JP6528519B2 - Process for producing bicyclic amine compound - Google Patents

Description

  The present invention relates to a process for the preparation of bicyclic amine compounds.

  The bicyclic amine compound is known, for example, as a compound useful for medical and agricultural chemicals intermediates, catalysts for organic synthesis, chemical adsorbents, antibacterial agents and the like (see, for example, Patent Document 1).

  As a method for producing a bicyclic amine compound, the present applicant has the following formula

[In formula, R < ₁ > -R < ₈ > respectively independently represents a hydrogen atom, a C1-C4 alkyl group, a hydroxyl group, a hydroxymethyl group, or a C1-C4 alkoxy group. In addition, X represents a carbon atom or a nitrogen atom, and Y represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, or a hydroxyalkyl group having 1 to 4 carbon atoms. ]
Is intramolecularly dehydrated in the gas phase in the presence of a solid catalyst in the presence of a solid catalyst, and

[Wherein, R _{1 to} R ₈ , X and Y are as defined above. ]
In the method for producing a compound represented by
A _a M _b P _c O _d
[Wherein, A represents one or more elements selected from the group consisting of Si, Al, Mg, Ti and Zr, M represents an alkali metal, P represents phosphorus, and O represents oxygen] . The subscripts a to d represent the number of moles of each element, b / a = 0.001 to 0.3 (molar ratio), c / a = 0.001 to 0.3 (molar ratio), and d is The bonding state of each atom represents an optional value. However, when A represents two or more elements, the subscript a represents the number of moles of the element having the largest number of moles. ]
Patent application has already been made for a method for producing a bicyclic amine compound using an inorganic oxide represented by the following (see Patent Document 2).

  Patent Document 2 discloses a production method by a gas phase reaction and describes that by-product tar content can be reduced by using a specific solid catalyst. However, since no study has been made on the inhibition of catalyst deterioration and long-term operation evaluation has been carried out for only about one week, there is still a problem to be solved in industrial continuous production.

JP, 2010-037325, A JP, 2012-149048, A

  An object of the present invention is to provide a production method for efficiently obtaining a bicyclic amine compound while having sufficient catalytic activity and suppressing deterioration of the catalyst as much as possible to maintain the catalytic activity for a long time.

  As a result of intensive studies to solve the above problems, the present inventors have found that the condensation of the phosphoric acid component which is one of the catalyst deterioration factors can be suppressed by the addition of an alkaline earth metal element, and the above problems Means for solving the problem have been found, and the present invention has been completed. That is, the present invention is a method for producing a bicyclic amine compound as shown below.

  [1] The following formula (1)

[In formula, R < ₁ > -R < ₈ > respectively independently represents a hydrogen atom, a C1-C4 alkyl group, a hydroxyl group, a hydroxymethyl group, or a C1-C4 alkoxy group. In addition, X represents a carbon atom or a nitrogen atom, and Y represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, or a hydroxyalkyl group having 1 to 4 carbon atoms. ]
From the compound represented by the following formula (2)

[Wherein, R _{1 to} R ₈ , X and Y are as defined above. ]
In the method for producing a compound represented by the following formula (3)
A _a M _b N _c P _d O _e (3)
[Wherein, A represents a metal, M represents an alkali metal, N represents an alkaline earth metal, P represents phosphorus, and O represents oxygen. The subscripts a to e represent the number of moles of each element, b / a = 0.001 to 0.3 (molar ratio), c / a = 0.001 to 0.1 (molar ratio), d / a = 0 .001 to 0.3 (molar ratio), and e represents a value which can be arbitrarily taken depending on the bonding state of each atom. ]
Using the inorganic oxide shown by these as a catalyst, The manufacturing method of the bicyclic amine compound characterized by the above-mentioned.

  [2] The process for producing a bicyclic amine compound as described in [1] above, wherein in the formulas (1) and (2), Y is a hydrogen atom or a hydroxymethyl group.

  [3] The method for producing a bicyclic amine compound according to the above [1] or [2], wherein in the formulas (1) and (2), X is a nitrogen atom.

[4] In the formulas (1) and (2), R _{1 to} R ₈ each independently represent a hydrogen atom, a methyl group, an ethyl group, an isopropyl group or a hydroxymethyl group (however, R _{1 to} R ₈ Are not all the same substituent groups.) The method for producing a bicyclic amine compound according to any one of the above [1] to [3].

