JP7088690B2 - Method for producing aromatic compounds - Google Patents

Description

The present invention relates to a method for producing an aromatic compound, and more specifically, to a method for producing an aromatic compound by directly reducing a nitro group using an aromatic nitro compound as a raw material.

Aromatic nitro compounds are important basic raw materials used in medical and agricultural chemicals, dyes, polymers and the like. The nitro group is a strong electron-withdrawing group, and in aromatic compounds, it has long been used as a useful substituent as a stepping stone for introducing a substituent to the meta position and as a substituent for inducing an aromatic nucleophilic substitution reaction. It is being utilized. Further, the nitro group can be converted into a hydrogen atom by reducing it to an amino group and then passing through a diazonium salt. As described above, the procedure for constructing a molecular skeleton utilizing the characteristics of the nitro group is one of the basics of synthetic organic chemistry and is industrially valuable (for example, Patent Document 1 and Non-Patent Document 1). ).

International Publication No. 2009/100169

J. Org. Chem. 1986, 51, 5127-5133

When substituting a nitro group with a hydrogen atom, as described in the background art, it is usually necessary to carry out two different reactions: reduction to an amino group and conversion of a diazonium salt. These procedures have problems that the number of steps is long and the production takes time due to the convenience of post-reaction treatment and purification work. Furthermore, since the diazonium salt is an intermediate that is unstable depending on the compound species and sometimes has a risk of explosion, there is a problem that careful handling is required.
An object of the present invention is to provide a novel technique for producing an aromatic compound using an aromatic nitro compound as a raw material, which has higher production efficiency and is superior in terms of safety.

（式中、Ｒ^１は、各々独立して、シクロヘキシル基又はｔｅｒｔ－ブチル基を表す。Ｒ^２は、各々独立して、水素原子、メチル基、メトキシ基、イソプロピル基、イソプロポキシ基、ジメチルアミノ基、又はスルホン酸基を表す。）
で表されるホスフィン化合物を共存させて反応を進行させることを特徴とする［１］から［４］のいずれか一つに記載の製造方法。 Applicants have shown that by reacting an aromatic nitro compound with a proton-supplied compound in the presence of a metal catalyst, the compound in which the nitro group of the aromatic nitro compound is replaced with a hydrogen atom is highly selective in a one-step reaction. I found that I could get it.
The gist of the present invention is as follows.
[1] A method for producing an aromatic compound, which comprises reacting an aromatic nitro compound with a proton supply compound in the presence of a metal catalyst to directly reduce the nitro group of the aromatic nitro compound to a hydrogen atom. ..
[2] The production method according to [1], wherein the proton-supplied compound is a primary or secondary alcohol compound.
[3] The production method according to [1] or [2], wherein the metal catalyst is a transition metal catalyst.
[4] The production method according to [3], wherein the transition metal catalyst is a palladium or nickel compound.
[5] The metal catalyst and the following general formula (4)

(In the formula, R ¹ independently represents a cyclohexyl group or a tert-butyl group, and R ² independently represents a hydrogen atom, a methyl group, a methoxy group, an isopropyl group, an isopropoxy group, or a dimethylamino. Represents a group or a sulfonic acid group.)
The production method according to any one of [1] to [4], wherein the reaction proceeds in the coexistence of the phosphine compound represented by.

According to the present invention, the conversion reaction of a nitro group into a hydrogen atom, which has conventionally required a multi-step reaction, can be carried out in only one step. Since the process is short and the time required for manufacturing can be shortened, it is possible to provide an industrially superior manufacturing method having higher production efficiency than the conventional technique. Further, since the present invention is a process that does not go through a diazonium salt, it has an advantage in terms of safety. The obtained aromatic compound can be obtained with a higher purity aromatic compound by a simple purification operation such as column chromatography, distillation and recrystallization. Further, if necessary, it can be converted into another compound through several steps.

Hereinafter, the present invention will be specifically described.

The present invention is a method for producing an aromatic compound, which comprises reacting an aromatic nitro compound with a proton supply compound in the presence of a metal catalyst to directly reduce the nitro group of the aromatic nitro compound to a hydrogen atom.

The aromatic nitro compound is not particularly limited, and examples thereof include a nitrated aromatic hydrocarbon compound and a nitrated heteroaromatic compound. The aromatic nitro compound is not particularly limited, and examples thereof include compounds represented by the following general formula (1).

In the formula, Ar ¹ represents an aromatic hydrocarbon group which may have a substituent or a heteroaromatic group which may have a substituent, and n represents an integer of 1 to 3.

