Carbon-nitrogen bond formation method

Abstract

To provide a method for forming a carbon-nitrogen bond that proceeds under relatively mild conditions using a catalyst with low toxicity and high safety, and that enables mass production of a target compound by simple means.SOLUTION: A carbon-nitrogen bond is formed by reacting a nitrogen atom-containing compound with a haloalkane or alcohol in the presence of an amine compound (A) represented by the general formula (1) in the figure.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a method for forming a carbon-nitrogen bond by reacting a nitrogen atom-containing compound with a haloalkane or an alcohol to form a carbon-nitrogen bond, for example.

Background Art

[0002] The selective formation of carbon-nitrogen bonds is a core reaction process in fine chemicals synthesis and occupies an important position in organic synthetic chemistry. In reactions for forming carbon-nitrogen bonds, transition metal complexes have long been used in stoichiometric amounts or near-stoichiometric amounts. Although the use of transition metal complexes enables various amination reactions to be successfully adjusted, usually, strict reaction conditions, expensive metal catalysts, or oxygen-sensitive procedures are required.

[0003] Therefore, what is needed is a method for forming a carbon-nitrogen bond that can be carried out under less severe conditions and uses an environmentally friendly catalyst. Regarding the formation of carbon-nitrogen bonds by hydroamination, various transition metal catalysts have been studied so far, but there are few reported examples in which an intermolecular reaction proceeds using a cyclic amine as a raw material. Recently, a reaction example of 1,2,4-triazole and a haloalkane using 1,8-diazabicyclo[5.4.0]-7-undecene has been reported (see Non-Patent Document 1). However, this method has limitations on substrates due to the use of a strong base catalyst and is inferior in versatility.

Prior Art Documents

Non-Patent Documents

[0004]

Non-Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] The present invention has been made in view of the above background art, and an object thereof is to provide a carbon-nitrogen bond formation method in which a reaction proceeds under relatively mild conditions by using a catalyst with low toxicity and high safety, and a target compound can be produced by a simple means.

Means for Solving the Problems

[0006] As a result of intensive studies to solve the above problems, the present inventors have found a carbon-nitrogen bond formation method described below and have completed the present invention.

[0007] That is, the present disclosure includes the following embodiments.

[0008] [1] A method for forming a carbon-nitrogen bond, comprising reacting a nitrogen atom-containing compound with a haloalkane or an alcohol in the presence of an amine compound (A) represented by the following general formula (1) to form a carbon-nitrogen bond.

[0009]

Chemical formula

[0010] [In the above general formula (1), R 1 ~R 5 each independently represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, a hydroxymethyl group, or an alkoxy group having 1 to 4 carbon atoms, and a and b are each independently 0 or 1, and satisfy the relationship a + b = 1.] [2] The method for forming a carbon-nitrogen bond according to the above [1], wherein the amine compound (A) represented by the above general formula (1) is 1,4-diazabicyclo[2.2.2]octane-2-methanol (that is, in the general formula (1), R 1 ~R 5 are all hydrogen atoms, a = 0, and b = 1.).

[0011] [3] The method for forming a carbon-nitrogen bond according to [1] or [2] above, wherein a nitrogen atom-containing compound represented by the following general formula (2) is reacted with a haloalkane or alcohol represented by the following formula (3) to form a carbon-nitrogen bond and produce a compound represented by the following formula (4).

[0012] [Chemical formula]

[0013] [In the above general formula (2), R 6 , R 7 are the same or different and each represents a hydrogen atom or a non-metal atom-containing group, and R 6 , R 7 may combine with each other to form a ring together with the adjacent nitrogen atoms.]

[0014] [Chemical formula]

[0015] [In the above general formula (3), R 8 to R10 are the same or different and each represents a hydrogen atom or a non-metal atom-containing group, and at least two of R 8 to R10 may combine with each other to form a ring together with the adjacent carbon atoms. X is a hydroxyl group or a halogen.]

[0016] [Chemical formula]

[0017] [In the above general formula (4), R 6 to R 10 have the same definitions as above.] [4] The method for forming a carbon-nitrogen bond according to [3] above, wherein the amount of the compound represented by the above compound (3) is in the range of 0.1 to 10 moles per 1 mole of the compound represented by the above formula (2).

