JP2000119228A - Method for producing optically active benzylamines - Google Patents

Abstract

(57) [Problem] To provide a method for producing optically active benzylamines. SOLUTION: After reacting a complex of a group VIII transition metal with an optically active phosphine compound to prepare a catalyst, the compound represented by the general formula (1) (Wherein R _{1 and} R ₂ are hydrogen, halogen, alkyl, aralkyl, aryl, alkenyl, alkoxyl, etc.) and immediately react with hydrogen by charging with imines A method for producing an optically active benzylamine represented by the formula:

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to optically active benzylamines (2) useful as synthetic intermediates of pharmaceutical and agricultural chemicals or synthetic intermediates of many general-purpose chemicals, or useful as optical resolving agents for carboxylic acids. It relates to an advantageous method for producing optically active amines (3).

[0002]

2. Description of the Related Art Conventionally, the following two methods have been generally used to obtain optically active amines as synthetic intermediates. A method for obtaining optically active amines from the corresponding racemic amines by optical resolution using an optically active carboxylic acid. A method of deriving from naturally occurring optically active amines.
More recently, many catalytic asymmetric syntheses have been studied, for example, ASYMMETRIC CATALYSIS IN ORGANIC SYNTHESIS By
R. Noyori, (A Wiley-Interscience Publication, John
Wiley & Sons, Inc).

[0003]

However, the above-mentioned conventional method has a limited range of application and is not always sufficient for industrially obtaining a large amount depending on the required optically active amines. In addition, the asymmetric synthesis method using a complex catalyst which has been recently developed has not always been practically satisfactory in yield and enantiomeric excess of the product. Therefore, development of a more excellent asymmetric synthesis of optically active amines by a hydrogenation reaction has been desired.

[0004]

The inventors of the present invention have conducted intensive studies to develop a new route of using a relatively versatile imine as a raw material and subjecting it to an asymmetric hydrogenation reaction. Invented the invention.

That is, in the present invention, after preparing a catalyst by reacting a complex of a group VIII transition metal with an optically active phosphine compound, the compound represented by the general formula (1) (Wherein, R ₁ and R ₂ represent a hydrogen atom, a halogen atom, an alkyl group which may have a substituent, an aralkyl group which may have a substituent, and an aryl which may have a substituent. Group, an alkenyl group which may have a substituent, an alkoxyl group which may have a substituent, an aryloxy group or an alkyloxycarbonyl group, respectively, or a cyclic compound in which R ₁ and R ₂ are bonded. Wherein R ₃ represents a phenyl group which may have a substituent.), And immediately reacting with hydrogen with an imine represented by the general formula (2): (Wherein, R ₁ , R ₂ and R ₃ have the same meanings as described above).
And the optically active benzylamines obtained above,
General formula (3) characterized in that the R ₃ CH ₂ -group is removed by a hydrogenation reaction in the presence of a transition metal catalyst. (In the formula, R ₁ and R ₂ represent the same meaning as described above.)
And a process for producing an optically active amine represented by the formula:

[0006]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The general formula (1) used in the present invention
In the substituents R ₁ and R ₂ of the imines represented by, a halogen atom is a fluorine atom, a chlorine atom, a bromine atom, an iodine atom or the like, and an alkyl group is, for example, a methyl group, an ethyl group, an n-propyl group, Isopropyl group, n-
Butyl group, isobutyl group, t-butyl group, n-amyl group, neopentyl group, n-hexyl group, cyclohexyl group, n-octyl group, n-nonyl group, menthyl group, 2,
3,4-trimethyl-3-pentyl group, 2,4-dimethyl-3-pentyl group and the like, and aralkyl groups such as benzyl group, 2-phenylethyl group, 2-naphthylethyl group and diphenylmethyl group are aryl. Examples of the group include a phenyl group, a naphthyl group, a biphenyl group, a furyl group, and a thiophenyl group, and examples of the alkenyl group include 2-methyl-
A 1-propenyl group, a 2-butenyl group, a trans-β-styryl group, a 3-phenyl-1-propenyl group, a 1-cyclohexenyl group, and the like, and the alkoxyl group is a methoxy group, an ethoxy group, an n-propoxy group, -Butoxy group and the like, and the aryloxy group is a phenoxy group and the like,
Examples of the alkyloxycarbonyl group include a methoxycarbonyl group, an ethoxycarbonyl group, a t-butyloxycarbonyl group, a benzyloxycarbonyl group, and a phenyloxycarbonyl group. As a substituent when these groups are further substituted with a substituent,
The same halogen atom as described above, the same alkoxyl group as described above, the same aryloxy group as described above, a methyl group, an ethyl group, an isopropyl group, an n-butyl group, a t-butyl group, a n-amyl group, n Lower alkyl groups such as -hexyl group; lower alkylthio groups such as n-propylthio group and t-butylthio group; arylthio groups such as phenylthio group; nitro groups; and hydroxyl groups.

