Fragrance and flavor compositions comprising aromatic derivatives

Abstract

The present application relates to 1-ethynyl-4-pentylbenzene and related compounds, methods of making them, and methods of using them as flavor and fragrance ingredients in food, cosmetic, pharmaceutical, consumer, and other compositions and products.

Description

FRAGRANCE AND FLAVOR COMPOSITIONS COMPRISING AROMATIC DERIVATIVES CROSS-REFERENCE TO RELATED APPLICATIONS This application is an international application which claims priority to, and the benefit of, U.S. Provisional Applic. Ser. No. 63 / 535,728, filed on Aug. 31, 2023, and U.S. Provisional Applic. Ser. No. 63 / 624,739, filed on Jan. 24, 2024, the contents of each of which are hereby incorporated by reference in their entireties. FIELD OF THE APPLICATION

[0001] The present application relates to 1-ethynyl-4-pentylbenzene, and related compounds, methods of making them, and methods of using them as flavor and fragrance ingredients in food, cosmetic, pharmaceutical, consumer, and other compositions and products. BACKGROUND

[0002] Scent is an important factor used to produce a sense of anticipation, quality, palatability, and security to many consumer products. Flavor is particularly important for foodstuffs. Identifying effective aromas and flavors to impart in a product is an element that contributes to the success of the product, and is useful in product marketing, consumer satisfaction, and consumer retention. Grainy, floral, muguet, orris, fresh, fruity, apple, and pear notes may be particularly desirable for certain flavors and fragrances and may be used in toiletries, cosmetics, household cleaners, room sprays, laundry, and fine fragrance applications, such as in perfumes and toilet water, dental hygiene products (such as toothpastes and mouthwashes), orally administered medications, and food products.

[0003] Considerable work is performed by many scientists relating to identifying new substances which can be used, alone or in combinations, to impart to, or enhance, the aroma or flavor of various consumable materials, including, e.g., cosmetics, cleaners, and foodstuffs. While there may be some trends in the relationship between chemical structure and flavor or fragrance— such as common use of low molecular weight aldehydes and alcohols as flavors and fragrances—the precise aroma associated with a molecule is exceedingly difficult to predict. Small changes in structure, such a lengthening or shortening a functional group by just one carbon atom, can have profound and unexpected effects on a compound’s flavor or fragrance profile. The art of flavor and fragrance prediction is stiwl in its infancy.

[0004] Using a proprietary predictive method, the inventors have identified 1-ethynyl-4- pentylbenzene as a new ingredient useful in flavors and fragrances. It is believed that this compound has not been previously identified as a flavor or fragrance ingredient, nor has its smell or odor been previously described.

[0005] This application describes the surprising and unexpected olfactive qualities of 1- ethynyl-4-pentylbenzene, and analogs and derivatives thereof, and their use as fragrance and flavor ingredients, and potential applications thereof. BRIEF SUMMARY

[0006] In one aspect, the application relates to compounds of Formula I:wherein: R1is H, CH3, CH2CH3,CH2CH2CH3, or CH(CH3)2; R2, R4, R5, and R6, are each independently selected from H, C1-3alkyl (e.g., CH3), OH, CHO, or OC1-3alkyl (e.g., OCH3); X is selected from -O-, -CH2-, -C(O)-, -CH(OH)-, and -CH(OR)-; Y is selected from -CH2CH2CH2CH2-, -CH2CH2OCH2-, -CH2OCH2CH2-, - OCH2CH2CH2-, -CH2CH2CH2-, -CH2CH2O-, -CH2OCH2-, -OCH2CH2-,- CH2CH2CH2CH2CH2-, -OCH2CH2CH2CH2-, -CH2OCH2CH2CH2-, -CH2CH2OCH2CH2-, - CH2CH2CH2OCH2-, -CH2CH2CH2CH2O-, -CH2CH2CH2CH2CH2CH2-, - OCH2CH2CH2CH2CH2-, -CH2OCH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2-, - CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2O-, - CH2CH2CH2CH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2CH2-, -CH2OCH2CH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2CH2-, -CH2CH2CH2OCH2CH2CH2-, -CH2CH2CH2CH2OCH2CH2-, - CH2CH2CH2CH2CH2OCH2-, and -CH2CH2CH2CH2CH2CH2O-,wherein said group Y is optionally substituted by one or more groups selected from C1-3alkyl (e.g., CH3), OH, CHO, and OC1-3alkyl (e.g., OCH3); or X-Y is absent; R3is selected from H, Rb, OH, ORb, OC(O)Rb, CN, COOH, COORb, C(O)Rb, and CHO; and each Rbis independently optionally substituted C1-6alkyl (e.g., CH3or CH2CH3), C2-6alkenyl (e.g., allyl or 2-methylprop-1-enyl), CH2C3-6cycloalkyl (e.g., cyclopropylmethyl), C3-6cycloalkyl (e.g., cyclopropyl), C4-6cycloalkenyl (e.g., cyclopentenyl), optionally substituted phenyl, or optionally substituted benzyl; optionally provided that the compound is not 1-ethynyl-4-methylbenzene, 1-ethynyl- 2,4-dimethylbenzene, 1-ethynyl-3-methylbenzene, 1-ethynyl-4-propylbenzene, 1-ethynyl-4- butylbenzene, 1-ethynyl-4-pentylbenzene, or 1-ethynyl-4-hexylbenzene.

[0007] In some embodiments, the compound of Formula I is 1-ethynyl-4-methylbenzene, 1- ethynyl-2,4-dimethylbenzene, 1-ethynyl-3-methylbenzene, 1-ethynyl-4-propylbenzene, 1-ethynyl-4- butylbenzene, 1-ethynyl-4-pentylbenzene, or 1-ethynyl-4-hexylbenzene.

[0008] In another aspect, the application relates to fragrance and flavor compositions comprising the compound of Formula I, optionally comprising one or more additives, additional fragrance or flavor ingredients, or a combination of additives and fragrance or flavor ingredients. In some embodiments, the application relates to fragrance and flavor compositions comprising 1- ethynyl-4-methylbenzene, 1-ethynyl-2,4-dimethylbenzene, 1-ethynyl-3-methylbenzene, 1-ethynyl-4- propylbenzene, 1-ethynyl-4-butylbenzene,1-ethynyl-4-pentylbenzene, or 1-ethynyl-4-hexylbenzene.

[0009] In another aspect, the application relates to products, such as consumer products, comprising such fragrance and flavor compositions comprising the compound of Formula I, e.g., products comprising 1-ethynyl-4-propylbenzene, 1-ethynyl-4-butylbenzene, or 1-ethynyl-4- pentylbenzene.

[0010] In another aspect, the present disclosure provides a method of making compound of Formula I.

[0011] The details of one or more embodiments of the application are set forth in the accompanying description below. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. In the case of conflict, the present specification will control.

[0012] Other features and advantages of the application will be apparent from the following detailed description, examples, and claims.DETAILED DESCRIPTION

[0013] The inventors have unexpectedly found that 1-ethynyl-4-pentylbenzene has a unique aroma and flavor characterized by very grainy, floral, muguet, orris, fresh slightly fruity, apple, and pear notes. It has thus been determined to be useful in imparting and providing desirable aromas and / or flavors to the products to which it is added. Other Compounds of Formula I are expected to likewise have pleasant or desirable flavors and / or aromas. Such Compounds are therefore potentially useful for products where the inclusion of a pleasing fragrance or flavor is desired, including, but not limited to, perfumes, household products, laundry products, personal care products, cosmetics, dental hygiene products, orally administered medications, and food products. The Compounds of Formula I may be employed in varying amounts depending upon the specific fragrance or flavor product application, the nature and amount of other flavor or fragrance ingredients present, and the desired aroma and / or flavor of the product.

[0014] In a first aspect, the present disclosure provides a compound of Formula I (Compound 1):wherein: R1is H, CH3, CH2CH3, CH2CH2CH3, or CH(CH3)2; R2, R4, R5, and R6, are each independently selected from H, C1-3alkyl (e.g., CH3), OH, CHO, or OC1-3alkyl (e.g., OCH3); X is selected from -O-, -CH2-, -C(O)-, CH(OH), and -CH(OR)-; Y is selected from -CH2CH2CH2CH2-, -CH2CH2OCH2-, -CH2OCH2CH2-, - OCH2CH2CH2-, -CH2CH2CH2-, -CH2CH2O-, -CH2OCH2-, -OCH2CH2-,- CH2CH2CH2CH2CH2-, -OCH2CH2CH2CH2-, -CH2OCH2CH2CH2-, -CH2CH2OCH2CH2-, - CH2CH2CH2OCH2-, -CH2CH2CH2CH2O-, -CH2CH2CH2CH2CH2CH2-, - OCH2CH2CH2CH2CH2-, -CH2OCH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2-, - CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2O-, -CH2CH2CH2CH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2CH2-, -CH2OCH2CH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2CH2-, -CH2CH2CH2OCH2CH2CH2-, -CH2CH2CH2CH2OCH2CH2-, - CH2CH2CH2CH2CH2OCH2-, and -CH2CH2CH2CH2CH2CH2O-, wherein said group Y is optionally substituted by one or more groups selected from C1-3alkyl (e.g., CH3), OH, CHO, and OC1-3alkyl (e.g., OCH3); or X-Y is absent; R3is selected from H, Rb, OH, ORb, OC(O)Rb, CN, COOH, COORb, C(O)Rb, and CHO; and each Rbis independently optionally substituted C1-6alkyl (e.g., CH3or CH2CH3), C2-6alkenyl (e.g., allyl or 2-methylprop-1-enyl), CH2C3-6cycloalkyl (e.g., cyclopropylmethyl), C3-6cycloalkyl (e.g., cyclopropyl), C4-6cycloalkenyl (e.g., cyclopentenyl), optionally substituted phenyl, or optionally substituted benzyl; optionally provided that the compound is not 1-ethynyl-4-methylbenzene, 1-ethynyl-2,4- dimethylbenzene, 1-ethynyl-3-methylbenzene, 1-ethynyl-4-propylbenzene, 1-ethynyl-4- butylbenzene, 1-ethynyl-4-pentylbenzene, or 1-ethynyl-4-hexylbenzene.

