JP6865135B2 - How to treat the composition - Google Patents

Description

The present invention relates to a method for treating a composition.

For example, the reaction in a solution containing a solvent (reaction solvent) such as ethanol is quenched with water, and then the reaction product is extracted with an organic solvent having low compatibility with water (for example, ethyl acetate). (See, for example, Patent Document 1).

However, with such a method, the reaction solvent dissolves in the aqueous phase, and it is difficult to separate, recover, and reuse the reaction solvent.

Further, since the aqueous phase contains a reaction solvent which is an organic solvent, the distribution coefficient of the reaction product between the organic phase and the aqueous phase may decrease, and the yield of the reaction product may decrease. It was.

Japanese Patent No. 5603169

An object of the present invention is to provide a method for treating a composition capable of efficiently separating reaction products and suitably recovering a reaction solvent.

Such an object is achieved by the following invention.
The method for treating the composition of the present invention is a first mixed solution containing a 2-cycloalkenone compound which is a reaction product, a salt produced in the process of synthesizing the reaction product, and a first organic solvent which is an alcohol solvent. And the salt addition process to obtain a salt addition solution by adding salt to
An extraction in which a second organic solvent, which is an aliphatic hydrocarbon that is incompatible with the salt-added solution at an arbitrary ratio, is mixed with the salt-added solution, and the reaction product is extracted into the second organic solvent. It possesses a step,
The salt produced in the synthesis process of the reaction product and the salt added in the salt addition step are the same substance.
The salt is a metal salt containing an alkali metal and a halogen.
When the solubility parameter of the second organic solvent is SP2 [(cal / cm ³ ) ^1/2 ] and the solubility parameter of the first organic solvent is SP1 [(cal / cm ³ ) ^1/2 ], it is 0. It is characterized in that the relationship of << SP2-SP1 | ≦ 19 is satisfied.

The method for treating the composition of the present invention preferably further includes a second organic solvent evaporation step of evaporating the second organic solvent from the extract containing the reaction product and the second organic solvent.

In the method for treating the composition of the present invention, it is preferable to recover the second organic solvent evaporated in the second organic solvent evaporation step and reuse it in the extraction step.

In the method for treating the composition of the present invention, the reaction product is extracted in the extraction step, and the first organic solvent is evaporated from the second mixed solution containing the first organic solvent and the salt. It is preferable to further have an organic solvent evaporation step of.

In the method for treating the composition of the present invention, it is preferable to recover the first organic solvent evaporated in the first organic solvent evaporation step and reuse it as a reaction solvent at the time of synthesizing the reaction product.

In the method for treating the composition of the present invention, it is preferable that the balance obtained by removing the first organic solvent from the second mixed solution is reused in the salt addition step.

The processing method of the composition of the present invention, the 2-cycloalkenone compounds are 3-halo - is preferably one synthesized from cycloalkanone compound.

In the method for treating the composition of the present invention, the 2-cycloalkenone compound preferably has a chemical structure represented by the following formula (1).

（式（１）中のｎは１〜８の整数である。）

(N in equation (1) is an integer from 1 to 8.)

According to the present invention, it is possible to provide a method for treating a composition capable of efficiently separating the reaction product and preferably recovering the reaction solvent.

FIG. 1 is a flowchart showing a preferred embodiment of the method for treating the composition of the present invention.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings.
[Processing method of composition]
First, a method for treating the composition of the present invention will be described.
FIG. 1 is a flowchart showing a preferred embodiment of the method for treating the composition of the present invention.

The method for treating the composition of the present invention includes a salt addition step of adding a salt to a first mixed solution containing a reaction product and a first organic solvent to obtain a salt-added solution, and an arbitrary ratio with the salt-added solution. It is characterized by having an extraction step of mixing an incompatible second organic solvent with the salt-added liquid and extracting the reaction product in the second organic solvent (see FIG. 1).

As a result, the reaction product can be efficiently separated, and the reaction solvent (first organic solvent) can also be suitably recovered. Further, in the treatment method of the present invention, since quenching using an aqueous solution containing a quenching agent is unnecessary, it is possible to prevent the quenching agent from being contained in the system and remove the quenching agent and the substance derived from the quenching agent. Processing for this can be omitted.

<Salt addition process>
In the salt addition step, salt is added to the first mixed solution containing the reaction product and the first organic solvent to obtain a salt-added solution.

This makes it possible to preferably perform extraction with the second organic solvent in the subsequent extraction step.

The salt used in this step is soluble in the first organic solvent.
As a result, the reaction product can be more efficiently extracted with the second organic solvent in the subsequent extraction step.

As the salt used in this step, a metal salt can be preferably used.
As a result, the reaction product can be more efficiently extracted with the second organic solvent in the subsequent extraction step.

As the metal salt that can be used in this step, various metal salts can be used.
From the viewpoint of cations, examples of the metal salt include alkali metal (lithium, sodium, potassium, etc.) salt, alkaline earth metal (magnesium, calcium, barium, etc.) salt and the like.

From the viewpoint of anions, metal salts include, for example, halide (fluoride, chloride, bromide, iodide) salts, oxoate salts (acetate, formate, propionate, oxalate, citric acid). Carboxylates such as salts, perchlorates, chlorates, chlorites, hypochlorites, perbrominates, bromines, bromines, hypobromines, periodates, iodic acids Halogenoxoic acids such as salts, iodic acid, hypochlorous acid, sulfates, sulfites, sulfonates, sulfinates, nitrates, nitrites, phosphates, phosphites, carbonates, borates. , Chromate, dichromate, permanganate, etc.).

In this step, a plurality of kinds of salts and complex salts can be used.
In this step, the salt may be used as a substantially pure substance (including those containing a small amount (for example, 1% by mass or less) of impurities (for example, impurities as unavoidable components)) or other substances. It may be used as a mixture with components (for example, a solution or dispersion having a high concentration (90% by mass or more)).

The amount of the salt used in this step varies depending on the type of the first organic solvent and the like, but is preferably 1 part by mass or more and 100 parts by mass or less with respect to 100 parts by mass of the first organic solvent, and is preferably 3 parts by mass or more. It is more preferably 50 parts by mass or less, and further preferably 5 parts by mass or more and 25 parts by mass or less.

As a result, the reaction product can be more efficiently extracted with the second organic solvent in the subsequent extraction step while suppressing the amount of salt used.

In this step, it is preferable to add a salt to the first mixed solution while stirring the first mixed solution.

As a result, the salts can be efficiently and uniformly mixed, the separation from the second organic solvent is improved in the subsequent extraction step, and the reaction product can be extracted more efficiently with the second organic solvent. ..

Further, in this step, for example, a salt may be added to the heated first mixed solution, or a heated salt may be added to the first mixed solution.

The first mixed solution contains a reaction product produced by a predetermined chemical reaction and a first organic solvent.

In the first mixed solution, the first organic solvent may function as a solvent for dissolving the reaction product as a solute, or as a dispersion medium for dispersing the reaction product as a dispersoid. It may be functional.

The first organic solvent is not particularly limited, but is preferably an organic solvent that is compatible with water at an arbitrary ratio.