In the imines (1), the phenyl group which may have a substituent of R ₃ includes a phenyl group, a p-fluorophenyl group, a p-chlorophenyl group, an m-bromophenyl group and a p-methylphenyl group. And the like.

The imines (1) can be easily produced from ketones. Specific examples of the imines (1) in the present invention include, for example, acetophenone, propiophenone, benzaldehyde, benzalacetone, 3-methylcyclohexanone, 3-chlorobenzophenone, methyl isobutyl ketone, cyclohexyl methyl ketone, and 2-naphthophenone , 1-indanone, etc., and a benzylamine which may have a substituent by dehydration-condensation in a usual manner (for example, by heating and refluxing in a solvent such as toluene in the presence of an acid catalyst) to synthesize. Imines can be mentioned.

As the optically active phosphine compound used in this reaction, a known phosphine compound used for asymmetric synthesis using a transition metal can be used. Specifically, for example, (R) -2,2'-bis (dicyclohexylphosphino) -6,
6'-dimethyl-1,1'-biphenyl, (R) -2,2'-bis (diphenylphosphino) -1,1'-binaphthyl, (S, S) -2,3-bis (diphenylphosphino ) Butane, (R) -1-cyclohexyl-1,
2-bis (diphenylphosphino) ethane, (R, R) -2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis (diphenylphosphino) butane, (R, R) -1 , 2-Bis [(o-methoxyphenyl) -phenylphosphino] ethane, (R, R) -5,6-bis
(Diphenylphosphino) -2-norbornene, and the like.

The amount of the above-mentioned optically active phosphine compound varies depending on the reaction conditions and economical efficiency, but is usually 1 mol based on the molar ratio of the complex of the Group VIII transition metal coexisting in the reaction system.
/ 10 to 50 times the amount, preferably 9
/ 10 to 5 times the amount.

The complex of the Group VIII transition metal is, for example, a compound represented by the following general formula (4) (Wherein, M ¹ represents a Group VIII transition metal such as rhodium, ruthenium, iridium, platinum, X represents a hydrogen atom, a halogen atom, a carboxyl group, an alkoxy group or a hydroxy group, and L represents an organic ligand. And m and n each represent an integer of 0 to 6). In the above, the organic ligand (L) is
Olefin ligands, including CO, NO, NH ₂ , NH _3, etc.
Examples include acetylene ligands, aromatic compound ligands, organic oxygen-containing compound ligands, organic sulfur-containing compound ligands, and organic nitrogen-containing compound ligands.

The olefin ligands include, for example, ethylene, allyl, butadiene, cyclohexene,
Examples thereof include 1,3-cyclohexadiene, 1,5-cyclooctadiene, cyclooctatriene, norbornadiene, acrylate, methacrylate, cyclopentadienyl, and pentamethylcyclopentadienyl. Also commonly used as a ligand 5
The five-membered ring compound also includes a five-membered ring compound represented by the following general formula (5). (Wherein, Ra to Re are the same or different and each have a hydrogen atom, a halogen atom, an alkyl group which may have a substituent, an aralkyl group which may have a substituent, An aryl group which may be substituted, an alkenyl group which may have a substituent, an alkoxyl group which may have a substituent, or an alkyloxycarbonyl group. Atom, bromine atom, iodine atom, etc., as the alkyl group, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, t-butyl group, n-
Amyl group, neopentyl group, n-hexyl group, cyclohexyl group, n-octyl group, n-nonyl group, menthyl group,
2,3,4-trimethyl-3-pentyl group, 2,4-dimethyl-3-pentyl group and the like, and aralkyl groups such as benzyl group, 2-phenylethyl group, 2-naphthylethyl group and diphenylmethyl group. An aryl group includes a phenyl group, a naphthyl group, a biphenyl group, a furyl group, and a thiophenyl group; and an alkenyl group includes a 2-methyl-1-propenyl group, a 2-butenyl group, and a trans-β.
-Styryl group, 3-phenyl-1-propenyl group, 1-
Cyclohexenyl group and the like, alkoxyl group as methoxy group, ethoxy group, n-propoxy group, t-butoxy group and the like, aryloxy group as phenoxy group and the like, and alkyloxycarbonyl group as methoxycarbonyl group and ethoxycarbonyl. Group, t-butyloxycarbonyl group, benzyloxycarbonyl group, phenyloxycarbonyl group and the like. When these groups are further substituted with a substituent, examples of the substituent include the same halogen atom as described above, the same alkoxyl group as described above, the same aryloxy group as described above,
Methyl group, ethyl group, isopropyl group, n-butyl group, t
Lower alkyl groups such as -butyl group, n-amyl group and n-hexyl group, lower alkylthio groups such as n-propylthio group and t-butylthio group, arylthio groups such as phenylthio group, nitro group, hydroxyl group and the like. . The number of substituents is any number from 1 to 5, and the substitution position can be selected at any position.

