JP2006248952A - Production method of ketone - Google Patents

Abstract

（式中、Ｒ¹は水素原子又は有機基を示す）で表されるアルコールと、下記式（２）
【化２】

（式中、Ｒ²、Ｒ³は、同一又は異なって、水素原子又は有機基を示す。Ｒ²及びＲ³は互いに結合して隣接する窒素原子と共に環を形成していてもよい）で表される窒素原子含有化合物とを反応させて、下記式（３）
【化３】

（式中、Ｒ¹、Ｒ²、Ｒ³は前記に同じ）で表されるケトンを生成させる。
【選択図】 なし
PROBLEM TO BE SOLVED: To provide a method capable of easily producing a ketone having a nitrogen atom at the α-position, such as α-aminoketone, with good yield.
In the presence of a group VIII element compound of the periodic table, the following formula (1)
[Chemical 1]

(Wherein R ¹ represents a hydrogen atom or an organic group) and the following formula (2)
[Chemical 2]

(Wherein R ² and R ³ are the same or different and each represents a hydrogen atom or an organic group. R ² and R ³ may be bonded to each other to form a ring with an adjacent nitrogen atom). And a nitrogen atom-containing compound to be reacted to form the following formula (3)
[Chemical 3]

(Wherein, R ¹ , R ² and R ³ are the same as above).
[Selection figure] None

Description

  The present invention relates to a method for producing a ketone using a periodic table group VIII element compound catalyst, more specifically, from a nitrogen atom-containing compound such as propargyl alcohol and amine using a periodic table group VIII element compound catalyst catalyst. The present invention relates to a method for producing a ketone having a nitrogen atom at the α-position, such as aminoketone.

  α-Amino ketone is a useful compound as a synthetic intermediate for β-amino alcohol. As a method for producing α-aminoketone, a method of reacting an α-diazocarbonyl compound and an amine is known (see Non-Patent Document 1). However, this method has problems such as a low yield and the need to use a reagent that is difficult to handle.

J. et al. Chem. Soc. Perkin Trans. 1, 1999, 3079

  Accordingly, an object of the present invention is to provide a method capable of easily and efficiently producing a ketone having a nitrogen atom at the α-position such as α-aminoketone.

  As a result of intensive studies to achieve the above object, the present inventors reacted propargyl alcohol or a derivative thereof with a nitrogen atom-containing compound such as a primary or secondary amine using a specific catalyst. It has been found that a ketone compound in which an acetylmethyl group or the like is bonded to a nitrogen atom of a nitrogen atom-containing compound can be efficiently obtained under mild conditions, and the present invention has been completed.

（式中、Ｒ¹は水素原子又は有機基を示す）
で表されるアルコールと、下記式（２）

（式中、Ｒ²、Ｒ³は、同一又は異なって、水素原子又は有機基を示す。Ｒ²及びＲ³は互いに結合して隣接する窒素原子と共に環を形成していてもよい）
で表される窒素原子含有化合物とを反応させて、下記式（３）

（式中、Ｒ¹、Ｒ²、Ｒ³は前記に同じ）
で表されるケトンを生成させることを特徴とするケトンの製造法を提供する。 That is, the present invention provides the following formula (1) in the presence of a group VIII element compound of the periodic table.

(Wherein R ¹ represents a hydrogen atom or an organic group)
And an alcohol represented by the following formula (2)

(In the formula, R ² and R ³ are the same or different and represent a hydrogen atom or an organic group. R ² and R ³ may be bonded to each other to form a ring with the adjacent nitrogen atom)
Is reacted with a nitrogen atom-containing compound represented by the following formula (3):

(Wherein R ¹ , R ² and R ³ are the same as above)
A method for producing a ketone, characterized in that a ketone represented by the formula:

  According to the production method of the present invention, a ketone compound having a nitrogen atom at the α-position, such as α-aminoketone, can be produced easily and in good yield under mild conditions.

[Group VIII element compound of the periodic table]
In the present invention, a Group VIII element compound (including a simple metal) is used as a catalyst. Examples of Group VIII elements of the periodic table include iron, ruthenium, osmium, cobalt, rhodium, iridium, nickel, palladium, and platinum. Among these, platinum group elements such as ruthenium, rhodium, palladium, osmium, iridium and platinum are preferable. In particular, iridium is preferred.

  Periodic table group VIII element compounds include a wide range of inorganic and organic compounds including group VIII elements of the periodic table. Examples of the inorganic compound include simple metals, oxides, sulfides, hydroxides, halides, sulfates, oxo acids containing periodic group VIII elements or salts thereof, and inorganic complexes. Examples of the organic compound include cyanide, organic acid salt (such as acetate), and organic complex. Among these, organic compounds such as organic complexes are preferable. The ligand of the complex includes a known ligand. The valence of the periodic table group VIII element in the periodic table group VIII element compound is about 0 to 6, preferably 0 to 3. In particular, in the case of an iridium compound, monovalent or trivalent is preferable. The Group VIII element compounds of the periodic table can be used alone or in combination of two or more.

  A typical example of a periodic table group VIII element compound is shown by taking iridium as an example. Examples of inorganic compounds include metal iridium, iridium oxide, iridium sulfide, iridium hydroxide, iridium fluoride, iridium chloride, iridium bromide, Examples thereof include iridium iodide, iridium sulfate, iridium acid or a salt thereof (for example, potassium iridate), an inorganic iridium complex [for example, hexaammineiridium (III) salt, chloropentammineiridium (III) salt, and the like].

