Catalyst containing activated carbon adsorbed with a ruthenium complex, and method for producing a reduction product using the same

Abstract

The present invention addresses the problem of providing a catalyst which exhibits high reusability and is capable of reducing the amount of residual metals in a reaction liquid in a process wherein an optically active reduction product is produced by an asymmetric reduction reaction of an organic compound. The present invention relates to a catalyst that contains an activated carbon on which a ruthenium complex represented by general formula (1-1) and / or (1-2) is adsorbed.　(In the formulae, j, k, X, Y, and R1 to R10 are as defined in claim 1.)

Description

Technical Field

[0001] The present invention relates to a catalyst containing activated carbon adsorbed with a novel ruthenium complex, and a method for producing a reduction product, which includes a step of reducing an organic compound using the same.

Background Art

[0002] It has been reported many times that ruthenium complexes having an optically active diamine as a ligand have excellent performance as homogeneous catalysts for asymmetric reduction reactions. For example, when using these catalysts, it becomes possible to efficiently produce optically active alcohols by asymmetric reduction of ketones and imines using molecular hydrogen, formic acid, formate, etc. as a hydrogen source. Among them, many optically active diamine ligands have been developed to enhance the performance of the catalyst (see Patent Documents 1, 2, and 3, and Non-Patent Documents 1 and 2). Many efforts have been made to immobilize such ruthenium complexes on a solid-phase carrier and make them function as heterogeneous catalysts. The complex supported on the solid-phase carrier can impart characteristics that homogeneous catalysts do not have, such as the catalyst being reusable and the amount of dissolved metal remaining after the reaction can be reduced, and it is expected to lead to the solution of important issues such as reduction of environmental load and improvement of production cost. As a method for immobilizing a ruthenium complex for asymmetric reduction, a method of crosslinking a ligand and a functional group on the surface of a carrier has been studied, and it has been found that loading on silica (see Patent Document 4 and Non-Patent Document 3) and various polymers (see Non-Patent Document 4) etc. is effective.

[0003] In addition, a method has been reported in which the inside of the pores of a specific carrier is chemically modified to directly immobilize the complex without crosslinking the ligand of the complex and the surface of the carrier (see Non-Patent Document 5). The above-mentioned loading methods require newly chemically modifying conventional ruthenium complexes and catalyst carriers, which leads to an increase in the cost of producing the target optically active alcohol, so the industrial applicability is limited. Furthermore, depending on the catalyst and reaction substrate used, a decrease in catalyst efficiency and asymmetric yield may be observed due to immobilization on the carrier. As an example of a supported catalyst that does not require chemical modification of the complex and the support, the use of activated carbon as the support is known, and activated carbon-supported catalysts obtained by supporting RuCl2(PPh3)3 complex or [RuCl(p-cymene)]2 complex have been reported to be useful for the oxidation reactions of alcohols and diols (see Non-Patent Documents 6 and 7). On the other hand, there is no synthetic example of an activated carbon-supported complex useful for an asymmetric reduction reaction. For example, regarding a carbon material-supported ruthenium catalyst effective for the reduction of ketones, it is limited to an example of an activated carbon-supported ruthenium nanoparticle catalyst that gives a racemic alcohol (see Non-Patent Document 8).

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Non-Patent Documents

[0005]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

Non-Patent Document 4

Non-Patent Document 5

Non-Patent Document 6

Non - Patent Document 7

Non - Patent Document 8

Summary of the Invention

Problems to be Solved by the Invention

[0006] An object of the present invention is to provide a catalyst that exhibits high reusability and can reduce the amount of residual metal in the reaction solution in a method for producing an optically active reduction product by an asymmetric reduction reaction of an organic compound. Another object of the present invention is to provide the catalyst by a simple method that does not require chemical modification of the complex and the carrier.

Means for Solving the Problems

[0007] As a result of intensive studies on the loading of a complex onto a solid phase carrier to solve the above problems, it was found that by using activated carbon as the carrier, a ruthenium complex having an optically active diamine as a ligand can be loaded by a simple method. Furthermore, it was found that the catalyst containing activated carbon adsorbed with the ruthenium complex according to the present invention gives a catalytic efficiency comparable to that of the complex catalyst and an equivalent asymmetric yield for the asymmetric reduction reaction of ketones. The catalyst of the present invention hardly shows metal elution into the reaction solution. Furthermore, it was found that hardly any decrease in the catalytic efficiency and asymmetric yield in the asymmetric reduction reaction is observed even during reuse, and thus the present invention was completed. That is, the present invention includes the following contents.

[0008] 〔1〕A catalyst comprising activated carbon adsorbed with a ruthenium complex represented by the following general formula (1 - 1) and / or (1 - 2).

Chemical formula

Chemical formula

[0009] [2] R 4 and R 5 are bonded to each other to form a crosslinking site of the divalent group represented by the above formula (W), Z is an oxygen atom, n 1 is 1, n 2 is 2, The catalyst according to [1] above. [3] R 1 is a 4-methylphenyl group or a methyl group, R 2 and R 3 are phenyl groups, R 6 、R 7 、R 9 、and R 10 are hydrogen atoms, R 8 is a methyl group, The catalyst according to [2] above. [4] R 4 and R 5 do not form the crosslinking site of the divalent group represented by the formula (W), R 4 is a hydrogen atom, The catalyst according to [1] above. [5] R 1 is a 4-methylphenyl group, 2,3,4,5,6-pentafluorophenyl group, methyl group, isobutyl group, benzyl group, 2',5'-dimethylbenzyl group or 10-camphyl group, R 2 and R 3 are phenyl groups or are bonded to each other to form a cyclohexane ring, R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 are a hydrogen atom, a methyl group or an isopropyl group, the catalyst according to [4] above. [6] The catalyst according to any one of [1] to [5] above, wherein the total mass of the ruthenium complex is 0.1% by mass or more and 25% by mass or less based on the total mass of the activated carbon. [7] The specific surface area of the activated carbon is 800 m 2 / g or more and 2000 m 2 / g or less, the catalyst according to any one of [1] to [6] above. [8] A method for producing a reduction product, comprising a step of reducing an organic compound in the presence of the catalyst according to any one of [1] to [7] above and a hydrogen donor. [9] A method for producing an optically active alcohol, comprising a step of reducing the carbonyl group of a carbonyl compound in the presence of the catalyst according to any one of [1] to [7] above and a hydrogen donor.

[10] A method for producing an optically active amine, comprising a step of reducing the imino group of an imine compound in the presence of the catalyst according to any one of [1] to [7] above and a hydrogen donor. The production method according to any one of [8] to

[10] above, wherein the hydrogen donor is at least one selected from the group consisting of formic acid, an alkali metal formate, an alcohol having a hydrogen atom at the α-carbon atom of a hydroxyl group-substituted carbon, and hydrogen gas. In the present invention, "adsorption" and "support" are used synonymously.

Advantages of the Invention

[0010] The present invention can provide a catalyst that exhibits high reusability and can reduce the amount of residual metal in the reaction solution in a method for producing an optically active reduction product by an asymmetric reduction reaction of an organic compound. Further, the present invention can provide the catalyst by a simple method that does not require chemical modification of the complex and the carrier.

Brief Description of the Drawings

[0011]

Figure 1

Figure 2

Figure 3

Figure 4

Modes for Carrying Out the Invention

[0012] 〔Catalyst〕 The catalyst of the present invention is characterized by containing activated carbon as a carrier adsorbed with a tethered ruthenium complex and / or a non-tethered ruthenium complex represented by the following formula (1-1) and / or (1-2). The tethered ruthenium complex and / or non-tethered ruthenium complex used in the present invention will be described later, and these ruthenium complexes have a ligand having a benzene ring as a basic structure. In the catalyst according to the present invention, it is considered that the aromatic rings, particularly the benzene ring structures, possessed by both the activated carbon and the ruthenium complex interact with each other and are adsorbed to each other. This is supported by the results shown in FIG. 3, that is, when (R,R)-Ts-DENEB and a π-conjugated compound coexist, an interaction occurs between the aromatic ring on the ruthenium and the π-conjugated compound, and the peak (4.5 ppm to 6.2 ppm) attributed to the proton around the aromatic ring on the ruthenium shifts to the high magnetic field side. Further, in the catalyst of the present invention, although not particularly limited, the total mass of the ruthenium complex is preferably in the range of 0.1% by mass to 25% by mass, and 1% by mass to 10% by mass, with respect to the total mass of the activated carbon. This is preferable because it can suppress the ruthenium elution amount from the catalyst of the present invention after the reaction and enhance the reusability while exhibiting the desired functions as a catalyst. Further, in the catalyst of the present invention, it is more preferable that the ruthenium complex is uniformly supported on the surface or inside of the activated carbon. Here, in the present invention, the loading amount (or adsorption amount) of the complex with respect to the total mass of the activated carbon in the catalyst can be a value calculated from the amount of the unadsorbed complex measured by analysis in the production process as in this example, but as an objective value, the value calculated by the activated carbon surface analysis by SEM-EDS as in Analysis 2 in this example can be adopted as the loading amount.

[0013] In the complex of the present invention, neither the ligand of the ruthenium complex nor the activated carbon as the carrier requires chemical modification for mutual binding. Therefore, compared with ruthenium complexes supported on silica or ruthenium complexes supported on polymers, which have been conventionally used, there is an advantage that synthesis is easy. And in this catalyst, since it contains activated carbon as a carrier and the ruthenium complex can be recovered in a state adsorbed on the activated carbon, it has high reusability. Here, in the catalyst of the present invention, the ruthenium complex is more preferably of the tether type. This is because there is a covalent bond between the benzene ring site and the diamine site on ruthenium, so the release of the ligand from ruthenium is suppressed, and thus the activity as a catalyst tends to be high. Due to the structure of the catalyst of the present invention containing a ruthenium complex adsorbed on activated carbon, its catalytic activity is improved. For example, when used in the production of chiral alcohols, the optical purity obtained tends to be improved. Further, when the catalyst according to the present invention is contained in a highly polar solvent such as water or ethanol, the bond between the activated carbon and the ruthenium complex tends to be stronger. Hereinafter, the activated carbon and the ruthenium complex constituting the catalyst according to the present invention will be described, and then the method for adsorbing the ruthenium complex on the activated carbon will be described.

[0014] 〔Activated Carbon〕 The specific surface area of the activated carbon as the carrier in the present invention is generally 700 to 3000 m 2 / g, preferably 800 to 2000 m 2 / g, more preferably 1200 to 1800 m 2 / g. The specific surface area of the activated carbon used in the present invention affects the adsorption amount of the target complex. In the present invention, the specific surface area of the activated carbon can be a value measured by a method specified in, for example, JIS Z8830:2013 (ISO 9277:2010). Since the average pore diameter of the adsorbent of the present invention affects the reaction activity of the catalyst, those having an average pore diameter of 1.0 to 5.0 nm are preferred, and more preferably those having an average pore diameter of 1.5 to 4.0 nm are used. The average pore diameter of the adsorbent of the present invention is determined from the pore volume determined from the nitrogen adsorption amount and the specific surface area.

[0015] Activated carbon usually has acidic groups on its surface. The types of acidic groups on the surface of activated carbon vary depending on the activated carbon, but can be evaluated by measuring the amount of acidic groups. Among them, since acidic groups affect the reactivity of the catalyst, there is no particular limitation, but it is preferable that the acid component is as small as possible. Specifically, it is preferable that the acid component in the activated carbon measured with sodium hydroxide is small. From the above viewpoints, in the adsorbent of the present invention, the amount of acidic groups measured with sodium hydroxide is preferably 0.50 mmol / g or less, more preferably 0.20 mmol / g or less, and even more preferably 0.10 mmol / g or less.

[0016] The shape of the adsorbent of the present invention can adopt any of granular, powdery, and fibrous forms. That is, when the adsorbent of the present invention is made of activated carbon, any of granular activated carbon, powdered activated carbon, and fibrous activated carbon can be adopted. Here, granular activated carbon means activated carbon having a particle size of 0.150 mm or more as defined in JIS K1474. Here, the particle size of 0.150 mm or more as defined in JIS K1474 is synonymous with the particle size measured according to the provisions of JIS K1474 being 0.150 mm or more. Specifically, a sample with a particle size range of 0.150 mm or more is 95 mass fraction% or more. On the other hand, powdered activated carbon refers to those having a particle size of less than 0.150 mm as defined in JIS K1474. Also, fibrous activated carbon means activated carbon having a fibrous shape.

[0017] The average particle size of the adsorbent of the present invention is not particularly limited, and activated carbon of each particle size can be used. However, from the viewpoints of operability before and after the reaction and reaction efficiency, it is preferably 0.1 μm to 10,000 μm, more preferably 1 μm to 3,000 μm. The ignited residue contained in the activated carbon used as the carrier of the present invention may cause unexpected side reactions in the catalytic reaction. Therefore, it is preferably 10% or less, more preferably 1% or less.

[0018] The activation method of the activated carbon of the present invention is not particularly limited. For example, it can be obtained by a production method including a step of performing steam activation treatment or chemical activation treatment using an activated carbon precursor. The raw material of the activated carbon used in the carrier of the present invention is not particularly limited as long as it is a commonly used carbon source, and examples thereof include wood, wood powder, coconut shell, coal, carbonized phenol resin, etc. Among these, from the viewpoint of low impurity content, plant raw materials are preferred, and wood powder, coconut shell, etc. are more preferred. The post-activation process is also not particularly limited, and any activated carbon produced through known washing processes, heat treatment processes, and crushing and classification processes necessary to satisfy the above characteristics can be used.

