WO2015075981A1 - Method for producing carbonyl compound - Google Patents

Abstract

In order to provide a method for producing a carbonyl compound with an improved yield, the present invention produces a carbonyl compound represented by general formula (I) by removing the carbonylalkoxy from a compound represented by general formula (II) while in the presence of a tertiary amine organic carboxylate and a halide salt. (In the formula, R¹ represents a C1-4 alkyl group.)

Description

Method for producing carbonyl compound

The present invention relates to a method for producing a carbonyl compound, and more particularly to a method for producing a carbonyl compound by dealkoxycarbonylating a β-ketoester compound.

As compounds that can be used as active ingredients such as agricultural and horticultural agents and industrial material protecting agents, Patent Document 1 discloses certain 2- (halogenated hydrocarbon substitution) -5-benzyl-1-azolylmethylcyclopenes. Tanol derivatives are described. In this document, as part of the steps in the method for producing the derivative, a 1-benzyl-2-oxocyclopentanecarboxylic acid alkyl ester derivative, which is a β-ketoester compound, is protected from 2-benzyl-5 having a hydroxy group protected. , 5-bis (hydroxymethyl) cyclopentanone derivatives are described.

International Publication WO2011 / 077071 (released on June 16, 2011)

In order to produce 2- (halogenated hydrocarbon-substituted) -5-benzyl-1-azolylmethylcyclopentanol derivatives, which are used as active ingredients in agricultural and horticultural agents, at lower cost and in large quantities, It is required to improve the yield of 2-benzyl-5,5-bis (hydroxymethyl) cyclopentanone derivative in which is protected.

Therefore, the present invention has been made in view of the above problems, and an object of the present invention is to provide a novel production method capable of producing a carbonyl compound from a β-ketoester compound at a low cost and in a high yield.

A method for producing a carbonyl compound according to the present invention is a method for producing a carbonyl compound represented by the following general formula (I) from a compound represented by the following general formula (II), which is an organic carboxylate of a tertiary amine And a compound in which dealkoxycarbonylation of the compound represented by the following general formula (II) is carried out in the presence of a halogenated salt.

(In the general formula (II), Z ¹ represents a substituted or unsubstituted alkyl group, cycloalkyl group, aryl group or heterocyclic group, and Z ³ and Z ² independently represent a hydrogen atom, or a substituted or unsubstituted group. Represents a substituted alkyl group, cycloalkyl group, aryl group or heterocyclic group, and R ¹ represents an alkyl group having 1 to 4 carbon atoms, and Z ¹ and Z ² may be bonded to each other.

(In general formula (I), Z ¹ , Z ² and Z ³ are the same as Z ¹ , Z ² and Z ^{3 in} general formula (II), respectively.)

By the method for producing a carbonyl compound according to the present invention, a carbonyl compound can be produced from a β-ketoester compound at a low cost and in a high yield.

As a result of intensive studies by the present inventors, the hydroxy group was protected from a 1-benzyl-3,3-bis (hydroxymethyl) -2-oxocyclopentanecarboxylic acid alkyl ester derivative in which the hydroxy group was protected. -In the production process of obtaining a benzyl-2,2-bis (hydroxymethyl) cyclopentanone derivative, by performing a reaction using (a) an organic carboxylate of a tertiary amine, and (b) a halogenated salt. The yield of 5-benzyl-2,2-bis (hydroxymethyl) cyclopentanone derivatives protected with a hydroxy group was found to be improved, and carbonyl compounds were also used in reactions using other β-ketoester compounds. It has been found that it can be produced at a low cost and with a high yield, and the present invention has been completed.

Hereinafter, an embodiment of a method for producing a carbonyl compound according to the present invention will be described.

The method for producing a carbonyl compound according to the present invention is a method for producing a carbonyl compound represented by the following general formula (I) from a β-ketoester compound represented by the following general formula (II) (hereinafter referred to as compound (II)). In the presence of (a) an organic carboxylate salt of a tertiary amine and (b) a halogenated salt, the compound (II) is subjected to dealkoxycarbonylation, which is represented by the general formula (I). This is a method for obtaining a carbonyl compound.

Here, Z ¹ represents an alkyl group, a cycloalkyl group, an aryl group or a heterocyclic group, and the alkyl group, cycloalkyl group, aryl group and heterocyclic group may have a substituent. .

The number of carbon atoms of the alkyl group in Z ¹ is not particularly limited, and examples of the alkyl group include alkyl groups having 1 to 8 carbon atoms. Examples of the alkyl group having 1 to 8 carbon atoms include a methyl group, an ethyl group, a (1-methyl) ethyl group, an n-propyl group, a 1-methylpropyl group, a 2-methylpropyl group, and 1,1-dimethylethyl. Group, n-butyl group, n-pentyl group, n-hexyl group, n-heptyl group, n-octyl group and the like.

The number of carbon atoms constituting the ring of the cycloalkyl group in Z ¹ is not particularly limited, and examples of the cycloalkyl group include cycloalkyl groups having 3 to 6 carbon atoms. Examples of the cycloalkyl group having 3 to 6 carbon atoms include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group.

Examples of the aryl group in Z ¹ include a phenyl group, a naphthyl group, an indene group, an azulene group, and a diphenyl group.

There is no particular limitation on the number of atoms constituting the ring of the heterocyclic group in Z ^1. Examples of the heterocyclic group include 3 to 6-membered aliphatic heterocyclic groups and 5 to 6-membered aromatic heterocyclic groups. Can be mentioned. Examples of the heterocyclic ring constituting the 3- to 6-membered aliphatic heterocyclic ring include azetidine, aziridine, piperidine, piperazine, morpholine, pyrrolidine, oxetane, tetrahydrofuran and tetrahydropyran. Examples of the heterocyclic ring constituting the 5- to 6-membered aromatic heterocyclic group include thiophene, pyridine, thiazole, furan, pyrrole, oxazole, isoxazole, isothiazole, triazole, furasan, imidazole, pyrazole, pyrazine, and pyrimidine. , Triazine and pyridazine. In addition, examples of the heterocyclic group in Z ¹ include condensed heterocyclic rings such as indole, benzofuran, benzothiophene, quinoline, and quinoxaline.

Examples of the substituent that the alkyl group, cycloalkyl group, aryl group and heterocyclic group in Z ¹ may have include a halogen atom, an aliphatic hydrocarbon group, an aromatic hydrocarbon group, an aromatic heterocyclic group, one or more hydrogen atoms Examples thereof include an aliphatic hydrocarbon group in which an atom is substituted with an aromatic hydrocarbon group or an aromatic heterocyclic group, an alkoxy group, an alkylcarbonylalkyl group, an amide group, a cyano group, and a nitro group. Further, the hydrogen atom in these substituents may be further substituted with a halogen atom, a hydroxy group, an alkoxy group, an alkyl group, a haloalkyl group, an aromatic hydrocarbon group, an aromatic heterocyclic group or the like. Further, the hydroxy group may be protected by a protecting group that protects the hydroxy group.

Z ² and Z ³ independently represent a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group or a heterocyclic group, and the alkyl group, cycloalkyl group, aryl group and heterocyclic group each represent a substituent. You may have. The alkyl group, cycloalkyl group, aryl group, and heterocyclic group in Z ² and Z ³ , and the substituent that the alkyl group, cycloalkyl group, aryl group, and heterocyclic group may have are each alkyl in Z ¹ Examples thereof include the same groups as the substituents that the group, cycloalkyl group, aryl group and heterocyclic group, and the alkyl group, cycloalkyl group, aryl group and heterocyclic group may have.

Z ² and Z ³ may be the same as each other or different from each other.

Z ¹ and Z ² may be bonded to each other to form a ring together with the carbon atom to which Z ¹ is bonded and the carbon atom to which Z ² is bonded.

R ¹ represents an alkyl group having 1 to 4 carbon atoms. Examples of the alkyl group having 1 to 4 carbon atoms include methyl group, ethyl group, (1-methyl) ethyl group, n-propyl group, 1-methylpropyl group, 2-methylpropyl group, n-butyl group and 1 , 1-dimethylethyl group and the like.