[0015] In further embodiments, of the first aspect, the present disclosure provides: 1.1 Compound 1, wherein the compound is not 1-ethynyl-4-pentylbenzene; 1.2 Compound 1, wherein the compound is not 1-ethynyl-4-methylbenzene, 1- ethynyl-2,4-dimethylbenzene, 1-ethynyl-3-methylbenzene, 1-ethynyl-4- propylbenzene, 1-ethynyl-4-butylbenzene, or 1-ethynyl-4-hexylbenzene; 1.3 Compound 1, wherein the compound is not a compound wherein: (a) R1and R2are H, and X-Y-R3is n-butyl, n-pentyl, n-hexyl, or n-nonyl; (b) R1and R2are H, X is -C(O)-, and Y-R3is n-butyl, n-octyl, or n-undecyl; (c) R1and R2are H, X is -CH(OH)-, and Y-R3is n-butyl, n-octyl, or n-undecyl; (d) R1and R2are H, X is -O-, and Y-R3is n-butyl, n-pentyl, or n-hexyl; 1.4 Compound 1, or any of 1.1-1.3, wherein R1is H; 1.5 Compound 1, or any of 1.1-1.3, wherein R1is CH3; 1.6 Compound 1, or any of 1.1-1.3, wherein R1is CH2CH3; 1.7 Compound 1, or any of 1.1-1.3, wherein R1is CH2CH2CH3; 1.8 Compound 1, or any of 1.1-1.3, wherein R1is CH(CH3)2; 1.9 Compound 1, or any of 1.1-1.8, wherein R2is H or OH; 1.10 Compound 1, or any of 1.1-1.8, wherein R2is C1-3alkyl (e.g., CH3) or OC1-3alkyl (e.g., OCH3);1.11 Compound 1, or any of 1.1-1.8, wherein R2is CHO; 1.12 Compound 1, or any of 1.1-1.11, wherein R4is H or OH; 1.13 Compound 1, or any of 1.1-1.11, wherein R4is C1-3alkyl (e.g., CH3) or OC1-3alkyl (e.g., OCH3); 1.14 Compound 1, or any of 1.1-1.13, wherein R5is H or OH; 1.15 Compound 1, or any of 1.1-1.13, wherein R5is C1-3alkyl (e.g., CH3) or OC1-3alkyl (e.g., OCH3); 1.16 Compound 1, or any of 1.1-1.15, wherein R6is H or OH; 1.17 Compound 1, or any of 1.1-1.15, wherein R6is C1-3alkyl (e.g., CH3) or OC1-3alkyl (e.g., OCH3); 1.18 Compound 1, or any of 1.1-1.11, wherein R2, R4, R5, and R6, are each independently selected from H and C1-3alkyl; 1.19 Compound 1.18, wherein said C1-3alkyl is selected from methyl or ethyl; 1.20 Compound 1.19, wherein said C1-3alkyl is methyl; 1.21 Compound 1, or any of 1.1-1.20, wherein X is -O-; 1.22 Compound 1, or any of 1.1-1.20, wherein X is -CH2-; 1.23 Compound 1, or any of 1.1-1.22, wherein X is -C(O)-; 1.24 Compound 1, or any of 1.1-1.22, wherein X is -CH(OH)-; 1.25 Compound 1, or any of 1.1-1.24, wherein Y is -CH2CH2CH2CH2-, - CH2CH2OCH2-, -CH2OCH2CH2-, or -OCH2CH2CH2-; 1.26 Compound 1, or any of 1.1-1.24, wherein Y is -CH2CH2CH2-, -CH2CH2O-, - CH2OCH2-, or -OCH2CH2-; 1.27 Compound 1, or any of 1.1-1.24, wherein Y is -CH2CH2CH2CH2-, or - CH2CH2CH2-; 1.28 Compound 1, or any of 1.1-1.24, wherein Y is -CH2CH2CH2CH2-; 1.29 Compound 1, or any of 1.1-1.24, wherein X-Y is absent; 1.30 Compound 1, or any of 1.1-1.29, wherein R3is H; 1.31 Compound 1, or any of 1.1-1.29, wherein R3is Rb; 1.32 Compound 1, or any of 1.1-1.29, wherein R3is OH, ORb, or OC(O)Rb; 1.33 Compound 1.32, wherein R3is ORband ORbis selected from methoxy, ethoxy, propoxy. Isopropoxy, n-butoxy, s-butoxy, isobutoxy, and t-butoxy; 1.34 Compound 1, or any of 1.1-1.29, wherein R3is CN, COOH, COOR, C(O)Rb, or CHO;1.35 Compound 1, or any of 1.1-1.34, wherein Rbis optionally substituted C1-6alkyl (e.g., CH3or CH2CH3); 1.36 Compound 1.35, wherein Rbis selected from methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, n-hexyl, isohexyl, sec-hexyl, and neohexyl; 1.37 Compound 1, or any of 1.1-1.34, wherein Rbis optionally substituted C3-6cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl) or C4-6cycloalkenyl (e.g., cyclopentenyl, such as cyclopent-1-eneyl); 1.38 Compound 1, or any of 1.1-1.34, wherein Rbis optionally substituted CH2C3-6cycloalkyl (e.g., cyclopropylmethyl); 1.39 Compound 1, or any of 1.1-1.34, wherein Rbis optionally substituted phenyl or optionally substituted benzyl; 1.40 Compound 1, or any of 1.1-1.39, wherein the compound of Formula I is a compound of Formula Ia:Formula Ia wherein X, Y, and R3are as defined in any preceding formula; 1.41 Compound 1, or any of 1.1-1.39, wherein the compound of Formula I is a compound of Formula Ib:Formula Ib wherein R3is as defined in any preceding formula; 1.42 Compound 1, or any of 1.1-1.39, wherein the compound of Formula I is:; 1.43 Compound 1, or any of 1.1-1.39, wherein the compound of Formula I is a compound of Formula Ic:Formula Ic wherein Raand R3are as defined in any preceding formula; 1.44 Compound 1, or any of 1.1-1.39, wherein the compound of Formula I is a compound of Formula Id:Formula Id wherein Rais as defined in any preceding formula (e.g., wherein Rais CH2CH3); 1.45 Any preceding compound, wherein the compound has a molecular weight selected from the range of to 172 to 500, or 172 to 450, or 172 to 400, or 172 to 350, or 172 to 300, or 172 to 250, or 172 to 225, or 172 to 200, or 172 to 190; 1.46 Any preceding compound, wherein the compound is selected from the group consisting of:1.47 Any preceding compound, wherein the compound is selected from the group consisting of:1.48 Any preceding compound wherein if the compound has an acidic or basic atom or functional group, then the compound is in the form of a salt, e.g., a base addition salt or an acid addition salt; 1.49 Any preceding compound, wherein the compound has a pleasing taste and / or aroma, e.g., as judged by a trained flavor or fragrance chemist or master perfumer (e.g., toasted coconut or other nutty aromas and / or tastes).

[0016] In a second aspect, the present disclosure provides a flavor composition and / or a fragrance composition (Composition 1) comprising Compound 1, or any of 1.1-1.49, in admixture with one or more non-toxic, orally acceptable, pharmaceutically acceptable, cosmetically acceptable, or acceptable for a household product, carriers or excipients. In particular embodiments, the second aspect provides: 1.1 Composition 1, wherein the composition is a fragrance composition. 1.2 Composition 1, wherein the composition is a flavor composition. 1.3 Composition 1, or any of Compositions 1.1-1.2, wherein the composition comprises the Compound 1, or any of 1.1-1.49, in an amount of 0.1 to 100% by weight of thecomposition, e.g., 0.1 to 90%, or 0.1 to 80%, or 0.1 to 70%, or 0.1 to 60%, or 0.1 to 50%, or 0.1 to 40%, or 0.1 to 30%, or 0.1 to 20%, or 0.1 to 15%, or 0.1 to 10%, or 0.1 to 7.5%, or 0.1 to 5%, or 0.1 to 4%, or 0.1 to 3%, or 0.1 to 2%, or 0.1 to 1%, or 10 to 100%, or 20 to 100%, or 30 to 100%, or 40 to 100%, or 50 to 100%, or 60 to 100%, or 70 to 100%, or 80 to 100%, or 90 to 100%, or 95 to 100%, or 25 to 75%, or 50 to 75%, or 75 to 95%, by weight of the composition. 1.4 Composition 1, or any of Compositions 1.1-1.3, wherein the composition further comprises one or more other flavors or fragrances. 1.5 Composition 1, or any of Compositions 1.1-1.4, wherein the composition further comprises one or more solvents. 1.6 Composition 1.5, wherein the one or more solvents are selected from water, methanol, ethanol, propanol, isopropanol, dimethyl ether, diethyl ether, diisopropyl ether, methyl tert-butyl ether, ethylene glycol, propylene glycol, glycerin, triethyl citrate, triacetin, triglycerides, liquid waxes, propylene glycol derivatives (e.g., polypropylene glycols or ethylene oxide / propylene oxide copolymers), ethylene glycol derivatives (e.g., polyethylene glycols or ethylene oxide / propylene oxide copolymers), other alcohols or ethers, or any combination thereof. 1.7 Composition 1, or any of composition 1.1 to 1.6, wherein the composition is a liquid. 1.8 Composition 1, or any of compositions 1.1 to 1.6, wherein the composition is a soft or waxy solid. 1.9 Composition 1, or any of compositions 1.1-1.8, wherein the composition further comprises one or more of a polymer, gelling agent, powdery substrate, surfactant, emollient, plasticizer, wetting agent, swelling agent, or active agent (e.g., an oral care active or a medicinal active agent), or any other additives as described herein. 1.10 Composition 1, or any of Compositions 1.1-1.9, wherein the composition does not comprise any ingredient or component that would not be safe for ingestion, application to the oral cavity, or topical application to the skin or hair; 1.11 Composition 1, or any of Compositions 1.1-1.10, wherein the composition does not comprise any ingredient or component which is unsafe for, or not approved for, use in a food, cosmetic composition, pharmaceutical composition, oral care composition, or consumer cleaning composition.

[0017] As used herein, the term “fragrance composition” means a mixture of fragrance ingredients (e.g., including a Compound of Formula I) with one or more non-toxic, cosmeticallyacceptable, or acceptable for a household product, carriers or excipients, such as solvents. For example, the fragrance ingredient(s) may be dissolved in a suitable solvent or mixed with a powdery substrate, with additional auxiliary substances added (e.g., additives), if desired. A fragrance composition is used, and intended to be used, to provide or impart a desired odor or aroma to a product, such as a cosmetic product or household product (e.g., household cleaners). Thus, a fragrance composition is used as an ingredient or component in a final product, such as a cosmetic product or consumer product, for which a particular fragrance is desired. Examples of products having fragrance compositions include, but are not limited to, perfumes, soaps, insect repellants and insecticides, detergents, household cleaning agents, air fresheners, room sprays, pomanders, candles, cosmetics, toilet waters, pre- and aftershave lotions, talcum powders, hair-care products, body deodorants, anti-perspirants, and pet litter. A fragrance composition should have enough of its fragrance ingredients so that it is effective to provide the desired odor or aroma to the final product, and this depends both on the concentration of the fragrance ingredient(s) in the composition and the concentration of the composition used in the product.

[0018] As used herein, the term “flavor composition” means a mixture of flavor ingredients (e.g., including a Compound of Formula I) with one or more non-toxic, orally acceptable, or pharmaceutically acceptable, carriers or excipients, such as solvents. For example, the flavor ingredient(s) may be dissolved in a suitable solvent or mixed with a suitable solid, semi-solid, or liquid excipients, with additional auxiliary substances added (e.g., additives), if desired. A flavor composition is used, and intended to be used, to provide or impart a desired flavor and aroma to a product, such as a food product or oral pharmaceutical product. Thus, a flavor composition is used as an ingredient or component in a final product, such as a food or oral pharmaceutical product, for which a particular flavor is desired. Examples of products having flavor compositions include, but are not limited to, oral care compositions (e.g., dental hygiene products such as mouth wash, toothpaste, floss, and breath fresheners), pharmaceutical compositions (e.g., orally administered medications including liquids, tablets or capsules), and food products. A flavor composition should have enough of its flavor ingredients so that it is effective to provide the desired flavor and aroma to the final product, and this depends both on the concentration of the flavor ingredients in the composition and the concentration of the composition used in the product.

[0019] Fragrance and flavor ingredients and mixtures of fragrance and flavor ingredients that may be used in combination with the disclosed compound for the manufacture of fragrance and flavor compositions include, but are not limited to, natural products including extracts, animal products and essential oils, absolutes, resinoids, resins, and concretes, and synthetic fragrancematerials which include, but are not limited to, alcohols, aldehydes, ketones, ethers, acids, esters, acetals, phenols, ethers, lactones, furansketals, nitriles, acids, and hydrocarbons, including both saturated and unsaturated compounds and aliphatic carbocyclic and heterocyclic compounds, and animal products. As used herein, the terms “fragrance ingredient” and “flavor ingredient” refer to ingredients other than the Compounds of Formula I which are used to impart a flavor or a fragrance to a composition or product.

