6-isopropyl-2,4-dimethylcyclohexen-1-ol compounds as fragrance ingredients

Abstract

The present invention refers to 6-isopropyl-2,4-dimethylcyclohexen-1-ol derivatives, to a method of their production, and fragrance compositions and fragranced articles comprising them.

Claims

1. A compound of formula (I) ##STR00002## wherein the dotted line between C-3 to C-4 together with the carbon-carbon bond forms a single bond and the dotted line between C-4 and C-5 together with the carbon-carbon bond forms a double bond; or wherein the dotted line between C-3 to C-4 together with the carbon-carbon bond forms a double bond and the dotted line between C-4 and C-5 together with the carbon-carbon bond forms a single bond.

2. The compound according to claim 1 selected from 6-isopropyl-2,4-dimethylcyclohex-3-en-1-ol, 6-isopropyl-2,4-dimethylcyclohex-4-en-1-ol, and mixtures thereof.

3. A method comprising utilizing a compound of formula (I) ##STR00003## wherein the dotted line between C-3 to C-4 together with the carbon-carbon bond forms a single bond and the dotted line between C-4 and C-5 together with the carbon-carbon bond forms a double bond; or wherein the dotted line between C-3 to C-4 together with the carbon-carbon bond forms a double bond and the dotted line between C-4 and C-5 together with the carbon-carbon bond forms a single bond; as fragrance, alone or in combination with a base material as a fragrance composition; the method comprising mixing the compound of formula (I) or fragrance composition directly, entrapped with an entrapment material, or bonded to a substrate adapted to release the compound upon application of an external stimulus, with a consumer product base.

4. A fragranced article comprising as odorant a compound of formula (I) as defined in claim 1, or a mixture thereof, and a consumer product base.

5. The fragranced article according to claim 4 wherein the consumer product base is selected from fine perfumery, household products, laundry products, fabric care products, body care products, cosmetic products and air care products.

6. A method of improving, enhancing or modifying a consumer product base comprising adding to the consumer product base an olfactory acceptable amount of a compound of formula (I) as defined in claim 1.

7. A fragrance composition comprising a compound of formula (I) as defined in claim 1 and at least one other compound selected from the group consisting of 2,4,7-trimethyloct-6-en-1-ol, 2,4,7-trimethylocta-2, 6-di en-1-ol, 2,4,7-trimethylocta-3, 6-dien-1-ol, 2,4,7-trimethyloctan-1-ol, and bis((3-methylbut-2-en-1-yl)oxy)methane.

8. The fragrance composition according to claim 7 wherein the compound of formula (I) is 6-isopropyl-2,4-dimethylcyclohex-3-en-1-ol.

Description

EXAMPLE 1

6-isopropyl-2,4-dimethylcyclohex-3-en-1-one

1a) Preparation of ethyl 6-isopropyl-2,4-dimethylcyclohex-3-ene-1-carboxylate

(1) Ethyl (Z)-4-methylpent-2-enoate (28.4 g, 0.2 mol) and (E)-2-methylpenta-1,3-diene (24.6 g, 0.3 mol) were placed in an autoclave. The reactor was sealed and heated to 200 C. for 20 h, the pressure reached 4.5 bar during the course of the reaction. The reaction mixture was distilled over a 10 cm Widmer column to afford ethyl 6-isopropyl-2,4-dimethylcyclohex-3-ene-1-carboxylate (13.47 g, 30% yield) as a colourless oil. Bp 78 C., 0.08 mbar.

1b) Preparation of (6-isopropyl-2,4-dimethylcyclohex-3-en-1-yl)methanol

(2) Ethyl 6-isopropyl-2,4-dimethylcyclohex-3-ene-1-carboxylate (6 g, 26.7 mmol) was dissolved in 30 ml hexane and cooled to 78 C. Diisobutylaluminum hydride (1M, 26.7 mmol) was added drop wise over 30 minutes, keeping the temperature below 65 C.

(3) The mixture was poured onto HCl 2M and extracted with ether to afford (6-isopropyl-2,4-dimethylcyclohex-3-en-1-yl)methanol (4.5 g, 95% yield) as a colorless liquid.

