JP4362720B2 - Method for producing alicyclic aldehyde - Google Patents

Description

      The present invention relates to a method for producing an alicyclic aldehyde in which an aromatic ring of an aromatic aldehyde is hydrogenated. More specifically, the present invention relates to a method for producing a high-purity alicyclic aldehyde used as a raw material for a fragrance or a pharmaceutical / agrochemical intermediate in a high yield and industrially advantageously.

  As a method for producing an alicyclic aldehyde, a corresponding alicyclic carboxylic acid ester is reduced to obtain a desired alicyclic aldehyde (see, for example, Patent Document 1), and a corresponding alicyclic alcohol is oxidized to obtain. A method for obtaining an alicyclic aldehyde (for example, see Patent Document 2), a method for obtaining a desired alicyclic aldehyde by reducing the corresponding alicyclic carboxylic acid (for example, see Patent Document 3 or 4), and the like. A method of formylating an alicyclic olefin with carbon monoxide or carbon dioxide and hydrogen is known (for example, see Patent Document 5 or 6). However, the method for reducing the alicyclic carboxylic acid ester includes a step of converting the alicyclic carboxylic acid into an ester, which is complicated as a process. Moreover, the method of reducing an alicyclic carboxylic acid must carry out reaction under severe conditions, or must use a compound that is difficult to obtain industrially. Furthermore, even when the corresponding olefin or alcohol is used as a starting material, a reaction step such as Diels-Alder reaction must be added.

US Pat. No. 3,660,416 U.S. Pat. No. 3,901,896 European Patent Application Publication No. 439115 International Publication No. 00/12457 JP-A-5-246925 Japanese Patent Laid-Open No. 2001-233895

  An object of the present invention is to provide a method for producing an alicyclic aldehyde in a high yield and industrially advantageously.

  As a result of intensive studies to achieve the above object, the present inventor has obtained an alicyclic acetal by acetalizing an aromatic aldehyde to protect a formyl group and then hydrogenating it, and then hydrolyzing it. The method for producing the desired alicyclic aldehyde by deprotecting the acetal was found.

The present invention has been completed based on such findings.
That is, this invention relates to the manufacturing method of the alicyclic aldehyde characterized by making the following process AC essential.
Step A: Aromatic aldehyde is acetalized with alcohol to form aromatic acetal.
Step B: The aromatic acetal obtained in Step A is hydrogenated to an alicyclic acetal in the presence of a catalyst containing one or more noble metals selected from rhodium, palladium and ruthenium, and an acid .
Step C: The alicyclic acetal obtained in Step B is hydrolyzed to obtain an alicyclic aldehyde.

  According to the present invention, a high-purity alicyclic aldehyde that is used as a fragrance, a pharmaceutical or agrochemical intermediate, and the like can be produced with good yield and industrially advantageously.

<Step A: Acetalization of aromatic aldehyde>
First, a method for producing an aromatic acetal from an aromatic aldehyde will be described.

  In the method for producing an aromatic acetal of the present invention, the aromatic aldehyde used as a raw material may be a compound in which one or more formyl groups are introduced on the aromatic ring, and is not particularly limited. From among them, it can be appropriately selected according to the purpose of use.

  Examples of this aromatic aldehyde include benzaldehyde, p-tolualdehyde, ortho-tolualdehyde, metatolualdehyde, 2,4-dimethylbenzaldehyde, 2,5-dimethylbenzaldehyde, 3,4-dimethylbenzaldehyde, 2,4,5- Trimethylbenzaldehyde, 2,4,6-trimethylbenzaldehyde, para-normal propyl benzaldehyde, ortho-normal propyl benzaldehyde, methanol-propyl benzaldehyde, para-isopropyl benzaldehyde, ortho-isopropyl benzaldehyde, meta-isopropyl benzaldehyde, para-normal butyl benzaldehyde, ortho-normal butyl benzaldehyde, meta Normal butylbenzaldehyde, paraisobutylbenzaldehyde, ortho Butyl benzaldehyde, metaisobutyl benzaldehyde, para secondary butyl benzaldehyde, ortho secondary butyl benzaldehyde, meta secondary butyl benzaldehyde, para tertiary butyl benzaldehyde, ortho tertiary butyl benzaldehyde, meta tertiary butyl benzaldehyde, α-naphthaldehyde, β-naphthaldehyde, Examples thereof include 2-tetralin carbaldehyde, 4-biphenyl carbaldehyde, parahydroxybenzaldehyde, orthohydroxybenzaldehyde, paramethoxybenzaldehyde, orthomethoxybenzaldehyde, phthalaldehyde, isophthalaldehyde, and terephthalaldehyde.

