JP2015124153A - Method for manufacturing alcohol by hydrogenation of carboxylic acid compound, ruthenium complex used for manufacturing method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for obtaining alcohol by hydrogenation of carboxylic acid compound efficiently by using a homogeneous system catalyst, especially a method for obtaining alcohol by hydrogenation of various carboxylic acid compound by the homogeneous system catalyst efficiently even under alleviation condition.SOLUTION: There is provided a method of manufacturing alcohol by hydrogenation of a carboxylic acid compound in a presence of a ruthenium complex represented by RuXYZand a specific alkali metal salt.

Description

  The present invention relates to a method for producing an alcohol by hydrogenation of a carboxylic acid compound, and a ruthenium complex used in the production method.

  Hydrogen transfer reactions such as hydrogenation reactions are widely used for the synthesis of low molecular and high molecular organic compounds.

  For example, Non-Patent Document 1 shows that a specific ruthenium complex is useful for synthesizing an alcohol by hydrogenating an ester or carbon dioxide. Other examples of hydrogenating amides are also known.

  However, there are few examples of hydrogenation of carboxylic acid compounds using molecular catalysts. This is because the carboxylic acid compound has a carboxyl group that is stable with respect to the hydrogenation reaction, so that the hydrogenation reaction is generally difficult. In addition, in the conventional carboxylic acid compound hydrogenation method, when a homogeneous catalyst is used, the substrate dependency is high. Therefore, depending on the type of substrate, the central metal, ligand, reaction conditions, etc. of the catalyst are changed each time. It was necessary to change significantly.

  For this reason, not only amides and esters but also carboxylic acid compounds can be applied to the synthesis of low-molecular and high-molecular organic compounds as long as the alcohol can be synthesized by a hydrogenation reaction. It is more useful because it can be synthesized.

  For example, when a heterogeneous binuclear metal cluster catalyst or a heterogeneous catalyst is used, there are reported examples (Non-Patent Documents 2 to 3). However, in Non-Patent Document 2, when a homogeneous catalyst composed of a single metal is used, hydrogenation of the carboxylic acid compound is difficult, and a high pressure is required, and further, ring reduction proceeds. Moreover, in nonpatent literature 3, since it is accompanied by decarboxylation depending on a substrate, substrate generality and selectivity are scarce. For this reason, it cannot be said that it is the method excellent in the generality of the substrate which can be made to advance on moderate conditions.

  On the other hand, in Non-Patent Document 4, when a specific carboxylic acid substrate is used by combining a specific complex, a specific ligand, and a specific additive, cyclic esters, cyclic ethers, alcohols, and the like are desired. It has been shown that the following compounds can be obtained. However, even if a general carboxylic acid compound is used, whether the reaction proceeds in the same manner is not shown, and it is described only when a special carboxylic acid substrate is used.

  Thus, since it is difficult to directly reduce the carboxylic acid compound to obtain an alcohol depending on the substrate, the reduction reaction is usually carried out after intramolecular esterification of the carboxylic acid compound.

  On the other hand, Patent Document 1 also describes hydrogenation of propionic acid, butyric acid and the like, and is said to be excellent in substrate generality, but requires high temperature (190 ° C. or higher), and the reaction is performed under mild conditions. Cannot be advanced. In Patent Document 1, a tridentate ligand such as Triphos (1,1,1-tris (diphenylphosphinomethyl) ethane) is particularly useful as a ligand used in the ruthenium complex. Yes.

  For this reason, a method for obtaining an alcohol by hydrogenating various carboxylic acid substrates under mild conditions using a homogeneous catalyst has not yet been achieved, and such a method is required.

US Patent Application Publication No. 2005/0234269

Angew. Chem. Int. Ed. 2012, 51, 7499-7502 Tetrahedron Lett. 1995, 36, 1059-1062 Chem. Commun. 2010, 46, 6279-6281 Angew. Chem. Int. Ed. 2010, 49, 5510-5514

  In general, the hydrogenation reaction of a substrate having an inactive carbonyl group such as an ester or amide is generally effective when carried out under basic conditions. However, when a carboxylic acid compound is used as the substrate, the reaction system is in an acidic condition, and the conditions for hydrogenating esters and amides cannot be applied as they are.

  Under such circumstances, an object of the present invention is to provide a method for obtaining an alcohol by efficiently hydrogenating a carboxylic acid compound using a homogeneous catalyst. Specifically, an object of the present invention is to provide a method for efficiently hydrogenating various carboxylic acid compounds using a homogeneous catalyst under mild conditions to obtain an alcohol.

  Another object of the present invention is to provide a novel ruthenium complex that can be used in the method.

  The present inventors have intensively studied to solve the above problems.

  As a result, it was found that by adding an alkali metal salt to a specific ruthenium complex, an alcohol can be obtained by hydrogenating a carboxylic acid compound efficiently even under mild conditions. Among the ruthenium complexes used at this time, some are novel compounds not described in any literature.

  Based on such knowledge, the present inventors have further studied and completed the present invention.

That is, the present invention includes the following alcohol production method and ruthenium complex.
Item 1. A method for producing an alcohol by hydrogenating a carboxylic acid compound,
Comprising a step of hydrogenating a carboxylic acid compound in a hydrogen atmosphere in the presence of a ruthenium complex and an alkali metal salt,
The ruthenium complex has the general formula (1):
Ru _m X _n Y _p Z _q
[Wherein X is the same or different and each represents a halogen atom, RCOO- (wherein R is an optionally substituted alkyl group or an optionally substituted aryl group), or β-diketonate; Is a ligand containing one or more phosphorus atoms; Z is a ligand other than X and Y; m is an integer of 1 or more; n is an integer of 1 or more; p is an integer of 0 to 6; An integer of 2; the number of phosphorus atoms coordinated to the ruthenium atom is 2 to 10 times that of the ruthenium atom. ]
The manufacturing method which is a compound shown by these.
Item 2. Item 2. The production method according to Item 1, wherein in the ruthenium complex, ruthenium is divalent or trivalent.
Item 2-1. Item 3. The method according to Item 1 or 2, wherein in the general formula (1), X is the same or different and each is a chlorine atom, a group represented by CH ₃ COO—, or acetylacetonato.
Item 2-2. In the general formula (1), Y is a phosphine ligand, The manufacturing method in any one of claim | item 1-2-1.
Item 3. Item 3. The production method according to any one of Items 1 to 2-2, wherein Y is a phosphine ligand having an optionally substituted aryl group in General Formula (1).
Item 3-1. In the general formula (1), Y represents triphenylphosphine, tri (3,5-xylyl) phosphine, tri (4-methylphenyl) phosphine, tri (3-methylphenyl) phosphine, tri (2-methylphenyl). Phosphine, tris (4-trifluoromethylphenyl) phosphine, tri (4-methoxyphenyl) phosphine, tri (3-methoxyphenyl) phosphine, tri (2-methoxyphenyl) phosphine, tris (3,5-dimethoxyphenyl) phosphine Tris (3,5-dimethyl-4-methoxyphenyl) phosphine, Tris [3,5-bis (1,1-dimethylethyl) -4-methoxyphenyl] phosphine, Tris (3,5-difluorophenyl) phosphine, Tri (1-naphthyl) phosphine, trimethylphosphine , Triethylphosphine, tri-n-propylphosphine, triisopropylphosphine, tri-n-butylphosphine, tri-t-butylphosphine, tripentylphosphine, tri-n-hexylphosphine, tri-n-heptylphosphine, trioctyl Phosphine, tricyclopentylphosphine, tricyclohexylphosphine, methyldiphenylphosphine, cyclohexylmethylphenylphosphine, dicyclohexylphenylphosphine, 1,2-bis (diphenylphosphino) benzene, bisdiphenylphosphinomethane, 1,2-bis (diphenylphosphine) Fino) ethane, 1,3-bis (diphenylphosphino) propane, 1,4-bis (diphenylphosphino) butane, 1,5-bis (diphenylphosphino) pen 1,1′-bis (diphenylphosphino) ferrocene, 1,2-bis (bis (3,5-dimethylphenyl) phosphino) ethane, 1,3-bis (bis (3,5-dimethylphenyl) phosphino ) Propane, 1,4-bis (bis (3,5-dimethylphenyl) phosphino) butane, 1,4-bis (bis (3,5-di-t-butylphenyl) phosphino) butane, 1,4-bis (Bis (3,5-dimethoxyphenyl) phosphino) butane, 2,2′-bis (diphenylphosphino) -1,1′-binaphthyl, 2,2′-bis (bis (3,5-dimethylphenyl) phosphino ) -1,1′-binaphthyl, 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene, bis (diphenylphosphinoethyl) phenylphosphine, 1,1,1-tris (diph Nylphosphinomethyl) ethane, 1,1,1-tris (bis (3,5-dimethylphenyl) phosphinomethyl) ethane, 1,1,1-tris (diphenylphosphino) methane, or tris (2-diphenyl) Item 4. The production method according to any one of Items 1 to 3, which is (phosphinoethyl) phosphine.
Item 4. In the general formula (1), Z is hydride, oxygen atom, water molecule, carbon monoxide, nitric oxide, cyanide ion, thiocyanate, amine, aromatic hydrocarbon, unsaturated hydrocarbon, heterocyclic compound, Item 1 is a carbonyl compound, a lower alkoxy group, β-diketonate, dimethyl sulfoxide, phosphine oxide, nitrile, nitrogen molecule, hydrogen molecule, oxygen molecule, carbon dioxide, N-heterocyclic carbene, triflate, tosylate, or trifurylimide. The manufacturing method in any one of -3-1.
Item 5. In the general formula (1), m is an integer of 1 to 4, n is an integer of 1 to 6, p is an integer of 1 to 4, and q is 0 or 1, The manufacturing method in any one of.
Item 6. The ruthenium complex has the general formula (1A):
Ru _m X _n Y _p Z _q
[Wherein X is the same or different and each is a halogen atom or RCOO- (wherein R is an optionally substituted alkyl group or an optionally substituted aryl group); Y is the same as defined above] Z is a ligand other than X and Y; m, n and q are the same as above; p is an integer of 1 to 6; the number of phosphorus atoms coordinated to the ruthenium atom is 2 to 10 times that of the ruthenium atom; is there. ]
Or a compound represented by the general formula (1B):

[Wherein, R ⁹ and R ¹⁰ are the same or different and each may be an alkyl group which may be substituted, or an aryl group which may be substituted; a bond shown by a solid line and a broken line is a single bond or a double bond It is. ]
Item 6. The production method according to any one of Items 1 to 5, which is a compound represented by the formula:
Item 7. The ruthenium complex is
General formula (1A-1):
RuX _n Y _p Z _q
[Wherein, X, Y, Z, n, p and q are the same as above. ]
A compound represented by
General formula (1A-2):
Ru ₂ X _n Y _{p '} Z' _q
[Wherein, X, Y, Z, n, p and q are the same as above. ]
Or a compound represented by the general formula (1B):