[0019] [Ruthenium complex] The ruthenium complexes represented by general formulas (1-1) and (1-2) contained in the catalyst of the present invention will be described in detail. The ruthenium complexes represented by general formulas (1-1) and (1-2) used in the present invention are characterized by having a diamine ligand, an aromatic compound (arene) ligand, and an anionic group. In general formulas (1-1) and (1-2) used in the present invention, a solid line represents a single bond, a double line represents a double bond, a dashed line represents a coordination bond, Ru represents a ruthenium atom, N represents a nitrogen atom, S represents a sulfur atom, and O represents an oxygen atom. The * mark in general formulas (1-1) and (1-2) indicates that the carbon atom with the * mark may be an asymmetric carbon atom. When the carbon atom is an asymmetric carbon atom, it may be in the form of its optically active isomer, a mixture of optically active isomers, or a racemate (including racemic compounds). As a preferred embodiment of the present invention, when these carbon atoms are asymmetric carbon atoms, these optically active isomers are included. [Chemical formula]

[0020] In general formula (1-1), j and k are integers of 0 or 1, and j + k does not become 1. General formula (1-1) shows the case where j and k are 1, and general formula (1-2) shows the case where j and k in general formula (1-1) are 0. When j and k are 1, the bond between the ruthenium atom and the nitrogen atom is a coordination bond indicated by a dashed line, and when j and k are 0, the bond between the ruthenium atom and the nitrogen atom is a covalent bond indicated by a solid line. In general formula (1-1), X represents an anionic group and Y represents a hydrogen atom. Examples of the anionic group represented by X in general formula (1-1) include a trifluoromethanesulfonyloxy group, a p-toluenesulfonyloxy group, a methanesulfonyloxy group, a benzenesulfonyloxy group, a hydrogen atom, or a halogen atom, etc. Preferred X includes a hydrogen atom and a halogen atom, specifically a fluorine atom, a chlorine atom, and a bromine atom, etc., and for example, a chlorine atom is particularly preferred. The hydrogen atom in Y of general formula (1-1) and the hydrogen atom at the position of X in general formula (1-1) (that is, the hydrogen atom bonded to Ru in general formula (1-2)) may be not only ordinary hydrogen atoms but also isotopes of hydrogen atoms. A preferred isotope is a deuterium atom.

[0021] <Sulfonyl moiety (R 1 )> R in general formulas (1-1) and (1-2) 1 represents an alkyl group; a 10-campharyl group; an aryl group which may have a substituent; or an aralkyl group which may have a substituent.

[0022] ≪Sulfonyl moiety (R 1 ): Alkyl group≫ R in general formulas (1-1) and (1-2) 1Examples of the alkyl group represented by [alkyl group] include linear or branched alkyl groups having 1 to 10 carbon atoms, preferably 1 to 5 carbon atoms. Specific examples of the alkyl group include, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, t-butyl group, n-pentyl group, n-hexyl group, n-heptyl group, n-octyl group, n-nonyl group, and n-decyl group. In addition, R in the general formulas (1-1) and (1-2) 1 The alkyl group represented by [alkyl group] may have one or more substituents selected from halogen atoms such as fluorine atom, chlorine atom, and bromine atom. For example, perfluoroalkyl groups such as trifluoromethyl group, pentafluoroethyl group, and heptafluoropropyl group can be mentioned.

[0023] ≪Sulfonyl moiety (R 1 ): An aryl group which may have a substituent ≫ R in the general formulas (1-1) and (1-2) 1 Examples of the aryl group represented by [aryl group] include aromatic monocyclic groups, aromatic polycyclic groups, or aromatic condensed ring groups having 6 to 30 carbon atoms, preferably aromatic monocyclic groups, aromatic polycyclic groups, or aromatic condensed ring groups having 6 to 15 carbon atoms, and particularly preferably aromatic monocyclic groups having 6 to 12 carbon atoms. Specific examples of the aryl group having 6 to 30 carbon atoms include, for example, phenyl group, naphthyl group, anthryl group, phenanthryl group, indenyl group, etc., and preferably phenyl group.

[0024] In addition, R in the general formulas (1-1) and (1-2) 1 The aryl group represented by [aryl group] is an alkyl group having 1 to 10 carbon atoms, a halogenated alkyl group having 1 to 10 carbon atoms, a halogen atom, a cyano group (-CN), an amino group, an alkylamino group (-NR 11 R 12 ), a 5- or 6-membered cyclic amino group, an acylamino group (-NH-CO-R 11 ), a hydroxyl group, an alkoxy group (-OR 11 ), an acyl group (-CO-R 11 ), a carboxyl group, an alkoxycarbonyl group (-COOR 11)、a phenoxycarbonyl group, and an alkylthio group (-SR 11 ) may have one or more substituents selected therefrom.

[0025] The alkyl group as a substituent can be selected from the groups defined as the alkyl group represented by R in the above general formulas (1-1) and (1-2), but preferably includes a linear or branched alkyl group having 1 to 5 carbon atoms. Further, the alkyl group as a substituent may have one or more substituents selected from halogen atoms such as a fluorine atom, a chlorine atom, and a bromine atom. 1 -NR 11 R 12 The alkylamino group represented by (wherein R 11 , R 12 each independently represents a hydrogen atom; an alkyl group having 1 to 10 carbon atoms; or a cycloalkyl group having 3 to 10 carbon atoms.) includes, for example, a monoalkylamino group or a dialkylamino group such as an N-methylamino group, an N,N-dimethylamino group, an N,N-diisopropylamino group, or an N-cyclohexylamino group. Examples of the 5- or 6-membered cyclic amino group include unsaturated or saturated heterocyclic groups having 5 to 6 members and having 1 or 2 nitrogen atoms, such as a pyrrolidinyl group, a piperidino group, and a morpholinyl group.

[0026] -CO-R 11 The acyl group represented by (wherein R 11 represents a hydrogen atom; an alkyl group having 1 to 10 carbon atoms; or a cycloalkyl group having 3 to 10 carbon atoms.) includes a formyl group, an acetyl group, a propionyl group, a butyryl group, a pivaloyl group, a pentanoyl group, or a hexanoyl group. -NH-CO-R 11 The acylamino group represented by (wherein R 11 represents a hydrogen atom; an alkyl group having 1 to 10 carbon atoms; or a cycloalkyl group having 3 to 10 carbon atoms.) includes a formylamino group, an acetylamino group, a propionylamino group, a pivaloylamino group, a pentanoylamino group, or a hexanoylamino group. -O-R11 An alkoxy group represented by (where R 11 represents a hydrogen atom; an alkyl group having 1 to 10 carbon atoms; or a cycloalkyl group having 3 to 10 carbon atoms). Examples thereof include a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an s-butoxy group, an isobutoxy group, a t-butoxy group, an n-pentyloxy group, a 2-methylbutoxy group, a 3-methylbutoxy group, a 2,2-dimethylpropyloxy group, an n-hexyloxy group, a 2-methylpentyloxy group, a 3-methylpentyloxy group, a 4-methylpentyloxy group, a 5-methylpentyloxy group, or a cyclohexyloxy group, etc.

[0027] -COO-R 11 An alkoxycarbonyl group represented by (where R 11 represents a hydrogen atom; an alkyl group having 1 to 10 carbon atoms; or a cycloalkyl group having 3 to 10 carbon atoms). Examples thereof include a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an isopropoxycarbonyl group, an n-butoxycarbonyl group, a t-butoxycarbonyl group, a pentyloxycarbonyl group, a hexyloxycarbonyl group, or a 2-ethylhexyloxycarbonyl group, etc. -SR 11 An alkylthio group represented by (where R 11 represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms; or a cycloalkyl group having 3 to 10 carbon atoms). Examples thereof include a methylthio group, an ethylthio group, an n-propylthio group, an isopropylthio group, an n-butylthio group, an s-butylthio group, an isobutylthio group, a t-butylthio group, a pentylthio group, a hexylthio group, or a cyclohexyl group, etc.

[0028] R in the general formulas (1-1) and (1-2) 1Specific examples of the aryl group which may have a substituent, as represented by [the formula], include a phenyl group, o-, m- and p-tolyl groups, o-, m- and p-ethylphenyl groups, o-, m- and p-isopropylphenyl groups, o-, m- and p-t-butylphenyl groups, 2,4,6-trimethylphenyl group, 2,4,6-triisopropylphenyl group, 4-trifluoromethylphenyl group, 2,4,6-trichlorophenyl group, pentafluorophenyl group and the like.

[0029] ≪Sulfonyl moiety (R 1 ): aralkyl group (which may have a substituent)≫ The aralkyl group represented by R in General Formulas (1-1) and (1-2) 1 includes, for example, a benzyl group, a phenethyl group and the like. Further, the aralkyl group represented by R in General Formulas (1-1) and (1-2) 1 may have an alkyl group having 1 to 10 carbon atoms as a substituent. Specific examples of the aralkyl group substituted with the specific substituent, as represented by R in General Formulas (1-1) and (1-2) 1 include, for example, o-, m- and p-methylbenzyl groups, 2,6-dimethylbenzyl group, 2,4,6-trimethylbenzyl group, 2,4,6-triisopropylbenzyl group and the like.

[0030] <Diamine moiety (R 2 ,R 3 )> R and R in General Formulas (1-1) and (1-2) 2 and R 3 each independently represent a hydrogen atom; or a phenyl group, or R 2 and R 3 are bonded to each other to form a 4- to 8-membered cycloalkane ring together with the carbon atom to which R 2 and R 3 are bonded.

[0031] ≪Diamine moiety (R 2 ,R 3 ): phenyl group≫ R in General Formulas (1-1) and (1-2) 2and R 3 The phenyl group represented by 3 may have one or more substituents selected from an alkyl group, a halogen atom, and an alkoxy group. The alkyl group as a substituent is the R in the general formulas (1-1) and (1-2) described above 2 and R 3 and can be selected from the groups defined as the alkyl group represented by 3 , but preferably a linear or branched alkyl group having 1 to 5 carbon atoms. Examples of the halogen atom as a substituent include a fluorine atom or a chlorine atom. Examples of the alkoxy group as a substituent include a linear or branched alkoxy group having 1 to 10 carbon atoms, preferably 1 to 5 carbon atoms. Specific alkoxy groups include, for example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, s-butoxy group, isobutoxy group, t-butoxy group, n-pentyloxy group, n-hexyloxy group, n-heptyloxy group, n-octyloxy group, n-nonyloxy group, and n-decyloxy group.

[0032] <<Diamine moiety (R 2 , R 3 ): R 2 and R 3 form a ring>> When R 2 and R 3 in the general formulas (1-1) and (1-2) are bonded to each other, R 2 and R 3 together with the carbon atom to which they are bonded form a linear or branched alkylene group having 2 to 10 carbon atoms, preferably 3 to 10 carbon atoms, and together with adjacent carbon atoms form a 4- to 8-membered ring, preferably a 5- to 8-membered cycloalkane ring. These rings may have an alkyl group such as a methyl group, an isopropyl group, or a t-butyl group as a substituent. <Substituent on amine (R 4 )> R 4 in the general formulas (1-1) and (1-2) represents a hydrogen atom; or an alkyl group which may have a substituent, or R 5It may combine to form a crosslinking site of the divalent group represented by formula (W). When forming the crosslinking site, the ruthenium complex becomes a tether type.

[0033]

Chemical formula

[0034] ≪Substituent on amine (R 4 ): Alkyl group≫ Examples of the alkyl group represented by R in general formulas (1-1) and (1-2) 4 include linear or branched alkyl groups having 1 to 10 carbon atoms, preferably 1 to 5 carbon atoms. Specific examples of the alkyl group include, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, t-butyl group, n-pentyl group, n-hexyl group, n-heptyl group, n-octyl group, n-nonyl group, and n-decyl group. In addition, the alkyl group represented by R in general formulas (1-1) and (1-2) 4 may have one or more substituents selected from halogen atoms such as fluorine atom, chlorine atom, and bromine atom. For example, perfluoroalkyl groups such as trifluoromethyl group, pentafluoroethyl group, and heptafluoropropyl group can be mentioned.

[0035] ≪Substituent on amine (R 4 ): When forming the crosslinking site≫ R in general formulas (1-1) and (1-2) 4 is R 5When combining to form the crosslinking site of the divalent group represented by formula (W), Z in general formula (W) represents a methylene group or an oxygen atom. Preferred Z includes an oxygen atom. n in general formula (W) 1 represents an integer of 1 or 2, and preferred n 1 is 1. n 2 represents an integer from 1 to 3, and preferred n 2 is 2.

[0036] <The arene moiety (R 5 -R 10 )> R of the arene moiety represented by general formulas (1-1) and (1-2) 5 , R 6 , R 7 , R 8 , R 9 , R 10 each independently represents a hydrogen atom; an alkyl group; a hydroxyl group; or an alkoxy group. Alternatively, R 5 may form a crosslinking site with R 4 as shown in the said formula (W).

[0037] ≪The arene moiety (R 5 -R 10 ): Alkyl group ≫ The alkyl group represented by R 5 , R 6 , R 7 , R 8 , R 9 , R 10 in general formulas (1-1) and (1-2) includes linear or branched alkyl groups having 1 to 10 carbon atoms, preferably 1 to 5 carbon atoms. Specific alkyl groups include, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, t-butyl group, n-pentyl group, n-hexyl group, n-heptyl group, n-octyl group, n-nonyl group, and n-decyl group, etc.

[0038] ≪The arene moiety (R 5 -R 10 ): Alkoxy group ≫ R in general formulas (1-1) and (1-2) 5 , R 6 ,R 7 , R 8 ,R 9 , R 10 The alkoxy group represented by the formula (I) includes a straight-chain or branched alkoxy group having 1 to 10 carbon atoms, preferably 1 to 5 carbon atoms. Specific examples of the alkoxy group include a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an s-butoxy group, an isobutoxy group, a t-butoxy group, an n-pentyloxy group, an n-hexyloxy group, an n-heptyloxy group, an n-octyloxy group, an n-nonyloxy group, and an n-decyloxy group.

[0039] R in general formulas (1-1) and (1-2) 4 and R 5 When R is a complex that does not form a bridging moiety as shown in formula (W) (i.e., a non-tethered ruthenium complex), 4 is preferably a hydrogen atom, and / or R 1 is preferably 4-methylphenyl, 2,3,4,5,6-pentafluorophenyl, methyl, isobutyl, benzyl, 2',5'-dimethylbenzyl or 10-camphoryl, and / or R 2 and R 3 are preferably a phenyl group or are bonded together to form a cyclohexane ring, and / or R 5 , R 6 , R 7 , R 8 , R 9 , R 10 is preferably a hydrogen atom, a methyl group, or an isopropyl group.

