JPS5938392A - Manufacture of 2-propargyl-3-methyl-4-hydroxy-2- cyclopentenone - Google Patents

Abstract

PURPOSE:To manufacture efficiently 2-propargyl-3-methyl-4-hydroxy-2-cyclopentenone, by using 2-(3-butynyl)-5-methylfuran as a starting material and by applying a bromine method or an electrolytic oxidation method. CONSTITUTION:2-(3-Butynyl)-5-methylfuran is dissolved in a lower alcohol, and bromine or a soln. of bromine in a lower alcohol is added in the presence of NaOH or the like to prepare 2,5-dialkoxy-2-(3-butynyl)-5-methyldihydrofuran. The starting material may be electrolytically oxidized in a lower alcohol solvent using an electrode of Pt or the like. After adding an acid catalyst such as sulfuric acid or hydrochloric acid, the intermediate product is hydrolyzed at -10-80 deg.C. The resulting cis-3-nonene-2,6-dione-8-yne is reacted at -20-50 deg.C in the presence of a basic catalyst such as Na or Ca to manufacture efficiently 2-propargyl-3-methyl-4-hydroxy-2-cyclopentenone.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a l1jfft method for 2-propargyl-8-methyl-4-hydroquine-2-cyclobentenone (hereinafter abbreviated as propargylcyclobentenone) represented by formula (1).

Propargyl cyclobentenone is a useful intermediate for pyrethroid insecticides, and at the same time, it can also be used as an intermediate for pharmaceuticals such as prostagranone, and as an intermediate for fragrances such as jasmone. Extremely high.

Conventionally, various proposals have been made regarding the production method of propargylcyclobentenone, but all of them suffer from various drawbacks in terms of yield, complexity of operation, and environmental issues, and none of them are necessarily industrially satisfactory. It wasn't.

Against this background, the present inventors have made intensive studies on the method for producing the compound, and as a result, have discovered a novel and extremely advantageous method for producing the compound.

The amount of bromine is 1:1 to 5 times, preferably 1.5 to 3 times, by mole relative to 2-(8-butynyl)-5-methylfuran. Bromine may be added all at once, but since there is a risk of rapid temperature rise due to reaction heat, it is preferable to add bromine dropwise over 0.5 to 5 hours.

In the above reaction, the presence of an alkali is not necessarily required, but its presence is more advantageous in terms of reaction time, reaction yield, etc. Examples of such alkalis include soda carbonate, potassium carbonate, caustic soda, and caustic potash, and the amount used is 1 to 10 times the molar amount of M2-(8-butynyl)-5-methylfuran, preferably 1.5 to 1.5 times. It is 3 times the mole.

5-methyldihydrofuran is obtained, but considering that 2゜al'j 5-di/F-xy-2-(3-butynyl)-5-methyldihydrofuran is thermally unstable, In order to obtain 8-butynyl)-5-methyldihydrofuran, which is preferable to leave the crude product to the next step of hydrolysis without performing distillation isolation, well-known furan As in the case of electrolytic oxidation, electrolytic oxidation may be carried out using an electrode material such as platinum or carbon in a lower alcohol solvent in which a suitable supporting electrolyte is dissolved. Examples of the supporting electrolyte here include sulfuric acid, lithium perchlorate, sodium methoxide, and ammonium nitrate. The electrolysis temperature is -60° to 20°C, preferably 10°C or lower.

Examples of lower alcohols include the same alcohols as mentioned in the bromine method, with methanol being particularly preferred.

An electrician who supplies electricity should use 1.8 to 5 fluoride 1 to 1 mole of raw material 2-(8-butynyl)-5-methylfuran.
mol, preferably 2 to 1 mole of B Faraday. After the reaction, the conventional method as described above. More purpose (7) 2.5-
As a result, -2-(8-butynyl)-5-methyldihydrofuran can be obtained.

The 2°alco-5-di-tJF-x-2-(8-butynyl)-5-methyldihydrofuran obtained by the bromine method or electrode oxidation method is a mixture of cis and trans isomers.
The production ratio varies depending on the method or electrolytic oxidation conditions, but by hydrolyzing this mixture, cis-
From 8-nonene--5-methyl-dihydrofuran@),
The hydrolysis reaction to obtain cis-8-nonen-2,5-dione-8-yne is carried out in the presence of an acidic catalyst in water or a mixed solvent of water and an organic solvent inert to the reaction.

Examples of organic solvents that are inert to the reaction include ethers such as diethyl ether, tetrahydrofuran, dimethoxyethane, and dioxane, halogenated hydrocarbons such as methylene chloride, chloroform, and trichloroethylene, and non-containing solvents such as dimethylformamide and dimethylholpoquine. Examples include protic solvents, aromatic hydrocarbons such as benzene and toluene, and mixed solvents thereof.

The amount of 1-sib solvent used is usually 1 to 4 times the amount of 2,5-di/IP-x-2-(8-butynyl)-5-methyldihydrofuran.
0M amount times, preferably 5 to 20 times by weight, and in the case of a mixed solvent of water and organic solvent, the weight ratio of water to organic solvent is arbitrary, but usually 0.1 to 10.

The acidic catalysts used here include organic acids such as ensulfonic acid and benzoic acid, acidic sodium sulfate, acidic sodium phosphate, etc. The amount of such acidic catalysts used is 2.
．． The amount is usually 0.001 to 1 mole, preferably 0.01 to 0.6 mole, relative to 5-dino-oxy-2-(8-butynyl)-5-methyldihydrofuran.

The reaction temperature is usually -1θ to 80°C, preferably 0 to 50°C. The reaction time is usually 30 minutes to 8 hours, but if the reaction time is too long, by-products tend to increase, so it is desirable to terminate the reaction when the reaction raw materials are consumed. After the reaction, the desired cis-
Although 8-nonene-2,5-dione-8-yne can be isolated, it is thermally unstable, so it is desirable to use the reaction solution after hydrolysis for the next reaction.

The solvent used in the next reaction to obtain the desired 2-propargyl-8-methyl-4-hydroxy-2-cyclobentenone from cis-8-nonen-2,5-dione-8-yne can be used in the previous hydrolysis. The one used can be applied as is, and the amount of solvent is also the same.

The basic catalysts used here include hydroxides of alkali metals such as sodium and potassium, alkaline earth metals such as calcium and barium, basic salts such as carbonates, bicarbonates, and acetates, triethylamine and pyridine. Examples include amines such as, basic ion exchange resins, etc. The amount of the basic catalyst to be used is generally 0.01 to 20 times, preferably 0.1 to 5 times, by mole based on cis-8-nonene-2,5-dione-8-yne. The reaction temperature is usually -20 to 5
The temperature is 0°C, preferably 0°C or lower. Reaction time is usually 1/8
The reaction time is approximately 5 hours, but since by-products tend to increase if the reaction is carried out for too long, it is desirable to terminate the reaction when the reaction raw materials are consumed.

After the reaction, the reaction solution is neutralized and the desired 2-propargyl-8-methyl-4-hydroxy-3 is obtained by conventional methods such as extraction and distillation.
- You can get cyclobentenonka.

The present invention will be explained below with reference to Examples.

Example 1 6.70 g of 2-(3-butynyl)-5-methylfuran and 1.0 g of sodium methylate were dissolved in 60 g of methanol, and a current of 0.5 A was applied at -4° C. using a carbon electrode for 6.7 g.
After flowing for 7 hours (1 mol at 2.5° C.), 41.02 g of anhydrous ammonium chloride was added. Methanol was distilled off, ether was added to the residue, the precipitate was separated, the ether was distilled off from the filtrate, and the filtrate was distilled under reduced pressure to give 2,5-dimethoxy-2-(3-butynyl)-5. - 6.87 g of methyldihydrofuran were obtained.

Yield 65.0%, boiling point 84-89℃/8.5 vra
sHfGO and the following NMI (from the peak ratio cis: trans = 34:66 N, M, 几 data (CDCyLs solvent, internal standard T8 (
S, δppm.

90MI (z) 2.10-2.2g (broadt, BH, c) 1.9
6-2.00 (d, It, b) 1.5f3 (8
, 8 fl, & (trB118)) 1.49 (s , 8
H,a(cis)) 2,5-dimethoxy-2-(B-butynyl)-5-methyldihydrofuran obtained from the above reaction2. Disperse Og in water 20- and add 10% acetic acid aqueous solution7.
859 and stirred at room temperature for 1 hour, carbon tetrachloride 2
0m7! The mixture was extracted 8 times with carbon tetrachloride, and the residue was purified by column chromatography (7,1,44 g of cis-8-nonen-2,,5-dione-8-yne was obtained.

Yield 9496 NMR data (0CL4 solvent, internal standard TM8
゜δppm, 90■1z) 6.28 (s, 2fi, e) 2.4 to 2.8 (broad, 4H, C! & d) 2.2
8 (s, 8R, b) 1.81 (tjH, a) Shisagi-8-nonene-2゜5-dione- obtained from the above reaction
1.0 g of 8-yne was dissolved in 20 g of water and 20 g of chloroform.
After cooling to 0℃, add 2f of 5N caustic water.
After adding R1 and stirring for 1 hour, the mixture was neutralized with IN aqueous hydrochloric acid. The chloroform layer was separated, and the aqueous layer was extracted several times with chloroform. The chloroform layers were combined, dried over magnesium sulfate, and the chloroform was distilled off. The residue was purified by column chromatography to obtain 0.48F 2-propargyl-8-methyl-4-hydroxy-2-cyclobentenone. Yield 48.0% NMR data (CDC, 4a solvent internal standard TM
8゜δppm, 99 MJ (z) 2.28 (s, 8H, b) 1.93-2.03 (t, n, a) Example 2 2-(8-butynyl)-5-methylfuran 2, 68F
was dissolved in 40°C of methanol, 5.529% of potassium carbonate was added at -20°C, and then bromine was added to the methanol solution.
Methanol mixture (8.88 g of bromine, 20 g of methanol)
) was added dropwise in 1 hour.

After stirring at -20° C. for 1 hour, stirring was continued for an additional 45 minutes at room temperature. After filtering the reaction solution, methanol was distilled off. 200 ml of water was added to the residual solution and extracted three times with 100 ml of ether, and the ether layer was dried over magnesium sulfate. The ether was distilled off to give 8.55f of oil.

(2,5-dimethoxy-2-(8-butynyl)-5-methyldihydrofuran mso% yield 72.4%, GO
The oily substance obtained by the above reaction was dispersed in 100% water in cis:trans, 0.1 g of 2N sulfuric acid was added, and the mixture was stirred at room temperature for 1 hour. 2.5-dimethoxy-2-(8-butynyl)-5 by gas chromatography analysis
-Methyldihydrofuran disappears and cis-3-nonene-2
After confirming that ,5-dione-8-yne was produced, 100% of chloroform was added to the above reaction solution, and 100% of 5N caustic water was added with stirring after cooling to 0°C. After stirring for 1 hour, IN Neutralized with hydrochloric acid water.

The chloroform layer was separated, and the aqueous layer was extracted several times with chloroform. The chloroform layers were combined and dried over magnesium sulfate, and the chloroform was distilled off. The residue was purified by column chromatography to obtain 0.89F 2-propargyl-3-methyl-4-hydroxy-2-cyclobentenone. 2.5-dimethoxy-2-(8-butynyl)-
Total yield from 5-methyldihydrofuran: 41.0% Example 8 6.70 f of 2-(3-butynyl)-5-methylfuran and 1 g of lithium perchlorate were dissolved in 60 methanol, and using a platinum electrode. After passing a current of 0.5 A for 7 hours at 0 to 2°C (1 mol of 2,6F), methanol was distilled off. Ether was added to the residue, and the ether solution was washed with water and then separated. After drying the ether phase with magnesium sulfate, the ether was distilled off to give 9.529 as an oil.

(2,5-dimethoxy-2-(3-butynyl)-5-methyldihydrofuran content: 170.2%) Yield a s, 2
9i Disperse the oily substance obtained by the above reaction in 100-g of water, add 1 g of acidic ion exchange resin (Amberlite IR
-120B) and stirred at room temperature for 2 hours, the raw material 2',5-dimethoxy-2-(
8-butynyl)-5-methyldihydrofuran disappears,
After confirming that cis-8-nonene-2,5-dione-8-yne was produced, the ion exchange resin was distributed from house to house. Chloroform 100- was added to the P solution, cooled to -2°C, and 10 ml of 5N caustic water was added while stirring. After stirring for 1 hour, it was neutralized with IN hydrochloric acid water. The chloroform layer was separated, and the aqueous layer was extracted several times with chloroform. After the chloroform layers were combined and dried over magnesium sulfate, the chloroform was distilled off. The residue was purified by column chromatography to obtain 2.209 2-propargyl-8-methyl-4-hydroxy-2-cyclobentenone. Total yield 48.0% from 2.5-dimethoxy-2-(8-butynyl)-5-methyldihydrofuran.

Claims (1)

[Claims] Reacting 2-(8-butynyl)-6-methylfuran with bromine and a lower alcohol in the presence or absence of an alkali to obtain a lower methyldihydrofuran and then in the presence of an acidic catalyst. 2-Pro A characterized by
Method for producing 8-methyl-4-hydroxy-mecyclopentenone.