Method for producing deuterium compounds

Abstract

This invention provides a method for producing deuterium compounds that can be obtained efficiently. [Solution] A method for producing a deuterium compound includes a deuteration step of contacting a compound having at least one of an aromatic ring and a heterocycle with a deuterium source in the presence of a solvent and a catalyst, wherein the solvent includes at least one of 2-propanol and hexafluoro-2-propanol, the catalyst includes iridium, and the deuterium source includes at least one of heavy water and a deuteration solvent.

Description

Technical Field

[0001] The present invention relates to a method for producing a deuterium compound.

Background Art

[0002] A deuterium atom is a kind of stable isotope of a hydrogen atom and has physical properties different from those of a hydrogen atom. Therefore, a deuterated compound not only has physical properties different from those of a normal compound but may also exhibit different chemical reactivity. Specifically, by deuterating a compound, it may be possible to endow the compound with new functions. Therefore, the application of deuterated compounds to various functional materials such as electronic materials and organic EL materials is expected.

[0003] Patent Document 1 discloses a method for deuterating an aromatic ring. This method for deuterating an aromatic ring is carried out using an activated catalyst. In this method for deuterating an aromatic ring, a compound having an aromatic ring is reacted with a deuterium source in the coexistence of a catalyst selected from an activated platinum catalyst, rhodium catalyst, ruthenium catalyst, nickel catalyst, and cobalt catalyst to deuterate the compound having an aromatic ring.

[0004] In the method for deuterating an aromatic ring disclosed in Patent Document 1, the activated catalyst selected from a platinum catalyst, rhodium catalyst, ruthenium catalyst, nickel catalyst, and cobalt catalyst is said to be one activated by contacting a so-called platinum catalyst, rhodium catalyst, ruthenium catalyst, nickel catalyst, or cobalt catalyst with hydrogen gas or deuterium gas.

[0005] In the method for deuterating aromatic rings disclosed in Patent Document 1, an activated catalyst may be used, which may be an unactivated catalyst that has been activated beforehand. Furthermore, if hydrogen gas or deuterium gas is present in the reaction system, an unactivated catalyst can also be used in the same way. It is disclosed that hydrogen gas or deuterium gas can be present in the reaction system by passing hydrogen gas or deuterium gas directly through the reaction solution, or by replacing the sealed deuterating reaction system of the present invention with hydrogen gas or deuterium gas.

[0006] Patent Document 1 discloses a method in which an aromatic ring compound such as phenol, platinum carbon or potassium platinum chloride as a catalyst, and heavy water are suspended, the sealed reaction system is hydrogen-purged, and then the reaction is carried out in an oil bath at 160°C for about 24 hours (i.e., in a batch manner) to produce deuterated compounds, with a deuterated rate of 65 to 99%.

[0007] Patent Document 2 discloses a method for deuterating aromatic compounds. In this method, a deuterium source selected from heavy water and a deuterating solvent is brought into contact with the aromatic compound in the presence of at least one solution selected from 2-propanol, 2-butanol, and 3-pentanol, and a catalyst selected from a platinum catalyst, a rhodium catalyst, and a ruthenium catalyst. This method allows for efficient deuterating of the hydrogen in the target aromatic compound without pre-activating the catalyst with hydrogen gas or deuterium gas, or without introducing hydrogen gas or deuterium gas into the reaction system.

[0008] In the deuteration method for aromatic compounds disclosed in Patent Document 2, the reaction time for the deuteration reaction is usually 1 to 50 hours. Patent Document 2 discloses, as an example, a case in which various aromatic compounds are reacted in a test tube (i.e., in a batch process) for a reaction time ranging from 3 to 24 hours with an aromatic compound such as biphenyl and a platinum catalyst such as platinum carbon, and deuterated with heavy water, resulting in a deuteration rate of 9% to 99%. [Prior art documents] [Patent Documents]

[0009] [Patent Document 1] International Publication No. 2004 / 011400 [Patent Document 2] Japanese Patent Publication No. 2014-111561 [Overview of the project] [Problems that the invention aims to solve]

[0010] In conventional techniques, producing deuterium compounds by deuterating compounds such as those containing aromatic rings required long reaction times of 24 hours or batch reaction control (see, for example, Patent Documents 1 and 2). As a result, it was sometimes not possible to efficiently obtain deuterium compounds.

[0011] This invention has been made in view of the above circumstances, and its purpose is to provide a method for producing deuterium compounds that can be obtained efficiently. [Means for solving the problem]

[0012] The method for producing a deuterium compound according to the present invention, in order to achieve the above objective, The process includes a deuteration step in which a compound having at least one of an aromatic ring and a heterocycle is brought into contact with a deuterium source in the presence of a solvent and a catalyst. The solvent comprises at least one of 2-propanol and hexafluoro-2-propanol. The catalyst contains iridium, The deuterium source includes at least one of heavy water and a deuterating solvent. [Effects of the Invention]

[0013] According to this disclosure, it is possible to provide a method for producing deuterium compounds that can be obtained efficiently. [Brief explanation of the drawing]

[0014] [Figure 1] It is a diagram for explaining the configuration of the reaction apparatus used in the examples. [Figure 2] It is a diagram for explaining the configuration of another reaction apparatus used in the examples.