The aromatic hydrocarbon group which may have the above-mentioned substituent is not particularly limited, but for example, a phenyl group which may have a substituent, a biphenyl group which may have a substituent, and the like. It has a naphthyl group which may have a substituent, an anthrasenyl group which may have a substituent, a pyrenyl group which may have a substituent, a terphenyl group which may have a substituent, and a substituent. Examples thereof include a phenanthrasenyl group which may have a substituent, a peryleneyl group which may have a substituent, a triphenylenyl group which may have a substituent and the like.

The heteroaromatic group which may have the above-mentioned substituent is not particularly limited, but for example, a furanyl group which may have a substituent, a benzofuranyl group which may have a substituent, and a substitution. A dibenzofuranyl group which may have a group, a phenyldibenzofuranyl group which may have a substituent, a dibenzofuranylphenyl group which may have a substituent, and a thienirenyl group which may have a substituent. , A benzothienyl group which may have a substituent, a dibenzothienirenyl group which may have a substituent, a phenyldibenzothienylenel group which may have a substituent, and a substituent may be present. Dibenzothienylenylphenyl group, pyridylenyl group which may have a substituent, pyrimidyl group which may have a substituent, pyrazil group which may have a substituent, quinolyl group which may have a substituent. , An isoquinolyl group which may have a substituent, a carbazolyl group which may have a substituent, a 9-phenylcarbazolyl group which may have a substituent, an acridinyl group which may have a substituent, A benzothiazolyl group which may have a substituent, a quinazolyl group which may have a substituent, a quinoxalyl group which may have a substituent, a 1,6-naphthyldinyl group which may have a substituent, or a substituent. Examples thereof include a 1,8-naphthyldinyl group which may have a group.

Further, the substituent on the aromatic hydrocarbon group which may have the above-mentioned substituent and the heteroaromatic group which may have the substituent is not particularly limited, but for example, a methyl group. , Ethyl group, alkyl group having 3 to 18 carbon atoms (for example, n-propyl group, i-propyl group, n-butyl group, sec-butyl group, tert-butyl group, n-hexyl group, cyclohexyl group, cyclohexadi Enyl group, octyl group, benzyl group, phenethyl group, etc.), alkyl halide group with 1-18 carbon atoms (eg, trifluoromethyl group, etc.), methoxy group, ethoxy group, alkoxy group with 3-18 carbon atoms (eg, trifluoromethyl group, etc.) For example, n-propyloxy group, i-propyloxy group, n-butyloxy group, sec-butyloxy group, tert-butyloxy group, n-hexyloxy group, cyclohexyloxy group, cyclohexadienyloxy group, octyloxy group, benzyl. Oxy group, phenethyloxy group, etc.), halogenated alkoxy group having 1-18 carbon atoms (for example, trifluoromethoxy group, etc.), phenyl group, trill group, pyridyl group, pyrimidyl group, carbazolyl group, dibenzothienyl group, or dibenzo Examples include a furanyl group.

Regarding Ar ¹ , an aromatic hydrocarbon group having 6 to 30 carbon atoms which may have a substituent or an aromatic hydrocarbon group having 3 to 30 carbon atoms which may have a substituent may be present in terms of excellent production efficiency of the aromatic compound. It is preferably an aromatic hydrocarbon group having 6 to 20 carbon atoms which may have a substituent, or a heteroaromatic group having 3 to 20 carbon atoms which may have a substituent. Is more preferable. More specifically, a phenyl group, a biphenyl group, a naphthyl group, a terphenyl group, a dibenzofuranyl group, a phenyldibenzofuranyl group, a dibenzofuranylphenyl group, a dibenzothienylenyl group, a phenyldibenzothienylenyl group, a dibenzothie Nirenylphenyl group, pyridyl group, phenylpyridyl group, pyridylphenyl group, pyrimidyl group, pyrazil group, quinolyl group, isoquinolyl group, carbazolyl group, or 9-phenylcarbazolyl group (these substituents are methyl group, butyl group). It is even more preferably substituted with a group, a hexyl group, an octyl group, a methoxy group, a phenyl group, a trill group, a pyridyl group, a pyrimidyl group, a carbazolyl group, a dibenzothienyl group, or a dibenzofuranyl group). Phenyl group, biphenyl group, naphthyl group, dibenzofuranyl group, phenyldibenzofuranyl group, dibenzofuranylphenyl group, dibenzothienyl group, phenyldibenzothienylenyl group, dibenzothienylenylphenyl group, pyridyl group, quinolyl group, Alternatively, it is even more preferably a carbazolyl group (these substituents may be substituted with a methyl group, a butyl group, a hexyl group, an octyl group, or a methoxy group).

The proton-supplied compound described above is not particularly limited, and examples thereof include primary and secondary alcohol compounds. The primary or secondary alcohol compound is not particularly limited, and examples thereof include compounds represented by the following general formula (2).

In the formula, the two Ar ^2s independently represent a hydrogen atom, an alkyl group which may have a substituent, or an aromatic group which may have a substituent.