As the organic iridium compound, for example, an organic iridium complex can be used in addition to iridium cyanide. Examples of the organic iridium complex include tris (acetylacetonato) iridium, dodecacarbonyltetrairidium (0), chlorotricarbonyliridium (I), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (Coe) ₂ ] ₂ ), di-μ-chlorotetrakis (ethylene) diiridium (I), di-μ-chlorobis (1,5-cyclooctadiene) diiridium (I) ([IrCl (cod)] ₂ ), Di-μ-chlorodichlorobis (1,2,3,4,5-pentamethylcyclopentadienyl) diiridium (III) ([Cp ^* IrCl ₂ ] ₂ ), trichlorotris (triethylphosphine) iridium ( III), pentahydridobis (trimethylphosphine) iridium (V), chlorocarbonylbis (trif Sulfonyl phosphine) iridium (I), chlorotris (triphenylphosphine) iridium _{(I) (IrCl (PPh 3} ) 3), chloroethylene bis (triphenylphosphine) iridium (I), dichlorobis (tricyclohexylphosphine) hydride iridium (IrHCl ₂ (PCy ₃ ) ₂ ), (pentamethylcyclopentadienyl) dicarbonyliridium (I), bis {1,2-bis (diphenylphosphino) ethane} iridium (I) chloride, pentamethylcyclopentadienyl Bis (ethylene) iridium (I), carbonylmethylbis (triphenylphosphine) iridium (I), (1,5-cyclooctadiene) (diphosphine) iridium (I) halide, 1,5-cyclooctadiene (1 , 2-bis (Gife Nylphosphino) ethane) iridium (I) hexafluorophosphate, (1,5-cyclooctadiene) bis (trialkylphosphine) iridium (I) halide, bis (1,5-cyclooctadiene) iridium tetrafluoroborate ([Ir (cod) ₂ ] ⁺ BF ₄ ⁻ ), (1,5-cyclooctadiene) (acetonitrile) iridium tetrafluoroborate, and the like.

Preferred iridium compounds include iridium complexes. Among these, organic iridium complexes, in particular, unsaturated hydrocarbons such as cyclopentene, dicyclopentadiene, cyclooctene, 1,5-cyclooctadiene, ethylene, pentamethylcyclopentadiene, benzene, toluene; nitriles such as acetonitrile; Ethers such as tetrahydrofuran; organic iridium complexes having phosphines such as triphenylphosphine as a ligand [for example, di-μ-chlorotetrakis (cyclooctene) diiridium (I), di-μ-chlorotetrakis (ethylene) Diiridium (I), di-μ-chlorobis (1,5-cyclooctadiene) diiridium (I), di-μ-chlorodichlorobis (1,2,3,4,5-pentamethylcyclopentadienyl ) Diiridium (III), chlorotris (trif Sulfonyl phosphine) iridium (I) (IrCl (PPh _{3) 3),} chloroethylene bis (triphenylphosphine) iridium (I), dichlorobis (tricyclohexylphosphine) hydride iridium, bis (1,5-cyclooctadiene) iridium tetra Fluoroborate, (1,5-cyclooctadiene) (acetonitrile) iridium tetrafluoroborate and the like] are preferable.

Examples of Group VIII element compounds other than iridium compounds include compounds corresponding to the above iridium compounds [for example, dichlorobis (1,5-cyclooctadiene) dirhodium ([RhCl (cod)] ₂ ), dichloro (1 , 5-cyclooctadiene) ruthenium (RuCl ₂ (cod)), dichloro (1,5-cyclooctadiene) platinum (PtCl ₂ (cod)), etc.], literatures (for example, the Chemical Society of Japan, 4th edition). Well-known compounds described in, for example, Experimental Experimental Chemistry Courses 17 and 18, published by Maruzen Co., Ltd.). In the periodic table group VIII element compounds (for example, platinum group element compounds) other than iridium, for example, cyclopentene, dicyclopentadiene, cyclooctene, 1,5-cyclooctadiene, ethylene, pentamethylcyclopentadiene, benzene, toluene, etc. An organic complex having, as a ligand, nitriles such as acetonitrile; ethers such as tetrahydrofuran; phosphines such as triphenylphosphine is particularly preferable. Of the periodic table group VIII element compounds, platinum group element compounds are preferred.

  The group VIII element compound of the periodic table can be used as it is or in a form supported on a carrier. Examples of the carrier include conventional carriers for supporting a catalyst, for example, metal oxides such as silica, alumina, silica-alumina, zeolite, titania, and magnesia, activated carbon, hydrotalcite, and hydroxyapatite. In the carrier-supported catalyst, the amount of the periodic table group VIII element compound supported is, for example, about 0.1 to 50% by weight, preferably about 1 to 20% by weight, based on the carrier. The catalyst can be supported by a conventional method such as an impregnation method, a precipitation method, or an ion exchange method.

  The amount of the periodic table group VIII element compound can be appropriately selected depending on the type of raw material, the type of catalyst, and the like, but in general, the alcohol represented by the formula (1) and the nitrogen represented by the formula (2) used as the raw material. For example, 0.0001 to 1 mol, preferably 0.001 to 0.3 mol, and more preferably about 0.005 to 0.1 mol with respect to 1 mol of the smaller component of the atom-containing compound.

