3-(Cyclohex-1-En-1-Yl)Propionates and Their Use in Perfume Compositions

(19) TZZ _T

(11) EP 2 862 599 B1

(12) EUROPEAN PATENT SPECIFICATION

(45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61Q 13/00 (2006.01) A61Q 15/00 (2006.01) 31.08.2016 Bulletin 2016/35 C07C 69/608 (2006.01) C11D 3/00 (2006.01) C11D 3/50 (2006.01) C11B 9/00 (2006.01) (2006.01) (21) Application number: 14188994.9 A61K 8/37

(22) Date of filing: 15.10.2014

(54) 3-(cyclohex-1-en-1-yl)propionates and their use in perfume compositions 3-(cyclohex-1-en-1-yl)propionate und ihre Verwendung in Duftstoffzusammensetzungen 3- (cyclohex-1-en-1-yl)propionates et leur utilisation dans des compositions de parfum

(84) Designated Contracting States: (56) References cited: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB EP-A1- 0 411 460 EP-A2- 1 078 912 GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO EP-A2- 1 167 507 PL PT RO RS SE SI SK SM TR • Ju Meyoung ET AL: "Coupling Reaction of (30) Priority: 18.10.2013 US 201314057147 Alkenes with alpha-Bromo Carboxylic Acid Derivatives Using Nickel Boride and Borohydride (43) Date of publication of application: Exchange Resin in Methanol", J. Org. Chem., 14 22.04.2015 Bulletin 2015/17 November 1997 (1997-11-14), pages 2755-2757, XP055165234, Retrieved from the Internet: (73) Proprietor: INTERNATIONAL FLAVORS & URL:http://pubs.acs.org/doi/pdf/10.1021/jo FRAGRANCES INC. 972019z [retrieved on 2015-01-27] New York, NY 10019 (US) • EIICHI NAKAMURA ET AL: "Carbon-carbon bond-forming reactions of zinc homoenolate of (72) Inventors: esters. A novel three-carbon nucleophile with • Levorse JR., Anthony, T. general synthetic utility", JOURNAL OF THE Westfield, NJ 07090 (US) AMERICAN CHEMICALSOCIETY, vol. 109, no. 26, • Giffin, Nicole, L. 1 December 1987 (1987-12-01), pages 8056-8066, Hazlet, NJ 07730 (US) XP055165261, ISSN: 0002-7863, DOI: 10.1021/ja00260a018 (74) Representative: Lawrence, John • "SAFC Flavors & Fragrances", , 10 November Barker Brettell LLP 2011 (2011-11-10), pages 1-196, XP055165513, 100 Hagley Road U.S.A. Retrieved from the Internet: Edgbaston URL:http://www.sigmaaldrich.com/content/da Birmingham B16 8QQ (GB) m/sigma-aldrich/docs/SAFC/General_Informat ion/1/safc_flavors_and_fragrances_catalog. pdf [retrieved on 2015-01-28]

Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 2 862 599 B1

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Description

Field of the Invention

5 [0001] The present invention relates to fragrance formulations, a method of using certain chemical entities as fragrance materials and a method of using the same as malodor counteracting materials.

Background of the Invention

10 [0002] There is an ongoing need in the fragrance industry to provide new chemicals to give perfumers and other persons the ability to create new fragrances for perfumes, colognes and personal care products. Those with skill in the art appreciate how small differences in chemical structures can result in unexpected and significant differences in odor, notes and characteristics of molecules. These variations allow perfumers and other persons to apply new compounds in creating new fragrances. For example, benzene compounds that differ slightly in substituents possess completely 15 different odor profiles [Ishikawa, et al., International Journal of Quantum Chemistry 79: 101-108 (2000)]. In the case of tert-butyl cyclohexanes, the odor is said to be dependent on the compounds’ conformation and therefore analogs adopting same conformation possess similar odor. Accordingly, many trans-compounds are shown to share pronounced urine- perspiration-type odor,while the corresponding cis-compoundsare odorlessor at the mostpossess weak and undefinable flowery or woody odor. However, some other trans- and cis-tert-butyl cyclohexanes are shown to possess opposite 20 sensory activities [Ohloff, et al., Helvetica Chimica Acta 66, Fasc. 5: 1343-1354 (1983)]. Thus, it is hard for those with skill in the art to predict a given structure would be effective in sensory activities. Identifying desirable fragrance chemica ls continues to pose difficult challenges. [0003] Another effort in the fragrance industry has been made to provide new chemicals to treat and control malodors. "Malodor" is a term used to describe undesirable or unpleasant odor. Common sources of malodors include body 25 perspiration, smoke, environmental odor such as mold and mildew, bathroom, and etc. Conventional perfumes including a variety of fragrance materials are developed to mask malodors, which generally function via two mechanisms: first, the fragrance materials blend with the malodor compound to provide a different and more desirable aroma; and second, the fragrance materials are employed to overwhelm the malodor compound. However, a large quantity of fragrance materials is required for both mechanisms, which in itself is often undesirable. 30 [0004] A method of counteracting malodors is described for example in EP 1167507, which discloses the use of 1- cyclohexyl-ethyl-butyrate, 1-(cyclohexyl)ethyl acetate, 1-cyclohexyl-ethanol or (4-isopropyl-cyclohexyl)propionate for this purpose. [0005] Nonetheless, there remains a need for new chemicals that are effective in counteracting malodors. [0006] The structurally similar compounds ethyl 3-(cyclohex-1-en-1-yl)propionate and 2-propyl 3-(cyclohex-l-en-1- 35 yl)propionate are known in the art [Meyoung et al., J. Org. Chem. 63: 2755-2757 (1997); Nakamura et al., J. Am. Chem. Soc.109: 8056-8066 (1987)]. However, nothing is known about their olfactory profile.

Summary of the Invention

40 [0007] The present invention provides compositions and their use in enhancing, improving or modifying the fragrance of perfumes, colognes, toilet waters, fabric care products, personal products, and the like, and the unexpected advantageous use thereof in counteracting malodors.

