High-throughput electrochemical oxidation method

Abstract

The present invention relates to an electrochemical method for preparing alkylenedicarboxylic acids, preferably adipic acid and its alkylated derivatives, and more preferably 3-ethyladipic acid, by a ring-opening oxidation reaction.

Description

[Technical Field]

[0001] The present invention relates to an electrochemical method for preparing alkylenedicarboxylic acids, preferably adipic acid and its alkylated derivatives, and more preferably 3-ethyladipic acid, by a ring-opening oxidation reaction. [Background technology]

[0002] The production of adipic acid releases millions of tons of harmful gases each year, which have a significant impact on climate change. The standard production method involves oxidizing a cyclohexanone / cyclohexanol mixture (KA oil) derived from fossil fuels with nitric acid. Approximately 300 kg of N2O is produced for every ton of adipic acid synthesized. This N2O is a greenhouse gas and, on a 100-year timescale, has 298 times the greenhouse effect of CO2. Adipic acid is primarily used as a monomer in the polycondensation reaction with hexamethylenediamine to produce nylon 6,6. This reaction, with a market size exceeding 3 million tons per year, simultaneously generates large amounts of N2O emissions. Although manufacturers had already agreed to reduce these harmful emissions by 1995, there is still a strong demand for new approaches to replace conventional processes, starting materials, or adipic acid itself. Twenty-five years ago, Noyori et al. made a crucial contribution to enabling a more climate-friendly and environmentally conscious method of synthesizing adipic acid (Sato, K. A “Green” Route to Adipic Acid: Direct Oxidation of Cyclohexenes with 30 Percent Hydrogen Peroxide. Science 1998, 281 (5383), 1646-1647). For this purpose, they prepared adipic acid by oxidizing cyclohexene in an aqueous hydrogen peroxide solution at 75-90°C. They used 1 mol% each of Na2WO4 and quaternary ammonium bisulfite as phase-transfer catalysts. The resulting epoxide intermediate was ring-opened in an acidic medium. A 90% adipic acid yield was achieved. However, the starting materials for this reaction were not of biological origin. In particular, the required hydrogen peroxide is relatively energy-intensive, expensive, and requires considerable safety precautions. Tungsten and phase-transfer catalysts can only be reused once, resulting in significant losses and leaving behind waste. Furthermore, one of the goals of chemical research is the shift from fossil resources to renewable resources. One possible method is to utilize bio-derived raw materials such as lignin.Lignin is primarily used as an energy source in the paper industry. It is the world's largest aromatic raw material because it does not compete with food resources and is renewable.

[0003] In recent years, a method has been developed to synthesize adipic acid by bacterial transformation of lignocellulose followed by catalytic hydrogenation. Li et al. have also investigated other bacterial methods for producing adipic acid from bio-based platform molecules such as 5-hydroxymethylfurfural, glucose, γ-valerolactone, and phenolic compounds (Lang, M.; Li, H. Sustainable Routes for the Synthesis of Renewable Adipic Acid from Biomass Derivatives. ChemSusChem 2022, 15 (1)). However, challenges remain in scaling up such biotechnological processes to an industrial scale. It has been shown that sugars can be selectively converted to 3-dehydroadipic acid by combining biotransformation with subsequent electrosynthesis. A simpler method for scaling up is the electrochemical oxidation of cyclohexanol in a flow reactor.

[0004] Electrochemistry is a high-performance, environmentally and economically sustainable approach in organic reactions due to its cost efficiency and high atom efficiency. However, in electro-synthesis, it is necessary to control and optimize several important parameters. The versatility of electrochemical reactions using a non-separated diaphragm structure is a promising one that enables the scale-up of many conversion reactions. This is particularly prominent in flow-through electrolyzers. Flow-through electrolyzers have many advantages compared to batch electrolyzers. Due to the short electrode distance, the ohmic resistance is low and the heat removal efficiency is excellent. Furthermore, the surface area to volume ratio is also better than that of batch electrolyzers, leading to an improvement in mass transfer efficiency. By increasing the electrode surface area while keeping the electrode distance constant, these characteristics can be further improved. When the geometric anode surface area is expanded in this way, the production rate of the target compound generally increases linearly. Scaled flow-through electrolyzers can also be equipped with a cooling device. Generally, cooling is performed by providing a flow path for the temperature control fluid on the back of the electrode. The construction of flow-through electrolyzers is generally a prerequisite for continuous manufacturing processes and an important element in scale-up to industrial scale.

[0005] Existing alcohol oxidation protocols are based on the use of Ni(O)OH electrodes. In the 1970s, the amplified electro-oxidation power of nickel hydroxide oxide, a heterogeneous mediator, was discovered in the oxidation of aliphatic alcohols. The importance of the stable, complete and regular activation of nickel electrodes has been emphasized in recent years by Cantillo et al. (Jud, W.; Salazar, C. A.; Imbrogno, J.; Verghese, J.; Guinness, S. M.; Desrosiers, J.-N.; Kappe, C. O.; Cantillo, D. Electrochemical Oxidation of Alcohols Using Nickel Oxide Hydroxide as Heterogeneous Electrocatalyst in Batch and Continuous Flow. Org. Proc. Res. Dev. 2022, 26 (5), 1486-1495).

[0006] The following methods are also disclosed in the prior art documents: Johannes Kaulen and Hans-Jurgen Schafer (Tetrahedron 1982, 38(22), 3299-3308) disclose the conversion of unsubstituted cyclohexanol to unsubstituted adipic acid on a Ni(O)OH electrode. This electrode is designed as a flat electrode, and the product has not actually been isolated. Hans-Jurgen Schafer (Top. Curr. Chem, 1987, 142, 101-129) has obtained similar results.

[0007] Johannes Kaulen ("Oxidation of Diols and Secondary Alcohols on Nickel Hydroxide Electrodes. Application to the Selective Oxidation of Hydroxysteroids", University of Münster doctoral thesis, 1981) discloses research on the electrochemical oxidation of cyclohexanol. He achieved a significant conversion rate on a nickel hydroxide electrode at a relatively high temperature, and part of it was accompanied by the ring-opening formation of adipic acid. B.V. Lyalin and V.A. Petrosyan (Russian J. Electrochem., 2010, 46(11), 1199-1214) disclose the preparation of unsubstituted adipic acid and the oxidation of carbohydrates.

[0008] In "Electrosynthesis of Adipic Acid by Undivided Cell Electrolysis" (Russian Chem. Bull., International Edition, Vol. 53 No. 3 pp. 688-692, March 2004), the same authors disclose the ring-opening electrochemical oxidation of cyclohexanol to adipic acid on a nickel hydroxide electrode. This paper reports that the maximum yield of adipic acid was 46.7% with a simultaneous current yield of 11.5%. As by-products of this reaction, succinic acid and glutaric acid were produced at yields of 6.3% and 11.5% respectively. These components are produced by the oxidative elimination of CH2 groups from the C6 core structure of cyclohexanol.

