MUNRO DAVID (GB)
| CH652113A5 | 1985-10-31 | |||
| EP0328116A1 | 1989-08-16 |
| 1. | 2 (4Tert .amylcyclohexyl) propan1ol. |
| 2. | The alcohol of claim 1, in the form of the cis isomer and/or the trans iso er. |
| 3. | The alcohol of claim 2, as a mixture of cis and trans isomers. |
| 4. | The alcohol of any one of the preceding claims, prepared by FC alkylation of benzene by isoamylene and propylene oxide, followed by catalytic reduction. |
| 5. | A perfume comprising the alcohol of any one of the preceding claims in an olfactively effective amount. |
| 6. | A perfume according to claim 5, wherein the alcohol is present in an amount of at least 0.01% by weight. |
| 7. | A perfume according to claim 6, wherein the alcohol is present in an amount of 0.1% 80% by weight. |
| 8. | A perfumed product comprising the alcohol according any one of claims 14 or a perfume according to any one of claims 57. |
Field of the Invention
This invention concerns a novel substituted 2-cyclohexyl- propan-1-ol and its use in perfumes and perfumed products.
Background of the invention
Various substituted 2-cyclohexyl-propan-1-ols are known in the perfumery literature. Thus, CH 652 113 (Firmenich) describes 2- (4-ter .butyl-cyclohexyl) -propan-1-ol and its use in perf mes. The compound has musky, woody and sandalwood odour notes and has a heavy and oriental character. The 4-isopropyl analogue is described in S. Arctander, Perfume and Flavor Chemicals as having a rosy, balsamic, mild, floral and woody odour. Dialkyl-substituted 2-cyclohexyl-propan-l-ols in which the alkyl groups are Cl- C4 are described in EP 0 328 116 as compounds with a woody, floral, vetiverol-like odour.
On the other hand, 1- (4-tert.alkyl-cyclohexyl) -ethanols and propan-1-ols are known from GB 1 476 720 as compounds with a sandalwood odour. It is noted therein that the lowest homologue 1- (4-tert .butyl-cyclohexyl) -ethanol (having 12 carbon atoms) has the highest odour strength and intensity and that the odour diminishes with increasing molecular weight. Compounds with more than 15 carbon atoms were considered to be too weak to have a detectable sandalwood odour.
Summary of the Invention
The present invention provides 2- (4-tert .amylcyclohexyl) - propan-1-ol of the formula below as well as perfumes and perfumed products comprising this compound in olfactively effective amounts.
Detailed description of the invention
The novel substituted 2-cyclohexyl-propan-l-ol of the invention is a powerful fragrance material with an odour which has the unusual combination of strong sandalwood and muguet odour notes. Thus, the odour is much fresher and less heavy than the odour of its tert.butyl homologue known from CH 652 113. Also, in view of what is described in GB 1 476 720, the odour is unexpectedly strong in spite of the fact that the compound has 14 carbon atoms. The unusual combination of odour notes provides new creative opportunities in perfumery.
The alcohol according to the invention may be used as such to impart, strengthen or improve the odour of a wide variety of products, or it may be used as a component of a perfume to contribute its odour character to the overall odour of such perfume. For the purposes of this invention a perfume is intended to mean a mixture of fragrance materials, if desired mixed with or dissoved in a suitable solvent or mixed with a solid substrate, which is used to impart a desired odour to the skin and/or any product for which an agreeable odour is indispensible or desirable. Examples of such products are: fabric washing powders, washing liquids, fabric softeners and other fabric care products; detergents and household cleaning, scouring and disinfection products; air fresheners, room sprays and pomanders; soaps, bath and shower gels, shampoos, hair conditioners and other personal cleansing products; cosmetics such as creams, ointments, toilet waters, preshave, aftershave, skin and other lotions, talcum powders, body deodorants and antiperspirants, etc.
Other fragrance materials which can be advantageously combined with the alcohol according to the invention in a perfume are, for example, natural products such as extracts, essential oils, absolutes, resinoids, resins, concretes etc., but also synthetic materials such as hydrocarbons, alcohols, aldehydes, ketones, ethers, acids, esters, acetals, ketals, nitriles, etc., including saturated and unsaturated compounds, aliphatic, carbocyclic and heterocyclic compounds.
Such fragrance materials are mentioned, for example, in S. Arctander, Perfume and Flavor Chemicals (Montclair, N.J., 1969) , in S. Arctander, Perfume and Flavor Materials of Natural Origin (Elizabeth, N.J., 1960) and in "Flavor and Fragrance Materials - 1991", Allured Publishing Co. Wheaton, 111. USA.
