Process for preparing caryophyllene oxide

Abstract

The present invention relates to a method for oxidizing beta-caryophyllene with oxygen, in particular atmospheric oxygen, which avoids the use of catalysts, enzymes and solvents. Furthermore, the present invention provides a mixture comprising certain caryophyllene oxides as well as their use as a flavor and/or fragrance. The present invention also relates to products and semi-finished products comprising the mixture according to the invention.

Claims

1. A method for oxidizing beta-caryophyllene comprising: (i) reacting 60 to 95 wt. % of beta-caryophyllene and 2 to 20 wt. % of alpha-humulene with oxygen at a temperature of 80 to 150 C. without a catalyst, without an enzyme, and without a solvent for 10 to 60 hours, and forming a reaction mixture comprising compounds (1), (2), and (3), ##STR00004## wherein the reaction is carried out until a ratio of unreacted beta-caryophyllene to a sum of the compounds (1), (2), and (3) in the reaction mixture is 4:1 to 1:4 (unreacted beta-caryophyllene:sum of compounds (1), (2), and (3)); (ii) after carrying out the reaction of (i) and reaching the ratio of 4:1 to 1:4, heating the reaction mixture to a temperature of 110 to 150 C. until the reaction mixture has a peroxide value of less than 30 meq O/kg; (iii) distilling the reaction mixture to obtain a fraction comprising the compounds (1), (2), and (3); and (iv) optionally, crystalizing the fraction comprising the compounds (1), (2), and (3).

2. The method of claim 1, wherein pure oxygen or ambient air is supplied to the reaction in an amount of 10 to 1000 l/h per kg of educt.

3. The method of claim 1, wherein the reaction mixture is heated in (ii) for 1 to 3 hours.

4. The method of claim 1, further comprising adding a co-solvent to the reaction mixture before the distillation.

5. The method of claim 1, further comprising adding water to the fraction in a ratio of 4:1 to 2:1 (fraction:water) while stirring and subsequently removing the water by distillation.

6. The method of claim 1 comprising the crystallizing, wherein the fraction is crystallized using a mixture of alcohols with 1 to 3 carbon atoms.

7. The method of claim 1, wherein 85 to 95% of the beta-caryophyllene and 4 to 15% of the alpha-humulene are reacted.

8. The method of claim 7, wherein the reaction mixture comprises compounds (1), (2), (3) and (4) ##STR00005##

9. The method of claim 7, wherein the fraction comprises 75 to 90% of compound (1), 4 to 12% of compound (2), 0.1 to 5% of compound (3), and 0.1 to 5% of compound (4).

10. A method for oxidizing beta-caryophyllene comprising: (i) reacting 60 to 95 wt. % of beta-caryophyllene and 2 to 20 wt. % of alpha-humulene with oxygen at a temperature of 80 to 150 C. without a catalyst, without an enzyme, and without a solvent for 10 to 60 hours, and forming a reaction mixture comprising compounds (1), (2), and (3), ##STR00006## wherein the reaction is carried out until a ratio of unreacted beta-caryophyllene to a sum of the compounds (1), (2), and (3) in the reaction mixture is 4:1 to 1:4 (unreacted beta-caryophyllene:sum of compounds (1), (2), and (3)); (ii) optionally, heating the reaction mixture to a temperature of 110 to 150 C.; (iii) adding a co-solvent to the reaction mixture and then distilling the reaction mixture with the added co-solvent to obtain a fraction comprising the compounds (1), (2), and (3), wherein the co-solvent is polyethylene glycol and is added in a ratio of 3:1 to 1:1 (reaction mixture:polyethylene glycol); and (iv) optionally, crystalizing the fraction comprising the compounds (1), (2), and (3).

11. The method of claim 1 comprising: (i) reacting the beta-caryophyllene and the alpha-humulene with the oxygen at a temperature of 80 to 130 C. without the catalyst, without the enzyme, and without the solvent for 15 to 40 hours, and forming the reaction mixture comprising compounds (1), (2), and (3), ##STR00007## wherein the reaction is carried out until a ratio of the unreacted beta-caryophyllene to the sum of the compounds (1), (2), and (3) in the reaction mixture is 2:1 to 1:2 (unreacted beta-caryophyllene:sum of compounds (1), (2), and (3)); (ii) after carrying out the reaction of (i) and reaching the ratio of 2:1 to 1:2, heating the reaction mixture to the temperature of 110 to 150 C. until the reaction mixture has a peroxide value of less than 30 meq O/kg; (iii) adding a co-solvent of polyethylene glycol to the reaction mixture in a ratio of 3:1 to 1:1 (reaction mixture:co-solvent), and distilling the reaction mixture with the co-solvent to obtain the fraction comprising the compounds (1), (2), and (3), and (iv) optionally, crystalizing the fraction comprising the compounds (1), (2), and (3).