[0040] R in general formulas (1-1) and (1-2) 4 and R 5 Specific examples of complexes that do not form a crosslinking moiety represented by formula (W) (i.e., non-tethered ruthenium complexes) include, but are not limited to, the following compounds. In the following, the compound names and their abbreviations (in parentheses) used in this specification are listed together. Chloro(benzene)[(R,R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((R,R)-Ts-DPEN)(benzene)) Chloro(benzene)[(S,S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((S,S)-Ts-DPEN)(benzene)) Chloro(mesitylene)[(R,R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((R,R)-Ts-DPEN)(mesitylene)) Chloro(mesitylene)[(S,S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((S,S)-Ts-DPEN)(mesitylene)) Chloro(mesitylene)[(R,R)-N-(methanesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((R,R)-Ms-DPEN)(mesitylene)) Chloro(mesitylene)[(S,S)-N-(methanesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((S,S)-Ms-DPEN)(mesitylene)) Chloro(mesitylene)[(R,R)-N-(benzylsulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((R,R)-BnSO2-DPEN)(mesitylene)) Chloro(mesitylene)[(S,S)-N-(benzylsulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((S,S)-BnSO2-DPEN)(mesitylene)) Chloro(mesitylene)[(R,R)-N-(isobutanesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((R,R)-i-BuSO2-DPEN)(mesitylene)) Chloro(mesitylene)[(S,S)-N-(isobutanesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((S,S)-i-BuSO2-DPEN)(mesitylene)) Chloro(mesitylene)[(R,R)-N-(2‘,6’-dimethylbenzylsulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((R,R)-2’,6’-(CH3)2BnSO2-DPEN)(mesitylene)) Chloro(mesitylene)[(S,S)-N-(2‘,6’-dimethylbenzylsulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((S,S)-2’,6’-(CH3)2BnSO2-DPEN)(mesitylene)) Chloro(p-cymene)[(R,R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((R,R)-Ts-DPEN)(p-cymene)) Chloro(p-cymene)[(S,S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((S,S)-Ts-DPEN)(p-cymene)) (p-cymene)[(R,R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) triflate (Ru(OTf)((R,R)-Ts-DPEN)(p-cymene)) (p-cymene)[(S,S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) triflate (Ru(OTf)((S,S)-Ts-DPEN)(p-cymene)) (p-cymene)[(R,R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) hydride (RuH((R,R)-Ts-DPEN)(p-cymene)) (p-cymene)[(S,S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) hydride (RuH((S,S)-Ts-DPEN)(p-cymene)) (p-cymene)[(R,R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (Ru((R,R)-Ts-DPEN)(p-cymene)) (p-cymene)[(S,S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (Ru((S,S)-Ts-DPEN)(p-cymene)) Chloro(p-cymene)[(R,R)-N-(methanesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((R,R)-Ms-DPEN)(p-cymene)) Chloro(p-cymene)[(S,S)-N-(methanesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((S,S)-Ms-DPEN)(p-cymene)) Chloro(p-cymene)[(R,R)-N-(pentafluorobenzenesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((R,R)-Fs-DPEN)(p-cymene)) Chloro(p-cymene)[(S,S)-N-(pentafluorobenzenesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((S,S)-Fs-DPEN)(p-cymene)) Chloro(p-cymene)[(R,R)-N-(benzylsulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((R,R)-BnSO2-DPEN)(p-cymene)) Chloro(p-cymene)[(S,S)-N-(benzylsulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((S,S)-BnSO2-DPEN)(p-cymene)) Chloro((p-cymene)[(R,R)-N-(isobutanesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((R,R)-i-BuSO2-DPEN)(p-cymene)) Chloro(p-cymene)[(S,S)-N-(isobutanesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((S,S)-i-BuSO2-DPEN)(p-cymene)) Chloro(p-cymene)[(R,R)-N-(2‘,6’-dimethylbenzylsulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((R,R)-2’,6’-(CH3)2BnSO2-DPEN)(p-cymene)) Chloro(p-cymene)[(S,S)-N-(2‘,6’-dimethylbenzylsulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((S,S)-2’,6’-(CH3)2BnSO2-DPEN)(p-cymene)) Chloro(p-cymene)[(R,R)-N-((1R)-camphorsulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((R)-Cs-(R,R)-DPEN)(p-cymene)) Chloro(p-cymene)[(S,S)-N-((1S)-camphorsulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((S)-Cs-(S,S)-DPEN)(p-cymene)) Chloro(p-cymene)[(R,R)-N-(p-toluenesulfonyl)-1,2-cyclohexanediamine]ruthenium(II) (RuCl((R,R)-Ts-DACH)(p-cymene)) Chloro(p-cymene)[(S,S)-N-(p-toluenesulfonyl)-1,2-cyclohexanediamine]ruthenium(II) (RuCl((S,S)-Ts-DACH)(p-cymene))

[0041] R in general formulas (1-1) and (1-2) 4 and R 5 When it is a complex that forms a cross-linking site shown in formula (W) (that is, a tether-type ruthenium complex), Z is preferably an oxygen atom, and / or, n 1 is preferably 1, and / or, n 2 is preferably 2, and / or, R 1 is preferably a 4-methylphenyl group or a methyl group, and / or, R 2 and R 3 are preferably phenyl groups, and / or, R6 , R 7 , R 9 , R 10 is preferably a hydrogen atom, and / or R 8 is preferably a methyl group.

[0042] In general formulas (1-1) and (1-2), R 4 and R 5 form a complex having a cross-linking site represented by formula (W) (that is, a tether-type ruthenium complex). Specific examples thereof include, but are not limited to, the following compounds. Hereinafter, the compound name and the abbreviation (in parentheses) in this specification are shown together. Chloro[(R,R)-N-[2-[2-(4-methylbenzyloxy)ethyl]amino-1,2-diphenylethyl]-p-toluenesulfonamide]ruthenium(II) ((R,R)-Ts-DENEB (registered trademark)) Chloro[(S,S)-N-[2-[2-(4-methylbenzyloxy)ethyl]amino-1,2-diphenylethyl]-p-toluenesulfonamide]ruthenium(II) ((S,S)-Ts-DENEB (registered trademark)) Chloro[(R,R)-N-[2-[2-(4-methylbenzyloxy)ethyl]amino-1,2-diphenylethyl]-methanesulfonamide]ruthenium(II) ((R,R)-Ms-DENEB (registered trademark)) Chloro[(S,S)-N-[2-[2-(4-methylbenzyloxy)ethyl]amino-1,2-diphenylethyl]-methanesulfonamide]ruthenium(II) ((S,S)-Ms-DENEB (registered trademark)) Chloro[(R,R)-N-[2-(3-phenylpropyl)amino-1,2-diphenylethyl]-p-toluenesulfonamide]ruthenium(II) (RuCl(benz-C3-teth-(R,R)-Ts-DPEN)) Chloro[(S,S)-N-[2-(3-phenylpropyl)amino-1,2-diphenylethyl]-p-toluenesulfonamide]ruthenium(II) (RuCl(benz-C3-teth-(S,S)-Ts-DPEN)) Chloro[(R,R)-N-[2-(3-phenylpropyl)amino-1,2-diphenylethyl]-methanesulfonamide]ruthenium(II) (RuCl(benz-C3-teth-(R,R)-Ms-DPEN)) Chloro[(S,S)-N-[2-(3-phenylpropyl)amino-1,2-diphenylethyl]-methanesulfonamide]ruthenium(II) (RuCl(benz-C3-teth-(S,S)-Ms-DPEN))

[0043] The ruthenium complex, which is a constituent of the catalyst according to the present invention, can be synthesized by those skilled in the art by, for example, the methods described in Japanese Patent No. 3040353 and Japanese Patent No. 5718178. Alternatively, the ruthenium complex available on the market may be used.

[0044] <Method for producing catalyst: Regarding the state of the complex and the preparation solvent> The catalyst of the present invention can be obtained by reacting a ruthenium complex of the general formula (1-1) and / or (1-2) with activated carbon in a solvent. During the preparation, the state of the complex is not particularly limited, but it is preferably dissolved in the preparation solvent. The solvent used in this case is not particularly limited, but protic polar solvents such as methanol, ethanol, and water are preferred, and methanol is particularly preferred. When the complex is difficult to dissolve in the preparation solvent, two or more solvents may be mixed and used as necessary. In addition, in the catalyst of the present invention, although not particularly limited, as described above, it is preferably prepared such that the total mass of the ruthenium complex is usually in the range of 0.1% by mass to 25% by mass with respect to the total mass of the activated carbon. <<Support conditions: Heating and stirring conditions>> During the reaction, it may be stirred or left standing. During the preparation, heating may or may not be carried out. The reaction solution immediately after the start of the preparation generally shows a dark brown color, while the decolorization of the reaction solution as the attachment progresses is observed over time. The preparation end time varies depending on the type and supported amount of the activated carbon and the complex, but in practical use, various conditions may be set so that the attachment is completed within 12 hours to 7 days. The solvent after the preparation may be removed by evaporation or by filtration. <<Support conditions: Washing and drying conditions>> The activated carbon powder obtained after removing the preparation solvent is washed with an organic solvent. The washing solvent is not particularly limited, but it is preferable to use the same solvent as that used during the preparation. The obtained activated carbon-supported complex may or may not contain the washing solvent, but it is preferably removed by drying under reduced pressure. The degree of vacuum during drying under reduced pressure is not particularly limited, but it is preferably approximately 20 torr or less. Heating may be carried out if necessary, and the heating temperature is preferably 40 °C or lower.

[0045] <Catalytic reaction> Using the catalyst of the present invention described above, and in the presence of a hydrogen donor, an organic compound can be reduced to produce a reduction product. The reduction reaction of the present invention includes a method of reducing a carbonyl group of a carbonyl compound such as ketones to produce an alcohol, and / or a method of reducing an imino group of an imine compound to produce an amine, using the catalyst according to the present invention and in the presence of a hydrogen donor. Further, when the above-mentioned activated carbon-supported ruthenium complex is an optically active substance, the carbonyl group of the carbonyl compound can be asymmetrically reduced to produce an optically active alcohol, and the imino group of the imine compound can be reduced to produce an optically active amine.

[0046] The hydrogen donor is not particularly limited as long as it is generally used in hydrogen transfer reduction reactions such as formic acid or its alkali metal salts, and alcohols having a hydrogen atom at the α-position of a carbon atom substituted with a hydroxyl group, such as isopropanol. Hydrogen gas can also be used as the hydrogen donor. As the solvent used in the reaction, if the hydrogen donor is a liquid, it can be used. However, it is also possible to use non-hydrogen donating solvents such as toluene, tetrahydrofuran, acetonitrile, dimethylformamide, dimethyl sulfoxide, acetone, methylene chloride, or water, methanol, ethanol, n-butanol alone or in combination.

[0047] ≪When using formate≫ When carrying out the reduction reaction and using formate as the hydrogen donor, it is preferable to use water in combination with an organic solvent to dissolve the hydrogen donor. The organic solvent to be used is not particularly limited, but a solvent that is easily miscible with water is preferable, and examples include methanol, ethanol, n-butanol, etc.

[0048] ≪When using formic acid≫ When carrying out the reduction reaction and using formic acid as the hydrogen donor, it is preferably carried out in the presence of a base such as tertiary organic amines or inorganic bases, and more preferably in the presence of tertiary organic amines. The amine to be used is not particularly limited, and examples include tertiary organic amines such as trimethylamine, triethylamine, triisopropylamine, 1,4-diazabicyclo[2,2,2]octane (DABCO), 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU). In this case, formic acid and the amine may be added to the reaction system separately or mixed and then added to the reaction system. When used in a mixture, formic acid and the amine can be mixed and used at any ratio. Alternatively, an azeotropic mixture of formic acid and the amine may be prepared in advance and used. Preferred azeotropic mixtures of formic acid and the amine include, for example, formic acid triethylamine (5:2 (molar ratio)) azeotropic mixture. When the catalyst according to the present invention is used as a reduction catalyst, the amount used is preferably such that the molar ratio (S / C) of the substrate (carbonyl compound or imines) (S) to ruthenium metal atoms (C) is selected from the range of 10 to 1,000,000, preferably 50 to 15,000.

[0049] ≪Amount of hydrogen donor≫ As the amount of the hydrogen donor relative to the carbonyl compound, usually an equimolar amount or more is used. When the hydrogen donor is formic acid or its salt, an amount of 1.5 times the molar amount or more is preferable, and it is used in the range of 40 times the molar amount or less, preferably 20 times the molar amount or less. From the viewpoint of molecular efficiency, it is preferably 2 to 20 times the molar amount. On the other hand, when the hydrogen donor is isopropanol or the like, it is used in a large excess relative to the substrate from the viewpoint of the reaction equilibrium, and is usually used in the range of 100 times the molar amount or less.

[0050] ≪Details of reaction conditions≫ The reaction temperature is selected from the range of -20 to 100°C, preferably 0 to 70°C. The reaction pressure is not particularly limited, and it is usually carried out under 0.5 to 2 atmospheres, preferably normal pressure. When hydrogen gas is used, it is usually 5 MPa or less. The reaction time varies depending on the catalyst ratio to the substrate, but it is carried out in the range of 1 to 100 hours, usually 2 to 50 hours.

[0051] ≪Regarding reuse≫ After completion of the reaction, the catalyst according to the present invention and the reaction solution of the reduced target product can be separated by a simple method such as decantation or filtration. Further, the catalyst of the present invention separated by decantation or the like can be reused as it is for the next reaction. From the reaction solution after removing the catalyst, the produced product or optically active substance can be separated and purified by general operations such as distillation, extraction, chromatography, and recrystallization. ≪Regarding flow reaction≫ In addition, in the reduction reaction of the present invention, a continuous flow reaction can be carried out by taking advantage of the characteristics of the ruthenium complex supported on activated carbon. That is, after filling the activated carbon-supported ruthenium complex into a column, while maintaining the column at the above-mentioned reaction temperature, a substrate, a hydrogen donor, and a solvent are fed by a metering pump, so that a catalyst separation operation is not required, and an organic compound can be reduced to produce a reduction product. The reaction conditions are the same as those described above. The reaction can be carried out, for example, by preparing a mixed solution of a substrate, a solvent, a base, and a hydrogen donor and feeding it to a column using an HPLC pump. When the hydrogen donor is hydrogen gas, a substrate, a solvent, and a base are mixed, the mixed solution is fed to the column, and hydrogen gas is passed through the column to cause the reaction.

Examples

[0052] Hereinafter, examples of the compound of the present invention and the catalytic reaction using the catalyst of the present invention will be described in detail, but the present invention is not limited by these examples. In the examples, the apparatuses and conditions used for measuring physical properties are as follows.

