JPH1072410A - Racemization of optically active amine using catalytic reduction catalyst - Google Patents

Abstract

PROBLEM TO BE SOLVED: To efficiently racemize an optically active amine by treating a specific amine compound with a catalytic reduction catalyst. SOLUTION: (A) An optically active amine of the formula [R<1> is a (substituted) aryl or a (substituted) heterocyclic group; R<2> is a (substituted) 1-8C alkyl, a (substituted) 1-8C alkoxy or a (substituted) aryl or a (substituted) heterocyclic group; R<3> and R<4> are each H or a (substituted) 1-4C alkyl; A is a 1-10C alkylene; * is the position of an asymmetric carbon atom] (e. g. optically active 3-methyl-2-phenylbutylamine) is treated with (B) a catalytic reduction catalyst. Preferably, the reaction is carried out in the absence of hydrogen and in the presence of ammonia and a Raney catalyst such as a Raney nickel catalyst or a Raney cobalt catalyst.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for racemizing an optically active amine represented by the following formula (1), comprising reacting the optically active amine with a catalytic reduction catalyst. More specifically, the present invention relates to a method for the racemization of the optically active amine, which comprises reacting a catalytic reduction catalyst in the presence of ammonia and / or in the absence of hydrogen.

[0002]

2. Description of the Related Art The following equation (1):

Embedded image Wherein R ¹ is an unsubstituted aryl group; an aryl group substituted with 1 to 5 C _{1 to} C ₄ alkyl groups, C _{1 to} C ₄ alkoxy groups and / or halogen atoms; or unsubstituted or substituted R ² represents a C ₁ -C ₈ alkyl group; a C ₁ -C ₈ alkyl group substituted with 1 to 3 aryl groups; a C ₁ -C ₈ alkoxy group; unsubstituted aryl group not identical to, or R ^_1;; C ^{1 ~C} ₈ alkoxy group substituted with an aryl group 1-5 C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy and / or halogen An aryl group substituted with an atom; or an unsubstituted or substituted heterocyclic group, wherein R ³ and R ⁴ may be the same or different and include a hydrogen atom, a C ₁ -C ₄ alkyl group,
Represents a C ₁ -C ₄ alkyl group or a C ₁ -C ₄ alkyl-CO— group substituted with one aryl group, A represents a C ₁ -C ₁₀ alkylene group, and * represents the position of an asymmetric carbon atom. Are useful as an optical resolving agent or an asymmetric auxiliary group, as a metal ligand in an asymmetric reaction, or as a pharmaceutical intermediate.

In particular, R ¹ is phenyl, R ² is isopropyl, R ³ and R ⁴ are both hydrogen atoms,
Is an optically active amine represented by the formula (1), wherein
That is, optically active 3-methyl-2-phenylbutylamine (PBA) is a compound useful as an optical resolving agent. This compound can be used to prepare racemic ibubrofen [2- (4-isobutylphenyl) -propionic acid] or ketoprofen [2
-(3-benzoylphenyl) -propionic acid] and the like,
It has been used as an optical resolving agent for obtaining only one optically active isomer useful as an antiphlogistic analgesic, antipyretic or antirheumatic agent (JP-A-5-229886 and JP-A-8-151344).

At present, optically active PBA can be obtained by resolving racemic PBA with an optically active acid such as mandelic acid (Japanese Patent Application Laid-Open No. Sho 61-172853), or
Can be obtained by selectively hydrolyzing the amide with an enzyme (Application No. 7-215722).
Further, a method utilizing a reaction of enzymatically hydrating nitrile with an enzyme has been developed (JP-A-7-3034).
96).

Generally, when an optically active compound having one configuration is desired, and the optically active compound is obtained by optical resolution of a racemate, the desired optically active compound is obtained in a yield of at most 50%. And only 50% of the undesired optically active compound remains. Therefore, when an optically active compound is obtained by an optical resolution method, the configuration of the undesired optically active compound is inverted and / or
Alternatively, development of a racemization method is important for increasing the yield of a desired optically active compound.