12. The method of claim 11, wherein the polyethylene glycol is PEG 600.

13. The method of claim 11, wherein the reaction mixture further comprises compound (4) ##STR00008##

14. The method of claim 13, wherein the fraction comprises: 75 to 90% of compound (1), 4 to 12% of compound (2), 0.1 to 5% of compound (3), and 0.1 to 5% of compound (4).

15. The method of claim 13, wherein the fraction comprises: 80 to 90% compound (1), 6 to 10% compound (2), 0.2 to 3% compound (3) and 0.5 to 3% compound (4).

16. The method of claim 13 comprising the crystallizing, wherein the fraction is crystallized using a mixture of an alcohol with 1 to 3 carbon atoms and water.

17. A method for oxidizing beta-caryophyllene comprising: (i) reacting 60 to 95 wt. % of beta-caryophyllene and 2 to 20 wt. % of alpha-humulene with oxygen at a temperature of 80 to 150 C. without a catalyst, without an enzyme, and without a solvent for 10 to 60 hours, and forming a reaction mixture comprising compounds (1), (2), and (3), ##STR00009## wherein the reaction is carried out until a ratio of unreacted beta-caryophyllene to a sum of the compounds (1), (2), and (3) in the reaction mixture is 4:1 to 1:4 (unreacted beta-caryophyllene:sum of compounds (1), (2), and (3)); (ii) optionally, heating the reaction mixture to a temperature of 110 to 150 C.; (iii) distilling the reaction mixture to obtain a fraction comprising the compounds (1), (2), and (3), wherein the distilling comprises adding a co-solvent of polyethylene glycol to the reaction mixture, and distilling the reaction mixture with the co-solvent to obtain the fraction comprising the compounds (1), (2), and (3); and (iv) optionally, crystalizing the fraction comprising the compounds (1), (2), and (3).

18. The method of claim 17, wherein the co-solvent of polyethylene glycol is added to the reaction mixture in a ratio of 3:1 to 1:1 (reaction mixture:co-solvent).

19. The method of claim 17, wherein the polyethylene glycol is PEG 600.

Description

EXAMPLE 1: OXIDATION OF CARYOPHYLLENE TO CARYOPHYLLENE OXIDE (LABORATORY SCALE)

(1) 1200 g of an enriched caryophyllene containing fraction from clove oil (comprising 89.3% beta-caryophyllene as well as 8.6% alpha-humulene) are gassed for 16 h at 120 C. with an amount of air of 180 Uh via a glass frit (160-250 m). After this time, a ratio of non-reacted caryophyllene to the sum of all formed caryophyllene oxides of 1.4:1 was reached. Subsequently, the mixture is stirred for 2 h at 125 C. without further addition of air to destroy peroxides formed before distillation. After this heating step, the PV is at <30 meq O/kg and 450 g PEG 600 is added to the mixture and distilled with a DN 30 distillation column with 20 theoretical trays. A vacuum of 1 mbar is applied and the sump temperature is slowly increased from 130 C. to 225 C. After removing a head fraction with a head temperature of 75-100 C., a main fraction (280 g) is obtained at a head temperature between 100-103 C. The main fraction comprises 78% caryophyllene oxid (1R,4R,6R,10S & 1R,4S,6S,10S or compounds (1) & (3)) as well as 12% isocaryophyllene oxide (compound (2)) and 10% epoxyhumulene (compound (4)). The main fraction is recrystallized with 140 ml isopropanol and 70 ml water, filtrated off at 0 C., washed with isopropanol/water (2:1) and dried until mass is constant. 185.3 g of the composition (84.6% (1R,4R,6R,10S)-caryophyllene oxide [CAS 1139-30-6] (compound (1)), 8.8% (1R,4R,6S,10S)-isocaryophyllene oxide [CAS 60594-22-1] (compound (2)), 1.8% (1R,4S,6S,10S)-caryophyllene oxide [CAS 103475-43-0] (compound (3)) 1.8% ((1R,3E,7E,11R))-epoxyhumulene [CAS 19888-34-7] (compound (4)) are obtained.

(2) Beispiel 2: Oxidation of Caryophyllene to Caryophyllene Oxide (Pilot Scale)

(3) 600 kg of an enriched caryophyllene containing fraction from clove oil (comprising 89.5% beta-caryophyllene as well as 8.2% alpha-humulene) are gassed for 30 h at 120 C. with an amount of air of 16 m.sup.3/h via a gap (1.2 mm). After this time, a ratio of non-reacted caryophyllene to the sum of all formed caryophyllene oxides of 1:2 was reached. Subsequently, the mixture is stirred for 2 h at 125 C. without further addition of air to destroy peroxides formed before distillation. After this heating step, the PV is at <30 meq O/kg and 280 kg PEG 600 is added to the mixture and distilled with a column with 20 theoretical trays. A final vacuum of 2 mbar is applied stepwise and the sump temperature is slowly increased to 170 C. After removing a head fraction with a head temperature of up to 105 C., a main fraction (180 kg) is obtained at a head temperature between 105-115 C. For sensory preparation, the main fraction is heated to 80 C. and 60 kg of water are added and subsequently distilled off at 500-100 mbar and 80-95 C. Subsequently, it is recrystallized with 300 l ethanol/water (2:1). The precipitate is pressed out at 5 C., washed with ethanol/water 2:1 and dried until mass is constant. 85.3 kg der of the composition (88.7% (1R,4R,6R,10S)-caryophyllene oxide [CAS 1139-30-6] (compound (1)), 8.1% (1R,4R,6S,10S)-isocaryophyllene oxide [CAS 60594-22-1] (compound (2)), 0.3% (1R,4S,6S,10S)-caryophyllene oxide [CAS 103475-43-0] (compound (3)) 1.3% ((1R,3E,7E,11R))-epoxyhumulene [CAS 19888-34-7] (compound (4)) are obtained.

(4) Beispiel 3: Sensory Evaluation of (1R,4R,6S,10S)-Isocaryophyllene Oxide (Compound (2))

(5) In an expert panel (n=5) the sensory impressions of the two main components are compared. To this end, a sample comprising 2 ppm caryophyllene oxide (>95% (1R,4R,6R,10S)-caryophyllene oxide [CAS 1139-30-6] (compound (1)) is compared to a sample, which comprises 2 ppm ioscaryophyllene oxide (>96% (1R,4R,6S,10S)-Isocaryophyllenoxid [CAS 60594-22-1] (compound (2)). The samples are each prepared on a 5% sugar solution. Compound (2) is evaluated as significantly more intense (5.5 to 4 on a scale to 10) than compound (1). Furthermore, the profile has stronger woody notes, which remind of grapefruit and nootkatone. Caryophyllene oxide is described as more terpenic.

(6) Beispiel 4: Sensory Evaluation of the Mixture According to the Invention from Example 2

(7) In an expert panel (n=6) the sensory impressions of the mixture according to the invention from example 2 are compared to currently commercially available caryophyllene oxide (>95% (1R,4R,6R,10S)-caryophyllene oxide [CAS 1139-30-6] (compound (1)). To this end, a sample of 2 ppm each of the substances to be compared are prepared on 5% sugar solution.

(8) TABLE-US-00001 mixture according (1R,4R,6R,10S)- to the invention caryophyllene oxide [CAS (example 2) 1139-30-6] (compound (1)) impact 5.5 4 woody 5 4 comments nootkatone, mango, cedar wood, adhesive perfumery

(9) Overall, the mixture according to the invention is described as more intense, also the further descriptors provide a preferable profile for the chosen applications compared to the previously obtainable quality.

WORKING EXAMPLES

(10) The amounts of the ingredients in the working examples are givenunless explicitly described otherwise for the respective examplein [g].

Working Example 1: Thyme AromaType White

(11) TABLE-US-00002 Ingredient amount in [G] camphene 9 carvacrol 40 cymol, para 216 eucalyptol 10 limonene, D 34 linalool 60 origanum oil 50 pinene, alpha laevo 15 pinene, beta 7 terpinene, gamma 32 terpineol, alpha 18 thymol 500 Mixture according to the invention 9 (example 2)

Working Example 2: Tooth Paste

(12) TABLE-US-00003 Part Ingredient amount in [G] A purified water 23.08 sorbitol (70%) 45.00 Solbrol M, sodium salt (Bayer AG, 0.15 p-hydroxybenzoic acid alkylester) trisodium phosphate 0.10 sodium monofluorophosphate 1.12 polyethylene glycol 1500 5.00 B Sident 9 (abrasive silicon dioxide) 10.00 Sident 22 S (thickening silicon dioxide) 8.00 sodium carboxymethylcellulose 0.90 titanium dioxid 0.50 C purified water 4.60 sodium laury sulfate 1.50 D thyme aroma - type white 0.05 (working example 1)

(13) The ingredients of parts A and B are premixed separately and well stirred together under vacuum at 25 to 30 C. for 30 min. Part C is premixed and added to parts A and B, D is added and the mixture is well stirred under vacuum at 25-30 C. for 30 min. After relaxation, the tooth paste is ready and can be filled.

Working Example 3: Carrot Aroma

(14) TABLE-US-00004 Ingredient amount in [G] acetyl methyl carbinol 8.00 aldehyde C6 0.80 aldehyde C8 0.70 aldehyde C10 0.70 bay oil 20.00 benzaldehyde 7.00 bisabolene, beta 35.00 caproic acid 8.00 caprylic acid 15.00 carene, delta-3 1.80 caryophyllene 95.00 mixture according to the invention 20.00 (example 2) Dimethyl sulfide 0.30 ionone, beta 9.50 isovaleric acid 5.00 carrot seed oil 45.00 palmarosa oil 3.00 vegetable oil triglycerides 350.00 pinene, beta 11.00 phellandrene 55.00 triacetin 309.20

Working Example 4: Melt Extrudate with Carrot Aroma

(15) TABLE-US-00005 Part Ingredient amount in [G] A emulsifier Dimodan HR 10.6 glucose syrup powder DE43-47 58.,2 caramelised sugar syrup powder ERC 16000 5 maltodextrin DE17-20 878.9 water 22.3 B carrot aroma 25 (working example 3)

(16) The matrix substances (part A) are mixed and put on an extruder. The aroma (part B) is then dosed in during the extrusion process.

(17) The melt extrudate obtained can for example be dosed into a dry green or black tea base at 50 g/kg.

Working Example 5: Mango Aroma

(18) TABLE-US-00006 Ingredient amount in [G] acetyl methyl carbinol 48.00 undecalactone, gamma 5.00 allyl caproate 3.20 bis(2-methyl-3-furfuryl)-disulfide 0.14 buchu leaf oil 0.25 caryophyllene 16.00 decalactone, gamma 16.00 dimethyl sulfide 32.00 dodecalactone, delta 3.20 ethyl acetate 100.00 ethyl butyrate 48.00 furaneol 32.00 cis-3-hexenol 130.00 cis-3-hexenyl acetate 12.00 hexenyl acetate 1.50 Isoamyl acetate 48.00 limonene D 115.00 linalyl acetate 16.00 mandarin oil (5fach) 5.00 L-menthyl acetate 8.00 menthyl furanthiol, 2, 3 0.02 myrcene 6.50 pinene, alpha laevo 16.00 triacetin 306.19 vanillin 16.00 mixture according to the invention 16.00 (example 1)

Working Example 6: Spray Dried Composition Type Mango

(19) TABLE-US-00007 Ingrdient amount in [KG] maltodextrin DE17-20 700 starch waxy corn Capsul 150 drinking water 1100 mango aroma 200 (working example 5)

(20) The drinking water is provided in a contained and the maltodextrin and the starch are dissolved therein. Subsequently, the aroma is emulsified into the carrier solution with a Turrax. The temperature of the spray solution should not exceed 30 C. The mixture is then spray dried (desired temperature inlet: 185-195 C., desired temperature outlet: 70-75 C.).

Working Example 7: Aroma Type Green Tea

(21) TABLE-US-00008 Ingredient amount in [G] aldehyde C6 1.0 geraniol 1.0 gerany lacetate 4.3 2-trans hexenal 18.5 3-cis-hexenol 7.0 3-cis hexenyl acetate 10.0 hexyl acetate 1.0 linalool L 14.5 linalool oxide 2.8 linalyl acetate 25.0 tocopherol, alpha 3.0 triacetin 883.4 wintergreen oil 25.0 mixture according to the invention 3.5 (working example 2)

Working Example 8: Aroma Type Grapefruit

(22) TABLE-US-00009 Ingredient amount in [G] acetyl methyl carbinol 8.000 aldehyde C10 6.500 ethanol 717.945 caproic acid 10.000 caryophyllene 25.000 citronella oil 6.000 decalactone, gamma 12.500 ethyl acetate 40.000 ethyl isovalerate 25.000 2-ethyl methyl butyrate 34.000 3-ethyl methyl thiopropionat 15.000 geraniol 4.000 grapefruit essential oil 20.000 3-cis hexenyl butyrate 20.000 lime oil (cold-pressed) 30.000 lime oil (distilled) 8.000 1,8-menthene thiol 0.005 methyl cinnamate 12.000 methyl thiobutyrate 0.350 nootkaton 0.700 mixture according to the invention 5.000 (working example 1)

Working Example 9: Aroma Type Orange

(23) TABLE-US-00010 Ingredient Einsatz in [G] acetaldehyde 0.50 acetaldehyde diethylacetal 1.00 aldehyde C6 1.50 aldehyde C8 6.00 aldehyde C9 0.90 aldehyde C10 10.00 aldehyde C12 0.50 caryophyllene 0.80 citral 6.00 citronellal 1.00 citronellol 0.50 ethyl butyrate 5.00 ethyl caproate 0.30 ethyl caprylate 0.10 2-ethyl methyl butyrate 0.10 geraniol 0.30 geranyl acetate 0.10 2-trans hexenal 1.50 3-cis hexenol 0.30 linalool L 10.00 nerol 0.90 nootkaton 1.00 orange oil 933.18 1-penten-3-one 0.02 sinensal 2.00 4-terpinenol 1.00 terpineol, alpha 2.50 valencene 12.00 mixture according to the invention 1.00 (working example 2)

Working Example 10: Sugar-Free Chewing Gum

(24) TABLE-US-00011 amount amount amount Part Ingredient in [G] in [G] in [G] A chewing gum base, Company 30.00 30.00 30.00 Jagum T B sorbitol, pulverised 38.45 38.45 38.50 Isomalt (Palatinit GmbH) 9.50 9.50 9.50 xylitol 2.00 2.00 2.00 mannitol 3.00 3.00 3.00 aspartame 0.10 0.10 0.10 acesulfame K 0.10 0.10 0.10 Emulgum (Colloides 0.30 0.30 0.30 Naturels, Inc.) C sorbitol, 70% 14.00 14.00 13.45 glycerol 1.00 1.00 1.00 D Symcool WS5 0.05 0.05 0.05 aroma type mango 1.50 1.00 (working example 5) aroma type grapefruit 1.50 (working example 8) aroma type orange 1.00 (working example 9)

(25) Parts A to D are mixed and kneaded intensively. The raw mass can be processed to ready-to-eat chewing gums e.g. in form of this strips.

Working Example 11: Fruit Gum

(26) TABLE-US-00012 amount amount amount Ingredient in [G] in [G] in [G] water 23.60 23.60 23.60 sucrose 34.50 34.50 34.50 glucose syrup, DE 40 31.89 31.89 31.89 Iso Syrup C* Tru Sweet 01750 1.50 1.50 1.50 (Cerestar GmbH) gelatine 240 Bloom 8.20 8.20 8.20 yellow and red dye 0.01 0.01 0.01 citric acid 0.20 0.20 0.20 aroma type mango 0.10 (working example 5) aroma type grapefruit 0.10 (working example 8) aroma type orange 0.10 (working example 9)

Working Example 12: Instant Beverage

(27) TABLE-US-00013 Ingrdient amount in [G] sugar (sucrose) ad 100 citric acid 12.00 trisodium citrate 0.70 tricalcium phosphate 0.60 vitamin C 0.66 Grindsted JU 543 Stabilizer System (Danisco) 0.90 saccharin 0.56 aroma type mango (spray dried) 1.10 (working example 6)

(28) 45 g of this instant beverage powder were each dissolved in 1000 mL while stirring.

Working Example 13: Carbonized Soft Drink

(29) TABLE-US-00014 amount amount amount Ingredient in [G] in [G] in [G] sugar (sucrose) 8 8 8 citric acid 0.15 0.15 0.15 aroma type mango 0.05 (working example 5) aroma type grapefruit 0.02 (working example 8) aroma type orange 0.10 (working example 8) drinking water ad 1000 ad 1000 ad 1000

(30) The ingredients were mixed in the stated order and filled up to 100% with water. The mixtures are filled into glass bottles and carbonized.