[0053] 1) Gas chromatography (GC): GC-4000Plus type apparatus (manufactured by GL Sciences Inc.) [Measurement condition 1] Column: CP-Chirasil-DEX CB (manufactured by Agilent Technologies), sample introduction part: 250 °C, sample detection part: 250 °C, measurement temperature: 120 °C, retention time: 15 minutes. [Measurement condition 2] Column: CP-Chirasil-DEX CB (manufactured by Agilent Technologies), sample introduction part: 250 °C, sample detection part: 250 °C, measurement temperature: 120 °C, retention time: 30 minutes. [Measurement condition 3] Column: CP-Chirasil-DEX CB (manufactured by Agilent Technologies), sample introduction part: 250 °C, sample detection part: 250 °C, measurement temperature: 150 °C, retention time: 25 minutes. [Measurement condition 4] Column: CP-Chirasil-DEX CB (manufactured by Agilent Technologies), sample introduction part: 250 °C, sample detection part: 250 °C, measurement temperature: 120 °C, retention time: 35 minutes. [Measurement Condition 5] Column: CP-Chirasil-DEX CB (manufactured by Agilent), Sample Introduction Part: 250 °C, Sample Detection Part: 250 °C, Measurement Temperature: 60 °C, Holding Time: 30 minutes.

[0054] 2) Plasma (ICP) Emission Spectrometer Inductively coupled plasma optical emission spectrometry (ICP-OES) was used for the analysis of the eluted metal amount. In the examples, the apparatus and conditions used for the analysis of the eluted ruthenium amount were as follows. Apparatus: Optima8300 (manufactured by Perkin Elmer) RF Output: 1.5 kW Plasma Gas Flow Rate: 12 mL / min (argon gas) Auxiliary Gas Flow Rate: 0.4 L / min (argon gas) Carrier Gas Flow Rate: 0.35 L / min (argon gas) Sample Introduction Rate: 0.8 mL / min Chamber: Cyclone Chamber

[0055] 3) Proton Nuclear Magnetic Resonance Spectroscopy ( 1 1H NMR): 400-MR DD2 type apparatus (resonance frequency: 400 MHz) (manufactured by Agilent)

[0056] 4) SEM-EDS SEM-EDS was used for the analysis of ruthenium on the catalyst. Analytical Apparatus: TM-3000 (manufactured by Hitachi High-Technologies Corporation) Analysis Software: SwiftED Ver.1.7 (manufactured by Oxford Instruments Co., Ltd.) Acceleration Voltage: 15 kV The characteristic X-ray energies of the elements to be analyzed are as shown in Table 1.

[0057]

Table 1

[0058] The activated carbon used in this example is as shown in Table 2.

Table 2

[0059] [Example 1] Preparation of a catalyst (Catalyst 1) containing chloro[(R,R)-N-[2-[2-(4-methylbenzyloxy)ethyl]amino-1,2-diphenylethyl]-p-toluenesulfonamide]ruthenium(II) adsorbed on powdered activated carbon (A1) Chloro[(R,R)-N-[2-[2-(4-methylbenzyloxy)ethyl]amino-1,2-diphenylethyl]-p-toluenesulfonamide]ruthenium(II) ((R,R)-Ts-DENEB (manufactured by Takasago International Corporation), 40.7 mg, 0.0626 mmol), dehydrated toluene (39 mL), and dehydrated ethanol (2 mL) were added to a 200 mL beaker and completely dissolved to prepare a complex solution. After adding activated carbon (A1, 5.00 g) to a 300 mL beaker, the complex solution was added over 1 minute. The resulting suspension was allowed to stand until the solvent evaporated. Dehydrated toluene (30 mL) and dehydrated ethanol (1.5 mL) were added to the resulting solid component, stirred for 1 minute, and then filtered. After transferring the resulting solid to a 300 mL beaker, dehydrated toluene (30 mL) and dehydrated ethanol (1.5 mL) were added, stirred for 1 minute, and then filtered. The solid component recovered by filtration was vacuum dried at 40 °C for 24 hours to obtain 6.56 g of Compound 1. The filtrate was concentrated under reduced pressure, and the amount of ruthenium contained in the recovered residue was measured by ICP analysis. As a result, the unadsorbed ruthenium component was 0.3% of the ruthenium component used, so the adsorption rate of the complex was 99.7%, and the loading amount of the complex on the activated carbon was found to be 0.81% by mass.

[0060] [Example 2] Preparation of a catalyst (Catalyst 2) containing the (R,R)-Ts-DENEB complex adsorbed on powdered activated carbon (A2) Compound 2 (6.62 g) was obtained in the same manner as in Example 1, except that A2 (5.00 g) was used for the activated carbon. The filtrate was concentrated under reduced pressure, and the amount of ruthenium contained in the recovered trace residue was measured by ICP analysis. As a result, since the unadsorbed ruthenium component was 0.7%, the adsorption rate of the complex was 99.3%, and the supported amount of the complex on the activated carbon was found to be 0.80 mass%.

[0061] [Example 3] Preparation of a catalyst (Catalyst 3) containing the (R,R)-Ts-DENEB complex adsorbed on powdered activated carbon (B1) Compound 3 (6.10 g) was obtained in the same manner as in Example 1, except that B1 (5.00 g) was used for the activated carbon. When the filtrate was concentrated under reduced pressure, the unadsorbed complex was recovered as a solid-phase component. Since the mass of the recovered complex was 8.9 mg, the adsorption rate of the complex was 78.1%, and the supported amount of the complex on the activated carbon was 0.63 mass%.

[0062] [Example 4] Preparation of a catalyst (Catalyst 4) containing the (R,R)-Ts-DENEB complex adsorbed on powdered activated carbon (B2) Compound 4 (6.17 g) was obtained in the same manner as in Example 1, except that B2 (5.00 g) was used for the activated carbon. When the filtrate was concentrated under reduced pressure, the unadsorbed complex was recovered as a solid-phase component. Since the mass of the recovered complex was 9.0 mg, the adsorption rate of the complex was 77.9%, and the supported amount of the complex on the activated carbon was 0.63 mass%.

[0063] [Example 5] Preparation of a catalyst (Catalyst 5) containing the (R,R)-Ts-DENEB complex adsorbed on powdered activated carbon (C1) Compound 5 (5.74 g) was obtained in the same manner as in Example 1, except that C1 (5.00 g) was used for the activated carbon. The filtrate was concentrated under reduced pressure, but no solid-phase component was recovered. That is, the adsorption rate of the complex was 100%, and the supported amount of the complex on the activated carbon was 0.81 mass%.

[0064] [Example 6] Preparation of a catalyst (Catalyst 6) containing the (R,R)-Ts-DENEB complex adsorbed on powdered activated carbon (C2) Compound 6 (5.85 g) was obtained in the same manner as in Example 1, except that C2 (5.00 g) was used for the activated carbon. The filtrate was concentrated under reduced pressure, and the amount of ruthenium contained in the recovered trace residue was measured by ICP analysis. As a result, since the unadsorbed ruthenium component was 1.0%, the adsorption rate of the complex was 99.0%, and it was found that the supported amount of the complex on the activated carbon was 0.80 mass%.

[0065] [Example 7] Preparation of a catalyst (Catalyst 7) containing an (R,R)-Ts-DENEB complex adsorbed on powdered activated carbon (M) Compound 7 (5.82 g) was obtained in the same manner as in Example 1, except that M (5.00 g) was used for the activated carbon. The filtrate was concentrated under reduced pressure, but the solid phase component was not recovered. That is, the adsorption rate of the complex was 100%, and the supported amount of the complex on the activated carbon was 0.81 mass%.

[0066] [Example 8] Preparation of a catalyst (Catalyst 8) containing an (R,R)-Ts-DENEB complex adsorbed on granular activated carbon (A1, granular) Compound 8 (6.02 g) was obtained in the same manner as in Example 1, except that A1 (granular, 5.00 g) was used for the activated carbon. The filtrate was concentrated under reduced pressure, but the solid phase component was not recovered. That is, the adsorption rate of the complex was 100%, and the supported amount of the complex on the activated carbon was 0.81 mass%.

[0067] [Example 9] Preparation of a catalyst (Catalyst 9) containing an (R,R)-Ts-DENEB complex adsorbed on granular activated carbon (A2, granular) Compound 9 (6.56 g) was obtained in the same manner as in Example 1, except that A2 (granular 5.00 g) was used for the activated carbon. The filtrate was concentrated under reduced pressure, but the solid phase component was not recovered. That is, the adsorption rate of the complex was 100%, and the supported amount of the complex on the activated carbon was 0.81 mass%.

[0068] [Example 10] Preparation of a catalyst (Catalyst 10) containing an (R,R)-Ts-DENEB complex adsorbed on granular activated carbon (B1 granular) Compound 10 (5.84 g) was obtained in the same manner as in Example 1, except that B1 (granular, 5.00 g) was used for the activated carbon. When the filtrate was concentrated under reduced pressure, the unadsorbed complex was recovered as a solid-phase component. Since the mass of the recovered complex was 12.0 mg, the adsorption rate of the complex was 70.5%, and the loading amount of the complex on the activated carbon was 0.57% by mass.

[0069] [Example 11] Preparation of a catalyst (Catalyst 11) containing an (R,R)-Ts-DENEB complex adsorbed on granular activated carbon (B2, granular) Compound 11 (6.01 g) was obtained in the same manner as in Example 1, except that B2 (granular, 5.00 g) was used for the activated carbon. When the filtrate was concentrated under reduced pressure, the unadsorbed complex was recovered as a solid-phase component. Since the mass of the recovered complex was 12.1 mg, the adsorption rate of the complex was 70.3%, and the loading amount of the complex on the activated carbon was 0.57% by mass.

[0070] [Example 12] Preparation of a catalyst (Catalyst 12) containing an (R,R)-Ts-DENEB complex adsorbed on granular activated carbon (C2, granular) Compound 12 (5.60 g) was obtained in the same manner as in Example 1, except that the activated carbon was changed to C2 (granular, 5.00 g). The filtrate was concentrated by an evaporator, but the solid-phase component was not recovered. That is, the adsorption rate of the complex was 100%, and the loading amount of the complex on the activated carbon was 0.81% by mass. Table 3 shows the preparation results of catalysts containing Ts-DENEB catalysts adsorbed on various activated carbons.

[0071] Table 3: Preparation results of catalysts containing Ts-DENEB catalysts adsorbed on activated carbon

Table 3

[0072] [Example 13] Preparation of a catalyst (Catalyst 13) containing an (R,R)-Ts-DENEB complex adsorbed on granular activated carbon (A2, granular) (R,R)-Ts-DENEB (199.9 mg, 0.307 mmol) was charged into a 200 mL eggplant flask with a branch, and nitrogen substitution was carried out. Then, dehydrated toluene (57 mL) and dehydrated ethanol (3 mL) were added and dissolved. Subsequently, activated carbon (A2, granular, 4.96 g) manufactured by Osaka Gas Chemical Co., Ltd. was added, and the mixture was allowed to stand at room temperature for 1 week under a nitrogen atmosphere. After removing the supernatant by vacuum filtration, the filtered solid was transferred to a 300 mL beaker. Dehydrated toluene (30 mL) and dehydrated ethanol (1.5 mL) were added and stirred for 1 minute, followed by filtration. The same operation was repeated twice, and the solid component recovered by filtration was vacuum dried at 40 °C for 24 hours to obtain 6.12 g of Compound 13. When the filtrate was concentrated under reduced pressure, the unadsorbed complex was recovered as a solid phase component. Since the mass of the recovered complex was 107.0 mg, the adsorption rate of the complex was 46.5%, and the loading amount of the complex on the activated carbon was 1.9% by mass.

[0073] [Example 14] Preparation of a catalyst (Catalyst 14) containing a Ts-DENEB complex adsorbed on granular activated carbon (A2, granular) Compound 14 (6.20 g) was obtained in the same manner as in Example 13, except that the charged amount of Ts-DENEB was changed to 400.4 mg (0.616 mmol), the charged amount of activated carbon A2 (granular) was changed to 5.00 g, the charged amount of dehydrated toluene was changed to 114 mL, and the charged amount of dehydrated ethanol was changed to 6 mL. When the filtrate was concentrated using an evaporator, the unadsorbed complex was recovered as a solid phase component. Since the mass of the recovered complex was 278.5 mg, the adsorption amount of the complex on the activated carbon was 30.4%, and the loading amount of the complex on the activated carbon was 2.4% by mass.

[0074] [Example 15] Preparation of a catalyst (Catalyst 15) containing an (R,R)-Ts-DENEB complex adsorbed on granular activated carbon (A2, granular) (R,R)-Ts-DENEB (199.7 mg, 0.307 mmol) was charged into a 200 mL eggplant-shaped flask equipped with a stopper, and the flask was purged with nitrogen. Subsequently, dehydrated methanol (60 mL) was added and dissolved. Subsequently, activated carbon (A2, granular, 4.87 g) manufactured by Osaka Gas Chemical Co., Ltd. was added, and the mixture was allowed to stand at room temperature for 1 week under a nitrogen atmosphere. After removing the supernatant by vacuum filtration, the separated solid was transferred to a 300 mL beaker. Dehydrated methanol (30 mL) was added and stirred for 1 minute, followed by filtration. The same operation was repeated twice, and the solid component recovered by filtration was vacuum dried at 40 °C for 24 hours to obtain 5.03 g of Compound 15. When the filtrate was concentrated under reduced pressure, the unadsorbed complex was recovered as a solid phase component. Since the mass of the recovered complex was 6.9 mg, the adsorption amount of the complex onto the activated carbon was 96.5%, and the supported amount as the complex was 3.9 mass%.

[0075] [Example 16] Preparation of a catalyst (Catalyst 16) containing an (R,R)-Ts-DENEB complex adsorbed on granular activated carbon (A2, granular) Compound 16 (5.12 g) was obtained in the same manner as in Example 15, except that the charged amount of (R,R)-Ts-DENEB was changed to 400.0 mg (0.615 mmol), the charged amount of activated carbon (A2, granular) was changed to 4.96 g, and the charged amount of dehydrated methanol was changed to 120 mL. When the filtrate was concentrated under reduced pressure, the unadsorbed complex was recovered as a solid phase component. Since the mass of the recovered complex was 34.2 mg, the adsorption amount of the complex onto the activated carbon was 91.4%, and the supported amount as the complex on the activated carbon was 7.3 mass%.

