JPS6137743A - 1,1-bis(p-isobutylphenyl)ethane - Google Patents

Abstract

NEW MATERIAL:1,1-Bis(p-isobutylphenyl)ethane of formula I. USE:A raw material of p-isobutylstyrene (abbreviated as PBS) which is an intermediate for the economical production of alpha-(p-isobutylphenyl)propionic acid useful as a drug such as anti-inflammatory agent, etc. PREPARATION:1mol of acetaldehyde having a concentration of <=1wt% is made to react with >=1mol, preferably >=2.2mol of isobutylbenzene of formula II (abbreviated as IBB) in the presence of sulfuric acid having a concentration of >=75wt%, preferably 80-90wt% as a catalyst, at <=40 deg.C, preferably -20-+20 deg.C, preferably for 3-10hr under atmospheric pressure to obtain the compound of formula I. The catalytic decomposition of the compound of formula I gives PBS economically in high yield, and the by-produced IBB can be reused as a raw material of the compound of formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to 1,1-bis(p-inbutylphenyl)ethane. This compound is used as an intermediate for economically producing α-(p-inbutylphenyl)propionic acid, which is useful as a medicine such as an anti-inflammatory agent, at low cost.

[Prior art and problems to be solved by the invention] α-
(p-Inbutylphenyl)propionic acid (IPA) has been proposed to be synthesized by various methods. One of them is p-isobutylstyrene (PBS).
A method has been proposed for producing it by the hydroformation reaction or Retuppe reaction (Japanese Patent Application Laid-open No. 52-52
No. 1338, No. 52-6233, No. 52-97930
No. 59-10545).

This method using PBS is a simple and stable compound, and because hydroformation and Reppe reactions do not require expensive reagents, IPA
This is an economically superior method for producing.

However, all conventional methods for producing PBS use expensive and unstable reagents such as Grignard reagent or expensive starting materials such as p-isobutylacetophenone, as described in the above-mentioned literature. ing.

Therefore, an inexpensive method for producing PBS has been desired.

[Means for solving the problems] That is, the present invention provides 1,1-
Bis(p-inbutylphenyl)ethane (B B E)
It is related to.

PBS can be obtained in good yield by catalytically cracking the BBE.

Also, one of the methods for manufacturing the above-mentioned BBE is as follows.

For example, there is a method in which isobutylbenzene (IBB) is reacted with acetaldehyde in the presence of a sulfuric acid catalyst.

Therefore, the production of PBS via BBE of the present invention is carried out according to the following reaction formula.

(IBB) p-Inbutylstyrene (PBS) That is, by using the BBE of the present invention, PB'S can be economically produced by easy-to-operate catalytic cracking, and IBB is also produced as a by-product.

This by-product IBB can be reused as a raw material for BBE.

Next, a reaction for producing BBE of the present invention by reacting IBB with acetaldehyde using a sulfuric acid catalyst will be described.

In this reaction, the sulfuric acid concentration during the reaction is maintained at 75% by weight or more (based on the total of sulfuric acid and water), preferably 80-95% by weight. When the sulfuric acid concentration in the reaction solution is higher than 95% by weight, not only the production of polymers increases, but also
Side reactions such as sulfonation of the aromatic nucleus of IBB occur and the objective is not effectively achieved, and if the sulfuric acid concentration in the reaction solution is lower than 75% by weight, the reaction is not achieved effectively. As a result of the formation of a polymer, or the reaction being stopped midway, a large amount of 1-(p-isobutylphenyl)ethanol, which is a reaction intermediate, is produced, which is undesirable.

Since this reaction is a dehydration reaction, water is produced as the reaction progresses, and the sulfuric acid concentration of sulfuric acid water in the reaction solution decreases. Therefore, in order to maintain the above sulfuric acid concentration during the reaction,
Sulfuric acid can also be added continuously into the reaction system. As for substances added to maintain the sulfuric acid concentration, those having a sulfuric acid concentration exceeding 90% by weight, such as concentrated sulfuric acid, fuming sulfuric acid, and sulfuric anhydride, are preferable. If the sulfuric acid concentration is less than 90% by weight, the amount of sulfuric acid added will be large, making it uneconomical.