When such an organic solvent is used as a reaction solvent in a conventional treatment method (a method of extracting a reaction product into an organic phase using water and an organic solvent having low compatibility with water), the aqueous phase is used at the time of extraction. It was practically impossible to recover it, or it was very costly and difficult to recover. On the other hand, in the present invention, even when an organic solvent compatible with water at an arbitrary ratio is used as the first organic solvent, the first organic solvent can be preferably recovered. Therefore, when an organic solvent compatible with water at an arbitrary ratio is used as the first organic solvent, the effect according to the present invention is more remarkably exhibited.

Examples of the first organic solvent include monovalent alcohols such as methanol, ethanol, propanol and butanol, and alcohol solvents such as polyhydric alcohols such as ethylene glucol; diethyl ether, dibutyl ether, cyclopentyl methyl ether, 1,2-. Ether-based solvents such as dimethoxyethane and tetrahydrofuran; halide-based solvents such as chloroform, dichloromethane, chlorobenzene and carbon tetrachloride; aromatic hydrocarbons such as benzene; alicyclic hydrocarbons such as cyclopentane; aromatics such as pyridine Heterocyclic compound; aliphatic heterocyclic compound such as dioxane; sulfur compound such as carbon disulfide; ketone solvent such as acetone; nitrile solvent such as acetonitrile; ester solvent such as ethyl acetate; N, N- Examples thereof include amide solvents such as dimethylformamide (DMF), and one or a combination of two or more selected from these can be used, but alcohol solvents are preferable, and methanol and ethanol are more preferable.

As a result, the range of selection of the second organic solvent (second organic solvent having low compatibility with the salt-added liquid) to be used in the subsequent extraction step is widened. In addition, the recovery of the first organic solvent in the first organic solvent evaporation step described in detail later becomes easier, and the recovery rate of the first organic solvent can be further increased.

Further, the first organic solvent is usually used as a reaction solvent at the time of synthesizing the reaction product, but if the first organic solvent is as described above, the reaction product can be synthesized more. It can be suitably advanced. In particular, when the reaction is for synthesizing a 2-cycloalkenone compound (among others, a cyclic compound having a cyclic structure including a 3-methyl-2-alkenone structure) from a 3-halo-cycloalkanone compound, the reaction is concerned. Can proceed more favorably.

The content of the first organic solvent in the first mixed liquid is preferably 20% by mass or more and 98% by mass or less, and more preferably 30% by mass or more and 95% by mass or less.

Thereby, in the subsequent extraction step, the reaction product can be extracted more efficiently with the second organic solvent, and the unintentional transfer of the salt into the extract can be prevented more effectively. it can.

Prior to this step, for the purpose of adjusting the content of each component in the first mixed solution, dilution with a solvent, concentration by evaporating the first organic solvent, or the like may be performed.

The reaction product contained in the first mixed solution may be any compound, but is usually an organic compound.

The reaction product contained in the first mixed solution may be a high molecular weight material of a protein, but is preferably a compound having a molecular weight of 1000 or less, and more preferably a compound having a molecular weight of 500 or less. A compound having a molecular weight of 300 or less is preferable, and a compound having a molecular weight of 300 or less is more preferable.

As a result, the reaction product can be more efficiently extracted with the second organic solvent in the subsequent extraction step.

In particular, the reaction product contained in the first mixed solution is preferably a 2-cycloalkenone compound synthesized from a 3-halo-cycloalkanone compound.

As a result, the reaction product can be more efficiently extracted with the second organic solvent in the subsequent extraction step. Further, the range of selection of a suitable combination of the first organic solvent contained in the first mixed solution and the second organic solvent used in the extraction step is widened.

Further, the 2-cycloalkenone compound preferably has a chemical structure represented by the following formula (1).

（式（１）中のｎは１〜８の整数である。）
これにより、前述した効果がより顕著に発揮される。

(N in equation (1) is an integer from 1 to 8.)
As a result, the above-mentioned effect is more prominently exhibited.

The content of the reaction product in the first mixed solution is preferably 1% by mass or more and 70% by mass or less, and more preferably 4% by mass or more and 60% by mass or less.

Thereby, in the subsequent extraction step, the reaction product can be extracted more efficiently with the second organic solvent, and the unintentional transfer of the salt into the extract can be prevented more effectively. it can.

The first mixed solution may contain at least the reaction product and the first organic solvent, but more preferably contains a salt produced in the process of synthesizing the reaction product.

As a result, the reaction product can be more efficiently extracted with the second organic solvent in the subsequent extraction step.

The salt produced in the process of synthesizing the reaction product and the salt added in this step may be different substances, but are preferably the same substance.
As a result, the salt recovered in the subsequent step can be suitably reused in the salt addition step.

The content of the salt (salt produced in the process of synthesizing the reaction product) in the first mixed solution is preferably 1 part by mass or more and 100 parts by mass or less, and 1 part by mass or more and 50 parts by mass or less. It is more preferable that the amount is 1 part by mass or more and 25 parts by mass or less.

Thereby, in the subsequent extraction step, the reaction product can be extracted more efficiently with the second organic solvent, and the unintentional transfer of the salt into the extract can be prevented more effectively. it can.

<Extraction process>
Next, the salt-added liquid and the second organic solvent that are incompatible with the salt-added liquid at an arbitrary ratio are mixed.

Thereby, the reaction product contained in the salt-added liquid (first mixed liquid) can be extracted into the phase of the second organic solvent in a high yield. As a result, the reaction product can finally be isolated in high yield.

The second organic solvent used in this step may be incompatible with the salt-added solution at an arbitrary ratio, but preferably has low compatibility with the salt-added solution. Specifically, for example, the solubility of the second organic solvent in the salt-added solution (mass of the second organic solvent dissolved in 100 g of the salt-added solution) is preferably 15 or less, preferably 10 or less. Is more preferable, and 5.0 or less is further preferable.
As a result, the reaction product can be extracted more efficiently with the second organic solvent.

Further, the second organic solvent is preferably more hydrophobic than the first organic solvent.
As a result, the reaction product can be extracted more efficiently with the second organic solvent.

Further, when the solubility parameter of the second organic solvent is SP2 [(cal / cm ³ ) ^1/2 ] and the solubility parameter of the first organic solvent is SP1 [(cal / cm ³ ) ^1/2 ], it is 0. It is preferable to satisfy the relationship of << SP2-SP1 | ≦ 19, more preferably the relationship of 3 ≦ | SP2-SP1 | ≦ 19 is satisfied, and the relationship of 5 ≦ | SP2-SP1 | ≦ 19 is satisfied. Is even more preferable.
As a result, the reaction product can be extracted more efficiently with the second organic solvent.

The solubility parameter (SP value) δ [(cal / cm ³ ) ^1/2 ] is used as an index of compatibility and affinity of a plurality of substances, and is defined by the formula represented by the following formula (A). Will be done.

δ = (ΔE ^V / V ₀ ) ^1/2 ÷ 2.046 [(cal / cm ³ ) ^1/2 ] …… (A)
^{However, ΔE V [10 6 N ·} m · mol -1] is the heat of _{^{vaporization, V 0 [m 3 · mol}} -1] is the volume per 1 mol. The difference in the solubility parameter of two substances is closely related to the energy required for the two substances to be compatible, and the smaller the difference in solubility parameter, the more energy is required for the two substances to be compatible. It will be small. That is, when two substances are present, in general, the smaller the difference in solubility parameter, the higher the affinity and compatibility.