Examples of fragrance materials which can be used in combination with the alcohol according to the invention are: geraniol, geranyl acetate, linalol, linalyl acetate, tetrahydrolinalol, citronellol, citronellyl acetate, dihydromyrcenol, dihydromyrcenyl acetate, tetrahydro- myrcenol, terpineol, terpinyl acetate, nopol, nopyl acetate, 2-phenylethanol, 2-phenylethyl acetate, benzyl alcohol, benzyl acetate, benzyl salicylate, styrallyl acetate, benzyl benzoate, amyl salicylate, dimethylbenzyl-carbinol, trichloromethylphenylcarbinyl acetate, p-tert-butyl- cyclohexyl acetate, isononyl acetate, vetiveryl acetate, vetiverol, α-hexylcinnamaldehyde, 2-methyl-3- (p-tert- butylphenyl)propanal, 2-methyl-3- (p-isopropylphenyl) - propanal, 3- (p-tert-butylphenyl) -propanal, 2,4-dimethyl- cyclohex-3-enyl-carboxaldehyde, tricyclodecenyl acetate, tricyclodecenyl propionate, 4- (4-hydroxy-4-methylpentyl) - 3-cyclohexenecarboxaldehyde, 4- (4-methyl-3-pentenyl) - 3-cyclohexenecarboxaldehyde, 4-acetoxy-3-pentyl- tetrahydropyran, 3-carboxymethyl-2-pentylcyclopentane , 2-n-heptylcyclopentanone, 3-methyl-2-pentyl-2- cyclopentenone, n-decanal, n-dodecanal, 9-decenol-l, phenoxyethyl isobutyrate, phenyl-acetaldehyde dimethyl-
acetal, phenylacetaldehyde diethylacetal, geranyl nitrile, citronellyl nitrile, cedryl acetate, 3-isocamphyl- cyclohexanol, cedryl methyl ether, isolongifolanone, aubepine nitrile, aubepine, heliotropin, coumarin, eugenol, vanillin, diphenyl oxide, hydroxycitronellal, ionones, methylionones, isomethylionones, irones, cis-3-hexenol and esters thereof, indan musks, tetralin musks, isochroman musks, acrocyclic ketones, macrolactone musks, ethylene brassylate.
Solvents which can be used for perfumes which contain the alcohol according to the invention are, for example: ethanol, isopropanol, diethyleneglycol monoethyl ether, dipropylene glycol, diethyl phthalate, triethyl citrate, isopropyl myristate, etc.
The quantities in which the alcohol according to the invention can be used in perfumes or in products to be perfumed may vary within wide limits and depend, inter alia, on the nature of the product, on the nature and the quantity of the other components of the perfume in which the compound is used and on the olfactive effect desired. It is therefore only possible to specify wide limits, which, however, provide sufficient information for the specialist in the art to be able to use the alcohol according to the invention for his specific purpose. In perfumes an amount of 0.01% by weight or more of the alcohol according to the invention will generally have a clearly perceptible olfactive effect. Preferably the amount is 0.1 - 80% by weight, more preferably at least 1% . The amount of the alcohol according to the invention present in products will generally be at least 10 ppm by weight, preferably at least 100 ppm, more preferably at least 1000 ppm.
However, levels of up to about 20% by weight may be used in particular cases, depending on the product to be perfumed.
The alcohol occurs in a cis and a trans isomer, and the invention covers both separately as well as all mixtures thereof.
The alcohol may be conveniently prepared from 4-tert.amyl- cyclohexanone by reaction with triethyl-2-phosphono- propionate followed by catalytic reduction and reduction with LiAlH 4 . Alternatively it may be prepared by Friedel- Crafts alkylation of benzene with isoamylene followed by alkylation of tert .amylbenzene with propylene oxide and catalytic reduction of 2- (4-tert .amylphenyl) -propan-1-ol . The reaction products consist of a mixture of the cis and trans isomers, which may be separated by routine methods. However, for the use as fragrance material such separation is unnecessary.
Example 1
Synthesis of 2- (4-tert .amylcyclohexyl) -propan-1-ol
A) Synthesis of Ethyl 2- (4- tertiary-amyl-cyclohexylidenyl) - propionate
In a 2-litre 3-necked flask, equipped with mechanical stirrer, condenser with calcium chloride guard tube, thermometer, and pressure-equalised addition funnel triethyl-2-phosphonopropionate (75g, 0.315 mole) was added dropwise under nitrogen to a stirred solution of sodium ethoxide (freshly prepared from 7.5g sodium in 250ml ethanol) . A gradual temperature rise occurred during the addition, reaching 48 C C. 4-Tertiary-amylcyclohexanone (53g, 0.315 mole) was then immediately added dropwise, with stirring under nitrogen, over the course of a further hour. This was sufficient to maintain the reaction temperature between 45-50°C. Following complete addition, the reaction mixture was stirred for a further hour. A 1ml aliquot was quenched in 4ml of a l/l diethyl ether/water mixture, and the organic layer analysed by both TLC (silica stationary phase, chloroform eluent) , and by packed-column glc [SE52; 100-200C, 4C/min] . These indicated the reaction to be complete, glc recorded a 94.6% : 4.2% mixture of isomers, assigned cis- and trans-ethyl 2- (4- ertiary-amyl- cyclohexylidenyl) -propionate.
Most ethanol was removed under reduced pressure. The residue was partitioned between dichloromethane (500ml) and water (500ml) . The organic layer was separated, washed with water (500ml) and then dried over anhydrous magnesium sulphate. Flash chromatography of the organic residue gave a colourless oil (66. lg, 83%) . A sample was vacuum distilled to give a colourless oil, bp 98°C/l mbar.
B) Synthesis of Ethyl 2- (4- fcertiary-amylcyclohexyl) - propionate
Ethyl 2- (4- tertiary-amylcyclohexylidenyl)propionate (60. Og , 0.238 moles) was dissolved in ethanol (250ml) , within a 1 litre Buchi autoclave, and 5% Pd/C (6g) added. The reaction mixture was stirred at ambient temperature under a hydrogen pressure of 6bar for 6 hours, monitoring the reaction by packed-column glc (SE52; 100-200°C, 4C/minute) . At the end of this time, the reaction was complete to give ethyl 2- (4- tertiary-amylcyclohexyl)propionate as a mixture of three geometical isomers, retention times: 26.329min (3.2%) , 27.149min (7.5%) , 28.320min (87.0%) . The catalyst was removed by vacuum filtration through a bed of Celite, which was thoroughly washed with ethanol. Removal of solvent under reduced pressure gave a pale green oil, which was flash chromatographed (silica stationary phase, chloroform eluent) , to give the title compound as a colourless oil (54.9g, 91%) . Distillation under reduced pressure through a short Vigreux column gave a colourless oil, bp 100°C/ 1 mbar (47.8g, 79%) .
C) Synthesis of 2- (4- ertiary-amylcyclohexyl)propan-1-ol
In a 2 litre 3-necked flask, equipped with mechanical stirrer, condenser with calcium chloride guard tube, thermometer, and pressure-equalised addition funnel, ethyl 2- (4- tertiary-amylcyclohexyl)propionate (llOg, 0.43 moles) was added dropwise under nitrogen to a stirred suspension of lithium aluminium hydride (30g, 0.79 moles) in tetrahydrofuran (300ml) , maintaining the temperature below
30°C by ice-water cooling. After complete addition, the reaction mixture was cooled to 0°C and 50ml ethyl acetate was carefully added dropwise. This was followed by dropwise addition of 50 ml water, then 50ml 15% aqueous NaOH solution. The reaction mixture was vacuum-filtered through Celite, the Celite pad was thoroughly washed with 1 litre diethyl ether. The solvent was removed under reduced pressure to give a colourless oil (89.2g) . TLC (stationary phase: silica, eluent : CHC190%, ethyl acetate 10%) indicated a clean reaction. Flash chromatography (as TLC) gave a colourless oil (84.1 g, 91%) .
The product was further analysed by capillary glc (SE54; 25m x 0.2mm, d f 3.3 x 10 "7 m, 50-280°C, 3°C/min) . This suggested the two major products, acounting for 97% of the total, to be the cis- (6.5%) and trans- (90.2%) isomers of 2- (4- tertiary-amylcyclohexyl)propan-l-ol, M+ 212. The technique of gc-smelling indicated that the sandalwood odour was associated almost exclusively with these isomers, minor by¬ products having weak or indefinable odour.
Retention Time: min Area: % M+ Odour
47.711 1.373 188 very faint
49.901 6.529 212 sandalwood/muguet
50.675 90.160 212 sandalwood/muguet
54.915 0.924 212 faint,woody
13 C NMR (CDC1.)
66.757 (CH 2 0H) , 45.571 (CH (CH 3 ) CH 2 OH) , 40.962 (CHCH(CH 3 )CH 2 OH) , 39.728 (CH-C (CH 3 ) 2 C 2 H 5 ) , 34.746 (quaternary) , 33.025 (CH 2 ring) , 32.778 (CH 2 ring) , 30.264 (CH 2 , -amyl) , 27.336 (CH 2 ring) , 27.191 (CH 2 , ring) , 24.350 (CH 3 x2, t-amyl) , 13.686 (CH 3 ) , 8.355 (CH 3 ) .
Example 2
A sandalwood base with a fresh floral note was prepared according to the following recipe: relative amounts by volume
Karanal (Q) , 10% w/w in diethyl phthalate 10
Coumarin, 20% w/w in diethyl phthalate 10
Citronellol 7
Geranium bourbon 7 Phenylethyl alcohol 3
Patchouli, acid washed 2
Peru balsam oil 2 α-Ionone 2
Vetyver oil 1 Traseolide (Q) 1
Cinnamic alcohol 1
Jasmopyran 1
2- (4-Tert.amylcyclohexyl) -propan-1-ol 20
(Q) > fragrance materials marketed by Quest International, Ashford, Kent, United Kingdom