Examples of the tertiary amine that forms the organic carboxylate of tertiary amine include trimethylamine, triethylamine, ethyldimethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine, triisobutylamine, Tri-sec-butylamine, tri-tert-butylamine, tri-n-pentylamine, tri-n-hexylamine, tri-n-octylamine, diethylisopropylamine, diisopropylethylamine, tricyclopropylamine, tricyclobutylamine, tetra Aliphatic amines such as methylethylenediamine, tricyclopentylamine and tricyclohexylamine; N-methylpyrrolidine, N-ethylpyrrolidine, N-methylpiperidine, N-ethylpiperidine, N- -Butylpiperidine, N-methylhexamethyleneimine, N-ethylhexamethyleneimine, N-methylmorpholine, N-ethylmorpholine, N-butylmorpholine, N, N'-dimethylpiperazine, N, N'-diethylpiperazine, 1 , 5-diazabicyclo [4.3.1] no-5-ene, 1,4-diazabicyclo [2.2.2] octane, 1,8-diazabicyclo [5.4.0] unde-7-cene, etc. And nitrogen-containing heterocyclic aliphatic amines; and nitrogen-containing heterocyclic aromatic amines such as pyridine, collidine, picoline and lutidine. Among them, triethylamine, trimethylamine, ethyldimethylamine, N-methylpyrrolidine, pyridine, collidine or picoline is preferable, triethylamine, trimethylamine, pyridine or picoline is more preferable, and triethylamine or pyridine is more preferable. Particularly preferred is triethylamine.

The organic carboxylic acid constituting the organic carboxylate of the tertiary amine is preferably an organic monocarboxylic acid, more preferably a saturated or unsaturated aliphatic monocarboxylic acid, and even more preferably a saturated aliphatic monocarboxylic acid. The saturated aliphatic carboxylic acid preferably has 1 to 8 carbon atoms, more preferably 1 to 4 carbon atoms. Examples of the organic carboxylic acid include formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and isovaleric acid. Among these, formic acid, acetic acid and propionic acid are preferable, and acetic acid is particularly preferable.

From the above, preferred specific examples of the tertiary amine organic carboxylates include trimethylamine acetate, triethylamine formate, triethylamine acetate, triethylamine propionate, pyridine acetate, 2-picoline Examples thereof include acetate, acetate of 3-picoline and acetate of 4-picoline. Of these, triethylamine acetate or pyridine acetate is preferred.

The amount of the organic amine salt of the tertiary amine is, for example, 0.3 to 10 times mol, preferably 0.5 to 5 times mol, more preferably the compound (II). 0.8-3 moles.

An organic carboxylate of a tertiary amine can be generated by adding a tertiary amine and an organic carboxylic acid to the reaction system. The addition of the tertiary amine and the organic carboxylic acid is not limited to the case where the tertiary amine and the organic carboxylic acid are separately added to the reaction system, and the reaction system is prepared by mixing a tertiary amine and the organic carboxylic acid in advance. May be added. The mixing ratio of the tertiary amine and the organic carboxylic acid may be 1: 1. However, when the reaction is carried out on a compound whose yield is expected to decrease in the reaction under acidic conditions, such as compound (IIc) and compound (IId) described later, the organic carboxylic acid becomes excessive. In order to prevent the reaction system from becoming acidic, it is preferable to use more tertiary amine than organic carboxylic acid. In this case, for example, the amount of the tertiary amine is preferably 1.01 to 5 times mol and more preferably 1.05 to 2 times mol with respect to the organic carboxylic acid.

The halide salt is not particularly limited as long as halide ions can be supplied into the system. For example, other metal salts such as quaternary ammonium salts, alkali metal salts, alkaline earth metal salts, and transition metal salts can be used. Can be mentioned. Of these, quaternary ammonium salts and alkali metal salts are preferred.

The halogenated quaternary ammonium salt is not limited, and examples of the group bonded to the nitrogen atom of the quaternary ammonium cation constituting the halogenated quaternary ammonium salt include an alkyl group, a substituted or unsubstituted aralkyl group ( Arylalkyl group) and a substituted or unsubstituted aryl group, and the same or different groups may be used. Further, the carbon number of the alkyl group is not limited, and is, for example, 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms, and more preferably 1 to 2 carbon atoms. In the case of an aralkyl group, the alkyl moiety has, for example, 1 to 5 carbon atoms, preferably 1 to 2 carbon atoms. The aryl part of the aralkyl group is, for example, an aryl having 6 to 14 carbon atoms, and a phenyl group is particularly preferable. As the aryl group, an aryl group having 6 to 14 carbon atoms is preferable, and a phenyl group is more preferable. The substituent that the aralkyl group and aryl group may have is not particularly limited as long as it does not affect the reaction, and examples thereof include a halogen atom, an alkyl group, an alkoxy group, a phenyl group, a cyano group, and a nitro group.

Examples of the halogen atom as a substituent include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

Examples of the alkyl group as a substituent include an alkyl group having 1 to 4 carbon atoms, and specifically include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, and sec-butyl group and tert-butyl group. Among them, an alkyl group having 1 to 3 carbon atoms is preferable, an alkyl group having 1 to 2 carbon atoms is more preferable, and a methyl group is further preferable.

Examples of the alkoxy group as a substituent include an alkoxy group having 1 to 4 carbon atoms, and specific examples include a methoxy group, an ethoxy group, and an n-propoxy group.

Examples of the halide ions constituting the halogenated quaternary ammonium salt include fluoride ions, chloride ions, bromide ions, and iodide ions. Of these, fluoride ion, chloride ion and bromide ion are preferable, and chloride ion and bromide ion are more preferable.

Among the halogenated quaternary ammonium salts, a quaternary ammonium salt represented by the following general formula (III) can be mentioned as a more preferable compound in terms of relatively high solubility in an organic solvent.

In general formula (III), R ² to R ⁵ independently represent an alkyl group, a substituted or unsubstituted aralkyl group, or a substituted or unsubstituted aryl group.

The alkyl group is preferably an alkyl group having 1 to 8 carbon atoms, more preferably an alkyl group having 1 to 4 carbon atoms, and particularly preferably an alkyl group having 1 to 2 carbon atoms.

The aralkyl group is preferably an aralkyl group having 1 to 5 carbon atoms in the alkyl portion, and more preferably an aralkyl group having 1 to 2 carbon atoms in the alkyl portion. As the aryl in the aralkyl group, an aryl group having 6 to 14 carbon atoms is preferable, and a phenyl group is more preferable.

As the aryl group, an aryl group having 6 to 14 carbon atoms is preferable, and a phenyl group is more preferable.

Examples of the substituent that the aralkyl group and aryl group may have include the substituents described above.

In the general formula (III), L ⁻ represents a halide ion, preferably a fluoride ion, a chloride ion or a bromide ion, and more preferably a chloride ion or a bromide ion.

As a more preferable form of the quaternary ammonium salt represented by the general formula (III), in the general formula (III), R ² to R ⁵ are independently an alkyl group having 1 to 4 carbon atoms, substituted or unsubstituted. And a quaternary ammonium salt which is a substituted or unsubstituted phenyl group, and L ⁻ is a chloride ion or a bromide ion. Further, as a more preferable form of the quaternary ammonium salt represented by the general formula (III), in the general formula (III), R ² to R ⁵ are independently an alkyl group having 1 to 4 carbon atoms, Quaternary ammonium salts in which L ⁻ is a chloride ion or a bromide ion can be mentioned.

In order to achieve this reaction, it is only necessary to supply halide ions into the reaction system, and the type of halogenated quaternary ammonium salt is not particularly limited. Specific examples of halogenated quaternary ammonium salts include tetramethylammonium chloride, tetramethylammonium bromide, tetraethylammonium chloride, tetraethylammonium bromide, tetraethylammonium iodide, methyltriethylammonium chloride, methyltriethylammonium bromide, ethyltrimethylammonium chloride. , Ethyltrimethylammonium bromide, benzyltrimethylammonium chloride, benzyltrimethylammonium bromide, benzyltriethylammonium chloride, benzyltriethylammonium bromide, (4-chlorobenzyl) trimethylammonium chloride, (4-chlorobenzyl) benzyltrimethylammonium bromide, (4- Methylben Le) benzyltrimethylammonium chloride, mention may be made of (4-methylbenzyl) benzyl bromide, phenyl trimethyl ammonium chloride, phenyl trimethyl ammonium bromide, phenyl triethylammonium chloride, and phenyl triethylammonium bromide and the like. Among them, tetramethylammonium chloride, tetramethylammonium bromide, tetraethylammonium chloride, tetraethylammonium bromide, benzyltrimethylammonium chloride, benzyltrimethylammonium bromide, benzyltriethylammonium chloride, benzyltriethylammonium bromide, phenyltrimethylammonium chloride, and phenyltrimethylammonium bromide From the viewpoint of low cost, tetramethylammonium chloride, tetramethylammonium bromide, tetraethylammonium chloride, and tetraethylammonium bromide are more preferable.

