WO2008068310A1 - Use of campholenic derivatives as fragrant ingredients in perfumery and flavouring - Google Patents

Use of campholenic derivatives as fragrant ingredients in perfumery and flavouring Download PDF

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Publication number
WO2008068310A1
WO2008068310A1 PCT/EP2007/063435 EP2007063435W WO2008068310A1 WO 2008068310 A1 WO2008068310 A1 WO 2008068310A1 EP 2007063435 W EP2007063435 W EP 2007063435W WO 2008068310 A1 WO2008068310 A1 WO 2008068310A1
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Prior art keywords
trimethyl
hex
enyl
cyclopent
enal
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PCT/EP2007/063435
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French (fr)
Inventor
Jean Mane
Caroline Plessis
Jean-Jacques Chanot
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V. Mane Fils
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Priority claimed from EP06291891A external-priority patent/EP1930317A1/en
Application filed by V. Mane Fils filed Critical V. Mane Fils
Priority to EP07847910A priority Critical patent/EP2094650B1/en
Priority to AT07847910T priority patent/ATE525347T1/en
Priority to DK07847910.2T priority patent/DK2094650T3/en
Priority to MX2009006094A priority patent/MX2009006094A/en
Priority to ES07847910T priority patent/ES2373865T3/en
Priority to PL07847910T priority patent/PL2094650T3/en
Priority to BRPI0719945-7A priority patent/BRPI0719945A2/en
Priority to JP2009539758A priority patent/JP2010511677A/en
Publication of WO2008068310A1 publication Critical patent/WO2008068310A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/31—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing rings other than six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/30—Compounds having groups
    • C07C43/303—Compounds having groups having acetal carbon atoms bound to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/44—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reduction and hydrolysis of nitriles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C47/00—Compounds having —CHO groups
    • C07C47/02—Saturated compounds having —CHO groups bound to acyclic carbon atoms or to hydrogen
    • C07C47/105—Saturated compounds having —CHO groups bound to acyclic carbon atoms or to hydrogen containing rings
    • C07C47/11—Saturated compounds having —CHO groups bound to acyclic carbon atoms or to hydrogen containing rings monocyclic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C47/00—Compounds having —CHO groups
    • C07C47/20—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms
    • C07C47/225—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms containing rings other than six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/04—Saturated compounds containing keto groups bound to acyclic carbon atoms
    • C07C49/105—Saturated compounds containing keto groups bound to acyclic carbon atoms containing rings
    • C07C49/11—Saturated compounds containing keto groups bound to acyclic carbon atoms containing rings monocyclic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
    • C07C49/21—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing rings other than six-membered aromatic rings
    • 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
    • C11B9/0026—Essential oils; Perfumes compounds containing an alicyclic ring not condensed with another ring
    • C11B9/003—Essential oils; Perfumes compounds containing an alicyclic ring not condensed with another ring the ring containing less than six carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/10—Systems containing only non-condensed rings with a five-membered ring the ring being unsaturated

Definitions

  • the present invention relates to the field of fragrances and flavours. More particularly, the invention relates to new campholenic derivatives and to their use in the fields of perfumery and flavouring.
  • campholenic derivatives having a C 1 -C 4 or C 1 -C 5 alkyl or C 2 -C 4 or C2-C5 alkenyl chain branched in position 1' of the campholene cycle, have been described in the literature as odorants, as in EP 0 203 528, EP 0 466 019, EP 1 008 579, EP 0 841 318 or in US 5,057,158. Particularly, these documents deal with cyclopentanebutanol, cyclopentenbutenol and cyclopentenepentenol derivatives, presenting a characteristic sandalwood oil odour.
  • the Applicant focused on a new family of cyclopentane or cyclopentene compounds substituted with a side chain of at least 6 carbon atoms.
  • the Applicant found that one compound of this family, 3 -methyl-6- (2 , 2 , 3-trimethyl- cyclopent-3-enyl ) -hex-4-enal was known but no organoleptic properties were ever disclosed for this compound.
  • campholenic derivatives are usually known for their sandalwood fragrance
  • the new campholenic derivatives presented unexpected odours, such as floral, fruity or marine.
  • the need of new compounds is of great importance for the development of the flavour and fragrance industry, which recently had to face stricter international regulatory requirements about the use of certain materials, as well as environmental concerns and customer demands for improved performance. Being able of manufacturing new fragrant compounds is therefore a challenge.
  • this new approach figures out a technical problem which is to propose new flavour or fragrant compounds, preferably by a simple and inexpensive manufacturing process .
  • fragment and fragment, as used herein, are used interchangeably whenever a compound or a mixture of compounds is referred to, which is intended to pleasantly stimulate the sense of smell.
  • flavouring relates to the flavouring of any liquid or solid, human or animal, in particular of drinks, dairy products, ice creams, soups, sauces, dips, dishes, meat products, culinary assistances, salted biscuits or snacks. It also means the flavouring of beers, wines and tobaccos .
  • organoleptic compound such as for example fragrances and flavours, as used herein, refers to compounds of the invention which stimulate the sense of smell or taste, and are thus perceived as having a characteristic odour and/or flavour.
  • olfactory effective amount means a level or amount of fragrant/flavouring compound present in a material at which the incorporated compound exhibits a sensory effect.
  • masking is meant reducing or eliminating malodour or bad flavour perception generated by one or more molecules entering in the composition of a product.
  • alkyl or “alkyl group”, in the present invention, means any linear or branched saturated hydrocarbon chain, having preferably 1, 2, 3, 4 or 5 carbon atoms and herein referred to as C1- 5 alkyl group, such as for example methyl, ethyl, propyl, isopropyl, butyl, t- butyl, pentyl .
  • alkenyl or "alkenyl group”, in the present invention, means any linear or branched mono or poly unsaturated hydrocarbon chain, having preferably 2, 3, 4 or 5 carbon atoms and herein referred to as C 2 ⁇ 5 alkenyl group, such as for example ethenyl, propenyl, butenyl, or pentenyl .
  • isomer in the present invention, means molecules having the same chemical formula, which means same number and types of atoms, but in which the atoms are arranged differently.
  • the term “isomer” includes structural isomers, geometric isomers, optical isomers and stereoisomers .
  • This invention thus relates to campholenic derivative of general formula (I) wherein
  • Rl, R2 , R3 , R4 and R5 represent, each independently, a hydrogen atom or a linear or branched C 1 -C 5 alkyl or C 2 -C 5 alkenyl group,
  • Y represents a CN, a C(O)R6 or a CR ⁇ (ORa) (OR ⁇ ) group, wherein R6 represents a hydrogen atom or a linear or branched C 1 -C 5 alkyl or C 2 -C 5 alkenyl group, and Ra and R ⁇ represent simultaneously a linear or branched Ci-C 5 alkyl or C 6 -C 5 alkenyl group or form together a cycle, and preferably Y represents CN, CHO, C(O)CH 3 ,
  • R6 represents a hydrogen atom, a methyl or an ethyl group and Ra and R ⁇ represent simultaneously a linear or branched C1-C 5 alkyl or C 2 -C 5 alkenyl group or form together a cycle
  • the side chain optionally, has a double bond between Cl and C2 and/or between C3 and C4 • Provided that the derivative is not 3-methyl-6- (2,2, 3-trimethyl-cyclopent-3-enyl) -hex-4-enal .
  • the compounds of the invention are those of general formula (I) hereabove, wherein • Rl, P2, R3 , R4 and R5 represent, each independently, a hydrogen atom or a methyl or an ethyl group,
  • Y represents a CN, a C(O)R6 or a CR6 (ORa) (OR ⁇ ) group, wherein R6 represents a hydrogen atom or a linear or branched C1-C5 alkyl or C2-C 5 alkenyl group, and Ra and R ⁇ represent simultaneously a linear or branched C 1 -C 5 alkyl or C 2 -C 5 alkenyl group or form together a cycle, and preferably Y represents CN, CHO, C(O)CH 3 , C(O)C 2 H 5 , or CR6 (ORa) (OR ⁇ ) , wherein R6 represents a hydrogen atom, a methyl or an ethyl group and Ra and R ⁇ represent simultaneously a linear or branched C 1 -C 5 alkyl or C 2 -C 5 alkenyl group or form together a cycle,
  • the compounds of the invention are those of general formula (I) hereabove, wherein
  • Rl, R2, R3 , R4 and R5 represent, each independently, a hydrogen atom or a linear or branched C1-C 5 alkyl or C 2 -C 5 alkenyl group
  • Y represents CN, CHO, C(O)CH 3 , C(O)C 2 H 5 , or CR6 (ORa) (OR ⁇ )
  • R6 represents a hydrogen atom, a methyl or an ethyl group
  • Ra and R ⁇ represent simultaneously a linear or branched C 1 -C 5 alkyl or C 2 -C 5 alkenyl group or form together a cycle
  • the 5-membered ring is saturated or has a double bond between C3 ' and C4 ' in formula (I)
  • the side chain optionally, has a double bond between Cl and C2 and/or between C3 and C4
  • the compounds of the invention are those of general formula (I) hereabove, wherein
  • Rl, R2 , R3 , R4 and R5 represent, each independently, a hydrogen atom or a methyl or an ethyl group