  In the present invention, a group VIII element compound of the periodic table such as an organic complex can be used in combination with an appropriate ligand. Examples of the ligand include a phosphorus atom-containing ligand, an oxygen atom-containing ligand, a nitrogen atom-containing ligand, and a carbon-carbon double bond-containing ligand. As the ligand, a phosphorus atom-containing ligand can be suitably used. Examples of the phosphorus atom-containing ligand include monocycloalkyl ligands such as tricycloalkylphosphine such as tricyclohexylphosphine, trialkylphosphine such as trimethylphosphine and tributylphosphine, and triarylphosphine such as triphenylphosphine; -Bis (diarylphosphino) ethane, 1,3-bis (diphenylphosphino) propane, 1,4-bis (diphenylphosphino) butane, 2,3-bis (diphenylphosphino) butane, etc. (Fino) bidentate ligands such as alkanes.

  The amount of the ligand used can be appropriately selected within a range that does not inhibit the reaction, but generally, about 0.5 to 10 mol, preferably 1 to 5 mol, per 1 mol of the periodic table group VIII element compound. Degree.

  Moreover, the usage-amount of a ligand is a component (especially nitrogen atom containing compound) of the smaller one among the alcohol represented by Formula (1) used as a raw material, and the nitrogen atom containing compound represented by Formula (2), for example. You may select from the range of about 0.001-1 mol with respect to 1 mol, Preferably it is about 0.005-0.3 mol, More preferably, it is about 0.01-0.1 mol.

[base]
In the present invention, the reaction may be performed in the presence of a base. The use of a base may improve the reaction rate and reaction selectivity. The base may be any of an inorganic base, an organic base, a Lewis base and the like, and a base usually used for aldol condensation is preferable.

  Examples of the inorganic base include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide, and cesium hydroxide; alkali metal carbonates such as lithium carbonate, sodium carbonate, potassium carbonate, and cesium carbonate; hydrogen carbonate Alkali metal hydrogen carbonates such as sodium, potassium hydrogen carbonate and cesium hydrogen carbonate; Alkaline earth metal hydroxides such as magnesium hydroxide, calcium hydroxide and barium hydroxide; Alkaline earth such as magnesium carbonate, calcium carbonate and barium carbonate Metal carbonates; silver carbonate and the like.

  Examples of the organic base include alkali metal alkoxides such as sodium methoxide and sodium ethoxide; alkali metal organic acid salts such as sodium acetate; amines such as triethylamine, piperidine, N-methylpiperidine and pyridine (tertiary amine and the like) And nitrogen-containing heterocyclic compounds.

  Among these, in particular, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal carbonates such as sodium carbonate and cesium carbonate, alkali metal hydrogen carbonates such as sodium hydrogen carbonate, alkali metal alkoxides and alkali metals Alkali metal element-containing bases such as organic acid salts are preferred.

  The amount of base added varies depending on the type of raw material and the type of group VIII element compound in the periodic table, but usually contains the alcohol represented by formula (1) and the nitrogen atom represented by formula (2) used as the raw material. It is about 0.001-0.5 mol with respect to 1 mol of components (especially nitrogen atom containing compound) of the smaller one among compounds, Preferably it is about 0.005-0.2 mol.

[Alcohol represented by Formula (1)]
In the alcohol represented by formula (1) (propargyl alcohol or a derivative thereof), R ¹ represents a hydrogen atom or an organic group. The organic group may be any group that does not inhibit this reaction (for example, a group that is non-reactive under the reaction conditions in the present method). For example, a hydrocarbon group, a heterocyclic group, a substituted oxycarbonyl group ( An alkoxycarbonyl group, an aryloxycarbonyl group, an aralkyloxycarbonyl group, a cycloalkyloxycarbonyl group, etc.), a carboxyl group, a substituted or unsubstituted carbamoyl group, a cyano group, an acyl group (an acetyl, propionyl group or other aliphatic acyl group; aceto; Acetyl group; aromatic acyl group such as benzoyl group), substituted oxy group (alkoxy group such as C _1-6 alkoxy group such as methoxy group and ethoxy group); C _2-6 alkenyloxy group such as vinyloxy group and allyloxy group Alkenyloxy groups such as cyclohexyloxy groups; cycloalkyloxy groups such as cyclohexyloxy groups; Aralkyloxy groups such as benzyloxy group; alkoxy aryloxy group such as a group and acyloxy group such as acetoxy group), etc., and they are like two or more bonded groups. The carboxyl group or the like may be protected with a protective group known or commonly used in the field of organic synthesis, and may be substituted with a metal.

  The hydrocarbon group and the heterocyclic group also include a hydrocarbon group and a heterocyclic group having a substituent. The hydrocarbon group includes an aliphatic hydrocarbon group, an alicyclic hydrocarbon group, an aromatic hydrocarbon group, and a group in which these are bonded. Examples of the aliphatic hydrocarbon group include 1 to 20 carbon atoms (preferably 1 to 1) such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl, hexyl, decyl, and dodecyl groups. 10, more preferably an alkyl group of about 1 to 3); an alkenyl group of about 2 to 20 carbon atoms (preferably 2 to 10, more preferably 2 to 3) such as vinyl, allyl, 1-butenyl group; Examples thereof include alkynyl groups having about 2 to 20 carbon atoms (preferably 2 to 10, more preferably 2 to 3) such as propynyl groups.