[0009] In one modified embodiment, European Patent Application Publication No. 2907898 (US Patent Application Publication No. 2015 / 0225861) discloses the use of nickel foam at a reaction temperature of 80°C in the oxidative ring cleavage of 3,3,5-trimethylcyclohexanol. This reaction was carried out in a highly diluted solution and yielded low results.

[0010] Schmitt et al. (Beilstein J. Org. Chem., 2015, 11, 473-480) have disclosed lignin cleavage in various oxo-substituted aromatics using various electrodes. Oxidation to the corresponding acids was unsuccessful.

[0011] International Publication No. 2021 / 249775 discloses an electrochemical preparation method for alkylenedicarboxylic acids by ring-opening oxidation using a doped Ni(O)OH foaming electrode. This method is carried out in an alkaline aqueous solution. Preferred cosolvents may be alcohols or DMSO.

[0012] Chinese Patent Application Publication No. 111229267 discloses a foamed electrode, but does not disclose the preparation of alkanedicarboxylic acids by ring-opening oxidation.

[0013] Known methods are unsatisfactory in all respects. Specifically, reactions with very small electrode areas often have the disadvantage of not exhibiting the effects that occur under scaled-up reaction conditions, resulting in low space-time yields. Furthermore, even a ninefold increase in electrode area does not allow for comparable main product yields. Moreover, to date, only data on mixing operations using standard magnetic stirrers or chemical additions have been reported (AL Rauen, F. Weinelt, SR Waldvogel, Green Chem. 2020, 22, 5956-5960; and H.-J. Schafer, Electrochem I, Top. Curr. Chem. 1987, 142, 101-129). [Prior art documents] [License]

[0014] [License 1] European Patent Publication No. 2907898 [License 2] U.S. Patent and Trademark Office Publication No. 2015 / 0225861 [License 3] International Publication No. 2021 / 249775 パンフレット [License 4] China Patent Publication No. 111229267 [Non-licensed literature]

[0015] [Non-licensed Document 1] Sato, K. A “Green” Route to Adipic Acid: Direct Oxidation of Cyclohexenes with 30 Percent Hydrogen Peroxide. Science 1998, 281 (5383), 1646-1647 [Non-licensed Document 2] Lang, M.; Li, H. Sustainable Routes for the Synthesis of Renewable Adipic Acid from Biomass Derivatives. ChemSusChem 2022, 15 (1) [Non-licensed Document 3] Jud, W.; Salazar, CA; Imbrogno, J.; Verghese, J.; Guinness, SM; Desrosiers, J.-N.; Kappe, CO; Cantillo, D. Electrochemical Oxidation of Alcohols Using Nickel Oxide Hydroxide as Heterogeneous Electrocatalyst in Batch and Continuous Flow. Org. Proc. Res. Dev. 2022, 26 (5), 1486-1495 [Non-Patent Document 4] Tetrahedron 1982, 38(22), 3299-3308 [Non-Patent Document 5] Top. Curr. Chem, 1987, 142, 101-129 [Non-Patent Document 6] "Oxidation of diols and secondary alcohols in nickel hydroxide electrodes: Applications to selective oxidation of hydroxysteroids," University of Münster doctoral dissertation, 1981. [Non-Patent Document 7] Russian J. Electrochem., 2010, 46(11), 1199-1214 [Non-Patent Document 8] "Electrosynthesis of Adipic Acid by Non-Diaphragm Cell Electrolysis" (Russian Chem. Bull., International Edition, Vol. 53 No. 3 pp. 688-692, March 2004) [Non-Patent Document 9] Beilstein J. Org. Chem., 2015, 11, 473-480 [Non-Patent Document 10] AL Rauen, F. Weinelt, SR Waldvogel, Green Chem. 2020, 22, 5956-5960; and H.-J. Schafer, Electrochem I, Top. Curr. Chem. 1987, 142, 101-129 [Overview of the Initiative] [Problems that the invention aims to solve]

[0016] Therefore, the object of the present invention is to provide a method that is superior to known methods.

[0017] This objective is achieved through the subject matter of the claims and specification.

[0018] In a first embodiment, the present invention Scheme (I):

[0019] [ka]

[0020] (In the formula, [ka] R represents a single or double bond, and R is present or absent accordingly. R is either hydrogen or an acyl radical, and an acyl radical is a radical of an aliphatic monocarboxylic acid with 2 to 8 carbon atoms. The present invention relates to a method for electrochemically preparing an alkanedicarboxylic acid (b) by a ring-opening oxidation reaction in an emulsion of at least one type of cyclic reactant (a) within an electrolytic cell.

[0021] A is a hydrocarbon having 3 to 30 carbon atoms, and all ring carbons of A in cyclic reactant (a) of scheme (I) have at least one hydrogen substituent and / or at least one alkyl substituent. Oxidation is carried out with a metal electrode containing at least partially nickel and / or cobalt, and cyclic reactant (a) is continuously supplied to the electrolytic cell.

[0022] Surprisingly, it was found that implementing this method, which is based on an emulsion of cyclic reactant (a), significantly improved the power efficiency and yield of the conversion.

[0023] The method of the present invention enables the efficient electrochemical synthesis of adipic acid derivatives, particularly in a flow electrolytic process. The cyclic reactant (a) used may be partially obtained from lignocellulose, such as 4-alkylcyclohexanol, as a renewable raw material source. This has significant economic implications when implemented on a large scale. The method according to the present invention is particularly useful for the industrial implementation of the electrochemical synthesis of such adipic acid derivatives, especially in a continuous reaction system.

[0024] The method claimed in accordance with the present invention enables the efficient oxidation of the cyclic reactant of general formula (a), particularly the larger-scale, more efficient oxidation of 4-alkylcyclohexanol to 3-alkyladipic acid in a flow system, and allows for improved product yield through the continuous input of the cyclic reactant of general formula (a) and, consequently, an improved continuous reaction method. A further advantage of the method according to the present invention compared to chemical oxidation methods is that it avoids the use of chemical oxidizing agents such as nitric acid.

[0025] Figure 1 shows a flow-type electrolytic cell for carrying out the method according to the present invention. Figure 2 shows a graphical evaluation of the parameter results by plotting the qNMR yield of 3-ethyladipic acid after electrochemical oxidation of 4-ethylcyclohexanol. Figures 3 and 4 show the change in the qNMR yield of 3-propyl adipic acid when 4-propyl cyclohexanone is supplied and not supplied during the application process. The cyclic reactant (a) is preferably continuously supplied to the electrolytic cell.

