Patent ES-2187344-A1 (ES)
Title: Preparation of furanone derivative useful for various purpose e.g. in soft drink formulations involves converting dihydrotagetone isolated from plant species of Tagetes
Inventor: ARUN KUMAR SINHA
IPC: C12G3/04
Filed: 2001-04-04
Abstract: Preparation of coconut flavored two chiral centered 5-isobutyl-3-methyl-4,5-dihydro-2(3H)-furanone (I) involves converting a bifunctional acyclic monoterpene ketone, dihydrotagetone isolated from plant species of Tagetes. (I) is a new analog of natural whisky lactone and coconut aldehyde. Conversion of a bifunctional acyclic monoterpene ketone dihydrotagetone (II), isolated from the plant species Tagetes into coconut flavored two chiral centered 5-isobutyl-3-methyl-4,5-dihydro-2(3H)-furanone of formula (I) involves: (a) Adsorbing Tagetes minuta oil on an adsorbent selected from alumina or silica gel (b) Loading adsorbent obtained from step (a) on a soxhlet extractor and washing with a non polar solvent (cold percolation) selected from petroleum ether or hexane for removing the non polar constituents (c) Isolating the dihydrogetone (II) rich fraction using hot hexane percolation with increasing percentage of ethylacetate (0.2 - 5)% (d) Concentrating the separated fractions under reduced pressure to obtain (II) rich concentrate (e) Loading the concentrate on alumina or silica gel column and eluting the column with a non polar solvent selected from hexane or petroleum ether (f) Eluting the column further with increasing percentage of ethyl acetate (up to 5)% in hexane (g) Concentrating the resulting hexane-ethylacetate fractions under reduced pressure to obtain (II) in at least 99% purity (h) Providing (II) in organic solvent selected from ether selected from tetrahydrofuran, dimethoxyethane or dioxane, alcohol selected from butanol or t-butyl alcohol, ketone selected from acetone or methyl ethyl ketone (i) Oxidizing (II) in presence of an oxidizing reagent selected from sodium meta-periodate, potassium meta-periodate or ruthenium tetraoxide in the range of 2 - 8 times moles of (II) and a co-oxidizing agent selected from potassium permanganate or sodium permanganate in the range of 0.1 - 0.6 times mole of (II) (j) Adding a base selected from sodium carbonate, sodium bicarbonate, potassium carbonate, lithium carbonate or sodium hydroxide in the range of (1 - 4 times of (II)) to the above solution (k) Maintaining the temperature between -15 - 90degreesC during oxidation from (h) to (j) for 4 - 48 hours (l) Destroying the excess permanganate from the above reaction mixture with saturated solution of sodium bisulfite or sodium metabisulfite (m) Filtering the above reaction mixture, washing, acidifying and removing the solvent under reduced pressure, followed by extraction and chromatography to obtain 2,6-dimethyl-4-oxo-heptanoic acid (III) with at least 68% yield (n) Providing (III) under stirring in a solvent selected from tetrahydrofuran, dimethoxyetane or dioxane, alcohol (e.g. methanol, butanol and t-butyl alcohol) and chlorinated solvent (e.g. dichloromethane and chloroform) (o) Adding a base selected from sodium bicarbonate, sodium hydroxide or potassium carbonate to the resultant solution to make salt of the oxy acid of (III) (p) Reducing salt of oxo acid of (III) to hydroxy acid in the presence of reducing agent selected from sodium borohydride or lithium aluminum hydride in the range of 0.5 - 3 times mole at reaction temperature -15 - 50degreesC and (q) Removing the organic solvent under vacuum and acidifying the cooled aqueous alcoholic solution at -10 - 0degreesC with an acid selected from hydrochloric acid, sulfuric acid, acetic acid or acetic anhydride for 30 minutes - 8 hours and finally isolating 5-isobutyl-3-mehtyl-4,5-dihydro-2(3H)-furanone of formula (I) (also named as 4-isobutyl-2-methyl-4-butanolide) in at least 76% yield by extraction and chromatography. Independent claims are also included for the following: (1) a stable compound (III) as an analog of natural 2,6-dimethyl-5-oxo-heptanoic acid found in essential oil of Mentha x piperita, having acidic sweet aroma, containing oxo and carboxylic acid, capable of undergoing conversion into several value added products such as corresponding 4-oxo ester, 4-hydroxy ester and 4-hydroxy acid by estrificatio