. Davis, D.L. Sullivan, Preparation of dodecanedioic acid, 1991, US Patent Publication No. 5026461). Divided cells are often used, resulting in a more complicated cell structure (CN 101092705). Known methods that do not require additional transition metal catalysts are potentiostatic, require two-phase mixtures, and have low current yields, which makes them less scalable and economical (S.Torii, T.Inokuchi, R.Oi, J.Org.Chem. 1982, 47, 47-52; U.Baumer, Electrochimica Acta 2003, 48, 489-495).

[0004] Moreover, the processes known from the prior art only provide access to a small substrate spectrum or require prior functionalization, and the prior art mainly describes the synthesis of the corresponding carboxylic acid esters, so that the generation of the carboxylic acid requires an additional hydrolysis step, which requires additional time and resources.

[0005] Increased material inputs, often in excess, result in the use of expensive transition metals as electrocatalysts or electrode materials, and the use of chemical oxidants, generating reagent waste that may require expensive and complex disposal or regeneration. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] China Patent Application Publication No. 101092705 [Patent Document 2] US Patent Publication No. 5,026,461 Summary of the Invention [Problem to be solved by the invention]

[0007] The object of the present invention is to provide a sustainable, resource-saving process that allows the production of α,ω-dicarboxylic acids and ketocarboxylic acids from cycloalkenes. [Means for solving the problem]

[0008] This object has been achieved by the subject matter of the claims and the specification.

[0009] The present invention relates to a process for the preparation of unsubstituted or at least monosubstituted α,ω-dicarboxylic or ketocarboxylic acids by electrochemical oxidation of unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkenes, (a) providing at least one unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkene; (b) providing at least one organic nitrate; (c) electrochemically oxidizing the unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkene provided in step (a) in the presence of the organic nitrate provided in step (b) in an electrolysis cell in a reaction medium in the presence of oxygen; The present invention provides a method comprising:

[0010] The process of the present invention has the special features of high selectivity, low usage of auxiliary chemicals, and the use of electric current as an oxidant, with the attendant low production of waste products.

[0011] Surprisingly, it has been found that the electrochemical oxidation method according to the invention allows the introduction of oxygen functional groups into cycloalkenes using atmospheric oxygen. This allows the use of chemical oxidants such as reactive peroxides or expensive catalysts with complex ligand systems to be dispensed with. At the same time, the use of toxic and / or potentially carcinogenic substances can be reduced or even completely avoided. The developed method is a cheap and environmentally friendly alternative to existing synthetic methods. Thanks to the simple and safe process conditions, it can also be scaled up to industrial scale, thus producing larger quantities of the desired product. The invention therefore allows a significant optimization of previously costly and time-consuming processes.

[0012] Surprisingly, it has also been found that the process according to the invention makes it possible to prepare unsubstituted or at least monosubstituted α,ω-dicarboxylic acids and ketocarboxylic acids from cycloalkenes using an electric current, using a nitrate salt which acts both as a conductive salt and as an electrochemical mediator.

[0013] Surprisingly, it has also been found that the process according to the invention can be carried out at ambient pressure and temperature, which is likewise advantageous for energy efficiency and therefore environmental compatibility.

[0014] The process according to the invention can use unsubstituted or at least monosubstituted mono- or polyunsaturated monocyclic or bicyclic cycloalkenes.It is preferred to use unsubstituted or at least monosubstituted mono- or polyunsaturated monocyclic cycloalkenes, and unsubstituted or at least monosubstituted mono-unsaturated monocyclic cycloalkenes are particularly preferred.The cycloalkenes used according to the invention contain an intracyclic unsaturated bond.

[0015] The unsubstituted or at least monosubstituted, mono- or polyunsaturated, monocyclic cycloalkenes used in the process according to the invention may preferably have 5 to 12 carbon atoms, particularly preferably 6 to 12 carbon atoms, very particularly preferably 8 to 12 carbon atoms in the ring system. These cycloalkenes may be mono- or polyunsaturated, with monounsaturated cycloalkenes being preferred. These cycloalkenes may each be unsubstituted or mono- or polysubstituted. If they are mono- or polysubstituted, they are preferably substituted with 1, 2, 3, 4 or 5 substituents, each independently selected from the group consisting of methyl, phenyl or benzyl. The phenyl or benzyl substituents themselves may each be unsubstituted or mono- or polysubstituted with 1, 2 or 3 substituents, each independently selected from the group consisting of F, Cl, Br and NO2.

[0016] The unsubstituted or at least monosubstituted, mono- or polyunsaturated, bicyclic cycloalkenes used in the process according to the invention may preferably have 7 to 18 carbon atoms, particularly preferably 7 to 12 carbon atoms, very particularly preferably 7 to 10 carbon atoms in the ring system. These cycloalkenes may be mono- or polyunsaturated, with monounsaturated cycloalkenes being preferred. These cycloalkenes may each be unsubstituted or mono- or polysubstituted. If they are mono- or polysubstituted, they are preferably substituted with one, two, three, four or five substituents, each independently selected from the group consisting of methyl, phenyl or benzyl. The phenyl or benzyl substituents themselves may each be unsubstituted or mono- or polysubstituted with one, two or three substituents, each independently selected from the group consisting of F, Cl, Br and NO2.

[0017] It is particularly preferred that the cycloalkene is selected from the group consisting of cyclohexene, cycloheptene, cyclooctene, cyclononene, cyclodecene, cycloundecene, cyclododecene, 1-phenylcyclohex-1-ene, bicyclo[2.2.1]hept-2-ene, α-pinene and carene.