Mode for Carrying Out the Invention

[0015] A method for producing a deuterium compound according to an embodiment of the present invention will be described.

[0016] First, an overview of the method for producing a deuterium compound according to this embodiment will be described.

[0017] The method for producing a deuterium compound according to this embodiment includes a deuteration step of contacting a compound having at least one of an aromatic ring and a heterocyclic ring with a deuterium source in the coexistence of a solvent and a catalyst. The solvent contains at least one of 2-propanol (IPA) and hexafluoro-2-propanol (HFIP), the catalyst contains iridium, and as the deuterium source, it contains at least one of heavy water and a deuterated solvent.

[0018] In the method for producing a deuterium compound according to this embodiment, a deuterium compound can be efficiently obtained.

[0019] Specifically, in the method for producing a deuterium compound according to this embodiment, due to the catalytic action of iridium, hydrogen gas or deuterium gas is generated from a solvent containing at least one of 2-propanol and hexafluoro-2-propanol and a deuterium source containing at least one of heavy water and a deuterated solvent. Therefore, hydrogen gas or deuterium gas is supplied into the reaction system of the deuteration reaction without introducing hydrogen gas or deuterium gas from outside the reaction system. Thus, an efficient deuteration reaction can be carried out without requiring an additional step of adding hydrogen gas or deuterium gas from outside the reaction system and without requiring a prior catalyst activation step.

[0020] Hereinafter, the method for producing a deuterium compound according to this embodiment will be described in detail.

[0021] As described above, in the method for producing a deuterium compound according to this embodiment, a step is performed in which a compound having an aromatic ring or a heterocyclic ring (hereinafter sometimes referred to as an aromatic compound or the like) and a deuterium source are brought into contact with each other in the coexistence of a solvent and a catalyst, and a deuterium compound obtained by deuterating the compound having an aromatic ring or a heterocyclic ring is obtained.

[0022] <{ The aromatic compound or the like is not particularly limited as long as it is a compound having light hydrogen (hydrogen with a mass number of 1) and at least one ring structure selected from the group consisting of an aromatic ring and a heterocyclic ring, that is, a compound having at least one of an aromatic ring and a heterocyclic ring. The aromatic compound or the like may be a compound having only one of an aromatic ring and a heterocyclic ring, or may be a compound having both an aromatic ring and a heterocyclic ring. Further, the number of ring structures contained in the compound may be one or two or more.

[0023] In addition, in the aromatic ring of the compound, the number of carbon atoms constituting one ring skeleton is not particularly limited, but is preferably 5 or more and 7 or less, more preferably 5 or 6, and particularly preferably 6.

[0024] Compounds having a light hydrogen atom and an aromatic ring include, for example, benzene, toluene, o-xylene, m-xylene, p-xylene, phenol, o-cresol, m-cresol, p-cresol, pyrocatechol, resorcinol, hydroquinone, naphthalene, anthracene, phenanthrene, pyrene, perylene, 1-naphthol, 2-naphthol, biphenyl, azulene, 1-antrol, 2-antrol, 9-antrol, and 1-phenantrol. Examples include 2-phenanthol, 3-phenanthol, 4-phenanthol, 9-phenanthol, aniline, diphenylamine, 2,6-dimethylaniline, benzidine, benzoic acid, salicylic acid, 1-naphthoic acid, 2-naphthoic acid, phthalic acid, isophthalic acid, terephthalic acid, benzaldehyde, salicylic acid, 1-naphthaldehyde, 2-naphthaldehyde, phthalaldehyde, isophthalaldehyde, terephthalaldehyde, etc.

[0025] The heterocycle of a compound is one in which a heteroatom is present in the ring skeleton. The heteroatom is preferably an oxygen atom, nitrogen atom, sulfur atom, phosphorus atom, or silicon atom, with nitrogen or sulfur atom being more preferred. The heterocycle may be aromatic or non-aromatic, but aromatic is preferred.

[0026] In a compound's heterocycle, the number of heteroatoms in a single ring skeleton is not particularly limited, depending on the total number of atoms constituting the ring skeleton, but is preferably 1 to 3, and more preferably 1 or 2. If there are multiple heteroatoms in a single ring skeleton, these multiple heteroatoms may all be of the same type, some may be of the same type, or all may be of different types. If a single ring skeleton contains multiple types of heteroatoms, the combination is not particularly limited, but a combination of nitrogen atoms and sulfur atoms is preferred. The compound's heterocycle may be monocyclic or polycyclic, but if it is polycyclic, it is preferably bicyclic or tricyclic.

