JP2008088071A - Method for producing 2-cyclopentylcyclopentanone compound - Google Patents

Abstract

【選択図】なしThe present invention provides a method for producing a 2-cyclopentylcyclopentanone compound useful as a perfume raw material.
SOLUTION: A cyclopentanone compound of (2) is subjected to aldol condensation to obtain a reaction mixture containing the compound represented by (3), and then contacted with carbon dioxide to carry out a neutralization reaction, followed by hydrogenation. A process for producing the compound represented by (1), characterized in that

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Description

  The present invention relates to a method for producing a 2-cyclopentylcyclopentanone compound useful as a fragrance production raw material or a fragrance component.

  A 2-cyclopentylcyclopentanone compound such as 2-cyclopentylcyclopentanone is useful as a raw material for producing a fragrance or a fragrance component.

  Conventionally, the method described in Patent Document 1 is known as a method for producing 2-cyclopentylcyclopentanone. In this method, (i) a mixture of cyclopentanone and an aqueous sodium hydroxide solution is subjected to dehydration condensation under heating and refluxing, and after cooling, the organic phase is separated by a liquid separation operation. Neutralized with dilute hydrochloric acid, excess acid was removed using a saturated aqueous solution of sodium hydrogen carbonate, washed with water and dried over anhydrous sodium sulfate. (Iii) Subsequently, the obtained organic phase was distilled under reduced pressure by 2- Cyclopentylidenecyclopentanone is obtained, (iv) Further, a hydrogenation reaction using active supported palladium (Pd / C) as a catalyst is performed, and (v) cyclopentylcyclopentanone is subsequently obtained by distillation under reduced pressure. is there.

  However, this method involves a complicated processing operation after dehydration condensation, and is inconvenient for mass production of cyclopentylcyclopentanone. That is, after dehydration condensation, the organic phase is separated and neutralized with dilute hydrochloric acid to prevent the formation of multimers in the vacuum distillation step of 2-cyclopentylidenecyclopentanone or 2-cyclopentylcyclopentanone. In addition, unless the operations of removing excess acid with saturated aqueous sodium hydrogen carbonate solution, washing with water, drying and isolating 2-cyclopentylidenecyclopentanone are performed, the target 2-cyclopentylcyclopentanone will be removed. Yield decreased.

On the other hand, Patent Document 2 discloses a method for producing a glycidyl compound by opening a halohydrin compound obtained by an addition reaction between an alcohol or the like and an epihalohydrin in the presence of a basic compound. A step of neutralizing the basic compound by introducing carbon dioxide into the reaction system, and a step of removing the basic compound remaining in the neutralized product using a solid acid mainly composed of silica and alumina. The manufacturing method of the glycidyl compound characterized by including is disclosed.
JP-A-55-127316 Japanese Patent Laid-Open No. 4-82880

  The present invention provides a method for efficiently and industrially producing a 2-cyclopentylcyclopentanone compound, which is useful as a raw material for fragrance production or a fragrance component, using a cyclopentanone compound such as cyclopentanone as a raw material compound. The issue is to provide.

In order to solve the above-mentioned problems, the present inventors have intensively studied a method for producing 2-cyclopentylcyclopentanone described in Patent Document 1. As a result, after neutralizing by adding carbon dioxide to the reaction mixture (organic phase) after the aldol condensation reaction of cyclopentanone, a hydrogenation reaction was performed continuously, which was necessary in the past. After the phase neutralization, operations such as removal of excess acid with a saturated aqueous solution of sodium hydrogen carbonate, water washing, drying and isolation of 2-cyclopentylidenecyclopentanone can be omitted, and in a shorter time than in the past. The hydrogenation reaction was completed, and the knowledge that a 2-cyclopentylcyclopentanone compound was obtained very efficiently and with high yield was obtained, and the present invention was completed based on this knowledge.
Thus, according to the present invention, [I] Formula (2)

(In the formula, R ^{1 to} R ⁴ each independently represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms.) A cyclopentanone compound represented by the formula (1) is subjected to aldol condensation in the presence of a basic compound. , Formula (3)

(Wherein R ^{1 to} R ⁴ represent the same meaning as described above.)
Obtaining a reaction mixture containing a 2-cyclopentylidenecyclopentanone compound represented by:
[II] a step of performing a neutralization reaction by contacting the reaction mixture obtained in the step [I] with carbon dioxide; and

[III] Subsequent to the step [II], a step of hydrogenating the carbon-carbon double bond of the 2-cyclopentylidenecyclopentanone compound represented by the formula (3),
Formula (1), characterized in that

The manufacturing method of 2-cyclopentyl cyclopentanone compound shown by these is provided.
In the production method of the present invention, it is preferable to use cyclopentanone as the cyclopentanone compound represented by the formula (2).