As the alicyclic hydrocarbon group, a cycloalkyl group having about 3 to 20 members (preferably 3 to 15 members, more preferably 5 to 8 members) such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cyclooctyl groups; Cycloalkenyl groups of about 3 to 20 members (preferably 3 to 15 members, more preferably 5 to 8 members) such as pentenyl and cyclohexenyl groups; perhydronaphthalen-1-yl group, norbornyl, adamantyl, tetracyclo [4 4.0.1, ^2,5 . 1 ^7,10 ] bridged cyclic hydrocarbon groups such as dodecan-3-yl groups. Examples of the aromatic hydrocarbon group include aromatic hydrocarbon groups having about 6 to 14 (preferably 6 to 10) carbon atoms such as phenyl and naphthyl groups.

The hydrocarbon group in which an aliphatic hydrocarbon group and an alicyclic hydrocarbon group are bonded includes a cycloalkyl-alkyl group such as cyclopentylmethyl, cyclohexylmethyl, 2-cyclohexylethyl group (for example, C _3-20 cycloalkyl- C _1-4 alkyl group and the like). The hydrocarbon group in which an aliphatic hydrocarbon group and an aromatic hydrocarbon group are bonded to each other includes an aralkyl group (for example, a C _7-18 aralkyl group) and an alkyl-substituted aryl group (for example, about 1 to about 4). A phenyl group substituted with a C _1-4 alkyl group or a naphthyl group).

Preferred hydrocarbon groups include C _1-10 alkyl groups, C _2-10 alkenyl groups, C _2-10 alkynyl groups, C _3-15 cycloalkyl groups, C _6-14 aromatic hydrocarbon groups, C _3-15 A cycloalkyl-C _1-4 alkyl group, a C _7-14 aralkyl group and the like are included.

  The hydrocarbon group includes various substituents such as halogen atoms, oxo groups, hydroxyl groups, substituted oxy groups (for example, alkoxy groups, aryloxy groups, aralkyloxy groups, acyloxy groups, etc.), carboxyl groups, substituted oxycarbonyls. Groups (alkoxycarbonyl groups, aryloxycarbonyl groups, aralkyloxycarbonyl groups, etc.), substituted or unsubstituted carbamoyl groups, cyano groups, nitro groups, acyl groups, substituted or unsubstituted amino groups, sulfo groups, heterocyclic groups, etc. You may have. The hydroxyl group and carboxyl group may be protected with a protective group commonly used in the field of organic synthesis. In addition, an aromatic or non-aromatic heterocycle may be condensed with the ring of the alicyclic hydrocarbon group or aromatic hydrocarbon group.

The heterocyclic ring constituting the heterocyclic group for R ¹ includes an aromatic heterocyclic ring and a non-aromatic heterocyclic ring. Examples of such a heterocyclic ring include a heterocyclic ring containing an oxygen atom as a hetero atom (for example, 5-membered ring such as furan, tetrahydrofuran, oxazole, isoxazole, and γ-butyrolactone ring, 4-oxo-4H-pyran, tetrahydro 6-membered ring such as pyran, morpholine ring, condensed ring such as benzofuran, isobenzofuran, 4-oxo-4H-chromene, chroman, isochroman ring, 3-oxatricyclo [4.3.1.1 ^4,8 ] undecane 2-one ring, a bridged ring such as 3-oxatricyclo [4.2.1.0 ^4,8 ] nonan-2-one ring), a heterocycle containing a sulfur atom as a hetero atom (for example, thiophene, 5-membered ring such as thiazole, isothiazole, thiadiazole ring, 6-membered ring such as 4-oxo-4H-thiopyran ring, benzothiophene ring Any condensed ring), heterocycles containing nitrogen atoms as heteroatoms (eg, 5-membered rings such as pyrrole, pyrrolidine, pyrazole, imidazole, and triazole rings, 6-membered rings such as pyridine, pyridazine, pyrimidine, pyrazine, piperidine, and piperazine rings) Ring, indole, indoline, quinoline, acridine, naphthyridine, quinazoline, a condensed ring such as a purine ring, etc.). In addition to the substituents that the hydrocarbon group may have, the heterocyclic group includes an alkyl group (eg, a C _1-4 alkyl group such as a methyl or ethyl group), a cycloalkyl group, an aryl group It may have a substituent such as (for example, phenyl, naphthyl group).

Preferred R ¹ is a hydrogen atom, a hydrocarbon group (eg, C _1-10 alkyl group, C _2-10 alkenyl group, C _2-10 alkynyl group, C _3-15 cycloalkyl group, C _6-14 aromatic group) Hydrocarbon group, C _3-12 cycloalkyl-C _1-4 alkyl group, C _7-14 aralkyl group, etc.).

  Representative examples of the alcohol represented by the formula (1) include propargyl alcohol, 1-methylpropargyl alcohol, 1-ethylpropargyl alcohol, 1-propylpropargyl alcohol, 1-isopropylpropargyl alcohol, 1-cyclohexylpropargyl alcohol, 1 -Phenylpropargyl alcohol, 1-benzylpropargyl alcohol, 1- (2-pyridyl) propargyl alcohol and the like.

