Production of α,ω-dicarboxylic acids and ketocarboxylic acids by electrochemical oxidation of cycloalkenes

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 method for producing unsubstituted or at least monosubstituted α,ω-dicarboxylic acids and ketocarboxylic acids by electrochemically oxidizing unsubstituted or at least monosubstituted mono-unsaturated or polyunsaturated cycloalkenes in an electrolytic cell in a reaction medium in which oxygen is present, in the presence of an inorganic or organic nitrate.

Background Art

[0002] [ α,ω-dicarboxylic acids and ketocarboxylic acids are important substrates in organic synthetic chemistry and are monomer components in polymer synthesis, and are thus highly relevant for industrial applications. Conventional methods for obtaining these substrates from cycloalkenes basically involve transition metal-catalyzed reactions and the use of chemical oxidants.

[0003] So far, there has been very little description of an electrochemical process for the synthesis of dicarboxylic acids from cycloalkenes by direct C=C bond cleavage. Known processes usually involve mediation and also use expensive transition metal catalysts. They usually require an additional oxidizing agent that is electrochemically regenerated (Chinese Patent Application Publication No. 101092705; U.-St. Baumer, H.J. Schafer, J. Appl. Electrochem. 2005, 35, 1283 - 1292). Furthermore, 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, Method for Preparing Dodecanedioic Acid, U.S. Patent Application Publication No. 5026461 in 1991). Divided cells are often used, resulting in a more complex cell structure (Chinese Patent Application Publication No. 101092705). Known methods that do not require an additional transition metal catalyst are potentiostatic, require a two-phase mixture, and have low current yields. Therefore, scalability and economy cannot be ensured (S. Torii, T. Inokuchi, R. Oi, J. Org. Chem. 1982, 47, 47 - 52; U. Baumer, Electrochimica Acta 2003, 48, 489 - 495).

[0004] Furthermore, the processes known from the prior art provide routes only to a small substrate spectrum or require pre-functionalization. Additionally, since the prior art mainly describes the synthesis of the corresponding carboxylic acid esters, an additional hydrolysis step is required for the production of carboxylic acids, which requires additional time and resources.

[0005] With an increase in the amount of material input, often excessively, expensive transition metals are used as electrocatalysts or electrode materials and chemical oxidizing agents are used, resulting in reagent waste, and in some cases, expensive and complex waste disposal or regeneration is required.

Prior Art Documents

Patent Documents

[0006] [Patent Document 1] Chinese Patent Application Publication No. 101092705 Specification [Patent Document 2] U.S. Patent Application Publication No. 5026461 [Overview of the Initiative] [Problems that the invention aims to solve]

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

[0008] This objective was achieved through the subject matter of the claims and the specification.

[0009] The present invention relates to a method for producing unsubstituted or at least monosubstituted α,ω-dicarboxylic acids or ketocarboxylic acids by electrochemical oxidation of unsubstituted or at least monosubstituted monounsaturated or polyunsaturated cycloalkenes. (a) A step of preparing at least one unsubstituted or at least one substituted monounsaturated or polyunsaturated cycloalkene, (b) A step of preparing at least one organonitrate, (c) In an electrolytic cell in a reaction medium containing oxygen, electrochemically oxidize the unsubstituted or at least monosubstituted monounsaturated or polyunsaturated cycloalkene prepared in step (a) in the presence of the organic nitrate prepared in step (b), This provides a method that includes [something].

[0010] The method of the present invention has special characteristics such as high selectivity, low use of auxiliary chemicals, use of electric current as an oxidizing agent, and consequently, low generation of waste.

[0011] Remarkably, the electrochemical oxidation method according to the present invention has been found to enable the introduction of oxygen functional groups into cycloalkenes using atmospheric oxygen. This eliminates the need for chemical oxidizers such as reactive peroxides and expensive catalysts with complex ligand systems. At the same time, it reduces or even completely eliminates the use of toxic and / or potentially carcinogenic substances. The developed method is an inexpensive and environmentally friendly alternative to existing synthesis methods. Thanks to its simple and safe process conditions, it can be scaled up to industrial scale, allowing for the production of larger quantities of the desired product. Therefore, the present invention can significantly optimize processes that were previously costly and time-consuming.