The alkyl group which may have the above-mentioned substituent is not particularly limited, and examples thereof include an alkyl group having 1 to 18 carbon atoms, and the above-mentioned alkyl group is not particularly limited, but for example. Examples of a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, a sec-butyl group, an n-hexyl group, a cyclohexyl group, a cyclohexadienyl group, an octyl group, a benzyl group and the like are exemplified. Can be done.

The aromatic group which may have the above-mentioned substituent is not particularly limited, but for example, an aromatic hydrocarbon group which may have a substituent or a hetero which may have a substituent may be present. Aromatic groups are mentioned. For the aromatic hydrocarbon group which may have a substituent and the heteroaromatic group which may have a substituent, the aromatic hydrocarbon group which may have a substituent in Ar ¹ and the above-mentioned Ar 1 may have a substituent, respectively. Similar to a heteroaromatic group which may have a substituent.

Ar ² is preferably an aromatic hydrocarbon group having 1 to 18 carbon atoms or an aromatic hydrocarbon group which may have a substituent, from the viewpoint of excellent production efficiency of the aromatic compound. Methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, cyclohexyl group, benzyl group, phenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methyl More preferably, it is a phenyl group or a 2,4,6-trimethylphenyl group.

That is, as the above-mentioned proton supply compound, methanol, ethanol, n-propanol, i-propanol, n-butanol, i-butanol, cyclohexanol, 1,1-dicyclohexylmethanol, benzyl alcohol, 1,1-diphenylmethanol, Even more, 1,1-bis (2-methylphenyl) methanol, 1,1-bis (3-methylphenyl) methanol, 1,1-bis (4-methylphenyl) methanol, or dimesitylmethanol. preferable.

In the present invention, in the presence of a metal catalyst, the compound represented by the general formula (1) is reacted with the proton supply compound, and the nitro group of the compound represented by the general formula (1) is directly attached to the hydrogen atom. When reduced, an aromatic compound represented by the following general formula (3) is obtained.

In the formula, Ar ¹ and n represent the same as those represented by the general formulas (1) and (2).

In the present invention, since the nitro group is converted into a hydrogen atom, a new bond with the hydrogen atom is formed on the carbon to which the nitro group is bonded.

In the production method of the present invention, the molar ratio represented by the above-mentioned aromatic nitro compound (mol) ÷ the above-mentioned proton supply compound (mol) is not particularly limited, but is in the range of 0.1 to 10.0. preferable. From the viewpoint of economy, the molar ratio is more preferably 0.2 to 5.0, further preferably 0.33 to 3.0, and the range is 0.5 to 2.0. Is even more preferable.

n represents an integer of 1 to 3. From the viewpoint of more selective synthesis of the desired aromatic compound, it is preferably an integer of 1 to 2, and more preferably 1.