As a method of racemizing an amine compound in which the carbon at the α-position of the amino group is an asymmetric carbon, a method of heating with a catalytic reduction catalyst such as Raney nickel or Raney cobalt under hydrogen pressure (Japanese Patent Application Laid-Open No. Sho 63-63) 185943), a method utilizing an imine produced by a reaction with a carbonyl compound (JP-A-63-23824, JP-A-7-1881).
20), a method using sodium hydride or sodium amide [DE-OS (German Published Specification) 2,348,80
1], a method using a carrier such as alumina or sodium activated by a polycyclic aromatic substance (JP-A-50-5032).
8, JP-A-50-50344, JP-A-50-4923
5) are being developed. However, to date, there is no known method for efficiently racemizing an amine compound (for example, PBA) in which the carbon at the β-position and beyond of the amino group is an asymmetric carbon.

[0007]

In view of these facts, the present inventors have found that industrially practicable amine compounds in which the carbon at the β-position of the amino group and beyond are asymmetric carbons (for example, PBA) Tried to develop a method to racemize efficiently.

[0008]

SUMMARY OF THE INVENTION Surprisingly, surprisingly, the amine compound having an asymmetric carbon at the β-position and beyond of the amino group is reacted with a catalytic reduction catalyst to reduce the efficiency of the amine compound. Have been found to be able to racemically. Furthermore, they have found that when a catalytic reduction catalyst is allowed to act in the presence of ammonia and / or in the absence of hydrogen, racemization proceeds more efficiently.

That is, the present invention provides the following formula (1):

Embedded image Wherein R ¹ is an unsubstituted aryl group; an aryl group substituted with 1 to 5 C _{1 to} C ₄ alkyl groups, C _{1 to} C ₄ alkoxy groups and / or halogen atoms; or unsubstituted or substituted R ² represents a C ₁ -C ₈ alkyl group; a C ₁ -C ₈ alkyl group substituted with 1 to 3 aryl groups; a C ₁ -C ₈ alkoxy group; unsubstituted aryl group not identical to, or R ^_1;; C ^{1 ~C} ₈ alkoxy group substituted with an aryl group 1-5 C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy and / or halogen An aryl group substituted with an atom; or an unsubstituted or substituted heterocyclic group, wherein R ³ and R ⁴ may be the same or different and include a hydrogen atom, a C ₁ -C ₄ alkyl group,
Represents a C ₁ -C ₄ alkyl group or a C ₁ -C ₄ alkyl-CO— group substituted with one aryl group, A represents a C ₁ -C ₁₀ alkylene group, and * represents the position of an asymmetric carbon atom. The racemization method of an optically active amine represented by
It is intended to provide a racemization method characterized by causing a catalytic reduction catalyst to act on the amine. The process is preferably carried out in the presence of ammonia and / or in the absence of hydrogen.

When the racemization of an optically active compound is carried out with a base, a hydrogen abstraction reaction on an asymmetric carbon is essential. Therefore, the more asymmetric carbon to which the more acidic hydrogen is bonded, the more easily racemization occurs at that position. The acidity of the hydrogen bonded to the carbon at the β-position and beyond of the amino group is lower than the acidity of the hydrogen bonded to the carbon at the α-position of the amino group due to reduced induction effects. Therefore, a method capable of efficiently racemizing an amine compound having an asymmetric carbon at the α-position of an amino group,
It cannot be predicted that the same can be applied to amine compounds having an asymmetric carbon at the β-position or beyond.

As described above, several methods for racemizing an amine compound having an asymmetric carbon at the α-position of an amino group are known. These methods include a method of heating with a catalytic reduction catalyst such as Raney nickel or Raney cobalt under hydrogen pressure (JP-A-63-185943). However, this method has not been applied to amine compounds having an asymmetric carbon at the β-position or beyond, and when this method is applied to such an amine compound, other sodium hydride or sodium amide may be used. A decrease in efficiency was expected as in the method used. The present inventors, under such circumstances, the method using a catalytic reduction catalyst is superior to other methods,
It has been found that amine compounds having an asymmetric carbon at the β-position of the amino group or beyond can be efficiently racemized.
Furthermore, it has been found that when a catalytic reduction catalyst is used in the presence of ammonia and / or in the absence of hydrogen, the decomposition of an amine compound accompanying the racemization reaction is suppressed or the efficiency is improved, and the present invention has been completed. I came to.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION The optically active amine compound to which the method of the present invention can be applied is an amine compound represented by the above formula (1) having an asymmetric carbon at the β-position of an amino group or beyond. is there. In the present specification, the aryl group is
A monovalent aromatic hydrocarbon group, for example, phenyl,
And biphenylyl or naphthyl groups.