[0012] Surprisingly, the method according to the present invention has also been found to enable the production of unsubstituted or at least monosubstituted α,ω-dicarboxylic acids and ketocarboxylic acids from cycloalkenes using an electric current, by using a nitrate that functions as both a conductive salt and an electrochemical mediator.

[0013] Surprisingly, the method according to the present invention has also been found to be implementable at ambient pressure and temperature, which is equally advantageous in terms of energy efficiency and, consequently, environmental compatibility.

[0014] The method according to the present invention can use unsubstituted or at least one-substituted monounsaturated or polyunsaturated monocyclic or bicyclic cycloalkenes. It is preferable to use unsubstituted or at least one-substituted monounsaturated or polyunsaturated monocyclic cycloalkenes, and particularly preferable to use unsubstituted or at least one-substituted monounsaturated monocyclic cycloalkenes. The cycloalkenes used according to the present invention contain intraring unsaturated bonds.

[0015] The unsubstituted or at least monosubstituted monounsaturated or polyunsaturated monocyclic cycloalkenes used in the methods according to the present invention may have, preferably, 5 to 12 carbon atoms, particularly preferably 6 to 12 carbon atoms, and most particularly preferably 8 to 12 carbon atoms in the ring system. These cycloalkenes may be monounsaturated or polyunsaturated, with monounsaturated cycloalkenes being preferred. Each of these cycloalkenes may be unsubstituted, monosubstituted, or polysubstituted. If they are monosubstituted or polysubstituted, they are preferably substituted with one, two, three, four, or five substituents independently selected from the group consisting of methyl, phenyl, or benzyl. The phenyl or benzyl substituents themselves may be unsubstituted, or monosubstituted or polysubstituted with one, two, or three substituents independently selected from the group consisting of F, Cl, Br, and NO2.

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

[0017] The cycloalkene is particularly preferably 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 the step of preparing at least one organic nitrate. This nitrate functions both as a conductive salt and as a mediator of the electrochemical oxidation method according to the invention. General formula: [Cation 4 [NO3 - It is preferred to use an organic salt of. [Cation + is as follows: - 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-C16 alkyl, especially straight-chain or branched C1-C8 alkyl.). An ammonium ion having - General structure (I):

[0019]

Chemical formula

[0020] (wherein R 1 and R 2 are each independently selected from the group consisting of straight-chain or branched C1-C18 alkyl, especially straight-chain or branched C1-C8 alkyl, and R 3 is selected from the group consisting of H and straight-chain or branched C1-C18 alkyl, especially H and straight-chain or branched C1-C8 alkyl.). <00001 / 0>An imidazolium cation of - General structure (II): ​

[0021] [ka]

[0022] (In the formula, R 1 R is selected from the group consisting of C1-C18 alkyl groups, particularly linear or branched C1-C8 alkyl groups, 2 , R 3 and R 4 Each of these is independently selected from the group consisting of H and linear or branched C1-C18 alkyl groups, particularly H and C linear or branched 1-C8 alkyl groups. The pyridinium cation, and -General structure [R 1a R 2a R 3a R 4a P + ](where R 1a , R 2a , R 3a , R 4a The phosphonium ion is independently selected from the group consisting of C1-C16 alkyl groups, particularly linear or branched C1-C8 alkyl groups. It is selected from the group consisting of the following.

[0023] When an imidazolium cation-based organic nitrate is used in the method according to the present invention, the general formula is (I) (wherein R 1 and R 2 Each of these is independently selected from the group consisting of linear or branched C1-C18 alkyl groups, particularly linear or branched C1-C8 alkyl groups, and R 3 A cation of hydrogen is preferred. Particularly preferred is the cation of general formula (I) (wherein in each case, R 1 is methyl, and R 2 Is it ethyl, or R 1 is methyl, and R 2 Is it methyl, or R 1 is methyl, and R 2 It is butyl, and R 3 It is hydrogen. ) It is the imidazolium cation.

[0024] When a pyridinium cation-based nitrate is used in the method according to the present invention, the general formula is (II) (wherein R 1 The cation is preferably a linear or branched C1-C18 alkyl group, particularly a linear or branched C1-C8 alkyl group. Particularly preferred is the cation of general formula (II) (wherein R is the cation of the formula). 1 The radical R is a linear or branched C1-C18 alkyl group, particularly a linear or branched C1-C8 alkyl group. 2 , R 3 and R 4 Each of the following is independently selected from the group consisting of linear or branched C1-C8 alkyl groups, and is preferably a monosubstituted at the 2, 3, or 4 position, a disubstituted at the 2,4, 2,5, or 2,6 positions, or a trisubstituted at the 2,4, and 6 positions.) It is a pyridinium cation.