  Among these, benzaldehyde, p-tolualdehyde, 2,4-dimethylbenzaldehyde, 3,4-dimethylbenzaldehyde, 2,4,5-trimethylbenzaldehyde from the point of industrial utility value of the obtained alicyclic aldehyde Paraisopropyl benzaldehyde and paraisobutyl benzaldehyde are preferable. The quality of these aromatic aldehydes may be those usually commercially available.

  Examples of the acetalizing agent used in the acetalization reaction of the present invention include methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-methyl-1-propanol, Alcohols such as 2-butanol, 2-methyl-2-propanol, ethylene glycol, 1,2-propanediol, 1,3-propanediol, neopentyl glycol, pentaerythritol and sorbitol are used. Among these, particularly suitable acetalizing agents include ethylene glycol, pentaerythritol, and sorbitol. The amount of the acetalizing agent used is preferably 5 to 100 mol in the case of a monohydroxy compound and 2 to 100 mol in the case of a polyhydroxy compound with respect to 1 mol of the aromatic aldehyde.

  In the acetalization, the aromatic aldehyde and the acetalizing agent can be appropriately combined. For example, 2-phenyl-1,3-dioxolane can be obtained from benzaldehyde and ethylene glycol. Similarly, 2- (2,4-dimethylphenyl) -1,3-dioxolane can be obtained from 2,4-dimethylbenzaldehyde and ethylene glycol.

  In the acetalization reaction in the present invention, a reaction solvent is preferably used, and aromatic or aliphatic hydrocarbons having 6 to 9 carbon atoms are particularly desirable. Examples of the reaction solvent include hexane, heptane, octane, nonane, toluene and the like. The amount of the solvent used at this time is preferably 1 to 50% by weight, more preferably 5 to 40% by weight as the aromatic aldehyde concentration in the reaction solution.

  In the present invention, the acetalization reaction is preferably performed while refluxing hydrocarbons as solvents. Further, since it is a dehydration reaction, it is necessary to remove water generated during the reaction. The reaction temperature is selected from the reflux temperature range of the solvent used. The reaction is usually completed in 5 to 48 hours.

  In the acetal reaction, an acid catalyst is used, and examples thereof include p-toluenesulfonic acid, hydrochloric acid, sulfuric acid, acetic acid, nitric acid, zeolite, and the like, and 0.01 to 1. In the case of 0 mol and zeolite, it is preferable to use 0.5 to 10 g.

  After the acetalization reaction, the aromatic acetal obtained by distilling the reaction solution can be subjected to a hydrogenation reaction in Step B. The distillation residual liquid at this time may be recycled to the acetalization reactor. The ratio of returning the remaining liquid can be appropriately determined according to the reaction. Next, the hydrogenation reaction of the obtained aromatic acetal will be described.

<Step B: Hydrogenation of aromatic acetal>
The hydrogenation reaction of the aromatic acetal in the present invention can proceed without a reaction solvent or with a reaction solvent. Examples of the reaction solvent include hydrocarbons, halogenated hydrocarbons, esters, ketones, ethers, alcohols, aliphatic acids, and the like, and methanol and tetrahydrofuran are particularly preferable. The aromatic acetal concentration in the reaction solution at this time is preferably 5 to 50% by weight, more preferably 10 to 40% by weight. In addition, an acid can be added to the reaction substrate or the reaction solvent in order to accelerate the hydrogenation reaction. Examples of the acid include saturated aliphatic carboxylic acids such as acetic acid, propionic acid, and butyric acid, and inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, zeolite, and heteropolyacid. The acid concentration in the reaction solution at this time is preferably 0.1 to 20% by weight, and more preferably 0.5 to 10% by weight.

  In the present invention, it is preferable to use a catalyst containing a noble metal as the hydrogenation reaction catalyst. As the noble metal, one or more selected from rhodium, palladium and ruthenium are preferable, and rhodium alone is particularly preferable. Furthermore, a catalyst in which the noble metal is supported on a carrier is particularly preferable. As the carrier, carbon or alumina is preferable, and alumina is particularly preferable. The shape of the catalyst is not particularly limited, and a powder, a crushed shape for a fixed bed, a pellet shape, or the like is selected according to the hydrogenation reaction. The amount supported on the carrier is preferably 0.5 to 30% by weight, more preferably 0.5 to 10% by weight, based on the total amount of the catalyst.

  In the production method of the present invention, there are batch mode and continuous mode as the hydrogenation reaction mode, which can be appropriately selected.