[0018] [5] The amount of the amine compound (A) used is in the range of 0.001 to 10 moles with respect to 1 mole of the compound represented by the above formula (2) and the compound represented by the above formula (3) which is the smaller one of the two compounds, according to the method for forming a carbon-nitrogen bond described in the above [3] or [4].

Advantages of the Invention

[0019] According to the method of the present disclosure, a catalyst with low toxicity and high safety is used and the reaction proceeds under relatively mild conditions, and the target compound can be produced by a simple means. Further, the method of the present invention has few restrictions on the substrate, is excellent in versatility, and the product and the catalyst can be easily separated.

[0020] Therefore, the method of the present disclosure is suitable for mass production of the target product and is extremely useful in terms of green chemistry.

Modes for Carrying Out the Invention

[0021] The method for forming a carbon-nitrogen bond according to one aspect of the present disclosure is to react a nitrogen atom-containing compound with a haloalkane or an alcohol in the presence of the amine compound (A) represented by the above general formula (1) to form a carbon-nitrogen bond.

[0022] In the above general formula (1), R 1 ~R 5 each independently represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, a hydroxymethyl group, or an alkoxy group having 1 to 4 carbon atoms.

[0023] The R 1 ~R 5 is not particularly limited, but specifically, each independently, a hydrogen atom, a hydroxyl group, a hydroxymethyl group, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, a sec-butoxy group, or a tert-butoxy group, etc. can be exemplified.

[0024] Among these, preferably, each is independently a hydrogen atom, a methyl group, an ethyl group, a hydroxymethyl group, or a methoxy group.

[0025] Specific examples of the amine compound (A) represented by the general formula (1) include, for example, the following compounds (Exemplary Compound 1 to Exemplary Compound 28), but the present invention is not limited thereto.

[0026]

Chemical formula

[0027] As the amine compound (A), in the general formula (1), R 1 ~R 5 are each independently a hydrogen atom, a methyl group, an ethyl group, or a hydroxymethyl group (provided that not all of R 1 ~R 5 represent the same substituent), those in which all of R 1 ~R 5 are methyl groups, or those in which all of R 1 ~R 5 are hydrogen atoms are preferred. In the general formula (1), those in which R 1 ~R 5 are each independently a hydrogen atom or a methyl group are more preferred. In the general formula (1), those in which all of R 1 ~R 5 are hydrogen atoms (i.e., 1,4-diazabicyclo[2.2.2]octane-2-methanol, which is the above Exemplary Compound -1) are even more preferred.

[0028] The method for producing the above-mentioned amine compound (A) is not particularly limited. For example, it can be produced by the methods described in Khimiya Geterotsiklicheskikh Soedinenil, 10, 1404 (1980), International Publication No. 95 / 18104 pamphlet, etc. Also, it can be produced by intramolecular cyclization of ethylene oxide adducts of hydroxyalkylpiperazines induced by the methods described in Journal of Medicinal Chemistry (1993), 36(15), 2075 - 2083 and Japanese Patent Application Laid-Open No. 2010-120887. Furthermore, for example, it can be produced by the method described in Japanese Patent Application Laid-Open No. 2010-37325, that is, by the cyclization reaction of dihydroxyalkylpiperazines.

[0029] The above-mentioned amine compound (A) having a substituent can be produced by using the corresponding substituted piperazine. The method for producing the substituted piperazine can be produced by known techniques related to the synthesis of the above-mentioned hydroxyalkylpiperazines and the like.

[0030] The above-mentioned amine compound (A) has an acute toxicity LD 50 which is > 2000 (mg / kg), and is characterized as a catalyst with high safety compared to bicyclic amines such as 1,8-diazabicyclo[5.4.0]-7-undecene, quinuclidine, and quinuclidinol.

[0031] Since the above-mentioned amine compound (A) has a hydroxyl group, it has high polarity and is easily soluble in polar solvents such as dimethylformamide. Therefore, the product and the catalyst can be easily separated during purification.

[0032] In the above-mentioned method for forming a carbon-nitrogen bond, in the presence of the above-mentioned amine compound (A), a nitrogen atom-containing compound is reacted with a haloalkane or alcohol, etc. to form a carbon-nitrogen bond. Hereinafter, typical methods for forming a carbon-nitrogen bond will be specifically described.

