Method for producing deuterium compounds

Abstract

The present invention provides a method for producing a deuterium compound, which allows the deuterium compound to 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, the solvent including at least one of 2-propanol and hexafluoro-2-propanol, the catalyst including iridium, and the deuterium source including at least one of heavy water and a deuterated solvent.

Description

[Technical field]

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

[0002] Deuterium atoms are a type of stable isotope of hydrogen atoms and have different physical properties from hydrogen atoms. Therefore, deuterated compounds not only have different physical properties from normal compounds, but can also exhibit different chemical reactivity. Specifically, by deuterizing a compound, it is possible to give the compound new functions. For this reason, it is expected that deuterated compounds will be applied to various functional materials, including electronic materials and organic electroluminescence materials.

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

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

[0005] In the method for deuteration of aromatic rings disclosed in Patent Document 1, it is possible to use an unactivated catalyst that has been activated in advance as the activated catalyst, and it is also possible to use an unactivated catalyst in the same manner if hydrogen gas or deuterium gas is present in the reaction system. It is also disclosed that in order to make hydrogen gas or deuterium gas present in the reaction system, hydrogen gas or deuterium gas can be passed directly through the reaction solution, or the sealed deuteration reaction system of the present invention can be replaced with hydrogen gas or deuterium gas.

[0006] Patent Document 1 discloses a case in which an aromatic compound such as phenol, platinum carbon or potassium platinum chloride as a catalyst, and heavy water were suspended, the sealed reaction system was substituted with hydrogen, and the reaction was carried out in an oil bath at 160°C for about 24 hours (i.e., a batchwise reaction) to deuterate the compound, and the deuteration rate was 65 to 99%.

[0007] Patent Document 2 discloses a method for deuteration of an aromatic compound. In this method for deuteration of an aromatic compound, it is said that hydrogen in a target aromatic compound can be deuterized efficiently by contacting an aromatic compound with a deuterium source selected from heavy water and a deuterated solvent in the coexistence 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, without activating the catalyst with hydrogen gas or deuterium gas in advance or without having hydrogen gas or deuterium gas coexist in the reaction system.

[0008] In the method for deuteration of an aromatic compound disclosed in Patent Document 2, the reaction time of the deuteration reaction is generally 1 hour to 50 hours. Patent Document 2 discloses, as an example, a case in which various aromatic compounds were reacted with an aromatic compound such as biphenyl and a platinum catalyst such as platinum on carbon, along with a solvent such as 2-propanol and heavy water, in a test tube (i.e., in a batch process) for a reaction time range of 3 hours to 24 hours to deuterate the compounds, and the deuteration rate was 9% to 99%. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] International Publication No. 2004 / 011400 [Patent Document 2] JP 2014-111561 A Summary of the Invention [Problem to be solved by the invention]

[0010] In the prior art, when a compound such as a compound having an aromatic ring is deuterized to produce a deuterium compound, a long reaction time such as 24 hours is required, or a batch reaction control is required (see, for example, Patent Documents 1 and 2, respectively). Therefore, there are cases where deuterium compounds cannot be obtained efficiently.

[0011] The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a method for producing a deuterium compound, which can efficiently obtain a deuterium compound. [Means for solving the problem]

[0012] In order to achieve the above object, the present invention provides a method for producing a deuterium compound, comprising the steps of: The method includes a deuteration step of contacting a compound having at least one of an aromatic ring and a heterocycle with a heavy hydrogen 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 comprises iridium; The deuterium source includes at least one of heavy water and a deuterated solvent. Effect of the Invention

[0013] According to the present disclosure, it is possible to provide a method for producing a deuterium compound, which is capable of efficiently obtaining a deuterium compound. [Brief description of the drawings]

[0014] [Figure 1] FIG. 1 is a diagram illustrating the configuration of a reaction apparatus used in the examples. [Diagram 2] FIG. 2 is a diagram illustrating the configuration of another reaction apparatus used in the examples. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

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

[0016] First, an outline 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 the present embodiment 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 coexistence of a solvent and a catalyst, the solvent including at least one of 2-propanol (IPA) and hexafluoro-2-propanol (HFIP), the catalyst including iridium, and the deuterium source including at least one of deuterium 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] In detail, in the method for producing a deuterium compound according to the present embodiment, 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 by the catalytic action of iridium, so that 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. Therefore, an efficient deuteration reaction can be performed without requiring a step of adding hydrogen gas or deuterium gas from outside the reaction system and without requiring a step of activating a catalyst in advance.