[0076] [Example 17] Preparation of a catalyst (Catalyst 17) containing an (R,R)-Ts-DENEB complex adsorbed on granular activated carbon (C2, granular) Compound 17 was obtained in the same manner as in Example 16, except that the activated carbon was changed to C2 (granular, 4.90 g). When the filtrate was concentrated under reduced pressure, the unadsorbed complex was recovered as a solid phase component. Since the mass of the recovered complex was 44.2 mg, the adsorption amount of the complex onto the activated carbon was 89.0%, and the supported amount as the complex on the activated carbon was 7.2 mass%.

[0077] [Example 18] Preparation of a catalyst (Catalyst 18) containing an (R,R)-Ts-DENEB complex adsorbed on granular activated carbon (A2, granular) To a 200 mL beaker were added (R,R)-Ts-DENEB (400.0 mg, 0.0615 mmol) and dehydrated methanol (100 mL) and dissolved to prepare a complex solution. To a 300 mL beaker was added activated carbon (A2, granular, 5.00 g), and then the complex solution was added over 1 minute. The resulting suspension was allowed to stand until the solvent had evaporated. Dehydrated methanol (30 mL) was added to the resulting solid component, stirred for 1 minute, and then filtered. The same operation was repeated twice, and the solid component recovered by filtration was vacuum dried at 40 °C for 24 hours to obtain 5.10 g of Compound 18. When the filtrate was concentrated under reduced pressure, the unadsorbed complex was recovered as a solid phase component. Since the mass of the recovered complex was 15.7 mg, the adsorption rate of the complex was 96.1%, and the loading amount of the complex on the activated carbon was 7.7% by mass.

[0078] [Example 19] Preparation of a catalyst (Catalyst 19) containing an (R,R)-Ts-DENEB complex adsorbed on granular activated carbon (C2, granular) Compound 19 was obtained in the same manner as in Example 18 except that the activated carbon was changed to C2 (granular, 5.00 g). When the filtrate was concentrated under reduced pressure, the unadsorbed complex was recovered as a solid phase component. Since the mass of the recovered complex was 15.1 mg, the adsorption rate of the complex was 96.2%, and the loading amount of the complex on the activated carbon was 7.7% by mass.

[0079] [Example 20] Preparation of a catalyst (Catalyst 20) containing an (R,R)-Ts-DENEB complex adsorbed on granular activated carbon (C2, granular) Compound 20 was obtained in the same manner as in Example 17 except that the charged amount of (R,R)-Ts-DENEB was changed to 1200.0 mg (1.846 mmol). When the filtrate was concentrated under reduced pressure, the unadsorbed complex was recovered as a solid phase component. Since the mass of the recovered complex was 109.4 mg, the adsorption rate of the complex was 90.9%, and the loading amount of the complex on the activated carbon was 21.8% by mass. Table 4 shows the preparation results of the catalysts containing the (R,R)-Ts-DENEB complex adsorbed on activated carbon obtained under various preparation conditions.

[0080] Table 4: Preparation results of the catalysts containing the (R,R)-Ts-DENEB complex adsorbed on activated carbon obtained under various preparation conditions

Table 4

[0081] <Analysis 1> Photographing of ruthenium element mapping images of Catalyst 17 and Catalyst 19 by SEM-EDS For Catalyst 17 and Catalyst 19, the integration time was set to 900 seconds, and SEM images and element mapping images with ruthenium as the target element were obtained using SEM-EDS. The results are shown in Figure 4. From these element mapping images, it was confirmed that (R,R)-Ts-DENEB was widely dispersed on the activated carbon.

[0082] <Analysis 2> Calculation of the mass percentage of (R,R)-Ts-DENEB in the surface analysis of activated carbon by SEM-EDS for Catalyst 17 and Catalyst 19 The surface analysis of Catalyst 17 and Catalyst 19 was measured by SEM-EDS. As the elements to be analyzed, nine elements including carbon, nitrogen, oxygen, sodium, magnesium, phosphorus, potassium, calcium, and zinc, which are expected to be contained in activated carbon, and three elements including sulfur, chlorine, and ruthenium, which are contained in (R,R)-Ts-DENEB, were selected, for a total of 12 elements. The mass percentage of (R,R)-Ts-DENEB adsorbed on the activated carbon was calculated from the mass percentage of ruthenium on the activated carbon surface obtained by SEM-EDS. The results are shown in Table 5.

Table 5

[0083] <Analysis 3> Calculation of the mass percentage of (R,R)-Ts-DENEB by elemental analysis of the ash of Catalyst 17 and Catalyst 19 Approximately 150 mg of the sample, which was dried for 3 hours in an electric dryer adjusted to 115 °C ± 5 °C for each of the catalysts 17 and 19 and then cooled for 1 hour in a desiccator (using silica gel as the desiccant), was weighed into a crucible. Subsequently, the sample was placed in an electric furnace heated to 850 °C and heated for 7 hours under an air atmosphere. After cooling in air, the weight of the ash was measured, and then the obtained ash was analyzed by SEM-EDS using the same method as in Analysis 2 (however, in this analysis, the integration time was set to 300 seconds, and a total of 14 elements were targeted, adding two elements, aluminum and silicon, which may be mixed in from the crucible, to the 12 elements described in Analysis 2). The mass percentage of (R,R)-Ts-DENEB adsorbed on the activated carbon was determined by the following formula. The results are shown in Table 6.

[0084]

Number

[0085]

Table 6

[0086] It was found that the mass percentage of (R,R)-Ts-DENEB calculated from the surface composition of the activated carbon in Analysis 2 showed good agreement with the value calculated from the ash composition in Analysis 3. From this result, it was inferred that (R,R)-Ts-DENEB was uniformly supported on the surface and inside of the activated carbon.

[0087] [Example 21] Preparation of a catalyst (Catalyst 21) containing a chloro[(R,R)-N-[2-[2-(4-methylbenzyloxy)ethyl]amino-1,2-diphenylethyl]-p-methanesulfonamide]ruthenium(II) complex adsorbed on granular activated carbon (C2, granular) Chloro[(R,R)-N-[2-[2-(4-methylbenzyloxy)ethyl]amino-1,2-diphenylethyl]-p-methanesulfonamide]ruthenium(II) ((R,R)-Ms-DENEB, 142.2 mg, 0.248 mmol) was charged into a 200 mL eggplant-shaped flask, and nitrogen substitution was performed. Subsequently, dehydrated methanol (48 mL) was added and dissolved. Subsequently, activated carbon (C2, granular, 2.00 g) manufactured by Osaka Gas Chemical Co., Ltd. was added, and the mixture was allowed to stand at room temperature for 1 week under a nitrogen atmosphere. After removing the supernatant by vacuum filtration, the filtered solid was transferred to a 300 mL beaker. Dehydrated methanol (25 mL) was added and stirred for 1 minute, followed by filtration. The same operation was repeated twice, and the solid component recovered by filtration was vacuum dried at 40 °C for 24 hours to obtain Compound 21. When the filtrate was concentrated under reduced pressure, the unadsorbed complex was recovered as a solid phase component. Since the mass of the recovered complex was 20.0 mg, the adsorption amount of the complex to the activated carbon was 85.9%, and the supported amount of the complex on the activated carbon was 6.1% by mass.

[0088] [Example 22] Preparation of a catalyst (Catalyst 22) containing a chloro[(R,R)-N-[2-(3-phenylpropyl)amino-1,2-diphenylethyl]-p-toluenesulfonamide]ruthenium(II) complex adsorbed on granular activated carbon (C2, granular) Compound 22 was obtained in the same manner as in Example 21 except that the complex was changed to chloro[(R,R)-N-[2-(3-phenylpropyl)amino-1,2-diphenylethyl]-p-toluenesulfonamide]ruthenium(II) (RuCl(benz-C3-teth-(R,R)-Ts-DPEN), 153.1 mg, 0.247 mmol, manufactured by STREM). When the filtrate was concentrated under reduced pressure, the unadsorbed complex was recovered as a solid phase component. Since the mass of the recovered complex was 22.3 mg, the adsorption amount of the complex to the activated carbon was 85.4%, and the supported amount of the complex on the activated carbon was 6.5% by mass.

[0089] [Example 23] Preparation of a catalyst (Catalyst 23) containing a chloro(p-cymene)[(R,R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) complex adsorbed on granular activated carbon (C2, granular) Compound 23 was obtained in the same manner as in Example 21, except that the complex was changed to chloro(p-cymene)[(R,R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) (RuCl((R,R)-Ts-DPEN)(p-cymene), manufactured by Takasago Perfumery Co., Ltd., 157.8 mg, 0.248 mmol). When the filtrate was concentrated under reduced pressure, the unadsorbed complex was recovered as a solid-phase component. Since the mass of the recovered complex was 33.9 mg, the adsorption amount of the complex onto the activated carbon was 78.5%, and the supported amount of the complex on the activated carbon was 6.2% by mass.

[0090] [Example 24] Preparation of a catalyst (Catalyst 24) containing a chloro(benzene)[(R,R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) complex adsorbed on granular activated carbon (C2, granular) Compound 24 was obtained in the same manner as in Example 21, except that the complex was changed to chloro(benzene)[(R,R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]ruthenium(II) ((R,R)-RuCl(Ts-DPEN)(benzene), manufactured by Takasago Perfumery Co., Ltd., 43.3 mg, 0.247 mmol). When the filtrate was concentrated under reduced pressure, the unadsorbed complex was recovered as a solid-phase component. Since the mass of the recovered complex was 29.1 mg, the adsorption amount of the complex onto the activated carbon was 79.7%, and the supported amount of the complex on the activated carbon was 5.7% by mass. The examination results of various complexes adsorbed on the activated carbon are shown in Table 7.

[0091] Table 7: Examination results of the supported amounts of various complexes adsorbed on the activated carbon

Table 7

[0092] [Example 25] Production of (R)-1-phenylethyl alcohol by asymmetric hydrogen transfer reaction of acetophenone using a catalyst (Catalyst 1) containing (R,R)-Ts-DENEB complex adsorbed on activated carbon (A1)

Chemical formula

[0093] [Example 26] Production of (R)-1-phenylethyl alcohol by asymmetric hydrogen transfer reaction of acetophenone using a catalyst (Catalyst 2) containing (R,R)-Ts-DENEB complex adsorbed on activated carbon (A2) The target (R)-1-phenylethyl alcohol was produced in the same manner as in Example 25, except that Catalyst 2 (0.43 g, 0.005 mmol, 0.5 mol%) prepared in Example 2 was used as the catalyst. Conversion rate: 99.0%, selectivity: 100%, optical purity: 96.9% ee (by GC analysis). Here, the conversion rate is shown as ([amount of acetophenone charged] - [amount of acetophenone remaining after reaction]) / [amount of acetophenone charged] × 100, and the selectivity is shown as ([amount of (R)-1-phenylethyl alcohol produced] + [amount of (S)-1-phenylethyl alcohol produced]) / ([amount of acetophenone charged] - [amount of acetophenone remaining after reaction]) × 100. When the reaction solution was analyzed by ICP emission spectroscopic analysis, elution of 0.2% of ruthenium on the activated carbon was observed.

[0094] [Example 27] Production of (R)-1-phenylethyl alcohol by asymmetric hydrogen transfer reaction of acetophenone using a catalyst (Catalyst 3) containing (R,R)-Ts-DENEB complex adsorbed on activated carbon (B1) The target (R)-1-phenylethyl alcohol was produced in the same manner as in Example 25, except that Catalyst 3 (0.55 g, 0.005 mmol, 0.5 mol%) prepared in Example 3 was used as the catalyst. Conversion rate: 96.2%, selectivity: 100%, optical purity: 96.8% ee (by GC analysis). When the reaction solution was analyzed by ICP emission analysis, elution of 0.2% of ruthenium on the activated carbon was observed.

[0095] [Example 28] Production of (R)-1-phenylethyl alcohol by asymmetric hydrogen transfer reaction of acetophenone using a catalyst (Catalyst 4) containing (R,R)-Ts-DENEB complex adsorbed on activated carbon (B2) The target (R)-1-phenylethyl alcohol was produced in the same manner as in Example 25, except that Catalyst 4 (0.77 g, 0.007 mmol, 0.7 mol%) prepared in Example 4 was used as the catalyst. Conversion rate: 97.4%, selectivity: 100%, optical purity: 96.6% ee (by GC analysis). When the reaction solution was analyzed by ICP emission spectroscopic analysis, elution of 0.8% of ruthenium on the activated carbon was observed.

[0096] [Example 29] Production of (R)-1-phenylethyl alcohol by asymmetric hydrogen transfer reaction of acetophenone using a catalyst (Catalyst 5) containing (R,R)-Ts-DENEB complex adsorbed on activated carbon (C1) The target (R)-1-phenylethyl alcohol was produced in the same manner as in Example 25, except that Catalyst 5 (0.43 g, 0.005 mmol, 0.5 mol%) prepared in Example 5 was used as the catalyst. (Conversion rate: 0.5%) When the reaction solution was analyzed by ICP emission spectroscopic analysis, elution of 0.4% of ruthenium on the activated carbon was observed.

[0097] [Example 30] Production of (R)-1-phenylethyl alcohol by asymmetric hydrogen transfer reaction of acetophenone using a catalyst (Catalyst 6) containing (R,R)-Ts-DENEB complex adsorbed on activated carbon (C2) The target (R)-1-phenylethyl alcohol was produced in the same manner as in Example 25, except that Catalyst 6 (0.43 g, 0.005 mmol, 0.5 mol%) prepared in Example 6 was used as the catalyst. Conversion rate: 56.7%, Selectivity: 100%, Optical purity: 97.1% ee (by GC analysis). When the reaction solution was analyzed by ICP emission spectroscopic analysis, elution of 0.2% of ruthenium on the activated carbon was observed.

[0098] [Example 31] Production of (R)-1-phenylethyl alcohol by asymmetric hydrogen transfer reaction of acetophenone using a catalyst (Catalyst 7) containing (R,R)-Ts-DENEB complex adsorbed on activated carbon (M) The target (R)-1-phenylethyl alcohol was produced in the same manner as in Example 25, except that Catalyst 7 (0.43 g, 0.005 mmol, 0.5 mol%) prepared in Example 7 was used as the catalyst. Conversion rate: 95.7%, Selectivity: 100%, Optical purity: 96.3% ee (by GC analysis). When the reaction solution was analyzed by ICP emission spectroscopic analysis, elution of 0.2% of ruthenium on the activated carbon was observed.