  [5] The method for producing a bicyclic amine compound according to any one of the above [1] to [4], wherein in the formula (3), A is Al or Si.

  [6] The bicyclic group according to any one of the above [1] to [5], wherein in the formula (3), M is at least one selected from the group of Na, K, Rb and Cs. Method for producing an amine compound.

  [7] The bicyclic group according to any one of the above [1] to [6], wherein in the formula (3), N is at least one selected from the group of Mg, Ca, Sr and Ba Method for producing an amine compound.

  Hereinafter, the present invention will be described in detail.

  In the present invention, the hydroxyl group-containing cyclic amine compound represented by the above formula (1) is intramolecularly dehydrated in the gas phase in the presence of an inorganic oxide catalyst to obtain a bicyclic amine represented by the above formula (2) It is characterized by obtaining a compound.

  In the present invention, X in the above formula (1) represents a carbon atom or a nitrogen atom, and Y represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, or a hydroxyalkyl group having 1 to 4 carbon atoms.

In the present invention, the substituents R _{1 to} R ₈ in the above formula (1) are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, a hydroxymethyl group or an alkoxy having 1 to 4 carbon atoms. Represents a group.

  In the present invention, among the compounds represented by the above formula (1), specific examples of the compound in which X is a carbon atom include, for example, the following compounds (exemplified compound numbers 1 to 6). The invention is not limited to these.

  In addition, among the bicyclic amine compounds represented by the above formula (2), specific examples of the compound in which X is a carbon atom can include, for example, the following compounds (exemplified compound numbers 7 to 10). The present invention is not limited to these.

  Next, the intramolecular dehydration reaction of the hydroxyl group-containing cyclic amine compound of the present invention using an inorganic oxide catalyst will be described.

  In the present invention, the inorganic oxide catalyst is not particularly limited, but is preferably a solid catalyst in which an acid component, a base component, or both of them are supported on a carrier.

  As a carrier of a solid catalyst, for example, an inorganic oxide is used. The inorganic oxide is not particularly limited, and examples thereof include silicon oxide, aluminum oxide, aluminosilicate, zeolite, magnesium oxide, titanium oxide, zirconium oxide and the like.

  As an acid component, it is preferable to use an inorganic acid. The inorganic acid is not particularly limited, but for example, phosphoric acid, phosphonic acid, phosphinic acid, phosphine oxide, various phosphates, sulfonic acid and the like can be mentioned as preferable ones.

  It is preferable to contain an alkali metal element and an alkaline earth metal element as the base component. The alkali metal element is not particularly limited, and examples thereof include Li, Na, K, Rb and Cs. The alkaline earth metal element is not particularly limited, and examples thereof include Mg, Ca, Sr, Ba and the like.

  Although it does not specifically limit as a raw material of such a base component, For example, those oxides, a hydroxide, a halide, carbonate, nitrate, a sulfate etc. are mentioned. In the present invention, the preparation method of the solid catalyst is not particularly limited, but for example, a preparation method generally performed can be used. Specifically, the above-described solid catalyst raw material (for example, catalyst carrier, raw material for acid component, raw material for base component, etc.) is dissolved or suspended in water, and after steps such as stirring, heating, concentration, drying, etc. For example, a method of forming a solid catalyst through molding and calcination is further exemplified.

  Although it does not specifically limit as a calcination temperature of a solid catalyst, Usually, it is the range of 300-1100 degreeC, Preferably it is the range of 400-700 degreeC. By setting the temperature in the range of 400 to 700 ° C., physical properties such as acid-base strength and specific surface area of the solid catalyst can be improved, and catalyst activity and selectivity can be further enhanced.

  In addition, the calcination of the solid catalyst is not particularly limited, but may be performed in the atmosphere of air or nitrogen.

  There is no particular limitation on the method of adding the alkaline earth metal element to the solid catalyst, and even if the alkaline earth metal and the support are simultaneously mixed and fired, or the support is fired, an aqueous solution of alkaline earth metal salt and You may knead | mix and carry.

  In the present invention, the intramolecular dehydration reaction is mainly carried out in the gas phase, preferably in a fixed bed flow system.

  According to the present invention, by including an alkaline earth metal in the catalyst component, the life of the catalyst can be extended as compared with the prior art, and a bicyclic amine compound can be industrially continuously and stably produced. is there.

