WO2011110614A1

WO2011110614A1 - Organic compounds

Info

Publication number: WO2011110614A1
Application number: PCT/EP2011/053581
Authority: WO
Inventors: David C. Bom; Philip A. Christenson; Felix Flachsmann; Melanie Rizzi
Original assignee: Givaudan SA
Current assignee: Givaudan SA
Priority date: 2010-03-11
Filing date: 2011-03-10
Publication date: 2011-09-15
Anticipated expiration: 2012-09-11

Abstract

Disclosed are compounds of formula (I) wherein n is 1 or 2; and the dotted line together with carbon - carbon bond represents a single bond or a double bond. Furthermore, flavour and fragrance compositions comprising at least one compound of formula (I) and a method of their production are disclosed.

Description

Organic compounds

This disclosure relates to a new class of compounds possessing fruity peach odor notes and to flavour and fragrance compositions comprising them. This disclosure relates furthermore to a method of their production.

The flavour and fragrance industry is always interested in new compounds that may enhance, improve, or modify the aroma and/or taste in a product. In particular there is an ongoing demand for compounds having unique organoleptic profiles suitable for use in a variety of products, including consumable and topically-applied products.

It is widely recognised that the flavour of consumable products consists of two parts, namely aroma and taste. In general the part that is perceived olfactively in the nasal cavity is described by the term "aroma", whereas the part termed "taste" is used to describe the sensorial impact perceived in the mouth, and more particularly on the tongue. By modifying taste or aroma of a consumable product, one is modifying its flavour.

It has surprisingly been found that the compounds of formula (I) as herein below defined constitute new fruity peach odor notes with tropical sulfur side-notes even though the subjected compounds of formula (I) do not comprise a sulfur atom

Accordingly, in a first aspect there is provided the use as fragrance or flavour of a compound of formula (I)

wherein n is 1 or 2; and

the dotted line together with carbon - carbon bond represents a single bond or a double bond. The compounds of formula (I) may be used alone, as mixtures thereof, or in

combination with a base material. As used herein, the "base material" includes all known odorant molecules selected from the extensive range of natural products and synthetic molecules currently available, such as essential oils, alcohols, aldehydes and ketones, ethers and acetals, esters and lactones, macrocycles and heterocycles, and/or in admixture with one or more ingredients or excipients conventionally used in conjunction with odorants in fragrance and flavour compositions, for example, carrier materials, and other auxiliary agents commonly used in the art. As used herein, "flavour compositions" means any composition comprising at least one compound of formula (I) and a base material suitable for consumables, e.g. diluent conventionally used in conjunction with flavouring compounds, such as ethylene glycol, propylene glycol, glycerol, triacetine, triethylcitrate, diethyl phthalate, dimethyl phthalate, benzylic alcohol, ethanol, and vegetal oils.

As used herein, "fragrance composition" means any composition comprising at least one compound of formula (I) and a base material suitable for consumer products, e.g. a diluent conventionally used in conjunction with odorants, such as dipropyleneglycol (DPG), iso propyl my ri state (IPM), triethylcitrate (TEC) and alcohol (e.g. ethanol).

The following list comprises examples of known odorant molecules, which may be combined with the compounds of formula (I):

- essential oils and extracts, e.g. tree moss absolute, basil oil, fruit oils such as bergamot oil and mandarine oil, myrtle oil, palmarose oil, patchouli oil, petitgrain oil, jasmine oil, rose oil, sandalwood oil, wormwood oil, lavender oil or ylang-ylang oil;

- alcohols, e.g. cinnamic alcohol, cis-3-hexenol, citronellol, Ebanol™, eugenol, farnesol, geraniol, Super uguet™, linalool, menthol, nerol, phenylethyl alcohol, rhodinol, Sandalore™, terpineol or Timberol™;

- aldehydes and ketones, e.g. anisaldehyde, cc-amylcinnamaldehyde, Georgywood™, hydroxycitronellal, Iso E^® Super, Isoraldeine^®, Hedione^®, Lilial^®, maltol, Methyl cedryl ketone, methylionone, verbenone or vanillin; - ethers and acetals, e.g. Ambrox , geranyl methyl ether, rose oxide or

Spirambrene™;

- esters and lactones, e.g. benzyl acetate, Cedryl acetate, γ-decalactone, Helvetolide^®, γ-undecalactone or Vetivenyl acetate;

- macrocycles, e.g. Ambrettolide, Ethylene brassylate or Exaltolide^® ;

- heterocycles, e.g. isobutylquinoline.

