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WO2024261201A1 - Nouveaux composés - Google Patents

Nouveaux composés Download PDF

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Publication number
WO2024261201A1
WO2024261201A1 PCT/EP2024/067363 EP2024067363W WO2024261201A1 WO 2024261201 A1 WO2024261201 A1 WO 2024261201A1 EP 2024067363 W EP2024067363 W EP 2024067363W WO 2024261201 A1 WO2024261201 A1 WO 2024261201A1
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Prior art keywords
group
methyl
equiv
mmol
methylcyclohex
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English (en)
Inventor
Marc LINIGER
Andreas Goeke
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Givaudan SA
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Givaudan SA
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/50—Perfumes
    • C11D3/502—Protected perfumes
    • C11D3/507—Compounds releasing perfumes by thermal or chemical activation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C323/24—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/25—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/52—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/60—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
    • C07D307/64—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B9/00—Essential oils; Perfumes
    • C11B9/0007—Aliphatic compounds
    • C11B9/0011—Aliphatic compounds containing S
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated

Definitions

  • the present invention relates to compounds of formula I and their uses as precursors in the generation of fragrant thiols.
  • Thiol compounds are some of the strongest odourants used in perfume. The perception of their odour, of course, will depend upon their concentration, purity and in some cases, isomeric purity. However, generally speaking, when they are used in even in low amounts, they have the ability to greatly influence the overall olfactory impression of perfume compositions. They also tend to be rather labile compounds and degrade rapidly. For these reasons, although they can be very rewarding compounds to work with in the art of composing perfumes, they can also be difficult to dose correctly.
  • the compounds described in US 2010/0310479 are an example of thiols that are useful in perfumery, but which are unstable and decompose over time in, for example, liquid detergents.
  • WO 2003/049666 describes p-thiocarbonyl precursor compounds which are capable of liberating fragrance molecules.
  • the released fragrance molecules are not a fragrant thiols.
  • Other B-thiocarbonyl compounds and their use in perfumery applications are described in the prior art in WO 2021/123144, WO 2021/122997, WO 2015/032885, WO 2001/035768, Cerny et al. (Food Chemistry 141 (2013) 1078-1086), Starkenmann et al. (J. Agric. Food Che. 56 (2008) 9575-9580), Begnaud et al. (Flavour Fragr. J. 31 (2016) 235-240), Starkenmann et al. (Flavour Fragr. J. 23 (2008) 369-381).
  • n is 0 or 1;
  • R 2a is selected from the group consisting of hydrogen, C1-4 alkyl group, -N(R 6a )R 6b , -N(R 7a )C(O)R 7b , and -N(R 8a )C(O)OR 8b ;
  • R 2b is selected from the group consisting of hydrogen and a C1-4 alkyl group
  • R 3 is selected from the group consisting of -O- and -N(R 9 )-;
  • R 4 is selected from the group consisting of hydrogen, a Ci-is alkyl group, a Ci-is alkenyl group, and an aryl group, which Ci-is alkyl, Ci-is alkenyl and aryl groups is optionally substituted by one or more -OH or phenyl groups;
  • R 5 is selected from the group consisting of hydrogen, a C1-4 alkyl group and -C(O)R 10 ;
  • R 6a , R 6b , R 7a , R 7b , R 8a , R 8b and R 9 are each independently selected from the group consisting of hydrogen and a C1-4 alkyl group, which C1-4 alkyl group is optionally substituted by one or more phenyl group; and
  • R 10 is a C1-4 alkyl group; or a salt or solvate thereof; provided that:
  • R 1 when R 1 is an unsubstituted Ci-is alkyl or a Ci-is alkenyl group or a Ci-is alkyl or a
  • Ci-is alkenyl group substituted by one or more 0, -OR 5 or groups and R 2a is -NH2 or -NHC(O)CHs and R 2b is hydrogen, then R 4 is not hydrogen; and
  • Salts of the compound of formula I may be prepared in accordance with techniques that are well known to those skilled in the art.
  • the compound of formula I may be reacted with the appropriate organic acid or mineral acid.
  • Salt switching techniques may also be used to convert one salt into another salt.
  • salts include acid addition salts, for example, salts formed with inorganic acids such as hydrochloric, hydrobromic, sulfuric and phosphoric acid, with carboxylic acids or with organo-sulfonic acids; base addition salts; metal salts formed with bases, for example, the sodium and potassium salts.
  • the compounds disclosed herein may exist in unsolvated as well as solvated forms with solvents such as water, and it is intended that the invention embraces both solvated and unsolvated forms of the compounds of the invention.
  • solvate refers to a complex of variable stoichiometry formed by a solute and solvent. Such solvents for the purpose of the invention may not interfere with the activity of the solute. Examples of suitable solvents include, but are not limited to, water, methanol, ethanol, and acetic acid. Solvates in which water is the solvent molecule are typically referred to as hydrates. Hydrates include compositions containing stoichiometric amounts of water, as well as compositions containing variable amounts of water.
  • alkyl groups defined herein may be straight-chain or, when there is a sufficient number (e.g. a minimum of three) of carbon atoms, be branched- chain.
  • Alkyl groups that may be mentioned include methyl, ethyl, propyl, iso-propyl, butyl, tert-butyl, methylbutyl, pentyl, methylpentyl, hexyl, methylhexyl, ethylhexyl, heptyl, methylheptyl, octyl, methyloctyl, decyl, octadecyl groups.
  • an alkyl chain may be cyclic, (e.g. monocyclic or bicyclic) and so form a cycloalkyl group.
  • Such cycloalkyl groups may be bridged (so forming, for example, fused ring systems such as three fused cycloalkyl groups).
  • the points of attachment of cycloalkyl groups may be via any atom in the ring system.
  • such cycloalkyl groups may also be part cyclic, e.g.
  • alkylene-cycloalkyl group for example, -CH2-C3H5
  • the points of attachment of cycloalkyl groups may be via any atom in the ring system.
  • Cycloalkyl groups that may be mentioned include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclo[2.2. l]heptyl, and cyclooctyl groups.
  • Heterocycloalkyl groups that may be mentioned include non-aromatic monocyclic heterocycloalkyl groups in which at least one (e.g. one to four) of the atoms in the ring system is other than carbon (i.e. a heteroatom, e.g. sulphur, oxygen or, particularly, nitrogen), and in which the total number of atoms in the ring system is from four to six.
  • the point(s) of attachment of heterocycloalkyl groups may be via any atom in the ring system including (where appropriate) a heteroatom (such as a nitrogen atom), or an atom on any fused carbocyclic ring that may be present as part of the ring system.
  • substituents include those defined herein.