Examples of the acetylene ligand include acetylene, 1,2-dimethylacetylene, 1,4-pentadiyne, and 1,2-diphenylacetylene.

As the aromatic compound ligand, benzene,
Examples thereof include p-cymene, mesitylene, hexamethylbenzene, naphthalene, and anthracene. Examples of the aromatic compound often used as a ligand include a cyclic aromatic compound represented by the following general formula (6). Can be (Wherein, Ra ′ to Rf ′ are the same or different, and are a hydrogen atom,
Represents a saturated or unsaturated hydrocarbon group, an allyl group, a functional group containing a heteroatom, for example, methyl, ethyl, propyl, isopropyl, butyl, t-butyl, pentyl, hexyl,
Alkyl groups such as heptyl, cycloalkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, groups such as benzyl, vinyl, allyl, phenyl and unsaturated hydrocarbons such as naphthyl, hydroxyl groups, alkoxy groups, alkoxycarbonyl groups and the like Functional groups containing heteroatoms can be indicated. The number of substituents is an arbitrary number of 1 to 6, and the substitution position is arbitrary. )

Examples of the organic oxygen compound ligand include, for example, acetate, benzoate, acetylacetonate and the like. As the organic sulfur-containing compound ligand,
For example, dimethyl sulfoxide, dimethyl sulfide,
Examples thereof include thiophene, carbon disulfide, carbon sulfide, and thiophenol. As the organic nitrogen-containing compound ligand, for example, acetonitrile, benzonitrile, t-butyl isocyanide, pyridine, 1,10-phenanthroline,
2,2′-bipyridyl and the like are exemplified.

The complex of the Group VIII transition metal in the present invention includes, for example, chlorotris (triphenylphosphine) rhodium (I), cyclopentadienylbis (triphenylphosphine) rhodium (I), bis (cyclooctadiene) Diiododirhodium (I), chloro (cyclopentadienyl) bis (triphenylphosphine) ruthenium (II), chloro (pentamethylcyclopentadienyl) (1,3-bis (diphenylphosphino) propane) ruthenium (II) ), Chloro (pentamethylcyclopentadienyl) (1,5-cyclooctadiene)
Ruthenium (II), dichlorotris (triphenylphosphine) ruthenium (II), chlorotris (triphenylphosphine) iridium (I), pentamethylcyclopentadienylbis (ethylene) iridium (I), (ethylene) bis (triphenyl) Phosphine)
Platinum (0), trans- [chloro (ethyl) bis (triethylphosphine) platinum (II)], cis- [diethylbis (triethylphosphine) platinum (II)], dichloro (norbornadiene) platinum (II), tetrakis (triphenyl) Examples thereof include phosphine) platinum (0), and among them, a ruthenium complex has particularly high activity. Of course, the complex used in the present invention is not limited to these.

The amount of the complex of the above-mentioned group VIII transition metal varies depending on the reaction conditions and economical efficiency, but is usually from 1/100 to 1 / molar as the molar ratio to the imine (1) as the reaction substrate.
About 100,000 can be used, preferably 1 /
It is in the range of about 200 to 1 / 10,000.