3-(cyclohex-1-en-1-yl)propionates are represented by Formula I set forth below: 45 [0008]

55 wherein R is selected from the group consisting of ethyl and 2-propyl. [0009] One embodiment of the invention relates to a fragrance formulation in accordance with claim 1 herein. [0010] Another embodiment of the invention relates to a method of improving, enhancing or modifying a fragrance

2 EP 2 862 599 B1

formulation through the addition of an olfactory acceptable amount of the novel 3-(cyclohex-1-en-1-yl)propionates represented by Formula I provided above in accordance with claim 4 herein. [0011] Another embodiment of the invention relates to a fragrance product comprising the novel 3-(cyclohex-1-en-1- yl)propionates represented by Formula I provided above in accordance with claim 6 herein. 5 [0012] Another embodiment of the invention relates to a method of counteracting a malodor comprising the step of introducing a malodor counteracting effective amount of the novel 3-(cyclohex-1-en-1-yl)propionates represented by Formula I provided above in accordance with claim 8 herein. [0013] Another embodiment of the invention relates to a malodor counteracting composition comprising the novel 3-(cyclohex-1-en-1-yl)propionates represented by Formula I provided above in accordance with claim 9 herein. 10 [0014] These and other embodiments of the present invention will be apparent by reading the following specification.

Detailed Description of the Invention

[0015] In one embodiment of the present invention, the compounds used in the present invention are represented by 15 the following structures:

25 [0016] Those with skill in the art will recognize that:

Structure I is ethyl 3-(cyclohex-1-en-1-yl)propionate; and Structure II is 2-propyl 3-(cyclohex-1-en-1-yl)propionate.

30 [0017] The compounds of the present invention can be prepared from bicyclononalactone (commercially available from International Flavors & Fragrances Inc.). The reaction steps can be depicted by a scheme shown as follows:

40 wherein MSA represents methanesulfonic acid; and wherein Ris defined as above.

[0018] The above preparation is detailed in the Examples. Materials were purchased from Aldrich Chemical Company unless noted otherwise. 45 [0019] The compounds used in the present invention are surprisingly found to possess powerful and complex fragrance effect such as, for example, fruity and woody notes supported by a spiciness aspect. [0020] The use of the compounds of the present invention is widely applicable in current perfumery products, including the preparations of perfumes and colognes, the perfuming of personal care products such as soaps, shower gels, and hair care products, fabric care products, air fresheners, and cosmetic preparations. The present invention can also be 50 used to perfume cleaning agents, such as, but not limited to detergents, dishwashing materials, scrubbing compositions, window cleaners and the like. In these preparations, the compounds of the present invention can be used alone or in combination with other perfuming compositions, solvents, adjuvants and the like. The nature and variety of the other ingredients that can also be employed are known to those with skill in the art. Many types of fragrances can be employed in the present invention, the only limitation being the compatibility with the other components being employed. Suitable 55 fragrances include but are not limited to fruits such as almond, apple, cherry, grape, pear, pineapple, orange, strawberry, raspberry; musk, flower scents such as lavender-like, rose-like, iris-like, carnation-like. Other pleasant scents include herbal and woodland scents derived from pine, spruce and other forest smells. Fragrances may also be derived from various oils, such as essential oils, or from plant materials such as peppermint, spearmint and the like.