  • Alkenyl groups are unsaturated alkyl groups (i.e. having at least one carbon-carbon double bond). Unless otherwise specified, alkenyl groups defined herein may be straight-chain or, when there is a sufficient number (i.e. a minimum of two or three, as appropriate) of carbon atoms, be branched-chain. Alkenyl groups that may be used include ethenyl, propenyl, butenyl, pentenyl, pentadienyl, hexenyl, and hexadienyl groups.
  • an alkenyl chain may be cyclic, (e.g. monocyclic or bicyclic) and so form a cycloalkenyl group.
  • Such cycloalkenyl groups may be bridged (so forming, for example, fused ring systems such as three fused cycloalkenyl groups).
  • the points of attachment of cycloalkenyl groups may be via any atom in the ring system.
  • Cycloalkenyl groups that may be mentioned include cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl and cyclohexadienyl groups.
  • Aryl groups that may be mentioned include Ce-io aryl groups. Such groups may be monocyclic or bicyclic and have between 6 and 10 ring carbon atoms, in which at least one ring is aromatic. Ce-io aryl groups include phenyl, naphthyl and the like. The points of attachment of aryl groups may be via any atom of the ring system. However, when aryl groups are bicyclic, they are linked to the rest of the molecule via an aromatic ring.
  • heteroaryl when used herein refers to an aromatic group containing one or more heteroatom(s) (e.g. one to four heteroatoms) preferably selected from N, O and S. Heteroaryl groups include those which have from 5 to 6 members. The points of attachment of heteroaryl groups may be via any atom in the ring system including (where appropriate) a heteroatom (such as a nitrogen atom). Substituents on heteroaryl groups may, where appropriate, be located on any atom in the ring system including a heteroatom. For the avoidance of doubt, optional substituents include those defined herein. Particular heteroaryl groups that may be mentioned include furanyl groups.
  • Compounds of formula I may contain double bonds and may thus exist as E (entadel and Z (zusammen) geometric isomers about each individual double bond. All such isomers and mixtures thereof are included within the scope of the invention.
  • Compounds of the invention may also contain one or more asymmetric atoms (e.g. asymmetric carbon atoms) and may therefore exhibit optical isomerism and/or diastereoisomerism.
  • Diastereoisomers may be separated using conventional techniques, e.g. chromatography or fractional crystallisation.
  • the various stereoisomers may be isolated by separation of a racemic or other mixture of the compounds using conventional, e.g. fractional crystallisation or HPLC, techniques.
  • the desired optical isomers may be made by reaction of the appropriate optically active starting materials under conditions which will not cause racemisation or epimerisation (i.e.
  • a 'chiral pool' method by reaction of the appropriate starting material with a 'chiral auxiliary' which can subsequently be removed at a suitable stage, by derivatisation (i.e. a resolution, including a dynamic resolution), for example with a homochiral acid followed by separation of the diastereomeric derivatives by conventional means such as chromatography, or by reaction with an appropriate chiral reagent or chiral catalyst all under conditions known to the skilled person.
  • derivatisation i.e. a resolution, including a dynamic resolution
  • a homochiral acid followed by separation of the diastereomeric derivatives by conventional means such as chromatography
  • reaction with an appropriate chiral reagent or chiral catalyst all under conditions known to the skilled person.
  • All stereoisomers including but not limited to diastereoisomers, enantiomers and atropisomers
  • mixtures thereof e.g. racemic mixtures
  • stereochemistry of any particular chiral atom is not specified, then all stereoisomers are contemplated and included as the compounds of the invention. Where stereochemistry is specified by a solid wedge or dashed line representing a particular configuration, then that stereoisomer is so specified and defined.
  • R 1 is selected from the group consisting of a Ci-is (e.g. Ci e) alkyl group, a C3-8 cycloalkyl group, a C3-6 cycloalkenyl group, and a 5- to 6-membered heteroaryl group, wherein Ci-is alkyl, C3-8 cycloalkyl, C3-6 cycloalkenyl group, and heteroaryl groups are as defined herein.
  • Ci-is e.g. C1-6, such as C1-3
  • R 5 is as defined herein.
  • R 5 is selected from the group consisting of hydrogen, a methyl group, and -C(O)CH3.
  • R 1 is selected from the group consisting of 2-methylfuran-3- yl, furan-2-ylmethyl, 1-phenylethyl, l-hydroxyhexan-3-yl, l-acetoxyhexan-3-yl, benzyl, phenethyl, 6-isopropyl-3-methylcyclohex-2-en-l-yl, 5-methyl-2-(propan-2- ylidene)cyclohexyl, l-isopropyl-4-methylcyclo-hex-3-en-l-yl, 2-(4-methylcyclohex-3-en- 1-y I) propan -2-yl, 4-isopropyl-l-methylcyclohex-2-en-l-yl, 4-isopropyl-l- methylcyclohex-3-en-l-yl, l-methyl-4-(propan-2-ylidene)cyclohexyl, 3-isopropyl-6- methylcyclo
  • R 1 is selected from the group consisting of 2-methylfuran-3-yl, furan-2-ylmethyl, 1-phenylethyl, l-hydroxyhexan-3-yl, l-acetoxyhexan-3-yl, 2-(4- methylcyclohex-3-en-l-yl)propan-2-yl, 3-isopropyl-6-methylcyclohex-2-en-l-yl, 1- hydroxy-2-methylpentan-2-yl, l-methoxy-3-methylbutan-3-yl, 2-methoxy-4- methylpentan-4-yl, 4-methylpentan-2-ol-4-yl, l-methoxyhexan-3-yl and 2- methylpentan-4-on-2-yl.
  • R 1 is selected from the group consisting of:
  • R 1 is selected form the group consisting of
  • R 2a is -NH2 and R 2b is hydrogen.
  • R 3 is -N(R 9 )-, wherein R 9 is as defined herein (e.g. hydrogen).
  • R 4 is selected from the group consisting of hydrogen, methyl, ethyl, butyl (e.g. n-butyl), hexyl (e.g. n-hexyl), benzyl, 1-phenylethyl, ethylhexyl, octyl (e.g. iso-octyl), octadecyl, 2-phenylethyl, hydroxyethyl, hydroxybutyl, and hydroxydecyl groups.
  • R 4 is a C1-8 alkyl group (e.g. methyl, ethyl, or butyl) group.
  • R 2b is selected from the group consisting of hydrogen and a C1-4 alkyl group
  • n 1
  • R x -X V wherein n, R 1 , R 2a , R 2b R 3 , and R 4 are as defined above and X is a suitable leaving group (such as a chlorine atom, a bromide atom or a tosyl group), in the presence of, as appropriate, a suitable base (e.g. potassium carbonate and/or potassium iodide) and/or a suitable solvent (e.g. toluene or acetone) according to procedures know to the person skilled in the art.
  • a suitable base e.g. potassium carbonate and/or potassium iodide
  • solvent e.g. toluene or acetone
  • the skilled person would expect that in the synthesis of a precursor adapted to release a fragrant thiol, the fragrant thiol would be employed as a reagent to both introduce the sulphur atom and form the cleavable carbon-sulphur bond in the formed precursor. This is expected, not least, because it is the most labile bond.