According to the present invention, it is possible to greatly simplify the treatment operation in the production process of a 2-cyclopentylcyclopentanone compound, and to produce a high-quality 2-cyclopentylcyclopentanone compound very efficiently with a high yield.
That is, even if carbon dioxide used for neutralization is used excessively, the excess carbon dioxide can be easily removed out of the system as a gas. Therefore, it is not necessary to remove excess acid using a saturated aqueous solution of sodium hydrogen carbonate as in the case of using dilute hydrochloric acid, and further, each operation of washing with water, drying and isolation of 2-cyclopentylidenecyclopentanone is omitted. can do. In addition, since the hydrogenation reaction is carried out following the neutralization of the organic phase with carbon dioxide, the hydrogenation reaction can be completed in a shorter time than in the prior art. Therefore, according to the present invention, a 2-cyclopentylcyclopentanone compound can be produced very efficiently and with a high yield.

Hereinafter, the present invention will be described in detail.
2-cyclopentylcyclopentanone compound represented by the above formula (1) of the present invention [hereinafter referred to as 2-cyclopentylcyclopentanone compound (1). ] Is a cyclopentanone compound represented by the formula (2) [hereinafter referred to as cyclopentanone compound (2). ] Is subjected to aldol condensation in the presence of a basic compound to give a 2-cyclopentylidenecyclopentanone compound represented by the above formula (3) [hereinafter referred to as 2-cyclopentylidenecyclopentanone compound (3). ], A neutralization reaction is carried out by bringing the reaction mixture into contact with carbon dioxide, and the carbon-carbon double bond of the 2-cyclopentylidenecyclopentanone compound (3) is subsequently hydrogenated. It is characterized by.

That is, in the production method of the present invention,
(A) In the step [I], the cyclopentanone compound (2) is subjected to aldol condensation in the presence of a basic compound to obtain a reaction mixture (a) containing the 2-cyclopentylidenecyclopentanone compound (3). Get
(B) In step [II], the reaction mixture (a) is brought into contact with carbon dioxide to carry out a neutralization reaction to obtain a neutralization reaction mixture (b); and
(C) In step [III], following step [II], the carbon-carbon double bond of 2-cyclopentylidenecyclopentanone compound (3) is hydrogenated to give a 2-cyclopentylcyclopentanone compound. A reaction mixture containing (1) will be obtained.

(A) Process [I]
In step [I], cyclopentanone compound (2) is subjected to aldol condensation in the presence of a basic compound to obtain reaction mixture (a) containing 2-cyclopentylidenecyclopentanone compound (3).

  In the aldol condensation, in the presence of a basic compound in an inert solvent, one molecule of the cyclopentanone compound (2) is dehydrated and condensed with the cyclopentanone compound (2) to form a 2-cyclopentylidenecyclopentanone compound ( This is a reaction to produce 3).

In the cyclopentanone compound (2) used in the present invention, in formula (2), R ^{1 to} R ⁴ each independently represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms. Among them, R ^{1 to} R ⁴ are each independently preferably a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, more preferably a hydrogen atom or a methyl group, and all of them being hydrogen atoms. Is particularly preferred.

  Specific examples of the cyclopentanone compound (2) include cyclopentanone, 3-methylcyclopentanone, 3-ethylcyclopentanone, 3-n-propylcyclopentanone, 3-isopropylcyclopentanone, 3-n -Butylcyclopentanone, 3-isobutylcyclopentanone, 3-t-butylcyclopentanone, 3-n-pentylcyclopentanone, 3-n-hexylcyclopentanone, 3,4-dimethylcyclopentanone, 3, , 4-diethylcyclopentanone, 3,3,4-trimethylcyclopentanone, 3,3,4,4-tetramethylcyclopentanone, and the like. In the present invention, among these, it is particularly preferable to use cyclopentanone.

  The basic compound used for the aldol condensation is not particularly limited. For example, alkali metal alcoholates such as sodium methylate, sodium ethylate, potassium methylate and potassium ethylate; alkaline earth metal alcoholates such as magnesium methylate and magnesium ethylate; alkaline metal water such as sodium hydroxide and potassium hydroxide Oxides; alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide; alkali metal carbonates such as sodium carbonate and potassium carbonate; alkaline earth metal carbonates such as magnesium carbonate and calcium carbonate; pyridine, triethylamine, And amines such as 1,4-diazabicyclo [2.2.2] octane (DABCO) and 1,8-diazabicyclo [5.4.0] 7-undecene (DBU). These may be used alone or in combination of two or more. Among these, the use of alkali metal hydroxides and alkali metal alcoholates is preferred from the viewpoint of obtaining the desired product with good yield.