[0026] The method according to the present invention is particularly carried out such that oxidation is carried out with the following parameters. That is, - The reaction temperature is 10 to 60 °C, preferably 10 to 50 °C, more preferably 10 to 30 °C, more preferably 20 to 28 °C, and most preferably 24 to 26 °C, and / or - The flow rate of the reaction medium is 20 to 100 mL / min -1 preferably 20 to 80 mL / min -1 more preferably 40 to 60 mL / min -1 most preferably 45 to 55 mL / min -1 and / or - The concentration of the cyclic reactant (a) is 0.1 to 1 M, preferably 0.1 to 0.7 M, more preferably 0.1 to 0.5 M, more preferably 0.17 to 0.23 M, and most preferably 0.18 to 0.22 M, and / or - The applied current density is 1 to 10 mA / cm -2 preferably 2 to 8 mA / cm -2 more preferably 3 to 7 mA / cm -2 most preferably 4 to 6 mA / cm -2 (wherein the area value is based on the geometric anode surface area that does not take into account the internal surface area of the foam in any case). Preferably, - The reaction temperature is 25 ± 2.5 °C, and / or - The flow rate of the reaction medium is 50 ± 5 mL / min -1 and / or - The concentration of the reactant (a) is 0.2 ± 0.02 M, and / or - The applied current density is 5.0 ± 0.5 mA / cm -2 (wherein the area value is based on the geometric anode surface area that does not take into account the internal surface area of the foam in any case).

[0027] The method according to the present invention is preferably carried out such that the emulsion of the cyclic reactant (a) is present in water.

[0028] The emulsion used in the method according to the present invention preferably contains at least one base, preferably at least one inorganic base or one organic base.

[0029] In principle, useful inorganic or organic bases include all conventional bases used in electrochemical reactions, as known to those skilled in the art. In the method according to the present invention, one or more bases, particularly N(R), are added to the emulsion. A )4OH (in the formula, each R A These are independently H or linear or branched C 1-4 -It is alkyl.) It is preferable to use one base independently selected from the group including NaOH, KOH, LiOH, Na2CO3, K2CO3, and Li2CO3, preferably one base selected from the group including NaOH and KOH. It is particularly preferable to use NaOH as the base in the emulsion.

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

[0031] Another feature of the method according to the present invention is that it does not require the addition of surfactants to stabilize the emulsion. Depending on the type of cyclic reactant (a) used and the resulting alkanedicarboxylic acid, these reactants themselves may have surfactant properties, particularly in the presence of a base, and these may, in some cases, have an advantageous effect on stabilizing the emulsion.

[0032] The emulsion is preferably stable after formation until at least one cyclic reactant (a) undergoes a ring-opening oxidation reaction in a non-diaphragm electrolytic cell. The emulsion is preferably maintained at a temperature of 10-50°C, more preferably 10-30°C, most preferably 20-28°C, and even more preferably 24-26°C during and / or after its formation.

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

[0034] The metal electrodes used in the method according to the present invention are preferably nickel, cobalt, and optionally iron-based electrodes. These metal electrodes preferably contain 0 to 100% by weight of nickel and 100 to 0% by weight of cobalt, or 10 to 100% by weight of nickel and 0 to 90% by weight of iron, based on the total nickel and iron content in the electrode.

[0035] The content of other metals in the metal electrode is preferably 10% by weight or less, more preferably 5% by weight or less, even more preferably 2% by weight or less, and even more preferably 1% by weight or less, relative to the total content of the metals.

[0036] The metal electrodes preferably contain V, W, and Mo in amounts of 1% by weight or less, more preferably 0.1% by weight or less, and even more preferably 0.01% by weight or less, respectively. It should be noted that these metals are particularly susceptible to corrosion in alkaline aqueous emulsions.

[0037] A metal electrode useful in the method of the present invention is more preferably one that contains at least 80% by weight, preferably at least 90% by weight, and even more preferably at least 95% by weight of nickel, based on the total weight of the metal in the electrode.

[0038] Nickel and / or cobalt, and optionally iron, may be present on the substrate in the metal electrode, in which case the substrate is at least one material selected from the group including steel, copper, titanium, carbon, and preferably graphite.

[0039] The metal electrode may be doped with at least one element from the fifth and / or sixth main groups, more preferably one or more elements, preferably one element selected from the group including phosphorus, arsenic, selenium, and sulfur.

[0040] The dopant content value indicates the elemental state of the dopant, relative to the mass of the metal in the electrode.

[0041] If the metal electrode is doped with phosphorus, it may preferably contain 2 to 10% by weight, more preferably 3 to 9% by weight, and most preferably 4 to 9% by weight of phosphorus. In all cases, the phosphorus is considered in its elemental state and is based on the mass of the metal in the electrode.

[0042] The phosphorus dopant content can preferably be measured according to DIN EN ISO 5427, Appendix D.1.

[0043] The thickness of the metal electrode is preferably 2 mm or more, more preferably 3 mm or more, even more preferably 5 mm or more, and particularly preferably more than 6 mm.

[0044] The metal electrode used in the method according to the present invention is preferably a Ni(O)OH foam electrode, and in any case contains, preferably at least 80% by weight, more preferably at least 85%, 90%, 95%, 98%, or 99% by weight, even more preferably at least 99.9% by weight, and even more preferably at least 99.99% by weight, of the metal content of the Ni(O)OH foam electrode.

[0045] The metal electrode is preferably pretreated by contacting it with a base, preferably at least one inorganic base and / or at least one organic base, before oxidation.

[0046] Conventional inorganic and organic bases known to those skilled in the art are suitable for use in the contact process. Preferably, N(R) A )4OH, N(R A )4 acetate (in the formula, R A Each of these is independently H or linear or branched C 1-4 -It is alkyl.) One or more bases, preferably one, are used, independently selected from the group including NaOH, sodium acetate, KOH, potassium acetate, LiOH, lithium acetate, Na2CO3, K2CO3, and Li2CO3, and more preferably selected from the group including NaOH and KOH.

[0047] The base is preferably used in an aqueous solution during the contact step, and the concentration of the base is preferably 10 mM to 10 M, more preferably 0.2 to 5 M, even more preferably 0.5 to 1.5 M, and even more preferably 1 ± 0.1 M.

[0048] Metal electrodes can be brought into contact with a base, particularly by spray coating, immersion, jetting, or a flow system.

