JPH01128941A - Production of p-isobutylstyrene - Google Patents

Abstract

PURPOSE:To advantageously obtain the titled compound, by passing 1,1-di(p- isobutylphenyl)ethane through steps of decomposition, separation of decomposition products, hydrogenation of a fraction mainly containing the unreacted raw material and redecomposition of the above-mentioned treated fraction. CONSTITUTION:(i) 1,1-Di(p-isobutylphenyl)ethane (A) is brought into contact with an acid catalyst in the presence of an inert gas and decomposed into the titled compound (B) and pisobutylbenzene (C). (ii) A fraction mainly containing the compound (A), fraction mainly containing the compound (B) and fraction mainly containing the compound (C) are decomposed from the resultant reaction mixture by distillation. (iii) Furthermore, a fraction mainly containing the compound (A) is then brought into contact and subjected to hydrogenation treatment with a hydrogenation catalyst in the presence of hydrogen. (iv) The resultant hydrogenated fraction is then returned to the step (i) and redecomposed to suppress deterioration of the decomposition catalyst with time in redecomposing the unreacted raw material and economically afford the high-purity compound useful as a raw material for ibuprofen(medicine) on an industrial scale.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a method that makes it possible to produce highly pure p-isobutylstyrene economically and on an industrial scale. More specifically, 1.1-di(p-
A step of decomposing isobutylphenyl)ethane, a step of separating the decomposition product, a step of hydrogenating the recovered fraction mainly containing l,1-di(p-isobutylphenyl)ethane, and a step of hydrogenating the recovered fraction mainly containing l,1-di(p-isobutylphenyl)ethane. High-purity p-
The present invention relates to a method for producing isobutylstyrene.

P-isobutylstyrene, which is the object of the method of the present invention, is useful as a raw material for producing ibuprofen (chemical name: α-(3-isobutylphenyl)propionic acid), a pharmaceutical product with antipyretic, analgesic, and antiinflammatory effects. It is a compound that serves as an intermediate.

[Prior art and problems to be solved by the invention] p-
Using isobutylstyrene as a raw material, it is doroesterified with -carbon oxide and water or alcohol in the presence of a transition metal catalyst, or hydroformylated with -carbon oxide and water to form α-(3-inbutylstyrene). phenyl)
Propionaldehyde is obtained and oxidized to produce α-(3-isobutylphenyl), which is useful as a pharmaceutical.
Propionic acid (trade name: ibuprofen) is obtained.

Conventionally, various methods of decomposing 1,1-diarylethane under an acid catalyst have been proposed as methods for producing alkylstyrenes such as p-isobutylstyrene. For example, Industry, ral and Engineering
g Chemistry.

Vol, 46. No. 4.652 (1954) J
internal of (:chemical an
d Engineering Data.

Vol.9. No.], 104 (1964) 1
& ECProduct Re5earch a
nd Development.

Vol, 3. No. I, 16 (1964) In the above document, methylstyrene, dimethylstyrene, ethylstyrene, isopropylstyrene,
It describes a method for decomposing 1.1-diarylethane such as 1.1-ditolylethane and 1.1-dixylylethane for the purpose of producing t-butylstyrene.

Furthermore, regarding specific disclosed technologies such as methods for improving decomposition catalysts, for example, U.S. Pat. , 422,318 discloses a method for decomposing asymmetric diarylethanes, U.S. Patent No. 2,864,872 discloses a method using silica as a decomposition catalyst, and U.S. Pat. , Method for decomposing dixylylethane using a fluidized catalyst, U.S. Patent No. 3
, 025,330 proposes a method for obtaining methylstyrene from ditolylethane, and U.S. Patent No. 2,976.333 and U.S. Patent No. 2.976.334 propose a method for improving decomposition catalysts. Efforts are continuing to industrialize the production of alkylstyrenes by decomposition.

In the method of decomposing 1.1-diarylethane, 1.1
Not all of the -diarylethane is decomposed and converted into alkylstyrene and alkylbenzene, and it is inevitable that unreacted 1,1-diarylethane will remain unreacted and be included in the reaction mixture. This is also clear from the fact that even in the method proposed in the above-mentioned publication, the purpose conversion in the reaction is as low as 40% to 60%.

The same is true for the decomposition of 1.1-di(p-isobutylphenyl)ethane, with an average decomposition rate of 40% to 60%.
The authors found that it was in the range of %. In other words, 60 to 41% of unreacted 1,1-diarylethane remains.