[0033] [Method for Forming Carbon-Nitrogen Bond] In the presence of the above-mentioned amine compound (A), when the nitrogen atom-containing compound represented by the above formula (2) is reacted with the haloalkane or alcohol represented by the above formula (3), a carbon-nitrogen bond is formed, and the compounds represented by the above formula (4) are respectively produced.

[0034] In the above general formula (2), R 6 , R 7 indicate the same or different hydrogen atoms or non-metal atom-containing groups. R 6 , R 7 may be bonded to each other to form a ring together with the adjacent nitrogen atoms.

[0035] In the above general formula (3), R 8 ~R 10 indicate the same or different hydrogen atoms or non-metal atom-containing groups. In formula (3), at least two of R 8 ~R 10 may be bonded to each other to form a ring together with the adjacent carbon atoms.

[0036] The non-metal atoms in the non-metal atom-containing groups in the above R 6 ~R 10 are not particularly limited, and examples thereof include halogen atoms, carbon atoms, oxygen atoms, sulfur atoms, nitrogen atoms, etc.

[0037] Examples of the non-metal atom-containing groups in the above R 6 ~R 10 include, for example, halogen atoms, hydrocarbon groups, heterocyclic groups, carboxyl groups, substituted oxycarbonyl groups, substituted or unsubstituted carbamoyl groups, cyano groups, acyl groups, nitro groups, substituted sulfinyl groups, substituted sulfonyl groups, sulfuric acid groups, sulfuric acid ester groups, hydroxyl groups, substituted oxy groups, mercapto groups, substituted thio groups, groups formed by bonding a plurality of these, etc. The above carboxyl group, sulfuric acid group, hydroxyl group, and mercapto group may be protected by a protecting group. As the above protecting group, a protecting group commonly used in the field of organic synthesis can be used.

[0038] Examples of the halogen atom corresponding to the non-metal atom-containing group include fluorine, chlorine, bromine, and iodine atoms.

[0039] Examples of the hydrocarbon group corresponding to the non-metal atom-containing group include aliphatic hydrocarbon groups, alicyclic hydrocarbon groups, aromatic hydrocarbon groups, and groups formed by bonding a plurality of these groups.

[0040] Examples of the aliphatic hydrocarbon group include linear or branched aliphatic hydrocarbon groups having 1 to 20 carbon atoms (preferably 1 to 10, more preferably 1 to 8), such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, hexyl, decyl, dodecyl, tetradecyl, hexadecyl, vinyl, allyl, ethynyl, 1-propynyl groups (e.g., alkyl groups, alkenyl groups, alkynyl groups, etc.).

[0041] Examples of the alicyclic hydrocarbon group include alicyclic hydrocarbon groups having 3 to 20 carbon atoms (preferably 3 to 15), such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cyclooctyl, cyclodecyl, cyclododecyl, norbornyl, adamantyl groups (e.g., cycloalkyl groups, cycloalkenyl groups, bridged carbocyclic groups, etc.).

[0042] Examples of the aromatic hydrocarbon group include aromatic hydrocarbon groups having about 6 to 14 carbon atoms, such as phenyl and naphthyl groups.

[0043] Examples of the group formed by bonding a plurality of these groups include a group formed by bonding an aliphatic hydrocarbon group and an alicyclic hydrocarbon group, and a group formed by bonding an aliphatic hydrocarbon group and an aromatic hydrocarbon group.

[0044] Examples of the group formed by bonding of the aliphatic hydrocarbon group and the alicyclic hydrocarbon group include cyclopentylmethyl, cyclohexylmethyl, cyclohexylethyl group, etc. Examples of the group formed by bonding of the aliphatic hydrocarbon group and the aromatic hydrocarbon group include aralkyl groups such as benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl; 2-methylphenyl, 3-methylphenyl, 4-methylphenyl group, etc.