[0018] Step (b) of the method according to the invention comprises providing at least one organic nitrate salt, which acts both as a conductive salt and as a mediator in the electrochemical oxidation method according to the invention, having the general formula: [Cation + ][NO3 - ] It is preferable to use an organic salt of [Cation + ] is the following: -General structure [R 1 R 2 R 3 R 4 N + ](wherein, R 1 , R 2 , R 3 , R 4 are each independently selected from the group consisting of C1 to C16 alkyl, particularly straight or branched C1 to C8 alkyl, -General structure (I):

[0019] [ka]

[0020] (In the formula, R 1 and R 2 are each independently selected from the group consisting of linear or branched C1-C18 alkyl, in particular linear or branched C1-C8 alkyl; R 3 is selected from the group consisting of H and linear or branched C1-C18 alkyl, particularly H and linear or branched C1-C8 alkyl. imidazolium cation, -General structure (II):

[0021] [ka]

[0022] (In the formula, R 1 is selected from the group consisting of C1-C18 alkyl, in particular linear or branched C1-C8 alkyl, R 2 , R 3 and R 4 are each independently selected from the group consisting of H and straight or branched C1-C18 alkyl, particularly H and C straight or branched C1-C8 alkyl. the pyridinium cation, and -General structure [R 1a R 2a R 3a R 4a P + ](wherein, R 1a , R 2a , R 3a , R 4a are each independently selected from the group consisting of C1 to C16 alkyl, particularly straight or branched C1 to C8 alkyl. is selected from the group consisting of:

[0023] When organic nitrates based on imidazolium cations are used in the process according to the invention, they are represented by the general formula (I), where R 1 and R 2 are each independently selected from the group consisting of linear or branched C1-C18 alkyl, in particular linear or branched C1-C8 alkyl; R 3 is hydrogen. Particularly preferred are cations of the general formula (I) (wherein in each case R 1 is methyl, R 2 is ethyl, or R 1 is methyl, R 2 is methyl, or R 1 is methyl, R 2 is butyl, and R 3 is hydrogen.) is the imidazolium cation.

[0024] When nitrates based on pyridinium cations are used in the process according to the invention, they are represented by the general formula (II), where R 1 is a linear or branched C1-C18 alkyl, particularly a linear or branched C1-C8 alkyl. Particularly preferred are cations of the general formula (II) (wherein R 1 is linear or branched C1-C18 alkyl, in particular linear or branched C1-C8 alkyl, and the radical R 2 , R 3 and R 4 are each independently selected from the group consisting of straight or branched C1-C8 alkyl, and are preferably monosubstituted at the 2-, 3- or 4-positions, disubstituted at the 2-, 4-, 2-, 5- or 2-, 6-positions, or trisubstituted at the 2-, 4-, and 6-positions.)

[0025] In principle, more than one of the abovementioned nitrates can also be used in the process according to the invention. 1 R 2 R 3 R 4 N + ][NO3 - ], or organic ammonium nitrate of composition [R 1a R 2a R 3a R 4a P + ][NO3 - It is preferable to use organic phosphonium salts of the composition [R 1 R 2 R 3 R 4 N + ][NO3 - Particularly preferred are organic ammonium nitrates of the formula:

[0026] It is particularly preferred that the organic ammonium nitrate is tetra-n-butylammonium nitrate or methyltri-n-octylammonium nitrate. It is particularly preferred that the organic phosphonium nitrate is tetra-n-butylphosphonium nitrate or methyltri-n-octylphosphonium nitrate. The organic imidazolium nitrate is preferably 1-butyl-3-methylimidazolium nitrate.

[0027] The organic nitrate used in the process according to the invention is most preferably tetra-n-butylammonium nitrate or methyltri-n-octylammonium nitrate.

[0028] The order in which the components used in the process according to the invention are provided may vary, as may the order in which the individual components are contacted with each other or with their respective reaction media.

[0029] In one embodiment of the process according to the invention, the unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkene or the inorganic or organic nitrate is charged first, combined with the reaction medium, preferably at least partially or completely dissolved in the reaction medium or mixed in the reaction medium, and then the other of these two components in each case is added. In another embodiment of the process according to the invention, the unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkene and the inorganic or organic nitrate are charged first, and then combined with the reaction medium, preferably at least partially or completely dissolved in the reaction medium or mixed in the reaction medium. Furthermore, in the process according to the invention, it is also possible that the unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkene and the inorganic or organic nitrate are added to the reaction medium, simultaneously or successively, preferably at least partially or completely dissolved in the reaction medium or mixed in the reaction medium.

[0030] The reaction medium used in the process according to the invention is liquid under the conditions in which the process is carried out and is capable of partially or completely dissolving the components used, i.e. in particular the unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkenes and the inorganic or organic nitrates. If at least one of these components is used in liquid form, it is preferred that the reaction medium is readily miscible with said components.

[0031] The process according to the invention preferably uses a polar aprotic reaction medium for the electrochemical oxidation, which can be used in anhydrous form, in dry form or in a mixture with water.

[0032] In the method according to the invention, when inorganic nitrate, especially potassium nitrate or sodium nitrate, is used, the reaction medium is preferably an aprotic reaction medium that advantageously contains water and is mixed with water.The water content of the reaction medium can vary.The water content is preferably at most 20% by volume, particularly preferably at most 15% by volume, very particularly preferably at most 10% by volume, and even more preferably at most 5% by volume, based on the total amount of the reaction medium in each case.

