JPH10273455A - Production of alcohols - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce alcohols useful as a synthetic intermediate, etc., for medicines and agrochemicals by hydrogenating a carbonyl compound with hydrogen in the presence of a homogeneous hydrogenating catalyst, a base and a nitrogen-containing organic compound in a liquid reactional medium. SOLUTION: A carbonyl compound represented by the formula (R<1> and R<2> are each an aromatic monocyclic ring, an aromatic polycyclic ring, etc.) is hydrogenated with hydrogen usually under 1 atm in the presence of a transition complex metallic complex of a group VIII metal (e.g. rhodium solubilized with a liquid reactional medium under reactional conditions) at (1/100) to (1/10,000) molar ratio thereof to the carbonyl compound, a base (preferably an alkali metal, a quaternary ammonium salt, etc.) in an amount of 0.5-100 equiv. for the metallic complex and a nitrogen-containing organic compound (preferably an amine compound or an amine derivative) in an amount of 1-10 equiv. for the metallic complex in the case of a monoamine compound or in an amount of 0.5-20 equiv. for the metallic complex in the case of a diamine compound in preferably 20-50 wt.% liquid reactional medium at 15-100 deg.C to afford the objective alcohols (e.g. benzhydrol) in high yield at a high efficiency.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION The invention of this application relates to a high yield and high efficiency of alcohols which are useful as intermediates for the synthesis of pharmaceuticals and agrochemicals or many general-purpose chemicals by hydrogenation of carbonyl compounds. And a method for producing the same.

[0002]

2. Description of the Related Art It has been well known to hydrogenate carbonyl compounds using homogeneous catalysts to produce the corresponding alcohols. For example (1) Comprehe
nsive Organometallic Chemistry, Vol. 4, p. 931 (1982), Eds, G Wilkinson, FGAStone and
A method using a ruthenium complex described in EW Abel and (2) Inorg Nucl. Chem. Letters, Vol.
65 (1976), J. Organomet. Chem., Vol.
9, 239 (1977); Chem. Letters, 261 (1982) and Tetrahedron Letters, Vol. 35,
Method using a rhodium complex described on page 4963 (1994), (3) J. Am. Chem. Soc., Vol. 115,3.
A method using an iridium complex described in page 318 (1993) is known.

However, in the case of these conventional methods,
There has been a problem that the noble metal complex used as a catalyst has a low hydrogenation activity and requires conditions of relatively high temperature or high hydrogen pressure, so that it is not always suitable for practical use. Accordingly, the invention of this application overcomes the above-mentioned drawbacks of the prior art and provides a method for producing an alcohol by hydrogenating a carbonyl compound with high yield and high efficiency using a new catalyst system having high activity. It is an object.

[0004]

SUMMARY OF THE INVENTION The present invention solves the above-mentioned problems by providing a carbonyl compound with hydrogen in a liquid reaction medium in the presence of a homogeneous hydrogenation catalyst, a base and a nitrogen-containing organic compound. And a method for producing alcohols, characterized by hydrogenating hydrogen.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION As described above, the method for producing alcohols of the present invention is characterized by using a three-component catalyst system comprising a homogeneous hydrogenation catalyst, a base and a nitrogen-containing organic compound. More specifically, said homogeneous hydrogenation catalyst is secondly soluble in a liquid reaction medium under reaction conditions.
It is preferable to constitute a transition metal complex of a Group VIII metal. The metals in this case are rhodium, ruthenium,
Palladium, iridium, or platinum are indicated as desirable, among which are ruthenium, which is available relatively inexpensively and constitutes a very active catalyst system.

As the base, more specifically, an alkali metal or alkaline earth metal hydroxide, a salt thereof, or a quaternary ammonium salt is mentioned. The nitrogen-containing organic compound is preferably an aliphatic, alicyclic, aromatic, or heterocyclic amine compound or amine derivative. With the above-mentioned new three-component catalyst system, the carbonyl group of the carbonyl compound is hydrogenated in the presence of hydrogen and converted into alcohols. There is no particular limitation on the type of carbonyl compound. Various types may be used.