[0020] Examples of esters which may be used as fragrance ingredients or flavor ingredients in the compositions and products of the present disclosure include, but are not limited to, acrylic acid esters (methyl, ethyl, etc.), acetoacetic acid esters (methyl, ethyl, etc.), anisic acid esters (methyl, ethyl, etc.), benzoic acid esters (allyl, isoamyl, ethyl, geranyl, linalyl, phenylethyl, hexyl, cis-3- hexenyl, benzyl, methyl, etc.), anthranilic acid esters (cinnamyl, cis-3-hexenyl, methyl, ethyl, linalyl, isobutyl, etc.), N-methylanthranilic acid esters (methyl, ethyl, etc.), isovaleric acid esters (amyl, allyl, isoamyl, isobutyl, isopropyl, ethyl, octyl, geranyl, cyclohexyl, citronellyl, terpenyl, linalyl, cinnamyl, phenylethyl, butyl, propyl, hexyl, benzyl, methyl, rhodinyl, etc.), isobutyric acid esters (isoamyl, geranyl, citronellyl, terpenyl, cinnamyl, octyl, nellyl, phenylethyl, phenylpropyl, phenoxyethyl, butyl, propyl, isopropyl, hexyl, benzyl, methyl, ethyl, linalyl, rhodinyl, etc.), undecylenic acid esters (allyl, isoamyl, butyl, ethyl, methyl, etc.), octanoic acid esters (allyl, isoamyl, ethyl, octyl, hexyl, butyl, methyl, linalyl, etc.), octenoic acid esters (methyl, ethyl, etc.), octynecarboxylic acid esters (methyl, ethyl, etc.), caproic acid esters (allyl, amyl, isoamyl, methyl, ethyl, isobutyl, propyl, hexyl, cis-3-hexenyl, trans-2-hexenyl, linalyl, geranyl, cyclohexyl, etc.), hexenoic acid esters (methyl, ethyl, etc.), valeric acid esters (amyl, isopropyl, isobutyl, ethyl, cis-3- hexenyl, trans-2-hexenyl, cinnamyl, phenylethyl, methyl, etc.), formic acid esters (anisyl, isoamyl, isopropyl, ethyl, octyl, geranyl, citronellyl, cinnamyl, cyclohexyl, terpenyl, phenylethyl, butyl, propyl, hexyl, cis-3-hexenyl, benzyl, linalyl, rhodinyl, etc.), crotonic acid esters (isobutyl, ethyl, cyclohexyl, etc.), cinnamic acid esters (allyl, ethyl, methyl, isopropyl, propyl, 3-phenylpropyl, benzyl, cyclohexyl, methyl, etc.), succinic acid esters (monomethyl, diethyl, dimethyl, etc.), acetic acid esters (anisyl, amyl, α-amylcinnamyl, isoamyl, isobutyl, isopropyl, isobornyl, isoeugenyl, eugenyl, 2-ethylbutyl, ethyl, 3-octyl, p-cresyl, o-cresyl, geranyl, α- or β-santalyl, cyclohexyl, cycloneryl, dihydrocuminyl, dimethyl benzyl carbinyl, cinnamyl, styralyl, decyl, dodecyl, terpenyl, guainyl, neryl, nonyl, phenyl ethyl, phenylpropyl, butyl, furfuryl, propyl, hexyl, cis-3-hexenyl, trans- 2-hexenyl, cis-3-nonenyl, cis-6-noneyl, cis-3-cis-6-nonadienyl, 3-methyl-2-butenyl, heptyl, benzyl, bornyl, myrcenyl, dihydromyrcenyl, myrtenyl, methyl, 2-methylbutyl, menthyl, linalyl, rhodinyl, etc.), salicylic acid esters (allyl, isoamyl, phenyl, phenylethyl, benzyl, ethyl, methyl, etc.),cyclohexylalkanoic acid esters (ethyl cyclohexylacetate, allyl cyclohexylpropionate, allyl cyclohexylbutyrate, allyl cyclohexylhexanoate, allyl cyclohexyldecanoate, allyl cyclohexylvalerate, etc.), stearic acid esters (ethyl, propyl, butyl, etc.), sebacic acid esters (diethyl, dimethyl, etc.), decanoic acid esters (isoamyl, ethyl, butyl, methyl, etc.), dodecanoic acid esters (isoamyl, ethyl, butyl, etc.), lactic acid esters (isoamyl, ethyl, butyl, etc.), nonanoic acid esters (ethyl, phenylethyl, methyl, etc.), nonenoic acid esters (allyl, ethyl, methyl, etc.), hydroxyhexanoic acid esters (ethyl, methyl, etc.), phenylacetic acid esters (isoamyl, isobutyl, ethyl, geranyl, citronellyl, cis-3-hexenyl, methyl, etc.), phenoxyacetic acid esters (allyl, ethyl, methyl, etc.), furancarboxylic acid esters (ethyl furancarboxylate, methyl furancarboxylate, hexyl furancarboxylate, isobutyl furaneopentyl glycol diacetateropionate, etc.), propionic acid esters (anisyl, allyl, ethyl, amyl, isoamyl, propyl, butyl, isobutyl, isopropyl, benzyl, geranyl, cyclohexyl, citronellyl, cinnamyl, tetrahydrofurfuryl, tricyclodecenyl, heptyl, bornyl, methyl, menthyl, linallyl, terpenyl, α-methylpropionyl, β- methylpropionyl, etc.), heptanoic acid esters (allyl, ethyl, octyl, propyl, methyl, etc.), heptinecarboxylic acid esters (allyl, ethyl, propyl, methyl, etc.), myristic acid esters (isopropyl, ethyl, methyl, etc.), phenylglycidic acid esters (ethyl phenylglycidate, ethyl 3-methylphenylglycidate, ethyl p-methyl-β-phenylglycidate, etc.), 2-methylbutyric acid esters (methyl, ethyl, octyl, phenyl ethyl, butyl, hexyl, benzyl, etc.), 3-methylbutyric acid esters (methyl, ethyl, etc.), butyric acid esters (anisyl, amyl, allyl, isoamyl, methyl, ethyl, propyl, octyl, guainyl, linallyl, geranyl, cyclohexyl, citronellyl, cinnamyl, nellyl, terpenyl, phenylpropyl, β-phenylethyl, butyl, hexyl, cis-3-hexenyl, trans-2-hexenyl, benzyl, rhodinyl, etc.), and hydroxybutyric acid esters (methyl, ethyl, menthyl or the like of 3-hydroxybutyric acid esters).

[0021] Examples of alcohols which may be used as fragrance ingredients or flavor ingredients, or as solvents, in the compositions and products of the present disclosure include, but are not limited to, aliphatic alcohols (isoamyl alcohol, 2-ethylhexanol, 1-octanol, 3-octanol, 1- octene-3-ol, 1-decanol, 1-dodecanol, 2,6-nonadienol, nonanol, 2-nonanol, cis-6-nonenol, trans-2, cis- 6-nonadienol, cis-3, cis-6-nonadienol, butanol, hexanol, cis-3-hexenol, trans-2-hexenol, 1- undecanol, heptanol, 2-heptanol, 3-methyl-1-pentanol, etc.); terpene alcohols (borneol, isoborneol, carveol, geraniol, α- or β-santalol, citronellol, 4-thujanol, terpineol, 4-terpineol, nerol, myrcenol, myrtenol, dihydromyrcenol, tetrahydromyrcenol, nerolidol, hydroxycitronellol, farnesol, perilla alcohol, rhodinol, linalool, etc.); and aromatic alcohols (anisic alcohol, α-amylcinnamic alcohol, isopropylbenzylcarbinol, carvacrol, cumin alcohol, dimethylbenzylcarbinol, cinnamic alcohol, phenyl allyl alcohol, phenylethylcarbinol, β-phenylethyl alcohol, 3-phenylpropyl alcohol, benzyl alcohol, etc.).

[0022] Examples of aldehydes which may be used as fragrance ingredients or flavor ingredients in the compositions and products of the present disclosure include, but are not limited to, aliphatic aldehydes (acetaldehyde, octanal, nonanal, decanal, undecanal, 2,6-dimethyl-5-heptanal, 3,5,5-trimethylhexanal, cis-3, cis-6-nonadienal, trans-2, cis-6-nonadienal, valeraldehyde, propanal, isopropanal, hexanal, trans-2-hexenal, cis-3-hexenal, 2-pentenal, dodecanal, tetradecanal, trans-4- decenal, trans-2-tridecenal, trans-2-dodecenal, trans-2-undecenal, 2,4-hexadienal, cis-6-nonenal, trans-2-nonenal, 2-methylbutanal, etc.); aromatic aldehydes (anisic aldehyde, α-amylcinnamic aldehyde, α-methylcinnamic aldehyde, cyclamen aldehyde, p-isopropylphenylacetaldehyde, ethylvanillin, cumin aldehyde, salicylaldehyde, cinnamic aldehyde, o-, m- or p-tolylaldehyde, vanillin, piperonal, phenylacetaldehyde, heliotropin, benzaldehyde, 4-methyl-2-pheny-2-pentenal, p- methoxycinnamic aldehyde, p-methoxybenzaldehyde, etc.); and terpene aldehydes (geranial, citral, citronellal, α-sinensal, β-sinensal, perillaldehyde, hydroxycitronellal, tetrahydrocitral, myrtenal, cyclocitral, isocyclocitral, citronellyloxyacetaldehyde, neral, α-methylenecitronellal, myracaldehyde, vernaldehyde, safranal, etc.).

[0023] Examples of ketones which may be used as fragrance ingredients or flavor ingredients in the compositions and products of the present disclosure include, but are not limited to, cyclic ketones (1-acetyl-3,3-dimethyl-1-cyclohexene, cis-jasmone, α-, β- or γ-irone, ethyl maltol, cyclotene, dihydronootkatone, 3,4-dimethyl-1,2-cyclopentadione, sotolon, α-, β-, γ- or δ-damascone, α-, β- or γ-damascenone, nootkatone, 2-sec-butylcyclohexanone, maltol, α-, β- or γ-ionone, α-, β- or γ-methylionone, α-, β- or γ-isomethylionone, furaneol, camphor, etc.); aromatic ketones (acetonaphthone, acetophenone, anisylideneacetone, raspberry ketone, p-methyl acetophenone, anisylacetone, p-methoxy acetophenone, etc.); and chain ketones (diacetyl, 2-nonanone, diacetyl, 2- heptanone, 2,3-heptanedione, 2-pentanone, methyl amyl ketone, methyl nonyl ketone, β-methyl naphthyl ketone, methyl heptanone, 3-heptanone, 4-heptanone, 3-octanone, 2,3-hexanedione, 2- undecanone, dimethyloctenone, 6-methyl-5-hepten-2-one, etc.).