Further, by adding a hydrogen halide salt of a tertiary amine that forms the organic carboxylate described above, a halogenated quaternary ammonium salt can be generated in the reaction system and used. When the dealkylation of the alkoxycarbonyl group proceeds by the action of the tertiary amine hydrogen halide salt, an alkyl halide is produced. This reacts with the tertiary amine present in the system to give a halogenated quaternary ammonium salt in the system. In this case, the type of tertiary amine to be used is not particularly limited, but inexpensive triethylamine, trimethylamine, pyridine or picoline is preferable from the viewpoint that it can be used for general purposes. Further, examples of the hydrogen halide forming the hydrogen halide salt include hydrogen fluoride, hydrogen chloride, hydrogen bromide, and hydrogen iodide. Among them, hydrogen chloride and hydrogen bromide are preferable.

Examples of the alkali metal constituting the alkali metal halide salt include lithium, sodium, potassium, rubidium and cesium. Among these, lithium, sodium and potassium are more preferable.

On the other hand, examples of the halide ions constituting the alkali metal halide salt include fluoride ions, chloride ions, bromide ions, and iodide ions.

Specific examples of alkali metal halides include lithium chloride, lithium bromide, lithium iodide, sodium chloride, sodium bromide, sodium iodide, potassium chloride, potassium bromide, potassium iodide, rubidium chloride, rubidium bromide. And rubidium iodide, cesium chloride, cesium bromide and cesium iodide. Among these, lithium chloride, lithium bromide, lithium iodide, sodium chloride, sodium bromide, sodium iodide, potassium chloride, potassium bromide and potassium iodide are preferable, and lithium chloride, lithium bromide, lithium iodide, bromide Sodium and potassium bromide are more preferred.

Examples of the alkaline earth metal constituting the alkaline earth metal halide salt include beryllium, magnesium, calcium, strontium and barium.

On the other hand, examples of the halide ions constituting the alkaline earth metal halide salt include fluoride ions, chloride ions, bromide ions, and iodide ions.

Specific examples of the alkaline earth metal halide salt include magnesium chloride, magnesium bromide, magnesium iodide, calcium chloride, calcium bromide, calcium iodide, strontium chloride, strontium bromide, barium chloride and barium bromide. be able to.

The metal constituting the halogenated metal salt other than the alkali metal halide salt and the alkaline earth metal halide salt is preferably a metal that becomes a monovalent or divalent cation, for example, transition metals such as copper and silver, and Zinc etc. can be mentioned.

On the other hand, examples of the halide ions constituting the metal halide salt include fluoride ions, chloride ions, bromide ions, and iodide ions.

Specific examples of metal halide salts other than alkali metal halide salts and alkaline earth metal halide salts include copper chloride, copper bromide, copper iodide, zinc chloride, zinc bromide, silver chloride and silver bromide. Can be mentioned.

As the halogenated salt, only one kind of compound may be used, or a plurality of compounds may be used in combination. Further, halogenated quaternary ammonium salts, tertiary amine hydrogen halide salts, halogenated alkali metal salts, halogenated alkaline earth metal salts, and other metal halide salts may be used in combination. A combination of both a halogenated quaternary ammonium salt and a halogenated alkali metal salt may be used. From the viewpoint of yield, it is preferable to use a halogenated quaternary ammonium salt.

The amount of the halogenated salt (the total amount when a plurality of compounds are included) is, for example, 0.01 to 10 times mol, preferably 0.02 to 3 times the amount of compound (II). The molar ratio is more preferably 0.05 to 1 times.

The dealkoxycarbonylation reaction may be carried out in a solvent. The solvent is not particularly limited as long as it does not participate in the reaction, and for example, amides such as N, N-dimethylformamide, N, N-dimethylacetamide and N-methyl-2-pyrrolidone can be preferably used. It is also possible to react by adding other solvents such as toluene to these solvents. Moreover, when the organic carboxylate of a tertiary amine is a liquid, it may be used as a solvent itself and the reaction may be carried out in a system that does not use any other solvent.

The reaction temperature is, for example, 0 to 250 ° C., preferably room temperature to 200 ° C., more preferably 50 to 180 ° C., and further preferably 100 to 130 ° C. When the reaction temperature is high, a heating device using a heat transfer oil is necessary, but if it is about 130 ° C., inexpensive steam can be used. Thereby, since capital investment and running cost can be suppressed more cheaply, the carbonyl compound according to the present invention can be produced at a lower cost.

In the production method according to the present invention, by using both an organic carboxylate and a halogenated salt of a tertiary amine, for example, compared with a case of using only an organic carboxylate of a tertiary amine, The reaction can be carried out at a lower reaction temperature. The reaction time is, for example, 0.05 hours to several days, preferably 0.1 hours to 5 days, and more preferably 0.5 hours to 2 days.

It should be noted that the reaction proceeds without problems even if it is not under an inert gas. However, when the reaction is carried out at a high temperature for a long period of time, depending on the type of amine to be used, if the reaction proceeds in the air, air oxidation may occur and the reaction solution may be colored. In such a case, it is more preferable to carry out the reaction in an inert gas atmosphere such as nitrogen and argon.

Other reaction conditions can be easily designed and set by those skilled in the art by referring to conventionally known production methods.

As used herein, “dealkoxycarbonylation” means that —CO ₂ R ¹ is finally replaced with a hydrogen atom. From the viewpoint that —CO ₂ R ¹ is removed from the β-ketoester compound to obtain a carbonyl compound, this is the same as the hydrolysis and decarboxylation of the β-ketoester compound. However, in the production method according to the present invention using (a) an organic carboxylate salt of a tertiary amine and (b) a halogenated quaternary ammonium salt or an alkali metal halide salt, the reaction is carried out in the absence of water. As it proceeds, “dealkoxycarbonylation” in the present invention is clearly distinguished from reactions involving hydrolysis that require water. If water is present in the reaction system, hydroxide ions may be generated from water molecules under conditions containing a base, which may cause undesired side reactions. Preferably it is not.

In the production method according to the present invention, the reaction is carried out using (a) an organic carboxylate salt of a tertiary amine and (b) a halogenated salt instead of an acid and an alkali. The reaction can be carried out under Therefore, even a compound that is unstable with respect to an acid or an alkali and whose yield is expected to decrease under an acidic condition or a basic condition can be reacted with a high yield.

As the reaction mechanism of dealkoxycarbonylation in the method for producing a carbonyl compound according to the present invention, for example, the following two reaction mechanisms are presumed if a halogenated quaternary ammonium salt is taken as an example of the halogenated salt:
(Reaction mechanism 1)
In this reaction mechanism, the reaction proceeds by a small amount of hydrogen halide generated from a carboxylic acid derived from a tertiary amine carboxylate and a halide ion derived from a halogenated quaternary ammonium salt. When the halogen atom of the hydrogen halide attacks the alkyl group of the alkyl ester group in the compound (II), the compound (II) is dealkylated to generate β-ketocarboxylic acid. A compound represented by the general formula (I) is produced by decarboxylation of the produced β-ketocarboxylic acid. The generated alkyl halide reacts with a tertiary amine in the system to produce a halogenated quaternary ammonium salt. From this fact, since halide ions are regenerated in the system, the reaction proceeds without problems even when the amount of the halide salt is less than or equal to the alkyl ester group.
(Reaction mechanism 2)
The halide ion of the halogenated quaternary ammonium salt attacks the alkyl group of the alkyl ester group of the compound (II) to generate an alkyl halide, and a Clapco type decarboxylation reaction proceeds. The anion produced | generated on the obtained ketone receives a proton supply from the carboxylic acid in a system, and the compound shown by general formula (I) is produced | generated. On the other hand, the generated alkyl halide reacts with a tertiary amine in the system to produce a halogenated quaternary ammonium salt. From this fact, since halide ions are regenerated in the system, the reaction proceeds without problems even when the amount of the halide salt is less than or equal to the alkyl ester group.
Further, as described above, in both cases of Reaction Mechanisms 1 and 2, a halogenated quaternary ammonium salt is formed by the reaction of an alkyl halide generated in the system with a tertiary amine. Therefore, even if a halogenated salt other than the halogenated quaternary ammonium salt is used, it is considered that the reaction system coexists with the halogenated quaternary ammonium salt as the reaction proceeds. When the reaction is carried out by adding a tertiary amine hydrogen halide salt to the reaction system, the reaction rate is expected to increase because a large amount of hydrogen halide is present in the system. If the amount of the hydrogen halide salt is too large, the acidity in the system also increases, so that when using a compound that is unstable to acids, attention must be paid to the amount used. The amount used can be appropriately selected by those skilled in the art.