It is a figure which shows the change of the yield by reaction time in an Example and a comparative example. It is a figure which shows the chart of P-NMR of the solid catalyst obtained by the reference example.

  The present invention will be described in more detail based on the following reference examples and examples, but the present invention is not construed as being limited thereto.

Reference Example 1 (Preparation of Catalyst A)
A mixture of 60.0 g of commercially available aluminum oxide (manufactured by Sumitomo Chemical Co., Ltd.) and 0.70 g of calcium nitrate as a catalyst carrier with 100 ml of water and evaporated to dryness using an evaporator is then evaporated at 600.degree. Baking time. This was mixed with 19.1 g of cesium carbonate and 4.75 g of an aqueous phosphoric acid solution, 100 ml of water was added, and the mixture was evaporated to dryness using an evaporator. The solid is dried in a muffle furnace at 200 ° C. for 4 hours in an air atmosphere, crushed to 3.5 mesh, and a catalyst for gas phase reaction (A = Al, M = Cs, N = Ca, a = 1, b = 0 1, c = 0.0025, d = 0.07 (hereinafter referred to as catalyst A).

Reference Example 2 (Preparation of Catalyst B)
A catalyst was prepared according to the method described in Reference Example 1 except that 1.39 g of calcium nitrate was used in Reference Example 1, and a catalyst for gas phase reaction (A = Al, M = Cs, N = Ca, a = 1, b = 0.1, c = 0.005, d = 0.07 (hereinafter referred to as catalyst B). The said catalyst measured P-NMR.

Reference Example 3 (Preparation of Catalyst C)
A catalyst was prepared according to the method described in Reference Example 1 except that 2.80 g of calcium nitrate was used in Reference Example 1, and a catalyst for gas phase reaction (A = Al, M = Cs, N = Ca, a = 1, b = 0.1, c = 0.01, d = 0.07 (hereinafter referred to as catalyst C).

Reference Example 4 (Preparation of Catalyst D)
A catalyst was prepared according to the method described in Reference Example 1 except that 0.77 g of barium nitrate was used instead of calcium nitrate in Reference Example 1, and a catalyst for gas phase reaction (A = Al, M = Cs, N = Ba, a = 1, b = 0.1, c = 0.0025, d = 0.07 (hereinafter referred to as "catalyst D").

Reference Example 5 (Preparation of Catalyst E)
A catalyst was prepared according to the method described in Reference Example 1 except that 1.54 g of barium nitrate was used instead of calcium nitrate in Reference Example 1, and a catalyst for gas phase reaction (A = Al, M = Cs, N = Ba, a = 1, b = 0.1, c = 0.005, d = 0.07 (hereinafter referred to as catalyst E). The said catalyst measured P-NMR.

Reference Example 6 (Preparation of Catalyst F)
A catalyst was prepared according to the method described in Reference Example 1 except that 3.09 g of barium nitrate was used instead of calcium nitrate in Reference Example 1, and a catalyst for gas phase reaction (A = Al, M = Cs, N = Ba, a = 1, b = 0.1, c = 0.01, d = 0.07 (hereinafter referred to as "catalyst F").

Reference Example 7 (Preparation of Catalyst G)
A catalyst was prepared according to the method described in Reference Example 1 except that 1.24 g of strontium nitrate was used instead of calcium nitrate in Reference Example 1, and a catalyst for gas phase reaction (A = Al, M = Cs, N = Sr, a = 1, b = 0.1, c = 0.005, d = 0.07 (hereinafter referred to as "catalyst G").

Reference Example 8 (Preparation of Catalyst H)
As a catalyst carrier, 30.0 g of commercially available aluminum oxide (manufactured by Sumitomo Chemical Co., Ltd.), 9.5 g of cesium carbonate and 2.38 g of a phosphoric acid aqueous solution were mixed, 100 ml of water was added, and the mixture was evaporated to dryness using an evaporator. The solid is dried in a muffle furnace at 200 ° C. for 4 hours in an air atmosphere, crushed to 3.5 mesh, and a catalyst for gas phase reaction (A = Al, M = Cs, a = 1, b = 0.1, d = 0.07 (hereinafter referred to as catalyst H)). The said catalyst measured P-NMR.

Reference Example 9 (Preparation of Catalyst I)
A catalyst was prepared according to the method described in Reference Example 1 except that 42.1 g of calcium nitrate was used in Reference Example 1, and a catalyst for gas phase reaction (A = Al, M = Cs, N = Ca, a = 1, b = 0.1, c = 0.15, d = 0.07 (hereinafter referred to as catalyst I).