[0025] In principle, the method according to the present invention may also use two or more of the above-mentioned nitrates. Nitrates according to the present invention, in particular composition [R 1 R 2 R 3 R 4 N + ][NO3 - ] Organic ammonium nitrate salts, or composition [R 1a R 2a R 3a R 4a P + ][NO3 - It is preferable to use an organic phosphonium salt of the composition [R 1 R 2 R 3 R 4 N + ][NO3 - Organic ammonium nitrate salts of ] are particularly preferred.

[0026] The organic ammonium nitrate is particularly preferably tetra-n-butylammonium nitrate or methyltri-n-octylammonium nitrate. The organic phosphonium nitrate is particularly preferably 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 method according to the present invention is most preferably tetra-n-butylammonium nitrate or methyltri-n-octylammonium nitrate.

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

[0029] In one embodiment of the method according to the present invention, an unsubstituted or at least monosubstituted monounsaturated or polyunsaturated cycloalkene, or an inorganic or organic nitrate, is first added and combined with the reaction medium, preferably 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 method according to the present invention, an unsubstituted or at least monosubstituted monounsaturated or polyunsaturated cycloalkene and an inorganic or organic nitrate are first added and then combined with the reaction medium, preferably partially or completely dissolved in the reaction medium or mixed in the reaction medium. Furthermore, in the method according to the present invention, it is also possible to add an unsubstituted or at least monosubstituted monounsaturated or polyunsaturated cycloalkene and an inorganic or organic nitrate to the reaction medium and simultaneously or successively, preferably partially or completely dissolved in the reaction medium or mixed in the reaction medium.

[0030] The reaction medium used in the method according to the present invention is a liquid under the conditions under which the method is carried out and can partially or completely dissolve the components used, i.e., particularly unsubstituted or at least monosubstituted monounsaturated or polyunsaturated cycloalkenes and inorganic or organic nitrates. When at least one of these components is used in liquid form, the reaction medium is preferably easily miscible with the above components.

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

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

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

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

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

[0037] The reaction medium is, similarly, very preferably, acetonitrile, isobutyronitrile, or adiponitrile, mixed with water as needed.

[0038] When one or more of the above components are mixed with water and used as a reaction medium, the water content is preferably up to 20% by volume, particularly preferably up to 15% by volume, particularly preferably up to 10% by volume, and even more preferably up to 5% by volume, relative to the total volume of the reaction medium.

[0039] To carry out the method according to the present invention, it may be advantageous to add further solubilizing components to the reaction medium. Suitable and advantageous components can be identified by simple preliminary tests of their dissolution behavior.

[0040] Examples of solubilizing components include primary alcohols, secondary alcohols, monoketones, or dialkyl carbonates, or mixtures of at least two of these components (mixed with water as necessary). The method according to the present invention is preferably C 1-6 Alcohols can be used, and particularly preferred solubilizing components may be selected from the group consisting of methanol, ethanol, isopropanol, 2-methyl-2-butanol, or mixtures of at least two of these components (mixed with water as needed).

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

[0042] When one or more of these solubilizing components are used in combination with water, the water content is preferably up to 20% by volume, particularly preferably up to 15% by volume, very particularly preferably up to 10% by volume, and even more preferably up to 5% by volume, relative to the total amount of the solubilizing components and water.

[0043] In all cases, the solubilizing component may be added in an amount of less than 50% by volume, more preferably less than 30% by volume, and very preferably less than 10% by volume, relative to the total amount of the reaction medium.

[0044] In all cases, the method according to the present invention preferably uses 0.1 to 2.0 equivalents, preferably 0.2 to 1.0 equivalents, particularly preferably 0.3 to 0.8 equivalents, and most particularly preferably 0.4 to 0.8 equivalents of an inorganic or organic nitrate, based on the amount of an unsubstituted or at least monosubstituted monounsaturated or polyunsaturated cycloalkene.