  • Y represents CN, CHO, C(O)CH 3 , C(O)C 2 H 5 , or CR6 (ORa) (OR ⁇ ) , wherein R6 represents a hydrogen atom, a methyl or an ethyl group and Ra and R ⁇ represent simultaneously a linear or branched Ci-C 5 alkyl or C 2 -C 5 alkenyl group or form together a cycle,
  • the 5-membered ring and the side chain are unsaturated, preferably the side chain is mono-unsaturated
  • the compounds of the invention are those of general formula (I) hereabove, wherein
  • Rl, R2 , R3 , R4 and R5 represent, each independently, a hydrogen atom or a linear or branched C 1 -C 5 alkyl or C 2 -C 5 alkenyl group,
  • Y represents CN, CHO, C(O)CH 3 , C(O)C 2 H 5 , or CR6 (ORa) (OR ⁇ ) , wherein R6 represents a hydrogen atom, a methyl or an ethyl group and Ra and R ⁇ represent simultaneously a linear or branched Ci-C 5 alkyl or C 2 -C 5 alkenyl group or form together a cycle,
  • the 5-membered ring and the side chain are unsaturated, preferably the side chain is mono-unsaturated
  • the can ⁇ pholenic derivatives of the invention are of general formula (Ia) ,
  • Rl, R2 , R3 , R4 and R5 represent, each independently, a hydrogen atom or a linear or branched C 1 -C 5 alkyl or C 2 -C 5 alkenyl group, and preferably Rl, R2 , R3 , R4 and R5 represent, each independently, a hydrogen atom or a methyl or an ethyl group,
  • the side chain is optionally unsaturated between Cl and C2 and/or between C3 and C4 in formula (Ia) .
  • campholenic derivatives of the invention are of general formula (Ib) ,
  • Rl, R2 , R3 , R4 and R5 represent, each independently, a hydrogen atom or a linear or branched Ci-C 5 alkyl or C 2 -C 5 alkenyl group, and preferably Rl, R2 , R3 , R4 and R5 represent, each independently, a hydrogen atom or a methyl or an ethyl group, • the 5-membered ring is saturated or has a double bond between C3 ' and C4 ' , and
  • Rg represents a hydrogen atom, a linear or branched C1- 5 alkyl or C2-5 alkenyl group, preferably, R 6 is a hydrogen atom or a methyl group, more preferably Rg is a hydrogen atom,
  • the derivative is not 3 -methyl-6- (2,2, 3-trimethyl-cyclopent-3-enyl) -hex-4-enal .
  • campholenic derivatives of the invention are of general formula (Ic) ,
  • Rl, R2 , R3 , R4 and R5 represent, each independently, a hydrogen atom or a linear or branched C 1 -C 5 alkyl or C 2 -C 5 alkenyl group, and preferably Rl, R2 , R3 , R4 and R5 represent, each independently, a hydrogen atom or a methyl or an ethyl group,
  • R 0 - and R ⁇ represent simultaneously a linear or branched C 1 -C5 alkyl or C 2 -C 5 alkenyl group, preferably, R ⁇ and R ⁇ are simultaneously a methyl or an ethyl group, or • R ⁇ and R ⁇ form together a cycle, preferably a 5- membered ring or a 6-membered ring.
  • This invention relates to the compounds of formula (I), as described above, but also to any of their various isomers .
  • campholenic derivatives of the invention are selected in the group comprising:
  • the invention relates to the use of the compounds of formula (I) as described above, and to the use of one or more isomers of 3 -methyl-6- (2 , 2 , 3-trimethyl- cyclopent-3-enyl ) -hex-4-enal as fragrant or flavouring agents .
  • This invention also relates to a fragrant or flavouring composition containing at least one campholenic derivative of the invention and/or 3-methyl-6- (2 , 2 , 3- trimethyl-cyclopent-3-enyl) -hex-4-enal , which has never been described as an organoleptic compound.
  • This invention includes any fragrant or flavouring composition comprising one or more isomers of a compound of formula (I), and/or 3-methyl-6- (2 , 2 , 3-trimethyl-cyclopent- 3-enyl ) -hex-4-enal .
  • this invention relates to a composition comprising at least two or three isomers of a compound of formula (I), and/or 3-methyl-6- (2,2, 3-trimethyl-cyclopent-3-enyl) -hex-4-enal .
  • the compounds of the invention may be used alone or in combination with other perfuming or flavouring ingredients, solvents, additives or fixatives, commonly used and that the man skilled in the art is able to choose in regard of the desired effect and the nature of the product to perfume or flavour.
  • the invention relates to the use of at least one campholenic derivative or composition containing them as described above in the perfumery field for the preparation of perfumed bases and concentrates, fragrances, perfumes and similar products; topic compositions; cosmetic compositions such as for example face and body creams, cleansers, facial treatments, talc powders, hair oils, shampoos, hair lotions, bath oils and salts, shower and bath gels, soaps, body anti-perspirants and deodorizers, pre-shave, shaving and post-shave creams and lotions, creams, toothpastes, mouth baths, pomades; cleaning products, such as for example softeners, detergents, air deodorizers and household cleaning supplies. Therefore, the invention also relates to a fragrant composition including at least one compound of formula (I) or one or more isomers of a compound of formula
  • the invention relates to the use of the compounds or composition as described above, as flavouring agents for the preparation of flavouring compositions or articles, such as for example drinks, dairy products, ice creams, soups, sauces, dips, dishes, meat products, culinary assistances, salted biscuits or snacks and also beers, wines and tobaccos. Therefore, the invention also relates to a flavoured composition including at least one compound of formula (I) or one or more isomers of a compound of formula (I) .
  • the invention relates to the use of the compounds or composition as described above, as masking agents of odours and/or flavours, and to any pharmaceutical, cosmetic or food composition containing at least one compound of formula (I) or one or more isomers of a compound of formula (I) . Therefore, this invention also relates to any composition comprising at least one compound of formula (I) , as herein described, in combination with any suitable excipient, especially pharmaceutical or cosmetic or dietary excipient.
  • the compounds of the invention may be used in a concentration comprised in a range from 0.001% to 99% in weight, preferably from 0.1% to 50% in weight, more preferably from 0.1% to 30% in weight. It is known by the man skilled in the art that these values depend of the nature of the composition/article to be perfumed and/or flavoured, the desired intensity of the perfume and/or flavour, and of the nature of the other ingredients present in said composition or article. According to a preferred embodiment of the invention, compounds are used in an olfactory effective amount.
  • the new derivatives of the present invention can be easily prepared by different ways with reactions known by the person of the art.
  • derivatives of general formula (I), as above described, wherein Y is a C(O)R.6 group and wherein the double bond between C2-C3 is absent may be prepared by a Claisen rearrangement, as shown in Scheme 1, from compounds of formula (II), wherein Rl to R6 are as described hereabove.
  • the molecules of formula (II) can be obtained via the condensation of an appropriately substituted Grignard reagent with campholenaldehyde, saturated or not, followed by transetherification with the adequate vinyl ether or reaction with appropriate allylic halides, according to known procedures.
  • the new derivatives of formula (I), wherein Ri_ 5 have the meaning as defined in formula (I) , wherein Y is a CN group, may be obtained via a Knoevenagel-Doebner condensation between compound of formula (III) and cyanoacetic acid or ethyl cyanoacetate, followed by reduction of one or more double bonds, as shown in Scheme 2.
  • Compounds (III) are obtained from campholenaldehyde and appropriate oxo-compounds by crotonisation, according to procedures known in the art, and may be used directly or Its oc, ⁇ -insaturation may be reduced before the Knoevenagel condensation.
  • R 1 H, C r C 5 -alkyl, -alkenyl
  • (S) - (-) Campholenic aldehyde and its (R) - (+ ) -enantiomer may be prepared from (lR)-( + ) and (IS) - (-) - ⁇ -pinene, respectively.
  • the double bond may be hydrogenated to prepare compounds of formula (I), as described before, where the cyclic double bond is absent.
  • 4-Ethyl-6- (2,2, 3-trimethyl-cyclopentyl) -hexanenitrile was prepared from 2-ethyl-4- (2 , 2 , 3 -trimethyl-cyclopent-3-enyl) - but-2-enal (prepared from campholenaldehyde and propanal, via known procedure) and cyanoacetic acid according to example 5.
  • Cis-isomer 6 0.8 (s, 3H), 1.1 (s, 3H), 1.55-1.65 (m, 3H), 1.65-2.6 (m, 9H), 5.15-5.25 (m, IH), 5.25-5.55 (m, 2H),
  • 6- (2 , 2 , 3-Trimethyl-cyclopentyl) -hex-4-enal was obtained from 6- (2 , 2 , 3-Trimethyl-cyclopentyl) -hex-4-enenitrile, according to example 8.
  • the product is obtained as a cis/ trans mixture (90:10) .
  • Cis-isomer ⁇ 12.57 & 19.67, 23.09, 24.28, 25.86, 28.31, 35.60, 42.25, 46.66, 50.66, 121.63, 126.41, 132.67, 148.50,
  • 4-Ethyl-6- (2,2, 3-trimethyl-cyclopentyl ) -hexanal was prepared from 4-ethyl-6- (2 , 2 , 3-trimethyl-cyclopentyl) - hexanenitrile according to example 8.
  • the compound was purified by column chromatography and consists in a (50:50) mixture of isomers.
  • the crude compound was purified by column chromatography.
  • Aldehyde from example 12 was alkylated with methyl iodide, according to known procedure, via its diisobutylenamine, obtained with diisobutylamine through azeotropic water removal in toluene in the presence of catalytic amount of PTSA.
  • the obtained product was purified by column chromatography, it consists in a mixture of isomers, 2 observable groups in MMR, ratio (60:40), composed each of 2 diastereoisomers .
  • Cis-isomer 1H-NMR (200MHz, CDCl 3 ): ⁇ 0.77 (s, 3H), 0.97 (s, 3H), 1.17
  • Example 20 Fragrance composition containing 6- (2,2,3 - trimethy1-eyelopent-3 -enyl ) -hex-4-enal
  • compositions were used in a shampoo base at usual dilution, known from the person of the art, and the samples containing the compound of formula (I) showed a greener note, vegetables-type, a bit mushroom, imparting very natural aspect to the lily of the valley note.