[Wherein, R ⁹ and R ¹⁰ are the same as above; the bonds indicated by the solid and broken lines are single bonds or double bonds. ]
Item 7. The production method according to Item 6, which is a compound represented by:
Item 7-1. The ruthenium complex has the general formula (1A-2a):

[Wherein, X ^{1 to} X ⁴ are the same or different and each is a halogen atom; R ^{1 to} R ⁴ are the same or different and each may be substituted aryl group; one R ¹ and one R ² and / or one R ³ and one R ⁴ may be bonded to each other to form a ring together with the adjacent —P—Ru—P—. ]
Or a compound represented by the general formula (1B):

[Wherein, R ⁹ and R ¹⁰ are the same as above; the bonds indicated by the solid and broken lines are single bonds or double bonds. ]
Item 8. The production method according to any one of Items 1 to 7, which is a compound represented by the formula:
Item 8. The alkali metal salt has the general formula (3):
MW
[Wherein M is an alkali metal;
W is
-BR ⁵ ₄ (R ⁵ is the same or different, and each may be an optionally substituted alkyl group or an optionally substituted aryl group),
_{^{-N (SO 2 R 6) 2}} (R 6 are identical or different, may be each substituted alkyl group, or an optionally substituted aryl group),
—OR ⁷ (R ⁷ is the same or different, and each may be an optionally substituted alkyl group, an optionally substituted acyl group, or —SO ₂ R ⁸ (R ⁸ is an optionally substituted alkyl group, A group represented by an aryl group which may be substituted))), or β-diketonate. ]
Item 8. The production method according to any one of Items 1 to 7, which is a salt represented by:
Item 9. Item 9. The method according to any one of Items 1 to 8, wherein a ligand Y ′ containing one or more phosphorus atoms is added in the hydrogenation reaction step.
Item 9-1. Item 10. The production method according to any one of Items 1 to 9, wherein the ligand Y ′ is a phosphine ligand.
Item 9-2. Item 10. The production method according to Item 9 or 9-1, wherein the ligand Y ′ is a phosphine ligand having an optionally substituted aryl group.
Item 9-3. The ligand Y ′ is triphenylphosphine, tri (3,5-xylyl) phosphine, tri (4-methylphenyl) phosphine, tri (3-methylphenyl) phosphine, tri (2-methylphenyl) phosphine, tris. (4-trifluoromethylphenyl) phosphine, tri (4-methoxyphenyl) phosphine, tri (3-methoxyphenyl) phosphine, tri (2-methoxyphenyl) phosphine, tris (3,5-dimethoxyphenyl) phosphine, tris ( 3,5-dimethyl-4-methoxyphenyl) phosphine, tris [3,5-bis (1,1-dimethylethyl) -4-methoxyphenyl] phosphine, tris (3,5-difluorophenyl) phosphine, tri (1 -Naphthyl) phosphine, trimethylphosphine, triethyl Sphin, tri-n-propylphosphine, triisopropylphosphine, tri-n-butylphosphine, tri-t-butylphosphine, tripentylphosphine, tri-n-hexylphosphine, tri-n-heptylphosphine, trioctylphosphine, tri Cyclopentylphosphine, tricyclohexylphosphine, methyldiphenylphosphine, cyclohexylmethylphenylphosphine, dicyclohexylphenylphosphine, 1,2-bis (diphenylphosphino) benzene, bisdiphenylphosphinomethane, 1,2-bis (diphenylphosphino) ethane 1,3-bis (diphenylphosphino) propane, 1,4-bis (diphenylphosphino) butane, 1,5-bis (diphenylphosphino) pentane, 1,1′-bi (Diphenylphosphino) ferrocene, 1,2-bis (bis (3,5-dimethylphenyl) phosphino) ethane, 1,3-bis (bis (3,5-dimethylphenyl) phosphino) propane, 1,4- Bis (bis (3,5-dimethylphenyl) phosphino) butane, 1,4-bis (bis (3,5-di-t-butylphenyl) phosphino) butane, 1,4-bis (bis (3,5- Dimethoxyphenyl) phosphino) butane, 2,2′-bis (diphenylphosphino) -1,1′-binaphthyl, 2,2′-bis (bis (3,5-dimethylphenyl) phosphino) -1,1′- Binaphthyl, 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene, bis (diphenylphosphinoethyl) phenylphosphine, 1,1,1-tris (diphenylphosphino Methyl) ethane, 1,1,1-tris (bis (3,5-dimethylphenyl) phosphinomethyl) ethane, 1,1,1-tris (diphenylphosphino) methane, or tris (2-diphenylphosphinoethyl) The manufacturing method in any one of claim | item 9 -9-2 which is phosphine.
Item 9-4. The production method according to any one of Items 1 to 9-3, wherein the hydrogenation step is performed in the presence of a solvent.
Item 9-5. Item 5. The production method according to Item 9-4, wherein the solvent is an aromatic hydrocarbon, an ether, or an alcohol.
Item 9-6. The said hydrogenation process is a manufacturing method in any one of claim | item 1 -9-5 which is a process made to react at 0-190 degreeC under the hydrogen pressure of 0.1-20 MPa.
Item 10. A method for producing an alcohol by hydrogenating a carboxylic acid compound,
A step of hydrogenating a carboxylic acid compound in a hydrogen atmosphere in the presence of a ruthenium complex and a ligand Y ″ containing one or more phosphorus atoms,
The said carboxylic acid compound is a manufacturing method which does not have a ketone group.
Item 11. Item 11. The production method according to Item 10, wherein in the ruthenium complex, ruthenium is trivalent.
Item 12. The ruthenium complex has the general formula (1B):

[Wherein, R ⁹ and R ¹⁰ are the same or different and each may be an alkyl group which may be substituted, or an aryl group which may be substituted; a bond shown by a solid line and a broken line is a single bond or a double bond It is. ]
Item 12. The production method according to Item 10 or 11, which is a compound represented by:
Item 13. Item 13. The production method according to any one of Items 10 to 12, wherein the ligand Y ″ has an optionally substituted aryl group.
Item 14. The ligand Y ″ is triphenylphosphine, tri (3,5-xylyl) phosphine, tri (4-methylphenyl) phosphine, tri (3-methylphenyl) phosphine, tri (2-methylphenyl) phosphine, tris. (4-trifluoromethylphenyl) phosphine, tri (4-methoxyphenyl) phosphine, tri (3-methoxyphenyl) phosphine, tri (2-methoxyphenyl) phosphine, tris (3,5-dimethoxyphenyl) phosphine, tris ( 3,5-dimethyl-4-methoxyphenyl) phosphine, tris [3,5-bis (1,1-dimethylethyl) -4-methoxyphenyl] phosphine, tris (3,5-difluorophenyl) phosphine, tri (1 -Naphthyl) phosphine, trimethylphosphine, triethyl Phosphine, tri-n-propylphosphine, triisopropylphosphine, tri-n-butylphosphine, tri-t-butylphosphine, tripentylphosphine, tri-n-hexylphosphine, tri-n-heptylphosphine, trioctylphosphine, tri Cyclopentylphosphine, tricyclohexylphosphine, methyldiphenylphosphine, cyclohexylmethylphenylphosphine, dicyclohexylphenylphosphine, 1,2-bis (diphenylphosphino) benzene, bisdiphenylphosphinomethane, 1,2-bis (diphenylphosphino) ethane 1,3-bis (diphenylphosphino) propane, 1,4-bis (diphenylphosphino) butane, 1,5-bis (diphenylphosphino) pentane, 1,1′- (Diphenylphosphino) ferrocene, 1,2-bis (bis (3,5-dimethylphenyl) phosphino) ethane, 1,3-bis (bis (3,5-dimethylphenyl) phosphino) propane, 1,4- Bis (bis (3,5-dimethylphenyl) phosphino) butane, 1,4-bis (bis (3,5-di-t-butylphenyl) phosphino) butane, 1,4-bis (bis (3,5- Dimethoxyphenyl) phosphino) butane, 2,2′-bis (diphenylphosphino) -1,1′-binaphthyl, 2,2′-bis (bis (3,5-dimethylphenyl) phosphino) -1,1′- Binaphthyl, 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene, bis (diphenylphosphinoethyl) phenylphosphine, 1,1,1-tris (diphenylphosphite) Methyl) ethane, 1,1,1-tris (bis (3,5-dimethylphenyl) phosphinomethyl) ethane, 1,1,1-tris (diphenylphosphino) methane, or tris (2-diphenylphosphinoethyl) The manufacturing method in any one of claim | item 10-13 which is a phosphine.
Item 14-1. Item 15. The production method according to any one of Items 10 to 14, wherein the hydrogenation step is performed in the presence of a solvent.
Item 14-2. Item 14. The production method according to Item 10-14, wherein the solvent is an aromatic hydrocarbon, an ether, or an alcohol.
Claim | item 14-3. The said hydrogenation process is a manufacturing method in any one of claim | item 10-14-2 which is a process made to react at 0-190 degreeC under the hydrogen pressure of 0.1-20 MPa.
Item 15. General formula (1A-2a1):

[Wherein, X ^{1 to} X ⁴ are the same or different and each is a halogen atom; R ^{1 to} R ⁴ are the same or different and each is an optionally substituted aryl group. ]
Ruthenium complex represented by

  According to the present invention, high temperature and high pressure are not required for the carboxylic acid compound, that is, even under mild conditions, hydrogenation can proceed efficiently and alcohol can be obtained. Is expensive.

  In addition, it is possible to obtain an alcohol in a very high yield by selecting a substrate, a complex and an alkali metal salt. In this case, since the selectivity of alcohol is high, there is a high possibility that it will lead to an energy conservation law.

  Furthermore, in the production method of the present invention, a catalyst that is easy to handle even at room temperature and in the air and can be synthesized easily can be used economically, and is highly practical and convenient.

It is a result (ORTEP) of the X-ray single-crystal structure analysis of the ruthenium complex (compound 2a) obtained by the synthesis example 1.

1. 1st aspect (manufacturing method)
The method for producing an alcohol in the first aspect of the present invention includes a step of hydrogenating a carboxylic acid compound in a hydrogen atmosphere in the presence of a ruthenium complex and an alkali metal salt.

(1) Ruthenium complex The ruthenium complex used in the present invention in the first aspect is represented by the general formula (1):
Ru _m X _n Y _p Z _q
[Wherein X is the same or different and each represents a halogen atom, RCOO- (wherein R is an optionally substituted alkyl group or an optionally substituted aryl group), or β-diketonate; Is a ligand containing one or more phosphorus atoms; Z is a ligand other than X and Y; m is an integer of 1 or more; n is an integer of 1 or more; p is an integer of 0 to 6; An integer of 2; the number of phosphorus atoms coordinated to the ruthenium atom is 2 to 10 times that of the ruthenium atom. ]
It is a compound shown by these.