[0027] Examples of compounds containing a light hydrogen atom and a heterocycle include pyrrole, furan, thiophene, imidazole, 1-methylimidazole, 2-methylimidazole, 1,2-dimethylimidazole, 2-methyl-5-nitroimidazole, 1,2-dimethyl-5-nitroimidazole, 2-methyl-5-nitroimidazole-1-ethanol, pyrazole, oxazole, isoxazole, thiazole, isothiazole, and 1,2,3-triazole. Examples include 1,2,4-triazole, pyridine, pyrazine, pyridazine, pyrimidine, 2H-pyran, 4H-pyran, piperidine, piperazine, morpholine, quinoline, isoquinoline, purine, indole, benzimidazole, 2-hydroxybenzimidazole, 2-aminobenzimidazole, benzothiophene, phenazine, phenothiazine, nicotinic acid, isonicotinic acid, nicotinaldehyde, isonicotinaldehyde, etc.

[0028] Compounds having a light hydrogen atom and an aromatic ring, and compounds having a light hydrogen atom and a heterocycle, may be compounds in which at least one hydrogen atom of the compounds specifically exemplified above is substituted with a substituent. The number of hydrogen atoms substituted with substituents depends on the type of aromatic ring or heterocycle, but is preferably 1 to 3. The substituent is not particularly limited as long as it does not hinder the effects of the present invention. Specifically, examples of substituents include alkyl groups, alkenyl groups, alkynyl groups, aryl groups, arylalkyl groups, alkoxy groups, aryloxy groups, alkoxyalkyl groups, aryloxyalkyl groups, alkoxycarbonylalkyl groups, alkoxycarbonyl groups, aryloxycarbonyl groups, alkylcarbonyloxyalkyl groups, alkylcarbonyloxy groups, arylcarbonyloxy groups, hydroxyalkyl groups, hydroxyaryl groups, hydroxyl groups, carboxyl groups, amino groups, cyano groups, nitro groups, and halogen atoms.

[0029] Compounds having at least one of a light hydrogen atom, an aromatic ring, and a heterocycle may, for example, be compounds obtained by removing hydrogen atoms from the compounds having a light hydrogen atom and an aromatic ring as specifically exemplified above, compounds obtained by removing hydrogen atoms from the compounds having a light hydrogen atom and a heterocycle, or compounds obtained by removing hydrogen atoms from a compound having a light hydrogen atom and an aromatic ring and compounds obtained by removing hydrogen atoms from a compound having a light hydrogen atom and a heterocycle, and these may have a structure in which the atoms from which hydrogen atoms have been removed are bonded to each other. The combination of compounds that are bonded to each other is not particularly limited and can be selected from the group consisting of, for example, compounds having only an aromatic ring, compounds having only a heterocycle, and compounds having both an aromatic ring and a heterocycle. Furthermore, the number of the above compounds that are bonded is not particularly limited, but it is preferably 2 or 3, and more preferably 2. Examples of such compounds include 2-(4-thiazoyl)benzimidazole, 1-phenylisoquinoline, 1-phenylpyrazole, p-tolylpyridine, and phenylpyridine.

[0030] The solvent used for deuteration (hereinafter sometimes referred to as the reaction solvent) is a solvent containing at least one selected from 2-propanol and hexafluoro-2-propanol, that is, a solvent containing at least one of 2-propanol and hexafluoro-2-propanol.

[0031] The reaction solvent may be a solvent containing (or using in combination) 2-propanol and hexafluoro-2-propanol. When 2-propanol and hexafluoro-2-propanol are used together as the reaction solvent, the ratio of these solvents can be appropriately selected depending on the purpose, for example, depending on the solubility of the aromatic compound to be deuterated.

[0032] The reaction solvent may contain solvents other than 2-propanol and hexafluoro-2-propanol. By reducing the proportion of 2-propanol and hexafluoro-2-propanol in the solvent, it may be possible to increase the proportion of deuterium atoms in the deuteration reaction system. Since 2-propanol and hexafluoro-2-propanol have a free proton, which is a light hydrogen atom, in their hydroxyl groups, the presence of these solvents reduces the proportion of deuterium atoms in the deuteration reaction system. Therefore, by reducing the proportion of 2-propanol and hexafluoro-2-propanol in the reaction solvent, it may be possible to increase the proportion of deuterium atoms in the deuteration reaction system and thereby increase the deuteration rate of aromatic compounds, etc., obtained as a result of the deuteration reaction.

[0033] Other reaction solvents besides 2-propanol and hexafluoro-2-propanol may include, preferably, hydrocarbon solvents such as n-hexane, n-heptane, n-octane, n-nonane, n-decane, cyclohexane, cycloheptane, cyclooctane, cyclononane, and cyclodecane; ether solvents such as diethyl ether, diisopropyl ether, and tetrahydrofuran; ester solvents such as methyl acetate, ethyl acetate, and isopropyl acetate; and amide solvents such as N,N-dimethylformamide and N,N-dimethylacetamide. Ethyl acetate is more preferred, but solvents may be selected as appropriate depending on the solubility of aromatic compounds, etc.

[0034] A deuterium source is a molecule (including compounds) or ion that supplies deuterium to the reaction system. Deuterium is a stable isotope of hydrogen with a mass number of 2, and is deuterium (D or 2 This is represented by the letter H.