[0020] The method for producing a deuterium compound according to this embodiment will be described in detail below.

[0021] As described above, in the method for producing a deuterium compound according to the present embodiment, a step of contacting a compound having an aromatic ring or a heterocycle (hereinafter, may be referred to as an aromatic compound or the like) with a deuterium source in the coexistence of a solvent and a catalyst is carried out to obtain a deuterium compound obtained by deuterating the compound having an aromatic ring or a heterocycle.

[0022] The aromatic compound etc. is not particularly limited as long as it is a compound having a 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 heterocycle, that is, a compound having at least one of an aromatic ring and a heterocycle. The aromatic compound etc. may be a compound having only one of an aromatic ring and a heterocycle, or a compound having both an aromatic ring and a heterocycle. The number of ring structures contained in the compound may be one 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 to 7, more preferably 5 or 6, and particularly preferably 6.

[0024] Examples of compounds having a light hydrogen atom and an aromatic ring include 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-anthrol, 2-anthrol, 9-anthrol, and 1-phenanthroline. Examples of the aromatic hydrocarbons include phenylalanine, 2-phenanthrol, 3-phenanthrol, 4-phenanthrol, 9-phenanthrol, 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, and terephthalaldehyde.

[0025] The heterocycle of the compound has a heteroatom in the ring skeleton, and the heteroatom is preferably an oxygen atom, a nitrogen atom, a sulfur atom, a phosphorus atom, or a silicon atom, and more preferably a nitrogen atom or a sulfur atom. The heterocycle may be either aromatic or non-aromatic, but is preferably aromatic.

[0026] In the heterocyclic ring of the compound, the number of heteroatoms in one ring skeleton is not particularly limited depending on the total number of atoms constituting the ring skeleton, but is preferably 1 to 3, more preferably 1 or 2. When the number of heteroatoms in one ring skeleton is multiple, these multiple heteroatoms may all be the same type, some may be the same type, or all may be different types. When one ring skeleton contains multiple types of heteroatoms, the combination is not particularly limited, but a combination of a nitrogen atom and a sulfur atom is preferred. The heterocyclic ring of the compound may be either monocyclic or polycyclic, but when it is polycyclic, it is preferably bicyclic or tricyclic.

[0027] Examples of compounds having hydrogen 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 of the aromatic hydrocarbon radicals 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, and isonicotinaldehyde.

[0028] The compound having hydrogen and an aromatic ring and the compound having hydrogen and a heterocycle may be a compound 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 a substituent is preferably 1 to 3, depending on the type of aromatic ring or heterocycle. The substituent is not particularly limited as long as it does not interfere with the effects of the present invention. Specifically, examples of the substituent include an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an arylalkyl group, an alkoxy group, an aryloxy group, an alkoxyalkyl group, an aryloxyalkyl group, an alkoxycarbonylalkyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, an alkylcarbonyloxyalkyl group, an alkylcarbonyloxy group, an arylcarbonyloxy group, a hydroxyalkyl group, a hydroxyaryl group, a hydroxyl group, a carboxy group, an amino group, a cyano group, a nitro group, and a halogen atom.

[0029] The compound having at least one of hydrogen and an aromatic ring and a heterocycle may be, for example, a compound having hydrogen and an aromatic ring as specifically exemplified above, from which hydrogen atoms have been removed, a compound having hydrogen and a heterocycle, or a compound having hydrogen and an aromatic ring from which hydrogen atoms have been removed and a compound having hydrogen and a heterocycle from which hydrogen atoms have been removed, which are bonded to each other between the atoms from which hydrogen atoms have been removed. The combination of the compounds bonded to each other in this case is not particularly limited, and may be selected from the group consisting of a compound having only an aromatic ring, a compound having only a heterocycle, and a compound having an aromatic ring and a heterocycle. The number of the compounds bonded to each other is not particularly limited, but 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 a 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 (combined use of) 2-propanol and hexafluoro-2-propanol. When 2-propanol and hexafluoro-2-propanol are used in combination as the reaction solvent, the ratio of these solvents may be appropriately selected depending on the purpose, for example, the solubility of the aromatic compound to be deuterated, etc.