3 EP 2 862 599 B1

[0021] A list of suitable fragrances is provided in US Pat. No. 4,534,891. Another source of suitable fragrances is found in Perfumes. Cosmetics and Soaps, Second Edition, edited by W. A. Poucher, 1959. Among the fragrances provided in this treatise are acacia, cassie, chypre, cyclamen, fern, gardenia, hawthorn, heliotrope, honeysuckle, hyacinth, jasmine, lilac, lily, magnolia, mimosa, narcissus, freshly-cut hay, orange blossom, orchid, reseda, sweet pea, trefle, tuberose, 5 vanilla, violet, wallflower, and the like. [0022] The compounds used in the present invention can be used in combination with a complementary fragrance compound. The term "complementary fragrance compound" as used herein is defined as a fragrance compound selected from the group consisting of 2-[(4-methylphenyl)methylene]-heptanal (Acalea), iso-amyl oxyacetic acid allylester (Allyl Amyl Glycolate), (3,3-dimethylcyclohexyl)ethyl ethyl propane-1,3-dioate (Applelide), (E/Z)-1-ethoxy-1-decene (Arctical), 10 2-ethyl-4-(2,2,3-trimethyl-3-cyclo-penten-1-yl)-2-buten-1-ol (Bacdanol), 2-methyl-3-[(1,7,7-trimethylbicyclo[2.2.1]hept- 2-yl)oxy] exo-1-propanol (Bornafix), 1,2,3,5,6,7-hexahydro-1,1,2,3,3-pentamethyl-4H-inden-4-one (Cashmeran), trimethylcyclopentenylmethyloxabicyclooctane (Cassiffix), 1,1-dimethoxy-3,7-dimethyl-2,6-octadiene (Citral DMA), 3,7- dimethyl-6-octen-1-ol (Citronellol), 3A,4,5,6,7,7A-hexahydro-4,7-methano-1H-inden-5/6-yl acetate (Cyclacet), 3A,4,5,6,7,7A-hexahydro-4,7-methano-1H-inden-5/6-yl propinoate (Cyclaprop), 3A,4,5,6,7,7A-hexahydro-4,7-meth- 15 ano-1G-inden-5/6-yl butyrate (Cyclobutanate), 1-(2,6,6-trimethyl-3-cyclohexen-1-yl)-2-buten-1-one (Delta Damascone), 3-(4-ethylphenyl)-2,2-dimethyl propanenitrile (Fleuranil), 3-(O/P-ethylphenyl) 2,2-dimethyl propionaldehyde (Floraloz- one), tetrahydro-4-methyl-2-(2-methylpropyl)-2H-pyran-4-ol (Floriffol), 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl- cyclopenta-gamma-2-benzopyran (Galaxolide), 1-(5,5-dimethyl-1-cyclohexen-1-yl)pent-4-en-1-one (Galbascone), E/Z- 3,7-dimethyl-2,6-octadien-1-yl acetate (Geranyl Acetate), α-methyl-1,3-benzodioxole-5-propanal (Helional), 1-(2,6,6- 20 trimethyl-2-cyclohexen-1-yl)-1,6-heptadien-3-one (Hexalon), (Z)-3-hexenyl-2-hydroxybenzoate (Hexenyl Salicylate, CIS-3), 4-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3-buten-2-one (Ionone α), 1-(1,2,3,4,5,6,7,8-octahydro-2,3,8,8-tetrame- thyl-2-naphthalenyl)-ethan-1-one (Iso E Super), methyl 3-oxo-2-pentyleyclopentaneacetate (Kharismal), 2,2,4-trimethyl- 4-phenyl-butanenitrile (Khusinil), 3,4,5,6,6-pentamethylhept-3-en-2-one (Koavone), 3/4-(4-hydroxy-4-methyl-pentyl) cyclohexene-1-carboxaldehyde (Lyral), 3-methyl-4-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3-buten-2-one (Methyl Ionone γ), 25 1-(2,6,6-trimethyl-2-cyclohexen-1-yl) pent-1-en-3-one (Methyl Ionone α Extra, Methyl Ionone N), 3-methyl-4-phenylbu- tan-2-ol (Muguesia), cyclopentadec-4-en-1-one (Musk Z4), 3,3,4,5,5-pentamethyl-11,13-dioxatricyclo[7.4.0.0<2,6>]tri- dec-2(6)-ene (Nebulone), 3,7-dimethyl-2,6-octadien-1-yl acetate (Neryl Acetate), 3,7-dimethyl-1,3,6-octatriene (Oci- mene), ortho-tolylethanol (Peomosa), 3-methyl-5-phenylpentanol (Phenoxanol), 1-methyl-4-(4-methyl-3-pentenyl) cyclohex-3-ene-1-carboxaldehyde (Precyclemone B), 4-methyl-8-methylene-2-adamantanol (Prismantol), 2-ethyl- 30 4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol (Sanjinol), 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten- 1-ol (Santaliff), Terpineol, 2,4-dimethyl-3-cyclohexene-1-carboxaldehyde (Triplal), decahydro-2,6,6,7,8,8-hexamethyl- 2H-indeno[4,5-B]furan (Trisamber), 2-tert-butylcyclohexyl acetate (Verdox), 4-tert-butylcyclohexyL acetate (Vertenex), acetyl cedrene (Vertofix), 3,6/4,6-dimethylcyclohex-3-ene-1-carboxaldehyde (Vertoliff), and (3Z)-1-[(2-methyl-2-prope- nyl)oxy]-3-hexene (Vivaldie). 35 [0023] The terms "fragrance formulation", "fragrance composition", and "perfume composition" mean the same and refer to a consumer composition that is a mixture of compounds including, for example, alcohols, aldehydes, ketones, esters, ethers, lactones, nitriles, natural oils, synthetic oils, and mercaptans, which are admixed so that the combined odors of the individual components produce a pleasant or desired fragrance. The fragrance formulation of the present invention is a consumer composition comprising a compound of the present invention. The fragrance formulation of the 40 present invention may comprise a compound of the present invention and further a complementary fragrance compound as defined above. [0024] The term "fragrance product" means a consumer product containing a fragrance ingredient that adds fragrance or masks malodor. Fragrance products may include, for example, perfumes, colognes, bar soaps, liquid soaps, shower gels, foam baths, cosmetics, skin care products such as creams, lotions and shaving products, hair care products for 45 shampooing, rinsing, conditioning, bleaching, coloring, dyeing and styling, deodorants and antiperspirants, feminine care products such as tampons and feminine napkins, baby care products such as diapers, bibs and wipes, family care products such as bath tissues, facial tissues, paper handkerchiefs or paper towels, fabric products such as fabric softeners and fresheners, air care products such as air fresheners and fragrance delivery systems, cosmetic preparations, cleaning agents and disinfectants such as detergents, dishwashing materials, scrubbing compositions, glass and metal cleaners 50 such as window cleaners, countertop cleaners, floor and carpet cleaners, toilet cleaners and bleach additives, washing agents such as all-purpose, heavy duty, and hand washing or fine fabric washing agents including laundry detergents and rinse additives, dental and oral hygiene products such as toothpastes, tooth gels, dental flosses, denture cleansers, denture adhesives, dentifrices, tooth whitening and mouthwashes, health care and nutritional products and food products such as snack and beverage products. The fragrance product of the present invention is a consumer product that contains 55 a compound of the present invention. The fragrance product of the present invention may contain a compound of the present invention and further a complementary fragrance compound as defined above. [0025] The term "improving" in the phrase "improving, enhancing or modifying a fragrance formulation" is understood to mean raising the fragrance formulation to a more desirable character. The term "enhancing" is understood to mean