  First, in the batch system, the aromatic acetal is hydrogenated at a hydrogen partial pressure of 0.01 MPa or more in the presence of a catalyst containing 0.5 to 10 parts by weight of the noble metal with respect to 100 parts by weight of the aromatic acetal. . If the amount of the noble metal is less than 0.5 parts by weight with respect to 100 parts by weight of the aromatic acetal, the hydrogenation reaction does not proceed sufficiently, and the upper limit is 10 parts by weight. Disadvantageous. The preferred amount of the precious metal is in the range of 0.5 to 5.0 parts by weight with respect to 100 parts by weight of the aromatic acetal.

  On the other hand, if the hydrogen partial pressure is less than 0.01 MPa, a desired reaction conversion rate cannot be obtained, and the object of the present invention cannot be achieved. A preferable hydrogen partial pressure is in the range of 0.01 to 15 MPa. The reaction temperature is preferably in the range of 0 to 180 ° C. The reaction time depends on the reaction temperature and other conditions and cannot be determined in general, but usually about 30 to 360 minutes is sufficient.

Next, in the continuous flow type, the aromatic acetal has a speed of 1 to 100 parts by weight / hr per 1 part by weight of the noble metal, that is, a weight hourly space velocity (WHSV) 1 to 1 in the packed bed of the catalyst containing the noble metal. It is supplied at 100 hr ⁻¹ and hydrogenated at a hydrogen partial pressure of 0.01 MPa or more.
If the WHSV is less than ¹ hr ⁻¹ , the production efficiency is low and impractical, and if it exceeds 100 hr ⁻¹ , the desired reaction conversion cannot be obtained and the object of the present invention cannot be achieved. A preferred WHSV is in the range of 3-50 hr ⁻¹ .

  Further, the hydrogen partial pressure and the reaction temperature are as described in the batch system. In addition, as a continuous reaction form, although a full liquid type, a perfusion type, etc. can be considered, a perfusion type is more preferable.

Examples of the material used for the hydrogenation reactor include stainless steel such as SUS304, SUS316, and SUS316L.
Moreover, the container which performed the glass lining process to iron or stainless steel used for a normal pressure-resistant container can also be used conveniently.

  When methanol or tetrahydrofuran is used as the reaction solvent, the product alicyclic acetal is dissolved in the solvent. Therefore, after separating the noble metal catalyst if necessary, the filtrate is distilled to separate the solvent and the alicyclic acetal. By doing so, an alicyclic acetal can be obtained.

  In the hydrogenation, the aromatic acetal as a raw material may be completely hydrogenated or partially hydrogenated depending on the type of the desired alicyclic aldehyde. Examples of complete hydrogenation include 2-phenyl-1,3-dioxolane and 2- (2,4-dimethylphenyl) -1,3-dioxolane to 2-cyclohexyl-1,3-dioxolane or 2- (2 , 4-Dimethylcyclohexyl) -1,3-dioxolane. Examples of the partially hydride include a compound having a tetralin skeleton when the raw material is an aromatic acetal having a naphthalene skeleton. In addition, when the raw material is an aromatic acetal having a biphenyl skeleton or a skeleton having a structure in which two benzene rings are bonded via various linking groups, a compound having one having a benzene ring and the other having a cyclohexane ring structure Can be mentioned.

  After the hydrogenation reaction, the distillation residual liquid obtained by distilling the alicyclic acetal may be recycled to the hydrogenation reactor. The ratio of returning the remaining liquid can be appropriately determined according to the reaction.

<Step C: Hydrolysis of alicyclic acetal>
The alicyclic acetal obtained in Step B can be further hydrolyzed to give an alicyclic aldehyde. For example, cyclohexyl aldehyde can be obtained by hydrolyzing 2-cyclohexyl-1,3-dioxolane. Similarly, 2- (2,4-dimethylcyclohexyl) -1,3-dioxolane can be converted into 2,4-dimethylcyclohexyl. An aldehyde is obtained. The hydrolysis reaction is preferably performed using water as a solvent, more preferably in the presence of an acid such as acetic acid, hydrochloric acid or sulfuric acid, and particularly preferably in the presence of acetic acid.

  In the method of the present invention, an alicyclic aldehyde is produced by hydrolyzing the alicyclic acetal with 0.1 to 10 times mol of acid and 0.1 to 100 times water. To do. At this time, normal quality water and acid can be used as they are. When the amount of water and acid is less than this range, the reaction rate is not sufficient. On the other hand, when the amount is more than this range, recovery of the produced alicyclic aldehyde is difficult.