The term "C ₁ -C ₄ alkyl group" and "C ₁ -C ₈ alkyl group" mean a linear or branched alkyl group having 1 to 4 and 1 to 8 carbon atoms, respectively. Thus, the C ₁ -C ₄ alkyl group, e.g., methyl, ethyl, n- propyl, isopropyl, include such n- butyl or t- butyl group, a C ₁ -C ₈ alkyl group, C ₁ ~ C ₄
In addition to the alkyl group, for example, an n-pentyl, neopentyl, n-hexyl or n-octyl group is included.

A C ₁ -C ₄ alkoxy group and a C ₁ -C ₈ alkoxy group are alkoxy groups each consisting of a linear or branched alkyl group having 1 to 4 and 1 to 8 carbon atoms, respectively. Means a group. Therefore, C _1-
C ₄ alkoxy groups include, for example, methoxy, ethoxy, n
-Propoxy, isopropoxy, n-butoxy or t-butoxy groups and the like, and C ₁ -C ₈ alkoxy groups include
In addition to the ₁ -C ₄ alkoxy group, for example, n- pentyloxy, neo-pentyloxy, and the like n- hexyloxy or n- octyloxy group.

The halogen atom means fluorine, chlorine, bromine or iodine.

1-5 C ₁ -C ₄ alkyl groups, C ₁ -C ₄
The aryl group substituted with an alkoxy group and / or a halogen atom is the above-mentioned definition substituted with 1 to 5 C ₁ -C ₄ alkyl groups and C ₁ -C ₄ alkoxy groups and / or halogen atoms. Means an aryl group. If there are a plurality of substituents, they may be selected from the same or different groups or halogen atoms. Examples of such substituted aryl groups include, for example, p-, m- or o-fluoro, chloro, bromo, methoxy, ethoxy, butoxy, methyl, ethyl, propyl, butyl, isobutylphenyl, or mesityl Group, pentafluorophenyl group and the like.

C ₁ -substituted by one to three aryl groups
C ₄ alkyl group and C ₁ -C ₈ alkyl group are 1 to 3
C _{1 as} defined above, substituted with an aryl group as defined above.
It refers to -C ₄ alkyl groups and C ₁ -C ₈ alkyl group. Such aryl-substituted alkyl groups include, for example, 1- or 2-phenylethyl, 2,2-diphenylethyl, 1,1,1-triphenylethyl groups, and the like.

C ₁ -substituted with ₁ to 3 aryl groups
A C ₄ alkoxy group and a C ₁ -C ₈ alkoxy group are
A C ₁ -C ₄ alkoxy group and a C ₁ -C ₈ alkoxy group as defined above, which are substituted with ３3 aryl groups as defined above. Such aryl-substituted alkoxy groups include, for example, benzyloxy, diphenylmethoxy, triphenylmethoxy and the like.

The C ₁ -C ₄ alkyl-CO- group means an acyl group in which a C ₁ -C ₄ alkyl group as defined above is bonded to a carbonyl group, such as acetyl, propionyl,
Butyryl, isobutyryl, valeryl or pivaloyl groups and the like. C ₁ -C ₄ alkylene group and C ₁ -C
₁₀ alkylene groups are 1 to 4 and 1 to 10, respectively.
Means a linear or branched alkylene group having carbon atoms, for example, methylene, ethylene, propylene,
Butylene, 1- or 2-methylethylene, 1,1-, 1,
It includes a 2- or 2,2-dimethylethylene group and the like.

Unsubstituted or substituted heterocyclic groups include, for example, furyl, thienyl, oxazolyl, thiazolyl,
Pyridyl, pyrimidinyl, or N-alkylpyrrolyl, imidazolyl, pyrazolyl groups and the like are included.