The above-mentioned metal catalyst is not particularly limited, and examples thereof include a palladium catalyst and a nickel catalyst. The palladium catalyst is not particularly limited, but for example, palladium (II) chloride, palladium (II) bromide, palladium (II) acetate, palladium acetylacetonate (II), and dichlorobis (benzonitrile) palladium (II). ), Dichlorobis (acetoyl) palladium (II), dichlorobis (triphenylphosphine) palladium (II), dichlorotetraammine palladium (II), dichloro (cycloocta-1,5-diene) palladium (II), palladium trifluoroacetate (II). ) And other divalent palladium compounds, tris (dibenzylideneacetone) dipalladium (0), tris (dibenzilidenacetone) dipalladium chloroform complex (0), tetrakis (triphenylphosphine) palladium (0) and other 0-valent palladium compounds. Can be mentioned. Further, a polymer-fixed palladium catalyst, an immobilized palladium catalyst such as palladium carbon, and the like can also be exemplified. Coordinating compounds such as phosphine compounds may coexist with these palladium catalysts. The coordinating compound is not particularly limited, and is, for example, a monodentate arylphosphin such as triphenylphosphine, tri (o-tolyl) phosphine, tri (mesityl) phosphine, tri (cyclohexyl) phosphine, and tri (isopropyl). ) Unidental alkyl phosphines such as phosphin, tri (tert-butyl) phosphine, 2-dicyclohexylphosphino-2', 6'-dimethoxybiphenyl, 2-dicyclohexylphosphino-2', 6'-diisopropoxybiphenyl, 2- Dicyclohexylphosphino-2'-methylbiphenyl, 2-dicyclohexylphosphino-2', 4', 6'-triisopropylbiphenyl, 2- (di-tert-butylphosphino) -2', 4', 6'- Triisopropylbiphenyl, 2-dicyclohexylphosphino-3,6-dimethoxy-2', 4', 6'-triisopropylbiphenyl, 2- (dicyclohexylphosphino) biphenyl, 2- (di-tert-butylphosphino)- Buchwald phosphine compounds such as 2'-(N, N-dimethylamino) biphenyl, 2-dicyclohexylphosphino-2'-(N, N-dimethylamino) biphenyl, 1,2-bis (diphenylphosphino) ethane, 1 , 2-Bis (diphenylphosphino) propane, 1,2-bis (dicyclohexylphosphino) ethane, 1,2-bis (diphenylphosphino) butane, 1,2-bis (diphenylphosphino) ferrocene, etc. Phosphin, 1,3-bis (2,6-diisopropylphenyl) -4,5-dihydro-1H-imidazolium chloride, 1,3-bis (2,6-diisopropylphenyl) imidazolium chloride, 1,3-bis (2,4,6-trimethylphenyl) -4,5-dihydro-1H-imidazolium chloride, 1,3-bis (2,4,6-trimethylphenyl) imidazolium chloride, 1,3-di-tert- Butylimidazole-2-iriden, 1,3-di-tert-butylbenzimidazolinium chloride, 1,3-bis (1-adamantyl) imidazolinium tetrafluoroborate, 1,3-diisopropylimidazolinium tetrafluoro Borate, 1,3-di-tert-butyl imidazolinium tetrafluoroborate, 1,3-dicyclohexyl imidazolinium chloride, 1,3-dicyclohexyl imidazolinium tetra Fluorobolate, 1,3-Dicyclohexylbenzimidazolinium chloride, 1-methyl-3-propylimidazolinium tetrafluoroborate, 1- (1-adamantyl) -3- (2,4,6-trimethylphenyl) imidazole Nium chloride, 2-benzylimidazo [1,5-a] quinolinium chloride, 2-benzylimidazo [1,5-a] quinolinium hexafluorophosphate, 1,3-bis (1-adamantyl) benzimidazo Linium chloride, 1,3-bis (2-cyclohexylnaphthalen-1-yl) imidazolinium tetrafluoroborate, 3-mesityl-1-methyl-1H-benzoimidazoliniuiodide, 2-cyclohexyl-5 -(2,4,6-triisopropylphenyl) imidazole [1,5-a] pyridinium chloride, 2- (1-adamantyl) -5- (2,4,6-triisopropylphenyl) imidazole [1,5- a] Pyridinium chloride, 2- [2,6-bis (diphenylmethyl) -4-methylphenyl] -5- (2,4,6-triisopropylphenyl) imidazole [1,5-a] pyridinium chloride, 2- {2,6-bis [bis (2-naphthyl) methyl] -4-methylphenyl} -5- (2,4,6-triisopropylphenyl) imidazole [1,5-a] pyridinium chloride, 2- (2) , 6-Diisopropylphenyl) -5- (2,4,6-triisopropylphenyl) Imidazo [1,5-a] pyridinium chloride, 2- (2,4,6-trimethylphenyl) -5- (2,4) , 6-Triisopropylphenyl) Imidazo [1,5-a] N-heterocarbene compounds such as pyridinium chloride and the like can be mentioned. When a coordinating compound such as a phosphine compound is allowed to coexist in the palladium catalyst, the palladium compound and the phosphine compound or the N-heterocarbene compound may be mixed and prepared in advance for reaction.

Examples of the nickel catalyst include a compound composed of a nickel salt and the above-mentioned phosphine compound. The nickel salt indicates a compound containing a nickel element as an active ingredient, and for example, a nickel salt having a valence of 0 to a valence of 2 is indicated. Specifically, nickel halides such as nickel fluoride (II), nickel chloride (II), nickel bromide (II), nickel iodide (II), nickel (0) powder, nickel sulfate (II), nitrate. Inorganic salts such as nickel (II) and nickel perchlorate (II), nickel (II) formate, nickel (II) oxalate, nickel acetate (II), nickel benzoate (II), nickel acetylacetonate (II). Organic acid nickel salts such as.

Among these metal catalysts, it is preferable to use a palladium catalyst from the viewpoint of advancing the desired reaction.

Further, from the viewpoint of more selectively advancing the desired reaction, it is desirable that the Buchwald phosphine compound coexists in the metal catalyst, and the Buchwald phosphine compound is not particularly limited, but for example, the following general formula is used. The phosphine compound represented by (4) is more preferable. Of these, 2-dicyclohexylphosphino-3,6-dimethoxy-2', 4', 6'-triisopropylbiphenyl is particularly preferable.

In the formula, R ¹ independently represents a cyclohexyl group or a tert-butyl group. R ² independently represents a hydrogen atom, a methyl group, a methoxy group, an isopropyl group, an isopropoxy group, a dimethylamino group, or a sulfonic acid group.

The N-heterocarbene compound is not particularly limited, but is preferably an N-heterocarbene compound represented by the following formula (5) or (6), for example.

