WO2003011802A1 - ISO-β-BISABOLOL ALS DUFT-UND AROMASTOFF - Google Patents
ISO-β-BISABOLOL ALS DUFT-UND AROMASTOFF Download PDFInfo
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- WO2003011802A1 WO2003011802A1 PCT/EP2002/007546 EP0207546W WO03011802A1 WO 2003011802 A1 WO2003011802 A1 WO 2003011802A1 EP 0207546 W EP0207546 W EP 0207546W WO 03011802 A1 WO03011802 A1 WO 03011802A1
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- WIPO (PCT)
- Prior art keywords
- bisabolol
- iso
- configuration
- mixture
- fragrance
- Prior art date
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- 239000003205 fragrance Substances 0.000 title claims abstract description 41
- 239000000126 substance Substances 0.000 title abstract description 20
- 229940036350 bisabolol Drugs 0.000 title 1
- UZUXPANAZFDWJO-UHFFFAOYSA-N iso-beta-bisabolol Natural products CC(=C)CCCC(C)C1(O)CCC(C)=CC1 UZUXPANAZFDWJO-UHFFFAOYSA-N 0.000 claims abstract description 80
- WTVHAMTYZJGJLJ-HUUCEWRRSA-N (1s)-4-methyl-1-[(2r)-6-methylhept-5-en-2-yl]cyclohex-3-en-1-ol Chemical compound CC(C)=CCC[C@@H](C)[C@]1(O)CCC(C)=CC1 WTVHAMTYZJGJLJ-HUUCEWRRSA-N 0.000 claims abstract description 78
- 239000000203 mixture Substances 0.000 claims abstract description 58
- 238000000034 method Methods 0.000 claims description 16
- 238000000926 separation method Methods 0.000 claims description 11
- 240000000513 Santalum album Species 0.000 claims description 9
- 235000008632 Santalum album Nutrition 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 9
- FQTLCLSUCSAZDY-UHFFFAOYSA-N (+) E(S) nerolidol Natural products CC(C)=CCCC(C)=CCCC(C)(O)C=C FQTLCLSUCSAZDY-UHFFFAOYSA-N 0.000 claims description 6
- FQTLCLSUCSAZDY-SDNWHVSQSA-N (6E)-nerolidol Chemical compound CC(C)=CCC\C(C)=C\CCC(C)(O)C=C FQTLCLSUCSAZDY-SDNWHVSQSA-N 0.000 claims description 6
- 238000004817 gas chromatography Methods 0.000 claims description 6
- WASNIKZYIWZQIP-AWEZNQCLSA-N nerolidol Natural products CC(=CCCC(=CCC[C@@H](O)C=C)C)C WASNIKZYIWZQIP-AWEZNQCLSA-N 0.000 claims description 6
- CXUNYWSOIZUEAV-UHFFFAOYSA-N 2,6-dimethyl-2-(4-methylpent-4-enyl)-1-oxaspiro[2.5]oct-5-ene Chemical compound CC(=C)CCCC1(C)OC11CC=C(C)CC1 CXUNYWSOIZUEAV-UHFFFAOYSA-N 0.000 claims description 5
- FQTLCLSUCSAZDY-ATGUSINASA-N Nerolidol Chemical compound CC(C)=CCC\C(C)=C\CC[C@](C)(O)C=C FQTLCLSUCSAZDY-ATGUSINASA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 230000002829 reductive effect Effects 0.000 claims description 3
- XCQMKMYPKNZRCW-UHFFFAOYSA-N 3,7,11-trimethyldodeca-1,6,11-trien-3-ol Chemical compound CC(=C)CCCC(C)=CCCC(C)(O)C=C XCQMKMYPKNZRCW-UHFFFAOYSA-N 0.000 claims description 2
- 230000002708 enhancing effect Effects 0.000 claims description 2
- 238000007363 ring formation reaction Methods 0.000 claims description 2
- 238000003821 enantio-separation Methods 0.000 claims 1
- 125000003700 epoxy group Chemical group 0.000 claims 1
- 239000002243 precursor Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 10
- 241000234435 Lilium Species 0.000 abstract description 2
- 230000004048 modification Effects 0.000 abstract description 2
- 238000012986 modification Methods 0.000 abstract description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 38
- 239000000243 solution Substances 0.000 description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- 239000012074 organic phase Substances 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- IZMWJUPSQXIVDN-UHFFFAOYSA-N 4-bromo-2-methylbut-1-ene Chemical compound CC(=C)CCBr IZMWJUPSQXIVDN-UHFFFAOYSA-N 0.000 description 6
- POKCGQXKNIJLCR-UHFFFAOYSA-N 4-methylcyclohex-3-en-1-one Chemical compound CC1=CCC(=O)CC1 POKCGQXKNIJLCR-UHFFFAOYSA-N 0.000 description 6
- 239000002274 desiccant Substances 0.000 description 6
- 239000010671 sandalwood oil Substances 0.000 description 6
- 230000001953 sensory effect Effects 0.000 description 6
- 241000755716 Convallaria Species 0.000 description 5