[0033] The polar aprotic reaction medium is preferably selected from the group consisting of aliphatic nitriles, aliphatic ketones, cycloaliphatic ketones, dialkyl carbonates, cyclic carbonates, lactones, aliphatic nitroalkanes, dimethylsulfoxide, esters and ethers, or a combination of at least two of these components.

[0034] The reaction medium is particularly preferably selected from the group consisting of acetonitrile, isobutyronitrile, adiponitrile, acetone, dimethyl carbonate, methyl ethyl ketone, 3-pentanone, cyclohexanone, nitromethane, nitropropane, tert-butyl methyl ether, dimethyl sulfoxide, γ-butyrolactone and ε-caprolactone, or a combination of at least two of these components.

[0035] The reaction medium is very particularly preferably selected from the group consisting of acetonitrile, isobutyronitrile, adiponitrile, dimethyl carbonate and acetone, or a combination of at least two of these components.

[0036] The reaction medium is very particularly preferably acetonitrile, isobutyronitrile or adiponitrile in dry or anhydrous form.

[0037] The reaction medium is likewise very particularly preferably acetonitrile, isobutyronitrile or adiponitrile, optionally mixed with water.

[0038] If one or more of the abovementioned components are used in the reaction medium mixed with water, the water content is preferably at most 20% by volume, particularly preferably at most 15% by volume, particularly preferably at most 10% by volume and even more preferably at most 5% by volume, in each case based on the total amount of the reaction medium.

[0039] To carry out the method according to the invention, it may be advantageous to add further solubilizing components to the reaction medium. Suitable advantageous components may be identified by simple preliminary testing of the solubility behavior.

[0040] Examples of solubilizing components include primary alcohols, secondary alcohols, monoketones, or dialkyl carbonates, or a mixture of at least two of these components, optionally mixed with water. The method according to the invention preferably comprises the steps of: 1-6 Alcohols can be used, and particularly preferred solubilizing components can be selected from the group consisting of methanol, ethanol, isopropanol, 2-methyl-2-butanol, or a mixture of at least two of these components, optionally mixed with water.

[0041] The reaction medium used is particularly preferably dimethyl carbonate, optionally containing at least one C 1-6It is mixed with an alcohol, in particular one selected from the group consisting of methanol, ethanol, isopropanol and 2-methyl-2-butanol, and optionally mixed with water.

[0042] If one or more of these solubilizing components are used mixed with water, the water content is preferably at most 20% by volume, particularly preferably at most 15% by volume, very particularly preferably at most 10% by volume and even more preferably at most 5% by volume, in each case based on the total amount of solubilizing component and water.

[0043] The solubilizing components may be added preferably in an amount of less than 50% by volume, particularly preferably less than 30% by volume and very particularly preferably less than 10% by volume, in each case relative to the total amount of the reaction medium.

[0044] In the process according to the invention, it is preferable to use 0.1 to 2.0 equivalents, preferably 0.2 to 1.0 equivalents, particularly preferably 0.3 to 0.8 equivalents and very particularly preferably 0.4 to 0.8 equivalents of inorganic or organic nitrate relative to the amount of unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkene in each case.

[0045] According to the invention, the electrochemical oxidation of unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkenes is carried out in an electrolytic cell in a reaction medium in the presence of oxygen, in the presence of inorganic or organic nitrates.

[0046] To this end, an oxygen-containing gas atmosphere is advantageously provided in spatial communication with the reaction medium.

[0047] The proportion of oxygen in the gas atmosphere may vary, and is preferably 10 volume % to 100 volume %, particularly preferably 15 volume % to 30 volume %, particularly preferably 15 volume % to 25 volume %, and particularly preferably 18 volume % to 22 volume %.

[0048] In one embodiment, the proportion of oxygen in the gas atmosphere may be 10% by volume to 100% by volume, particularly preferably 15% by volume to 100% by volume, and particularly preferably 20% by volume to 100% by volume.

[0049] It is particularly preferred if the gas atmosphere is air.

[0050] It is advantageous if the gas exchange between the gas atmosphere and the reaction medium is carried out, preferably by introducing a gas atmosphere into the reaction medium or by stirring the liquid phase in the presence of a gas atmosphere.

[0051] Gas exchange between the gas atmosphere and the reaction medium, in particular stirring, can be used to control the electrochemical oxidation, for example by stirrer geometry or stirrer speed.

[0052] The amount of oxygen dissolved in the reaction medium is preferably at least 1 mmol, particularly preferably at least 5 mmol, per litre of reaction medium.

[0053] It is likewise preferred if the amount of oxygen dissolved in the reaction medium is at least 10 mmol per litre of reaction medium.

[0054] The process according to the invention for the preparation of unsubstituted or at least monosubstituted α,ω-dicarboxylic acids and ketocarboxylic acids by electrochemical oxidation of unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkenes in the presence of inorganic or organic nitrates in an electrolytic cell in a reaction medium in the presence of oxygen may be carried out either in a divided or in a non-divided electrolytic cell, preferably in a non-divided electrolytic cell.

[0055] The non-split electrolytic cell preferably used according to the present invention has at least two electrodes.For this purpose, anodes and cathodes made of conventional materials can be used, for example anodes and cathodes made of glassy carbon, boron-doped diamond (BDD) or graphite.The use of glassy carbon electrodes is preferred.

[0056] The undivided electrolytic cell preferably comprises at least one glassy carbon anode or at least one glassy carbon cathode, preferably where both the anode and the cathode are glassy carbon electrodes.

[0057] The distance between the electrodes can vary within a certain range. The distance is preferably 0.1 mm to 2.0 cm, particularly preferably 0.1 mm to 1.0 cm, and particularly preferably 0.1 mm to 0.5 cm.