  The ruthenium complex used in the present invention may be a mononuclear complex or a polynuclear complex, but is preferably a mononuclear complex or a binuclear complex, and more preferably a binuclear complex.

  The valence of ruthenium in the ruthenium complex used in the present invention in the first aspect may be any number, but is preferably divalent or trivalent, and more preferably divalent. In addition, the case where the valence of ruthenium is unknown in the reaction system is included.

  In the general formula (1), the group represented by X is a halogen atom, a group represented by RCOO—, or β-diketonate.

  As a halogen atom shown by X, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom etc. are mentioned, for example, A chlorine atom is preferable.

  In addition, R in the group represented by RCOO— is, for example, an optionally substituted alkyl group or an optionally substituted aryl group.

  As the alkyl group represented by R, for example, a saturated linear or branched aliphatic alkyl group having 1 to 20 carbon atoms (particularly 1 to 12, more preferably 1 to 6, particularly 1 to 4) is preferable. Examples thereof include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, and a tert-butyl group.

  The substituent in the case where the alkyl group represented by R is substituted is not particularly limited, but a halogen atom such as a fluorine atom, a chlorine atom or a bromine atom; an alkyl group such as a methyl group or an ethyl group; a methoxy group, an ethoxy group or the like Nitro group; amino group; hydroxy group; cyano group; silyl group such as trimethylsilyl group; thiol group and the like. The number of substituents when substituted with a substituent can be, for example, about 1 to 3.

  Examples of the aryl group represented by R include a phenyl group, a naphthyl group, a pyrenyl group, a toluyl group, a xylyl group, a mesityl group, a pyridyl group, a furyl group, a thiophenyl group, and a pyrrolyl group.

  The substituent in the case where the aryl group represented by R is substituted is not particularly limited, but a halogen atom such as a fluorine atom, a chlorine atom or a bromine atom; an alkyl group such as a methyl group or an ethyl group; a methoxy group or an ethoxy group Nitro group; amino group; hydroxy group; cyano group; silyl group such as trimethylsilyl group; thiol group and the like. The number of substituents when substituted with a substituent can be, for example, about 1 to 3.

Among these, as R, an unsubstituted alkyl group is preferable, and a methyl group, an ethyl group, and an n-propyl group are more preferable. Therefore, the group represented by RCOO— represented by X is preferably a group represented by CH ₃ COO—, C ₂ H ₅ COO—, C ₃ H ₇ COO— or the like, and a group represented by CH ₃ COO—. Is more preferable.

  Examples of the β-diketonate represented by X include acetylacetonate.

X satisfying the above conditions is particularly preferably a chlorine atom, a group represented by CH ₃ COO—, or acetylacetonato.

  In the general formula (1), the ligand represented by Y is a ligand containing one or more phosphorus atoms, and specifically, a phosphine ligand is preferable. As such a ligand, any of a monodentate ligand, a bidentate ligand, a tridentate ligand and a tetradentate ligand can be used, but a monodentate ligand or a bidentate ligand is preferred.

  In addition, the ligand containing one or more phosphorus atoms is preferably a ligand having an optionally substituted aryl group from the viewpoint of the yield of alcohol by hydrogenation (reduction) of the carboxylic acid compound. In addition, examples of the aryl group which may be substituted include the same aryl groups as the above R, and include a phenyl group, a naphthyl group, a pyrenyl group, a toluyl group, a xylyl group, a mesityl group, a pyridyl group, and a furyl group. , A thiophenyl group, a pyrrolyl group and the like are preferable.

Specific examples of the ligand Y containing at least one phosphorus atom that can be used in the present invention include monodentate ligands such as trialkylphosphine such as trimethylphosphine; tricyclohexylphosphine (PCy ₃ ) and the like. Tricycloalkylphosphine; triphenylphosphine, tri (4-fluorophenyl) phosphine, tri (2-tolyl) phosphine, tri (3-tolyl) phosphine, tri (4-tolyl) phosphine, tris [4- (trifluoromethyl ) Phenyl] phosphine, tri (4-anisyl) phosphine, tri (2,4-xylyl) phosphine, tri (3,5-xylyl) phosphine, tri (2,4,6-trimethoxyphenyl) phosphine Phosphine; triheteroarylphosphine such as tri-2-furanylphosphine And bidentate ligands include bisdiphenylphosphinomethane (dppm), 1,2-bis (diphenylphosphino) ethane (dppe), 1,3-bis (diphenylphosphino) propane ( dppp), 1,4-bis (diphenylphosphino) butane (dppb), 1,5-bis (diphenylphosphino) pentane (dpppn), 1,6-bis (diphenylphosphino) hexane (dppphe), 1, 2-bis (diphenylphosphino) benzene, 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene, 2,2′-bis (diphenylphosphino) -1,1′-binaphthyl (BINAP), 1,1′-bis (diphenylphosphino) ferrocene, 1,4-bis (bis (3,5-dimethylphenyl) phosphino) Butane, 1,4-bis (bis (3,5-di-t-butylphenyl) phosphino) butane, and the like. Examples of the tridentate ligand include bis (2-diphenylphosphinoethyl) phenylphosphine, 1,1,1-tris (diphenylphosphinomethyl) ethane, 1,1,1-tris (bis (3,5-dimethylphenyl) phosphinomethyl) ethane, and the like. Examples of the tetradentate ligand include tris (2-diphenylphosphinoethyl) phosphine and the like. Among them, a monodentate or bidentate ligand having a monovalent aromatic hydrocarbon group which may be substituted is preferable, and specifically, triphenylphosphine, tri (3,5-xylyl) phosphine, bisdiphenyl. Phosphinomethane (dppm), 1,3-bis (diphenylphosphino) propane (dppp), 1,4-bis (diphenylphosphino) butane (dppb), 1,5-bis (diphenylphosphino) pentane (dpppn) ), 1,1′-bis (diphenylphosphino) ferrocene, 2,2′-bis (diphenylphosphino) -1,1′-binaphthyl (BINAP), bis (diphenylphosphinoethyl) phenylphosphine, 1,1 , 1-tris (diphenylphosphinomethyl) ethane, 1,4-bis (bis (3,5-dimethylphenyl) phosphite ) Butane, 1,4-bis (bis (3,5-di -t- butyl-phenyl) phosphino) butane, etc. are preferable.

  These ligands Y may be contained in the ruthenium complex to be charged, or may be formed in the ruthenium complex in the system.

In the general formula (1), the ligand represented by Z is a ligand other than X and Y, and is not particularly limited as long as it can coordinate to Ru. Specifically, hydrogen atom (hydride; H ⁻ ), oxygen atom (oxo group; O ²⁻ ), water molecule (H ₂ O), carbon monoxide (CO), aromatic hydrocarbon (benzene, naphthalene, pyrene) , Cyclopentadiene, p-cymene, etc.), lower alkoxy groups (C1-4 alkoxy groups such as methoxy groups), β-diketonates (acetylacetone, etc.), dimethyl sulfoxide, nitric oxide (NO), unsaturated hydrocarbons (cyclo octadiene, acetylene, 2-methylallyl, etc.), cyanide ion ^(- CN), thiocyanate (NCS ^-), amines (ammonia, triethylamine, etc.), heterocyclic compounds (pyridine, thiophene, THF), carbonyl compounds (formaldehyde, Acetone, ethyl acetate, DMF, etc.), phosphine oxide, nitrile (acetononitrile) Etc.), molecular nitrogen (N _2), hydrogen molecules _(H 2), oxygen molecules _(O 2), carbon dioxide _(CO 2), N-heterocyclic carbenes, triflate _(CF 3 SO ₃ ^-), tosylate (p- CH ₃ C ₆ H ₄ SO ₃ ⁻ ), trifurylimide ((CF ₃ SO ₂ ) ₂ N ⁻ ) and the like, and water molecules (H ₂ O), carbon monoxide (CO), aromatic hydrocarbons ( Cyclopentadiene, p-cymene and the like), 1,3-diketone (acetylacetone and the like), dimethyl sulfoxide, cyclooctadiene and the like are preferable.

  In the general formula (1), m is an integer of 1 or more. From the viewpoint of the yield of alcohol by hydrogenation (reduction) of the carboxylic acid compound, m is preferably an integer of 1 to 4, more preferably 1 or 2, and even more preferably 2.

  In General formula (1), n is an integer greater than or equal to 1, and the integer of 1-6 is preferable from a viewpoint of the yield of the alcohol by hydrogenation (reduction) of a carboxylic acid compound. In addition, when the ruthenium complex of the present invention is a mononuclear complex (m = 1), n is preferably an integer of 1 to 3, and more preferably 1 or 2. Moreover, when the ruthenium complex of the present invention is a polynuclear complex (m = 2), n is preferably an integer of 2 to 6, and more preferably an integer of 3 to 5.

  In General formula (1), p is an integer of 0-6, and the integer of 1-4 is preferable from a viewpoint of the yield of the alcohol by hydrogenation (reduction) of a carboxylic acid compound.

  In the general formula (1), q is an integer of 0 to 2, and 0 or 1 is preferable from the viewpoint of the yield of alcohol by hydrogenation (reduction) of the carboxylic acid compound.

  The number of phosphorus atoms coordinated to the ruthenium atom is preferably 2 to 10 times that of the ruthenium atom, more preferably 2 to 6 times, and even more preferably 2 to 3 times.

Preferred examples of the ruthenium complex used in the present invention include, for example, the general formula (1A):
Ru _m X _n Y _p Z _q
[Wherein X is the same or different and each is a halogen atom or RCOO- (wherein R is an optionally substituted alkyl group or an optionally substituted aryl group); Y is the same as defined above] Z is a ligand other than X and Y; m, n and q are the same as above; p is an integer of 1 to 6; the number of phosphorus atoms coordinated to the ruthenium atom is 2 to 10 times that of the ruthenium atom; is there. ]
(Hereinafter, also referred to as ruthenium complex (1A)).

  In general formula (1A), Y, m, n, and q are the same as described above.

  In general formula (1A), X is a halogen atom or RCOO—, and specific examples and preferred examples of the halogen atom and RCOO— are as described above.

  In the general formula (1A), Z is a ligand other than X and Y, and specific examples and preferred examples thereof are as described above.

  In general formula (1A), p is an integer of 1-6, and an integer of 2-4 is more preferable.

Preferred examples of such a ruthenium complex (1A) include, for example, the general formula (1A-1):
RuX _n Y _p Z _q
[Wherein, X, Y, Z, n, p and q are the same as those in the general formula (1A)). ]
(Hereinafter also referred to as ruthenium complex (1A-1)).

  In general formula (1A-1), X, Y, Z, n, p, and q are the same as the above (general formula (1A)).

