Title of Invention

A PROCESS FOR PRODUCING 4-HYDROXY 6-METHYL-3-(4-METHYL-2-PENTENOYL)-2-PYRONE

Abstract

ABSTRACT 801/MAS/2001 The present invention relates to a 4-Hydroxy-6-methyl-3-(4-methyl-2-pentenoyl)-2-pyrone is obtained by allowing 2,3-dihydro-7-memyl-2-(l-methylethyl)-4H,5H-pyrano[4,3-b]pyran-4,5-dione to react with at least one inorganic compound selected from alkali hydroxides, alkaline earth hydroxides, alkali carbonates, alkaline earth carbonates and alkali fluorides in an alcohol, water or a mixture thereof, at a temperature ranging from -20 to 100°C and recovering the pyrone derivative from the reaction mixture in a known manner.

Full Text

The present invention relates to a process for producing 4-hydroxY-6-inethyl-3-(4-methyl-2-pentenoyl)-2-pyrone. Inmore details, it relates to a process for producing 4-hydroxy-6-methyl-3-(4-methyl-2-pentenoyl)-2-pyrone from 2,3-dihydro-7-inethyl-2-(l-methylethyl)-4H,5H-pyrano[4,3-b]pyran-4,5-dione, Background Arts 4-Hydroxy-6-methyl-3-{4-methylpentanoyl)-2-pyrone of formula (1): is a compound which can be utilized as an active ingredient of insecticides, and it can be obtained by a catalytic reduction of 4-hydroxy-6-raethyl-3-(4-methyl-2-pentenoyl)-2-pyrone of formula (2): Therefore, it is useful to afford a process for producing the compound of formula (2). The present invention has a subject to provide a process for producing 4-hydroxy-6-methyl-3-(4-m'ethyl-2-pentenoyl)-2-pyrone that is an intermediate compound for manufacturing 4-hydroxy-6-methyl-3-(4-methylpentanoyl)-2-pyrone. Summary of the Invention The present invention provides a process for producing 4-hydroxy-6-methyl-3-{4-methyl-2-pentenoyl)-2-pyrone of formula (2) from 2,3-dihydro-7-methyl-2-(l-methylethyl)-4H,5H-pyrano [4,3-b]pyran-4,5-dione of formula (3): under a specific condition. 4-Hydroxy-6-methyl-3-(4-methyl-2-pentenoyl) - 2 -pyrone of formula (2) can be derived to an insecticidal active ingredient, 4-hydroxy-6-raethyl-3-(4-methylpentanoyl)-2-pyrone, by a catalytic reduction procedure. Namely, the present invention provides a process for producing 4-hydroxy-6-methyl-3-(4-methyl-2-pentenoyl)-2-pyrone which comprises allowing 2,3-dihydro-7-methyl-2-(l-methylethyl) -4H, 5H-pyrano[4,3-b]pyran-4,5-dione to react with at least one inorganic compound selected from alkali hydroxides, alkaline earth hydroxides, alkali carbonates, alkaline earth carbonates and alkali fluorides in an alcohol, water or a mixture thereof. Detailed Description of the Invention The process of the present invention is carried out in an alcohol, water or a mixture thereof. Examples of the alcohol used for the reaction include lower alcohols, for example, C1-C5 alcohols. Typical examples eire methanol, ethanol, 2-propanoland2-methyl-2-propanol. Amixture of the lower alcohol with water can be utilized as well as a mixture of two or more of the lower alcohols. In the present invention, the other solvent that is inert to the reaction of the present invention can be used together. Therefore, the phrase "in an alcohol, water or a mixtiore thereof" means " in the presence of at least one solvent selected from alcohols and water, and the amount of the solvent is enough for dissolving the inorganic compound selected from alkali hydroxides, alkaline earth hydroxides, alkali carbonates, alkaline earth carbonates and alkali fluorides." The amount of the solvent selected from alcohols and water is usually 1ml to 1000ml based on Ig of 2.3-dihydro-7-methyl-2-(1-methylethyl)-4H.5H-pyrano[4,3-b] pyran-4,5-dione. Examples of the inert solvent include aliphatic hydrocarbons (e.g. hexane), aromatic hydrocarbons (e.g. toluene), ketones (e.g. methyl isobutyl ketone), esters (e.g. ethyl acetate), ethers (e.g. tetrahydrofuran, diethyl ether), amides (e.g. N,N-dimethylformamide), halogenated hydrocarbons (e.g. chloroform), dimethyl sulfoxide, aliphatic nitriles (e.g. acetonitrile), tertiary amines (e.g. triethylamine) and nitrogen-containing aromatic heterocycles (e.g. pyridine). Examples of the alkali hydroxide include lithium hydroxide, sodium hydroxide and potassium hydroxide, and examples of the alkaline earth hydroxide include magnesium hydroxide, calcium hydroxide and barium hydroxide. In the present invention, alkali carbonate means normal salt of alkali metal carbonate. Therefore, examples of the alkali carbonate include lithium carbonate, sodium carbonate and potassium carbonate. Examples of the alkaline earth carbonate include magnesium carbonate, calcium carbonate and barium carbonate. Examples of the alkali fluoride include cesium fluoride. An amount of the alkali hydroxides, alkaline earth hydroxides, alkali carbonates alkaline earth carbonates or alkali metal fluorides used for the reaction is- usually 1 to 10 moles, preferable 1 to 5 moles against 1 mole of a starting material, 2,3-dihydro-7-methyl-2-(1-methylethyl)-4H,5H-pyrano[4,3-b] pyran-4,5-dione. The reaction temperature for the process of the invention is usually -20 to lOO'C, provided that it is usually under a boiling point of a solvent when the boiling point of the solvent used for the reaction is below 100^3. The reaction period varies depending on the other reaction conditions and it is usually momentary to 24 hours. The starting material for the process of the invention, 2,3-dihydro-7-methyl-2-(1-methylethyl)-4H,5H-pyrano[4,3-b] pyran-4,5-dione, can be prepared by a condensation reaction of dehydroacetic acid with isobutyraldehyde in the presence of piperidine in chloroform according to the description of Chemistry and Industry pp. 1306-1307 (1969). Further, 4-hydroxy-6-methyl-3-(4-methyl-2-pentenoyl)-2-pyrone obtained by the process of the invention can be subjected to a reduction, such as hydrogenat ion in the presence of a transition metal catalyst, to give 4-hydroxy-6-methyl-3-{4-niethylpentanoyl)-2-pyrone that is useful as an active ingredient of insecticides. Accordingly, the present invention provides a process for producing 4-hydroxy-6-methyl-3-(4-methyl-2-pentenoyI)-2-pyrone which comprises allowing 2,3-dihydro-7-methyl-2-(l-methylethyl)-4H,5H-pyrano[4,3-b]pyran-4,5-dione to react with at least one inorganic compound selected from alkali hydroxides, alkaline earth hydroxides, alkali carbonates, alkaline earth carbonates and alkali fluorides in an alcohol, water or a mixture thereof at -20 to lOO^C, acidifying the reaction mixture and isolating the product in a known manner. Examples Hereinafter, the present invention is further illustrated by production examples and so on in detail, although the present invention is not limited in any sense to these examples. Production example 1 In 10ml of methanol. 222mg of 2,3-dihydro-7-methyl-2-Cl-methylethyl) -4H,5H-pyrano[4,3-b]pyran-4, 5-dione were dissolved, and 200mg of potassium hydroxide were added thereto and stirred at room temperature for 1 hour. After that, methyl t-butyl ether and 3% hydrochloric acid were added to the reaction mixture. The separated organic layer was washed with saturated brine once, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 130mg of 4-hydroxy-6-methyl-3-(4-methyl-2-pentenoyl)-2-pyrone. ^H-NMR (CDCI3. TMS) 5 (ppm) : 1.13 (6H, d) , 2.27 (3H, s), 2.60 (IH, m), 5.93 (IH. s), 7.23 (IH, dd), 7.58 (IH, d) Production example 2 To a mixture of 450mg of 2,3-dihydro-7-methyl-2-(l-methylethyl)-4H,5H-pyrano[4,3-b]pyran-4,5-dione and 40ml of 2-propanol, 400mg of potassium carbonate were added and stirred at room temperature for 12 hours. The reaction mixture was then concentrated, and methyl t-butyl ether and 3% hydrochloric acid were added thereto. The separated organic layer was washed with saturated brine once, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 340mg of 4-hydroxy-6-methyl- 3-(4-methyl-2-pentenoyl)-2-pyrone. Production example 3 To a mixture of 200mg of 2,3-dihydro-7-methyl-2-(l-methylethyl)-4H,5H-pyrano[4,3-b]pyran-4,5-dione and 10ml of water, 200mg of lithium hydroxide monohydrate were added and stirred at room temperature for 1 hour. After that, methyl t -butyl ether and 3% hydrochloric acid were added to the reaction mixture. The separated organic layer was washed with saturated brine once, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 178mg of 4-hydroxy-6-methyl-3-(4-methyl-2-pentenoyl)-2-pyrone. Production example 4 A mixture of 108mg of 2,3-dihydro-7-methyl-2-(l-methylethyl)-4H,5H-pyrano[4,3-b]pyran-4,5-dione, 200mg of cesium fluoride and 5ml of 2-methyl-2-propanol was stirred for 2 hours under reflux-heating. After that, methyl t-butyl ether and 3% hydrochloric acid were added to the reaction mixture. The separated organic layer was washed with saturated brine once, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 86mg of 4-hydroxy-6-methyl-3-(4-methyl-2-pentenoyl)-2-pyrone. Production example 5 To a mixture of 189mg of 2,3-dihydro-7-methyl-2-(l-methylethyl) - 4H,5H-pyrano[4,3-b]pyran-4,5-dione, 4ml of toluene and 4ml of water, 0.20g of sodium hydroxide was added and stirred. After 4 hours, methyl t-butyl ether and 3% hydrochloric acid were added to the reaction mixture. The separated organic layer was washed with saturated brine once, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 82mg of 4-hydroxy-6-methyl-3-(4-methyl-2-pentenoyl)-2-pyrone. Next, a process for producing 4-hydroxy-6-methyl-3-{4-methylpentanoyl)-2-pyrone by reducing 4-hydroxy-6-methyl-3-(4-methyl-2-pentenoyl)-2-pyrone is illustrated as reference production example. Reference production example Under nitrogen, 2.8gof 4-hydroxy-6-methyl-3-(4-methyl-2-pentenoyl)-2-pyrone was dissolved in ethyl acetate and 0.14g of 5% palladium/CEirbon was added thereto. The nitrogen in the reaction vessel was substitutedby hydrogen and the reaction mixture was stirred at room temperature for 5 hours. After that, the reaction mixture was filtered through a Celite pad and the Celite pad was washed with 50ml of ethyl acetate. The solution combined the filtrate with the washing solution was washed with 0.1% hydrochloric acid once, water twice and saturated brine once, subsequently. The organic layer was dried over anhydrous magnesiiom sulfate and concentrated under reduced pressure to give a residue, which was subjected to silica gel column chromatography (eluent: hexane/ethyl acetate = 6/1) to give 2.68g of 4-hydroxy-6-methyl-3-{4-methylpentanoyl)-2-pyrone. ^H-NMR (CDCI3, TMS) d (ppm) : 0.94 (6H, d) , 1.54 (2H, q) , 1.63 (IH, m), 2.27 {3H, s), 3.08 (2H, t), 5.93 (IH, s), 17.88 (IH, s) Furthermore, it is shown by reference example that 4-hydroxy-6-methyl-3-{4-methylpentanoyl)-2-pyrone obtained above is useful as an active ingredient'of insecticides. Reference example (Knock-down test against housefly) A half part of 4-hydroxy-6-methyl-3-(4-methylpentanoyl)-2-pyrone was dissolved in 10 parts of dichloromethane and mixed with 89.5 parts of Isopar M (isoparaf f in produced by Exxon Chemical) for preparing 0.5% oil solution. Part (s) means part (s) by weight. Ten adult houseflies {Musca domestica) including 5 males and 5 females were released in a 70cm-cubic glass chamber (volume: 0.34cm^). By a spray-gun, 0.7ml of the above oil solution was applied at a pressure of 0. 9kg/cm^ from a small window on the wall of the chamber. After 15 minutes from application, knocked-down houseflies were observed. As a result of two repetitions, the knocked-down ratio was 95%. WE CLAIM: 1. A process for producing 4-hydroxy-6-methyl-3-(4-methyl-2-pentenoyl)-2-pyrone which comprises allowing 2,3-dithydro-7-methyl-2-(l-methylethyl)-4H,5H-pyrano[4,3-b]pyran-4,5-dione to react with at least one inorganic compound selected from alkali hydroxides, alkaline earth hydroxides, alkali carbonates, alkaline earth carbonates and alkali fluorides in an alcohol, water or a mixture thereof at -20 to 100°C, acidifying the reaction mixture and isolating the product in a known manner. 2. The process as claimed in claim 1, wherein 2,3-dihydro-7-methyl-2-(l-methylethyl)-4H,5H-pyrano[4,3-b]pyran-4,5-dione is reacted with at least one inorganic compound selected from alkali hydroxides, alkaline earth hydroxides, alkali carbonates, alkaline earth carbonates and alkali fluorides in an alcohol at -20 to 100°C, acidifying the reaction mixture and isolating the product in a known manner. 3. The process as claimed in claim 1, wherein 2,3-dihydro-7-methyl-2-(l-methylethyl)-4H,5H-pyrano[4,3-b]pyran-4,5-dione is reacted with at least one inorganic compound selected from alkali hydroxides, alkaline earth hydroxides, alkali carbonates, alkaline earth carbonates and alkali fluorides in water at -20 to 100°C, acidifying the reaction mixture and isolating the product in a known manner. 4. The process as claimed in claim 1, wherein said inorganic compound is an alkali hydroxide. 5. The process as claimed in claim 4, wherein said alkali hydroxide is lithium hydroxide, sodium hydroxide or potassium hydroxide. 6. The process as claimed in claim 1, wherein said inorganic compound is an alkaline earth hydroxide. 7. The process as claimed in claim 6, wherein said alkaline earth hydroxide is magnesium hydroxide, calcium hydroxide or barium hydroxide. 8. The process as claimed in claim 1, wherein said inorganic compound is an alkali carbonate. 9. The process as claimed in claim 8, wherein said alkali carbonate is lithium carbonate, sodium carbonate or potassium carbonate. 10. The process as claimed in claim 1, wherein said inorganic compound is an alkaline earth carbonate. 11. The process as claimed in claim 10, wherein said alkaline earth carbonate is magnesium carbonate, calcium carbonate or barium carbonate. 12. The process as claimed in claim 1, wherein said inorganic compound is an alkali fluoride. 13. The process as claimed in claim 12, wherein the alkali fluoride is cesium fluoride. 14. A process for producing pyrone compounds substantially as herein described and exemplified.

Documents:

0801-mas-2001 abstract.pdf

0801-mas-2001 claims.pdf

0801-mas-2001 correspondence-others.pdf

0801-mas-2001 correspondence-po.pdf

0801-mas-2001 description (complete).pdf

0801-mas-2001 form-1.pdf

0801-mas-2001 form-26.pdf

0801-mas-2001 form-3.pdf

0801-mas-2001 form-5.pdf

0801-mas-2001 others.pdf