The compounds according to formula (I) may be used in a broad range of fragrance and flavour applications, e.g. in any field of fine and functional perfumery, such as perfumes, air care products, household products, laundry products, body care products, cosmetics and consumables, such as foodstuff and beverages.

The compounds can be employed in widely varying amounts, depending upon the specific application and on the nature and quantity of other ingredients. The proportion is typically from 0.001 to 1 weight percent of the fragrance application. In some embodiments, compounds of formula (I) may be employed in a fabric softener in an amount of from 0.001 to 0.2 weight percent. In other embodiments, compounds of formula (I) may be used in fine perfumery in amounts of from 0.001 to 1 weight percent, in certain embodiments between 0.001 and 0.5 weight percent. However, these values are given only by way of example, since the experienced perfumer may also achieve effects or may create novel accords with lower or higher concentrations.

In flavour applications, the compounds of the formula (I) may be employed in the range from 0.001 % to 5% by weight, more particular from 0.1% to 1% by weight. However, these values are given only by way of example, since the experienced flavourist may also achieve effects with lower or higher concentrations.

Flavoured applications for which the compounds of formula (I) are particularly suitable are foodstuffs and beverages such as yogurt, fruit juices, jams, carbonated beverages, chewing gum, candy, chocolate, chocolate fillings, flavoured waters, baked goods, toothpaste, mouthwash, ice cream, and cake icing. This list of products is given by way of illustration and is not to be regarded as being in any way limiting. The compounds as described hereinabove may be employed in a product base simply by directly mixing the compound of formula (1), a mixture thereof, or a flavour or fragrance composition with the product base, or they may, in an earlier step, be entrapped with an entrapment material, for example, polymers, capsules,

microcapsules and nanocapsules, liposomes, film formers, absorbents such as carbon or zeolites, cyclic oligosaccharides and mixtures thereof. The compounds of formula (I) may be dissolved or dispersed in a carrier material, such as a fat, or enrobed with maltose-dextrin, gelatine, gum Arabic and the like. They may be mixed with the food ingredients ready to be prepared or mixed with one of the ingredients, and then mixed with the product base.

In a further aspect the compounds of formula (I) may be chemically bonded to substrates, which are adapted to release the molecule upon application of an external stimulus such as light, enzyme, temperature, moisture, or the like, and then mixed with the product base.

Thus, the additionally there is provided a method of manufacturing a flavour or fragrance application, comprising the incorporation of a compound of formula (I), as a flavour or fragrance ingredient, either by directly admixing the compound to the product base or by admixing a flavour or fragrance composition comprising a compound of formula (I), which may then be mixed with the product base, using conventional techniques and methods. Through the addition of an olfactory acceptable amount of a compound of formula (1) as hereinabove described, or a mixture thereof, the organoleptic profile of the product base will be improved, enhanced or modified.

Thus, in a further aspect there is provided a method for improving, enhancing or modifying a product base by means of the addition thereto of an organolepticly acceptable amount of a compound of formula (I), or a mixture thereof. There is also provided a fragrance application comprising:

a) as odorant a compound of formula (I), or a mixture thereof; and

b) a product base.

As used herein, ..product base" in conjunction with fragrance applications is meant a composition for use as a consumer product to fulfill specific actions, such as cleaning, softening, and caring or the like. Examples of such products include fine perfumery, e.g. perfume and eau de toilette; fabric care, household products and personal care products such as laundry care detergents, rinse conditioner, personal cleansing composition, detergent for dishwasher, surface cleaner; laundry products, e.g. softener, bleach, detergent; body care products, e.g. shampoo, shower gel; air care products and cosmetics, e.g. deodorant, vanishing creme. This list of products is given by way of illustration and is not to be regarded as being in any way limiting.

In a further aspect there is provided a flavour application comprising:

(a) as aroma a compound of formula (I), or a mixture thereof; and

(b) a product base.