However, as long as the reaction proceeds using (a) an organic carboxylate of a tertiary amine and (b) a halogenated salt, the reaction mechanism of the carbonyl compound according to the present invention is the above reaction mechanism. And is not limited to other specific reaction mechanisms. Moreover, not only the case of progressing by a single reaction mechanism, but also progressing by a plurality of reaction mechanisms.

In the method for producing a carbonyl compound according to the present invention, a compound in which the α-position of the ketone is alkylated, which is produced as a by-product when Clapco decarboxylation occurs, is not produced. This does not occur in the case of the reaction mechanism 1, but even in the case of the reaction mechanism 2, there is a proton supply source in the system, and even if an anion is generated at the α-position of the ketone, it is quickly neutralized. It is thought to be due to.

A preferred embodiment of the method for producing a carbonyl compound according to the present invention is represented by the following general formula (IIa) in the presence of (a) an organic carboxylate salt of a tertiary amine and (b) a halogenated salt. A carbonyl compound represented by the general formula (Ia) is obtained by dealkoxycarbonylating a β-ketoester compound having a cyclopentane ring (hereinafter referred to as the compound (IIa)) to obtain a carbonyl compound represented by the general formula (Ia). It is a manufacturing method.

Y represents an alkyl group or haloalkyl group having 1 to 6 carbon atoms, an alkenyl group or haloalkenyl group having 2 to 6 carbon atoms, an alkynyl group or haloalkynyl group having 2 to 6 carbon atoms, or the alkyl group, haloalkyl A group, an alkenyl group, a haloalkenyl group, an alkynyl group or a haloalkynyl group in which part of the hydrogen atoms is substituted with —OG (G represents a protecting group for a hydroxy group).

Examples of the alkyl group having 1 to 6 carbon atoms include methyl group, ethyl group, (1-methyl) ethyl group, n-propyl group, 1-methylpropyl group, 2-methylpropyl group, n-butyl group, 1 -Methylbutyl group, 2-methylbutyl group, 1-ethylpropyl group, 1,1-dimethylethyl group and the like can be mentioned. Among these, an alkyl group having 1 to 4 carbon atoms is preferable, a methyl group and an ethyl group are more preferable, and a methyl group is further preferable.

Examples of the haloalkyl group having 1 to 6 carbon atoms include chloromethyl group, dichloromethyl group, trichloromethyl group, 2-chloroethyl group, 1-chloroethyl group, 2,2-dichloroethyl group, 1,2-dichloroethyl group, 2 , 2,2-trichloroethyl group, 3-chloropropyl group, 2,3-dichloropropyl group, 1-chloro-1-methylethyl group, 2-chloro-1-methylethyl group, 2-chloropropyl group, 4 -Chlorobutyl group, 5-chloropentyl group, fluoromethyl group, difluoromethyl group, trifluoromethyl group, 2-fluoroethyl group, 1-fluoroethyl group, 2,2-difluoroethyl group, 1,2-difluoroethyl group 2,2,2-trifluoroethyl group, 3-fluoropropyl group, 2,3-difluoropropyl group, 1-fluoro-1-methyl Ethyl group, 2-fluoro-1-methylethyl group, 2-fluoropropyl group, 3,3,3-trifluoropropyl group, 2,2,3,3-tetrafluoropropyl group, 2,2,3,3 , 3-pentafluoropropyl group, 4-fluorobutyl group, 5-fluoropentyl group, bromomethyl group, dibromomethyl group, tribromomethyl group, 2-bromoethyl group, 1-bromoethyl group, 2,2-dibromoethyl group, 1,2-dibromoethyl group, 2,2,2-tribromoethyl group, 3-bromopropyl group, 2,3-dibromopropyl group, 1-bromo-1-methylethyl group, 2-bromo-1-methyl Ethyl group, 2-bromopropyl group, 4-bromobutyl group, 5-bromopentyl group, iodomethyl group, diiodomethyl group, 2-iodoethyl group, 1-iodoethyl 2,2-diiodoethyl group, 1,2-diiodoethyl group, 2,2,2-triiodoethyl group, 3-iodopropyl group, 2,3-diiodopropyl group, 1-iodo-1-methylethyl group 2-iodo-1-methylethyl group, 2-iodopropyl group, 4-iodobutyl group and the like. Among these, a haloalkyl group having 1 to 4 carbon atoms is preferable, and a haloalkyl group having 1 to 3 carbon atoms is more preferable.

Examples of the alkenyl group having 2 to 6 carbon atoms include ethenyl group, 1,2-dimethylethenyl group, 4-methyl-1,3-butadienyl group, 1-propenyl group, 2-propenyl group, 2-methyl- Examples include 2-propenyl group, 3-methyl-2-propenyl group, 2-butenyl group, 3-butenyl group, and 3-methyl-3-butenyl group. Of these, an alkenyl group having 2 to 4 carbon atoms is preferred.

Examples of the haloalkenyl group having 2 to 6 carbon atoms include 2-chloroethenyl group, 2,2-dichloroethenyl group, 2-chloro-2-propenyl group, 3,3-dichloro-2-propenyl group, 2,3 -Dichloro-2-propenyl group, 3,3-dichloro-2-methyl-2-propenyl group, 3-chloro-2-butenyl group, 2-fluoroethenyl group, 2,2-difluoroethenyl group, 2- Fluoro-2-propenyl group, 3,3-difluoro-2-propenyl group, 2,3-difluoro-2-propenyl group, 3,3-difluoro-2-methyl-2-propenyl group, 3-fluoro-2- Butenyl, 2-bromoethenyl, 2,2-dibromoethenyl, 2-bromo-2-propenyl, 3,3-dibromo-2-propenyl, 2,3-dibromo-2-propenyl Group, 3,3-dibromo-2-methyl-2-propenyl group, 3-bromo-2-butenyl group, 2-iodoethenyl group, 2,2-diiodoethenyl group, 2-iodo-2-propenyl group, 3,3 -Diiodo-2-propenyl group, 2,3-diiodo-2-propenyl group and the like can be mentioned. Of these, a haloalkenyl group having 2 to 4 carbon atoms is preferred.

Examples of the alkynyl group having 2 to 6 carbon atoms include ethynyl group, 1-propynyl group, 2-propynyl group, 1-butynyl group, and 2-butynyl group. Of these, an alkynyl group having 2 to 4 carbon atoms is preferable.

Examples of the haloalkynyl group having 2 to 6 carbon atoms include 2-fluoroethynyl group, 2-chloroethynyl group, 3-fluoro-2-propynyl group, 3-chloro-2-propynyl group, and 3-bromo-2 -A propynyl group etc. can be mentioned. Of these, a haloalkynyl group having 2 to 4 carbon atoms is preferable.

The protecting group G in —OG is a protecting group that protects a hydroxy group, and is not particularly limited as long as it is a protecting group that dissociates under appropriate conditions to form a hydroxy group. Examples of the protecting group G include a protecting group that dissociates under acidic conditions and a protecting group that cleaves under reducing conditions such as a hydrogenation reaction.

N represents an integer of 0-6. n is preferably 0 to 3, and more preferably 0 to 2. When n is 2 or more, the plurality of Ys may be the same or different from each other. When n is 2 or more, two Y may be bonded to one carbon atom. When n is 2 or more, a plurality of Ys may be bonded to each other to form a ring together with the carbon atom to which each Y is bonded.

X is a halogen atom, an alkyl group having 1 to 4 carbon atoms, a haloalkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a haloalkoxy group having 1 to 4 carbon atoms, a phenyl group, a cyano group, or a nitro group. Represents a group.

Examples of the halogen atom in X include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, among which a fluorine atom, a chlorine atom and a bromine atom are preferable, and a fluorine atom and a chlorine atom are more preferable.

Specific examples of the alkyl group having 1 to 4 carbon atoms in X include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, and a tert-butyl group. Can be mentioned. Among them, an alkyl group having 1 to 3 carbon atoms is preferable, an alkyl group having 1 to 2 carbon atoms is more preferable, and a methyl group is further preferable.