[0035] Examples of deuterium sources include heavy water or deuterated solvents.

[0036] As a deuterium source, heavy water is preferable considering cost and availability, but any deuterated solvent (deuterated solvent) such as a compound having deuterated free protons, such as deuterated methanol, or a deuterated aromatic compound, such as deuterated benzene, can be used.

[0037] When heavy water is used as a deuterium source, the purity of the heavy water is not particularly limited, but preferably 90 atom% or higher, more preferably 95 atom% or higher, and especially preferably 99 atom% or higher can be used.

[0038] The catalyst used contains at least iridium. The iridium in the catalyst may be in metallic form or in the form of an iridium-containing compound. This allows for the deuterating of a compound having at least one of an aromatic ring and a heterocycle by contacting an aromatic compound with a deuterium source in the presence of a reaction solvent and a catalyst, while simultaneously generating hydrogen gas or deuterium gas from the solvent containing the deuterium source. More specifically, by using a catalyst containing at least iridium, hydrogen gas or deuterium gas can be generated from the solvent containing the deuterium source during the deuterating process, thereby promoting deuterating and efficiently obtaining a deuterium compound. Note that the meaning of hydrogen gas or deuterium gas includes the case of at least one of hydrogen gas and deuterium gas, and the case of hydrogen gas and deuterium gas.

[0039] The catalyst may include, along with iridium, known metals belonging to groups 3 to 11 (i.e., transition metals) that have catalytic function in the deuteration reaction. The catalyst may contain one or more transition metals other than iridium. When the catalyst contains two or more transition metals other than iridium, the combination and ratio can be appropriately selected depending on the purpose. The transition metals contained in the catalyst may be in metallic form or in the form of a compound containing transition metals. Further inclusion of transition metals in the catalyst further promotes deuteration during the deuteration process, allowing for efficient acquisition of deuterium compounds.

[0040] The transition metals other than iridium included in the catalyst are preferably platinum, palladium, rhodium, and ruthenium, with platinum and palladium being particularly preferred.

[0041] In other words, the catalyst may contain, along with iridium, at least one platinum group metal selected from platinum, palladium, rhodium, and ruthenium. The platinum group metals contained in the catalyst may be in metallic form or in the form of compounds containing these metals. Further inclusion of these platinum group metals in the catalyst further promotes deuteration during the deuteration process, allowing for more efficient acquisition of deuterium compounds.

[0042] The catalyst may be a co-supported catalyst of iridium and the platinum group metal described above. In this embodiment, a supported catalyst refers to one in which iridium and the platinum group metal are supported on a common carrier.

[0043] The catalyst support can be a support generally used in immobilized catalysts on which transition metals (including platinum group metals) are supported. The support may be, for example, activated alumina, activated carbon, silica, ceria, or a resin polymer. Activated alumina is preferred as the support.

[0044] While the specific shape of the reaction vessel or reaction tube in the deuteration process is not specified, an extrusion flow reactor (tubular reactor, PFR, so-called flow reactor) is preferred because it allows for a smaller reactor size, a shorter reaction time, and efficient acquisition of deuterium compounds.

[0045] The preferred apparatus configuration and operation are described below, using the example of a case where the reactor in the deuteration process is an extrusion-flow reactor with a reaction tube.

[0046] A cylindrical container (column) may be used as the reaction tube. The reaction tube may be packed with the catalyst described above (for example, a co-supported catalyst consisting of iridium and platinum). Hereafter, the reaction tube packed with the catalyst will be referred to as a reaction column.

[0047] By passing a fluid containing a reaction solvent in which aromatic compounds, etc., are dissolved (a solution obtained by dissolving aromatic compounds, etc., in a reaction solvent) and a deuterium source (heavy water, for example) through this reaction column (hereinafter referred to as the raw material solution), a reaction field for the deuteration reaction can be constructed.

[0048] The deuteration reaction can be carried out by heating the raw material solution supplied to the reaction column. The reaction temperature of the deuteration reaction (i.e., the temperature at which the raw material solution is heated) can be appropriately adjusted considering the type of substrate contained in the aromatic compound, the concentration of the raw material solution, etc., but it is preferably 40°C to 250°C, and more preferably 100°C to 180°C.

[0049] The reaction apparatus preferably has a heating mechanism that heats the reaction column to heat the raw material solution supplied to the reaction column. Heating the raw material solution promotes the deuteration reaction. The heating mechanism can be any heat source or heating method that allows the temperature to be set within a desired range. For example, a heating method using an oil bath, a heating method using a tubular furnace, or a heating method using microwave irradiation can be selected.

[0050] Furthermore, it is preferable that a pressure control valve (a so-called back pressure valve) be provided in the downstream channel of the reaction column (the channel leading to the outlet of the reaction column) to maintain the pressure inside the reaction column, which is the reaction field (so-called back pressure, hereafter sometimes referred to as reaction pressure), at or above a certain pressure.