Therefore, in the decomposition of 1,1-di(p-isobutylphenyl)ethane, in order to economically produce p-inbutylstyrene, a large amount of unreacted 1,1-di(p-isobutylphenyl)ethane must be produced. The reuse of materials becomes an essential condition. That is, 1,1-di(p
- Is it possible to return the fraction mainly containing (isobutylphenyl)ethane to the decomposition process and obtain p-isobutylstyrene with purity and properties suitable for the purpose of use even with the addition of a recycling process? It can be said that this determines whether the decomposition reaction is a technology that can be applied industrially or not.

However, when the present inventors investigated how to carry out the decomposition reaction of 1,1-di(p-isobutylphenyl)ethane industrially and economically, they found that unreacted 1,1-di(p-isobutylphenyl)ethane was (
It was discovered that if the fraction mainly containing p-isobutylphenyl)ethane was decomposed as it was, the catalyst used for decomposition would deteriorate severely over time, and the properties of the resulting p-isobutylstyrene would be unfavorable. This is the completed version. That is, in conventional decomposition methods, it has been industrially impossible to recycle a large amount of unreacted fractions as they are. Therefore, conventional decomposition methods cannot be said to be industrially advantageous.

[Means for solving the problem] In view of the above-mentioned circumstances, the present invention includes the following step (I),
Provided is a method for producing a-isobutylstyrene characterized by comprising step (II), step (III) and step (IV), the method comprises producing highly purified a-isobutylstyrene by decomposing 1,1-di(p-isobutylphenyl)ethane. The object of the present invention is to provide a method that enables industrial and economical production of p-isobutylstyrene.

Step (I): 1,1-di(p-inbutylphenyl)ethane is contacted with an acid catalyst in the presence of an inert gas, and p-
A step of decomposing into isobutylstyrene and p-isobutylbenzene, step (n): The reaction mixture obtained in the decomposition step (I) is distilled to mainly contain 1,1-di(p-isobutylphenyl)ethane. A step of separating into a fraction, a fraction mainly containing p-inbutylstyrene, and a fraction mainly containing p-isobutylbenzene, Step (■): 1. obtained in the separation step (II).
A step of hydrogenating a fraction mainly containing 1-di(p-isobutylphenyl)ethane by contacting it with a hydrogenation catalyst in the presence of hydrogen, and step (rv): @obtained in the hydrogenation step (III). The fraction mainly containing 1,1-di(p-isobutylphenyl)ethane is subjected to the decomposition step (I
) and re-decompose it.

Further, the present invention will be explained in detail.

Step (1) in the method of the present invention is 1.1-di(p-
This is a step in which isobutylphenyl)ethane is brought into contact with an acid catalyst in the presence of an inert gas to decompose it into p-isobutylstyrene and p-isobutylbenzene. Decomposition process (I
), methods using acid catalysts that have been proposed so far can be applied.

1.1-Di(p-isobutylphenyl)ethane is a compound in which two phenyl groups having an isobutyl group at the p-position are substituted on the same carbon of ethane.

Any 1.1-di(p-isobutylphenyl)ethane produced by a known method can be used. 1. Specific examples of methods for producing 1-di(p-isobutylphenyl)ethane include a method in which p-isobutylbenzene is reacted with acetaldehyde or acetylene in the presence of sulfuric acid, a method using a free sol fluorine catalyst such as aluminum chloride, etc. There is a method in which p-isobutylbenzene and 1,1-dichloroethane are reacted in the presence of .

In the method of the present invention, it is appropriate to contact the acid catalyst in a diluted state in the presence of an inert gas.

As the inert gas, in addition to inorganic gases such as hydrogen, helium, argon, nitrogen, and water vapor, any gas that does not inhibit the acid activity of the acid catalyst such as methane, ethane, and propane may be used. Can be done. Inert gases may be used alone or in appropriate mixtures. Industrially, water vapor is the preferred inert gas to handle. Dilution with an inert gas is preferably carried out so that the molar ratio expressed by (inert gas, t, t-di(ρ-isobutylphenyl)ethane) is 50 F or less. Upper limit of the number of moles for dilution There is no particular problem, and the larger the number of moles, the more preferable, but in practical terms, the upper limit of the molar ratio is 500.

The acid catalyst to be contacted is a protonic acid, a solid acid, or a protonic acid-supported solid acid. Examples of protonic acids include phosphoric acid,
Inorganic protonic acids such as sulfuric acid, hydrochloric acid, heteropolyacids such as silicotungstic acid and phosphotungstic acid, and permeable protonic acids such as benzene sulfonic acid and toluenesulfonic acid. Examples of solid acids include synthetic solid acid catalysts such as silica alumina, silica magnesia, and zeolite, natural solid acid substances such as activated clay, acid clay, kaolin, and attapulgite, as well as natural solid acid substances that do not have acid activity like silica and alumina. It may also be a protonic acid-supported solid acid catalyst obtained by impregnating and supporting the protonic acid on an inorganic porous carrier.