Examples of such a ruthenium complex (1A-1) include RuCl ₂ (PPh ₃ ) ₃ (Ph is a phenyl group, the same shall apply hereinafter), RuCl ₂ (PPh ₃ ) ₄ , RuCl (OAc) (PPh ₃ ) ₃ ( Ac is an acetyl group, the same applies hereinafter, RuCl ₂ (CO) ₂ (PPh ₃ ) ₂ , RuHCl (CO) (PPh ₃ ) ₃ , CpRuCl (PPh ₃ ) ₂ (Cp is a cyclopentadienyl group, the same applies hereinafter), CpRuCl (dppm) (dppm is bisdiphenylphosphinomethane, the same applies hereinafter), (p-cymene) RuCl ₂ (PCy ₃ ) (Cy is a cyclohexyl group), and the like, and alcohol by hydrogenation (reduction) of carboxylic acid compounds in terms of _{yield, RuCl 2 (PPh 3) 3} , RuCl 2 (PPh 3) 4, RuCl (OAc) ( _{Ph 3) 3, RuCl 2 (} CO) 2 (PPh 3) 2, RuHCl (CO) (PPh 3) 3, CpRuCl (PPh 3) 2, is preferably such _{CpRuCl (dppm), RuCl 2 (} PPh 3) 3, RuCl ₂ (PPh ₃ ) ₄ , RuCl (OAc) (PPh ₃ ) ₃ , RuHCl (CO) (PPh ₃ ) _3, etc. are more preferred, RuCl ₂ (PPh ₃ ) ₃ , RuCl (OAc) (PPh ₃ ) ₃ etc. Is more preferable.

Moreover, as another preferable example of a ruthenium complex (1A), for example, general formula (1A-2):
Ru ₂ X _n Y _p Z _q
[Wherein, X, Y, Z, n, p and q are the same as those in the general formula (1A)). ]
(Hereinafter also referred to as a ruthenium complex (1A-2)).

  In general formula (1A-2), X, Y, Z, n, p, and q are the same as the above (general formula (1A)).

  Among the ruthenium complexes (1A-2), from the viewpoint of the yield of alcohol by hydrogenation (reduction) of the carboxylic acid compound, in particular, the general formula (1A-2a):

[Wherein, X ^{1 to} X ⁴ are the same or different and each is a halogen atom; R ^{1 to} R ⁴ are the same or different and each may be substituted aryl group; one R ¹ and one R ² and / or one R ³ and one R ⁴ may be bonded to each other to form a ring together with the adjacent —P—Ru—P—. ]
(Hereinafter also referred to as ruthenium complex (1A-2a)) is preferred.

In the general formula (1A-2a), X ^{1 to} X ⁴ are halogen atoms, and examples thereof include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom, and a chlorine atom is preferable.

In the general formula (1A-2a), R ^{1 to} R ⁴ are aryl groups which may be substituted. For example, phenyl group, naphthyl group, pyrenyl group, toluyl group, xylyl group, mesityl group, pyridyl group, furyl Group, thiophenyl group, pyrrolyl group and the like, and a phenyl group is preferable.

However, one R ¹ and one R ² , and / or one R ³ and one R ⁴ may be bonded to each other to form a ring with adjacent —P—Ru—P—. . In the case of forming a ring, the ring that can be formed is not particularly limited, but specifically,

[R ^{1 to} R ⁴ are the same or different and the same as above. ]
Etc.

In the case of forming a ring in this way, R ^{1 to} R ⁴ are aryl groups which may be substituted, for example, phenyl group, naphthyl group, pyrenyl group, toluyl group, xylyl group, mesityl group, pyridyl group, A furyl group, a thiophenyl group, a pyrrolyl group, etc. are mentioned, and a phenyl group is preferable.

  Examples of the ruthenium complex (1A-2a) described above include:

[3,5-xylyl is 3,5-xylyl group; the same applies hereinafter]
From the viewpoint of the yield of alcohol by hydrogenation (reduction) of the carboxylic acid compound, ruthenium complex (1A-2a1a) and the like are preferable.

  As still another preferred embodiment of the ruthenium complex used in the present invention, the general formula (1B):

[Wherein, R ⁹ and R ¹⁰ are the same or different and each may be an alkyl group which may be substituted, or an aryl group which may be substituted; a bond shown by a solid line and a broken line is a single bond or a double bond It is. ]
The compound shown by these is also mentioned.

R ⁹ and R ¹⁰ are an optionally substituted alkyl group or an optionally substituted aryl group, and specific examples thereof include those described above. The preferable example is also the same.

  As a ruthenium complex satisfying such conditions, specifically,

Etc.

In addition, as the ruthenium complex, Ru (NH ₃ ) ₆ Cl ₃ , Ru (NH ₃ ) ₅ Cl ₃ , RuCl ₃ and its hydrate, RuI ₃ and its hydrate, ruthenium (III) nitrosyl nitrate, nitrosyl chloride Ruthenium (III), ruthenium acetate (III), ruthenium trifluoroacetate (III), dichloro (1,5-cyclooctadiene) ruthenium (II) polymer, dichloro (pentamethylcyclopentadienyl) ruthenium (II) polymer, Dichloro (p-cymene) ruthenium (II) dimer, dichloro (hexamethylbenzene) ruthenium (II) dimer, dichloro (mesitylene) ruthenium (II) dimer, benzeneruthenium (II) chloride dimer, tetrakis (dimethylsulfoxide) dichlororutheni Beam (II), chloro (pentamethylcyclopentadienyl) (cyclooctadiene) ruthenium (II), tricarbonyl dichlororuthenium (II) dimer, triruthenium dodecacarbonyl and the like can be used.

  The ruthenium complex used in the present invention is preferably a ruthenium complex (1A-2) or a ruthenium complex (1B), even though a ruthenium complex (1A-2) or a ruthenium complex (1B) is preferred.

  Such a ruthenium complex may be known or commercially available, or may be synthesized.

(2) Alkali metal salt In the present invention, an alkali metal salt is used to obtain an alcohol without hydrogenating a carboxylic acid or a compound and passing through an intermediate such as an ester or a cyclic ester. By forming a cationic ruthenium complex therein, the carboxylic acid compound can be hydrogenated to obtain an alcohol even under acidic conditions.

  From such a viewpoint, the alkali metal salt is preferably one having low basicity and high ionicity. However, if an excessive amount of carboxylic acid is used, the reaction can proceed even if a strong base (NaH or the like) is used.

As such an alkali metal salt, the general formula (3):
MW
[Wherein M is an alkali metal;
W is
-BR ⁵ ₄ (R ⁵ is the same or different, and each may be an optionally substituted alkyl group or an optionally substituted aryl group),
_{^{-N (SO 2 R 6) 2}} (R 6 are identical or different, may be each substituted alkyl group, or an optionally substituted aryl group),
—OR ⁷ (R ⁷ is the same or different, and each may be an optionally substituted alkyl group, an optionally substituted aryl group, or —SO ₂ R ⁸ (where R ⁸ is an optionally substituted alkyl group, A group represented by an aryl group which may be substituted))), or β-diketonate. ]
Is preferred.

  The alkali metal is not particularly limited and includes lithium, sodium, potassium, rubidium, cesium, and the like, and sodium, potassium, cesium, and the like are preferable from the viewpoint of the yield of alcohol by hydrogenation (reduction) of the carboxylic acid compound. .

As R ⁵ is in -BR ⁵ ₄ represented by W, the same alkyl group or aryl group represented by R are exemplified. Examples of the substituent are the same. Of these, a substituted or unsubstituted aryl group is preferred, and a substituted or unsubstituted phenyl group is particularly preferred from the viewpoint of the yield of alcohol by hydrogenation (reduction) of a carboxylic acid compound. Such ^-BR _{5 4,} for example, tetraphenyl borate, include [3,5- (trifluoromethyl) phenyl] borate.

Examples of R ⁶ in —N (SO ₂ R ⁶ ) ₂ represented by W include the same as the alkyl group or aryl group represented by R. Examples of the substituent are the same. Of these, a substituted or unsubstituted alkyl group is preferable, and a substituted or unsubstituted methyl group, ethyl group, propyl group, and the like are particularly preferable from the viewpoint of the yield of alcohol by hydrogenation (reduction) of the carboxylic acid compound. Examples of such —N (SO ₂ R ⁶ ) ₂ include NTf ₂ (Tf is a trifluoromethanesulfonyl group, the same shall apply hereinafter) and the like.

As R ⁷ is in the -OR ⁷ represented by W, the same alkyl groups represented by R are exemplified. Examples of the substituent are the same.

Further, R ⁷ in the -OR ⁷ may be an acyl group which may be substituted. As an acyl group, a formyl group, an acetyl group, a propionyl group etc. are mentioned, for example, An acetyl group is preferable. When it has a substituent, examples of the substituent include a halogen atom such as a fluorine atom, a chlorine atom and a bromine atom, an alkyl group such as a methyl group and an ethyl group; an alkoxy group such as a methoxy group and an ethoxy group; a nitro group; an amino group; A hydroxy group; a cyano group; a silyl group such as a trimethylsilyl group; and a thiol group. The number of substituents when substituted with a substituent can be, for example, about 1 to 3.

Further, R ⁷ in -OR ⁷ is, -SO 2 _R 8 may be a group represented by ^{(R 8} is an optionally substituted alkyl group, a group represented by optionally substituted aryl group) . Here, examples of R ⁸ include the same alkyl groups or aryl groups represented by R above. Examples of the substituent are the same.

Among these, as ^{R 7} in -OR ⁷ represented by W, from the viewpoint of an alcohol by hydrogenation of carboxylic acid compound (reduction) yield, substituted or unsubstituted acyl group, or _-SO 2 ^{R 8} are preferably, An acetyl group, a tosyl group and the like are particularly preferable.

Examples of such —OR ⁷ represented by W include —OCOCH ₃ , —OTs (Ts is a tosyl group, the same applies hereinafter) and the like.

  Examples of β-diketonate include acetylacetone and the like.

Examples of the alkali metal salt that satisfies such conditions include LiBPh ₄ , LiB (3,5- (CF ₃ ) ₂ Ph) ₄ , NaBPh ₄ , NaB (3,5- (CF ₃ ) ₂ Ph) ₄ , _{KBPh 4, KB (3,5- (CF} 3) 2 Ph) 4, CsBPh 4, CsB (3,5- (CF 3) 2 Ph) 4, LiOTs, NaOTs, KOTs, CsOTs, LiNTf 2, NaNTf 2, KNTf ₂ , CsNTf ₂ , LiOTf, NaOTf, KOTf, CsOTf, LiH, NaH, KH, CsH, Li (acac) (acac is acetylacetonato; the same applies hereinafter), Na (acac), K (acac), Cs (acac ), LiOAc, NaOAc, KOAc, CsOAc, LiOH, NaOH, KOH, CsOH, Li (Ot -Bu) (t-Bu is a tert-butyl group; the same shall apply hereinafter), Na (Ot-Bu), K (Ot-Bu), Cs (Ot-Bu) and the like. Hydrogenation (reduction of carboxylic acid compounds) From the viewpoint of the yield of alcohol due to (A), LiBPh ₄ , NaBPh ₄ , KBPh ₄ , CsBPh ₄ , LiOTs, NaOTs, KOTs, CsOTs, etc. are preferred, and NaBPh ₄ , KBPh ₄ , CsBPh ₄ , NaOTs, etc. are preferred. In addition, these alkali metal salts may be used independently and may be used in combination of 2 or more type. In addition, the alkali metal salt can be used as it is, or may be used as a hydrate or a solvate. However, it is preferably used as it is from the viewpoint of the yield of alcohol by hydrogenation (reduction) of the carboxylic acid compound.