4 EP 2 862 599 B1

making the fragrance formulation greater in effectiveness or providing the fragrance formulation with an improved character. The term "modifying" is understood to mean providing the fragrance formulation with a change in character. [0026] The term "olfactory acceptable amount" is understood to mean the amount of a compound in a fragrance formulation, wherein the compound will contribute its individual olfactory characteristics. However, the olfactory effect 5 of the fragrance formulation will be the sum of effect of each of the fragrance ingredients. Thus, the compounds of the present invention can be used to improve or enhance the aroma characteristics of the fragrance formulation, or by modifying the olfactory reaction contributed by other ingredients in the formulation. The olfactory acceptable amount may vary depending on many factors including other ingredients, their relative amounts and the olfactory effect that is desired. 10 [0027] The amount of the compounds of the present invention employed in a fragrance formulation varies from 0.005 to 70 weight percent, preferably 0.05 to 50 weight percent, more preferably from 0.5 to 25 weight percent, and even more preferably from 1 to 10 weight percent. Those with skill in the art will be able to employ the desired amount to provide desired fragrance effect and intensity. In addition to the compounds of the present invention, other materials can also be used in conjunction with the fragrance formulation to encapsulate and/or deliver the fragrance. Some well- 15 known materials are, for example, but not limited to, polymers, oligomers, other non-polymers such as surfactants, emulsifiers, lipids including fats, waxes and phospholipids, organic oils, mineral oils, petrolatum, natural oils, perfume fixatives, fibers, starches, sugars and solid surface materials such as zeolite and silica. [0028] When used in a fragrance formulation these ingredients provide additional notes to make a fragrance formulation more desirable and noticeable, and add the perception of value. The odor qualities found in these materials assist in 20 beautifying and enhancing the finished accord as well as improving the performance of the other materials in the fragrance. [0029] Inaddition, the compounds used inthe present invention arealso surprisingly foundto provide superior ingredient performance and possess unexpected advantages in malodor counteracting applications such as body perspiration, environmental odor such as mold and mildew, bathroom, and etc. The compounds used in the present invention substantially eliminate the perception of malodors and/or prevent the formation of such malodors, thus, can be utilized with 25 a vast number of functional products. [0030] Examples of the functional products are provided herein to illustrate the various aspects of the present invention. The functional products may include, for example, a conventional room freshener (or deodorant) composition such as room freshener sprays, an aerosol or other spray, fragrance diffusers, a wick or other liquid system, or a solid, for instance candles or a wax base as in pomanders and plastics, powders as in sachets or dry sprays or gels, as in solid gel sticks, 30 clothes deodorants as applied by washing machine applications such as in detergents, powders, liquids, whiteners or fabric softeners, fabric refreshers, linen sprays, closet blocks, closet aerosol sprays, or clothes storage areas or in dry cleaning to overcome residual solvent notes on clothes, bathroom accessories such as paper towels, bathroom tissues, sanitary napkins, towellets, disposable wash cloths, disposable diapers, and diaper pail deodorants, cleansers such as disinfectants and toilet bowl cleaners, cosmetic products such as antiperspirant and deodorants, general body deodorants 35 in the form of powders, aerosols, liquids or solid, or hair care products such as hair sprays, conditioners, rinses, hair colors and dyes, permanent waves, depilatories, hair straighteners, hair groom applications such as pomade, creams and lotions, medicated hair care products containing such ingredients as selenium sulphide, coal tar or salicylates, or shampoos, or foot care products such as foot powders, liquids or colognes, after shaves and body lotions, or soaps and synthetic detergents such as bars, liquids, foams or powders, odor control such as during manufacturing processes, 40 such as in the textile finishing industry and the printing industry (inks and paper), effluent control such as in processes involved in pulping, stock yard and meat processings, sewage treatment, garbage bags, or garbage disposal, or in product odor control as in textile finished goods, rubber finished goods or car fresheners, agricultural and pet care products such as dog and hen house effluents and domestic animal and pet care products such as deodorants, shampoo or cleaning agents, or animal litter material and in large scale closed air systems such as auditoria, and subways and 45 transport systems. [0031] Thus, it will be seen that the composition of the invention is usually one in which the malodor counteractant is present together with a carrier by means of which or from which the malodor counteractant can be introduced into air space wherein the malodor is present, or a substrate on which the malodor has deposited. For example, the carrier can be an aerosol propellant such as a chlorofluoro-methane, or a solid such as a wax, plastics material, rubber, inert powder 50 or gel. In a wick-type air freshener, the carrier is a substantially odorless liquid of low volatility. In several applications, a composition of the invention contains a surface active agent or a disinfectant, while in others, the malodor counteractant is present on a fibrous substrate. In many compositions of the invention there is also present a fragrance component which imparts a fragrance to the composition. The fragrances stated above can all be employed. [0032] Malodor counteracting effective amount is understood to mean the amount of the inventive malodor counter- 55 actant employed in a functional product that is organoleptically effective to abate a given malodor while reducing the combined intensity of the odor level, wherein the given malodor is present in air space or has deposited on a substrate. The exact amount of malodor counteractant agent employed may vary depending upon the type of malodor counteractant, the type of the carrier employed, and the level of malodor counteractancy desired. In general, the amount of malodor

5 EP 2 862 599 B1

counteractant agent present is the ordinary dosage required to obtain the desired result. Such dosage is known to the skilled practitioner in the art. In a preferred embodiment, when used in conjunction with malodorous solid or liquid functional products, e.g., soap and detergent, the compounds of the present invention may be present in an amount ranging from about 0.005 to about 50 weight percent, preferably from about 0.01 to about 20 weight percent, and more 5 preferably from about 0.05 to about 5 weight percent, and when used in conjunction with malodorous gaseous functional products, the compounds of the present invention may be present in an amount ranging from about 0.1 to 10 mg per cubic meter of air. [0033] The following are provided as specific embodiments of the present invention. As used herein all percentages are weight percent unless otherwise noted, ppm is understood to stand for parts per million, L is understood to be liter, 10 mL is understood to be milliliter, g is understood to be gram, Kg is understood to be kilogram, mol is understood to be mole and mmHg be millimeters (mm) of mercury (Hg). IFF as used in the examples is understood to mean International Flavors & Fragrances Inc., New York, NY, USA.

EXAMPLE I 15 [0034]

25 [0035] Preparation of Ethyl 3-(Cyclohex-1-en-1-yl)propionate (Structure I): A 2-L reaction flask equipped a reflux condenser and a Dean Stark trap was charged with bicyclononalactone (commercially available from IFF) (600 g, 3.89 mol), butanol (432 g, 5.8 mol) and methanesulfonic acid (MSA) (18.7 g, 0.19 mol). The reaction mixture was heated to reflux at 110-120°C for 4-6 hours. Water ( ∼50 mL) was collected in the Dean Stark trap. The reaction mixture was then cooled to an ambient temperature, neutralized with aqueous sodium carbonate (Na2CO3) (10%, 100 mL) and washed 30 with brine (1 L). Flash vacuum distillation at a boiling point of 160-175°C and a pressure of 3 mmHg afforded crude butyl 3-(cyclohex-1-en-1-yl)propionate. Subsequently, a 3-L reaction flask equipped a reflux condenser was charged with the crude butyl 3-(cyclohex-1-en-1-yl)propionate (700 g) from the previous step, ethanol (1 L) and MSA (10 g, 0.1 mol). The reaction mixture was heated to reflux at 80-100°C for 8 hours. The reaction mixture was then cooled to an ambient

temperature, neutralized with aqueous Na 2CO3 (10%, 2 L) and washed with brine (1L). The organic layer was separated 35 from the aqueous layer in a separatory funnel and further fractional distilled to afford product ethyl 3-(cyclohex-1-en-1- yl)propionate (379 g) with a boiling point of 127-131°C and a pressure of 3 mmHg. 1 [0036] H NMR (500 MHz, CDCl 3): 5.41 ppm (m, 1H), 4.12 ppm (q, 2H, J=7.15 Hz), 2.40 ppm (t, 2H, J=7.00 Hz), 2.25 ppm (t, 2H, J=7.00 Hz)), 1.90-2.00 ppm (m, 4H), 1.50-1.64 ppm (m, 4H), 1.25 ppm (t, 3H, J=7.15 Hz).