Reference Example 10 (Preparation of Catalyst J)
A catalyst was prepared according to the method described in Reference Example 1 except that 4.76 g of iron nitrate nonahydrate was used instead of calcium nitrate in Reference Example 1, and a catalyst for gas phase reaction (A = Al, M = Cs, N) = Fe, a = 1, b = 0.1, c = 0.01, d = 0.07 (hereinafter referred to as catalyst J).

Reference Example 11 (Preparation of Catalyst K)
A catalyst was prepared according to the method described in Reference Example 1 except that 1.07 g of vanadium oxide was used instead of calcium nitrate in Reference Example 1, and a catalyst for gas phase reaction (A = Al, M = Cs, N = V, a = 1, b = 0.1, c = 0.01, d = 0.07 (hereinafter referred to as "catalyst K").

Reference Example 12 (Preparation of Catalyst L)
A catalyst was prepared according to the method described in Reference Example 1 except that 4.71 g of chromium nitrate nonahydrate was used instead of calcium nitrate in Reference Example 1, and a catalyst for gas phase reaction (A = Al, M = Cs, N) = Cr, a = 1, b = 0.1, c = 0.01, d = 0.07 (hereinafter referred to as catalyst L).

Reference Example 13 (Preparation of Catalyst M)
A catalyst was prepared according to the method described in Reference Example 1 except that 3.38 g of manganese nitrate hexahydrate was used instead of calcium nitrate in Reference Example 1, and a catalyst for gas phase reaction (A = Al, M = Cs, N) = Mn, a = 1, b = 0.1, c = 0.01, d = 0.07 (hereinafter referred to as catalyst M).

Example 1 (Synthesis of Exemplified Compound 10 Using Catalyst A)
Exemplified compound 6 [N- (2,3-dihydroxypropyl) piperazine] was dissolved in water to prepare a raw material of 11.25 wt% aqueous solution. In a quartz reaction tube having a diameter of 15 mm, a ceramic Raschig ring (3 mm in diameter × 3 mm in length × 1 mm in thickness) was packed so that 20 ml of catalyst A and 23 cm in length at the upper and lower portions. The temperature of the catalyst layer was maintained at 380 ° C., and from above, the raw material containing Exemplified Compound 6 prepared above was dropped at a rate of 0.3 g / min for 24 hours. The reaction mixture gas obtained was cooled by a condenser, and the reaction product was analyzed by gas chromatography. The conversion of Exemplified Compound 6 was 97%, the selectivity to Exemplified Compound 10 was 54%, and the total yield was Was 52%. The reaction results are shown in Table 1.

Example 2 (Synthesis of Exemplified Compound 10 Using Catalyst B)
The procedure described in Example 1 was followed except that in Example 1 catalyst B prepared in Reference Example 2 was used instead of catalyst A. As a result of gas chromatography analysis of the reaction liquid, the conversion of Exemplified Compound 6 was 97%, the selectivity to Exemplified Compound 10 was 56%, and the total yield was 54%. The reaction results are shown in Table 1.

Example 3 (Synthesis of Exemplified Compound 10 Using Catalyst C)
The procedure described in Example 1 was followed except that in Example 1 catalyst C prepared in Reference Example 3 was used instead of catalyst A. As a result of gas chromatography analysis of the reaction liquid, the conversion of Exemplified Compound 6 was 99%, the selectivity to Exemplified Compound 10 was 39%, and the total yield was 39%. The reaction results are shown in Table 1.

Example 4 (Synthesis of Exemplified Compound 10 Using Catalyst D)
The procedure described in Example 1 was followed except that in Example 1 catalyst D prepared in Reference Example 4 was used instead of catalyst A. As a result of gas chromatography analysis of the reaction solution, the conversion ratio of Exemplified Compound 6 was 95%, the selectivity to Exemplified Compound 10 was 53%, and the total yield was 51%. The reaction results are shown in Table 1.

Example 5 (Synthesis of Exemplified Compound 10 Using Catalyst E)
The procedure described in Example 1 was followed except that in Example 1 catalyst E prepared in Reference Example 5 was used instead of catalyst A. As a result of gas chromatography analysis of the reaction solution, the conversion ratio of Exemplified Compound 6 was 95%, the selectivity to Exemplified Compound 10 was 55%, and the total yield was 52%. The reaction results are shown in Table 1.