(3) Ligand Y ′ containing at least one phosphorus atom
In the production method of the present invention, as described above, a ligand may be introduced into the ruthenium complex, but separately from the ruthenium complex, a ligand Y ′ containing one or more phosphorus atoms is introduced. May be. Although it does not restrict | limit especially as ligand Y 'which can be used in this case, The same ligand as the above-mentioned ligand Y can be used.

  That is, any of a monodentate ligand, a bidentate ligand, a tridentate ligand, and a tetradentate ligand can be used, and it is preferable to have an optionally substituted aryl group. Among them, triphenylphosphine, tri (4-fluorophenyl) phosphine, tri (3-tolyl) phosphine, tri (4-tolyl) phosphine, tris [4- (trifluoromethyl) phenyl] phosphine, tri (4-anisyl) ) Phosphine, tri (2,4,6-trimethoxyphenyl) phosphine, tri-2-furanylphosphine, 1,2-bis (diphenylphosphino) ethane, 1,2-bis (diphenylphosphino) benzene, 4 , 5-bis (diphenylphosphino) -9,9-dimethylxanthene, 1,1,1-tris (diphenylphosphinomethyl) ethane, tris (2-diphenylphosphinoethyl) phosphine and the like are preferable.

(4) Hydrogenation reaction In the production method of the present invention, specifically, hydrogen is added to a substrate (carboxylic acid compound) in the presence of a ruthenium complex, an alkali metal salt, and a ligand as required. Initiates the reaction to obtain alcohol.

  The substrate to be used for the reaction is not particularly limited as long as it is a carboxylic acid compound, and a wide variety of carboxylic acid compounds can be used. In this respect, the present invention is useful in comparison with the prior art in which hydrogenation reaction can only occur on a special substrate and the complex needs to be changed depending on the substrate.

  In the present invention, not only a carboxylic acid having only one carboxyl group, but also a carboxylic acid compound having a plurality of these groups can cause a hydrogenation reaction to obtain an alcohol. That is, alcohols can be obtained by hydrogenating a wide variety of carboxylic acid compounds, including carboxylic acids that cannot be intramolecularly esterified.

  In addition, when the substrate has a functional group (a ketone group, an ether group, an ester group, an amide bond, a double bond, etc.) other than the carboxyl group, it can be hydrogenated in the same manner as the carboxyl group. The functional group can be protected and only the carboxyl group can be hydrogenated (reduced). The protection of the functional group can be performed according to a conventional method. The same applies when the substrate has a plurality of carboxyl groups.

  However, from the viewpoint of the yield of alcohol by hydrogenation (reduction) of the carboxylic acid compound, it is preferable not to have a functional group other than a carboxyl group, to have only one carboxyl group, and to have other functional groups. More preferred are carboxylic acid compounds.

  A wide variety of carboxylic acid compounds can be used as such substrates. For example, acetic acid, propionic acid, butyric acid, valeric acid, hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, benzoic acid, 3-phenylpropionic acid On acid, 3-cyclohexylpropionic acid, 3- (4-chlorophenyl) acrylic acid, formic acid, lauric acid, myristic acid, pentadecylic acid, palmitic acid, palmitoleic acid, margaric acid, stearic acid, oleic acid, vacenoic acid, linoleic acid , Linolenic acid, 3-hydroxypropionic acid, lactic acid, malonic acid, malic acid, fumaric acid, succinic acid, xylonic acid, glutaric acid, itaconic acid, levulinic acid, aconitic acid, citric acid, gluconic acid, glucaric acid, lysine, Glutamic acid, 2,5-furandicarboxylic acid, aspartic acid, serine, The threonine and the like can be used.

  The amount of the ruthenium complex used can be appropriately selected depending on the type of the substrate (carboxylic acid compound). From the viewpoint of the yield of alcohol by hydrogenation (reduction) of the carboxylic acid compound, for example, the substrate (carboxylic acid compound) ) It is usually about 0.0001 to 1 mol, preferably about 0.001 to 0.1 mol, more preferably about 0.003 to 0.07 mol with respect to 1 mol.

  In the production method of the present invention, the reaction system is preferably set to acidic reaction conditions. Specifically, the amount of the substrate (carboxylic acid compound) is preferably excessive with respect to the alkali metal salt. Specifically, the amount of the alkali metal salt used is usually 0.02-1 with respect to 1 mol of the substrate (carboxylic acid compound) from the viewpoint of the yield of alcohol by hydrogenation (reduction) of the carboxylic acid compound. Mol, preferably 0.03 to 0.5 mol, more preferably 0.04 to 0.2 mol.

  The amount of the alkali metal salt used is preferably excessive with respect to the ruthenium complex. Specifically, from the viewpoint of the yield of alcohol by hydrogenation (reduction) of the carboxylic acid compound, 1 mol of the ruthenium complex. On the other hand, it is usually 2 to 100 mol, preferably 3 to 50 mol, more preferably 4 to 20 mol.

  In the case of introducing a ligand, the amount of the ligand used is usually from 0.05 to 1 mol per 1 mole of ruthenium complex, for example, from the viewpoint of the yield of alcohol by hydrogenation (reduction) of the carboxylic acid compound. The amount can be 100 mol, preferably 0.5 to 10 mol, more preferably 1 to 5 mol.

  The hydrogenation of the present invention is preferably performed in a solvent.

  Examples of the solvent include ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran (THF), dioxane (1,4-dioxane and the like), t-butyl methyl ether, cyclopentyl methyl ether, 1,2-dimethoxyethane, diglyme and triglyme. Aromatic hydrocarbons such as benzene, trifluoromethylbenzene, toluene, xylene and mesitylene; aliphatic hydrocarbons such as pentane, hexane, heptane, cyclopentane, cyclohexane, octane, nonane, decane and petroleum ether; isopropanol, n- Examples thereof include branched C3-6 alcohols such as butyl alcohol, tert-butyl alcohol and sec-butyl alcohol. These solvents may be used alone or in combination of two or more. Of these, aromatic hydrocarbons or C3-C6 alcohols are preferable, trifluoromethylbenzene, toluene, mesitylene, tert-butyl alcohol, and the like are more preferable, and toluene is particularly preferable.

  In the hydrogenation step of the present invention, hydrogen is added to the substrate (carboxylic acid compound), and hydrogen gas can be used as the hydrogen. The hydrogen partial pressure during hydrogenation (hydrogen pressure) is usually about 0.1 to 20 MPa, preferably about 0.5 to 10 MPa, from the viewpoint of the yield of alcohol by hydrogenation (reduction) of the carboxylic acid compound. More preferably, it can be set to about 0.7 to 8 MPa.

  Although the reaction temperature and reaction time may vary depending on the type of substrate (carboxylic acid compound), the reaction temperature is usually about 0 to 190 ° C. from the viewpoint of the yield of alcohol by hydrogenation (reduction) of the carboxylic acid compound. The temperature may be about 10 to 170 ° C., more preferably about 20 to 160 ° C. The reaction time is usually about 10 minutes to 50 hours, preferably about 1 to 30 hours, from the viewpoint of alcohol yield in hydrogenation (reduction). In this reaction, usually an autoclave or the like can be used.

  In the hydrogenation of the present invention, a ruthenium complex, an alkali metal salt, and a ligand as required are reacted in the presence or absence of hydrogen, and then a substrate (carboxylic acid compound) is reacted in the presence of hydrogen. You can also. A catalytically active species having a high hydrogenation-reduction ability is once prepared by the reaction of a ruthenium complex, an alkali metal salt and, if necessary, a ligand. Therefore, hydrogen is efficiently produced by reacting this with a substrate (carboxylic acid compound). An additive reaction product can be obtained. In this case, in any reaction, the conditions can be the same as described above.

  After completion of the reaction, a hydrogenated reaction product (alcohol) can be obtained through normal isolation and purification steps.

2. Second aspect (manufacturing method)
The method for producing an alcohol according to the second aspect of the present invention includes a step of hydrogenating a carboxylic acid compound in a hydrogen atmosphere in the presence of a ruthenium complex and a ligand Y ″ containing one or more phosphorus atoms.

(1) Ruthenium complex The ruthenium complex used in the present invention is not particularly limited. Among these, as an example of a particularly preferable ruthenium complex, from the viewpoint of the yield of alcohol by hydrogenation (reduction) of a carboxylic acid compound, the general formula (2):

[Wherein, R ⁹ and R ¹⁰ are the same as above; the bonds indicated by the solid and broken lines are single bonds or double bonds. ]
The compound shown by these is mentioned.

R ⁹ and R ¹⁰ are the same as described above, and specific examples and preferred examples thereof are also the same.

  As a ruthenium complex satisfying such conditions, specifically,

Etc.

  In the present invention, other preferable examples of preferable ruthenium complexes include, for example, bis (2,4-dimethylpentadienyl) ruthenium (II), bis (2-methylallyl) (1,5-cyclooctadiene). Ruthenium (II), bis (cyclopentadienyl) ruthenium (II), bis (ethylcyclopentadienyl) ruthenium (II), tris (acetonitrile) cyclopentadienylruthenium (II) hexafluorophosphate, bis (penta And methylcyclopentadienyl) ruthenium (II).

(2) Ligand Y "containing one or more phosphorus atoms
In the hydrogenation step of the present invention, the ligand Y ″ is used to hydrogenate a carboxylic acid compound to obtain an alcohol without passing through an intermediate such as an ester or a cyclic ester. Examples of the ligand Y ″ include the same ligands as the ligand Y containing one or more phosphorus atoms.

  That is, any of a monodentate ligand, a bidentate ligand, a tridentate ligand, and a tetradentate ligand can be used, and it is preferable to have an optionally substituted aryl group. Among them, tri (3,5-xylyl) phosphine, 1,3-bis (diphenylphosphino) propane, 1,4-bis (diphenylphosphino) butane, 1,5-bis (diphenylphosphino) pentane, 2 , 2′-bis (diphenylphosphino) -1,1′-binaphthyl, 1,1′-bis (diphenylphosphino) ferrocene, bis (2-diphenylphosphinoethyl) phenylphosphine, or 1,1,1- Tris (diphenylphosphinomethyl) ethane and the like are preferable.

(3) Hydrogenation reaction In the production method of the present invention, specifically, in the presence of a ruthenium complex and a ligand, hydrogen is added to a substrate (carboxylic acid compound) to cause a hydrogenation reaction, and an alcohol is produced. obtain.