Examples of the haloalkyl group having 1 to 4 carbon atoms in X include, for example, a dichloromethyl group, a trichloromethyl group, a 2-chloroethyl group, a 1-chloroethyl group, a 2,2-dichloroethyl group, a 1,2-dichloroethyl group, 2 , 2,2-trichloroethyl group, 3-chloropropyl group, 2,3-dichloropropyl group, 1-chloro-1-methylethyl group, 2-chloro-1-methylethyl group, 2-chloropropyl group, 4 -Chlorobutyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 1-fluoroethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, 2,2,2 -Trifluoroethyl group, 3-fluoropropyl group, 2,3-difluoropropyl group, 1-fluoro-1-methylethyl group, 2-fur B-1-Methylethyl group, 2-fluoropropyl group, 3,3,3-trifluoropropyl group, 2,2,3,3-tetrafluoropropyl group, 2,2,3,3,3-pentafluoro Propyl group, 4-fluorobutyl group, dibromomethyl group, tribromomethyl group, 2-bromoethyl group, 2,2-dibromoethyl group, 1,2-dibromoethyl group, 2,2,2-tribromoethyl group, 3-bromopropyl group, 2,3-dibromopropyl group, 1-bromo-1-methylethyl group, 2-bromo-1-methylethyl group, 2-bromopropyl group, diiodomethyl group, 2,2-diiodoethyl group, 1,2-diiodoethyl group, 2,2,2-triiodoethyl group, 2,3-diiodopropyl group, 1-iodo-1-methylethyl group and 2-iodo-1-methylethyl Group, and the like. Among these, a haloalkyl group having 1 to 3 carbon atoms is preferable, a haloalkyl group having 1 to 2 carbon atoms is more preferable, and a trihaloalkyl group having 1 carbon atom is more preferable.

Examples of the alkoxy group having 1 to 4 carbon atoms in X include a methoxy group, an ethoxy group, and an n-propoxy group. Among these, an alkoxy group having 1 to 3 carbon atoms is preferable, an alkoxy group having 1 to 2 carbon atoms is more preferable, and a methoxy group is further preferable.

Examples of the haloalkoxy group having 1 to 4 carbon atoms in X include, for example, a trifluoromethoxy group, a difluoromethoxy group, a 1,1,2,2,2-pentafluoroethoxy group, and a 2,2 and 2-trifluoroethoxy group. Etc. Among these, a haloalkoxy group having 1 to 3 carbon atoms is preferable, a haloalkoxy group having 1 to 2 carbon atoms is more preferable, and a dihalomethoxy group and a trihalomethoxy group are further preferable.

X is preferably a halogen atom.

M represents an integer from 0 to 5. m is preferably an integer of 0 to 3, more preferably an integer of 0 to 2, and still more preferably 0 or 1. When m is 2 or more, a plurality of Xs may be the same or different from each other. When m is 1 or more, X may be located at any of positions 2 to 6 of the benzene ring, but when m is 1, a position where 4-substituted benzyl is preferred.

In a preferred example, m is an integer from 0 to 2, and when m is 1 or 2, X is a halogen atom.

R ¹ is the same as R ¹ in the general formula (II).

The type and amount of tertiary amine organic carboxylate used in the reaction for dealkoxycarbonylation of compound (IIa), the type and amount of halogenated salt, the type of solvent, the reaction conditions for the reaction, etc. These are the same as the above-mentioned types and amounts of tertiary amine organic carboxylates, the types and amounts of halogenated salts, the types of solvents, and the reaction conditions.

More preferable examples of the compound (IIa) include, for example, a compound represented by the following general formula (IIa-1) and a compound represented by the following general formula (IIa-2).

A more preferred embodiment of the method for producing a carbonyl compound according to the present invention is represented by the following general formula (IIb) in the presence of (a) an organic carboxylate salt of a tertiary amine and (b) a halide salt. A carbonyl compound represented by the general formula (Ib) is obtained by subjecting a β-ketoester compound having a cyclopentane ring (hereinafter referred to as the compound (IIb)) to dealkoxycarbonylation. It is a manufacturing method of a compound.

Here, Y ¹ and Y ² are each independently an alkyl group or haloalkyl group having 1 to 6 carbon atoms, or a hydrogen atom of a part of the alkyl group or haloalkyl group is -OG ¹ (G ¹ is a hydroxy group protecting group). Represents a group substituted by (represents a group).

Examples of the alkyl group and haloalkyl group having 1 to 6 carbon atoms in Y ¹ and Y ² are the same as the alkyl group and haloalkyl group having 1 to 6 carbon atoms in Y described above.

The protecting group G ¹ is a protecting group that protects a hydroxy group, and is not particularly limited as long as it is a protecting group that dissociates under appropriate conditions to form a hydroxy group. The protecting group G ^1, for example, protecting groups which dissociate under acidic conditions. Examples of the protecting group that can be dissociated under acidic conditions include, for example, an alkoxymethyl group having 1 to 4 carbon atoms such as a methoxymethyl group and an ethoxymethyl group, an alkoxyethyl group, a methyl group, an ethyl group, and a t-butyl group. Such as an alkyl group having 1 to 4 carbon atoms, a substituted or unsubstituted benzyl group, a substituted or unsubstituted tetrahydropyranyl group, a substituted or unsubstituted tetrahydrofuranyl group, an allyl group, a triethylsilyl group and a t-butyldimethylsilyl group The silyl group of can be mentioned. In addition, the protective groups in the two hydroxy groups may be bonded to each other, such as when two hydroxy groups are simultaneously protected by acetals such as methylene acetal and ethylidene acetal.

Also included are protecting groups that cleave under reducing conditions. Protecting groups that are cleaved under reducing conditions include substituted or unsubstituted benzyl groups such as benzyl and p-methoxybenzyl groups.

Y ¹ and Y ² may be bonded to each other to form a ring together with the carbon atom to which Y ¹ and Y ² are bonded.

^{Further, R} 1, X and m are the same as ^R 1, X and m in the above general formula (IIa).

The type and amount of tertiary amine organic carboxylate used in the reaction for dealkoxycarbonylation of compound (IIb), the type and amount of halogenated salt, the type of solvent, the reaction conditions for the reaction, etc. These are the same as the above-mentioned types and amounts of tertiary amine organic carboxylates, the types and amounts of halogenated salts, the types of solvents, and the reaction conditions.

Another preferred embodiment of the method for producing a carbonyl compound according to the present invention is represented by the following general formula (IIc) in the presence of (a) an organic carboxylate of a tertiary amine and (b) a halogenated salt. A β-ketoester compound having a cyclopentane ring (hereinafter referred to as compound (IIc)) is dealkoxycarbonylated to obtain a carbonyl compound represented by general formula (Ic) (hereinafter referred to as compound (Ic)). It is a manufacturing method of compound (Ic).

Here, G ² and G ³ independently represent a protecting group protecting a hydroxy group, and specifically represent a protecting group that dissociates under acidic conditions. Note that G ² and G ³ are bonded to each other to form an oxygen atom to which G ² and G ³ are bonded, a carbon atom to which the oxygen atom is bonded, and a cyclo atom to which the carbon atom is bonded. A ring may be formed together with the carbon atom of the pentane ring.

Examples of the protecting group when G ² and G ³ are not bonded include, for example, an alkoxymethyl group having 1 to 4 carbon atoms, such as a methoxymethyl group and an ethoxymethyl group, a 1-ethoxyethyl group, and 1 An alkoxy moiety such as a methyl-1-methoxyethyl group having 1 to 4 carbon atoms, an alkyl group having 1 to 4 carbon atoms such as a t-butyl group and a methyl group, a substituted or unsubstituted benzyl group, a substituted Alternatively, an unsubstituted tetrahydropyranyl group, a substituted or unsubstituted tetrahydrofuranyl group, and silyl groups such as an allyl group, a triethylsilyl group, and a t-butyldimethylsilyl group can be exemplified.