As used herein, by "product base" in conjunction with flavour applications is meant a consumable, not containing a compound of formula (I) as hereinabove defined. By "consumable" is meant a product such as foodstuffs and beverages, or personal care products that are intended to be introduced into the oral cavity of a human or animal and remain there for a certain period of time before being ingested or removed from the mouth. Such products include compositions in their processed, partially processed or unprocessed state.

To the best of our knowledge none of the compounds falling within the definition of formula (I) are described in the literature and are thus novel in their own right.

Accordingly, in a further aspect there is provided a compound of formula (!)

wherein n is 1 or 2; and

the dotted line together with carbon - carbon bond represents a single bond or a double bond. The compounds of formula (I) comprise several chiral centres and as such may exist as a mixture of stereoisomers, or they may be resolved as isomerically pure forms.

Resolving stereoisomers adds to the complexity of manufacture and purification of these compounds and so it is preferred to use the compounds as mixtures of their stereoisomers simply for economic reasons. However, if it is desired to prepare individual stereoisomers, this may be achieved according to methods known in the art, e.g. preparative HPLC and GC, crystallization or stereoselective synthesis.

In particular embodiments are compounds of formula (I) selected from the group consisting of 6-(2-(4-methylcyclohex-3-enyl)propyl)tetrahydro-2H-pyran-2-one, 6-(2-(4- methylcyclohexyl)propyl)tetrahydro-2H-pyran-2-one, 7-(2-(4-methylcyclohex-3- enyl)propyl)oxepan-2-one and 7-{2-(4-methylcycIohexyl)propyl)oxepan-2-one.

The compounds of formula (I) may be prepared by Baeyer-Villiger oxidation starting from the corresponding olefine under conditions known to the person skilled in the art. The corresponding olefins may be prepared by radical addition of the corresponding cycloalkanone to limonene (e.g. (+)-!imonene), as described for example by Iwahama, T. et al. {Chem Comm. 2000, 23, 2317-2318).

The disclosure is now further described with reference to the following non-limited examples. These examples are for the purpose of illustration only and it is understood that variations and modifications can be made by one skilled in the art.

Example 1 : 6-(2- (4-methyl cy clohex-3-enyI) pro py I )tetra hyd ro-2 H -py ran-2-one

Molecular sieves (4 A, 28 g) were placed in a 1 L round bottom flask and activated under vacuum (7 mbar) for five minutes using a heat gun and shaking to mix beads. The sieves were cooled under vacuum and then placed under argon. Next, a solution of trans-cyclohexane-1 ,2-diamine (3.99g, 34.9 mmol) in anhydrous THF (35 ml) was added followed by a solution of tin tetrachloride (1 M, 34.9 ml, 34.9 mmol). The resulting mixture was cooled to 0°C and treated with a solution of bis-trimethylsilylperoxide (50 g, 280 mmol) dissolved in anhydrous dichloromethane (150 ml). The contents were stirred for 15 minutes at 0°C. Finally, a solution of 2-(2-(4-methylcyclohex-3- enyl)propyl)cyclopentanone (30.9 g, 140 mmol) dissolved in anhydrous

dichloromethane (about 84 mf) was added in portions over 5 minutes at 0° C. After stirring five minutes the reaction was warmed to ambient temperature at which point it began refluxing. The reaction was cooled in the ice bath to control the exotherm. After five minutes, the reaction was warmed to room temperature at which point no further rise in temperature was observed. After 3hours, sodium sulfite (42 g) was added and the reaction was stirred overnight. The next morning the contents were poured onto a pad of silica gel (about 300 g) and the pad was washed with 3:2 hexane/EtOAc (1500 ml). The solvent was evaporated providing a crude, clear oil. This oil was dissolved in a small amount of dichloromethane and purified by flash chromatography on silica gel using a gradient of 100% hexane to 50:50 hexane/EtOAc. The product containing fractions were concentrated and the resulting oil was distilled under high vacuum (1 mbar) to remove last traces of solvent. After distillation a total of 10.8 g (32.6%) was obtained as a clear oil. Based on NMR and GC/MS it was clear that it was a mixture of diastereoisomers.