[Nitrogen atom-containing compound represented by formula (2)]
In the nitrogen atom-containing compound represented by the formula (2), R ² and R ³ are the same or different and represent a hydrogen atom or an organic group. R ³ and R ⁴ may be bonded to each other to form a ring together with the adjacent nitrogen atom. The nitrogen atom-containing compound represented by the formula (2) includes primary amines, secondary amines (chain secondary amines, cyclic amines), amides, lactams, and the like. Of these, secondary amines and lactams are particularly suitable.

The organic group may be any group that does not inhibit this reaction (for example, a group that is non-reactive under the reaction conditions in this method), and examples thereof include the same organic groups as those described above for R ¹ . The Representative organic groups include hydrocarbon groups, acyl groups, heterocyclic groups, and the like. Examples of the hydrocarbon group, acyl group, and heterocyclic group are the same as the hydrocarbon group, acyl group, and heterocyclic group in R ¹ . The hydrocarbon group, acyl group and heterocyclic group also include a hydrocarbon group having a substituent, an acyl group and a heterocyclic group (including cases where a ring is condensed to these). The substituent is not particularly limited as long as it does not inhibit the reaction, and examples thereof include the same substituents that the hydrocarbon group and heterocyclic group in R ¹ and the like may have.

The ring formed by combining R ² and R ³ together with the adjacent nitrogen atom other than the nitrogen atom shown in formula (2), such as a pyrrolidine ring, piperidine ring, piperazine ring, morpholine ring, thiomorpholine ring, etc. And a non-aromatic ring having about 3 to 20 members (preferably 3 to 15 members, more preferably 5 to 12 members) which may contain a hetero atom such as a nitrogen atom, an oxygen atom or a sulfur atom. Ring or heterocyclic ring). These rings have various substituents such as halogen atoms, alkyl groups (eg, C _1-6 alkyl groups such as methyl, ethyl, propyl, isopropyl and butyl groups), alkenyl groups (eg, vinyl, allyl groups). C _2-6, etc. alkenyl group), an alkynyl group such as (e.g., C _2-6 alkynyl group such as propynyl group), a cycloalkyl group, a cycloalkenyl group, an aryl group (e.g., phenyl group, naphthyl group), Aralkyl groups (eg, benzyl group, phenylethyl group, etc.), oxo groups, hydroxyl groups, substituted oxy groups (eg, alkoxy groups, aryloxy groups, aralkyloxy groups, acyloxy groups, etc.), carboxyl groups, substituted oxycarbonyl groups ( Alkoxycarbonyl group, aryloxycarbonyl group, aralkyloxycarbonyl group, etc. , Substituted or unsubstituted carbamoyl group, a cyano group, a nitro group, an acyl group (e.g., an acyl group of the illustration), a substituted or unsubstituted amino group, a sulfo group, a heterocyclic group (e.g., heterocycle in said R ¹ And a group represented as a formula group). In addition, the above rings include aromatic hydrocarbon rings such as benzene rings, alicyclic rings such as cyclohepentane rings and cyclohexane rings, aromatic heterocyclic rings such as pyridine rings, and non-aromatic heterocycles such as piperidine rings. The ring may be condensed.

Preferred R ² and R ³ include a hydrogen atom, a hydrocarbon group (for example, a C _1-10 alkyl group, a C _2-10 alkenyl group, a C _2-10 alkynyl group, a C _3-15 cycloalkyl group, a C _{6- 14} aromatic hydrocarbon group, C _3-12 cycloalkyl-C _1-4 alkyl group, C _7-14 aralkyl group, etc.), heterocyclic group (for example, at least selected from nitrogen atom, oxygen atom and sulfur atom) Heterocyclic groups having about 3 to 15 membered heterocycles containing one heteroatom) and the like. It is also preferred that R ² and R ³ form a nitrogen-containing ring of about 3 to 20 members with the adjacent nitrogen atom.

  Representative examples of the primary amine among the nitrogen atom-containing compounds represented by the formula (2) include, for example, methylamine, ethylamine, propylamine, isopropylamine, butylamine, isobutylamine, t-butylamine, pentylamine. , Saturated or unsaturated aliphatic primary amines having about 1 to 30 carbon atoms (preferably 1 to 20, more preferably 1 to 15) such as hexylamine, decylamine, ethylenediamine and allylamine; cyclopentylamine, cyclohexylamine, 1 Saturated or unsaturated alicyclic primary amines such as aminoadamantane; aromatic primary amines such as aniline, toluidine, benzylamine, 2-phenylethylamine; heterocyclic primary amines such as 2-aminopyridine Etc.

  Typical examples of the chain secondary amine among the nitrogen atom-containing compounds represented by the formula (2) include dimethylamine, diethylamine, dipropylamine, dibutylamine, N-methylaniline, N-ethylaniline, diphenylamine. Etc.

  Among the nitrogen atom-containing compounds represented by formula (2), typical examples of cyclic amines include pyrrolidine, piperidine, 2-methylpiperazine, 3-methylpiperazine, 4-methylpiperidine, 4-hydroxypiperidine, perhydroazo. Syn, piperazine, morpholine, thiomorpholine, 1,2,3,4-tetrahydroquinoline, 6-methyl-1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, indoline, isoindoline Etc.