[0024] Examples of acetals which may be used as fragrance ingredients or flavor ingredients in the compositions and products of the present disclosure include, but are not limited to, acetaldehyde diethyl acetal, acetaldehyde diamyl acetal, acetaldehyde dihexyl acetal, acetaldehyde propylene glycol acetal, acetaldehyde ethyl cis-3-hexenyl acetal, benzaldehyde glycerin acetal, benzaldehyde propylene glycol acetal, citral dimethyl acetal, citral diethyl acetal, citral propylene glycol acetal, citral ethylene glycol acetal, phenylacetaldehyde dimethyl acetal, citronellyl methyl acetal, acetaldehyde phenylethylpropyl acetal, hexanal dimethyl acetal, hexanal dihexyl acetal, hexanal propylene glycol acetal, trans-2-hexenal diethyl acetal, trans-2-hexenal propylene glycolacetal, cis-3-hexenal diethyl acetal, heptanal diethyl acetal, heptanal ethylene glycol acetal, octanal dimethyl acetal, nonanal dimethyl acetal, decanal dimethyl acetal, decanal diethyl acetal, 2- methylundecanal dimethyl acetal, citronellal dimethyl acetal, Ambersage (manufactured by Givaudan), ethyl acetoacetate ethylene glycol acetal, and 2-phenylpropanal dimethyl acetal.

[0025] Examples of phenols which may be used as fragrance ingredients or flavor ingredients in the compositions and products of the present disclosure include, but are not limited to, eugenol, isoeugenol, 2-methoxy-4-vinylphenol, thymol, carvacrol, guaiacol, and chavicol, and vanillin.

[0026] Examples of ethers and epoxides which may be used as fragrance ingredients or flavor ingredients in the compositions and products of the present disclosure, but are not limited to, anethole, 1,4-cineole, dibenzyl ether, linalool oxide, limonene oxide, nerol oxide, rose oxide, methyl isoeugenol, methyl chavicol, isoamyl phenyl ethyl ether, β-napthyl methyl ether, phenyl propyl ether, p-cresyl methyl ether, vanillyl butyl ether, α-terpinyl methyl ether, citronellyl ethyl ether, geranyl ethyl ether, rose furan, theaspirane, decylmethyl ether, and methylphenyl methyl ether.

[0027] Examples of lactones which may be used as fragrance ingredients or flavor ingredients in the compositions and products of the present disclosure include, but are not limited to, γ- or δ-decalactone, γ-heptalactone, γ-nonalactone, γ- or δ-hexylactone, γ- or δ-octalactone, γ- or δ- undecalactone, δ-dodecalactone, δ-2-decenolactone, methyl lactone, 5-hydroxy-8-undecenoic acid δ- lactone, jasmine lactone, menthalactone, dihydrocoumarin, octahydrocoumarin, and 6- methylcoumarin.

[0028] Examples of furans which may be used as fragrance ingredients or flavor ingredients in the compositions and products of the present disclosure include, but are not limited to, furan, 2- methylfuran, 3-methylfuran, 2-ethylfuran, 2,5-diethyltetrahydrofuran, 3-hydroxy-2- methyltetrahydrofuran, 2-(methoxymethyl)furan, 2,3-dihydrofuran, furfural, 5-methylfurfural, 3-(2- furyl)-2-methyl-2-propenal, 5-(hydroxymethyl)furfural, 2,5-dimethyl-4-hydroxy-3(2H)-furanone (furaneol), 4,5-dim ethyl-3-hydroxy-2(5H)-furanone (sotolon), 2-ethyl-4-hydroxy-5-methyl-3(2H)- furanone (homofuraneol), 5-ethyl-3-hydroxy-4-methyl-2(5H)-furanone (homosotolon), 3-methyl- 1,2-cyclopentanedione (cyclotene), 2(5H)-furanone, 4-methyl-2(5H)-furanone, 5-methyl-2(5H)- furanone, 2-methyl-3(2H)-furanone, 5-methyl-3(2H)-furanone, 2-acetylfuranone, 2-acetyl-5- methylfuran, furfuryl alcohol, methyl 2-furancarboxylate, ethyl 2-furancarboxylate, and furfuryl acetate.

[0029] Examples of hydrocarbons which may be used which may be used as fragrance ingredients or flavor ingredients in the compositions and products of the present disclosure include,but are not limited to, α- or β-bisabolene, β-caryophyllene, p-cymene, terpinene, terpinolene, cadinene, cedrene, longifolene, farnesene, limonene, ocimene, myrcene, α- or β-pinene, 1,3,5- undecatriene and valencene.

[0030] Examples of acids that may be used which may be used as fragrance ingredients or flavor ingredients in the compositions and products of the present disclosure include, but are not limited to, geranic acid, dodecanoic acid, myristic acid, stearic acid, lactic acid, phenylacetic acid, pyruvic acid, trans-2-methyl-2-pentenoic acid, 2-methyl-cis-3-pentenoic acid, 2-methyl-4-pentenoic acid, and cyclohexanecarboxylic acid.

[0031] The fragrance and flavor compositions of the application may comprise as additional fragrance or flavor ingredients one or more natural extracts or oils including, but not limited to, anise, orange, lemon, lime, mandarin, petitgrain, bergamot, lemon balm, grapefruit, elemi, olibanum, lemongrass, neroli, marjoram, angelica root, star anise, basil, bay, calamus, chamomile, caraway, cardamom, cassia, cinnamon, pepper, perilla, cypress, oregano, cascarilla, ginger, parsley, pine needle, sage, hyssop, tea tree, mustard, horseradish, clary sage, clove, cognac, coriander, estragon, eucalyptus, fennel, guaiac wood, dill, cajuput, wormseed, pimento, juniper, fenugreek, garlic, laurel, mace, myrrh, nutmeg, spruce, geranium, citronella, lavender, lavandin, palmarosa, rose, rosemary, sandalwood, oakmoss, cedarwood, vetiver, linaloe, bois de rose, patchouli, labdanum, cumin, thyme, ylang ylang, birch, capsicum, celery, tolu balsam, genet, immortelle, benzoin, jasmine, cassie, tuberose, reseda, marigold, mimosa, opoponax, orris, vanilla and licorice. Each of these natural extracts or oils comprises a complex mixture of chemical compounds, which may include those compounds described above. Additional fragrance ingredients may be isolated from natural products, for example, geraniol and citronellal may be isolated from citronella oil, citral may be isolated from lemon-grass oil, eugenol may be isolated from clove oil, and linalool may be isolated from rosewood oil. Animal products used in fragrance compositions include, but are not limited to, musk, ambergris, civet and castoreum. The natural ingredients described herein may also be produced synthetically, and may include the compounds disclosed herein, and be used as fragrance and / or flavor ingredients in the fragrance and flavor compositions of the present application.

[0032] Examples of fragrance ingredients used in perfumes, air fresheners, laundry detergents, pet litters, cleaning products, liquid and bar soaps, shampoos and conditioners, cosmetics, deodorants, and personal hygiene products include, but are not limited to: hexyl cinnamic aldehyde; amyl cinnamic aldehyde; amyl salicylate; hexyl salicylate; terpineol; 3,7-dimethyl-cis-2,6- octadien-1-ol; 2,6-dimethyl-2-octanol; 2,6-dimethyl-7-octen-2-ol; 3,7-dimethyl-3-octanol; 3,7- dimethyl-trans-2,6-octadien-1-ol; 3,7-dimethyl-6-octen-1-ol; 3,7-dimethyl-1-octanol; 2-methyl-3-(para-tert-butylphenyl)-propionaldehyde; 4-(4-hydroxy-4-methylpentyl)-3-cyclohexene-1- carboxaldehyde; tricyclodecenyl propionate; tricyclodecenyl acetate; anisaldehyde; 2-methyl-2- (para-iso-propylphenyl)-propionaldehyde; ethyl-3-methyl-3-phenyl glycidate; 4-(para- hydroxyphenyl)-butan-2-one; 1-(2,6,6-trimethyl-2-cyclohexen-1-yl)-2-buten-1-one; para- methoxyacetophenone; para-methoxy-alpha-phenylpropene; methyl-2-n-hexyl-3-oxo-cyclopentane carboxylate; undecalactone gamma, geraniol; geranyl acetate; linalool; linalyl acetate; tetrahydrolinalool; citronellol; citronellyl acetate; dihydromyrcenol; dihydromyrcenyl acetate; tetrahydromyrcenol; terpinyl acetate; nopol; nopyl acetate; 2-phenylethanol; 2-phenylethyl acetate; benzyl alcohol; benzyl acetate; benzyl salicylate; benzyl benzoate; styrallyl acetate; dimethylbenzylcarbinol; trichloromethylphenylcarbinyl methylphenylcarbinyl acetate; isononyl acetate; vetiveryl acetate; vetiverol; 2-methyl-3-(p-tert-butylphenyl)-propanal; 2-methyl-3-(p- isopropylphenyl)-propanal; 3-(p-tert-butylphenyl)-propanal; 4-(4-methyl-3-pentenyl)-3- cyclohexenecarbaldehyde; 4-acetoxy-3-pentyltetrahydropyran; methyl dihydrojasmonate; 2-n- heptylcyclopentanone; 3-methyl-2-pentyl -cyclopentanone; n-decanal; n-dodecanal; 9-decenol-1; phenoxyethyl isobutyrate; phenylacetaldehyde dimethylacetal; phenylacetaldehyde diethylacetal; geranonitrile; citronellonitrile; cedryl acetal; 3-isocamphylcyclohexanol; cedryl methyl ether; isolongifolanone; aubepine nitrile; aubepine; heliotropine; eugenol; vanillin; diphenyl oxide; hydroxycitronellal ionones; methyl ionones; isomethyl ionones; irones; cis-3-hexenol and esters thereof; indane musk fragrances; tetralin musk fragrances; isochroman musk fragrances; macrocyclic ketones; macrolactone musk fragrances; and ethylene brassylate.

[0033] The fragrance and flavor ingredients in a given product’s fragrance or flavor composition are selected based on the intended use of the product and the product’s desired aroma. For example, flavor ingredients used in toothpaste, mouth wash, and dental hygiene products may be selected to impart “freshness” and include, but are not limited to, spearmint oil, peppermint oil, star anise oil, lemon oil, and menthol.

[0034] Flavor compositions may be used to mask the unpleasant taste of orally administered medications. For example, if a medication is salty, a flavor composition that has cinnamon, raspberry, orange, maple, butterscotch, or glycyrrhiza (licorice) flavor may be used to mask the taste. If a medication is overly sweet, a flavor composition that has a berry, vanilla, or acacia flavor may render the medication more palatable. In the case of bitter tasting medications, flavor compositions that have cocoa, chocolate-mint, wild cherry, walnut, glycyrrhiza (licorice), and eriodictyon flavors might be used, whereas sour medications may be improved by flavor compositions that have fruity,citrus, or cherry flavors. These flavors may be provided by the natural or synthetic flavor ingredients discussed herein.

