WO2008009914A1

WO2008009914A1 - Thiophenemethyl salicylate and related compounds as flavours and fragrances

Info

Publication number: WO2008009914A1
Application number: PCT/GB2007/002687
Authority: WO
Inventors: Luca Turin
Original assignee: Flexitral, Inc.
Priority date: 2006-07-17
Filing date: 2007-07-17
Publication date: 2008-01-24
Also published as: EP2046772A1

Abstract

The present invention provides a compound or mixture of compounds having the formula (I):wherein R1 and R2 represent, independently, linear or branched C1-4 alkyl, n = O to 4 and m = 0 to 3, and their use as flavours and/or fragrances. The invention also provides methods to confer, improve, enhance or modify a taste or flavour property or the aroma, fragrance or odour characteristics of a composition, product, preparation or article. The present invention further provides compositions, products, preparations or articles containing as a flavour and/or fragrance ingredient a compound or mixture of compounds of the invention as described above.

Description

Thiophenemethyl Salicylate and Related Compounds as Flavours and

Fragrances

The present invention relates generally to the field of fragrances and flavours. More particularly, the present invention concerns thiophenemethyl salicylate and related compounds that provide perfumes, flavourants and other articles with properties and advantages not shared by other chemicals. These components find utility in an}' and all applications requiring certain aroma and flavour themes. The invention also relates to mixtures of these compounds, methods for their preparation and their use as odourant and flavourant materials for application to a variety of substrates.

There are a large number and variety of known fragrances and flavourants used as ingredients in perfumes and in a varied range of other products. However, many aromachemicals include double bonds and/or other reactive groups that are potentially susceptible to reaction and may result in a limited useful lifetime. Further, many essential oil fragrances have recently been determined to cause allergic reactions, and it is becoming increasingly difficult to bring products containing such fragrances/flavours to market. For example, benzyl salicylate (which has the chemical structure shown below) has a slight odour and is used as a solvent for synthetic musks and a fixer in perfume compositions.

However, benzyl salicylate has a very faint odour which not everyone can smell. Moreover, benzyl salicylate is though to be allergenic.

There is also a demand for new flavours and fragrances that have novel or improved fragrance and/or flavour profiles and/or other properties that make them particularly useful for use as fragrances and/or flavours. The listing or discussion of a prior-published document in this specification should not necessarily be taken as an acknowledgement that the document is part of the state of the art or common general knowledge.

The present invention addresses the foregoing deficiencies by providing the compounds, use, methods, substrate, composition, product, preparation or article, beverage composition, flavouring composition, food composition, chewing gum composition pharmaceutical composition, orally deliverable matrix and article of manufacture as defined in the claims.

The present invention provides compounds of formula (I):

wherein R¹ and R² represent, independently, linear or branched Ci_-4 alkyl, n = 0 to 4 and m = O to 3.

By linear or branched Cμ alkyl we mean methyl, ethyl, «-propyl, z-propyl, n- butyl, z-butyl, s-butyl or z^*-butyl. If n > 1, each R¹ group may be the same or different. If m > 1, each R² group also may be the same or different.

Preferably, n = 0 and/or m = 0. Thus in a preferred aspect, the invention relates to the thiophenemethyl salicylate compounds having the formula:

, such as

2-thiophene methanol 3-thiophene methanol salicylate ester salicylate ester

A preferred group of compounds of the invention are those in which the salicylate- type group is attached to the 2-position of the thiophene ring. Specific examples of such compounds include 2-thiopene methanol salicylate ester illustrated above.

All of the above compounds will be referred to hereinafter as the compounds of the invention or the aromachemicals of the invention. For the avoidance of doubt, by the term "a compound or mixture of compounds" having the generic formula (I), we refer to one or more of the specific compounds which fall within the generic definition of the compounds of the invention set out above. Any of these compounds may be used in any of the applications described herein. Preferred compounds for use in the applications described herein include 2-thiophene methanol salicylate ester and 3-thiophene methanol salicylate ester.

The present invention provides a method for the preparation of a compound of

formula (I) comprising reacting a compound of formula

with

a compound of formula

, wherein R¹ and R² represent, independently, linear or branched Cj_-4 alkyl, n = 0 to 4, m = 0 to 3 and X is selected from the group consisting of -OMe, -OH and Cl. If n > 1, each R¹ group may be the same or different. If m > 1, each R group also may be the same or different. The CH₂OH group of the compound of formula

"' may be attached to the 2- or 3 -position of the thiophene ring (preferably the 2-position). Preferably, n = 0 and/or m = 0. Preferably X = -OMe. In which case, the reaction is carried out in the presence of an acid or base catalyst (e.g. sodium methoxide).