Example 6 (Synthesis of Exemplified Compound 10 Using Catalyst F)
The method described in Example 1 was followed except that in Example 1 catalyst F prepared in Reference Example 6 was used instead of catalyst A. As a result of gas chromatography analysis of the reaction liquid, the conversion of Exemplified Compound 6 was 98%, the selectivity to Exemplified Compound 10 was 41%, and the total yield was 40%. The reaction results are shown in Table 1.

Example 7 (Synthesis of Exemplified Compound 10 Using Catalyst G)
The procedure described in Example 1 was followed except that in Example 1 catalyst G prepared in Reference Example 7 was used instead of catalyst A. As a result of gas chromatography analysis of the reaction liquid, the conversion of Exemplified Compound 6 was 99%, the selectivity to Exemplified Compound 10 was 54%, and the total yield was 53%. The reaction results are shown in Table 1.

Example 8 (Synthesis of Exemplified Compound 7 Using Catalyst B)
The method described in Example 1 was followed except that, in Example 1, Catalyst B prepared in Reference Example 2 was used instead of Catalyst A, and Example Compound 3 was used instead of Example Compound 6. As a result of gas chromatography analysis of the reaction solution, the conversion of Exemplified Compound 3 was 99%, the selectivity to Exemplified Compound 7 was 38%, and the total yield was 38%. The reaction results are shown in Table 1.

Example 9 (Synthesis of Exemplified Compound 8 Using Catalyst B)
The method described in Example 1 was followed except that, in Example 1, Catalyst B prepared in Reference Example 2 was used instead of Catalyst A, and Example Compound 4 was used instead of Example Compound 6. As a result of gas chromatography analysis of the reaction liquid, the conversion of Exemplified Compound 4 was 99%, the selectivity to Exemplified Compound 8 was 45%, and the total yield was 45%. The reaction results are shown in Table 1.

Example 10 (Synthesis of Exemplified Compound 10 Using Catalyst B)
In Example 1, using the catalyst B prepared in Reference Example 2 in place of the catalyst A, the reaction is continued for 360 hours, and the reaction temperature is raised from the initial 380 ° C. to 406 ° C. to maintain high conversion. Otherwise followed the procedure described in Example 1. As a result of gas chromatography analysis of the reaction liquid, the conversion of Exemplified Compound 6 was 95%, the selectivity to Exemplified Compound 10 was 50%, and the total yield was 48%. The reaction results are shown in Table 1.

Example 11 (Synthesis of Exemplified Compound 10 Using Catalyst E)
In Example 1, using the catalyst E prepared in Reference Example 5 in place of the catalyst A, the reaction is continued for 360 hours, and the reaction temperature is raised from the initial 380 ° C. to 406 ° C. to maintain high conversion. Otherwise followed the procedure described in Example 1. As a result of gas chromatography analysis of the reaction solution, the conversion ratio of Exemplified Compound 6 was 95%, the selectivity to Exemplified Compound 10 was 53%, and the total yield was 50%. The reaction results are shown in Table 1.

Comparative Example 1 (Synthesis of Exemplified Compound 10 Using Catalyst H)
The procedure described in Example 1 was followed except that in Example 1 catalyst H prepared in Reference Example 8 was used instead of catalyst A. As a result of gas chromatography analysis of the reaction liquid, the conversion of Exemplified Compound 6 was 97%, the selectivity to Exemplified Compound 10 was 56%, and the total yield was 54%. The reaction results are shown in Table 2.

Comparative Example 2 (Synthesis of Exemplified Compound 10 Using Catalyst H)
In Example 1, using the catalyst H prepared in Reference Example 8 in place of the catalyst A, the reaction is continued for 360 hours, and the reaction temperature is raised from the initial 380 ° C. to 424 ° C. to maintain high conversion. Otherwise followed the procedure described in Example 1. As a result of gas chromatography analysis of the reaction liquid, the conversion ratio of Exemplified Compound 6 was 94%, the selectivity to Exemplified Compound 10 was 44%, and the total yield was 41%. The reaction results are shown in Table 2.