The temperature at which the material is brought into contact with the acid catalyst can be appropriately selected depending on the type of acid catalyst, but is in the range of 200°C to 650'C.

For contact with protonic acid, the temperature is preferably 200°C to 350°C, and for contact with solid acid, the temperature is 300°C to 600°C.
is preferred.

In step (I) of the present invention, 1,1-di(p-isobutylphenyl)ethane is decomposed by contacting it with an acid catalyst under the above dilution and temperature conditions. The decomposition method can be selected as appropriate depending on the type of acid catalyst, but in consideration of equipment corrosion and continuity, gas phase contact using a solid acid catalyst or a protonic acid-supported solid acid catalyst is preferred. In gas phase catalytic cracking, if the raw material 1,1-di(p-isobutylphenyl)ethane is kept in the gas phase under the above-mentioned diluted conditions with the inert gas, it can be used at normal pressure, elevated pressure, or reduced pressure. Either is fine. Furthermore, as the reaction mode for decomposition, any of fixed bed, moving bed, and fluidized bed may be used.

The decomposition reaction in step (I) can be expressed as a chemical formula as follows.

(p-fso-C4)Ph-CH(CH3)-(p-4
so-C4) Ph-(p-iso-G4)Ph-(:
H-CH2+ (p-iso-C4)Ph-H raw material 1
．． Decomposition of 1-di(p-isobutylphenyl)ethane yields ρ-isobutylstyrene and ρ-isobutylbenzene. The p-isobutylbenzene obtained by decomposition does not substantially produce other isomers, so if the fraction containing p-isobutylbenzene is simply separated and collected by distillation, the remaining unreacted 1 , 1-di(p-isobutylphenyl)ethane is again 1
．． It can be reused as a raw material for producing 1-di(p-isobutylphenyl)ethane.

Step (II) in the method of the present invention is a decomposition step (I)
The reaction mixture obtained in step 1 is separated into a fraction mainly containing unreacted l,1-di(p-isobutylphenyl)ethane, a fraction mainly containing p-isobutylstyrene, and a fraction mainly containing p-isobutylbenzene. It is a process.

In the decomposition step (I), 1,1-di(p-isobutylphenyl)ethane is not completely decomposed, and unreacted 1,1-di(p-isobutylphenyl)ethane is present in the decomposition reaction mixture together with the target products p-isobutylstyrene and p-isobutylbenzene. .1-di(p-isobutylphenyl)ethane remains. In step (rl), one of the purposes is to separate p-isobutylstyrene, which is the target product, to obtain a purity suitable for the subsequent use. It is also important in industrial practice to separate the -di(p-isobutylphenyl)ethane so that it can be reused for decomposition.

That is, in the separation step (II), p generated by decomposition is
- A fraction mainly containing isobutylstyrene, a fraction mainly containing isobutylbenzene, and further recovered as unreacted,
This is a step of separating the 1,1-di(p-isobutylphenyl)ethane fraction to be reused.

As the separation method, any conventionally known physical means or chemical means can be selected. For example, physical means include solvent extraction and separation methods that take advantage of differences in solubility and distribution coefficients in solvents, adsorption separation methods that take advantage of differences in adsorption properties, crystallization separation methods that take advantage of differences in melting point and freezing point, and Distillation separation methods that take advantage of differences can be applied.

Among these means, distillation separation means is actually preferred because of its ease of operation. In addition, the process of the present invention (
Isobutylbenzene, P in the reaction mixture obtained in I)
-isobutylstyrene and 1,1-di(p-isobutylphenyl)ethane can be easily separated by conventional distillation means. In the distillation operation, the target product is p-, which is easily thermally polymerized.
Since it is isobutylstyrene, vacuum distillation operating at reduced pressure is preferred. The degree of vacuum and other distillation conditions are selected as appropriate. In view of the purpose of the present invention, unreacted 1 to be recovered
．． The boiling point of the fraction containing 1-di(p-isobutylphenyl)ethane is 330 to 370°C, preferably 340 to 365°C, in terms of normal pressure.

The present inventors recycled the fraction mainly containing 1,1-di(p-isobutylphenyl)ethane separated in the above step (n) to the decomposition step (I) as it was, and re-decomposed it. The present invention was completed after discovering that the decomposition catalyst used in (I) deteriorates quickly over time and that the properties of the obtained p-isobutylstyrene are unfavorable in terms of actual use.