The solubility parameter can be obtained experimentally or by calculation. Several methods have been proposed for determining the solubility parameter by calculation. For example, for relatively high molecular weight materials, the Small method (PA Small: JA Appl. Chem, 3,71 (1953)). Can be used. Further, for materials having a relatively low molecular weight, the method of Hildebrand (JH Hildebrand and RL Scott: The Solution of Non-Electrories, ACS Monograph Series, 1950) can be used. By using these methods, the solubility parameter can be obtained as a more appropriate value, and the solubility parameter can be easily obtained.

Therefore, the solubility parameters of the first organic solvent and the second organic solvent can be easily obtained as the solubility parameters by using the method of Hildebrand. For materials that cannot be calculated by the method described above, the solubility parameter can be obtained in accordance with the "solubility test" ("Solvent Pocket Handbook", p22, edited by the Society of Synthetic Organic Chemistry). When the solubility parameter of the material is known, the solubility parameter may use that value.

Examples of the second organic solvent include aliphatic hydrocarbons such as hexane, heptane and decane, hydrocarbon solvents such as aromatic hydrocarbons such as benzene, toluene and xylene; and halides such as dichloromethane and chlorobenzene. Solvents and the like can be mentioned, and one or a combination of two or more selected from these can be used, but aliphatic hydrocarbons are preferable, and hexane is more preferable.

As a result, the reaction product can be extracted more efficiently with the second organic solvent. In particular, the reaction product can be extracted more efficiently while more effectively preventing the salt from migrating (extracting) to the phase of the second organic solvent. In addition, the range of preferable combinations of the first organic solvent and the second organic solvent is widened. Therefore, for example, when the first organic solvent is used as the reaction solvent in the step of synthesizing the reaction product, the range of choice of the reaction solvent is widened, and the yield of the reaction product can be further improved. .. In addition, the recovery of the second organic solvent in the second organic solvent evaporation step described in detail later becomes easier, and the recovery rate of the second organic solvent can be further increased.

This step can be performed using, for example, a separating funnel or the like.
Further, in this step, the extraction process may be performed a plurality of times. In this case, the number of extraction processes in this step is preferably 2 or more and 4 or less.

When performing the extraction treatment a plurality of times in this step, the extract (phase of the second organic solvent) obtained by the extraction treatment a plurality of times may be mixed and used in the subsequent steps.

The amount of the second organic solvent used in this step per extraction varies depending on the type of reaction product, the type of the first organic solvent, etc., but is 1 mass by mass with respect to 100 parts by mass of the first mixed solution. The amount is preferably 1900 parts by mass or more, more preferably 5 parts by mass or more and 900 parts by mass or less, and further preferably 10 parts by mass or more and 400 parts by mass or less.

As a result, the reaction product can be extracted more efficiently while suppressing the amount of the second organic solvent used. In addition, the transfer of the salt to the phase of the second organic solvent can be prevented more effectively.

The second organic solvent phase obtained in the extraction step generally has a relatively low salt content, but even if the second organic solvent phase is desalted. Good.

Thereby, for example, the stability of the reaction product can be improved. It is also advantageous in improving the efficiency (yield of reaction product) when the purification treatment is performed later.

In particular, by subjecting the phase of the second organic solvent to desalting treatment prior to the second solvent evaporation step described in detail later, the above-mentioned effects are more prominently exhibited.

In the desalting treatment for the phase of the second organic solvent, for example, a solvent having a higher polarity than the second organic solvent and not mixed with the second organic solvent at an arbitrary ratio is mixed with the phase of the second organic solvent. Then, it can be preferably carried out by separating the liquids.

By adopting such a method, the above-mentioned effects can be obtained, and the first organic solvent contained in the phase of the second organic solvent can also be effectively removed.

As the solvent (solvent having a higher polarity than the second organic solvent and not mixed with the second organic solvent at an arbitrary ratio), water is preferably used, although it depends on the type of the second organic solvent and the like. Can be done.

<Second organic solvent evaporation step>
In the present embodiment, after the above-mentioned extraction step, a second organic solvent evaporation step of evaporating the second organic solvent from the extract containing the reaction product and the second organic solvent is further provided (). (See FIG. 1).

This makes it possible to increase the content of the reaction product and facilitate subsequent handling of the reaction product.

The second organic solvent evaporated in this step is preferably recovered.
As a result, the second organic solvent can be effectively utilized, which is preferable from the viewpoint of resource saving and reduction of production cost (purification cost) of the reaction product.

In particular, the second organic solvent evaporated in this step is preferably reused in the extraction step.
As a result, even if the purity (purification degree) of the second organic solvent is not higher than necessary, the extraction step can be suitably performed, and from the viewpoint of resource saving and reduction of the production cost (purification cost) of the reaction product. Is preferable.

The removal of the second organic solvent in this step can be performed, for example, by heating the extract or placing it in a reduced pressure environment. More specifically, it can be preferably carried out using an evaporator.

In this step, the second organic solvent may be evaporated substantially completely, or the second organic solvent may be evaporated so that a part of the second organic solvent remains.

The content of the reaction product after the second organic solvent is removed in this step is preferably 90% by mass or more, more preferably 95% by mass or more, and 98% by mass or more. Is even more preferable.

Further, the reaction product (component extracted by the second organic solvent) may be purified by, for example, chromatography or the like. More specifically, the component extracted by the second organic solvent has a cyclic structure containing the (E) -3-methyl-2-alkenone structure as described in detail later as the desired reaction product. When the cyclic compound is contained and the isomer or unreacted product of the compound is contained, the target reaction product is separated, and the other isomers or unreacted product are returned to the addition step described in detail later for re-reaction. You may use it.
Thereby, the yield of the target compound can be further improved.

<First organic solvent evaporation step (salt concentration step)>
Further, in the present embodiment, a first organic solvent evaporation step is performed in which the reaction product is extracted in the above-mentioned extraction step and the first organic solvent is evaporated from the second mixed solution containing the first organic solvent and the salt. It also has (see FIG. 1).

Thereby, for example, the first organic solvent separated (distilled) by evaporation can be recovered and effectively utilized.

More specifically, in this step, the first organic solvent evaporated in the first organic solvent evaporation step can be recovered and reused as a reaction solvent at the time of synthesizing the reaction product.

As a result, the first organic solvent can be more preferably reused including the step of synthesizing the reaction product, which is particularly preferable from the viewpoint of resource saving and reduction of the production cost of the reaction product.

The removal of the first organic solvent in this step can be performed, for example, by heating the second mixed solution or placing it in a reduced pressure environment. More specifically, it can be preferably carried out using an evaporator.

In this step, the first organic solvent may be evaporated substantially completely, or the first organic solvent may be evaporated so that a part of the first organic solvent remains in the balance.

The content of the salt in the balance after the first organic solvent is removed in this step is preferably 80% by mass or more, more preferably 85% by mass or more, and 90% by mass or more. It is even more preferable to have it.

Further, the balance obtained by removing the first organic solvent from the second mixed solution may be reused in the salt addition step.

The balance thus obtained contains the salt as a main component and can be suitably reused in the salt addition step.

Further, even if the balance contains impurities, the impurities are often components originally contained in the first mixed liquid. In particular, due to the relationship of the partition coefficient between the first organic solvent and the second organic solvent, the balance may contain a relatively large amount of the reaction product as an impurity, but the balance may be contained. Can be reused in the salt addition step to improve the yield of the reaction product as a whole.

<Synthesis process>
The above-mentioned first mixed solution may contain a reaction product and a first organic solvent, and the types of the reaction product and the first organic solvent are not particularly limited, but usually, the first organic solvent is used. Is the reaction solvent used in the step of synthesizing the reaction product.

