Summary of the Invention In one aspect the invention provides an ether having the structure For brevity and simplicity, such materials are referred to herein as the"ether"or"ethers", the"novel ether"or"novel ethers"or the"ether of the invention"or"ethers of the invention".

The ether of the invention occurs in a number of different isomeric forms and the invention includes within its scope each individual isomer and also mixtures of two or more of the isomers.

The different isomers are as follows: (la) (1S, 2R, 4R) 4-(2-methylpropyl)-1- (1b)(1R,2S, 4S) 4-(2-methylpropyl)-1- methoxy-2-methylcyclohexane methoxy-2-methylcyclohexane (2a) (IS, 2S, 4R) 4-(2-methylpropyl)-1- (2b) (1R, 2R, 4S) 4-(2-methylpropyl)-1- methoxy-2-methylcyclohexane methoxy-2-methylcyclohexane (3a) (1R, 2S, 4R) 4-(2-methylpropyl)-1- (3b) (1S, 2R, 4S) 4-(2-methylpropyl)-1- methoxy-2-methylcyclohexane methoxy-2-methylcyclohexane (4a) (1R, 2R, 4R) 4- (2-methylpropyl)-l- (4b) (1S, 2S. 4S) 442-methylpropyl)-1- methoxy-2-methylcyclohexane-methoxy-2-methylcyclohexane The ethers of the invention, individually and collectively, exhibit interesting fragrance properties or odour characteristics, generally herbal, floral or buttery in nature, and so 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 (or fragrance composition) 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 dissolved 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 indispensable or desirable. Examples of such products are : fabric washing powders, washing liquids, washing tablets, 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 an ether 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 an ether 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, dimethylbenzylcarbinol, trichloromethylphenylcarbinyl acetate, p-tert-butyl- cyclohexyl acetate, isononyl acetate, vetiveryl acetate, vetiverol, a-hexylcinnamaldehyde, 2-methyl-3- (p-tert-butylphenyl) propanal, 2-methyl-3- (p-isopropylphenyl) propanal, 3- (p-tert-butylphenyl)-propanal, 2,4-dimethylcyclohex-3-enyl-carboxaldehyde, tricyclodecenyl acetate, tricyclodecenyl propionate, 4- (4-hydroxy-4-methylpentyl)- <BR> <BR> <BR> <BR> 3-cyclohexenecarboxaldehyde, 4- (4-methyl-3-pentenyl)-3-cyclohexenecarboxaldehyde, 4-acetoxy-3-pentyl-tetrahydropyran, 3-carboxymethyl-2-pentylcyclopentane, 2-n-heptyl- cyclopentanone, 3-methyl-2-pentyl-2-cyclopentenone, n-decanal, n-dodecanal, 9-decen-1-ol, phenoxyethyl isobutyrate, phenylacetaldehyde dimethyl acetal, phenylacetaldehyde diethyl acetal, geranyl nitrile, citronellyl nitrile, cedryl acetate, 3-isocamphylcyclohexanol, 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, macrocyclic ketones, macrolactone musks, ethylene brassylate.

Solvents which can be used for perfumes which contain an ether 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 an ether 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 ether 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 ether according to the invention for his specific purpose. In perfumes an amount of 0.01% by weight or more of the ether according to the invention will generally have a perceptible olfactive effect. Typically, the amount of the ether according to the invention in a perfume is from 0.01% to 25% by weight, preferably from 1% to 5% by weight. The amount of the ether according to the invention present in products will generally be from 1 to 10,000 ppm by weight, preferably from 10 to 1000 ppm, depending on the product to be perfumed.

In a further aspect the invention thus provides a perfume comprising an ether of the invention in an olfactively effective amount.

The invention also covers a perfumed product comprising an ether of the invention.

The ethers of the invention are also useful as intermediates in the preparation of other compounds, particularly other fragrance compounds. The ethers find particular application in the production of 3- (2-methylpropyl)-l-methylcyclohexanol (also known as 1-methyl-3- (2-methylpropyl) cyclohexan-1-ol) (as described in WO 98/47842), which is a very useful fragrance material, e. g. by a two stage process comprising as the first stage an elimination reaction performed on one or more of the ethers preferably together with one or more 4- (2- methylpropyl)-2-methyl-cyclohexanols (known alcohols as disclosed in WO 99/55811), e. g. using 4-methylbenzenesulphonic acid (pTSA) catalyst and cyclohexane solvent. This reaction results in production of a mixture of the three isomeric alkenes, 5- (2-methylpropyl)- 1-methyl-l-cyclohexene, 1-methylidene-3- (2-methylpropyl) cyclohexane and 3- (2- methylpropyl)-l-methyl-cyclohexene, as disclosed in our co-pending application under the reference C 81.02/Q. In the second stage, this mixture of alkenes is hydrated to produce 3- (2-methylpropyl)-1-methylcyclohexanol (1-methyl-3-(2-methylpropyl) cyclohexan-1-ol).