Among the amine compounds represented by the above formula (1), there is a preferable group to which the present method is applied. That is,
The method comprises the step of: wherein R ¹ is an unsubstituted phenyl or naphthyl group; a phenyl or naphthyl group substituted with ¹ to 5 C ₁ -C ₄ alkyl groups, C ₁ -C ₄ alkoxy groups and / or halogen atoms; An unsubstituted heterocyclic group,
R ² is a C ₁ -C ₄ alkyl group; a C ₁ -C ₄ alkyl group substituted with 1 to 3 phenyl groups; a C ₁ -C ₄ alkoxy group;
A C ₁ -C ₄ alkoxy group substituted with 1 to 3 phenyl groups; or an unsubstituted heterocyclic group, wherein R ³ and R ⁴ are the same or different and are a hydrogen atom, a C ₁ -C ₄ alkyl group or A C ₁ -C ₄ alkyl group substituted with 1 to 3 phenyl groups and used for racemizing an optically active amine represented by the formula (1) wherein A is a C ₁ -C ₆ alkylene group. Is preferred.

More preferably, the method comprises the step of: wherein R ¹ is unsubstituted phenyl or 1 to 5 C ₁ -C ₄ alkyl,
₁ -C ₄ phenyl group substituted with an alkoxy group and / or a halogen atom, R ² is in C ₁ -C ₄ alkyl group or one to three C ₁ -C ₄ alkyl group substituted with a phenyl group To racemize an optically active amine represented by the formula (1) wherein R ³ and R ⁴ are the same or different and are a hydrogen atom or a C ₁ -C ₄ alkyl group, and A is a methylene or ethylene group. Used.

More preferably, the method comprises the following formula:
(2):

Embedded image [Wherein, R ⁵ is a hydrogen atom, a C ₁ -C ₄ alkyl group, a C ₁ -C ₄
An alkoxy group or a halogen atom, R ⁶ is C ₁ -C
_Represents an alkyl group, R ⁷ represents a hydrogen atom or a C ₁ -C ₄ alkyl group, and * represents the position of an asymmetric carbon atom].

More preferably, the method is characterized in that R ⁵ is hydrogen, methyl, methoxy or chlorine and R ⁶
Is an isopropyl group, and R ⁷ is a hydrogen atom or an ethyl group, and is used for racemizing the optically active amine represented by the above formula (2). Most preferably, the method comprises treating R ⁵
Is a hydrogen atom, R ⁶ is an isopropyl group, and R ⁷ is a hydrogen atom.
Used to racemize (PBA).

The racemic form of the amine compound represented by the above formula (1) or (2) can be obtained by a known organic synthesis or from a commercial product. The optically active amine compound to be racemized according to the present method is often a residue obtained by optically resolving such a racemate and separating one desired optically active form. Therefore, the optically active amine compound used in the present method has an optical purity of almost 100%.
ee (enantiomeric excess), or
Lower than that, it may be about 20 to 99% ee.

In the present method, racemizing an optically active amine means converting an amine having a relatively high optical purity into an amine having a lower optical purity. That is, according to the present method, the racemization ratio represented by
% Or more, preferably 80% or more, more preferably 95%
% Or more.

(Equation 1)

In the present method, the catalytic reduction catalyst means a metal catalyst used for catalytic reduction. As metal,
Precious metals such as platinum and palladium, nickel, cobalt,
Iron, copper, etc. are used. As a form, for example, platinum may be platinum black, colloidal platinum, platinum oxide, etc.
Nickel may be reduced nickel, Urushibara nickel, nickel formate, or the like. Nickel, cobalt, iron and the like may be in the form of a Raney catalyst such as Raney nickel, Raney cobalt and Raney iron. A form in which a carrier is used in combination may be, for example, palladium-carbon, palladium-calcium carbonate, platinum-barium sulfate, nickel-diatomaceous earth, copper chromite, or the like. Among these catalysts, preferred for the present process are Raney catalysts, particularly preferred are Raney nickel or Raney cobalt, and more preferred are catalysts prepared from aluminum alloys of nickel and cobalt. All of the above catalysts can be obtained from commercial products. The amount of the catalyst used is not particularly limited, but the catalyst is used in an amount of 0.01 to 1.0 part by weight, preferably 0.05 to 0.5 part by weight, based on 1 part by weight of the amine compound.