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

[0046] For this purpose, it is advantageous that an oxygen-containing gas atmosphere is provided in spatial communication with the reaction medium.

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

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

[0049] It is particularly preferable that the gas atmosphere be air.

[0050] Gas exchange between the gas atmosphere and the reaction medium is preferably performed by introducing the gas atmosphere into the reaction medium or by stirring the liquid phase in the presence of the gas atmosphere.

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

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

[0053] It is equally preferable that the amount of oxygen dissolved in the reaction medium is at least 10 millimoles per liter of reaction medium.

[0054] The present invention provides a method for producing unsubstituted or at least monosubstituted α,ω-dicarboxylic acids and ketocarboxylic acids by electrochemically oxidizing an unsubstituted or at least monosubstituted monounsaturated or polyunsaturated cycloalkene in an electrolytic cell in an oxygen-containing reaction medium, in the presence of an inorganic or organic nitrate. This method may be carried out in either a segmented electrolytic cell or a non-segmented electrolytic cell, with the non-segmented electrolytic cell being preferred.

[0055] A non-divided electrolytic cell preferably used in accordance with the present invention has at least two electrodes. For this purpose, anodes and cathodes made of conventional materials, such as glassy carbon, boron-doped diamond (BDD), or graphite, may be used. The use of glassy carbon electrodes is preferred.

[0056] A non-divided electrolytic cell preferably comprises at least one glassy carbon anode or at least one glassy carbon cathode. It is preferable that both the anode and cathode are glassy carbon electrodes.

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

[0058] The method according to the present invention may further be carried out in batch or sequentially, preferably in a non-divided flow-through electrolytic cell.

[0059] In all cases, the method according to the present invention is preferably carried out with a charge amount of at least 190C(2F) to 970C(10F), preferably 290C(3F) to 870C(9F), particularly preferably 330C(3.5F) to 820C(8.5F), very particularly preferably 380C(4F) to 775C(8F), and most preferably 380C(4F) to 580C(6F) per millimoles of unsubstituted or at least monosubstituted monounsaturated or polyunsaturated cycloalkene used.

[0060] In the method according to the present invention, electrochemical oxidation is preferably carried out with a constant current.

[0061] The current density at which the method according to the present invention is implemented is preferably at least 5 mA / cm². 2 Or at least 10mA / cm 2 Or at least 15 mA / cm 2 Or at least 20mA / cm 2 , or 20mA / cm 2 ~50mA / cm 2 Therefore, the reported surface area represents the geometric area of ​​the electrode.

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

[0063] The method according to the present invention can be carried out over a wide temperature range, for example, 0°C to 60°C, preferably 5°C to 50°C, particularly preferably 10°C to 40°C, and most particularly preferably 15°C to 30°C.

[0064] The method according to the present invention can be carried out under high or low pressure. When the method according to the present invention is carried out under high pressure, a pressure of up to 16 bar is preferred, and a pressure of up to 6 bar is particularly preferred.

[0065] The method according to the present invention may also preferably be carried out at atmospheric pressure.

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

[0067] The following embodiments further illustrate the present 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 suppliers (TCI, Aldrich, and Acros, etc.). Oxygen was obtained as is from Nippon Gases Deutschland GmbH in Düsseldorf, Germany, at quality 2.5, and used without modification.

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

[0070] High-performance liquid chromatography (HCM) was performed using a Shimadzu HPLC-MS instrument equipped with a SIL 20A HT autosampler, 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 vol%) (from 10% ACN to 90% ACN in 10 minutes + 100% ACN in 10 minutes). Mass spectrometry was performed using a Shimadzu LCMS-2020 instrument manufactured by Shimadzu, 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] Gas introduction for GP1 / GP2 / GP3: Gas introduction was controlled using two Brooks Instrument BV 5850S ​​mass flow controllers (MFCs) manufactured in Wienendaal, Netherlands. One controller was used for oxygen introduction, and the other for nitrogen introduction. The controllers were controlled by Smart DDE and Matlab R2017b software. Volumetric flow rate was additionally monitored by a DK800 float principle flow meter manufactured by Krohne Messtechnik GmbH in Duisburg. In all experiments conducted, the overall volumetric flow rate remained constant at 20 mL / min. This is also the maximum achievable volumetric flow rate, although limited by the MFCs used. The ratio of the volumetric flow rates of the two gases was adjusted using the MFCs and their software. Gas cylinders from the following suppliers were used: oxygen 2.5 from Nippon Gases Deutschland GmbH in Düsseldorf, nitrogen 4.8 from Westfalen AG in Münster, or nitrogen 5.0 from Nippon Gases Deutschland GmbH in Düsseldorf. In this regard, the device included a gas distributor with a gas adapter and a (Teflon®) lid for the electrolytic cell.

