WO1994018150A1 - Hexanone derivates, their preparation and use - Google Patents

Abstract

Hexanone derivates have general formula (I), in which, independently, the residue R1 denotes hydrogen or a methyl group, the residues R?2 and R3¿ stand for hydrogen or an alkyl group with 1 to 3 C atoms, the residue R3 stands for hydrogen, an alkyl group with 1 to 3 C atoms or an alkoxy group with 1 to 3 C atoms, and the residues R?4 and R5¿ stand for hydrogen or a methyl group and in which: a) the positions C-7/C-8, C-8/C-9 or C-8/C-15 are either all linked by a C-C single bond or one of the positions C-7/C-8, C-8/C-9 or C-8/C-15 is linked by a C=C double bond, and the positions C-4/C-5 are either linked by a C-C simple bond or by a C=C double bond. These compounds constitute odoriferous substances with interesting nuances and great radiation.

Description

'' Hexanone derivatives, their preparation and use ¹

Field of the Invention

The invention relates to new hexanone derivatives of the general formula (I) specified below, a process for their preparation and their use as fragrances.

State of the art

Many natural fragrances are available in completely inadequate amounts, measured according to need. For example, 5,000 kg of rose petals are required to obtain 1 kg of rose oil; the consequences are a very limited world annual production and a high price. It is therefore clear that the fragrance industry has a constant need for new fragrances with interesting fragrance notes in order to supplement the range of naturally available fragrances and to make the necessary adaptations to changing fashionable tastes, as well as the constantly increasing need for odor improvers for everyday products To cover needs such as cosmetics and cleaning agents.

It is known from the literature that special derivatives of tetrahydroionol in which the C atoms are substituted in the immediate vicinity of the group —CH (OH) - alkyl have interesting olfactory properties (cf. EJBrunke et al., Dragoco Report 1980 , 199-203). Of particular importance are those derivatives in which the side chain of the tetrahydroionol is terminally extended by two carbon atoms; this compound, l- (2,6,6-trimethylcyclohexyl) hexan-3-ol, is the subject of two patent applications, see DE-0S 2807584 (Dragoco) and EP-PS 118817 (Firmenich). As a diastereomeric mixture, ie as a mixture of its ice and trans isomers, 1- (2,6,6-trimethylcyclohexyl) hexan-3-ol is known under the trade name "Timberol". Its smell is said to be powdery-woody, animal and its fixative properties are the subject of the above-mentioned German patent application (cf. KHSchulte-Elte et al., Helvetica Chiica Acta 1985 (68) 1961-1985). However, it has been demonstrated that only the trans compound has the stated odor designation for "Timberol"; the cis isomer, on the other hand, has an indefinably floral note of low intensity (see KHSchulte-Elte, loc. cit.). It is therefore not surprising that not only the diastereomer mixture is commercially available, but also the trans isomer itself ("norlimbanol"; see KHSchulte-Elte, loc. Cit.).

The different odor profiles of eis and trans-l- (2,6,6-trimethylcyclohexyl) hexan-3-ol are an example of the phenomenon familiar to the person skilled in the art in the field addressed here, that slight changes in a certain basic structure are starch and drastically change the smell quality of a fragrance.

German patent application DE-OS 2442024 (BASF AG) discloses unsaturated ketones which are obtained by reacting alpha-ionone or a methyl homologue thereof with a vinyl magnesium halide. In this Grignard reaction, a vinyl group is introduced into the starting materials. According to the description of DE-OS 2442024, the vinyl-substituted ketones have fragrance properties which - at least in one component - are similar to those of the ketones from which they were produced. The other component is described as sweet, dry and "towards" amber.

Description of the invention

From the relationships described above it becomes clear that there is generally a constant need for synthetic fragrances which can be produced cheaply and with a constant quality and which have desired olfactory properties, ie which have pleasant, near-natural and qualitatively novel odor profiles of sufficient intensity and are able to advantageously influence the fragrance of cosmetic and consumer goods. We therefore searched for compounds that should have characteristic, new odor profiles with high adhesive strength, odor intensity and radiance.