Hereinafter, the synthesis of the reaction product will be described with reference to more specific examples. In the following description, a 2-cycloalkenenone compound (particularly, a cyclic compound having a cyclic structure including (E) -3-methyl-2-alkenone structure represented by the following formula (11)) is synthesized as a reaction product. The method will be typically described.

（式（１１）中のＺは二価基である。）

(Z in formula (11) is a divalent group.)

The 2-cycloalkenone compound represented by the above formula (11) is expected to be used as a precursor of useful substances such as fragrances and physiologically active substances.

In the synthesis step according to the present embodiment, a halogen is derived from a 3-halocycloalkanone compound (particularly, a cyclic compound having a cyclic structure including a 3-halo-3-methylalkanone structure represented by the following formula (6)). Desorb hydrogen halide (desorption step).

（式（６）中のＸはハロゲン原子であり、Ｚは二価基である。）

(X in formula (6) is a halogen atom and Z is a divalent group.)

As a result, a cyclic compound having a cyclic structure including a 3-methyl-2-alkenone structure is obtained. In particular, by satisfying the following conditions, a cyclic compound having a cyclic structure including the (E) -3-methyl-2-alkenone structure represented by the above formula (11) can be highly selected and yielded. Can be obtained at a rate. The high content (selectivity) of the cyclic compound having a cyclic structure including the (E) -3-methyl-2-alkenone structure in the product thus increases the content (selectivity) of the cyclic compound (E) -3-methyl-2-alkenone. A cyclic compound having a cyclic structure including a structure can be easily separated from a cyclic compound having a cyclic structure containing an isomer (Z) -3-methyl-2-alkenone structure, and has a higher purity. The target compound can be obtained more preferably.

In particular, when the 3-halo-3-methylcycloalkanone compound represented by the following formula (2) is used as the 3-halocycloalkanone compound, the above tendency is remarkable, and the following formula (1) The (E) -3-methyl-2-cycloalkenone compound represented by (E) is obtained with particularly high selectivity and a particularly high yield.

（式（２）中のｎは１〜８の整数であり、Ｘはハロゲン原子である。）

(N in the formula (2) is an integer of 1 to 8, and X is a halogen atom.)

（式（１）中のｎは１〜８の整数である。）

(N in equation (1) is an integer from 1 to 8.)

The (E) -3-methyl-2-cycloalkenone compound represented by the above formula (1) is, for example, a fragrance having a higher aroma than (R)-(-)-3-methylcyclopentadecanone. Hyaluronic acid, a fragrance with a strong fragrance, a fragrance with a long-lasting fragrance, and a bioactive substance with a stronger hyaluronic acid synthesis promoting action (physiological activity) than (R)-(-)-3-methylcyclopentadecanone. It is expected as a precursor capable of converting into a physiologically active substance or the like having a physiological activity other than the acid synthesis promoting action. Further, the compound in which n in the formula (1) is 1 to 5, 7 or 8 is a novel compound having such high expectations.

This step can be performed using a base.
By using a base, hydrogen halide is eliminated from the 3-halocycloalkanone compound, a neutralization reaction occurs, and a salt is formed.

Examples of the base include hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide; inorganic bases such as coal oxides such as sodium carbonate, sodium ethoxide, potassium ethoxide and sodium t-butoxide. Alkoxides such as potassium t-butoxide; amides such as sodium bis (trimethylsilyl) amide, potassium bis (trimethylsilyl) amide, lithium diisopropylamide; diazabicyclondensen, benzyltrimethylammonium hydroxide, tetramethylammonium hydroxide, etc. Examples include organic bases such as amines.

The amount of the base used in this step is preferably 1.0 equivalent or more and 3.0 equivalent or less, and 1.0 equivalent or more and 2.0 equivalent or less, relative to the 3-halocycloalkanone compound. More preferably, it is 1.0 equivalent or more and 1.5 equivalent or less.

As a result, the amount of the base used is suppressed, and the increase in the production cost of the cyclic compound having a cyclic structure containing the (E) -3-methyl-2-alkenone structure is suppressed, while the increase in the production cost of the cyclic compound (E) -3-methyl-2 is suppressed. -The yield and productivity of the cyclic compound having a cyclic structure including an alkenone structure can be further improved.

Further, in this step, it is preferable to use the above-mentioned base dissolved in a solvent.
Thereby, the production of by-products can be suppressed more effectively.

As the solvent, any solvent may be used as long as it can dissolve the base. For example, a monovalent alcohol such as methanol, ethanol, propanol and butanol, and an alcohol-based solvent such as polyhydric alcohol such as ethylene glucol. Solvents; ether solvents such as diethyl ether, dibutyl ether, cyclopentylmethyl ether, 1,2-dimethoxyethane, tetrahydrofuran; halide solvents such as chloroform, dichloromethane, chlorobenzene, carbon tetrachloride; aromatic hydrocarbons such as benzene; Alicyclic hydrocarbons such as cyclopentane; aromatic heterocyclic compounds such as pyridine; aliphatic heterocyclic compounds such as dioxane; sulfur compounds such as carbon disulfide; ketone solvents such as acetone; acetonitrile and the like Examples thereof include a nitrile solvent; an ester solvent such as ethyl acetate; an amide solvent such as N, N-dimethylformamide (DMF), and one or a combination of two or more selected from these can be used. , Alcohol-based solvent is preferable, and methanol and ethanol are more preferable.

Thereby, a cyclic compound having a cyclic structure including the (E) -3-methyl-2-alkenone structure can be obtained with higher selectivity and higher yield.

When methanol and ethanol are used in combination, the amount of methanol used with respect to 100 parts by mass of ethanol is preferably 2 parts by mass or more and 30 parts by mass or less, and more preferably 3 parts by mass or more and 20 parts by mass or less. It is more preferably more than 10 parts by mass and less than 10 parts by mass.

Thereby, a cyclic compound having a cyclic structure including the (E) -3-methyl-2-alkenone structure can be obtained with particularly high selectivity and a particularly high yield.

The amount of the solvent used in this step is not particularly limited, but the mass ratio is preferably 0.3 times or more and 50 times or less, and more preferably 0.5 times or more and 20 times or less. preferable.

As a result, the amount of solvent used can be suppressed, the increase in production cost can be suppressed, the reaction rate of the desired reaction can be made sufficiently high, and the progress of side reactions can be suppressed more effectively.

The reaction temperature in this step is preferably −60 ° C. or higher and 10 ° C. or lower, more preferably −50 ° C. or higher and 5 ° C. or lower, and further preferably −40 ° C. or higher and 0 ° C. or lower. ..

Thereby, the progress of the side reaction can be suppressed more effectively while making the reaction rate of the target reaction sufficiently high.

The treatment time (reaction time) in this step is preferably 20 minutes or more and 48 hours or less, more preferably 30 minutes or more and 36 hours or less, and further preferably 1 hour or more and 24 hours or less.

As a result, the desired reaction is sufficiently advanced, the yield is increased, and the productivity of the compound having a cyclic structure containing the (E) -3-methyl-2-alkenone structure is further improved. Can be.
Further, this step may be performed in a plurality of stages.

For example, this step has a first step of carrying out the reaction at a first temperature and a second step of carrying out the reaction at a second temperature which is a temperature higher than the first step. May be good.