For example, various aliphatic, alicyclic, aromatic and heterocyclic ketone compounds can be mentioned. More specifically, hydrogenation of a carbonyl compound using a highly active ruthenium complex catalyst and a ternary catalyst comprising an alkali metal or alkaline earth metal salt or a quaternary ammonium salt and an amine compound will be described. General formula

[0008]

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[0009] carbonyl compound represented by (R ¹ and R ² are unsubstituted or, an aromatic optionally having substituent indicates a monocyclic or aromatic polycyclic group. Further R ¹ and R ² is May be bonded to form a ring.)

[0010]

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(X represents a hydrogen atom, a halogen atom, a carboxyl group, an alkoxy group, or a hydroxy group, L represents an organic ligand, and n represents an integer of 1 to 4 depending on the nature of the ligand used.) A ruthenium complex represented by the general formula

[0012]

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(M represents an alkali metal or an alkaline earth metal, Y represents a hydroxy group, an alkoxy group, a mercapto group, or a naphthyl group);
General formula

[0014]

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(R ³ , R ⁴ , R ⁵ may be the same or different and each represents a hydrogen atom, an alkyl group, an aryl group, or an unsaturated hydrocarbon group.) Or general formula

[0016]

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(R ⁶ , R ⁷ , R ⁸ , and R ⁹ may be the same or different and each represents a hydrogen atom, an alkyl group,
Z represents an aryl group or an unsaturated hydrocarbon group, and Z between N and N represents a group selected from a hydrocarbon group having 1 to 5 carbon atoms, a cyclohydrocarbon group, an aryl group, and an unsaturated hydrocarbon group. Show. ) Is used as a catalyst.

The above is not limited to the ruthenium complex catalyst system, and other Group VIII metals can be similarly considered. In any case, when the carbonyl compound represented by the above general formula as a raw material is specifically exemplified, each of R ¹ and R ^{2 in} the formula is phenyl, 2-methylphenyl, 2-ethylphenyl, 2-isopropylphenyl , 2-tert-butylphenyl, 2-methoxyphenyl, 2-chlorophenyl, 2-vinylphenyl, 3
-Methylphenyl, 3-ethylphenyl, 3-isopropylphenyl, 3-methoxyphenyl, 3-chlorophenyl, 3-vinylphenyl, 4-methylphenyl, 4-
Ethylphenyl, 4-isopropylphenyl, 4-tert
Aromatic mono- and polycyclic groups such as -butylphenyl, 4-vinylphenyl, cumenyl, mesityl, xylyl, 1-naphthyl, 2-naphthyl, anthryl, phenanthryl and indenyl groups may be used. Examples of the carbonyl compound in the case where R ¹ and R ² are bonded to form a ring include, for example, fluorenone, anthrone, dibenzosuberone and the like.

In the ruthenium complex represented by the above general formula, X in the formula represents a hydrogen atom, a halogen atom, a carboxyl group, an alkoxy group, or a hydroxy group;
Is an organic ligand, and this ligand can be CO, an organic nitrogen compound ligand, a phosphine ligand, an organic arsenic compound ligand, or the like. The phosphine ligand has the general formula P
R ′ R ″ R ″ ″, and R ′, R ″, R ″ ″
May be the same or different, and may represent an aliphatic group, an alicyclic group or an aromatic group. Further, it may be a bidentate phosphine ligand. For example, tertiary phosphines such as trimethyl phosphine, triethyl phosphine, tributyl phosphine, triphenyl phosphine, tricyclohexyl phosphine, tri (p-tolyl) phosphine, diphenyl methyl phosphine, dimethyl phenyl phosphine, and bisdiphenyl phosphinomethane, bis diphenyl phosphine Preferred examples include bidentate tertiary phosphine compounds such as finoethane, bisdiphenylphosphinopropane, bisdiphenylphosphinobutane, bisdimethylphosphinoethane, and bisdimethylphosphinopropane.

Of the above complexes, rhodium, iridium, palladium and platinum complexes are preferably used in addition to ruthenium. Among them, the ruthenium complex has high activity. Specifically,

[0021]

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And the like. Of course, the complexes used in the present invention are not limited to these. For example, although the amount of the metal complex used varies depending on the reaction vessel and economical efficiency, the molar ratio of the metal complex to the carbonyl compound as the reaction substrate is 1/100 to 1 / 100,0.
00, preferably 1/500 to 1/1
The range is 0000.