This racemization reaction can be usually carried out by heating and stirring the optically active amine together with the catalytic reduction catalyst in a closed vessel such as an autoclave. Further, usually, the void in the reaction vessel is replaced with an inert gas such as nitrogen. The reaction solvent is not particularly required, but if desired, an inert organic solvent such as water or toluene may be used.

It has been found that this racemisation reaction is advantageously carried out in the presence of ammonia. When ammonia is present in the reaction system, the decomposition of the amine compound and the by-product of the high-boiling secondary amine are suppressed, so that the racemization of the amine compound can be achieved with a high recovery rate. In the present method, the form of ammonia to be used is not particularly limited, and may be an aqueous solution or a gaseous form. However, from the viewpoint of operability, ammonia is usually used as an aqueous solution, and its concentration is 5 to 28.
%. The amount of ammonia added is not particularly limited, but usually 0.1 to 3.0 equivalents of ammonia, preferably 0.2 to 2.0 equivalents to 1 equivalent of the raw material optically active amine.
Add 1.5 equivalents to the reaction system.

Further, it has been found that the present racemization reaction is advantageously carried out in the absence of hydrogen. In this method, the conditions under hydrogen pressure as in the method disclosed in the above-mentioned JP-A-63-185943 are not essential, and the presence of hydrogen may lower the chemical purity of the amine compound obtained after the reaction. Therefore, it may be preferable to carry out the racemization in the absence of hydrogen.

The reaction temperature of the racemization reaction is usually 10
The temperature is 0 to 250 ° C, preferably 150 to 200 ° C, and more preferably 160 to 180 ° C. The reaction time varies depending on the type and amount of the catalyst used, the concentration and amount of ammonia, the reaction temperature and the reaction conditions such as the stirring state, etc., but is usually within 50 hours, more usually 10 to 25 hours.

After completion of the reaction, the reaction mixture is extracted with an organic solvent under acidic conditions to transfer the by-products to the organic layer and the amine compounds to the aqueous layer. As the organic solvent, toluene, hexane, ether, ester, or the like that is immiscible with water can be used. Next, the aqueous layer is made alkaline with a base such as sodium hydroxide, and extracted with an organic solvent as described above to obtain the desired amine compound. By this operation, an amine compound having sufficiently high purity can be obtained. However, if necessary, distillation or the like can be performed to obtain a target amine compound having higher purity.

[0033]

EXAMPLES The present invention will be described more specifically based on examples, but the present invention is not limited to these examples. In Examples, the optical purity of PBA was measured by high performance liquid chromatography under the following conditions, and expressed as an enantiomeric excess (% ee). Column: CRAWNPAK CR (+) [Daicel] 0.4 × 15 cm Eluent: 0.1N HClO ₄ aqueous solution / methanol = 85 /
15 Flow rate: 0.8 ml / min Temperature: 40 ° C. Detection: UV 210 nm The chemical purity of PBA is measured by gas chromatography under the following conditions, and the simple area percentage (%)
It was expressed by. Column: CBPI-M25-0.25 [Shimadzu Corporation] Column bath: 40 ° C, heating rate 10 ° C / min, 250 ° C, 1
Hold for 9 minutes Vaporization chamber: 270 ° C Detection: FID, 290 ° C

Example 1 (R) using Raney nickel catalyst
-Racemization of PBA In a SUS316 autoclave having a capacity of 230 ml, (R)
-PBA [optical purity 47.2% ee, chemical purity 98.9%]
(40.00 g), Raney nickel catalyst (8.0 g) and 28
% Ammonia water (18.6 g) was charged, sealed, and replaced with nitrogen. Next, stirring was started, and the reaction was carried out at a temperature of 165 ° C. and an internal pressure of 17 kg / cm ² G for 22.5 hours. After completion of the reaction, the reaction solution was cooled and the reaction solution was analyzed. As a result, it was found that the optical purity of PBA was 7.1% ee and the chemical purity was 93.8%. The reaction mixture was filtered and the filter cake was washed with toluene (40
g) and then with water (40 g). The filtrate and the washing solution were combined, and 35% hydrochloric acid (22.94 g) was added thereto for extraction. 29% aqueous sodium hydroxide solution
(31.26 g) and made alkaline, and fresh toluene
(60 g) for extraction. The aqueous layer was extracted once more with fresh toluene (60 g). These toluene extracts were combined and concentrated under reduced pressure to give 36.68 g of a residue (chemical purity 9%).
5.7%). The residue was purified by distillation under reduced pressure. As a result, the optical purity was 7.1% ee, and the chemical purity was 99.6%.
33.52 g of PBA was obtained. Recovery rate is 83.8%,
The racemization ratio was 85.0%.