It has now been found that the compounds of the general formula (I) meet the above requirements excellently in all respects and can advantageously be used as fragrances with differently nuanced odor notes with good adhesive strength. In this context, it should be pointed out that the compounds (I) according to the invention differ in their odor profiles in a more characteristic manner from the above-mentioned tetrahydroionol derivatives known from the prior art, which could be regarded as structurally related in a strongly classifying view Differentiate way.

The present invention therefore relates to hexanone derivatives of the general formula (I)

in which independently of one another the radical R * is hydrogen or a methyl group, the radical R2 is hydrogen or an alkyl group with 1 to 3 C atoms, the radical R3 is hydrogen, an alkyl group with 1 to 3 C atoms or an alkoxy group with 1 to 3 C atoms Atoms and the radicals R ^ and R5 are hydrogen or a methyl group and where

(a) positions C-7 / C-8, C-8 / C-9 or C-8 / C-15 are either all linked by a CC single bond or one of positions C-7 / C-8, C -8 / C-9 or C-8 / C-15 is linked by a C = C double bond and (b) positions C-4 / C-5 are linked either by a CC single bond or by a C = C double bond.

In a preferred embodiment of the invention, the radical R * is hydrogen. In a further preferred embodiment, the radicals R2 and R3 are hydrogen, methyl or ethyl, hydrogen and methyl again being very particularly preferred.

It has also been found that within the compounds (I) claimed according to the invention, those in which one of the positions C-7 / C-8, C-8 / C-9 or C-8 / C- 15 is linked by a C = C double bond. Within this group, those compounds (I) are of greatest importance in which the positions C-4 / C-5 are additionally linked by a C-C single bond, i.e. where the side chain of the six-ring is saturated. An example of this is 4- (2,6,6-trimethylcyclohex-1-en-1-yl) -heptan-2-one, the odor profile of which can be described as a strongly woody, cedar, Boisambrene forte note.

The new compounds (I) are prepared by conventional synthetic methods of organic chemistry. However, a process is particularly preferred in which allyl alcohols of the general formula (II)

wherein the radicals Rl, R ^ and R5 are hydrogen or a methyl group, and one of the positions Ca / Cb, Cb / Cc or Cb / Cd is linked by a C = C double bond, with a corresponding enol ether or an appropriate orthoester and, if desired, the C = C double bonds present in the compounds (I) obtained are partially or completely hydrogenated. In the process according to the invention which is preferred for the preparation of the hexanone derivatives (I), an acetal is initially formed which, after splitting off a molecule of alcohol - also intermediately - changes into a vinylallyl ether which is in a [3,3] sigmatropic U storage according to Claisen leads to the corresponding compound (II). KC Brannock developed this type of reaction based on special allyl alcohols and isobutyraldehyde in J.Am.Chem.Soc. 1959, 81, 3379. The reaction of the allyl alcohol with the aldehyde is generally carried out in the presence of a catalytically effective amount of an acid, for example a sulfonic acid, carboxylic acid or Lewis acid.

The C = C double bonds of the hexanone derivatives (I) obtained primarily by Claisen rearrangement can, as already mentioned, be further hydrogenated if desired. It has been found that the hydrogenation of the C = C double bonds linking positions C-4 / C-5, C-8 / C-9 and C-8 / C-15 of the hexanone derivatives (I) can generally be carried out under the standard conditions for hydrogenations known to the person skilled in the art; Standard conditions are understood to mean that the compound to be hydrogenated is brought into contact with hydrogen in a solvent at elevated pressure and elevated temperature and in the presence of a catalyst such as Pd / carbon. The hydrogenation of a C = C double bond of the six-membered ring connecting the C-7 / C-8 positions, on the other hand, requires more drastic conditions and / or the use of special hydrogenation catalysts such as are customary for the hydrogenation of aromatic compounds. The fact that the C = C double bonds have different affinities for the addition of hydrogen opens up the possibility, desired according to the invention, of selectively carrying out a partial or complete hydrogenation of the C = C double bonds present by choosing the reaction conditions.