In the present reaction, it is desirable to add an additive which is usually used in the hydrogenation reduction reaction of the imines (1) in order to improve the yield and the selectivity (optical purity of the product). Specific examples of such an additive include amine compounds such as benzylamine, normal butylamine and triethylamine; iodides such as tetranormal butylammonium iodide, bismuth triiodide and potassium iodide; and imide compounds such as phthalimide. Is exemplified. The amount of these additives used depends on VI
It is used in an amount of about 0.1 to 20 mol, preferably about 1 to 5 mol, per 1 mol equivalent of the complex of the group II transition metal.

In the present invention, a solvent is usually used.
As such a solvent, those that solubilize the reaction raw materials and the catalyst system are preferably used. Specific examples include, for example, aromatic solvents such as toluene and xylene, aliphatic solvents such as pentane and hexane, halogen-containing hydrocarbon solvents such as methylene chloride, ethers, ether solvents such as tetrahydrofuran, methanol, ethanol, and 2-propanol. Alcohol solvents such as butanol and benzyl alcohol, and organic solvents containing heteroatoms such as acetonitrile, DMF, N-methylpyrrolidone, pyridine and DMSO can be used. These solvents can be used alone,
It can also be used as a mixed solvent. The amount of the solvent to be used can be appropriately determined depending on the solubility of the reaction substrate and economic efficiency.

It is preferable that the transition metal catalyst used in the present invention is sufficiently reacted before being mixed with the starting imines (1). That is, for example, a complex of a Group VIII transition metal and an optically active phosphine compound are dissolved in a solvent and stirred for 30 minutes to 20 hours, preferably for 45 minutes to 6 hours, and then, if necessary, an additive is added and further stirred for about 10 minutes. To prepare a catalyst complex. On the other hand, the imines (1) as a raw material are prepared in another container, for example, as a solution.
These two solutions are mixed, immediately transferred to an autoclave, and pressurized with hydrogen gas to carry out a hydrogenation reaction (here, immediately means as quickly as possible).

In the present invention, the pressure of hydrogen is usually from 1 to
A range of about 200 atm, preferably a range of about 3 to 100 atm is desirable.

The reaction can be carried out usually at a temperature in the range of about -40 to 120 ° C.
The reaction can be carried out at a temperature of about 25 to 50 ° C.

The reaction time varies depending on the reaction conditions such as the concentration of the reaction substrate, the temperature and the pressure, but the reaction is usually completed in about 1 hour to 100 hours.

The reaction in the present invention can be carried out either in a batch mode or a continuous mode.

As the optically active benzylamines (2) thus obtained, specifically, for example, N-benzyl-
Phenethylamine, N-parabromobenzyl-phenethylamine, N-parachlorobenzyl-2,4-dichlorophenethylamine, N-paramethylbenzyl-2,4-dichlorophenethylamine, N-metachlorobenzyl-1-cyclohexylethylamine, N -Orthobromobenzyl-1-cyclohexylethylamine, and the like.

In the present invention, as the transition metal catalyst used for removing the R ₃ CH ₂ — group of the benzylamine represented by the general formula (2), rhodium, platinum, palladium, iridium, osmium and the like are used. These metal catalysts may be heterogeneous catalysts supported on activated carbon, silica gel, pumice or the like, or may be homogeneous catalyst complexes soluble in solvents. Specifically, PtO ₂ , Pd-C, Pd-A
l ₂ O ₃ , Rh-Pd-C, Raney Ni, Pt-C, RhCl [PPh ₃ ] ₃ , and the like.

The amount of the transition metal catalyst to be used varies depending on the reaction conditions and economy, but it can be usually used in a molar ratio of about 0.1 to 10 ^-4 times, preferably about 10 to ⁴ times, with respect to the amine compound (2) as a reaction substrate. , 0.05 to 10 ^-2 times. In this reaction, a solvent is usually used. As such a solvent, a solvent that does not hinder the hydrogenation reaction is used. Specific examples include aromatic solvents such as toluene and xylene, pentane, aliphatic solvents such as hexane, ethers, ether solvents such as tetrahydrofuran, methanol, ethanol, 2-propanol,
Alcohol solvents such as butanol and benzyl alcohol, and these solvents can be used alone or as a mixed solvent. The amount of the solvent to be used can be appropriately determined depending on the solubility of the reaction substrate and economic efficiency.

In the present invention, the pressure of hydrogen is usually from 1 to
A range of about 200 atm, preferably a range of about 3 to 100 atm is desirable.