[0051] By installing a back pressure valve and maintaining the reaction pressure above a certain level, the generation of bubbles (vaporization) when the raw material solution is heated in the reaction column (for example, when the solvent in the raw material solution reaches a temperature above its boiling point at atmospheric pressure) is suppressed. This reduces the residence time of the fluid inside the reaction column and the resulting shortening of the reaction time, thereby allowing the deuteration reaction to be sufficiently promoted.

[0052] By installing a back pressure valve to maintain the reaction pressure above a certain level, the hydrogen and deuterium gases produced by the catalytic action of iridium dissolve immediately into the reaction solvent, contributing to the acceleration of deuteration.

[0053] Furthermore, by providing a back pressure valve and maintaining the reaction pressure above a certain level, the precipitation of aromatic compounds in the reaction column can be suppressed when using aromatic compounds with low solubility. More specifically, when some of the solvent in the raw material solution vaporizes, aromatic compounds tend to precipitate from the raw material solution, and such precipitation can cause blockage of the reaction column. Therefore, by providing a back pressure valve and maintaining the reaction pressure above a certain level, the vaporization of the solvent in the raw material solution can be suppressed, thereby preventing the precipitation of aromatic compounds and the resulting blockage of the reaction column.

[0054] The reaction pressure is preferably adjusted to be above atmospheric pressure, for example, preferably between 0.5 MPa and 3 MPa in gauge pressure, and more preferably between 1 MPa and 2 MPa.

[0055] By raising the reaction pressure above the lower limit mentioned above, the vaporization of the solvent in the raw material solution is suppressed, as described above. At the same time, the deuterium gas generated in the deuteration reaction system becomes more easily soluble in the solvent, which further promotes the deuteration reaction, resulting in higher reaction efficiency and a shorter reaction time.

[0056] Furthermore, by keeping the reaction pressure below the above upper limit, a high level of effectiveness in suppressing the decomposition of substrates and deuterium compounds contained in aromatic compounds, etc., can be obtained. In addition, if the reaction pressure is below the above upper limit, a reactor with high pressure resistance becomes unnecessary, making it possible to produce the target product at a low cost.

[0057] The reaction column is preferably airtight in all parts except the inlet and outlet. "Airtight" means that it is tightly closed without any gaps, and "high airtightness" means that it can maintain this tightly closed state without gaps well.

[0058] The residence time of the raw material solution in the reaction column can be adjusted as appropriate, taking into account the type of substrate contained in the aromatic compound, the concentration of the raw material solution, the reaction temperature, etc., but it is preferably 10 seconds to 600 seconds, more preferably 60 seconds to 300 seconds, and particularly preferably 100 seconds to 200 seconds. The residence time of the raw material solution in the reaction column may be adjusted by the dimensions of the reaction tube, the type and output of the pump or pump mechanism used for liquid delivery.

[0059] In a deuteration reaction, the amount of the starting material solution supplied to the reaction column and the proportion (concentration) of each component in the starting material solution can be appropriately adjusted considering the type of aromatic compound, the target deuteration rate, etc. For example, the proportion of heavy water in the starting material solution can be set so that the proportion of deuterium in the total amount of deuterium and light hydrogen contributing to the deuteration reaction in the reaction system, including aromatic compounds, is equal to or greater than the target deuteration rate.

[0060] The proportion (concentration) of each component in the raw material solution may be adjusted by preparing the raw material solution in a batch manner, or by continuously mixing each component using a continuous mixer (e.g., a micromixer).

[0061] The materials used to form the reaction column and the flow channel piping connected to the reaction column are not particularly limited, as long as they are not corroded by heavy water and organic solvents. Suitable materials for forming the reaction column and the flow channel piping connected to the reaction column include, for example, metal alloys such as stainless steel, resins such as fluororesin (e.g., PFTF), borosilicate glass, and quartz tubes.

[0062] The reaction apparatus may have a pump or pump mechanism (hereinafter referred to as "pump, etc.") used for transporting the raw material solution. The pump, etc. used for transporting the raw material solution is not particularly limited, and any industrially usable pump can be appropriately selected. It is preferable that the pump, etc. does not generate pulsation during transport. Specific examples of pumps, etc. include plunger pumps, gear pumps, rotary pumps, and diaphragm pumps.

[0063] The components of the reaction apparatus other than the reaction column, heating mechanism, back pressure valve, and pump (hereinafter referred to as peripheral equipment) are not particularly limited. Peripheral equipment can be appropriately selected according to the purpose. Examples of peripheral equipment include sensors and tanks for storing the manufactured deuterium compounds (deuterated compounds). [Examples]

[0064] The method for producing the deuterium compound according to this embodiment will be described below based on the examples.

[0065] (Example 1) In Example 1, a deuteration reaction (deuteration step) was carried out using the reaction apparatus 100 shown in Figure 1 to deuterate 1-naphthol, such as an aromatic compound.