[0058] The process according to the invention can furthermore be carried out batchwise or continuously, preferably in an undivided flow-through electrolytic cell.

[0059] It is preferred if the process according to the invention is carried out with a charge amount of at least 190 C (2F) to 970 C (10F), preferably 290 C (3F) to 870 C (9F), particularly preferably 330 C (3.5F) to 820 C (8.5F), very particularly preferably 380 C (4F) to 775 C (8F) and most preferably 380 C (4F) to 580 C (6F), in each case per mmol of unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkene used.

[0060] The electrochemical oxidation in the method according to the invention is preferably carried out galvanostatically.

[0061] The current density at which the method according to the invention is carried out is preferably at least 5 mA / cm 2 Or at least 10mA / cm 2 Or at least 15mA / cm 2 Or at least 20mA / cm 2 , or 20mA / cm 2 ~50mA / cm 2 where the reported surface area represents the geometric area of ​​the electrode.

[0062] An important advantage of the method according to the invention is that the oxidizing agent used is electric current, which is a particularly environmentally friendly agent when it is obtained from renewable resources, i.e. in particular from biomass, solar thermal energy, geothermal energy, hydroelectric power, wind power or photovoltaic power.

[0063] The process according to the invention can be carried out in a wide temperature range, for example at temperatures from 0°C to 60°C, preferably from 5°C to 50°C, particularly preferably from 10°C to 40°C, very particularly preferably from 15°C to 30°C.

[0064] The process according to the invention can be carried out at elevated pressure or at reduced pressure. If the process according to the invention is carried out at elevated pressure, pressures up to 16 bar are preferred, pressures up to 6 bar are particularly preferred.

[0065] The process according to the invention can likewise preferably be carried out at atmospheric pressure.

[0066] The products produced by the process according to the invention may be isolated / purified by conventional methods known to those skilled in the art, in particular by extraction, crystallization, centrifugation, precipitation, distillation, evaporation or chromatography.

[0067] The following examples further illustrate the invention but are not intended to limit the scope of the invention. EXAMPLES

[0068] General Information and Methods Chemicals of analytical quality were obtained and used from commonly used sources, such as TCI, Aldrich, and Acros. Oxygen was obtained at 2.5 quality from Nippon Gases Deutschland GmbH, Düsseldorf, Germany, and was used as received.

[0069] The electrode material used was glassy carbon (Sigradur® G, HTW Hochtemperatur Werkstoffe GmbH, Tierhaupten, Germany).

[0070] High-performance liquid chromatography was performed on a Shimadzu HPLC-MS instrument equipped with a SIL 20A HT autosampler, a CTO-20AC column oven, two LC-20AD pump modules for eluent gradient adjustment, an SPD-M20A diode array detector, a CBM-20A system controller, and a Eurospher II 100-5 C18 column (150 × 4 mm, Knauer, Berlin). Eluent: acetonitrile / water / formic acid (1% by volume) (10% ACN to 90% ACN in 10 min + 100% ACN in 10 min). Mass spectrometry measurements were performed on a Shimadzu LCMS-2020 instrument, Japan.

[0071] 1H-NMR and 13C-NMR spectra were recorded at 25 °C using a Bruker Avance II 400 (400 MHz, 5 mm BBFO probe with Z gradient and ATM, SampleXPress60 autosampler, Analytische Messtechnik, Karlsruhe, Germany).

[0072] GP1 / GP2 / GP3 Gas Introduction: Gas introduction was carried out in a controlled manner by two model 5850S ​​mass flow controllers (MFC) from Brooks Instrument BV, Veenendaal, The Netherlands. One controller was used for the introduction of oxygen and the other for the introduction of nitrogen. The controllers were controlled by Smart DDE and Matlab R2017b software. The volumetric flow rate was additionally monitored by a DK800 float principle flowmeter from Krohne Messtechnik GmbH, Duisburg. In all experiments carried out, the total volumetric flow rate was constant at 20 mL / min. This is the maximum achievable volumetric flow rate, although it is limited by the MFC used. The ratio of the volumetric flows of the two gases was adjusted using the MFC and its software. Gas cylinders from the following suppliers were used: oxygen 2.5 from Nippon Gases Deutschland GmbH, Düsseldorf, nitrogen 4.8 from Westfalen AG, Münster, or nitrogen 5.0 from Nippon Gases Deutschland GmbH, Düsseldorf. In this regard, the apparatus was equipped with a gas distributor including a gas adapter and a (Teflon) lid for the electrolysis cell.

[0073] General Procedure GP1 Undivided Teflon cells used for electrolysis have been described in the literature: (a) C. Gutz, B. Klockner, S. R. Waldvogel, Org. Process Res. Dev. 2016, 20, 26-32; b) A. Kirste, G. Schnakenburg, F. Stecker, A. Fischer, S. R. Waldvogel, Angew. Chem. Int. Ed. 2010, 49, 971-975; Angew. Chem. 2010, 122, 983-987. (See SI).) The full range of these cells with stainless steel blocks is also commercially available as IKA Screening Systems (IKA-Werke GmbH & Co. KG, Staufen, Germany). The dimensions of the electrodes were 7 cm × 1 cm × 0.3 cm.

[0074] A 5 mL undivided Teflon pot cell was initially charged with cycloalkane (1.0 mmol) and tetrabutylammonium nitrate (0.5 equiv.) dissolved in acetonitrile (5 mL). The cell was fitted with glassy carbon electrodes spaced 0.5 cm apart. The immersed surface area of ​​the electrodes was 1.8 cm. 2 After the cell was fixed to a stainless steel block, it was heated at 5°C with a current density of 10 mA / cm 2 Constant current electrolysis was carried out at .