¹H-NMR (CDCI₃; 300 MHz): 0.76-0.80 (m, 3 H), 1.14-1.88 (m, 17 H), 2.22-2.58 (m, 2 H), 4.22-4.31 (br m, 1 H), 5.25 (br s, 1 H); ¹³C NMR (CDCI₃; 75 MHz): 15.4, 15.9, 16.1, 16.5, 18.5, 18.6, 23.5, 25.0, 25.3, 26.9, 27.2, 27.5, 28.0, 28.1, 28.8, 29.2, 29.3, 29.5, 30.8, 30.9, 31.0, 32.47, 32.54, 33.3, 33.4, 37.7, 38.3, 38.9, 39.0, 40.3, 40.6, 40.9, 120.6, 120.8, 120.89, 120.92, 133.94, 133.97, 134.0, 134.2; GC/MS calculated for C_1SH₂₄0₂ 236, observed 236.

Odour description: cooked peach, apricot, creamy, mango, tropical, slightly soapy.

Example 2: 6-(2-(4-m ethy I cy do h exy I)p ro py l)tetrahyd ro-2 H - pyra n-2-o n e

2-(2-(4-methylcyclohex-3-enyl)propyl)cyclopentanone (Nectaryl™, 10.0 g, 45 mmoi) was dissolved in ethy! acetate (50 ml) and palladium 10% on charcoal (1.0 g) was added to the solution. The resulting black suspension was stirred for 2 hours under 1 atmosphere of hydrogen, and then filtered over celite. The solvent was concentrated and the residue was bulb-to-bulb distilled at 120°C/0.6 mbar to yield 9.1 g (91%) of dihydro-Nectaryl as a colourless oil. This product (5.0 g, 22 mmol) was dissolved in CH₂CI₂ (100 ml) and m-chloro perbenzoic acid (7.8 g, 45 mmol, 2 equiv.) and KHC0₃ (4.5 g, 45 mmol, 2 equiv.) were added. The white suspension was heated to reflux under stirring for 3 hours, then poured on 20% aqueous NaHS0₃-solution (200 ml). The phases were separated and the aqueous layer was extracted twice with CH₂CI₂. The combined organic layers were dried over MgS0₄ and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with cyclohexane/MTBE 10:1. After concentration and high vacuum drying, the product was obtained (2.2 g, 42%) as a viscous, slightly yellow oil.

¹H-NMR (CDCI₃, 400 MHz): 4.38-4.26 (m, 1 H), 2.62-2.52 (m, 1 H), 2.47-2.36 (m, 1 H), 1.83 (m, 6 H), 1.28 (m, 11 H), 0.86 (series of d, 6 H).

MS (El, 70 eV): 238 (M\ <1), 220 (4), 202 (10), 176 (12), 124 (100), 114 (3), 99 (40), 95 (52), 55 (62). Odour description (10% solution in DPG): fruity, Iactonic smell, reminiscent of peach.

Example 3: Perfuming composition suitable for a body care product parts by weight

Butyl acetate 10.0

Dimethyl benzyl carbinyl acetate 50.0

Hexenal 0.3

Ethyl caproate 3.0 gamma-Decalactone 40.0

Geraniol 40.0

Hexenaf-2-trans at 10% TEC 4.0

HexenoI-3-cis 4.0 beta-lonone 200.0

(Z)-Hex-3-enyl isobutyrate 2.0

2-Methyl-4-oxo-4H-pyran-3-yl isobutyrate 0.4 cis-Jasmone 2.0

2,4,4,7-Tetramethylnona-6,8-dien-3-one oxime ⁾ 8.0

Linalool 400.0

Diethyl malonate 20.0

Isopropyl 2-Methylbutyrate 4.0

Orange oil ess. 150.0

2-Ethyl-N-methy!-N-(3-methylphenyl)-butanamide (Paradisamide) 10.0

Ethyl Pelargonate 6.0

Dipropylene glycol 46.3

TOTAL 1000.0

1) 1% solution in isopropyl myristate / triethylcitrate 90/10

Replacement of 40 parts by weight of dipropylene glycol by 6-{2-(4-methy!cyclohex-3- enyI)propyl)tetrahydro-2H-pyran-2-one (compound of Example 1) provides lift to the juicy natural peach effect and brings depth and increased performance to the composition.