[0066] The catalyst used was a supported catalyst consisting of iridium (Ir) only, supported on a θ-alumina powder carrier (model: JRC-ALO-10) manufactured by Nippon Light Metal Co., Ltd. The amount of iridium (Ir) supported in the supported catalyst was 5.0 wt%. Therefore, no transition metals other than iridium (Ir) were supported in this supported catalyst, and the ratio (weight ratio, hereinafter referred to as the support ratio) of the amount of iridium supported to the amount of other transition metals supported in this supported catalyst was 1:0.

[0067] The raw material solution was prepared according to the following formula. 2-propanol (IPA) was used as the reaction solvent. Heavy water was used as the deuterium source.

[0068] The raw material solution was prepared by measuring the reaction solvent (IPA) and the deuterium source in a mixing ratio of 3:7 (3:7), and by mixing and dissolving them so that the concentration of aromatic compounds, etc., in the raw material solution was 0.1 M.

[0069] The reaction apparatus 100 comprises a reaction column 2 filled with catalyst and supplied with a raw material solution, a liquid delivery pump 1 that supplies the raw material solution to the reaction column 2, a back pressure valve 3 that adjusts the back pressure of the reaction column 2, and a reaction solution receiving flask 4 that stores the reaction solution, which is the post-reaction solution discharged from the reaction column 2. The liquid delivery pump 1, the reaction column 2, the back pressure valve 3, and the reaction solution receiving flask 4 are connected by piping in this order.

[0070] In the reaction apparatus 100, a raw material solution, which is a mixture of a solution in which aromatic compounds etc. are dissolved in a reaction solvent and heavy water as a deuterium source, is passed through a reaction column 2 packed with a catalyst to bring the aromatic compounds etc. into contact with the deuterium source.

[0071] The liquid transfer pump 1 draws up the raw material solution from a raw material container (not shown) that stores the raw material solution and supplies it to the reaction column 2. A HARBARD syringe pump (model: PHD ULTRA H70-3005) was used as the liquid transfer pump 1.

[0072] For reaction column 2, a cylindrical container made of stainless steel (SUS304) with an outer diameter of 6.45 mm, an inner diameter of 4.45 mm, and a length of 50 mm was used, which had high airtightness except for the inlet and outlet. In other words, in this embodiment, the airtightness of the reaction system is ensured (airtightness of the reaction system: Yes).

[0073] 0.75 g of the supported catalyst was packed into reaction column 2 and immersed in a 100°C oil bath (Yamato Scientific Co., Ltd., Model: BO500). In other words, the reaction temperature in this example was set to 100°C.

[0074] Reaction column 2 was used as a so-called flow reactor. The supply rate of the raw material solution continuously supplied to reaction column 2 and the pressure inside reaction column 2 (back pressure, reaction pressure) were adjusted to 0.1 mL / min and 0.5 MPa by adjusting the output of the liquid delivery pump 1 and the opening of the back pressure valve 3.

[0075] Table 1 shows the conditions for Example 1 described above.

[0076] [Table 1]

[0077] The deuteration reaction was carried out according to the conditions described above, and the reaction solution was collected in reaction solution receiving flask 4. During the deuteration reaction, the generation of bubbles, which are thought to be hydrogen and deuterium gases, was observed in reaction column 2. However, no vaporization of the solvent was observed during the deuteration reaction.

[0078] The deuterium compounds contained in the reaction solution were identified by NMR (nuclear magnetic resonance) analysis as follows.

[0079] A nuclear magnetic resonance spectrometer (JEOL Ltd., model: JNM-ECS400) was used for NMR analysis.

[0080] First, regarding the undeuterated sample (aromatic compounds, etc.) and the deuterated sample (deuterated compounds contained in the reaction solution), 1 By measuring 1H-NMR, we confirmed that deuteration had progressed, as peaks observed in the non-deuterated samples disappeared or were significantly reduced in the deuterated samples.

[0081] The NMR measurement method and the deuteration rate calculation method were performed as follows: The sample (deuterium compound contained in the reaction solution) was dissolved using an NMR solvent containing an internal standard substance, 1 1H-NMR measurements were performed. The deuterated fraction (average deuterated fraction) of the aromatic ring was then calculated based on the integrated value of the proton peak of the internal standard or intramolecular standard site.

[0082] The deuteration rate in this example was 58%.

[0083] The yield was calculated by thoroughly removing the solvent components (including heavy water) from the reaction solution using a rotary evaporator under reduced pressure, and then measuring the weight of the residue. Specifically, the yield was calculated based on the weight of the aromatic compounds used in preparing the raw material solution and the weight of the residue. The formula used was: Yield (%) = Weight of Residue / Weight of Aromatic Compounds × 100.

[0084] The yield in this embodiment was 99% (hereinafter sometimes referred to as ">99%").

[0085] Thus, by using iridium as a catalyst, efficient deuteration of aromatic compounds and the like was achieved. Specifically, continuous deuteration was achieved without requiring long residence times, and the operation of introducing hydrogen gas or deuterium gas from outside the reaction system was eliminated. Furthermore, the step of activating the catalyst was also eliminated. This is thought to be because, during the deuteration reaction (deuteration step), hydrogen gas or deuterium gas was generated from the solvent (raw material solution) containing the deuterium source, thereby promoting the deuteration of aromatic compounds and the like, and efficiently obtaining deuterized compounds such as aromatic compounds.