By way of example, the thiophene salicylate compounds of the invention (i.e. wherein m = n= 0) may be prepared according to the following reaction scheme:

salicylic acid

2-/3-thiophenemethyl salicylate

The compounds of the invention may be isolated from their reaction mixtures using conventional techniques including, for example, recrystallisation, filtration, column chromatography and distillation.

Surprisingly, it has been found that the compounds of the invention possess an odour profile which is sweet- floral, green, and reminiscent of benzyl salicylate.

It has also been unexpectedly found that the compounds of the invention have an odour which is about 3 times stronger than benzyl salicylate. Moreover, the compounds of the invention are believed not to be allergenic. For example, 2- thiopene methanol salicylate ester possesses sweet, floral and mild balsamic notes and has excellent blending capabilities. It may be used as the foundation for heavy florals such as ylang, gardenia, etc.

The present invention provides the use of a compound or mixture of compounds of the invention as a flavour and/or fragrance. The present invention also provides a method to confer, improve, enhance or modify the taste or flavour property of a composition, product, preparation or article which comprises adding thereto a flavour effective amount of a compound or mixture of compounds of the invention as described above.

The composition, product preparation or article may be in the form of a beverage, a flavouring, a food, a chewing gum, a pharmaceutical or an orally deliverable matrix.

The present invention further provides a method to confer, improve, enhance or modify the aroma, fragrance or odour characteristics of a composition, product, preparation or article which comprises adding thereto an aroma, fragrance or odour effective amount of a composition or mixture of compounds of the invention.

The composition product, preparation or article may be in the form of a perfume, a body odorant, deodorant or antiperspirant, a detergent, a bleach product or a disinfectant.

The present invention provides a substrate treated with a compound or mixture of compounds of the invention and a method for treating a substrate with a compound or mixture of compounds of the invention.

The present invention also provides compositions, products, preparations or articles containing as a flavour and/or fragrance ingredient a compound or mixture of compounds of the invention as described above.

The compounds of the invention can be included in virtually any article of manufacture that can include fragrance or flavourant compounds. Examples include hypochlorite (bleach) compositions, detergents, flavourings and fragrances, beverages, including alcoholic beverages, and the like. The compounds of the invention can be used in applications like soaps, shampoos, denture cleanser tablets, 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 of the invention is not limited to the above-mentioned products, as they may 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 compounds of the invention also find utility in foods, flavourings, beverages such as beer and soda, denture cleansers (tablets), flavoured orally-delivered products such as lozenges, candies, chewing gums, matrices, pharmaceuticals and the like. These uses are described in more detail below.

The compounds of the invention can be used as perfuming ingredients, as single compounds or as mixtures thereof. The compounds can 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 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.

In all of the above applications, the compounds of the invention 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 person skilled in the art will be able to choose the latter through their general knowledge and as a function of the nature of the product to be perfumed and of the desired olfactive effect. 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 compounds, as well as essential oils of natural or synthetic origin. A large number of these ingredients described in reference textbooks such as the book of S. Arctander, Perfume and Flavour Chemicals, 1969, Montclair, NJ. , USA, the contents of which are hereby incorporated by reference in its entirety, or its more recent versions, or in other works of similar nature.

The proportions in which the compounds of the invention 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 odour 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 the invention are typically present at concentrations between about 0.01 and about 30% (e.g. 0.1 to 20%), or even more, by weight of these compounds relative to the weight of the composition, product or article in which they are incorporated. It will be appreciated that the amount by weight of a compound of the invention in a particular composition or product will depend on the nature of the composition. For example, a washing powder will typically contain less than 1 % by weight of a compound of the invention while a fine fragrance may contain more than 20 % by weight of a compound of the invention.

The compounds may be used in detergents such as those 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 aspects are described in more detail below. In addition to the compounds of the invention, the compositions described herein may 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 aesthetics of the detergent composition (e.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 Ci_-18 alkyl benzene sulfonates ("LAS") and primary, branch-chain and random Cio_-2o alkyl sulfates ("AS"), and the like. Preferred compositions incorporating only synthetic detergents have a detergent level of from about 0.5% to 50%. Compositions containing soap preferably comprise from about 10% to about 90% soap.