  Of the nitrogen atom-containing compounds represented by the formula (2), typical examples of amides include N-free compounds such as acetamide, N-methylacetamide, propanamide, N-methylpropanamide, butanamide, pentanamide, and hexaneamide. Substituted or monosubstituted aliphatic carboxylic acid amides; N-unsubstituted or monosubstituted alicyclic carboxylic acid amides such as cyclohexanecarboxamide; N-unsubstituted or monosubstituted aromatic carboxylic acid amides such as benzamide or N-methylbenzamide; 2 -N-unsubstituted or monosubstituted heterocyclic carboxylic acid amides such as pyridinecarboxamide.

  Representative examples of lactams among the nitrogen atom-containing compounds represented by formula (2) include 2-pyrrolidone (γ-butyrolactam), 2-pyridone (δ-valerolactam), and ε-caprolactam.

  In the present invention, a compound having a moiety corresponding to propargyl alcohol and a moiety corresponding to a primary or secondary amine in the same molecule (propargyl alcohol derivative having a primary or secondary amino group) It can also be used as a reaction raw material. In this case, a cyclic compound reacted in the molecule is obtained.

[reaction]
The reaction of the alcohol represented by the formula (1) and the nitrogen atom-containing compound represented by the formula (2) is performed in the presence or absence of a solvent. Examples of the solvent include aliphatic hydrocarbons such as hexane, heptane, and octane; alicyclic hydrocarbons such as cyclohexane; aromatic hydrocarbons such as benzene, toluene, xylene, and ethylbenzene; chloroform, dichloromethane, 1,2- Halogenated hydrocarbons such as dichloroethane; ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran and dioxane; amides such as N, N-dimethylformamide and N, N-dimethylacetamide. These solvents are used alone or in admixture of two or more.

  The ratio of the alcohol represented by the formula (1) and the nitrogen atom-containing compound represented by the formula (2) can be appropriately selected in consideration of the reactivity, the raw material cost and the like. Usually, the usage-amount of alcohol represented by Formula (1) is about 0.1-100 mol with respect to 1 mol of nitrogen atom containing compounds represented by Formula (2), Preferably it is 0.5-50 mol. The degree is more preferably about 0.8 to 10 mol.

  A small amount of a carbonyl compound (ketone or aldehyde) corresponding to the alcohol represented by the formula (1) may be added to the reaction system. The reaction rate may be improved by adding the carbonyl compound.

  The reaction may be performed in the presence of a polymerization inhibitor. The reaction temperature can be appropriately selected according to the reaction components and the type of catalyst, and is, for example, about 20 to 200 ° C, preferably about 40 to 180 ° C, and more preferably about 50 to 130 ° C. The reaction may be carried out at normal pressure or under reduced pressure or increased pressure. The atmosphere of the reaction is not particularly limited as long as the reaction is not inhibited, and may be any of an air atmosphere, a nitrogen atmosphere, an argon atmosphere, and the like. Further, the reaction can be carried out by any method such as batch, semi-batch and continuous methods.

  In the method of the present invention, a ketone (α-aminoketone or the like) represented by the corresponding formula (3) is produced by the reaction under mild conditions. After completion of the reaction, the reaction product can be separated and purified by separation means such as filtration, concentration, distillation, extraction, crystallization, recrystallization, column chromatography, etc., or a separation means combining these. The ketone represented by the formula (3) thus obtained can be used as an intermediate raw material for fine chemicals.

  Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not limited to these examples.

Example 1
The reactor was charged with propargyl alcohol (2 mmol), morpholine (1 mmol), di-μ-chlorobis (1,5-cyclooctadiene) diiridium (I) ([IrCl (cod)] ₂ ) (0.01 mmol). ), Sodium carbonate (0.03 mmol) and toluene (2 ml) were added, and the mixture was stirred at 100 ° C. for 3 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (acetylmethyl) morpholine (= α-morpholinoacetone) was obtained in a yield of 50%. The conversion rate of morpholine was 76%.

Example 2
The reactor was charged with propargyl alcohol (2 mmol), morpholine (1 mmol), di-μ-chlorobis (1,5-cyclooctadiene) diiridium (I) ([IrCl (cod)] ₂ ) (0.02 mmol). ), Sodium carbonate (0.03 mmol) and toluene (2 ml) were added, and the mixture was stirred at 100 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (acetylmethyl) morpholine was obtained in a yield of 72%. The conversion rate of morpholine was 96%.

Example 3
The reactor was charged with propargyl alcohol (2 mmol), morpholine (1 mmol), di-μ-chlorobis (1,5-cyclooctadiene) diiridium (I) ([IrCl (cod)] ₂ ) (0.01 mmol). ) And toluene (2 ml) were added, and the mixture was stirred at 100 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (acetylmethyl) morpholine was obtained in a yield of 68%. The conversion rate of morpholine was 95%.

Example 4
The reactor was charged with propargyl alcohol (2 mmol), morpholine (1 mmol), di-μ-chlorobis (1,5-cyclooctadiene) diiridium (I) ([IrCl (cod)] ₂ ) (0.02 mmol). ), Sodium carbonate (0.03 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (acetylmethyl) morpholine was obtained in a yield of 76%. The conversion rate of morpholine was 91%.

Example 5
The reactor was charged with propargyl alcohol (2 mmol), morpholine (1 mmol), chlorotris (triphenylphosphine) iridium (I) (IrCl (PPh ₃ ) ₃ ) (0.02 mmol), sodium carbonate (0.03 mmol). And toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (acetylmethyl) morpholine was obtained in a yield of 70%. The conversion rate of morpholine was 85%.