  • this approach would carry with it the disadvantage in the sense that a reagent in the formation of the precursor would be the highly potent fragrant thiol.
  • Using such reagents having such potent odours is not efficient in that the reaction vessel in its manufacture will need to be scrupulously cleaned before it can be used for other purposes, in a time-consuming and costly process.
  • a perfume composition comprising the compound of formula I as defined in the first aspect of the invention. All embodiments and particular features thereof described herein in respect of the first aspect of the invention are disclosed herein in respect of the third aspect of the invention.
  • perfume compositions in accordance with the third aspect of the invention may be prepared in accordance with standard and/or accepted manufacturing practice.
  • a fragrance composition contains perfume ingredients independently selected from at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine or at least ten ingredients from one or more of the aforementioned categories of ingredients.
  • musky or woody complementary perfume ingredients include but are not limited to l,4-dioxacyclohexadecane-5, 16-dione, 4-tert-butylcyclohexyl acetate, [3R- (3a,3ap,6a,7p,8aa)]-octahydro-6-methoxy-3,6,8,8-tetramethyl-lH-3a,7- metha noazulene, l-(2,3,8,8-Tetramethyl-l,2,3,4,5,6,7,8-octahydronaphthalen-2- yl)ethanone and 3-Methyl-5-(2,2,3-trimethylcyclopent-3-en-l-yl)pentan-2-ol.
  • ingredients that can be used to complement the compounds of the present invention in flavour or perfumery applications include but are not limited to (E)-3,7-dimethylocta- 2,6-dienal (e.g. CITRAL); l-methyl-4-prop-l-en-2-yl-cyclohexene (e.g. LIMONENE); 3,7- dimethyloct-6-enal (e.g. CITRONELLAL); (2E,6Z)-3,7-dimethylnona-2,6-dienenitrile (e.g. LEMONILE); l-methyl-4-propan-2-ylcyclohexa-l,4-diene (e.g.
  • E -3,7-dimethylocta- 2,6-dienal
  • l-methyl-4-prop-l-en-2-yl-cyclohexene e.g. LIMONENE
  • 3,7- dimethyloct-6-enal e.g. CITRONELLAL
  • HEXENYL-3-CIS TIGLATE 2,4,6-trimethylcyclohex-3-enecarbaldehyde (e.g. ISOCYCLOCITRAL); (Z)-l- (l-ethoxyethoxy)hex-3-ene (e.g. LEAF ACETAL); methyl non-2-ynoate (e.g. METHYL OCTYNE CARBONATE); (E)-methyl non-2-enoate (e.g. NEOFOLIONE); (2E,6Z)-nona-2,6- dienal (e.g. NONADIENAL); (2Z,6E)-2,6-nonadien-l-ol (e.g.
  • BENZYL CINNAMATE BENZYL CINNAMATE
  • butyl acetate 2-methylpropyl acetate
  • 2- cyclohexylethyl acetate (E)- 1-(2, 6, 6-tri methylcyclohexa- 1, 3-d ien-l-y I) but-2-en- 1-one (e.g. DAMASCENONE);
  • E)-l-(2,6,6-trimethylcyclohex-2-en-l-yl)but-2-en-l-one e.g. DAMASCONE ALPHA
  • E)-l-(2,6,6-trimethyl-l-cyclohexenyl)but-2-en-l-one e.g.
  • DAMASCONE BETA l-(2,6,6-trimethyl-l-cyclohex-3-enyl)but-2-en-l-one
  • DAMASCONE DELTA 6-pentyltetrahydro-2H-pyran-2-one
  • DECALACTONE DELTA 6-pentyltetrahydro-2H-pyran-2-one
  • 5-hexyloxolan-2-one e.g. DECALACTONE GAMMA
  • 2-methyl-l-phenylpropan-2-yl butanoate e.g. DIMETHYL BENZYL CARBINYL BUTYRATE
  • 6-heptyltetrahydro-2H-pyran- 2-one e.g.
  • DODECALACTONE DELTA 5-octyloxolan-2-one (e.g. DODECALACTONE GAMMA); ethyl acetate; ethyl 3-oxobutanoate (e.g. ETHYL ACETOACETATE); ethyl butanoate (e.g. ETHYL BUTYRATE); ethyl 3-phenylprop-2-enoate (e.g. ETHYL CINNAMATE); ethyl hexanoate (e.g. ETHYL HEXANOATE); ethyl 2-methylpropanoate (e.g. ETHYL ISOBUTYRATE); ethyl 3-methylbutanoate (e.g.
  • ETHYL ISOVALERATE ethyl 2- methylbutanoate (e.g. ETHYL METHYL-2-BUTYRATE); ethyl octanoate (e.g. ETHYL OCTANOATE); ethyl heptanoate (e.g. ETHYL OENANTHATE); ethyl propionate; ethyl 2-(2- methyl-l,3-dioxolan-2-yl)acetate (e.g. FRUCTONE); (Z)-hex-3-en-l-yl acetate (e.g.
  • HEXENYL-3-CIS ACETATE (Z)-hex-3-en-l-yl 2-methyl butanoate (e.g. HEXENYL-3-CIS METHYL-2- BUTYRATE); hexyl acetate; hexyl butanoate (e.g. HEXYL BUTYRATE); hexyl 2- methylpropanoate (e.g. HEXYL ISOBUTYRATE); hexyl propionate; 3-methylbutyl acetate (e.g. ISOAMYL ACETATE); 3-methylbutyl butanoate (e.g. ISOAMYL BUTYRATE); 3- methylbutyl propanoate (e.g.
  • ISOAMYL PROPIONATE 2-methylpropyl benzoate (e.g. ISOBUTYL BENZOATE); 3-methylbutyl 3-methylbutanoate (e.g. ISOPENTYL ISOVALERATE); isopropyl 2-methylbutanoate (e.g. ISOPROPYL METHYL-2-BUTYRATE); (Z)-hex-3-en-l-yl methyl carbonate (e.g. LIFFAROME); 2-methyl-4-oxo-4H-pyran-3-yl 2- methylpropanoate (e.g. MALTYL ISOBUTYRATE); ethyl 2-methylpentanoate (e.g. MANZANATE); heptan-2-one (e.g.
  • METHYL AMYL KETONE butyl 2-methylpentanoate (e.g. METHYL CAMOMILLE); methyl 3-phenylprop-2-enoate (e.g. METHYL CINNAMATE); 5-hexyl-5-methyloxolan-2-one (e.g. METHYL DECALACTONE GAMMA); 6-methylhept-5- en-2-one (e.g. METHYL HEPTENONE PURE); methyl 2-methylbutanoate (e.g. METHYL METHYL- 2 BUTYRATE); (E)-2-methylpent-2-enoic acid (e.g.