[0035] Examples of flavor ingredients used in flavor compositions for food products also include, but are not limited to, glucosyl steviol glycosides, isomenthols, carbonothoic acids, cassyrane, 1,5-octadien-3-ol, 2-mercaptoheptan-4-ol, 43-(methylthio)decanal, (4Z,7Z)-trideca-4,7- dienal, persicaria odorata oil, Amacha leaves extract, glutamyl-2-aminobutyric acid, glutamyl-2- aminobutyric acid, glutamyl-norvalyl-glycine, glutamyl-norvaline, N1-(2,3-Dimethoxybenzyl)-N2- (2-(pyridin-2-yl)ethyl) oxalamide, 1-(2-hydroxy-4-methylcyclohexyl)ethanone, Mexican lime oil, Persian lime oil, 6-methoxy-2,6-dimethylheptanal, 3,5-undecadien-2-one, 2,5-undecadien-1-ol, triethylthialdine.4-methylpentyl 4-methylvalerate, (R)-N-(1-methoxy-4-methylpentan-2-yl)-3,4- dimethylbenzamide, 2 N-acetyl glutamate, 1,3-propanediol, Szechuan pepper extract, Tasmannia lanceolata extract, Mentha longifolia oil, mangosteen distillate, ethyl 3-(2- hydroxyphenyl)propanoate, 1-cyclopropanemethyl-4-methoxybenzene, prenyl thioisobutyrate, prenyl thioisovalerate, matairesinol, stevioside, 1-(2,4-dihydroxyphenyl)-3-(3-hydroxy-4- methoxyphenyl)propan-1-one, ethyl 5-formyloxydecanoate, 3-[3-(2-isopropyl-5-methyl- cyclohexyl)ureido]butyric acid ethyl ester, 2-Isopropyl-4-methyl-3-thiazoline, 2,6,10-trimethyl-9- undecenal, 5-mercapto-5-methyl-3-hexanone, Meyer lemon oil, teviol glycoside extract, stevia rebaudiana, rebaudioside A 60%, rubescenamine, 4-amino-5-(3-(isopropylamino)-2,2-dimethyl-3- oxopropoxy)-2-methylquinoline-3-carboxylic acid, 3-methyl-5-(2,2,3-trimethylcyclopent-3-en-1- yl)pent-4-en-2-ol, (1-Methyl-2-(1,2,2-trimethylbicyclo[3.1.0]hex-3-ylmethyl)cyclopropyl)methanol, erospicata oil, and curly mint oil. See L. J. Marnett et al., GRAS Flavoring Substances 26, Food Technology, 44-45 (2013).

[0036] Preferred solvents and excipients for use in the compositions and products of the present disclosure include, but are not limited to, triethyl citrate, triacetin, glycerol, propylene glycol, dipropylene glycol, isopropyl myristate, ethanol, water, triglycerides, liquid waxes, propylene glycol derivatives (e.g., polymers), and ethylene glycol derivatives (e.g., polymers).

[0037] The amount of a given fragrance or flavor ingredient in a fragrance or flavor composition cannot be categorically described because it varies depending on the type product being scented or flavored, the intended use of the product, and the desired aroma and / or taste of the product. The amount of a fragrance or flavor ingredient in a fragrance or flavor composition is usually in the range of from about 1% to about 99% by mass of the fragrance composition. When the amount of the ingredient is too small, a sufficient strength of the scent or flavor may not be obtained. Further, when the amount of the ingredient is too large, a larger amount of the agent(s)needed to solubilize the ingredient may be needed, which may in turn reduce the desired aromatic or flavor properties of the end product by inhibiting volatilization or other mechanisms by which the flavor or fragrance is dispersed when the product is used or consumed. The amount of each of the fragrance and flavor ingredients in a given fragrance or flavor composition must therefore be selected based upon the aromatic and / or flavor characteristics of the selected ingredient, the overall composition of the product, and the intended aromatic and / or flavor effect.

[0038] Additives may be used in the flavor and fragrance compositions of the present disclosure. Additives that may be used include, but are not limited to, solvents, surfactants, pH adjusters, buffers, thickening agents, desiccants, emulsifiers, foaming agents, stabilizers, antioxidants, and disintegrating agents. Other fragrance and flavor composition additives will be selected in accordance with the intended use of the composition.

[0039] Solvents, for example water-soluble organic solvents, which may be used in the flavor and fragrance compositions of the present disclosure include, but are not limited to, ethanol, propanol, isopropanol, butanol, 3-methoxy-3-methyl-1-butanol, benzyl alcohol, ethyl carbitol (diethylene glycol monoethyl ether), ethylene glycol, propylene glycol, dipropylene glycol, butylene glycol, hexylene glycol, glycerin, ethylene glycol monomethyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, and dipropylene glycol monomethyl ether. These water- soluble solvents may be used solely or in combination. The content of the water-soluble organic solvent in the compositions of the application may be determined according to the desired composition properties, and is usually from about 1% to about 99% by mass.

[0040] Oil-soluble organic solvents which may be used with the flavor and fragrance compositions of the application include, but are not limited to, isoparaffin, paraffin, limonene, pinene, triethyl citrate, benzyl benzoate, isopropyl myristate, triacetin, and silicone.

[0041] Preferred solvents include, but are not limited to, triethyl citrate, triacetin, glycerol, ethanol, water, triglycerides, liquid waxes, propylene glycol derivatives, and ethylene glycol derivatives.

[0042] In some embodiments, the flavor and fragrance compositions and products of the present disclosure may further comprise other substances, including, but not limited to, sequestering agents, preservatives, antioxidants, deodorizers, sterilization agents, ultraviolet absorbers, pH adjusters, insecticidal components, components for protection from insects, insect repellents, colorants, excipients, and buffers. The substances used in, or in addition to, the fragrance and flavor compositions of the present application may be determined by the product in which the composition is included. When the substance is used in a flavor or fragrance composition, it may be an additive.When the substance is used alongside a flavor or fragrance composition, it may be considered as part of a product composition that comprises a fragrance or flavor composition.

[0043] Excipients that may be used in the fragrance and flavoring compositions and products of the present disclosure may vary depending on the use of the intended product and its overall composition. In some instances, the excipient may be included in the fragrance or flavor composition or may, alternatively, be independent of the composition. Excipients used in or with flavoring compositions of an orally administered medication may include, but are not limited to, tablet coatings, such as a cellulose ether hydroxypropyl methylcellulose, synthetic polymer, shellac, corn protein zein or other polysaccharides, and gelatin. In contrast, cosmetic excipients may include, but are not limited to, Carbopol 940 ETD, triethanolamine, purified water, glycerin, imidazolidinyl urea, EDTA, polyvinyl alcohol, methyl parabens phenoxyethanol 0, ethyl alcohol 1, peg 7 glyceryl cocoate, peg 6 triglyceryl caproic glycerides, acemulogar LAM V, isopropyl myristate, tegosoft CT, xanthan gum, sepicide CL, polyquaternium 7, and Vaseline oils. Additional suitable excipients for use with or in a flavor and / or fragrance composition for a given product will be readily selected by those having ordinary skill in the art.

[0044] Buffers that may be used with the fragrance and flavoring compositions of the present application may vary depending on the use of the intended product and its overall composition. In some instances, the buffer may be included in the fragrance or flavor composition or may, alternatively, be independent of the composition. Examples of buffers that may be used in or with the fragrance and flavor compositions of the application include, but are not limited to, citrates, acetates, and phosphates. For example, trisodium citrate may be used as a flavor or as a preservative, and is known to impart tartness to a flavor, but also acts as a buffer. Trisodium citrate is an ingredient in a variety of sodas and other beverages, as well as drink mixes and bratwurst. In cosmetic products, disodium hydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate and, and citric acid may be used to buffer the pH of the product. In toothpaste, calcium carbonate and / or dicalcium phosphate may be used as pH buffers. Additional suitable buffers for use with or in a flavor and / or fragrance composition for a given product will be readily selected by those having ordinary skill in the art.

[0045] In a third aspect, the present disclosure provides a product which comprises Compound 1, or any of 1.1-1.49, or Composition 1 or any of 1.1 to 1.11. In some embodiments, the product may be selected from the following: personal care products (e.g., a soap, skin cream or lotion, balm, shampoo, body wash, shower gel, hydrating cream, deodorant, antiperspirant, after- shave lotion, cologne, perfume, or other hair care or skin care product), sunscreens, insect repellantsand insecticides, detergents, household cleaning agents (e.g., a surface cleaner, a metal cleaner, a wood cleaner, a glass cleaner, a body cleaner such as a soap, a dish-washing detergent, or a laundry detergent), air fresheners, room sprays, pomanders, candles, cosmetics (e.g., perfumes, colognes, nail polish, eye liner, mascara, lipstick, foundation, concealer, blush, bronzer, eye shadow, lip liner, lip balm), toilet waters, talcum powders, and pet litter.

[0046] Having now described some embodiments of the application, it should be apparent to those skilled in the art that the foregoing is merely illustrative and not limiting, having been presented by way of example only. The embodiments of the application can therefore be in other specific forms without departing from the spirit or essential characteristics thereof.

[0047] Those skilled in the art should recognize or be able to ascertain, using no more than routine experimentation, equivalents to the specific embodiments of the application. It is therefore to be understood that the embodiments described herein are presented by way of example only and that the scope of the application is thus indicated by the appended claims and equivalents thereto, and that the application may be practiced otherwise than as specifically described in the foregoing description.

[0048] The term “about,” when used to describe one of the compositions of the application, refers to a recited percentage ±5%, ±4%, ±3%, ±2.5%, ±2%, ±1.5%, ±1%, ±0.75%, ±0.5%, ±0.25%, or ±0.1%. In one embodiment, the term “about,” refers to a recited percentage ±5%. For example, “about 50%” refers to the range 45% to 55%. In one embodiment, the term “about,” refers to a recited percentage ±2.5%. In one embodiment, the term “about,” refers to a recited percentage ±1%. In one embodiment, the term “about,” refers to a recited percentage ±0.5%. In one embodiment, the term “about,” refers to a recited percentage ±0.1%.

[0049] As used herein, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a fragrance ingredient” includes not only a single fragrance ingredient but also a combination or mixture of two or more different fragrance ingredients, reference to “an additive” includes a single additive as well as two or more additives, and the like.

[0050] As used herein, the phrases “for example,” “for instance,” “such as,” or “including” are meant to introduce examples that further clarify more general subject matter. These examples are provided only as an aid for understanding the disclosure, and are not meant to be limiting in any fashion. Furthermore, as used herein, the terms “may,” “optional,” “optionally,” or “may optionally” mean that the subsequently described circumstance may or may not occur, so that the description includes instances where the circumstance occurs and instances where it does not. Forexample, the phrase “optionally present” means that an object may or may not be present, and, thus, the description includes instances wherein the object is present and instances wherein the object is not present.

[0051] As used herein, “optionally substituted” means that the indicated core or functional group is either unsubstituted or substituted by one or more groups up to the maximum permitted by the rules of valency, wherein said groups are selected from: halo, hydroxy, cyano, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6haloalkyl, C1-6-alkoxy, -O-Si(Rx)3, -O-Rx, -C(O)H, -C(O)- Rx, -C(O)-O-Rx, -C(O)-NH-Rx, -C(O)-N-(Rx)(Rx), -O-C(O)-Rx, -NH(Rx)-C(O)-Rx, -N(Rx)(Rx)-C(O)- Rx),-NH(Rx), -N(Rx)(Rx), heterocycloalkyl, aryl, and heteroaryl; wherein each of said C1-6alkyl, C3-6cycloalkyl, heterocycloalkyl, aryl or heteroaryl is further optionally substituted by one or more halo, hydroxy, cyano, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6haloalkyl, -O-Si(Rx)3, -O-Rx, -C(O)H, -C(O)-Rx, -C(O)-O-Rx, -C(O)-NH-Rx, -C(O)-N-(Rx)(Rx), -O-C(O)-Rx, -NH(Rx)-C(O)-Rx, - N(Rx)(Rx)-C(O)-Rx),-NH(Rx), -N(Rx)(Rx), heterocycloalkyl, aryl, and heteroaryl; and wherein each Rxis independently selected from hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, heterocycloalkyl, aryl and heteroaryl.

