JPS6120529B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the general formula The present invention relates to a method for producing cyclopentenones represented by the formula (wherein R is an alkyl group). The compound represented by the general formula () includes diasmone analogs known as fragrances, and is also important as a useful intermediate for physiologically active cyclopentanoids, such as prostaglandins. Various methods are known as conventional methods for producing the compound represented by the above general formula (), but a typical method is a method using a ring-closing reaction of 1,4-diketone (RAEllison,
Synthesis, 397 (1973)). however,
In either method, it takes time and effort to derive the raw materials used in these methods from available industrial raw materials, and it is economically unfavorable to adopt them as industrial production methods. As a result of intensive research into ways to overcome these drawbacks and easily obtain the target compound, the inventors of the present invention have developed a method for easily obtaining the target compound by using β,γ-enone, which is easily obtained from α-β-unsaturated carbonyl compounds, as a starting material. The present invention was completed by discovering a method for ring-closing. General formula used as raw material in the method of the present invention The β,γ-enone represented by the formula (wherein R is an alkyl group) can be easily formed by reacting an α-β-unsaturated carbonyl compound with a halide in the presence of a base (see, for example, Matsui et al.
, Agr. Biol. Chem., 28, 95 (1964)). The first step of the present invention is β, γ of the general formula ()
-It is an essential condition that the enone and halogen are reacted. The amount of halogen used is β,
It is used in an approximately equimolar amount to γ-enone. When carrying out the reaction, it is preferable to use a solvent, for example methylene chloride, carbon tetrachloride, chloroform,
Aprotic solvents that do not react with halogens such as halogenated hydrocarbons, n-hexane, and toluene can be used. The reaction in the first step is −100 to 10
Preferably, it is carried out at °C. At temperatures above 10℃, the general formula
Reactions tend to occur on the carbon adjacent to the carbonyl group in (), making it difficult to form the desired product in the next step. The compound formed in this first step is unstable, and although sufficient confirmation cannot be obtained, it is presumed to have the following structure. (In the formula, R is an alkyl group and X is a halogen.) The second step of the present invention requires that the reaction product after removing the solvent from the reaction mixture of the first step be treated with a base. Bases include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, sodium methoxide, and potassium.
Alkali metal alkoxides such as t-butoxide, alkali metal amides such as sodium amide, alkali metals, and organic amines such as triethylamine and pyridine can be suitably used.
The amount of the base to be used is preferably 2 to 4 molar equivalents per 1 mole of the compound of the general formula (). When carrying out the second step, it is preferable to use a solvent, and for example, common organic solvents that do not directly participate in the reaction, such as water, alcohols, cyclic and acyclic ethers, hydrocarbons, and aprotic solvents, can be used. The reaction temperature in the second step is generally 0
~180°C, preferably room temperature to 50°C. Hereinafter, the present invention will be explained in more detail with reference to Examples. Example 1 3-isopropenyl-2-octanone 685mg
(4.07 mmol) in methylene chloride (10 ml) under cooling with dry ice-acetone.
20 mg (4.05 mmol) of methylene chloride (5 ml) solution
It was dripped in minutes. After further stirring for 20 minutes, the mixture was returned to room temperature and the solvent was distilled off under reduced pressure to obtain an oily substance.
This product was immediately mixed with 10 ml of 2N-NaOH aqueous solution and stirred at 55°C for 16 hours. Thereafter, the reaction mixture was extracted with ether, and the ether layer was washed with saturated brine, dried over Na ₂ SO ₄ , the solvent was distilled off, and 2-n-pentyl-3-methyl-2-cyclopentenone was extracted. (= dihydrdiasmone) 413mg
(yield 61%). Physical properties of the product: Boiling point: 108-114℃/11mmHg NMR (CCI ₄ ) δ: 0.89, 1.26 (more than (-CH ₂ )-
₃ CH ₃ ), 2.04 (3H, s)

【formula】 Around 2.00, 2.35 (

[Formula]) IR (liquid film): 1700, 1645cm ^-1 . MS (70eV) m/e: 166 (12.3%) (M ⁺ ), 151
(51.4%), 137 (23.8%), 123 (23.3%), 110
(100.0%), 1.9 (25.6%), 95 (15.0%). Example 2 3-isopropenyl-2-octanone 193 mg
(1.15 mmol) in methylene chloride (8.0 ml),
Bromine 193 mg (1.21 mmol) under cooling with ice-salt cryogen
A solution of methylene chloride (2.0 ml) was added dropwise. The solvent was distilled off at room temperature to obtain an oil, to which 3 ml of methanol and 2.0 ml of 4N-NaOH aqueous solution were added.
The mixture was heated to reflux at ℃ for 17 hours. After that, it was extracted with ether, and the ether layer was washed with saturated brine, dried over Na ₂ SO ₄ , the solvent was distilled off, and 2-n-pentyl-3
-Methyl-2-cyclopentenone (=dihydrdiasmone) 92 mg (yield 48%) was obtained. Example 3 3-isopropenyl-2-octanone 341 mg
(2.0 mmol) in methylene chloride (5.0 ml), a solution of 336 mg (2.1 mmol) of bromine in methylene chloride (3.0 ml) was added dropwise over about 15 minutes while cooling with an ice-salt cryogen.
Thereafter, 1.0 g of sodium bicarbonate powder was added, and stirring was continued while the mixture was returned to room temperature. After removing the sodium bicarbonate by filtration, the solvent was removed from the filtrate under reduced pressure at room temperature to obtain an oil. To this was added 5.0 ml of dioxane and 2.0 ml of 4N aqueous sodium hydroxide solution, and the mixture was stirred at room temperature for 48 hours. Next, extraction was performed with ether, and the ether layer was washed with saturated brine, dried over Na ₂ SO ₄ , and the solvent was distilled off to give 2-n-pentyl-3-methyl-2-cyclopentenone (= dihydrodid Yasmon) 138 mg (yield 41%) was obtained. Examples 4-8 By the same method as in Example 3, the compound of general formula () was obtained from the compound of general formula () in the yield shown in the table. The structure was confirmed by MS, IR and NMR spectra.

【table】

Claims (1)

[Claims] 1. General formula A general formula characterized by reacting a β,γ-enone represented by with a halogen, and then treating the reaction product with a base. A method for producing cyclopentenones represented by the following: [wherein R is an alkyl group] ]. 2 The reaction between β,γ-enone and halogen is −100
carried out at ~10 °C and treatment of the reaction product with base at 0
A method according to claim 1, comprising carrying out at a temperature of -180<0>C.