Example 6
The reactor was charged with propargyl alcohol (2 mmol), morpholine (1 mmol), di-μ-chlorodichlorobis (1,2,3,4,5-pentamethylcyclopentadienyl) diiridium (III) ([Cp ^* IrCl ₂ ] ₂ ) (0.02 mmol), sodium carbonate (0.03 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (acetylmethyl) morpholine was obtained in a yield of 6%. The conversion rate of morpholine was 30%.

Example 7
To the reactor was added propargyl alcohol (2 mmol), morpholine (1 mmol), bis (1,5-cyclooctadiene) iridium tetrafluoroborate ([Ir (cod) ₂ ] ⁺ BF ₄ ⁻ ) (0.02 mmol). , Sodium carbonate (0.03 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (acetylmethyl) morpholine was obtained in a yield of 84%.

Example 8
The reactor was charged with propargyl alcohol (2 mmol), morpholine (1 mmol), dichlorobis (tricyclohexylphosphine) hydridoiridium (IrHCl ₂ (PCy ₃ ) ₂ ) (0.02 mmol), sodium carbonate (0.03 mmol) and Toluene (2 ml) was added and stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (acetylmethyl) morpholine was obtained in a yield of 56%. The conversion rate of morpholine was 64%.

Example 9
The reactor was charged with propargyl alcohol (2 mmol), morpholine (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ) (0.02 mmol), carbonic acid. Sodium (0.03 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (acetylmethyl) morpholine was obtained in a yield of 86%. The conversion rate of morpholine was 95%.

Example 10
A reactor is charged with propargyl alcohol (2 mmol), morpholine (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ) (0.012 mmol), carbonic acid. Sodium (0.03 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 40 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (acetylmethyl) morpholine was obtained in a yield of 97%. The conversion rate of morpholine was 100%.

Example 11
The reactor was charged with 1-methylpropargyl alcohol (2 mmol), morpholine (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ) (0.02 mmol). ), Sodium carbonate (0.03 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (1-acetylethyl) morpholine was obtained in a yield of 23%.

Example 12
The reactor was charged with 1-phenylpropargyl alcohol (2 mmol), morpholine (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ) (0.02 mmol). ), Sodium carbonate (0.03 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (1-acetyl-1-phenylmethyl) morpholine was obtained in a yield of 31%.

Example 13
The reactor was charged with propargyl alcohol (2 mmol), piperidine (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ) (0.02 mmol), carbonic acid. Sodium (0.03 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (acetylmethyl) piperidine was obtained in a yield of 42%.

Example 14
The reactor was charged with propargyl alcohol (2 mmol), dibutylamine (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ) (0.02 mmol), Sodium carbonate (0.03 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N-acetylmethyl-N, N, -dibutylamine was obtained in a yield of 83%.

Example 15
The reactor was charged with propargyl alcohol (2 mmol), 2-methylpiperidine (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ) (0.02 mmol). ), Sodium carbonate (0.03 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N-acetylmethyl-2-methylpiperidine was obtained in a yield of 18%.

Example 16
The reactor was charged with propargyl alcohol (2 mmol), 2-pyrrolidone (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ) (0.02 mmol). , Sodium carbonate (0.03 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography to obtain N-acetylmethyl-2-pyrrolidone in a yield of 5%.

Example 17
The reactor was charged with propargyl alcohol (2 mmol), piperazine (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ) (0.02 mmol), carbonic acid. Sodium (0.03 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (acetylmethyl) piperazine was obtained in a yield of 35% and N, N'-bis (acetylmethyl) piperazine was obtained in a yield of 22%. Was obtained.

Example 18
A reactor is charged with propargyl alcohol (2 mmol), aniline (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ) (0.02 mmol), carbonic acid. Sodium (0.03 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (acetylmethyl) aniline was obtained in a yield of 30%.

Example 19
The reactor was charged with propargyl alcohol (2 mmol), thiomorpholine (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ) (0.02 mmol), Sodium carbonate (0.03 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (acetylmethyl) thiomorpholine was obtained in a yield of 50%.

Example 20
The reactor was charged with propargyl alcohol (2 mmol), N-ethylaniline (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ) (0.02 mmol). ), Sodium carbonate (0.03 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N-acetylmethyl-N-ethylaniline was obtained in a yield of 36%.

Example 21
A reactor was charged with propargyl alcohol (2 mmol), butylamine (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ) (0.02 mmol), carbonic acid. Sodium (0.03 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (acetylmethyl) butylamine was obtained in a yield of 36%.

Example 22
The reactor was charged with propargyl alcohol (2 mmol), diphenylamine (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ) (0.02 mmol), carbonic acid. Sodium (0.03 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N-acetylmethyl-N, N-diphenylamine was obtained in a yield of 19%.

Example 23
The reactor was charged with propargyl alcohol (2 mmol), 3-methylpiperidine (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ) (0.02 mmol). ), Sodium carbonate (0.03 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N-acetylmethyl-3-methylpiperidine was obtained in a yield of 56%.

Example 24
The reactor was charged with propargyl alcohol (2 mmol), 1,2,3,4-tetrahydroisoquinoline (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] _2. ) (0.012 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N-acetylmethyl-1,2,3,4-tetrahydroisoquinoline was obtained in a yield of 36%. The conversion of 1,2,3,4-tetrahydroisoquinoline was 95%.