The compositions described 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 of the invention can be incorporated into beverages and impart various flavourings 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 flavoured beverage. The beverage compositions can be in liquid or powdered form. The beverage compositions can also include one or more flavouring agents; artificial colorants; vitamin additives; preservatives; caffeine additives; water; acidulants; thickeners; buffering agents; emulsifiers; and/or fruit juice concentrates.

Artificial colorants that may be used include caramel color, yellow 6 and yellow 5. Useful vitamin additives include vitamin B2, vitamin B6, vitamin B 12, vitamin C (ascorbic acid), niacin, pantothenic acid, biotin and folic acid. Suitable preservatives include sodium or potassium benzoate. Salts that may be used include sodium, potassium and magnesium 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. The beverage may, for example, be 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: Flavour Concentrate, including one or more of the compounds of the invention herein (22.22 ml), 80% Phosphoric Acid (5.55 g),

Citric Acid (0.267 g), Caffeine (1.24 g), artificial sweetener, sugar or com syrup

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

Flavoured food and pharmaceutical compositions including one or more of the compounds of the invention can also be prepared. The compounds of the invention 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 of the invention can be released into the orally-deliverable polymeric matrix material as the composition is chewed and held in the mouth, thus prolonging the flavour of the composition. In the case of dried powders and mixes, the flavour can be made available as the product is consumed or be released into the matrix material as the composition is further processed. When two flavours are combined with the polymeric particles, the relative amounts of the additives can be selected to provide simultaneous release and exhaustion of the compounds.

Flavoured compositions of the invention may include an orally-deliverable 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 and are non-degradable in the digestive tract; and one or more compounds of the invention entrapped within the internal pore networks. The compounds of the invention are released as the matrix is chewed, dissolved in the mouth, or undergoes further processing selected from the group consisting of liquid addition, dry 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, jellies, pastes, powders, dry blends, dehydrated food mixes, baked goods, batters, doughs, tablets, and lozenges.

A flavourless gum base can be combined with a compound or a mixture of compounds of the invention to a desired flavour concentration. In one method for producing such gum based products a blade mixer is heated to about 110 ⁰F, 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 compound or compounds of the invention are 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.

The compounds of the invention may be incorporated into a system that can release a fragrance in a controlled manner. These include substrates such as air fresheners, laundry detergents, fabric softeners, deodourants, lotions, and other household items. The fragrances are generally one or more derivatives of essential oils as described herein, each present in different quantities. US Patent No. 4,587,129, the contents of which are hereby incorporated by reference in their entirety, describes a method for preparing gel articles that 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 release properties, i.e. they release the fragrance component continuously over a long period of time.

The present invention is illustrated by the following non-limiting example.

EXAMPLE Synthesis of 2-thiophene methanol salicylate ester

MW = 234.276

^C12^H10°3^S

In a 100ml round bottom flask equipped with a distillation apparatus, methyl salicylate (33g, 0.22 mol), 2-methanol-thiophene (25g, 0.22 mol) and sodium methoxide (0.5g, 0.02 mol) were heated at 95⁰C during 12 hours. The reaction was followed by ¹H NMR. The mixture was taken into dichloromethane, filtered and after evaporation of the solvent, the crude product was purified by column chromatography on silica gel eluting with ethyl acetate/hexane (l %/99%) to give the desired product and methyl salicylate which was removed under distillation (122⁰CC at 15mbar). 2-thiophene methanol salicylate ester crystallised as a white solid (13.8g, 59 mmol).

Substitution of 2-methanol-thiophene by 3-methanol-thiophene in the method described above yields 3-thiophene methanol salicylate ester:

Claims

1. A compound of formula (I):

wherein R¹ and R² represent, independently, linear or branched C_1-4 alkyl, n = 0 to 4 and m = 0 to 3, provided that the compound is not 2-thiophene methanol salicylate ester.

2. A compound according to claim 1 wherein n = 0.

3. A compound according to claim 1 or 2 wherein m — 0.

4. A compound according to claim 1 wherein n = 1 to 4 and m = 1 to 3.

5. The use of a compound or mixture of compounds having the formula:

wherein R I 1 and A R represent, independently, linear or branched C_1-4 alkyl, n = 0 to 4 and m = 0 to 3, as a flavour or fragrance.

6. A method to confer, improve, enhance or modify a taste or flavour property of a composition , product, preparation or article which comprises adding thereto a flavour effective amount of a compound or mixture of compounds having the formula:

wherein R¹ and R² represent, independently, linear or branched Cj_-4 alkyl, n = 0 to 4 and m = 0 to 3.

