AU2004241286B2

AU2004241286B2 - Alkoxy alkylsulfanyl phenols

Info

Publication number: AU2004241286B2
Application number: AU2004241286A
Authority: AU
Inventors: Luca Turin
Original assignee: Flexitral Inc
Current assignee: Flexitral Inc
Priority date: 2003-05-20
Filing date: 2004-05-20
Publication date: 2007-12-06
Anticipated expiration: 2024-05-20
Also published as: ZA200509293B; GB2417956A; MXPA05012669A; CN1798504A; WO2004103962A3; AU2004241286A1; GB0525822D0; EP1631147A4; GB2417956B; KR20060021856A; WO2004103962A2; CA2526243A1; JP2007506802A; EP1631147A2

Description

WO 20041103962 PCT/US520041015875 ALKOXY ALKYLSULFANYL PHENOLS FIELD OF THE INVENTION The present invention relates generally to the field of fragrances.

More particularly, the present invention relates to aromachemicals that provide perfumes and other articles with unique properties and advantages 00oo not shared by other aromachemicals.

SBACKGROUND OF THE INVENTION There are a large number and variety of known fragrances used as ingredients in perfumes and in a varied range of other products. For example, perfumes for application in laundry detergents, fabric softeners, rinse conditioners and other products intended for use on textile fibers primarily contain fragrances. While many natural perfume chemicals, such as essential oils, oil of rose and oil of cloves, and animal secretions, such as musk, are known, a large number of synthetic odoriferous chemicals possessing aroma characteristics have been developed. Synthetic aroma chemicals have added a new dimension to the art of perfuming, since these synthetics are usually stable compounds and are relatively inexpensive, as compared with the natural perfume chemicals. For example, ethylene glycol monoaryl ethers are known fragrance compounds having a mild rose odor and are useful for food, cosmetic and pharmaceutical applications. See, for example, U. S. Pat. Nos.

1,881,200; 2,451,149 and 4,404, 407. Moreover, synthetics lend themselves more easily to manipulation than natural perfume chemicals since natural perfume chemicals are usually a complex mixture of substances. Accordingly, for these and other reasons, there is a great desire in the art of fragrance chemistry for new compounds possessing specific characteristic aromas, in particular, floral (carnation). Exemplary patents disclosing compounds exhibiting carnation odor notes are US 6,177, 400 and 4,464, 291.

WO 2004/103962 PCT/US2004/015875 Novel fragrance and flavor aromachemicals are disclosed herein as 0 well as methods of making the derivatives, uses of the aromachemicals and articles of manufacture including the aromachemicals. These novel o derivatives find utility in any and all applications requiring certain aroma themes. The invention also relates to mixtures of these derivatives, methods for their preparation and their use as perfume materials for application to a variety of substrates.

00 oo SUMMARY OF THE INVENTION SIn the present invention compounds having the formula

R

1 O-CeH 3 0H-SR (I) wherein: R is a straight or branched chain, saturated or unsaturated hydrocarbyl group; preferably, alkyl or alkenyl, having 1-8 carbon atoms; and RI is a straight or branched chain, saturated or unsaturated hydrocarbyl group; preferably, alkyl or alkenyl, having 1-8 carbon atoms are used as aromachemicals.

The invention provides compositions, products, preparations or articles having improved aroma, fragrance or odor characteristics containing a compound as defined above.

Another embodiment of the invention relates of compositions, products, preparations or articles having improved flavor or taste characteristics containing a composition or compound as defined above.

A further embodiment of the invention concerns methods to confer, improve, enhance or modify the taste or flavor property of a composition, WO 2004/103962 PCT/US2004/015875 3 A further embodiment of the invention concerns methods to confer, improve, enhance or modify the taste or flavor property of a composition, product, preparation or article which comprises adding thereto a flavor effective amount of a compound described above or a mixture thereof.

A still further embodiment of the invention relates to a method to confer, improve, enhance or modify the aroma, fragrance or odor characteristics of compositions, products, preparations or articles which comprises adding thereto an aroma, fragrance or odor effective amount of a compound described above or a mixture thereof.

An additional embodiment of the invention concerns articles of manufacture comprising a compound described above or a mixture thereof.