[0032] The reaction solvent may contain a solvent other than 2-propanol and hexafluoro-2-propanol. By reducing the ratio of 2-propanol or hexafluoro-2-propanol in the solvent, the ratio of deuterium atoms in the deuteration reaction system may be improved. Since 2-propanol and hexafluoro-2-propanol have free protons, which are light hydrogen atoms, in the hydroxyl group, the presence of these solvents reduces the ratio of deuterium atoms in the deuteration reaction system. Therefore, by reducing the ratio of 2-propanol or hexafluoro-2-propanol in the reaction solvent, the ratio of deuterium atoms in the deuteration reaction system may be increased, and the deuteration rate of aromatic compounds, etc. obtained as a result of the deuteration reaction may be increased.

[0033] Examples of solvents that may be contained in the reaction solvent other than 2-propanol and hexafluoro-2-propanol include 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 preferable, but the solvent may be appropriately selected depending on the solubility of the aromatic compound, etc.

[0034] A deuterium source is a molecule (including a compound) or ion that supplies deuterium (deuterium) to a reaction system. Deuterium is a stable isotope of hydrogen with a mass number of 2, and is designated D or 2 It is written as H.

[0035] An example of a deuterium source is deuterium water or a deuterated solvent.

[0036] As the deuterium source, it is preferable to use deuterium water in consideration of cost and availability, but it is also possible to use deuterated solvents (deuterated solvents) such as compounds having a deuterated free proton, such as deuterated methanol, and deuterated aromatic compounds, such as deuterated benzene.

[0037] When using heavy water as the heavy hydrogen source, the purity of the heavy water is not particularly limited, and is preferably 90 atom % or more, more preferably 95 atom % or more, and particularly preferably 99 atom % or more.

[0038] The catalyst used contains at least iridium. The iridium contained in the catalyst may be in the form of metal or a compound containing iridium. This allows the raw material compound to be deuterized while generating hydrogen gas or deuterium gas from a solvent containing a deuterium source during the deuteration step of deuterizing a compound having at least one of an aromatic ring and a heterocycle by contacting an aromatic compound or the like with a deuterium source in the presence of a reaction solvent and a catalyst. In more detail, by using a catalyst containing at least iridium, hydrogen gas or deuterium gas can be generated from a solvent containing a deuterium source during the deuteration step, thereby promoting deuteration and efficiently obtaining a deuterium compound. The meaning of hydrogen gas or deuterium gas includes the meaning of at least one of hydrogen gas and deuterium gas, and the meaning of hydrogen gas and deuterium gas.

[0039] The catalyst may contain, in addition to iridium, a metal belonging to Groups 3 to 11 (i.e., a transition metal) that is known to have a catalytic function for a deuteration reaction. The catalyst may contain one type of transition metal other than iridium, or may contain two or more types. When the catalyst contains two or more types of transition metals other than iridium, the combination and ratio thereof may be appropriately selected depending on the purpose. The transition metal contained in the catalyst may be in a metallic state or in a state of a compound containing a transition metal. When the catalyst further contains a transition metal, deuteration during the deuteration step is further promoted, and a deuterium compound can be efficiently obtained.

[0040] The transition metal other than iridium contained in the catalyst is preferably platinum, palladium, rhodium or ruthenium, and particularly preferably platinum or palladium.

[0041] That is, the catalyst may contain at least one platinum group metal selected from platinum, palladium, rhodium, and ruthenium together with iridium. The platinum group metal contained in the catalyst may be in a metallic state or in a compound state containing such a metal. When the catalyst further contains such a platinum group metal, deuteration in the deuteration step is further promoted, and deuterium compounds can be obtained more efficiently.

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

[0043] The catalyst carrier may be a carrier generally used in an immobilized catalyst carrying a transition metal (including platinum group metals). The carrier may be, for example, activated alumina, activated carbon, silica, ceria, or a resin polymer. It is preferable to use activated alumina as the carrier.