[0099] [Comparative Example 1] Production of (R)-1-phenylethyl alcohol by asymmetric hydrogen transfer reaction of acetophenone using (R,R)-Ts-DENEB The target (R)-1-phenylethyl alcohol was produced in the same manner as in Example 25 except that Ts-DENEB (3.3 mg, 0.005 mmol, 0.5 mol%) was used as the catalyst. Conversion rate: 93.5%, selectivity: 100%, optical purity: 94.4% ee (by GC analysis). Table 8 shows the activity test results of various activated carbon-supported catalysts and homogeneous catalysts shown in Examples 25 to 31 and Comparative Example 1.

[0100] Table 8: Activity test results of various catalysts and homogeneous catalysts

Table 8

[0101] [Example 32] Measurement of change over time in the asymmetric hydrogen transfer reaction of acetophenone using a catalyst (Catalyst 3) containing a ruthenium complex adsorbed on activated carbon

Chemical formula

[0102] [Example 33] Hot Filtration Test in the Asymmetric Hydrogen Transfer Reaction of Acetophenone Using the Catalyst (Catalyst 3) Containing the Ts-DENEB Complex Adsorbed on Activated Carbon Two 80 mL Schlenk tubes were prepared. One was charged with a stirrer chip and equipped with a glass filter with glass fiber filter paper. The other was charged with a stirrer chip, Catalyst 3 (0.17 g, 0.016 mmol, 0.16 mol%) prepared in Example 3, and potassium formate (1.68 mmol, 1.68 g, 20 mmol). Then, the inside of each apparatus was purged with nitrogen. Subsequently, distilled water (5.0 mL), ethanol (2.0 mL), and acetophenone (0.12 mL, 1.0 mmol) were sequentially charged into the Schlenk tube containing the reagents. Each Schlenk tube was heated to 60 °C in an oil bath and stirred at 750 rpm using a stirrer. One hour after the start of heating and stirring, the suspension was transferred to a pre-prepared 80 mL Schlenk tube with a cannula, and the liquid phase component was filtered off inside the Schlenk tube under nitrogen. Then, heating and stirring were continued at 60 °C. 0.1 mL of the reaction solution during heating was sampled with a syringe, and the change in conversion rate over time was measured. The transition of the conversion rate is shown in Figure 2 together with the results of Example 32. As shown in Figure 2, when the solid component is removed during the heating reaction, the reaction completely stops. That is, in this catalytic reaction, it was found that the complex eluted in the liquid phase component does not function, but the complex adsorbed on the activated carbon functions.

[0103] [Example 34] Production of (R)-1-Phenylethyl Alcohol by the Asymmetric Hydrogen Transfer Reaction of Acetophenone Using the Catalyst (Catalyst 8) Containing the (R,R)-Ts-DENEB Complex Adsorbed on Activated Carbon (A1, Granular) [Chemical Formula]

[0104] [Reaction (First Reaction)] A mechanical stirrer, a condenser, a thermometer, and a three-way cock were attached to a 50 mL four-necked round-bottom flask. Catalyst 8 (0.86 g, 0.01 mmol, 0.5 mol%) prepared in Example 8 and potassium formate (3.36 g, 40 mmol) were charged, and the inside of the apparatus was purged with nitrogen. Subsequently, distilled water (10 mL), ethanol (5.0 mL), and acetophenone (0.23 mL, 2.0 mmol) were sequentially charged, heated to 60 °C in an oil bath, and stirred at 250 rpm for 2.5 hours using a mechanical stirrer to produce the target (R)-1-phenylethyl alcohol. Conversion rate: 98.3%, selectivity: 100%, optical purity: 97.2% ee (by GC analysis). In addition, data for the case of reacting (stirring) for 1 hour were also collected to show the change over time.

[0105] [Preparation of catalyst washing solution] 67.20 g of potassium formate was charged into a 500 mL eggplant-shaped flask with a branch, and the inside was purged with nitrogen. 200 mL of distilled water and 100 mL of dehydrated ethanol were sequentially charged to dissolve potassium formate and prepare a catalyst washing solution.

[0106] [Reuse operation of catalyst (second reaction)] After the reaction was completed, stirring was stopped, and the supernatant was removed with a syringe. The solid component was washed twice with 5 mL of the prepared catalyst washing solution to recover Compound 8. 1.68 g (40 mmol) of potassium formate was charged into this flask, and the inside of the apparatus was purged with nitrogen. Subsequently, distilled water (10 mL), dehydrated ethanol (5.0 mL), and acetophenone (0.23 mL, 2.0 mmol) were sequentially charged, heated to 60 °C in an oil bath, and stirred for 2.5 hours using a mechanical stirrer to produce the target (R)-1-phenylethyl alcohol. Conversion rate: 99.0%, selectivity: 100%, optical purity: 96.6% ee (by GC analysis). In addition, data for the case of reacting (stirring) for 1 hour were also collected to show the change over time. [Reuse operation of catalyst (reactions after the third time)] The catalyst was reused by the same operation after the second reaction. The conversion rate, optical purity, and ruthenium elution amount of each reaction are as shown in Table 9.

[0107] Table 9: Conversion rate, optical purity, and ruthenium elution amount of each reaction in Example 34 [Table 9]

[0108] [Example 35] Production of (R)-1-phenylethyl alcohol by asymmetric hydrogen transfer reaction of acetophenone using a catalyst (Catalyst 9) containing (R,R)-Ts-DENEB complex adsorbed on activated carbon (A2, granular) Using Catalyst 9 (0.86 g, 0.01 mmol, 0.5 mol%) as the catalyst, the target (R)-1-phenylethyl alcohol was produced by the same operation as in Example 34 except that the heating and stirring time was changed to 2 hours. Conversion rate: 99.4%, selectivity: 100%, optical purity: 97.0% ee (by GC analysis). In addition, by preparing and recycling the catalyst washing solution under the same conditions as in Example 34 (however, the heating and stirring time in this example was 2 hours), the target (R)-1-phenylethyl alcohol was produced. The conversion rate, optical purity, and ruthenium elution amount of each reaction are as shown in Table 10.

[0109] Table 10: Conversion rate, optical purity, and ruthenium elution amount of each reaction in Example 35 [Table 10]

[0110] [Example 36] Production of (R)-1-phenylethyl alcohol by asymmetric hydrogen transfer reaction of acetophenone using a catalyst (Catalyst 10) containing (R,R)-Ts-DENEB complex adsorbed on activated carbon (B1, granular) Using Catalyst 10 (1.22 g, 0.01 mmol, 0.5 mol%) as the catalyst, the target (R)-1-phenylethyl alcohol was produced by the same operation as in Example 34. Conversion rate: 97.5%, selectivity: 100%, optical purity: 97.0% ee (by GC analysis). Under the same conditions as in Example 34 (however, in this example, the heating and stirring time was 2 hours), the target (R)-1-phenylethyl alcohol was produced by preparing and recycling the catalyst cleaning solution. The conversion rate, optical purity, and ruthenium elution amount of each reaction are as shown in Table 11.

[0111] Table 11: Conversion rate, optical purity, and ruthenium elution amount of each reaction in Example 36

Table 11

[0112] [Example 37] Production of (R)-1-phenylethyl alcohol by asymmetric hydrogen transfer reaction of acetophenone using a catalyst (catalyst 11) containing (R,R)-Ts-DENEB complex adsorbed on activated carbon (B2, granular) Using catalyst 11 (1.22 g, 0.01 mmol, 0.5 mol%) as the catalyst, the target (R)-1-phenylethyl alcohol was produced by the same operation as in Example 34 except that the heating and stirring time was changed to 2 hours. Conversion rate: 96.9%, selectivity: 100%, optical purity: 96.7% ee (by GC analysis). Under the same conditions as in Example 34 (however, in this example, the heating and stirring time was 2 hours), the target (R)-1-phenylethyl alcohol was produced by preparing and recycling the catalyst cleaning solution. The conversion rate, optical purity, and ruthenium elution amount of each reaction are as shown in Table 12.

[0113] Table 12: Conversion rate, optical purity, and ruthenium elution amount of each reaction in Example 37

Table 12

[0114] [Example 38] Production of (R)-1-phenylethyl alcohol by asymmetric hydrogen transfer reaction of acetophenone using a catalyst (catalyst 15) containing (R,R)-Ts-DENEB complex adsorbed on activated carbon (A2, granular) Using catalyst 15 (171.1 mg, 0.01 mmol, 0.5 mol %), the target (R)-1-phenylethyl alcohol was produced in the same manner as in Example 34, except that the heating and stirring time was changed to 2 hours. Conversion rate: 99.7%, selectivity: 100%, optical purity: 97.1% ee (by GC analysis). Note that under the same conditions as in Example 34 (however, in this example, the heating and stirring time was 2 hours), the catalyst cleaning solution was prepared and reused to produce the target (R)-1-phenylethyl alcohol. The conversion rate, optical purity, and ruthenium elution amount of each reaction are as shown in Table 13.

[0115] Table 13: Conversion rate, optical purity, and ruthenium elution amount of each reaction in Example 38

Table 13

[0116] [Example 39] Production of (R)-1-phenylethyl alcohol by asymmetric hydrogen transfer reaction of acetophenone using a catalyst (catalyst 16) containing (R,R)-Ts-DENEB complex adsorbed on activated carbon (A2, granular) Using catalyst 16 (97.0 mg, 0.01 mmol, 0.5 mol %), the target (R)-1-phenylethyl alcohol was produced in the same manner as in Example 34, except that the heating and stirring time was changed to 3 hours. Conversion rate: 99.2%, selectivity: 100%, optical purity: 96.9% ee (by GC analysis). Note that under the same conditions as in Example 34 (however, in this example, the heating and stirring time was 3 hours), the catalyst cleaning solution was prepared and reused to produce the target (R)-1-phenylethyl alcohol. The conversion rate, optical purity, and ruthenium elution amount of each reaction are as shown in Table 14.

[0117] Table 14: Conversion rate, optical purity, and ruthenium elution amount of each reaction in Example 39

Table 14

[0118] [Example 40] Production of (R)-1-phenylethyl alcohol by asymmetric hydrogen transfer reaction of acetophenone using a catalyst (Catalyst 17) containing an (R,R)-Ts-DENEB complex adsorbed on activated carbon (C2, granular) The target (R)-1-phenylethyl alcohol was produced in the same manner as in Example 34, except that Catalyst 17 (90.9 mg, 0.01 mmol, 0.5 mol%) was used as the catalyst. Conversion rate: 99.7%, selectivity: 100%, optical purity: 97.7% ee (by GC analysis). In addition, the target (R)-1-phenylethyl alcohol was produced by preparing and reusing the catalyst washing solution under the same conditions as in Example 34 (however, in this example, the heating and stirring time may be 3 hours). The conversion rate, optical purity, and ruthenium elution amount of each reaction are as shown in Table 15.

[0119] Table 15: Conversion rate, optical purity, and ruthenium elution amount of each reaction in Example 40

Table 15

[0120] [Example 41] Production of (R)-1-phenylethyl alcohol by asymmetric hydrogen transfer reaction of acetophenone using a catalyst (Catalyst 20) containing an (R,R)-Ts-DENEB complex adsorbed on activated carbon (C2, granular) The target (R)-1-phenylethyl alcohol was produced in the same manner as in Example 34, except that Catalyst 20 (36.3 mg, 0.01 mmol, 0.5 mol%) was used as the catalyst and the heating and stirring time was changed to 2 hours. Conversion rate: 100.0%, selectivity: 100%, optical purity: 97.5% ee (by GC analysis). Note that under the same conditions as in Example 34 (however, in this example, the heating and stirring time may be 3 hours), the target (R)-1-phenylethyl alcohol was produced by preparing and reusing the catalyst cleaning solution. The conversion rate, optical purity, and ruthenium elution amount of each reaction are as shown in Table 16.

[0121] Table 16: Conversion rate, optical purity, and ruthenium elution amount of each reaction in Example 41

Table 16

[0122] As is clear from the comparison between Example 40 and Example 41, when the amount of (R,R)-Ts-DENEB complex adsorbed on activated carbon is increased, the ruthenium elution amount after the reaction tends to increase. Therefore, from the perspective of practicality, it is desirable that the total mass of the (R,R)-Ts-DENEB complex to be adsorbed is 25% by mass or less based on the total mass of the activated carbon.

[0123] [Example 42] Production of (R)-1-phenylethyl alcohol by asymmetric hydrogen transfer reaction of acetophenone using a catalyst (Catalyst 21) containing an (R,R)-Ms-DENEB complex (manufactured by Takasago Perfumery Co., Ltd.) adsorbed on activated carbon (C2, granular) The target (R)-1-phenylethyl alcohol was produced by the same operation as in Example 34 except that Catalyst 21 (100.7 mg, 0.01 mmol, 0.5 mol%) was used as the catalyst. Conversion rate: 100%, selectivity: 100%, optical purity: 96.6% ee (by GC analysis). Note that under the same conditions as in Example 34 (however, in this example, the heating and stirring time was 2 hours), the target (R)-1-phenylethyl alcohol was produced by preparing and reusing the catalyst cleaning solution. The conversion rate, optical purity, and ruthenium elution amount of each reaction are as shown in Table 17.

[0124] Table 17: Conversion rate, optical purity, and ruthenium elution amount of each reaction in Example 42

Table 17

[0125] [Example 43] Production of (R)-1-phenylethyl alcohol by asymmetric hydrogen transfer reaction of acetophenone using a catalyst (Catalyst 23) containing a RuCl((R,R)-Ts-DPEN)(p-cymene) complex adsorbed on activated carbon (C2, granular) The target (R)-1-phenylethyl alcohol was produced by the same procedure as in Example 34 except that Catalyst 23 (120.0 mg, 0.01 mmol, 0.5 mol%) was used as the catalyst. Conversion: 94.3%, selectivity: 100%, optical purity: 94.8% ee (by GC analysis). In addition, the target (R)-1-phenylethyl alcohol was produced by preparing and reusing the catalyst washing solution under the same conditions as in Example 34 (however, in this example, the heating and stirring time was 2 hours). The conversion, optical purity and ruthenium elution amount of each reaction are as shown in Table 18.