The fragrance composition above may be used, for example, in shampoo or body wash applications. Example 4: tropical fruit flavor compositions

Panelists tasted the flavors given in Table 1 below at 0.08% (w/w) in water containing 10% sucrose and 0.1 % citric acid. The base flavor (Mixture A) delivered a tropical, slightly green, peely, fresh jack-fruit character. In mixture B, the addition of 6-(2-(4- methylcyclohex-3-enyl)propyl)tetrahydro-2H-pyran~2-one (0.3% of the flavor formula, 2.4ppm in the beverage) moved the flavor profile towards a riper, fleshier

mango/passion fruit character with increased tropical sulfur notes and heavier, creamier peach notes, compared to the base flavor. It may be emphasized that no sulfur containing flavor components were used in any of the flavor composition.

In summary, when added to a base of a balanced, fresh, slightly green, peely jack fruit type flavor, as a main effect, a compound of formula (I) imparts ripeness by

counteracting green and peely notes, moving the flavor profile towards a creamier, fleshier fruit character. In addition it emphasizes a sulfury, meaty note typical for ripe tropical fruits, such as mango and passion fruit. Therefore, the compounds of formula (I), in particular 6-(2-(4-methyIcyclohex-3-enyl)propyl)tetrahydro-2H-pyran-2-one, has differentiating value, especially for ripe, tropical fruit flavors without sulfur containing components.

Table 1: Flavor com ositions

1) 1-(2,6,6-trimethylcyclohexa-1 ,3-dienyl)but-2-en-1-one

2) 1-methyl-4-(propan-2-ylidene)cyclohex-1-ene

3) MCT = medium chain triglycerides (e.g. Captex^® 355 from ABITEC Corporation) 4) 2-(5-methyl-5-vinyltetrahydrofuran-2-yl)propan-2-ol

Although the embodiments have been described in detail through the above description and the preceding examples, these examples are for the purpose of illustration only and it is understood that variations and modifications can be made by one skilled in the art without departing from the spirit and the scope of the disclosure. It should be understood that the embodiments described above are not only in the alternative, but can be combined.

Claims

1. A compound of formula (I)

wherein n is 1 or 2; and

the dotted line together with carbon - carbon bond represents a single bond or a double bond.

2. A compound according to claim 1 selected from the group consisting of

6-(2-(4-methylcyclohex-3-enyl)propyl)tetrahydro-2H-pyran-2-one,

6- (2-(4-methylcyclohexyl)propyl)tetrahydro-2H-pyran-2-one,

7- (2-(4-methylcyclohex-3-enyl)propyl)oxepan-2-one, and

7-(2-(4-methylcyclohexyl)propyl)oxepan-2-one.

3. A flavour or fragrance application comprising a compound of formula (I) as defined in claim 1 or 2, or a mixture thereof and a product base.

4. A flavour application according to claim 3 wherein the product base is selected from the group consisting of foodstuff and beverages.

5. A fragrance application according to claim 3 wherein the product base is selected from the group consisting of fine fragrance, household products, laundry products, body care products, cosmetic products and air care products.

6. A flavour or fragrance composition comprising a compound of formula (I) as defined in claim 1 or 2, or a mixture thereof, and at least one other odorant.

7. A flavour or fragrance composition comprising a compound of formula (I) as defined in claim 1 or 2, or a mixture thereof and a diluent.

8. A method of imparting or modify the flavour or fragrance properties of a composition comprising adding to said composition a compound of formula (I) as defined in claim 1 or 2, or a mixture thereof in an effective amount.

9. The use as flavour or fragra (I)

wherein n is 1 or 2; and

10. The use according to claim 9 wherein the compound of formula (I) is selected from the group consisting of 6-(2-(4-methyIcyclohex-3-enyl)propyl)tetrahydro-2H-pyran-2-one,

6- (2-{4-methylcyclohexyl)propyl)tetrahydro-2H-pyran-2-one,

7- (2~(4-methylcyclohex-3-enyl)propyl)oxepan-2-one, and

7-(2-(4-methylcyclohexyl)propyl)oxepan-2-one.