[0049] The metal electrode and the base may be in contact with each other over a relatively wide temperature range. The metal electrode is preferably brought into contact with the base at a temperature of 10 to 40°C, more preferably 18 to 27°C.

[0050] Prior to oxidation by the method of the present invention, it is advantageous to perform electrochemical activation of the metal electrodes, preferably without polarity reversal. Specifically, one or more salts of nickel and / or cobalt, and optionally iron, are suitable for this step. When using nickel or cobalt salts, suitable salts are selected from the group including Ni2SO4 and CoSO4, in particular.

[0051] For the electrochemical activation of the metal electrode, one or more salts are preferably present in a basic aqueous solution, preferably at a concentration of 0.05 to 0.15 M.

[0052] Useful bases are conventional bases known to those skilled in the art. Preferably, N(R A )4OH, N(R A )4 acetate (in the formula, R A Each of these is independently H or linear or branched C 1-4 -It is alkyl.) One or more bases, particularly one base, are used, independently selected from the group including NaOH, sodium acetate, KOH, potassium acetate, LiOH, lithium acetate, Na2CO3, K2CO3, and Li2CO3, and more preferably selected from the group including NaOH and KOH.

[0053] The concentration of the base used in activating the metal electrode is preferably 10 mM to 10 M, preferably 0.2 to 5 M, more preferably 0.5 to 1.5 M, and most preferably 1 ± 0.1 M.

[0054] The metal electrode is activated with a charge of preferably 2 to 10 coulombs, preferably 5 to 7 coulombs.

[0055] The metal electrode can be activated over a wide temperature range. Preferably, the metal electrode is activated at a temperature of 10-40°C, more preferably 18-27°C.

[0056] In a preferred embodiment of the method according to the present invention, a cyclic reactant represented by general formula (a) of scheme (I) is used, where, [ka] represents a single bond, R is a hydrogen or acyl radical, the acyl radical is a radical of an aliphatic monocarboxylic acid having 2 to 6 carbon atoms, A is a hydrocarbon having 3 to 10 carbon atoms, and all ring carbons of A in cyclic reactant (a) of scheme (I) have at least one hydrogen substituent and / or at least one alkyl substituent.

[0057] In a particularly preferred embodiment of the method according to the present invention, a cyclic reactant represented by general formula (a) of scheme (I) is used, where, [ka] The symbol represents a single bond, where R is -H and A is -CH2-CH2-CH2-, -CH2-C(H)(CH3)-CH2-, -CH2-C(H)(CH2CH3)-CH2-, or -CH2-C(H)(CH2CH2CH3)-CH2-.

[0058] In a more particularly preferred embodiment of the method according to the present invention, a cyclic reactant represented by general formula (a) of scheme (I) is used, where, [ka] ∫ represents a single bond, R is hydrogen, and the concentration of the cyclic reactant (a) is 0.1 to 1 M, preferably 0.1 to 0.7 M, more preferably 0.1 to 0.5 M, even more preferably 0.17 to 0.23 M, and most preferably 0.18 to 0.22 M.

[0059] Equally preferred is an embodiment of the method according to the present invention according to scheme (II).

[0060] [ka]

[0061] During the ceremony, -R 1 , R 2 and R 3These are either the same or different hydrogen atoms or linear or branched alkyl radicals having 1 to 8 carbon atoms, preferably 1 to 5 carbon atoms, preferably R 1 , R 2 and R 3 At least one of them is such an alkyl radical, - Preferably, R 1 , R 2 and R 3 Only one of them is a linear or branched alkyl radical having 1 to 4 carbon atoms, more preferably R 1 and R 3 is hydrogen, R 2 These are linear or branched alkyl radicals having 1 to 4 carbon atoms.

[0062] In a more particularly preferred embodiment of the method according to the present invention, the cyclic reactant (a) is 4-methylcyclohexanol, 4-ethylcyclohexanol, or 4-propylcyclohexanol, and more particularly 4-methylcyclohexanol, 4-ethylcyclohexanol, or 4-n-propylcyclohexanol.

[0063] Advantageously, the method according to the present invention can be carried out in a non-diaphragm electrolytic cell.

[0064] The cathode material used in the method according to the present invention is preferably stainless steel, platinum, or nickel, or a mixture thereof, and more preferably stainless steel.

[0065] The following embodiments further illustrate the present invention, but do not limit its scope. [Brief explanation of the drawing]

[0066] [Figure 1] Figure 1 shows a flow-type electrolytic cell for carrying out the method according to the present invention. [Figure 2]Figure 2 shows a graphical evaluation of the parameter results by plotting the qNMR yield of 3-ethyladipic acid after electrochemical oxidation of 4-ethylcyclohexanol. [Figure 3] Figure 3 shows the change in the qNMR yield of 3-propyladipic acid with respect to the applied charge. [Figure 4] Figure 4 shows the change in the qNMR yield of 3-propyladipic acid with respect to the amount of applied charge, accompanied by the supply of 4-propylcyclohexanone. [Examples]

[0067] General information and methods For chemical products, analytical-grade samples obtained from standard suppliers (TCI, Aldrich, Rotisolv, Fisher Chemical, VWR, Thermos Scientific, Acros, etc.) were used. Solvents were purified by standard methods such as distillation or desalting. Unless otherwise specified, the reaction conditions were atmospheric pressure and room temperature.

[0068] The electrodes used in the reaction were commercially available, with small channels on the inlet and outlet sides, and were made of stainless steel (1.4571) and Recemat® nickel foam. These were compatible with the IKA ElectraSyn flow 6-18 apparatus. For activation, a separate metal plate electrode (6 × 18 cm²) was cut from stainless steel (1.4571) available in the university workshop. A TDK Lambda Genesys 750W / 1500W power supply was used as the galvanostat. The reaction mixture was pumped through an Ismapren hose (size 16) using an Ismatec Reglo Digital Masterflex® peristaltic pump (model: 78018-42). A heating circuit was installed and connected to an IKA WICO CBC 5C cooling / circulation thermostat (model: RN41).

[0069] Melting point measurement: The melting point was measured using an M-565 instrument (Buchi GmbH, Essen, Germany). The heating rate was 1°C / min.

[0070] NMR method: Using a Bruker Avance III 600 NMR spectrometer (Bruker, probe head: 5 mm, TCI-CryoProbe head with Z gradient and ATM), at 25°C, 1H (600 MHz) and 13 The inverse gate spectrum of C151MHz was recorded. The chemical shift (δ) was reported in parts per million (ppm). For quantification, 1,3,5-trimethoxybenzene was used as an internal standard. 13 This was performed by integrating each signal in the C inverse gate spectrum (δ = (55.4 ± 0.02) ppm). The DMSO-d6 signal (δ = 39.52 ppm) was selected as the reference.

