WO2008009926A2 - Remplacements de safrole - Google Patents

Remplacements de safrole Download PDF

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Publication number
WO2008009926A2
WO2008009926A2 PCT/GB2007/002707 GB2007002707W WO2008009926A2 WO 2008009926 A2 WO2008009926 A2 WO 2008009926A2 GB 2007002707 W GB2007002707 W GB 2007002707W WO 2008009926 A2 WO2008009926 A2 WO 2008009926A2
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WO
WIPO (PCT)
Prior art keywords
compound
compounds
mixture
composition
article
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/GB2007/002707
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English (en)
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WO2008009926A3 (fr
Inventor
Luca Turin
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Flexitral Inc
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Flexitral Inc
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Publication date
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Publication of WO2008009926A2 publication Critical patent/WO2008009926A2/fr
Publication of WO2008009926A3 publication Critical patent/WO2008009926A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
    • C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Preparation or treatment thereof
    • A23L2/52—Adding ingredients
    • A23L2/56—Flavouring or bittering agents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/20—Synthetic spices, flavouring agents or condiments
    • A23L27/205—Heterocyclic compounds
    • A23L27/2052—Heterocyclic compounds having oxygen or sulfur as the only hetero atoms

Definitions

  • the present invention relates generally to the field of flavours and fragrances. More particularly, the present invention relates to new flavour and fragrance compounds. These compounds find utility in any and all applications requiring flavours and fragrances.
  • the invention also provides mixtures of these compounds, methods for their preparation and their use as perfume materials for application in a variety of substrates and their use in flavouring and articles of manufacture and compositions including the compounds.
  • flavours and fragrances used as ingredients in perfumes and in a varied range of other products.
  • aromachemicals include double bonds and/or other reactive groups that are potentially susceptible to reaction and may result in a limited useful lifetime.
  • essential oil fragrances have recently been determined to cause allergic reactions, and it is becoming increasingly difficult to bring products containing such fragrances to market. Some known flavours and fragrances are thought to be carcinogenic.
  • Safrole a phenolic ether obtained primarily from sassafras oil, which is a colourless or slightly yellow liquid, C 10 H 10 O 2 , molecular wt 162.18, with density of 1.096 at 20 0 C, and melting point about 11 0 C.
  • the oil is insoluble in water, very soluble in alcohol, miscible with ether and chloroform.
  • the DL 50 oral is 1.950 mg/kg in rats and 2.350 mg/kg in mice (Budavaris 1989). It has the formula:
  • Safrole has a "root beer” type smell, with liquorice and leather notes. Safrole is important to several products. It is used as an ingredient in popular beverages, such as "pinga com sassafras” in Brazil, and was once used as an ingredient for "root beer” in the United States. It has been used as a topical antiseptic and pediculicide. Safrole is an important raw material for the chemical industry because of two of its derivatives: heliotropin, which is widely used as a fragrance and flavouring agent, and piperonyl butoxide (PBO), a vital ingredient of pyrethroid insecticides.
  • heliotropin which is widely used as a fragrance and flavouring agent
  • PBO piperonyl butoxide
  • Natural pyrethrum in particular would not be an economical insecticide without the addition of PBO as a synergist and the future of the natural pyrethrum industry is linked to the continued availability of PBO.
  • Safrole also has many fragrance applications in household products such as floor waxes, polishes, soaps, detergents, and cleaning agents.
  • 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 present invention addresses the foregoing deficiencies by providing the compounds, use, methods, substrate, composition, product, preparation or article, beverage composition, flavouring compositions, 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:
  • R straight chain or branched Cj, C 2 or C 3 alkyl or alkenyl.
  • R is methyl or vinyl.
  • These compounds which have the chemical names 5-(methylthio)-l,3-benzodioxole and 5-(vinylthio)-l,3-benzodioxole, are shown below. These compounds are also known as 4-(methylthio)-l,2- (methylenedioxy)benzene and 4-(vinylthio)-l ,2-(methylenedioxy)benzene.
  • the compounds of the invention are thought to have Safrole-like flavour and fragrance properties.
  • 4-(methylthio)-l,2-(methylenedioxy)benzene has an odour character which is spicy, leathery and powerful.
  • the compounds of the invention are believed to be non-toxic replacements for Safrole. Alteration of the basic Safrole molecule to remove a benzylic position removes the opportunity for formation of a benzylic/allylic cation, thereby addressing concerns about the potential for the formation of DNA adducts.
  • the compounds of the invention may be prepared by standard synthetic methods known in the art.
  • the thioethers may be synthesised by reacting Safrole with an appropriate sulphur reagent (e.g. mercaptan).
  • an appropriate sulphur reagent e.g. mercaptan
  • its synthesis may be realised either by free-radical and/or a photochemical process or utilising heterogeneous catalysts.
  • the compounds of the invention may be prepared by forming the Grignards reagent by reaction of 4-bromo-l,2-(methylenedioxy)benzene with magnesium turnings.
  • the Grignards reagent may then be reacted an appropriate sulphur reagent (e.g. dialkyl sulphide or 2-chloroethyl thiocyanate) to produce the compounds of the invention. This reaction scheme is illustrated below.
  • the present invention provides for the use of the compounds of the invention and mixtures thereof as a flavour and/or fragrance.
  • the compounds of the invention are particularly useful as flavourants.
  • the present invention also provides compositions, products, preparations or articles containing a compound or mixture of compounds of the invention as described above.
  • the present invention also provides methods 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 composition or mixture of compounds of the invention as described above.
  • a method to confer, improve, enhance or modify the aroma, fragrance or odour characteristics of compositions, products, preparations or articles which comprises adding thereto an aroma, fragrance or odour effective amount of a composition or mixture of compounds of the invention as described above is also provided.
  • 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, flavorings 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.
  • 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 compounds of the invention 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.
  • 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, with or 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Flavor 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 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.
  • the compounds of the invention are typically present at concentrations between about 0.01 and about 30%, 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.
  • TAED tetraacetylethylenediamine
  • 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.
  • 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.).
  • 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 C] -18 alkyl benzene sulfonates ("LAS") and primary, branch-chain and random Ci 0-20 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.
  • 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 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, root beer, malt beverages, or other flavored beverage.
  • the beverage compositions can be in liquid or powdered form.
  • the beverage compositions can be in ready to drink or "concentrated” 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 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 beverage such as a cola or root beer 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 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 including sweets such as hard or soft candies
  • 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.
  • 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.
  • 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 flavor of the composition.
  • the flavor can be made available as the product is consumed or be released into the matrix material as the composition is further processed.
  • 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 indh ⁇ dually 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 flavorless gum base can be combined with a compound or a mixture of compounds of the invention to a desired flavor concentration.
  • a blade mixer is heated to about 110 0 F, 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, 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.
  • 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.
  • all or a portion of those derivatives that include an aldehyde group can be modified to include an acetal group, which can cause the formulations to release fragrance over a period of time as the acetal hydrolyzes to form the aldehyde compound.
  • the crude product was purified by column chromatography on silica gel eluting the ethyl acetate/hexane (2 % / 98 %) to give a mixture of the desired product and impurities. This mixture was distilled under pressure (25 mbar) and the impurities were removed at 198 0 C. to afford safrane.
  • This compound was prepared by adding 3,4-(methylenedioxy)phenylmagnesium bromide (47 cm 3 , 0.047 mol, see Example 1 for its preparation) to a stirring solution of 2-chloroethyl thiocyanate (5.0 g, 0.041 mol) in anhydrous THF (40 cm3) over 10 mins while keeping the reaction temperature below 40 0 C. The solution was stirred for a further 15 mins, then potassium t-butoxide (9.2 g, 0.082 mol) in THF (20 cm 3 ) was added in one-shot while the reaction temperature was kept below 55°C with occasional cooling. The reaction mixture was stirred for a further 20 mins. The reaction was quenched with ammonium chloride (sat.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Nutrition Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Fats And Perfumes (AREA)
  • Confectionery (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Cosmetics (AREA)