- 235000009046 Convallaria majalis Nutrition 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 238000006735 epoxidation reaction Methods 0.000 description 4
- 238000004508 fractional distillation Methods 0.000 description 4
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 4
- OVKDFILSBMEKLT-UHFFFAOYSA-N p-Mentha-1,8-dien-4-ol Chemical compound CC(=C)C1(O)CCC(C)=CC1 OVKDFILSBMEKLT-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 150000005671 trienes Chemical class 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 238000003747 Grignard reaction Methods 0.000 description 3
- RKOTXQYWCBGZLP-UHFFFAOYSA-N N-[(2,4-difluorophenyl)methyl]-2-ethyl-9-hydroxy-3-methoxy-1,8-dioxospiro[3H-pyrido[1,2-a]pyrazine-4,3'-oxolane]-7-carboxamide Chemical compound CCN1C(OC)C2(CCOC2)N2C=C(C(=O)NCC3=C(F)C=C(F)C=C3)C(=O)C(O)=C2C1=O RKOTXQYWCBGZLP-UHFFFAOYSA-N 0.000 description 3
- 239000012159 carrier gas Substances 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- UZUXPANAZFDWJO-CABCVRRESA-N (1r)-4-methyl-1-[(2r)-6-methylhept-6-en-2-yl]cyclohex-3-en-1-ol Chemical compound CC(=C)CCC[C@@H](C)[C@@]1(O)CCC(C)=CC1 UZUXPANAZFDWJO-CABCVRRESA-N 0.000 description 2
- QAQYEKYGWFCCSV-UHFFFAOYSA-N 2-(1-hydroxy-4-methylcyclohex-3-en-1-yl)propyl 4-methylbenzenesulfonate Chemical compound C1CC(C)=CCC1(O)C(C)COS(=O)(=O)C1=CC=C(C)C=C1 QAQYEKYGWFCCSV-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- MTFXRMMKOMFBRP-UHFFFAOYSA-N 6-bromo-2-methylhept-1-ene Chemical compound CC(Br)CCCC(C)=C MTFXRMMKOMFBRP-UHFFFAOYSA-N 0.000 description 2
- 101710134784 Agnoprotein Proteins 0.000 description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 2
- 235000019568 aromas Nutrition 0.000 description 2
- 229940074775 beta-bisabolol Drugs 0.000 description 2
- 238000003965 capillary gas chromatography Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 150000002924 oxiranes Chemical class 0.000 description 2
- 230000008447 perception Effects 0.000 description 2
- 238000012746 preparative thin layer chromatography Methods 0.000 description 2
- 229940090181 propyl acetate Drugs 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- HMUPSIMESDUGFM-UHFFFAOYSA-N 1-(1-hydroxypropan-2-yl)-4-methylcyclohex-3-en-1-ol Chemical compound OCC(C)C1(O)CCC(C)=CC1 HMUPSIMESDUGFM-UHFFFAOYSA-N 0.000 description 1
- HXXQHOCALKIDMB-UHFFFAOYSA-N 1-methyl-4-(6-methylhept-6-en-2-yl)cyclohexene Chemical compound CC(=C)CCCC(C)C1CCC(C)=CC1 HXXQHOCALKIDMB-UHFFFAOYSA-N 0.000 description 1
- XWPIATLQDLHMJV-UHFFFAOYSA-N 2-[4-methyl-1-(4-methylphenyl)sulfonyloxycyclohex-3-en-1-yl]propyl 4-methylbenzenesulfonate Chemical compound C1CC(C)=CCC1(OS(=O)(=O)C=1C=CC(C)=CC=1)C(C)COS(=O)(=O)C1=CC=C(C)C=C1 XWPIATLQDLHMJV-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- AMKGKYQBASDDJB-UHFFFAOYSA-N 9$l^{2}-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1[B]2 AMKGKYQBASDDJB-UHFFFAOYSA-N 0.000 description 1
- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 241000221035 Santalaceae Species 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000006197 hydroboration reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000001256 steam distillation Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000007070 tosylation reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C35/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring
- C07C35/02—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring monocyclic
- C07C35/08—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring monocyclic containing a six-membered rings
- C07C35/18—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring monocyclic containing a six-membered rings with unsaturation at least in the ring
-
- 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
Definitions
- the invention relates to the new substance iso- ⁇ -bisabolol, i.e. (1S / R) -1 - [(1 S / R) - 1, 5-dimethyl-hex-5-enyl] -4-methyl-cyclohex-3-en-1-ol and its use as a fragrance and / or flavoring.