  • POMAROSE 3- methylbut-2-en-l-yl acetate (e.g. PRENYL ACETATE); 4-(4-hydroxyphenyl)butan-2-one (e.g. RASPBERRY KETONE); (4aR,8aS,E)-6-ethylideneoctahydro-2H-5,8- methanochromene (e.g. RHUBOFLOR); 1,1-diethoxycyclohexane (e.g. RUM ACETAL); 6- hexyltetrahydro-2H-pyran-2-one (e.g. UNDECALACTONE DELTA); and mixtures thereof.
  • PRENYL ACETATE 4-(4-hydroxyphenyl)butan-2-one
  • (4aR,8aS,E)-6-ethylideneoctahydro-2H-5,8- methanochromene e.g. RHUBOFLOR
  • 1,1-diethoxycyclohexane e.
  • the perfume compositions according to the invention are useful as such in fine perfumery, or can be used to fragrance all manner of consumer products, such as household care, personal care, laundry care and cosmetic products.
  • consumer products such as household care, personal care, laundry care and cosmetic products.
  • examples of such products include cosmetics, shampoos, shower gels, deodorants, antiperspirants, laundry detergents (in solid or liquid forms), rinse conditioners, fabric softeners, detergents for dishwashers, surface cleaners, in particular for hard and soft surfaces, soaps, especially bar soap, and air care products, especially air freshener or fine fragrances.
  • the compounds of the invention may be formulated at various concentrations, depending upon the particular hedonic effect the perfumer or flavourist would like to create.
  • the amount of the compound of the invention present in a perfume or flavour composition is from about 0.0001 to about 10 weight (wt.) %, preferably from about 0.001 to about 1 wt.%, and even more preferably from about 0.001 to about 0.5 wt.% of total weight of the perfume or flavour composition.
  • Perfume or flavour compositions may be incorporated into consumer products in typical dilutions, for example from about 0.5 to about 10 wt.% based on the weight of the consumer product.
  • the compounds of the invention are useful as precursors for the generation of fragrance molecules in consumer product, such as personal, laundry, or household care products.
  • Compounds of the invention are useful because they are capable of degrading under ambient conditions, e.g. of moisture and/or temperature and exposure to oxygen, to release highly potent fragrance molecules, particularly thiols, may give off a pleasant aroma (e.g. citrus fruits, cassis, coffee aromas). This is desirable in certain consumer (e.g. cosmetics, cleaning such as but not limited to house cleaning, leave on and rinse-off applications, air-care such as but not limited to air freshener, and laundry) applications. Another possible application area is for fine fragrances.
  • the fragrance molecules are unstable and decompose over time in, e.g. liquid detergents, and cannot be overdosed due to their potency, as this may be unpleasant for a consumer.
  • the compounds of the inventions, and compositions and consumer products comprising said compounds provide a 'reservoir' for slow release of such highly fragrance molecules, particularly thiols, over time.
  • a compound of formula II wherein : n is 0 or 1;
  • R 22a is selected from the group consisting of hydrogen, C1-4 alkyl group, -N(R 26a )R 26b , -N(R 27a )C(O)R 27b , and -N(R 28a )C(O)OR 28b ;
  • R 22b is selected from the group consisting of hydrogen and a C1-4 alkyl group
  • R 22a is selected from the group consisting of hydrogen, methyl, -NH2, -NH(O)CH3, -NHC(O)C(CH 3 ) 3 , and -NHCOOCH 2 Ph;
  • R 25 is selected from the group consisting of hydrogen, a methyl group, and -C(O)CH3.
  • the compounds of the invention are therefore particularly useful as they may deliver the olfactive impression of fragrant thiols to any composition or consumer product in which they are employed, whilst avoiding any stability and overdosing issues which are associated with the direct inclusion of the thiols fragrant into said compositions and consumer products. Moreover, the compounds of the invention ensure that the olfactive signal of a fragrant thiol is unencumbered or attenuated by the release of a fragrant (or odorous) counterpart, which may create formulation complexities for the skilled perfumer/flavourist when designing and preparing desirable consumer products.
  • fragrance precursors e.g. compounds of the invention
  • use of compounds of the present invention commonly takes place under ambient air at a temperature of from about -20 °C to about 100 °C, preferably from about -10 °C to about 60 °C, even more preferably from about 0 °C to about 40 °C, in particular at room temperature (about 25 °C).
  • Doublet dd Doublet of doublets ddd: Doublet of doublets of doublets dddd: Doublet of doublets of doublets of doublets dq: Doublet of quartets dt: Doublet of triplets
  • NMR Nuclear magnetic resonance q: quartet sat: Saturated s: Singlet t: Triplet td: Triplet of doublets tdd : Triplet of doublets of doublets
  • GC-MS parameters Column properties: Trajan (SGE) Capillary GC Column BPX5, 0.22 mm ID x 0.25 pm film thickness x 12 m length, 5% phenyl-95% methylpolysiloxane; Carrier gas: Helium at 1 ml/min constant flow; Temperature program : starting at 50 °C, hold for 2 min, then with 20 °C/min to 240 °C, 35 °C/min to 300 °C, hold for 3 min; Injector temperature: 230 °C; Injector method : split (1:50) injection of 1 pL; Detector: Quadrupole Mass Spectrometer (MS), mass range used m/z 25-450.
  • SGE Trajan
  • SGE Capillary GC Column BPX5, 0.22 mm ID x 0.25 pm film thickness x 12 m length, 5% phenyl-95% methylpolysiloxane
  • Carrier gas Helium at 1 ml/min constant
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : green, salty, roasted.
  • Odour description (1% solution in EtOH on paper blotter, 24 h): green, sulfurous, vegetable, onion, boiled vegetable.
  • Odour description (1% solution in EtOH on paper blotter, 24 h): green, sulfurous, cassis, watermelon, eucalyptus bud, sweaty, neocaspirene, cassyrane.
  • Example 5 isooctyl 3-((l-hvdroxyhexan-3-yl)thio)propanoate (mixture of isooctyl ester isomers)
  • the compound was obtained from isooctyl 3-mercaptopropanoate (8.90 g, 40.8 mmol, 1.0 equiv, CAS 30374-01-7), DBU (4.51 g, 32.6 mmol, 0.8 equiv) and hex-2-enal (4.0 g, 40.8 mmol, 1.0 equiv) followed by treatment of the intermediate with NaBH4 (0.96 g, 25.3 mmol, 0.8 equiv) according to the procedure of example 3 as a colourless oil (6.97 g, 69% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h): green, sulfurous, vegetable, onion, gassy.