The amount of sulfuric acid used is usually 1 to 10 times the mole of acetaldehyde to be charged, preferably 2 to 7 times the mole. Sulfuric acid can be recovered after use, adjusted to a predetermined concentration, and reused.

As the acetaldehyde to be reacted with IBB, paraldehyde, hydrated acetaldehyde, etc. can also be used.

In this reaction, it is preferable to carry out the reaction while maintaining the acetaldehyde concentration in the reaction system at 1% by weight or less. If the acetaldehyde concentration is higher than this, the reaction tends to stop midway, and as a result, the intermediate 1-(
The amount of p-butylphenyl) ethanol produced increases,
Efficiency decreases. In addition to side reactions such as monopolymerization,
This is not preferable because the purity of the sulfuric acid used decreases, making recovery and reuse difficult.

IBB that can be obtained by any conventionally known method can be used, including pure products as well as inert solvents, such as
It can also be used diluted with aliphatic hydrocarbons such as hexane or pentane.

The amount of IBB used is usually in excess of acetaldehyde, for example, at least 2 times the mole, preferably at least 2.2 times the mole. If IBB is less than this, the reaction will not be effectively achieved and polymers will also be produced, which is not preferable.

The upper limit of the usage amount of IBB is determined mainly from an economic point of view, and in practical terms, it is, for example, 100 times the mole or less, preferably 2 times the mole or less.
It becomes 0 times mole or less.

In the production of BBE, the reaction temperature is set at 40°C while stirring.
Hereinafter, it is necessary to maintain the temperature preferably at -20 to 20°C. If the temperature exceeds 40°C, side reactions such as polymerization reactions and IBB sulfonation reactions will rapidly increase, which is not preferable. For this reason, it is desirable to cool the reactor externally or internally.

A preferred reaction format is one reactant, IB, in the reactor.
B and sulfuric acid of a predetermined concentration are prepared, a predetermined amount of acetaldehyde or its IBB solution is sequentially added little by little over 2 hours or more to react, and at the same time, sulfuric acid with a higher concentration than the sulfuric acid water in the reaction solution is added during the reaction, The purpose is to maintain the sulfuric acid concentration of the sulfuric acid water in the reaction system.

Addition time of acetaldehyde or its IBB solution is 2
If the reaction time is shorter than that, the concentration of acetaldehyde in the reaction solution will increase, and the amount of polymerized product will increase.

Since the reaction of the present invention has a relatively high reaction rate, a long reaction time is not necessarily required. Preferably it is 3 to 10 hours.

The reaction pressure is not particularly limited, but it is preferably carried out at normal pressure or autogenous pressure at the reaction temperature of a closed reactor.

After the reaction is complete, the stirring is stopped and the reaction mixture is poured into the reactor.
Or move it to a stationary layer and leave it stationary. The lower layer is a sulfuric acid layer that dissolves most of the sulfonated substances such as IBB produced in the sulfonation reaction as a side reaction, but this layer can be recovered, adjusted to a predetermined concentration, and reused. The upper hydrocarbon layer contains most of the BBE, unreacted IBB, and by-product hydrocarbons. Separate this upper layer and remove the remaining sulfuric acid with NaOH, KOH, Ca(OH)2. Ha2Go3
Neutralize with an alkali or its aqueous solution and wash with water.

At this time, a solvent such as ether or n-hexane may be added for the purpose of preventing the formation of an emulsion due to sulfonated substances or the like.

IBB and BBE can be obtained by distilling the hydrocarbon layer after neutralization, preferably under reduced pressure. In the method of the present invention, no isomerization of unreacted product IBB occurs, so IBB obtained by distillation can be recycled and reused without special purification.

In addition, the BBE obtained in this way has an isobutyl group substituted at the p-position and is symmetrical, so
By catalytic cracking, high-purity PBS can be easily obtained in good yield.

For catalytic cracking of BBH, acid catalysts such as inorganic protic acids such as phosphoric acid, sulfuric acid, hydrochloric acid, and heteropolyacids, and organic protic acids such as p-toluenesulfonic acid are preferred, as well as silica, silica/alumina, and silica.・
Synthetic silica/alumina catalysts such as magnesia and synthetic zeolite, and clay-based silica/alumina produced from natural clay minerals such as kaolin, attapulgite, acid clay, and Fuller's top.
These include solid acids such as alumina catalysts, or supported solid acids in which the proton acid is supported on these solid acids. Aprotic acids represented by metal halides such as aluminum chloride, iron chloride, iron bromide, and zinc chloride are also used in some cases.

The decomposition temperature is 200-650℃ depending on the catalyst and reaction phase.
For example, for gas phase catalytic cracking using a protic acid catalyst, the temperature is 200 to 350°C, preferably 250 to 325°C, and for gas phase catalytic cracking using a solid acid catalyst, the temperature is 300°C. ~650°C, preferably 350~5
It is in the range of 00°C.

The decomposition pressure, catalytic decomposition time, etc. can be appropriately selected within conventionally known ranges.

After cooling and recovering the decomposition products, PBS is distilled off.
and IBB can be recovered with high purity.

[Effects of invention The BBE of this invention is a symmetrical diarylalkane.

Being a symmetrical diarylalkane, its decomposition products are mainly PBS and IBB. PBS for asymmetric
The yield of PBS and IBB is extremely low and is not practical.
It cannot be used as a raw material for economically producing at low cost.

In addition, from the decomposition products of BBE, PBS or IBB
can be easily separated by simple distillation. Therefore, inexpensive and highly pure PBS can be obtained from the decomposition of BBE.

From the PBS obtained in this way,
No. 2-51338, No. 52-97930 and No. 59
- IPA by the method described in Publication No. 10545 etc.
can be obtained. Note that α-(p-inbutylphenyl)propionaldehyde is obtained from hydroformation using hydrogen and carbon monoxide, but this aldehyde easily becomes IPA by oxidation.

[Example] The present invention will be explained in more detail below using Examples.

: Superintendent' Uni Experiment No. 9I IBB 402g (3 moles) and 95% by weight sulfuric acid 6
00 g (5.8% Jl/) was supplied to a 21 round bottom flask equipped with a stirrer, and the outside was cooled with ice to maintain the temperature below 10°C. 44 g (1 mol) of acetaldehyde and IB with stirring
A mixed solution of 67 g (0.5 moles) of B was gradually quenched over 4 hours.The reaction temperature was maintained at 10°C or lower.After the quenching was completed, the mixture was stirred for an additional 2 hours. After the reaction was completed, the reaction solution was transferred to a separating funnel and allowed to stand still. After removing the sulfuric acid in the lower layer, about 2% NaOH aqueous solution was added while shaking until the solution became neutral.

The lower aqueous layer was removed, the oil layer was placed in a distillation pot, and the product was purified by vacuum distillation to obtain 260 g of RBE exhibiting the physical properties described below. The yield of BBH was 88 mol% based on acetaldehyde.

The acetaldehyde concentration in the reaction solution during the addition of the acetaldehyde solution was 0.5% by weight or less, and the sulfuric acid concentration in the reaction solution at the end of the reaction was 93% by weight. Distillation temperature range 60-80
When the fraction at 0.degree. C. was analyzed by GLC and NMR, it was confirmed that it was exactly the same substance as IBB used as the raw material.

Physical properties of BBE Ura point 180-183℃ 73 mmHg (colorless liquid)
Viscosity 17.0cSt (640℃) Infrared absorption spectrum (liquid film method) 2960cm, 1540cm, 14
80cm-'1390cm, 1370cm, 1
210cm-”850cm, 800cm-
1 nuclear magnetic resonance spectrum (CC14 solvent, δppm
)6.95 (8H single line) 3.7~4.2 (IH quadruple line) 2.39 (4I4 double line) 1.58
(3H doublet) 0.87 (12H doublet) 1.6~2.2 (2H multiplet) Mass spectrometry spectrum (El, ?OeV) m/e
<Batan coefficient) Elemental analysis theoretical value C: 89.80) 1: 10.20 Analysis value C: 89.83 H: 10.06 Experiment No.
2-4 BBE was produced by reacting in the same manner as in Experiment No. 1, except that the molar ratio of IBB and acetaldehyde was changed. The results are shown in Table 1.

Experiment Nos. 5 to 8 BBE was produced in the same manner as in Experiment No. 1 except that the sulfuric acid concentration was changed. The results are shown in Table 2.

Experiment NNO3 9IBB402 (3 mol) and 95% concentration by weight of sulfuric acid 6
00 g (5.8 mol) was supplied to a 21 round bottom flask equipped with a stirrer, and the outside was cooled with ice to maintain the temperature below 10°C. 44 g (1 mol) of acetaldehyde and 67 g of IBB under stirring
(0.5 mol) was gradually added dropwise over 4 hours. At the same time, 100 g (1 mol) of 98% concentration sulfuric acid
was gradually added dropwise over 4 hours. The reaction temperature was maintained at 10° C. or below, and stirring was continued for an additional 2 hours after each dropwise addition.

After the reaction was completed, the reaction solution was transferred to a separating funnel and allowed to stand still.

After removing the lower layer of sulfuric acid, add about 2% laO while shaking.
An aqueous H solution was added until the mixture became neutral. The lower aqueous layer was extracted and the oil layer was distilled under reduced pressure to purify the product.The yield of BBE was 89% based on acetaldehyde. The acetaldehyde concentration in the reaction solution during addition of the acetaldehyde solution was 0.5% by weight or less, and the sulfuric acid concentration after the reaction was completed was 95% by weight.

Experiment No. 10 402 g (3 moles) of IBB and 40 sulfuric acid with a concentration of 85% by weight
0 g (3.5 mol) was supplied to a two-pronged round bottom flask equipped with a stirrer, and the outside was cooled with ice to maintain the temperature below 10°C. 44 g (1 mol) of acetaldehyde and 67 g of IBB under stirring
(0.5 mol) was gradually added dropwise over 4 hours. At the same time, 150 g of 3.0% oleum was gradually added dropwise over 4 hours. The reaction temperature was kept below 10°C. After the extinction was completed, stirring was continued for an additional 2 hours.

After the reaction was completed, BBE was obtained in the same manner as in Experiment No. 1. The yield of BBE was 87% based on acetaldehyde. The sulfuric acid concentration after the reaction was 88 parts.

ElΩL1 1.1-His(p-inbutylphenyl)ethane (B
Experiment No. 11 Production of p-inbutylstyrene (PBS) and isobutylbenzene (I' B B ) by decomposition of BE) Experiment No. 11 , BBE obtained in 1
148 g (0.5 mol) and 50 g (0.02 mol) of silicotungstic acid as a catalyst were charged and heated to 280° C. for decomposition. When the temperature exceeded 200°C, hydrogen was flowed from the gas introduction device at a rate of 1 liter/minute, and the mixture was led together with the decomposition products to a distillation cooling device, where they were cooled and the decomposition products were collected.

The decomposition operation was carried out until the distillation of decomposition products was no longer observed.

As a result of GLC analysis of the distillate, p-isobutylethylbenzene (PBE) in which the double bond of PBS was hydrogenated was found.
7%, IBB47%, PB339% and BBE of raw material
It was 6%.

When each component was separated and confirmed by MASS, IR, and NMR, it was confirmed that both IBB and BBE were exactly the same as those used as the raw material, and no side reactions such as isomerization of isobutyl groups had occurred.

The butyl group in PBE and PBS was also an isobutyl group, and the substitution position was at the P-position.

Experiment Nos. 12 to 14 According to Experiment No. 11, catalytic cracking reactions were carried out by changing the catalyst. The results are shown in Table 3.

Table 3 Experiment No. 15 A synthetic silica/alumina-based FCC-HA catalyst (manufactured by Catalysts & Chemicals Co., Ltd.) was adjusted to have a particle size of 0.5III to IIIm, and 51 samples were packed into a stainless steel tube with an inner diameter of 10+am and a length of 601III. The BBE obtained in Experiment No. 1 is 5+m
l/hr, hydrogen 200ml/win and water 30ml
/hr was decomposed by passing it through a catalyst layer through a preheating tube at a temperature of 450° C. The decomposed product was ice-cooled, and after separating gas and liquid, the decomposition rate and selectivity of the organic layer were confirmed by GLC analysis.

The composition of the decomposition product is IBB 30wt%, PBE 6wt%, P
BS26wt%, BBE37wt%, unknown 1wt%
It was confirmed that the decomposition was performed with high selectivity. Further, structural analysis of each component was conducted in the same manner as in Experiment No. 11, and it was confirmed that the isobutyl group was not isomerized and that the p-position selectivity of the decomposition product was high.

Experiment No. 16-25 Regarding various solid acids instead of FCC-HA catalyst...
In the same manner as Experiment No. 15, the BBE obtained in Experiment No. 1 was catalytically cracked. The results are shown in Table 4.

Table 4 [Synthesis and decomposition of asymmetric diarylalkane] Reference experiment N
o-1 Synthesis of asymmetric diarylalkane 670 g (5 mol) of IBB and 100 g of 95% sulfuric acid were placed in a flask equipped with a stirrer and cooled on ice to a temperature of 10°C. IB8134g (1
A mixture of 1 mole) and 104 g (1 mole) of styrene was destroyed in 4 hours. After the extinction was completed, the reaction was further stirred for 1 hour to complete the reaction. After separating and removing the sulfuric acid layer, wash with neutralized water for 3 s.
Distillation was performed under reduced pressure of moH to obtain 120 g of 1-(p-inbutylphenyl)-1-phenylethane (PBPE), which is a fraction with a distillation temperature of 145 to 160°C.

Reference Experiment No. 2 In the same manner as Reference Experiment No. 1, P was used instead of styrene.
- Using methylstyrene ttag (1 mol), 1-(p-inbutylphenyl)-1-(p-)lyl)ethane (PBTE), which is a fraction with a distillation temperature of 150 to 165°C,
Obtained 0g.

Comparative experiment N001 PBPE and PBT synthesized in reference experiments N081 and 2
E was subjected to catalytic cracking in the same manner as in Experiment No. 15. In all cases, the weight decomposition rate was 55 to 60%.

However, as shown in the chemical formula below, the decomposition at A and B
The ratio of the decomposition in A to the decomposition in A/B is 9 to 8, and the decomposition in A is higher than that in PBS of the target product.

That is, the decomposition was overwhelming in the direction of returning to the raw material styrene or p-methylstyrene.

R: H or CH3 In the case of PBPH, the composition of the decomposition product was as follows.

Benzene 2 wt% Ethylbenzene 2 wt% Styrene 17 wt% IBB 20 wt% PBE 1 wt%PB
S 2wt%PBPE
The results of 55 wt% or more indicate that the efficiency of decomposition into PBS is poor and that in order to reuse the raw material IBB, it is necessary to go through a complicated purification process.

Experimental work on the production of α-(p-inbutylphenyl)propionaldehyde (IPN) from p-inbutylstyrene (PBS), 26 Experiment No. 30 g of PBS obtained in 15, rhodium hydride carbonyl tristyrene 0.3g of phenylphosphine,
Place in an autoclave with an internal volume of 500 m1 and equipped with a stirrer.
Heated to 60°C, pressurized to 50 kg/crn2 with an equimolar mixed gas of hydrogen and carbon monoxide, and allowed to react until no absorption of the mixed gas was observed. After the reaction was completed, it was cooled to room temperature. The remaining mixed gas was discharged, and the contents were transferred to a vacuum simple distillation apparatus to obtain 34 g of a N fraction with a distillation temperature range of 60 to b.

Composition of crude IPN fraction PBE O, 3 wt% PBS O, 1 wt% IPN 89.9 wt% NPN
This crude IPN fraction containing 9.7 wt% was again subjected to vacuum distillation to obtain a boiling point range of 70-b. The purity of this IPN was 99.6%.

In addition, the structure was confirmed by comparing it with a standard product through IR analysis and the like.

Claims (1)

[Claims] (1) 1,1-bis(p-inbutylphenyl)ethane, which is expressed by the formula below, ▲There are mathematical formulas, chemical formulas, tables, etc.▼