Thereby, while more effectively suppressing the progress of the side reaction, the residual unreacted component is more effectively suppressed, and a cyclic structure containing the target (E) -3-methyl-2-alkenone structure is provided. The cyclic compound can be obtained with higher selectivity and higher yield. In addition, the time required for the entire step can be shortened, and the productivity of the cyclic compound having a cyclic structure including the (E) -3-methyl-2-alkenone structure can be further improved.

When this step is divided into a plurality of stages in this way, the first temperature is preferably −60 ° C. or higher and −10 ° C. or lower, and more preferably −50 ° C. or higher and −15 ° C. or lower. , −40 ° C. or higher and −20 ° C. or lower is more preferable. The second temperature is preferably −25 ° C. or higher and 10 ° C. or lower, more preferably −20 ° C. or higher and 5 ° C. or lower, and further preferably −15 ° C. or higher and 0 ° C. or lower.
As a result, the above-mentioned effect is more prominently exhibited.

The treatment time at the first temperature is preferably 5 minutes or more and 12 hours or less, more preferably 10 minutes or more and 8 hours or less, and further preferably 20 minutes or more and 3 hours or less. The treatment time at the second temperature is preferably 5 minutes or more and 12 hours or less, more preferably 10 minutes or more and 8 hours or less, and further preferably 20 minutes or more and 3 hours or less.
As a result, the above-mentioned effect is more prominently exhibited.

In the method as described above, a cyclic compound having a cyclic structure including the (E) -3-methyl-2-alkenone structure is synthesized with high selectivity, and is usually a by-product (Z) -3-methyl. -2- The amount of cyclic compound or the like having a cyclic structure including an alkenone structure is sufficiently small.

In the product obtained by the above method, the structure of (Z) -3-methyl-2-alkenone with respect to 100 parts by mass of the cyclic compound having a cyclic structure containing the structure of (E) -3-methyl-2-alkenone. The content of the cyclic compound having a cyclic structure containing the above is preferably 20 parts by mass or less, more preferably 14 parts by mass or less, and further preferably 9 parts by mass or less.

The synthetic method as described above can be applied to the production of a cyclic compound having a cyclic structure including various (E) -3-methyl-2-alkenone structures. Among them, a 10-membered ring or a 17-membered ring It is preferably applied to the production of a cyclic compound having the following cyclic structure.

Thereby, the target compound can be produced with higher yield and higher selectivity. Further, these compounds are compounds that are particularly expected to be used as useful substances such as fragrance precursors and physiologically active substances.

Further, the synthesis method as described above can be applied to the production of a cyclic compound having a cyclic structure including various (E) -3-methyl-2-alkenone structures, among which (E) -3. -Preferably, it is applied to the production of methyl-2-cycloalkenones. In other words, the compound produced by the above method is preferably a homocyclic compound in which the ring portion of the cyclic structure is composed of only carbon atoms.

Thereby, the target compound can be produced with higher yield and higher selectivity. Further, these compounds are compounds that are particularly expected to be used as useful substances such as fragrance precursors and physiologically active substances.

Then, the cyclic compound having a cyclic structure containing the (E) -3-methyl-2-alkenone structure obtained as described above is, for example, a cyclic structure containing an optically active 3-methyl-2-alkanone structure. Can be used as a raw material (precursor) for a cyclic compound (for example, an optically active 3-methyl-2-cycloalkanone compound).

Thereby, a cyclic compound having a cyclic structure including an optically active 3-methyl-2-alkanone structure (for example, an optically active 3-methyl-2-cycloalkanone compound) can be obtained inexpensively and efficiently.

Specifically, an optically active 3-methyl-2-cycloalkanone compound can be obtained by asymmetric hydrogenating a cyclic compound having a cyclic structure containing (E) -3-methyl-2-alkenone structure. Be done.

Asymmetric hydrogenation can be performed, for example, by a method of asymmetric hydrogenation using a ruthenium-optically active phosphine complex as a catalyst.

Next, a cyclic structure containing a 3-halocycloalkanone compound (particularly, a 3-halo-3-methylalkanone structure represented by the above formula (6)) subjected to the synthesis step (elimination step) as described above. A method for synthesizing a cyclic compound (with) is described.

The 3-halocycloalkanone compound (particularly, a cyclic compound having a cyclic structure containing a 3-halo-3-methylalkanone structure) is a cyclic compound having a cyclic structure containing a 3-methyl-3-alkenone structure. (Z) A raw material cyclic compound containing at least one of a cyclic compound having a cyclic structure containing a 3-methyl-2-alkenone structure and a cyclic compound having a cyclic structure containing a 3-methylene-alkanone structure. It can be preferably obtained by adding hydrogen halide (addition step).

A cyclic compound having a cyclic structure containing a 3-methyl-3-alkenone structure that can be used as a raw material cyclic compound, a cyclic compound having a cyclic structure containing a (Z) -3-methyl-2-alkenone structure, and a cyclic compound having a cyclic structure. A cyclic compound having a cyclic structure containing a 3-methylene-alkanone structure can be represented by the following formula (3), the following formula (4), and the following formula (5), respectively.

（式（３）中のＺは二価基である。）

(Z in formula (3) is a divalent group.)

（式（４）中のＺは二価基である。）

(Z in formula (4) is a divalent group.)

（式（５）中のＺは二価基である。）

(Z in formula (5) is a divalent group.)

By this addition step, the compound represented by the above formula (3), the above formula (4), and the above formula (5) is a 3-halocycloalkanone compound (3-halo-3-3) represented by the above formula (6). It is converted to a cyclic compound having a cyclic structure containing a methylalkanone structure).

In particular, in the case of producing the 3-halo-3-methylcycloalkanone compound represented by the above formula (2), the 3-methyl-3-cycloalkenone compound represented by the following formula (7) is used as a raw material cyclic compound. , At least one of (Z) -3-methyl-2-cycloalkenone compound represented by the following formula (8) and 3-methylene-3-cycloalkanone compound represented by the following formula (9) is used. be able to.

（式（７）中のｎは１〜８の整数である。）

(N in equation (7) is an integer from 1 to 8.)

（式（８）中のｎは１〜８の整数である。）

(N in equation (8) is an integer from 1 to 8.)

（式（９）中のｎは１〜８の整数である。）

(N in equation (9) is an integer from 1 to 8.)

When the raw material cyclic compound to be used in the addition step contains at least one of the compound represented by the above formula (7), the compound represented by the above formula (8), and the compound represented by the above formula (9), the said compound. The raw material cyclic compound can be suitably synthesized, for example, by an intramolecular condensation reaction (intramolecular condensation step) using the diketone compound represented by the following formula (10) as a raw material.

（式（１０）中のｍは、７〜１４である。）

(M in the formula (10) is 7-14.)

By the above-mentioned intramolecular condensation reaction, a mixture containing a plurality of raw material cyclic compounds (cyclic compound having a cyclic structure including 3-methyl-3-alkenone structure, (Z) -3-methyl-2-alkenone structure) (A mixture containing two or more compounds selected from the group consisting of a cyclic compound having a cyclic structure containing a 3-methylene-alkanone structure and a cyclic compound having a cyclic structure containing a 3-methylene-alkanone structure) can be obtained in good yield. it can.

The diketone compound used in the intramolecular condensation reaction can be obtained, for example, by reacting an aliphatic diiodide (compound represented by I (CH ₂ ) _l I) with ketones in the presence of an inorganic alkaline compound. Can be done.