  • the compound was obtained from 6-methylheptyl 3-((l-hydroxyhexan-3- yl)thio)propanoate (6.0 g, 18.8 mmol, 1.0 equiv), pyridine (2.7 mL, 33.9 mmol, 1.8 equiv) and acetyl chloride (2.19 g, 28.3 mmol, 1.5 equiv) according to the procedure of example 4 to give a colourless oil (2.93 g, 43% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h): green, sulfurous, cassis, watermelon, eucalyptus bud, sweaty, neocaspirene, cassyrane, straw, leaf.
  • the compound was obtained from methyl 3-mercaptopropanoate (2.54 g, 21.1 mmol, 1.0 equiv), DBU (2.34 g, 16.9 mmol, 0.8 equiv) and hex-2-enal (2.08 g, 21.1 mmol, 1.0 equiv) followed by treatment of the intermediate with NaBH4 (0.59 g, 15.6 mmol, 0.8 equiv) according to the procedure of example 3 as a colourless oil (1.94 g, 45% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : cassis, sulfurous, onion, leek.
  • the compound was obtained from methyl 3-((l-hydroxyhexan-3-yl)thio)propanoate (1.08 g, 4.90 mmol, 1.0 equiv), pyridine (0.71 mL, 8.82 mmol, 1.8 equiv) and acetyl chloride (0.52 mL, 7.35 mmol, 1.5 equiv) according to the procedure of example 4 to give a colourless oil (0.53 g, 37% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : green sulphurous, cassis, sweaty.
  • the compound was obtained from furan-2-ylmethanethiol (2.0 g, 17.5 mmol, 1.0 equiv), methyl acrylate (1.51 g, 17.5 mmol, 1.0 equiv) and DBU (2.42 g, 17.5 mmol, 1.0 equiv) according to the procedure of example 3 to give an orange oil (2.79 g, 80% yield).
  • the compound was obtained from furan-2-ylmethanethiol (1.0 g, 8.76 mmol, 1.0 equiv), ethyl acrylate (0.97 g, 9.64 mmol, 1.1 equiv) and DBU (1.21 g, 8.76 mmol, 1.0 equiv) according to the procedure of example 3 to give a pink oil (1.84 g, 98% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : sulphurous, green, rubbery, burnt, coffee.
  • the compound was obtained from furan-2-ylmethanethiol (1.0 g, 8.76 mmol, 1.0 equiv), butyl acrylate (1.24 g, 9.64 mmol, 1.1 equiv) and DBU (1.21 g, 8.76 mmol, 1.0 equiv) according to the procedure of example 3 to give a pink oil (2.02 g, 95% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : sulphurous, green, rubbery, burnt, coffee, slightly fruity.
  • the compound was obtained from 2-methylfuran-3-thiol (1.0 g, 8.76 mmol, 1.0 equiv), ethyl acrylate (0.97 g, 9.64 mmol, 1.1 equiv) and DBU (1.21 g, 8.76 mmol, 1.0 equiv) according to the procedure of example 3 to give a yellow oil (1.26 g, 66% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : sulfurous, green, broth, gaiac wood, roasted chicken, milky, warm milk, sulfurol.
  • the compound was obtained from 2-methylfuran-3-thiol (1.97 g, 17.2 mmol, 1.0 equiv), 2-hydroxyethyl acrylate (2.00 g, 17.2 mmol, 1.0 equiv) and DBU (2.62 g, 17.2 mmol, 1.0 equiv) according to the procedure of example 3 to give a yellow oil (1.20 g, 30% yield).
  • Odour description 1% solution in EtOH on paper blotter, 24 h: sulphurous, burnt, foodlike, saussage, warm milk, sulfurol.
  • the compound was obtained from furan-2-ylmethanol (5.0 g, 51 mmol, 1.05 equiv), 3- mercaptopropanoic acid (5.2 g, 49 mmol, 1.0 equiv) and p-toluenesulfonic acid monohydrate (0.46 g, 5 mol%) according to the procedure of example 1 to give a yellow oil (3.3 g, 27% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : strong, anjeruk, salty, burnt, green, rubbery, mandarin peel.
  • the compound was obtained from (l-bromoethyl)benzene (11.5 g, 62.2 mmol, 1.0 equiv), butyl 3-mercaptopropanoate (10.1 g, 62.2 mmol, 1.0 equiv), K2CO3 (17.2 g, 124 mmol, 2.0 equiv) and KI (1.03 g, 10 mol%) according to the procedure of example 2 to afford a yellow oil (12.7 g, 76% yield).
  • the compound was ebtained from (l-bromeethyl)benzene (1.30 g, 7.00 mmol, 1.0 equiv), 3-mercaptepropaneic acid (0.74 g, 7.00 mmcl, 1.0 equiv), K2CO3 (1.93 g, 14.0 mmcl, 2.0 equiv) and KI (0.12 g, 10 mol%) according to the procedure of example 2 to afford a yellow oil (0.45 g, 20% yield, mixture of diastereoisomers).
  • Odour description (1% solution in EtOH on paper blotter, 24 h): sulphurous, burnt, rubbery, mandarin peel.
  • the compound was obtained from (l-bromoethyl)benzene (1.30 g, 7.00 mmol, 1.0 equiv), methyl 2-mercaptoacetate (0.74 g, 7.00 mmol, 1.0 equiv), K2CO3 (1.93 g, 14.0 mmol, 2.0 equiv) and KI (0.12 g, 10 mol%) according to the procedure of example 2 to afford a yellow oil (1.04 g, 71% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h): sulphurous, burnt, rubbery, mandarin peel.
  • the compound was obtained from (l-bromoethyl)benzene (2.00 g, 10.8 mmol, 1.0 equiv), 2-ethylhexyl 3-mercaptopropanoate (2.36 g, 10.8 mmol, 1.0 equiv), K2CO3 (2.99 g, 21.6 mmol, 2.0 equiv) and KI (0.18 g, 10 mol%) according to the procedure of example 2 to afford a yellow oil (3.0 g, 86% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h): sulphurous, burnt, rubbery, mandarin peel.
  • the compound was obtained from (l-bromoethyl)benzene (2.00 g, 10.8 mmol, 1.0 equiv), octadecyl 3-mercaptopropanoate (3.88 g, 10.8 mmol, 1.0 equiv), K2CO3 (2.99 g, 21.6 mmol, 2.0 equiv) and KI (0.18 g, 10 mol%) according to the procedure of example 2 to afford a yellow oil (2.8 g, 56% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h): sulphurous, burnt, rubbery, mandarin peel.
  • Example 22 isooctyl 3-((l-phenylethyl)thio)propanoate (mixture of isooctyl ester isomers)
  • the compound was obtained from (l-bromoethyl)benzene (2.00 g, 10.8 mmol, 1.0 equiv), isooctyl 3-mercaptopropanoate (3.88 g, 10.8 mmol, 1.0 equiv, CAS 30374-01- 7), K2CO3 (2.99 g, 21.6 mmol, 2.0 equiv) and KI (0.18 g, 10 mol%) according to the procedure of example 2 to afford a yellow oil (2.7 g, 77% yield).