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Abstract

This invention relates to campholenic derivatives of general formula (I) wherein Rl, R2, R3, R4 and R5 represent, each independently, a hydrogen atom or a linear or branched C1-C5 alkyl or C2-C5 alkenyl group, Y represents a CN, a C(O)R6 or a CR6 (ORα) (ORβ) group, wherein R6 represents a hydrogen atom or a linear or branched C1-C5 alkyl or C2-C5 alkenyl group, and Rα and Rβ represent simultaneously a linear or branched C1, C2, C3, C4 or C5 alkyl or C2, C3, C4 or C5 alkenyl group and can form together a cycle, the 5-membered ring is saturated or has a double bond between C3 ' and C4 ' in formula (I), and the side chain, optionally, has a double bond between C1 and C2 and/or between C3 and C4, provided that the derivative is not 3-methyl-6- (2, 2, 3-trimethyl-cyclopent-3-enyl) -hex-4-enal; and their use as fragrant or flavouring agent.

Description

USE OF CAMPHOLENIC DERIVATIVES AS FRAGRANT INGREDIENTS IN PERFUMERYAND FLAVOURING
[FIELD OF THE INVENTION]
The present invention relates to the field of fragrances and flavours. More particularly, the invention relates to new campholenic derivatives and to their use in the fields of perfumery and flavouring.
[BACKGROUND]
Several campholenic derivatives, having a C1-C4 or C1-C5 alkyl or C2-C4 or C2-C5 alkenyl chain branched in position 1' of the campholene cycle, have been described in the literature as odorants, as in EP 0 203 528, EP 0 466 019, EP 1 008 579, EP 0 841 318 or in US 5,057,158. Particularly, these documents deal with cyclopentanebutanol, cyclopentenbutenol and cyclopentenepentenol derivatives, presenting a characteristic sandalwood oil odour.
[PROBLEM TO BE SOLVED]
The Applicant focused on a new family of cyclopentane or cyclopentene compounds substituted with a side chain of at least 6 carbon atoms. The Applicant found that one compound of this family, 3 -methyl-6- (2 , 2 , 3-trimethyl- cyclopent-3-enyl ) -hex-4-enal was known but no organoleptic properties were ever disclosed for this compound.
Surprisingly, and despite the fact that campholenic derivatives are usually known for their sandalwood fragrance, the new campholenic derivatives presented unexpected odours, such as floral, fruity or marine. The need of new compounds is of great importance for the development of the flavour and fragrance industry, which recently had to face stricter international regulatory requirements about the use of certain materials, as well as environmental concerns and customer demands for improved performance. Being able of manufacturing new fragrant compounds is therefore a challenge.
In other words, this new approach figures out a technical problem which is to propose new flavour or fragrant compounds, preferably by a simple and inexpensive manufacturing process .
[DEFINITIONS] The terms "fragrance" and "fragrant", as used herein, are used interchangeably whenever a compound or a mixture of compounds is referred to, which is intended to pleasantly stimulate the sense of smell.
The terms "flavour" and "flavouring", as used herein, are used interchangeably whenever a compound or a mixture of compounds is referred to, which is intended to stimulate the sense of taste and smell. Also in the meaning of the invention, the term "flavouring" relates to the flavouring of any liquid or solid, human or animal, in particular of drinks, dairy products, ice creams, soups, sauces, dips, dishes, meat products, culinary assistances, salted biscuits or snacks. It also means the flavouring of beers, wines and tobaccos .
The term "organoleptic compound", such as for example fragrances and flavours, as used herein, refers to compounds of the invention which stimulate the sense of smell or taste, and are thus perceived as having a characteristic odour and/or flavour. The term "olfactory effective amount", as used herein, means a level or amount of fragrant/flavouring compound present in a material at which the incorporated compound exhibits a sensory effect.
By the term "masking" is meant reducing or eliminating malodour or bad flavour perception generated by one or more molecules entering in the composition of a product.
The term "alkyl" or "alkyl group", in the present invention, means any linear or branched saturated hydrocarbon chain, having preferably 1, 2, 3, 4 or 5 carbon atoms and herein referred to as C1-5 alkyl group, such as for example methyl, ethyl, propyl, isopropyl, butyl, t- butyl, pentyl .
The term "alkenyl" or "alkenyl group", in the present invention, means any linear or branched mono or poly unsaturated hydrocarbon chain, having preferably 2, 3, 4 or 5 carbon atoms and herein referred to as C2^5 alkenyl group, such as for example ethenyl, propenyl, butenyl, or pentenyl .
The term "isomer", in the present invention, means molecules having the same chemical formula, which means same number and types of atoms, but in which the atoms are arranged differently. The term "isomer" includes structural isomers, geometric isomers, optical isomers and stereoisomers .
This invention thus relates to campholenic derivative of general formula (I)
Figure imgf000005_0001
wherein
• Rl, R2 , R3 , R4 and R5 represent, each independently, a hydrogen atom or a linear or branched C1-C5 alkyl or C2-C5 alkenyl group,
• Y represents a CN, a C(O)R6 or a CRβ (ORa) (ORβ) group, wherein R6 represents a hydrogen atom or a linear or branched C1-C5 alkyl or C2-C5 alkenyl group, and Ra and Rβ represent simultaneously a linear or branched Ci-C5 alkyl or C6-C5 alkenyl group or form together a cycle, and preferably Y represents CN, CHO, C(O)CH3,
C(O)C2H5, or CR6 (ORa) (ORβ) , wherein R6 represents a hydrogen atom, a methyl or an ethyl group and Ra and Rβ represent simultaneously a linear or branched C1-C5 alkyl or C2-C5 alkenyl group or form together a cycle
• the 5-membered ring is saturated or has a double bond between C3 ' and C4' in formula (I), and
• the side chain, optionally, has a double bond between Cl and C2 and/or between C3 and C4 • Provided that the derivative is not 3-methyl-6- (2,2, 3-trimethyl-cyclopent-3-enyl) -hex-4-enal .
Advantageously, the compounds of the invention are those of general formula (I) hereabove, wherein • Rl, P2, R3 , R4 and R5 represent, each independently, a hydrogen atom or a methyl or an ethyl group,
• Y represents a CN, a C(O)R6 or a CR6 (ORa) (ORβ) group, wherein R6 represents a hydrogen atom or a linear or branched C1-C5 alkyl or C2-C5 alkenyl group, and Ra and Rβ represent simultaneously a linear or branched C1-C5 alkyl or C2-C5 alkenyl group or form together a cycle, and preferably Y represents CN, CHO, C(O)CH3, C(O)C2H5, or CR6 (ORa) (ORβ) , wherein R6 represents a hydrogen atom, a methyl or an ethyl group and Ra and Rβ represent simultaneously a linear or branched C1-C5 alkyl or C2-C5 alkenyl group or form together a cycle,
• the 5-membered ring is saturated or has a double bond between C3 ' and C4 ' in formula (I), and • the side chain, optionally, has a double bond between Cl and C2 and/or between C3 and C4
• Provided that the derivative is not 3 -methyl-6-
(2,2, S-trimethyl-cyclopent-S-enyl) -hex-4-enal .
Advantageously, the compounds of the invention are those of general formula (I) hereabove, wherein
• Rl, R2, R3 , R4 and R5 represent, each independently, a hydrogen atom or a linear or branched C1-C5 alkyl or C2-C5 alkenyl group, Y represents CN, CHO, C(O)CH3, C(O)C2H5, or CR6 (ORa) (ORβ) , wherein R6 represents a hydrogen atom, a methyl or an ethyl group and Ra and Rβ represent simultaneously a linear or branched C1-C5 alkyl or C2-C5 alkenyl group or form together a cycle, • the 5-membered ring is saturated or has a double bond between C3 ' and C4 ' in formula (I), and
• the side chain, optionally, has a double bond between Cl and C2 and/or between C3 and C4
• Provided that the derivative is not 3 -methyl-6- (2,2, 3-trimethyl-cyclopent-3-enyl) -hex-4-enal . According to another advantageous embodiment, the compounds of the invention are those of general formula (I) hereabove, wherein
• Rl, R2 , R3 , R4 and R5 represent, each independently, a hydrogen atom or a methyl or an ethyl group, and
• Y represents CN, CHO, C(O)CH3, C(O)C2H5, or CR6 (ORa) (ORβ) , wherein R6 represents a hydrogen atom, a methyl or an ethyl group and Ra and Rβ represent simultaneously a linear or branched Ci-C5 alkyl or C2-C5 alkenyl group or form together a cycle,
