CS255230B1 - Process for preparing 4-methyl-3,6-heptadione - Google Patents

Abstract

The solution relates to a method for preparing 4-methyl-3,5-heptadione, an aggregation pheromone of the striped leafworm, or an intermediate for the preparation of other pheromones, in particular serricorone and serricorol, the sex pheromones of the tobacco budworm or the aggregation pheromones of the rice weevil and the corn weevil. The method of preparation is characterized in that diethyl ketone is condensed in the presence of botrifluoride etherate with propionic anhydride and the resulting difluoro(4-methyl-3,5-heptadionato)boron complex is decomposed by the action of an alkaline agent.

Description

(54) A process for the preparation of 4-methyl-3,6-heptadione

The present invention relates to a process for the preparation of 4-methyl-3,5-heptadione, an aggregated pheromone, or an intermediate product for the preparation of other pheromones, in particular serricorone and serricorol, sex pheromones of tobacco woodworm or migratory pheromones. The method is characterized in that the diethyl ketone is condensed in the presence of botrifluoride etherate with propionic anhydride and the resulting difluoro (4-methyl-3,5-heptadionato) boronate complex is decomposed by treatment with an alkaline agent.

The present invention relates to a process for the preparation of 4-methyl-3,5-heptadione, an aggregated pheromone (Sitona lineatus), (Blight et al., Naturwiss. 71, 480 (1984). 4-Methyl-3,5-heptadione it is also an important intermediate for the preparation of other pheromones, in particular serricorone and serricorol, sex pheromones of tobacco worm (Lasioderma serricorne) (Sakakibara M., Sea K.: Tetrahedron Lett. 1979, 2401; Jap. pat. 59,163380) and aggregation pheromones rice weevil (Sitophilus oryzae) and corn weevil (Sitophilus zeamais) (Schmuff NR et al. Tetrahedron Lett. 1984, 1533).

The processes known to date for the preparation of 4-methyl-3,5-heptadione are based either on 3,5-heptadione, which is methylated according toorganism and taylor (Blight et al., Naturwiss. 71, 480 (1984)) or diethyl ketone, which is either first condensed with propionaldehyde in the presence of the diisopropylamine Li salt and the resulting hydroxyketone is oxidized to the desired product in the next step (Smith AB, Levenberg A .: Synthesis 1981, 567) or condensation is performed with ethyl propionate in the presence of sodium hydride (Sakakibara M. , Sea K .: Tetrahedron Lett. 1979, 2401).

In another method, the condensation of diethyl ketone with propionic anhydride is carried out by catalytic saturation with BF 2 gas (House HO, Gannen WF: J. Org. Chem. 23, $ 7 $ (1958)) to give 4-methyl-3,5 -heptadione in 36% yield.

It has now been found that the condensation of diethyl ketone with pripionic anhydride to 4-methyl-3,5-heptadione is preferably carried out with boron trifluoride etherate, and crystalline difluoro (4-methyl-3,5-heptadionato) boron complex is isolated from the reaction mixture. which after decrystallization is decomposed to the desired product.

The present invention provides a process for the preparation of 4-methyl-3,5-heptadione characterized in that diethyl ketone is condensed with propionic anhydride in the presence of boron trifluoride etherate, optionally in an inert organic solvent, at a temperature of 50 ° C to the boiling point of the reaction mixture. to give difluoro (4-methyl-3,5-heptadionato) boron complex which, after isolation in a crystalline state, is purified by recrystallization, then the complex is decomposed to 4-methyl-3,5-heptadione by treatment with an alkaline agent.

The reaction is carried out by mixing the reactants and heating to 50 ° C to the boiling point of the reaction mixture for 2 to 10 hours. Preferably, the reaction is carried out in the absence of a solvent by heating the reaction mixture to boiling for 3-4 hours. The reaction mixture was quenched by pouring into ice water and the oil was extracted with ether. The ethereal solution was washed with water, NaHCO 3 solution, water, dried and evaporated. under vacuum to dryness. The residue is then extracted with hot petroleum ether and the crystalline boric complex precipitates from the solution by cooling.

The pure difluoro (4-methyl-3,5-heptadionato) boron complex prepared by recrystallization is decomposed by heating to boiling in an aqueous alkaline solution, preferably an aqueous sodium acetate solution. The 4-methyl-3,5-heptadione is isolated by shaking into ether, routine treatment of the solution, evaporation of the solvent and vacuum distillation of the residue.

The progress of the condensation reaction and the decomposition of the complex were monitored by thin layer chromatography on silica gel and by gas chromatography in a manner known to those skilled in the art.

The condensation reaction of the present invention providing a crystalline complex is advantageous because it allows for an easy, fast and efficient purification operation of the intermediate product - crystallization - and the final product 4-methyl-3,5-heptadione obtained in the next step does not require additional purification by efficient distillation as is common in prior art processes. The yield of the product prepared by the process of the invention is substantially higher than the yields of the known processes.

The invention is illustrated in more detail by the following non-limiting example.

Example

In a three-necked flask (250 mL) equipped with a reflux condenser with a chloro-calcium cap and an addition funnel, boron trifluoride ether (20 mL) was added dropwise to a mixture of diethyl ketone (8.6 g; 0.1 mol) and propionic aldehyde (26 g; 0.2 mol). ml).

After addition of the entire amount of etherate (about 10 min), the temperature rises to 35 ° C and the reaction mixture is then refluxed for 3 hours, then poured into ice water (100 mL) and extracted with ether (3x50 mL). The ether extract was shaken successively with water, saturated NaHCO 3 solution, again with water, and after drying over anhydrous MgSO 4, the ether was evaporated in vacuo. The brown oily residue was extracted with hot petroleum ether (3 x 100 mL). The petroleum ether extract was left to crystallize in the refrigerator overnight.

The precipitated crystals were aspirated and recrystallized from petroleum ether. Crystallization yielded 13.8 g of the BF ₂ complex of mp 48-49 ° C, NMR (CDCl 3 THS) 1.24 (6H, t), 2.64 (4H, g), 1.94 (2H, s) , which was further decomposed by refluxing (5 h) with 38 g of sodium acetate (CH 3 CO ₂ x x 3 H ₂ O) dissolved in 76 ml of water. Extraction with ether (3 x 50 ml) and usual work-up yielded 10.3 g (72.5% th) of 4-methyl-3,5-heptadione of bp 79-81 ° C / 12 mmHg after distillation from the collar.

Claims (1)

SUBJECT OF THE INVENTION Process for preparing 4-methyl-1,3,5-heptadione, characterized in that diethyl ketone is condensed with propionic anhydride in the presence of boron trifluoride etherate, optionally in an inert organic solvent, at a temperature of 50 ° C to the boiling point of the reaction mixture to form difluoro ( 4-methyl-3,5-heptadionato) boronate complex which, after isolation in a crystalline state, is purified by recrystallization, and the complex is decomposed to 4-methyl-3,5-heptadione by treatment with an alkaline agent.