  • the compound was obtained from (l-bromoethyl)benzene (1.4 g, 7.6 mmol, 1.0 equiv), N-ethyl-3-mercaptopropanamide (1.0 g, 7.6 mmol, 1.0 equiv), K2CO3 (2.1 g, 15 mmol, 2.0 equiv) and KI (0.13 g, 10 mol%) according to the procedure of example 2 to afford a yellow oil (1.0 g, 56% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h): sulphurous, burnt, rubbery, mandarin peel.
  • Methyl 3-mercaptopropanoate (5.0 g, 42 mmol, 1.0 equiv) and butan-l-amine (5.8 g, 75 mmol, 1.8 equiv) were stirred at room temperature over night.
  • the reaction mixture was poured on water, diluted with MTBE and the layers were separated.
  • the organic layer was washed with water, 2M aq. HCI, brine, dried over MgSO4 and filtered.
  • the solvent was removed under reduced pressure to give crude N-butyl-3-mercaptopropanamide (4.8 g, 71%), which was used without further purification.
  • the compound was obtained from (l-bromoethyl)benzene (1.4 g, 7.6 mmol, 1.0 equiv), N-butyl-3-mercaptopropanamide (1.2 g, 7.6 mmol, 1.0 equiv), K2CO3 (2.1 g, 15 mmol, 2.0 equiv) and KI (0.13 g, 10 mol%) according to the procedure of example 2 to afford a colorless oil (1.3 g, 65% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h): sulphurous, burnt, anjeruk, mandarine.
  • the compound was obtained from (l-bromoethyl)benzene (1.4 g, 7.6 mmol, 1.0 equiv), 3-mercapto-N-methylpropanamide (0.9 g, 7.6 mmol, 1.0 equiv), K2CO3 (2.1 g, 15 mmol, 2.0 equiv) and KI (0.13 g, 10 mol%) according to the procedure of example 2 to afford a colorless oil (0.47 g, 28% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h): green, burnt, burnt mandarin peel, anjeruk.
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : green, burnt, burnt mandarin peel, anjeruk.
  • the compound was obtained from (l-bromoethyl)benzene (1.4 g, 7.6 mmol, 1.0 equiv), methyl 2-mercaptopropanoate (0.91 g, 7.6 mmol, 1.0 equiv), K2CO3 (2.1 g, 15 mmol, 2.0 equiv) and KI (0.13 g, 10 mol%) according to the procedure of example 2 to afford a colorless oil (0.95 g, 76% yield, 1 : 1 mixture of diastereoisomers).
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : green, burnt, burnt mandarin peel, anjeruk, soft floral, rosy, creamy, heavy, fatty, acetophenone.
  • the compound was obtained from ethyl 3-mercaptopropanoate (1.00 g, 7.45 mmol, 1.0 equiv), (chloromethyl)benzene (1.04 g, 8.20 mmol, 1.1 equiv) and 7M NH3 in methanol (5.3 mL, 37.3 mmol, 5 equiv) according to the procedure of example 16 to give a colorless oil (1.22 g, 73% yield).
  • the compound was obtained from ethyl 3-mercaptopropanoate (1.00 g, 7.45 mmol, 1.0 equiv), (l-chloroethyl)benzene (1.15 g, 8.20 mmol, 1.1 equiv) and 7M NH3 in methanol (5.3 mL, 37.3 mmol, 5 equiv) according to the procedure of example 16 to give a colorless oil (0.47 g, 84% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : green, salty, roasted.
  • Odour description (1% solution in EtOH on paper blotter, 24 h): sulphourous, gassy, unpleasant.
  • Odour description (1% solution in EtOH on paper blotter, 24 h): green, sulfurous, grapefruit juice, tropical fruit, passion fruit juice, mango, multivitamin juice.
  • the compound was obtained from 2,6,6-trimethylbicyclo[3.1.1]hept-2-ene (2.0 g, 14.7 mmol, 1.0 equiv), butyl 3-mercaptopropanoate (2.38 g, 14.7 mmol, 1.0 equiv) and boron trifluoride diethyl etherate (0.78 mL, 6.12 mmol, 0.4 equiv) according to the procedure of example 31 to give a colorless oil (4.02 g, 91% crude yield).
  • the analytical data were identical to those reported above.
  • Odour description 1% solution in EtOH on paper blotter, 24 h: sulphurous, fruity, grapefruit juice, gazy.
  • Individual isomers of example 31 were separated by preparative HPLC and their structure was determined by 2D-NMR spectroscopy:
  • Example 32 Reaction product of 6,6-dimethyl-2-methylenebicvclor3.1.11heptane with methyl 3-mercaptopropanoate:
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : sulphurous, grapefruit, juicy, pink grapefruit.
  • the compound was obtained from (-)-p-pinene (2.89 g, 21.2 mmol, 1.0 equiv), ethyl 3- mercaptopropanoate (2.85 g, 21.2 mmol, 1.0 equiv) and boron trifluoride diethyl etherate (1.12 mL, 8.85 mmol, 0.4 equiv) according to the procedure of example 31 to give a colorless oil (4.3 g, 75% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : sulphurous, grapefruit, juicy, pink grapefruit, passion fruit, tropical fruit.
  • the compound was obtained from (-)-p-pinene (1.00 g, 7.34 mmol, 1.0 equiv), octadecyl 3-mercaptopropanoate (2.63 g, 7.34 mmol, 1.0 equiv) and boron trifluoride diethyl etherate (0.39 mL, 3.06 mmol, 0.4 equiv) according to the procedure of example 31 to give a colorless oil (1.67 g, 46% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : weak, sulphurous, citrus, grapefruit.
  • the compound was obtained from (-)-p-pinene (2.00 g, 14.7 mmol, 1.0 equiv), 2- ethylhexyl 3-mercaptopropanoate (3.21 g, 14.7 mmol, 1.0 equiv) and boron trifluoride diethyl etherate (0.78 ml_, 6.12 mmol, 0.4 equiv) according to the procedure of example 31 to give a colorless oil (2.8 g, 54% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h): green, citrus, sulphurous, grapefruit juice, corps pamplemousse.
  • Example 36 Transesterification product of example 31 with 2-phenylethan-l-ol :
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : green, sulphurous, grapefruit, juicy, slightly floral, rosy.
  • Example 37 Ester saponification product of example 31 using KOH :
  • the compound was obtained from butyl 3-((6-isopropyl-3-methylcyclohex-2-en-l- yl)thio)propanoate (2.00 g, 6.70 mmol, 1.0 equiv, mixture of structural isomers, example 31, AICI3 procedure was used) and KOH (1.77 g, 26.8 mmol, 4.0 equiv, 85%) according to the procedure of example 26 to give a brown oil (0.72 g, 44% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : green, sulphurous, grapefruit, juicy.