DETAILED DESCRIPTION OF THE INVENTION Preferred aromachemicals of the invention are those having the formula:

OH

WO 2004/103962 PCT/US2004/015875 4 A particularly preferred aromachemical is 2-methoxy-4-methylsulfanylphenol having the formula:

OH

SCH

3 The aromachemicals of the invention may be prepared according to the reaction scheme set forth in the examples which outlines the synthesis of 2-methoxy-4methylsulfanylphenol.

The aromachemicals of the invention possess the odor profile: floral, carnation, spicy, and smoky. Examples of suitable articles of manufacture in which the derivatives of the invention may be incorporated include perfumes and colognes, candles, air fresheners, detergent compositions and disinfectants.

The compositions, products, preparations and articles in which the compounds and derivatives of the invention may be incorporated include candles, air fresheners, perfumes, fragrances, colognes, soaps, bath or shower gels, shampoos or other hair care products, cosmetic preparations, body odorants, deodorants or antiperspirants, liquid or solid fabric detergents or softeners, bleach products (hypochlorites), disinfectants, all-purpose household or industrial cleaners, foods, flavorings, beverages such as beer and soda, denture cleansers (tablets), flavored orally-delivered products such as lozenges, candies, chewing gums, matrices, pharmaceuticals and the like.

The compounds can be used as perfuming ingredients, as single compounds or as mixture thereof, preferably at a range of at least about 30% by weight of the perfume composition, more preferably at a range of at least about 60% by weight of the composition.

WO 20041103962 5 PCTIUS2004/015875 The compounds of formula can even be used in their pure state or as mixtures, without added components. The olfactive characteristics of the individual compounds are also present in mixtures thereof, and mixtures of O these compounds can be used as perfuming ingredients. This may be particularly advantageous where separation and/or purification steps can be avoided by using compound mixtures.

00oo The compounds of formula can be included in virtually any article of manufacture that can include conventional aromachemicals, or for that Smatter, other fragrances, whether natural or artificial. Examples include Sbleach, detergents, flavorings and fragrances, beverages, including alcoholic Sbeverages, and the like. The derivatives of the invention can be used in applications like soaps, shampoos, body deodorants and antiperspirants, solid or liquid detergents for treating textiles, fabric softeners, detergent compositions and/or all-purpose cleaners for cleaning dishes or various surfaces, for both household and industrial use. Of course, the use of the compounds is not limited to the above-mentioned products, as they be used in other current uses in perfumery, namely the perfuming of soaps and shower gels, hygiene or hair-care products, as well as of body deodorants, air fresheners and cosmetic preparations, and even in fine perfumery, namely in perfumes and colognes. The products of the invention also find utility in foods, flavorings, beverages such as beer and soda, denture cleansers (tablets), flavored orally-delivered products such as lozenges, candies, chewing gums, matrices, pharmaceuticals and the like. These uses are described in more detail below.

In all cited applications, the compounds of formula can be used alone, in admixture with each other, or in admixture with other perfuming ingredients, solvents or adjuvants of current use in the art. The nature and the variety of these co-ingredients do not require a more detailed description here, which, moreover, would not be exhaustive, and the WO 20041103962 6 PCTIUS2004/015875 person skilled in the art will be able to choose the latter through its general knowledge and as a function of the nature of the product to be perfumed and of the desired olfactive effect.

z These perfuming ingredients typically belong to chemical classes as varied as alcohols, aldehydes, ketones, esters, ethers, acetates, nitrites, terpene hydrocarbons, sulfur- and nitrogen containing heterocyclic Icompounds, as well as essential oils of natural or synthetic origin. A large oo number of these ingredients described in reference textbooks such as the book of S. Arctander, Perfume and Flavor Chemicals, 1969, Montclair, N. J. SUSA, the contents of which are hereby incorporated by reference in its Sentirety, or its more recent versions, or in other works of similar nature.

The proportions in which the compounds of formula can be incorporated in the various products vary within a large range of values.

These values depend on the nature of the article or product that one desires to perfume and the odor effect searched for, as well as on the nature of the co-ingredients in a given composition when the compounds are used in admixture with perfuming co-ingredients, solvents or adjuvants of current use in the art.