7. A method according to claim 6, wherein said composition, product, preparation or article is in the form of a beverage, a flavouring, a food, a chewing gum, a pharmaceutical or an orally deliverable matrix.

8. A method to confer, improve, enhance or modify an aroma, fragrance or odour characteristics of a composition, product, preparation or article which comprises adding thereto an aroma, fragrance or odour effective amount of a compound or mixture of compounds having the formula:

wherein R¹ and R² represent, independently, linear or branched C_1-4 alkyl, n = 0 to 4 and m = 0 to 3.

9. A method according to claim 8 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.

10. A method for treating a substrate to impart flavourant/fragrance releasing characteristics thereto comprising treating the substrate with a compound or mixture of compounds having the formula:

wherein R and R^~ represent, independently, linear or branched Ci_-4 alkyl, n = 0 to 4 and m = O to 3.

11. A substrate treated with a compound or mixture of compounds having the formula:

wherein R¹ and R² represent, independently, linear or branched Ci_-4 alkyl, n = 0 to 4 and m = 0 to 3.

12. A composition, product, preparation or article containing as a flavour and/or fragrance ingredient a compound or mixture of compounds having the formula:

wherein R¹ and R² represent, independently, linear or branched Ci_-4 alkyl, n = 0 to 4 and m = 0 to 3, optionally in admixture with other perfuming ingredients, solvents, or adjuvants of current use in the art.

13. A composition, product, preparation or article according to claim 12 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.

14. A composition, product, preparation or article according to claim 13, wherein the compound or mixture of compounds is in admixture with at least one bleach ingredient and/or at least one detergent ingredient and/or at least one disinfectant ingredient.

15. A composition, product, preparation or article according to claim 13 in the form of a body odorant, deodorant or antiperspirant wherein the compound or mixture of compounds is in admixture with other body odorant, deodorant or antiperspirant ingredients, solvents and/or adjuvants.

16. A beverage composition comprising as a flavourant a compound or mixture of compounds having the formula:

wherein R¹ and R² represent, independently, linear or branched C_M alkyl, n = 0 to 4 and m = 0 to 3.

17. A flavouring composition, product or article comprising as a flavouring ingredient a compound or mixture of compounds having the formula:

wherein R¹ and R² represent, independently, linear or branched C_1-4 alkyl, n = 0 to 4 and m = 0 to 3, and optionally a solvent, adjuvant and/or another flavouring ingredient.

18. A food composition, product, preparation or article comprising as a flavouring ingredient a compound or mixture of compounds having the formula:

wherein R¹ and R² represent, independently, linear or branched Cj_-4 alkyl, n = 0 to 4 and m = 0 to 3, and optionally a solvent, adjuvant, and/or another food ingredient.

19. A chewing gum composition, product, preparation or article comprising as a flavouring ingredient a compound or mixture of compounds having the formula:

wherein R¹ and R² represent, independently, linear or branched C_1-4 alkyl, n = 0 to 4 and m = 0 to 3, and optionally a solvent, adjuvant, and/or another chewing gum ingredient.

20. A pharmaceutical composition, product, preparation or article comprising as a flavouring ingredient a compound or mixture of compounds having the formula:

wherein R¹ and R² represent, independently, linear or branched C_1-4 alkyl, n = 0 to 4 and m = 0 to 3, and a pharmaceutical active ingredient.

21. An orally-deliverable matrix comprising as a flavouring ingredient a compound or mixture of compounds having the formula:

wherein R¹ and R² represent, independently, linear or branched Ci_-4 alkyl, n = 0 to 4 and m = 0 to 3, and at least one matrix material.

22. An article of manufacture comprising packaging material and an aroma, odour, fragrance, taste or flavour enhancing agent contained within the packaging material, wherein the agent is effective for the enhancement of the aroma, odour, fragrance, taste or flavour of a composition, preparation, product or article to which it is added, and wherein the packaging material comprises a label which indicates that the agent can be used for enhancing aroma, odour, fragrance, taste or flavour, and wherein the agent is a compound or mixture of compounds having the formula:

23. A use, method, substrate, composition, product, preparation or article, beverage composition, flavouring composition, food composition, chewing gum composition pharmaceutical composition, orally deliverable matrix and article of manufacture according to any of claims 5 to 22 wherein n = 0.

24. A use, method, substrate, composition, product, preparation or article, beverage composition, flavouring composition, food composition, chewing gum composition pharmaceutical composition, orally deliverable matrix and article of manufacture according to any of claims 5 to 23, wherein m = 0.