[0044] The specific shape of the reaction vessel or reaction tube of the reaction apparatus in the deuteration step is not limited, but a plug flow type reactor (tubular reactor, PFR, so-called flow reactor) is preferred because it allows the reaction apparatus to be made compact and the reaction time to be shortened, and therefore deuterium compounds can be efficiently obtained.

[0045] A preferred apparatus configuration and operation will be described below, taking as an example a case where the reaction apparatus in the deuteration step is a plug flow type reactor having a reaction tube.

[0046] The reaction tube may be a cylindrical vessel (column). The reaction tube may be filled with the above-mentioned catalyst (for example, a co-supported catalyst in which iridium and platinum are co-supported). Hereinafter, the reaction tube filled with the catalyst is referred to as a reaction column.

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

[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 in consideration of the type of substrate contained in the aromatic compound or the like and the concentration of the raw material solution, but is preferably 40°C or higher and 250°C or lower, and more preferably 100°C or higher and 180°C or lower.

[0049] The reaction apparatus preferably has a heating mechanism for heating the reaction column to heat the raw material solution supplied to the reaction column. By heating the raw material solution, the deuteration reaction is promoted. The heating mechanism may have any heat source or heating method as long as it can set the temperature during heating 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 may be selected.

[0050] In addition, a flow path downstream of the reaction column (a flow path continuing from the outlet of the reaction column) may be provided with a pressure control valve (a so-called back pressure valve) for maintaining the pressure in the reaction column, which serves as a reaction field (so-called back pressure, hereinafter sometimes referred to as reaction pressure), at or above a certain pressure.

[0051] By providing a back pressure valve and maintaining the reaction pressure at or above a certain pressure, it is possible to suppress the generation of bubbles (vaporization) when the raw material solution is heated in the reaction column (for example, when the temperature of the solvent in the raw material solution reaches or exceeds the boiling point at atmospheric pressure (normal pressure)), thereby suppressing the reduction in the fluid residence time inside the reaction column and the resulting shortening of the reaction time, and thereby sufficiently promoting the deuteration reaction.

[0052] By providing a back pressure valve to maintain the reaction pressure at a certain level or higher, hydrogen gas and deuterium gas generated by the catalytic action of iridium are instantly dissolved in the reaction solvent, contributing to the promotion of deuteration.

[0053] In addition, by providing a back pressure valve and maintaining the reaction pressure at a certain pressure or higher, it is possible to suppress the precipitation of aromatic compounds, etc. in the reaction column when aromatic compounds, etc. with low solubility are used. In more detail, when a part of the solvent in the raw solution evaporates, aromatic compounds, etc. are likely to precipitate from the raw solution, and such precipitation may cause clogging of the reaction column. Therefore, by providing a back pressure valve and maintaining the reaction pressure at a certain pressure or higher, it is possible to suppress the evaporation of the solvent in the raw solution, and to suppress the precipitation of aromatic compounds, etc. and the resulting clogging of the reaction column.

[0054] The reaction pressure is preferably adjusted to atmospheric pressure or higher, and for example, is preferably 0.5 MPa or more and 3 MPa or less, and more preferably 1 MPa or more and 2 MPa or less, in terms of gauge pressure.

[0055] By setting the reaction pressure to be equal to or higher than the above lower limit, evaporation of the solvent in the raw material solution is suppressed as described above, and the deuterium gas generated in the deuteration reaction system is easily dissolved in the solvent, so that the deuteration reaction is more effectively promoted, and high reaction efficiency and a shortened reaction time are realized.

[0056] In addition, by keeping the reaction pressure at or below the upper limit, a high effect of suppressing decomposition of the substrate and deuterium compounds contained in aromatic compounds etc. is obtained. In addition, if the reaction pressure is at or below the upper limit, a reactor with high pressure resistance is not required, and the target product can be produced at low cost.

[0057] It is preferable that the reaction column is airtight in the portions other than the inlet and the outlet. "Airtight" means that the column is tightly closed without any gaps, and "high airtightness" means that the column can be well maintained in a state where the column is tightly closed without any gaps.

[0058] The residence time of the raw solution in the reaction column can be appropriately adjusted taking into consideration the type of substrate contained in the aromatic compound or the like, the concentration of the raw solution, the reaction temperature, etc., but is preferably from 10 to 600 seconds, more preferably from 60 to 300 seconds, and particularly preferably from 100 to 200 seconds. The residence time of the raw solution in the reaction column may be adjusted by the dimensions of the reaction tube and the type and output of the pump or pump mechanism used to deliver the solution.