  The usage-amount of a basic compound is 0.001-0.1 mol normally with respect to 1 mol of cyclopentanone compounds (2), Preferably it is 0.01-0.05 mol.

  The aldol condensation is performed in an inert solvent. The inert solvent to be used is not particularly limited as long as it is stable with respect to the basic compound. Specific examples thereof include water; alcohols such as methanol and ethanol; aliphatic hydrocarbon solvents such as n-hexane, n-heptane and n-octane; and alicyclic hydrocarbons such as cyclopentane, cyclohexane and cycloheptane. Examples of the solvent include aromatic hydrocarbon solvents such as benzene, toluene, ethylbenzene, and xylene; ether solvents such as diethyl ether, dibutyl ether, tetrahydrofuran, and dioxane; mixed solvents composed of two or more of these solvents.

The aldol condensation proceeds smoothly in a temperature range of usually 20 to 180 ° C, preferably 40 to 140 ° C, more preferably 60 to 100 ° C.
The reaction pressure is not particularly limited, but is usually 0.05 to 0.2 MPa, preferably 0.08 to 0.12 MPa.
The reaction time is usually several minutes to several tens of hours.

(B) Process [II]
In step [II], the reaction mixture (a) obtained in step [I] is brought into contact with carbon dioxide to carry out a neutralization reaction to obtain a neutralization reaction mixture (b).

The carbon dioxide used is carbon dioxide alone or a gas containing carbon dioxide as a main component. Specific examples include carbon dioxide gas; dry ice; a mixed gas of carbon dioxide with air, nitrogen, argon, and the like.
As long as the effects of the present invention are not impaired, the form and concentration of carbon dioxide are not particularly limited.

  As a method of bringing the reaction mixture (a) into contact with carbon dioxide, carbon dioxide is introduced into the reaction mixture (a) until the basic compound remaining in the reaction mixture (a) is completely neutralized; And a method of adding a stoichiometric amount or more of dry ice to the mixture (a) with respect to the remaining basic compound.

Completion of the neutralization reaction can be confirmed by, for example, a color reaction of phenolphthalein or a pH meter.
Further, since the excessively supplied carbon dioxide can be easily removed out of the system as carbon dioxide, it is not necessary to strictly control the supply amount of carbon dioxide. Usually, the operation of the step [III] can be continued to be exhausted out of the system as carbon dioxide gas without particularly performing the operation of removing carbon dioxide.

(C) Process [III]
In the step [III], following the step [II], by hydrogenating the carbon-carbon double bond of the 2-cyclopentylidenecyclopentanone compound (3) present in the neutralization reaction mixture (b), A reaction mixture containing the 2-cyclopentylcyclopentanone compound (1) is obtained.

  In the method of the present invention, since the reaction mixture (a) is neutralized with carbon dioxide, the hydrogenation reaction of the 2-cyclopentylidenecyclopentanone compound (3) is conventionally required in the mixture. The removal of excess acid with saturated aqueous sodium hydrogen carbonate solution, washing with water and drying can be omitted, and as a result, the isolation of 2-cyclopentylidenecyclopentanone to improve purity is also omitted. In addition, since the hydrogenation reaction of the 2-cyclopentylidenecyclopentanone compound (3) is carried out following the step [II], it is compared with the hydrogenation reaction in the conventional method for producing a 2-cyclopentylcyclopentanone compound. The hydrogenation reaction can be completed in a short time, and a high-quality 2-cyclopentylcyclopentanone compound can be produced very efficiently and with a high yield. Kill.

The hydrogenation reaction is preferably carried out by a catalytic hydrogen reduction method using a hydrogenation catalyst.
The hydrogenation catalyst to be used is not particularly limited as long as it is generally used for the hydrogenation reaction of olefins. Specific examples thereof include (a) a supported metal catalyst formed by supporting a transition metal such as palladium, ruthenium, rhodium, platinum, nickel on a support such as carbon, alumina, silica, diatomaceous earth, (b) titanium, Examples thereof include homogeneous catalysts composed of organic transition metal compounds such as cobalt and nickel and organometallic compounds such as lithium, magnesium, aluminum and tin, and (c) metal complex catalysts such as rhodium and ruthenium. Among these, the use of the supported metal catalyst (a) is preferable because the target product can be obtained with high versatility and yield.

