Novel Derivatives of 6-Hydroxyhexanoates as Fragrance Ingredients

This invention is concerned with novel compounds of the formula ##STR1## wherein: R.sub.1 is chosen from the group consisting of alkyl radicals having one to four carbon atoms and alkenyl radicals having two to four carbon atoms, and

R.sub.2 is chosen from the group consisting of hydrogen, alkyl radicals having one to three carbon atoms, alkenyl radicals having two to three carbon atoms, methoxy and ethoxy.

The invention is also concerned with fragrance compositions containing these novel compounds of formula I and a process for the manufacture of the compounds.

The alkyl and alkenyl radicals represented by R.sub.1 and R.sub.2 can be normal straight-chain radicals or branched radicals. Typical examples of such radicals are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, vinyl, allyl, propenyl, methallyl, and the like. It should also be understood that formula I is intended to embrace all geometric isomers which are possible.

The compounds I have particularly valuable organoleptic properties and are especially useful as odorant substances. This invention is, therefore, also concerned with the use of the compounds as odorant substances.

Among the especially preferred compounds are ethyl 6-acetoxyhexanoate, ethyl 6-isobutyryloxy-hexanoate and allyl 6-propionyloxy-hexanoate. Also preferred are methyl 6-formyloxy-hexanoate, allyl 6-formyloxy-hexanoate, isobutyl 6-formyloxy-hexanoate, allyl 6-acetoxy-hexanoate, isobutyl 6-acetoxy-hexanoate and ethyl 6-ethoxycarbonyloxy-hexanoate.

The invention is also concerned with a process for the manufacture of the compounds I. Said process comprising the esterification of a compound of the formula

wherein R.sub.1 has the above significance.

The esterification of the alcohols II is carried out by using the usual acylating agents, e.g. acyl halides or acid anhydrides. The procedure using the acid anhydrides is preferred. The procedure using the acid anhydrides is preferably carried out in the presence of phosphoric acid. The reaction using acyl halides is preferably carried out in the presence of tertiary amines such as pyridine or N,N-dimethylaniline.

The carbonate esters I (R.sub.2 =methoxy or ethoxy) are manufactured in a manner similar to methods known in the art by reacting the alcohols II with chloroformic acid esters in the presence of tertiary amines such as pyridine or N,N-dimethylaniline.

The esters I are conveniently purified by distillation under reduced pressure. They are colorless to slightly yellow colored liquids. They are insoluble in water, but soluble in organic solvents such as e.g. alcohols, ethers, ketones, esters, hydrocarbons and halogenated hydrocarbons.

As mentioned above, the compounds of general formula I have particularly valuable organoleptic properties and are distinquished, in particular, by a combination of fruity notes and pronounced tenacity. They also can be used to intensify woody musk notes of odorant substance compositions without, at the same time, interfering with their individual odor.

Of particular interest are the raspberry notes, which are particularly pronounced in ethyl 6-acetoxy-hexanoate and ethyl 6-isobutyryloxy-hexanoate. While a number of substances having a raspberry odor are already known, e.g. piperonylacetone or p-hydroxybenzylacetone, these are, without exception, compounds which are many times more expensive to produce based on structural considerations.

It is a surprising and unexpected finding that in the case of ethyl 6-acetoxy-hexanoate and ethyl 6-ethoxycarbonyloxy-hexanoate the woody note characteristic of conventional raspberry compositions is now intensified and a pronounced fixative effect occurs without at the same time, having a detrimental effect on the fruity notes.

The other compounds of structure I are also distinquished by fruity notes, although in certain cases flowery side-notes are also noted. Of special interest are methyl 6-propionyloxy-hexanoate (narcissus) and isobutyl 6-acetoxy-hexanoate (after nerolidol).

Based on their olfactory notes, the compounds of formula I are particularly suitable for the intensification of fruity notes and as intensifiers of musk notes. Moreover, they are suitable for modifying an extremely wide range of known compositions, e.g.

(a) flowery compositions in which e.g. the warm musk notes are to be intensified (e.g. for men's colognes),

(b) chypre compositions (extract types, compositions of the feminine direction),

(c) tobacco and woody and fougere compositions (extract types of the masculine direction), and

(d) compositions with green notes, where especially a desired intensification and rounding-off and harmonizing effect are achieved.

As odorant substances the compounds of formula I are particularly suitable, in combination with a series of natural and synthetic odorant substances, such as e.g.

Such as angelica root oil, galbanum oil, vetiver oil, patchouli oil, sandalwood oil, mandarin oil, muscatel sage, ylang-ylang oil, cedar oil, pine oil, lavendar oil, bergamot oil, lemon oil, orange oil, coriander oil, oak moss, castoreum, ciste labdanum, calmus oil, geranium oil, jasmine absolute, rose oil, cassis absolute, narcissus absolute, verveine absolute, grapefruit extracts, etc.