[0059] In the deuteration reaction, the amount of the raw solution supplied to the reaction column and the ratio (concentration) of each component in the raw solution may be appropriately adjusted in consideration of the type of aromatic compound, etc., the target deuteration rate, etc. For example, the ratio of heavy water contained in the raw solution may be set so that the ratio of the amount of deuterium to the total amount of deuterium and protium contributing to the deuteration reaction in the reaction system including aromatic compounds, etc. is equal to or greater than the target deuteration rate.

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

[0061] The material (materials) forming the reaction column and the flow path 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 path piping connected to the reaction column include, for example, metal alloys such as stainless steel, resins such as fluororesins (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 feeding the raw material solution. The pump, etc. used for feeding the raw material solution is not particularly limited, and may be appropriately selected from those that can be used industrially. The pump, etc. is preferably one that does not generate pulsation during feeding. Specific examples of the pump, etc. include a plunger pump, a gear pump, a rotary pump, and a diaphragm pump.

[0063] In the reaction apparatus, the components other than the reaction column, the heating mechanism, the back pressure valve, and the pump (hereinafter referred to as peripheral equipment) are not particularly limited. The peripheral equipment can be appropriately selected depending on the purpose. Examples of the peripheral equipment are a sensor and a tank for storing the produced deuterium compound (deuterated compound). EXAMPLES

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

[0065] Example 1 In Example 1, a deuteration reaction (deuteration step) for deuterizing 1-naphthol as an aromatic compound or the like was carried out using a reaction apparatus 100 shown in FIG.

[0066] The catalyst used was a supported catalyst in which only iridium (Ir) was supported on a θ-alumina powder support (type: JRC-ALO-10) made by Nippon Light Metal Co., Ltd. The amount (content) of iridium (Ir) in the supported catalyst was 5.0 wt%. Therefore, this supported catalyst does not support any transition metals other than iridium (Ir), and the ratio (weight ratio, hereafter referred to as the support ratio) of the amount of iridium supported to the amount of transition metals other than iridium in this supported catalyst was 1:0.

[0067] The raw material solution was prepared according to the following recipe: 2-propanol (IPA) was used as the reaction solvent, and deuterium oxide 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 and by mixing and dissolving the aromatic compounds and other components so that the concentration of the aromatic compounds in the raw material solution was 0.1 M.

[0069] The reaction apparatus 100 includes a reaction column 2 filled with a catalyst and supplied with a raw material solution, a liquid delivery pump 1 for supplying the raw material solution to the reaction column 2, a back pressure valve 3 for adjusting the back pressure of the reaction column 2, and a reaction solution receiving flask 4 for storing the reaction solution that is a 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 filled with a catalyst, thereby performing an operation of contacting the aromatic compounds, etc. with the deuterium source.

[0071] The liquid delivery pump 1 draws up the raw material solution from a raw material container (not shown) storing the raw material solution, and supplies it to the reaction column 2. As the liquid delivery pump 1, a syringe pump (model: PHD ULTRA H70-3005) manufactured by HARBARD was used.

[0072] The reaction column 2 was 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, and with high airtightness except for the inlet and outlet. In other words, in this example, the airtightness of the reaction system was guaranteed (airtightness of the reaction system: yes).

[0073] The reaction column 2 was packed with 0.75 g of the supported catalyst and immersed in an oil bath (manufactured by Yamato Scientific, model: BO500) at 100° C. In other words, the reaction temperature in this example was set to 100° C.

[0074] The reaction column 2 was used as a so-called flow reactor. The supply rate of the raw material solution continuously supplied to the reaction column 2 and the pressure inside the 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] The conditions for the above-described Example 1 are shown in Table 1.

[0076] [Table 1]

[0077] The deuteration reaction was carried out under the conditions described above, and the reaction solution was collected in the reaction solution receiving flask 4. During the deuteration reaction, the generation of bubbles thought to be hydrogen and deuterium gas was confirmed in the reaction column 2. Furthermore, evaporation of the solvent during the deuteration reaction was not confirmed.