- the invention further relates to preferred configuration isomers (diastereomers, enantiomers) of iso- ⁇ -bisabolol with particularly pronounced sensory properties and corresponding mixtures of configuration isomers.
- the invention also relates to fragrance and / or flavoring compositions which comprise an organoleptically active (effective) amount of iso- ⁇ -bisabolol or one or more configuration isomers of iso- ⁇ -bisabolol.
- the invention also relates to methods for modifying a fragrance or aroma composition and methods for imparting or enhancing a fragrance or aroma to a basic composition using iso- ⁇ -bisabolol (or the corresponding configuration isomers). Finally, the invention also relates to methods for the production or manufacture of iso-ß-bisabolol, 'its configurational isomers and the corresponding mixtures of configurational isomers.
- fragrances and aromas that can be produced cheaply and with consistent quality, remain stable in contact with other substances if possible, and have desired olfactory or taste properties.
- Fragrances should have pleasant, near-natural scent notes of sufficient intensity and should be able to influence the fragrance of cosmetic or technical consumer goods in an advantageous manner.
- Flavorings should be well tolerated, be pronounced of typical flavor components of popular dishes or even be identical to them and be able to contribute to positively influencing the taste of foods, orally administered medicaments and the like. Finding fragrance and aroma substances that meet these requirements has proven to be relatively complex and regularly requires extensive investigations, in particular if interesting novel fragrance notes or flavors are sought.
- Flavoring substances on the other hand, have not been sufficiently researched.
- the object of the present invention is to provide a fragrance and aroma substance, taking into account the general framework conditions described above, which is particularly capable of imparting a floral, lily-of-the-valley fragrance to conventional fragrance or aroma base compositions, or the existing fragrance of such compositions to modify advantageously.
- the substances to be specified should offer the perfumer or flavorist a versatile alternative to the fragrances with floral fragrance previously used or described when composing fragrances or aromas.
- a lengthy process that is usually only carried out by specialists, it is not enough to achieve a fragrance or aroma image that already exists in the imagination, to use any fragrance or aroma substance in the manner of a template, that in the literature a certain smell or aroma aspect has been assigned.
- the smell or aroma characteristics of a composition cannot be precisely predicted in the sense of an addition if only the components of the composition are known, because these components are subject to unpredictable interactions in the mixture.
- the invention is based on the surprising finding that the new substance iso- ⁇ -bisabolol according to formula A below and its configuration isomers according to formulas 1-4 below are outstandingly suitable for use as a fragrance and aroma substance and for solving the above-mentioned objects.
- Iso-ß-bisabolol has a very strongly floral, lily-of-the-valley and extremely pleasant smell, so that even small amounts of this substance can cause a sensorially perceptible modification of a fragrance or aroma (basic) composition.
- the configuration isomers of iso-ß-bisabolol with R configuration on the (hydroxy-functionalized) C1 are particularly effective in terms of sensors. Accordingly, mixtures of two or more configuration isomers of iso- ⁇ -bisabolol are preferred in which the molar ratio of configuration isomers with R configuration at C1 to configuration isomers with S configuration at C1 is greater than 1 and preferably greater than 2.
- Individual configuration isomers and mixtures of two or three configuration isomers of iso- ⁇ -bisabolol can be obtained by conventional separation operations using chiral auxiliaries from a mixture which contains all of the configuration isomers of iso- ⁇ -bisabolol.
- a mixture or a fraction of such a mixture can be separated by means of chiral gas chromatography, in which case it is then possible in particular to separate the configuration isomers configured at the C1 atom R (particularly valuable in terms of sensors) from the corresponding S-configured isomers, cf. see the examples below.
- Fragrance and / or flavoring compositions according to the invention comprise an organoleptically active (effective) amount of iso- ⁇ -bisabolol, it being possible to use both a single and a mixture of a plurality of configuration isomers of iso- ⁇ -bisabolol.
- Configuration isomers with R configuration on the C1 atom are again preferably used, in particular (R, R) -Iso- ⁇ -bisabolol.
- the S-configured configuration isomers can also be used in a corresponding manner.
- Existing fragrance or aroma compositions can be added by adding a fragrance or aroma-modifying amount of iso-ß-bisabolol (with the aforementioned preferences regarding the configuration isomers) modified, that is, changed with regard to their sensory properties.
- existing fragrance or aroma compositions can be given a floral, lily-of-the-valley-like odor by adding iso- ⁇ -bisabolol.
- a sensory effective amount of iso-ß-bisabolol (again with the above-mentioned preferences with regard to the configuration isomers) can be used to impart or intensify a fragrance or aroma of a basic composition which, for example, is not or only weakly fragrant in the absence of iso-ß-bisabolol ) and the components of the basic composition are mixed.
- Iso-ß-bisabolol is a naturally occurring substance, which z. B. from East Indian sandalwood oil.
- GC-sniffing column: DBWax
- DBWax GC-sniffing of East Indian sandalwood revealed a sensorially unknown compound that could subsequently be identified as iso-ß-bisabolol (see the examples here further down).
- East Indian sandalwood oil which is made from the heartwood of Santalum album L. (Santalaceae) by steam distillation, is known as one of the oldest perfume raw materials (cf.Lit .: EJ Brunke, K.-G. Fahlbusch, G.
- Iso-ß-bisabolol can also be obtained by 3,7,11-trimethyl-1, 6,10-dodecatrien-3-ol [CAS-No. 7212-44-4] (nerolidol) and / or 3,7,11-trimethyl-1,6,11-dodecatrien-3-ol [CAS no. 22143-53-5] (isonerolidol) is cyclized in the presence of acid so that iso-ß-bisabolol, optionally along with other cyclization products, is formed.
- Example 1 Synthesis of (1S / R) -1 - [(1S / R) -1,5-dimethyl-hex-5-enyl] -4-methyl-cyclohex-3-en-1-ol, i.e. Iso-ß-bisabolol
- the above-mentioned route epoxidation, reductive epoxide opening
- diastereomerically pure, racemic iso-ß-bisabolol can be prepared.
- the Grignard compound is prepared under standard conditions: 4-bromo-2-methyl-but-1 dissolved in THF (5 ml) is slowly added dropwise to Mg chips (0.40 g, 16.5 mmol) in Et 2 O (10 ml) -en [CAS-No .: 20038-12-4] (2.0 g, 13.4 mmol) to; a cloudiness shows the start of the reaction.
- the mixture is heated under reflux for a further 30 min and then cooled to -10 ° C.
- a 0.1 M solution of Li 2 [CuCl] (5 ml, 0.5 mmol) in THF is added dropwise and stirring is continued at -10 ° C. for 30 min.
- the tosylate to be used is in a 2-stage process [I) regioselective hydroboration of 1-isopropenyl-4-methylcyclohex-3-en-1-ol [CAS-No .: 3419-02-1, 28342-82-7, 38630 -70-5, 73069-45-1] and II) subsequent tosylation of the primary hydroxyl function].
- the solution is cooled to 0 ° C., then first H 2 O (6 ml) is added and then 3 M NaOH solution (7.3 ml, 22 mmol) and then 30% H 2 O 2 solution (7.3 ml, 64.4 mmol).
- the mixture is allowed to warm to room temperature and is stirred for a further 3 h.
- the organic phase is separated off and the H 2 O phase is extracted with Et 2 O (2 ⁇ 30 ml).
- the combined organic phases are washed successively with H 2 O (2 ⁇ 20 ml), aqueous NaHSO 3 solution (20 ml) and NaCl solution (20 ml) and dried over Na 2 SO 4 .
- GC-MS Diastereomer a): 170 (13), 155 (2), 152 (23), 139 (6), 121 (27), 111 (62), 110 (64), 102 (100), 95 ( 33), 94 (98), 93 (63), 87 (92), 84 (76), 77 (23), 72 (41), 69 (73), 68 (85), 67 (61), 59 ( 27), 56 (45), 55 (46), 54 (48), 43 (48), 41 (45).
- the Grignard compound is prepared under standard conditions: The 4-bromo-2-methyl-but dissolved in Et 2 O (5 ml) is slowly added dropwise to Mg chips (0.15 g, 6.2 mmol) in Et 2 O (10 ml) -1-en [CAS-No .: 20038-12-4] (0.75 g, 5 mmol) to; a cloudiness shows the start of the reaction. The mixture is heated under reflux for a further 30 min and then cooled to -20 ° C. A 0.1 M solution of Li 2 [CuCl 4 ] (2 ml, 0.2 mmol) in THF is added dropwise and stirring is continued at -20 ° C. for 30 min.
- Example 4 Isolation of Iso- ⁇ -Bisabolol from East Indian Sandelhoizöl (Santalum album)
- Example 5 Synthesis of (1S / R) -1 - [(1S / R) -1,5-dimethyl-hex-5-enyl] -4-methyl-cyclohex-3-en-1-ol, i.e. Iso-ß-bisabolol, and its isolation from the product mixture
- a fraction is sensory due to the presence of a compound with a strongly floral, lily of the valley -like, very pleasant smell. This is iso-ß-bisabolol. This is further enriched by fractional distillation on a Sulzer column.
- the fraction selection is made sensorially (GC sniffing). The sensorically strongest fraction on the Sulzer distillation is then separated by means of column chromatography (silica gel, step gradient hexane / Et 2 O, 1% steps.
- fraction selection is again sensor-based (GC-Sniffi ⁇ g), provided that no peak can be seen in the chromatogram.
- the pure substance is finally isolated by means of two-dimensional preparative capillary gas chromatography [Agilent HP6890;
- Iso-ß-bisabolol from Example 2 (2 diastomeric enantiomer pairs, i.e. a total of 4 configuration isomers) is separated by chiral gas chromatography.
- the conditions of gas chromatography were as follows:
- Carrier gas N 2 (1.4 ml / min) detector GC sniffing, flame ionization detector
- the diastereomer pairs according to formulas 1 and 3 (first pair) or 2 and 4 (second pair) are first separated from the synthetic configuration isomer mixture according to example 2 by means of preparative HPLC (silica gel).
- Suitable HPLC conditions are: Device Knauer HPLC pump 64 sample Synthetic diastereomer mixture (1: 1: 1: 1) Injection 150 ⁇ l 25% solution in the eluent
- GC sniffing shows under the GC conditions according to Example 6 that the compound according to formula -2 has a very strongly floral, lily-of-the-valley, very pleasant smell, while the compounds according to formulas 4, 1, 3 smell weaker.
- the compound of formula 2 is (R, R) -lso-ß-bisabolol, i.e. (1R) -1 - [(1R) -1,5-dimethyl-hex-5-enyl] -4-methyl-cyclohex-3-en-1-ol.
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/483,276 US20040186042A1 (en) | 2001-07-09 | 2002-07-06 | Iso-$g(b)-bisabolol as fragrance and aroma substance |
JP2003516997A JP2004536148A (ja) | 2001-07-09 | 2002-07-06 | 芳香および香気物質としてのイソ−β−ビサボロール |
EP02791446A EP1412313A1 (de) | 2001-07-09 | 2002-07-06 | ISO-$g(b)-BISABOLOL ALS DUFT-UND AROMASTOFF |
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DE10132520.7 | 2001-07-09 | ||
DE10132520 | 2001-07-09 | ||
DE10139290.7 | 2001-08-09 | ||
DE10139290A DE10139290A1 (de) | 2001-08-09 | 2001-08-09 | Iso-ß-Bisabolol als Duft- und Aromastoff |
Publications (1)
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WO2003011802A1 true WO2003011802A1 (de) | 2003-02-13 |
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PCT/EP2002/007546 WO2003011802A1 (de) | 2001-07-09 | 2002-07-06 | ISO-β-BISABOLOL ALS DUFT-UND AROMASTOFF |
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US (1) | US20040186042A1 (de) |
EP (1) | EP1412313A1 (de) |
JP (1) | JP2004536148A (de) |
WO (1) | WO2003011802A1 (de) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108698964A (zh) * | 2016-02-26 | 2018-10-23 | 巴斯夫农业公司 | 制备萜品烯-4-醇的方法 |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