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

[0074] In a 5 mL non-divided Teflon® pot cell, cycloalkane (1.0 mmol) and tetrabutylammonium nitrate (0.5 equivalents) were initially added and dissolved in acetonitrile (5 mL). Glassy carbon electrodes were attached to the cell at 0.5 cm intervals. The immersion surface area of ​​the electrodes was 1.8 cm². 2 The cell was fixed to a stainless steel block, and the temperature was 5°C with a current density of 10 mA / cm². 2 Constant current electrolysis was performed.

[0075] After applying a charge of 4–8 F to the cycloalkene, the solvent was first removed by distillation. Next, the conductive salt was removed by extraction using 10 mL of ethyl acetate and 10 mL of water. The organic phase was washed with 10 mL of NaOH aqueous solution. The aqueous phase was adjusted to pH 1 with 1 M of HCl aqueous solution, and this phase was extracted with 2 × 10 mL of ethyl acetate. The organic phase was dried with calcium chloride, the solvent was removed by distillation, and the resulting product was dried under high vacuum. Any differences from GP1, for example, regarding the solvent, are evident from the following example.

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

[0077] In a 5 mL non-divided Teflon® pot cell, cycloalkane (0.1-1.0 mmol) and tetrabutylammonium nitrate (0.5-2.0 equivalents) were initially added and dissolved in acetonitrile (5 mL). Glassy carbon electrodes were attached to the cell at 0.5 cm intervals. The immersion surface area of ​​the electrodes was 1.8 cm². 2 The cell was fixed to a stainless steel block, and the temperature was 5-50°C, with a current density of 5-10 mA / cm². 2 Constant current electrolysis was performed.

[0078] After applying a charge of 4–8F to the cycloalkene, the solvent was first removed by distillation. Next, the conductive salt was 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. Next, 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 with magnesium sulfate, the solvent was removed by distillation, and the resulting product was dried under high vacuum. For example, any differences from GP1 regarding the solvent are evident from the following example.

[0079] General Procedure GP3 Electrolysis was performed in a non-segmented flow-through cell (IKA, electrode area: 2cm × 6cm). For this purpose, cycloalkenes (0.5–5 mmol) and conductive salts (0.4–1.0 equivalents) were dissolved in solvent (5–10 mL) in a reservoir (20 mL snap-cap vial). The reservoir temperature was 20–50°C. Using a peristaltic pump, the reaction solution was delivered to a Y-piece or T-piece at a flow rate of 5–18 mL / min, to which oxygen gas (100 vol%) was introduced at a flow rate of 10–20 mL / min. This segmented flow was then sent to the cell (electrode distance: 0.05 cm). After passing through the cell, the reaction solution was returned to the reservoir and re-aspirated. Electrolysis was performed at a constant current (5–20 mA / cm²). 2The reaction was performed at a substrate-based charge of 2-4F. After electrolysis, 1,3,5-trimethoxybenzene was added to the reaction solution as a GC standard (previously: external calibration of the analyte). Three drops of the reaction solution were eluted by passing approximately 330 mg of silica gel at 60M using ethyl acetate. Approximately 1.5 mL of the filtrate was collected in a GC vial, and the residual reaction products were analyzed by GC-FID. The yield of dicarboxylic acid was determined by extraction separation. The solvent of the organic phase was removed by distillation, and the residue was placed in an aqueous NaOH solution (1M, 10 mL) and washed with 10 mL of diethyl ether or 10 mL of n-pentane. Next, 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 sodium sulfate, the solvent was removed by distillation, and 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 equivalent) was subjected to constant current electrolysis under an oxygen atmosphere (100 vol%) using 8F. The solvent was removed by distillation, and the mixture was dried under high vacuum to obtain a colorless solid product (yield: 16%, 0.023 g, 0.16 mmol). 1 ¹H-NMR (400MHz, DMSO-d6) δ[ppm] = 12,00 (s, 2H); 2.22-2.18 (m, 4H); 1.51-1.47 (m, 4H). The analytical data was consistent with the literature values.