[0045] The heterocyclic rings constituting the heterocyclic group corresponding to the non-metal atom-containing group include aromatic heterocyclic rings and non-aromatic heterocyclic rings. Examples of such heterocyclic rings include heterocyclic rings containing a nitrogen atom as a hetero atom (for example, 5-membered rings such as imidazole, pyrrole, pyrazole, 6-membered rings such as pyridine, pyrimidine, pyrazine, triazole, etc.), heterocyclic rings containing an oxygen atom as a hetero atom (for example, 5-membered rings such as furan, tetrahydrofuran, oxazole, isoxazole, 6-membered rings such as 4-oxo-4H-pyran, tetrahydropyran, condensed rings such as benzofuran, isobenzofuran, 4-oxo-4H-chromene, chroman, isochroman, etc.), heterocyclic rings containing a sulfur atom as a hetero atom (for example, 5-membered rings such as thiophene, thiazole, isothiazole, thiadiazole, 6-membered rings such as 4-oxo-4H-thiopyran, condensed rings such as benzothiophene, etc.), etc.

[0046] Examples of the substituted oxycarbonyl group corresponding to the non-metal atom-containing group include C 1-10 alkoxy-carbonyl groups such as methoxycarbonyl group, ethoxycarbonyl group, propyloxycarbonyl group, isopropyloxycarbonyl group, butyloxycarbonyl group, t-butyloxycarbonyl group; C 2-10 alkenyloxycarbonyl groups such as vinyloxycarbonyl group; C 3-15 cycloalkyloxycarbonyl groups such as cyclohexyloxy-carbonyl group; C 6-14 aryloxy-carbonyl groups such as phenyloxycarbonyl group; C 7-15 aralkyloxycarbonyl groups such as benzyloxycarbonyl group, etc.

[0047] Examples of the substituted or unsubstituted carbamoyl group corresponding to the non-metal atom-containing group include a carbamoyl group, a methylcarbamoyl group, a dimethylcarbamoyl group, and the like.

[0048] Examples of the acyl group corresponding to the non-metal atom-containing group include C aliphatic acyl groups such as a formyl group, an acetyl group, a propionyl group, a butyryl group, a valeryl group, a hexanoyl group, an acryloyl group, a methacryloyl group, and an acetoacetyl group; C alicyclic acyl groups such as a cyclohexanecarbonyl group; C aromatic acyl groups such as a benzoyl group; and heterocyclic acyl groups such as a 2-thenoyl group. 1-10 aliphatic acyl group; C alicyclic acyl groups such as a cyclohexanecarbonyl group 3-15 alicyclic acyl group; C aromatic acyl groups such as a benzoyl group 6-14 aromatic acyl group; and heterocyclic acyl groups such as a 2-thenoyl group are exemplified.

[0049] Examples of the substituted sulfinyl group corresponding to the non-metal atom-containing group include alkylsulfinyl groups such as a methylsulfinyl group, and arylsulfinyl groups such as a phenylsulfinyl group (including those having a substituent on the aromatic ring).

[0050] Examples of the substituted sulfonyl group corresponding to the non-metal atom-containing group include alkylsulfonyl groups such as a methanesulfonyl group, cycloalkylsulfonyl groups such as a cyclohexanesulfonyl group, and arylsulfonyl groups such as a benzenesulfonyl group (including those having a substituent on the aromatic ring).

[0051] Examples of the sulfuric acid ester group corresponding to the non-metal atom-containing group include a p-toluenesulfonyloxy group.

[0052] Examples of the substituted oxy group corresponding to the non-metal atom-containing group include C alkoxy groups such as a methoxy group, an ethoxy group, an isopropyloxy group, and a butoxy group; cycloalkyloxy groups such as a cyclohexyloxy group; aryloxy groups such as a phenoxy group; and acyloxy groups such as an acetyloxy group and a propionyloxy group. 1-6 alkoxy group; cycloalkyloxy groups such as a cyclohexyloxy group; aryloxy groups such as a phenoxy group; and acyloxy groups such as an acetyloxy group and a propionyloxy group are exemplified.

[0053] Examples of the substituted thio group corresponding to the non-metal atom-containing group include C-substituted thio groups such as methylthio and ethylthio groups 1-6 alkylthio groups; cycloalkylthio groups such as cyclohexylthio group; arylthio groups such as phenylthio group; acylthio groups such as acetylthio group, and the like.

[0054] In the above formula (2), R 6 , R 7 Examples of the ring formed by bonding with each other and together with the adjacent nitrogen atom include 3- to 10-membered nitrogen-containing rings such as pyrrolidine ring and piperidine ring.