  • Alternative procedure reaction product of 6,6-dimethyl-2- methylenebicyclo[3.1.1]heptane with 3-mercaptopropanoic acid.
  • the compound was obtained from (-)-p-pinene (2.0 g, 14.7 mmol, 1.0 equiv), 3- mercaptopropanoic acid (1.56 g, 14.7 mmol, 1.0 equiv) and boron trifluoride diethyl etherate (0.78 mL, 6.12 mmol, 0.4 equiv) according to the procedure of example 31 to give a colorless oil (2.11 g, 59% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : sulphurous, green, garlic, sweaty, grapefruit peel.
  • the compound was obtained from (-)-p-pinene (2.00 g, 14.7 mmol, 1.0 equiv), 2- mercaptopropanoic acid (1.56 g, 14.7 mmol, 1.0 equiv) and boron trifluoride diethyl etherate (0.87 g, 6.13 mmol, 0.4 equiv) according to the procedure of example 31 to give a colorless oil (2.04 g, 57% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : sulphurous, green, animalic, leathery, burnt, grapefruit peel.
  • the compound was obtained from (-)-p-pinene (2.20 g, 16.1 mmol, 1.0 equiv), methyl 2-mercaptopropanoate (1.94 g, 16.1 mmol, 1.0 equiv) and boron trifluoride diethyl etherate (0.94 g, 6.62 mmol, 0.4 equiv) according to the procedure of example 31 to give a colorless oil (2.13 g, 53% yield).
  • the compound was obtained from (-)-p-pinene (1.14 g, 8.39 mmol, 1.0 equiv), 3- mercapto-N-methylpropanamide (1.00 g, 8.39 mmol, 1.0 equiv) and boron trifluoride diethyl etherate (0.50 g, 3.52 mmol, 0.4 equiv) according to the procedure of example 31 to give a colorless oil (1.09 g, 51% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : green, sulphurous, gazy, garlic, grapefruit.
  • the compound was obtained from (-)-p-pinene (2.00 g, 14.7 mmol, 1.0 equiv), methyl 2-mercaptoacetate (1.56 g, 14.7 mmol, 1.0 equiv) and boron trifluoride diethyl etherate (0.87 g, 6.13 mmol, 0.4 equiv) according to the procedure of example 31 to give a colorless oil (2.32 g, 65% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : sulphurous, green, burnt, garlic.
  • Example 42 Transesterification product of example 31 with butane-l,4-diol :
  • the compound was obtained from butyl 3-((6-isopropyl-3-methylcyclohex-2-en-l- yl)thio)propanoate (1.00 g, 3.35 mmol, 1.0 equiv, mixture of structural isomers, example 36), butane-l,4-diol (0.60 g, 6.70 mmol, 2.0 equiv) and titanium(IV) propan-2-olate (48 mg, 5 mol%) according to the procedure of example 36 to give a colorless oil (0.38 g, 36% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : green, sulphurous, grapefruit, juicy.
  • Example 43 Transesterification product of example 31 with decane-1, 10-diol :
  • the compound was obtained from butyl 3-((6-isopropyl-3-methylcyclohex-2-en-l- yl)thio)propanoate (1.00 g, 3.35 mmol, 1.0 equiv, mixture of structural isomers, example 31), decane-1, 10-diol (1.17 g, 6.70 mmol, 2.0 equiv) and titanium(IV) propan-2-olate (48 mg, 5 mol%) according to the procedure of example 36 to give a colorless oil (0.38 g, 28% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : green, sulphurous, grapefruit, juicy.
  • Example 44 Reaction product of 6,6-dimethyl-2-methylenebicvclor3.1.11heDtane with isooctyl 3-mercaptopropanoate (mixture of isooctyl ester isomers) :
  • the compound was obtained from (-)-p-pinene (2.00 g, 14.7 mmol, 1.0 equiv), isooctyl 3-mercaptopropanoate (3.21 g, 14.7 mmol, 1.0 equiv, CAS 30374-01-7) and boron trifluoride diethyl etherate (0.87 g, 6.13 mmol, 0.4 equiv) according to the procedure of example 31 to give a colorless oil (2.79 g, 54% yield).
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : weak, cassis.
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : weak, burnt, sulfury, anjeruk.
  • Example 46 Reaction product of 2-(4-methylcvclohexyl)propan-2-ol with ethyl 2-amino- 3-mercaptopropa noate hydrochloride:
  • the compound was obtained from 2-(4-methylcyclohexyl)propan-2-ol (2.0 g, 12.8 mmol, 1.0 equiv), (R)-ethyl 2-amino-3-mercaptopropanoate hydrochloride (2.38 g, 12.8 mmol, 1.0 equiv), ZnC (1.74 g, 12.8 mmol, 1.0 equiv) and triethylamine (1.30 g, 12.8 mmol, 1.0 equiv) according to the procedure of example 45 to give a colorless oil (1.77 g, 48% crude yield, 16% GC purity as a complex mixture with monoterpenes and monoterpene alcohols).
  • Odour description (1% solution in EtOH on paper blotter, 24 h): green, juicy, citrus, grapefruit, natural, bitter pith, juicy.
  • Diastereoisomer 1 13 C NMR (151 MHz, benzene-de, 6/ppm) : 174.0, 144.9, 120.8, 60.8,
  • Diastereoisomer 2 13 C NMR (151 MHz, benzene-de, 6/ppm) : 174.0, 146.1, 120.2, 60.6,
  • Diastereoisomer 1 13 C NMR (151 MHz, benzene-de, 6/ppm) : 174.0, 135.6, 123.5, 60.8,
  • Diastereoisomer 2 13 C NMR (151 MHz, benzene-de, 6/ppm) : 173.9, 136.8, 122.9, 60.7,
  • the compound was obtained from rac. )-2-(4-methylcyclohex-3-en-l-yl)propan-2-ol (2.0 g, 13.0 mmol, 1.0 equiv), (R)-ethyl 2-amino-3-mercaptopropanoate hydrochloride (2.41 g, 13.0 mmol, 1.0 equiv), ZnC (1.77 g, 13.0 mmol, 1.0 equiv) and triethylamine (1.31 g, 13.0 mmol, 1.0 equiv) according to the procedure of example 45 to give a yellow oil (2.07 g, 56% crude yield, 46% purity along with a mixture of monoterpenes and monoterpene alcohols).
  • the compound was obtained from (S)-2-(4-methylcyclohex-3-en-l-yl)propan-2-ol (2.0 g, 13.0 mmol, 1.0 equiv), (R)-ethyl 2-acetamido-3-mercaptopropanoate (2.48 g, 13.0 mmol, 1.0 equiv), ZnCH (1.77 g, 13.0 mmol, 1.0 equiv) and triethylamine (1.31 g, 13.0 mmol, 1.0 equiv) according to the procedure of example 45 to give a yellow oil (2.41 g, 57% crude yield, 60% purity along with a mixture of monoterpenes and monoterpene alcohols).