[0086] The evaluation results (yield and deuteration rate) are shown in Table 1.

[0087] Examples 2-10, as shown in Table 1, differed from Example 1 in that they used a supported catalyst (co-supported catalyst) in which a transition metal other than iridium was supported on the support along with iridium. In each of these examples, one or more of the following were different from Example 1: the amount of iridium (Ir) supported, the type of transition metal other than iridium supported on the support along with iridium, the amount of the transition metal other than iridium supported, and the support ratio, while all other aspects remained the same as in Example 1. In Examples 5-8, palladium (Pd), rhodium (Rh), ruthenium (Ru), platinum, and palladium (Pt / Pd) were used as the transition metal other than iridium in that order. The evaluation results of these examples are also shown in Table 1.

[0088] Example 11 differs from Example 3 in that the type of aromatic compound, etc., was 2-hydroxycarbazole, as shown in Table 1, but otherwise it was the same as Example 3. The evaluation results of this example are also shown in Table 1.

[0089] Examples 12-14 differ from Example 3 in that they used hexafluoro-2-propanol (HFIP) or a solvent mixture of 2-propanol (IPA) and ethyl acetate as the reaction solvent, as shown in Table 1, and that the deuteration reaction was carried out using a different reactor, Reactor 200, as shown in Figure 2, from Reactor 100. Otherwise, they were the same as Example 3.

[0090] The reaction apparatus 200 differs from the reaction apparatus 100 in that it has two liquid transfer pumps 11 and 12 arranged in parallel as liquid transfer pumps 1, and a micromixer 5 is positioned between the liquid transfer pumps 11 and 12 and the reaction column 2, but otherwise it is the same as the reaction apparatus 100.

[0091] In the reaction apparatus 200, the first liquid supplied from the liquid transfer pump 11 and the second liquid supplied from the liquid transfer pump 12 are continuously supplied to the micromixer 5 and continuously mixed in the micromixer 5 to prepare a raw material solution. The raw material solution prepared in the micromixer 5 is supplied to the reaction column 2.

[0092] In this embodiment, the first liquid is a reaction solvent in which an aromatic compound or the like is dissolved. The second liquid is heavy water.

[0093] In the first liquid, aromatic compounds were dissolved such that when the first liquid and the second liquid were mixed to form the raw material solution, the concentration of aromatic compounds in the raw material solution was 0.1 M.

[0094] In Examples 13 and 14, the mixing ratio of 2-propanol (IPA) and ethyl acetate in the first solution was adjusted so that the mixing ratio of the reaction solvent and the deuterium source in the raw material solution, i.e., the mixing ratio of 2-propanol (IPA), ethyl acetate, and heavy water in the raw material solution, was as shown in Table 1.

[0095] The outputs of the liquid transfer pumps 11 and 12 were adjusted so that the mixing ratio of the reaction solvent and the deuterium source in the raw material solution matched the values ​​in Table 1. The evaluation results of these examples are also shown in Table 1.

[0096] Comparative Example 1 differs from Example 1 in that, as shown in Table 1, it uses a supported catalyst in which only platinum (Pt), a transition metal other than iridium, is supported instead of iridium, and the amount of platinum supported as the transition metal other than iridium is the value shown in Table 1. Otherwise, it is the same as Example 1. The evaluation results for Comparative Example 1 are also shown in Table 1. No bubbles were observed in reaction column 2 during the deuteration reaction.

[0097] Comparative Example 2 differs from Example 3 in that it does not use the reactor 100, but instead involves placing the raw material solution into a test tube filled with the supported catalyst and reacting it for 5 minutes to obtain the reaction solution. Otherwise, it is the same as Example 3. In Comparative Example 2, the test tube is open to the outside, and the reaction system is not sealed (reaction system airtightness: none). The evaluation results for Comparative Example 2 are also shown in Table 1.

[0098] Comparative Example 3 differed from Example 12 in that only ethyl acetate was used as the reaction solvent; otherwise, it was the same as Example 12. The evaluation results for Comparative Example 3 are also shown in Table 1.

[0099] A comparison of the results between Example 1 and Example 2-14 revealed that when a metal belonging to Groups 3 to 11 other than iridium (transition metals, especially platinum group metals) is included as a catalyst, the deuteration rate is improved compared to when it is not included.

[0100] Based on the results of Example 2-14, when the catalyst is a co-supported catalyst, it can be said that the iridium support ratio in the co-supported catalyst is preferably 0.5% by weight or more and 6% by weight or less of the co-supported catalyst.

[0101] Furthermore, it can be said that the supporting ratio of the transition metal in the co-supported catalyst is preferably 0.3% by weight or more and 10% by weight or less of the co-supported catalyst, more preferably 0.3% by weight or more and 5.0% by weight or less.