[0071] Liquid chromatography: Photodiode array analysis was performed using a Shimadzu DUGA-20A3 instrument equipped with a Knauer C18 column (Eurospher II, 100-5 C18, 150 × 4 mm). The column was adjusted to 25°C and the flow rate to 1 mL / min. The aqueous eluent was buffered with formic acid (0.8 mL / 2.5 L) and stabilized with acetone (5 vol%). The sample was prepared by extracting the carboxylic acid product mixture from the reaction mixture by acid-base extraction with ethyl acetate, drying with MgSO4, and then evaporating the solvent. The product was filtered (using a VWR 13 mm syringe filter with a 0.45 μm PTFE membrane) and dissolved and diluted in acetonitrile (MS quality). This organic solution was analyzed by liquid chromatography.

[0072] High-resolution mass spectra were acquired using a G6545A Q-ToF (Agilent GmbH, Waldbronn, Germany) equipped with a dual AJS electrospray ion source (dual AJS ESI). The MS parameters were as follows: mass range: 80-3200 m / z, scan rate: 1 spectral second. -1Atomizer pressure: 25 psig, Capillary voltage: 3500V, Fragmenter: 50V, Skimmer: 45V, Dry gas temperature: 275℃, Dry gas flow rate: 10 L / min -1 Sheath gas temperature: 350℃, sheath gas flow rate: 10L / min -1 Mass calibration was performed on the day of measurement using an external standard. The mass accuracy of the measurement results was within 5 ppm. Chromatographic separation was performed using a 1260 Infinity II HPLC system (Agilent GmbH, Waldbronn, Germany) equipped with an Agilent EclipsePlus C18 RRHP (2.1 × 50 mm, 2.1 μm) analytical column. This system included a G7111B 1260 quaternary pump, a G7129A 1260 vial sampler, and a G7116A 1260 multi-column thermostat. The eluents were 98% H2O, 2% ACN, 0.05% formic acid (eluent A) and 2% H2O, 98% ACN, 0.05% formic acid (eluent B). Flow rate: 200 μL / min -1 To separate the two components at the specified flow rate, the following gradient elution method was employed: starting with 10% B for 1 minute, linearly increasing to 95% B after 10 minutes, holding at 95% B for 30 minutes, and returning to 10% B after 33 minutes. The column was equilibrated with 10% B and held for 15 minutes until the next measurement. The injection volume was 2 μL. Data was recorded using Agilent MassHunter Workstation LC / MS software version 11.0, and data analysis was performed using Agilent MassHunter Workstation Qualitative Analysis software version 10.0.

[0073] MALDI TOF MS: An Autoflex MALDI TOF mass spectrometer (equipped with smartbeam® II Nd:YAG laser (355nm)) manufactured by Bruker Daltonik GmbH (28359 Bremen Fahrenheitstrasse 4, Germany) was used. Images were measured in linear mode. 2-[(2E)-3-(4-tert-butylphenyl)-2-methylprop-2-enilidene]malononitrile (DCTB) was used as the matrix.

[0074] electrolytic cell The geometric anode surface area is 10⁸ cm². 2 A flow-type electrolytic cell was used (Figure 1). This cell has a modular structure and further consists of a self-supporting frame and a cage for foam electrodes (both with an effective geometric surface area of ​​108 cm²). 2 It features a channel behind the electrode, making it particularly effective for large-scale electrolysis in flow mode. Furthermore, it enables major heat dissipation through the channel behind the electrode, resulting in superior temperature control compared to commercially available small flow electrolytic devices (which can only be adjusted to a specific temperature by the reservoir).

[0075] Figure 1 shows a schematic diagram of the reaction apparatus in a non-diaphragm flow electrolytic cell, in which a stainless steel cathode and a nickel foam anode are in contact with a nickel-plated electrode. The distance between the electrodes was 3 mm. For the cooling circuit, water was used to control the temperature between 25 and 50°C. The reaction mixture was emulsified in an IKA Magic lab mixing unit (IKA-Werke GmbH & Co. KG, Staufen, Germany) equipped with a DR mixing element.

[0076] Activation of nickel anodes: First, an activation solution was prepared containing 0.1 M NiSO4 (aq), 0.1 M NaOAc (aq), and 5 mM NaOH (aq). This activation solution (420 mL) was placed in a polymethyl methacrylate (PMMA) beaker-type tank. A stainless steel electrode (6 × 18 cm) was immersed and connected. Before fully immersing and connecting the nickel foam anode at a distance of 10 mm, it was immersed in or thoroughly rinsed with a 1 M sodium hydroxide solution, and then dried dropwise. 5.0 mA / cm -2 A current density of 9 cm was applied for 30 minutes. -2 This corresponded to the charge. The activation solution was stirred at 300 rpm. Subsequently, the activated dark nickel foam was rinsed with demineralized water. The stainless steel cathode was cleaned by briefly immersing it in dilute sulfuric acid (4M), then rinsed with water and polished with sandpaper (300 grit) until a visually uniform shine was achieved. The tank was then set up again. SEM images showed that the original surface morphology was not completely restored by the cleaning process, but the above activation method was successfully applied to the cleaned nickel foam.

[0077] Performance of flow-type electrolysis: As described above, a commercially available modular IKA ESF 6-18 flow electrolytic apparatus was used. This apparatus is non-diaphragm type and consists of a nickel foam anode (Recemat® RCM-Ni4753.05) connected by a nickel plate and a stainless steel cathode (1.4571), each measuring 6 × 18 cm. 2 A polytetrafluoroethylene (PTFE) spacer (0.4 mm) was used. The nickel foam anode was activated as described above.

[0078] A commercially available IKA magic LAB® mixing unit was connected to an IKA magic PLANT® stirring vessel. An electrolyte containing NaOH(aq)(1M) and each cyclic 4-alkylcyclohexanol reaction product (1) was emulsified in the stirring vessel. This mixing unit, equipped with a high-performance DR mixing element, circulated the liquid to a storage vessel and then returned the liquid to the storage vessel. The flow rate was 12,000 rpm (approximately 70 L / hour). It was supplied from the bottom of an upright flow tank by a peristaltic pump. The output tube was connected to the storage vessel to ensure the removal of generated hydrogen. A Python software control device and a TDK Lambda Genesys galvanostat were used to apply and monitor a specified amount of charge and current density. After electrolysis was complete, the reaction mixture was pumped in the reverse direction. Next, the tank was continuously washed with methyl tert-butyl ether (MTBE, 80 mL) and a 1 M sodium hydroxide solution (80 mL). All fractions were combined and post-processed by liquid-liquid extraction using a 2L perforator.