• the 5-membered ring and the side chain are unsaturated, preferably the side chain is mono-unsaturated
• Provided that the derivative is not 3-methyl-6-
(2,2, S-trimethyl-cyclopent-S-enyl) -hex-4-enal .
According to another advantageous embodiment, the compounds of the invention are those of general formula (I) hereabove, wherein
• Rl, R2 , R3 , R4 and R5 represent, each independently, a hydrogen atom or a linear or branched C1-C5 alkyl or C2-C5 alkenyl group,
• Y represents CN, CHO, C(O)CH3, C(O)C2H5, or CR6 (ORa) (ORβ) , wherein R6 represents a hydrogen atom, a methyl or an ethyl group and Ra and Rβ represent simultaneously a linear or branched Ci-C5 alkyl or C2-C5 alkenyl group or form together a cycle,
• the 5-membered ring and the side chain are unsaturated, preferably the side chain is mono-unsaturated
• Provided that the derivative is not 3-methyl-6- (2,2, 3-trimethyl-cyclopent-3-enyl) -hex-4-enal . According to a first embodiment of the invention, the canαpholenic derivatives of the invention are of general formula (Ia) ,
Figure imgf000008_0001
Wherein
• Rl, R2 , R3 , R4 and R5 represent, each independently, a hydrogen atom or a linear or branched C1-C5 alkyl or C2-C5 alkenyl group, and preferably Rl, R2 , R3 , R4 and R5 represent, each independently, a hydrogen atom or a methyl or an ethyl group,
• the 5-membered ring is saturated or has a double bond between C3 ' and C4 ' , and
• the side chain is optionally unsaturated between Cl and C2 and/or between C3 and C4 in formula (Ia) .
According to a second embodiment of the invention, the campholenic derivatives of the invention are of general formula (Ib) ,
Figure imgf000008_0002
wherein
• Rl, R2 , R3 , R4 and R5 represent, each independently, a hydrogen atom or a linear or branched Ci-C5 alkyl or C2-C5 alkenyl group, and preferably Rl, R2 , R3 , R4 and R5 represent, each independently, a hydrogen atom or a methyl or an ethyl group, • the 5-membered ring is saturated or has a double bond between C3 ' and C4 ' , and
• the side chain is optionally unsaturated between Cl and C2 and/or between C3 and C4 in formula (Ib) , and • Rg represents a hydrogen atom, a linear or branched C1-5 alkyl or C2-5 alkenyl group, preferably, R6 is a hydrogen atom or a methyl group, more preferably Rg is a hydrogen atom,
• Provided that the derivative is not 3 -methyl-6- (2,2, 3-trimethyl-cyclopent-3-enyl) -hex-4-enal .
According to a third embodiment of the invention, the campholenic derivatives of the invention are of general formula (Ic) ,
Figure imgf000009_0001
wherein
• Rl, R2 , R3 , R4 and R5 represent, each independently, a hydrogen atom or a linear or branched C1-C5 alkyl or C2-C5 alkenyl group, and preferably Rl, R2 , R3 , R4 and R5 represent, each independently, a hydrogen atom or a methyl or an ethyl group,
• the 5-membered ring is saturated or has a double bond between C3 ' and C4 ' in formula (Ic), and
• the side chain is optionally unsaturated between Cl and C2 and/or between C3 and C4 in formula (Ic), and
• R0- and Rβ represent simultaneously a linear or branched C1-C5 alkyl or C2-C5 alkenyl group, preferably, Rα and Rβ are simultaneously a methyl or an ethyl group, or • Rα and Rβ form together a cycle, preferably a 5- membered ring or a 6-membered ring.
This invention relates to the compounds of formula (I), as described above, but also to any of their various isomers .
According to a preferred embodiment of the invention, the campholenic derivatives of the invention are selected in the group comprising:
6- (2 , 2 , 3-trimethyl-cyclopent-3--enyl) -hex-4-enenitrile,
(4E) -6- (2 , 2 , S-trimethyl-cyclopent-S-enyl) -hex-4-enenitrile,
(4Z) -6- (2 , 2 , 3-trimethyl-cyclopent-3-enyl) -hex-4-enenitrile,
(+) -6- ( (IR) -2,2,3-trimethyl-cyclopent-3-enyl) -hex-4- enenitrile, (- ) -6- ( (IS) -2 , 2 , S-trimethyl-cyclopent-S-enyl) - hex-4-enenitrile, (4E) -6- ( (IR) -2,2, 3-trimethyl-cyclopent-3- enyl) -hex-4-enenitrile, (4Z) -6- ( (IR) -2 , 2 , 3-trimethyl- cyclopent-3-enyl) -hex-4~enenitrile, (4E) -6- ( (IS) -2 , 2 , 3- trimethyl-cyclopent-3-enyl) -hex-4-enenitrile, (4Z)-S- ( (IS) - 2 , 2 , S-trimethyl-cyclopent-S-enyl) -hex-4-enenitrile, 6-
(2,2, 3-trimethyl-cyclopentyl) -hex-4-enenitrile, ( 4E) -S-
(2,2, 3-trimethyl-cyclopentyl) -hex-4-enenitrile, ( 4Z) -S-
(2,2, 3-trimethyl-cyclopentyl ) -hex-4-enenitrile, 4-methyl-6-
(2,2, 3-trimethyl-cyclopent-3-enyl) -hex-4-enenitrile, ( 4Z) - 4-methyl-6- (2,2, S-trimethyl-cyclopent-S-enyl) -hex-4- enenitrile, ( 4E) -4-methyl-6- (2,2, 3-trimethyl-cyclopent-3- enyi) -hex-4-enenitrile, 4-methyl-6- (2,2, 3-trimethyl- cyclopentyl) -hexanenitrile, 4-ethyl-6- (2,2, 3-trimethyl- cyclopentyl) -hexanenitrile, 4-methyl-6- (2,2, 3-trimethyl- cyclopentyl) -hex-3-enenitrile, 6- (2 , 2 , 3-trimethyl- cyclopent-3-enyl) -hex-4-enal , ( 4E) -6- (2 , 2 , 3-trimethyl- cyclopent-3-enyl) -hex-4-enal, (4Z) -6- (2, 2 , 3-trimethyl- cyclopent-3-enyl) -hex-4-enal, (+) -6- ( (IR) -2, 2 , 3-trimethyl- cyclopent-3-enyl) -hex-4-enal, (-)-6-((lS)-2,2, 3-trimethyl- cyclopent-3-enyl) -hex-4-enal, (4Z) -6- ( (IR) -2 , 2 , 3-trimethyl- cyclopent-3-enyl) -hex-4-enal, (4Z) -S- ( (IS) -2, 2, 3-trimethyl- cyclopent-3-enyl) -hex-4-enal, (4Z) -6- ( (IS) -2, 2, 3-trimethyl- cyclopent-3-enyl) -hex-4-enal, (4Z) -6- ( (IR) -2 , 2 , 3-trimethyl- cyclopent-3-enyl) -hex-4-enal , 6- (2 , 2 , 3 -trimethy1- cyclopentyl) -hex-4-enal, (4Z) -6- (2,2, 3-trimethyl- cyclopentyl) -hex-4-enal, (4E) -6- (2,2, 3-trimethyl- cyclopentyl) -hex-4-enal , 4-methyl-6- (2,2, 3-trimethyl- cyclopent-3-enyl) -hex-4-enal, ( 4E) -4-methyl-6- (2 , 2 , 3- trimethyl-cyclopent-3-enyl ) -hex-4-enal , ( 4Z) -4-methyl-6- (2,2, S-trimethyl-cyclopent-S-enyl) -hex-4-enal , 4-methyl- 6- (2,2,3-trimethyl-cyclopentyl) -hexanal , 4-ethyl-6- (2,2,3- trimethyl-cyclopentyl) -hexanal , 3-methyl-6- (2,2,3- trimethyl-cyclopentyl) -hexanal , 2 , 4-dimethyl-6- (2 , 2 , 3- trimethy1-eyelopentyl) -hexanal, 7- (2 , 2 , 3-trimethyl- cyclopent-3-enyl ) -hept-5-en-2-one, (4E) -7- (2 , 2 , 3-trimethyl- cyclopent-3-enyl) -hept-5-en-2-one, (4Z)-7-(2,2, 3-trimethyl- cyclopent-3-enyl) -hept-5-en-2-one, 2- ( 6, 6-diethoxy-3-ethyl- hexyl) -1 , 1 , 5-trimethyl-cyclopentane, 4- ( 6 , 6-diethoxy-hex-2- enyl) -1,5, 5-trimethyl-cyclopentene, 4- ( (2E) -6, 6-diethoxy- hex-2-enyl) -1,5, 5-trimethyl-cyclopentene, 4- ( (2Z) -6, 6- diethoxy-hex-2-enyl) -1,5, 5-trimethyl-cyclopentene.
In another aspect, the invention relates to the use of the compounds of formula (I) as described above, and to the use of one or more isomers of 3 -methyl-6- (2 , 2 , 3-trimethyl- cyclopent-3-enyl ) -hex-4-enal as fragrant or flavouring agents . This invention also relates to a fragrant or flavouring composition containing at least one campholenic derivative of the invention and/or 3-methyl-6- (2 , 2 , 3- trimethyl-cyclopent-3-enyl) -hex-4-enal , which has never been described as an organoleptic compound. This invention includes any fragrant or flavouring composition comprising one or more isomers of a compound of formula (I), and/or 3-methyl-6- (2 , 2 , 3-trimethyl-cyclopent- 3-enyl ) -hex-4-enal . According to a preferred embodiment, this invention relates to a composition comprising at least two or three isomers of a compound of formula (I), and/or 3-methyl-6- (2,2, 3-trimethyl-cyclopent-3-enyl) -hex-4-enal .
The compounds of the invention may be used alone or in combination with other perfuming or flavouring ingredients, solvents, additives or fixatives, commonly used and that the man skilled in the art is able to choose in regard of the desired effect and the nature of the product to perfume or flavour. In a first embodiment, the invention relates to the use of at least one campholenic derivative or composition containing them as described above in the perfumery field for the preparation of perfumed bases and concentrates, fragrances, perfumes and similar products; topic compositions; cosmetic compositions such as for example face and body creams, cleansers, facial treatments, talc powders, hair oils, shampoos, hair lotions, bath oils and salts, shower and bath gels, soaps, body anti-perspirants and deodorizers, pre-shave, shaving and post-shave creams and lotions, creams, toothpastes, mouth baths, pomades; cleaning products, such as for example softeners, detergents, air deodorizers and household cleaning supplies. Therefore, the invention also relates to a fragrant composition including at least one compound of formula (I) or one or more isomers of a compound of formula
(I) ■
In a second embodiment, the invention relates to the use of the compounds or composition as described above, as flavouring agents for the preparation of flavouring compositions or articles, such as for example drinks, dairy products, ice creams, soups, sauces, dips, dishes, meat products, culinary assistances, salted biscuits or snacks and also beers, wines and tobaccos. Therefore, the invention also relates to a flavoured composition including at least one compound of formula (I) or one or more isomers of a compound of formula (I) .
In a third embodiment, the invention relates to the use of the compounds or composition as described above, as masking agents of odours and/or flavours, and to any pharmaceutical, cosmetic or food composition containing at least one compound of formula (I) or one or more isomers of a compound of formula (I) . Therefore, this invention also relates to any composition comprising at least one compound of formula (I) , as herein described, in combination with any suitable excipient, especially pharmaceutical or cosmetic or dietary excipient.
The compounds of the invention may be used in a concentration comprised in a range from 0.001% to 99% in weight, preferably from 0.1% to 50% in weight, more preferably from 0.1% to 30% in weight. It is known by the man skilled in the art that these values depend of the nature of the composition/article to be perfumed and/or flavoured, the desired intensity of the perfume and/or flavour, and of the nature of the other ingredients present in said composition or article. According to a preferred embodiment of the invention, compounds are used in an olfactory effective amount.
The new derivatives of the present invention can be easily prepared by different ways with reactions known by the person of the art. For instance, derivatives of general formula (I), as above described, wherein Y is a C(O)R.6 group and wherein the double bond between C2-C3 is absent, may be prepared by a Claisen rearrangement, as shown in Scheme 1, from compounds of formula (II), wherein Rl to R6 are as described hereabove. The molecules of formula (II) can be obtained via the condensation of an appropriately substituted Grignard reagent with campholenaldehyde, saturated or not, followed by transetherification with the adequate vinyl ether or reaction with appropriate allylic halides, according to known procedures.
Figure imgf000014_0001
Figure imgf000014_0002
Ri= H, CrC5-alky!, -alkenyl
Figure imgf000014_0003
(I)
Scheme 1
The new derivatives of formula (I), wherein Ri_5 have the meaning as defined in formula (I) , wherein Y is a CN group, may be obtained via a Knoevenagel-Doebner condensation between compound of formula (III) and cyanoacetic acid or ethyl cyanoacetate, followed by reduction of one or more double bonds, as shown in Scheme 2. Compounds (III) are obtained from campholenaldehyde and appropriate oxo-compounds by crotonisation, according to procedures known in the art, and may be used directly or Its oc, β-insaturation may be reduced before the Knoevenagel condensation.
Figure imgf000015_0001
R1 = H, CrC5-alkyl, -alkenyl
Figure imgf000015_0002
Scheme 2
When derivatives of formula (I), with Y being a cyano group, are obtained, the compounds of formula (I) wherein Y is a C(0)R6 group, are easy to prepare, for instance via a reduction with diisobutyialuminumhydride or via an alkylation with phosphonium derivatives . Compounds of formula (I), wherein Y is a CR6 (ORa) (ORβ) group are then simply obtained from (I), with Y being a C(O)Re group via acetalisation with the appropriate alcohol or diol . Campholenaldehyde, the starting material, is either commercial or prepared from oc-pinene, via pinene oxide, according to known procedure. (S) - (-) Campholenic aldehyde and its (R) - (+ ) -enantiomer may be prepared from (lR)-( + ) and (IS) - (-) -α-pinene, respectively. The double bond may be hydrogenated to prepare compounds of formula (I), as described before, where the cyclic double bond is absent.
Following examples detail the processes of preparation of the compounds of the invention and their use. These examples are presented with an only goal of illustration and shall not be regarded as limiting the scope of the invention.
Example 1: Preparation of 6- (2 , 2 , 3-trimethyl-cyclopent-3- enyl ) -hex-4-enenitrile
A suspension of ( 3 -cyano-propyl) -triphenylphosphonium chloride (readily prepared by known reaction between triphenylphosphine and 4-chloro-butyronitrile) in toluene, with potassium carbonate, commercial campholenaldehyde and a catalytic amount of benzoic acid, was refluxed for 24 hours. The mixture was then cooled down and filtered. The filtrate was washed twice with warm water, dried over magnesium sulphate and the solvents were evaporated to give a crude oil, which was triturated with t-butyl methyl ether to precipitate most of the phosphine oxide. After filtration, the solvents were evaporated and the crude oil distilled. The compound thus obtained is a cis/ trans (90:10) mixture. Bp = 98-100°C/0.76-0.79 torr Cis-isomer :
1H-NMR (200MHz, CDCl3) : δ 0.83 (s, 3H) , 1.03 (s, 3H) , 1.6-
1.65 (m, 3H) , 1.75-1.95 (m, 2H) , 1.95-2.4 (m, 3H) , 2.4-2.55
(m, 4H) , 5.2-5.3 (m, IH) , 5.35-5.7 (3, 2H) . 13C-NMR (50MHz, CDCl3) : δ 13.02, 17.93, 20.13, 23.76, 26.28,
28.32, 35.93, 47.15, 50.66, 119.82, 212.99, 125.57, 133.51,
148.83.
Trans- isomer : selected data
1H-NMR (200MHz, CDCl3) : δ 0.80 (s, 3H) , 1.01 (s, 3H) . 13C-NMR (50MHz, CDCl3) : δ 18.14, 28.81, 33.69, 50.41,
122.08, 126.41, 134.25, 148.89.
IR (film, cm"1) : 798m, 1013w, 1360m, 1444m, 1463m, 1653w,
2246w, 2835m, 2866s, 2895s, 2930s, 2956s, 3013w, 3035w.
MS (EI, intensity (%) ) : 203 (M+, 10), 188 (100), 171 (38), 160 (19), 147 (35), 133 (19), 121 (31), 109 (83), 108 (91),
107 (26), 105 (24), 95 (26), 94 (31), 93 (44), 91 (44), 81
(19), 79 (40), 77 (33), 55 (36), 53 (27), 41 (72), 39 (26).
Example 2: Preparation of (+) - (1 'R) - (6- (2 , 2 , 3-trimethyl- cyclopent-3-enyl ) -hex-4-enenitrile
It was prepared from (R) - ( + ) -campholenaldehyde according to example 1. αD(neat) = + 1.92°
Example 3: Preparation of 6- (2 , 2, 3-trimethyl-cyclopentyl) - hex-4-enenitri1e
6- (2 , 2 , 3-Trimethyl-cydopentyl) -hex-4-enenitrile was prepared from 2H-dihydro-campholenaldehyde and (3-cyano- propyl ) -triphenylphosphonium chloride, according to example 1. The product is obtained as a cisl trans (90:10) mixture. Bp = 82°C/0.02 torr
Ci s- isomer :
1H-NMR (200MHz, CDCl3) : δ 0.53 (s, 3H) , 0.82 (d, 3H, J = 6.7Hz) , 0.88 (s, 3H) , 1.05-1.25 (m, 2H) , 1.25-1.55 (m, 2H) ,
1.55-1.90 (m, 3H) , 2.05-2.25 (m, IH) , 2.27-2.47 (m, 4H) ,
5.20-5.40 (m, IH) , 5.45-5.65 (m, IH) .
13C-NMR (50MHz, CDCl3) : δ 13.82, 14.33, 17.47, 23.24, 25.60,
28.13, 28.27, 29.85, 44.97, 50.89, 119.34, 124.67, 133.30. Trans- isomer :
1H-NMR (200MHz, CDCl3, selected data) : δ 0.50 (s, 3H) , 0.84
(s, 3H) .
13C-NMR (50MHz, CDCl3) : δ 12.54, 17.67, 19.65, 25.80, 27.84,
28.01, 33.69, 35.45, 50.18, 50.52, 119.34, 125.05, 133.03. IR (film, cm"1) : 1367m, 1388w, 1428m, 1453m, 1465m, 166Ow,
171Ow, 1727w, 2247m, 2870s, 2955s, 3013m.
MS (EI, intensity (%) ) : 205 (M+, 1), 190(7), 188(4),
162(8), 148(13), 134(8), 120(6), 111(72), 109(18), 95(24),
84(33), 70(22), 69(100), 67(25), 55(38), 41(41).
Example 4: Preparation of 4-methyl-β- (2 , 2 , 3-trimethyl- cyclopent-3-enyl ) -hex-4-enenitrile
To a suspension of (3-cyano-propyl) -triphenylphosphonium chloride (see Example 1) in tetrahydrofurane was added portionwise one molar equivalent of potassium tert- butoxide. After stirring at room temperature for 30 minutes, the mixture was cooled down (ice bath) before slowly adding methyl iodide. The mixture was further stirred for 1 hour and another one equivalent of potassium tert-butoxide was added portionwise. After stirring at room temperature for another hour, campholenaldehyde was added and the reaction mixture was further stirred overnight. The reaction mixture was poured into water : t-butyl methyl ether (50:50) . The separated aqueous phase was acidified and extracted three times with t-butyl methyl ether. The combined organic layers were washed twice with water, then with saturated aqueous sodium bicarbonate and with brine. After drying over magnesium sulphate, the solvents were evaporated and the crude product purified by distillation. Bp = 104-106°C/0.7-0.8 torr The compound is obtained as a cis/ trans (50:50) mixture.
1H-NMR (200MHz, CDCl3): δ 0.79 (s, 3H), 0.99 (s, 3H), 1.58- 1.63 (m, 3H), 1.63-2.53 (m, 12H), 2.41 (s, 3H), 5.2-5.25 (m, IH) , 5.25-5.38 (m, IH) . 13C-NMR (50MHz, CDCl3): δ 12.57, 15.64 & 15.84, 16.31 & 22.72, 19.68, 25.84 & 25.87, 27.56, 28.36 & 28.5, 35.07, 35.48 & 35.52, 46.68, 50.34 & 50.53, 119.47 & 119.52, 121.56 Sc 121.69, 127.43 & 128.48, 130.79 & 130.9, 148.41 & 148.49. IR (film, cm"1): 799m, 1013w, 13560m, 1382w, 1445m, 1462m, 1691w, 2246w, 2835m, 2866m, 2930s, 2956s, 3036w. S (EI, intensity (%), cis isomer): 217 (M+, 12), 202 (19), 185 (13), 146 (12), 122 (45), 121 (93), 109 (100), 108 (93), 107 (83), 95 (31), 93 (48), 91 (48), 81 (63), 79 (54), 77 (35), 67 (76), 55 (37), 53 (34), 41 (66), 39 (23). S (EI, intensity (%) , trans isomer): 217 (M+, 15), 202 (27), 185 (5), 146 (10), 122 (54), 121 (100), 109 (99), 108 (100), 107 (90), 95 (33), 93 (48), 91 (50), 81 (64), 79 (53), 77 (35), 67 (75), 55 (35), 53 (33), 41 (61), 39 (22). Example 5: Preparation of 4-methyl-6- (2 , 2 , 3-trimethyl- cyclopentyl) -hexanenitrile
2-Methyl-4- (2,2, 3-trimethyl-cyclopent-3-enyl) -but-2-enal (obtained from known procedure) was condensed with cyanoacetic acid in the presence of 2,6-lutidine at room temperature to afford 4-methyl-6- (2 , 2 , 3-trimethyl- cyclopent-3-enyl) -hexa-2 , 4-dienenitrile . After removal of the heavy by-products, the crude 4-methyl-6- (2 , 2 , 3- trimethyl-cyclopent-3-enyl ) -hexa-2 , 4-dienenitrile was hydrogenated under H2 pressure (pH2 = 20 bars ; room temperature) to give 4-methyl-6- (2, 2, 3-trimethyl- cyclopentyl) -hexanenitrile.
Bp = 95°C/0.07 torr 1H-NMR (200MHz, CDCl3): δ 0.49 (s, 3H), 0.82 (d, 3H, J =
6.7 Hz), 0.85 (s, 3H), 0.91 (2 d, 3H, J = 6.3 Hz), 1.0-1.8
(m, 13H) , 2.25-2.42 (m, 2H) .
13C-NMR (50MHz, CDCl3) : δ 13.91 & 14.43, 14.93 & 15.0, 18.77
Sc 19.06, 25.68 & 25.72, 27.5 & 27.69, 28.24 & 28.38, 30.13, 32.1 & 32.27, 32.55, 35.35 & 35.65, 42.32, 45.24, 50.85 &
51.17.
IR (film, cm"1) : 1365m, 1385w, 1427w, 1465m, 2246w, 2869s,
2955s.
MS (EI, intensity (%)): 221 (M+, 3), 206 (6), 204 (9), 178 (18), 84 (100), 83 (26), 70 (56), 69 (83), 55 (58), 41
(45) .
Example 6: Preparation of 4-ethyl-6- (2 , 2, 3-trimethyl- cyclopentyl) -hexanenitrile
4-Ethyl-6- (2,2, 3-trimethyl-cyclopentyl) -hexanenitrile was prepared from 2-ethyl-4- (2 , 2 , 3 -trimethyl-cyclopent-3-enyl) - but-2-enal (prepared from campholenaldehyde and propanal, via known procedure) and cyanoacetic acid according to example 5.
The compound is obtained as a mixture of isomers (70:30). Bp = 112°C/0.03 torr
1H-NMR (200MHz, CDCl3, common protons): δ 0.46 (s, 3H), 0.7-0.9 (m, 9H), 0.9-1.5 (m, 12H), 1.5-1.85 (m, 3H). Major isomers: δ 2.27 (t, 2H, J = 7.4 Hz); minor isomers: 6 2.54 (t, 2H, J" = 7.2 Hz) . 13C-MMR (50MHz, CDCl3) :
Major isomers: δ 10.18 & 10.52, 13.73 & 13.76, 14.27, 14.52 & 14.66, 24.72 & 25.16, 25.54 & 25.58, 27.0 & 27.27, 28.19 Sc 28.23, 28.58 & 28.83, 29.97 & 30.04, 31.31 & 31.39, 38.05 & 38.25, 42.12 & 42.15, 45.08 & 45.11, 50.93 & 51.14, 119.89.
Minor isomers (selected data): δ 10.55 & 10.88, 25.46 & 25.92, 26.97 & 27.05, 30.68 & 31.02, 39.12 & 39.23, 50.99. IR (film, cm'1) : 1118w, 1244w, 1367m, 1384w, 1461m, 1738w, 2247w, 2869s, 2956s. MS (EI, intensity (%) ) : 235 (M+, 1), 220 (3), 192 (10), 84 (162), 83 (26), 70 (67), 69 (89), 55 (49), 41 (43).
Example 7: Preparation of 4-methyl-6- (2 , 2 , 3-trimethyl- cyclopentyl) -hex-3-enenitrile
2-Methyl-4- (2,2, 3-trimethyl-cyclopentyl ) -butyraldehyde
(easily obtained from 2-methyl-4- (2 , 2 , 3-trimethyl- cyclopent-3-enyl ) -but-2-enal) was condensed with cyanoacetic acid in the presence of 2,6-lutidine at room temperature to afford 4-methyl-6- (2 , 2 , 3-trimethyl- cyclopentyl) -hex-3-enenitrile, as a (40:60) mixture of isomers . Bp = 95°C/0.03 torr 1H-NMR (200MHz, CDCl3) : δ 0.49 (s, 3H) , 0.75-0.9 (m, 6H) ,
0.9-1.4 (m, 5H) , 1.4-1.6 (m, 2H) , 1.6-2.1(m, 3H) , 1.65 (s,
3H) , 3.03 (d, 2H, J = 6.9 Hz) , 5.1-5.2 (m, IH) . Minor isomer (selected data) : δ 1.73 (d, 3H, J = 1.3 Hz) .
13C-NMR (50MHz, CDCl3) :
Major isomer: δ 13.82, 14.37, 16.16, 16.39, 25.56, 28.04,
28.46, 30.05, 38.4, 42.25, 45.11, 50.29, 111.11, 118.63,
142.96. Minor isomer: δ 13.82, 14.37, 16.02, 16.39, 23.13, 28.15,
28.25, 28.46, 31.13, 38.4, 42.31, 45.19, 50.61, 111.72,
118.63, 143.09.
IR (film, cm"1) : 92Ow, 1049w, 1366m, 1386m, 1418w, 1453m,
1466m, 1669w, 1754w, 225Ow, 2869s, 2954s. MS (EI, intensity (%) ) : 219(M+,1), 204(5), 179(8), 124(9),
109(26), 95(16), 84(67), 83(32), 81(17), 70(44), 69(100),
67(26) , 55(40) , 41(49) .
219(M+,1), 204(7), 124(15), 109(69), 95(23), 84(49),
83(26), 82(36), 81(20), 70(35), 69(100), 67(30), 55(39), 41 (48) .
Example 8: Preparation of 6- (2 , 2 , 3-trimethyl-cyclopent-3- enyl ) -hex-4-enal
A IM solution of diisobutylaluminium hydride in toluene was added dropwise to a solution of 6- (2 , 2 , 3-trimethyl- cyclopent-3-enyl ) -hex-4-enenitrile at such a rate that the temperature remains under 400C. After the addition, the solution was heated at 800C for 2 hours. The hydrolysis was carefully performed pouring the reaction solution into a mixture of acetic acid and ice. The aqueous phase was extracted twice with t-butyl methyl ether and the combined organic phases were washed twice with water, with an aqueous saturated solution of sodium bicarbonate and with brine. After drying over magnesium sulphate, the solvents were evaporated to give a crude oil. The purification consisted in a bulb-to-bulb evaporation prior to distillation.
Bp = 76-78°C/0.2 torr
1H-NMR (200MHz, CDCl3) :
Cis-isomer: 6 0.8 (s, 3H), 1.1 (s, 3H), 1.55-1.65 (m, 3H), 1.65-2.6 (m, 9H), 5.15-5.25 (m, IH), 5.25-5.55 (m, 2H),
9.78 (t, IH, J" = 1.5 Hz) .
Trans-isomer : (selected data) δ 0.76 (s, 3H), 0.97 (s, 3H),
9.66 (m, IH).
13C-NMR (50MHz, CDCl3) : {cis isomer) δ 12.58, 19.67, 20.11, 25.85, 27.77, 35.52, 43.76, 46.69, 50.31, 121.6, 127.2,
131.09, 148.49, 202.15.
IR (film, cm"1) : 798m, 1013w, 1360m, 1384w, 1409w, 1444m,
1463m, 1727s, 2719w, 2833m, 2866m, 2894s, 2930s, 2955s,
3010m, 3035w. MS (EI, intensity (%)): 206 (M+, 8), 191 (19), 173 (12),
147 (28), 121 (30), 109 (48), 108 (100), 107 (45), 105
(20), 97 (21), 95 (36), 93 (52), 91 (36), 81 (27), 79 (65),
77 (30), 69 (36), 67 (76), 55 (46), 53 (21), 43 (24), 41
(80) , 39 (26) .
Example 9: Preparation of ( + ) - (l.'R) -6- (2 , 2, 3-trimethyl- cyclopent-3 -enyl ) -hex-4-enal
It was prepared from nitrile of example 2, according to example 8. αD(neat) = + 2° Example 10: Preparation of 6- (2 , 2 , 3-trimethyl-cyclopentyl) - hex-4-enal
6- (2 , 2 , 3-Trimethyl-cyclopentyl) -hex-4-enal was obtained from 6- (2 , 2 , 3-Trimethyl-cyclopentyl) -hex-4-enenitrile, according to example 8.
The product is obtained as a cis/ trans mixture (90:10) .
Cls-isomer :
1H-MMR (200MHz, CDCl3): δ 0.51 (s, 3H), 0.80 (d, 3H, J" =
6.7Hz), 0.86 (s, 3H), 1.05-1.25 (m, 2H), 1.25-1.90 (m, 5H), 2.02-2.2.20 (m, IH), 2.25-2.52 (m, 4H), 5.12-5.50 (m, 2H),
9.74 (t, IH, J = 1.5Hz) .
13C-NMR (50MHz, CDCl3): δ 13.82, 14.24, 20.03, 25.60, 28.15,
29.87, 42.18, 43.74, 44.99, 50.97, 126.75, 131.28, 202.01.
Trans-isomer : 1H-NMR (200MHz, CDCl3, selected data): δ 0.47 (s, 3H), 0.97
(s, 3H), 9.72 (t, IH, J = 1.6Hz).
13C-NMR (50MHz, CDCl3): 12.52, 13.24, 25.13, 25.79, 27.72,
35.48, 42.09, 43.41, 45.10, 50.28, 127.16, 130.99, 201.92.
IR (film, cm"1) : 1366m, 1388m, 1409w, 1453m, 1466m, 1728s, 2719m, 2870s, 2955s, 3010m.
MS (EI, intensity (%)): 208 (M+, 1), 193(3), 124(6),
111(33), 109(25), 95(28), 80(25), 79(22), 69(100), 67(24),
55(38) , 41(40) .
Example 11: Preparation of 4-methyl-6- (2 , 2 , 3-trimethyl- cyclopent-3-enyl) -hex-4-enal
4-Methyl-6- (2,2, 3-trimethyl-cyclopent-3-enyl) -hex-4-enal was prepared from 4-methyl-6- (2 , 2 , 3-trimethyl-cyclopent-3- enyl) -hex-4-enenitrile according to example 8, as a (60:40) cis/ trans mixture. 1H-NMR (200MHz, CDCl3) :
Cis-isomer: δ 0.77 (s, 3H) , 0.97 (s, 3H) , 1.55-1.65 (m, 3H) , 1.65-1.70 (m, 3H) , 1.70-2.05 (m, 4H) , 2.05-2.25 (m, 2H) , 2.25-2.55 (m, 3H) , 5.15-5.25 (m, 2H) , 9.77 (t, IH, J = 1.7 Hz) .
Trans- isomer: (selected data) δ 1.57-1.60 (m, 3H) , 9.74 (t, IH, J" = 1.9 Hz) . 13C-NMR (50MHz, CDCl3) :
Cis-isomer: δ 12.57 & 19.67, 23.09, 24.28, 25.86, 28.31, 35.60, 42.25, 46.66, 50.66, 121.63, 126.41, 132.67, 148.50,
202.28.
Trans- isomer: δ 12.57 & 19.67, 16.13, 25.88, 28.45, 31.96,