1c) Preparation of 6-isopropyl-2,4-dimethylcyclohex-3-ene-1-carbaldehyde

(4) Pyridinium chlorochromate (8.66 g, 40.2 mmol) and molecular sieve powder 4A (25 g) was suspended in dichloromethane (150 ml) and cooled to 10 C. with an ice bath. Crude (6-isopropyl-2,4-dimethylcyclohex-3-en-1-yl)methanol (4.5 g) was added to the cooled suspension and the mixture was then stirred at room temperature for 3 h. The suspension was diluted with hexane (250 ml) and the solids were filtrated and the solution concentrated in vacuum. The residue was distilled bulb-to-bulb (120 C., 0.5 mbar) to give 6-isopropyl-2,4-dimethylcyclohex-3-ene-1-carbaldehyde (4 g, 83% yield) as a colorless liquid.

1d) Preparation of (E/Z)-4-((6-isopropyl-2,4-dimethylcyclohex-3-en-1-ylidene)methyl)morpholine

(5) 6-Isopropyl-2,4-dimethylcyclohex-3-ene-1-carbaldehyde (2.2 g, 12.2 mmol) was placed in a distillation flask and toluene (20 ml) was added. Morpholine (1.3 g, 14.6 mmol) and para-toluene sulfonic acid monohydrate (23 mg, 0.12 mmol) was added and the mixture was refluxed over a Dean-Stark water separator for 2 h. The mixture was concentrated and the residue was purified by chromatography over aluminium oxide with hexane/MtBE 95:5 as the eluent. Pure (E/Z)-4-((6-isopropyl-2,4-dimethylcyclohex-3-en-1-ylidene)methyl)morpholine (1.8 g, 59% yield) was obtained as a colorless liquid.

1e) Preparation of (2R*,6S*)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-one and (2S*,6S*)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-one

(6) (E/Z)-4-((6-Isopropyl-2,4-dimethylcyclohex-3-en-1-ylidene)methyl)morpholine (1.47 g, 5.9 mmol) was placed in a reactor and acetonitrile (15 ml) was added. Cu(I)Cl (58 mg, 0.59 mmol) was added and oxygen was bubbled though the stirred mixture for 6 h at room temperature. The reaction mixture was diluted with ether and washed with water and brine. The organic solution was concentrated and the residue was separated by chromatography over SiO.sub.2 with hexane/MtBE as the eluent to yield rel-(2R,6S)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-one (100 mg, 10% yield) and rel-(2S,6S)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-one (300 mg, 31% yield) as single diasteromers.

EXAMPLE 2

6-isopropyl-2,4-dimethylcyclohex-3-en-1-ol

2.1 Preparation of rel-(1R,2R,6S)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-ol and rel-(1S,2R,6S)-6-isopropyl-2,4-dimethyloyclohex-3-en-1-ol

(7) Aluminum hydride (46 mg, 1.2 mmol) was suspended in THF (5 ml) and the mixture was cooled to 20 C. Compound rel-(2R,6S)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-one (90 mg, 0.5 mmol) was added in portions and the mixture was left to reach room temperature. The reaction mixture was treated with HCl 2M and extracted with ether. The organic layers were combined, washed and concentrated to afford rel-(1R,2R,6S)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-ol and rel-(1S,2R,6S)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-ol (80 mg, 79% yield) as a colorless liquid.

(8) .sup.1H-NMR rel-(1R,2R,6S)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-ol (600 MHz, C.sub.6D.sub.6): 5.22-5.21 (m, 1H); 3.64-3.69 (m, 1H); 2.25-2.20 (m, 1H); 1.99-1.94 (m, 1H); 1.81 (dd, J=16.9, 4.9, 1H); 1.71-1.63 (m, 1H); 1.66-1.61 (m, 1H); 1.59 (bs, 3H); 1.00 (d, J=7.2, 3H); 0.85 (d, J=7.2, 3H); 0.84 (d, J=6.8, 3H). .sup.13C-NMR rel-(1R,2R,6S)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-ol (150 MHz, C.sub.6D.sub.6): 132.1 (s), 125.4 (d), 70.8 (d), 40.7 (d), 35.2 (d), 29.4 (t), 26.4 (d), 23.5 (q), 20.6 (q), 17.2 (q), 16.4 (q).). MS (EI, tR 9.92 min.): m/z (relative intensity) 168 (5, [M]+), 107 (60), 106 (26), 91 (15), 83 (73), 82 (100), 71 (28), 67 (48), 55 (16), 43 (20), 41 (25)

(9) .sup.1H-NMR rel-(1S,2R,6S)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-ol (600 MHz, C.sub.6D.sub.6): 5.20-5.18 (m, 1H); 3.66 (bs, 1H); 2.11-2.06 (m, 1H); 1.79-1.74 (m, 2H); 1.74-1.70 (m, 1H); 1.59 (bs, 3H); 1.16-1.11 (m, 1H); 0.98 (d, J=6.4, 3H); 0.90 (d, J=6.8, 3H); 0.85 (d, J=7.2, 3H). .sup.13C-NMR rel-(1S,2R,6S)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-ol (150 MHz, C.sub.6D.sub.6): 132.8 (s), 123.6 (d), 70.7 (d), 46.7 (d), 39.2 (d), 30.4 (t), 29.1 (d), 23.7 (q), 20.9 (2q), 19.7 (q).

2.2 Preparation of rel-(1S,2R,6R)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-ol and rel-(1R,2R,6R)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-ol

(10) Aluminum hydride (80 mg, 2.1 mmol) was suspended in THF (5 ml) and the mixture was cooled to 20 C. Compound (2S*,6S*)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-one (320 mg, 1.9 mmol) was added in portions and the mixture was left to reach room temperature. The reaction mixture was treated with HCl 2M and extracted with ether. The organic layers were combined, washed and concentrated to afford a mixture of rel-(1 S,2R,6R)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-ol and rel-(1R,2R,6R)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-ol (280 mg, 79% yield) as a colorless liquid.

(11) .sup.1H-NMR rel-(1S,2R,6R)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-ol (600 MHz, C.sub.6D.sub.6): 5.07 (s, 1H); 3.03 (td, J=10.2, 5.3 Hz, 1H); 2.25-2.19 (m, 1H); 2.07-2.01 (m, 1H); 1.70-1.68 (m, 2H); 1.57 (bs, 3H); 1.57-1.53 (m, 1H); 1.06 (d, J=6.8 Hz, 3H); 0.88 (d, J=7.2 Hz, 3H); 0.81 (d, J=6.8 Hz, 3H). .sup.13C-NMR rel-(1S,2R,6R)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-ol (150 MHz, C.sub.6D.sub.6): 132.5 (s), 126.0, 75.5, 45.6, 40.5 (4d), 29.7 (t), 25.7 (d), 23.3, 20.7, 19.1, 15.5 (4q). MS (EI, tR 9.92 min.): m/z (relative intensity) 168 (6, [M]+), 125 (17), 107 (42), 83 (74), 82 (100), 71 (32), 67 (51), 55 (18), 43 (34), 41 (40), 39 (18)

(12) .sup.1H-NMR rel-(1R,2R,6R)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-ol (600 MHz, C.sub.6D.sub.6): 4.96 (s, 1H); 3.72 (bd, J=4.5, 1H); 2.13-2.07 (m, 1H); 1.83 (dd, J=17.7, 6.2, 1H); 1.72-1.65 (m, 1H); 1.68-1.64 (m, 1H); 1.57 (bs, 3H); 1.07-1.03 (m, 1H); 1.00 (d, J=7.2, 3H); 0.97 (d, J=6.4 Hz, 3H); 0.88 (d, J=7.2 Hz, 3H). .sup.13C-NMR rel-(1R,2R,6R)-6-isopropyl-2,4-dimethylcyclohex-3-en-1-ol (150 MHz, C.sub.6D.sub.6): 133.4 (s), 123.8 (d), 69.1 (d), 46.4 (d), 37.0 (d), 30.4 (t), 29.5 (d), 23.2 (q), 20.8 (q), 20.7 (q), 17.4 (q). MS (EI, tR 9.92 min.): m/z (relative intensity) 168 (8, [M]+), 125 (22), 107 (52), 106 (18), 83 (73), 82 (100), 71 (28), 67 (48), 55 (16), 43 (21), 41 (27)

EXAMPLE 3

Preparation of 2,4,7-trimethyloctan-1-ol

(13) An autoclave was charged with 2,4,7-trimethyloct-6-en-1-ol (15.0 g, 88 mmol) and 20% palladium on carbon (150 mg, 1% [w]). The autoclave was flushed with nitrogen and then pressurized to 40 bar with hydrogen. The hydrogenation was performed at 150 C. for 20 hours. After cooling to room temperature, the catalyst was removed by filtration and the product was purified by flash distillation (b.p. 85 C., 0.23 mbar) to afford 2 (11.5 g, 76% yield).

(14) .sup.1H-NMR (400 MHz, CDCl.sub.3) mixture of diastereomers ratio 1/1.3:3.59-3.34 (m, 4H); 1.61-1.81 (m, 4H); 1.56-1.39 (m, 4H); 1.33-1.04 (m, 10H); 0.97-0.80 (m, 26H). .sup.13C-NMR (100 MHz, CDCl.sub.3) mixture of diastereomers ratio 1/1.3:69.0, 68.0, 41.1, 40.7, 36.3, 36.2, 35.7, 34.3 (8t); 33.2, 33.1, 30.3, 30.2, 28.3 (6d); 22.9, 22.8, 22.6, 22.5, 20.4, 19.4, 17.3, 16.3.

EXAMPLE 4

Preparation of bis((3-methylbut-2-en-1-yl)oxy)methane

(15) A three neck flask, equipped with a Dean-Stark water separator, was charged with 3-methylbut-2-en-1-ol (40.0 g, 464 mmol), formaldehyde (17.43 g, 232 mmol, 40% in water), triethylamine hydrochloride (1.5 g, 11 mmol) and toluene (100 ml). The mixture was refluxed for 20 hours. The reaction mixture was cooled to room temperature and diluted with methyl tert.-butyl ether (100 ml). The organic solution was washed twice with water (50 ml) and with brine (50 ml), then dried over MgSO.sub.4 and concentrated. The crude product was purified by column chromatography and bulb-to-bulb distillation to give bis((3-methylbut-2-en-1-yl)oxy)methane (I) (6.0 g, 33 mmol, 14% yield).

(16) .sup.1H-NMR (300 MHz, CDCl.sub.3): 5.44-5.31 (m, 2H); 4.69 (s, 2H); 4.07 (br d, J=6.99 Hz, 4H); 1.76 (s, 6H); 1.70 (s, 6H). .sup.13C-NMR (75 MHz, CDCl.sub.3): 137.4 (2s); 120.6 (2d), 93.7 (t); 63.7 (2t); 25.7 (2q); 17.9 (2q).

EXAMPLE 5

Perfuming Composition (Unisex) to be Applied @ 1% in Shower Gel

(17) TABLE-US-00001 parts per Ingredient weight Dipropylene Glycol (DPG) 27 Hexyl acetate 17 Hexyl salicyclate 580 570 Javanol 1 Lilial (3-(4-(tert-butyl)phenyl)-2-methylpropanal) 200 Manzanate (ethyl 2-methylpentanoate) 3 Methyl Laitone (8-methyl-1-oxaspiro[4.5]decan-2-one ) 100 @ 10% TEC Methyl Pamplemousse 20 (6,6-dimethoxy-2,5,5-trimethylhex-2-ene) Milk Lactone (decenoic acid) 20 Nerolione (1-(3-methylbenzofuran-2-yl)ethan-1-one) 10 @ 10% TEC Paradisamined (2-ethyl-N-methyl-N-(m-tolyl)butanamide) 20 Pomarose (5,6,7-trimethylocta-2,5-dien-4-one) 1 Zinarine (2-(2,4-dimethylcyclohexyl)pyridine) 1 6-isopropyl-2,4-dimethylcyclohex-3-en-1-ol 0 10 TOTAL 1000 1000

(18) The accord above is a milky fruity accord to illustrate a juicy, over ripe fig with a clear milky facet. The addition of 10 parts of 6-isopropyl-2,4-dimethylcyclohex-3-en-1-ol results in an accord with more lift, with a natural fig leaf facet.