Abstract

La présente invention concerne un composé ou un mélange de composés répondant à la formule (I) : dans laquelle R représente un groupe alkyle en C<SUB>1</SUB> à C<SUB>3</SUB> à chaîne linaire ou ramifiée ou un groupe alcényle. La présente invention concerne également leurs procédés de préparation, leur utilisation en tant que matériaux de parfum pour une application à une variété de substrats et leur utilisation dans la parfumerie et dans des articles de fabrication.
PCT/GB2007/002707 2006-07-17 2007-07-17 Remplacements de safrole Ceased WO2008009926A2 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US83123006P 2006-07-17 2006-07-17
US60/831,230 2006-07-17
US82825406P 2006-10-05 2006-10-05
US60/828,254 2006-10-05

Publications (2)

Publication Number Publication Date
WO2008009926A2 true WO2008009926A2 (fr) 2008-01-24
WO2008009926A3 WO2008009926A3 (fr) 2008-10-09

Family

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PCT/GB2007/002707 Ceased WO2008009926A2 (fr) 2006-07-17 2007-07-17 Remplacements de safrole

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8514616B2 (en) 2009-02-17 2013-08-20 Nec Corporation Magnetic memory element and magnetic memory

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB841921A (en) * 1958-02-11 1960-07-20 Polak & Schwarz Internationaal 2-piperonyl-propanal, a new perfume, and process for making same
JPS549271A (en) * 1977-06-22 1979-01-24 Mitsubishi Chem Ind Ltd 3',4'-methylenedioxyphenylbutanal
JP2521739B2 (ja) * 1987-01-27 1996-08-07 新日本薬品株式会社 肝臓疾患治療剤

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8514616B2 (en) 2009-02-17 2013-08-20 Nec Corporation Magnetic memory element and magnetic memory

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Publication number Publication date
WO2008009926A3 (fr) 2008-10-09

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