As an example, the compounds of formula are typically present at concentrations between about 0.1 and about 10%, or even more, by weight of these compounds relative to the weight of the perfuming composition in which they are incorporated. Far lower concentrations than those mentioned above can be used when the compounds are directly applied for perfuming the various consumer products cited beforehand.

The compounds may be used in detergents containing bleaching agents and activators such as, for example, tetraacetylethylenediamine (TAED), hypohalites, in particular hypochlorite, peroxygenated bleaching agents such as, for example, perborates, etc. The compounds can also be used in body deodorants and antiperspirants, for example, those containing aluminum salts. These embodiments are described in more detail below.

WO 2004/103962 7 PCT/US2004015875 In addition to the compounds described herein, the compositions herein include a detersive surfactant and optionally, one or more additional detergent ingredients, including materials for assisting or enhancing cleaning performance, treatment of the substrate to be cleaned, or to modify the z aesthetics of the detergent composition g. perfumes, colorants, dyes, etc.). Non-limiting examples of synthetic detersive surfactants useful herein typically at levels from about 0.5% to about 90%, by weight, include the conventional C1-18 alkyl benzene sulfonates and primary, branch- 00oo chain and random CIO-20 alkyl sulfates and the like.

SPreferred compositions incorporating only synthetic detergents have Sa detergent level of from about 0.5% to 50%. Compositions containing soap Spreferably comprise from about 10% to about 90% soap.

The compositions herein can contain other ingredients such as enzymes, bleaches, fabric softening agents, dye transfer inhibitors, suds suppressors, and chelating agents, all well known within the art.

The compounds described herein can be incorporated into beverages and impart various flavorings to the beverages. The beverage composition can be a cola beverage composition, and can also be coffee, tea, dairy beverage, fruit juice drink, orange drink, lemon-lime drink, beer, malt beverages, or other flavored beverage. The beverages can be in liquid or powdered form. The beverage compositions can also include one or more flavoring agents; artificial colorants; vitamin additives; preservatives; caffeine additives; water; acidulants; thickeners; buffering agents; emulsifiers; and or fruit juice concentrates.

Artificial colorants which may be used include caramel color, yellow 6 and yellow 5. Useful vitamin additives include vitamin B2, vitamin B6, vitamin B12, vitamin C (ascorbic acid), niacin, pantothenic acid, biotin and folic acid.

Suitable preservatives include sodium or potassium benzoate. Salts which may be used include sodium, potassium and magnesium WO 20041103962 8 PCTIUS2004/01 5875 chloride. Exemplary emulsifiers are gum arabic and purity gum, and a useful thickener is pectin. Suitable acidulants include citric, phosphoric and malic acid, and potential buffering agents include sodium and potassium citrate.

z In one embodiment, the beverage is a carbonated cola beverage.

The pH is generally about 2.8 and the following ingredients can be used to make the syrup for these compositions: Flavor Concentrate, including one or more of the derivatives described herein (22.22 ml), 80% Phosphoric Acid 00oo (5.55 Citric Acid (0.267 Caffeine (1.24 artificial sweetener, sugar or

(N

com syrup (to taste, depending on the actual sweetener) and Potassium SCitrate (4.07 The beverage composition can be prepared, for example, by Smixing the foregoing syrup with carbonated water in a proportion of 50 ml syrup to 250 ml of carbonated water.

Flavored food and pharmaceutical compositions including one or more of the compounds described herein can also be prepared. The compounds can be incorporated into conventional foodstuffs using techniques well known to those of skill in the art. Alternatively, the compounds can be incorporated within polymeric particles, which can, in turn, be dispersed within and/or over a surface of an orally-deliverable matrix material, which is usually a solid or semi-solid substrate. When used in chewable compositions, the compounds can be released into the orally-deliverable polymeric matrix material as the composition is chewed and held in the mouth, thus prolonging the flavor of the composition. In the case of dried powders and mixes, the flavor can be made available as the product is consumed or be released into the matrix material as the composition is further processed. When two flavors are combined with the polymeric particles, the relative amounts of the additives can be selected to provide simultaneous release and exhaustion of the compounds.