[0052] As used herein, the term “ C1-6-alkyl” means a saturated linear or branched free radical consisting essentially of 1 to 6 carbon atoms and a corresponding number of hydrogen atoms. Exemplary C1-6-alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, and thexyl. Other C1-6-alkyl groups will be readily apparent to those of skill in the art given the benefit of the present disclosure. The terms “C1-3-alkyl”, “C1-4-alkyl”, etc., have equivalent meanings, i.e., saturated linear or branched free radical consisting essentially of 1 to 3 (or 4) carbon atoms and a corresponding number of hydrogen atoms. The similar terms “C2-6-alkenyl,” “C2-6-alkynyl,” “C3-6-cycloalkyl,” “C1-6-haloalkyl,” “C1-6- alkoxy,” and the like, refer to corresponding functional groups having the stated number of carbon atoms, wherein “alkenyl” refers to an unsaturated linear or branched free radical having at least one double bond, “alkynyl” refers to an unsaturated linear or branched free radical having at least one triple bond, “haloalkyl” refers to an alkyl radical having at least one halogen atom attached to a carbon atom, and “alkoxy” refers to an alkyl radical having at least one oxygen atom attached to the alkyl radical and wherein the attachment point of the functional group is through the oxygen (i.e., to form an ether). Exemplary alkenyl groups include vinyl and allyl. Exemplary alkynyl groups include ethynyl and propynyl. Exemplary haloalkyl groups include fluoromethyl, difluoromethyl, trifluoromethyl, 3,3,3-trifluorethyl, and like groups with chlorine, bromine or iodine. “Cycloalkyl”refers to a carbocyclic ring attached via a ring carbon atom. Exemplary cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

[0053] As used herein, the term “heteroaryl” means an aromatic free radical having 5 to 20 atoms (i.e., ring atoms) that form a ring, wherein at least one atom (e.g., 1 to 5) of the ring atoms are carbon and at least one atom of the remaining ring atoms is a nitrogen, sulfur, or oxygen. Heteroaryl rings include monocyclic, bicyclic fused, and polycyclic fused ring systems provided that at least one ring of the ring system has at least one heteroatom (N, S, or O), and all rings are aromatic. Exemplary 5-membered heteroaryl groups include furyl, thienyl (thiophenyl), pyrrolyl, oxazolyl, thiazolyl, pyrazolyl, isothiazolyl, isoxazolyl, imidazolyl, triazolyl, oxadiazolyl, thiadiazolyl, and tetrazolyl. Exemplary 6-membered heteroaryl groups include pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, and 1,2,4-triazinyl. Exemplary fused heteroaryl groups include benzoxazolyl, benzothiazolyl, benzisothiazolyl, benzisoxazolyl, benzimidazolyl, indolyl, quinolinyl, isoquinolinyl, quinazolinyl, and quinoxalinyl. Other heteroaryl groups will be readily apparent to those of skill in the art given the benefit of the present disclosure. In general, the heteroaryl group typically is attached to the main structure via a carbon atom. However, those of skill in the art will realize that certain other atoms, e.g., hetero ring atoms, can be attached to the main structure.

[0054] As used herein, the term “aryl” means an aromatic free radical having 5 or 6 atoms (i.e., ring atoms) that form a ring, wherein all of the ring atoms are carbon. Exemplary aryl groups include phenyl and naphthyl.

[0055] As used herein, the term “heterocycloalkyl” means an aromatic free radical having 3 to 20 atoms (i.e., ring atoms) that form a ring, wherein at least one atom (e.g., 1 to 5) of the ring atoms are carbon and at least one atom of the remaining ring atoms is a nitrogen, sulfur, or oxygen, and wherein at least one ring is non-aromatic. Heterocycloalkyl rings include monocyclic, bicyclic fused, bicyclic spiro-joined, polycyclic bridged, and polycyclic fused ring systems, provided that at least one ring of the ring system has at least one heteroatom (N, S, or O) and at least one ring of the ring system is non-aromatic (e.g., saturated). Exemplary saturated heterocycloalkyl groups include azetidinyl, aziridinyl, oxiranyl, oxetanyl, tetrahydrofuranyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, and thiomorpholinyl. Heterocycloalkyl rings systems include ring systems in which an aromatic ring is fused to a nonaromatic ring, such as will be obtained by partial reduction of a polycyclic aromatic ring system. Exemplary ring systems of this category include indolinyl, tetrahydroquinolinyl, and tetrahydroisoquinolinyl. Other heterocycloalkyl groups will be readily apparent to those of skill in the art given the benefit of the present disclosure. A heterocycloalkylgroups can be attached to the main structure either through a carbon atom or a nitrogen atom of the ring.

[0056] The term “compound,” as used herein, unless otherwise indicated, refers to any specific chemical compound disclosed herein and includes tautomers, regioisomers, geometric isomers, and where applicable, stereoisomers, including optical isomers (enantiomers) and other stereoisomers (diastereomers) thereof, as well as pharmaceutically acceptable salts and derivatives thereof where applicable, in context. Within its use in context, the term compound generally refers to a single compound, but also may include other compounds such as stereoisomers, regioisomers and / or optical isomers (including racemic mixtures) as well as specific enantiomers or enantiomerically enriched mixtures of disclosed compounds. The term also refers, in context to prodrug forms of compounds which have been modified to facilitate the administration and delivery of compounds to a site of activity. The term also refers to any specific chemical compound in which one or more atoms have been replaced with one or more different isotopes of the same element.

[0057] The entire disclosure of each of the patent documents and scientific articles referred to herein is incorporated by reference in its entirety for all purposes. The function and advantages of these and other embodiments will be more fully understood from the following non-limiting examples. The examples are intended to be illustrative in nature and are not to be considered as limiting the scope of the embodiments discussed herein. EXAMPLES

[0058] There are also several known synthetic routes to provide alkynylbenzenes from the corresponding halobenzenes. For example, reactions in the form of:are disclosed in: Khan et al., WO 2017 / 180923; Miao et al., CN108191711 (2018); Miao et al., CN1030877211 (2013); Wang et al., Liquid Crystals 46(2):257-71 (2019); Li et al., Org. & Biomolec. Chem.21(29): 5935-38 (2023); Xu, Org. Lett.16(3):948-51 (2014); Muller et al., Bioconjugate Chem.28(9):2372-83 (2017).

[0059] Compounds of the present disclosure can be made according to known methods published in the art. For example, the following synthetic schemes may be employed to arrive at compounds of the present disclosure:

[0060] Scheme 1. Ethynylation.

[0061] Scheme 2. Ketone core synthesis and ethynylation

[0062] Scheme 3. Ether core synthesis and ethynylation.

[0063] Further elaboration of functional groups within the group R in Schemes 2 and 3, may be carried out according to standard methods, e.g., ester hydrolysis, ketone reduction, alcohol oxidation, ester formation, and terminal alkyne carboxylation.

[0064] 1-ethynyl-4-pentylbenzene is obtained and its olfactory qualities are studied. Both the neat liquid compound and a 10% dilution of the compound in ethanol are examined by an experienced fragrance chemist (a master perfumer). It is found that the compound exhibits an odor characterized very grainy, floral, muguet, and orris, with fresh slightly fruity, apple, and pear notes.

[0065] Synthetic Examples

[0066] The Compounds of Examples 1 to 13 may be prepared according to the procedures described hereinbelow. The Compounds of Examples 14-20 (1-ethynyl-5-pentyl benzene, 1-ethynyl- 4-butylbenzene, 1-ethynyl-6-hexyl benzene, 1-ethynyl-4-methyl benzene, 1-ethynyl-2,4- dimethylbenzene, 1-ethynyl-3-methyl benzene, 1-ethynyl-4-propyl benzene) are commercially available and were purchased on the open market.

[0067] 1H-NMR spectra were recorded at 400 MHz on a Bruker Avance AV-I- 400 instrument or on a Bruker Avance AV-II-400 instrument. Chemical shift values are expressed in ppm-values relative to tetramethylsilane unless noted otherwise. The following abbreviations or their combinations are used for multiplicity of NMR signals: br = broad, d = doublet, m = multiplet, q = quartet, quint = quintet, s = singlet and t = triplet.

[0068] Example 1: 5-ethynyl-1,3-dimethyl-2-pentylbenzene

[0069] Step 1: benzyl N-(4-bromo-3,5-dimethylphenyl)carbamate

[0070] A solution of 4-bromo-3,5-dimethylaniline (10 g, 49.98 mmol, 1.00 equiv) in ACN (100 mL) and H2O (20 mL) was treated with benzyl chloroformate (12.79 g, 74.97 mmol, 1.50 equiv) at 0°C for 5 min under nitrogen atmosphere, followed by the addition of NaHCO3 (12.60 g, 149.94 mmol, 3.00 equiv) in portions at room temperature. The resulting mixture was stirred at room temperature for 1 h under nitrogen atmosphere. The reaction was quenched with water at roomtemperature. The resulting mixture was extracted with EtOAc (60 mL). The combined organic layers were washed with water (2x60 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (5:1) to afford the title compound (9.8 g, 58.67%yield) as a yellow oil.

[0071] Step 2: benzyl N-{3,5-dimethyl-4-[(1E)-pent-1-en-1-yl]phenyl}carbamate

[0072] A solution of benzyl N-(4-bromo-3,5-dimethylphenyl)carbamate (9.8 g, 29.32 mmol, 1.00 equiv) in dioxane (90 mL) and H2O (10 mL) was treated with 4,4,5,5-tetramethyl-2-[(1E)-peot- 1-en-1-yl]-1,3,2-dioxaborolane (6.90 g, 35.19 mmol, 1.20 equiv) and Na2CO3(9.32 g, 87.97 mmol, 3.00 equiv) at room temperature for 3 min under nitrogen atmosphere followed by the addition of CataCXium A Pd G3(2.14 g, 2.93 mmol, 0.10 equiv) at room temperature. The resulting mixture was stirred at 100°C for 1 h under nitrogen atmosphere. The reaction was quenched with water at room temperature. The resulting mixture was extracted with EtOAc (60 mL). The combined organic layers were washed with water (3x60 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (10:1) to afford the title compound (8 g, 84.35%yield) as a yellow oil.

[0073] Step 3: 3,5-dimethyl-4-pentylaniline

[0074] A solution of benzyl N-{3,5-dimethyl-4-[(1E)-pent-1-en-1-yl]phenyl}carbamate (8 g, 24.73 mmol, 1.00 equiv) and Pd / C (800 mg, 7.52 mmol, 0.30 equiv) in EA (100 mL) was stirred at room temperature for 2 h under hydrogen atmosphere. The resulting mixture was filtered; the filter cake was washed with EA (3x10 mL). The filtrate was concentrated under reduced pressure. The resulting mixture was concentrated under vacuum to afford the title compound (3.5 g, 73.96%yield) as a yellow oil.

[0075] Step 4: 5-iodo-1,3-dimethyl-2-pentylbenzene

[0076] A solution of 3,5-dimethyl-4-pentylaniline (3.5 g, 18.29 mmol, 1.00 equiv) in ACN (30 mL) and H2O (5 mL) was treated with TsOH (4.73 g, 27.44 mmol, 1.50 equiv) at 0°C for 10 min under nitrogen atmosphere followed by the addition of NaNO2(1.51 g, 21.95 mmol, 1.20 equiv) in portions at 0°C. The resulting mixture was stirred at room temperature for 30 min under nitrogen atmosphere. To the mixture was added KI (7.29 g, 43.91 mmol, 2.40 equiv) in portions over 3 min at 0°C. The resulting mixture was stirred at room temperature for additional 2 h. The reaction was quenched with sat. NaHCO3(aq.) at room temperature. The resulting mixture was extracted with EtOAc (40 mL). The combined organic layers were washed with water (3x40 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residuewas purified by silica gel column chromatography, eluted with PE / EA (12:1) to afford the title compound (4 g, 72.35%yield) as a yellow oil.