  Examples of supported metal catalysts include palladium / carbon (Pd / C), palladium / alumina, palladium / silica, palladium / diatomaceous earth, ruthenium / carbon (Ru / C), ruthenium / alumina, ruthenium / silica, platinum / Alumina, platinum / silica, nickel / silica, nickel / alumina, nickel / diatomaceous earth, etc. may be mentioned. Of these, palladium-based or ruthenium-based hydrogenation catalysts are preferable.

  The usage-amount of a hydrogenation catalyst is 0.0001-1 mol normally with respect to 1 mol of 2-cyclopentylidene cyclopentanone compounds (3), Preferably it is 0.001-0.5 mol.

  This hydrogenation reaction can be carried out by adding a hydrogenation catalyst directly to the neutralization reaction mixture (b) and stirring the whole volume in a hydrogen gas atmosphere. It can also be carried out by adding a hydrogenation catalyst to a solution diluted with an appropriate solvent and stirring the whole volume in a hydrogen gas atmosphere.

The solvent used in the latter case is not particularly limited as long as it is an inert solvent for the hydrogenation reaction. Specific examples thereof include alcohols such as methanol, ethanol, n-propanol and isopropanol; aromatic hydrocarbon solvents such as benzene and toluene; aliphatic hydrocarbons such as n-pentane, n-hexane and n-heptane. Solvents; cycloaliphatic hydrocarbon solvents such as cyclopentane, cyclohexane and cycloheptane; ether solvents such as diethyl ether, diisopropyl ether, tetrahydrofuran, 1,2-dimethoxyethane and ethylene glycol diethyl ether;
Among these, from the viewpoint that the hydrogenation catalyst can be uniformly dispersed and the target product can be obtained in good yield, the use of an alcohol solvent is preferred, and the use of ethanol is particularly preferred.

  The usage-amount of a solvent is 1-1000 weight part normally with respect to 1 weight part of 2-cyclopentylidene cyclopentanone compounds (3), Preferably it is 5-100 weight part.

  After completion of the hydrogenation reaction, the target 2-cyclopentylcyclopentanone compound (1) can be isolated by filtering off the hydrogenation catalyst and subjecting the filtrate to a known separation / purification method. . Further, the hydrogenation catalyst collected by filtration and recovered can be used repeatedly.

  Examples of the separation / purification method of the 2-cyclopentylcyclopentanone compound (1) include a distillation method, column chromatography, and recrystallization method. From the viewpoint of work efficiency, a distillation method, particularly a vacuum distillation method is used. preferable.

  The 2-cyclopentylcyclopentanone compound (1) obtained by the present invention is useful as a fragrance component or a fragrance production intermediate.

  Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples. However, the present invention is not limited to the following examples. In the following, all “parts” are based on weight.

(Example 1)
Cyclopentanone 1426.5 parts and sodium hydroxide 5 wt% aqueous solution 473 parts were charged into a reactor and reacted under heating and refluxing conditions for 10 hours. After cooling the reaction solution, the aqueous phase was removed by liquid separation. 10 parts of dry ice was added to the organic phase to neutralize sodium hydroxide remaining in the organic phase. 1.5 parts of 10% Pd / C (50% water-containing product) was added to the neutralized organic phase, and the hydrogenation reaction was performed at a liquid temperature of 50 ° C. to 60 ° C. under normal pressure. The reaction was completed in 15 hours. did. After the catalyst was filtered off, 1050 parts of 2-cyclopentylcyclopentanone was obtained by performing vacuum distillation using a precision distillation column.

(Example 2)
When the operation was performed in the same manner as in Example 1 except that a carbon dioxide cylinder was used instead of dry ice and 10 parts of gaseous carbon dioxide was added, the hydrogenation reaction was completed in 15.5 hours. Further, 1020 parts of 2-cyclopentylcyclopentanone was obtained by vacuum distillation using a precision distillation column.

Claims (2)

[I] Formula (2)

(In the formula, R ^{1 to} R ⁴ each independently represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms.) A cyclopentanone compound represented by the formula (1) is subjected to aldol condensation in the presence of a basic compound. , Formula (3)

(Wherein R ^{1 to} R ⁴ represent the same meaning as described above.)
Obtaining a reaction mixture containing a 2-cyclopentylidenecyclopentanone compound represented by:
[II] A step of carrying out a neutralization reaction by contacting the reaction mixture obtained in step [I] with carbon dioxide, and [III] step [II], followed by 2-cyclohexane represented by the above formula (3) Hydrogenating a carbon-carbon double bond of a pentylidenecyclopentanone compound;
Formula (1), characterized in that

The manufacturing method of 2-cyclopentyl cyclopentanone compound shown by these.   The production method according to claim 1, wherein the cyclopentanone compound represented by the formula (2) is cyclopentanone.