In one embodiment, the flavored composition includes an orallydeliverable matrix material; a plurality of water insoluble polymeric particles dispersed in the orally-deliverable matrix material, where the polymeric particles individually define networks of internal pores WO 2004/103962 PCT/US2004/015875 and are non-degradable in the digestive tract and one or more derivatives as described herein entrapped within the internal pore networks. The compounds are released as the matrix is chewed, dissolved in the mouth, or undergoes O further processing selected from the group consisting of liquid addition, dry o blending, stirring, mixing, heating, baking, and cooking. The orally-deliverable matrix material can be selected from the group consisting of gums, latex materials, crystallized sugars, amorphous sugars, fondants, nougats, jams, 00oO jellies, pastes, powders, dry blends, dehydrated food mixes, baked goods, batters, doughs, tablets, and lozenges.

SA flavorless gum base can be combined with a compound of formula S(I) or other suitable compounds as described herein to a desired flavor concentration. Typically, a blade mixer is heated to about 10 0 F(43.5 0 the gum base is preheated so that it is softened, and the gum base is then added to the mixer and allowed to mix for approximately 30 seconds. The flavorcompound is then added to the mixer and mixed for a suitable amount of time. The gum can be then removed from the mixer and rolled to stick thickness on waxed paper while warm.

In one embodiment, the compounds described herein are incorporated into a system which can release a fragrance in a controlled manner. These include substrates such as air fresheners, laundry detergents, fabric softeners, deodorants, lotions, and other household items. The fragrances are generally one or more derivatives of essential oils as described herein, each present in different quantities. U. S. Pat. No. 4,587, 129, the contents of which are hereby incorporated by reference in their entirety, describes a method for preparing gel articles which contain up to 90% by weight of fragrance or perfume oils. The gels are prepared from a polymer having a hydroxy (lower alkoxy) 2-alkeneoate, a hydroxy (lower alkoxy) lower alkyl 2-alkeneoate, or a hydroxy poly (lower alkoxy) lower alkyl 2-alkeneoate and a polyethylenically unsaturated crosslinking agent. These materials have continuous slow WO 2004/103962 PCT/US2004/015875 release properties, i. they release the fragrance component continuously over a long period of time. Advantageously, all or a portion of those derivatives that include an aldehyde group can be modified to include an 0 acetal group, which can cause the formulations to release fragrance over a period of time as the acetal hydrolyzes to form the aldehyde compound.

Having hereby disclosed the subject matter of the present invention, oo it should be apparent that many modifications, substitutions, and variations of the present invention are possible in light thereof. It is to be understood that the present invention can be practiced other than as specifically described.

SSuch modifications, substitutions and variations are intended to be within the scope of theappended claims.

EXAMPLE 1 Preparation of 2-methoxy-4-methylsulfanylphenol 1.4-Hydroxy-3-methoxy-benzene thiol

SO

3 K SH OMe OMe OH OH A solution of Guaiacol sulfonic acid potassium salt (1.7g) in benzene was heated to reflux in a Dean-Stark apparatus to remove water. The benzene solution was allowed to cool, treated with triphenylphosphine (6.8g) and 18-crown-6 (0.85g), fitted with a condenser and degassed. A degassed solution of iodine (1.23g) in benzene (10mL) was prepared separately, added to the reaction mixture and the solution refluxed overnight. A 10% mixture of water in WO 20041103962 PCTIUS2004/015875 dioxane (8mL) was added to the reaction and reflux continued for a further Shours. The reaction was allowed to cool and the organic solution washed with water (2 x 40mL), dried over MgSO4 and concentrated to give a colorless O solid. Flash column chromatography using dichloromethane as eluant gave the title compound as a colorless oil (0.60g, 62%).

2.2-methoxy-4-methylsulfanylphenol C1 l OMe OMe OH

OH

OO

To a solution of sodium hydroxide (0.050g) in methanol (2mL) was added 4hydroxy-3- methoxy-benzene thiol (0.20g) and stirring continued for minutes. Methyl iodide 060mL) was added slowly and the solution stirred ovemight at room temperature. Water (2mL) was added, the solution extracted with dichloromethane, the organic layer dried over MgSO4 and concentrated to give a colorless oil. Flash column chromatography using dichloromethane as eluant gave the title compound as a colorless oil (0.05 Ig).

Having hereby disclosed the subject matter of the present invention, it should be apparent that many modifications, substitutions, and variations of the present invention are possible in light thereof. It is to be understood that the present invention can be practiced other than as specifically described.