On the other hand, examples of the protecting group when G ² and G ³ are bonded to each other include, for example, methylene acetal, ethylidene acetal, t-butyl methylidene ketal, 1-t-butyl ethylidene ketal, 1-phenyl ethylidene ketal, acrolein Acetal, isopropylidene ketal (acetonide), cyclopentylidene ketal, cyclohexylidene ketal, cycloheptylidene ketal, benzylidene acetal, p-methoxybenzylidene acetal, 2,4-dimethoxybenzylidene ketal, 3,4-dimethoxybenzylidene ketal, 2-nitrobenzylidene acetal, 4-nitrobenzylidene acetal, mesitylene acetal, 1-naphthaldehyde acetal, benzophenone ketal, camphor ketal, Methoxymethylene acetal, ethoxymethylene acetal, dimethoxymethylene orthoester, 1-methoxyethylidene orthoester, 1-ethoxyethylidene orthoester, methylidene orthoester, phthalide orthoester, 1,2-dimethoxyethylidene orthoester, α- Methoxybenzylidene orthoester, 2-oxacyclopentylidene orthoester, butane-2,3-bisacetal, cyclohexane-1,2-diacetal, bisdihydropyranketal, di-t-butylsilylene, 1,3- (1, Mention may be made of 1,3,3-tetraisopropyl) disilixanilidene and 1,1,3,3-tetra-t-butoxydisiloxanilidene.

^{Further, R} 1, X and m are the same as ^R 1, X and m in the above general formula (IIa).

The type and amount of tertiary amine organic carboxylate used in the reaction for dealkoxycarbonylation of compound (IIc), the type and amount of halogenated salt, the type of solvent, the reaction conditions of the reaction, etc. These are the same as the above-mentioned types and amounts of tertiary amine organic carboxylates, the types and amounts of halogenated salts, the types of solvents, and the reaction conditions.

G ² and G ³ are protecting groups that dissociate under acidic conditions. Therefore, when obtaining compound (Ic) from compound (IIc) by the reaction of hydrolysis and decarboxylation, the yield of compound (Ic) is reduced when the reaction is carried out under acidic conditions. On the other hand, the inventors of the present application have conducted various studies. As a result, when compound (IIc) is hydrolyzed and decarboxylated under basic conditions, a side reaction occurs in which the cyclopentane ring is opened, resulting in compound (Ic). It was found that the yield of was reduced. Therefore, in the reaction for obtaining the compound (Ic) from the compound (IIc), a reaction under neutral or nearly neutral conditions is desired. Here, according to the production method of the present invention in which dealkoxycarbonylation is carried out using (a) an organic carboxylate of a tertiary amine and (b) a halogenated salt, the neutral or near neutral condition The reaction can be carried out with Therefore, the production method of the present invention in which dealkoxycarbonylation is carried out using (a) an organic carboxylate of a tertiary amine, and (b) a halogenated salt, reacts under neutral or nearly neutral conditions. In the method for producing the compound (Ic) from the compound (IIc) desired to be performed, a particularly excellent effect is exhibited.

In addition, the side reaction in which the cyclopentane ring opens when hydrolyzed and decarboxylated under basic conditions is not limited to the reaction in the compound (IIc), but the compound (IIa) and the compound (IIb) having a cyclopentane ring. It can occur in the reaction in Therefore, for some reason, when the reaction of hydrolysis / decarboxylation under acidic conditions is not desirable in compound (IIa) and compound (IIb), for example, the yield is reduced by hydrolysis / decarboxylation under acidic conditions. In this case, the production method of the present invention in which dealkoxycarbonylation is carried out using (a) an organic carboxylate of a tertiary amine and (b) a halogenated salt is particularly preferably used.

In the case where G ² and G ³ are bonded to each other to form a ring, a preferred embodiment is as follows: (a) an organic carboxylate of a tertiary amine, and (b) a halogenated salt, Production of a carbonyl compound represented by the general formula (Id) is obtained by subjecting a β-ketoester compound having a cyclopentane ring represented by the formula (IId) to dealkoxycarbonylation to obtain a carbonyl compound represented by the general formula (Id). Is the method.

Here, G ⁴ and G ⁵ independently represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkenyl group having 1 to 4 carbon atoms, a phenyl group, a naphthyl group, or a benzyl group. The phenyl and naphthyl groups in G ⁴ and G ^{5 and} the phenyl moiety in the benzyl group are alkyl groups having 1 to 4 carbon atoms such as methyl and ethyl groups; alkoxy groups having 1 to 4 carbon atoms such as methoxy and ethoxy groups A nitro group; or a halogen atom such as a fluorine atom and a chlorine atom. G ⁴ and G ⁵ may be bonded to each other to form a ring together with the carbon atom to which G ⁴ and G ⁵ are bonded. Among these, G ⁴ and G ⁵ are each independently more preferably a hydrogen atom or an alkyl group having 1 to 4 carbon atoms such as a methyl group, an ethyl group and an n-propyl group. More preferably a group or an ethyl group, and particularly preferably G ⁴ and G ⁵ are both methyl groups.

^{Further, R} 1, X and m are the same as ^R 1, X and m in the above general formula (IIa).

The type and amount of tertiary amine organic carboxylate used in the reaction for dealkoxycarbonylation of the β-ketoester compound represented by the general formula (IId), the type and amount of halogenated salt, the type of solvent, The reaction conditions and the like of the reaction are the same as the types and amounts of the tertiary amine organic carboxylates, the types and amounts of halogenated salts, the types of solvents, and the reaction conditions, respectively.

A particularly preferred embodiment of the method for producing a carbonyl compound according to the present invention is represented by the following general formula (IIe) in the presence of (a) an organic carboxylate salt of a tertiary amine and (b) a halogenated salt. This is a method for producing a carbonyl compound represented by the general formula (Ie), wherein a carbonyl compound represented by the general formula (Ie) is obtained by dealkoxycarbonylation of a β-ketoester compound having a cyclopentane ring.

Here, G ⁶ and G ⁷ independently represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms such as a methyl group, an ethyl group, and an n-propyl group. Among these, independently, a hydrogen atom, a methyl group, or an ethyl group is preferable, and both G ⁶ and G ⁷ are more preferably a methyl group.

X ¹ represents a hydrogen atom, a chlorine atom or a fluorine atom.

R ¹ is the same as R ¹ in the general formula (IIa).

As described above, the method for producing a carbonyl compound according to the present invention is a method for producing a carbonyl compound represented by the following general formula (I) from a compound represented by the following general formula (II), which is a tertiary amine. In the presence of the organic carboxylate and halogenated salt, the compound represented by the following general formula (II) is subjected to dealkoxycarbonylation.

(In the general formula (II), Z ¹ represents a substituted or unsubstituted alkyl group, cycloalkyl group, aryl group or heterocyclic group, and Z ³ and Z ² independently represent a hydrogen atom, or a substituted or unsubstituted group. Represents a substituted alkyl group, cycloalkyl group, aryl group or heterocyclic group, and R ¹ represents an alkyl group having 1 to 4 carbon atoms, and Z ¹ and Z ² may be bonded to each other.

(In general formula (I), Z ¹ , Z ² and Z ³ are the same as Z ¹ , Z ² and Z ^{3 in} general formula (II), respectively.)

In the method for producing a carbonyl compound according to the present invention, the halogenated salt is preferably a halogenated quaternary ammonium salt or a metal halide salt.

In the method for producing a carbonyl compound according to the present invention, the halogenated quaternary ammonium salt can be preferably used by generating it in the system by using a tertiary amine hydrogen halide salt.

In the method for producing a carbonyl compound according to the present invention, the metal halide salt is preferably an alkali metal halide salt.

In the method for producing a carbonyl compound according to the present invention, the halogenated quaternary ammonium salt is preferably a compound represented by the following general formula (III).

(In the general formula (III), R ² to R ⁵ independently represent an alkyl group, a substituted or unsubstituted aralkyl group, or a substituted or unsubstituted aryl group, and L ⁻ represents a halide ion. Yes.)

In the method for producing a carbonyl compound according to the present invention, in the general formula (III), R ² to R ⁵ are independently an alkyl group having 1 to 4 carbon atoms, a substituted or unsubstituted benzyl group, or a substituted group. or an unsubstituted phenyl group, L ^- is preferably a chloride ion or bromide ion.

Also, the method for producing a carbonyl compound according to the present invention may be a method using the above tertiary amine organic carboxylate as a solvent and not using any other solvent.

In the method for producing a carbonyl compound according to the present invention, the tertiary amine constituting the organic carboxylate of the tertiary amine is preferably triethylamine, trimethylamine, pyridine or picoline.

In the method for producing a carbonyl compound according to the present invention, the organic carboxylic acid constituting the organic carboxylate of the tertiary amine is preferably an aliphatic monocarboxylic acid.

In the method for producing a carbonyl compound according to the present invention, the compound represented by the general formula (II) is a compound represented by the following general formula (IIa), and the carbonyl compound represented by the general formula (I) is A carbonyl compound represented by the following general formula (Ia) is preferable.