  The substrate to be used for the reaction is not particularly limited as long as it is a carboxylic acid compound, and a wide variety of carboxylic acid compounds can be used. In this respect, the present invention is useful in comparison with the prior art in which hydrogenation reaction can only occur on a special substrate and the complex needs to be changed depending on the substrate.

  In the present invention, not only a carboxylic acid having only one carboxyl group, but also a carboxylic acid compound having a plurality of these groups can cause a hydrogenation reaction to obtain an alcohol. That is, alcohols can be obtained by hydrogenating a wide variety of carboxylic acid compounds, including carboxylic acids that cannot be intramolecularly esterified.

  In addition, when the substrate has a functional group (a ketone group, an ether group, an ester group, an amide bond, a double bond, etc.) other than the carboxyl group, it can be hydrogenated in the same manner as the carboxyl group. The functional group can be protected and only the carboxyl group can be hydrogenated (reduced). The protection of the functional group can be performed according to a conventional method. The same applies when the substrate has a plurality of carboxyl groups.

  However, from the viewpoint of the yield of alcohol by hydrogenation (reduction) of the carboxylic acid compound, it is preferable not to have a functional group other than a carboxyl group, to have only one carboxyl group, and to have other functional groups. More preferred are carboxylic acid compounds.

  As such a substrate, a wide variety of carboxylic acid compounds can be used, and the same substrate as in the first embodiment can be used. The same applies to preferred embodiments.

  The amount of the ruthenium complex used can be appropriately selected depending on the type of the substrate (carboxylic acid compound). From the viewpoint of the yield of alcohol by hydrogenation (reduction) of the carboxylic acid compound, for example, the substrate (carboxylic acid compound) ) It is usually about 0.0001 to 1 mol, preferably about 0.001 to 0.1 mol, more preferably about 0.003 to 0.07 mol with respect to 1 mol.

  In addition, the amount of the ligand used is usually 0.05 to 100 mol, preferably 0 with respect to 1 mol of the ruthenium complex, from the viewpoint of the yield of alcohol by hydrogenation (reduction) of the carboxylic acid compound. 5 to 10 mol, more preferably 1 to 5 mol.

  The hydrogenation of the present invention is preferably performed in a solvent.

  As the solvent, the same solvent as in the first embodiment can be used. The same applies to preferred embodiments.

  In the hydrogenation step of the present invention, hydrogen is added to the substrate (carboxylic acid compound), and hydrogen gas can be used as the hydrogen. The hydrogen partial pressure during hydrogenation (hydrogen pressure) is usually about 0.1 to 20 MPa, preferably about 0.5 to 10 MPa, from the viewpoint of the yield of alcohol by hydrogenation (reduction) of the carboxylic acid compound. More preferably, it can be set to about 0.7 to 8 MPa.

  Although the reaction temperature and reaction time may vary depending on the type of substrate (carboxylic acid compound), the reaction temperature is usually about 0 to 190 ° C. from the viewpoint of the yield of alcohol by hydrogenation (reduction) of the carboxylic acid compound. The temperature may be about 10 to 170 ° C., more preferably about 20 to 160 ° C. The reaction time is usually about 10 minutes to 50 hours, preferably about 1 to 30 hours, from the viewpoint of alcohol yield in hydrogenation (reduction). In this reaction, usually an autoclave or the like can be used.

  In the hydrogenation of the present invention, a ruthenium complex, an alkali metal salt, and a ligand as required are reacted in the presence or absence of hydrogen, and then a substrate (carboxylic acid compound) is reacted in the presence of hydrogen. You can also. A catalytically active species having a high hydrogenation-reduction ability is once prepared by the reaction of a ruthenium complex, an alkali metal salt and, if necessary, a ligand. Therefore, hydrogen is efficiently produced by reacting this with a substrate (carboxylic acid compound). An additive reaction product can be obtained. In this case, in any reaction, the conditions can be the same as described above.

  After completion of the reaction, a hydrogenated reaction product (alcohol) can be obtained through normal isolation and purification steps.

3. Third aspect (new ruthenium complex)
Of the ruthenium complexes used in the production method of the present invention described above (particularly the first aspect), the general formula (1A-2a1):

[Wherein, X ^{1 to} X ⁴ are the same or different and each is a halogen atom; R ^{1 to} R ⁴ are the same or different and each is an optionally substituted aryl group (R ¹ and R ² , R ³ And R ⁴ are not bonded to form a ring with adjacent -P-Ru-P-). ]
The compound represented by, for example,

These are novel compounds not described in any literature.

  This group of compounds can be used as a catalyst for producing an alcohol by hydrogenating a carboxylic acid compound. In particular, it can be used in the production method of the present invention.

  Hereinafter, the novel ruthenium complex of the present invention has, for example, the following reaction formula:

[Wherein, X ^{1 to} X ⁴ and R ^{1 to} R ⁴ are the same as the above (general formula (1A-2a1)); X ⁵ is the same or different and each is a halogen atom, and any ^one of X ^{1 to} X ⁴ R ⁶ is the same or different and each is an optionally substituted aryl group and is the same as any one of R ^{1 to} R ⁴ . ]
Can be synthesized according to

Compound represented by RuX ⁵ ₃ used as a raw material is a ruthenium halide. In the formula, all of X ⁵ are halogen atoms, and specific examples thereof include those described above. Further, X ⁵ are the same as any of X ¹ to X ⁴ in the novel ruthenium complex finally obtained.

As such a ruthenium halide, specifically, RuCl ₃ , RuBr ₃ , RuF ₃ , RuI _{3 and the} like can be used. These may be used as they are, or may be used as hydrates or solvates.

Moreover, PR ⁶ ₃ used as a ligand is a phosphorus atom described above the same as the ligand Y containing one or more. R ⁶ is an aryl group which may be substituted, and is the same as any ^one of R ^{1 to} R ⁴ in the finally obtained new ruthenium complex.

The amount of the ligand PR ⁶ ₃ is preferably in the excess relative to ruthenium halides, specifically, from the viewpoint of the alcohol yield by hydrogenation of carboxylic acid compound (reduction), ruthenium halogen It is usually 2 to 100 mol, preferably 3 to 50 mol, and more preferably 4 to 20 mol per mol of the compound.

  This reaction can usually be carried out in a solvent. Examples of the solvent include diethyl ether, tetrahydrofuran (THF), dioxane, t-butyl methyl ether, cyclopentyl methyl ether, 1,2-dimethoxyethane, diglyme and other ethers; benzene, toluene, xylene, mesitylene and other aromatic carbonization Hydrogen: aliphatic hydrocarbons such as pentane, hexane, heptane, cyclopentane, cyclohexane, octane, nonane, decane, petroleum ether; methanol, ethanol, isopropanol, n-butyl alcohol, tert-butyl alcohol, sec-butyl alcohol, etc. A branched C1-6 alcohol etc. are mentioned. These solvents may be used alone or in combination of two or more. Of these, aromatic hydrocarbons or C1-C6 alcohols are preferred, C1-C6 alcohols are more preferred, and methanol, ethanol, and the like are particularly preferred.

  The reaction atmosphere is not particularly limited, but is preferably an inert gas atmosphere. Specifically, a nitrogen gas atmosphere, an argon gas atmosphere, or the like may be used.

  The reaction temperature and reaction time may vary depending on the type of ruthenium halide, but from the viewpoint of yield, the reaction temperature is usually about 0 to 190 ° C, preferably about 10 to 170 ° C, more preferably 20 to 160. It can be set to about ° C. The reaction time is generally about 10 minutes to 50 hours, preferably about 20 minutes to 30 hours, from the viewpoint of yield. In this reaction, usually an oil bath or the like can be used.

  After completion of the reaction, a new ruthenium complex can be obtained through normal isolation and purification steps.

  Next, the present invention will be described with reference to examples, but the present invention is not limited to the following examples.

  [Synthesis Example 1: Synthesis of Ruthenium Complex 2a]

In a 75 mL Young Schlenk container purged with argon gas, degassed by stirring, ruthenium chloride hydrate (RuCl ₃ · nH ₂ O: Ru content 40%, 125.7 mg, 0.50 mmol) and nitrogen bubbling for about 30 minutes. Vaporized dehydrated methanol (25 mL) was contained. Thereafter, the Young Schlenk container was placed in an oil bath, and the components in the Young Schlenk container were stirred and heated to 80 ° C. to cause reaction. As a result, the color of the reaction solution changed from brown to dark green. Heating was terminated after 1 hour, and the temperature of the reaction solution was returned to room temperature. Then, while introducing argon gas into the container, tri (3,5-xylyl) phosphine (1039.4 mg, 3.0 mmol) and dehydrated methanol (10 mL) degassed as described above were added, and the oil bath was used at 80 ° C. When the reaction solution was reacted for 24 hours, the color of the reaction solution changed to red, and brown crystals were formed.

  Next, before the temperature of the reaction solution is lowered, the produced brown crystals are collected by filtration with washing with hot methanol under an argon gas atmosphere, dried under reduced pressure, and 179.6 mg (0.10 mg) of the ruthenium complex as reddish brown crystals. mmol, 41%).

The spectrum data of the obtained ruthenium complex 2a were as follows.
³¹ P { ¹ H} NMR (243MHz, C ₆ D ₆ ): δ 61.1 (d, J = 39.5 Hz), 52.1 (d, J = 39.5 Hz), HRMS (ESI, (RuCl {P (3,5- xylyl) ₃ } ₂ ) ⁺ ) Calcd for C ₄₈ H ₅₄ ClP ₂ Ru ⁺ : 829.2433. Found m / z = 829.2580.

  In addition, the result (ORTEP) of the X-ray single-crystal structure analysis of the obtained ruthenium complex 2a is shown in FIG. In order to clarify the structure, hydrogen atoms are omitted.

[Example 1: Example of first aspect]
Example 1-1

  Reduction (hydrogenation) of 3-phenylpropionic acid was performed by the following method.

  To a dried glass tube (30 mL), a stir bar, 3-phenylpropionic acid (150.2 mg, 1.0 mmol), ruthenium complex 2a (17.5 mg, 0.010 mmol) obtained in Synthesis Example 1, sodium tetraphenylborate ( A tube containing 34.2 mg, 0.10 mmol) and containing this mixture was inserted into the autoclave. Next, after the inside of the autoclave was replaced with an argon gas atmosphere, dehydrated toluene (3.0 mL) was added while the argon gas was kept flowing. Hydrogen gas was introduced into the autoclave from a hydrogen gas cylinder connected via a stainless steel tube, and the inside of the autoclave was replaced with hydrogen gas. That is, a hydrogen gas pressure of 1.5 MPa was applied to the autoclave, and then the hydrogen gas pressure was released from the leak valve. This operation (substitution-replacement) was repeated 10 times. Finally, the hydrogen gas pressure in the autoclave was set to 4 MPa, and the reaction was performed at 160 ° C. for 24 hours using a thermostatic bath.

After completion of the reaction, the autoclave was immersed in an ice bath and cooled to room temperature. Then, the leak valve of the autoclave was gently opened, and the hydrogen gas inside was released into the air. Next, the tube was taken out from the autoclave to obtain a reaction product (solution). This solution was transferred to a 100 mL eggplant flask using chloroform, and then concentrated under reduced pressure using an evaporator. ^An internal standard (mesitylene) was added for ¹ H NMR analysis. The yield of the reaction product was calculated based on the integrated value of the amount of hydrogen atoms of the internal standard substance. As a result, the yields of 3-phenylpropyl alcohol and 3-phenylpropyl 3-phenylpropionate were 65% and 12%, respectively.

  The result of Example 1-1 corresponds to entry 2 of Table 1 described later.

Example 1-2
In Example 1-1, the substrate, ruthenium complex, additive (alkali metal salt), and hydrogenation conditions were the same as Example 1-1 except that the conditions described in Table 1 were adopted. Reduction (hydrogenation) was performed. In addition, as raw materials other than the ruthenium complex 2a synthesized in Synthesis Example 1, a commercially available product or one synthesized by a known method was used. The results are shown in Table 1.

[Example 2: Example of second aspect]
Example 2-1

  Reduction (hydrogenation) of 3-phenylpropionic acid was performed by the following method.

  To a dry glass tube (30 mL), stir bar, 3-phenylpropionic acid (150.2 mg, 1.0 mmol), tris (acetylacetonato) ruthenium (8.0 mg, 0.020 mmol), 1,4-bis (diphenylphosphine). A tube containing fino) butane (8.5 mg, 0.020 mmol) and containing this mixture was inserted into the autoclave. Next, after the inside of the autoclave was replaced with an argon gas atmosphere, dehydrated toluene (3.0 mL) was added while the argon gas was kept flowing. Hydrogen gas was introduced into the autoclave from a hydrogen gas cylinder connected via a stainless steel tube, and the inside of the autoclave was replaced with hydrogen gas. That is, a hydrogen gas pressure of 0.8 MPa was applied to the autoclave, and then the hydrogen gas pressure was released from the leak valve. This operation (substitution-replacement) was repeated 10 times. Finally, the hydrogen gas pressure in the autoclave was set to 1 MPa, and the reaction was performed at 160 ° C. for 24 hours using a thermostatic bath.

After completion of the reaction, the autoclave was immersed in an ice bath and cooled to room temperature. Then, the leak valve of the autoclave was gently opened, and the hydrogen gas inside was released into the air. Next, the tube was taken out from the autoclave to obtain a reaction product (solution). This solution was transferred to a 100 mL eggplant flask using chloroform, and then concentrated under reduced pressure using an evaporator. ^An internal standard (mesitylene) was added for ¹ H NMR analysis. The yield of the reaction product was calculated based on the integrated value of the amount of hydrogen atoms of the internal standard substance. As a result, the yields of 3-phenylpropyl alcohol and 3-phenylpropyl 3-phenylpropionate were 45% and 16%, respectively.

  The result of Example 2-1 corresponds to entry 1 in Table 2 described later.

Example 2-2
In Example 2-1, reduction (hydrogenation) was performed in the same manner as in Example 2-1, except that the conditions described in Table 2 were adopted. The results are shown in Table 2.

  [Example 3: Effect of ligand addition to ruthenium complex (part 1)]

Example 3-1
Reduction (hydrogenation) of 3-phenylpropionic acid was performed by the following method.

In a dry glass tube (30 mL), stir bar, 3-phenylpropionic acid (150.2 mg, 1.0 mmol), dichlorotetrakis (dimethylsulfoxide) ruthenium (II) (cis-RuCl ₂ (dmso) ₄ ) (9.69 mg 0.020 mmol), sodium tetraphenylborate (34.2 mg, 0.10 mmol), and triphenylphosphine (10.49 mg, 0.04 mmol), and a tube containing this mixture was inserted into the autoclave. Next, after the inside of the autoclave was replaced with an argon gas atmosphere, dehydrated toluene (3.0 mL) was added while the argon gas was kept flowing. Hydrogen gas was introduced into the autoclave from a hydrogen gas cylinder connected via a stainless steel tube, and the inside of the autoclave was replaced with hydrogen gas. That is, a hydrogen gas pressure of 1.5 MPa was applied to the autoclave, and then the hydrogen gas pressure was released from the leak valve. This operation (substitution-replacement) was repeated 10 times. Finally, the hydrogen gas pressure in the autoclave was set to 8 MPa, and the reaction was performed at 160 ° C. for 24 hours using a thermostatic bath.

After completion of the reaction, the autoclave was immersed in an ice bath and cooled to room temperature. Then, the leak valve of the autoclave was gently opened, and the hydrogen gas inside was released into the air. Next, the tube was taken out from the autoclave to obtain a reaction product (solution). This solution was transferred to a 100 mL eggplant flask using chloroform, and then concentrated under reduced pressure using an evaporator. ^An internal standard (mesitylene) was added for ¹ H NMR analysis. The yield of the reaction product was calculated based on the integrated value of the amount of hydrogen atoms of the internal standard substance. As a result, the yields of 3-phenylpropyl alcohol and 3-phenylpropyl 3-phenylpropionate were 31% and 15%, respectively.

  The result of Example 3-1 corresponds to entry 2 in Table 3 described later.

Example 3-2
In Example 3-1 above, reduction (hydrogenation) was performed in the same manner as in Example 3-1, except that the conditions described in Table 3 were employed. The results are shown in Table 3.

  [Example 4: Effect of addition of ligand to ruthenium complex (part 2)]

  In entry 3 in Table 3 above, hydrogen reduction (hydrogenation reaction) was performed in the same manner as entry 3 in Table 3 except that the conditions described in Table 4 were adopted. The results are shown in Table 4. It should be noted that entry 3 in Table 3 and entry 1 in Table 4 have the same conditions.

  [Example 5: Effect of addition of alkali metal salt to ruthenium complex (part 1)]

  In entry 5 of Table 1, reduction (hydrogenation) was performed in the same manner as entry 5 of Table 1 except that the conditions described in Table 5 were employed. The results are shown in Table 5. Note that entry 5 in Table 1 and entry 2 in Table 5 have the same conditions.

  [Example 6: Effect of solvent addition on ruthenium complex]

  In entry 5 of Table 1, reduction (hydrogenation) was performed in the same manner as entry 5 of Table 1 except that the conditions described in Table 6 were adopted. The results are shown in Table 6. It should be noted that entry 5 in Table 1 and entry 1 in Table 6 have the same conditions.

  [Example 7: Effect of amount of solvent added to ruthenium complex]

  In entry 5 of Table 1, reduction (hydrogenation) was performed in the same manner as entry 5 of Table 1 except that the conditions described in Table 7 were adopted. The results are shown in Table 7. It should be noted that entry 5 in Table 1 and entry 2 in Table 7 have the same conditions.

  [Example 8: Effect of addition of ligand to ruthenium complex (part 3)]

Example 8-1
Reduction (hydrogenation) of 3-phenylpropionic acid was performed by the following method.

In a dry glass tube (30 mL), stir bar, 3-phenylpropionic acid (150.2 mg, 1.0 mmol), dichlorotris (triphenylphosphine) ruthenium (II) (RuCl ₂ (PPh ₃ ) ₃ ) (19.18 mg 0.020 mmol), sodium tetraphenylborate (34.2 mg, 0.10 mmol), and 1,2-bis (diphenylphosphino) ethane (7.97 mg, 0.02 mmol), and the tube containing this mixture was placed in an autoclave. Inserted into. Next, after the inside of the autoclave was replaced with an argon gas atmosphere, dehydrated toluene (3.0 mL) was added while the argon gas was kept flowing. Hydrogen gas was introduced into the autoclave from a hydrogen gas cylinder connected via a stainless steel tube, and the inside of the autoclave was replaced with hydrogen gas. That is, a hydrogen gas pressure of 1.5 MPa was applied to the autoclave, and then the hydrogen gas pressure was released from the leak valve. This operation (substitution-replacement) was repeated 10 times. Finally, the hydrogen gas pressure in the autoclave was set to 8 MPa, and the reaction was performed at 160 ° C. for 24 hours using a thermostatic bath.

After completion of the reaction, the autoclave was immersed in an ice bath and cooled to room temperature. Then, the leak valve of the autoclave was gently opened, and the hydrogen gas inside was released into the air. Next, the tube was taken out from the autoclave to obtain a reaction product (solution). This solution was transferred to a 100 mL eggplant flask using chloroform, and then concentrated under reduced pressure using an evaporator. ^An internal standard (mesitylene) was added for ¹ H NMR analysis. The yield of the reaction product was calculated based on the integrated value of the amount of hydrogen atoms of the internal standard substance. As a result, the yields of 3-phenylpropyl alcohol and 3-phenylpropyl 3-phenylpropionate were 3% and 8%, respectively.

  The result of Example 8-1 corresponds to entry 1 of Table 8 described later.

Example 8-2
In Example 8-1 described above, reduction (hydrogenation) was performed in the same manner as in Example 8-1 except that the conditions described in Table 8 were employed. The results are shown in Table 8.

  [Example 9: Effect of addition of ligand to ruthenium complex (part 4)]

Example 9-1
Reduction (hydrogenation) of 3-phenylpropionic acid was performed by the following method.

To a dried glass tube (30 mL), stir bar, 3-phenylpropionic acid (150.2 mg, 1.0 mmol), (1,5-cyclooctadiene) ruthenium (II) polymer ([Ru (cod) Cl ₂ ]. _n ) (5.60 mg, 0.020 mmol), sodium tetraphenylborate (34.2 mg, 0.10 mmol), and 1,2-bis (diphenylphosphino) ethane (7.97 mg, 0.02 mmol), containing this mixture The tube was inserted into the autoclave. Next, after the inside of the autoclave was replaced with an argon gas atmosphere, dehydrated toluene (3.0 mL) was added while the argon gas was kept flowing. Hydrogen gas was introduced into the autoclave from a hydrogen gas cylinder connected via a stainless steel tube, and the inside of the autoclave was replaced with hydrogen gas. That is, a hydrogen gas pressure of 1.5 MPa was applied to the autoclave, and then the hydrogen gas pressure was released from the leak valve. This operation (substitution-replacement) was repeated 10 times. Finally, the hydrogen gas pressure in the autoclave was set to 8 MPa, and the reaction was performed at 160 ° C. for 24 hours using a thermostatic bath.

After completion of the reaction, the autoclave was immersed in an ice bath and cooled to room temperature. Then, the leak valve of the autoclave was gently opened, and the hydrogen gas inside was released into the air. Next, the tube was taken out from the autoclave to obtain a reaction product (solution). This solution was transferred to a 100 mL eggplant flask using chloroform, and then concentrated under reduced pressure using an evaporator. ^An internal standard (mesitylene) was added for ¹ H NMR analysis. The yield of the reaction product was calculated based on the integrated value of the amount of hydrogen atoms of the internal standard substance. As a result, the yields of 3-phenylpropyl alcohol and 3-phenylpropyl 3-phenylpropionate were 13% and 15%, respectively.

  The result of Example 9-1 corresponds to entry 1 of Table 9 described later.

Example 9-2
In Example 9-1 described above, reduction (hydrogenation) was performed in the same manner as in Example 9-1 except that the conditions described in Table 9 were employed. The results are shown in Table 9.

  [Example 10: Effect of addition of solvent and ligand to ruthenium complex]

  In entry 4 of Table 2, reduction (hydrogenation) was performed in the same manner as entry 4 of Table 2 except that the conditions described in Table 10 were employed. The results are shown in Table 10. Note that entry 4 in Table 2 and entry 2 in Table 10 have the same conditions.

  [Example 11: Effect of addition of alkali metal salt to ruthenium complex (part 2)]

Example 11-1
Reduction (hydrogenation) of 3-phenylpropionic acid was performed by the following method.

  In a dry glass tube (30 mL), stir bar, 3-phenylpropionic acid (150.2 mg, 1.0 mmol), tris (acetylacetonato) ruthenium (8.0 mg, 0.020 mmol), tri (3,5-xylyl) A tube containing phosphine (20.79 mg, 0.060 mmol), sodium acetate (8.20 mg, 0.10 mmol) and containing this mixture was inserted into the autoclave. Next, after the inside of the autoclave was replaced with an argon gas atmosphere, dehydrated toluene (3.0 mL) was added while the argon gas was kept flowing. Hydrogen gas was introduced into the autoclave from a hydrogen gas cylinder connected via a stainless steel tube, and the inside of the autoclave was replaced with hydrogen gas. That is, a hydrogen gas pressure of 1.5 MPa was applied to the autoclave, and then the hydrogen gas pressure was released from the leak valve. This operation (substitution-replacement) was repeated 10 times. Finally, the hydrogen gas pressure in the autoclave was set to 4 MPa, and the reaction was performed at 160 ° C. for 24 hours using a thermostatic bath.

After completion of the reaction, the autoclave was immersed in an ice bath and cooled to room temperature. Then, the leak valve of the autoclave was gently opened, and the hydrogen gas inside was released into the air. Next, the tube was taken out from the autoclave to obtain a reaction product (solution). This solution was transferred to a 100 mL eggplant flask using chloroform, and then concentrated under reduced pressure using an evaporator. ^An internal standard (mesitylene) was added for ¹ H NMR analysis. The yield of the reaction product was calculated based on the integrated value of the amount of hydrogen atoms of the internal standard substance. As a result, the yields of 3-phenylpropyl alcohol and 3-phenylpropyl 3-phenylpropionate were 62% and 18%, respectively.

  The result of Example 11-1 corresponds to entry 1 of Table 11 described later.

Example 11-2
In Example 11-1, reduction (hydrogenation) was performed in the same manner as in Example 11-1, except that the conditions described in Table 11 were employed. The results are shown in Table 11.

Claims (15)

A method for producing an alcohol by hydrogenating a carboxylic acid compound,
Comprising a step of hydrogenating a carboxylic acid compound in a hydrogen atmosphere in the presence of a ruthenium complex and an alkali metal salt,
The ruthenium complex has the general formula (1):
Ru _m X _n Y _p Z _q
[Wherein X is the same or different and each represents a halogen atom, RCOO- (wherein R is an optionally substituted alkyl group or an optionally substituted aryl group), or β-diketonate; Is a ligand containing one or more phosphorus atoms; Z is a ligand other than X and Y; m is an integer of 1 or more; n is an integer of 1 or more; p is an integer of 0 to 6; An integer of 2; the number of phosphorus atoms coordinated to the ruthenium atom is 2 to 10 times that of the ruthenium atom. ]
The manufacturing method which is a compound shown by these. The production method according to claim 1, wherein in the ruthenium complex, ruthenium is divalent or trivalent. In the said General formula (1), Y is a phosphine ligand which has the aryl group which may be substituted, The manufacturing method of Claim 1 or 2. In the general formula (1), Z is hydride, oxygen atom, water molecule, carbon monoxide, nitric oxide, cyanide ion, thiocyanate, amine, aromatic hydrocarbon, unsaturated hydrocarbon, heterocyclic compound, A carbonyl compound, a lower alkoxy group, β-diketonate, dimethyl sulfoxide, phosphine oxide, nitrile, nitrogen molecule, hydrogen molecule, oxygen molecule, carbon dioxide, N-heterocyclic carbene, triflate, tosylate, or trifurylimide. The manufacturing method in any one of 1-3. In the said General formula (1), m is an integer of 1-4, n is an integer of 1-6, p is an integer of 1-4, q is 0 or 1. 4. The production method according to any one of 4 above. The ruthenium complex has the general formula (1A):
Ru _m X _n Y _p Z _q
[Wherein X is the same or different and each is a halogen atom or RCOO- (wherein R is an optionally substituted alkyl group or an optionally substituted aryl group); Y is the same as defined above] Z is a ligand other than X and Y; m, n and q are the same as above; p is an integer of 1 to 6; the number of phosphorus atoms coordinated to the ruthenium atom is 2 to 10 times that of the ruthenium atom; is there. ]
Or a compound represented by the general formula (1B):

[Wherein, R ⁹ and R ¹⁰ are the same or different and each may be an alkyl group which may be substituted, or an aryl group which may be substituted; a bond shown by a solid line and a broken line is a single bond or a double bond It is. ]
The manufacturing method in any one of Claims 1-5 which is a compound shown by these. The ruthenium complex is
General formula (1A-1):
RuX _n Y _p Z _q
[Wherein, X, Y, Z, n, p and q are the same as above. ]
A compound represented by
General formula (1A-2):
Ru ₂ X _n Y _p Z _q
[Wherein, X, Y, Z, n, p and q are the same as above. ]
Or a compound represented by the general formula (1B):

[Wherein, R ⁹ and R ¹⁰ are the same as above; the bonds indicated by the solid and broken lines are single bonds or double bonds. ]
The manufacturing method of Claim 6 which is a compound shown by these. The alkali metal salt has the general formula (3):
MW
[Wherein M is an alkali metal;
W is
-BR ⁵ ₄ (R ⁵ is the same or different, and each may be an optionally substituted alkyl group or an optionally substituted aryl group),
_{^{-N (SO 2 R 6) 2}} (R 6 are identical or different, may be each substituted alkyl group, or an optionally substituted aryl group),
—OR ⁷ (R ⁷ is the same or different, and each may be an optionally substituted alkyl group, an optionally substituted acyl group, or —SO ₂ R ⁸ (R ⁸ is an optionally substituted alkyl group, A group represented by an aryl group which may be substituted))), or β-diketonate. ]
The manufacturing method in any one of Claims 1-7 which is a salt shown by these. The production method according to claim 1, wherein a ligand Y ′ containing one or more phosphorus atoms is added in the hydrogenation reaction step. A method for producing an alcohol by hydrogenating a carboxylic acid compound,
A step of hydrogenating a carboxylic acid compound in a hydrogen atmosphere in the presence of a ruthenium complex and a ligand Y ″ containing one or more phosphorus atoms,
The said carboxylic acid compound is a manufacturing method which does not have a ketone group. The production method according to claim 10, wherein in the ruthenium complex, ruthenium is trivalent. The ruthenium complex has the general formula (1B):

[Wherein, R ⁹ and R ¹⁰ are the same or different and each may be an alkyl group which may be substituted, or an aryl group which may be substituted; a bond shown by a solid line and a broken line is a single bond or a double bond It is. ]
The manufacturing method of Claim 10 or 11 which is a compound shown by these. The production method according to claim 10, wherein the ligand Y ″ has an aryl group which may be substituted. The ligand Y ″ is triphenylphosphine, tri (3,5-xylyl) phosphine, tri (4-methylphenyl) phosphine, tri (3-methylphenyl) phosphine, tri (2-methylphenyl) phosphine, tris. (4-trifluoromethylphenyl) phosphine, tri (4-methoxyphenyl) phosphine, tri (3-methoxyphenyl) phosphine, tri (2-methoxyphenyl) phosphine, tris (3,5-dimethoxyphenyl) phosphine, tris ( 3,5-dimethyl-4-methoxyphenyl) phosphine, tris [3,5-bis (1,1-dimethylethyl) -4-methoxyphenyl] phosphine, tris (3,5-difluorophenyl) phosphine, tri (1 -Naphthyl) phosphine, trimethylphosphine, triethyl Phosphine, tri-n-propylphosphine, triisopropylphosphine, tri-n-butylphosphine, tri-t-butylphosphine, tripentylphosphine, tri-n-hexylphosphine, tri-n-heptylphosphine, trioctylphosphine, tri Cyclopentylphosphine, tricyclohexylphosphine, methyldiphenylphosphine, cyclohexylmethylphenylphosphine, dicyclohexylphenylphosphine, 1,2-bis (diphenylphosphino) benzene, bisdiphenylphosphinomethane, 1,2-bis (diphenylphosphino) ethane 1,3-bis (diphenylphosphino) propane, 1,4-bis (diphenylphosphino) butane, 1,5-bis (diphenylphosphino) pentane, 1,1 ′ Bis (diphenylphosphino) ferrocene, 1,2-bis (bis (3,5-dimethylphenyl) phosphino) ethane, 1,3-bis (bis (3,5-dimethylphenyl) phosphino) propane, 1,4- Bis (bis (3,5-dimethylphenyl) phosphino) butane, 1,4-bis (bis (3,5-di-t-butylphenyl) phosphino) butane, 1,4-bis (bis (3,5- Dimethoxyphenyl) phosphino) butane, 2,2′-bis (diphenylphosphino) -1,1′-binaphthyl, 2,2′-bis (bis (3,5-dimethylphenyl) phosphino) -1,1′- Binaphthyl, 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene, bis (diphenylphosphinoethyl) phenylphosphine, 1,1,1-tris (diphenylphosphine) Sufinomethyl) ethane, 1,1,1-tris (bis (3,5-dimethylphenyl) phosphinomethyl) ethane, 1,1,1-tris (diphenylphosphino) methane, or tris (2-diphenylphosphinoethyl) The production method according to any one of claims 10 to 13, which is phosphine. General formula (1A-2a1):

[Wherein, X ^{1 to} X ⁴ are the same or different and each is a halogen atom; R ^{1 to} R ⁴ are the same or different and each may be substituted aryl group; one R ¹ and one R ² and / or one R ³ and one R ⁴ may be bonded to each other to form a ring together with the adjacent —P—Ru—P—. ]
Ruthenium complex represented by

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