For the base represented by the general formula MY,
Is an alkali metal or an alkaline earth metal, and Y is
Hydroxyl, alkoxy, mercapto, or
A naphthyl group, specifically KOH, KOCH_Three, K
OCH (CH_Three)_Two, KC_TenH ₈, LiOH, LiOCH
_Three, LiOCH (CH_Three)_TwoEtc. are preferred.
Is done. Use quaternary ammonium salts in the same way
Can be.

The amount of the base to be used is 0.5 to 100 equivalents, preferably 2 to 40 equivalents, relative to the metal complex. When using an amine compound in the present invention, diamine represented by the general formula NR ³ R ⁴ R monoamines or general formula represented by ^{5 NR 6 R 7 -Z-NR} 8 R 9 is preferred. Here, R ³ , R ⁴ , R ⁵ , R ⁶ , R
⁷ , R ⁸ and R ⁹ each represent a hydrogen atom and a carbon number of 1 to 10;
And the same or different among the alkyl group, cycloalkyl group, allyl group, and aryl group, and includes cyclic amines. Z represents a group selected from an alkyl group having 1 to 5 carbon atoms, a cycloalkyl group, and an aryl group. Examples of the above amine compounds include methylamine, ethylamine, propylamine, butylamine, pentylamine,
Hexylamine, cyclopentylamine, cyclohexylamine, benzylamine, dimethylamine, diethylamine, dipropylamine, dihexylamine, dicyclopentylamine, dicyclohexylamine, dibenzylamine, diphenylamine, phenylethylamine,
Monoamine compounds such as piperidine and piperazine, and further methylenediamine, ethylenediamine, 1,2-diaminopropane, propylenediane, 1,3-diaminopropane, 1,4-diaminobutane, 2,3-diaminobutane, and 1,2-cyclohexane Pentanediamine, 1,2-cyclohexanediamine, N-methylethylenediamine,
N, N'-dimethylethylenediamine, N, N, N'-
Examples thereof include diamine compounds such as trimethylethylenediamine, N, N, N ', N'-tetramethylethylenediamine, o-phenylenediamine, and p-phenylenediamine.

The amount of the amine compound used is preferably 1 to 10 equivalents, more preferably 2 to 4 equivalents, and more preferably 0.5 to 20 equivalents for the diamine compound, based on the transition metal complex. , Preferably in the range of 1-2 equivalents. The three components of the transition metal complex, the base, and the amine compound that constitute the catalyst system are indispensable components for the reaction to proceed smoothly. If any one component is insufficient, sufficient reaction activity cannot be obtained. Specifically, a comparative example will be described.

As the liquid solvent in the present invention, various solvents can be used as long as they solubilize the reaction raw materials and the catalyst system. Examples include aromatic solvents such as toluene and xylene, aliphatic solvents such as pentane and hexane, halogen-containing hydrocarbon solvents such as methylene chloride, ether solvents such as ether and tetrahydrofuran, methanol, ethanol, 2-propanol and butanol. And an organic solvent containing a hetero atom such as acetonitrile, DMF and DMSO, and the like. Among them, alcohol-based solvents are preferred because the product is alcohol. Even more preferred is 2-propanol. These liquid solvents can be used alone or as a mixed solvent.

The amount of the solvent is determined based on the solubility and economical efficiency of the reaction substrate. In the case of 2-propanol, the reaction can be carried out at a substrate concentration of as low as 1% or less and in a state close to no solvent containing only the substrate, but preferably at 20 to 50% by weight. In the present invention, the pressure of hydrogen is sufficient to be 1 atm because the catalyst system is extremely active. However, in consideration of economy, the pressure is set to 1 to 100 atm, preferably 3 to 50 atm. Is desirable. High activity can be maintained even when the pressure is set to 10 atm or less in consideration of economy of the whole process.