35.53, 42.13, 46.66, 50.51, 121.68, 125.35, 132.74, 148.50,
202.61.
Example 12: Preparation of 4-methyl-6- (2 , 2 , 3-trimethyl- cyclopentyl) -hexanal
4-Methyl-6- (2,2, 3-trimethyl-cyclopentyl) -hexanal was prepared from 4-methyl-6- (2 , 2 , 3-trimethyl-cyclopentyl) - hexanenitrile according to example 8.
1H-NMR (200MHz, CDCl3): δ 0.49 (s, 3H), 0.74-0.91 (m, 6H), 0.82 (d, 3H, J = 6.1 Hz), 0.91-1.56 (m, 10H), 1.56-1.85 (m, 4H), 2.35-2.5 (3, 2H), 9.78 (t, IH, J = 1.9 Hz). 13C-NMR (50MHz, CDCl3): δ 13.92 & 14.42, 19.29 & 19.6, 25.71 Sc 25.74, 27.66 & 27.85, 28.28 & 28.42, 28.69 & 29.21, 30.17, 32.68 & 32.93, 35.8 & 36.08, 41.71 & 41.83, 42.31, 45.27, 50.95 & 51.26, 203.04.
IR (film, cm'1) : 1365w, 1387w, 1465m, 1729s, 2714w, 2869s, 2931s, 2955s.
MS (EI, intensity (%) ) : 224 (M+, 2), 207 (6), 163 (9), 110 (20), 109 (36), 95 (34), 85 (33), 84 (70), 83 (34), 81 ( 29 ) , 70 ( 79 ) , 69 ( 100 ) , 67 ( 23 ) , 57 ( 19 ) , 55 ( 66 ) , 43 ( 22 ) , 41 ( 55 ) .
Example 13: Preparation of 4-ethyl-6- (2 , 2 , 3-trimethyl- cyclopentyl) -hexanal
4-Ethyl-6- (2,2, 3-trimethyl-cyclopentyl ) -hexanal was prepared from 4-ethyl-6- (2 , 2 , 3-trimethyl-cyclopentyl) - hexanenitrile according to example 8. The compound was purified by column chromatography and consists in a (50:50) mixture of isomers.
1H-NMR (200MHz, CDCl3): δ 0.45 (s, 3H), 0.7-0.95 (m, 9H), 0.78 (d, 3H, J = 6.7 Hz), 0.95-1.35 (m, 12H), 1.35-1.65 (m, 3H), 1.65-1.85 (m, 3H), 2.34 & 2.38 (2 td, 2H, J = 1.7 & 1.5 Hz, J = 7.8 Sc 7.6 Hz), 9.73 (t, IH, J = 1.9 Hz).
13C-NMR (50MHz, CDCl3): δ 10.45 & 10.77, 13.78, 14.30, 24.93 Sc 25.68, 25.24, 25.58, 27.19 & 27.21, 28.24, 30.03, 31.87 & 31.90, 38.55 & 38.68, 41.20 & 41.42, 42.18, 45.14, 51.07 & 51.11, 202.98. IR (film, cm"1) : 1051m, 1103m, 1367m, 1385m, 1461s, 1728s, 2715w, 2869s, 2955s.
MS (EI, intensity (%) ) : 238 (M+, 1), 223(4), 209(4), 177(6), 123(8), 110(20), 109(27), 99(19), 95(27), 84(66), 83(37), 81(26), 70(79), 69(100), 67(23), 57(19), 55(81), 43(30), 41(65) .
Example 14: Preparation of 3-methyl-6- (2 , 2 , 3-trimethyl- cyclopentyl) -hexanal
3 -Methyl-6- (2 , 2 , 3-trimethyl-cyclopentyl ) -hexanal was obtained, following the procedure of example 8, from a nitrile prepared according to example 5 from 5- (2, 2, 3- trimethyl-cyclopent-3-enyl) -pent-3 ~en-2 -one (prepared from campholenaldehyde and acetone) .
The crude compound was purified by column chromatography.
1H-NMR (200MHz, CDCl3): δ 0.47 (s, 3H), 0.80 (d, IH, J = 6.7Hz), 0.83 (s, 3H), 0.94 (2d, IH, J = 6.6 Hz), 1.0-1.55
(m, 10H), 1.55-1.85 (m, 2H), 2.03 (o, IH, J" = 6.5 Hz), 2.18
Sc 2.24 (td, 2H, J = 2.2 Hz, J = 7.7 Hz) & 2.34 & 2.42 (td,
2H, J = 2 Hz, J = 5.8 Hz) , 9.74 (t, IH, J = 2.2 Hz) .
13C-NMR (50MHz, CDCl3) : 6 13.85, 14.31, 19.86 & 20.05, 25.63, 26.14 & 26.22, 28.12 & 28.25, 28.21, 30.12, 30.47 &
30.58, 37.28 & 37.39, 42.20, 45.19, 20.79 & 50.85, 50.99 &
51.17, 202.99 & 203.02.
IR (film, cm"1) : 1127w, 1367m, 1384m, 1464s, 1728s, 2712m,
2869s, 2954s. MS (EI, intensity (%) ) : 224 (M+, 1), 109(13), 95(21),
84(61), 83(28), 81(22), 70(86), 69(100), 67(18), 55(52),
43 (23) , 41(51) .
Example 15: Preparation of 2 , 4-dimethyl-6- (2 , 2 , 3-trimethyl- cyclopentyl) -hexanal
Aldehyde from example 12 was alkylated with methyl iodide, according to known procedure, via its diisobutylenamine, obtained with diisobutylamine through azeotropic water removal in toluene in the presence of catalytic amount of PTSA.
The obtained product was purified by column chromatography, it consists in a mixture of isomers, 2 observable groups in MMR, ratio (60:40), composed each of 2 diastereoisomers .
Major isomers:
1H-NMR (200MHz, CDCl3): δ 0.48 (s, 3H), 0.80 (d, 3H, J =
6.7 Hz), 0.83 (s, 3H), 0.87 (d, 3H, J = 6.5 Hz), 0.92-1.51 (m, 10H) , 1.06 (d, 3H, J = 6.9 Hz) , 1.51-1.87 (m, 3H) , 9.55 (d, IH, J = 1.6 Hz) , 9.57 (d, IH, J = 1.5 Hz) . 13C-NMR (50MHz, CDCl3) : δ 13.85, 14.10 & 14.26, 14.35, 19.66 & 19.99, 25.64, 27.63, 28.20, 30.10, 30.51 & 30.95, 35.73 & 36.02, 38.17 & 38.51, 42.24, 44.13, 45.20, 50.83 & 51.17, 205.40.
Minor isomers :
1H-NMR (200MHz, CDCl3, selected data) : 5 0.88 (d, 3H, J" = 6.6 Hz) , 1.05 (d, 3H, J = 7.0 Hz) , 9.59 (2d, IH, J" = 2.0
Hz) .
13C-NMR (50MHz, CDCl3): δ 13.24 & 13.38, 13.85, 14.35, 19.10
& 19.43, 25.68, 27.42, 28.34, 30.10, 30.41 & 30.60, 36.40 &
36.67, 37.33 & 37.92, 42.24, 44.23, 45.20, 50.88 & 51.14, 205.35.
IR (film, cm""1): 1367w, 138Ow, 1464m, 1709m, 1729s, 2704w,
2870s, 2956s.
MS (EI, intensity (%) ) : 238 (M+), 223 (1), 180 (6), 125
(15), 109 (32), 99 (22), 97 (22), 95 (27), 84 (62), 83 (37), 81 (21), 71 (20), 70 (73), 69 (100), 57 (21), 55
(72) , 43 (39) , 41 (57) .
Example 16: Preparation of 7- (2 , 2 , 3-trimethyl-cyclopent-3- enyl ) ~hept-5-en-2-one
7- (2 , 2 , S-Trimethyl-cyclopent-S-enyl) -hept-5-en-2-one was prepared from nitrile of example 1 according to known procedure. It is obtained as a (95:5) cis/ trans mixture. Bp = 76-78°C/0.04 torr 1H-NMR (200MHz, CDCl3): δ 0.78 (s, 3H), 0.98 (s, 3H), 1.55- 1.65 (m, 3H), 1.65-1.9 (m, 2H), 1.9-2.4 (m, 5H), 2.13 (s, 3H), 2.4-2.55 (m, 2H), 5.15-5.25 (m, IH), 5.25-5.5 (m, 2H). 13C-NMR (50MHz, CDCl3) : δ 12.59, 19.69, 21.71, 25.86, 27.73, 29.92, 35.52, 43.55, 46.69, 50.38, 121.61, 127.75, 130.65, 148.51, 208.43.
IR (film, cm"1): 578w, 798m, 1013w, 1161m, 1361s, 1412m, 1438s, 1462s, 1654w, 1719s, 2836m, 2867s, 2957s, 3009m, 3036m.
MS (EI, intensity (%)): 220(M+,2), 205(3), 187(4), 162(5), 150(8), 147(38), 121(17), 109(34), 108(86), 107(24), 93(51), 91(31), 81(20), 79(36), 77(24), 67(41), 55(22), 43 (100) , 41(28) .
Example 17: Preparation of 2- (6, 6-diethoxy-3-ethyl-hexyl) - 1,1, 5-trimethyl-cyclopentane
2- ( 6 , 6-Diethoxy-3-ethyl-hexyl) -1,1, 5-trimethyl-cyclopentane was prepared by treating compound of example 13 with ethanol, in presence of triethylorthoformate with catalytic amount of PTSA. The crude product was pure enough not to be further purified. It consists in a (50:50) mixture of isomers.
1H-NMR (200MHz, CDCl3): 6 0.47 (s, 3H), 0.75-0.9 (m, 3H), 0.8 (d, 3H, J = 6.7 Hz), 0.83 (s, 3H), 0.9-1.37 (m, 10H) , 1.19 (t, 6H, J = 7.1 Hz), 1.37-1.67 (m, 3H), 1.67-1.85 (m, 2H) , 3.56 (m, 4H) , 4.45 (t, IH, J = 5.7 Hz) . 13C-NMR (50MHz, CDCl3): δ 10.68 & 10.99, 13.87, 14.37, 15.33, 25.58 & 26.02, 25.67, 27.36 & 27.41, 27.64 & 28.01, 28.33, 30.15, 30.47 & 30.74, 32.16 & 32.20, 38.98 & 39.05, 42.25, 51.23, 60.67, 103.32. IR (film, cm"1) : 1016m, 1064s, 1126s, 1345w, 1375m, 1460m, 2870s, 2956s. S (EI, intensity (%) ) : 312 (M+, 1), 268(1), 103(100), 95(9), 75(31), 69(22), 55(15), 47(14), 41(9). Example 18: Preparation of 4- (6, 6-diethoxy~hex-2-enyl) - 1,5, 5-trimethyl-cyclopentene
4- { 6 , 6-Diethoxy-hex-2-enyl ) -1 , 5 , 5-trimethyl-cyclopentene was prepared according to example 17, starting from aldehyde of example 8. Bp = 94°C/0.07 torr
Cis-isomer : 1H-NMR (200MHz, CDCl3): δ 0.77 (s, 3H), 0.97 (s, 3H), 1.17
(t, 6H, J" = 7.1), 1.50-1.90 (m, 7H), 1.90-2.35 (m, 5H),
3.54 (m, 4H), 4.46 (t, IH, J = 5.7), 5.15-5.25 (m, IH),
5.25-5.47 (m, 2H) .
13C-NMR (50MHz, CDCl3): 512.51, 15.28, 19.63, 22.57, 25.82, 27.69, 33.46, 35.49, 46.6550.45, 60.84, 102.33, 121.67,
128.84, 129.89, 148.37.
Trans- i s omer : selected data
1H-NMR ( 200MHz , CDCl3 ) : δ 0 . 74 ( s , 3H ) , 0 . 95 ( s , 3 H ) .
13C-NMR (50MHz, CDCl3): δ 129.60, 130.42. IR (film, cm"1) : 798w, 1014w, 1064s, 1130s, 136Ow, 1375m,
1444m, 1744w, 2871s, 1931s, 2957s, 3007m, 3037w.
Example 19: Olfactive description of the campholenic derivatives of the invention
The odours of the compounds of the invention have been described by a professional evaluation panel and are gathered in table 1 hereinafter. Table 1:
Figure imgf000031_0001
Example 20: Fragrance composition containing 6- (2,2,3 - trimethy1-eyelopent-3 -enyl ) -hex-4-enal
A lily of the valley type accord was prepared as described from the following ingredients:
Benzyl acetate 10 10
Cinnamic alcohol 20 20
Lemon ess . 10 10
Citronellol 65 65
Citronellyl acetate 100 100
Geraniol 90 90
Cis-3-Hexenol 15 15
Cis-3 -Hexenyl acetate 5 5
Indol 5 5
Lemarome® 10 10
Methyl heptenone, 10% MIP 10 10
Nerol 10 10
Phenylethyl alcohol 100 100
6- (2 , 2 , 3-Trimethyl-cyclopent- - 50
3-enyl) -hex-4-enal
DPG 550 500
These 2 compositions were used in a shampoo base at usual dilution, known from the person of the art, and the samples containing the compound of formula (I) showed a greener note, vegetables-type, a bit mushroom, imparting very natural aspect to the lily of the valley note.