Examples 2 and 3 The reaction was carried out in the same manner as in Example 1 except that the reaction temperature and the reaction time were changed or no aqueous ammonia was added. The results are shown in Table 1 below together with the results of Example 1. From these results, it can be seen that although the racemization proceeds efficiently even in the absence of ammonia, the chemical purity of PBA slightly decreases, and it is desirable to add aqueous ammonia.

Examples 4 to 6 The reaction of Example 1 was carried out in the presence of hydrogen without adding aqueous ammonia. Hydrogen was injected after purging with nitrogen. These results are also shown in Table 1 below. From these results, although racemization proceeds efficiently even in the presence of hydrogen, PBA
It can be seen that the chemical purity of the compound decreases.

[Table 1] Example (R) -PBA Catalyst amount 28% ammonia Hydrogen reaction Reaction Optical chemistry number Quantity Near water Temperature Time Purity Purity (g) (g) (g) (kg / cm ² G) (° C) (hr) (% ee ) (%) 1 40.00 8.0 18.6 − 165 22.5 7.1 93.8 2 20.00 4.0 9.3 − 160 15 9.7 92.8 3 20.00 1.0 − − 170 15 2.1 72.7 4 10.00 1.0 − 4 160 7 32.6 62.9 5 10.00 1.0 − 4 160 20 5.5 27.2 6 10.00 1.0 − 4 180 7 5.4 40.0

Examples 7 to 11 Example 1 was carried out by changing the amount of catalyst and the concentration of aqueous ammonia.
The reaction was carried out in the same manner as in. The ammonia water concentration is 28
% Ammonia water as it was or by adding water to dilute it. The results are shown in Table 2 below together with the results of Examples 1 and 2. From these results, it can be seen that although the chemical purity is slightly lowered by lowering the ammonia concentration, the speed of the racemization is increased.

[Table 2] Example (R) -PBA Catalyst amount 28% Ammonia Ammonia reaction Reaction Optical chemistry number Amount Near water Concentration Temperature Time Purity Purity (g) (g) (g) (%) (° C) (hr) (% ee) (% ) 1 40.00 8.0 18.6 28.0 165 22.5 7.1 93.8 2 20.00 4.0 9.3 28.0 160 15 9.7 92.8 7 20.00 4.0 9.3 19.6 160 15 8.3 88.6 8 20.00 6.0 9.3 17.0 160 15 5.6 83.2 9 20.00 8.0 9.3 15.1 160 20 3.2 80.3 10 20.00 2.0 9.3 23.0 170 15 2.0 87.9 11 20.00 4.0 9.3 19.6 170 15 0.1 82.3

Examples 12-14 With Raney cobalt catalyst
Racemization of (R) -PBA A reaction was carried out in the same manner as in Example 1, except that a Raney cobalt catalyst was used as the racemization catalyst and the amount of the catalyst was changed. The results are shown in Table 3 below. From these results, it can be seen that the racemization reaction proceeds efficiently even when the Raney cobalt catalyst is used, similarly to the Raney nickel catalyst.

[Table 3]  Example (R) -PBA amount of catalyst 28% ammonia reaction reaction optical chemistry number amount near water temperature time time purity purity(g) (g) (g) (° C) (hr) (% ee) (%) 12 20.00 2.0 9.3 160 15 26.6 94.5 13 20.00 4.0 9.3 160 15 6.9 88.414 20.00 6.0 9.3 160 15 4.4 88.0

[0039]

As described above, by using this method, an optically active amine having an asymmetric carbon at the β-position of the amino group and beyond, for example, optically active PBA can be efficiently racemized. That is, by combining this method with the optical resolution method, it is possible to efficiently produce an optically active amine having one desired configuration.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code Agency reference number FI Technical indication location C07C 211/15 8828-4H C07C 211/15 211/29 8828-4H 211/29 213/00 7457- 4H 213/00 // C07B 61/00 300 C07B 61/00 300