(In the general formula (IIa), R ¹ represents an alkyl group having 1 to 4 carbon atoms, Y represents an alkyl group or haloalkyl group having 1 to 6 carbon atoms, an alkenyl group or haloalkenyl group having 2 to 6 carbon atoms) A part of hydrogen atoms of the alkyl group, haloalkyl group, alkenyl group, haloalkenyl group, alkynyl group or haloalkynyl group is -OG (G is a hydroxy group) And n represents an integer of 0 to 6. When n is 2 or more, a plurality of Y may be the same or different from each other, and n is 2 or more. In this case, a plurality of Y may be bonded to each other to form a ring together with the carbon atom to which each Y is bonded, where X is a halogen atom, an alkyl group having 1 to 4 carbon atoms, or 1 carbon atom. Represents a haloalkyl group having 4 to 4, an alkoxy group having 1 to 4 carbon atoms, a haloalkoxy group having 1 to 4 carbon atoms, a phenyl group, a cyano group or a nitro group, m represents an integer of 0 to 5, and m is 2 or more And the plurality of Xs may be the same or different.)

(In the general formula (Ia), X, Y, m and n are the same as X, Y, m and n in the general formula (IIa), respectively.)

In the method for producing a carbonyl compound according to the present invention, the compound represented by the general formula (IIa) is a compound represented by the following general formula (IIb), and the carbonyl compound represented by the general formula (Ia) is A carbonyl compound represented by the following general formula (Ib) is preferable.

(In General Formula (IIb), Y ¹ and Y ² independently represent an alkyl group having 1 to 6 carbon atoms or a haloalkyl group, or a hydrogen atom in a part of the alkyl group or haloalkyl group is -OG ¹ (G ¹ Represents a hydroxy-protecting group, and Y ¹ and Y ² may be bonded to each other to form a ring together with the carbon atom to which Y ¹ and Y ² are bonded. R ^1, X and m are each the same as ^R 1, X and m in the general formula (IIa).)

(In the general formula (Ib), ^X, Y 1, ^{Y 2} and m are the same as each ^X in the general formula ^(IIb), and Y 1, ^{Y 2} and m.)

In the method for producing a carbonyl compound according to the present invention, the compound represented by the general formula (IIb) is a compound represented by the following general formula (IIc), and the carbonyl compound represented by the general formula (Ib) is A carbonyl compound represented by the following general formula (Ic) is preferable.

(In General Formula (IIc), G ² and G ³ independently represent a protecting group that dissociates under acidic conditions, and G ² and G ³ may be bonded to each other. R ¹ , X, and m are These are the same as R ¹ , X and m in the general formula (IIa).

(In the general formula ^{(Ic), X, G 2} , G 3 and m are the same as ^X, G 2, ^{G 3} and m of each of the above general formula (IIc).)

In the method for producing a carbonyl compound according to the present invention, a tertiary amine is added to the compound represented by the general formula (IIc), and then an organic carboxylic acid in an amount smaller than the added amount of the tertiary amine is added. It is preferable to carry out dealkoxycarbonylation by adding an organic carboxylate of the tertiary amine in the reaction system by adding.

In the method for producing a carbonyl compound according to the present invention, the compound represented by the general formula (IIc) is a compound represented by the following general formula (IId), and the carbonyl compound represented by the general formula (Ic) is A carbonyl compound represented by the following general formula (Id) is preferable.

(In the general formula (IId), G ⁴ and G ⁵ are independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkenyl group having 1 to 4 carbon atoms, or a substituted or unsubstituted phenyl group or naphthyl group. or a benzyl group, G ⁴ and G ⁵ bonded to each other, G ⁴ and G ⁵ may also form a ring with the carbon atom to which they are attached .R ^{1, X} and m are each the general (It is the same as R ¹ , X and m in the formula (IIa).)

(In the general formula ^{(Id), X, G 4} , G 5 and m are the same as ^X, G 4, ^{G 5} and m respectively above general formula (IId).)

Examples will be shown below, and the embodiments of the present invention will be described in more detail. Of course, the present invention is not limited to the following examples, and it goes without saying that various aspects are possible in detail. Further, the present invention is not limited to the above-described embodiments, and various modifications can be made within the scope shown in the claims, and the present invention is also applied to the embodiments obtained by appropriately combining the disclosed technical means. It is included in the technical scope of the invention. Moreover, all the literatures described in this specification are used as reference.

[Example 1]
To tetramethylammonium chloride (0.45 g) was added dimethylacetamide (2.5 ml), triethylamine (3.0 ml), and acetic acid (1.2 ml), and then 2- (4-chlorobenzyl) -8,8 -Dimethyl-1-oxo-7,9-dioxaspiro [4.5] decane-2-carboxylic acid methyl ester (Compound 1) (5.0 g) was added, and the mixture was stirred at 125 ° C. for 12 hours for reaction. Toluene was added, and the mixture was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and the aqueous layer was extracted with toluene. The organic layer was dried over anhydrous sodium sulfate, concentrated and then purified on a silica gel column to give 2- (4-chlorobenzyl) -8,8-dimethyl-7,9-dioxaspiro [4.5] decan-1-one. (Hereinafter referred to as the target product). Yield: 97.2%.

[Example 2]
The target product was obtained in the same manner as in Example 1 except that tetraethylammonium bromide (0.86 g) was used instead of tetramethylammonium chloride and the reaction was performed at 110 ° C. for 12 hours. Yield: 99.7%.

Example 3
Tetraethylammonium bromide (0.30 g) was used instead of tetramethylammonium chloride, no solvent (dimethylacetamide) was used, and 110 ° C. for 2 hours, then 115 ° C. for 3 hours, then 120 ° C. The target product was obtained in the same manner as in Example 1 except that the reaction was performed for 11 hours. Yield: 98.3%.

Example 4
Dimethylacetamide (2 ml) and toluene (2 ml) were added to tetraethylammonium bromide (0.344 g), and then triethylamine (0.98 ml) and acetic acid (0.394 g) were added. Compound 1 was added to the resulting crude solution. (2.0 g) was added, and the target product was obtained in the same manner as in Example 1 except that the reaction was carried out at 110 ° C. to 114 ° C. for 10 hours. Yield: 98.4%.

Example 5
The target product was obtained in the same manner as in Example 4 except that lithium bromide (0.142 g) was used instead of tetraethylammonium bromide and the mixture was stirred at 110 ° C. to 114 ° C. for 12 hours. Yield: 97.3%.

Example 6
Acetic acid (0.394 g) and triethylamine (0.98 ml) were dissolved in dimethylacetamide (4 ml) and added to compound 1 (2.0 g), followed by addition of triethylamine hydrochloride (0.451 g) at about 120 ° C. The reaction was allowed for 5 hours. Ethyl acetate and aqueous sodium bicarbonate were added to the reaction solution, and the mixture was partitioned. The organic layer was washed with saturated brine, and then the aqueous layer was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and then concentrated to obtain the desired product. Yield: 98.7%.

Example 7
To tetraethylammonium bromide (0.473 g) was added dimethylacetamide (2 ml), triethylamine (1.1 ml), and acetic acid (0.45 g), and then 3- (4-chlorobenzyl) -2-oxocyclopentanecarboxylic acid. Acid methyl ester (1.0 g) was added and the reaction was allowed to stir at 115-120 ° C. for 12 hours. Toluene was added, and the mixture was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and the aqueous layer was extracted with toluene. The organic layer was dried over anhydrous sodium sulfate, concentrated and then purified with a silica gel column to give 2- (4-chlorobenzyl) cyclopentanone. Yield: 87.2%.

Example 8
To tetraethylammonium bromide (0.593 g), dimethylacetamide (2 ml), triethylamine (1.3 ml), and acetic acid (0.564 g) were added, and then 3- (4-chlorophenyl) -3-oxopropionic acid methyl ester (1.0 g) was added and the reaction was allowed to stir at 120 ° C. for 10 hours. Ethyl acetate was added, and the mixture was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and the aqueous layer was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, concentrated and then purified on a silica gel column to give 1- (4-chlorophenyl) ethan-1-one. Yield: 91.2%.

Example 9
After mixing dimethylacetamide (4 ml), triethylamine (1.4 ml) and acetic acid (0.611 g), 1- (4-chlorobenzyl) -3,3-dimethyl-2-oxocyclopentanecarboxylic acid methyl ester ( 2.0 g) was added, and then triethylamine hydrochloride (0.47 g) was added and reacted at 120 ° C. for 17 hours. Ethyl acetate was added, and the mixture was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and the aqueous layer was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, concentrated and purified by a silica gel column to give 5- (4-chlorobenzyl) -2,2-dimethylcyclopentanone. Yield: 98.5%.