[0075] After using a charge amount of 4-8F on the cycloalkene, the solvent was first removed by distillation. Then, the conductive salts were removed by extraction using 10 mL of ethyl acetate and 10 mL of water. The organic phase was washed with aqueous NaOH (1M, 10 mL). The aqueous phase was adjusted to pH 1 with aqueous HCl (1M) and this phase was extracted with 2 × 10 mL of ethyl acetate. The organic phase was dried over calcium chloride and the solvent was distilled off, after which the obtained product was dried under high vacuum. If there are any differences from GP1, for example with regard to the solvent, it will be clear from the following examples.

[0076] General Procedure GP2 Undivided Teflon cells used for electrolysis have been described in the literature: (a) C. Gutz, B. Klockner, S. R. Waldvogel, Org. Process Res. Dev. 2016, 20, 26-32; b) A. Kirste, G. Schnakenburg, F. Stecker, A. Fischer, S. R. Waldvogel, Angew. Chem. Int. Ed. 2010, 49, 971-975; Angew. Chem. 2010, 122, 983-987 (see SI).) The full range of these cells with stainless steel blocks is also commercially available as IKA Screening Systems (IKA-Werke GmbH & Co. KG, Staufen, Germany). The dimensions of the electrodes were 7 cm × 1 cm × 0.3 cm.

[0077] A 5 mL undivided Teflon pot cell was initially charged with cycloalkanes (0.1–1.0 mmol) and tetrabutylammonium nitrate (0.5–2.0 equiv.) dissolved in acetonitrile (5 mL). The cell was fitted with glassy carbon electrodes spaced 0.5 cm apart. The immersed surface area of ​​the electrodes was 1.8 cm. 2 After the cell was fixed to a stainless steel block, it was heated at 5 to 50°C and a current density of 5 to 10 mA / cm. 2 Constant current electrolysis was carried out at .

[0078] After using a charge amount of 4-8F on the cycloalkene, the solvent was first removed by distillation. Then, the conductive salts were removed by extraction using 10 mL of ethyl acetate and 10 mL of aqueous HCl (0.1 M). The solvent of the organic phase was removed by distillation and the residue was placed in aqueous NaOH (1 M, 10 mL) and washed with 10 mL of diethyl ether or 10 mL of n-pentane. Then, the aqueous phase was adjusted to pH 1 by dropwise addition of concentrated aqueous HCl and this phase was extracted with 2 × 10 mL of ethyl acetate. The organic phase was dried over magnesium sulfate and the solvent was distilled off, after which the obtained product was dried under high vacuum. If there are any differences from GP1, for example with regard to the solvent, it will be clear from the following examples.

[0079] General Procedure GP3 Electrolysis was carried out in a non-segmented flow-through cell (IKA, electrode area: 2 cm × 6 cm). For this, cycloalkenes (0.5–5 mmol) and conductive salts (0.4–1.0 equiv.) were dissolved in solvent (5–10 mL) in a reservoir (20 mL snap-cap vial). The temperature of the reservoir was 20–50 °C. Using a peristaltic pump, the reaction solution was delivered at a flow rate of 5–18 mL / min to a Y-piece or T-piece, into which oxygen gas (100% by volume) was introduced at a flow rate of 10–20 mL / min. This segmented flow was delivered to the cell (electrode distance: 0.05 cm). After passing through the cell, the reaction solution was returned to the reservoir, where it was re-aspirated. Electrolysis was carried out at a constant current (5–20 mA / cm 2), with a charge amount of 2-4F based on the substrate. After electrolysis, 1,3,5-trimethoxybenzene was added to the reaction solution as a GC standard (previously: external calibration of the analyte substrate). Three drops of the reaction solution were eluted through about 330 mg of silica gel 60M using ethyl acetate. About 1.5 mL of the filtrate was collected in a GC vial and the residual reactants were analyzed by GC-FID. The dicarboxylic acid yield measurement was carried out by extractive separation. The solvent of the organic phase was distilled off, the residue was placed in aqueous NaOH (1M, 10 mL) and washed with 10 mL of diethyl ether or 10 mL of n-pentane. The aqueous phase was then adjusted to pH 1 by dropwise addition of concentrated aqueous HCl, and this phase was extracted with 2 × 10 mL of ethyl acetate. The organic phase was dried over sodium sulfate, and after distillation of the solvent, the dicarboxylic acid product was dried under high vacuum.

[0080] Experimental Example 1: Production of 1,6-hexanedioic acid According to GP1, cyclohexene (0.082 g, 1.0 mmol, 1.0 equiv.) was electrolyzed galvanostatically under oxygen atmosphere (100% by volume) by applying 8F. The solvent was distilled off and dried under high vacuum to give the product as a colorless solid (yield: 16%, 0.023 g, 0.16 mmol). 1 H-NMR (400 MHz, DMSO-d6) δ [ppm] = 12.00 (s, 2H); 2.22-2.18 (m, 4H); 1.51-1.47 (m, 4H). Analytical data were in agreement with literature values.