The reaction can be carried out usually at a temperature in the range of about -100 to 250 ° C.
Carried out at ~ 150 ° C. The reaction time varies depending on the reaction conditions such as the concentration of the reaction substrate, the temperature, the pressure, and the like, and can be usually terminated when the raw material amine compound (2) has disappeared. Further, the reaction in the present invention can be carried out in either a batch system or a continuous system.

Examples of the optically active amines (3) thus obtained include, for example, phenethylamine, parabromophenethylamine, 2,4-dichlorophenethylamine, 2,4-dibromophenethylamine, 1-cyclohexylethylamine and the like. No.

[0031]

According to the present invention, benzylamines can be obtained with excellent yield and excellent optical purity. Such optically active benzylamines (2) and optically active amines (3) can be used as optical resolving agents for carboxylic acids, and are also versatile as intermediates for the synthesis of optically active pharmaceutical and agricultural chemicals.

[0032]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

Example 1 6.0 mg (0.009 mmo) of [IrCl (cod)] ₂ complex was placed in a Schlenk tube (20 ml).
l) and (+)-DIOP [(4S, 5S)-(+)-4,5-bis (diphenylphosphinomethyl) -2,2-dimethyl-1,3-dioxolane] 10.8mg
(0.022 mmol), and further 1.25 ml of toluene and 1.25 m
l of methanol was added. This solution was purged with argon, and then stirred for 15 hours to prepare a catalyst complex solution. On the other hand, N
100 mg (0.36 mmol) of-[1- (2,4-dichlorophenyl) ethylidene] benzylamine was charged into another Schlenk tube (20 ml), and 1.25 ml of toluene and 1.25 ml of methanol were added thereto. This solution was degassed and replaced with argon. Thereafter, the imine solution was transferred to an autoclave whose inside was replaced with argon simultaneously with the catalyst complex solution prepared above. After sufficiently replacing the inside of the autoclave with hydrogen, hydrogen was pressurized to 50 atm. The mixture was stirred at 30 ° C. for 23 hours to cause a hydrogenation reaction.
After completion of the reaction, the reaction mixture was concentrated, the solvent was distilled off, dissolved in ether (20 ml), passed through a silica gel column to remove the complex catalyst, etc., and concentrated again. Chlorphenyl) ethyl] benzylamine 95.9 mg (0.34 mmol, yield 95
%, 29% ee).

Reference Example 1 6.0 mg (0.009 mmo) of [IrCl (cod)] ₂ complex was placed in a Schlenk tube (20 ml).
l) and (+)-DIOP [(4S, 5S)-(+)-4,5-bis (diphenylphosphinomethyl) -2,2-dimethyl-1,3-dioxolane] 10.8mg
(0.022 mmol), and further 1.25 ml of toluene and 1.25 m
l of methanol was added. This solution was purged with argon, and then stirred for 1 hour to prepare a catalyst complex solution. On the other hand, N-
[1- (2,4-dichlorophenyl) ethylidene] benzylamine
100 mg (0.36 mmol) was put into another Schlenk tube (20 ml),
To this was added 1.25 ml of toluene and 1.25 ml of methanol. This solution was degassed and replaced with argon. Thereafter, this imine solution was mixed with the catalyst complex solution prepared above in a Schlenk tube and stirred for 1 hour. Thereafter, the inside was transferred to an autoclave whose inside was replaced with argon. After sufficiently replacing the inside of the autoclave with hydrogen, hydrogen was pressurized to 50 atm. 3
The mixture was stirred at 0 ° C. for 23 hours to cause a hydrogenation reaction. After the reaction,
The reaction mixture was concentrated, the solvent was distilled off, dissolved in ether (20 ml), passed through a silica gel column to remove the complex catalyst, etc., concentrated again, and then the target N- [1- (2,4-dichlorophenyl) ethyl 39.3 mg (0.14 mmol, 39% yield, 33% ee) of benzylamine were obtained.