[0081] Experimental Example 2: Production of 1,8-octanedioic acid According to GP1, cyclooctene (0.110 g, 1.0 mmol, 1.0 equivalent) was subjected to constant current electrolysis under an oxygen atmosphere (100 vol%) using 4F. The solvent was removed by distillation, and the product was dried under high vacuum to obtain a colorless solid product (yield: 47%, 0.082 g, 0.47 mmol). 1 ¹H-NMR (400MHz, DMSO-d6) δ[ppm] = 11.98 (s, 2H); 2.18 (t, J=7.4Hz, 4H); 1.49-1.46 (m, 4H); 1.27-1.24 (m, 4H). The analytical data was consistent with the literature values.

[0082] Experimental Example 3: Preparation of 1,12-dodecanedioic acid According to GP1, cyclododecene (0.166 g, 1.0 mmol, 1.0 equivalent) was subjected to constant current electrolysis under an oxygen atmosphere (100 vol%) using 8F. Isobutyronitrile (5 mL) was used as the solvent. The solvent was removed by distillation, and the product was dried under high vacuum to obtain a colorless solid product (yield: 53%, 0.121 g, 0.53 mmol). 1 ¹H-NMR (400MHz, DMSO-d6) δ[ppm] = 11.98 (s, 2H); 2.18 (t, J=7.6Hz, 4H); 1.51-1.46 (m, 4H); 1.24 (s, 12H). The analytical data was consistent with the literature values.

[0083] Experimental Example 4: Production of 6-oxo-6-phenylhexanoic acid According to GP1, 1-phenylcyclohexa-1-ene (0.158 g, 1.0 mmol, 1.0 equivalent) was subjected to constant current electrolysis under an oxygen atmosphere (100 vol%) using 4F. The solvent was removed by distillation, and the product was dried under high vacuum to obtain a colorless solid product (yield: 16%, 0.034 g, 0.16 mmol). 1 ¹H-NMR (400MHz, 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=7.0Hz,2H); 2.25 (t,J=7.0Hz,2H); 1.66-1.52 (m,4H). The analytical data were consistent with the literature values.

[0084] Experimental Example 5: 1,3-Cyclopentanedioic acid According to GP1, bicyclo[2.2.1]hepto-2-ene (0.094 g, 1.0 mmol, 1.0 isospheric) was subjected to constant current electrolysis under an oxygen atmosphere (100 vol%) using 4F. The solvent was removed by distillation, and the product was dried under high vacuum to obtain a colorless, highly viscous liquid product (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: The following example describes the additional synthesis of 1,8-octanedioic acid according to Scheme 1 using GP1 / GP2.

[0086] [ka]

[0087] [Table 1]

[0088] Experimental Example 7: The following example describes the additional synthesis of 1,12-dodecanedioic acid according to Scheme 2 using GP1 / GP2.

[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 additional synthesis of 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. A method for producing unsubstituted or at least monosubstituted α,ω-dicarboxylic acids or unsubstituted or at least monosubstituted ketocarboxylic acids by electrochemical oxidation of an unsubstituted or at least monosubstituted monounsaturated cycloalkene or an unsubstituted or at least monosubstituted polyunsaturated cycloalkene. (a) A step of preparing at least one unsubstituted or at least one substituted monounsaturated cycloalkene or an unsubstituted or at least one substituted polyunsaturated cycloalkene, (b) A step of preparing at least one organic nitrate, (c) In an electrolytic cell in which oxygen is present in the reaction medium, the unsubstituted or at least one-substituted monounsaturated cycloalkene or the unsubstituted or at least one-substituted polyunsaturated cycloalkene prepared in step (a) is electrochemically oxidized in the presence of the organic nitrate prepared in step (b), Includes, The substituents of the monounsaturated cycloalkene or the polyunsaturated cycloalkene are independently selected from the group consisting of methyl, phenyl, or benzyl. The phenyl or benzyl substituents themselves are either unsubstituted or contain F, Cl, Br, and NO, respectively. ２ A method in which the substituents are monosubstituted or polysubstituted with substituents independently selected from the group consisting of the above.