Further, the raw material cyclic compound obtained by the intramolecular condensation reaction includes a cyclic compound having a cyclic structure containing the (E) -3-methyl-2-alkenone structure (for example, (E) -3-methyl-2-cyclo). Alkenone compound) may be contained. However, the content of the cyclic compound having a cyclic structure containing the (E) -3-methyl-2-alkenone structure in the mixture thus obtained (mixture containing a plurality of types of cyclic compounds) is usually low. Therefore, in order to obtain a cyclic compound having a cyclic structure containing the (E) -3-methyl-2-alkenone structure with high purity, isomerization by the addition step described in detail later and the desorption step described above Is preferable.

The intramolecular condensation reaction can be efficiently obtained by subjecting the diketone compound represented by the above formula (10) to a vapor phase condensation reaction in the presence of a compound of Group 2 of the Periodic Table of the Elements as a catalyst.

As a result, the process of removing the catalyst after the condensation reaction can be omitted or simplified, and the productivity of the raw material cyclic compound can be further improved.

Examples of the compound (catalyst) of Group 2 of the Periodic Table of the Elements include magnesium oxide, calcium oxide, zinc oxide and the like, and one or a combination of two or more selected from these can be used. Of these, zinc oxide is preferable.

As a result, the intramolecular condensation reaction can be allowed to proceed more efficiently, the reaction time can be shortened, and the yield of the raw material cyclic compound can be made higher.

The form of the catalyst in the intramolecular condensation reaction is not particularly limited, but is usually pellets or tablets.
The BET specific surface area of the catalyst ^{is preferably 10 m 2} / g or less.

Thereby, the yield of the raw material cyclic compound can be made higher, and the deterioration of the catalyst can be suppressed more effectively.

In the intramolecular condensation reaction, a solvent or an inert gas is usually used for the purpose of suppressing the intermolecular condensation reaction as a side reaction. More specifically, a reaction in which a raw material diketone compound is dissolved in a solvent, the solution is vaporized under a carrier of an inert gas in an evaporation part such as an evaporation tube or an evaporation can, and then a catalyst is filled. By introducing it into a tube, the intramolecular condensation reaction can be suitably allowed to proceed.

Examples of the solvent in the intramolecular condensation reaction include hydrocarbons, and in particular, aliphatic hydrocarbons having 6 or more and 14 or less carbon atoms, aromatic hydrocarbons, and the like can be preferably used. More specifically, for example, toluene, xylene, decalin, hexane, heptane, octane, nonane, decane, dodecane, tetradecane and the like can be mentioned. As the solvent, the second organic solvent recovered in the above-mentioned second organic solvent evaporation step may be used. Further, the solvent used in the intramolecular condensation reaction may be reused in the above-mentioned extraction step, or may be reused in another intramolecular condensation reaction.

The amount of the solvent used is not particularly limited, but it is preferably 10 times or more and 100 times or less in terms of mass ratio with respect to the raw material diketone compound.

As a result, the progress of side reactions can be more effectively suppressed while suppressing the amount of solvent used and the increase in production cost.

The inert gas may be any gas that is inert in the intramolecular condensation reaction, and examples thereof include helium, argon, carbon dioxide, and nitrogen, and one or a combination of two or more selected from these is used. be able to.

The amount of the inert gas used is preferably 0.2 L or more and 20 L or less with respect to 1 g of the raw material diketone compound.

As a result, the progress of the side reaction can be more effectively suppressed while suppressing the amount of the inert gas used and the increase in the production cost.

The partial pressure of the diketone compound during the intramolecular condensation reaction _{is preferably 50 mmH 2} O or more and 500 mmH ₂ O or less.

Thereby, the yield of the raw material cyclic compound can be further increased while suppressing the progress of the side reaction more effectively.

The temperature of the portion (evaporation portion) where the composition containing the raw material diketone compound is evaporated is preferably 200 ° C. or higher and 450 ° C. or lower, more preferably 300 ° C. or higher and 400 ° C. or lower, and 350 ° C. or higher and 380 ° C. or lower. The following is more preferable.
I.

As a result, the intramolecular condensation reaction can be allowed to proceed more efficiently, the reaction time can be shortened, and the yield of the raw material cyclic compound can be made higher.

The rate of supply of the raw material diketone compound to the site where the catalyst is present is not particularly limited, but the LHSV of the diketone compound is preferably 0.002 or more and 0.10 or less.

Thereby, the conversion rate to the cyclic compound can be made higher while more effectively preventing the progress of the side reaction. In addition, it is possible to more effectively prevent a decrease in catalytic activity, and it is possible to stably produce a cyclic compound for a longer period of time with excellent productivity.

On the other hand, if the supply rate of the diketone compound is too slow, the reaction rate of the diketone compound decreases, and the conversion rate to the cyclic compound decreases. Further, if the supply rate of the diketone compound is too fast, the side reaction tends to proceed and the catalytic activity tends to decrease.

The conversion rate of the diketone compound to the raw material cyclic compound is preferably 40% or more and 80% or less.

Thereby, the cyclic compound can be obtained more efficiently while more effectively preventing the progress of the side reaction.

On the other hand, if the conversion rate of the diketone compound to the raw material cyclic compound is too high, the intermolecular condensation reaction as a side reaction tends to proceed, and the process of removing an unintended product becomes complicated. Further, if the conversion rate of the diketone compound to the raw material cyclic compound is too low, the intermolecular condensation reaction as a side reaction is suppressed and the selectivity to the raw material cyclic compound is improved, but the residual rate of the unreacted diketone compound is high. Become.

The unreacted diketone compound can be recovered and reused in the intramolecular condensation reaction.

Although the catalytic activity gradually decreases with the lapse of the reaction time, the catalyst use time until the catalyst reactivation can be lengthened by gradually increasing the reaction temperature.

For example, even if the reaction temperature is raised to a predetermined temperature (for example, a temperature of 360 ° C. or higher and 400 ° C. or lower), the conversion rate to the raw material cyclic compound does not increase, and when it decreases, the supply of the diketone compound as a raw material is stopped. Then, the catalyst may be reactivated.

The reactivation of the catalyst can be carried out, for example, by introducing air or oxygen into the site (catalyst layer) where the catalyst is present and incinerating and removing the high boiling point by-products accumulated in the catalyst layer. The introduction rate of air or oxygen is not particularly limited. The reactivation temperature is preferably 400 ° C. or higher, more preferably 450 ° C. or higher and 500 ° C. or lower.

The reaction product is obtained in liquid form, for example, by collecting at 20 ° C. or higher and 60 ° C. or lower. The main composition of this reaction product is the solvent used, the above-mentioned raw material cyclic compound, and the unreacted diketone compound.

By further cooling the obtained reaction product solution, most of the unreacted diketone compound can be crystallized and separated, and the recovered unreacted diketone compound can be suitably reused (for example, recycled). Can be done.

In the addition step, for example, the reaction product obtained as described above may be used as it is, or at least a part of the unreacted diketone compound from the reaction product may be simplified by crystallization separation as described above. You may use the one which has been removed from the above, or the one which has at least a part of the solvent removed, and further, the one which has been removed by a purification treatment such as distillation to remove most of the compound other than the raw material cyclic compound.