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

[0079] For the NMR analysis, a nuclear magnetic resonance apparatus (manufactured by JEOL Ltd., model: JNM-ECS400) was used.

[0080] First, for non-deuterated samples (aromatic compounds, etc.) and deuterated samples (deuterium compounds contained in the reaction solution), 1 H-NMR was measured, and it was confirmed that deuteration had progressed, as peaks observed in the non-deuterated sample disappeared or were significantly reduced in the deuterated sample.

[0081] The NMR measurement method and the deuteration rate calculation method were performed as follows. That is, a sample (a deuterium compound contained in a reaction solution) was dissolved in an NMR solvent containing an internal standard substance, 1 H-NMR was measured. The deuteration rate (average deuteration rate) of the aromatic ring portion was calculated based on the integral value of the proton peak of the internal standard substance or the intramolecular standard portion.

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

[0083] The yield was calculated by thoroughly distilling off the solvent components (including heavy water) of the reaction solution under reduced pressure using a rotary evaporator, and then measuring the weight of the residue. In other words, the yield was calculated based on the weight of the aromatic compounds, etc. used in preparing the raw material solution and the weight of the residue. Specifically, the yield was calculated as "yield (%) = weight of residue / weight of aromatic compounds, etc. x 100".

[0084] The yield in this example was 99% (hereinafter sometimes expressed as ">99%").

[0085] In this way, by using iridium as a catalyst, it was possible to realize efficient deuteration of aromatic compounds, etc. Specifically, continuous deuteration was realized without requiring a long residence time, and the operation of introducing hydrogen gas or deuterium gas from outside the reaction system was also eliminated. In addition, the step of activating the catalyst was also eliminated. This is believed to be because hydrogen gas or deuterium gas was generated from a solvent (raw material solution) containing a deuterium source during the deuteration reaction (deuteration step), which promoted the deuteration of aromatic compounds, etc., and allowed deuterium compounds of aromatic compounds, etc. to be obtained efficiently.

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

[0087] As shown in Table 1, Examples 2-10, unlike Example 1, used a supported catalyst (co-supported catalyst) in which a transition metal other than iridium was supported on a carrier together with iridium. In each of these Examples, one or more of the amount of iridium (Ir), the type of transition metal other than iridium supported on the carrier together with iridium, and the amount and support ratio of the transition metal other than iridium were different from those of Example 1, and the rest were the same as Example 1. In Examples 5-8, palladium (Pd), rhodium (Rh), ruthenium (Ru), platinum, and palladium (Pt / Pd) were used in this order as the transition metal other than iridium. The evaluation results of these Examples are also shown in Table 1.

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

[0089] As shown in Table 1, Examples 12-14 were different from Example 3 in that hexafluoro-2-propanol (HFIP) or a mixture of 2-propanol (IPA) and ethyl acetate was used as a reaction solvent, and that the deuteration reaction was carried out using a reaction apparatus 200 shown in FIG. 2, which was different from the reaction apparatus 100. The rest of the examples were the same as Example 3.

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

[0091] In the reaction apparatus 200, a first liquid supplied from a liquid supply pump 11 and a second liquid supplied from a liquid supply 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, and the second liquid is heavy water.

[0093] An aromatic compound etc. was dissolved in the first liquid so that the concentration of the aromatic compound etc. in the raw solution would be 0.1 M when the first liquid and the second liquid were mixed to form the raw solution.

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

[0095] The outputs of the liquid delivery pumps 11 and 12 were adjusted so that the mixture ratio of the reaction solvent and the deuterium source in the raw material solution was the value shown 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 a supported catalyst was used in which only platinum (Pt), a transition metal other than iridium, was supported instead of iridium, as shown in Table 1, and the amount of platinum supported as a transition metal other than iridium was set to the value shown in Table 1, but the rest was the same as Example 1. The evaluation results of Comparative Example 1 are also shown in Table 1. Note that no generation of bubbles was confirmed in reaction column 2 during the deuteration reaction.

[0097] Comparative Example 2 differs from Example 3 in that the reaction apparatus 100 was not used, and the raw material solution was charged into a test tube filled with a supported catalyst and reacted for 5 minutes to obtain a reaction solution, but the rest was the same as Example 3. In Comparative Example 2, the test tube was open to the outside, and the reaction system was not sealed (sealability of the reaction system: none). The evaluation results of Comparative Example 2 are also shown in Table 1.