[0126] Table 18: Conversion, optical purity and ruthenium elution amount of each reaction in Example 43

Table 18

[0127] Next, the effects on the reaction conversion and optical purity in the production of (R)-1-phenylethyl alcohol by the asymmetric hydrogen transfer reaction of acetophenone caused by the catalyst of the present invention were compared with the following Comparative Examples 2 and 3. The results are shown in Table 19.

[0128] [Comparative Example 2] Production of (R)-1-phenylethyl alcohol by asymmetric hydrogen transfer reaction of acetophenone using (R,R)-Ts-DENEB complex An 80 mL Schlenk reaction tube was charged with a stirrer chip, Ts-DENEB (6.5 mg, 0.01 mmol, 0.5 mol %), and potassium formate (3.36 g, 40 mmol), and the inside of the apparatus was purged with nitrogen. Subsequently, distilled water (10 mL), ethanol (5.0 mL), and acetophenone (0.23 mL, 2.0 mmol) were sequentially charged, heated to 60 °C in an oil bath, and stirred at 750 rpm for 2.5 hours using a stirrer to produce the target (R)-1-phenylethyl alcohol. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 19.

[0129] [Comparative Example 3] Production of (R)-1-phenylethyl alcohol by asymmetric hydrogen transfer reaction of acetophenone using (R,R)-Ts-DENEB complex in the presence of formic acid-triethylamine An 80 mL Schlenk reaction tube was charged with a stirrer chip and (R,R)-Ts-DENEB (6.5 mg, 0.01 mmol, 0.5 mol %), and the inside of the apparatus was purged with nitrogen. Subsequently, acetophenone (0.23 mL, 2.0 mmol) and a formic acid-triethylamine mixed solution (5:2, 2.0 mL, 20 mmol) were sequentially charged, heated to 60 °C in an oil bath, and stirred at 750 rpm for 1 hour using a stirrer to produce the target (R)-1-phenylethyl alcohol. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 19.

[0130] Table 19: Reaction conversion rate and optical purity calculated from GC analysis results

Table 19

[0131] The effects on the reaction conversion rate and optical purity in the production of (R)-1-(4'-chlorophenyl)ethanol by the asymmetric hydrogen transfer reaction of 4'-chloroacetophenone caused by the catalyst of the present invention were investigated. The results are shown in Table 20.

[0132] [Example 44] Production of (R)-1-(4'-chlorophenyl)ethanol by asymmetric hydrogen transfer reaction of 4'-chloroacetophenone using a catalyst (Catalyst 17) containing (R,R)-Ts-DENEB complex adsorbed on activated carbon (C2, granular) Using 4'-chloroacetophenone (0.31 g, 2.0 mmol) as the raw material, the target (R)-1-(4'-chlorophenyl)ethanol was produced by the same procedure as in Example 40 except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 20. GC retention time (measurement condition 2); 4'-chloroacetophenone: 7.36 minutes, (R)-1-(4'-chlorophenyl)ethanol: 19.58 minutes, (S)-1-(4'-chlorophenyl)ethanol: 22.76 minutes.

[0133] [Example 45] Production of (R)-1-(4'-chlorophenyl)ethanol by asymmetric hydrogen transfer reaction of 4'-chloroacetophenone using a catalyst (Catalyst 16) containing (R,R)-Ts-DENEB complex adsorbed on activated carbon (A2, granular) Using 4'-chloroacetophenone (0.31 g, 2.0 mmol) as the raw material, the target (R)-1-(4'-chlorophenyl)ethanol was produced by the same procedure as in Example 39 except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 20.

[0134] [Comparative Example 4] Production of (R)-1-(4'-chlorophenyl)ethanol by asymmetric hydrogen transfer reaction of 4'-chloroacetophenone using (R,R)-Ts-DENEB complex Using 4'-chloroacetophenone (0.31 g, 2.0 mmol) as the raw material, the target (R)-1-(4'-chlorophenyl)ethanol was produced by the same procedure as in Comparative Example 2 except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 20.

[0135] [Comparative Example 5] Production of (R)-1-(4'-chlorophenyl)ethanol by Asymmetric Hydrogen Transfer Reaction of 4'-chloroacetophenone Using (R,R)-Ts-DENEB Complex in the Presence of Formic Acid-Triethylamine Using 4'-chloroacetophenone (0.31 g, 2.0 mmol) as the raw material, the target (R)-1-(4'-chlorophenyl)ethanol was produced by the same operation as in Comparative Example 3 except that the heating and stirring time was changed to 3 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 20. Yes.

[0136] Table 20: Reaction Conversion Rate and Optical Purity Calculated from GC Analysis Results

Table 20

[0137] The effects on the reaction conversion rate and optical purity in the production of (R)-1-(2'-chlorophenyl)ethanol by the asymmetric hydrogen transfer reaction of 2'-chloroacetophenone caused by the catalyst of the present invention were investigated. The results are shown in Table 21.

[0138] [Example 46] Production of (R)-1-(2'-chlorophenyl)ethanol by Asymmetric Hydrogen Transfer Reaction of 2'-chloroacetophenone Using a Catalyst (Catalyst 17) Containing (R,R)-Ts-DENEB Complex Adsorbed on Activated Carbon (C2, Granular) Using 2'-chloroacetophenone (0.31 g, 2.0 mmol) as the raw material, the target (R)-1-(2'-chlorophenyl)ethanol was produced by the same operation as in Example 40 except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 21. GC retention time (measurement condition 2); 2'-chloroacetophenone: 5.08 minutes, (R)-1-(2'-chlorophenyl)ethanol: 17.97 minutes, (S)-1-(2'-chlorophenyl)ethanol: 24.83 minutes.

[0139] [Example 47] Production of (R)-1-(2'-chlorophenyl)ethanol by asymmetric hydrogen transfer reaction of 2'-chloroacetophenone using a catalyst (Catalyst 16) containing (A2, granular) (R,R)-Ts-DENEB complex adsorbed on activated carbon Using 2'-chloroacetophenone (0.31 g, 2.0 mmol) as the raw material, the target (R)-1-(2'-chlorophenyl)ethanol was produced by the same operation as in Example 39 except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 21.

[0140] [Comparative Example 6] Production of (R)-1-(2'-chlorophenyl)ethanol by asymmetric hydrogen transfer reaction of 2'-chloroacetophenone using (R,R)-Ts-DENEB complex Using 2'-chloroacetophenone (0.31 g, 2.0 mmol) as the raw material, the target (R)-1-(2'-chlorophenyl)ethanol was produced by the same operation as in Comparative Example 2 except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 21.

[0141] [Comparative Example 7] Production of (R)-1-(2'-chlorophenyl)ethanol by asymmetric hydrogen transfer reaction of 2'-chloroacetophenone using (R,R)-Ts-DENEB complex in the presence of formic acid-triethylamine Using 2'-chloroacetophenone (0.31 g, 2.0 mmol) as the raw material, the target (R)-1-(2'-chlorophenyl)ethanol was produced by the same operation as in Comparative Example 3 except that the heating and stirring time was changed to 3 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 21.

[0142] Table 21: Reaction conversion rate and optical purity calculated from GC analysis results

Table 21

[0143] The effects on the reaction conversion rate and optical purity in the production of (R)-1-(4'-methoxyphenyl)ethanol by the asymmetric hydrogen transfer reaction of 4'-methoxyacetophenone caused by the catalyst of the present invention were investigated. The results are shown in Table 22.

[0144] [Example 48] Production of (R)-1-(4'-methoxyphenyl)ethanol by the asymmetric hydrogen transfer reaction of 4'-methoxyacetophenone using the (R,R)-Ts-DENEB complex (Catalyst 17) adsorbed on activated carbon (C2, granular) Using 4'-methoxyacetophenone (0.30 g, 2.0 mmol) as the raw material, the target (R)-1-(4'-methoxyphenyl)ethanol was produced by the same procedure as in Example 40, except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 22. GC retention time (measurement condition 2); 4'-methoxyacetophenone: 12.65 minutes, (R)-1-(4'-methoxyphenyl)ethanol: 19.09 minutes, (S)-1-(4'-methoxyphenyl)ethanol: 20.76 minutes.

[0145] [Example 49] Production of (R)-1-(4'-methoxyphenyl)ethanol by the asymmetric hydrogen transfer reaction of 4'-methoxyacetophenone using the catalyst (Catalyst 16) containing the (R,R)-Ts-DENEB complex adsorbed on activated carbon (A2, granular) Using 4'-methoxyacetophenone (0.30 g, 2.0 mmol) as the raw material, the target (R)-1-(4'-methoxyphenyl)ethanol was produced by the same procedure as in Example 39, except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 22.

[0146] [Comparative Example 8] Production of (R)-1-(4'-methoxyphenyl)ethanol by the asymmetric hydrogen transfer reaction of 4'-methoxyacetophenone using the (R,R)-Ts-DENEB complex Using 4'-methoxyacetophenone (0.30 g, 2.0 mmol) as the raw material, the target (R)-1-(4'-methoxyphenyl)ethanol was produced by the same operation as in Comparative Example 2 except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 22.

[0147] [Comparative Example 9] Production of (R)-1-(4'-methoxyphenyl)ethanol by asymmetric hydrogen transfer reaction of 4'-methoxyacetophenone using (R,R)-Ts-DENEB complex in the presence of formic acid-triethylamine Using 4'-methoxyacetophenone (0.30 g, 2.0 mmol) as the raw material, the target (R)-1-(4'-methoxyphenyl)ethanol was produced by the same operation as in Comparative Example 3 except that the heating and stirring time was changed to 3 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 22.

[0148] Table 22: Reaction conversion rate and optical purity calculated from GC analysis results

Table 22

[0149] The effects on the reaction conversion rate and optical purity in the production of (R)-1-(2'-methoxyphenyl)ethanol by the asymmetric hydrogen transfer reaction of 2'-methoxyacetophenone caused by the catalyst of the present invention were examined. The results are shown in Table 23.

[0150] [Example 50] Production of (R)-1-(2'-methoxyphenyl)ethanol by asymmetric hydrogen transfer reaction of 2'-methoxyacetophenone using a catalyst (Catalyst 17) containing (R,R)-Ts-DENEB complex adsorbed on activated carbon (C2, granular) Using 2'-methoxyacetophenone (0.30 g, 2.0 mmol) as the raw material, the target (R)-1-(2'-methoxyphenyl)ethanol was produced by the same operation as in Example 40 except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 23. GC retention time (measurement condition 2); 2'-methoxyacetophenone: 7.90 minutes, (R)-1-(2'-methoxyphenyl)ethanol: 18.29 minutes, (S)-1-(2'-methoxyphenyl)ethanol: 16.78 minutes.

[0151] [Example 51] Production of (R)-1-(2'-methoxyphenyl)ethanol by asymmetric hydrogen transfer reaction of 2'-methoxyacetophenone using a catalyst (catalyst 16) containing (R,R)-Ts-DENEB complex adsorbed on activated carbon (A2, granular) Using 2'-methoxyacetophenone (0.30 g, 2.0 mmol) as the raw material, the target (R)-1-(2'-methoxyphenyl)ethanol was produced by the same operation as in Example 39 except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 23.

[0152] [Comparative Example 10] Production of (R)-1-(2'-methoxyphenyl)ethanol by asymmetric hydrogen transfer reaction of 2'-methoxyacetophenone using (R,R)-Ts-DENEB complex Using 2'-methoxyacetophenone (0.30 g, 2.0 mmol) as the raw material, the target (R)-1-(2'-methoxyphenyl)ethanol was produced by the same operation as in Comparative Example 2 except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 23.

[0153] [Comparative Example 11] Production of (R)-1-(2'-methoxyphenyl)ethanol by asymmetric hydrogen transfer reaction of 2'-methoxyacetophenone using (R,R)-Ts-DENEB complex in the presence of formic acid-triethylamine Using 2'-methoxyacetophenone (0.30 g, 2.0 mmol) as the raw material, the target (R)-1-(2'-methoxyphenyl)ethanol was produced by the same operation as in Comparative Example 3 except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 23.

[0154] Table 23: Reaction conversion rate and optical purity calculated from GC analysis results [Table 23]

[0155] The effects on the reaction conversion rate and optical purity in the production of (R)-1-(4'-trifluoromethylphenyl)ethanol by the asymmetric hydrogen transfer reaction of 4'-trifluoromethylacetophenone caused by the catalyst of the present invention were examined. The results are shown in Table 24.

[0156] [Example 52] Production of (R)-1-(4'-trifluoromethylphenyl)ethanol by the asymmetric hydrogen transfer reaction of 4'-trifluoromethylacetophenone using a catalyst (Catalyst 17) containing an (R,R)-Ts-DENEB complex adsorbed on activated carbon (C2, granular) Using 4'-trifluoromethylacetophenone (0.38 g, 2.0 mmol) as the raw material, the target (R)-1-(4'-trifluoromethylphenyl)ethanol was produced by the same operation as in Example 40 except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 24. GC retention time (measurement condition 1); 4'-trifluoromethylacetophenone: 3.09 minutes, (R)-1-(4'-trifluoromethylphenyl)ethanol: 10.18 minutes, (S)-1-(4'-trifluoromethylphenyl)ethanol: 13.03 minutes.

[0157] [Example 53] Production of (R)-1-(4'-trifluoromethylphenyl)ethanol by the asymmetric hydrogen transfer reaction of 4'-trifluoromethylacetophenone using a catalyst (Catalyst 16) containing an (R,R)-Ts-DENEB complex adsorbed on activated carbon (A2, granular) Using 4'-trifluoromethylacetophenone (0.38 g, 2.0 mmol) as the raw material, the target (R)-1-(4'-trifluoromethylphenyl)ethanol was produced in the same manner as in Example 39 except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 24.

[0158] [Comparative Example 12] Production of (R)-1-(4'-trifluoromethylphenyl)ethanol by asymmetric hydrogen transfer reaction of 4'-trifluoromethylacetophenone using (R,R)-Ts-DENEB complex Using 4'-trifluoromethylacetophenone (0.38 g, 2.0 mmol) as the raw material, the target (R)-1-(4'-trifluoromethylphenyl)ethanol was produced in the same manner as in Comparative Example 2 except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 24.

[0159] [Comparative Example 13] Production of (R)-1-(4'-trifluoromethylphenyl)ethanol by asymmetric hydrogen transfer reaction of 4'-trifluoromethylacetophenone using (R,R)-Ts-DENEB complex in the presence of formic acid-triethylamine Using 4'-trifluoromethylacetophenone (0.38 g, 2.0 mmol) as the raw material, the target (R)-1-(4'-trifluoromethylphenyl)ethanol was produced in the same manner as in Comparative Example 3 except that the heating and stirring time was changed to 3 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 24.