That is, in the decomposition step in step (I), the raw material 1.1-
The ethane part of di(p-isobutylphenyl)ethane,
As shown in the following formula, dehydrogenation by the decomposition catalyst is Ph-el+(-C113)-Ph-+Ph-
C(-CH2)-Ph olefin, resulting in l
It has become clear that 1-di(p-isobutylphenyl)ethylene is inevitably produced as a by-product, albeit in a small amount.

Furthermore, since the boiling points are close to each other, this by-product 1,1-
Di(ρ-isobutylphenyl)ethylene is practically unreacted by conventional separation means such as distillation separation means.
It is not possible to separate it from 1-di(p-isobutylphenyl)ethane. Therefore, if the fraction mainly containing 1,1-di(p-isobutylphenyl)ethane recovered in step (1'l) was used again as a raw material for decomposition in step (I), it would be difficult to In addition to the rapid deterioration of the decomposition catalyst used in ) over time, the properties of the resulting target product, p-inbutylstyrene, are no longer suitable for the intended use.

The present inventors have repeatedly investigated the possibility of reusing the recovered 1,1-di(p-isobutylphenyl)ethane fraction in the cracking process. As a result, the 1,1-di(p-isobutylphenyl)ethane fraction contained in this fraction -isobutylphenyl)ethylene by hydrogenation treatment to 1.1
It has been found that if it is converted to -di(p-isobutylphenyl)ethane, it can be re-decomposed as a decomposition raw material in step (I) without any problem.

The step (In) in the method of the present invention is a separation step (TI
), the fraction mainly containing 1,1-di(p-isobutylphenyl)ethane is brought into contact with a hydrogenation catalyst in the presence of hydrogen and subjected to hydrogenation treatment to remove by-products contained in this fraction. This is a process in which the olefin portion of di(p-isobutylphenyl)ethylene is hydrogenated and added to convert it into paraffin.

It is important here to select conditions such that the aromatic ring present in 1,1-di(p-isobutylphenyl)ethane is not hydrogenated to become a cyclohexyl ring. That is, it is necessary to avoid nuclear hydrogenation of aromatic rings. Therefore, the hydrogenation catalyst here can be selected from conventionally known hydrogenation catalysts as long as it hydrogenates ethylenically carbon-carbon unsaturated double bonds and is inactive for nuclear hydrogenation of aromatic rings. You can choose as appropriate. Specific examples of these include Pd, Rh,
Examples include metal catalysts containing Pt and Ni-based metals. These metal catalysts can also be used by being supported on a suitable carrier such as silica, silica alumina, or carbon. The reaction conditions for hydrogenation may be any conditions as long as they do not hydrogenate aromatic rings. For example, the hydrogenation temperature is from normal temperature to 300°C, and the reaction pressure is from normal pressure to 300 kg/cm2.

1,1- obtained by hydrogenation treatment in step (I[[)
The p-isobutylstyrene obtained by returning the fraction mainly containing di(p-isobutylphenyl)ethane to the decomposition step (I) and decomposing it again in this step is sufficient for the purpose for which it is used. The properties are satisfactory.

The treatment in the hydrogenation treatment step (I [I) is a decomposition step (
It may be carried out on the fraction containing mainly 1,1-di(p-isobutylphenyl)ethane obtained in TI) alone. Also, new 1,1 to be supplied to step (I)
-di(p-isobutylphenyl)ethane and step (11)
) and the fraction mainly containing 1,1-di(p-isobutylphenyl)ethane obtained in step (tI
r) Hydrogenation treatment may be performed.

Furthermore, it goes without saying that each of the above steps can be performed continuously, or each step can also be performed in a batch manner. In any case, in the present invention, it is important to hydrogenate and reuse the fraction containing unreacted raw materials.

By subjecting p-isobutylstyrene obtained by the method of the present invention to hydroformylation or hydroesterification, ibuprofen, which is a pharmaceutical product, can be obtained with high purity. Therefore, a method for inducing ibuprofen from P-isobutylstyrene will be described below.

In a method using hydroformylation, realdehyde is obtained from p-isobutylstyrene using a transition metal complex catalyst, and this is oxidized to obtain ibuprofen.

Transition metal complex catalysts for hydroformylating p-isobutylstyrene include pt, Rh, lr, and Ru.
There are transition metal complex catalysts having active metals such as , Co, and Ni. Active metals include halogen group atoms, trivalent phosphorus compounds, π-allyl groups, amine groups, nitriles, oximes, olefins, hydrogen, or carbon monoxide, which can be used from 0 to the highest acid value. Complexes containing them as ligands can also be used.

