METHOD FOR THE MANUFACTURE OF a,ß-UNSATURATED KETONES

Abstract

A method for the manufacture of an α,β-unsaturated ketone, which method comprises oxidizing an alkene having —CH.sub.2— adjacent a carbon-carbon double bond to α,β-unsaturated ketone by passing air or oxygen through a solution of the hydrocarbon containing a catalyst consisting of N-hydroxyphthalimide (NHPI) and cobalt diacetate tetrahydrate at standard temperature and pressure during a period of at least 12 hours.

Claims

1. A method for the manufacture of an α,β-unsaturated ketone, which method comprises oxidizing an unsaturated hydrocarbon having —CH2- adjacent a carbon-carbon double band (“the alkene”) to α,β-unsaturated ketone by passing air or oxygen through a solution of the alkene containing a catalyst of N-hydroxyphthalimide (NHPI) and cobalt diacetate tetrahydrate at standard temperature and pressure during a period of at least 12 hours.

2. A method according to claim 1, comprising passing air through the solution at standard temperature and pressure during a period of at least 12 hours, for example, between 20 hours and 30 hours.

3. A method according to claim 1, wherein the alkene has between 4 and 30 carbon atoms, for example, between 5 and 20 carbon atoms or 10 and 15 carbon atoms.

4. A method according to claim 1, wherein the alkene is a straight- or branched-chain alkene having from 4 to 20 carbon atoms and formula: ##STR00005## wherein: R, R.sup.1 and R.sup.2 are independently hydrogen, a C1-Cs alkyl group, a C1-Cs alkenyl group or C6 or C10 aryl group; and R.sup.3 is a C1-Cs alkyl group, a C1-Cs alkenyl group or C6 or C10 aryl group.

5. A method according to claim 1, wherein the alkene comprises a 5- or 6-membered unsaturated carboxylic ring and has formula: ##STR00006## wherein: R is linked with R.sup.3, and R.sup.1 and R.sup.2 are each independently hydrogen, a C1-Cs alkyl group, a C1-Cs alkenyl group or a C6 or C10 aryl group and the unsaturated carbocyclic ring is optionally substituted by one or more of a bridging —CH2- group, a C1-Cs alkyl group, a C1-Cs alkenyl group, a C6 or C10 aryl group or fused with another 5- or 6-membered saturated carbocyclic ring which is optionally substituted by one or more of a C1-Cs alkyl group, a C1-Cs alkenyl group, a C6 or C10 aryl group; or R is linked with R.sup.3 and R.sup.1 is linked with R.sup.2 to form a 5- or 6-membered saturated carbocyclic ring fused with the 5- or 6-membered unsaturated carboxylic ring; and one or both of the carbocyclic rings being optionally substituted by a bridging —CH2- group, a C1-Cs alkyl group, a C1-Cs alkenyl group or fused with another 5- or 6-membered saturated carbocyclic ring which is optionally substituted by one or more of a C1-Cs alkyl group, a C1-Cs alkenyl group, a C6 or C10 aryl group.

6. A method according to claim 1, wherein the alkene is a hemiterpenoid, a monoterpenoid or a sesquiterpenoid.

7. A method according to claim 1, wherein the alkene is selected from the group of compounds consisting of: ##STR00007##

8. A method according to claim 1, wherein the alkene is valencene.

9. A method according to claim 1, wherein the solvent comprises one or more of methyl propyl ketone (MPK), methyl isopropyl ketone (MIPK), methyl butyl ketone (MBK) and methyl isobutyl ketone (MIBK), preferably wherein the solvent comprises methyl isobutyl ketone.

10. A method according to claim 1, wherein the amount of NHPI catalyst is less than 15% male equivalent of the alkene, preferably 12% male equivalent or less, more preferably 10% male equivalent or less.

11. A method according to claim 1, wherein the male ratio of cobalt diacetate tetrahydrate to NHPI catalyst is from 1:4 to 1:6, preferably about 1:5.

12. A method according to claim 1, wherein the amount of solvent is from 0.75 to 9.0 liters per kilogram of the alkene, preferably from 1 to 7.5 liters per kilogram, more preferably from 1 to 6 liters per kilogram.

13. A method according to claim 1, providing a conversion of the alkene greater than or equal to 70%.

14. A method according to claim 1, providing the α,β-unsaturated ketone substantially free from the corresponding alcohol.

15. A method according to claim 1, having a regioselectivity greater than 95%.

16. A method according to claim 1, further comprising quenching by water, extracting the α,β-unsaturated ketone into an organic solvent and washing the extract with 5 wt/wt % aqueous sodium hydroxide.

17. A method according to claim 1, wherein the α,β-unsaturated ketone is a fragrance compound.

18. A method according to claim 17, wherein the α,β-unsaturated ketone is nootkatone.

19. A method according to claim 1, adapted for manufacture of the α,β-unsaturated ketone on an industrial scale.

20. An industrial installation for manufacture of an α,β-unsaturated ketone according to the method of claim 1.

Description

[0073] The present invention will now be described in more detail with reference to the following non-limiting Examples and the accompanying drawings in which:

[0074] FIG. 1 is a scheme generally illustrating the chemical transformation of allylic oxidation of an alkene to an α,β-unsaturated ketone; and

[0075] FIG. 2 is a scheme illustrating aerobic oxidation of an alkene to an α,β-unsaturated ketone according to one embodiment of the present invention.

[0076] Referring now to FIG. 1, there is shown the allylic oxidation of an alkene having —CH.sub.2— adjacent a carbon-carbon double bond to an α,β-unsaturated ketone (R.sup.3 is an alkyl or aryl group). As may be seen, the allylic oxidation comprises a chemical transformation of the alkene providing for substitution of the two hydrogen atoms of the —CH.sub.2— adjacent the carbon-carbon double bond by a carbon-oxygen double bond.

[0077] The allylic oxidation is shown as being brought about by an aerobic oxidation over at least ten hours of a solution of the alkene using air and a catalyst comprising a mixture of NHPI and cobalt (II) acetate tetrahydrate without heating, i.e., at room temperature and at atmospheric pressure (viz., at standard temperature and pressure (STP)).

[0078] Referring now to FIG. 2, a similar aerobic oxidation is applied to the synthesis of the fragrance compound Nootkatone from Valencene (a sesquiterpene which is inexpensively obtained from Valencia oranges).

[0079] The synthesis of Nootkatone is achieved by an aerobic oxidation over twenty four hours of a solution of the alkene in methyl isobutyl ketone (MIBK) using air and a catalyst comprising a mixture of NHPI and cobalt (II) acetate tetrahydrate at room temperature and at atmospheric pressure (viz., at standard temperature and pressure (STP)).

[0080] The synthesis on laboratory and pilot plant scale is described in the following examples. In each case, the production of Nootkatone (and the absence of Nootkatol) was confirmed by .sup.1H and .sup.13C NMR spectroscopy with reference to library NMR spectra for Nootkatone.

EXAMPLE 1

Laboratory Scale

[0081] A stream of air was introduced into a stirred solution of N-hydroxyphthalimide (1.76 g, 0.01 mol, 0.1 eq), Co(OAc).sub.2 (0.58 g, 0.002 mol, 0.025 eq.) and (+)-valencene (20 g, 0.1 mol, 1 eq) in methyl isobutyl ketone (MIBK, 120 mL, f=6) in a 250 mL round-bottom flask at room temperature during a period of 24 hours and at a flow rate sufficient to create microbubbles.

[0082] The reaction was monitored by gas chromatography of aliquots of the solution to evaluate the conversion of (+)-valencene to (+)-nootkatone and the reaction quenched when the conversion reached the 70%. After removal of the air stream, the reaction mixture was washed twice with 50 ml of distilled water followed by once with 50 ml of 5% aqueous sodium hydroxide. The presence of nootkatone was confirmed by .sup.1H and .sup.13C NMR spectroscopy, and no nootkatol was detected.

EXAMPLE 2

Pilot Plant Scale

[0083] A stream of air was introduced into a stirred solution of N-hydroxyphthalimide (87.81 g, 0.489 mol, 0.1 eq), Co(OAc).sub.2 (29.5 g, 0.108 mol, 0.022 eq.) and (+)-valencene (1000 g, 4.89 mol, 1 eq) in methyl isobutyl ketone (MIBK, 3000 mL, f=3) in a 10 liter reactor at room temperature during a period of 24 hours and at a flow rate creating microbubbles.

[0084] The reaction was monitored by gas chromatography of aliquots of the solution to evaluate the conversion of (+)-valencene to (+)-nootkatone and the reaction quenched when the conversion reached 70%. After removal of the air stream, the reaction mixture was washed twice with 1000 ml of distilled water followed by one with 750 ml of 5% aqueous sodium hydroxide.

[0085] After removal of the MIBK solvent by vacuum distillation, rectification gave 694 g (65%) nootkatone. The (+)-nootkatone had 95% purity and was determined to be free from (+)-nootkatol.

[0086] It will be seen, therefore, that the present invention provides a method for the aerobic oxidation of alkenes to α,β-unsaturated ketones which is suitable to industrial scale. The method does not require oxygen or heating, and is carried out at atmospheric pressure so mitigating the risk of explosion and minimizing energy consumption as compared to the aforementioned methods.

[0087] The method uses less catalyst (in number and amount) as compared to the aforementioned methods and may use less solvent. It offers high conversion of alkene to α,β-unsaturated ketone and is highly selective and highly regioselective.

[0088] Low catalyst, low solvent, minimized energy consumption and high conversion, selectivity and regioselectivity mean that the method is highly suitable for use as a green (environmentally friendly) industrial process for the manufacture of fragrance compounds comprising α,β-unsaturated ketone.