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : green, sulphurous, grapefruit, creamy, mango.
  • Example 49 Reaction product of 2-(4-methylcvclohex-3-en-l-yl)propan-2-ol with ethyl (tert-butoxycarbonyl)cvsteinate: Synthesis of a mixture of structural isomers: ethyl N-(tert-butoxycarbonyl)-S-(l,7,7-trimethylbicyclo[2.2.
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : sulfurous, metallic, grapefruit, gaseous, then weak, grapefruit.
  • the compound was obtained from (S)-2-(4-methylcyclohex-3-en-l-yl)propan-2-ol (1.0 g, 6.48 mmol, 1.0 equiv), ethyl ((benzyloxy)carbonyl)-/_-cysteinate (1.84 g, 6.48 mmol, 1.0 equiv), ZnC (0.88 g, 6.48 mmol, 1.0 equiv) and triethylamine (0.66 g, 6.48 mmol, 1.0 equiv) according to the procedure of example 45 to give a colourless oil (1.39 g, 73% crude yield, >99% purity).
  • the compound was obtained from (S)-2-(4-methylcyclohex-3-en-l-yl)propan-2-ol (5.23 g, 33.9 mmol, 1.2 equiv), benzyl L-cysteinate hydrochloride (7.0 g, 28.3 mmol, 1.0 equiv, prepared according to W02010006682A1) and ZnC (3.85 g, 28.3 mmol, 1.0 equiv) in toluene followed by removal of a head fraction by Kugelrohr distillation (40 °C I 0.02 mbar) according to the procedure of example 45 to give a yellow oil (4.4 g, 23% yield, 86% purity along with a mixture of monoterpenes and monoterpene alcohols).
  • Comparative Example 8 Reaction product of 6,6-dimethyl-2- methylenebicvclor3.1.11 heptane with 3-(trimethoxysilyl)propane-l-thiol :
  • the compound was obtained from (-)-p-pinene (5.00 g, 36.7 mmol, 1.0 equiv), decane- l-thiol (6.40 g, 36.7 mmol, 1.0 equiv) and AICI3 (0.98 g, 7.34 mmol, 0.2 equiv) according to the procedure of example 31 to give a colorless oil (3.22 g, 28% yield).
  • the compound was obtained from dodecane-l-thiol (5.00 g, 24.7 mmol, 1.0 equiv), DBU (3.76 g, 24.7 mmol, 1.0 equiv) and (R)-5-methyl-2-(propan-2-ylidene)cyclohexan-l-one (4.14 g, 27.2 mmol, 1.1 equiv) according to the procedure of example 3 as a colorless oil (3.52 g, 40% yield, mixture of two diastereoisomers).
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : green, sulphurous, grapefruit, cassis.
  • Odour description (1% solution in EtOH on paper blotter, 24 h) : green (burnt citrus peel, anjeruk) fruity.
  • the compound was obtained from (-)-p-pinene (0.86 g, 6.3 mmol, 1.1 equiv), 3- mercaptopropanenitrile (0.50 g, 5.7 mmol, 1.0 equiv) and boron trifluoride diethyl etherate (81 mg, 0.57 mmol, 0.1 equiv) in CH2CI2 (10 mL) according to the procedure of example 31 to give a colorless oil (0.07 g, 3% yield).
  • Odour description (1% solution in EtOH on paper blotter, 48 h) : weak, slightly green (sulphurous, vegetable, tropical, juicy, grapefruit).
  • Test Example 1 Application in liquid detergent
  • a 40 °C machine wash cycle was performed using 55 g of the above prepared liquid detergent samples A to D and odour-neutral cotton/elastane mixed fabric T-shirts.
  • the wet and line-dried fabric (1, 4 and 7 days) was assessed by a panel of 4-6 experts with regard to odour intensity and quality.
  • the odour intensity was recorded on an intensity scale of 0 (odourless) to 5 (extremely strong).

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  • Wood Science & Technology (AREA)
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Abstract

L'invention concerne un composé de formule (I), dans laquelle n, R1, R2a, R2b, R3, et R4 sont tels que définis dans la description; ledit composé étant utile dans des produits de consommation tels que des produits de soins personnels, des produits d'entretien du linge et des produits d'entretien ménager.
PCT/EP2024/067363 2023-06-21 2024-06-20 Nouveaux composés Pending WO2024261201A1 (fr)

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WO2008134058A1 (fr) * 2007-04-30 2008-11-06 The Board Of Trustees Of The University Of Illinois Procédés déchalcogénatifs pour la préparation de sulfures allyliques
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WO2010006682A1 (fr) 2008-06-23 2010-01-21 Helmholtz-Zentrum für Infektionsforschung GmbH Procédé pour la fabrication d'intermédiaires pour la fabrication de nouveaux macrocycles qui sont des inhibiteurs de la dégradation protéasomique de p27, tels que l'argyrine et ses dérivés, et utilisations desdits macrocycles
US20100310479A1 (en) 2009-06-03 2010-12-09 Symrise Gmbh & Co. Kg Use of certain isopropyl methylcyclohexene thiols as fragrances and/or flavors
WO2015032885A1 (fr) 2013-09-09 2015-03-12 Firmenich Sa Dérivés de thioéther comme précurseurs pour une libération contrôlée de molécules actives
WO2019166315A1 (fr) 2018-03-02 2019-09-06 Givaudan Sa Précurseurs de thioéther pour cétones et aldéhydes odorants
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WO2008154765A1 (fr) * 2007-06-19 2008-12-24 Givaudan Sa Dérivés de cystéine agissant contre les mauvaises odeurs
WO2010006682A1 (fr) 2008-06-23 2010-01-21 Helmholtz-Zentrum für Infektionsforschung GmbH Procédé pour la fabrication d'intermédiaires pour la fabrication de nouveaux macrocycles qui sont des inhibiteurs de la dégradation protéasomique de p27, tels que l'argyrine et ses dérivés, et utilisations desdits macrocycles
US20100310479A1 (en) 2009-06-03 2010-12-09 Symrise Gmbh & Co. Kg Use of certain isopropyl methylcyclohexene thiols as fragrances and/or flavors
WO2015032885A1 (fr) 2013-09-09 2015-03-12 Firmenich Sa Dérivés de thioéther comme précurseurs pour une libération contrôlée de molécules actives
WO2019166315A1 (fr) 2018-03-02 2019-09-06 Givaudan Sa Précurseurs de thioéther pour cétones et aldéhydes odorants
WO2021122997A1 (fr) 2019-12-19 2021-06-24 Firmenich Sa Composés destinés à fournir une odeur florale et fruitée de longue durée
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