Such as C.sub.10 -, C.sub.11 -, C.sub.14 -aldehyde, hydroxycitronellal, cyclamen aldehyde, benzaldehyde, p-tert.-butyl-.alpha.-methyl-hydrocinnamaldehyde, citral, citronellal, 2,6-dimethyl-5-hepten-1-al, isovaleraldehyde, trans-2-hexenal, trans-2-octenal, n-octanal, n-nonanal, trans-2-cis-6-nonadienal, 2,4-decadienal, methylnonyl-acetaldehyde, Cyclal C (1,3-dimethylcyclohex-1-ene 4(and 5)-carboxaldehyde), 3 and 4-(4-methyl-4-hydroxyamyl)-.DELTA.3-cyclohexenecarboxaldehyde, etc.

Such as alpha-ionone, beta-ionone, methylionone, allylionone, acetanisole, 4-(para-hydroxyphenyl)-2-butanone, camphor, menthone, carvone, pulegone, p-methylacetophenone, methyl amyl ketone, etc.

Such as phenylacetaldehyde dimethyl acetal, phenylacetaldehyde glycerine acetal, 2-methyl-1,3-dioxolan-2-ethyl acetate, caproic aldehyde dimethyl acetal, Acetal R (mixed acetal of acetaldehyde with phenylethyl alcohol and n-propanol), etc.

Such as eugenol methyl ether, methyl 1-methyl-cyclododecyl ether, anethol, estragol, rosantolene (methylethylsaligenin), etc.

Such as vanillin, eugenol, creosol, chavicol, etc.

Such as butanol, n-hexanol, cis-3-hexenol, trans-2-cis-6-nonadienol, cis-6-nonenol, linalool, geraniol, rhodinol, nerol, citronellol, nerolidol, farnesol, benzyl alcohol, phenylethyl alcohol, cinnamylalcohol, terpineol, Patchone (4-tert.-butylcyclohexanol), etc.

Such as ethyl formate, ethyl acetate, isoamyl acetate, t-butylcyclohexyl acetate, Myraldylacetat.RTM. (Givaudan), benzyl acetate, styrallyl acetate, ethyl .alpha.-methyl-phenylglycidate, maltyl isobutyrate, dimethylbenzylcarbinyl acetate and butyrate, linalyl acetate, isobutyl acetate, n-amyl butyrate, n-amyl valerate, ethyl palmitate, cinnamyl formate, terpenyl acetate, geranyl acetate, hexyl salicylate, linalyl anthranilate, amyl salicylate, methyl dihydrojasmonate, benzyl salicylate.

Such as .gamma.-undecalactone, .gamma.-decalactone, .gamma.-nonalactone, .delta.-decalactone, .delta.-octalactone, coumarin, etc.

Such as geranylic acid, citronellylic acid, cinnamic acid, phenylacetic acid, etc.

Such as p-menthane-8-thiol-3-one, dimethyl sulphide and other sulphides and disulphides, etc.

Such as methyl anthranilate, indole, isobutylquinoline, various pyrazines, 5-methyl-heptan-3-one oxime, nitromusk, etc.

Such as musk ketone, macrocyclic musk substances such as Musk 174.RTM. (12-oxahexadecanolide), Sandela (isocamphylcyclohexanol), polycyclic musk substances such as Fixolid, Galaxolid.

The compounds of formula I can be used in wide limits which can extend in compositions, for example, from 0.1 (detergents)-50% (alcoholic solutions). It will be appreciated that these values are not limiting values, as the experienced perfumer can also achieve effects with even lower concentrations or can synthesize novel complexes with even higher amounts. The preferred concentrations range between 0.5 and 20%. The compositions manufactured with compounds I can be used for all kinds of perfumed consumer goods (eau de cologne, eau de toilette, extracts, lotions, creams, shampoos, soaps, salves, powders, deodorants, detergents, air fresheners, etc).

The compounds I can accordingly be used in the manufacture of compositions and, as will be evident from the above compilation, a wide range of known odorant substances can be used. In the manufacture of such compositions the known odorant substances enumerated above can be used according to methods known to the perfumer, such as e.g. from W. A. Poucher, Perfumes, Cosmetics and Soaps 2, 7th Edition, Chapman and Hall, London, 1974.

240 g of ethyl 6-hydroxy-hexanoate are placed in a round flask which is provided with a dropping funnel, a thermometer and a stirrer. A mixture of 180 g of acetic anhydride and 3 g of 85% phosphoric acid is added dropwise thereto within a half hour while stirring. During the addition the temperature is held at 25.degree. C. by cooling. Thereafter, the reaction mixture is heated slowly to 50.degree. C. and held at this temperature for 3 hours. After cooling the mixture is treated with ice-water and taken up in 500 ml of hexane. The hexane solution is washed with water, with 100 ml of a 10% sodium carbonate solution and thereupon neutral with water. After drying over sodium sulphate the solvent is distilled off. 282 g of crude product are obtained. Fractional distillation gives 223 g (yield 73.7% of theory) of chemically pure ethyl 6-acetoxy-hexanoate; 190 g thereof can be used as an olfactorily pure product without further treatment.

Further acyloxy-hexanoates R.sup.2 COO(CH.sub.2).sub.5 COOR.sup.1 (I) are manufactured in an analogous manner starting from the hydroxyesters HO(CH.sub.2).sub.5 COOR.sup.1 (II).

The hydroxyesters HO(CH.sub.2).sub.5 COOR.sup.1 (II) are accessible from .epsilon.-caprolactone and the corresponding R.sup.1 -alcohol R.sup.1 OH in the presence of, e.g., sodium bisulphate (NaHSO.sub.4):

The novel products I and their properties are compiled in the Table A hereinafter.

160 g of ethyl 6-hydroxy-hexanoate, 145.4 g of N,N-dimethylaniline and 200 ml of anhydrous toluene are placed in a round flask which is provided with a dropping funnel, a thermometer and a stirrer. 119.4 g of ethyl chloroformate are added dropwise at 25.degree. C. within a half hour while stirring. The reaction mixture is held under reflux for 3 hours. After cooling the reaction mixture is poured on to ice-water, the organic phase is washed twice with water, with 100 ml of a 5% hydrochloric acid solution and then neutral with water. After drying over sodium sulphate the solvent is distilled off. 173 g of crude product are obtained. Fractional distillation gives 112 g (yield 48.3% of theory) of chemically pure ethyl 6-ethoxycarbonyloxy-hexanoate; 75 g thereof can be used as an olfactorily pure product without further treatment.

Further alkoxycarbonyloxy-hexanoates R.sup.2 COO(CH.sub.2).sub.5 COOR.sup.1 (I) with R.sup.2 =methoxy and ethoxy are manufactured in an analogous manner starting from the hydroxyesters HO(CH.sub.2).sub.5 COOR.sup.1 (II).

The novel products and their properties are compiled in Table B hereinafter.

When 100 parts of ethyl 6-acetoxy-hexanoate are added to the above generally fruity base, the fruity note is brought very clearly in the direction of apple. Moreover, the powdery-fruity note of the Galaxolid-Agrumex complex is underlined in an advantageous manner, which confers to the base a character which is very natural and which has good adhesion.

By the addition of 100 parts of ethyl 6-acetoxy-hexanoate the above base of general fruity character is brought in the direction of muskmelon. The lactone-like sweet note is clearly intensified, which confers to the base more volume and substantially improved tenacity.

An addition of 100 parts of ethyl 6-acetoxy-hexanoate produces in the above conventional apricot base the typical pronounced velvety-soft note of overripe apricots; the resulting formulation is already well suited for the perfuming of cosmetic preparations; in other words; the base which results is now a true, complete perfume base. In the case of the conventional apricot base this is not the case as, although it can also produce an apricot nuance in a composition, the sweet, velvety note of the ripe fruit is subsequently missing in the composition.

When 100 parts of ethyl 6-acetoxy-hexanoate are added to the above flowery-green base, there results a base which is very much greener, more powdery and substantially stronger in odour. The novel ester combines the musk and the green notes (Galaxolid-Acetal R) with one another very advantageously. The base is very well suited for the perfuming of cosmetic preparations.

By the addition of 10% of ethyl 6-acetoxy-hexanoate the herby-green note of the above base is clearly intensified. Ethyl 6-acetoxy-hexanoate underlines the somewhat powdery, spicy note of the basic composition in an unsuspected manner, which brings more warmth and volume to the base. The novel formulation can now be used very well for men's colognes.

On the other hand, in not one of the above bases A to E can the effects specified be realized by replacing ethyl 6-acetoxy-hexanoate by the same amounts of the structurally similar compounds diethyl adipate or 1,6-diacetoxyhexane.

The addition of 100 parts of ethyl 6-ethoxycarbonyloxy-hexanoate intensifies the fruity-hesperidin aspect of the base and confers remarkable freshness to the novel composition. Compared with the composition without the addition, the novel composition is quite clearly preferred.

An addition of 100 parts of ethyl 6-ethoxycarbonyloxy-hexanoate leads to an unequivocal preference for the thus-prepared novel composition, as in it the desired effect in the direction of apple can be recognized substantially clearer than in the original base without the addition. A desired stylizing of a primary general-fruity note is therefore brought about by the addition of the novel compound I, the strawberry aspect ("fraise pure") changing into an apple note. Furthermore, this effect is unexpected, as the novel compound I has a fruity smell in the direction of raspberry, and therefore rather an intensification of the fruity-berry like note would have been expected.

The addition of 100 parts of ethyl 6-ethoxycarbonyloxy-hexanoate to the above base is extraordinarily favourable from the organoleptic point of view, as the fruity-juicy melon character is thereby significantly accentuated.