40 EXAMPLE II

[0037]

[0038] Preparation of 2-Propyl 3-(Cyclohex-1-en-1-yl)propionate (Structure II): A 3-L reaction flask equipped a reflux condenser was charged with crude butyl 3-(cyclohex-1-en-1-yl)propionate (421 g, 2 mol) (prepared as above in EXAMPLE I), 2-propanol (IPA) (2 L) and aqueous sodium hydroxide solution (NaOH) (50% by weight) (240 g, 3 mol). 55 The reaction mixture was heated to reflux at 80-85°C for 8 hours. The reaction mixture was then cooled to an ambient temperature and acidified with hydrochloric acid (HCl) (37%, 400 mL). Toluene (500 mL) was added and the reaction mixture was washed with brine (2 L). The organic layer was removed via a separatory funnel. Toluene was recovered using a Buchi Rotary Evaporator to afford solvent-free crude 3-(cyclohex-1-en-1-yl)propionic acid. Subsequently, a 2-L

6 EP 2 862 599 B1

reaction flask equipped a reflux condenser was charged with the crude 3-(cyclohex-1-en-1-yl)propionic acid from the previous step, IPA (1.5 L) and sulfuric acid (H 2SO4) (98%, 10 g). The reaction mixture was heated to reflux at 80-85°C for 4 hours. The reaction was then cooled to an ambient temperature, neutralized with aqueous Na 2CO3 (10%, 2 L) and washed with brine (1 L). The organic layer was separated from the aqueous layer in a separatory funnel and further 5 fractional distilled to afford product 2-propyl 3-(cyclohex-1-en-1-yl)propionate (20 g) with a boiling point of 124-128°C and a pressure of 3 mmHg. 1 [0039] H NMR (500 MHz, CDCl3): 5.41 ppm (m, 1H), 5.00 ppm (hep, 1H, J=6.25 Hz), 2.37 ppm (t, 2H, J=7.60 Hz), 2.24 ppm (t, 2H, J=7.60 Hz), 1.90-2.00 ppm (m, 4H), 1.50-1.64 ppm (m, 4H), 1.22 ppm (d, 6H, J=6.25 Hz)

10 COMPARATIVE EXAMPLE III

[0040]

[0041] Preparation of Allyl 3-(cyclohex-1-en-1-yl)propionate (Structure III): A 3-L reaction flask equipped a reflux 25 condenser was charged with crude 3-(cyclohex-1-en-1-yl)propionic acid (400 g, 2.5 mol) (prepared as above in EXAMPLE

II), methanol (MeOH) (2 L) and H2SO4 (98%, 18 g). The reaction mixture was heated to reflux at 65-75°C for 8 hours. The reaction mixture was then cooled to an ambient temperature and diluted with toluene (500 mL). The reaction mixture

was neutralized with aqueous Na 2CO3 (10%, 2 L) and washed with brine (1 L) to obtain crude methyl 3-(cyclohex-1-en- 1-yl)propionate. Subsequently, a 2-L reaction flask equipped a reflux condenser and a Dean Stark trap was charged 30 with the crude methyl 3-(cyclohex-1-en-1-yl)propionate from the previous step, allyl alcohol (CH2=CHCH2OH) (282 g, 4.8 mol) and sodium methoxide (NaOMe) (11 g, 0.2 mol). The reaction mixture was heated to reflux at 65-85°C for 8 hours. Methanol was removed. The reaction was then cooled to an ambient temperature, neutralized with aqueous acetic acid (10%, 2 L) and washed with brine (1 L). The organic layer was separated from the aqueous layer in a separatory funnel and further fractional distilled to afford product allyl 3-(cyclohex-1-en-1-yl)propionate (20 g) with a 35 boiling point of 140-146°C and a pressure of 3 mmHg. 1 [0042] H NMR (500 MHz, CDCl3): 5.86-5.95 ppm (m, 1H), 5.42 ppm (m, 1H), 5.20-5.34 ppm (m, 2H), 4.57 ppm (d, 2H, J=5.65 Hz), 2.44 ppm (t, 2H, J=7.75 Hz), 2.26 ppm (t, 2H, J=7.75 Hz), 1.90-2.00 ppm (m, 4H), 1.50-1.64 ppm (m, 4H)

COMPARATIVE EXAMPLES IV-VII 40 [0043] Additional 3-(cyclohex-1-en-1-yl)propionates (Structures IV-VII) were similarly prepared.

Ethyl 3-(cyclohex-3-en-1-yl)propionate (Structure IV):

45 [0044]

55 1 [0045] H NMR (500 MHz, CDCl 3): 5.57-5.49 ppm (bs, 2H), 4.10 ppm (t, 2H, J=7.15 Hz), 2.63-2.55 ppm (m, 2H), 2.32 ppm (t, 2H, J=7.00 Hz)), 2.20-1.40 ppm (m, 7H), 1.18 ppm (t, 3H, J=7.15 Hz)

7 EP 2 862 599 B1

Allyl 3-(cyclohex-3-en-1-yl)propionate (Structure V):

[0046]

[0047] 1H NMR (500 MHz, CDC13): 5.57-5.49 ppm (bs, 2H), 5.42 ppm (m, 1H), 5.20-5.34 ppm (m, 2H), 4.57 ppm (d, 15 2H, J=5.65 Hz), 2.44 ppm (t, 2H, J=7.75 Hz), 2.26 ppm (t, 2H, J=7.75 Hz), 2.20-1.40 ppm (m, 7H)

Methyl 3-(cyclohex-1-en-1-yl)propionate (Structure VI):

[0048] 20

30 1 [0049] H NMR (500 MHz, CDCl3): 5.41 ppm (m, 1H), 3.60 ppm (s, 3H), 2.40 ppm (t, 2H, J=7.00 Hz), 2.25 ppm (t, 2H, J=7.00 Hz), 1.90-2.00 ppm (m, 4H), 1.50-1.64 ppm (m, 4H)

Methyl 3-(cyclohex-3-en-1-yl)propionate (Structure VII):

35 [0050]

45 1 [0051] H NMR (500 MHz, CDCl3): 5.57-5.49 ppm (bs, 2H), 3.66 ppm (s, 3H), 2.63-2.55 ppm (m, 2H), 2.32 ppm (t, 2H, J=7.00 Hz)), 2.20-1.40 ppm (m, 7H)

EXAMPLE V 50 [0052] The above compounds (i.e., Structures I-VII) were evaluated for odor properties.