In the formula, each of R ⁷ , R ⁸ and R ⁹ independently has a hydrogen atom, a methyl group, an ethyl group, a linear, branched or cyclic alkyl group having 3 to 18 carbon atoms, and 1 to 18 carbon atoms. Represents a monocyclic, linked or condensed aromatic hydrocarbon group having 6 to 24 carbon atoms which may have an alkoxy group or a substituent. m represents an integer from 0 to 5.

The above-mentioned linear, branched or cyclic alkyl group having 3 to 18 carbon atoms is not particularly limited, and is, for example, n-propyl group, i-propyl group, n-butyl group and sec-butyl. Examples thereof include a group, a tert-butyl group, an n-hexyl group, a cyclohexyl group, a cyclohexadienyl group, an octyl group, a benzyl group, a phenethyl group and the like.

The above-mentioned alkoxy group having 1 to 18 carbon atoms is not particularly limited, but for example, a methoxy group, an ethoxy group, an n-propyloxy group, an i-propyloxy group, an n-butyloxy group and a sec-butyloxy group. , Methoxy-butyloxy group, n-hexyloxy group, cyclohexyloxy group, cyclohexadienyloxy group, octyloxy group, benzyloxy group, phenethyloxy group and the like.

The monocyclic, linked or condensed aromatic hydrocarbon group having 6 to 24 carbon atoms which may have the above-mentioned substituent is not particularly limited, but may have, for example, a substituent. A phenyl group, a biphenyl group which may have a substituent, a naphthyl group which may have a substituent, an anthrasenyl group which may have a substituent, a pyrenyl group which may have a substituent, and a substituent. Examples thereof include a terphenyl group which may have a substituent, a phenanthrasenyl group which may have a substituent, a peryleneyl group which may have a substituent, a triphenylenyl group which may have a substituent, and the like. can.

The substituent on the monocyclic, linked or condensed ring aromatic hydrocarbon group having 6 to 24 carbon atoms which may have the above-mentioned substituent is not particularly limited, but is not particularly limited, and is, for example, a methyl group or an ethyl. Group, alkyl group with 3 to 18 carbon atoms (eg n-propyl group, i-propyl group, n-butyl group, sec-butyl group, tert-butyl group, n-hexyl group, cyclohexyl group, cyclohexadienyl group , Octyl group, benzyl group, phenethyl group, etc.), alkyl halide group having 1 to 18 carbon atoms (for example, trifluoromethyl group, etc.), methoxy group, ethoxy group, alkoxy group having 3 to 18 carbon atoms (for example, for example. n-propyloxy group, i-propyloxy group, n-butyloxy group, sec-butyloxy group, tert-butyloxy group, n-hexyloxy group, cyclohexyloxy group, cyclohexadienyloxy group, octyloxy group, benzyloxy group , Fenetyloxy group, etc.), halogenated alkoxy group having 1 to 18 carbon atoms (for example, trifluoromethoxy group, etc.), phenyl group, tolyl group, pyridyl group, pyrimidyl group, carbazolyl group, dibenzothienyl group, or dibenzofuranyl. The group etc. can be mentioned.

m represents an integer of 1 to 5. From the viewpoint of highly selective synthesis of the desired N-heterocarbene compound, it is preferably an integer of 1 to 3, and more preferably an integer of 1 to 2.

The amount of the metal catalyst used is not particularly limited, but is usually preferably in the range of 0.01 to 20 mol% with respect to 1 mol of the aromatic nitro compound. If the metal catalyst is within the above range, the aromatic compound can be synthesized with a higher selectivity, but from the viewpoint of reducing the amount of the expensive metal catalyst used, a more preferable amount of the metal catalyst used is 1 mol of the aromatic nitro compound. On the other hand, it is in the range of 0.01 to 10 mol% in terms of metal.

The reaction according to the present invention is preferably a reaction in the presence of a base. The base used may be selected from an inorganic base and / or an organic base, and is not particularly limited, but more preferably sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, rubidium carbonate, and carbonic acid. Inorganic bases such as cesium, potassium phosphate, sodium phosphate, potassium fluoride, cesium fluoride, sodium-methoxydo, sodium-ethoxydo, potassium-methoxyd, potassium-ethoxydo, lithium-tert-butoxide, sodium-tert-butoxide, potassium- An organic base such as alkali metal alkoxide such as tert-butoxide, triethylamine, tributylamine, pyridine, diazabicycloundecene, diazabicyclononene, etc., from the viewpoint of improving the selectivity of the desired aromatic compound. Even more preferably, it is an inorganic base such as rubidium carbonate, cesium carbonate, potassium phosphate, sodium phosphate, cesium fluoride and the like.