Reference Example 2 6.0 mg (0.009 mmo) of [IrCl (cod)] ₂ complex was placed in a Schlenk tube (20 ml).
l) and (+)-DIOP [(4S, 5S)-(+)-4,5-bis (diphenylphosphinomethyl) -2,2-dimethyl-1,3-dioxolane] 10.8mg
(0.022 mmol), and further 1.25 ml of toluene and 1.25 m
l of methanol was added. After the solution was replaced with argon, the solution was stirred for 15 minutes to prepare a catalyst complex solution. On the other hand, N
100 mg (0.36 mmol) of-[1- (2,4-dichlorophenyl) ethylidene] benzylamine was charged into another Schlenk tube (20 ml), and 1.25 ml of toluene and 1.25 ml of methanol were added thereto. This solution was degassed and replaced with argon. Thereafter, the imine solution was transferred to an autoclave whose inside was replaced with argon simultaneously with the catalyst complex solution prepared above. After sufficiently replacing the inside of the autoclave with hydrogen, hydrogen was pressurized to 50 atm. The mixture was stirred at 30 ° C. for 23 hours to cause a hydrogenation reaction.
After completion of the reaction, the reaction mixture was concentrated, the solvent was distilled off, dissolved in ether (20 ml), passed through a silica gel column to remove the complex catalyst, etc., concentrated again, and then concentrated to the desired N- [1- (2,4-diamine). Chlorphenyl) ethyl] benzylamine 78.7 mg (0.28 mmol, yield 78)
%, 17% ee).

Example 2 6.0 mg (0.009 mmo) of [IrCl (cod)] ₂ complex was placed in a Schlenk tube (20 ml).
l) and (+)-DIOP [(4S, 5S)-(+)-4,5-bis (diphenylphosphinomethyl) -2,2-dimethyl-1,3-dioxolane] 8.9 mg (0.
018 mmol), and 1.25 ml of toluene and 1.25 ml of methanol were further added. After purging this solution with argon,
The mixture was stirred for 10 hours to prepare a catalyst complex solution. 13.3 mg (0.036 mmol) of tetrabutylammonium iodide was added to this solution, and the mixture was stirred for 10 minutes. On the other hand, 100 mg (0.36 mmol) of N- [1- (2,4-dichlorophenyl) ethylidene] benzylamine was charged into another Schlenk tube (20 ml), and 1.25 ml of toluene and 1.25 ml of methanol were added thereto. Was. This solution was degassed and replaced with argon. Thereafter, the imine solution was transferred to an autoclave whose inside was replaced with argon simultaneously with the catalyst complex solution prepared above. After sufficiently replacing the inside of the autoclave with hydrogen, hydrogen was pressurized to 50 atm. The mixture was stirred at 30 ° C. for 71 hours to cause a hydrogenation reaction. After completion of the reaction, the reaction mixture was concentrated, the solvent was distilled off, dissolved in ether (20 ml), passed through a silica gel column to remove the complex catalyst, etc., and concentrated again.
94.0 mg (0.335 mmol, yield 93.2%, 53% ee) of the desired N- [1- (2,4-dichlorophenyl) ethyl] benzylamine was obtained.

Example 3 6.0 mg (0.009 mmol) of [IrCl (cod)] ₂ complex was placed in a Schlenk tube (20 ml).
l) and (+)-MOD-DIOP [(4R, 5R)-(+)-4,5-bis (bis (4'-methoxy-3 ', 5'-dimethylphenyl) phosphinomethyl) -2, 2-
[Dimethyl-1,3-dioxolane] 15.8 mg (0.022 mmol) was added, and 1.25 ml of toluene and 1.25 ml of methanol were further added. This solution was purged with argon, and then stirred for 7 hours to prepare a catalyst complex solution. 26.6 mg (0.072 mmol) of tetrabutylammonium iodide was added to this solution, and the mixture was stirred for 10 minutes. On the other hand, 100 mg (0.36 mmol) of N- [1- (2,4-dichlorophenyl) ethylidene] benzylamine was added to another Schlenk tube (20 m
l), and 1.25 ml of toluene and 1.25 ml of methanol were added thereto. This solution was degassed and replaced with argon. Thereafter, the imine solution was transferred to an autoclave whose inside was replaced with argon simultaneously with the catalyst complex solution prepared above. After sufficiently replacing the inside of the autoclave with hydrogen, hydrogen was pressurized to 50 atm. The mixture was stirred at 30 ° C. for 20 hours to cause a hydrogenation reaction. After completion of the reaction, the reaction mixture was concentrated, the solvent was distilled off, dissolved in ether (20 ml), passed through a silica gel column to remove the complex catalyst, etc., concentrated again, and then the target N- [1- (2,
4-Dichlorophenyl) ethyl] benzylamine 95.0 mg (0.3
39 mmol, yield 94.2%, 54% ee) were obtained.