8 EP 2 862 599 B1

Chemical Name Compound Odor Profile

Powerful and complex with unique fruity Ethyl 3-(cyclohex-1-en-1- and woody combination. The woody 5 yl)propionate (Structure I) aspect, supported by spiciness, provided further dimension.

2-Propyl 3-(cyclohex-1-en-1- Fruity and sweet but less powerful and 10 yl)propionate (Structure II) complex than Structure I.

15 Allyl 3-(cyclohex-1-en-1- Fruity and green but unpleasant. yl)propionate (Structure III) Chemical, dirty and artificial.

Fruity but dirty and unpleasant. As dried, 20 Ethyl 3-(cyclohex-3-en-1- fruitinessdissipated quickly and a sweaty yl)propionate (Structure IV) and cumin-like character became predominant.

25 Allyl 3-(cyclohex-3-en-1- Fruity but with dirty metal and potato skin yl)propionate (Structure V) characters.

30 Methyl 3-(cyclohex-1-en-1- Less appealing, weaker and less yl)propionate (Structure VI) complex than Structure I.

35 Less appealing, weaker and less Methyl 3-(cyclohex-3-en-1- complex than Structure I and slightly yl)propionate (Structure VII) metallic.

40 [0053] Among Structures I-VII, Structures I and II exhibited desirable odors. In particular, Structure I possessed strong and complex odors, superior to the others. The advantageous properties of Structures I and II are unexpected.

EXAMPLE VI

45 [0054] Establishment of Malodor Models: A number of malodorous chemicals have been identified, which are associated with different types of malodors. Commercial samples of these chemicals (commercially available at Sigma- Aldrich Inc.) were thus used in the present invention as malodorous model compounds to assess the effectiveness of ethyl 3-(cyclohex-1-en-1-yl)propionate in counteracting malodors. [0055] A model of bathroom malodor was established using a solution of isovaleric acid ("IVA"). A model of sweat 50 malodor was established using a solution of 3-methyl-2-hexanoic acid. A model of mold/mildew malodors was established using a solution of 2-ethyl-1-hexanol. A model of smoke malodor was established by applying a solution of 3-acetyl pyridine. [0056] Preparation of Test Samples: Ethyl 3-(cyclohex-1-en-1-yl)propionate was prepared at a series of concentra- tions, ranging from 0.1% to 10% in diethyl phthalate ("DEP"). 55 [0057] A malodor material as established above (1 g) and a solution of ethyl 3-(cyclohex-1-en-1-yl)propionate in DEP (1 g) (1%) were pipetted into separate aluminum weighing dishes located at the bottom of a 32 oz. jar (1 L). For negative control samples (Malodor Alone), the malodor material (0.5 g) was pipetted into each of the two dishes located at the

9 EP 2 862 599 B1

bottom of jar. Jars were then capped and the samples were allowed to equilibrate for 24 hours before testing. [0058] Testing Procedure: Test samples were presented in a blind and pseudorandom order to a group of trained panelists (consisting of 20 females with a mean age of 45 years). The panelists were instructed to take the following steps: i) sniff malodor reference jars for familiarization prior to each testing session; ii) uncap a jar; iii) place their nos es 5 at a distance of about 3-4 inches above the opening; iv) take short sniffs for about 2 -3 seconds; and v) enter a rating of overall intensity and malodor intensity on a handheld computer. [0059] The overall and malodor intensity was rated using the Labeled Magnitude Scale (LMS) [Green, et al., Chemical Senses, 21(3): 323-334 (1996)]. Mean ("Malodor Intensity") and standard error of the mean ("SE",6 ) were obtained, where 0 represents "No Sensation" and 100 represents "The Strongest Imaginable Malodor Sensation". Percent malodor 10 reduction ("%MOR") represents the perceived reduction in mean malodor intensity of the sample containing the malodor in the presence of methyl 3-methyl cyclohexane carboxylate relative to the negative control (Malodor Alone). [0060] Test Results: The malodor test results are as follows:

No. Group %MOR 15 1 Sweat Malodor 86 2 Bathroom Malodor 79 3 Mold/Mildew Malodor 78

20 4 Smoke Malodor 88

[0061] The above test has demonstrated the effectiveness of 3-(cyclohex-1-en-1-yl)propionate in counteracting various types of malodor including sweat, bathroom, mold/mildew and smoke.

Claims

1. A fragrance formulation containing

30 (i) an olfactory acceptable amount of a compound of formula:

40 wherein R is selected from the group consisting of ethyl and 2-propyl and the olfactory acceptable amount is from 0.005 to 50 weight percent of the fragrance formulation; and (ii) a non-polymer selected from the group consisting of an oligomer, a surfactant, an emulsifier, a fat, a wax, a phospholipid, an organic oil, a mineral oil, a petrolatum, a natural oil, a perfume fixative, a fiber, a starch, a sugar and a solid surface material.

45 2. The fragrance formulation of claim 1, wherein the solid surface material is selected from the group consisting of zeolite and silica.

3. The fragrance formulation of claim 1, wherein the olfactory acceptable amount is (i) from 0.5 to 25 weight percent

50 of the fragrance formulation or (ii) from 1 to 10 weight percent of the fragrance formulation.

4. A method of improving, enhancing or modifying a fragrance formulation through the addition of an olfactory acceptable amount of a compound of formula:

10 EP 2 862 599 B1

wherein R is selected from the group consisting of ethyl and 2-propyl and the olfactory acceptable amount is from 0.005 to 50 weight percent of the fragrance formulation. 10 5. The method of claim 4, wherein the olfactory acceptable amount is (i) from 0.5 to 25 weight percent of the fragrance formulation; or (ii) from 1 to 10 weight percent of the fragrance formulation.