The amount of the base used is preferably 1.0 times or more the molar amount of the aromatic nitro compound used. If the amount of the base is less than 1.0 times the molar amount, the yield of the target aromatic coupling reaction product may be lower than that in the case where the amount of the base is 1.0 times the molar amount or more. Although the yield of the desired aromatic coupling reaction product does not change even if a large excess of base is added, the post-treatment operation after the reaction is completed becomes complicated, so that the more preferable amount of base is 1.0 to 1. It is in the range of 5.0 times the molar amount.

This reaction can usually be carried out in the presence of an inert solvent. The solvent used may be any solvent that does not significantly inhibit this reaction, and is not particularly limited, but is limited to aromatic organic solvents such as benzene, toluene and xylene, diethyl ether, tetrahydrofuran and dimethoxyethane. , 1,4-Dioxane, ether-based organic solvents such as cyclopentylmethyl ether, acetonitrile, dimethylformamide, dimethylsulfoxide, hexamethylphosphotriamide and the like. Of these, ether-based organic solvents such as diethyl ether, dimethoxyethane, tetrahydrofuran, 1,4-dioxane, and cyclopentyl methyl ether are more preferable.

This reaction can be carried out under normal pressure, under an atmosphere of an inert gas such as nitrogen or argon, or under pressure. The reaction is carried out in the range of 20 to 250 ° C., preferably in the range of 50 to 200 ° C., more preferably in the range of 100 to 160 ° C. in order to increase the yield of the desired aromatic compound. , Even more preferably, it is carried out in the range of 120 to 150 ° C.

In this reaction, a phase transfer catalyst may be used as an additive. The phase transfer catalyst is not particularly limited, but specifically, crown ethers such as 24-crown-8, 18-crown-6, 15-crown-5, 12-crown-4, tetra ( n-butyl) ammonium chloride, tetra (n-butyl) ammonium bromide, benzyltriethylammonium chloride, triethyl-n-dodecylammonium chloride, triethyl-n-dodecylammonium bromide, trimethyl-n-hexadecylammonium chloride, trimethyl-n- Examples thereof include quaternary ammonium salts such as hexadecyl ammonium bromide.

The reaction time required for this reaction is not constant depending on the amount, type, reaction temperature, etc. of the aromatic nitro compound, proton supply compound, metal catalyst, base, etc., but is preferably selected from a range of several minutes to 72 hours.

Hereinafter, the present invention will be specifically described with reference to Examples. However, these do not limit the present invention in any way.

Measuring equipment: Gas chromatography GC2014 manufactured by Shimadzu Corporation (analysis conditions: column used: BP-1, detector manufactured by SGE, detector: FID @ 290 ° C), NMR ECS-400 manufactured by Nippon Denshi Co., Ltd. (1H NMR, 400 MHz; 13C) NMR, 101 MHz).

Example 1
Under nitrogen, in a 15 mL screw vial tube, stir bar, 2-nitroanisole 92 mg (0.60 mmol), 2-propanol 54 mg (0.90 mmol), palladium acetylacetonate (II) 9.1 mg (0.030 mmol), 2-Dicyclohexylphosphino-3,6-dimethoxy-2', 4', 6'-triisopropylbiphenyl 32 mg (0.060 mmol), tripotassium phosphate 318 mg (1.5 mmol), 1,4-dioxane 3 mL, and 120 μL of n-tridecane was added as an internal standard substance. After tightly covering the vial tube, the mixture was heated and stirred at 130 ° C. for 4 hours. Next, the reaction solution was cooled to room temperature, a part of the reaction solution was collected, diluted with ethyl acetate, and gas chromatographic analysis was performed. As a result, anisole was detected in a yield of 96%.

Example 2
In Example 1, instead of using 2-nitroanisole 92 mg (0.60 mmol), 3-nitroanisole 92 mg (0.60 mmol) was used, and the same experimental operation was carried out except that heating and stirring were performed for 8 hours. However, anisole was detected in a yield of 71% by gas chromatography analysis.

Example 3
In Example 1, instead of using 2-nitroanisole 92 mg (0.60 mmol), 4-nitroanisole 92 mg (0.60 mmol) was used, and the same experimental operation was carried out except that heating and stirring were performed for 12 hours. However, anisole was detected in a yield of 62% by gas chromatography analysis.

Example 4
In Example 1, instead of using 92 mg (0.60 mmol) of 2-nitroanisole, 107 mg (0.60 mmol) of 4-t-butylnitrobenzene was used, and the same experimental operation was performed except that heating and stirring were performed for 12 hours. As a result, t-butylbenzene was detected in a gas chromatography analysis with a yield of 87%.