Specific examples include bistriphenylphosphine dichloro complex, bistributylphosphine dichloro complex, bistricyclohexylphosphine dichloro complex, π-allyltriphenylphosphine dichloro complex, triphenylphosphine piperidine dichloro complex, bisbenzonitrile dichloro complex, biscyclohexyl Oxime dichloro complex, 1.5.9-cyclododecatriene-dichloro complex, histriphenylphosphine dicarbonyl complex, bistriphenylphosphine acetate complex, bistriphenylphosphine cinitrate complex, bistriphenylphosphine sulfate complex, tetrakistriphenylphosphine complexes, and -chlorocarbonylbistriphenylphosphine complexes, hydridocarbonyltristriphenylphosphine complexes, bistalolochitracarbonyl complexes, dicarbonylacetylacetonate complexes, etc., which have -carbon oxide as part of the ligand.

Further, compounds capable of forming the above-mentioned complexes in the reaction system can also be used.

That is, compounds that can serve as ligands for the oxides, sulfates, chlorides, acetates, etc. of the active metals, i.e.,
A method may also be used in which phosphine, nitrile, allyl compound, amine, oxime, olefin, or carbon oxide is simultaneously present in the reaction system.

Examples of the phosphine include triphenylphosphine, tritolylphosphine, tributylphosphine, tricyclohexylphosphine, triethylphosphine, etc.
Examples of nitriles include benzonitrile, acrylonitrile, propionitrile, and pencil nitrile; examples of allyl compounds include allyl chloride and allyl alcohol; and examples of amines include hensylamine, pyridine, piperazine, and tri-butylamine. Examples of oximes include cyclohexyloxime, acetoxime, benzaldoxime, etc.; examples of olefins include 1,5-cyclooctadiene, L,5,9-cyclodecatriene, etc.

Furthermore, for the purpose of improving the reaction rate, inorganic halides such as hydrogen chloride and boron trifluoride, organic iodides such as methyl iodide, etc. can be added.

When these halides are added, they are used in an amount of 0.1 to 30 times the halogen atom, preferably 1 to 15 times the mole, per mole of the transition metal complex catalyst or active metal compound. If the amount added is less than 0.1 mol, it may vary depending on the type of catalyst, or the effect of addition may not be observed. On the other hand, when the amount exceeds 30 times the mole, the catalyst activity is rather reduced, and side reactions other than the desired reaction, such as addition of halogen to the double bond of p-isobutylstyrene, which is the starting material, become significant, which is not preferable.

The amount of the transition metal complex catalyst or the active metal compound capable of producing the transition metal catalyst used is 0.0001 to 0.5 mol, preferably 0.0 mol, per 1 mol of p-isobutylstyrene.
01~0°1 mole. Further, when an active metal compound is used, the amount of the compound that can be a ligand added is 0.8 to 10 mol, preferably 1 to 4 mol, per 1 mol of the active metal compound.

In the hydroformylation reaction, the reaction temperature is 40 to 200°C.
, preferably at 50 to 180°C.

If the reaction temperature is less than 40°C, the reaction rate will be significantly slow,
This cannot be implemented in practice. Furthermore, temperatures exceeding 150°C are undesirable because side reactions such as polymerization and decomposition of the transition metal complex catalyst occur.

The reaction pressure can be appropriately selected as long as it is 5 kg/cm2 or more. If it is less than 5 kg/cm2, the reaction becomes so slow that it cannot be practically carried out. Further, the higher the pressure, the more rapidly the reaction proceeds, which is preferable, but if the pressure is too high, it becomes necessary to greatly increase the pressure resistance of the reactor, and there are limits from the viewpoint of production equipment.

Therefore, in practice, a pressure of 500 kg/cm2 or less is sufficient.

The hydroformylation reaction may be carried out until no pressure decrease is observed due to the absorption of the mixed gas of -carbon oxide and hydrogen, and a reaction time of 4 to 20 hours is usually sufficient.

In the hydroformylation reaction using carbon monoxide and hydrogen, the carbon monoxide and hydrogen necessary for the reaction may be mixed in advance or in the form of a mixed gas, or each may be supplied separately to the reactor. The molar ratio of carbon monoxide and hydrogen when supplied to the reaction system can be selected as appropriate. That is, in the hydroformylation reaction, -carbon oxide and hydrogen are supplied and consumed at a molar ratio of 1:1. Therefore, since the component supplied in excess remains unreacted, if the other component is supplied once the pressure decrease is no longer observed, the reaction will proceed again. Therefore, depending on the size of the reactor and the type of reaction, it is most efficient to supply carbon oxide to hydrogen at a molar ratio of 1:1.

However, the supply method is not limited to the above-mentioned method, and an inert gas may coexist in the hydroformylation reaction.

In the hydroformylation of the present invention, an inert solvent can also be used for purposes such as removing reaction heat. Examples of solvents inert to hydroformylation include polar solvents such as ethers, ketones, and alcohols, and nonpolar solvents such as paraffins, cycloparaffins, and aromatic hydrocarbons. However, in general, sufficiently favorable results can be obtained without a solvent.

After the completion of the hydroformylation reaction, the obtained α-(3-
Ibuprofen, α-(
3-isobutylphenyl)propionic acid is obtained.

Next, a method for converting p-isobutylstyrene into α-(3-isobutylphenyl)propionic acid using a noble metal complex catalyst by doroesterification will be described.

The noble metal complex catalyst used in the above-mentioned doroesterification is a noble metal complex such as Pd, Rh, Ir, etc., and in particular, a complex of Pd. These precious metals include halogen atoms,
Trivalent phosphorus compounds or carbonyl complex compounds containing carbon monoxide or the like as a ligand are used. The noble metal, for example, palladium, has a valence of 0 to 2.

Specific examples of the catalyst include bistriphenylphosphine dichloropalladium, bistributylphosphine dichloropalladium, bistridichlorohexylphosphine dichloropalladium, π-allyltriphenylphosphine chloropalladium, triphenylphosphine piperidine cyclopalladium, and bisbenzonitrile dichloropalladium. , biscyclohexyloxime dichloropalladium,
l, 5゜9-cyclododecatriene-cyclovaladium, bistriphenylphosphine dicarbonyl palladium, bistriphenylphosphine palladium acetate, bistriphenylphosphine palladium nitrate, bistriphenylphosphine palladium sulfate, tetrakistriphenylphosphine palladium Examples include.

The catalyst can be used by being supplied to the reaction system as a complex, or a compound serving as a ligand can be separately supplied to the reaction system to form a complex in the reaction system.

The amount of the catalyst is 0.0001 to 0.5 mol, preferably 0.00 mol per 1.0 mol of p-inbutylstyrene.
The amount of the compound that can be a ligand is 1 to 0.1 mol, and the amount of the compound that can be a ligand is 1 to 1 mol of a noble metal that can be a nucleus of a complex such as Pd, Rh, Ir, etc.
The amount is 0.8 to 10 mol, preferably 1 to 4 mol.

For the doloesterification reaction, the reaction temperature is 40 to 150°C,
Preferably 70-120°C, carbon oxide pressure 30-70
0 kg/cm2, preferably 90-500 kg/c
Perform at a pressure of rn2. Furthermore, an acid such as hydrogen chloride or boron trifluoride may be added for the purpose of promoting the reaction.

In the hydroesterification reaction, when p-isobutylstyrene is reacted in the presence of water, a carboxylic acid that is α-(3-inbutylphenyl)propionic acid is obtained.

In addition, when reacted in the presence of a lower alcohol containing an arbitrary alkyl group, α-(3-inbutylphenyl)
Lower alcohol esters of propionic acid are obtained, for example with methyl alcohol the methyl ester is obtained.

Alcohols include methyl alcohol, ethyl alcohol, n
-propyl alcohol, isopropyl alcohol, n-
butyl alcohol, 5ec-butyl alcohol, ter
Lower alcohols having 1 to 4 carbon atoms such as t-butyl alcohol and isobutyl alcohol are preferred, and methyl alcohol is preferred.

After completion of hydroesterification, the reaction product can be easily separated by distillation, preferably under reduced pressure, to easily obtain the target compound α-(3
-isobutylphenyl)propionic acid or its alkyl ester and the catalyst. The recovered complex catalyst can also be used again.

When an alkyl ester of α-(3-isobutylphenyl)propionic acid is obtained, α-(3-inbutylphenyl)propionic acid is obtained by hydrolyzing it by a conventional method.

[Effects of the Invention] p-isobutylstyrene, which is the object of the present invention, is a substance that has favorable properties as a raw material for synthesis of ibuprofen, which is preferable as a pharmaceutical product, by converting it by, for example, a carbonylation reaction. The method of the present invention includes 1.
A method for producing high-purity p-isobutylstyrene by decomposing 1-di(p-isobutylphenyl)ethane, which causes less deterioration of the decomposition catalyst over time and enables industrial and economic implementation. be.

The present invention will be further explained below with reference to Examples.

Example 1: Synthesis of p-isobutylstyrene by decomposition of 1,1-di(p-isobutylphenyl)ethane Degree of vacuum 2 + obtained by reacting p-isobutylbenzene and acetaldehyde with a sulfuric acid catalyst
nmHg ~ 3 mm Distillation temperature 177 ° C ~ at 11 g
The 1.1-di(p-isobutylphenyl)ethane fraction (bromine number = 0.16) at 184°C was subjected to step (I) decomposition, step (■) separation, and step (III) hydrogenation as follows. processed.

Step (1): Decomposition Reaction Silica alumina catalyst N-631-L (trade name) manufactured by 8Koku Kagaku Co., Ltd., prepared in 15 to 25 meshes, was packed into a stainless steel reaction tube with an inner diameter of 12 mm to a height of 135 aun.

This was heated to a temperature of 500°C in an electric furnace, and the 1.1-di(p-isobutylphenyl)ethane fraction was added at 15ml/h.
The decomposition was carried out by continuously supplying water at a rate of 170 ml/hr. After cooling the reactor outlet, the oil layer was separated and analyzed by gas chromatography. The analysis results are shown below.

Gas chromatography Duram analysis results-1 Light fraction 2.7% by weight isobutylbenzene fraction 24.6% by weight p-isobutylethylbenzene fraction 2.3i1% p-isobutylstyrene fraction 24.81% by weight unreacted 1.
1-di(p-isotylphenyl)ethane fraction 44.3% by weight Nail fraction
1.3% by weight average decomposition season
55.1% step [1): Precision distillation of the decomposition product obtained in the separation and decomposition step (I),
p-isobutylstyrene fraction (3 mm 11 g ~ 4 mm) whose distillation temperature range is 74 ° C ~ 89 ° C under reduced pressure of IH (
recovery rate 73%) and unreacted 1.1-
A recovered fraction of di(ρ-isobutylphenyl)ethane (recovery rate 91%) was obtained.

The bromine number of the recovered 1,1-di(p-isobutylphenyl)ethane fraction was 3.5, and according to mass spectrometry, m/
The content of the component with e=292 [m/e of 1,1-di(p-isobutylphenyl)ethane=294] was 6.0%.

Step (■): Hydrogenation treatment A stainless steel reaction tube with an inner diameter of 10 mm was filled with palladium catalyst G-68B (trade name) manufactured by Nissan Girdler Co., Ltd. to a height of 80 mm, prepared to have a mesh size of 20 to 25. This is heated to a temperature of 180°C in an electric furnace, and the separation process (11
) The recovered 1.1-di(p-isobutylphenyl)ethane fraction was heated at 10 ml/hr and hydrogen at 200 ml/hr.
The hydrogenation treatment was carried out by supplying the hydrogen. The hydrogenation treatment was carried out at a pressure of 12 kg/cm2.

The bromine number of the treated 1,1-di(p-isobutylphenyl)ethane fraction was 0.18, and m
The content of the component /e = 292 was 0.5% or less.

Example 2: Hydrogenation 1. Decomposition of 1-di(p-isobutylphenyl)ethane fraction 1,1 hydrogenated in step (I[I) of Example 1
The -di(p-isobutylphenyl)ethane fraction was decomposed in the same manner as in step (I) of Example 1, and then subjected to precision distillation in the same manner as in step (TI) of Example 1. An isobutylstyrene fraction and a 1,1-di(p-isobutylphenyl)ethane fraction were obtained. The recovery rate of each fraction was almost the same as in the example. The analysis results for the reaction mixture are as follows.

Gas chromatoduram analysis results-2 Light fraction 2.6! bp-isobutylbenzene fraction 23.0% by weight Leu-isobutylethylbenzene fraction 2.2% by weight p-
Isobutylstyrene fraction 23.7% unreacted 1.1-di(p-isobutylphenyl)ethane fraction 47.21Q% heavy fraction
1.3% by weight average decomposition rate
The bromine number of 52.2% recovered 1,1-di(p-isobutylphenyl)ethane is 3.0, and the content of the component m/e = 292 by mass spectrometry is 5.5.
%Met.

Comparative Example 1: Re-decomposition of L,1-di(p-isobutylphenyl)ethane recovered fraction 1,1-di(p-
The isobutylphenyl)ethane fraction was decomposed as it was, that is, without hydrogenation, in the same manner as in step (I) of Example 1, and then subjected to precision distillation in the same manner as in step (II) of Example 1. , P-inbutylstyrene fraction and 1,1-
Di(p-isobutylphenyl)ethane distillate was obtained. The recovery rate of each fraction was almost the same as in the same example. The analysis results of the obtained reaction mixture are shown below.

Gas chromatography Duram analysis results-3 Light fraction 1.1% by weight benzene fraction 19.2% by weight ethylbenzene fraction 1.9% by weight p-isobutylstyrene fraction 19.4% by weight unreacted 1.1-di( p
-isobutylphenyl)ethane fraction 56.3% by weight heavy fraction
2.1% by weight average decomposition rate
The bromine number of 42.5% recovered 1,1-di(p-isobutylphenyl)ethane is 4.6, and the content of the component m/e = 292 is 8 according to mass spectrometry.
．． It was 5%.

Here, elapsed time 2 in Example 1.2 and Comparative Example 1
Changes in decomposition rate over time at 4 hr, 48 hr, and 72 hr were compared and measured and summarized in the following table.

Table 1 Comparison of decomposition rate (%) change over time (ratio of each decomposition rate when the decomposition rate at each elapsed time in Example 1 is set as 100) As can be seen from this table, the decomposition rate (%) was regenerated without hydrogenation treatment. When decomposed, the life of the decomposition catalyst will be significantly reduced. That is, it is clear that the unreacted fraction after decomposition cannot be recycled as it is.

However, as in the above embodiment, if this fraction is subjected to hydrogenation treatment, it becomes possible to recycle it sufficiently, making the decomposition reaction industrially advantageous.

Example 3: Hydroformylation reaction of p-isobutylstyrene fractions (part 1) Each p-isobutylstyrene fraction obtained in Example 1, Example 2, and Comparative Example 1 was subjected to a hydroformylation reaction.

30 g of p-inbutylstyrene fraction and 40 g of toluene were placed in a pressure-resistant reactor with an internal volume of 250 m1 equipped with a stirrer, kept at a temperature of 60°C, and heated to 70 kg/cm2 with an equimolar mixed gas of hydrogen and carbon monoxide. Pressure was applied and the mixture was allowed to react for 16 hours. After the reaction was completed, the mixture was cooled to room temperature, the remaining mixed gas was discharged, and the contents were analyzed using a gas chromatograph to compare reaction rates.

o as a catalyst for the p-isobutylstyrene fraction;
Oooi moles of rhodium hydridocarbonyltristriphenylphosphine and o,ooi moles of triphenylphosphine were used.

Table 2 Results of hydrofluormylation reaction (ρ-inbutylstyrene) (Note) Reaction rate: Value calculated from the amount of p-isobutylstyrene remaining after reaction, mol% relative to supplied p-isobutylstyrene Selectivity - carbonylation product Molar ratio of α-phenyl to β-phenyl in p-isobutylphenylpropionaldehyde Example 4: Droesterification reaction with p-isobutylstyrene fraction (Part 2) Example 12, Example 2, and Comparative Example 1 Each p- obtained in
A hydroesterification reaction was performed on the isobutylstyrene fraction.

30 g of p-isobutylstyrene fraction, 40 g of toluene and 15 g of methanol were placed in a pressure-resistant reactor with an internal volume of 250 m1 equipped with a stirrer, the temperature was kept at 90°C, and the pressure was increased to 80 kg/cm2 with -carbon oxide for 16 hours. Made it react. After the reaction was completed, the mixture was cooled to room temperature, the remaining mixed gas was discharged, and the contents were analyzed using a gas chromatograph to compare reaction rates.

As a catalyst, 0.0% for the p-isobutylstyrene fraction.
0003 moles of dichloropalladium tristriphenylphosphine and 0.0015 moles of triphenylphosphine were used.

Table 3 and Droesterification reaction results (p-isobutylstyrene) (Note) Reaction rate: A value calculated from the amount of p-isobutylstyrene remaining after the reaction, mol% relative to the supplied p-isobutylstyrene Selectivity: Carbonylation formation Molar ratio of α-phenyl to β-phenyl of (p-isobutylphenyl)propionic acid methyl ester, which is a compound Patent applicant: Nippon Petrochemical Co., Ltd.

Claims (1)

[Claims] (1) A method for producing p-isobutylstyrene, which comprises the following steps (I), (II), (III) and (IV). Step (I): 1,1-di(p-isobutylphenyl)
Ethane is contacted with an acid catalyst in the presence of an inert gas, and p-
Step (II) of decomposing isobutylstyrene and p-isobutylbenzene: A distillate mainly containing 1,1-di(p-isobutylphenyl)ethane is obtained by distilling the reaction mixture obtained in the decomposition step (I). Step (III): separating the unreacted 1,1-di( A step of hydrogenating a fraction mainly containing p-isobutylphenyl)ethane by contacting it with a hydrogenation catalyst in the presence of hydrogen, and step (IV): 1, obtained in the hydrogenation step (III). A recycling step in which a fraction mainly containing 1-di(p-isobutylphenyl)ethane is re-decomposed in the same manner as in the decomposition step (I).