[0077] Step 5: [2-(3,5-dimethyl-4-pentylphenyl) ethynyl] trimethylsilane

[0078] A solution of 5-iodo-1,3-dimethyl-2-pentylbenzene (4 g, 13.24 mmol, 1.00 equiv) in Et3N (40 mL) was treated with trimethylsilylacetylene (1.69 g, 17.21 mmol, 1.30 equiv) and PdCl(PPh3)2(0.4 g) at room temperature for 5 min under nitrogen atmosphere followed by the addition of CuI (0.13 g, 0.66 mmol, 0.05 equiv) in portions at room temperature. The resulting mixture was stirred at 80°C for 2 h under nitrogen atmosphere. The reaction was poured into water at room temperature. The resulting mixture was extracted with EtOAc (30 mL). The combined organic layers were washed with water (3x30 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (10:1) to the title compound (2.5 g, 69.31% yield) as a yellow oil.

[0079] Step 6: 5-ethynyl-1,3-dimethyl-2-pentylbenzene

[0080] A solution of [2-(3,5-dimethyl-4-pentylphenyl) ethynyl] trimethylsilane (2.5 g, 9.17 mmol, 1.00 equiv) and K2CO3(3.80 g, 27.52 mmol, 3.00 equiv) in MeOH (25 mL) was stirred at room temperature for 2 h under nitrogen atmosphere. Reaction progress was monitored by GCMS. At full conversion, the resulting mixture was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: CSH-30-Hexyl, 19*150 mm, 5 μm; Mobile Phase A: 0.1%TFA, Mobile Phase B: ACN; Flow rate: 20 mL / min; Gradient: 40% to 90% in 12min. This resulted in the Compound of Example 1 (576.8 mg, 31.39% yield, 95.13% purity) as a yellow oil. GC-MS: (EI+, m / z, M+): 200.2. 1H NMR (300 MHz, Chloroform-d, ppm) δ 7.16 (s, 2H), 3.00 (s, 1H), 2.66 – 2.54 (m, 2H), 2.31 (s, 6H), 1.49 – 1.34 (m, 6H), 0.99 – 0.90 (m, 3H).

[0081] Examples 2-7

[0082] Following the procedure of Example 1, additional compounds are prepared as shown in the following table. GC-MS 1

[0083] Example 8: 2-butyl-5-ethynyl-1,3-dimethylbenzene

[0084] Step 1: [2-(4-bromo-3,5-dimethylphenyl)ethynyl]trimethylsilane

[0085] A solution of 2-bromo-5-iodo-1,3-dimethylbenzene (5 g, 16.08 mmol, 1.00 equiv) in Diisopropylamine (50 mL) was treated with trimethylsilylacetylene (2.05 g, 20.90 mmol, 1.30 equiv) at room temperature for 5 min under nitrogen atmosphere followed by the addition of CuI (0.15 g, 0.80 mmol, 0.05 equiv) and dichlorobis(triphenylphosphine)palladium(II) (1.13 g, 1.61 mmol, 0.10 equiv) in portions at room temperature. The resulting mixture was stirred at 60°C for 2 h under nitrogen atmosphere. The reaction was quenched with sat. aq. NH4Cl (aq.) at room temperature. The resulting mixture was extracted with EtOAc (50 mL). The combined organic layers were washed with water (3x50 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (12:1) to afford the title compound (4.5 g, 99.50% yield) as a yellow oil.

[0086] Step 2: [2-(4-butyl-3,5-dimethylphenyl)ethynyl]trimethylsilane

[0087] A solution of trichloroindium tetrahydrate (8.34 g, 28.44 mmol, 2.00 equiv) in THF (40 mL) was treated with n-BuLi (5.47 g, 85.33 mmol, 6.00 equiv) at -10°C for 30min under nitrogen atmosphere, followed by the addition of [2-(4-bromo-3,5- dimethylphenyl)ethynyl]trimethylsilane (4 g, 14.22 mmol, 1.00 equiv) and Pd(dtbpf)Cl2(0.93 g, 1.42 mmol, 0.10 equiv) in portions at room temperature. The resulting mixture was stirred at 70°C overnight under nitrogen atmosphere. Reaction progress was monitored by GCMS. The reaction wasquenched with sat. NH4Cl (aq.) at room temperature. The resulting mixture was extracted with EtOAc (50 mL). The combined organic layers were washed with water (3x50 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (12:1) to afford the title compound (3.2 g, 87.05% yield) as a yellow oil. GC-MS: (EI+, m / z, M+): 215.10.1H NMR (300 MHz, Chloroform-d, ppm) δ 7.14 (s, 2H), 2.65 – 2.54 (m, 2H), 2.29 (s, 6H), 1.52 – 1.35 (m, 4H), 1.03 – 0.92 (m, 3H), 0.25 (d, J = 1.0 Hz, 9H).

[0088] Step 3: 2-butyl-5-ethynyl-1,3-dimethylbenzene

[0089] A solution of [2-(4-butyl-3,5-dimethylphenyl) ethynyl] trimethylsilane (2 g, 7.74 mmol, 1.00 equiv) and K2CO3(2.14 g, 15.48 mmol, 2.00 equiv) in MeOH (20 mL) was stirred at room temperature for 2 h under nitrogen atmosphere. Reaction progress was followed by GCMS. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (12:1) to afford the compound of Example 8 (550.9 mg, 38.22% yield, 98.79% purity) as a yellow oil. GC-MS: (EI+, m / z, M+): 186.10.1H NMR (300 MHz, Chloroform-d, ppm) δ 7.17 (s, 2H), 3.01 (s, 1H), 2.67 – 2.56 (m, 2H), 2.31 (s, 6H), 1.52 – 1.35 (m, 4H), 1.05 – 0.94 (m, 3H).

[0090] Examples 9-10

[0091] Following the procedure of Example 8, additional compounds are prepared as shown in the following table.

[0092] Example 11: 4-ethyl-1-ethynyl-2-methylbenzene

[0093] Step 1: 4-ethyl-2-methylaniline

[0094] A solution of benzenamine, 4-bromo-2-methyl- (16 g, 85.99 mmol, 1.00 equiv) in THF (30 mL) was treated with Pd(dppf)Cl2(7.02 g, 8.60 mmol, 0.10 equiv) and Cs2CO3(84.06 g, 257.99 mmol, 3.00 equiv) at room temperature for 5 min under nitrogen atmosphere followed by the addition of triethyl borane (12.64 g, 128.99 mmol, 1.50 equiv) in portions at room temperature. The resulting mixture was stirred at 70°C for 2 h under nitrogen atmosphere. The reaction was quenched with water at room temperature. The resulting mixture was extracted with EtOAc (100 mL). The combined organic layers were washed with brine (3x100 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (5:1) to afford the title compound (8 g, 68.62% yield) as a yellow oil.

[0095] Step 2: 4-ethyl-1-iodo-2-methylbenzene

[0096] A solution of 4-ethyl-2-methylaniline (1.50 g, 11.09 mmol, 1.00 equiv) in AcOH / H2O=10 / 1 (15 ml) was treated with TsOH (0.57 g, 3.38 mmol, 0.30 equiv), NaNO2(0.77 g, 11.09 mmol, 1.00 equiv) and KI (2.76 g, 16.64 mmol, 1.50 equiv) at room temperature overnight.The resulting mixture was extracted with EtOAc (20 mL). The combined organic layers were washed with water (3x20 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (6:1) to afford the title compound (2.3 g, 85.19% yield) as a light brown oil.

[0097] Step 3: 4-ethyl-1-iodo-2-methylbenzene

[0098] A solution of 4-ethyl-1-iodo-2-methylbenzene (1.10 g, 4.47 mmol, 1.00 equiv) in DMF (10 mL) was treated with CuI (0.09 g, 0.45 mmol, 0.10 equiv), ethynyltrimethylsilane (0.53 g, 5.36 mmol, 1.20 equiv), PdCl2(PPh3)2(0.37 g, 0.45 mmol, 0.10 equiv) and Et3N (1.36 g, 13.41 mmol, 3.00 equiv) at 50°C overnight under nitrogen atmosphere. The resulting mixture was filtered; the filter cake was washed with ethyl acetate (30 mL). The filtrate was concentrated under reduced pressure. dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (6:1) to afford the title compound (0.7 g, 72.53% yield) as a light brown oil.

[0099] Step 4: 4-ethyl-1-ethynyl-2-methylbenzene

[0100] Into a 100 mL round-bottom flask were added [2-(4-ethyl-2-methylphenyl) ethynyl] trimethylsilane (700 mg, 3.23 mmol, 1.00 equiv) and K2CO3(13.18 mg, 9.71 mmol, 3.00 equiv) at room temperature in MeOH (0.70 mL). This was stirred at room temperature for 3 h under air atmosphere. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (6:1) to afford the Compound of Example 11 (461.50 mg, 98.44%purity, 97.8% yield) as a brown liquid. GC-MS: (EI+, m / z, M+): 144.1.1H-NMR (300 MHz, Chloroform-d, ppm) δ 7.40 (d, J = 7.8 Hz, 1H), 7.07 (s, 1H), 7.00 (dd, J = 7.8, 1.8 Hz, 1H), 3.25 (s, 1H), 2.64 (q, J = 7.6 Hz, 2H), 2.45 (s, 3H), 1.24 (t, J = 7.6 Hz, 3H).

[0101] Examples 12-13

[0102] Following the procedure of Example 11, additional compounds are prepared as shown in the following procedure and table. The following steps provide the aniline intermediate corresponding to the product of step 1 of Example 11. The procedure for preparing the intermediate for the compound of Example 12 is shown below:

[0103] Step 1: benzyl N-(4-bromo-2,3-dimethylphenyl) carbamate

[0104] Into a 500 mL round-bottom flask were added 4-bromo-2,3-dimethylaniline (6 g, 29.98 mmol, 1.00 equiv), saturated aqueous sodium bicarbonate solution (7.56 g, 89.96 mmol, 3.00 equiv) and benzyl chloroformate (10.23 g, 59.97 mmol, 2.00 equiv) in acetone (60 mL) and H2O (60 mL). This was stirred at room temperature for 5 h in air. The resulting mixture was extracted with EtOAc (30 mL). The combined organic layers were washed with water (3x30 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (5:1) to afford the title compound (7.50 g, 75.12% yield) as a yellow oil.

[0105] Step 2: benzyl N-(2,3,4-trimethylphenyl) carbamate

[0106] Into a 500 mL round-bottom flask were added benzyl N-(4-bromo-2,3- dimethylphenyl) carbamate (7.50 g, 22.44 mmol, 1.00 equiv), trimethyl-1,3,5,2,4,6-trioxatriborinane (5.63 g, 44.88 mmol, 2.00 equiv), Pd(dppf)Cl2(1.83 g, 2.24 mmol, 0.10 equiv) and Cs2CO3(14.62 g, 44.88 mmol, 2.00 equiv) in THF (75 mL). The mixture was heated to 70 °C for overnight under nitrogen atmosphere. The resulting mixture was filtered; the filter cake was washed with THF (75 mL). The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (6:1) to afford the title compound (4.20 g, 69.41% yield) as a yellow oil.