Comparative Example 3 (Synthesis of Exemplified Compound 10 Using Catalyst I)
The procedure described in Example 1 was followed except that in Example 1 catalyst I prepared in Reference Example 9 was used instead of catalyst A. As a result of gas chromatography analysis of the reaction solution, the conversion ratio of Exemplified Compound 6 was 97%, the selectivity to Exemplified Compound 10 was 27%, and the total yield was 26%. The reaction results are shown in Table 2.

Comparative Example 4 (Synthesis of Exemplified Compound 10 Using Catalyst J)
The procedure described in Example 1 was followed, except that in Example 1 the catalyst J prepared in Reference Example 10 was used instead of catalyst A. As a result of gas chromatography analysis of the reaction liquid, the conversion of Exemplified Compound 6 was 95%, the selectivity to Exemplified Compound 10 was 46%, and the total yield was 44%. The reaction results are shown in Table 2.

Comparative Example 5 (Synthesis of Exemplified Compound 10 Using Catalyst K)
The procedure described in Example 1 was followed except that in Example 1 catalyst K prepared in Reference Example 11 was used instead of catalyst A. As a result of gas chromatography analysis of the reaction solution, the conversion ratio of Exemplified Compound 6 was 71%, the selectivity to Exemplified Compound 10 was 33%, and the total yield was 23%. The reaction results are shown in Table 2.

Comparative Example 6 (Synthesis of Exemplified Compound 10 Using Catalyst L)
The method described in Example 1 was followed except that in Example 1 the catalyst L prepared in Reference Example 12 was used instead of catalyst A. As a result of gas chromatography analysis of the reaction liquid, the conversion of Exemplified Compound 6 was 76%, the selectivity to Exemplified Compound 10 was 44%, and the total yield was 33%. The reaction results are shown in Table 2.

Comparative Example 7 (Synthesis of Exemplified Compound 10 Using Catalyst M)
The procedure described in Example 1 was followed except that in Example 1 catalyst M prepared in Reference Example 13 was used instead of catalyst A. As a result of gas chromatography analysis of the reaction solution, the conversion ratio of Exemplified Compound 6 was 71%, the selectivity to Exemplified Compound 10 was 47%, and the total yield was 33%. The reaction results are shown in Table 2.

  From the results in Tables 1 and 2, by adding an alkaline earth metal element, condensation of phosphoric acid, which is a catalyst component, can be suppressed, catalyst durability is improved over conventional catalysts, and reaction is performed for a long time Even when done, the catalyst performance was maintained.

  The present invention has the possibility of being used as a method for producing a bicyclic amine compound known as a compound useful for, for example, a pharmaceutical and agrochemical intermediate, a catalyst for organic synthesis, a chemical adsorbent, an antibacterial agent and the like.

Claims (4)

Following formula (1)
[In formula, R < ₁ > -R < ₈ > respectively independently represents a hydrogen atom, a C1-C4 alkyl group, a hydroxyl group, a hydroxymethyl group, or a C1-C4 alkoxy group. In addition, X represents a carbon atom or a nitrogen atom, and Y represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, or a hydroxyalkyl group having 1 to 4 carbon atoms. ]
From the compound represented by the following formula (2)
[Wherein, R _{1 to} R ₈ , X and Y are as defined above. ]
In the method for producing a compound represented by the following formula (3)
A _a M _b N _c P _d O _e (3)
[Wherein, A represents Al , M represents Cs , N represents at least one selected from the group of Ca and Ba , P represents phosphorus, and O represents oxygen. The subscripts a to e represent the number of moles of each element, b / a = 0.001 to 0.3 (molar ratio), c / a = 0.001 to 0.1 (molar ratio), d / a = 0 .001 to 0.3 (molar ratio), and e represents a value which can be arbitrarily taken depending on the bonding state of each atom. ]
Using the inorganic oxide shown by these as a catalyst, The manufacturing method of the bicyclic amine compound characterized by the above-mentioned. The method for producing a bicyclic amine compound according to claim 1, wherein Y is a hydrogen atom or a hydroxymethyl group in the formulas (1) and (2). The method for producing a bicyclic amine compound according to claim 1 or 2, wherein in the formulas (1) and (2), X is a nitrogen atom. In formulas (1) and (2), each of R _{1 to} R ₈ independently represents a hydrogen atom, a methyl group, an ethyl group, an isopropyl group, or a hydroxymethyl group (provided that all of R _{1 to} R ₈ are the same) The method for producing a bicyclic amine compound according to any one of claims 1 to 3, which does not become a substituent.