  The reaction temperature at which the hydrolysis reaction is advantageously carried out is preferably 0 to 100 ° C. The liquid mixture of alicyclic acetal, water, and acid may be simply stirred, or the liquid mixture may be heated to reflux. The hydrolysis reaction is completed by stirring the mixed solution and maintaining the state for about 1 minute to 360 minutes when the hydrolysis temperature is reached.

  This hydrolysis reaction is preferably performed in an inert gas atmosphere such as nitrogen gas.

  Further, a hydrocarbon having a boiling point of 50 ° C. or higher, a halogenated hydrocarbon, an ester, a ketone, an ether, an aliphatic acid, or the like may be added as the second solvent.

  After the hydrolysis reaction, the reaction solution is neutralized with alkali as necessary, or extracted with an organic solvent such as acetate ester, and then the reaction solvent or extraction solvent is heated to the boiling point or higher and removed. The remaining liquid is heated to the boiling point of the alicyclic aldehyde and distilled to obtain the alicyclic aldehyde as the final product.

  The solvent removed by distillation and the residual liquid after distillation of the alicyclic aldehyde may be recycled to the hydrolysis reactor. The ratio of returning the solvent and residual liquid to the hydrolysis reactor can be appropriately determined according to the degree of accumulation of impurities in the system.

  By carrying out the present invention as described above, a high-purity alicyclic aldehyde can be produced by a simple process and an industrially advantageous method.

  EXAMPLES Next, although an Example demonstrates this invention further in detail, this invention is not limited at all by these examples.

<Example 1>
Benzaldehyde (5.0 g), ethylene glycol (29.3 g), p-toluenesulfonic acid monohydrate (0.09 g), and benzene (250 ml) were placed in a 500 ml three-necked flask equipped with a reflux condenser equipped with a Dean-Stark water separator and refluxed for 21 hours. I let you. After allowing to cool, the reaction solution was washed with 50 ml of saturated aqueous sodium hydrogen carbonate and 50 ml of water. Subsequently, the organic layer was concentrated under reduced pressure, and then 6.3 g of the intended 2-phenyl-1,3-dioxolane was obtained by distillation under reduced pressure (yield 89%). The obtained 2-phenyl-1,3-dioxolane (4.0 g) and 5 wt% Rh-alumina powder catalyst (0.4 g), methanol (29.5 ml) and acetic acid (0.5 ml) were charged into a 100 ml shaking autoclave, and the system was filled with nitrogen. The gas was replaced twice with gas and then with hydrogen gas three times. The temperature was raised after setting the hydrogen pressure to 4.0 MPa, and a hydrogenation reaction was carried out at a reaction temperature of 40 ° C. for 120 minutes. The reaction solution was extracted from the autoclave, and the catalyst was filtered and separated with a vacuum filtration device (filter is a 1.0 micron membrane filter made of polytetrafluoroethylene (PTFE)) to obtain a colorless and transparent filtration reaction solution.

When the organic solvent in this filtration reaction liquid was distilled off by a rotary evaporator and the obtained residue was analyzed by a gas chromatography method, the conversion rate of 2-phenyl-1,3-dioxolane was 96%, 2-cyclohexyl-1, The 3-dioxolane selectivity was 87%.
Next, the residue was purified by distillation to obtain 2-cyclohexyl-1,3-dioxolane having a purity of 98.5%. The obtained 2-cyclohexyl-1,3-dioxolane (3.0 g), acetic acid (40 ml) and water (10 ml) were placed in a 200 ml eggplant-shaped flask and stirred at room temperature for 40 minutes. Thereafter, 100 ml of saturated aqueous sodium hydrogen carbonate was added, and the mixture was extracted with ethyl acetate (100 ml × 2 times). When the organic layer was concentrated under reduced pressure, 2-cyclohexyl-1,3-dioxolane did not remain, and 2.1 g of cyclohexyl aldehyde having a purity of 99% or more was obtained (yield 94%). The yield of cyclohexyl aldehyde was 70% based on the raw material aldehyde.