In the production of the diketone compound, for example, an aliphatic diiodide ( _{compound represented by I (CH 2} ) _l I) and a ketone are reacted in the presence of an inorganic alkaline compound, followed by a decarboxylation reaction. Can be obtained by performing.

As the ketones, for example, ethyl acetoacetate or the like can be used.
Further, as the inorganic alkaline compound, potassium carbonate or the like can be used.

Next, the details of the addition process will be described.
As described above, in the addition step, a cyclic compound having a cyclic structure containing a 3-methyl-3-alkenone structure, a cyclic compound having a cyclic structure containing a (Z) -3-methyl-2-alkenone structure, and a cyclic compound having a cyclic structure containing (Z) -3-methyl-2-alkenone structure. , 3-Halocycloalkanone compound (particularly 3-halo-3-3-) by adding hydrogen halide to the raw material cyclic compound containing at least one of the cyclic compounds having a cyclic structure containing a 3-methylene-alkanone structure. A cyclic compound having a cyclic structure containing a methylalkanone structure) is obtained.

Examples of the hydrogen halide include hydrogen fluoride, hydrogen chloride, hydrogen bromide, hydrogen iodide and the like, and among them, hydrogen chloride is preferable.

Thereby, the stability of the 3-halocycloalkanone compound can be made more suitable, and the 3-halocycloalkanone compound and the 2-cycloalkenone compound (particularly, (E) -3-methyl-) can be made more suitable. 2-Cyclic compound having a cyclic structure including an alkenone structure) is advantageous from the viewpoint of suppressing the production cost.

The amount of hydrogen halide used is preferably 1.0 equivalent or more and 100 equivalent or less, more preferably 1.5 equivalent or more and 30 equivalent or less, and 2.0 equivalent or more and 30 equivalent, relative to the raw material cyclic compound. It is more preferably 2.0 equivalents or more and 10 equivalents or less.

As a result, it is possible to efficiently produce the 3-halocycloalkanone compound in a shorter time while suppressing the amount of hydrogen halide used and the increase in the production cost of the 3-halocycloalkanone compound. -The productivity of halocycloalkanone compounds can be improved.

The hydrogen halide may be used in a gaseous state or a liquid state (condensed state), but is preferably used in a solution state.

As a result, the formation of by-products can be suppressed, and a cyclic compound having a cyclic structure containing a 3-halo-3-methylalkanone structure (E) -3-methyl-2-alkenone structure can be obtained. It is also advantageous from the viewpoint of the production cost of the cyclic compound having the cyclic structure including the cyclic compound and the safety.

Examples of the solvent constituting the hydrogen halide solution include aliphatic hydrocarbon solvents such as hexane, heptane and decane; aromatic hydrocarbons such as benzene, toluene and xylene; halide solvents such as dichloromethane and chlorobenzene. Alcohol-based solvents such as methanol, ethanol, propanol and butanol; ether-based solvents such as diethyl ether, dibutyl ether, cyclopentylmethyl ether, 1,2-dimethoxyethane and tetrahydrofuran; acetic acid; ester-based solvents such as ethyl acetate and the like. It is possible to use one kind or a combination of two or more kinds selected from these, but it is preferable to use an ethyl acetate solution. In particular, it is preferable to use an ethyl acetate solution having a hydrogen halide content of 1% by mass or more, and more preferably to use an ethyl acetate solution having a hydrogen halide content of 10% by mass or more.

Thereby, the yield of the cyclic compound (3-halocycloalkanone compound) having a cyclic structure including the 3-halo-3-methylalkanone structure can be made particularly excellent. Moreover, since the 3-halocycloalkanone compound can be efficiently produced in a shorter time, the productivity of the 3-halocycloalkanone compound can be made more excellent.

The reaction temperature in this step is preferably 5 ° C. or higher and 50 ° C. or lower, and more preferably 10 ° C. or higher and 40 ° C. or lower.

As a result, the reaction temperature can be controlled more easily, the increase in the production cost of the 3-halocycloalkanone compound can be suppressed, and the progress of the side reaction can be suppressed more effectively. In addition, the 3-halocycloalkanone compound can be efficiently produced in a shorter time, and the productivity of the 3-halocycloalkanone compound can be made more excellent.

The treatment time (reaction time) in this step is preferably 0.5 hours or more and 12 hours or less, and more preferably 1 hour or more and 8 hours or less.

Thereby, the desired reaction can be sufficiently proceeded, the yield can be made higher, and the productivity of the 3-halocycloalkanone compound can be made more excellent.

The 3-halocycloalkanone compound obtained as described above may be subjected to treatments such as removal of solvent and purification prior to the subsequent elimination step.

Although preferred embodiments of the present invention have been described above, the present invention is not limited thereto.

For example, the composition treatment method of the present invention may have steps other than the above-mentioned steps (for example, pretreatment step, intermediate treatment step, posttreatment step, etc.).

Alternatively, the method for treating the composition of the present invention may include the salt addition step and the extraction step described above, and other steps may be omitted.

Hereinafter, the present invention will be described in detail based on specific examples, but the present invention is not limited thereto. The treatments and measurements in the following examples, which did not indicate the temperature conditions, were carried out at room temperature (23 ° C.).

(Example 1)
First, (E) -3-methyl-2-cyclopentadecenone as a 2-cycloalkenenone compound (cyclic compound having a cyclic structure including a 3-methyl-2-alkenone structure) was synthesized as follows. ..

First, in a column having a diameter of 22 mm and a length of 40 cm, 40 mL of porcelain Rashihi having a diameter of 3 to 4 mm is filled in the upper part, and 60 mL of zinc oxide pellets (diameter 3 to 5 mm) having a ^{BET specific surface area of 5.2 m 2 / g is used as a catalyst.} The lower part was filled and heated so that the Rashihi layer temperature became 315 ° C. and the catalyst layer temperature became 360 ° C.

Intramolecular condensation is introduced into this heated column under a nitrogen (5 L / hour) carrier as an inert gas with a decane solution in which 5% by mass of 2,15-hexadecanedione is dissolved at a rate of 25 g / hour. The reaction was carried out. In addition, the reaction product was cooled to 30 to 50 ° C. and collected.

Then, a continuous reaction was carried out for 6 hours, and the reaction product was analyzed by gas chromatography. As a result, 3-methyl-3-cyclopentadesenone represented by the above formula (7) was represented by the above formula (8). Raw material cyclic compound consisting of a plurality of 15-membered cyclic compounds including (Z) -3-methyl-2-cycloheptadecenone and 3-methylene-3-cyclopentadecanone represented by the above formula (9). It was confirmed that a compound (n in each formula is 6) was produced.

Next, the raw material cyclic compound (27.9 g) was added to ethyl acetate (ethyl acetate solution of hydrogen chloride) (15.1 mass%, 143.0 g, hydrogen chloride content 592.2 mmol) to which hydrogen chloride gas was blown and dissolved. , 118.1 mmol) and reacted at room temperature for 2 hours.

Next, water and n-hexane were added, and the organic phase was washed with aqueous sodium hydrogen carbonate, water and saturated brine, and dried over sodium sulfate.

Next, the solvent of the organic phase was distilled off under reduced pressure, and 3-chloro-3-methylcyclopentadecanone (formula (2)) as a 3-halocycloalkanone compound (3-halo-3-methylcycloalkanone compound) was prepared. ) Was obtained in 30.5 g and a yield of 94.8%.