[0079] First, non-acidic components were extracted from the basic aqueous reaction mixture using MTBE. After acidifying the pH to 1-2, acidic components were extracted with ethyl acetate. The organic fraction was dried with MgSO4 to remove the solvent. The residual acidic fraction was weighed, and the product was extracted. 13 Quantitative analysis was performed by 13C reverse-gate NMR. 1,3,5-trimethoxybenzene (0.1 mmol) was used as an internal standard. Experimental Example 1 (Comparative Example):

[0080] [ka]

[0081] In the flow-type tank described above, an anodic oxidation reaction was carried out from 4-methylcyclohexanol (1') to 3-methyladipic acid (2').

[0082] Oxidation of 4-methylcyclohexanol: In a 100 mL beaker, 4-methylcyclohexanol (1', 10 mmol, c=0.1 M, isomer mixture) was mixed with a 1 M sodium hydroxide solution. The cell was maintained at 50°C using an external IKA-HBC-5 thermostat. The reaction mixture was pumped into the electrolytic cell at a flow rate of 61 mL / min. The applied current density was 5.0 mA / cm². -2 The reaction was set to a total charge of 8.0F. After the reaction, the product mixture was collected, and tert-butyl methyl ether was pumped into the vessel for acid-base extraction. For this purpose, the basic reaction medium was extracted three times with tert-butyl methyl ether (100 mL each time), acidified to pH 1-2 with 4.5 M sulfuric acid, and extracted four times with ethyl acetate (100 mL each time). After drying with MgSO4 and removing the solvent, the product mixture was analyzed by 1H and 13C reverse-gate NMR using 1,3,5-trimethoxybenzene as an internal standard.

[0083] Experimental Example 2: First, 4-ethylcyclohexanol was synthesized using the following method: 100 g of 4-ethylphenol (0.82 mol) was dissolved in 500 mL of methanol, and 10 g of ruthenium / carbon (5% Ru supported by C) was added to a 1 L autoclave. A hydrogen atmosphere (10 bar) was applied. The autoclave temperature was set to 120 °C. The yield of 4-ethylcyclohexanol (1'') was monitored by taking a sample (0.1 mL of reaction medium) once a day. Product formation was monitored by gas chromatography, and the reaction was stopped when no product formation was observed. 4-ethylphenol was purchased from Sigma Aldrich, and ruthenium was purchased from Heraeus Chemicals. 4-ethylcyclohexanol (1'') was synthesized on a 200 g scale, and the isolation yield after vacuum distillation was up to 95%. Next, electrochemical oxidation of 4-ethylcyclohexanol to 3-ethyl adipic acid was carried out according to Scheme 1 below.

[0084] [ka]

[0085] For this oxidation, experimental design screening was applied to parameters such as reaction temperature, flow rate, cyclic reactant concentration, and current density. Here again, a pre-activated nickel foam anode and a V5A stainless steel plate cathode were used. The reaction was carried out in a semistable emulsion of the cyclic reactant and 1M NaOH(aq) because the two liquids are immiscible under standard conditions.

[0086] To perform the screening, a Masterflex® PharMed® BPT system (L / S16, precision tubing) was installed. Pumping was performed using a Masterflex® Ismatec® 78018-42 peristaltic pump. Continuous mixing was performed using an IKA Magic lab / IKA Magic plant system equipped with a DR mixing element (IKA-Werke GmbH & Co. KG, Staufen, Germany). In all experiments, the mixing system was operated at 12,000 rpm (circulation rate ≈ 70 L / hour). -1 The system was operated in a flow electrolytic cell, and an optically semi-stable emulsion was achieved over the period from when it passed through the cell to when it returned to the mixer. The charge was 9F throughout all reactions.

[0087] The reaction mixture was post-processed as follows: After each experiment, the reaction mixture was collected in a vial and tert-butyl methyl ether (50 mL) was passed through the electrolyzer in cycle mode for 1 minute to minimize loss. The same procedure was followed with 1 M sodium hydroxide solution (50 mL). Acid-base extraction was then performed using a Ludwig perforator. Using a small stirrer bar made it easier to achieve high stirrer speeds. It was also necessary to replenish the solvent in the main compartment. The yellow basic reaction mixture was extracted overnight with MTBE. Subsequently, the two phases were separated, and the aqueous layer was acidified to pH 1-2 with 4.5 M H2SO4 (aq). Next, the neutralized crude product was extracted with ethyl acetate in the perforator. The two organic fractions were dried with MgSO4, and after removing the solvent under reduced pressure, the product was analyzed by 13C reverse-gate NMR using 1,3,5-trimethoxybenzene as an internal standard.

[0088] For isolation, the obtained carboxylic acid mixture was analyzed using a Vigreux column for 10 minutes. 0 ~10 -2 The main product was distilled under reduced pressure at millibars at 180-220°C. The remaining yellow substance was removed by recrystallization from heptane. If the ethyl ester of 3-ethyladipic acid was present, the product mixture was dissolved in a 3M sodium hydroxide solution, heated to 80°C, and vigorously stirred for 3 hours. Then, using a sufficiently large separatory funnel, it was extracted with tert-butyl methyl ether (one-third of the aqueous solution volume three times), acidified to pH 2-3 with 4.5M H2SO4 (aq), and extracted with ethyl acetate. The organic fraction was dried over MgSO4, and the solvent was removed to obtain crystals. Higher purity appeared to be obtained by a second recrystallization.

[0089] In the parameter DoE screening, four parameters—cyclic reactant concentration c, reaction temperature T, reaction medium flow rate φ, and current density j—were varied to reproduce the corresponding parameter limits shown in Table 1 below. In addition to the set parameter limits, center point tests were also performed. To confirm the reproducibility of the reaction, all experiments were repeated once, and the reaction order of these 18 chemical experiments was randomized. The reaction time ranged from 0.9 to 2.3 days. The quantitative NMR yield of the target product (2'') was approximately 40%. The maximum isolation yield was 39%. In all reactions reported here, the nickel foam anode was reused, reducing the amount of waste generated.

[0090] Table 1: Parameters for DoE screening. Geometric current density is calculated based on the geometric anode surface area (10⁸ cm²) of the anode foam. 2 This is based on the current value for ). Reaction conditions: 1M NaOH(aq), water, activation current = 7.5mA / cm -2 (geometric current density), activation current = 10Ccm -2 9F. The reaction flow rate φ is the cumulative flow rate through the two tubes. Each parameter has three data points.

[0091] [Table 1]

[0092] It was found that the flow rate and reactant concentration have the greatest impact on the yield of the desired product. -1 Furthermore, when the reactant concentration is low (especially 0.2-0.35 M), it has a positive effect on the yield of 3-ethyladipic acid. The analytical product spectrum for the oxidation reaction of 4-ethylcyclohexanol is shown below.

