JPH0764764B2 - 1,2-di (4-isobutylphenyl) ethylene - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a novel compound, 1,2-di (4-isobutylphenyl) ethylene. This novel compound is used as an intermediate for inexpensively and economically producing α- (4-isobutylphenyl) propionic acid which is useful as a drug having antipyretic, analgesic and antiphlogistic effects.

[Prior Art and Problems Thereof] α- (4-isobutylphenyl) propionic acid is an excellent drug because it has excellent antipyretic, analgesic and anti-inflammatory effects, and further has few side effects. For this reason, it has been conventionally proposed to synthesize by various methods. As one of them, 4
-A method of producing from isobutylstyrene by a hydroformylation reaction or a Reppe reaction is proposed. Specific examples of these include, for example, British Patent No.
1,565,235 and JP-A-52-97930 are proposed.

This method using 4-isobutylstyrene is an economically excellent method because 4-isobutylstyrene is a simple and stable substance and expensive reagents such as hydroformylation reaction and Reppe reaction are not used.

However, conventional methods for producing 4-isobutylstyrene all use expensive and unstable reagents such as Grineer's reagent or expensive starting materials such as 4-isobutylacetophenone, as described in the above-mentioned documents. Are using. Therefore, an inexpensive method for producing 4-isobutylstyrene has been desired.

In addition, as a method for producing alkyl styrene,
A method for producing a 1,1-diarylethane by catalytic decomposition has been conventionally proposed, for example, Industrial and Engineering Chemistry, Vol. 46, No, 4, 6
52 (1954) Journal of Chemical and Engineering Data.Vol.9, No.
1,104 (1964) I & EC Product Research and Development, Vol.3, No.
In the literature such as 1,16 (1964), 1,1 for the purpose of producing methylstyrene, dimethylstyrene, ethylstyrene, isopropylstyrene, and t-butylstyrene as alkylstyrene.
-Methods for decomposing 1,1-diarylethanes such as ditolylethane, 1,1-dixylylethane are described. That is, efforts for industrialization of production of alkylstyrene by decomposition have been continued.

However, in the method by this decomposition, it is inevitable that theoretically equimolar isobutylbenzene is by-produced at the same time as the production of the target 4-isobutylstyrene. Therefore, it was necessary to recover the by-produced isobutylbenzene and convert it into a decomposition raw material again.

On the other hand, when stilbene and ethylene are disproportionated, styrene can be obtained without by-products of alkylben, which is a preferable method.

The novel compound of the present invention that has not been described in the literature makes it possible for the first time to efficiently produce 4-isobutylstyrene.

[Means for Solving the Problem] That is, the present invention relates to 1,2-di (4-isobutylphenyl) ethylene, which is a novel compound represented by the following formula and not described in the literature.

The above compounds of the present invention also include trans and cis forms.

The 1,2-di (4-isobutylphenyl) ethylene of the present invention can be produced, for example, by the following method.

That is, isobutylbenzene is converted to di (4-isobutylphenyl) iodonium salt in concentrated sulfuric acid with potassium periodate and reacted with ethylene in the presence of a palladium catalyst to give 1,2-di (4- Isobutylphenyl) ethylene.

The halogen salt of the above-mentioned di (4-isobutylphenyl) iodonium salt is disclosed in JP-A-53-101331 and JP-B-57-53767.
No. 1, UK Patent No. 1,114,950, etc., and the method described in J. Amer, Chem. Soc., Vol. 81, 342 (1959). That is, isobutylbenzene and potassium periodate are mixed with stirring in acetic anhydride, then a mixture of acetic anhydride and concentrated sulfuric acid is added dropwise, and then a saturated ammonium chloride aqueous solution is added to precipitate a precipitate, which is then filtered and re-used. Crystallization gives the hydrochloride salt of the di (4-isobutylphenyl) iodonium salt. The formula of the reaction is as follows.

(Wherein R represents an aryl group) The counter ion such as Cl ⁻ in the above formula can be mutually ion-exchanged with any anion such as an anion composed of a metal halide, but a more preferable counter ion. Ions are halogen ions such as chlorine ions and bromine ions.

The other substance reacted with the di (4-isobutylphenyl) iodonium salt is ethylene.

This reaction can be achieved by using a transition metal such as palladium as a catalyst in a solvent and introducing ethylene gas in the presence of a basic substance such as potassium oxide to cause a reaction. The reaction is described below by equation.

^{2 [R-I + -R]} X - + CH 2 = CH 2 → R-CH = CH-R + 2RI + 2HX ( where R represents an aryl group) The amount of the base used, the reaction is di- (4-isobutylphenyl) iodonium The amount may be such that the acid generated from the counterion of the salt is neutralized. Therefore, when the amount used is less than the stoichiometric amount, the yield of the desired 1,2-di (4-isobutylphenyl) ethylene only decreases. Therefore, the amount can be appropriately selected. As the base that can be used in the above reaction, any base can be used as long as it is soluble in the solvent used. Specifically, tertiary alkylamines such as triethylamine, tripropylamine, tributylamine, dimethylaniline and diethylaniline, alkali metal salts of lower fatty acids such as sodium acetate, potassium acetate and sodium formate, alkalis such as sodium and potassium. Examples include carbon salts or bicarbonates of metals.

The catalyst used for the reaction with ethylene is VIII in the periodic table.
Group metal transition metal catalysts, such as palladium,
Rhodium, ruthenium, platinum, iridium, osmium, etc. are preferable, and a palladium catalyst is particularly preferable. These transition metal catalysts can be used as catalysts in various forms. That is, it can be used regardless of its oxidation number or complex. Taking palladium as an example, palladium supported on alumina or activated carbon, palladium halides such as palladium chloride, palladium oxide, two types of palladium such as palladium salts of lower fatty acids such as palladium acetate, and other bis (dibenzylideneacetone)
Complexes such as palladium can also be used. For rhodium, a carbonyl complex can also be used.

As the solvent to be used, any solvent can be used as long as it dissolves the di (4-isobutylphenyl) iodonium salt in any amount and does not participate in the reaction. For example, methanol,
In addition to lower alcohols such as ethanol, ketones such as acetone and methyl ethyl ketone, ethers such as dimethoxy etal and dioxane, various polar solvents such as dimethyl formamide, dimethyl sulfoxide, acetonitrile and tetrahydrofuran can be appropriately selected. When the base used can also serve as a solvent, it is not necessary to use a solvent.

A reaction time of 0.5 to 10 hours is usually sufficient. After completion of the reaction, the product is thoroughly washed with water and the reaction liquid is cooled, so that the desired product, 1,2-di (4-isobutylphenyl) ethylene, precipitates as crystals. The precipitated crystals are filtered, recrystallized from methanol and purified to obtain 1,2-di (4-isobutylphenyl) ethylene.

[Effects of the Invention] 1,2-di (4-
If isobutylphenyl) ethylene is used, α- (4
-Isobutylphenyl) propionic acid can be produced.

The present invention will be described in more detail below with reference to examples.

"Example 1" (a) Production of di (4-isobutylphenyl) iodonium salt A mixture of 107 g of potassium periodate, 134 g of isobutylbenzene and 400 ml of acetic anhydride was placed in a three-necked flask equipped with a cooling tube, and the temperature was 5 to 10 ° C. Stir at the temperature of. To this mixture, a mixture of 204 g of acetic anhydride and 196 g of concentrated acid was gradually added dropwise over 2 hours. The reaction temperature was kept at 5 to 10 ° C. The reaction solution was returned to room temperature and then stirred for 16 hours.

The reaction solution was poured into 600 ml of ice water, and then 100 g of potassium bromide was added to a saturated aqueous solution to precipitate crystals of diisobutylphenyliodonium salt. This result was separated from water by vacuum filtration, further washed with water, and then filtered under reduced pressure again. This was dried under vacuum at 50 ° C. to obtain 167 g of di (4-isobutylphenyl) iodonium bromide (melting point: 180-182 ° C.).

(B) Reaction of di (4-isobutylphenyl) iodonium salt with ethylene Di (4-isobutylphenyl) iodonium bromide 9
4.6g, tri-n-butylamine 37g, valadium acetate 42g
The mixture of 500 ml of methanol and methanol was placed in a flask equipped with a reflux condenser and a stirrer, and 100 ml / mi of ethylene gas was added.
The mixture was stirred at 50 ° C. for 16 hours while blowing at a flow rate of n.

After completion of the reaction, methanol was distilled off from the reaction solution under reduced pressure. After adding water 1 to this solution, it was extracted with toluene. The toluene layer was dried over magnesium sulfate, filtered, and toluene was distilled off under reduced pressure. By recrystallizing from this residual liquid using methanol as a recrystallization solvent, a melting point of 10
25 g of crystals at 6 ° C to 108 ° C were obtained.

This crystal had a purity of 98.0% and was confirmed to be paradiisobutylstilbene "1,2-di (4-isobutylphenyl) ethylene" by IR analysis and NMR analysis.

Elemental analysis (as _{C 22 H 28) C: 90.45} % (calcd: 90.35%) H: 9.55% (calcd: 9.65%) IR (KBr method, cm ^-1) 810,850,970,1370,1390,1470, 1610, 1910, 297
0, 3030.

NMR ( ¹ H-NMR, δ) 0.9 Doublet (12H) 1.8 to 2.0 Multiplet (2H) 2.5 Doublet (4H) 7.0 Singlet (2H) 7.0 to 7.5 Multiplet (8H) 1 ”Production of 4-isobutylstyrene An aqueous solution of 26.3 g of rhenium heptaoxide was impregnated with 100 g of γ-alumina for 24 hours, dried at 120 ° C., and then baked. Firing was carried out in air at 600 ° C. for 5 hours. Α, which is the filling material in the reaction tube
200 ml of catalyst were loaded with alumina. Activation is
According to the method of heating in a nitrogen stream prior to the reaction. It was treated at a pressure of 1 kg / cm ² and 590 ° C. for 2 hours.

After cooling to room temperature, a mixture of 1,2-di (4-isobutylphenyl) ethylene and benzene at a ratio of 1: 3 and ethylene were put in a reaction tube. The molar ratio of 1,2-di (4-isobutylphenyl) ethylene is 1:12 and SV is 6
And After reacting at 30 ° C. for 3 hours, the reaction solution was analyzed by gas chromatography to find 1,2-di (4-isobutylphenyl) ethylene and 4-isobutylstyrene with a conversion of 60%.

"Reference Experimental Example 2" α- (4
-Isobutylphenyl) propionaldehyde production 30 g of 4-isobutylstyrene obtained in Reference Example 1,
0.3 g of rhodium hydridocarbonyltristriphenylphosphine was placed in a pressure vessel equipped with a stirrer with a capacity of 500 ml, kept at a temperature of 60 ° C., and pressurized to 70 kg / cm ² with an equimolar mixed gas of hydrogen and carbon monoxide. The reaction was carried out for 12 hours. After completion of the reaction, the mixture was cooled, residual gas was released, and the reaction product was finely distilled to
26 g of a fraction having a distillation temperature of 70 to 76 ° C. at 3 mm Hg was obtained. This fraction had a purity of 98.7% and was compared with the standard by IR analysis and NMR analysis to obtain α- (4-isobutylphenyl).
It was confirmed to be propionaldehyde.

By oxidizing this fraction with potassium permanganate, which is a conventionally known oxidation method, ibuprofin, ie, α- (4-isobutylphenyl) propionic acid, which is a drug, was easily obtained. This was also confirmed and identified by the standard.

Claims (1)

[Claims] 1. 1,2-Di (4-isobutylphenyl) ethylene represented by the following formula (I).