The reaction temperature ranges from 15 ° C. to 1 in consideration of economy.
The temperature is preferably about 00 ° C., but the reaction can be carried out at around room temperature of 25 to 40 ° C. However, the present invention is characterized in that the reaction proceeds even at a low temperature of -30 to 0 degrees. The reaction time is the concentration of the reaction substrate,
It depends on the reaction conditions such as temperature and pressure.
The reaction is completed in 0 hours. Specific examples will be described in Examples.

The reaction can be carried out in a batch mode or a continuous mode. Hereinafter, the present invention will be described in more detail with reference to Examples.

[0030]

EXAMPLES Example 1 RuCl ₂ [P (C ₆ H ₅ ) ₃ ] ₃ (9.6 mg, 0.01 m
mol), KOH (0.02 mmol), ethylenediamine (0.01 mmol) and benzophenone (91 m
g, 5.0 mmol) was dissolved in 7 ml of 2-propanol, degassed, replaced with argon, and then transferred to a 100 ml glass autoclave. Hydrogen at a specified pressure (3
(Atmospheric pressure). After stirring the reaction solution for 30 minutes, the reaction pressure was returned to normal pressure, and the TLC monitor of the reaction solution (silica gel: n-hexane / ethyl acetate = 4 /
1) The product, benzhydrol, was identified and quantified by high performance liquid chromatography and NMR.
All of the reaction substrates were consumed and the product yield was over 99%. Example 2 RuCl ₂ [P (C ₆ H ₅ ) ₃ ] ₃ (9.6 mg, 0.01 m
mol), KOH (0.02 mmol), ethylenediamine (0.01 mmol) and 2-chlorobenzophenone (1.083 g, 5.0 mmol) were dissolved in 7 ml of 2-propanol, degassed, and purged with argon.
The entire amount was transferred to a 0 ml glass autoclave. Hydrogen was charged to a predetermined pressure (3 atm) to start the reaction. After stirring the reaction solution for 30 minutes, the reaction pressure was returned to normal pressure, and the TLC monitor of the reaction solution (silica gel: n-hexane / ethyl acetate = 4/1), high performance liquid chromatography and NM
The product, 2-chlorobenzhydrol, was identified and quantified by R. All of the reaction substrate was consumed and the product yield was 95%. Example 3 RuCl ₂ [P (C ₆ H ₅ ) ₃ ] ₃ (9.6 mg, 0.01 m
mol), KOH (0.02 mmol), ethylenediamine (0.01 mmol) and 3-chlorobenzophenone (1.083 g, 5.0 mmol) were dissolved in 7 ml of 2-propanol, degassed, and purged with argon.
The entire amount was transferred to a 0 ml glass autoclave. Hydrogen was charged to a predetermined pressure (3 atm) to start the reaction. After stirring the reaction solution for 30 minutes, the reaction pressure was returned to normal pressure, and the TLC monitor of the reaction solution (silica gel: n-hexane / ethyl acetate = 4/1), high performance liquid chromatography and NM
The product, 3-chlorobenzhydrol, was identified and quantified by R. All of the reaction substrates were consumed and the product yield was 98%. Example 4 RuCl ₂ [P (C ₆ H ₅ ) ₃ ] ₃ (9.6 mg, 0.01 m
mol), KOH (0.02 mmol), ethylenediamine (0.01 mmol) and 4-chlorobenzophenone (1.083 g, 5.0 mmol) were dissolved in 7 ml of 2-propanol, degassed, and purged with argon.
The entire amount was transferred to a 0 ml glass autoclave. Hydrogen was charged to a predetermined pressure (3 atm) to start the reaction. After stirring the reaction solution for 30 minutes, the reaction pressure was returned to normal pressure, and the TLC monitor of the reaction solution (silica gel: n-hexane / ethyl acetate = 4/1), high performance liquid chromatography and NM
The product, 4-chlorobenzhydrol, was identified and quantified by R. All of the reaction substrates were consumed and the product yield was 98%. Example 5 RuCl ₂ [P (C ₆ H ₅ ) ₃ ] ₃ (9.6 mg, 0.01 m
mol), KOH (0.02 mmol), ethylenediamine (0.01 mmol) and 2,4'-dichlorobenzophenone (1.255 g, 5.0 mmol) were dissolved in 7 ml of 2-propanol, degassed, and purged with argon. Thereafter, the whole amount was transferred to a 100 ml glass autoclave. Hydrogen was charged to a predetermined pressure (3 atm) to start the reaction. After the reaction solution was stirred for 30 minutes, the reaction pressure was returned to normal pressure, and the reaction product was subjected to TLC monitoring (silica gel: n-hexane / ethyl acetate = 4/1), high performance liquid chromatography, and NMR to indicate the product 2,4. '-Dichlorobenzhydrol was identified and quantified. All of the reaction substrate was consumed and the product yield was 96%. Example 6 RuCl ₂ [P (C ₆ H ₅ ) ₃ ] ₃ (9.6 mg, 0.01 m
mol), KOH (0.02 mmol), ethylenediamine (0.01 mmol) and 4,4'-difluorobenzophenone (1.091 g, 5.0 mmol) in 7 ml.
Was dissolved in 2-propanol, degassed, and purged with argon, and then the whole amount was transferred to a 100 ml glass autoclave. Hydrogen was charged to a predetermined pressure (3 atm) to start the reaction. After stirring the reaction solution for 30 minutes, the reaction pressure was returned to normal pressure, and the reaction product was subjected to TLC monitoring (silica gel: n-hexane / ethyl acetate = 4/1), high performance liquid chromatography and NMR to indicate the product 4,4. '-Difluorobenzhydrol was identified and quantified. All of the reaction substrates were consumed and the product yield was 98%. Example 7 RuCl ₂ [P (C ₆ H ₅ ) ₃ ] ₃ (9.6 mg, 0.01 m
mol), KOH (0.02 mmol), ethylenediamine (0.01 mmol) and 4-phenylbenzophenone (1.29 g, 5.0 mmol) were dissolved in 12 ml of 2-propanol, degassed, and purged with argon.
The entire amount was transferred to a 00 ml glass autoclave. Hydrogen was charged to a predetermined pressure (3 atm) to start the reaction. After stirring the reaction solution for 30 minutes, the reaction pressure was returned to normal pressure, and the TLC monitor of the reaction solution (silica gel: n-hexane / ethyl acetate = 4/1), high performance liquid chromatography and N
The product, 4-phenylbenzhydrol, was identified and quantified by MR. All of the reaction substrates were consumed and the product yield was 98%.