Then, 3-chloro-3-methylcyclopentadecanone (272 mg, 1.00 mmol) as the 3-halocycloalkanone compound (3-halo-3-methylcycloalkanone compound) obtained as described above. Lithium hydroxide monohydrate (62.9 mg, 1.50 mmol) was added to an ethanol solution containing ethanol (3.3 mL), and the mixture was stirred at 0 ° C. for 2 hours to promote the desorption reaction. A first mixed solution (first mixed solution A) containing the reaction product and the first organic solvent was obtained. The content of the first organic solvent contained in the first mixed solution is 88% by mass, and the content of the salt (lithium chloride) contained in the first mixed solution is 1.5% by mass. there were.

Next, while stirring the above first mixed solution, lithium chloride (250 mg) as a salt was added to obtain a salt-added solution (salt addition step).

Next, the salt-added solution was extracted three times using hexane as a second organic solvent (extraction step), the separated hexane phase (extract) was combined, and then hexane was evaporated using an evaporator. (Second organic solvent evaporation step). As a result, a solid reaction product could be obtained and hexane could be recovered with a high recovery rate.

In the extraction step, 150 parts by mass of hexane was used for each extraction with respect to 100 parts by mass of ethanol in the first mixed solution.

The obtained product was obtained with (E) -3-methyl-2-cyclopentadecenone as the (E) -3-methyl-2-cycloalkenone compound (a compound in which n of the formula (1) is 6). , (Z) -3-Methyl-2-cyclopentadeceneon, was an isomer mixture, and the yield was 96.8%. When the ratio was determined by gas chromatography (GC), (E) -3-methyl-2-cycloheptadesenone was 87.3%, and (Z) -3-methyl-2-cycloheptadesenone was 12. It was 7%.

(Example 2)
[Synthesis of (R)-(-)-3-methylcyclopentadecanol]
The mixture of (E) -3-methyl-2-cycloalkenone obtained in Example 1 was separated and purified by silica gel column chromatography (developing solvent: hexane / ethyl acetate 98/2 (volume ratio)). The obtained (E) -3-methyl-2-cyclopentadesenone (236 mg, 1.0 mmol) was added to Ru ₂ Cl ₄ [(S) -Tol-BINAP] _{2 Net 3} (1 mg, 0.0005 mmol) and methanol. Together with (1 mL), it was placed in a nitrogen-substituted 25 mL autoclave and reacted at 25 ° C. for 24 hours under 50 atm hydrogen pressure. Then, after distilling off the solvent, the obtained crude product was purified by silica gel column chromatography (developing solvent: hexane / ethyl acetate 20/1 (volume ratio)), and (R)-(-)-3. -Methylcyclopentadecanone was obtained in an amount of 226 mg (yield 95%).

(Comparative Example 1)
First, a first mixed solution was obtained in the same manner as in Example 1.
Then, an aqueous ammonium chloride solution was added to the first mixed solution (a liquid containing ethanol as the first organic solvent), and then the mixture was extracted twice with ethyl acetate. For extraction, 100 parts by mass of ethyl acetate was used for each extraction with respect to 100 parts by mass of the first mixed solution.
Next, the organic phase was washed with water and saturated brine, and dried over sodium sulfate.

The obtained product was obtained with (E) -3-methyl-2-cycloheptadecenone as a compound (E) -3-methyl-2-cycloarkenone (a compound in which n of formula (1) is 6). , (Z) -3-methyl-2-cycloheptadeceneon, was an isomer mixture, and the yield was 97.8%.

For Example 1 and Comparative Example 1, the conditions of the first mixed solution and the treatment conditions of the composition are summarized in Table 1.

In Example 1, the solubility of the second organic solvent in the salt-added solution (mass of the second organic solvent dissolved in 100 g of the salt-added solution) was 5.0 or less.

In the above-mentioned example, the target reaction product could be efficiently separated.
Further, in Example 1, hexane used as the second organic solvent could be recovered with a high recovery rate (90% or more).

Further, the hexane (second organic solvent) evaporated and recovered from the extract in Example 1 could be suitably reused in the extraction step for the salt-added solution obtained in the same manner as described above. ..

Further, ethanol is added from the second mixed solution (second mixed solution containing ethanol (first organic solvent) and salt) after the reaction product has been extracted in the extraction step of Example 1 using an evaporator. It was evaporated and separated into a solid mainly composed of salts and ethanol (first organic solvent evaporation step).

Further, in Example 1, ethanol as the first organic solvent could be recovered with a high recovery rate (90% or more).

Then, the first organic solvent separated as described above could be suitably reused in the same synthesis step (desorption step) as described above.

In addition, the salt separated as described above could be suitably reused in the same salt addition step as described above.

On the other hand, in Comparative Example 1, satisfactory results were not obtained. For example, in Comparative Example 1, ethanol (reaction solvent) could not be recovered because ethanol, which is a reaction solvent (first organic solvent), was dissolved in the aqueous phase.

The method for treating the composition of the present invention includes a salt addition step of adding a salt to a first mixed solution containing a reaction product and a first organic solvent to obtain a salt-added solution, and an arbitrary ratio with the salt-added solution. It has an extraction step of mixing an incompatible second organic solvent with the salt-added solution and extracting the reaction product in the second organic solvent. Therefore, the method for treating the composition of the present invention can efficiently separate the reaction product and can suitably recover the reaction solvent, and has industrial applicability.

Claims (8)

A salt is added to a first mixed solution containing a 2-cycloalkenone compound which is a reaction product, a salt produced in the synthesis process of the reaction product, and a first organic solvent which is an alcohol solvent to obtain a salt-added solution. Salt addition process and
An extraction in which a second organic solvent, which is an aliphatic hydrocarbon that is incompatible with the salt-added solution at an arbitrary ratio, is mixed with the salt-added solution, and the reaction product is extracted into the second organic solvent. It possesses a step,
The salt produced in the synthesis process of the reaction product and the salt added in the salt addition step are the same substance.
The salt is a metal salt containing an alkali metal and a halogen.
When the solubility parameter of the second organic solvent is SP2 [(cal / cm ³ ) ^1/2 ] and the solubility parameter of the first organic solvent is SP1 [(cal / cm ³ ) ^1/2 ], it is 0. A method for treating a composition, which satisfies the relationship of << SP2-SP1 | ≤19. The method for treating a composition according to claim 1, further comprising a second organic solvent evaporation step of evaporating the second organic solvent from the reaction product and the extract containing the second organic solvent. The method for treating a composition according to claim 2, wherein the second organic solvent evaporated in the second organic solvent evaporation step is recovered and reused in the extraction step. The claim further comprises a first organic solvent evaporation step in which the reaction product is extracted in the extraction step and the first organic solvent is evaporated from a second mixed solution containing the first organic solvent and the salt. The method for treating a composition according to any one of 1 to 3. The method for treating a composition according to claim 4, wherein the first organic solvent evaporated in the first organic solvent evaporation step is recovered and reused as a reaction solvent at the time of synthesizing the reaction product. The method for treating a composition according to claim 4 or 5, wherein the balance obtained by removing the first organic solvent from the second mixed solution is reused in the salt addition step. The 2-cycloalkenone compounds are 3-halo - processing method of a composition according to any one of cycloalkanone compound claims 1 is synthesized from compound 6. The method for treating a composition according to claim 7 , wherein the 2-cycloalkenone compound has a chemical structure represented by the following formula (1).

(N in equation (1) is an integer from 1 to 8.)

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