6. A fragrance product containing an olfactory acceptable amount of a compound of formula: 15

wherein R is selected from the group consisting of ethyl and 2-propyl and the olfactory acceptable amount is from 0.005 to 50 weight percent of the fragrance formulation, wherein the fragrance product is selected from the group 25 consisting of a perfume, a cologne, toilet water, a cosmetic product, a personal care product, a fabric care product, a cleaning agent and an air freshener, a bar soap, a liquid soap, a shower gel, a foam bath, a cosmetic, a skin care product, a hair care product, a deodorant, an antiperspirant, a feminine care product, a baby care product, a family care product, a fabric product, an air care product, a fragrance delivery system, a cosmetic preparation, a disinfectant, a washing agent, a dental and oral hygiene product, a health care and nutritional product and a food product. 30 7. The fragrance product of claim 6, wherein (i) the cleaning agent is selected from the group consisting of a detergent, a dishwashing material, a scrubbing composition, a glass cleaner, a metal cleaner, a countertop cleaner, a floor cleaner, a carpet cleaner, a toilet cleaner and a bleach additive; or (ii) the washing agent is selected from the group consisting of a laundry detergent and a rinse additive. 35 8. A method of counteracting a malodor comprising the step of introducing a malodor counteracting effective amount of a compound of formula:

45 wherein R is selected from the group consisting of ethyl and 2-propyl.

9. A composition containing a malodor counteracting effective amount of a compound of formula:

wherein R is selected from the group consisting of ethyl and 2-propyl, wherein the composition is incorporated in a functional product selected from the group consisting of a room freshener spray, a fragrance diffuser, a candle, a

11 EP 2 862 599 B1

sachet, a clothes deodorant, a detergent, a fabric softener, a fabric refresher, a linen spray, a disposable diaper, a diaper pail deodorant, an antiperspirant, a deodorant, a garbage bag, a car freshener, a pet care product, and an animal litter material.

5 10. The fragrance product of claim 6, wherein the olfactory acceptable amount is (i) from 0.5 to 25 weight percent of the fragrance formulation; or (ii) from 1 to 10 weight percent of the fragrance formulation.

Patentansprüche 10 1. Eine Duftformel, die Folgendes beinhaltet

(i) eine olfaktorisch akzeptable Menge einer Verbindung der Formel:

20 wobei R ausgewählt ist aus der Gruppe bestehend aus Ethyl und 2-Propyl und die olfaktorisch akzeptablen Menge zwischen 0,005 bis 50 Gewichtprozent der Duftformel liegt; und (ii) ein Nicht-Polymer ausgewählt aus der Gruppe bestehend aus einem Oligomer, einem Tensid, einem Emul- gator,einem Fett, einem Wachs,einem Phospholipid, einem organischenÖl, einem Mineralöl,einem Petrolatum, 25 einem Naturöl, einem Duftfixiermittel, einer Faser, einer Stärke, einem Zucker und einem festen Oberflächen- material.

2. Die Duftformel gemäß Anspruch 1, wobei das feste Oberflächenmaterial ausgewählt ist aus der Gruppe bestehend aus einem Zeolit und Kieselsäure. 30 3. Die Duftformel gemäß Anspruch 1, wobei die olfaktorisch akzeptable Menge (i) zwischen 0,5 und 25 Gewichtsprozent der Duftformel oder (ii) zwischen 1 und 10 Gewichtsprozent der Duftformel liegt.

4. Ein Verfahren zur Verbesserung, Weiterentwicklung oder Änderung einer Duftformel durch Hinzufügen einer olfak- 35 torisch akzeptablen Menge einer Verbindung der Formel:

wobei R ausgewählt ist aus der Gruppe bestehend aus Ethyl und 2-Propyl und die olfaktorisch akzeptable Menge zwischen 0,005 bis 50 Gewichtprozent der Duftformel liegt. 45 5. Das Verfahren gemäß Anspruch 4, wobei die olfaktorisch akzeptable Menge (i) zwischen 0,5 und 25 Gewichtsprozent der Duftformel oder (ii) zwischen 1 und 10 Gewichtsprozent der Duftformel liegt.

6. Ein Duftprodukt, das eine olfaktorisch akzeptable Menge einer Verbindung der folgenden Formel enthält: 50

wobei R ausgewählt ist aus der Gruppe bestehend aus Ethyl und 2-Propyl und die olfaktorisch akzeptable Menge

12 EP 2 862 599 B1

zwischen 0,005 und 50 Gewichtsprozent der Duftformel liegt, wobei das Duftprodukt ausgewählt ist aus der Gruppe bestehend aus einem Parfüm, einem Kölnischwasser, einem Eau de Toilette, einem Kosmetikprodukt, einem Kör- perpflegeprodukt, einem Stoffpflegeprodukt, einem Reinigungsprodukt und einem Lufterfrischer, einem Seifenstück, einer Flüssigseife, einem Duschgel, einem Schaumbad, einem Kosmetikmittel, einem Hautpflegeprodukt, einem 5 Haarpflegeprodukt, einem Deodorant, einem Antitranspirant, einem Frauenpflegemittel, einem Babypflegemittel, einem Familienpflegemittel, einem Fasererzeugnis, einem Lufterfrischer, einem Duftspendersystem, einem kosme- tischen Präparat, einem Desinfektionsmittel, einem Waschmittel, einem Zahnpflege- und Mundhygieneprodukt, einem Gesundheitsvorsorge- und Ernährungsprodukt und einem Nahrungsmittel.

10 7. Das Duftprodukt gemäß Anspruch 6, wobei (i) das Reinigungsprodukt ausgewählt ist aus der Gruppe bestehend aus einem Waschmittel, einem Spülmittel, einem Scheuermittel, einem Glasreiniger, einem Metallreiniger, einem Arbeitsplattenreiniger, einem Bodenreinigungsmittel, einem Teppichreinigungsmittel, einem Toilettenreiniger und einem Bleichmittel-Zusatzstoff oder wobei (ii) das Waschmittel ausgewählt ist aus der Gruppe bestehend aus einem Reinigungsmittel und einem Spülzusatzstoff. 15 8. Ein Verfahren zur Bekämpfung eines schlechten Geruchs, das den Schritt der Einführung einer wirksamen Menge eines Geruchsbekämpfungsmittels mit einer Verbindung der folgenden Formel aufweist:

25 wobei R ausgewählt ist aus der Gruppe bestehend aus Ethyl und 2-Propyl.