[0031]

As explained in detail above, the novel catalyst system according to the invention of the present application enables the hydrogenation of carbonyl compounds with high yield and high efficiency and the production of alcohols thereby.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ Identification symbol FI C07C 33/46 C07C 33/46 35/02 35/02 // C07B 61/00 300 C07B 61/00 300 (72) Inventor Ikari Yao Takao 8-1 Sotani-cho, Chikusa-ku, Nagoya, Aichi Prefecture Chaya Kasaka Coaters 907 (72) Inventor Takeshi Okuma 1505 Totagaya, Nagakute-machi, Aichi-gun, Aichi Prefecture Habitation 3-B (72) Inventor Ryoji Noyori Nisshin-shi, Aichi Prefecture 135-417 Nitta, Umemori-cho

Claims (6)

[Claims] 1. A process for producing alcohols, comprising hydrogenating a carbonyl compound with hydrogen in a liquid reaction medium in the presence of a homogeneous hydrogenation catalyst, a base and a nitrogen-containing organic compound. 2. The process according to claim 1, wherein the homogeneous hydrogenation catalyst comprises a transition metal complex of a Group VIII metal which is solubilized in a liquid reaction medium under the reaction conditions. 3. The method according to claim 2, which is a transition metal complex having a phosphine ligand of rhodium, ruthenium, iridium or platinum metal. 4. The method according to claim 1, wherein the base is a hydroxide or salt of an alkali metal or alkaline earth metal, or a quaternary ammonium salt. 5. The method according to claim 1, wherein the nitrogen-containing organic compound is an amine compound or an amine derivative. 6. A carbonyl compound represented by the general formula: (R ¹ and R ^{2 each} represent an unsubstituted or optionally substituted aromatic monocyclic or aromatic polycyclic group. Further, R ¹ and R ² are combined to form a ring. The method according to claim 1, wherein: