Tetrahydropyranyl esters as fragrances

Description

BACKGROUND OF THE INVENTION

[0001] The present invention relates to certain tetrahydropyranyl esters of formula (1.1) as defined below and their use as fragrances. STATE OF THE ART

[0002] For the production of consumer goods with specific organoleptic properties, i.e. products that have advantageous olfactory or gustatory properties, a wide variety of aroma chemicals (odorants and flavors) are available for the extremely diverse applications of these substances.

[0003] The use of various substituted tetrahydropyran compounds as aroma chemicals is known. For example, 2,4,4-substituted tetrahydropyranyl esters of the general formula (A) are valuable aroma chemicals:

[0004] EP 0383446 A2 describes the synthesis and olfactory properties of a variety of different 2,4,4-trisubstituted tetrahydropyranyl esters (A), wherein R< is methyl or ethyl and R< is straight-chain or branched C2-C4-alkyl or C2-C4-alkenyl. For this purpose, 3-methylbut-3-en-1-ol is first reacted with an aldehyde of the formula R< -CHO in the presence of an acidic catalyst, yielding a reaction mixture containing at least one 2-substituted 4-hydroxy-4-methyltetrahydropyran of the general formula (B):

[0005] The intermediate (B) is then subjected to acylation by reaction with a carboxylic acid anhydride under acidic conditions.

[0006] 4-Hydroxytetrahydropyran compounds and especially 2-substituted 4-hydroxy-4-methyltetrahydropyrans are also valuable compounds for use as aroma chemicals, and various processes for their preparation are known to the person skilled in the art, e.g. from EP 1 493 737 A1, WO 2011 / 147919, WO 2010 / 133473, WO 2011 / 154330 and WO 2014 / 060345. SUMMARY OF THE INVENTION

[0007] The invention relates to tetrahydropyranyl esters of the general formula (1.1) wherein R 1< is phenyl or phenyl substituted by C 1 -C 6 alkyl or C 1 -C 6 alkoxy.

[0008] The invention also relates to the use of these compounds (1.1) as fragrances.

[0009] The compounds (I.1) are obtainable by providing at least one 2-substituted 4-hydroxy-4-methyl-tetrahydropyran of the general formula (II.1) where R 1< has the meanings given above, and the compound of general formula (II.1) is subjected to a reaction with the ketene (III.1) CH 2 =C=O (III.1). DESCRIPTION OF THE INVENTION

[0010] Unless otherwise specified below, the terms "Tetrahydropyranyl ester", "4-hydroxy-tetrahydropyran compound", "2-substituted 4-hydroxy-4-methyl-tetrahydropyran", "2-substituted 4-methyl-tetrahydropyranyl-4-acetate"

[0011] Within the scope of the invention, cis / trans mixtures of any composition as well as the pure conformational isomers are included. The aforementioned terms also refer to all enantiomers in pure form as well as racemic and optically active mixtures of the enantiomers of these compounds.

[0012] Where cis and trans diastereomers of compounds (I.1) are referred to below, only one of the enantiomeric forms is shown. For illustrative purposes only, the isomers of 2-isobutyl-4-methyltetrahydropyran-4-yl acetate (I.1a) are shown below as examples (instead of the isobutyl group in compounds (I.1), however, there is a phenyl ring or a phenyl ring substituted by C 1 -C 6 alkyl or C 1 -C 6 alkoxy):

[0013] In the context of the present invention, C 1 -C 6 alkyl represents in particular methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl (2-methylpropyl), sec-butyl (1-methylpropyl), tert-butyl (1,1-dimethylethyl), n-pentyl, or n-hexyl. Specifically, C 1 -C 6 alkyl represents methyl, ethyl, n-propyl, isopropyl, or isobutyl.

[0014] In the context of the present invention, C 1 -C 6 -alkoxy represents, in particular, methoxy, ethoxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, sec-butyloxy, tert-butyloxy, n-pentyloxy, or n-hexyloxy. Specifically, C 1 -C 6 -alkoxy represents methoxy, ethoxy, n-propyloxy, isopropyloxy, or isobutyloxy.

[0015] Substituted phenyl may have one or more (e.g., 1, 2, 3, 4, or 5) substituents. These are selected from C 1 -C 6 alkyl and C 1 -C 6 alkoxy. Examples of substituted phenyl radicals are 2-, 3- and 4-methylphenyl, 2,4-, 2,5-, 3,5- and 2,6-dimethylphenyl, 2,4,6-trimethylphenyl, 2-, 3- and 4-ethylphenyl, 2,4-, 2,5-, 3,5- and 2,6-diethylphenyl, 2,4,6-triethylphenyl, 2-, 3- and 4-propylphenyl, 2,4-, 2,5-, 3,5- and 2,6-dipropylphenyl, 2,4,6-tripropylphenyl, 2-, 3- and 4-isopropylphenyl, 2,4-, 2,5-, 3,5- and 2,6-diisopropylphenyl, 2,4,6-triisopropylphenyl, 2-, 3- and 4-butylphenyl, 2,4-, 2,5-, 3,5- and 2,6-dibutylphenyl, 2,4,6-tributylphenyl, 2-, 3- and 4-isobutylphenyl, 2,4-, 2,5-, 3,5- and 2,6-diisobutylphenyl, 2,4,6-triisobutylphenyl, 2-, 3- and 4-sec-butylphenyl, 2,4-, 2,5-, 3,5- and 2,6-di-sec-butylphenyl, 2,4,6-tri-sec-butylphenyl, 2-, 3- and 4-tert-butylphenyl, 2,4-, 2,5-, 3,5- and 2,6-di-tert-butylphenyl and 2,4,6-tri-tert-butylphenyl.

[0016] In a preferred embodiment, R 1< is phenyl.

[0017] In a further preferred embodiment, the compounds (I.1) are selected from compounds of the formulas (IA.1), (IA.6), (IA.7), (IA.8) and (IA.9):

[0018] 4-Hydroxy-tetrahydropyran compounds of the general formula (II.1) suitable for use in the process described above (which is not part of the present invention) and processes for their preparation are known in principle to the person skilled in the art.

[0019] A 2-substituted 4-hydroxy-4-methyl-tetrahydropyran of the general formula (II.1) is used where R 1< has the meaning given above.

[0020] Preferably, to provide the 2-substituted 4-hydroxy-4-methyl-tetrahydropyran of the general formula (II.1) a) 3-Methylbut-3-en-1-ol of the formula (IV) with an aldehyde of the formula (V) R 1< -CHO (V) wherein R 1< has the meanings given above, in the presence of an acidic catalyst to obtain a reaction mixture which contains at least one 2-substituted 4-hydroxy-4-methyl-tetrahydropyran of the general formula (II.1) wherein R 1< has the meaning given above, b) optionally the reaction mixture from step a) is subjected to a separation to obtain at least one fraction enriched in the 2-substituted 4-hydroxy-4-methyl-tetrahydropyrans of the general formula (II.1).

[0021] Such methods are described, for example, in EP 1 493 737 A1, WO 2011 / 147919, WO 2010 / 133473, WO 2011 / 154330 and WO 2014 / 060345.

[0022] In a specific embodiment, the reaction mixture from step a) is subjected to a separation to obtain at least one fraction enriched in the 2-substituted 4-hydroxy-4-methyl-tetrahydropyrans of the general formula (1.1) and a fraction depleted in the 2-substituted 4-hydroxy-4-methyl-tetrahydropyrans of the general formula (1.1) (= step b)).

[0023] One of the starting materials for step a) of the process is 3-methylbut-3-en-1-ol (isoprenol) of formula (IV),

[0024] Isoprenol is readily accessible and commercially available on any scale from isobutene and formaldehyde using known processes. No special requirements are placed on the purity, quality, or production process of the isoprenol used. It can be used in step a) of the process in commercially available quality and purity. Isoprenol with a purity of 90% by weight or higher is preferred, particularly preferably with a purity of 95 to 100% by weight, and very particularly preferably with a purity of 97 to 99.9% by weight, or even more preferably with a purity of 98 to 99.8% by weight.

[0025] Another starting material for step a) of the process is an aldehyde of the formula (V) R 1< -CHO, where R 1< in the formula (V) has the meaning given above.

[0026] A preferred aldehyde of formula (V) is benzaldehyde.

[0027] Preferably, in step a), the 3-methylbut-3-en-ol (IV) and the aldehyde (V) are used in a molar ratio of about 1:2 to 2:1, particularly preferably from 0.7:1 to 2:1, in particular from 1:1 to 2:1. In a specific embodiment, in step a), the 3-methylbut-3-en-ol (IV) and the aldehyde (V) are used in a molar ratio of 1:1 to 1.5:1.

[0028] The reaction in step a) preferably takes place in the presence of an acidic catalyst. In principle, any acidic catalyst, i.e., any substance exhibiting Brönsted or Lewis acidity, can be used for the reaction in step a). Examples of suitable catalysts are protic acids, such as hydrochloric acid, sulfuric acid, phosphoric acid, methanesulfonic acid, and p-toluenesulfonic acid; acidic molecular element compounds, such as aluminum chloride, boron trifluoride, zinc chloride, tin tetrachloride, and titanium tetrachloride; oxidic acidic solids such as zeolites, silicates, aluminates, aluminosilicates, clays, and strongly acidic ion exchangers.

[0029] The term "strongly acidic cation exchanger" refers to a cation exchanger in the H +< form that contains strongly acidic groups. These strongly acidic groups are typically sulfonic acid groups. The acidic groups are typically bound to a polymer matrix, which may, for example, be gel-like or macroporous. Accordingly, a preferred embodiment of the process is characterized by the use of a strongly acidic cation exchanger containing sulfonic acid groups. Suitable strongly acidic cation exchangers are described in WO 2010 / 133473 and WO 2011 / 154330.

[0030] The reaction in step a) can optionally also be carried out in the presence of an external organic solvent that is inert under the reaction conditions. Suitable solvents include, for example, tert-butyl methyl ether, cyclohexane, decalin, hexane, heptane, ligroin, petroleum ether, toluene, or xylene. These solvents can be used alone or in mixtures. Preferably, the reaction in step a) is carried out without the addition of an external organic solvent.

[0031] Preferably, in step b), the reaction mixture from step a) is subjected to distillative separation to obtain at least one fraction enriched in the 2-substituted 4-hydroxy-4-methyltetrahydropyrans of the general formula (II.1) and a fraction depleted in the 2-substituted 4-hydroxy-4-methyltetrahydropyrans of the general formula (II.1). Suitable apparatus for distillative separation include distillation columns, such as tray columns, which may be equipped with bubble caps, sieve plates, sieve trays, packings, random packings, valves, side draws, etc., evaporators, such as thin-film evaporators, falling-film evaporators, forced circulation evaporators, Sambay evaporators (agitated thin-film evaporators), etc., and combinations thereof. The distillation columns may have separating internals, which are preferably selected from separating trays, ordered packings, e.g.Sheet metal or fabric packings, such as Sulzer Mellapak®, Sulzer BX, Montz B1 or Montz A3, or Kühni Rombopak, or random packings, such as Dixon rings, Raschig rings, high-flow rings, or Raschig Super rings. A preferred process for the preparation and isolation of 2-substituted 4-hydroxy-4-methyltetrahydropyranols by reacting 3-methylbut-3-en-1-ol (isoprenol) with the corresponding aldehydes in the presence of a strongly acidic cation exchanger and subsequent isolation or distillative separation in a dividing-wall column or in a thermally coupled arrangement of two distillation columns is described in WO 2011 / 154330.

[0032] In the process by which compounds (1.1) are obtainable, at least one 4-hydroxy-tetrahydropyran compound of the general formula (II.1) is reacted with a ketene of the formula (III.1) (CH 2 =C=O (ethenone)).

[0033] The ketene (III.1) is preferably produced by high-temperature pyrolysis of acetone or acetic acid at temperatures generally higher than 650 °C. The temperature for producing the ketene (III.1) is preferably in a range from 650 to 1000 °C, particularly preferably from 700 to 900 °C.

[0034] In a specific embodiment, the ketene (III.1) is prepared under reduced pressure. The pressure is preferably in a range from about 100 to 900 mbar, particularly preferably from 300 to 500 mbar, in particular from 350 to 450 mbar. In an alternative embodiment, the ketene (III.1) is prepared under ambient pressure ("atmospheric pressure"). The pressure is then preferably in a range from about 950 to 1050 mbar.

[0035] Since ketene (III.1) is an extremely reactive compound with a strong tendency to dimerize to form diketenes, the process uses ketene (III.1) that has been prepared immediately before the reaction in the process, e.g., by thermal cleavage of acetone, acetic acid or acetic anhydride or by dehydrochlorination of acetyl chloride with bases such as triethylamine.

[0036] In a first variant of the process, the ketene (III.1) is introduced into the reaction mixture below the liquid surface, allowing it to bubble through the reaction mixture. Advantageously, the ketene is introduced into the reaction mixture under vigorous stirring, so that essentially no ketene escapes into the gas phase in large quantities. The pressure of the ketene (III.1) must be sufficiently high to overcome the hydrostatic pressure of the reaction mixture above the ketene feed, optionally supported by an inert gas stream, e.g., nitrogen.

[0037] The ketene (III.1) can be fed in via any suitable device. Good distribution and rapid mixing are important. Suitable devices include, for example, gassing lances, which can be permanently installed, or preferably nozzles. The nozzles can be located on or near the reactor floor. For this purpose, the nozzles can be designed as openings in a hollow chamber surrounding the reactor. However, submerged nozzles with suitable supply lines are preferred. Several nozzles can be arranged, for example, in the form of a ring. The nozzles can point upwards or downwards. The nozzles preferably point diagonally downwards.

[0038] In a second variant of the process, the ketene (III.1) is prepared under reduced pressure and reacted under reduced pressure with at least one 4-hydroxytetrahydropyran compound of the general formula (II.1). The pressure during the preparation and reaction of the ketene (III.1) is preferably in a range from about 100 to 900 mbar, particularly preferably from 300 to 500 mbar, in particular from 350 to 450 mbar.

[0039] Processes and devices for the production of ethenone are described, for example, in Organic Syntheses, Coll. Vol. 1, p. 330 (1941) and Vol. 4, p. 39 (1925) as well as in Chemiker Zeitung 97, No. 2, pages 67 to 73 (1979).

[0040] An excess of the ketene compound (III.1) can lead to undesirable side reactions. Therefore, the reaction of the compound of general formula (II.1) with the ketene (III.1) is preferably carried out using at most equimolar amounts of the ketene compound (III.1). A slight molar excess of the compound of general formula (II.1) is preferred.

[0041] Preferably, the reaction of the 4-hydroxy-tetrahydropyran compound of the general formula (II.1) with the ketene (III.1) is carried out in such a way that accumulation of the ketene compound in the reaction mixture is avoided at any time during the reaction.

[0042] The reaction of the compound of general formula (II.1) with the ketene (III.1) is preferably carried out by introducing ketene into the reaction mixture until the compound (II.1) is essentially completely converted. "Essentially converted" is understood to mean a conversion of at least 98%, preferably at least 99%.

[0043] Preferably, the compound of general formula (II.1) is subjected to a reaction with ketene (III.1) at a temperature in the range from 0 to 150 °C, preferably from 10 to 120 °C.

[0044] In a first preferred embodiment, the compound of general formula (II.1) is subjected to a reaction with ketene (III.1) in the absence of an added catalyst.

[0045] In a second preferred embodiment, the compound of general formula (II.1) is subjected to a reaction with ketene (III.1) in the presence of a catalyst. Preferably, at least one zinc salt is used as the catalyst, which may also be present as a hydrate or multiple hydrate.

[0046] A zinc salt of a carboxylic acid, especially a monocarboxylic acid with 1 to 18 carbon atoms or a dicarboxylic acid with 2 to 18 carbon atoms, is particularly preferably used as the catalyst. These include, for example, zinc formate, zinc acetate, zinc propionate, zinc butyrate, zinc stearate, zinc succinate, or zinc oxalate. Zinc acetate is particularly preferred.

[0047] A major advantage of the process is that the catalysts usually only need to be used in very small quantities, which makes the process more cost-effective and facilitates the processing of the reaction mixture. This is especially true when using a zinc salt as a catalyst.

[0048] The catalyst is preferably used in an amount of 0.01 to 2 wt.%, particularly preferably 0.02 to 0.5 wt.%, based on the total amount of the compound (II.1).

[0049] To carry out the reaction, it is advantageous to carry out this reaction in a suitable reaction vessel which contains as essential components a good stirring and / or mixing device, a metering device for ketene, a heating device for starting the reaction and for maintaining the reaction temperature during the after-reaction, a cooling device for removing the heat of reaction of the exothermic reaction and a vacuum pump.

[0050] For optimal reaction control, it is advantageous to add the ketene in such a way that it is never present in excess in the reaction mixture and that the reaction mixture is always well mixed.

[0051] For optimal reaction control, it is also advantageous to avoid adding ketene too quickly and to clearly determine the end of the reaction.

[0052] For example, ketene can be detected by IR spectroscopy via the characteristic carbonyl vibration.

[0053] Using the described process, it is possible to prepare the compounds of general formula (1.1) in a technically simple manner with high purity and yet in excellent yields and space-time yields. Since the reactants are essentially completely converted into products, the described process is characterized by maximum atom economy.

[0054] The compositions obtainable by the process described are particularly advantageously suitable as a fragrance or for providing a fragrance.

[0055] For use as a fragrance, the compositions can be diluted as desired with at least one solvent commonly used in this field of application. Examples of suitable solvents include: ethanol, dipropylene glycol or its ethers, phthalates, propylene glycols, or diol carbonates, preferably ethanol. Water is also suitable as a solvent for diluting the fragrance compositions according to the invention and can advantageously be used together with suitable emulsifiers.

[0056] The fragrances obtained by the described process exhibit high stability and durability due to the structural and chemical similarity of the components.

[0057] The fragrances obtained by the described process are suitable for incorporation into cosmetic compositions as well as consumer goods and products, as described in more detail below. The fragrances can be incorporated into the aforementioned products or even applied to them. As is the case throughout the present invention, an organoleptically effective amount is understood to mean, in particular, an amount that, when used properly, is sufficient to evoke a fragrance impression in the user or consumer.

[0058] All conventional cosmetic compositions are suitable as cosmetic compositions. These preferably include perfume, eau de toilette, deodorants, soap, shower gel, bath gel, creams, lotions, sunscreens, compositions for cleansing and caring for hair, such as shampoo, conditioner, hair gel, hairspray in the form of liquids or foams, and other hair cleansing or caring products; compositions for decorative application to the human body, such as cosmetic sticks, for example, lipsticks, lip balms, concealers, blushers, eye shadow sticks, lip liners, eye liners, eyebrow pencils, concealer sticks, sunscreen sticks, anti-acne sticks, and similar products, as well as nail polishes and other nail care products.

[0059] The fragrances obtained by the described process are particularly suitable for use in perfumes, e.g., as eau de toilette, shower gels, bath gels, and body deodorants.

[0060] They are also suitable for flavoring consumer goods or durable goods into which they are incorporated or applied, thereby lending them a pleasant, fresh, green accent. Examples of consumer goods or durable goods include: air deodorizers (air care), cleaning or care products for textiles (especially detergents and fabric softeners), textile treatment products such as ironing aids, cleaning products, cleaning agents, care products for treating surfaces, for example, furniture, floors, kitchen equipment, glass panes and windows, as well as screens, bleach, toilet blocks, descaling agents, fertilizers, building materials, mold removers, disinfectants, car or vehicle care products, and the like. EXAMPLES

[0061] Gas chromatographic analyses were carried out using the following method: Column: DB WAX 30 mx 0.32 mm FD 0.25 µm Injector temperature: 200 °C; detector temperature 250 °C Temperature program: Initial temperature: 60 °C, at 2 °C / min to 120 °C, at 20 °C / min to 230 °C Retention times: trans-Tetrahydro-2-isobutyl-4-methylpyranyl-4-acetate (not according to the invention) t R = 15.1 min cis-Tetrahydro-2-isobutyl-4-methylpyranyl-4-acetate (not according to the invention) t R = 18.8 min trans-Tetrahydro-2-isobutyl-4-methylpyran-4-ol (not according to the invention) t R = 19.6 min cis-Tetrahydro-2-isobutyl-4-methylpyran-4-ol (not according to the invention) t R = 21.5 min

[0062] The concentrations of the obtained products (wt%) were determined by GC analysis using an internal standard. Example 1 (not according to the invention):

[0063] (Preparation of tetrahydro-2-isobutyl-4-methylpyranyl-4-acetate from tetrahydro-2-isobutyl-4-methylpyran-4-ol by reaction with ketene)

[0064] 127.08 g of tetrahydro-2-isobutyl-4-methylpyran-4-ol (0.74 mol; composition see Table 1, sample after 0 h) were initially charged at 90 °C. Ketene, obtained by the pyrolysis of acetone (0.411 mL / min) at 700 °C, was introduced below the liquid surface after cooling at 90 °C and with vigorous stirring. The pyrolysis conversion was approximately 48% (based on isolated, unreacted acetone), and the ketene content in the pyrolysis gas was 23 to 24%. After a reaction time of 7 h, the ketene introduction was interrupted and continued the following day. After a total reaction time of 10 h, the starting material had been converted, and the experiment was terminated. A total of 92.6 g of acetone (1.59 mol, 2.15 eq.; based on isolated, unreacted acetone) was converted during the pyrolysis. The composition of the samples is given in Table 1. The yield of tetrahydro-2-isobutyl-4-methylpyranyl-4-acetate was 89%.

[0065] Cis- and trans-tetrahydro-2-isobutyl-4-methylpyranyl-4-acetate were characterized by NMR spectroscopy: Cis-tetrahydro-2-isobutyl-4-methylpyranyl-4-acetate: 13< C NMR (125 MHz, CDCl 3 ): δ = 21.7, 22.3, 22.5, 23.2, 24.3, 37.7, 43.8, 45.4, 64.6, 72.7, 80.0, 170.3 ppm. Trans-tetrahydro-2-isobutyl-4-methylpyranyl-4-acetate: 13< C NMR (125 MHz, CDCl 3): δ = 22.37, 22.39, 23.2, 24.3, 26.2, 36.3, 42.5, 45.1, 63.4, 70.9, 79.3, 170.4 ppm. Table 1: Composition of the reaction mixture Reaktionszeit trans-Tetrahydro-2-isobutyl-4-methylpyranyl-4-acetat cis-Tetrahydro-2-isobutyl-4-methylpyranyl-4-acetat Summe Tetrahydro-2-isobutyl-4-methylpyranyl-4-acetat trans-Tetrahydro-2-isobutyl-4-methylpyran-4-ol cis-Tetrahydro-2-isobutyl-4-methylpyran-4-ol Summe Tetrahydro-2-isobutyl-4-methylpyran-4-ol [h] [%]* [%]* [%]* [%]* [%]* [%]* 0 0 0 0 22,8 77,1 99,9 2 3,1 16,0 19,1 16,9 52,9 69,8 4 7,4 35,0 42,4 15,6 34,5 50,1 6 11,6 49,8 61,4 13,7 18,9 32,6 7 15,2 60,7 75,9 10,6 8,4 19,0 8 18,6 73,4 92,0 1,5 2,4 3,9 9 20,6 74,4 95,0 0 0,4 0,4 10 21,2 73,9 95,1 0 0 0 * GC-Gew.-%

Claims

1. A compound of the general formula (I.1) in which R1 is phenyl or C1-C6-alkyl- or C1-C6-alkoxy-substituted phenyl.

2. The compound according to claim 1, selected from compounds of formulae (I-A.1), (I-A.6), (I-A.7), (I-A.8) and (I-A.9) 3. The use of compounds of formula (I.1) according to either of claims 1 and 2 as an odorant.