[0093] [ka]

[0094] Figure 2 shows a graphical evaluation of the parameter results by plotting the qNMR yield of 3-ethyladipic acid (2). The parameters tested were reaction temperature T (25°C, 37.5°C, 50°C) and reaction mixture flow rate φ (10 mL / min). -1 ,30mL / min -1 ,50mL / min -1 ), 4-ethylcyclohexanol concentration c(1)(0.2m, 0.35m, 0.5m), applied reaction current density j(3.0mA / cm²) -2 4.0mA / cm² -2 5.0mA / cm² -2 )

[0095] The screening results showed that a specific combination of the four parameters tested, namely a flow rate of 50 mL / min, was the optimal choice. -1 Reaction temperature 25°C, current density J5.0 mA / cm² -2 It was shown that a reactant concentration of 0.2 mol / L yielded the maximum yield. This allowed the yield of the desired product (2'') to significantly exceed 30%.

[0096] Using these parameters, the maximum quantitative NMR yield of the product was as follows: YqNMR (3-ethyl adipic acid) = 38% YqNMR (3-ethylglutaric acid) = 4% YqNMR (2-ethylglutaric acid) = 4% YqNMR (ethyl succinic acid) = 1%

[0097] After post-treatment, 2'' was isolated in 38% yield. This is the most efficient method of electrochemical synthesis for isolating 2'' reported to date. Characterization of 3-ethyl adipic acid (2'')

[0098] [ka]

[0099] 2'' was electrochemically synthesized from 4-ethylcyclohexanol (6.41 g, 50 mmol, 0.2 M) using the method described above. Product 2'' was obtained as a pale yellow crystalline solid by acid-base extraction, vacuum distillation, and recrystallization from n-heptane (3.31 g, 19 mmol, 30%).

[0100] 1 H NMR (600 MHz, DMSO-d6): δ [ppm] = 12.04 (s, 2H), 2.18 (t, J = 7.9 Hz, 2H), 2.12 (d, J = 6.9 Hz, 2H), 1.68 (hept, J = 6.5 Hz, 1H), 1.57 - 1.42 (m, 2H), 1.33 - 1.21 (m, 2H), 0.81 (t, J = 7.5 Hz, 3H). 13 C NMR (151 MHz, DMSO-d6): δ [ppm] = 174.75, 174.29, 38.07, 35.41, 31.20, 28.17, 25.63, 10.69. Melting point: (47.4~49.8)℃ HRMS(ESI+)m / z:C8H 14 O4+H + The calculated value is 175.0965[M+H + ] + Actual measured value: 175.0965

[0101] Experimental Example 3: In the flow-type tank described above, an anodic oxidation reaction of 4-propylcyclohexanol to 3-propyladipic acid was carried out, and the change in the yield of 3-propyladipic acid during the reaction process was analyzed. Table 2: Parameters for DoE screening. Geometric current density is calculated based on the geometric anode surface area (1225 cm²) of the anode foam. 2 This is based on the current value for ). Reaction conditions: 1M NaOH(aq), water, activation current = 7.5mA / cm -2 (geometric current density), activation current = 5Ccm -28.5F. The reaction flow rate φ is the cumulative flow rate through the two tubes. Each parameter has three data points.

[0102] [Table 2]

[0103] Figure 3 shows the change in the qNMR yield of 3-propyladipic acid with respect to the applied charge. The qNMR yield was analyzed using 1,3,5-trimethoxybenzene as the standard.

[0104] The formation of 3-propyladipic acid was influenced by the formation of 4-propylcyclohexanone. The rate of 3-propyladipic acid formation was 1F and maximum after 4-propylcyclohexanone reached its maximum concentration. The final yield exceeded 30%.

[0105] Subsequently, in order to maintain a constant rate of 3-propyladipic acid production, the reaction conditions were modified to stabilize the concentration of 4-propylcyclohexanone as much as possible. For this purpose, a constant amount of the reactants was supplied in accordance with the rate of 3-propyladipic acid production.

[0106] Surprisingly, a high yield of the desired product was observed here as well. This procedure has a positive effect on yield and also allows for continuous reactions.

[0107] Figure 4 shows the change in the qNMR yield of 3-propyladipic acid with respect to the amount of applied charge, in conjunction with the supply of 4-propylcyclohexanone. [Explanation of symbols]

[0108] 1. Flow-type electrolytic cell Self-standing frame and cage for 2 electrodes 3 Mixer 4 Emulsion 5 Stainless steel electrodes 6. Nickel foam electrode 7 Nickel plate electrodes 8 Cooling circuit 9 Cooling circuit 10 Cooling circuit 11 pumps

Claims

1. Scheme (I): 【Chemistry 1】 (In the formula, [Chemistry 1-2] R represents a single or double bond, and R is present or absent accordingly. R is hydrogen or an acyl radical, and the acyl radical is a radical of an aliphatic monocarboxylic acid having 2 to 8 carbon atoms. A is a hydrocarbon having 3 to 30 carbon atoms, and all ring carbons of A in the cyclic reactant (a) of scheme (I) have at least one hydrogen substituent and / or at least one alkyl substituent. The method involves electrochemically preparing an alkanedicarboxylic acid (b) by a ring-opening oxidation reaction in an emulsion of at least one type of cyclic reactant (a) within an electrolytic cell. The oxidation is carried out using a metal electrode containing at least partially nickel and / or cobalt. A method for continuously supplying the cyclic reactant (a) to the electrolytic cell.

2. The method according to claim 1, wherein no surfactant is added to stabilize the emulsion.

3. The oxidation described above is performed using the following parameters: A reaction temperature of -10 to 60°C, preferably 10 to 50°C, more preferably 10 to 30°C, even more preferably 20 to 27°C, most preferably 24 to 26°C, and / or -20~100mL / min －１ Preferably 20 to 80 mL / min －１ , more preferably 40-60 mL / min －１ Most preferably 45-55 mL / min －１ The reaction medium flow rate, and / or -0.1 to 1 M, preferably 0.1 to 0.7 M, more preferably 0.1 to 0.5 M, even more preferably 0.17 to 0.23 M, most preferably 0.18 to 0.22 M, and / or the concentration of the cyclic reactant (a), and / or -1~10mA / cm －２ Preferably 2 to 8 mA / cm² －２ More preferably 3 to 7 mA / cm² －２ Most preferably 4 to 6 mA / cm² －２ The applied current density is such that, in all cases, the area value is based on the geometric anode surface area, without considering the internal surface area of ​​the bubble. Preferably, the following parameters: A reaction temperature of -25 ± 2.5°C, and / or -50 ± 5 mL / min －１ of the reaction medium flow rate, and / or -0.2 ± 0.02 M concentration of reactant (a), and / or -5.0±0.5mA / cm －２ The applied current density is, in all cases, the area value is based on the geometric anode surface area, without considering the internal surface area of ​​the bubble. The method according to claim 1 or claim 2, performed by [method name].