The compounds of the general formula (II) can be obtained in a simple manner by adding ionones, irones or their corresponding alkyl derivatives (which, depending on the position of the C CC double bond in the six-membered ring, in their alpha-, beta- or may be in the a-form) by reduction of their carbonyl group with approximately complex hydrides into the corresponding allyl alcohols. The hexanone derivatives (I) according to the invention have remarkable odor properties. Another object of the invention is therefore the use of the compounds of general formula (I) as fragrances.

The compounds (I) in which R3 denotes a methyl group are distinguished by a woody odor which, due to its strong notes of sardwood and vetiver, stands out from the large number of natural and synthetic wood notes available to the perfumer.

In perfume compositions, the compounds (I) enhance the harmony and charisma as well as the adhesion, the dosage being matched to the desired fragrance note, taking into account the other constituents of the composition.

The olfactory profiles of the hexanone derivatives (I) were unpredictable in their complexity and the multitude of their shades and are thus further confirmation of the general experience that the olfactory properties of known fragrances do not allow any conclusions to be drawn about the properties of structurally related compounds, because neither Mechanism of fragrance perception and the influence of the chemical structure on the fragrance perception have been sufficiently researched, so it cannot normally be predicted whether a changed structure of known fragrances will change the olfactory properties and whether these changes will be assessed positively or negatively.

Because of their odor profile, the compounds of the formula (I) are particularly suitable for modifying and enhancing known compositions. In particular, their very strong power to fix volatile fragrances should be emphasized, which generally contributes to the refinement of the composition.

The compounds of formula (I) can be combined with numerous known fragrance ingredients, for example other fragrances of natural, synthetic or partially synthetic origin, essential oils and plant extracts. The range of natural fragrances can include both volatile and moderately volatile components and that of synthetic fragrances include representatives from practically all classes of substances. Examples are:

(a) Natural products such as tree moss absolute, basil oil, bay oil, agricultural oils such as berga ott oil, mandarin oil, etc., Elemi resin, mastic absolute, myrtle oil, palmarosa oil, patchouli oil, petitgrain oil, wormwood oil, myrrh oil, olibanum oil

(b) alcohols such as farnesol, geraniol, linalool, nerol, phenylethyl alcohol, rhodinol, cinnamon alcohol, Sandalore [3-methyl-5- (2.2.3-trimethylcyclopent-3-en-l-yl) pentan-2-ol] , Sandela [3-isocamphyl- (5) -cyclohexanol],

(c) aldehydes such as citral, HelionalR, α-hexylcinnamaldehyde, hydroxycitronellal, Lilial ^R [p-tert-butyl-α-methyldihydrocinnamaldehyde], methylnonyl acetaldehyde,

(d) ketones such as allyl ionone, α-ionone, β-ionone, isoraldein, methyl ionone,

(e) esters such as allylphenoxyacetate, benzyl salicylate, cinnamyl propionate, citronellyl acetate, citronellyl ethoxylate, decyl acetate, dimethylbenzylcarbyl acetate, ethyl acetoacetate, hexenyl isobutyrate, linalyl acetate, methyl dihydrojasate acetate, vyliveryl acetate, vyliveryl acetate, vyliveryl acetate, vyliveryl acetate, vyliveryl acetate, vyliveryl acetate, vyliveryl acetate, vyliveryl acetate, vetyl acetate,

(f) lactones such as gam a-undecalactone, l-0xaspiro [4.4] nonan-2-one, as well as various other components often used in perfumes ^* e, such as ketone musk, indole, p-menthan-8-thiol-3-one, Methyleugeno1, Ambroxan.

Also noteworthy is the way in which the compounds of structure (I) round off and harmonize the olfactory notes of a wide range of known compositions, but without dominating in an unpleasant manner. Those hexanone derivatives (I) in which the radicals R 1, R 2, R and R 5 are hydrogen and R 3 are a methyl or ethoxy group are particularly noteworthy in this regard.

The compounds according to the invention contain centers of chirality, so that these compounds can exist in different spatial forms. In the context of conventional syntheses, the compounds according to the invention are obtained as mixtures of the corresponding isomers and are used as such as fragrances. However, it may also be desirable to separate the diastereomer mixtures, for example chromatographically, into their individual components and to use the corresponding isomers as such. The usable proportions of the compounds according to the invention or their mixtures in fragrance compositions range from 1 to 70 percent by weight, based on the mixture as a whole. Mixtures of the compounds (I) according to the invention and compositions of this type can be used for perfuming cosmetic preparations such as lotions, creams, shampoos, soaps, ointments, powders, aerosols, toothpastes, mouthwashes, deodorants as well as in alcoholic perfumery (eg Eaux de Cologne , Eau de toilette, extras) can be used. There is also an application for perfuming technical products such as detergents and cleaning agents, fabric softeners and textile treatment agents or tobacco. To perfume these various products, the compositions are added to them in an olfactory effective amount, in particular in a concentration of 0.05 to 2 percent by weight, based on the entire product. However, these values should not represent any limit values, since the experienced perfume can achieve effects with even lower concentrations or can build up new complexes with even higher doses.

The following examples are intended to explain the subject matter of the invention and are not to be interpreted as restrictive.

B e i s p i e l e

1. Preparation of the precursors for the compounds according to the invention

Educt A: alpha-ionol

Execution: 19 g of sodium boranate were suspended in 200 ml of absolute ethanol in a 1-1 three-necked flask and 96 g of alpha-ionone (from Haarmann &Reimer; beta-ionone content: approx. 4%) were continuously added with stirring at room temperature dripped. After the weakly exothermic reaction had subsided, the mixture was refluxed for three hours and the mixture was then allowed to cool.

Work-up: The cooled reaction mixture was poured onto ammonium chloride / ice and extracted with ether. The organic phases were dried over sodium sulfate, filtered and concentrated. The distillation via Kugelrohr gave 77 g of ionol (73% of theory). The purity was determined by gas chromatography to be 92.4%.

Characterization: The IR spectrum of the product (film on NaCl) showed absorption bands at 3336 (-0H), 2962, 1451, 1382 and 1364 (geminal dimethyl groups), as well as at 1064 (C-0) cm ^-1 .

2. Preparation of the compounds according to the invention

Example 1: 4- (2 _f 6 _f 6-trimethylcyclohex-l-en-l-yl) -hept-5-en-2-one

This example illustrates the preparation of the compounds (I) according to the invention by Claisen rearrangement in the course of the reaction of an allyl alcohol with the enol ether of acetone.

Execution: 291 g (1.5 mol) beta-ionol (which had been prepared starting from beta-ionone - analogously to that described for starting material A) and 122.4 g (1.7 mol) 2 were in a reciprocating stirred autoclave -Methoxypropen together with 60 g cyclohexane and 3 g propionic acid heated for six hours under 10 bar nitrogen atmosphere at 190 ° C (autogenous pressure: 30 bar).

Workup: The reaction mixture was allowed to cool, the autoclave was let down and then the solvent was distilled off. The remaining residue of 325 g was distilled over on a Vigreux column. At top temperatures of 87-88 ° C / 0.06 mbar, 114.7 g of main run were obtained (28% of theory; GC purity: 96%).

Characterization: The IR spectrum of the product (film on NaCl) showed absorption bands at 2955, 2926, 2863, 1719 (C = 0), 1455, 1361, 1161 and 965 cm ^{* 1} .

Smell: cassis note, woody

Example 2; 4- (2,6,6-trimethylcyclohex-1-en-1-yl) -heptan-2-one

This example illustrates the largely selective hydrogenation of the C = C double bond of the compound according to Example 1.

Execution: 46.8 g (0.2 mol) of the compound according to Example 1 were dissolved in 100 g of ethanol and placed together with 2.5 g of Pd / C (5% palladium on activated carbon) in a hydrogenation autoclave. The mixture was hydrogenated at 80 ° C. and 20 bar hydrogen pressure for 2.5 hours.

Working up: For working up, the catalyst was filtered off from the reaction mixture, the solvent was stripped off and the residue of 44.8 g was fractionated on a rotating column column in a high vacuum. At head temperatures of 77-78 ° C / 0.03 mbar, 37.9 g of main run were obtained (67% of theory; GC purity: 87%).

Characterization: The IR spectrum of the product (film on NaCl) showed absorption bands at 2953, 2927, 2867, 1718 (C = 0), 1457, 1364, 1161 cm " ¹ .

Smell: strongly woody, sandalwood, vetiver, boisambrene forte note. Example 3: 3- (2 _f 6,6-Trimethylcyclohex-l-en-l-yl) - 2-methyl1-hex-4-enoate ethyl ester

This example illustrates the preparation of the compounds (I) according to the invention by Claisen storage in the course of the reaction of an allyl alcohol with an orthoester in the presence of an acid catalyst.

Execution: 100 ml of cyclohexane, 77.6 g (0.4 mol) of beta-ionol (which had been prepared starting from beta-ionone - analogously to that described for educt A), 79 g ( 0.45 mol) of triethyl orthopropionate [structure: C2H5-C (0C2H5) 3], 3 g of propionic acid and 1 g of 2,6-di-tert-butyl-4-methylphenol (BHT). After flushing with nitrogen, 5 bar of nitrogen were injected and the reaction mixture was heated to 190 ° C. for seven hours; an internal pressure of 18 bar built up.

Working up: For working up, the reaction mixture was allowed to cool, the solvent was stripped off and the residue was distilled under high vacuum on a 12 cm Vigreux column. The main fraction of 31 g was then further purified on a rotating column.

Characterization: The mixture obtained turned out to be a mixture of diastereomers after GC analysis. The boiling point of this mixture was 86-87 ° / 0.05 mbar. The yield was 13 g (15% of theory). The IR spectrum of the product (film on NaCl) showed absorption bands at 2930, 1735 (ester-CO), 1371 and 1337 (mixed dimethyl groups), 1174 and 1162 (0C-0-C) cπrl.

Smell: creamy, rum, chocolate, fruit ester, sandal notes, green, woody.

Example 4: Mixture of 3- (2 _f 6 _f 6-trimethylcyclohex-l-en-l-yl) -

4-methyl-hex-4-enoate and other isomers

This example illustrates the preparation of the compounds (I) according to the invention by Claisen rearrangement in the course of the implementation of a Allyl alcohol with an orthoester in the presence of an acid catalyst. A mixture of methylionols was used as the allyl alcohol, which was obtained by sodium boranate reduction of "Isoraldein 70 ^R ". The "Isoraldein 70 ^R " (from Haarmann & Reimer) is a mixture of ketones derived from alpha, beta and gam a ionone, the side chain of the latter compounds each having an additional methyl group in the vicinity of the Carries carbonyl group; The main component of the "isoraldein 70" is likely to be 3-methyl- (2,6,6-trimethylcyclohex-l-en-l-yl) -but-4-en-2-one.

Execution: 100 ml of cyclohexane, 83.2 g (0.4 mol) of a methylionol mixture (starting from "Isoraldein 70 ^R " (from Haarmann & Reimer) by reduction with sodium boranate - were analogous to a 1-1 autoclave as described for the preparation of the starting material A) 72.9 g (0.45 mol) of triethyl orthoacetate [structure: CH3-C (0C2Hs) 3], 3 g of propionic acid and 1 g of 2,6-di-tert. -butyl-4-methylphenol (BHT) filled. After flushing with nitrogen, 5 bar of nitrogen were injected and the reaction mixture was heated to 190 ° C. for seven hours; an internal pressure of 10 bar was built up.

Working up: For working up, the reaction mixture was allowed to cool, the solvent was removed on a rotary evaporator and the residue was distilled in an oil pump vacuum on a 12 cm Vigreux column. A major fraction of 49.8 g (45% of theory) passed over at head temperatures of 124-125 ° C./0.1 mbar.

Characterization: The IR spectrum of the product (film on NaCl) showed absorption bands at 2956, 1737 (ester-CO), 1447, 1367, 1324, 1254, 1155 and 1036 CΠT *.

Smell: spicy, fruity, creamy, woody, weak. Composition example

Perfume concentrate for perfuming soap (floral-fresh imagination):

Shares by weight

Bergamot oil 200

Isopropyl myristate 150

Sande1 synth. 100

Geraniol 100

Cyc1ohexy1sa1icy1at 80

Coumarin 80

Benzyl acetate 50 l-acetyl-2,2,4,6-tetramethylcyclohexa-4,6-diene 50

Cyc1ohexadecenone 40

Patchouli oil 30

Cedarwood oil 30

Tetrahydrogerany1acetone 20

Styrate 10

Evernyl 10

950

Addition of 50 parts of 4- (2,6,6-trimethyl-cyclo-hex-1-en-1-yl) -heptan-2-one (Example 2) to the mixture compared to the same amount of isopropyl myristate in the comparison sample gave a beautiful effect in such a way that the scent of the sweet, light citrus-wood note prevailing in the starting mixture with the aid of the compound according to the invention results in a radiantly dry, powdery-fresh citrus-wood note which is no longer so obtrusively reminiscent of lavender soap was changed.

Claims

Patent claims 1. Hexanone derivatives of the general formula (I)

in which, independently of one another, the radical R ^{1 is} hydrogen or a methyl group, the radical R ^{2 is} hydrogen or an alkyl group having 1 to 3 C atoms, the radical R ^{3 is} hydrogen, an alkyl group having 1 to 3 C atoms or an alkoxy group having 1 to 3 carbon atoms and the radicals R ⁴ and R5 are hydrogen or a methyl group and wherein (a) Positions C-7 / C-8, C-8 / C-9 or C-8 / C-15 are either all linked by a CC single bond or one of the positions C-7 / C-8 , C-8 / C-9 or C-8 / C-15 is linked by a C = C double bond and (b) positions C-4 / C-5 are linked either by a C-C single bond or by a C = C double bond. 2. Hexanone derivatives according to claim 1, wherein the radical R * means hydrogen. 3. hexanone derivatives according to claim 1 or 2, wherein the radicals R ² and R ^{3 are} hydrogen, methyl or ethyl. 4. hexanone derivatives according to any one of claims 1 to 3, wherein the radicals R ² and R ^{3 are} hydrogen or methyl. 5. Hexanone derivatives according to one of claims 1 to 4, wherein one of the positions C-7 / C-8, C-8 / C-9 or C-8 / C-15 linked by a C = C double bond is. 6. Hexanone derivatives according to claim 5, wherein the positions C-4 / C-5, are linked by a C-C single bond. 7. Process for the preparation of hexanone derivatives of the general formula (I)

in which, independently of one another, the radical R 1 is hydrogen or a methyl group and the radical R ^{2 is} hydrogen or an alkyl group with 1 to 3 C atoms, the radical R ^{3 is} hydrogen, an alkyl group with 1 to 3 C atoms or an alkoxy group with 1 to 3 C atoms and the radicals R ⁴ and R5 are hydrogen or a methyl group and where (a) Positions C-7 / C-8, C-8 / C-9 or C-8 / C-15 are either all linked by a CC single bond or one of the positions C-7 / C-8 , C-8 / C-9 or C-8 / C-15 is linked by a C = C double bond and (b) positions C-4 / C-5 are linked either by a C-C single bond or by a C = C double bond, characterized in that allyl alcohols of the general formula (II)

in which the radicals R 1, R ⁴ and R 5 are independently hydrogen or a methyl group and one of the positions Ca / Cb, C - b / Cc or Cb / Cd is linked by a C = C double bond to a corresponding enol ether or an appropriate orthoester and, if desired, the C = C double bonds present in the compounds (I) obtained are partially or completely hydrated. 8. Use of the hexanone derivatives (I) according to any one of claims 1 to 6 as fragrances. 9. fragrance compositions containing one or more of the hexanone derivatives of the formula (I) according to claims 1 to 6 in an amount of 1-70% by weight, based on the overall composition. 10. Use of one or more compounds of the formula (I) according to one of claims 1 to 6 as fragrances in cosmetic preparations, technical products or alcoholic perfumery.