Example 25
To the reactor, 1-phenylpropargyl alcohol (2 mmol), 1,2,3,4-tetrahydroisoquinoline (1 mmol), di-μ-chlorobis (1,5-cyclooctadiene) diiridium (I) ( IrCl (cod)] ₂ ) (0.012 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (1-acetyl-1-phenylmethyl) -1,2,3,4-tetrahydroisoquinoline was obtained in a yield of 13%. It was. The conversion of 1,2,3,4-tetrahydroisoquinoline was 44%.

Example 26
The reactor is charged with propargyl alcohol (2 mmol), indoline (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ) (0.012 mmol), and Toluene (2 ml) was added and stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (acetylmethyl) indoline was obtained in a yield of 33%. The conversion of indoline was 90%.

Example 27
The reactor was charged with 1-phenylpropargyl alcohol (2 mmol), indoline (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ) (0.012 mmol). ) And toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 20 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (1-acetyl-1-phenylmethyl) indoline was obtained in a yield of 42%. The conversion of indoline was 88%.

Example 28
The reactor was charged with propargyl alcohol (2 mmol), 1,2,3,4-tetrahydroquinoline (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] _2. ) (0.012 mmol) and toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N-acetylmethyl-1,2,3,4-tetrahydroquinoline was obtained in a yield of 18%. The conversion of 1,2,3,4-tetrahydroquinoline was 92%.

Example 29
The reactor was charged with propargyl alcohol (2 mmol), 6-methyl-1,2,3,4-tetrahydroquinoline (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe ) ₂ ] ₂ ) (0.012 mmol) and toluene (3 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N-acetylmethyl-6-methyl-1,2,3,4-tetrahydroquinoline was obtained in a yield of 21%. The conversion of 6-methyl-1,2,3,4-tetrahydroquinoline was 95%.

Example 30
The reactor was charged with propargyl alcohol (2 mmol), 4-hydroxypiperidine (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ) (0.012 mmol). ) And toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N-acetylmethyl-4-hydroxypiperidine was obtained in a yield of 23%. The conversion of 4-hydroxypiperidine was 93%.

Example 31
The same operation as in Example 30 was performed except that the reaction temperature was 100 ° C. As a result, N-acetylmethyl-4-hydroxypiperidine was obtained in a yield of 21%. The conversion of 4-hydroxypiperidine was 92%.

Example 32
Instead of di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ), dichlorobis (1,5-cyclooctadiene) dirhodium ([RhCl (cod)] ₂ ) The same operation as in Example 30 was performed except that (0.012 mmol) was used. As a result, N-acetylmethyl-4-hydroxypiperidine was obtained in a yield of 5%. The conversion of 4-hydroxypiperidine was 38%.

Example 33
Instead of di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ), dichloro (1,5-cyclooctadiene) ruthenium (RuCl ₂ (cod)) (0. The same operation as in Example 30 was performed except that 012 mmol) was used. As a result, N-acetylmethyl-4-hydroxypiperidine was obtained in a yield of 21%. The conversion of 4-hydroxypiperidine was 78%.

Example 34
Instead of di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ), dichloro (1,5-cyclooctadiene) platinum (PtCl ₂ (cod)) (0. The same operation as in Example 30 was performed except that 012 mmol) was used. As a result, N-acetylmethyl-4-hydroxypiperidine was obtained in a yield of 17%. The conversion of 4-hydroxypiperidine was 89%.

Example 35
Instead of di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ), di-μ-chlorobis (1,5-cyclooctadiene) diiridium (I) ([ The same procedure as in Example 30 was performed, except that IrCl (cod)] ₂ ) (0.012 mmol) was used. As a result, N-acetylmethyl-4-hydroxypiperidine was obtained with a yield of 15%. The conversion of 4-hydroxypiperidine was 75%.

Example 36
Instead of di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ), bis (1,5-cyclooctadiene) iridium tetrafluoroborate ([Ir (cod) ₂ ] ⁺ BF ₄ ^-) (0.012 mmol) was used was the same procedure as in example 30. As a result, N-acetylmethyl-4-hydroxypiperidine was obtained with a yield of 15%. The conversion of 4-hydroxypiperidine was 60%.

Example 37
The reactor was charged with propargyl alcohol (2 mmol), perhydroazepine (1 mmol), di-μ-chlorotetrakis (cyclooctene) diiridium (I) ([IrCl (coe) ₂ ] ₂ ) (0.012 mmol). And toluene (2 ml) were added, and the mixture was stirred at 80 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, the reaction solution was concentrated and purified by silica gel column chromatography. As a result, N- (acetylmethyl) perhydroazepine was obtained in a yield of 10%. The conversion rate of perhydroazepine was 90%.

Example 38
The same operation as in Example 37 was performed except that 0.03 mmol of sodium carbonate was added to the reaction system. As a result, N- (acetylmethyl) perhydroazepine was obtained in a yield of 18%. The conversion rate of perhydroazepine was 85%.

Claims (1)

In the presence of a group VIII element compound of the periodic table, the following formula (1)

(Wherein R ¹ represents a hydrogen atom or an organic group)
And an alcohol represented by the following formula (2)

(In the formula, R ² and R ³ are the same or different and represent a hydrogen atom or an organic group. R ² and R ³ may be bonded to each other to form a ring with the adjacent nitrogen atom)
Is reacted with a nitrogen atom-containing compound represented by the following formula (3):

(Wherein R ¹ , R ² and R ³ are the same as above)
A method for producing a ketone, characterized in that a ketone represented by the formula: