JPH0791215B2 - Process for producing α- (4-isobutylphenyl) propionic acid or its alkyl ester - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing α- (4-isobutylphenyl) propionic acid or its alkyl ester economically and in high purity. It is a thing. More specifically, a step of reacting isobutylbenzene with ethylene in the presence of an acid catalyst to produce p-isobutylethylbenzene, and the obtained p-isobutylethylbenzene is dehydrogenated in the presence of a dehydrogenation catalyst in the gas phase to produce p-isobutylethylbenzene. −
Process for producing isobutylstyrene, and the resulting p
Α- (4- by reacting isobutylstyrene with carbon monoxide and water or carbon monoxide and a lower alcohol in the presence of a transition metal complex carbonylation catalyst.
The present invention relates to an economical method for producing α- (4-isobutylphenyl) propionic acid or its alkyl ester, which comprises the step of producing isobutylphenyl) propionic acid or its alkyl ester.

Alkyl α- (4-isobutylphenyl) propionate, which is one of the target products of the present invention, is easily converted into α- (4-isobutylphenyl) propionic acid by hydrolysis with an acid or an alkali by a known method. It is known to be possible. This α- (4-isobutylphenyl) propionic acid is disclosed in British Patent No. 971700 and French Patent No.
1549758, Japanese Patent Publication No. 40-7178 and Japanese Patent Publication No. 40
As described in Japanese Patent No. 7491, a useful drug having an antipyretic, analgesic and anti-inflammatory effect (trade name; ibuprofen)
Is a compound.

[Problems to be Solved by Conventional Techniques and Inventions] α- (4-isobutylphenyl) propionic acid or its alkyl ester has been synthesized by various methods using many compounds as starting materials.

However, α- (4-isobutylphenyl) propionic acid or its alkyl ester is inexpensive and economical,
In addition, in order to synthesize with high purity, (a) use a simple compound as a starting material, (b) use a reaction in which an intermediate in each step is as simple and stable as possible, and (c) Use inexpensive reagents or catalysts without using expensive reagents, (d) Minimize the number of steps, and (e) Isobutyl groups are prone to isomerization. It is required to utilize reactions that do not cause isomerization as much as possible.

However, for example, JP-A-50-40541 and JP-A-51-1 proposed as a method for synthesizing α- (4-isobutylphenyl) propionic acid or its alkyl ester.
In both JP-A No. 52-65243 and JP-A No. 52-65243, a complicated and expensive starting material itself is used, or an unstable and difficult-to-handle reagent such as a Grignard reagent is used. Therefore, it is hard to say that it is a cheap and economical method.

Further, JP-A-49-13351 and JP-A-5-135351 which disclose a method for producing α (4-isobutylphenyl) propionic acid.
In each of the 0-4040 publications, isobutylbenzene is used as a starting material, but since aluminum chloride is used as a catalyst, the isobutyl group is easily isomerized and an expensive reagent is used.

Further, French Patent No. 1549758, Japanese Patent Publication No. 47-245
50, JP-A-49-95938, JP-A-52-57338, JP-A-52-97930, JP-A-52-131553, JP-A-53-7643, The methods described in JP-A-53-18535 and JP-A-56-154428 are p-type.
In this method, isobutylacetophenone is used as a starting material.

However, p-isobutylacetophenone cannot be said to be an inexpensive compound as described later. This is most economically synthesized from isobutylbenzene, but the conversion of isobutylbenzene to p-isobutylacetophenone is not unfavorable from an economical point of view. That is, in order to convert to p-isobutylacetophenone, acetyl chloride, which is an expensive and unstable raw material, must be used, and at least anhydrous aluminum chloride, which is very sensitive to water, is used as a reaction catalyst. It must be used in the same number of moles as acetyl chloride, ie in large quantities. For example, even if it is considered that the conversion reaction has a stoichiometric yield of 100%, it is necessary to use a large amount of 700 kg of anhydrous aluminum chloride in order to produce 1 ton of p-isobutylacetophenone. After the reaction, the aluminum hydroxide produced as a result of deactivating the anhydrous aluminum chloride is 410 kg and chloride ion is 750 kg, and the waste of 1160 kg, which greatly exceeds the target production amount of p-isobutylacetophenone, is harmless. Need to be processed. Therefore, it goes without saying that p-isobutylacetophenone itself as a starting material is expensive. Furthermore, the conversion of p-isobutylacetophenone to α- (4-isobutylphenyl) propionic acid is not necessarily an economical method from an industrial viewpoint, for example, via a complicated intermediate product.

Incidentally, JP-A-52-51338, JP-A-52-6233, JP-A-52-97930, and JP-A-59-10545.
Japanese Patent Laid-Open Publication No. 9-242242 proposes a method for producing α- (4-isobutylphenyl) propionic acid from p-isobutylstyrene by a hydroformylation reaction or a Reppe reaction. In the method using p-isobutylstyrene, p-isobutylstyrene is a simple and stable compound, and since the hydroformylation reaction and Reppe reaction do not consume expensive reagents, α- (4 -Isobutylphenyl) propionic acid is an economically excellent method, but in these conventional methods for producing p-isobutylstyrene, complicated reaction paths are used, expensive reagents are used, etc. Because of that, its advantages are lost.

According to JP-A-61-24537, isobutylbenzene and acetaldehyde are subjected to a condensation reaction in the presence of a sulfuric acid catalyst to give 1,1-bis (p-isobutylphenyl) ethane, which is catalytically decomposed with an acid catalyst. To give p-isobutylstyrene, and this p-isobutylstyrene is reacted with carbon monoxide and water or carbon monoxide and an alcohol in the presence of a carbonylation complex catalyst to form α- (4-isobutylphenyl) propionic acid or its A method of making an alkyl ester is disclosed. However, as described in the above publication, in the method using sulfuric acid, 1,1
-In the process of producing bis (p-isobutylphenyl) ethane, the sulfonation reaction of isobutylbenzene itself, which is a valuable raw material, cannot be avoided, and as a result, some isobutylbenzene is lost as a sulfonated compound, which is economical Unfavorable. Further, since this condensation reaction is a dehydration reaction, after the sulfuric acid is once used, the concentration of sulfuric acid as a catalyst decreases due to the generated water. The catalyst cannot be reused unless it is recovered by high-temperature distillation, which may cause corrosion. In addition, a large amount of sulfonate is dissolved in the sulfuric acid phase, and it is not easy to recover the catalyst concentration by simple distillation. Therefore, it is necessary to use a method such as adding water such as anhydrous sulfuric acid or fuming sulfuric acid to remove the produced water by a chemical reaction.

As described above, the conventional technique for producing α- (4-isobutylphenyl) propionic acid or its alkyl ester is not yet an economical method.

Therefore, as described above, p-isobutylstyrene is α
It is a useful intermediate for producing-(4-isobutylphenyl) propionic acid, and a method for inexpensively producing this p-isobutylstyrene is desired.

Dehydrogenation of p-isobutylethylbenzene can be considered as a method for inexpensively producing this p-isobutylstyrene. Furthermore, ethylation of isobutylbenzene with ethylene can be considered as a method for inexpensively producing this p-isobutylethylbenzene. However, nothing is known about each elementary reaction as well as such a combination. Furthermore, what would be expected from similar prior art techniques is that such simple reaction combinations are very difficult.

The ethylation reaction of monoalkylbenzene with ethylene using an acid catalyst has been well known. For example, Ku
According to ts, WM, & B.B.Corson, J.Org.Chem., 16,699, (1951), when toluene was reacted with ethylene under a silica-alumina catalyst, o: m: p = 29: 50: 21. Ethyltoluene is produced at a ratio of. Further, according to the study by the present inventors, when ethylene is reacted with ethylbenzene under a silica-alumina catalyst, diethylbenzene is produced at a ratio of o: m: p = 28: 31: 41 and is reacted with isopropylbenzene. Isopropylethylbenzene is produced at a ratio of o: m: p = 24: 39: 37 and is reacted with sec-butylbenzene to produce o: m: p
It was found that sec-butylethylbenzene was produced at a ratio of 12:49:39. Also, Allen, RH, & L.D.Yats, J.
According to Am.Chem.Soc., 83,2799 (1961), when toluene is reacted with ethylene under a hydrogen fluoride catalyst, o: m: p = 42:
It was confirmed that ethyltoluene was produced at a ratio of 33:25, and that this is an equilibrium composition. Also Schlat
ter, MJ, & R.D.Clark, J.Am.Chem.Soc., 75,361 (1953)
According to the above, when toluene is reacted with isobutene under a hydrogen fluoride catalyst, tert-butyltoluene is produced at a ratio of m: p = 67 to 7:33 to 93, and o-tert-butyltoluene is observed to be produced. Not not. However, when toluene is alkylated with 1-butene or 2-butene, o: m: p = 3
Sec-Butyltoluene is produced at a ratio of 5:33:32.
Furthermore, even if toluene is alkylated with propylene, o:
It has been confirmed that m: p = 41:26:33.

As described above, the orientation of the positional isomerism of the product obtained by the alkylation of monoalkylbenzene has to be examined specifically for each individual compound. Furthermore, most of these reaction products are a mixture of o-, m-, and p-positional isomers. However, it is also well known that it is generally difficult to distill and separate the three positional isomers of dialkylbenzene with high purity. For example, the o-, m-, and p-forms of xylene have a boiling point at atmospheric pressure (hereinafter, may be simply referred to as a boiling point) of 144.4 ° C and 139.1, respectively.
℃, 138.4 ℃, ethyl toluene o-, m-, p
The boiling points of the -forms are 165.2 ° C, 161.3 ° C, and 162.0 ° C, respectively, and although the o-form can be purified by distillation from the mixture of these positional isomers, the m-form and the p-form can be separated by distillation. Very difficult. The boiling points of o-, m-, and p-forms of isopropyltoluene are 178 ° C, 175 ° C, and
The boiling points of o-, m-, and p-forms of diethylbenzene are 183 ° C, 182 ° C, and 184 ° C, respectively, and the boiling points of o-, m-, and p-forms of sec-butyltoluene are 196 ° C and 196 ° C, respectively. 1
It is 94 ° C. and 197 ° C., and it is very difficult to distill and purify any component from these mixture of positional isomers with high purity. Furthermore, the boiling points of the o-, m-, and p-forms of isopropylethylbenzene are 193 ° C, 192 ° C, and 19 ° C, respectively.
It is 7 ° C., and the p-form can be purified by distillation from these regioisomer mixtures, but it is very difficult to separate the o-form and m-form by distillation.

However, the target product in the ethylation step (I) of the present invention is p-isobutylethylbenzene, but no method for alkylating isobutylbenzene with ethylene has been reported so far. Therefore, the ratio of regioisomers of isobutylethylbenzene in the reaction mixture and the method for separating and purifying high-purity p-isobutylethylbenzene from the mixture are not known. Of course, this p-isobutylethylbenzene is not known at all as a raw material for producing α- (4-isobutylphenyl) propionic acid.

Looking at the prior art in the dehydrogenation reaction of aromatic hydrocarbons, only one specific substituent of polyalkylbenzene having a plurality of alkyl groups having different structures and each alkyl group being possibly dehydrogenated Until now, no technique for selectively dehydrogenating hydrogen has been known. For example, JP-A-62-6528, JP-A-56-135425, and JP-A-58-1890.
No. 34, JP-A-59-120243, JP-A-61-158940, and the like, or a method for producing methylstyrene by dehydrogenating methylethylbenzene, or JP-A-56-
155648, JP-A-56-155649, JP-A-56-155650,
JP-A-56-155651, JP-A-56-155652, JP-A-60-
A method for producing tertiary butyl styrene by dehydrogenating tertiary butyl ethylbenzene as disclosed in Japanese Patent No. 115534, and further dehydrogenating diethylbenzene as disclosed in Japanese Patent Laid-Open No. 62-29537. A method for producing ethylstyrene or divinylbenzene and the like are disclosed. However, methylethylbenzene and tertiary-butylethylbenzene both have an ethyl group that can be dehydrogenated, but the other substituent is a methyl group and a tertiary-butyl group, both of which are dehydrogenated. There is no possibility. Therefore, the side reaction in the dehydrogenation reaction of these compounds is a cracking reaction, and the selectivity of the dehydrogenation reaction itself does not matter. In addition, when dehydrogenating diethylbenzene, it has two alkyl groups that can be dehydrogenated, that is, two ethyl groups, but when either one of the ethyl groups is dehydrogenated, ethylstyrene is produced. Since there is only one, it is not necessary to select one of the two substituents, and since the target product is diethylbenzene, the remaining ethyl group of the ethylstyrene may be further dehydrogenated. In other words, there is no distinction between the two ethyl groups, and there is no particular problem.

The technique for producing p-isobutylstyrene by selective dehydrogenation of p-isobutylethylbenzene in the present invention is fundamentally different from these known conventional techniques. In particular,
Substituents bonded to the aromatic nucleus of p-isobutylethylbenzene as a raw material are an ethyl group and an isobutyl group, both of which are dehydrogenated to produce a vinyl group and a 2-methyl-1-propenyl group or a 2-methyl- group, respectively. There is a possibility of becoming a 2-propenyl group (hereinafter, these may be referred to as a substituted propenyl group) and the like. That is, when only the ethyl group of p-isobutylethylbenzene is dehydrogenated, it becomes p-isobutylstyrene, and when only the isobutyl group is dehydrogenated, 4- (2'-methyl-1'-propenyl) ethylbenzene or 4- (2 ′ -Methyl-2′-
Propenyl) ethylbenzene etc. Further, when both the ethyl group and the isobutyl group are dehydrogenated, 4- (2 '
-Methyl-1'-propenyl) vinylbenzene or 4
-(2'-methyl-2'-propenyl) vinylbenzene and the like. Thus, p-isobutylethylbenzene has two different alkyl groups that can be dehydrogenated, and the product is completely different depending on which is dehydrogenated.

According to the Journal of Catalysis 34,167-174 (1974), the reaction rate constant for dehydrogenation of cumene is about twice that of ethylbenzene when using a Bi2UO6-oxidized uranium catalyst. ing. Also, the report Azer
According to b.Khim.Zh.1968, (2), 59-62 (Russ), when dehydrogenating isopropylethylbenzene and comparing the dehydrogenation selectivity of the alkyl group in the same molecule, only the isopropyl group was dehydrogenated. It is reported that the ratio of the amount of isopropenylethylbenzene produced to the amount of isopropylstyrene produced by dehydrogenating only ethyl groups is 2 or more, and if the reaction temperature is lowered to increase the selectivity, this ratio becomes 3 or more. . What is known from these publicly known documents is that a branched isopropyl group and a linear ethyl group are more easily dehydrogenated with a branched isopropyl group of about 2 to 3 times. Further, according to the study by the present inventors, when p-sec-butylethylbenzene was dehydrogenated in the presence of an iron oxide-based catalyst, the reaction temperature was 550 ° C., and the molar ratio of steam to p-sec-butylethylbenzene was 93, p. -Sec-Butylethylbenzene under the condition that the contact time with the catalyst is 0.2 seconds, p-s
ec-Butylethylbenzene conversion is 43.4% by weight, p-
The ratio of sec-butenylethylbenzene: p-sec-butylstyrene is about 2: 1, and sec-butyl group is about twice as easily dehydrogenated as ethyl group. It was confirmed that was never reversed. From this fact, it is considered that the branched type 4 sec-butyl group is more easily dehydrogenated than the linear type ethyl group, as in the above-mentioned literature of isopropylethylbenzene. However, the object of the present invention cannot be achieved by such a method.

That is, the target product of the dehydrogenation step of isobutylethylbenzene is p-isobutylstyrene in which only the ethyl group is dehydrogenated. Therefore, development of a dehydrogenation method of p-isobutylethylbenzene having a high selectivity of p-isobutylstyrene, that is, a method of selectively dehydrogenating only the ethyl group of the ethyl group and isobutyl group of p-isobutylethylbenzene has been sought. Was desired by.

Furthermore, the dehydrogenation reaction mixture obtained by dehydrogenating p-isobutylethylbenzene also contains impurities of olefins active in the hydrocarboxylation or hydroesterification reaction, and particularly 4- (2'-methyl- 1 '
-Propenyl) ethylbenzene, 4- (2'-methyl-
2'-propenyl) ethylbenzene, 4- (2'-methyl-1'-propenyl) vinylbenzene, 4- (2'-
The study by the present inventors revealed that methyl-2'-propenyl) vinylbenzene and the like pose a problem. Considering that the object of the present invention is a drug or a raw material intermediate thereof, the influence of these impurities in the hydrocarboxylation or hydroesterification step becomes a problem, and its solution has been desired.

[Means for Solving the Problem] The present invention comprises industrial and economical α- (4-isobutylphenyl) characterized by comprising the following steps (I), (II) and (III): The present invention provides a method for producing propionic acid or its alkyl ester.

Step (I): Isobutylbenzene is reacted with ethylene under the conditions of a reaction temperature of −10 to 600 ° C., an ethylene / isobutylbenzene ratio of 0.005 to 100 (molar ratio), and a reaction pressure of 1 kg / cm ² or more in the presence of acid contact. Producing p-isobutylethylbenzene by reacting with.

Step (II): The p-isobutylethylbenzene obtained in the above step (I) is used in a gas phase at a reaction temperature of 300 to 650 ° C., a reaction pressure of 50 kg / cm ² or less, a contact time of 0.005 to 20 seconds, and p-isobutylethylbenzene. Group IB, Group 2B, Group 6A, Group 7A and Group 8 in the periodic table under the condition of conversion of 80% by weight or less.
A step of producing p-isobutylstyrene by dehydrogenating in the presence of a dehydrogenation metal catalyst containing a metal selected from the group.

Step (III): The p-isobutylstyrene obtained in the above step (II) is treated with a transition metal complex carbonylation catalyst at a reaction temperature of 40 to 250 ° C. and a carbon monoxide pressure of 10 to 600 kg / cm ^2.
A step of producing α- (4-isobutylphenyl) propionic acid or an alkyl ester thereof by reacting with carbon monoxide and water or an alcohol under the conditions of.

The present invention will be described in more detail below.

Step (I) in the present invention is a step of reacting isobutylbenzene with ethylene in the presence of an acid catalyst to produce p-isobutylethylbenzene.

As the acid catalyst used in the step (I), a solid acid, an inorganic acid, an organic acid, a Friedel-Crafts catalyst, a heteropoly acid, an isopoly acid, which is a usual ethylation catalyst, can be used if the isomerization of the isobutyl group is difficult to occur. Acid catalysts such as acid and strong acid cation exchange resins can be used. For example, sulfuric acid,
Inorganic acids such as phosphoric acid; Friedel-Crafts catalysts such as aluminum chloride, zirconium chloride, zinc chloride, vanadium chloride, titanium chloride, beryllium chloride, boron fluoride, hydrogen fluoride; benzenesulfonic acid, p-toluenesulfonic acid, Organic acids such as trifluoromethanesulfonic acid;
Heteropoly acid; isopoly acid; solid acid such as silica-alumina and zeolite; strong acid type cation exchange resin such as bar fluorosulfonic acid resin represented by Nafion resin (trade name; manufactured by DuPont).

The reaction temperature is usually selected in the range of -10 to 600 ° C.
If the reaction temperature is lower than this range, the reaction rate becomes slow, and a long reaction time is required to increase the conversion rate of ethylation, which is not preferable. If the reaction temperature is higher than this range, the decomposition reaction or the structural isomerization of the isobutyl group becomes remarkable, and the side reaction such that the p-isobutylethylbenzene thus produced is further ethylated, which is not preferable.

Hereinafter, the more preferable ethylated acid catalyst will be described more specifically.

When silica-alumina is used as a catalyst, the silica-alumina used may be a natural type or a synthetic type, or a mixture thereof. The reaction temperature is preferably 150 to 600 ° C, more preferably 200 to 500 ° C. When using trifluoromethanesulfonic acid and / or hydrogen fluoride as a catalyst, the trifluoromethanesulfonic acid or hydrogen fluoride used can be used in pure form, in aqueous solution, or in a mixture thereof. As a result of the study by the present inventors, it was found that trifluoromethanesulfonic acid and hydrogen fluoride show almost the same catalytic effect for the ethylation of isobutylbenzene, and the products are also almost the same under the same conditions. did. The reaction temperature is preferably -10 to 20
The temperature is 0 ° C, more preferably -5 to 150 ° C.

When a heteropolyacid is used as a catalyst, the heteropolyacid used is, for example, silicotungstic acid, phosphotungstic acid, silicomolybdic acid, a group of heteropolyacids produced by molybdenum or tungsten such as phosphomolybdic acid, and as a hetero atom, P, B, V, As, Si, G
e, Sn, Ti, Zr, Ce, Th, Fe, Pt, Mn, Co, Ni, Te,
Those containing I, Al, Cr, Rh, Cu, Se and the like can be used. The reaction temperature is preferably 150 to 600 ° C, more preferably 200 to 500 ° C.

When zeolite is used as a catalyst, the zeolite used may be, for example, one containing HX type zeolite, HY type zeolite, or hydrogen zeolite such as hydrogen faujasite. These hydrogen zeolites are alkali metal salts such as NaX zeolite, NaY zeolite, and Na faujasite, which are partially or wholly converted to the proton form by cation exchange, and show strong solid acidity. The reaction temperature is preferably 100 to 400
C., more preferably 150 to 350.degree.

When a cation exchange resin such as Nafion resin is used, the reaction temperature is selected from the range of 50 to 300 ° C, preferably 100 to 250 ° C.

The reaction pressure of ethylene is not particularly limited as long as it is preferably 1 kg / cm ² or more. When the reaction pressure is lower than this range, the reaction rate becomes slow, and a long reaction time is required to increase the conversion rate of ethylation, which is practically impossible.

The molar ratio of ethylene / isobutylbenzene fed to the reactor is 0.005 to 100, preferably 0.01 to 50.
When the amount of ethylene is less than this ratio, the production of the target isobutylethylbenzene is less, and when the amount of ethylene supplied is larger than that in the reaction, there are many by-products of the diethyl form and above, which are not preferable.

The reaction form of ethylation may be either a gas phase or a liquid phase, and the reaction may be carried out in either a batch system or a flow system such as a fixed bed, a moving bed or a fluidized bed. The ethylene can be introduced into the reactor either in a closed system or a flow system.

Furthermore, a solvent can be appropriately used as long as it is inert to the reaction and can be easily separated from the desired product.

The isobutylethylbenzene in the reaction product reacted under the above conditions becomes a mixture of o-isobutylethylbenzene, m-isobutylethylbenzene and p-isobutylethylbenzene.

The three isobutylethylbenzene regioisomers in the ethylation reaction mixture obtained as described above have significant reactivity to the next step, the dehydrogenation reaction, and the next step, the hydroesterification reaction. P-isobutylethylbenzene, which is the starting material for the subsequent dehydrogenation step (II), must be separated and purified to high purity at this stage.

The present inventors have found that p-isobutylethylbenzene can be separated with high purity by distillation under specific conditions.

That is, the feed stream to the distillation column is a mixture containing at least the regioisomer of isobutylethylbenzene, and the weight ratio of the p-form to the total isobutylethylbenzene regioisomer mixture is 5% or more, preferably 10% or more. Use In the ethylation of isobutylbenzene, the p-isobutylethylbenzene content in the regioisomer mixture is usually about 60% at the maximum. The p-form content varies to some extent depending on the method for producing isobutylethylbenzene and the reaction conditions. Therefore, p-
What has a large body content may be used.

Components other than isobutylethylbenzene in the mixture are
There is no particular limitation as long as it does not hinder the achievement of the object of the present invention. Components other than isobutylethylbenzene in the mixture include, for example, benzene, toluene, xylene, ethylbenzene, isopropylbenzene, n-propylbenzene, sec-butylbenzene, n.
-Butylbenzene, tert-butylbenzene, isobutylbenzene, diethylisobutylbenzene, triethylisobutylbenzene, acetone, methyl ethyl ketone, diethyl ketone, diethyl ether, hexane, heptane, octane and the like may be used. If the ratio of the weight of the p-form to the total in the mixture of positional isomers is less than 5%, the target component in the mixture is too small, and even if highly precise distillation is performed, highly pure p-isobutylethylbenzene is effective. Cannot be separated by distillation.

As the distillation column used in the present invention, a distillation column having 20 or more theoretical plates, preferably 30 or more theoretical plates is used. If the theoretical plate number is less than 20, high-purity p-isobutylethylbenzene cannot be effectively separated by distillation.

In the present invention, the p-isobutylethylbenzene to be recovered is recovered as a fraction mainly containing a component in the range of 213 to 216 ° C. at the atmospheric pressure conversion boiling point.

The distillation method is not particularly limited, and may be continuous type, batch type, reduced pressure, normal pressure, increased pressure, single column type, multiple column type or the like.

The reaction mixture obtained by the above ethylation usually contains p
-In addition to isobutylethylbenzene, a large amount of m- / o-isobutylethylbenzene is produced. Therefore, when p-isobutylethylbenzene is separated by the above-mentioned distillation, a large amount of m- / o-isobutylethylbenzene and other isobutylpolyethylbenzene such as isobutyldiethylbenzene and isobutyltriethylbenzene remain. In the present invention, it was also found that even a large amount of these isomers can be effectively used.

That is, one of the methods is that the residual m-
at least part of / o-isobutylethylbenzene or isobutylpolyethylbenzene is returned to the ethylation step of step (I) as at least part of the raw material ethylene,
It is to use a ring. By doing so, the feed amount of the raw material ethylene can be reduced, the selectivity of isobutylbenzene is improved, and the by-product can be effectively used. M- that can be returned to step (I)
The amount of / o-isobutylethylbenzene or isobutylpolyethylbenzene can be appropriately determined in consideration of the reaction rate of ethylation and the like. Depending on the amount of m- / o-isobutylethylbenzene or isobutylpolyethylbenzene returned to the step (I), the amount of ethylene to be fed to the step (I) can be appropriately reduced.

Another method for effectively utilizing the by-product isomer is m
This is a method for producing p-isobutylethylbenzene by disproportionating-/ o-isobutylethylbenzene or isobutylpolyethylbenzene with a disproportionation catalyst.

That is, the present inventors have found that disproportionation of m- / o-isobutylethylbenzene or isobutylpolyethylbenzene with an acid catalyst produces p-isobutylethylbenzene.

As the catalyst for the disproportionation reaction and the reaction conditions therefor, the acid catalyst used for the ethylation reaction with ethylene and the reaction conditions therefor described in the step (I) can be used. For example, disproportionation catalysts include inorganic acids such as sulfuric acid, phosphoric acid, hydrogen fluoride; aluminum chloride, zirconium chloride, zinc chloride, vanadium chloride, titanium chloride, beryllium chloride,
Friedel-Crafts catalysts such as boron fluoride; benzenesulfonic acid, p-toluenesulfonic acid, trifluoromethanesulfonic acid and other organic acids; silicotungstic acid, silicomolybdic acid and other heteropolyacids; isopolyacid; silica-alumina, Solid acids such as zeolite; strong acid type cation exchange resins such as perfluorosulfonic acid resins typified by Nafion resin (trade name; manufactured by DuPont) and the like can be used.

The reaction temperature for disproportionation can be appropriately selected depending on the catalyst, but it is necessary to select the conditions under which side reactions such as decomposition reaction and isomerization reaction of isobutyl group do not occur as much as possible. Usually, it can be selected from the range of -10 to 600 ° C.

Hereinafter, some preferable disproportionation catalysts will be described in more detail.

When silica-alumina is used as a catalyst, the reaction temperature is preferably 150 to 600 ° C, more preferably 200 to 500 ° C. If the reaction temperature is lower than these ranges, the reaction rate becomes slow, and a long reaction time is required to increase the conversion ratio of disproportionation, which is not preferable. On the other hand, if the reaction temperature is higher than this range, decomposition reaction or skeletal isomerization of isobutyl group becomes remarkable, which is not preferable.

When using trifluoromethanesulfonic acid and / or hydrogen fluoride as a catalyst, the reaction temperature is preferably -10 to
200 ° C, more preferably -5 to 150 ° C.

When using a heteropolyacid as a catalyst, the reaction temperature is preferably 150 to 600 ° C, more preferably 200 to 500 ° C.

When using a catalyst containing a hydrogen zeolite such as HX type zeolite or HY type zeolite or hydrogen faujasite as a catalyst, the reaction temperature is preferably 100 to 400 ° C.,
More preferably, it is 150 to 350 ° C.

When a cation exchange resin such as Nafion resin is used, the reaction temperature is selected from the range of 50 to 300 ° C, preferably 100 to 250 ° C.

What is to be supplied for disproportionation is either the m- or o-form. Also, isobutyldiethylbenzene, isobutyltriethylbenzene, etc. can be supplied to disproportionate. Of course, a mixture of these can also be supplied. Further, in the disproportionation step, isobutylethylbenzene can be allowed to coexist if necessary.

It is also possible to use an appropriate solvent for the disproportionation reaction,
There is no particular limitation as long as it does not adversely affect the disproportionation reaction and the above-mentioned separation and purification of p-isobutylethylbenzene.

The reaction form of disproportionation may be disproportionation in either a gas phase or a liquid phase, and the reaction method may be a batch system, a continuous system, a fixed bed, a moving bed or a fluidized bed.

The reaction mixture obtained by the disproportionation reaction of the present invention is usually a mixture of regioisomers of isobutylethylbenzene containing the p-form. Therefore, the p-form can be separated from this by a method of separating p-isobutylethylbenzene by distillation from the reaction mixture in the ethyl reaction. That is, by using an isomer mixture containing at least 5% by weight, preferably 10% by weight or more of p-isobutylethylbenzene, distillation is carried out by a distillation column having 20 or more theoretical plates, preferably 30 or more theoretical plates, and the boiling point at atmospheric pressure is 213 to It is possible to separate and purify p-isobutylethylbenzene as a fraction mainly containing components in the range of 216 ° C.

The p-isobutylethylbenzene produced by the above disproportionation reaction can be supplied to the next step (II) alone or together with the p-form obtained in the above step (I).

Step (II) in the method of the present invention is a step of producing p-isobutylstyrene by dehydrogenating the p-isobutylethylbenzene obtained from the step (I) or the disproportionation step. More specifically, the present invention relates to a method for producing p-isobutylstyrene by selectively dehydrogenating only the ethyl group of p-isobutylethylbenzene in the presence of a dehydrogenation catalyst under specific conditions.

The dehydrogenation catalyst is a group IB, a group 2B, a group 6A or a group IB in the periodic table.
A metal catalyst containing a metal selected from 7A group and 8 group, specifically, iron, copper, zinc, nickel, palladium,
Platinum, cobalt, rhodium, iridium, ruthenium,
Metal compounds such as chromium, vanadium, niobium, molybdenum, titanium, zirconium, potassium, aluminum, calcium, magnesium, cerium, cesium, and rubidium are exemplified, and those in which these are appropriately combined can also be effectively used. Preferred is a catalyst containing at least one metal selected from iron, copper and chrome. These metals can be used alone as oxides, chlorides,
Any form such as sulfide and hydrotreated product can be used. In particular, iron oxide-based catalysts, copper-chromium-based catalysts and the like have high selectivity to p-isobutylstyrene and are effective for the purpose of the present invention.

Usually, the activity of the dehydrogenation catalyst gradually decreases due to coking, etc. if it is used for a long time.In that case, decoking the catalyst with air etc. at a high temperature of, for example, about 500 ° C. , The initial activity can be reproduced. Further, if necessary, hydrogen treatment may be carried out by placing in a stream of hydrogen at a temperature of 200 to 500 ° C.

The dehydrogenation temperature can be selected within the range of 300 to 650 ° C, preferably 400 to 650 ° C, depending on the composition of the catalyst, the contact time, the dilution molar ratio and the like. When the reaction temperature is higher than this range, not only the decomposition reaction but also the side reactions such as the further dehydrogenation of the produced p-isobutylstyrene are rapidly increased, and the selectivity of p-isobutylstyrene is significantly lowered. This is not preferable because not only the loss of p-isobutylethylbenzene is large, but also the product distribution becomes very complicated and it becomes difficult to separate p-isobutylstyrene and p-isobutylethylbenzene by distillation or the like. On the other hand, if the reaction temperature is lower than this range, the selectivity of p-isobutylethylbenzene is high, but the reaction rate is remarkably reduced and the economical efficiency is deteriorated.

Since the olefin produced by the dehydrogenation reaction is polymerizable, if the olefin concentration in the reaction layer is kept high at a high temperature, part of the p-isobutylstyrene produced will be polymerized and lost. In order to avoid this, it is effective to lower the olefin concentration by dilution by entraining a non-reducing gas such as nitrogen gas, helium gas, argon gas, steam, or oxygen gas. It can also be diluted with a solvent that is difficult to dehydrogenate such as benzene. Further, in order to maintain the catalytic activity of dehydrogenation, it is preferable to carry out dehydrogenation by entraining steam in the reaction layer. There is no particular limit to the amount of steam.

The reaction types in the dehydrogenation step (II) are fixed bed, moving bed,
Any of the fluidized beds can be used to achieve the objects of the invention.

The reaction pressure is not particularly limited as long as it can vaporize p-isobutylstyrene produced under the above reaction conditions,
Usually 50 kg / cm ² or less, preferably atmospheric pressure to 10 kg / cm ² is economical.

The contact time between the raw material p-isobutylethylbenzene and the catalyst can be appropriately selected in the range of 0.005 to 20 seconds, preferably 0.01 to 10 seconds, and more preferably 0.05 to 5 seconds. When the contact time is shorter than this, the reaction rate is low, which is not preferable. Further, if the contact time is longer than this, side reactions such as further dehydrogenation of the produced p-isobutylstyrene increase and the selectivity of p-isobutylstyrene decreases, which is also not preferable. It can be appropriately changed within the above range depending on the difference in various combinations such as reaction type, reaction gas composition, catalyst composition, reaction temperature, or preheating temperature of raw material gas.

Further, as a matter of course, the step (II) can be performed continuously or batchwise.

By the way, in the present invention, the reaction conditions and the influence of each factor on the reaction can be summarized by the relationship between the conversion of p-isobutylethylbenzene and the selectivity of p-isobutylstyrene. It became clear from.

That is, with respect to an arbitrary conversion rate x of p-isobutylethylbenzene obtained under the reaction conditions, the selectivity y to p-isobutylstyrene is a linear function y = ax + b (a and b are constants specific to the catalyst) It is in. FIG. 1 shows an example of the relationship between the conversion rate of p-isobutylethylbenzene and the selectivity rate of p-isobutylstyrene (hereinafter referred to as a dehydrogenation performance line) obtained in Examples described later. For example, if a certain condition is set within the above reaction conditions, the point on the dehydrogenation performance line corresponding to the conversion rate at that time indicates the selectivity of p-isobutylstyrene that is actually obtained. Therefore, depending on the performance line of the dehydrogenation catalyst used, reaction conditions may be selected so as to give a conversion rate of p-isobutylethylbenzene corresponding to the desired selectivity. For example, in the case of a copper-chromium-based catalyst, in the present invention, the conversion of p-isobutylethylbenzene is 80% by weight or less, preferably 60% by weight or less, more preferably 50% by weight or less.
It is appropriate to keep it at less than or equal to weight percent. Further, for example, in the case of an iron oxide catalyst, in the present invention, it is suitable to keep the conversion of p-isobutylethylbenzene at preferably 80% by weight or less, more preferably 70% by weight or less. When the conversion rate exceeds these ranges, the selectivity to p-isobutylstyrene is drastically lowered and the p-isobutylstyrene is departed from the dehydrogenation performance line, and not only by-products but also cracking products increase, which is not preferable. When the conversion rate is within the above range, the lower the conversion rate is, the higher the selectivity is. However, since the production rate of p-isobutylstyrene is the product of the conversion rate and the selectivity, the conversion rate is too low. However, this is not preferable because the burden on the separation and recovery operation of the unreacted p-isobutylethylbenzene by subsequent distillation or the like becomes large. Economically, it would be appropriate to keep the conversion above 5% by weight.

As described above, when p-isobutylethylbenzene was dehydrogenated by the method of the dehydrogenation step (II) of the present invention, contrary to the conventional expectation, only the ethyl group was unilaterally dehydrogenated, which was a surprisingly high selectivity. It is now possible to produce p-isobutylstyrene.

In step (III) of the present invention, p-isobutylstyrene obtained by the method of step (II) is converted to p-isobutylstyrene by hydrocarboxylation or hydroesterification with carbon monoxide and water or carbon monoxide and an alcohol. Conversion to α- (4-isobutylphenyl) propionic acid or its alkyl ester using a transition metal complex catalyst.

In the hydrocarboxylation reaction, p-isobutylstyrene is reacted in the presence of carbon monoxide and water to give α-
(4-Isobutylphenyl) propionic acid is obtained.
In the hydroesterification reaction, p-isobutylstyrene is reacted in the presence of carbon monoxide and a lower alcohol having a lower alkyl group to give α- (4-
An alkyl ester of isobutylphenyl) propionic acid is obtained. For example, methyl alcohol is α- (4
Methyl isobutylphenyl) propionate is obtained.

The transition metal complex catalyst used for the above-mentioned hydrocarboxylation or hydroesterification is a transition metal complex such as palladium, rhodium or iridium, and particularly a palladium complex. As these transition metals, those containing carbon monoxide as a ligand such as a halogen atom, a trivalent phosphorus compound or a carbonyl complex compound are used. A transition metal such as palladium having a valence of 0 to 2 is used.

Specific examples of the catalyst 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, bistriphenylphosphine dicarbonyl complex, bistriphenylphosphine acetate Complex, bistriphenylphosphine dinitrate complex, bistriphenylphosphine sulfate complex, tetrakistriphenylphosphine complex and chlorocarbonylbistriphenylphosphine complex having carbon monoxide as part of the ligand, hydridocarbonyltristriphenylphosphine complex , A bischlorotetracarbonyl complex, a dicarbonylacetylacetonate complex, and the like.

The catalyst can be supplied to the reaction system as a complex for use, or the compound serving as a ligand can be separately supplied to the reaction system to generate a complex in the reaction system for use.

The amount of the complex catalyst or the compound capable of forming a complex is p
-It is 0.0001 to 0.5 mol, preferably 0.001 to 0.1 mol, per 1 mol of isobutylstyrene. The amount of the compound that can serve as a ligand is 0.8 to 10 mol, preferably 1 to 4 mol, relative to 1 mol of a transition metal that can serve as a nucleus of a complex such as palladium, rhodium or iridium.

Further, an inorganic halide such as hydrogen chloride or boron trifluoride may be added for the purpose of promoting the reaction.

When these halides are added, the halogen atom is used in an amount of 0.1 to 30 times mol, preferably 1 to 15 times mol, relative to 1 mol of the complex catalyst or the compound capable of forming a complex. If the amount added is less than 0.1 mol, the effect of the addition may not be seen in some cases, depending on the type of catalyst. On the other hand, when it exceeds 30 times by mole, the catalytic activity is rather lowered and the desired reaction is suppressed, for example, halogen is added to the double bond of p-isobutylstyrene.

The hydrocarboxylation or hydroesterification reaction is
The reaction temperature is 40 to 250 ° C, preferably 70 to 120 ° C. If the reaction temperature is lower than 40 ° C., the reaction rate becomes remarkably slow and it cannot be practically carried out. Further, if the temperature exceeds 250 ° C., a polymerization reaction or decomposition of the complex catalyst occurs, which is not preferable.

The carbon monoxide pressure can be appropriately selected as long as it is 10 kg / cm ² or more.
If it is less than 10 kg / cm ² , the reaction becomes so slow that it cannot be practically performed. Further, the higher the carbon monoxide pressure, the faster the reaction proceeds, which is preferable, but too high a pressure naturally has a limit in terms of the production apparatus, such that the pressure resistance of the reactor needs to be very high. Therefore, a pressure of 600 kg / cm ² or less is practically sufficient.

The reaction may be carried out until absorption of carbon monoxide is no longer observed, and a reaction time of 4 to 20 hours is usually sufficient.

Alcohol is methyl alcohol, ethyl alcohol, n
-Propyl alcohol, isopropyl alcohol, n-
Lower alcohols having 1 to 4 carbon atoms such as butyl alcohol, sec-butyl alcohol and isobutyl alcohol are used, but methyl alcohol is preferable.

After completion of the hydrocarboxylation or hydroesterification reaction, the reaction product can be easily separated by extraction or distillation separation into high-purity α- (4-isobutylphenyl) propionic acid or its alkyl ester as a target compound and a catalyst. can do. The recovered complex catalyst can be reused.

The alkyl ester of α- (4-isobutylphenyl) propionic acid obtained by the present invention is easily hydrolyzed in the presence of an acid or an alkali catalyst by a conventional method to easily obtain α- (4-isobutylphenyl) propion. Can be converted to acid.

[Effect of the Invention] According to the method of the present invention, isobutylbenzene is directly ethylated with ethylene to produce p-isobutylethylbenzene, and the ethyl group of the obtained p-isobutylethylbenzene is selectively dehydrogenated to efficiently remove it. By converting to p-isobutylstyrene and selectively hydrocarboxylating or hydroesterifying this p-isobutylstyrene, it is possible to carry out industrially and economically.

In the step (I) of the present invention, p-isobutylethylbenzene can be separated and recovered with high purity by distillation from a mixture containing three positional isomers of isobutylethylbenzene produced by ethylation of isobutylbenzene, and the reaction product Components other than p-isobutylethylbenzene can be effectively converted to p-isobutylethylbenzene by recycling or disproportionation. That is, high-purity p-isobutylethylbenzene is separated from the ethylation reaction mixture of isobutylbenzene by the distillation method of the present invention, and other components are recycled as raw materials of step (I),
And / or disproportionation made it possible to increase the selectivity of isobutylbenzene to p-isobutylethylbenzene. With the establishment of these technologies, p
It is possible to avoid the large restriction which has been conventionally received that the substituent must be selectively introduced only at the -position.
It has become very economically advantageous.

Dehydrogenation of p-isobutylethylbenzene under the condition of the step (II) of the present invention makes it possible to produce p-isobutylstyrene having a high selectivity. Therefore, as described above, the dehydrogenation reaction mixture obtained by the method of the present invention is separated into, for example, an aqueous layer and a liquid separation layer,
After drying, high-purity p-isobutylstyrene and unreacted p can be obtained by only a few simple unit operations such as distillation.
-Isobutylethylbenzene is obtained. Further, this unreacted p-isobutylethylbenzene can be recovered and used again as a raw material for dehydrogenation. Further, the reaction mixture of step (II) can be used as it is as a raw material of step (III).

The reaction mixture obtained in the hydrocarboxylation or hydroesterification step (III) is a highly pure α- (4-isobutylphenyl) propionic acid that can be sufficiently used as an intermediate raw material for medicines by simple vacuum distillation or extraction. Alternatively, the alkyl ester can be separated.

Hereinafter, the present invention will be described in detail with reference to examples.

Example Here, as shown in the following examples, an ethylation step (I), a dehydrogenation step (II) and a hydrocarboxylation or hydroesterification step (III) were performed.

Production of p-isobutylethylbenzene [Step (I)] Example No. 1 600 ml of isobutylbenzene having a purity of 99.8% by weight and silica-
Alumina catalyst IS-28 (trade name; product of Catalyst Kasei Kogyo Co., Ltd.)
26 g and 26 g were charged in an autoclave 1, and the temperature was raised to 250 ° C. in the system while stirring, then ethylene was added and the reaction was carried out for 12 hours while maintaining the pressure at 20 kg / cm ² . After completion of the reaction, the catalyst was filtered off and analyzed by gas chromatography. The composition of the reaction mixture is shown in Table 1.

As a result, the conversion rate of isobutylbenzene was 19.7% by weight, and the p-
Ratio of the number of moles of isobutylethylbenzene (hereinafter, p-
The selectivity to isobutylethylbenzene) is 17.6.
%, Isobutylethylbenzene regioisomer is o: m: p
= 40: 31: 29.

Example No. 2 600 ml of isobutylbenzene having a purity of 99.8% by weight and silica-
Alumina catalyst N633L (trade name; product of JGC Chemicals Co., Ltd.) and 26 g were charged into an autoclave of 1, and the temperature of the system was set to 250 ° C. with stirring, and then ethylene was added to the mixture so that the pressure was 20 kg /
The reaction was carried out for 12 hours while maintaining the cm ² . After completion of the reaction, the catalyst was filtered off and analyzed by gas chromatography. The composition of the reaction mixture is shown in Table 2.

As a result, the conversion of isobutylbenzene was 40.0% by weight, p-
The selectivity to isobutylethylbenzene was 18.7%, and the positional isomer of isobutylethylbenzene was o: m: p = 37: 32: 31.

Example No. 3 A silica-alumina catalyst IS-28 (trade name; product of Catalysts & Chemicals Industry Co., Ltd.) was adjusted to a particle size of 1 mm to 2 mm, and an inner diameter of 12 mm and a length of 1 m.
64 ml (32.8 g) was filled in the stainless steel tube of, and the inside of the system was replaced with nitrogen.

Isobutylbenzene with a purity of 99.8% by weight is added to this reaction tank.
It was flowed at a flow rate of ml / hr, and ethylene was charged while keeping the temperature of the catalyst at 250 ° C. to a pressure of 20 kg / cm ^2, and the flow rate of ethylene was adjusted to a molar ratio of 1 with isobutylbenzene. The reaction mixture was cooled after 138 hours had passed since the start of the reaction,
After separating the gas and liquid, analysis by gas chromatography gave the composition shown in Table 3.

As a result, the conversion of isobutylbenzene was 21.2% by weight, p-
The selectivity to isobutylethylbenzene was 17.9%, and the position isomer of isobutylethylbenzene was o: m: p = 41: 30: 29.

Example No. 4 6 kg of the reaction mixture obtained in Example No. 3 was placed in a 10-necked three-necked flask, and a glass tube having an inner diameter of 30 mm and a length of 1.5 m was packed by Tokyo Special Wire Mesh Co., Ltd. Heli Pack No. When a batch distillation was performed using a distillation column having a theoretical plate number of 35 packed with .3 metal, 204 g (recovery rate 73.9%) of p-isobutylethylbenzene having a purity of 97% by weight or more was obtained.

Example No. 5 600 ml of isobutylbenze having a purity of 99.8% by weight and 30 ml of trifluoromethanesulfonic acid having a purity of 99% by weight were charged into an autoclave 1, and the temperature in the system was adjusted to 0 ° C. with stirring, and then ethylene was added. The reaction was carried out for 4 hours while maintaining the pressure at 10 kg / cm ² . After the reaction was completed, the reaction mixture was mixed with Ca (O
It was neutralized with H) 2, washed with water and analyzed by gas chromatography. The composition of the reaction mixture is shown in Table 4.

As a result, the conversion of isobutylbenzene was 7.5% by weight, p-
Selectivity to isobutylethylbenze 21.1%, o: m: p = 46:
It was 27:27.

Example No. 6 600 ml of isobutylethylbenzene having a purity of 99.8% by weight and 30 ml of trifluoromethanesulfonic acid having a purity of 99% by weight were mixed with each other.
The autoclave was charged and the temperature inside the system was adjusted while stirring.
After the temperature was raised to 90 ° C., ethylene was added and the reaction was carried out for 3.5 hours while maintaining the pressure at 20 kg / cm ² . After completion of the reaction, the reaction mixture was neutralized with Ca (OH) 2, washed with water and analyzed by gas chromatography. The composition of the reaction mixture is shown in Table 5.

As a result, the conversion of isobutylbenze was 38.7% by weight, the selectivity to p-isobutylethylbenzene was 16.9%, and o: m: p = 42:
It was 29:29.

Example No. 7 600 ml of isobutylbenzene having a purity of 99.8% by weight and 30 ml of trifluoromethanesulfonic acid having a purity of 99% by weight were charged into an autoclave 1, the temperature in the system was adjusted to 135 ° C. with stirring, and ethylene was added thereto. The reaction was carried out for 1 hour while maintaining the pressure at 10 kg / cm ² . After the reaction is complete, the reaction mixture is
After neutralizing with (OH) 2, it was washed with water and analyzed by gas chromatography. The composition of the reaction mixture is shown in Table 6.

As a result, the conversion of isobutylbenzene was 54.6% by weight, p-
Selectivity to isobutylethylbenzene 17.5%, o: m: p = 3
It was 7:31:32.

Example No. 8 600 ml of isobutylbenzene having a purity of 99.8% by weight and 30 ml of hydrogen fluoride having a purity of 99.7% by weight were charged into an autoclave 1, the temperature in the system was adjusted to 0 ° C. with stirring, and ethylene was added to adjust the pressure. The reaction was carried out for 3 hours while maintaining it at 20 kg / cm ² . After completion of the reaction, the reaction mixture was neutralized with Ca (OH) 2, washed with water and analyzed by gas chromatography. The composition of the reaction mixture is shown in Table 7.

As a result, the conversion of isobutylbenzene was 7.1% by weight, p-
Selectivity to isobutylethylbenzene 23.3%, o: m: p = 4
It was 3:27:30.

Example No. 9 600 ml of isobutylbenzene having a purity of 99.8% by weight and a purity of 99.7
30 ml of hydrogen fluoride of weight% was charged into the autoclave 1 and the temperature in the system was set to 25 ° C. with stirring, and then ethylene was added at normal pressure to carry out the reaction for 12 hours while maintaining the pressure at normal pressure. After completion of the reaction, the reaction mixture was neutralized with Ca (OH) 2, washed with water, and analyzed by gas chromatography. The composition of the reaction mixture is shown in Table 8.

As a result, the conversion of isobutylbenzene was 5.2% by weight, p-
Selectivity to isobutylethylbenzene 22.3%, o: m: p = 4
It was 8:25:27.

Example No.10 The reaction was repeated under the same conditions as in Example No.6, and 6 kg of the obtained reaction mixture was placed in a three-necked flask having a diameter of 30 mm.
Filler He made by Tokyo Special Wire Mesh Co., Ltd. in a glass tube with a length of 1.5 m
li Pack No.3 metal was packed in a distillation column with a theoretical plate number of 35, and 382 g of p-isobutylethylbenzene with a purity of 97% by weight or more was recovered.
80.6%).

Example No. 11 436 g of isobutylbenzene having a purity of 99.8% by weight and 4.46 g of phosphotungstic acid hydrate [P205 / 24WO3 · nH20] were charged into an autoclave 1 and the temperature in the system was adjusted to 25 while stirring.
After the temperature was set to 0 ° C., ethylene was introduced and the reaction was carried out for 12 hours while maintaining the pressure at 20 kg / cm ² . After completion of the reaction, the catalyst was filtered off and analyzed by gas chromatography. The composition of the reaction mixture is shown in Table 9.

As a result, the conversion of isobutylbenzene was 21.5% by weight, p-
The selectivity to isobutylethylbenzene was 20.4%, and the position isomer of isobutylethylbenzene was o: m: p = 40: 30: 30.

Example No. 12 426 g of isobutylbenzene having a purity of 99.8% by weight and 4.52 g of silicotungstic acid hydrate [SiO ₂ · 12WO 3 · 26H ₂ O] 4.52 g
The autoclave was charged and the temperature inside the system was adjusted while stirring.
After adjusting the temperature to 250 ℃, add ethylene and pressurize at 20kg / cm ²
The reaction was carried out for 12 hours while maintaining After completion of the reaction, the catalyst was filtered off and analyzed by gas chromatography. The composition of the reaction mixture is shown in Table 10.

As a result, the conversion of isobutylbenzene was 16.0% by weight, p-
The selectivity to isobutylethylbenzene was 19.6%, and the position isomer of isobutylethylbenzene was o: m: p = 39: 30: 31.

Example No. 13 600 ml of isobutylbenzene having a purity of 99.8% by weight and 6 g of phosphomolybdic acid hydrate [P2O5 · 24MoO3 · nH2O] were placed in an autoclave 1 and the temperature in the system was kept at 280 while stirring.
After the temperature was adjusted to 0 ° C, ethylene was introduced and the reaction was carried out for 12 hours while maintaining the pressure at 20 kg / cm ² . After completion of the reaction, the catalyst was filtered off and analyzed by gas chromatography. The composition of the reaction mixture is shown in Table 11.

As a result, the conversion of isobutylbenzene was 17.7% by weight, p-
The selectivity to isobutylethylbenzene was 20.6%, and the position isomer of isobutylethylbenzene was o: m: p = 38: 31: 31.

Example No.14 The reaction was repeated under the same conditions as in Example No.11, and 10 kg of the obtained reaction mixture was placed in a three-necked flask having a diameter of 30 m.
Filler H made by Tokyo Special Wire Mesh Co., Ltd. in a glass tube of m and 1.5 m in length
When a batch distillation was performed using a distillation column with 35 theoretical plates packed with eli Pack No.3 metal, 451 g of a fraction of p-isobutylethylbenzene with a purity of 97% by weight or more (recovery rate) was obtained.
85.1%).

Example No. 14A 522 g of isobutylbenzene having a purity of 99.8% by weight and 26,2 g of HX zeolite were charged into an autoclave 1 and the temperature in the system was adjusted to 160 ° C. with stirring, and ethylene was added to the mixture to a pressure of 20 kg / cm. ^The reaction was carried out for 12 hours while keeping it at ² . After completion of the reaction, the catalyst was filtered and analyzed by gas chromatography. The composition of the reaction mixture is shown below.

As a result, the conversion of isobutylbenzene was 29.6%, the selectivity to p-isobutylethylbenzene was 21.0%, and the position isomer of isobutylethylbenzene was o: m: p: = 39: 25: 36.

Example No. 14B Purity 99.8% by weight Isobutylbenzene 522 g and HY zeolite
26.1 g and 1 were charged into an autoclave 1, the temperature in the system was adjusted to 170 ° C. with stirring, ethylene was added, and the reaction was carried out for 12 hours while maintaining the pressure at 20 kg / cm ² . After completion of the reaction, the catalyst was filtered and analyzed by gas chromatography. The composition of the reaction mixture is shown in the following table.

As a result, the conversion of isobutylbenzene was 33.1% by weight, p
-The selectivity to isobutylethylbenzene is 19.6% by weight, and the regioisomer of isobutylethylbenzene is o: m: p = 40: 2.
It was 5:35.

Example No. 14C 522 g of isobutylbenzene having a purity of 99.8% by weight and 26.2 g of hydrogen faujasite were charged into an autoclave 1, the temperature in the system was adjusted to 200 ° C. with stirring, ethylene was added, and the pressure was adjusted to 20 Kg / cm ² . The reaction was carried out for 12 hours while maintaining it. After completion of the reaction, the catalyst was filtered and analyzed by gas chromatography. The results are shown in the table below.

As a result, the conversion of isobutylbenzene was 28.7% by weight, p
-Selectivity to isobutylethylbenzene 20.0%, regioisomer of isobutylethylbenzene is o: m: p: = 40: 25: 35
Met.

Example No.14D The reaction was repeated under the same conditions as in Example No.14B, 6 Kg of the resulting reaction mixture was placed in a three-necked flask having a diameter of 30 m.
Held by Tokyo Special Net Co., Ltd. in a glass tube of m and 1.5 m in length
When a batch distillation was carried out using a distillation column with 35 theoretical plates packed with iPack No. 3 metal, 388 g of a fraction of p-isobutylethylbenzene having a purity of 97% by weight or more (recovery rate 8
2.9%) was obtained.

Example No. 15 In the distillation of Example No. 14, the fractions other than p-isobutylethylbenzene were mixed and analyzed by glass chromatography. The results are shown in Table 12 below.

500 g of this mixture and 25 g of silica-alumina catalyst N633L were placed in an autoclave with an internal volume of 1, the gas phase portion in the system was replaced with nitrogen, and the disproportionation reaction was carried out at 270 ° C. for 24 hours with stirring,
The catalyst is filtered off from the reaction mixture and the organic phase is analyzed by gas chromatography. The results are shown in Table 13.

This disproportionation reaction mixture was placed in a 3-neck flask of 1,
Distillation in the same manner as in Example No. 14 yielded 15 g of a fraction of p-isobutylethylbenzene having a purity of 97% by weight or more.
(Recovery rate was 56.6%).

Example No. 16 Similarly to Example No. 15, 500 g of the mixture of Table 12 and a purity of 99.
25 g of wt% trifluoromethanesulfonic acid was placed in one autoclave, and a disproportionation reaction was carried out at 110 ° C. for 24 hours under stirring. The reaction mixture was neutralized with Ca (OH) 2 and washed with water, and the organic phase was subjected to gas chromatography. Table 14 shows the results of the analysis performed in Step 1.

This disproportionation reaction mixture was placed in a 3-neck flask of 1,
When distilled in the same manner as in Example No. 14, 16 g of a fraction of p-isobutylethylbenzene having a purity of 97% by weight or more was obtained.
(Recovery rate was 68.1%).

Example No. 17 Similarly to Example No. 15, 500 g of the mixture of Table 12 and a purity of 99.
25 g of 7 wt% hydrogen fluoride was put in one autoclave,
Disproportionation reaction is carried out at 110 ° C for 24 hours with stirring, and the reaction mixture is mixed with Ca.
Table 15 shows the results of gas chromatographic analysis of the organic phase after neutralization with (OH) 2 and washing with water.

This disproportionation reaction mixture was placed in a 3-neck flask of 1,
Distillation in the same manner as in Example No. 14 yielded 15 g of a fraction of p-isobutylethylbenzene having a purity of 97% by weight or more.
(Recovery rate was 65.2%).

Example No. 18 As in Example No. 15, 500 g of the mixture shown in Table 12 above and 25 g of phosphotungstic acid were put in one autoclave and stirred with stirring.
The results of disproportionation reaction at 50 ° C. for 24 hours, filtration of the catalyst from the reaction mixture and analysis of the organic phase by gas chromatography are shown in Table 16.

This disproportionation reaction mixture was placed in a 3-neck flask of 1,
Distillation in the same manner as in Example No. 14 yielded 19 g of a fraction of p-isobutylethylbenzene having a purity of 97% by weight or more.
(Recovery rate was 67.9%).

Example No. 18A In the same manner as in Example No. 15, 500 g of the mixture shown in Table 12 above and 25 g of HX zeolite were placed in an autoclave 1 and stirred at 170 ° C.
The following table shows the results of a disproportionation reaction at room temperature for 24 hours, filtering the catalyst from the reaction mixture and analyzing by gas chromatography.

This disproportionation reaction mixture was placed in a one-necked three-necked flask,
Distillation in the same manner as in Example No. 14 yielded 24 g of a fraction of p-ibutylethylbenzene having a purity of 97% by weight or more (recovery rate: 71.6%).

Example No. 18B In the same manner as in Example No. 15, 500 g of the mixture shown in Table 12 above and 25 g of HY zeolite were put into an autoclave 1 and stirred at 180 ° C.
The following table shows the results of a disproportionation reaction for 24 hours, filtration of the catalyst from the reaction mixture, and analysis by gas chromatography.

This disproportionation reaction mixture was placed in a one-necked three-necked flask,
When distilled in the same manner as in Example No. 14, 25 g of a fraction of p-ibutylethylbenzene having a purity of 97% by weight or more (recovery rate: 70.4%) was obtained.

Example No. 18C In the same manner as in Example No. 15, 500 g of the mixture shown in Table 12 and 25 g of hydrogen faujasite were placed in an autoclave 1 and subjected to disproportionation reaction at 200 ° C. for 24 hours under stirring to remove the catalyst from the reaction mixture. Separately, the results of gas chromatographic analysis of the organic phase are shown in the following table.

This disproportionation reaction mixture was placed in a one-necked three-necked flask,
Distillation in the same manner as in Example No. 14 yielded 23 g of a fraction of p-ibutylethylbenzene having a purity of 97% by weight or more (recovery rate: 65.7%).

Example No. 19 500 g of the mixture of Table 12 above and Deer-alumina catalyst N633L 250
Was placed in an autoclave having an internal volume of 1 and reacted under stirring with ethylene pressure of 20 kg / cm ² at 250 ° C. for 12 hours, the catalyst was filtered off from the reaction mixture, and the organic phase was analyzed by gas chromatography. As a result, the conversion of isobutylbenzene was 24.3% and the selectivity to p-isobutylethylbenzene was 27.8%.

The reaction mixture was placed in a 1-necked 3-neck flask and the
When distilled in the same manner as No. 14, 28 g of a fraction of p-isobutylethylbenzene having a purity of 97% by weight or more (recovery rate 7
It was 0.9%).

Example No. 20 500 g of the mixture shown in Table 12 above and 25 g of trifluoromethanesulfonic acid having a purity of 99% by weight were put into an autoclave having an internal volume of 1, and reacted under stirring with ethylene pressure of 20 kg / cm ² and 110 ° C. for 12 hours to carry out a reaction. Table 18 shows the results of gas chromatographic analysis of the organic phase after the mixture was neutralized with Ca (OH) 2 and washed with water. As a result, the conversion of isobutylbenzene was 26.3%, p
-The selectivity to isobutylethylbenzene was 29.2%.

The reaction mixture was placed in a 1-necked 3-neck flask and the
When distilled in the same manner as in No. 14, 32 g of a fraction of p-isobutylethylbenzene having a purity of 97% by weight or more (recovery rate 7
2.7%).

Example No. 21 500 g of the mixture shown in Table 12 above and hydrogen fluoride having a purity of 99.7% by weight 25
g in an autoclave with an internal volume of 1 and reacted under stirring at an ethylene pressure of 20 kg / cm ² and 110 ° C. for 12 hours.
Table 19 shows the results of gas chromatographic analysis of the organic phase after neutralization with a (OH) 2 and washing with water. As a result, the conversion of isobutylbenzene was 26.0% and the selectivity to p-isobutylethylbenzene was 29.5%.

The reaction mixture was placed in a 1-necked 3-neck flask and the
When distilled in the same manner as No. 14, 31 g of a fraction of p-isobutylethylbenzene having a purity of 97% by weight or more (recovery rate 7
0.5%).

Example No. 22 500 g of the mixture shown in Table 12 above and 25 g of phosphotungstic acid were put into an autoclave having an internal volume of 1, and ethylene pressure was 20 kg with stirring.
The reaction was carried out for 12 hours at 250 ° C./cm ² , the catalyst was filtered off from the reaction mixture, and the organic phase was analyzed by gas chromatography. The results are shown in Table 20. As a result, the conversion rate of isobutylbenzene
24.9%, selectivity to p-isobutylethylbenzene 26.8
%Met.

The reaction mixture was placed in a 1-necked 3-neck flask and the
When distilled in the same manner as No. 14, 26 g of a fraction of p-isobutylethylbenzene having a purity of 97% by weight or more (recovery ratio 6
6.7%).

Example No. 22A 500 g of the mixture shown in Table 12 above and 25 g of HX zeolite were put into an autoclave 1 and ethylene pressure was 20 Kg / cm ² at 160 ° C. under stirring.
The reaction is carried out for 12 hours, the catalyst is filtered off from the reaction mixture, and the organic phase is analyzed by gas chromatography. The results are shown in the following table. As a result, the conversion of isobutylbenzene was 26.8%, p
-The selectivity to isobutylethylbenzene was 22.2%.

The reaction mixture was placed in a one-necked 3-neck flask and the
When distilled in the same manner as No. 14, 22 g of a fraction of p-ibutylethylbenzene having a purity of 97% by weight or more (recovery rate 68.
8%).

Example No. 22B 500 g of the mixture shown in Table 12 above and 25 g of HY zeolite were placed in an autoclave 1 and stirred at 20 Kg / cm ² ethylene and 170 ° C. for 1 hour.
The reaction was carried out for 2 hours, the catalyst was filtered off from the reaction mixture, and the organic phase was analyzed by gas chromatography. The results are shown in the following table. As a result, the conversion of isobutylbenzene was 28.8%, p
-The selectivity to isobutylethylbenzene was 23.1%.

The reaction mixture was placed in a one-necked 3-neck flask and the
When distilled in the same manner as No. 14, 28 g of a fraction of p-ibutylethylbenzene having a purity of 97% by weight or more (recovery rate 71.
8%) was obtained.

Example No. 22B 1 g of 500 g of the mixture in Table 12 above and 25 g of hydrogen faujasite
Put in an autoclave of, ethylene pressure 20Kg / cm ² under stirring,
The reaction is carried out at 200 ° C. for 12 hours, the catalyst is filtered off from the reaction mixture, and the organic phase is analyzed by gas chromatography. The results are shown in the following table. As a result, the conversion of isobutylbenzene was 28.7
%, The selectivity to p-isobutylethylbenzene was 23.2%.

The reaction mixture was placed in a one-necked 3-neck flask and the
When distilled in the same manner as No. 14, 27 g of a fraction of p-ibutylethylbenzene having a purity of 97% by weight or more (recovery rate 69.
2%) was obtained.

Example No. 23 5 kg of a mixed solution of o-isobutylethylbenzene: m-isobutylethylbenzene: p-isobutylethylbenzene = 40: 47: 13 and 1,1-bis (p-isobutylphenyl) ethane 1 k
Put g into a 10-necked three-necked flask and fill a glass tube with an internal diameter of 30 mm and a length of 1.0 m by Tokyo Special Wire Mesh Co., Ltd. Heli Pack N
When distillation was carried out batchwise using a distillation column having a theoretical plate number of 24 packed with o.3 metal, 126 g (recovery rate 19.4%) of p-isobutylethylbenzene having a purity of 97% by weight or more was obtained.

Example No. 23A 600 ml of 99.8 wt% pure isobutylbenzene and Nafion resin pellets (NFION, trade name: Dubon, diameter 1 m
m and a length of 3 to 5 mm) (30 g) were charged into an autoclave (1), the temperature in the diameter was adjusted to 180 ° C. with stirring, and then ethylene was charged, and the reaction was carried out for 12 hours while maintaining the pressure at 20 kg / cm ² . After completion of the reaction, the catalyst was filtered off and analyzed by gas chromatography. The composition of the reaction mixture is shown in the table below.

As a result, the conversion of isobutylbenzene was 47.0% by weight, p-
The selectivity to isobutylethylene is 12.2% by weight, and the regioisomer of isobutylethylbenzene is o: m: p = 38: 29: 3.
Was 3.

Example 23B In the same manner as in Example No. 15, 500 g of the mixture shown in Table 12 and 30 g of Nafion resin pellets (NFION, trade name: manufactured by Dubon, diameter 1 mm, length 3 to 5 mm) were placed in an autoclave 1. The reaction was carried out at 180 ° C. for 24 hours with stirring, the catalyst was filtered off from the reaction mixture, and the organic phase was analyzed by gas chromatography. The results are shown in the table below.

This disproportionation reaction mixture was placed in a one-necked three-necked flask and distilled in the same manner as in Example No. 14. When 20% of a fraction of p-isobutylethylbenzene having a purity of 97% by weight or more (recovery rate 69.0%) was obtained. .

Example 23C 500 g of the mixture of Table 12 above and Nafion resin pellets (NFIO
N, trade name: Dubon, diameter 1mm, length 3-5mm) 30g and put into an autoclave with an internal capacity of 1 and react with ethylene pressure 20kg / cm ² , 180 ° C for 12 hours with stirring, and from the reaction mixture The catalyst is filtered off and the organic phase is analyzed by gas chromatography. The results are shown in the table below. As a result, the conversion of isobutylbenzene was 43.5% and the selectivity to p-isobutylethylbenzene was 21.8%.

The reaction mixture was placed in a 1-necked three-necked flask and used in Example N
When distilled in the same manner as in o.14, 40 g of a fraction of p-isobutylethylbenzene having a purity of 97% by weight or more (recovery rate: 75.
5%).

Production of p-isobutylstyrene [Step (II)] Example No. 24 An iron oxide-based dehydrogenation catalyst (G-64A manufactured by Nissan Gardler Co., Ltd.) having potassium and chromium as cocatalysts had a particle size of 1 mm to
Adjusted to 2mm, 20ml inside diameter 12mm, 1m long stainless steel tube
Filled.

10 ml / hr of p-isobutylethylbenzene (hereinafter sometimes referred to as PBE) and 90 ml / hr of water were passed through a catalyst layer at a temperature of 550 ° C. through a preheating tube to be dehydrogenated (contact time with the catalyst was 0.2. Second, steam molar ratio to p-isobutylethylbenzene 93). After cooling the dehydrogenated product and separating gas and water, the conversion of p-isobutylethylbenzene and the selectivity of p-isobutylstyrene (hereinafter sometimes referred to as PBS) were confirmed for the organic phase by gas chromatography. .

The organic phase of the dehydrogenated product is mainly PBE, PBS, 4 (2'-methyl-1'-propenyl) ethylbenzene (hereinafter 1-
Sometimes referred to as MPE), 4- (2'-methyl-2 '
-Propenyl) ethylbenzene (hereinafter sometimes referred to as 2-MPE), 4- (2'-methyl-1'-propenyl) vinylene (hereinafter sometimes referred to as 1-MPV), 4- (2'-methyl) It consisted of -2'-propenyl) vinylbenzene (hereinafter sometimes referred to as 2-MPV), and its composition was as shown in Table 21.

From this, it was found that the conversion rate of PBE was 31% and the selectivity of PBS was 83%, and it was confirmed that PBS was dehydrogenated with high selectivity.

When each component of the dehydrogenated product was separated and confirmed by Mass, IR, and NMR, p-isobutylethylbenzene was exactly the same as that used as the raw material, and the formation of sec-butylbenzene and tert-butylbenzene was confirmed. It was confirmed that side reactions such as isomerization of the isobutyl group did not occur. Also in PBS, the butyl group was an isobutyl group and the substitution position was the p-position.

Example Nos. 25 to 28 According to Example No. 24, the dehydrogenation reaction was carried out while changing the reaction temperature. The results obtained are shown in Table 2 together with the results of Example No. 24.
Shown in 2.

Example Nos. 29 to 33 According to Example No. 24, the dehydrogenation reaction was performed by changing the contact time. The results obtained are shown in Table 23.

Examples Nos. 34 to 38 Using a copper-chromium dehydrogenation catalyst consisting of 43% by weight of CuO, 42% by weight of Cr2O3 and 15% by weight of SiO2, Example No. 24
Then, the dehydrogenation reaction was carried out by changing the reaction temperature. The results obtained are shown in Table 24.

Examples No. 39 to 43 Using a copper-chromium dehydrogenation catalyst consisting of 18% by weight of Cr2O3, 39% by weight of CuO and 38% by weight of ZnO, the dehydrogenation reaction was carried out according to Example No. 24.

The results obtained are shown in Table 25.

Example 43A In accordance with Example No. 24, the metal of the dehydrogenation metal catalyst was changed, and PBE was dehydrogenated with the metal catalyst shown in the table below. All the metals were oxides, and those supported on silica were used. The results are shown in the table below. Metal conversion (%) Selectivity (%) Ag 31 62 Cg 12 64 Cr 22 61 Zz 13 52 Mo 16 53 W 11 59 Mn 11 61 Tc 12 60 Re 20 57 Ru 17 68 Os 12 70 Co 21 59 Rh 32 48 Ir 25 51 Ni 48 41 Pd 46 43 Pt 44 40 Preparation of α- (4-isobutylphenyl) propionic acid or its alkyl ester [Step (III)] Example No. 44: Hydrocarboxylation Obtained in Example No 24 The organic phase of the dehydrogenated product was purified by distillation to obtain 50 g of p-isobutylstyrene having a purity of 97.8% by weight, 5.5 g of bisdichlorotriphenylphosphine palladium, 80 g of 10% hydrochloric acid solution, and toluene 8 as a solvent.
0 ml was put into a 500 ml autoclave and pressurized with carbon monoxide to 100 kg / cm ² at room temperature with stirring, then, the temperature was raised to 120 ° C. and the pressure was increased to 300 kg / cm ² . After the reaction has stopped absorbing carbon monoxide,
The reaction continued for an hour.

After completion of the reaction, the reaction mixture was cooled to collect the reaction mixture, the oil layer and the aqueous layer were separated with a separating funnel, the oil layer was extracted 3 times with 50 ml of 8% aqueous sodium hydroxide solution, and the extracted aqueous solution was used as a separated aqueous layer. Mix and add pH to 2 with hydrochloric acid. Then, the mixture was extracted three times with 500 ml of chloroform, and the extract was decompressed to remove chloroform to obtain 52.3 g of pale yellow crystals of α- (4-isobutylphenyl) propionic acid. A conversion rate of p-isobutylstyrene of 100% and a selectivity to α- (4-isobutylphenyl) propionic acid of 89.0% were obtained.

Example No. 45 202.43 g of the organic phase of the dehydrogenated product obtained in Example No. 24, 5.5 g of bisdichlorotriphenylphosphine palladium 5.5%, 10%
Put 80 g of hydrochloric acid aqueous solution into a 500 ml autoclave, pressurize to 100 kg / cm ² with carbon monoxide at room temperature with stirring, and pressurize while raising the temperature to 120 ℃, 300 kg / cm ²
Pressurized to. The reaction was continued for 24 hours after the absorption of carbon monoxide disappeared.

After completion of the reaction, the reaction mixture was cooled to collect the reaction mixture, the oil layer and the aqueous layer were separated with a separating funnel, the oil layer was extracted 3 times with 50 ml of 8% aqueous sodium hydroxide solution, and the extracted aqueous solution was used as a separated aqueous layer. Mix and add pH to 2 with hydrochloric acid. After that, the mixture was extracted three times with 500 ml of chloroform, and the extract was decompressed to remove chloroform to obtain 50.2 g of pale yellow crystals of α- (4-isobutylphenyl) propionic acid. 100% conversion of p-isobutylstyrene, 87.3% selectivity to α- (4-isobutylphenyl) propionic acid, hydrocarbosylation of the substituted propenyl group of 4- (2'-methyl-1'-propenyl) ethylbenzene Rate of 0%, hydrocarboxylation rate of substituted propenyl group of 4- (2'-methyl-2'-propenyl) ethylbenzene 0.8%, of substituted propenyl group of 4- (2'-methyl-1'-propenyl) vinylbenzene Hydrocarboxylation rate of 0%, and 4- (2'-
A hydrocarboxylation rate of the substituted propenyl group of methyl-2'-propenyl) vinylbenzene of 0.6% was obtained.

Example No. 46: Hydroesterification 70.4 g of p-isobutylstyrene with a purity of 97.8% by weight obtained by purifying the organic phase of the dehydrogenated product obtained in Example No. 24 by distillation, 25.5 ml of methanol, and Toluene 40 ml as solvent, PdCl ₂ 0.0756 g as solvent, CuC as co-catalyst
l ₂ 0.0292g, plus the ligand triphenylphosphine
Add 0.2161g to a 200ml autoclave and stir 90 while stirring.
After the temperature was raised to ° C, the pressure was maintained at 70 kg / cm ² with carbon monoxide, and the reaction was carried out for 8 hours. After completion of the reaction, the reaction mixture was cooled, and the reaction mixture was analyzed by gas chromatography. As a result, the conversion of p-isobutylstyrene was 99.6%, and the selectivity to α- (4-isobutylphenyl) propionic acid methyl ester was 90.9%.
Got

Example No. 47 Organic phase 285.0 g of the dehydrogenated product obtained in Example No. 24, methanol 25.5 ml, PdCl ₂ 0.0756 g as a catalyst, CuCl ₂ 0.292 g as a cocatalyst, and triphenylphosphine as a ligand 0.2161 g was put in a 500 ml autoclave, and the temperature was raised to 90 ° C. with stirring, then, the pressure was maintained at 70 kg / cm ² with carbon monoxide, and the reaction was carried out for 8 hours. After completion of the reaction, the reaction mixture was cooled, and the reaction mixture was analyzed by gas chromatography. As a result, the conversion of p-isobutylstyrene was 99.8%, and the selectivity to α- (4-isobutylphenyl) propionic acid methyl ester was 88.9.
%, 4- (2'-ethyl-1'-propenyl) ethylbenzene substituted propenyl group hydroesterification rate 0%,
Hydroesterification rate of the substituted propenyl group of 4- (2'-methyl-2'-propenyl) ethylbenzene 0.6%, 4
Hydroesterification rate of substituted propenyl group of-(2'-methyl-1'-propenyl) vinylbenzene of 0%, and hydroesterification of substituted propenyl group of 4- (2'-methyl-2'-propenyl) vinylbenzene The rate was 0.3%.

Production of α- (4-isobutylphenyl) propionic acid by hydrolysis of α- (4-isobutylphenyl) propionic acid methyl ester Example No. 48 Methyl α- (4-isobutylphenyl) propionic acid of Example No. 46 30 g of the ester and 150 ml of a 10% aqueous sodium hydroxide solution were refluxed with stirring for about 3 hours for hydrolysis. After cooling, the mixture was allowed to stand and separated, and the lower aqueous phase was washed with normal hexane.

5% hydrochloric acid was added to the aqueous phase to adjust the pH to 2, and the separated oil was extracted with normal hexane and washed with water. Normal hexane was evaporated under reduced pressure to obtain 23.9 g of pale yellow crude α- (4-isobutylphenyl) propionic acid crystals.

Crude α- (4-isobutylphenyl) propionic acid was recrystallized in normal hexane solvent to give white purified α- (4-isobutylphenyl) propionic acid (melting point 75-76 ° C) crystals
20.7 g was obtained. The spectrum of this product was in agreement with the standard.

Example No. 49 100 g of the hydroesterification reaction mixture of Example No. 47 with 10%
150 ml of an aqueous sodium hydroxide solution was stirred and refluxed to carry out hydrolysis for about 3 hours. After cooling, the mixture was allowed to stand and separated, and the lower aqueous phase was washed with normal hexane.

5% hydrochloric acid was added to the aqueous phase to adjust the pH to 2, and the separated oil was extracted with normal hexane and washed with water. Normal hexane was separated by evaporation under reduced pressure to obtain 22.4 g of pale yellow crude α- (4-isobutylphenyl) propionic acid crystals.

Crude α- (4-isobutylphenyl) propionic acid was recrystallized in normal hexane solvent to give white purified α- (4-isobutylphenyl) propionic acid (melting point 75-76 ° C) crystals
19.9g was obtained. The spectrum of this product was in agreement with the standard.

Comparative Example No. 1 500 ml of ethylbenzene having a purity of 99.8% by weight was reacted with ethylene in the same manner as in Example No. 1. After completion of the reaction, the reaction mixture was analyzed by gas chromatography. The composition of the reaction mixture is shown in Table 26.

As a result, the conversion rate of ethylbenzene was 28.2% by weight, and the positional isomer of diethylbenzene was o: m: p = 28: 30: 42.

Comparative Example No. 2 Example N using 500 ml of 100 wt% isopropylbenzene
It was reacted with ethylene in the same manner as in o.1. After the reaction,
The reaction mixture was analyzed by gas chromatography. The composition of the reaction mixture is shown in Table 27.

As a result, the conversion of isopropylbenzene was 34.7% by weight, and the positional isomer of isopropylethylbenzene was o: m: p = 11:
It was 51:38.

Comparative Example No. 3 500 ml of sec-butylbenzene having a purity of 99.8% by weight was used in Example N.
It was reacted with ethylene in the same manner as in o.1. After the reaction,
The reaction mixture was analyzed by gas chromatography. The composition of the reaction mixture is shown in Table 28.

As a result, sec-butylbenzene conversion rate of 26.8% by weight, sec
-The regioisomer of butylethylbenzene is o: m: p = 12: 4
It was 9:39.

Comparative Example No. 4 In accordance with Example No. 24, dehydrogenation reaction of p-sec-butylethylbenzene (purity 97.5% by weight) was performed. Results are shown in Table 29.
It was the street.

[Brief description of drawings]

The figure shows the relationship between the conversion rate of PBE and the selectivity to PBS in the dehydrogenation reaction. In the figure, the solid line indicates the conversion rate of PBE in Examples No. 24-33 of the present invention using an iron oxide-based dehydrogenation catalyst.
It is a dehydrogenation performance straight line showing the selectivity to PBS.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI technical display location C07B 61/00 300

Claims (10)

[Claims] 1. The following steps (I) to (III) Step (I): isobutylbenzene in the presence of an acid catalyst at a reaction temperature of -10 to 600 ° C., ethylene / isobutylbenzene ratio of 0.005 to 100 (molar ratio). ), A step of producing p-isobutylethylbenzene by reacting with ethylene under a reaction pressure of 1 kg / cm ² or more, step (II): p-isobutylethylbenzene obtained in the step (I) in a gas phase, Periodic table 1B group, 2B group, 6A group under the conditions of reaction temperature of 300 to 650 ° C, reaction pressure of 50 kg / cm ² or less, contact time of 0.005 to 20 seconds, and p-isobutylethylbenzene conversion rate of 80% by weight or less. A step of producing p-isobutylstyrene by dehydrogenation in the presence of a dehydrogenation metal catalyst containing a metal selected from Group 7A and Group 8; Step (III): obtained in the above Step (II) P-isobutylstyrene, transition metal The presence of the body carbonylation catalyst, the reaction temperature 40-250 ° C., a carbon monoxide pressure 10~600kg / cm ²
Α- (4-isobutylphenyl), which comprises producing α- (4-isobutylphenyl) propionic acid or an alkyl ester thereof by reacting with carbon monoxide and water or an alcohol under the conditions of ) A method for producing propionic acid or an alkyl ester thereof. 2. The method according to claim 1, wherein at least part of o-isobutylbenzene, m-isobutylethylbenzene or isobutylpolyethylbenzene obtained from the reaction mixture of step (I) is recycled to step (I). Method. 3. At least a part of o-isobutylethylenebenzene, m-isobutylethylbenzene or isobutylpolyethylbenzene obtained from the reaction mixture of step (I) under the condition of -10 to 600 ° C. in the presence of an acid catalyst. The method according to claim 1, wherein p-isobutylethylbenzene is produced by a disproportionation reaction, and the obtained p-isobutylethylbenzene is used as a raw material in the step (II). 4. In the step (I) or claim 3, when isolating and purifying p-isobutylethylbenzene from the resulting isobutylethylbenzene regioisomer mixture by distillation, isobutyl is used as a feed stream to a distillation column. A mixture containing 5% by weight or more of p-isobutylethylbenzene in positional isomers of ethylbenzene was distilled by a distillation column having 20 or more theoretical plates, and the boiling point was 213 at atmospheric pressure.
The method according to claim 1 or 3, wherein p-isobutylethylbenzene is separated as a fraction mainly containing components in the range of -216 ° C. 5. The acid catalyst in step (I) and claim 3 is silica-alumina, and the reaction temperature is 150 to 600 ° C.
The method according to claim 1 or 3, wherein 6. The acid catalyst in step (I) and claim 3 is trifluoromethanesulfonic acid and / or hydrogen fluoride, and the reaction temperature is −10 to 200 ° C.
Or the method described in 3. 7. The method according to claim 1 or 3, wherein the acid catalyst in step (I) and claim 3 is a heteropolyacid, and the reaction temperature is 150 to 600 ° C. 8. The method according to claim 1 or 4, wherein HX-type zeolite, HY-type zeolite or hydrogen faujasite is used as the acid catalyst in the step (I) or 4, and the reaction is carried out at a reaction temperature of 100 to 400 ° C. 9. An alkyl ester of α- (4-isobutylphenyl) propionic acid obtained in the step (III) is hydrolyzed in the presence of an acid or an alkali catalyst to give α- (4-isobutyl). The method according to claim 1, wherein phenyl) propionic acid is produced. 10. The method according to claim 1, wherein the dehydrogenation metal catalyst in the step (II) contains at least one metal selected from iron, copper and chromium.