2. The method according to claim 1, wherein the unsubstituted or at least one-substituted monounsaturated cycloalkene or the unsubstituted or at least one-substituted polyunsaturated cycloalkene is monocyclic.

3. The method according to claim 2, wherein the unsubstituted or at least one-substituted monounsaturated cycloalkene or the unsubstituted or at least one-substituted polyunsaturated monocyclic cycloalkene has 5 to 12 carbon atoms in its ring system and is either unsubstituted or monosubstituted or polysubstituted.

4. The aforementioned unsubstituted or at least monosubstituted monounsaturated cycloalkenes or the aforementioned unsubstituted or at least monosubstituted polyunsaturated bicyclic cycloalkenes have 7 to 18 carbon atoms in the ring system, which are either unsubstituted or monosubstituted or polysubstituted with substituents independently selected from the group consisting of methyl, phenyl, or benzyl. The phenyl or benzyl substituents themselves are either unsubstituted or F, Cl, Br, and NO, respectively. ２ The method according to claim 2, wherein the substituents are monosubstituted or polysubstituted with substituents independently selected from the group consisting of the above.

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

6. The organic nitrates present are of the general formula [cation] ＋ ] [NO ３ － It is a nitrate of ] [cations] ＋ ] is as follows: - 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 - C16 alkyl). An ammonium ion having the same, -General structure (I): 【Chemistry 1】 (In the formula, R １ and R ２ Each is independently selected from the group consisting of linear or branched C1-C18 alkyl groups, R ３ (These are selected from the group consisting of H and linear or branched C1-C18 alkyl groups.) The imidazolium cation, -General structure (II): 【Chemistry 2】 (In the formula, R １ R is selected from the group consisting of C1 to C18 alkyl groups. ２ , R ３ and R ４ (Each element is independently selected from the group consisting of H and linear or branched C1-C18 alkyl groups.) The pyridinium cation, and -General structure [R １ａ R ２ａ R ３ａ R ４ａ P ＋ ] (wherein, R １ａ , R ２ａ , R ３ａ , R ４ａ The phosphonium ion is independently selected from the group consisting of C1 to C16 alkyl groups. The method according to claim 1, selected from the group consisting of the following.

7. In the imidazolium cation of the general formula (I), the radical R １ and R ２ Each is independently selected from the group consisting of linear or branched C1-C18 alkyl groups, R ３ The method according to claim 6, wherein is hydrogen.

8. In the pyridinium cation of the general formula (II) above, radical R １ The radical R is a linear or branched C1-C18 alkyl group. ２ , R ３ and R ４ The method according to claim 6, wherein each is independently selected from the group consisting of linear or branched C1 to C8 alkyl groups.

9. The method according to 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. The method according to claim 1, wherein (i) the unsubstituted or at least monosubstituted monounsaturated cycloalkene or the unsubstituted or at least monosubstituted polyunsaturated cycloalkene, or (ii) the organic nitrate is added first and combined with the reaction medium, and then the other of (i) the unsubstituted or at least monosubstituted monounsaturated cycloalkene or the unsubstituted or at least monosubstituted polyunsaturated cycloalkene, or (ii) the organic nitrate is added.

11. The method according to claim 1, wherein the unsubstituted or at least monosubstituted monounsaturated cycloalkene or the unsubstituted or at least monosubstituted polyunsaturated cycloalkene and the organic nitrate are first added, and then combined with the reaction medium.

12. The method according to claim 1, wherein the unsubstituted or at least monosubstituted monounsaturated cycloalkene or the unsubstituted or at least monosubstituted polyunsaturated cycloalkene and the organic nitrate are added simultaneously or sequentially to the reaction medium.

13. The method according to claim 1, wherein the reaction medium is a polar aprotic reaction medium that can exist as a mixture with water.

14. The reaction medium is a polar aprotic reaction medium mixed with water. The method according to claim 1, wherein the polar aprotic reaction medium is selected from the group consisting of aliphatic nitriles, aliphatic ketones, alicyclic ketones, dialkyl carbonates, cyclic carbonates, lactones, aliphatic nitroalkanes, dimethyl sulfoxides, esters and ethers, or at least two combinations thereof.