[0055] In the above formula (3), examples of the ring formed by bonding at least two of R 8 ~R 10 together with the adjacent carbon atoms include 3- to 20-membered (preferably 3- to 15-membered) non-aromatic carbon rings such as cyclopropane ring, cyclobutane ring, cyclopentane ring, cyclopentene ring, cyclohexane ring, cyclohexene ring, cyclooctane ring, cyclodecane ring, cyclododecane ring, decalin ring, norbornane ring, norbornene ring, adamantane ring (for example, cycloalkane rings, cycloalkene rings, bridged carbon rings, etc.); non-aromatic heterocyclic rings having at least one heteroatom selected from the group consisting of an oxygen atom and a sulfur atom such as oxirane ring, oxetane ring, oxolane ring, oxane ring, oxepane ring, thiolane ring, thiane ring, and the like. These rings may have substituents, or may be condensed with other rings (for example, non-aromatic rings, aromatic rings, etc.).

[0056] Specific examples of the above R 6 , R 7 include, in particular, a hydrogen atom, a hydrocarbon group which may have a substituent, an acyl group (for example, an acyl group having 1 to 20 carbon atoms, etc.), a substituted sulfonyl group [for example, a hydrocarbon group-substituted sulfonyl group which may have a substituent having 1 to 20 carbon atoms (for example, an alkylsulfonyl group, a cycloalkylsulfonyl group, an arylsulfonyl group, etc.), etc.], and R 6 and R 7It is also preferable that they combine to form a ring together with adjacent nitrogen atoms.

[0057] Also, the above-mentioned R 8 ~R 10 is preferably, in particular, a hydrogen atom or a hydrocarbon group which may have a substituent, and it is more preferable that at least one of R 8 ~R 10 is an aryl group, an aromatic heterocyclic group, or a 1-alkenyl group. It is also preferable that R 8 , R 9 combine to form an alicyclic carbon ring (including bridged rings) such as a cyclohexane ring, a cyclohexene ring, or an adamantane ring together with adjacent carbon atoms.

[0058] Typical examples of the nitrogen atom-containing compound represented by the above formula (2) include, for example, heterocycles containing a nitrogen atom as a heteroatom (e.g., condensed rings such as triazole, imidazole, pyrazole, etc.), benzenesulfonamide, p-toluenesulfonamide, p-chlorobenzenesulfonamide, amines such as aniline, p-chloroaniline, p-nitroaniline, etc. (especially aromatic amines), sulfonamides such as p-methoxybenzenesulfonamide, p-nitrobenzenesulfonamide, N-methyl-p-toluenesulfonamide, methanesulfonamide, etc. (alkylsulfonamide, cycloalkylsulfonamide, arylsulfonamide, heteroarylsulfonamide, etc.), amides such as acetamide, propionamide, isobutyramide, cyclohexanecarboxamide, cinnamic acid amide, benzamide, 2-thiophenecarboxamide, etc. (aliphatic carboxylic acid amide, alicyclic carboxylic acid amide, aromatic carboxylic acid amide, heterocyclic carboxylic acid amide, etc.).

[0059] Typical examples of the haloalkane represented by the above formula (3) include, for example, ethyl chloride, propyl chloride, isopropyl chloride, butyl chloride, ethyl bromide, propyl bromide, isopropyl bromide, butyl bromide, methyl iodide, ethyl iodide, propyl iodide, isopropyl iodide, butyl iodide, etc.

[0060] Typical examples of the alcohol represented by the above formula (3) include, for example, aliphatic alcohols such as ethanol, 1-propanol, 2-propanol, t-butanol, allyl alcohol, crotyl alcohol, 1-methyl-2-propenyl alcohol; alicyclic alcohols such as cyclohexyl alcohol, 2-cyclohexen-1-ol, 2-norbornol; aromatic alcohols such as benzyl alcohol, 1-phenylethyl alcohol, 1-(4-chlorophenyl)ethyl alcohol, 1-(4-methylphenyl)ethyl alcohol, 1-(2-naphthyl)ethyl alcohol, benzhydrol, trityl alcohol, cinnamyl alcohol; heterocyclic alcohols such as 2-thienyl alcohol and the like. Among these, when using so-called allyl alcohols having a carbon-carbon double bond at the β,γ positions of the hydroxyl group and so-called benzyl alcohols having an aromatic ring at the β position of the hydroxyl group, the N-allylation reaction and N-benzylation reaction proceed rapidly and the target compound can be obtained in a high yield. Further, when using a secondary alcohol as the alcohol, the target compound can be obtained in a high yield.