[0081] Experimental Example 2: Production of 1.8-octanedioic acid According to GP1, cyclooctene (0.110 g, 1.0 mmol, 1.0 equiv.) was electrolyzed galvanostatically under oxygen atmosphere (100% by volume) by applying 4F. The solvent was distilled off and dried under high vacuum to give the product as a colorless solid (yield: 47%, 0.082 g, 0.47 mmol). 1 H-NMR (400 MHz, DMSO-d6) δ [ppm] = 11.98 (s, 2H); 2.18 (t, J = 7.4 Hz, 4H); 1.49-1.46 (m, 4H); 1.27-1.24 (m, 4H). Analytical data were consistent with literature values.

[0082] Experimental Example 3: Production of 1,12-dodecanedioic acid According to GP1, cyclododecene (0.166 g, 1.0 mmol, 1.0 equiv.) was electrolyzed galvanostatically by applying 8F under oxygen atmosphere (100% by volume). Isobutyronitrile (5 mL) was used as the solvent. The solvent was distilled off and dried under high vacuum to give the product as a colorless solid (yield: 53%, 0.121 g, 0.53 mmol). 1 H-NMR (400 MHz, DMSO-d6) δ [ppm] = 11.98 (s, 2H); 2.18 (t, J = 7.6 Hz, 4H); 1.51-1.46 (m, 4H); 1.24 (s, 12H). Analytical data were consistent with literature values.

[0083] Experimental Example 4: Production of 6-oxo-6-phenylhexanoic acid According to GP1, 1-phenylcyclohex-1-ene (0.158 g, 1.0 mmol, 1.0 equiv.) was electrolyzed galvanostatically under oxygen atmosphere (100% by volume) with application of 4F. The solvent was distilled off and dried under high vacuum to give the product as a colorless solid (yield: 16%, 0.034 g, 0.16 mmol). 1 H-NMR (400 MHz, DMSO-d6) δ [ppm] = 12.17 (s, 1H); 7.98-7.93 (m, 2H); 7.65-7.60 (m, 1H); 7.53-7.50 (m, 2H); 3.03 (t, J = 7.0 Hz, 2H); 2.25 (t, J = 7.0 Hz, 2H); 1.66-1.52 (m, 4H). Analytical data were in agreement with literature values.

[0084] Experimental Example 5: 1,3-Cyclopentanedioic acid According to GP1, bicyclo[2.2.1]hept-2-ene (0.094 g, 1.0 mmol, 1.0 equiv.) was electrolyzed under oxygen atmosphere (100% by volume) with galvanostatic application of 4F. The solvent was distilled off and dried under high vacuum to give the product as a colorless, highly viscous liquid (yield: 20%, 0.031 g, 0.20 mmol). 1H-NMR (400MHz, DMSO-d6) δ[ppm]=12,14(s,2H);2.78-2.62(m,2H);2.13-2.06(m,1H);1.88-1.72(m,5H). 13C-NMR (101MHz, DMSO-d6) δ[ppm]=176.4;43.3;32.8;28.9.

[0085] Experimental Example 6: In the following example, the synthesis of additional 1,8-octanedioic acid according to Scheme 1 using GP1 / GP2 is described.

[0086] [ka]

[0087] [Table 1]

[0088] Experiment 7: In the next example, the synthesis of additional 1,12-dodecanedioic acid according to Scheme 2 using GP1 / GP2 is described.

[0089] [ka]

[0090] [Table 2]

[0091] Experimental Examples 6-GP1-02 and 7-GP2-14 are comparative examples.

[0092] Experimental Example 8: The following example describes the synthesis of additional 1,12-dodecanedioic acid according to Scheme 3 using GP3, carried out in an electrochemical flow-through reactor.

[0093] [ka]

[0094]

Table 3

Claims

1. 1. A process for the preparation of unsubstituted or at least monosubstituted α,ω-dicarboxylic or ketocarboxylic acids by electrochemical oxidation of unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkenes, (a) providing at least one unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkene; (b) providing at least one organic nitrate; (c) electrochemically oxidizing the unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkene provided in step (a) in the presence of the organic nitrate provided in step (b) in an electrolytic cell in a reaction medium in the presence of oxygen; Including, the substituents of the mono- or polyunsaturated cycloalkene are each independently selected from the group consisting of methyl, phenyl, or benzyl; The phenyl or benzyl substituents themselves are unsubstituted or substituted with F, Cl, Br, and NO, respectively. ２ and wherein the aryl group is mono- or polysubstituted with one, two, or three substituents each independently selected from the group consisting of:

2. 2. The process according to claim 1, wherein the unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkene is monocyclic, preferably unsaturated and monocyclic.

3. 3. The process according to claim 2, wherein the unsubstituted or at least monosubstituted, mono- or polyunsaturated, monocyclic cycloalkene has 5 to 12 carbon atoms, particularly preferably 6 to 12 carbon atoms, very particularly preferably 8 to 12 carbon atoms in the ring system and is unsubstituted or mono- or polysubstituted, preferably with 1, 2, 3, 4 or 5 substituents.

4. The unsubstituted or at least monosubstituted, mono- or polyunsaturated bicyclic cycloalkene has in the ring system 7 to 18 carbon atoms, particularly preferably 7 to 12 carbon atoms, very particularly preferably 7 to 10 carbon atoms, and is unsubstituted or mono- or polysubstituted, preferably with 1, 2, 3, 4 or 5 substituents, each of which is independently selected from the group consisting of methyl, phenyl or benzyl, The phenyl or benzyl substituents themselves are each unsubstituted or substituted with F, Cl, Br and NO. ２ The method of claim 2, wherein the aryl group is mono- or polysubstituted with one, two or three substituents each independently selected from the group consisting of:

5. 5. The process of claim 1, wherein the cycloalkene is selected from the group consisting of cyclohexene, cycloheptene, cyclooctene, cyclononene, cyclodecene, cycloundecene, cyclododecene, 1-phenylcyclohex-1-ene, bicyclo[2.2.1]hept-2-ene, α-pinene, and carene.