Example 5
In Example 1, instead of using 92 mg (0.60 mmol) of 2-nitroanisole, 109 mg (0.60 mmol) of methyl 3-nitrobenzoate was used, and instead of using 54 mg (0.90 mmol) of 2-propanol, di When the same experimental procedure was carried out using 242 mg (0.90 mmol) of mesitylmethanol and heating and stirring were carried out for 2 hours, methyl benzoate was detected in a yield of 78% by gas chromatography analysis.

Example 6
In Example 1, instead of using 92 mg (0.60 mmol) of 2-nitroanisole, 100 mg (0.60 mmol) of N, N-dimethyl-4-nitroaniline is used and 54 mg (0.90 mmol) of 2-propanol is used. Instead, 242 mg (0.90 mmol) of dimethylylmethanol was used, and the same experimental procedure was carried out except that heating and stirring were performed for 84 hours. As a result, the yield of N, N-dimethylaniline was 27 in the gas chromatography analysis. Detected in%.

Example 7
In Example 1, instead of using 92 mg (0.60 mmol) of 2-nitroanisole, 104 mg (0.60 mmol) of 1-nitronaphthalene was used, and 60 μL of n-decane was used instead of 120 μL of n-tridecane as an internal standard substance. When the same experimental operation was carried out except that heating and stirring were carried out for 4 hours, naphthalene was detected in a gas chromatography analysis with a yield of 87%.

Example 8
In Example 1, instead of using 2-nitroanisole 92 mg (0.60 mmol), 2-nitronaphthalene 104 mg (0.60 mmol) was used, and the same experimental operation was carried out except that heating and stirring were performed for 12 hours. Naphthalene was detected in a gas chromatography analysis with a yield of 59%.

Example 9
In Example 1, instead of using 92 mg (0.60 mmol) of 2-nitroanisole, 117 mg (0.60 mmol) of 2- (4-nitrophenyl) -1,3-dioxolane was used, and n-tridecane was used as an internal standard substance. When 60 μL of n-decane was used instead of 120 μL and the same experimental procedure was performed, 2-phenyl-1,3-dioxolane was detected in a gas chromatography analysis with a yield of 92%.

Example 10
In Example 1, instead of using 2-nitroanisole 92 mg (0.60 mmol), 2-methyl-2- (4-nitrophenyl) -1,3-dioxolan 126 mg (0.60 mmol) was used as an internal standard substance. When n-decane 60 μL was used instead of n-tridecane 120 μL and the same experimental procedure was carried out, 2-methyl-2-phenyl-1,3-dioxolane was detected in a gas chromatography analysis with a yield of 88%. rice field.

Example 11
Under nitrogen, in a 15 mL screw vial tube, stir bar, 3-nitrobiphenyl 120 mg (0.60 mmol), 2-propanol 54 mg (0.90 mmol), palladium acetylacetonate (II) 9.1 mg (0.030 mmol), 2-Dicyclohexylphosphino-3,6-dimethoxy-2', 4', 6'-triisopropylbiphenyl 32 mg (0.060 mmol), tripotassium phosphate 318 mg (1.5 mmol), and 1,4-dioxane 3 mL. added. After tightly covering the vial tube, the mixture was heated and stirred at 130 ° C. for 4 hours. The reaction was then cooled to room temperature and the reaction was filtered through silica gel (particle size 50 μL). The residue obtained by concentration was purified by medium pressure column chromatography (using Biotage SNAP Ultra column (particle size 25 μm), developing solvent = hexane / ethyl acetate) to obtain 79 mg of the desired biphenyl as a white powder (yield). Rate 85%). Identification of the target substance was carried out by 1H and 13C-NMR.

1H-NMR (CDCL3) = δ 7.62 (d, J = 7.3 Hz, 4H), 7.47 (t, J = 7.3 Hz, 4H), 7.37 (t, J = 7. 3 Hz, 2H)
13C-NMR (CDCL3) = δ 141.2, 128.7, 127.2, 127.1.

Example 12
In Example 11, the same experimental procedure was carried out except that 4-nitrobiphenyl 120 mg (0.60 mmol) was used instead of 3-nitrobiphenyl 120 mg (0.60 mmol). As a result, biphenyl was used as a white powder. 68 mg was obtained (yield 73%). Identification of the target substance was carried out by 1H and 13C-NMR.

1H-NMR (CDCL3) = δ 7.62 (d, J = 7.3 Hz, 4H), 7.46 (t, J = 7.3 Hz, 4H), 7.37 (t, J = 7. 3 Hz, 2H)
13C-NMR (CDCL3) = δ 141.2, 128.7, 127.2, 127.1.

Example 13
In Example 11, the same experimental procedure was carried out except that 4-nitro-4'-fluorobiphenyl 130 mg (0.60 mmol) was used instead of 3-nitrobiphenyl 120 mg (0.60 mmol). 93 mg of 4-fluorobiphenyl was obtained as a white powder (yield 90%). The identification of the target substance was carried out by 1H, 13C and 19F-NMR.