[0061] The above reaction is carried out in the presence or absence of a solvent. The solvent may be any solvent that does not inhibit the reaction, and examples include saturated aliphatic hydrocarbons such as pentane, hexane, heptane, octane, decane; saturated alicyclic hydrocarbons such as cyclopentane, cyclohexane, methylcyclohexane, cyclooctane; aromatic hydrocarbons such as benzene, toluene, xylene, ethylbenzene; amide compounds such as dimethylformamide; halogenated hydrocarbons such as methylene chloride; chain or cyclic ethers such as diethyl ether, diisopropyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane; nitro compounds such as nitromethane and the like.

[0062] The ratio of the compound represented by the above formula (2) to the compound represented by the above formula (3) can be appropriately selected. Generally, the amount of the compound represented by the above compound (3) used is, for example, in the range of 0.1 to 10 moles, preferably 0.3 to 3 moles, per 1 mole of the compound represented by the above formula (2).

[0063] Although the usage amount of the above amine compound (A) varies depending on the type of raw material, it is, for example, in the range of 0.001 to 10 moles, preferably 0.05 to 0.5 moles, per 1 mole of the compound in the smaller amount among the compound represented by the above formula (2) and the compound represented by the above formula (3).

[0064] The reaction temperature can be appropriately selected according to the type of raw material, etc., and is, for example, in the range of 20 to 250°C, preferably 50 to 150°C.

[0065] The above reaction can be carried out by conventional methods such as batch, semi-batch, continuous, etc. The above reaction may be carried out at normal pressure or under pressure. The reactor is not particularly limited, and any of a mixing and stirring type reactor, a fixed bed type reactor, etc. may be used.

[0066] By reacting the nitrogen atom-containing compound represented by the above formula (2) with the haloalkane or alcohol represented by the above formula (3), a dehydration reaction product represented by the above formula (4) is produced.

[0067] The above reaction may contain components other than the above amine compound (A), the nitrogen atom-containing compound represented by the above formula (2), and the haloalkane or alcohol represented by the above formula (3).

[0068] Examples of the above components include general components used in the carbon-nitrogen bond formation reaction. Specifically, for example, additional catalysts (such as inorganic bases such as potassium carbonate, calcium carbonate, sodium carbonate, etc.) can be mentioned.

[0069] Regarding each of these components, they can be used within the generally used range.

[0070] After the reaction is completed, the reaction product can be separated and purified by separation means such as filtration, concentration, distillation, extraction, crystallization, recrystallization, adsorption, column chromatography, etc. or separation means combining these.

Examples

[0071] Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not limited by these examples. The identification of the product was 1 performed by 1H-NMR.

[0072] <Raw materials> The following were used as raw materials.

[0073] Nitrogen atom-containing compound: 1,2,4-triazole (manufactured by Tokyo Chemical Industry Co., Ltd.) Haloalkane: 1-bromobutane (manufactured by Fujifilm Wako Pure Chemical Corporation) Amine compound (A): 1,4-diazabicyclo[2.2.2]octane-2-methanol (manufactured by Tosoh Corporation) Amine compound: 1,4-diazabicyclo[2.2.1]octane (manufactured by Tosoh Corporation) Inorganic base: potassium carbonate (manufactured by Kishida Chemical Co., Ltd.) Reaction solvent: N,N-dimethylformamide (manufactured by Tokyo Chemical Industry Co., Ltd.) Purification solvent: dichloromethane (manufactured by Fujifilm Wako Pure Chemical Corporation) Desiccant: magnesium sulfate (manufactured by Fujifilm Wako Pure Chemical Corporation) <NMR analysis> Measuring device: JNM-ECZ400S manufactured by JEOL Ltd. Example 1 In a 500 ml four-necked flask, 0.145 mol of 1,2,4-triazole, 0.011 mol of amine compound (A), and about 20 g of N,N-dimethylformamide were added, and the mixture was stirred at room temperature. After 30 minutes, 0.145 mol of potassium carbonate and about 40 g of N,N-dimethylformamide were added, and the mixture was stirred at room temperature. After 2 hours, 0.131 mol of 1-bromobutane was dissolved in about 50 g of N,N-dimethylformamide and added dropwise over 1 hour using a dropping funnel. After heating and stirring at 70 °C for 5.5 hours, potassium carbonate was filtered off, the filtrate was transferred to a separating funnel, 700 ml of distilled water and 100 ml of dichloromethane were added, and liquid separation was performed. 100 ml of dichloromethane was added again to the aqueous layer, and liquid separation was performed, and this operation was repeated twice. Magnesium sulfate was added to the organic layer for dehydration, and the filtrate was concentrated under reduced pressure to obtain a pure target product of 1-butyl-1,2,4-triazole (isolation yield 52%). The identification of the compound was 1 performed by 1H-NMR measurement.