Claims (9)

[Claims] 1. The following formula (1): Wherein R ¹ is an unsubstituted aryl group; an aryl group substituted with 1 to 5 C _{1 to} C ₄ alkyl groups, C _{1 to} C ₄ alkoxy groups and / or halogen atoms; or unsubstituted or substituted R ² represents a C ₁ -C ₈ alkyl group; a C ₁ -C ₈ alkyl group substituted with 1 to 3 aryl groups; a C ₁ -C ₈ alkoxy group;
A C ₁ -C ₈ alkoxy group substituted with 1 to 3 aryl groups; or an unsubstituted aryl group that is not the same as R ¹ ;
An aryl group substituted with 5 C ₁ -C ₄ alkyl groups, C ₁ -C ₄ alkoxy groups and / or halogen atoms; or an unsubstituted or substituted heterocyclic group, wherein R ³ and R ⁴ are may be the same or different, a hydrogen atom, C ₁ -C ₄ alkyl group, C ₁ substituted with 1-3 aryl group -C ₄ alkyl or C ₁ -C ₄ alkyl -C
A represents a C ₁ -C ₁₀ alkylene group, and * represents the position of an asymmetric carbon atom.] A method for the racemization of an optically active amine represented by the formula: A racemization method characterized by using a catalyst. 2. A phenyl or naphthyl group in which R ¹ is unsubstituted; a phenyl or naphthyl group substituted with ¹ to 5 C _{1 to} C ₄ alkyl groups, C _{1 to} C ₄ alkoxy groups and / or halogen atoms; Or an unsubstituted heterocyclic group wherein R ² is a C ₁ -C ₄ alkyl group; a C ₁ -C ₄ alkyl group substituted with 1 to 3 phenyl groups; a C ₁ -C ₄ alkoxy group; A C ₁ -C ₄ alkoxy group substituted with three phenyl groups; or an unsubstituted heterocyclic group, R ³ and R ⁴
Are the same or different and are a hydrogen atom, a C ₁ -C ₄ alkyl group or a C ₁ -C ₄ alkyl group substituted with 1 to 3 phenyl groups, and A is a C ₁ -C ₆ alkylene group. The racemization method according to claim 1, wherein the optically active amine represented by 1) is racemized. 3. R ¹ is an unsubstituted phenyl group or 1 to 5
C ₁ -C ₄ alkyl groups, C ₁ -C ₄ alkoxy groups and / or phenyl groups substituted with halogen atoms,
R ² is a C ₁ -C ₄ alkyl group or a C ₁ -C ₄ alkyl group substituted with 1 to 3 phenyl groups, and R ³ and R ⁴
Is the same or different and is a hydrogen atom or a C ₁ -C ₄ alkyl group, and A is a methylene or ethylene group;
The racemization method according to claim 2, wherein the optically active amine represented by the formula is racemized. 4. The following formula (2): [Wherein, R ⁵ is a hydrogen atom, a C ₁ -C ₄ alkyl group, a C ₁ -C ₄
An alkoxy group or a halogen atom, R ⁶ is C ₁ -C
_{4 represents} an alkyl group, R ⁷ represents a hydrogen atom or a C ₁ -C ₄ alkyl group, and * represents the position of an asymmetric carbon atom]. Racemization method. 5. R ⁵ is a hydrogen atom, a methyl group, a methoxy group or a chlorine atom, R ⁶ is an isopropyl group,
The racemization method according to claim 4, wherein the optically active amine represented by the formula (2) wherein R ⁷ is a hydrogen atom or an ethyl group is racemized. 6. The racemization method according to claim 1, wherein the catalytic reduction catalyst is allowed to act in the presence of ammonia. 7. The racemization method according to claim 1, wherein the catalytic reduction catalyst is allowed to act in the absence of hydrogen. 8. The racemization method according to claim 1, wherein the catalytic reduction catalyst is a Raney catalyst. 9. The racemization method according to claim 8, wherein the Raney catalyst is a Raney nickel catalyst or a Raney cobalt catalyst.