Example 10
After mixing dimethylacetamide (4 ml), pyridine (1.34 g), and acetic acid (1.02 g), 1- (4-chlorobenzyl) -3,3-dimethyl-2-oxocyclopentanecarboxylic acid methyl ester ( 2.0 g) was added, tetramethylammonium chloride (0.52 g) was added, and the mixture was reacted at 120 ° C. for 8 hours and 130 ° C. for 16 hours. Ethyl acetate was added, and the mixture was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and the aqueous layer was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, concentrated and purified by a silica gel column to give 5- (4-chlorobenzyl) -2,2-dimethylcyclopentanone. Yield: 96.3%.

[Reference Example 1]
Toluene (1 ml) was added to compound 1 (10.0 g), then suspended in 0.5 M aqueous sodium hydroxide solution (27.3 ml) and reacted at 110 ° C. Every 2 hours (3 times in total), a 0.5 M aqueous sodium hydroxide solution (27.3 ml) was added to continue the reaction, and the mixture was heated and stirred for a total of 9 hours. After completion of the reaction, the target product was obtained in the same manner as in Example 1. Yield: 80%.

[Reference Example 2]
Dimethylacetamide (1 ml) and triethylamine (1.7 ml) were added to compound 1 (2.0 g), and then acetic acid (0.63 ml) was added, followed by reaction at 155 ° C. for 11 hours while preventing distillate from returning. I let you. After completion of the reaction, the target product was obtained in the same manner as in Example 1. Yield: 94%.

The present invention can be used for the production of 2-benzyl-5,5-di (protected hydroxymethyl) -cyclopentanone derivatives used as raw materials for agricultural chemicals and the like.

Claims (14)

A method for producing a carbonyl compound represented by the following general formula (I) from a compound represented by the following general formula (II),
A method for producing a carbonyl compound, comprising subjecting a compound represented by the following general formula (II) to dealkoxycarbonylation in the presence of an organic carboxylate and a halogenated salt of a tertiary amine.

(In the general formula (II), Z ¹ represents a substituted or unsubstituted alkyl group, cycloalkyl group, aryl group or heterocyclic group, and Z ³ and Z ² independently represent a hydrogen atom, or a substituted or unsubstituted group. Represents a substituted alkyl group, cycloalkyl group, aryl group or heterocyclic group, and R ¹ represents an alkyl group having 1 to 4 carbon atoms, and Z ¹ and Z ² may be bonded to each other.

(In general formula (I), Z ¹ , Z ² and Z ³ are the same as Z ¹ , Z ² and Z ^{3 in} general formula (II), respectively.) The method for producing a carbonyl compound according to claim 1, wherein the halogenated salt is a halogenated quaternary ammonium salt or a metal halide salt. The method for producing a carbonyl compound according to claim 2, wherein the halogenated quaternary ammonium salt is generated in the system by using a tertiary amine hydrogen halide salt. 3. The method for producing a carbonyl compound according to claim 2, wherein the metal halide salt is an alkali metal halide salt. The said halogenated quaternary ammonium salt is a compound shown by the following general formula (III), The manufacturing method of the carbonyl compound of Claim 2 or 3 characterized by the above-mentioned.

(In the general formula (III), R ² to R ⁵ independently represent an alkyl group, a substituted or unsubstituted aralkyl group, or a substituted or unsubstituted aryl group, and L ⁻ represents a halide ion. Yes.) In the above general formula (III), R2 to R5 are independently an alkyl group having 1 to 4 carbon atoms, a substituted or unsubstituted benzyl group, or a substituted or unsubstituted phenyl group, and L- is a chloride. 6. The method for producing a carbonyl compound according to claim 5, which is an ion or bromide ion. The method for producing a carbonyl compound according to any one of claims 1 to 6, wherein the organic carboxylate of the tertiary amine is used as a solvent and no other solvent is used. The production of a carbonyl compound according to any one of claims 1 to 7, wherein the tertiary amine constituting the organic carboxylate of the tertiary amine is triethylamine, trimethylamine, pyridine or picoline. Method. The method for producing a carbonyl compound according to any one of claims 1 to 8, wherein the organic carboxylic acid constituting the organic carboxylate of the tertiary amine is an aliphatic monocarboxylic acid. The compound represented by the general formula (II) is a compound represented by the following general formula (IIa),
10. The method for producing a carbonyl compound according to any one of claims 1 to 9, wherein the carbonyl compound represented by the general formula (I) is a carbonyl compound represented by the following general formula (Ia).

(In the general formula (IIa), R ¹ represents an alkyl group having 1 to 4 carbon atoms, Y represents an alkyl group or haloalkyl group having 1 to 6 carbon atoms, an alkenyl group or haloalkenyl group having 2 to 6 carbon atoms) A part of hydrogen atoms of the alkyl group, haloalkyl group, alkenyl group, haloalkenyl group, alkynyl group or haloalkynyl group is -OG (G is a hydroxy group) And n represents an integer of 0 to 6. When n is 2 or more, a plurality of Y may be the same or different from each other, and n is 2 or more. In this case, a plurality of Y may be bonded to each other to form a ring together with the carbon atom to which each Y is bonded, where X is a halogen atom, an alkyl group having 1 to 4 carbon atoms, or 1 carbon atom. Represents a haloalkyl group having 4 to 4, an alkoxy group having 1 to 4 carbon atoms, a haloalkoxy group having 1 to 4 carbon atoms, a phenyl group, a cyano group or a nitro group, m represents an integer of 0 to 5, and m is 2 or more And the plurality of Xs may be the same or different.)

(In the general formula (Ia), X, Y, m and n are the same as X, Y, m and n in the general formula (IIa), respectively.) The compound represented by the general formula (IIa) is a compound represented by the following general formula (IIb),
11. The method for producing a carbonyl compound according to claim 10, wherein the carbonyl compound represented by the general formula (Ia) is a carbonyl compound represented by the following general formula (Ib).

(In General Formula (IIb), Y ¹ and Y ² independently represent an alkyl group having 1 to 6 carbon atoms or a haloalkyl group, or a hydrogen atom in a part of the alkyl group or haloalkyl group is -OG ¹ (G ¹ Represents a hydroxy-protecting group, and Y ¹ and Y ² may be bonded to each other to form a ring together with the carbon atom to which Y ¹ and Y ² are bonded. R ^1, X and m are each the same as ^R 1, X and m in the general formula (IIa).)

(In the general formula (Ib), ^X, Y 1, ^{Y 2} and m are the same as each ^X in the general formula ^(IIb), and Y 1, ^{Y 2} and m.) The compound represented by the general formula (IIb) is a compound represented by the following general formula (IIc),
The method for producing a carbonyl compound according to claim 11, wherein the carbonyl compound represented by the general formula (Ib) is a carbonyl compound represented by the following general formula (Ic).

(In General Formula (IIc), G ² and G ³ independently represent a protecting group that dissociates under acidic conditions, and G ² and G ³ may be bonded to each other. R ¹ , X, and m are These are the same as R ¹ , X and m in the general formula (IIa).

(In the general formula ^{(Ic), X, G 2} , G 3 and m are the same as ^X, G 2, ^{G 3} and m of each of the above general formula (IIc).) An organic carboxylic acid of the tertiary amine is added by adding a tertiary amine to the compound represented by the general formula (IIc) and then adding an organic carboxylic acid in an amount smaller than the added amount of the tertiary amine. 13. The method for producing a carbonyl compound according to claim 12, wherein a salt is generated in the reaction system to carry out dealkoxycarbonylation. The compound represented by the general formula (IIc) is a compound represented by the following general formula (IId),
14. The method for producing a carbonyl compound according to claim 12 or 13, wherein the carbonyl compound represented by the general formula (Ic) is a carbonyl compound represented by the following general formula (Id).

(In the general formula (IId), G ⁴ and G ⁵ are independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkenyl group having 1 to 4 carbon atoms, or a substituted or unsubstituted phenyl group or naphthyl group. or a benzyl group, G ⁴ and G ⁵ bonded to each other, G ⁴ and G ⁵ may also form a ring with the carbon atom to which they are attached .R ^{1, X} and m are each the general (It is the same as R ¹ , X and m in the formula (IIa).)

(In the general formula ^{(Id), X, G 4} , G 5 and m are the same as ^X, G 4, ^{G 5} and m respectively above general formula (IId).)