6. The organic nitrate present has the general formula: ＋ ][NO ３ － ] is a nitrate of [Cation ＋ ] is the following: -General structure [R １ R ２ R ３ R ４ N ＋ ] (wherein, R １ , R ２ , R ３ , R ４ are each independently selected from the group consisting of C1 to C16 alkyl, particularly straight or branched C1 to C8 alkyl; -General structure (I): 【Chemistry 1】 (In the formula, R １ and R ２ are each independently selected from the group consisting of linear or branched C1-C18 alkyl, in particular linear or branched C1-C8 alkyl; R ３ is selected from the group consisting of H and linear or branched C1-C18 alkyl, in particular H and linear or branched C1-C8 alkyl. imidazolium cation, -General structure (II): 【Chemistry 2】 (In the formula, R １ is selected from the group consisting of C1-C18 alkyl, in particular linear or branched C1-C8 alkyl, R ２ , R ３ and R ４ are each independently selected from the group consisting of H and straight or branched C1-C18 alkyl, particularly H and C1-C8 straight or branched alkyl. the pyridinium cation, and -General structure [R １ａ R ２ａ R ３ａ R ４ａ P ＋ ] (wherein, R １ａ , R ２ａ , R ３ａ , R ４ａ are each independently selected from the group consisting of C1-C16 alkyl, in particular straight or branched C1-C8 alkyl. The method according to any one of claims 1 to 5, wherein the compound is selected from the group consisting of:

7. In the imidazolium cation of general formula (I), the radical R １ and R ２ are each independently selected from the group consisting of linear or branched C1-C18 alkyl, in particular linear or branched C1-C8 alkyl; R ３ is hydrogen, and preferably, in each case, R １ is methyl, R ２ is ethyl, or R １ is methyl, R ２ is methyl, or R １ is methyl, R ２ is butyl, R ３ The method of claim 6 , wherein is hydrogen.

8. In the pyridinium cation of the general formula (II), the radical R １ is linear or branched C1-C18 alkyl, in particular linear or branched C1-C8 alkyl, and the radical R ２ , R ３ and R ４ are each independently selected from the group consisting of straight or branched chain C1-C8 alkyl, preferably mono-substituted at the 2-, 3- or 4-positions, di-substituted at the 2,4-, 2,5- or 2,6-positions, or tri-substituted at the 2,4, and 6-positions.

9. 7. The method of claim 6, wherein the organic nitrate is selected from the group consisting of tetra-n-butylammonium nitrate, methyltri-n-octylammonium nitrate, tetra-n-butylphosphonium nitrate, methyltri-n-octylphosphonium nitrate, and 1-butyl-3-methylimidazolium nitrate.

10. 10. The process according to any one of claims 1 to 9, wherein the unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkene or the organic nitrate is initially charged and combined with the reaction medium, preferably at least partially or completely dissolved in said reaction medium or mixed in said reaction medium, before the other of these two components in each case is added.

11. 11. The process according to any one of claims 1 to 10, wherein the unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkene or the organic nitrate is initially charged and combined with the reaction medium, preferably partially or completely dissolved in said reaction medium or mixed therein, before the other of these two components in each case is added.

12. 12. The process according to any one of claims 1 to 11, wherein the unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkene and the organic nitrate are charged first and then combined with the reaction medium, preferably at least partially or completely dissolved in or mixed with the reaction medium.

13. 13. The process according to any one of claims 1 to 12, wherein the unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkene and the organic nitrate are added to the reaction medium, simultaneously or successively, preferably at least partially or completely dissolved in or mixed with the reaction medium.

14. The process of any one of claims 1 to 13, wherein the reaction medium is a polar aprotic reaction medium which may be in anhydrous form, dry form or in a mixture with water.

15. said reaction medium being a polar aprotic reaction medium, optionally mixed with water; said polar aprotic reaction medium is selected from the group consisting of aliphatic nitriles, aliphatic ketones, cycloaliphatic ketones, dialkyl carbonates, cyclic carbonates, lactones, aliphatic nitroalkanes, dimethylsulfoxide, esters and ethers, or combinations of at least two of these components; The process according to any one of claims 1 to 14, wherein, if mixed with water, the water content is preferably at most 20% by volume, particularly preferably at most 15% by volume, very particularly preferably at most 10% by volume and even more preferably at most 5% by volume, in each case based on the total amount of the reaction medium.

16. 16. A process according to claim 14 or claim 15, in which the reaction medium present is a polar aprotic reaction medium selected from the group consisting of acetonitrile, isobutyronitrile, adiponitrile, acetone, dimethyl carbonate, methyl ethyl ketone, 3-pentanone, cyclohexanone, nitromethane, nitropropane, tert-butyl methyl ether, dimethyl sulfoxide, γ-butyrolactone and ε-caprolactone, or a combination of at least two of these components, in each case present optionally mixed with water.

17. 17. The method of claim 16, wherein a reaction medium is present that is selected from the group consisting of acetonitrile, isobutyronitrile, adiponitrile, dimethyl carbonate and acetone, or a combination of at least two of these components, optionally mixed with water.

18. 18. The process of claim 16 or claim 17, wherein the reaction medium is acetonitrile, isobutyronitrile or adiponitrile in dry or anhydrous form.

