JPH06263673A - Production of 3-allylphenols - Google Patents

Abstract

PURPOSE:To obtain the subject compound useful as an intermediate for pharmaceuticals and agrichemicals on an industrial scale in high yield at a low cost by reacting a specific 2,5-cyclohexadien-1-one derivative with an allylsilane. CONSTITUTION:The objective compound of formula II is produced by reacting a 4-t-butyldioxy-2,5-cyclohexadien-l-one of formula I [R is (substituted) alkyl or (substituted) phenyl; R<1>, R<2> and R<3> are H or 1-6C alkyl] with an allylsilane in the presence of a titanium halide compound. The starting compound of formula I is produced preferably by reacting a compound of formula III with t-butyl hydroperoxide in the presence of a ruthenium catalyst.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing 3-allylphenols.

[0002]

2. Description of the Related Art General formula 1 (In the formula, R represents an optionally substituted alkyl group or a phenyl group, and R ¹ , R ² and R ³ are the same or different and represent a hydrogen atom or an alkyl group having 1 to 6 carbon atoms.) 1 The 3-allylphenols shown are known and the compounds are known as useful intermediates for medicines and agricultural chemicals. However, a method for easily producing such 3-allylphenols in a high yield has not been known, and development of an industrially advantageous production method has been desired.

[0003]

DISCLOSURE OF THE INVENTION Problems to be Solved by the Invention
The present inventors have completed the present invention as a result of studying a method capable of industrially and easily producing the 3-allylphenols represented by the general formula 1 in good yield.

[0004]

That is, the present invention has the general formula (In the formula, R, R ¹ , R ³ and R ⁴ have the same meanings as described above), 4-t-butyldioxy-2,5-cyclohexadien-1-one is represented by a titanium halide compound The present invention provides a method for producing 3-allylphenols represented by the above general formula (1), which comprises reacting with allylsilanes in the presence.

In the present invention, 4 used as a raw material
Examples of 4-t-butyldioxy-2,5-cyclohexadiene-1-one include 4-t-butyldioxy-4-methyl-2,5-cyclohexadiene-1-one and 4-t
-Butyldioxy-4-ethyl-2,5-cyclohexadiene-1-one, 4-tert-butyldioxy-4-isopropyl-2,5-cyclohexadiene-1-one, 4
-T-Butyldioxy-4-hexyl 2,5-cyclohexadiene-1-one, 4-t-butyldioxy-4
-Phenyl-2,5-cyclohexadiene-1-one,
4-t-butyldioxy-4,6-di-t-butyl-2,5-cyclohexadiene-1-one, 4-t-butyldioxy-2,4,6-trimethyl-2,5-cyclohexadiene-1-one, 4-t- Butyldioxy-2,6-di-t-butyl-4-methyl-2,5-cyclohexadiene-1-one is exemplified.

The allylsilanes used as the other reaction raw material are typically represented by the general formula 4 CH ₂ ═CHCH ₂ Si (X) ₃ (wherein X is a halogen atom, a lower alkyl group or a lower alkoxyl group). Group or a phenyl group) is used, and specific examples thereof include allyltrichlorosilane, allyltriethoxysilane, allyltriisopropylsilane, allyltrimethylsilane, and allyltriphenylsilane.

Examples of the titanium halide compound used in this reaction include titanium tetrachloride and trichloromethoxy titanium. These titanium halide compounds may be used as they are, or may be used as an organic solvent solution such as a commercially available dichloromethane solution or toluene solution.

In the reaction of 4-t-butyldioxy-2,5-cyclohexadiene-1-ones with allylsilanes, the amount of allylsilane used is 4-t-butyldioxy-2,5-cyclohexadiene-1. The amount is usually 1 to 5 mole times, preferably 1 to 2 mole times with respect to the ionic compounds. The amount of titanium halide compound used is
The amount is usually 0.5 to 5 mol times, preferably 1 to 2 mol times, relative to 4-t-butyldioxy-2,5-cyclohexadiene-1-ones.

The reaction is usually carried out in a solvent, and as the solvent, halogenated hydrocarbons such as dichloromethane, chloroform and ethylene dichloride, aromatic hydrocarbons such as benzene, toluene, xylene, monochlorobenzene and dichlorobenzene, tetrahydrofuran and the like. There are no particular restrictions on the amount used, but usually 4-t-butyldioxy-2,5-cyclohexadiene-1 is used.
It is 1 to 30 times the weight of the on-types.

The reaction temperature is usually in the range of -100 ° C to the reflux temperature of the reaction system. The reaction time is not particularly limited, and the reaction mixture may be analyzed by LC or the like, and the time point at which the production rate of the target 3-allylphenols does not increase may be regarded as the reaction end point. After completion of the reaction, the reaction mixture is washed by a conventional method,
The desired 3-allylphenols can be obtained by performing filtration, extraction, drying, concentration and the like, and further purifying by silica gel column chromatography and the like if necessary.

The 3-allylphenols thus produced include 3-allyl-4-methylphenol, 3-allyl-4-ethylphenol, 3-allyl-4-isopropylphenol, 3-allyl-4-hexylphenol, 3-allyl-4-phenylphenol, 3-allyl-4,6-di-tert-butylphenol, 3-allyl-2,4,6-trimethylphenol, 3-allyl-2,
6-t-butyl-4-methylphenol and the like are exemplified.

It should be noted that 4-t which is a raw material in this reaction
-Butyldioxy-2,5-cyclohexadiene-1-ones are known and can be produced by any method. By producing a phenol represented by the formula (wherein R, R ¹ , R ³ and R ⁴ have the same meanings as described above) with t-butyl hydroperoxide in the presence of a ruthenium catalyst, 3 which is the target compound of the present invention
-Allylphenols can be produced more advantageously industrially.

That is, 4-t-butyldioxy-2,
As a method for producing 5-cyclohexadiene-1-ones, a method of reacting phenols with t-butyl hydroperoxide using pyridinium chromate or chromium oxide as a catalyst is known, but these methods are highly toxic catalysts. However, the yield of the product is very low, about 30%. However, the method using the ruthenium catalyst described above does not have such environmental problems, and yields better than phenols. The target compound can be obtained at a rate.

In the above-mentioned method for producing 4-t-butyldioxy-2,5-cyclohexadiene-1-one, examples of phenols represented by the above general formula 3 used as a raw material include p-cresol, p-ethylphenol, p-isopropylphenol, p-hexylphenol, p-phenylphenol, 4,6-di-t
-Butylphenol, 2,4,6-trimethylphenol, 2,6-di-t-butyl-4-methylphenol and the like.

Such phenols and t-butyl hydrope
Ru as a catalyst in the reaction with ruoxide₃(C
O)₁₂, RuCl₂(PPh₃)₃, RuCl₂(bpy)₂,
RuCl ₃・ NH₂O, Ru (OAc)₃, Ru (ac
ac)₃Ruthenium catalysts such as are used. Such a le
The thenium catalyst may be used as a mixture of these,
Heteropoly acid, silica gel, carbon powder
It may be used by being supported on powder or a polymer substance.

In the reaction of the above-mentioned phenols with t-butyl hydroperoxide, the amount of t-butyl hydroperoxide used is usually in the range of 1 to 10 mol times, preferably 2 to 6 mol times, relative to the phenols. . The amount of the ruthenium catalyst used is usually 0.01 to 50 mol%, preferably 0.1 to 10 mol% with respect to the phenols.
Is the range.

The reaction is usually carried out in a solvent, and as the solvent, halogenated hydrocarbons such as dichloromethane, chloroform and ethylene dichloride, esters such as ethyl acetate, nitriles such as acetonitrile, benzene, toluene, xylene and monochlorobenzene. , Aromatic hydrocarbons such as dichlorobenzene, and ketones such as acetone and methyl ethyl ketone are used, and the amount thereof is not particularly limited, but is usually 1 to 20 times by weight that of phenols.

The reaction temperature is usually in the range of 0 ° C. to the reflux temperature of the reaction system, preferably 10 to 50 ° C. The reaction time is not particularly limited, and the reaction mixture is analyzed by LC, etc., and the time point when the production rate of the desired 4-t-butyldioxy-2,5-cyclohexadiene-1-ones does not increase is regarded as the reaction end point do it. After completion of the reaction, the reaction mixture is purified by, for example, Florisil column chromatography and concentrated to obtain the desired 4-t-butyldioxy-2,5-cyclohexadien-1-ones.

[0019]

According to the method of the present invention, 3-allylphenols can be easily produced in good yield.
As a method for producing 4-t-butyldioxy-2,5-cyclohexadiene-1-ones, which are the raw materials, when the methods are combined by reacting phenols with t-butylhydroperoxide in the presence of a ruthenium catalyst In addition, 3-allylphenols can be produced industrially more advantageously.

[0020]

EXAMPLES The present invention will be described below with reference to examples, but it goes without saying that the present invention is not limited thereto.

Example 1 0.13 ml of titanium tetrachloride and anhydrous dichloromethane 1
A mixture of 0.16 ml of allyltrimethylsilane and 0.5 ml of anhydrous dichloromethane was added dropwise to the mixture of ml at −78 ° C. under an argon atmosphere. After stirring for 3 minutes at the same temperature, 4-t-butyldioxy-4-methyl-2,
A solution prepared by dissolving 0.191 g of 5-cyclohexadiene-1-one in 0.5 ml of dichloromethane was added dropwise over 5 minutes, and the mixture was stirred at the same temperature for 30 minutes and further at -5 ° C for 3 hours. 5m saturated aqueous sodium hydrogen carbonate solution in the reaction mixture
1 and 5 ml of dichloromethane were added, the mixture was stirred at room temperature for 30 minutes, and the insoluble material was filtered off. The filtrate was separated, the organic layer was dried over sodium sulfate and concentrated to give a residue, which was purified by silica gel column chromatography to obtain 0.081 g of 3-allyl-4-methylphenol. Yield 56%

The 4-t-butyldioxy-4-methyl-2,5-cyclohexadien-1-one used here was prepared by the following method. p-cresol 0.652
2. g, RuCl ₂ (PPh ₃ ) ₃ 0.173 g and anhydrous benzene 6 ml in a mixture at room temperature under argon atmosphere.
7.3 ml of a benzene solution of 3 molar t-butyl hydroperoxide was added dropwise over 2 hours. Then, the mixture was stirred at the same temperature for further 3 hours and then purified by Florisil column chromatography to give 4-t-butyldioxy-4-methyl-2,5-cyclohexadiene-1-one 1.0.
1 g (yield 85%) was obtained.

Claims (2)

[Claims] 1. A general formula (In the formula, R represents an optionally substituted alkyl group or a phenyl group, R ¹ , R ² and R ³ are the same or different and represent a hydrogen atom or an alkyl group having 1 to 6 carbon atoms). The compound represented by the general formula 1 is characterized in that 4-t-butyldioxy-2,5-cyclohexadiene-1-ones shown are reacted with allylsilanes in the presence of a titanium halide compound. (In the formula, R, R ¹ , R ² and R ³ have the same meanings as described above.) A method for producing 3-allylphenols. 2. A general formula (Wherein R, R ¹ , R ² and R ³ have the same meanings as described above), the phenols are reacted with t-butyl hydroperoxide in the presence of a ruthenium catalyst,
4-t-butyldioxy-2 represented by the general formula:
The method for producing 3-allylphenols according to claim 1, wherein 5-cyclohexadiene-1-ones are produced.