[0102] Furthermore, the loading ratio (weight ratio) of iridium to transition metal in the co-supported catalyst is preferably in the range of 1:0.05 to 1:12. In particular, considering that the deuteration rate in Examples 9 and 10 is somewhat lower than in the other examples, it is even more preferable that the ratio is in the range of 1:1 to 1:9.

[0103] A comparison of Examples 1-14 and Comparative Example 3 revealed that a good deuteration rate can be achieved if the reaction solvent is IPA or HEIP.

[0104] In particular, a comparison between Example 3 and Example 12 revealed that even when HEIP is used as the reaction solvent, a deuteration rate comparable to that achieved when IPA is used can be obtained.

[0105] Furthermore, a comparison of Examples 13 and 14 with Examples 1-11 (especially Example 3) revealed that a higher deuteration rate was achieved when ethyl acetate was mixed in, reducing the proportion of IPA in the reaction solvent. This result is thought to be because the decrease in the proportion of IPA in the reaction solvent reduced the amount of free protons (light hydrogen) derived from IPA in the reaction system, which in turn relatively increased the proportion of deuterium in the reaction system. Based on these results, it can be said that it is preferable for the reaction solvent to contain ethyl acetate in a mass ratio of 2 times or less to IPA.

[0106] A comparison of Comparative Example 2 with Examples 1-14 (particularly Example 3) revealed that in the method for producing deuterides containing iridium as a catalyst (the production method according to the method for producing deuterium compounds according to this embodiment), it is important that the reaction system is a closed system. This is because, in the method for producing deuterium compounds according to this embodiment, by using a catalyst containing at least iridium, hydrogen gas or deuterium gas is generated from a solvent containing a deuterium source during the deuteration reaction (deuteration step), thereby promoting deuteration. If the reaction system is an open system, the generated hydrogen gas or deuterium gas will volatilize out of the system and will not be able to contribute to promoting deuteration.

[0107] In other words, in the method for producing deuterium compounds according to this embodiment, by making the reaction system a sealed system, the generated hydrogen gas or deuterium gas is retained in the reaction system, and it is thought that these gases promote deuteration. In particular, in Examples 1-14, the back pressure of the reaction column 2 is maintained by the back pressure valve 3, and by making the reaction pressure 0.5 MPa or higher in gauge pressure, it is thought that the hydrogen gas or deuterium gas generated and retained in the reaction system immediately dissolves in the reaction solvent, contributing to the promotion of deuteration.

[0108] As described above, a method for producing deuterium compounds that can be efficiently obtained can be provided.

[0109] The embodiments disclosed herein are illustrative examples, and the embodiments of the present invention are not limited thereto. They can be modified as appropriate without departing from the purpose of the present invention. [Industrial applicability]

[0110] This invention can be applied to methods for producing deuterium compounds. [Explanation of symbols]

[0111] 1: Liquid transfer pump 11: Liquid transfer pump 12: Liquid transfer pump 100: Reaction apparatus 2: Reaction column 200: Reactor 3: Back pressure valve 4: Reaction solution receiving flask

Claims

1. The process includes a deuteration step in which a compound having at least one of an aromatic ring and a heterocycle is brought into contact with a deuterium source in the presence of a solvent and a catalyst. The solvent comprises at least one of 2-propanol and hexafluoro-2-propanol. The catalyst contains iridium, A method for producing a deuterium compound, comprising at least one of heavy water and a deuterating solvent as the deuterium source.

2. The method for producing a deuterium compound according to claim 1, wherein the deuteration step generates hydrogen gas or deuterium gas from a solvent containing the deuterium source.

3. The method for producing a deuterium compound according to claim 2, wherein the catalyst is a co-supported catalyst further comprising a metal belonging to Group 3 to Group 11 other than iridium.

4. The iridium support ratio in the co-supported catalyst is 0.5% by weight or more and 6% by weight or less of the co-supported catalyst. The method for producing a deuterium compound according to claim 3, wherein the supported metal ratio in the co-supported catalyst is 0.3% by weight or more and 10% by weight or less of the co-supported catalyst.

5. The method for producing a deuterium compound according to claim 3, wherein the weight ratio of iridium to the metal in the co-supported catalyst is in the range of 1:0.05 to 1:

12.

6. The method for producing a deuterium compound according to claim 4, wherein the weight ratio of iridium to the metal in the co-supported catalyst is in the range of 1:0.05 to 1:

12.

7. A method for producing a deuterium compound according to any one of claims 3 to 6, wherein the metal comprises at least one selected from platinum, palladium, rhodium, and ruthenium.

8. A method for producing a deuterium compound according to any one of claims 1 to 6, wherein a raw material solution obtained by mixing a solution of the compound dissolved in a solvent with heavy water as the deuterium source is passed through a reaction column packed with the catalyst to bring the compound into contact with the deuterium source.

9. A method for producing a deuterium compound according to any one of claims 1 to 6, wherein the deuterium source is heavy water.

10. The method for producing a deuterium compound according to any one of claims 1 to 6, wherein the deuteration step is performed in a closed system.

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