4. The method according to any one of claims 1 to 3, wherein the cyclic reactant (a) is present in water in the form of an emulsion.

5. The cyclic reactant (a) exists in water in the form of an emulsion. The emulsion contains at least one base, preferably N(R) Ａ ) ４ OH (in the formula, each R Ａ Each of these is independently H or linear or branched C １－４ It is alkyl. ), NaOH, KOH, LiOH, Na ２ CO ３ _K ２ CO ３ and Li ２ CO ３ The method according to any one of claims 1 to 4, comprising at least one base, preferably selected from the group consisting of NaOH and KOH, which is independently selected from the group consisting of the following.

6. In either case, the metal electrode contains 0% to 100% by weight of nickel and 100% to 0% by weight of cobalt, relative to the total content of nickel and cobalt in the electrode, or The method according to any one of claims 1 to 5, wherein in any case, the electrode contains 10% to 100% by weight of nickel and 0% to 90% by weight of iron, based on the total content of nickel and iron.

7. The aforementioned metal electrode is a Ni(O)OH foam electrode, The method according to any one of claims 1 to 6, wherein the Ni(O)OH foamed electrode contains, in any case, nickel as a metal in an amount of at least 80% by weight, preferably at least 85%, 90%, 95%, 98%, or 99% by weight, more preferably at least 99.9% by weight, and most preferably at least 99.99% by weight, relative to the metal content of the Ni(O)OH foamed electrode.

8. The metal electrode is pre-treated by contacting it with a base, preferably at least one inorganic base and / or at least one organic base, before the oxidation is performed. N(R) Ａ ) ４ OH, N(R Ａ ) ４ Acetate, NaOH, sodium acetate, KOH, potassium acetate, LiOH, lithium acetate, Na ２ CO ３ _K ２ CO ３ and Li ２ CO ３ Using one or more bases independently selected from the group consisting of, more preferably selected from the group consisting of NaOH and KOH, The aforementioned N(R) Ａ ) ４ OH and the N(R) Ａ ) ４ In acetate, each R Ａ Each of these is independently H or linear or branched C １－４ The method according to any one of claims 1 to 7, wherein the alkyl group is alkyl.

9. The method according to claim 8, wherein the base is used as an aqueous solution, and in particular the concentration of the base is 10 mM to 10 M, preferably 0.2 to 5 M, more preferably 0.5 to 1.5 M, most preferably 1 ± 0.1 M, and / or the metal electrode is brought into contact with the base at a temperature of 10 to 40°C, preferably 18 to 27°C.

10. The method according to any one of claims 1 to 9, wherein, prior to the oxidation, the metal electrode is electrochemically activated, preferably without polarity reversal.

11. The electrochemical activation is performed using one or more salts of nickel and / or cobalt, and optionally iron, more preferably Ni ２ SO ４ and / or CoSO ４ This is done using a salt selected from the group consisting of the following: The salt or a plurality of the salts are present in an aqueous basic solution. One or more bases, preferably one base, N(R) Ａ ) ４ OH, N(R Ａ ) ４ Acetate, NaOH, sodium acetate, KOH, potassium acetate, LiOH, lithium acetate, Na ２ CO ３ _K ２ CO ３ and Li ２ CO ３ Each is independently selected from the group consisting of, and more preferably selected from the group consisting of NaOH and KOH, The aforementioned N(R) Ａ ) ４ OH and N(R) Ａ ) ４ In acetate, each R Ａ Each of these is independently H or linear or branched C １－４ The method according to claim 9, wherein the alkyl group is used.

12. The method according to claim 10 or claim 11, wherein the metal electrode is electrochemically activated at a temperature of 10 to 40°C, preferably 18 to 27°C.

13. In the above formula (a) of scheme (I), [Chemistry 1-2] represents a single bond, R is hydrogen or an acyl radical, the acyl radical is a radical of an aliphatic monocarboxylic acid having 2 to 6 carbon atoms, A is a hydrocarbon having 3 to 10 carbon atoms, and all ring carbons of A in the cyclic reactant (a) of scheme (I) have at least one hydrogen substituent and / or at least one alkyl substituent. Preferably, [Chemistry 1-2] represents a single bond, R is hydrogen or an acyl radical, the acyl radical is a radical of an aliphatic monocarboxylic acid having 2 to 4 carbon atoms, A is a hydrocarbon having 3 to 9 carbon atoms, and all ring carbons of A in the cyclic reactant (a) of scheme (I) have at least one hydrogen substituent and / or at least one alkyl substituent. more, [Chemistry 1-2] The symbol represents a single bond, where R is -H and A is -CH. ２ -CH ２ -CH ２ -ien-CH ２ -C(H)(CH ３ ) - CH ２ -ien-CH ２ -C(H)(CH ２ CH ３ ) - CH ２ - or -CH ２ -C(H)(CH ２ CH ２ CH ３ ) - CH ２ - The method according to any one of claims 1 to 12. 【Request Item 14】 【Chemistry 1-2】 The method according to any one of claims 1 to 13, wherein is a single bond, R is hydrogen, and the concentration of the cyclic reactant (a) is 0.1 to 1 M, preferably 0.1 to 0.5 M, more preferably 0.17 to 0.23 M, and most preferably 0.18 to 0.22 M.

15. Scheme (II): 【Chemistry 2】 (In the formula, -R １ , R ２ and R ３ These are either the same or different hydrogen atoms or linear or branched alkyl radicals having 1 to 8 carbon atoms, preferably 1 to 5 carbon atoms, preferably R １ , R ２ and R ３ At least one of them is such an alkyl radical, - Preferably, R １ , R ２ and R ３ Only one of them is a linear or branched alkyl radical having 1 to 4 carbon atoms, more preferably R １ and R ３ is hydrogen, R ２ (These are linear or branched alkyl radicals having 1 to 4 carbon atoms.) The method according to any one of claims 1 to 14, carried out in accordance with the following:

16. The method according to any one of claims 1 to 15, wherein the cyclic reactant (a) is 4-methylcyclohexanol, 4-ethylcyclohexanol, or 4-propylcyclohexanol, preferably 4-methylcyclohexanol, 4-ethylcyclohexanol, or 4-n-propylcyclohexanol.

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