Example 4 6.0 mg (0.009 mmo) of [IrCl (cod)] ₂ complex was placed in a Schlenk tube (20 ml).
l) and (+)-MOD-DIOP [(4R, 5R)-(+)-4,5-bis (bis (4'-methoxy-3 ', 5'-dimethylphenyl) phosphinomethyl) -2, 2-
[Dimethyl-1,3-dioxolane] 15.8 mg (0.022 mmol) was added, and 1.25 ml of toluene and 1.25 ml of methanol were further added. This solution was purged with argon, and then stirred for 15 hours to prepare a catalyst complex solution. On the other hand, 100 mg (0.36 mmol) of N- [1- (2,4-dichlorophenyl) ethylidene] benzylamine was charged into another Schlenk tube (20 ml), and 1.25 ml of toluene and 1.25 ml of methanol were added thereto. Was. This solution was degassed and replaced with argon. Thereafter, the imine solution was transferred to an autoclave whose inside was replaced with argon simultaneously with the catalyst complex solution prepared above. After sufficiently replacing the inside of the autoclave with hydrogen, hydrogen was pressurized to 50 atm. 23 at 30 ° C
The mixture was stirred for hydrogenation reaction for an hour. After completion of the reaction, the reaction mixture was concentrated, the solvent was distilled off, dissolved in ether (20 ml), passed through a silica gel column to remove the complex catalyst, etc., concentrated again, and then concentrated to the desired N- [1- (2,4-diamine). 96.8 mg (0.345 mmol, 96.0% yield, 41% ee) of chlorophenyl) ethyl] benzylamine were obtained.

Example 5 90.0 mg (0.321 mmol, 54% ee) of N- [1- (2,4-dichlorophenyl) ethyl] benzylamine obtained in Example 3 was dissolved in 3 ml of ethanol to form a solution. . This solution was put into an autoclave, 5 mg of 10% Pd-C was added, and a hydrogenation reaction was performed at 40 ° C. for 20 hours under a hydrogen gas atmosphere of 2 atm. After completion of the reaction, the reaction mixture was concentrated, the solvent was distilled off, and the residue was purified and isolated by silica gel column chromatography and concentrated again.After that, the target 2,4-dichlorophenethylamine (59.1 mg, 0.311 mmol, 97.0% yield, 57.0 mg) was obtained.
4% ee).

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C07C 217/14 C07C 217/14 227/04 227/04 229/36 229/36 // C07B 61/00 300 C07B 61/00 300 F term (reference) 4G069 AA08 AA15 BA27A BA27B BC70A BC71A BC74A BC75A BD11A BD11B BE05A BE05B BE08A BE08B BE26A BE26B CB57 4H006 AA02 AC52 AC81 BA22 BA23 BA24 BA25 BA26 BA32 BA37 BA20 BA45 BP30 BT12 BU30 BU38 4H039 CA71 CB30 CF40

Claims (3)

[Claims] 1. After preparing a catalyst by reacting a complex of a Group VIII transition metal with an optically active phosphine compound, a compound represented by the general formula (1): (Wherein, R ₁ and R ₂ represent a hydrogen atom, a halogen atom, an alkyl group which may have a substituent, an aralkyl group which may have a substituent, and an aryl which may have a substituent. Group, an alkenyl group which may have a substituent, an alkoxyl group which may have a substituent, an aryloxy group or an alkyloxycarbonyl group, respectively, or a cyclic compound in which R ₁ and R ₂ are bonded. general formula good .R ₃ also form which comprises reacting immediately hydrogen were charged and imines represented by.) showing a phenyl group which may have a substituent (2) (Wherein, R ₁ , R ₂ and R ₃ have the same meanings as described above). 2. The method according to claim 1, wherein the optically active benzylamine is hydrogenated in the presence of a transition metal catalyst to give R ₃ CH _2-.
General formula (3) characterized by removing the group (In the formula, R ₁ and R ₂ represent the same meaning as described above.)
A method for producing an optically active amine represented by the formula: 3. A complex of a Group VIII transition metal represented by the general formula (4): (Wherein M ¹ represents a Group VIII transition metal of iridium, rhodium, ruthenium or platinum, X represents a hydrogen atom, a halogen atom, a carboxyl group, an alkoxy group or a hydroxy group, and L represents an organic ligand. , M and n each represent an integer of 0 to 6.) The method according to claim 1, which is a complex of a Group VIII transition metal represented by the formula: