PROCESS OF PRODUCTION OF 7,8-DIHYDRO-C15-ALDEHYDE

Abstract

The present invention relates to a new method to produce 7,8-dihydro-C.sub.15-aldehyde.

Claims

1. A process for the production of a compound of formula (I) wherein the process comprises as a first step (step (1)) an ethynylation of the compound of formula (III) ##STR00011## and as a second step (step (2)) a Meyer-Schuster rearrangement.

2. Process according to claim 1, wherein step (1) is carried out by a Grignard reaction.

3. Process according to claim 1, wherein step (1) is carried out by a catalytic reaction step.

4. Process according to claim 3, wherein the ethynylation (step (2)) is carried out as following ##STR00012## wherein R is K or Cs, in the presence of NH3 as solvent.

5. Process according to claim 3, wherein the pressure in step (2) is in the range from 2 bar to 15 bar.

6. Process according to claim 3, wherein the reaction temperature step (2) is between −40° C.-10° C.

7. Process according to anyone claim 1, wherein the rearrangement (step (2)) is carried out by using at least one transition metal-based catalyst.

8. Process according to claim 7, wherein the rearrangement is carried out by using at least one Vanadium-based catalyst.

9. Process according to claim 1, wherein in step (2) the substrate to catalyst ratio is from 5000:1 to 10:1, preferably from 1000:1 to 20:1.

10. Process according to claim 1, wherein the rearrangement (step (2) is carried out in at least one non polar or polar aprotic organic solvent in the presence of at least one organic acid having a pK value in the range of about 4.0 to about 6.5.

11. Process according to claim 10, wherein the non polar or polar aprotic organic solvent is chosen from the group consisting of aliphatic, cyclic and aromatic hydrocarbons (such as C.sub.7-C.sub.10-alkanes, C.sub.5-C.sub.7-cycloalkanes, benzene, toluene naphthalene, paraffin oil) and carboxylate esters (such as ethyl acetate).

12. Process according to claim 10, wherein the organic acid is chosen from the group consisting of acetic acid, propionic acid, chloropropionic acid, pivalic acid, acrylic acid, adipic acid, phenylacetic acid, benzoic acid and 4-tert.butyl-benzoic acid.

13. Process according to claim 1, wherein the rearrangement (step (2)) is carried out at a reaction temperature of 10° C. to 50° C., preferably 20° C. to 40° C.

Description

EXAMPLES

Example 1a (step 1)

Ethynylation of 7,8-dihydro-β-ionone via Grignard Reaction

[0078] In a 350 ml flask flushed with argon, 6.48 g (30.0 mmol) of dihydro-β-ionone was dissolved in 130 ml of anhydrous tetrahydrofuran at 24° C. The solution was cooled to −65° C. to −75° C. Within 20 min 88.5 ml (44.25 mmol) of a 0.5 M solution of ethynyl magnesium bromide in THF were added drop-wise. After complete addition, the cooling bath was removed and the pale yellow solution was allowed to warm to room temperature. After 1 hour at 24° C. the reaction was complete and 50 ml of a saturated ammonium chloride solution was added. After stirring for another 15 min the pale yellow solution was transferred to a separation funnel, diluted with 100 ml of n-hexane, and subsequently washed with saturated sodium bicarbonate solution (1×100 ml), dist. water (2×100 ml) and brine (1×100 ml). The aqueous layers were re-extracted with 100 ml of n-hexane. The combined organic layers were dried over sodium sulfate, concentrated at 35° C. under reduced pressure, and the crude product was purified by column chromatography. The purified product was obtained as pale yellow oil in 82% yield and 84.5% purity.

Example 1b (step 1)

Catalytic ethynylation of 7,8-dihydro-β-ionone with acetylene in NH.SUB.3 ./KOH

[0079] A 2-litre autoclave was set under nitrogen atmosphere. 680 g (39.93 mol) of ammonia were added and cooled to 0° C. With stirring the autoclave was pressurized with acetylene to 8.06 bara. Then 15 ml of an aqueous KOH solution (44%) were added drop wise. After complete addition of the KOH solution, 354.45 g (1.766 mol, 96.8% purity of 7,8-dihydro-β-ionone were added drop wise. With addition of the ketone the reaction started. When the addition of 7,8-dihydro-β-ionone was finished, another 15 ml of a KOH solution (44%) were added. After 2 hours the reaction mixture was diluted with 200 ml of toluene and the ammonia was released. At 0° C. (0 barg), the reaction mixture was transferred from the reactor into a flask. The reactor was rinsed with 200 ml of toluene, which was also added to the flask. From the combined mixture the solid KOH was removed at 10° C. by filtration. After that the liquid layer was diluted with 500 ml of water. Also at 10° C. the biphasic mixture was adjusted to pH 7.0 by slow addition of acetic acid (50%). The layers were separated and the aqueous layer was extracted with toluene. The combined organic phases were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was obtained in 85.97% purity (qNMR) and 95.7% yield.

Example 2 (step 2)

Meyer-Schuster rearrangement of 7,8-dihydroethynol (3-methyl-5-(2,6,6-trimethylcyclohex-1-enyl)pent-1-yn-3-ol

[0080] In a 1-litre flask with magnetic stir bar and condenser, 105.4 g (440.5 mmol) of crude 7,8-dihydroethynol (92.1% purity) were dissolved under argon atmosphere in 450 ml of xylene. With stirring, subsequently 12.29 g (13.76 mmol, 3.1 mol %) of tris(triphenylsilyl)(V) vanadate and 897 mg (7.31 mmol, 1.7 mol %) of benzoic acid were added and the light-brown solution was heated to reflux in an oil bath. After stirring at this temperature for 4 hours, the solution was concentrated on a rotary evaporator at reduced pressure and 50° C. water-bath temperature. The crude product was obtained as dark-brown suspension in 82% yield (125.14 g, 63.5% purity) and purified by column chromatography. (E/Z)-3-methyl-5-(2,6,6-trimethyl-cyclohex-1-enyl)pent-2-enal was obtained in 78% yield (81.9 g) and 92.63% purity.