Such modifications, substitutions and variations are intended to be within the scope of theappended claims.

Claims

1. The use as a flavour or fragrance of an alkoxy alkylsulfanyl O compound or a mixture of said compounds of the formula: R 1 0-C 6 H 3 0H-SR oo wherein: SR is a straight or branched chain, saturated or unsaturated hydrocarbyl group; preferably, alkyl or alkenyl, having 1-8 carbon atoms; and RI is a straight or branched chain, saturated or unsaturated hydrocarbyl group; preferably, alkyl or alkenyl, having 1-8 carbon atoms.

2. Use according to claim 1, wherein in the compound of formula R and R 1 are each CH 3

3. Use according to claim 1,wherein the compound of formula is: OH CH3 0 SCH 3

4. A composition, product, preparation or article comprising a compound as defined in any one of claims 1 to 3 which is in the form of a perfume, fragrance or cologne, a soap, a bath or shower gel, a shampoo or other hair care product, a cosmetic preparation, a body odorant, deodorant or antiperspirant, an air freshener, a liquid or solid fabric detergent or softener, bleach product, disinfectant or an all-purpose household or industrial cleaner. WO 2004/103962 PCT/US2004/015875 A composition, product, preparation or article of claim 4 in the form of a body odorant, deodorant or antiperspirant and comprising body odorant, deodorant or antiperspirant ingredients, solvents or adjuvants.

6. A detergent composition, product, preparation or article of claim 4, comprising detergent ingredients, solvents or adjuvants. 00oO 7. A bleach composition, product, preparation or article of claim 4, comprising bleach ingredients, solvents or adjuvants.

8. A composition, product, preparation or article of claim 4, comprising C\ disinfectant ingredients, solvents or adjuvants.

9. A composition, product, preparation or article comprising a compound as defined in any one of claims 1 to 3, in the form of a beverage, in admixture with other beverage ingredients, solvents or adjuvants. A composition, in the form of a flavouring and comprising a compound as defined in any one of claims 1 to 3 together with other flavoring ingredients, solvents or adjuvants.

11. A composition, product, preparation or article in the form of a food, comprising a compound as defined in any one of claims 1 to 3 in admixture with other food ingredients, solvents or adjuvants.

12. A composition, product, preparation or articlein the form of a chewing gum, comprising a compound as defined in any one of claims 1 to 3 and chewing gum ingredients, and optionally solvents or adjuvants.

13. A composition, product, preparation or article in the form of a pharmaceutical, comprising a compound as defined in any one of claims 1 to 3 as a flavouring ingredient in admixture with a pharmaceutical ingredient, and optionally solvents or adjuvants. WO 2004/103962 PCT/US2004015875

14. A composition, in the form of an orally deliverable matrix material, 0comprising a compound as defined in any one of claims 1 to 3 in admixture with a matrix material ingredients and optionally solvents or adjuvants. A method to confer, improve, enhance or modify the taste or flavor property of a composition, product, preparation or article which comprises adding thereto a flavor effective amount of a compound as defined in any one 00oo of claims 1 to 3. S16. The method of claim 15 wherein said composition, product, Spreparation or article is in the form of a beverage, a flavoring, a food, a chewing gum, a pharmaceutical, or an orally deliverable matrix.

17. A method to confer, improve, enhance or modify the aroma, fragrance or odor characteristics of a composition, product, preparation or article which comprises adding thereto an aroma, fragrance or odor effective amount of a compound as defined in any one of claims 1 to 3.

18. The method of claim 17 wherein said composition, product, preparation or article is in the form of a perfume, a body odorant, deodorant or antiperspirant, a detergent, a bleach product, or a disinfectant.

19. An article of manufacture comprising packaging material and an aroma, odor, fragrance, taste or flavor enhancing agent contained within the packaging material, wherein the agent is effective for the enhancement of the aroma, odor, fragrance, taste or flavor of a composition, preparation, product or article to which it is added, and wherein said packaging material comprises a label which indicates that said agent can be used for enhancing aroma, odor, fragrance, taste or flavor, and wherein the agent is a compound as defined in any one of claims 1 to 3. A composition, product, preparation or article comprising a compound as defined in anyone of claims 1 to 3 and as hereinbefore described.