Claims

CLAI&o
1. Campholenic derivatives of general formula (I)
Figure imgf000033_0001
wherein
• Rl, R2, R3 , R4 and R5 represent, each independently, a hydrogen atom or a linear or branched C1-C5 alkyl or C2-C5 alkenyl group,
• Y represents a CN, a C(O)R6 or a
CR6(ORa) (ORβ) group, wherein R6 represents a hydrogen atom or a linear or branched C1-C5 alkyl or C2-C5 alkenyl group, and Rα and Rβ represent simultaneously a linear or branched Ci, C2, C3, C4 or C5 alkyl or C2, C3 , C4 or C5 alkenyl group and can form together a cycle,
• the 5-membered ring is saturated or has a double bond between C3 ' and C4 ' in formula ( I ) , and
• the side chain, optionally, has a double bond between Cl and C2 and/or between C3 and C4,
• Provided that the derivative is not 3- methyl-6- (2,2, 3-trimethyl-cyclopent-3-enyl) - hex-4-enal .
2. Campholenic derivatives, according to Claim 1, of general formula (Ia),
Figure imgf000034_0001
wherein
• Rl, R2, R3, R4 and R5 represent, each independently, a hydrogen atom or a linear or branched C1-C5 alkyl or C2-C5 alkenyl group,
• the 5-membered ring is saturated or has a double bond between C3 ' and C4 ' in formula (Ia) , and
• the side chain is optionally unsaturated between Cl and C2 and/or between C3 and C4 in formula (Ia) ,
3. Campholenic derivatives, according to claim 1, of general formula (Ib),
Figure imgf000034_0002
wherein
Rl, R2, R3, R4 and R5 represent, each independently, a hydrogen atom or a linear or branched C1-C5 alkyl or C2-C5 alkenyl group , the 5-membered ring is saturated or has a double bond between C3 ' and C4 ' , the side chain is optionally unsaturated between Cl and C2 and/or between C3 and C4 in formula (Ib) , and • Re represents a hydrogen atom, a linear or branched Ci, C2, C3, C4 or C5 alkyl or C2» C3,
C4 or C5 alkenyl group, preferably, Re is a hydrogen atom or a methyl group, more preferably Re is a hydrogen atom,
• Provided that the derivative is not 3- methyl-6- (2,2, S-trimethyl-cyclopent-S-enyl) - hex-4-enal .
4. Campholenic derivatives, according to claim 1, of general formula (Ic) ,
Figure imgf000035_0001
wherein
• Rl, R2, R3, R4 and R5 represent, each independently, a hydrogen atom or a linear or branched C1-C5 alkyl or C2-C5 alkenyl group,
• the 5-membered ring is saturated or has a double bond between C3 ' and C4 ' in formula (Id) ,
• the side chain is optionally unsaturated between Cl and C2 and/or between C3 and C4 in formula (Id) , and
• R0, and Rβ represent simultaneously a linear or branched Ci, C2, C3, C4 or C5 alkyl or C2, C3, C4 or C5 aikenyl group, preferably, Rα and Rp are simultaneously a methyl or an ethyl group, • Rα and Rβ can form together a cycle, preferably a 5-membered ring or a 6-membered ring.
5. Campholenic derivatives, according to Claim 1, wherein said derivatives are selected in the group comprising: 6- (2 , 2 , S-trimethyl-cyclopent-S-enyl) -hex-4-enenitrile, (4E) -6- (2,2, 3-trimethyl-cyclopent-3-enyl ) -hex-4-enenitrile, (4Z) -6- (2,2, 3-trimethyl-cyclopent-3-enyl) -hex-4-enenitrile, (+) -6- ( (IR) -2,2, S-trimethyl-cyclopent-S-enyl) -hex-4-enenitrile, (- ) - 6-((lS)-2,2, 3 -trimethyl-cyclopent-3-enyl) -hex-4-enenitrile, (4E)-S- ( (IR) -2,2,3-trimethyl-cyclopent-3-enyl) -hex-4- enenitrile, (4Z)-S- ( (IR) -2,2, 3-trimethyl-cyclopent-3-enyl) - hex-4-enenitrile, (4E)-S- ( (IS) -2 , 2 , 3-trimethyl-cyclopent-3- enyl) -hex-4-enenitrile, (4Z) -6- ( (IS) -2 , 2 , 3-trimethyl- cyclopent-3-enyl) -hex-4-enenitrile, 6- (2 , 2 , 3-trimethyl- cyclopentyl) -hex-4-enenitrile, ( 4E) -6- (2 , 2 , 3-trimethyl- cyclopentyl) -hex-4-enenitrile, (4Z) -S- (2 ,2 , 3-trimethyl- cyclopentyl ) -hex-4-enenitrile, 4-methyl-6- (2,2, 3-trimethyl- cyclopent-3-enyl ) -hex-4-enenitrile, (4Z) -4-methyl-6- (2,2,3- trimethyl-cyclopent-3-enyl ) -hex-4-enenitrile, ( 4E) -4-methyl-6- (2,2, 3-trimethyl-cyclopent-3-enyl ) -hex-4-enenitrile, 4-methyl- 6- (2 , 2 , 3-trimethyl-cyclopentyl) -hexanenitrile e,, 4-ethyl-6- (2,2, 3-trimethyl-cyclopentyl) -hexanenitrile, 4 -methyl-6- (2,2, 3-trimethyl-cyclopentyl ) -hex-3-enenitril Iee,, 6- (2,2,3- trimethyl-cyclopent-3-enyl ) -hex-4-enal , (4E) -6- (2,2,3- trimethyl-cyclopent-3-enyl ) -hex-4-enal , (4Z) -6- (2,2,3- trimethyl-cyclopent-3-enyl ) -hex-4-enal , ( + ) -6-(( IR) -2 ,2,3- trimethyl-cyclopent-3-enyl) -hex-4-enal , (-) -6-( ( IS) -2,2,3- trimethyl-cyclopent-3-enyl) -hex-4-enal , (4Z) -6-( ( IR) -2,2,3- trimethyl-cyclopent-3-enyl ) -hex-4-enal , (4Z) -6-(( IS) -2 ,2,3- trimethyl-cyclopent-3-enyl ) -hex-4-enal , (4Z) -6-(( IS) -2,2,3- trimethyl-cyclopent-3-enyl ) -hex-4-enal , (4Z) -6-( ( IR) -2,2,3- trimethyl-cyclopent-3-enyl ) -hex-4-enal , 6- (2 , 2 , 3-trimethyl- cyclopentyl) -hex-4-enal , (4Z) -6- (2 ,2 , 3-trimethyl-cyclopentyl) - hex-4-enal , ( 4E) -6- (2,2, 3-trinaethyl-cyclopentyl) -hex-4-enal , 4-methyl-6- (2,2, S-trimethyl-cyclopent-S-enyl) -hex-4-enal , ( 4E) -4-methyl-6- (2,2, S-trimethyl-cyclopent-S-enyl) -hex-4-enal , (4Z) -4-methyl-6- (2,2, 3-trimethyl-cyclopent-3-enyl) -hex-4-enal, 4-methyl-6- (2,2, 3-trimethyl-cyclopentyl) -hexanal , 4-ethyl-6- (2,2, 3-trimethyl-cyclopentyl ) -hexanal , 3 -methyl-6- (2,2,3- trimethy1-cyclopentyl) -hexanal , 2 , 4-dimethyl-6- (2,2,3- trimethy1-cyclopentyl) -hexanal , 7- (2 , 2 , 3-trimethyl-cyclopent- 3-enyl) -hept-5-en-2-one, (4E) -7- (2, 2, 3-trimethyl-cyclopent-3- enyl) -hept-5-en-2-one, (4Z) -7- (2, 2, 3-trimethyl-cyclopent-3- enyl ) -hept-5-en-2-one, 2- ( 6 , 6-diethoxy-3-ethyl-hexyl) -1,1,5- trimethyl-cyclopentane, 4- ( 6 , 6-diethoxy-hex-2-enyl ) -1 , 5 , 5- trimethyl-cyclopentene, 4- ( ( 2E) -6 , 6-diethoxy-hex-2-enyl ) - 1,5, 5-trimethyl-cyclopentene, 4- ( (2Z) -6, 6-diethoxy-hex-2- enyl) -1,5, 5-trimethyl-cyclopentene .
6. Fragrant or flavouring composition containing at least one campholenic derivative according to any one of claims 1 to 5, and/or 3-methyl-6- (2 , 2 , 3-trimethyl-cyclopent-3- enyl) -hex-4-enal .
7. Use of a campholenic derivative according to anyone of claims 1 to 5, and/or 3 -methyl-6- (2 , 2 , 3-trimethyl- cyclopent-3-enyl) -hex-4-enal, or of a composition according to Claim 6, in perfumery for the preparation of perfumed bases and concentrates, fragrances, perfumes and similar products; topic compositions; cosmetic compositions such as face and body cream, cleansers, facial treatment, talc powders, hair oils, shampoos, hair lotions, bath oils and salts, shower and bath gels, soaps, body anti-perspirants and deodorizers, pre- shave, shaving and post-shave creams and lotions, creams, toothpastes, mouth baths, pomades; cleaning products, such as softeners, detergents, air deodorizers and household cleaning supplies .
8. Use of a campholenic derivative according to anyone of claims 1 to 5, and/or 3 -methyl-6- (2 , 2 , 3-trimethyl- cyclopent-3-enyl) -hex-4-enal, or of a composition according to Claim 6, as flavouring agents for the preparation of flavouring compositions or articles, such as drinks, dairy products, ice creams, soups, sauces, dips, dishes, meat products, culinary assistances, salted biscuits or snacks and also beers, wines and tobaccos.
9. Use of a campholenic derivative according to anyone of claims 1 to 5, and/or 3 -methyl-6- (2 , 2 , 3-trimethyl- cyclopent-3-enyl) -hex-4-enal, or of a composition according to Claim 6, as masking agents of odours and/or flavours, notably in a pharmaceutical, cosmetic or food composition.
10. Use of a campholenic derivative according to anyone of claims 1 to 5, and/or 3-methyl-6- (2 , 2 , 3-trimethyl- cyclopent-3-enyl) -hex-4-enal, or of a composition according to Claim 6, in combination with other perfumed or flavoured ingredients, solvents or additives.
PCT/EP2007/063435 2006-12-08 2007-12-06 Use of campholenic derivatives as fragrant ingredients in perfumery and flavouring WO2008068310A1 (en)

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EP07847910A EP2094650B1 (en) 2006-12-08 2007-12-06 Use of campholenic derivatives as fragrant ingredients in perfumery and flavouring
AT07847910T ATE525347T1 (en) 2006-12-08 2007-12-06 USE OF CAMPHOLE DERIVATIVES AS FRAGRANCE INGREDIENTS IN PERFUME AND FLAVORS
DK07847910.2T DK2094650T3 (en) 2006-12-08 2007-12-06 Use of campholene derivatives as fragrance ingredients in perfumes and flavors
MX2009006094A MX2009006094A (en) 2006-12-08 2007-12-06 Use of campholenic derivatives as fragrant ingredients in perfumery and flavouring.
ES07847910T ES2373865T3 (en) 2006-12-08 2007-12-06 USE OF CANPHOLENIC DERIVATIVES AS COMPONENTS OF FRAGRANCE IN PERFUMERY AND AROMATIZATION.
PL07847910T PL2094650T3 (en) 2006-12-08 2007-12-06 Use of campholenic derivatives as fragrant ingredients in perfumery and flavouring
BRPI0719945-7A BRPI0719945A2 (en) 2006-12-08 2007-12-06 Use of campholenic derivatives as perfumed ingredients in perfumery and fragrances
JP2009539758A JP2010511677A (en) 2006-12-08 2007-12-06 Use of camphorenic derivatives as aroma components in fragrances and flavorings

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013034657A1 (en) * 2011-09-07 2013-03-14 Givaudan Sa Fragrance compounds and compositions
US20160207862A1 (en) * 2013-09-06 2016-07-21 Takasago International Corporation Fragrance composition
WO2019122236A1 (en) 2017-12-21 2019-06-27 Firmenich Sa Method for identifying positive allosteric modulators for odorant receptors
WO2020127325A2 (en) 2018-12-19 2020-06-25 Firmenich Sa Use of volatile compounds to modulate the perception of floral muguet

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5839191B2 (en) * 2012-01-18 2016-01-06 高砂香料工業株式会社 Camphorenic derivative and perfume composition containing the same
JP5921226B2 (en) * 2012-02-02 2016-05-24 花王株式会社 How to search for Meuge flavor materials

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL130019B2 (en) * 1981-07-15 1984-06-30 Process for manufacture of odorizing agent
EP0466019A2 (en) * 1990-07-12 1992-01-15 Givaudan-Roure (International) S.A. Derivatives of dihydro campholenic aldehyde
EP1067118A1 (en) * 1999-07-05 2001-01-10 Givaudan SA Cyclopentylalkyl-nitriles and the use of odoriferous cyclopentylalkyl derivatives as fragrances

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3726418A1 (en) * 1987-08-07 1989-02-16 Dragoco Gerberding Co Gmbh USE OF CAMPHOLEN NITRILE AS A FRAGRANCE
ES2216757T3 (en) * 1999-07-05 2004-11-01 Givaudan Sa CYCLOPENTILALQUILNITRILOS AND THE USE OF ODORIFEROS CYCLOPENTILALQUILO DERIVATIVES AS FRAGRANCES.

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL130019B2 (en) * 1981-07-15 1984-06-30 Process for manufacture of odorizing agent
EP0466019A2 (en) * 1990-07-12 1992-01-15 Givaudan-Roure (International) S.A. Derivatives of dihydro campholenic aldehyde
EP1067118A1 (en) * 1999-07-05 2001-01-10 Givaudan SA Cyclopentylalkyl-nitriles and the use of odoriferous cyclopentylalkyl derivatives as fragrances

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DATABASE CAPLUS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; DERDZINSKI, KRZYSZTOF ET AL: "Preparation of 3-methyl-6-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-hexenol stereoisomers as perfume ingredients", XP002436398, retrieved from STN Database accession no. 1988:529379 *
WAWRZENCZYK, C. ET AL: "Juvenoids with cyclopentene ring. Synthesis of isopropyl 3,7-dimethyl-10-(2,2,3-trimethylcyclopent-3-en-1-yl)deca-2,8-dienoate and deca-2,4,8-trienoate", JOURNAL FUER PRAKTISCHE CHEMIE, vol. 326, no. 2, 1984, pages 213 - 221, XP009084701 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013034657A1 (en) * 2011-09-07 2013-03-14 Givaudan Sa Fragrance compounds and compositions
US9109186B2 (en) 2011-09-07 2015-08-18 Givaudan S.A. Fragrance compounds and compositions
US20160207862A1 (en) * 2013-09-06 2016-07-21 Takasago International Corporation Fragrance composition
EP3042891A4 (en) * 2013-09-06 2017-04-12 Takasago International Corporation Fragrance composition
US9643908B2 (en) * 2013-09-06 2017-05-09 Takasago International Corporation Fragrance composition
WO2019122236A1 (en) 2017-12-21 2019-06-27 Firmenich Sa Method for identifying positive allosteric modulators for odorant receptors
WO2020127325A2 (en) 2018-12-19 2020-06-25 Firmenich Sa Use of volatile compounds to modulate the perception of floral muguet

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