[0107] Step 3: 2,3,4-trimethylaniline

[0108] A solution of benzyl N-(2,3,4-trimethylphenyl) carbamate (4.2 g, 15.59 mmol, 1.00 equiv) and Pd / C (0.50 g, 4.678 mmol, 0.30 equiv) in MeOH (40 mL) was stirred at room temperature for overnight under hydrogen atmosphere. The resulting mixture was filtered; the filter cake was washed with MeOH (40 mL). The filtrate was concentrated under reduced pressure. Theresidue was purified by silica gel column chromatography, eluted with PE / EA (5:1) to afford the title compound (2 g, 95.23%yield) as a yellow oil.

[0109] Following the procedure of Example 11, additional compounds are prepared as shown in the following table. The procedures of steps 1 and 2 immediately above are combined with steps 2-4 of Example 11.

[0110] Odor Profile Determination

[0111] Odor profile for selected compounds within the scope of the disclosure is determined using assessments by one Master Perfumer and 4-6 trained sensory panelists. Sensory panelists are trained on our internal taxonomy with reference materials that include 11 grand families, and 62 subfamilies. Panelists are experienced in, but not trained in, an additional several hundred odor descriptors. Panelists are trained on usage of a rating scale, which also includes internal references. Panelists are not advanced to compound evaluation until they have completed and received a passing score on a Final Exam on the taxonomy that was curated by our perfumery team.

[0112] A single score is generated for the sensory panel by taking the arithmetic mean of all panelist scores for a given sample, for a given attribute. Alternatively, a single score may be generated by fitting all panelist scores to a model that can correct for differences in the intercept or slope of the latent function through which each panelist produces a rating given a percept, i.e. correction for inter-panelist variation.

[0113] The Master Perfumer, possessing a deep knowledge of fragrance ingredients, high level technical expertise, and who is recognized for their experience in creating complex perfumes, reviews, may augment sensory panel scores for improved accuracy.

[0114] Test samples are dissolved at a concentration of 10% w / v in ethanol. At time 0 (t = 0), new test blotters (White Paper Paddle Shaped Perfumery Blotters, measuring 5 x 0.5 inches) are dipped into the 10% solution of the text compound. Odor descriptions at time t = 0 are captured within 1-2 minutes of wetting the blotter to allow for evaporation of most of the ethanol solvent, permitting a more accurate determination of the test compound’s odor. Assessments are made at ambient temperature in a benchtop laboratory setting. For the longevity determination, blotters are stored in open air on the laboratory benchtop between assessments (no jar or other enclosure is used).

[0115] The results are shown in the table below:

[0116] The Examples provided herein are exemplary only and are not intended to be limiting in any way to the various aspects and embodiments of the invention described herein.

Claims

CLAIMS What is claimed:

1. A compound of Formula I:wherein: R1is H, CH3, CH2CH3,CH2CH2CH3,or CH(CH3)2; R2, R4, R5, and R6, are each independently selected from H, C1-3alkyl (e.g., CH3), OH, CHO, or OC1-3alkyl (e.g., OCH3); X is selected from -O-, -CH2-, -C(O)-, CH(OH), and -CH(OR)-; Y is selected from -CH2CH2CH2CH2-, -CH2CH2OCH2-, -CH2OCH2CH2-, - OCH2CH2CH2-, -CH2CH2CH2-, -CH2CH2O-, -CH2OCH2-, -OCH2CH2-,- CH2CH2CH2CH2CH2-, -OCH2CH2CH2CH2-, -CH2OCH2CH2CH2-, -CH2CH2OCH2CH2-, - CH2CH2CH2OCH2-, -CH2CH2CH2CH2O-, -CH2CH2CH2CH2CH2CH2-, - OCH2CH2CH2CH2CH2-, -CH2OCH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2-, - CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2O-, - CH2CH2CH2CH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2CH2-, -CH2OCH2CH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2CH2-, -CH2CH2CH2OCH2CH2CH2-, -CH2CH2CH2CH2OCH2CH2-, - CH2CH2CH2CH2CH2OCH2-, and -CH2CH2CH2CH2CH2CH2O-, wherein said group Y is optionally substituted by one or more groups selected from C1-3alkyl (e.g., CH3), OH, CHO, and OC1-3alkyl (e.g., OCH3); or X-Y is absent; R3is selected from H, Rb, OH, ORb, OC(O)Rb, CN, COOH, COORb, C(O)Rb, and CHO; and each Rbis independently optionally substituted C1-6alkyl (e.g., CH3or CH2CH3), C2-6alkenyl (e.g., allyl or 2-methylprop-1-enyl), CH2C3-6cycloalkyl (e.g., cyclopropylmethyl),C3-6cycloalkyl (e.g., cyclopropyl), C4-6cycloalkenyl (e.g., cyclopentenyl), optionally substituted phenyl, or optionally substituted benzyl; provided that the compound is not 1-ethynyl-4-methylbenzene, 1-ethynyl-2,4- dimethylbenzene, 1-ethynyl-3-methylbenzene, 1-ethynyl-4-propylbenzene, 1-ethynyl-4- butylbenzene, 1-ethynyl-4-pentylbenzene, or 1-ethynyl-4-hexylbenzene, and wherein the compound is not a compound wherein: (a) R1and R2are H, and X-Y-R3is n-butyl, n-pentyl, n-hexyl, or n-nonyl; (b) R1and R2are H, X is -C(O)-, and Y-R3is n-butyl, n-octyl, or n-undecyl; (c) R1and R2are H, X is -CH(OH)-, and Y-R3is n-butyl, n-octyl, or n-undecyl; (d) R1and R2are H, X is -O-, and Y-R3is n-butyl, n-pentyl, or n-hexyl.

2. A compound of Formula I:Formula I wherein: R1is H, CH3, CH2CH3, CH2CH2CH3, or CH(CH3)2; R2, R4, R5, and R6, are each independently selected from H, C1-3alkyl (e.g., CH3), OH, CHO, or OC1-3alkyl (e.g., OCH3); X is selected from -O-, -CH2-, -C(O)-, -CH(OH)-, and -CH(OR)-; Y is selected from -CH2CH2CH2CH2-, -CH2CH2OCH2-, -CH2OCH2CH2-, - OCH2CH2CH2-, -CH2CH2CH2-, -CH2CH2O-, -CH2OCH2-, -OCH2CH2-,- CH2CH2CH2CH2CH2-, -OCH2CH2CH2CH2-, -CH2OCH2CH2CH2-, -CH2CH2OCH2CH2-, - CH2CH2CH2OCH2-, -CH2CH2CH2CH2O-, -CH2CH2CH2CH2CH2CH2-, - OCH2CH2CH2CH2CH2-, -CH2OCH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2-, - CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2O-, - CH2CH2CH2CH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2CH2-, -CH2OCH2CH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2CH2-, -CH2CH2CH2OCH2CH2CH2-, -CH2CH2CH2CH2OCH2CH2-, - CH2CH2CH2CH2CH2OCH2-, and -CH2CH2CH2CH2CH2CH2O-,wherein said group Y is optionally substituted by one or more groups selected from C1-3alkyl (e.g., CH3), OH, CHO, and OC1-3alkyl (e.g., OCH3); or X-Y is absent; R3is selected from H, Rb, OH, ORb, OC(O)Rb, CN, COOH, COORb, C(O)Rb, and CHO; and each Rbis independently optionally substituted C1-6alkyl (e.g., CH3or CH2CH3), C2-6alkenyl (e.g., allyl or 2-methylprop-1-enyl), CH2C3-6cycloalkyl (e.g., cyclopropylmethyl), C3-6cycloalkyl (e.g., cyclopropyl), C4-6cycloalkenyl (e.g., cyclopentenyl), optionally substituted phenyl, or optionally substituted benzyl; for use as a flavor or fragrance ingredient.

3. A flavor composition and / or fragrance composition comprising a compound of Formula I:Formula I wherein: R1is H, CH3, CH2CH3, CH2CH2CH3, or CH(CH3)2; R2, R4, R5, and R6, are each independently selected from H, C1-3alkyl (e.g., CH3), OH, CHO, or OC1-3alkyl (e.g., OCH3); X is selected from -O-, -CH2-, -C(O)-, -CH(OH)-, and -CH(OR)-; Y is selected from -CH2CH2CH2CH2-, -CH2CH2OCH2-, -CH2OCH2CH2-, - OCH2CH2CH2-, -CH2CH2CH2-, -CH2CH2O-, -CH2OCH2-, -OCH2CH2-,- CH2CH2CH2CH2CH2-, -OCH2CH2CH2CH2-, -CH2OCH2CH2CH2-, -CH2CH2OCH2CH2-, - CH2CH2CH2OCH2-, -CH2CH2CH2CH2O-, -CH2CH2CH2CH2CH2CH2-, - OCH2CH2CH2CH2CH2-, -CH2OCH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2-, - CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2O-, - CH2CH2CH2CH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2CH2-, -CH2OCH2CH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2CH2-, -CH2CH2CH2OCH2CH2CH2-, -CH2CH2CH2CH2OCH2CH2-, - CH2CH2CH2CH2CH2OCH2-, and -CH2CH2CH2CH2CH2CH2O-,wherein said group Y is optionally substituted by one or more groups selected from C1-3alkyl (e.g., CH3), OH, CHO, and OC1-3alkyl (e.g., OCH3); or X-Y is absent; R3is selected from H, Rb, OH, ORb, OC(O)Rb, CN, COOH, COORb, C(O)Rb, and CHO; and each Rbis independently optionally substituted C1-6alkyl (e.g., CH3or CH2CH3), C2-6alkenyl (e.g., allyl or 2-methylprop-1-enyl), CH2C3-6cycloalkyl (e.g., cyclopropylmethyl), C3-6cycloalkyl (e.g., cyclopropyl), C4-6cycloalkenyl (e.g., cyclopentenyl), optionally substituted phenyl, and optionally substituted benzyl; in admixture with one or more non-toxic, orally acceptable, pharmaceutically acceptable, cosmetically acceptable, or acceptable for a household product, carriers or excipients.

4. The composition of claim 3, wherein R1is H.

5. The composition of claim 3 or 4, wherein R2, R4, R5, and R6, are each independently selected from HandC1-3alkyl.

6. The composition of claim 5, wherein said C1-3alkyl is selected from methyl or ethyl.

7. The composition of any one of claims 1-6, wherein Rbis optionally substituted C1-6alkyl (e.g., CH3or CH2CH3).

8. The composition of claim 7, wherein Rbis selected from methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, n-hexyl, isohexyl, sec-hexyl, and neohexyl.

9. The composition of claim 3 or 4, wherein the compound is selected from the group consisting of:

10. The composition of claim 3 or 4, wherein the compound is selected from the group consisting of:

11. The composition of any one of claims 3-11, wherein the composition further comprises one or more solvents.

12. The composition of any one of claims 3-11, wherein the composition further comprises one or more other flavors or fragrances.

13. A product comprising the compound of claim 1 or the composition of any one of claims 3 to 12, e.g., a product selected from the following: personal care products (e.g., a soap, skin cream or lotion, balm, shampoo, body wash, shower gel, hydrating cream, deodorant, antiperspirant, after-shave lotion, cologne, perfume, or other hair care or skin care product), sunscreens, insect repellants and insecticides, detergents, household cleaning agents (e.g., a surface cleaner, a metal cleaner, a wood cleaner, a glass cleaner, a body cleaner such as a soap, a dish-washing detergent, or a laundry detergent), air fresheners, room sprays, pomanders, candles, cosmetics (e.g., perfumes, colognes, nail polish, eye liner, mascara, lipstick, foundation, concealer, blush, bronzer, eye shadow, lip liner, lip balm), toilet waters, talcum powders, and pet litter.

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