19. The method of any one of claims 1 to 18, wherein the reaction medium comprises one or more solubilizing components.

20. 20. The method of claim 19, wherein the solubilizing component present is a primary alcohol, a secondary alcohol, a monoketone or a dialkyl carbonate, or a mixture of at least two of these components, optionally mixed with water.

21. aliphatic C １－６ 21. A process according to claim 19 or claim 20, wherein the alcohol is present as one or more solubilising components, preferably one or more alcohols selected from the group consisting of methanol, ethanol, isopropanol, 2-methyl-2-butanol and mixtures of at least two of these components, optionally mixed with water.

22. The reaction medium present is dimethyl carbonate, and optionally at least one C dimethyl carbonate selected from the group consisting of methanol, ethanol, isopropanol and 2-methyl-2-butanol. １－６ The method according to any one of claims 1 to 21, wherein the compound is mixed with an alcohol.

23. 23. The method of claim 22, wherein the reaction medium comprises water.

24. 24. The process according to any one of claims 19 to 23, wherein the one or more solubilizing components are present in an amount of less than 50% by volume, particularly preferably less than 30% by volume and very particularly preferably less than 10% by volume, in each case relative to the total amount of the reaction medium.

25. 25. The process according to claim 1, wherein the organic nitrate is used in an amount of from 0.1 to 2.0 equivalents, preferably from 0.2 to 1.0 equivalents, particularly preferably from 0.3 to 0.8 equivalents and very particularly preferably from 0.4 to 0.8 equivalents, in each case based on the amount of unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkene used.

26. 26. The process according to claim 1, wherein an oxygen-containing gas atmosphere is advantageously provided in spatial communication with the reaction medium, the proportion of oxygen in the gas atmosphere being preferably 10% to 100% by volume, particularly preferably 15% to 100% by volume, very particularly preferably 18% to 100% by volume and most preferably 20% to 100% by volume.

27. 27. The process according to claim 26, comprising providing an oxygen-containing gas atmosphere in spatial communication with the reaction medium, the proportion of oxygen in the gas atmosphere being between 10% and 100% by volume, preferably between 15% and 30% by volume, more preferably between 15% and 25% by volume, particularly preferably between 18% and 22% by volume.

28. 28. The method of claim 26 or claim 27, wherein the gas atmosphere is air.

29. A process according to any one of claims 26 to 28, wherein gas exchange between said gas atmosphere and said reaction medium is preferably carried out by introducing said gas atmosphere into said reaction medium or by stirring a liquid phase in the presence of said gas atmosphere.

30. 30. The method of claim 29, wherein the stirring is used to control the electrochemical oxidation.

31. A process according to any one of claims 1 to 30, wherein the amount of oxygen dissolved in the reaction medium is at least 1 mmol / L of reaction medium, preferably at least 5 mmol / L of reaction medium.

32. The method of any one of claims 1 to 31, carried out in a non-divided cell.

33. 33. The method of claim 32, wherein the undivided electrolytic cell comprises a glassy carbon anode, a graphite anode, or a BDD anode, preferably a glassy carbon anode.

34. 34. A method according to claim 32 or claim 33, wherein the undivided electrolytic cell comprises a glassy carbon cathode, a graphite cathode or a BDD cathode, preferably a glassy carbon cathode.

35. The method according to any one of claims 32 to 34, wherein the distance between the electrodes in the electrolysis cell is between 0.1 mm and 2.0 cm, preferably between 0.1 mm and 1.0 cm, particularly preferably between 0.1 mm and 0.5 cm.

36. 36. The process according to claim 1, wherein the charge amount is in each case at least 190 C (2F) to 970 C (10F), preferably 290 C (3F) to 870 C (9F), particularly preferably 330 C (3.5F) to 820 C (8.5F), very particularly preferably 380 C (4F) to 775 C (8F), most preferably 380 C (4F) to 580 C (6F), per millimole of unsubstituted or at least monosubstituted mono- or polyunsaturated cycloalkene.

37. The method according to any one of claims 1 to 36, wherein the electrochemical oxidation is carried out galvanostatically.

38. A current density of at least 5 mA / cm ２ , preferably 10 mA / cm ２ , more preferably 15 mA / cm ２ , particularly preferably 20 mA / cm ２ and the reported surface area represents the geometric area of ​​the electrode.

39. A current density of at least 20 mA / cm ２ ~50mA / cm ２ and the reported surface area represents the geometric area of ​​the electrode.

40. 40. The method according to any one of claims 1 to 39, wherein the current used for the electrochemical oxidation is obtained from a renewable resource, in particular biomass, solar thermal energy, geothermal energy, hydroelectric power, wind power or photovoltaic power.

41. The process according to any one of claims 1 to 40, wherein the electrochemical oxidation is carried out at a temperature of 0°C to 60°C, preferably 5°C to 50°C, particularly preferably 10°C to 40°C, very particularly preferably 15°C to 30°C.

42. The process of any one of claims 1 to 41, carried out at atmospheric pressure.

43. The process of any one of claims 1 to 42, carried out under reduced pressure.

44. The process according to any one of claims 1 to 43, which is carried out under elevated pressure, preferably up to 16 bar, particularly preferably up to 6 bar.

45. The process of any one of claims 1 to 44, which is carried out batchwise.

46. 46. ​​The process of any one of claims 1 to 45, which is carried out continuously, preferably continuously in a non-divided flow-through electrolytic cell.

47. 47. The process according to any one of claims 1 to 46, which is carried out without added catalyst, in particular without added transition metal catalyst.

48. 48. The method of any one of claims 1 to 47, wherein no additional oxidizing agent is added, except for oxygen or atmospheric oxygen.

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