  <Reference Example 1>
  The aromatic acetal hydrogenation reaction was performed under the same conditions as in Example 1 except that the hydrogenation reaction was performed under the following conditions. The reaction conditions were 4.0 g of 2-phenyl-1,3-dioxolane, 0.8 g of 5 wt% Rh-carbon powder catalyst (water content 50%), 30 ml of tetrahydrofuran were charged in a 100 ml shaking autoclave, and the system was filled with nitrogen And then twice with hydrogen gas. After raising the hydrogen pressure to 4.0 MPa, the temperature was raised, and a hydrogenation reaction was carried out at a reaction temperature of 70 ° C. for 120 minutes. The reaction solution was extracted from the autoclave, and the catalyst was filtered and separated with a vacuum filter (filter is a 1.0-micron PTFE membrane filter) to obtain a colorless and transparent filtration reaction solution.
  When the organic solvent in this filtration reaction liquid was distilled off by a rotary evaporator and the obtained residue was analyzed by gas chromatography, 2-phenyl-1,3-dioxolane conversion was 100%, 2-cyclohexyl-1, The 3-dioxolane selectivity was 11%. The yield of the obtained cyclohexyl aldehyde was 16% based on the raw material aldehyde, and the purity was 99% or more.

<Example 2 >
The reaction was performed under the same conditions as in Example 1 except that 2,4-dimethylbenzaldehyde was used as the starting aromatic aldehyde. As a result, the conversion rate of 2- (2,4-dimethylphenyl) -1,3-dioxolane in the hydrogenation reaction was 95%, and the selectivity of 2- (2,4-dimethylcyclohexyl) -1,3-dioxolane was 85%. Met. The yield of 2,4-dimethylcyclohexylaldehyde obtained was 68% based on the raw material aldehyde, and the purity was 99% or more.

<Comparative Example 1 (direct hydrogenation of aromatic aldehyde with Rh-carbon)>
4.0 g of 2,4-dimethylbenzaldehyde, 0.8 g of 5 wt% Rh-carbon powder catalyst (water content 50%) and 32 g of tetrahydrofuran were charged into a 100 ml shaking autoclave, the inside of the system was twice with nitrogen gas, then hydrogen The gas was replaced 3 times. After raising the hydrogen pressure to 4.0 MPa, the temperature was raised, and a hydrogenation reaction was carried out at a reaction temperature of 70 ° C. for 120 minutes. The reaction solution was extracted from the autoclave, and the catalyst was filtered and separated with a vacuum filter (filter is a 1.0-micron PTFE membrane filter) to obtain a colorless and transparent filtration reaction solution.
Tetrahydrofuran of the filtered reaction solution was distilled off with a rotary evaporator, and the resulting residue was analyzed by gas chromatography. As a result, pseudocumene was obtained with a conversion rate of 2,4-dimethylbenzaldehyde of 99% and a selectivity of 95%. It was. The desired 2,4-dimethylcyclohexylaldehyde was not obtained.

<Comparative Example 2 (direct hydrogenation of aromatic aldehyde with Ru-carbon)>
4.0 g of 2,4-dimethylbenzaldehyde, 0.8 g of 5 wt% Ru-carbon powder catalyst (water content 50%) and 32 g of tetrahydrofuran were charged into a 100 ml shaking autoclave, the inside of the system was twice with nitrogen gas, then hydrogen The gas was replaced 3 times. After raising the hydrogen pressure to 8.0 MPa, the temperature was raised, and a hydrogenation reaction was performed at a reaction temperature of 100 ° C. for 300 minutes. The reaction solution was extracted from the autoclave, and the catalyst was filtered and separated with a vacuum filter (filter is a 1.0-micron PTFE membrane filter) to obtain a colorless and transparent filtration reaction solution.
Tetrahydrofuran of the filtered reaction solution was distilled off by a rotary evaporator, and the resulting residue was analyzed by gas chromatography. As a result, the conversion of 2,4-dimethylbenzaldehyde was 99%, the selectivity was 95%, and 2,4 -Dimethylbenzyl alcohol was obtained. The desired 2,4-dimethylcyclohexylaldehyde was not obtained.

Claims (3)

The manufacturing method of the alicyclic aldehyde characterized by making the following process AC essential.
Step A: Aromatic aldehyde is acetalized with alcohol to form aromatic acetal.
Step B: The aromatic acetal obtained in Step A is hydrogenated to an alicyclic acetal in the presence of a catalyst containing one or more noble metals selected from rhodium, palladium and ruthenium, and an acid .
Step C: The alicyclic acetal obtained in Step B is hydrolyzed to obtain an alicyclic aldehyde. Wherein said catalyst is a manufacturing method of cycloaliphatic aldehydes of claim 1, wherein a is obtained by supporting the noble metal on carbon or alumina. The method for producing an alicyclic aldehyde according to claim 1 or 2 , wherein the hydrogenation temperature in Step B is 0 to 180 ° C and the hydrogen partial pressure is 0.01 to 15 MPa.