9. Eine Zusammensetzung, die eine wirksame Menge eines Geruchsbekämpfungsmittels mit einer Verbindung der folgenden Formel enthält:

35 wobei R ausgewählt ist aus der Gruppe bestehend aus Ethyl und 2-Propyl, wobei die Zusammensetzung einge- bunden ist in ein funktionales Produkt ausgewählt aus der Gruppe bestehend aus einem Raumerfrischungsspray, einem Duftzerstäuber, einer Kerze, einem Duftkissen, einem Kleidungs-Deodorant, einem Waschmittel, einem Weichspüler, einem Gewebeauffrischer, einem Leintuchspray, einer Wegwerfwindel, einem Windelabfalleimer-De- 40 odorant, einem Antitranspirant, einem Deodorant, einem Müllbeutel, einem Autoerfrischer, einem Haustierpflege- produkt und einem Haustierstreumaterial.

10. Das Duftprodukt gemäß Anspruch 6, wobei die olfaktorisch akzeptable Menge (i) zwischen 0,5 und 25 Gewichts- prozent der Duftformel oder (ii) zwischen 1 und 10 Gewichtsprozent der Duftformel liegt. 45

Revendications

1. Une formulation de fragrance contenant 50 (i) une quantité acceptable sur le plan olfactif d’un composé de la formule :

13 EP 2 862 599 B1

où R est sélectionné dans le groupe se composant d’éthyle et de 2-propyle et la quantité acceptable sur le plan olfactif est de 0,005 à 50% en poids de la formulation de fragrance, et (ii) un non-polymère sélectionné dans le groupe se composant d’un oligomère, un tensioactif, un émulsifiant, une graisse, une cire, un phospholipide, une huile organique, une huile minérale, une vaseline, une huile 5 naturelle, un fixateur de parfum, une fibre, un amidon, un sucre et un matériau à surface solide.

2. La formulation de fragrance selon la Revendication 1, où le matériau à surface solide est sélectionné dans le groupe se composant de zéolite et silice.

10 3. La formulation de fragrance selon la Revendication 1, où la quantité acceptable sur le plan olfactif est (i) de 0,5 à 25% en poids de la formulation de fragrance ou (ii) de 1 à 10% en poids de la formulation de fragrance.

4. Un procédé d’amélioration, de rehaussement ou de modification d’une formulation de fragrance par l’ajout d’une quantité acceptable sur le plan olfactif d’un composé de la formule : 15

où R est sélectionné dans le groupe se composant d’éthyle et de 2-propyle et la quantité acceptable sur le plan olfactif est de 0,005 à 50% en poids de la formulation de fragrance.

25 5. Le procédé selon la Revendication 4, où la quantité acceptable sur le plan olfactif est (i) de 0,5 à 25% en poids de la formulation de fragrance ou (ii) de 1 à 10% en poids de la formulation de fragrance.

6. Un produit de fragrance contenant une quantité acceptable sur le plan olfactif d’un composé de la formule :

où R est sélectionné dans le groupe se composant d’éthyle et de 2-propyle et la quantité acceptable sur le plan olfactif est de 0,005 à 50% en poids de la formulation de fragrance, où le produit de fragrance est sélectionné dans le groupe se composant d’un parfum, une eau de Cologne, une eau de toilette, un produit cosmétique, un produit 40 de soin personnel, un produit d’entretien pour textiles, un agent de nettoyage et un désodorisant, un savon en barre, un savon liquide, un gel douche, un bain moussant, un produit cosmétique, un produit de soins de la peau, un produit de soins capillaires, un déodorant, un antitranspirant, un produit d’hygiène féminine, un produit de soins pour bébé, un produit de soins de la famille, un produit pour textiles, un produit d’entretien de l’air, un système de diffusion de parfum, une préparation cosmétique, un désinfectant, un agent de lavage, un produit d’hygiène buccale 45 et dentaire, un produit nutritif et de soins de santé et un produit alimentaire.

7. Le produit de fragrance selon la Revendication 6, où (i) l’agent de nettoyage est sélectionné dans le groupe se composant d’un détergent, un matériau de lavage de vaisselle, une composition de récurage, un produit de nettoyage de verre, un produit de nettoyage de métaux, un produit de nettoyage de plan de travail, un produit de nettoyage 50 de sols, un produit de nettoyage de tapis, un produit de nettoyage de toilettes et un additif de blanchiment, ou (ii) l’agent de lavage est sélectionné dans le groupe se composant d’un détergent de lavage et d’un additif de rinçage.

8. Un procédé destiné à contrecarrer une mauvaise odeur comprenant l’opération d’introduction d’une quantité efficace pour contrecarrer une mauvaise odeur dans un composé de la formule : 55

14 EP 2 862 599 B1

où R est sélectionné dans le groupe se composant d’éthyle et de 2-propyle.

9. Une composition contenant une quantité efficace pour contrecarrer une mauvaise odeur d’un composé de la formule : 10

où R est sélectionné dans le groupe se composant d’éthyle et de 2-propyle, où la composition est incorporée dans un produit fonctionnel sélectionné dans le groupe se composant d’un spray désodorisant d’appartement, un diffuseur de parfum, une bougie, un sachet, un désodorisant pour vêtements, un détergent, un adoucissant pour textiles, un 20 rafraîchissant pour textiles, une couche jetable, un déodorant pour seau de couches usées, un antitranspirant, un déodorant, un sac à ordures, un désodorisant pour voiture, un produit de soins pour animaux de compagnie et un matériau de litière pour animaux.

10. Le produit de fragrance selon la Revendication 6, où la quantité acceptable sur le plan olfactif est (i) de 0,5 à 25% 25 en poids de la formulation de fragrance, ou (ii) de 1 à 10% en poids de la formulation de fragrance.

15 EP 2 862 599 B1

REFERENCES CITED IN THE DESCRIPTION

This list of references cited by the applicant is for the reader’s convenience only. It does not form part of the European patent document. Even though great care has been taken in compiling the references, errors or omissions cannot be excluded and the EPO disclaims all liability in this regard.

Patent documents cited in the description

• EP 1167507 A [0004] • US 4534891 A [0021]

Non-patent literature cited in the description

• ISHIKAWA et al. International Journal of Quantum • NAKAMURA et al. J. Am. Chem. Soc., 1987, vol. Chemistry, 2000, vol. 79, 101-108 [0002] 109, 8056-8066 [0006] • OHLOFF et al. Helvetica Chimica Acta, 1983, vol. • Perfumes. Cosmetics and Soaps. 1959 [0021] 66, 1343-1354 [0002] • GREEN et al. Chemical Senses, 1996, vol. 21 (3), • MEYOUNG et al. J. Org. Chem., 1997, vol. 63, 323-334 [0059] 2755-2757 [0006]