JPS6149313B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to 3,3,7-trimethyl2,9-dioxatricyclo[3.3.1.0 ⁴ , ⁷ ]nonane (general lineartin,
This name will be used below. 1,5,5-trimethyl-4-oxabicyclo[4.2.0]octa-3,7-dione (hereinafter referred to as the present compound), which is a synthetic intermediate of ), and a method for producing the same.

Insect pheromones have recently come to be used for the purpose of pest control because they exhibit strong attraction to insects. However, it is extremely difficult to isolate large amounts of pheromones from the natural world, so there is a strong desire to develop an economical method for synthesizing pheromones.

Insect pheromone synthesized using this compound,
Lineatin was isolated by Silverstein et al., and the following two putative structural formulas were submitted (Journal of Chemical Ecology, Vol. 3, 1977, p. 549).

The present inventors have previously synthesized and confirmed that the structural formula of is consistent with that of a natural product. Subsequently, as a result of further research, they discovered a method for selectively synthesizing linearatin using the present compound, which is a novel intermediate, and completed the present invention.

Hydroxylactone, which is a raw material compound of the present invention, can be synthesized, for example, as follows.

That is, it is obtained by a photocycloaddition reaction between vinyl acetate and a cyclopentenone derivative. is reacted with isoamyl nitrite in benzene using potassium tert-amylate as a base to give the ketoxime. in ethylene glycol,
After reaction with hydrazine, the oxime is obtained by treatment with potassium hydroxide. is reduced with titanium trichloride and hydrolyzed to obtain a hydroxyketone. is oxidized with metachloroperbenzoic acid to obtain the starting compound hydroxylactone.

Cyclopentenone is a known compound that can be easily obtained by heating isobutyl methacrylate in polyphosphoric acid (Journal of Chemical Society Parkin 1979).
274 pages).

The present invention will be explained in detail below.

After dissolving hydroxylactone in a solvent such as acetone, 1 to 10 equivalents of chromic acid-sulfuric acid mixed acid (Jones reagent) is added. Reaction time is 10-60 minutes,
The reaction temperature is 0-30°C. After the reaction is completed, the present compound is obtained by performing a usual post-treatment.

The mixture is further dissolved in a solvent such as ether, cooled, and diisobutylaluminum hydride is added dropwise. The reaction temperature is -70°C to +20°C, and the reaction time is within 60 minutes. Furthermore, add 5% to 30% hydrochloric acid and stir for 1 hour. Lineatin is obtained by extraction with a low boiling point solvent such as n-pentane, neutralization, and distillation.

Next, the present invention will be specifically explained with reference to Examples and Reference Examples.

Reference Example 1 Synthesis of (6,7)-acetoxy-1,4,4-trimethylbicyclo[3.2.0]heptane-2-one A solution of 25 g of cyclopentenone, 250 ml of vinyl acetate, and 90 ml of benzene was heated under a high-pressure mercury lamp (450 W). in
It was exposed to light for 50 hours. Later concentrated and distilled, 92-98
11.0 g of a fraction of °C/0.5 mmHg was obtained.

n ²⁰ _D 1.4620 Elemental analysis value C (%) H (%) Calculated value (as C ₁₂ H ₁₈ O ₃ ) 68.52 8.64 Actual value 68.27 8.71 Reference example 2 3-oximino-6-hydroxy-1,4,4
-Trimethylbicyclo[3.2.0]heptane-2
-Synthesis of 1.2g of tertiary amylpotassium in benzene
Dissolved in 20ml. A solution of 1.0 g of benzene (2 ml) was added under ice cooling, and the mixture was stirred for 30 minutes. Further, when 0.57 g of isoamyl nitrite was added, a reddish-purple color appeared. After stirring at room temperature for 36 hours, the mixture was made acidic with 1NHCl and separated. The residue was then washed with saturated sodium chloride solution and saturated brine, dried over magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain a brown oil. This was purified using silica gel column chromatography to yield 261 mg.
crystals were obtained.

mp 115-118℃ Elemental analysis value C (%) H (%) N (%) Calculated value (as C ₁₀ H ₁₅ NO ₃ ) 60.88 7.68 7.04 Actual value 60.90 8.22 6.81 Reference example 3 3-oximino-1,4, 4-trimethyl-6
-Synthesis of hydroxybicyclo[3.2.0]heptane 2050mg of ketoxime was mixed with 25% of ethylene glycol.
ml and added 0.7 ml of 80% hydrazine hydrate. After keeping at 40-50°C for 30 minutes, 750 mg of potassium hydroxide was added and kept at 150°C for 4 hours under an argon stream. After cooling, 50 ml of water was added, neutralized with 1NHCl, and extracted with methylene chloride. After washing with heavy soap and salt water, drying with magnesium sulfate,
Methylene chloride was distilled off to obtain 970 mg of crystals.

130-133℃, MSm/e; 183 (M ⁺ ) Reference example 4 Synthesis of 1,4,4-trimethyl-6-hydroxybicyclo[3.2.0] heptane-3-one 600 mg of oxime was dissolved in dimethoxyethane (10 ml)
and water (5 ml), 16% titanium trichloride (6 ml) was added thereto, and the mixture was kept at 50-60°C for 30 minutes under an argon stream. Cool and add water (20ml)
The mixture was extracted with methylene chloride, washed with heavy water and brine, and then dried over magnesium sulfate. 425 mg of an oil obtained by distilling off the solvent was purified by silica gel column chromatography to obtain 305 mg of an oil.

n ²⁰ _D 1.4787, MS; m/e 168 (M ⁺ ) Reference example 5 1,5,5-trimethyl-7-hydroxy-4
-Synthesis of oxabicyclo(4.2.0)oct-3-one Hydroxyketone (400 mg) was dissolved in methylene chloride (8 ml), and under ice-cooling, methachloroperbenzoic acid (770 mg) and hydrogen sulfur (480 mg) were added, and the mixture was dissolved at room temperature. After stirring overnight, 10% sodium thiosulfate (10
ml). After separating the layers, the aqueous layer was extracted three times with methylene chloride, the methylene chloride layers were combined, washed with saturated sodium chloride water and brine, dried over magnesium sulfate, and the methylene chloride was distilled off to form a colorless oil (415
mg) was obtained.

n ²⁰ _D 1.4845, MS; m/e 169 (M ⁺ -CH ₃ ) 166 (M ⁺ -H ₂ O) Example 1 1,5,5-trimethyl-4-oxabicyclo[4.2.0]octa-3 Synthesis of ,7-dione Dissolve hydroxylactone (410 mg) in acetone (10 ml) and add 8N chromic acid monosulfuric acid mixture (0.6 ml) under ice cooling. After 10 minutes, 3 drops of isopropyl alcohol were added and the mixture was further stirred for 30 minutes. After separating the layers with methylene chloride (10 ml) and water (10 ml), the aqueous layer was extracted once with methylene chloride, washed with brine, dried over magnesium sulfate, and the methylene chloride was distilled off to give a colorless oil (342 mg). ) was obtained.

n ²⁰ _D 1.4837, MS; m/e 182 (M ⁺ ) Reference example 6 Synthesis of 3,3,7-trimethyl-2,9-dioxatricyclo[3.3.1.0 ⁴ , ⁷ ]nonaneliniatin Ketolactone (300 mg ) to anhydrous ether (3
ml). This was heated at −70°C under an argon stream.
Add diisobutylaluminum hydride (25% n-hexane solution, 2.1ml) and incubate for 40 minutes.
It was kept at 70~-50℃. Next, 1N hydrochloric acid (5 ml) was added, the mixture was brought to room temperature, 6N hydrochloric acid (0.5 ml) was added, and the mixture was stirred for 1 hour. After adding n-pentane (2 ml) and separating the layers, washing with salt water, washing with sodium chloride water, and washing with salt water, the mixture was dried over magnesium sulfate, and the solvent was distilled off to obtain crude linearatin (110 mg). This was distilled to obtain 56 mg of colorless oil. b.p120~130℃/60mm
Hg, n ²⁰ _D 1.4625 MS; m/e168 (M ⁺ ) The infrared absorption spectrum and proton nuclear magnetic resonance spectrum were completely consistent with those of the natural product reported by Silverstein et al.

Claims (1)

[Claims] 1 formula 1,5,5-trimethyl-4-oxabicyclo[4.2.0]octa-3,7-dione2 represented by the formula 1,5,5-trimethyl-7-hydroxy-4-oxabicyclo[4.2.0]octa-3
-Formula characterized by the oxidation of on A method for producing 1,5,5-trimethyl-4-oxabicyclo[4.2.0]octa-3,7-dione shown by