15. The method according to claim 13, wherein the present reaction medium 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 at least two combinations thereof, and is present in mixture with water.

16. The method according to claim 15, wherein there is a reaction medium selected from the group consisting of acetonitrile, isobutyronitrile, adiponitrile, dimethyl carbonate, and acetone, or at least two combinations thereof, which is mixed with water.

17. The method according to claim 15, wherein the reaction medium is acetonitrile, isobutyronitrile, or adiponitrile.

18. The method according to claim 1, wherein the reaction medium comprises one or more solubilizing components that enable the dissolution of other substances.

19. The method according to claim 18, 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, and is mixed with water.

20. aliphatic C １－６ The method according to claim 18, wherein the alcohol is present as one or more alcohols selected from the group consisting of one or more solubilizing components, and is mixed with water.

21. The reaction medium present is dimethyl carbonate, and at least one C １－６ The method according to claim 1, wherein the alcohol is mixed with the method.

22. The method according to claim 21, wherein the reaction medium includes water.

23. The method according to claim 18, wherein the one or more solubilizing components are present in an amount of less than 50% by volume relative to the total amount of the reaction medium.

24. The method according to claim 1, wherein the organic nitrate is used in an amount of 0.1 to 2.0 mol per mole of unsubstituted or at least monosubstituted monounsaturated cycloalkene or 1 mol per mole of unsubstituted or at least monosubstituted polyunsaturated cycloalkene.

25. The method according to claim 1, wherein an oxygen-containing gas atmosphere is provided in spatial communication with the reaction medium.

26. The method according to claim 25, wherein an oxygen-containing gas atmosphere is provided that is spatially in communication with the reaction medium, and the proportion of oxygen in the gas atmosphere is 10% by volume to 100% by volume.

27. The method according to claim 25, wherein the gas atmosphere is air.

28. The method according to claim 25, wherein gas exchange between the gas atmosphere and the reaction medium is performed by introducing the gas atmosphere into the reaction medium or by stirring the reaction medium in the presence of the gas atmosphere.

29. The method according to claim 28, wherein stirring the reaction medium is used to control electrochemical oxidation.

30. The method according to claim 1, wherein the amount of oxygen dissolved in the reaction medium is at least 1 millimoles per liter of the reaction medium.

31. The method according to claim 1, wherein the anode and cathode are arranged in the same compartment without being separated.

32. The method according to claim 31, wherein the non-divided electrolytic cell comprises a glassy carbon anode, a graphite anode, or a BDD anode.

33. The method according to claim 31, wherein the non-divided electrolytic cell comprises a glassy carbon cathode, a graphite cathode, or a BDD cathode.

34. The method according to claim 31, wherein the distance between electrodes in the electrolytic cell is 0.1 mm to 2.0 cm.

35. The method according to claim 1, wherein the amount of charge used in the electrochemical oxidation step is at least 190 C (2 F (F: Faraday constant)) to 970 C (10 F (F: Faraday constant)) with respect to 1 millimolar unsubstituted or at least one-substituted monounsaturated cycloalkene or 1 millimolar unsubstituted or at least one-substituted polyunsaturated cycloalkene.

36. The method according to claim 1, wherein the electrochemical oxidation is carried out with a constant current.

37. Current density of at least 5 mA / cm² ２ The method according to claim 1, wherein the unit area of ​​the electric density represents the geometric area of ​​the electrode.

38. Current density of at least 20 mA / cm² ２ ~50 mA / cm ２ The method according to claim 1, wherein the unit area of ​​the electric density represents the geometric area of ​​the electrode.

39. The method according to claim 1, wherein the current used in the electrochemical oxidation is obtained from renewable resources.

40. The method according to any one of claims 1 to 39, wherein the electrochemical oxidation is carried out at a temperature of 0°C to 60°C.

41. The method according to claim 1, performed under atmospheric pressure.

42. The method according to claim 1, performed under reduced pressure, which is lower than atmospheric pressure.

43. The method according to claim 1, which is carried out under high pressure, which is higher than atmospheric pressure.

44. The method according to claim 1, performed in a batch manner.

45. The method according to claim 1, performed continuously.

46. The method according to claim 1, which is carried out without adding a catalyst.

47. The method according to claim 1, wherein oxygen or atmospheric oxygen is removed, and no other oxidizing agent is added.

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