[0098] Comparative Example 3 differs from Example 12 in that the reaction solvent was ethyl acetate alone, but the rest was the same as Example 12. The evaluation results of Comparative Example 3 are also shown in Table 1.

[0099] Comparison of the results of Example 1 and Examples 2-14 reveals that when a metal belonging to Groups 3 to 11 other than iridium (a transition metal, in particular a platinum group metal) is contained as a catalyst, the deuteration rate is improved compared to when it is not contained.

[0100] From the results of Example 2-14, when the catalyst is a co-supported catalyst, it can be said that the ratio of iridium supported 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 supported ratio of the transition metal in the co-supported catalyst is preferably 0.3% by weight to 10% by weight, and more preferably 0.3% by weight to 5.0% by weight.

[0102] In addition, the loading ratio (weight ratio) of iridium to transition metal in the co-loaded catalyst is preferably in the range of 1:0.05 to 1:12. In particular, considering that the deuteration rates of Examples 9 and 10 are somewhat lower than those of other Examples, the loading ratio is more preferably in the range of 1:1 to 1:9.

[0103] Comparison of Examples 1 to 14 with Comparative Example 3 revealed that a good deuteration rate could be achieved when the reaction solvent was IPA or HEIP.

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

[0105] Furthermore, a comparison of Examples 13 and 14 with Examples 1 to 11 (especially Example 3) revealed that a higher deuteration rate was achieved when ethyl acetate was mixed in to reduce the ratio of IPA in the reaction solvent. This result is believed to be due to the fact that the reduced ratio of IPA in the reaction solvent resulted in fewer free protons (light hydrogen) derived from IPA in the reaction system, which in turn resulted in a relative increase in the ratio of deuterium in the reaction system. From this result, it can be said that it is preferable for the reaction solvent to contain ethyl acetate in a mass ratio of IPA not more than twice that of IPA.

[0106] From a comparison between Comparative Example 2 and Examples 1-14 (especially Example 3), it was found that in the production method of a deuterium compound containing iridium as a catalyst (the production method according to the production method of a deuterium compound according to the present embodiment), it is important that the reaction system is a closed system. This is because, in the production method of a deuterium compound according to the present 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. However, if the reaction system is an open system, the generated hydrogen gas or deuterium gas will volatilize outside the system and will not contribute to promoting deuteration.

[0107] In other words, in the method for producing a deuterium compound according to the present embodiment, the reaction system is a closed system, so that the generated hydrogen gas or deuterium gas is retained in the reaction system, and it is considered that deuteration is promoted by these gases. Particularly in Example 1-14, the back pressure of the reaction column 2 is maintained by the back pressure valve 3, and the reaction pressure is set to 0.5 MPa or more in gauge pressure, so that the hydrogen gas or deuterium gas generated in the reaction system and retained in the reaction system is instantly dissolved in the reaction solvent, which is considered to contribute to the promotion of deuteration.

[0108] In this manner, a method for producing a deuterium compound can be provided that allows deuterium compounds to be obtained efficiently.

[0109] It should be noted that the embodiments disclosed in this specification are merely examples, and the present invention is not limited to these embodiments, and can be modified as appropriate without departing from the scope of the present invention. [Industrial Applicability]

[0110] The present invention can be applied to a method for producing a deuterium compound. [Explanation of symbols]

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

Claims

1. The method includes a deuteration step of contacting a compound having at least one of an aromatic ring and a heterocycle with a heavy hydrogen 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 comprises iridium; The method for producing a deuterium compound includes at least one of heavy water and a deuterated solvent as the deuterium source.

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

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

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

5. 4. 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. 5. 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. 7. The method for producing a deuterium compound according to claim 3, wherein the metal contains at least one selected from the group consisting of platinum, palladium, rhodium and ruthenium.

8. 7. The method for producing a deuterium compound according to claim 1, wherein a raw material solution obtained by mixing a solution obtained by dissolving the compound in a solvent and heavy water as the deuterium source is passed through a reaction column packed with the catalyst to contact the compound with the deuterium source.

9. The 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 claim 1 , wherein the deuteration step is carried out in a closed system.

Images