[0160] Table 24: Reaction conversion rate and optical purity calculated from GC analysis results

Table 24

[0161] The effects on the reaction conversion rate and optical purity in the production of (R)-1-(4'-cyanophenyl)ethanol by the asymmetric hydrogen transfer reaction of 4'-cyanoacetophenone caused by the catalyst of the present invention were investigated. The results are shown in Table 25.

[0162] [Example 54] Production of (R)-1-(4'-cyanophenyl)ethanol by the asymmetric hydrogen transfer reaction of 4'-cyanoacetophenone using a catalyst (Catalyst 17) containing an (R,R)-Ts-DENEB complex adsorbed on activated carbon (C2, granular) Using 4'-cyanoacetophenone (0.29 g, 2.0 mmol) as the raw material, the target (R)-1-(4'-cyanophenyl)ethanol was produced by the same operation as in Example 40 except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 25. GC retention time (measurement condition 3); 4'-cyanoacetophenone: 6.05 minutes, (R)-1-(4'-cyanophenyl)ethanol: 16.94 minutes, (S)-1-(4'-cyanophenyl)ethanol: 19.63 minutes.

[0163] [Example 55] Production of (R)-1-(4'-cyanophenyl)ethanol by the asymmetric hydrogen transfer reaction of 4'-cyanoacetophenone using a catalyst (Catalyst 16) containing an (R,R)-Ts-DENEB complex adsorbed on activated carbon (A2, granular) Using 4'-cyanoacetophenone (0.29 g, 2.0 mmol) as the raw material, the target (R)-1-(4'-cyanophenyl)ethanol was produced by the same operation as in Example 39 except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 25.

[0164] [Comparative Example 14] Production of (R)-1-(4'-cyanophenyl)ethanol by the asymmetric hydrogen transfer reaction of 4'-cyanoacetophenone using an (R,R)-Ts-DENEB complex Using 4'-cyanoacetophenone (0.29 g, 2.0 mmol) as the raw material, the target (R)-1-(4'-cyanophenyl)ethanol was produced by the same operation as in Comparative Example 2 except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 25.

[0165] [Comparative Example 15] Production of (R)-1-(4'-cyanophenyl)ethanol by asymmetric hydrogen transfer reaction of 4'-cyanoacetophenone using (R,R)-Ts-DENEB complex in the presence of formic acid-triethylamine Using 4'-cyanoacetophenone (0.29 g, 2.0 mmol) as the raw material, the target (R)-1-(4'-cyanophenyl)ethanol was produced by the same operation as in Comparative Example 3 except that the heating and stirring time was changed to 1 hour. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 25.

[0166] Table 25: Reaction conversion rate and optical purity calculated from GC analysis results

Table 25

[0167] The effects on the reaction conversion rate and optical purity in the production of (R)-1-(4'-tert-butylphenyl)ethanol by the asymmetric hydrogen transfer reaction of 4'-tert-butylacetophenone caused by the catalyst of the present invention were examined. The results are shown in Table 26.

[0168] [Example 56] Production of (R)-1-(4'-tert-butylphenyl)ethanol by asymmetric hydrogen transfer reaction of 4'-tert-butylacetophenone using a catalyst (Catalyst 17) containing (R,R)-Ts-DENEB complex adsorbed on activated carbon (C2, granular) Using 4'-tert-butylacetophenone (0.35 g, 2.0 mmol) as the raw material and distilled water (10 mL) and ethanol (10 mL) as the solvents, the target (R)-1-(4'-tert-butylphenyl)ethanol was produced in the same manner as in Example 40, except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 26. GC retention time (measurement condition 4); 4'-tert-butylacetophenone: 20.38 minutes, (R)-1-(4'-tert-butylphenyl)ethanol: 27.94 minutes, (S)-1-(4'-tert-butylphenyl)ethanol: 29.81 minutes.

[0169] [Example 57] Production of (R)-1-(4'-tert-butylphenyl)ethanol by asymmetric hydrogen transfer reaction of 4'-tert-butylacetophenone using a catalyst (catalyst 16) containing (R,R)-Ts-DENEB complex adsorbed on activated carbon (A2, granular) Using 4'-tert-butylacetophenone (0.35 g, 2.0 mmol) as the raw material and distilled water (10 mL) and ethanol (10 mL) as the solvents, the target (R)-1-(4'-tert-butylphenyl)ethanol was produced in the same manner as in Example 39, except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 26.

[0170] [Comparative Example 16] Production of (R)-1-(4'-tert-butylphenyl)ethanol by asymmetric hydrogen transfer reaction of 4'-tert-butylacetophenone using (R,R)-Ts-DENEB complex Using 4'-tert-butylacetophenone (0.35 g, 2.0 mmol) as the raw material and distilled water (10 mL) and ethanol (10 mL) as the solvents, the target (R)-1-(4'-tert-butylphenyl)ethanol was produced in the same manner as in Comparative Example 2, except that the heating and stirring time was changed to 5 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 26.

[0171] [Comparative Example 17] Production of (R)-1-(4'-tert-butylphenyl)ethanol by Asymmetric Hydrogen Transfer Reaction of 4'-tert-butylacetophenone Using (R,R)-Ts-DENEB Complex in the Presence of Formic Acid-Triethylamine Using 4'-tert-butylacetophenone (0.35 g, 2.0 mmol) as the raw material, distilled water (10 mL) and ethanol (10 mL) as the solvents, and performing the same operations as in Comparative Example 3 except that the heating and stirring time was changed to 3 hours, the target (R)-1-(4'-tert-butylphenyl)ethanol was produced. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 26.

[0172] Table 26: Reaction Conversion Rate and Optical Purity Calculated from GC Analysis Results

Table 26

[0173] The effects on the reaction conversion rate and optical purity in the production of (S)-pinacoly alcohol by the asymmetric hydrogen transfer reaction of pinacolin caused by the catalyst of the present invention were investigated. The results are shown in Table 27. [Example 58] Production of (S)-pinacoly alcohol by Asymmetric Hydrogen Transfer Reaction of Pinacolin Using a Catalyst (Catalyst 17) Containing (R,R)-Ts-DENEB Complex Adsorbed on Activated Carbon (C2, Granular) Using 181.8 mg (0.02 mmol, 1.0 mol%) of the catalyst and pinacolin (0.20 g, 2.0 mmol) as the raw material, and performing the same operations as in Example 40 except that the heating and stirring time was changed to 7 hours, the target (S)-pinacoly alcohol was produced. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 27. GC Retention Time (Measurement Condition 5); Pinacolin: 3.12 minutes, (S)-Pinacoly Alcohol: 9.13 minutes, (R)-Pinacoly Alcohol: 9.69 minutes.

[0174] [Example 59] Production of (S)-pinacolyl alcohol by asymmetric hydrogen transfer reaction of pinacoline using a catalyst (Catalyst 16) containing (R,R)-Ts-DENEB complex adsorbed on activated carbon (A2, granular) Using 194.0 mg (0.02 mmol, 1.0 mol%) of the catalyst and pinacoline (0.20 g, 2.0 mmol) as the raw material, the target (S)-pinacolyl alcohol was produced in the same manner as in Example 39 except that the heating and stirring time was changed to 7 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 27.

[0175] [Comparative Example 18] Production of (S)-pinacolyl alcohol by asymmetric hydrogen transfer reaction of pinacoline using (R,R)-Ts-DENEB complex Using 13.0 mg (0.02 mmol, 1.0 mol%) of the catalyst and pinacoline (0.20 g, 2.0 mmol) as the raw material, the target (S)-pinacolyl alcohol was produced in the same manner as in Comparative Example 2 except that the heating and stirring time was changed to 7 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 27.

[0176] [Comparative Example 19] Production of (S)-pinacolyl alcohol by asymmetric hydrogen transfer reaction of pinacoline using (R,R)-Ts-DENEB complex in the presence of formic acid-triethylamine Using 13.0 mg (0.02 mmol, 1.0 mol%) of the catalyst and pinacoline (0.20 g, 2.0 mmol) as the raw material, the target (S)-pinacolyl alcohol was produced in the same manner as in Comparative Example 3 except that the heating and stirring time was changed to 7 hours. The reaction conversion rate and optical purity calculated from the GC analysis results are shown in Table 27.

[0177] Table 27: Reaction conversion rate and optical purity calculated from GC analysis results

Table 27

[0178] <Analysis 4>1H NMR analysis in the coexistence of (R,R)-Ts-DENEB complex and π-conjugated compound 1 1H NMR analysis After adding (R,R)-Ts-DENEB (20.0 mg, 0.0308 mmol) and a predetermined amount of pyrene into an NMR sample tube, 0.7 mL of deuterated chloroform containing 0.05% of trimethylsilane was added and completely dissolved. The obtained solution's 1 When the 1H NMR was compared as shown in Figure 3, for the solution containing pyrene, a peak (4.5 ppm to 6.2 ppm) attributed to the protons around the aromatic ring on ruthenium shifted to the high magnetic field side. From this result, it was inferred that when (R,R)-Ts-DENEB and the π-conjugated compound coexist, an interaction occurs between the aromatic ring on ruthenium and the π-conjugated compound.

Claims

1. A catalyst for producing an optically active reduction product by an asymmetric reduction reaction of an organic compound, comprising activated carbon adsorbed with a ruthenium complex represented by the following general formula (1-1) and / or (1-2). 【Chemical 1】 (In the above formula, The solid line represents a single bond, the double line represents a double bond, and the dashed line represents a coordination bond; Ru represents a ruthenium atom, N represents a nitrogen atom, S represents a sulfur atom, and O represents an oxygen atom; * represents an asymmetric carbon atom; X represents an anionic group, and Y represents a hydrogen atom; R 1 is a linear or branched alkyl group having 1 to 10 carbon atoms; a 10-camphyl group; an alkyl group having 1 to 10 carbon atoms, a halogenated alkyl group having 1 to 10 carbon atoms, a halogen atom, a cyano group (-CN), an amino group, an alkylamino group (-NR 11 R 12 ), a 5- or 6-membered cyclic amino group, an acylamino group (-NH-CO-R 11 ), a hydroxyl group, an alkoxy group (-OR 11 ), an acyl group (-CO-R 11 ), a carboxyl group, an alkoxycarbonyl group (-COOR 11 ), a phenoxycarbonyl group, or an aryl group which may be substituted with an alkylthio group (-SR 11 ); or an aralkyl group which may be substituted with an alkyl group having 1 to 10 carbon atoms; R 11 and R 12 each independently represents a hydrogen atom; an alkyl group having 1 to 10 carbon atoms; or a cycloalkyl group having 3 to 10 carbon atoms; R 2 and R 3 each independently represents a hydrogen atom; or a phenyl group which may be substituted with an alkyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, or a halogen atom, or R 2 and R 3 are joined to each other to form a 4- to 8-membered cycloalkane ring together with the carbon atom to which R 2 and R 3 is attached; R 4 represents a hydrogen atom; or a linear or branched alkyl group having 1 to 10 carbon atoms which may have a substituent; R 5 to R 10 each independently represents a hydrogen atom; a linear or branched alkyl group having 1 to 10 carbon atoms; a hydroxyl group; or a linear or branched alkoxy group having 1 to 10 carbon atoms; R 4 and R 5 may be bonded to each other to form a crosslinking site of the divalent group represented by the following formula (W) to form a crosslinking site (W). [Chemical 2] (In formula (W), n 1 The wavy portion at the carbon chain end containing [n] binds to the carbon atom of the arene moiety instead of R in Formulas (1-1) and (1-2), and the wavy portion at the carbon chain end containing [n] in Formula (W) 5 binds to the nitrogen atom of the amine moiety instead of R in Formulas (1-1) and (1-2); 2 The wavy portion at the carbon chain end containing [n] binds to the carbon atom of the arene moiety instead of R in Formulas (1-1) and (1-2), and the wavy portion at the carbon chain end containing [n] in Formula (W) 4 binds to the nitrogen atom of the amine moiety instead of R in Formulas (1-1) and (1-2); Z represents a methylene group or an oxygen atom; n 1 is an integer of 1 or 2; n 2 is an integer of any one from 1 to 3.).)

2. R 4 and R 5 are bonded to each other to form a crosslinking site of the divalent group represented by the formula (W), The catalyst according to claim 1, wherein Z is an oxygen atom. n 1 is 1, n 2 wherein n is 2

3. The catalyst according to claim 2. R 1 is a 4-methylphenyl group or a methyl group, R 2 and R 3 is a phenyl group, R 6 、R 7 、R 9 、and R 10 is a hydrogen atom, R 8 is a methyl group,

4. The catalyst according to claim 1. R 4 and R 5 do not form a crosslinking site of the divalent group represented by the formula (W), R 4 is a hydrogen atom,

5. The catalyst according to claim 4. R 1 is a 4-methylphenyl group, 2,3,4,5,6-pentafluorophenyl group, methyl group, isobutyl group, benzyl group, 2',5'-dimethylbenzyl group or 10-camphyl group, R 2 and R 3 are each a phenyl group or are bonded to each other to form a cyclohexane ring, R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 is a hydrogen atom, a methyl group or an isopropyl group.

6. The catalyst according to any one of claims 1 to 5, wherein the total mass of the ruthenium complex is 0.1% by mass or more and 25% by mass or less based on the total mass of the activated carbon.

7.

8. The specific surface area of the activated carbon is 800 m 2 / g or more and 2000 m 2 / g or less, and the catalyst according to any one of claims 1 to 6. A method for producing a reduction product, comprising a step of reducing an organic compound in the presence of the catalyst according to any one of claims 1 to 7 and a hydrogen donor.

9. A method for producing an optically active alcohol, comprising a step of reducing a carbonyl group of a carbonyl compound in the presence of the catalyst according to any one of claims 1 to 7 and a hydrogen donor.

10. A method for producing an optically active amine, comprising a step of reducing an imino group of an imine compound in the presence of the catalyst according to any one of claims 1 to 7 and a hydrogen donor.

11. The production method according to any one of claims 8 to 10, wherein the hydrogen donor is at least one selected from the group consisting of formic acid, an alkali metal formate, an alcohol having a hydrogen atom at the α-carbon atom of a hydroxyl group-substituted carbon, and hydrogen gas. ​

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