[0074] 1 1H-NMR (CDCl3) δ (ppm) = 0.94~0.97 (t, 3H), 1.29~1.39 (m, 2H), 1.84~1.91 (m, 2H), 4.16~4.20 (t, 2H), 7.94 (s, 1H), 8.06 (s, 1H).

[0075] Example 2 The same operation as in Example 1 was carried out except that potassium carbonate was not used and only 0.011 mol of amine compound (A) was used as the catalyst. As a result, 1-butyl-1,2,4-triazole was produced at a yield of 7%.

[0076] Comparative Example 1 The same operation as in Example 1 was carried out except that 0.011 mol of 1,4-diazabicyclo[2.2.1]octane was used as the catalyst. As a result, 1-butyl-1,2,4-triazole was produced at a yield of 47%.

[0077] Comparative Example 2 The same operation as in Example 1 was carried out except that potassium carbonate was not used and only 0.011 mol of 1,4-diazabicyclo[2.2.1]octane was used as the catalyst. As a result, 1-butyl-1,2,4-triazole was produced at a yield of 2%.

Industrial Applicability

[0078] The reaction for forming a carbon-nitrogen atomic bond of the present disclosure is an important reaction in modern organic synthetic chemistry and is useful for the synthesis of functional organic molecules such as agricultural chemicals and pharmaceuticals.

Claims

1. A method for forming a carbon-nitrogen bond by reacting a nitrogen atom-containing compound with a haloalkane or an alcohol in the presence of an amine compound (A) represented by the following general formula (1). 【Chem. 1】 [In the above general formula (1), R １ ~R ５ each independently represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, a hydroxymethyl group, or an alkoxy group having 1 to 4 carbon atoms, a and b are each independently 0 or 1, and satisfy the relationship a + b = 1.]

2. The amine compound (A) represented by the above general formula (1) is 1,4-diazabicyclo[2.2.2]octane-2-methanol (that is, in the general formula (1), R １ ~R ５ are all hydrogen atoms, a = 0, and b = 1). The method for forming a carbon-nitrogen bond according to claim 1.

3. The method for forming a carbon-nitrogen bond according to claim 1, wherein a nitrogen atom-containing compound represented by the following general formula (2) is reacted with a haloalkane or an alcohol represented by the following formula (3) to form a carbon-nitrogen bond and a compound represented by the following formula (4) is produced. [Chemical 2] [In the general formula (2) above, R ６ , R ７ are the same or different and each represents a hydrogen atom or a non-metal atom-containing group, and R ６ , R ７ may be bonded to each other to form a ring together with the adjacent nitrogen atom.] 【Chemical Formula 3】 [In the general formula (3) above, R ８ to Ｒ１０ are the same or different and each represents a hydrogen atom or a non-metal atom-containing group, and at least two of R ８ to Ｒ１０ may combine with adjacent carbon atoms to form a ring. X is a hydroxyl group or a halogen.] 【Chemical 4】 [In the general formula (4) above, R ６ to R １０ have the same definitions as described above.]

4. The method for forming a carbon-nitrogen bond according to claim 3, wherein the amount of the compound represented by the above compound (3) used is in the range of 0.1 to 10 moles per 1 mole of the compound represented by the above formula (2).

5. The method for forming a carbon-nitrogen bond according to claim 3 or claim 4, wherein the amount of the amine compound (A) used is in the range of 0.001 to 10 moles per 1 mole of the compound with the smaller amount among the compound represented by the above formula (2) and the compound represented by the above formula (3).

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