1H-NMR (CDCL3) = δ 7.58-7.51 (m, 4H), 7.44 (t, J = 7.3 Hz, 2H), 7.34 (t, J = 7.5 Hz, 1H), 7.13 (t, J = 8.7, 2H)
13C-NMR (CDCL3) = δ 162.4 (d, J = 246.3 Hz), 140.2, 137.3 (d, J = 3.8 Hz), 128.8, 128.7 (d, J = 7.7 Hz), 127.2, 127.0, 115.6 (d, J = 21.1 Hz)
19F-NMR (C6F6) = δ-116.3.

Example 14
Under nitrogen, in a 15 mL screw vial tube, stirrer, 2-nitroanisole 92 mg (0.60 mmol), dimesitylmethanol 242 mg (0.90 mmol), palladium acetylacetonate (II) 9.1 mg (0.030 mmol). , 2-Dicyclohexylphosphino-3,6-dimethoxy-2', 4', 6'-triisopropylbiphenyl 32 mg (0.060 mmol), tripotassium phosphate 318 mg (1.5 mmol), 1,2-dimethoxyethane 3 mL , And 120 μL of n-tridecane was added as an internal reference material. After tightly covering the vial tube, the mixture was heated and stirred at 130 ° C. for 9 hours. Then, the reaction solution was cooled to room temperature, a part of the reaction solution was collected, diluted with ethyl acetate and analyzed by gas chromatography. Anisole was detected in a yield of 93%.

Example 15
In Example 14, the same experimental procedure was carried out except that 2-nitroanisole 92 mg (0.60 mmol) was used instead of 2-nitroanisole 92 mg (0.60 mmol). Anisole was detected in 77% yield.

Example 16
In Example 14, the same experimental operation was carried out except that 2-nitroanisole 92 mg (0.60 mmol) was used instead of 2-nitroanisole 92 mg (0.60 mmol) and heating and stirring were performed for 12 hours. However, anisole was detected in a gas chromatography analysis with a yield of 68%.

Example 17
In Example 14, the same experimental operation was performed except that 2-t-butylnitrobenzene 107 mg (0.60 mmol) was used instead of 2-nitroanisole 92 mg (0.60 mmol) and heating and stirring were performed for 8 hours. As a result, t-butylbenzene was detected in a gas chromatography analysis with a yield of 83%.

Example 18
In Example 14, instead of using 92 mg (0.60 mmol) of 2-nitroanisole, 104 mg (0.60 mmol) of 1-nitronaphthalene was used, and 60 μL of n-decane was used instead of 120 μL of n-tridecane as an internal standard substance. When the same experimental operation was carried out except that heating and stirring were carried out for 8 hours, naphthalene was detected in a gas chromatography analysis with a yield of 92%.

Example 19
In Example 14, instead of using 92 mg (0.60 mmol) of 2-nitroanisole, 104 mg (0.60 mmol) of 2-nitronaphthalene was used, and 60 μL of n-decane was used instead of 120 μL of n-tridecane as an internal standard substance. When the same experimental operation was carried out except that heating and stirring were carried out for 8 hours, naphthalene was detected in a gas chromatography analysis with a yield of 52%.

Example 20
Under nitrogen, in a 4 mL screw vial tube, stir bar, 4-nitroanisole 31 mg (0.20 mmol), 2-propanol 17 mg (0.30 mmol), palladium acetylacetonate (II) 0.61 mg (2.0 μmol), 2-Cyclohexyl-5- (2,4,6-triisopropylphenyl) imidazole [1,5-a] pyridinium chloride 1.8 mg (4.0 μmol), tripotassium phosphate 106 mg (0.50 mmol), 1 , 4-Dioxane 1 mL, and 20 μL of n-tridecane as an internal standard were added. After tightly covering the vial tube, the mixture was heated and stirred at 130 ° C. for 12 hours. Next, the reaction solution was cooled to room temperature, a part of the reaction solution was collected, diluted with ethyl acetate, and gas chromatographic analysis was performed. As a result, anisole was detected in a yield of 21%.

Claims (2)

A metal catalyst that is a palladium compound , and the following general formula (4)

(In the formula, R ¹ independently represents a cyclohexyl group or a tert-butyl group, and R ² independently represents a hydrogen atom, a methyl group, a methoxy group, an isopropyl group, an isopropoxy group, or a dimethylamino. Represents a group or a sulfonic acid group.)
The aromatic compound is characterized by reacting an aromatic nitro compound with a proton-supplied compound in the presence of the phosphine compound represented by the above, and directly reducing the nitro group of the aromatic nitro compound to a hydrogen atom. Production method. The production method according to claim 1, wherein the proton-supplied compound is a primary or secondary alcohol compound.