The invention also includes within its scope reaction products (direct or indirect) made from an ether of the invention, particularly 3- (2-methylpropyl)-l-methylcyclohexanol (1-methyl- 3- (2-methylpropyl) cyclohexan-l-ol).

This, in a further aspect, the invention includes within its scope a method of making an alkene comprising performing an elimination reaction on an ether of the invention to produce one or more alkenes, and preferably hydrating said one or more alkenes to produce one or more cycloalkanols typically having the following structure: where Rl represents a methyl or ethyl group, R2 represents hydrogen, R3 represents an ethyl, propyl, butyl, isobutyl or isoamyl group, R4 represents hydrogen and R5 represents hydrogen, or a methyl, ethyl, propyl, isobutyl or isoamyl group. Preferably the cycloalkanol is 3- (2-methylpropyl)-1-methylcyclohexanol.

Accordingly, the invention also includes within its scope a cycloalkanol, preferably 3- (2- methylpropyl)-l-methylcyclohexanol, produced by the above described method.

The ethers of the invention may be prepared by catalytic hydrogenation in typically a one pot conversion of 1- (4-methoxy-3-methylphenyl)-2-methyl-l-propanone to give 4- (2- methylpropyl)-l-methoxy-2-methylbenzene and then a mixture of the ethers together with 4- (2-methylpropyl)-2-methyl-cyclohexanols. If required, the ethers may be separated from the alcohol product using known techniques such as fractional distillation.

The ethers may alternatively be made by other routes, such as catalytic hydrogenation of 1- (4-methoxy-3-methylphenyl)-2-methyl-1-propanone to give 4- (2-methylpropyl)-l-methoxy- 2-methylbenzene which is separated from the reaction mixture and purified before a further catalytic hydrogenation reaction is carried out to give 4- (2-methylpropyl)-l-methoxy-2- methylcyclohexane, together with a small amount of 4- (2-methylpropyl)-2-methyl- cyclohexanol. The alcohol product may be removed from the ethers by the addition of boric acid to this hydrogenation reaction mixture, prior to purification of the ethers using known distillation techniques.

The resulting isomeric mixture may be used as such, either as a fragrance material or as an intermediate in preparation of other compounds. Alternatively the isomers may be separated, eg using known separation techniques such as chromatographic or distillation techniques. Isomers (other than enantiomers) may also be separated by derivatisation and crystallisation.

The invention will be further described, by way of illustration, in the following Examples.

Example 1, on a manufacturing plant scale, describes a 2 stage process for production of a mixture of ethers in accordance with the invention, mixed with 4- (2-methylpropyl)-2- methyl-cyclohexanols, followed by a two stage conversion to 3-(2-methylpropyl)-1- methylcyclohexanol. Example 2 describes an alternative route for production of the ethers of the invention on a laboratory scale.

Example 1 GC/GLC conditions utilised for analyses in the following Example: GC: Hewlett Packard HP 6890 Gas Chromatograph Column: HP-5 (SE54) 30m x 0.32mm (internal diameter) x 0.25pm df supplied by Hewlett Packard Carrier Gas: Hydrogen Solvent/Injection Volume: Acetone, 0.2111 Injector: 220°C, split 60: 1 Detector: FID, 280°C Temperature Prog.: 70°C (initial oven temperature), hold for 3 minutes, ramp at 10°C/min to 100°C, then ramp at 25°C/min to 280°C and hold for 4 minutes.

Stage 1. Friedel Crafts Acylation.

Experimental 1-methoxy-2-methylbenzene (methyl anisole) (261 kg, 98.6% pure, 2.109 kmol) and trifluoromethanesulphonic acid (triflic acid) (326g, 2.17 mol) (catalyst) were charged to a 1360 litre general purpose glass-lined reactor. The mixture was heated under nitrogen with stirring to a temperature of 150°C. Once at temperature, 1-methylpropanoic anhydride (365 kg, 2.31 kmol) was charged gradually to the reactor over a period of two hours while maintaining the reaction temperature at 150°C. The mixture was stirred for a further one and a half hours at this temperature. After cooling to 40°C the catalyst was neutralised with solid sodium carbonate (230 g, 2.16 mol) and the 2-methylpropanoic acid by-product was distilled off under reduced pressure (30 mBar) up to a pot temperature of 120°C. The resultant material was washed twice with a 5% w/w sodium carbonate solution (60 kg) to leave the crude product, 1- (4-methoxy-3-methylphenyl)-2-methyl-1-propanone, 93.9% pure by GC rpa. (385 kg, 1.88 kmol, 89.2% theoretical yield by analysis based on 1- methoxy-2-methylbenzene).

Distillation The crude material (381. 4 kg, 1.86 kmol) was purified by distillation under reduced pressure through a 5 theoretical plate packed column. The product, 1- (4-methoxy-3- methylphenyl)-2-methyl-1-propanone (345.5 kg, purity 97.7% rpa, 1.76 kmol) was collected at 137-140°C at 8mBar and crystallised on standing with a melting point of 22 °C. Thus, the overall yield of distilled product was 84.1% based on 1-methoxy-2- methylbenzene.

1-methoxy-2-1-methylpropanoic 1- (4-methoxy-3-methylphenyl)- 2-methylpropanoic acid methylbenzene anhydride 2-methyl-l-propanone Stage 2. Hydrogenation Experimental 1- (4-methoxy-3-methylphenyl)-2-methyl-1-propanone (60.0 kg, 97.3% pure by GC, 0.304 kmol) made as described above was charged to a high-pressure 100 litre reactor fitted with a stirrer and hydrogen supply. Distilled water (25.0 kg, 1.389 kmol), lactic acid co- catalyst, 85% aq. solution (2.0 kg, 18.9 mol) and hydrogenation catalyst (5% palladium on charcoal Type 87L paste ex Johnson Matthey, 1.2 kg) were charged to the reactor. After purging with nitrogen and hydrogen, for the first stage of hydrogenation, the stirring mixture was placed under a hydrogen atmosphere of 20 bar and taken to a temperature of 100°C over a period of 1 hr, maintaining the pressure of 20 bar gauge with the addition of more hydrogen gas. This temperature and pressure was maintained for a further hour until hydrogen addition effectively ceased (< 15 g/hr). For the second stage of hydrogenation, the pressure was raised to 48 bar gauge before heating to 140°C-150°C. This temperature and pressure was maintained for about 6-10 hours (with the reaction time depending on the quality of both the catalyst and feedstock) until hydrogen addition effectively ceased.

After cooling to room temperature the pressure was released and, after nitrogen purging, the mixture was filtered to remove the hydrogenation catalyst. The aqueous layer was separated from the crude product (55.4 kg).

Detailed GLC analysis of the crude product showed an isomeric mixture of 4- (2- methylpropyl)-l-methoxy-2-methylcyclohexanes and 4- (2-methylpropyl)-2- methylcyclohexanols constituting 93.3 % rpa of the product. According to this analysis, these desired products totalled 0.29 kmol, which corresponded to a 92.8% theoretical yield based on 1- (4-methoxy-3-methylphenyl)-2-methyl-l-propanone.

Distillation Distillation is not essential, but usefully the product ethers and alcohols are together separated from water, light heads and residues by a simple distillation up a short, packed column of about 5 theoretical plates: Typically, crude 4- (2-methylpropyl)-l-methoxy-2- methylcyclohexane/4- (2-methylpropyl)-2-methylcyclohexanol (55.4 kg, 93.3 % rpa pure by GC, 0.29 kmol) yielded an isomeric mixture of 4- (2-methylpropyl)-l-methoxy-2- methylcyclohexanes and 4- (2-methylpropyl)-2-methylcyclohexanols (52.4 kg, 96.0 % rpa pure by GC, 0.28 kmol) having a boiling range of 98-116°C/30 mBar.

1- (4-methoxy-3- 4- (2-methylpropyl)-1- 4- (2-methylpropyl)- 4- (2-methylpropyl)- methylphenyl)-2-methoxy-2-methylbenzene 1-methoxy-2-2-methylcyclohexanol methyl-1-propanone methylcyclohexane The ethers occur in a number of different isomeric forms as follows: (la) (IS, 2R, 4R) 4- (2-methylpropyl)-1- (lb) (1R, 2S, 4S) 4-(2-methylpropyl)-1- methoxy-2-methylcyclohexane methoxy-2-methylcyclohexane (2a) (I S, 2S, 4R) 4-(2-methylpropyl)-1- (2b) (1R, 2R, 4S) 4-(2-methylpropyl)-1- methoxy-2-methylcyclohexane methoxy-2-methylcyclohexane (3a) (1R, 2S, 4R) 4-(2-methylpropyl)-1- (3b)(1S, 2R, 4S) 4- (2-methylpropyl)-1- methoxy-2-methylcyclohexane methoxy-2-methycyclohexane (4a) (1R, 2R, 4R) 4- (2-methylpropyl)-1- (4b) (1S, 2S, 4S) 4- (2-methylpropyl)-1- methoxy-2-methylcyclohexane methoxy-2-methylcyclohexane The alcohols occur in a number of corresponding isomeric forms as follows: (5a) (IS, 2R, 4R) 4-(2-methylpropyl)-2- (5b)(1R, 2S, 4S) 4- (2-methylpropyl)-2- methylcyclohexanol methylcyclohexanol (6a) (IS, 2S, 4R) 4-(2-methylpropyl)-2- (6b) (1R, 2R, 4S) 4-(2-methylpropyl)-2- methylcyclohexanol methylcyclohexanol (7a) ( ! R, 2S, 4R) 4- (2-methylpropyl)-2- (7b) (IS, 2R, 4S) 4- (2-methylpropyl)-2- methylcyclohexanol methylcyclohexanol (8a) (1R, 2R, 4R) 4- (2-methylpropyl)-2- (8b) (t S, 2S, 4S) 4- (2-methylpropyl)-2- methylcyclohexanol methylcyclohexanol Stage 3. Elimination Experimental An isomeric mixture of 4-(2-methylpropyl)-1-methoxy-2-methylcyclohexanes and 4- (2- methylpropyl)-2-methylcyclohexanols (46.3 kg, 92.6 % rpa pure by GC, #0. 24 kmol) made as described above, 4-methylbenzenesulphonic acid monohydrate (pTSA catalyst) (1.4 kg, 7.4 mol) and cyclohexane (10.0 kg) were charged to a 100 litre glass-lined general purpose reactor. The stirred mixture was heated to a temperature of 150°C under a nitrogen atmosphere. The cyclohexane/water/methanol azeotrope was removed in the Dean & Stark, with the upper cyclohexane layer being returned to the flask. The quantity of cyclohexane was adjusted to maintain the flask temperature at 150°C-155°C. These conditions were maintained for 8 hours. After cooling to 40°C the mixture was washed twice with a 5% w/w sodium carbonate solution (9.0 kg) and dehydrated to leave the crude product 3- (2-methylpropyl)-l-methyl-l-cyclohexene/5- (2-methylpropyl)-l-methyl-l- cyclohexene (typically in the ratio 1: 2), 40.4 kg, 66.9 % rpa pure by GC (27.0 kg, 0.18 kmol) with trace amounts of 1-methylidene-3- (2-methylpropyl) cyclohexane, and unreacted starting materials 9.6 % rpa by GC (3.9 kg, 0.02 kmol). Thus, the chemical yield of this reaction was 75 % and the selectivity was 82 %.

Distillation The crude product (80.4 kg) from two such reactions, containing 64.5 % rpa pure by GC (0.34 kmol) of the desired alkenes was purified by careful fractional distillation under reduced pressure through a 30 theoretical plate packed column at a 20: 1 reflux ratio. The mixture of 3- (2-methylpropyl)-l-methyl-l-cyclohexene and 5- (2-methylpropyl)-l-methyl-l- cyclohexene was collected in the range 88-93°C/32-40mBar. The purified product (61 kg) contained 81.5 % rpa of the desired alkenes corresponding to a distillation yield of 96 %.

The product is a liquid at normal temperatures.

The unreacted starting materials remained in the distillation residues.

+methanol +H20 4- (2-methylpropyl)- 5- (2-methylpropyl)- 3- (2-methylpropyl)- 1-methoxy-2-1-methyl-1-1-methyl-1- methylcyclohexane cyclohexene cyclohexene <BR> 4- (2-methylpropyl)- 1-methylidene-3-<BR> 2-methylcyclohexanol (2-methylpropyl)<BR> cyclohexane Stage 4. Hydration Experimental A mixture of 3- (2-methylpropyl)-l-methyl-l-cyclohexene and 5-(2-methylpropyl)-1- methyl-1-cyclohexene (30.1 kg,"purity"82. 1 % rpa, 0.16 kmol) together with a small amount of 1-methylidene-3- (2-methylpropyl) cyclohexane, made as described above was charged to a 100 litre glass-lined general purpose reactor. 3-(2-methylpropyl)-1- methylcyclohexanol (0.3 kg, 1.76 mol) was added (this small amount of the desired end product acts as a phase transfer agent and helps the reaction initiate). The stirred mixture was cooled to-5°C and sulphuric acid, 76% w/w (20.4 kg, 0.158 kmol) was added slowly over 5 hours, maintaining the temperature in the range-6°C to-3°C. The stirred mixture was held at this temperature range for a further hour after the acid addition. The mixture was slowly added to water (80. 0 kg, 4.4 kmol) in a well-stirred quench vessel maintaining the temperature below 25°C, before separating the lower aqueous phase. The organic layer was washed with water (11.0 kg) while still maintaining the temperature below 25°C. The residual acid catalyst was neutralised by washing the reaction mixture with 5% sodium hydroxide solution (10.0 kg), maintaining a temperature below 30°C. The resultant product was washed twice with water (10.0 kg) at 50°C-55°C to leave the crude product (3- (2-methylpropyl)-l-methylcyclohexanol) (30.8 kg). GLC analysis showed that this crude product contained 52.55% rpa (0.095 kmol) of pure 3-(2-methylpropyl)-1- methylcyclohexanol, in the form of a mixture of trans and cis isomers. This corresponds to a chemical yield of 59.1 % based on 3- (2-methylpropyl)-l-methyl-l-cyclohexene/5- (2- methylpropyl)-1-methyl-1-cyclohexene.

Distillation The crude product (30.8 kg, 0.095 kmol) was purified by fractional distillation under reduced pressure through a packed column of about 15 theoretical plates. The product (3- (2-methylpropyl)-1-methylcyclohexanol (15.28 kg, 98.7 % by GC rpa, 0.089 kmol) was collected at 98-100°C, 15 mBar. This gave an overall yield of 55.1 % w/w of Perfumery Quality material based on 3- (2-methylpropyl)-l-methyl-l-cyclohexene/5- (2-methylpropyl)- 1-methyl-l-cyclohexene. The product, 3- (2-methylpropyl)-l-methylcyclohexanol was a mixture of approximately 35-45% cis, and about 55-65% trans isomers. The product may solidify on standing with a melting point of 20-25°C.

5- (2-methylpropyl)- 3- (2-methylpropyl)- 3- (2-methylpropyl)-<BR> <BR> <BR> l-methyl-l-l-methyl-l-l-methylcyclohexanol cyclohexene cyclohexene Example 2 Stage 1. Friedel-Crafts Acylation 1- (4-methoxy-3-methylphenyl)-2-methyl-1-propanone was prepared as outlined in Example 1.

Stage 2. Hydrogenation experimental 1-(4-methoxy-3-methylphenyl)-2-methyl-1-propanone (50.0g, 0.255mol) was charged to a high pressure 100ml reactor fitted with a stirrer and hydrogen supply. Distilled water (lO. Og, 0.556mol), lactic acid co-catalyst, 85% aq. solution (2.0g, 18.9mmol) and hydrogenation catalyst ( [5% palladium supported on carbon wet (40% w/w)]; l. Og) were then charged to the reactor. After purging with nitrogen and hydrogen, the stirring mixture was placed under a hydrogen atmosphere of 20 bar and taken to a temperature of 100°C, maintaining the pressure of 20 bar gauge with the addition of more hydrogen gas. This temperature and pressure were maintained until no more hydrogen addition was observed. After cooling to room temperature the pressure was released and, after nitrogen purging, the mixture was filtered to remove the hydrogenation catalyst. The aqueous layer was separated from the crude intermediate 4-(2-methylpropyl)-1-methoxy-2-methylbenzene).

The crude intermediate (4-(2-methylpropyl)-1-methoxy-2-methylbenzene) was separated from light heads and residues by simple distillation up a short, packed column.

The pure material (i. e. (4-(2-methylpropyl)-1-methoxy-2-methylbenzene), lO. Og, 0.05 mol) was returned to the high-pressure reactor. Fresh hydrogenation catalyst ( [essentially dry 5% rhodium supported on carbon] ; 0.2g), was then added to the reactor. After purging with nitrogen and hydrogen, the stirring mixture was placed under a hydrogen atmosphere of 50 bar and taken to a temperature of 50°C, maintaining the pressure of 50 bar gauge with the addition of more hydrogen gas. This temperature and pressure were maintained until no more hydrogen addition was observed. After cooling to room temperature the pressure was released and, after nitrogen purging, the mixture was filtered to remove the hydrogenation catalyst from the crude product (4-(2-methylpropyl)-1-methoxy-2-methylcyclohexane), which also contained small amounts of 4- (2-methylpropyl)-2-methylcyclohexanol.

Distillation Boric acid was added to the crude product prior to distillation to remove any alcohols. The product ethers were then separated from light heads and residues by simple distillation up a short, packed column