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JP5186696B2 (ja) * | 2006-12-28 | 2013-04-17 | 学校法人日本大学 | ポリエン類の環化反応 |
EP3094615A4 (de) | 2014-01-13 | 2017-11-08 | P2 Science, Inc. | Säuren aus terpen und ester sowie verfahren zur herstellung und verwendung davon |
WO2015191706A1 (en) * | 2014-06-10 | 2015-12-17 | P2 Science, Inc. | Terpene-derived compounds and methods for preparing and using same |
US10071944B2 (en) | 2014-06-20 | 2018-09-11 | P2 Science, Inc. | Film ozonolysis in a tubular or multitubular reactor |
WO2016019074A1 (en) | 2014-07-30 | 2016-02-04 | Georgia-Pacific Consumer Products Lp | Air freshener dispensers, cartridges therefor, systems, and methods |
WO2017144337A1 (en) * | 2016-02-26 | 2017-08-31 | BASF Agro B.V. | Process for preparing a mixture of terpene alcohols |
JP6992057B2 (ja) | 2016-06-10 | 2022-01-13 | クラリティ コスメティックス インコーポレイテッド | 非面皰形成性の毛髪および頭皮ケア製剤ならびにその使用方法 |
JP7028457B2 (ja) | 2016-06-21 | 2022-03-02 | ピー2・サイエンス・インコーポレイテッド | 過酸化物混合物の連続クエンチのためのフロースルー反応器およびそれを含む方法 |
US10696605B2 (en) | 2016-09-16 | 2020-06-30 | P2 Science, Inc. | Uses of vanadium to oxidize aldehydes and ozonides |
JP2022505298A (ja) | 2018-10-19 | 2022-01-14 | ピー2・サイエンス・インコーポレイテッド | オゾニドの不均化クエンチの新規方法 |
US20220168198A1 (en) | 2019-01-17 | 2022-06-02 | Symrise Ag | An antimicrobial mixture |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5089469A (en) * | 1991-04-25 | 1992-02-18 | International Flavors & Fragrances Inc. | Bisabolene-containing composition, process for preparing same, organoleptic uses thereof and uses thereof as insect repellent |
EP1189860B1 (de) * | 1999-06-28 | 2004-10-06 | Quest International B.V. | Riechstoffe |
-
2002
- 2002-07-06 US US10/483,276 patent/US20040186042A1/en not_active Abandoned
- 2002-07-06 EP EP02791446A patent/EP1412313A1/de not_active Withdrawn
- 2002-07-06 WO PCT/EP2002/007546 patent/WO2003011802A1/de not_active Application Discontinuation
- 2002-07-06 JP JP2003516997A patent/JP2004536148A/ja active Pending
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Title |
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ALPHA T ET AL: "Bisabolane sesquiterpenoids from Santalum austrocaledonicum", PHYTOCHEMISTRY, PERGAMON PRESS, GB, vol. 44, no. 8, April 1997 (1997-04-01), pages 1519 - 1522, XP004293011, ISSN: 0031-9422 * |
FLEISCHER T C ET AL: "Bisabolene sesquiterpenes and flavonoids from Friesodielsia enghiana", PHYTOCHEMISTRY, PERGAMON PRESS, GB, vol. 44, no. 2, January 1997 (1997-01-01), pages 315 - 318, XP004292790, ISSN: 0031-9422 * |
FRATER G ET AL: "Fragrance Chemistry", TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 54, no. 27, 2 July 1998 (1998-07-02), pages 7633 - 7703, XP004122481, ISSN: 0040-4020 * |
J. FALBE, M. REGITZ: "Römpp Lexikon, Chemie", 1996, GEORG THIEME VERLAG, STUTTGART, XP002216079 * |
R. FURSTOSS: "Microbiological Transformations. 27. The First Examples for Preparative-Scale Enantioselective or Diastereoselective Epoxide Hydrolyses Using Microorganisms. An Unequivocal Access to All Four Bisabolol Stereoisomers", J. ORG. CHEM., vol. 58, no. 20, 1993, pages 5528 - 5532, XP002216078 * |
VIG O P ET AL: "Terpenoids. XCII. A new route towards the synthesis of.gamma.-bisabolene", JOURNAL OF THE INDIAN CHEMICAL SOCIETY, THE INDIAN CHEMICAL SOCIETY, vol. LII, 1975, Calcutta, pages 614 - 616, XP002075193, ISSN: 0019-4522 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108698964A (zh) * | 2016-02-26 | 2018-10-23 | 巴斯夫农业公司 | 制备萜品烯-4-醇的方法 |
CN108698964B (zh) * | 2016-02-26 | 2021-12-24 | 巴斯夫农业公司 | 制备萜品烯-4-醇的方法 |
Also Published As
Publication number | Publication date |
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EP1412313A1 (de) | 2004-04-28 |
JP2004536148A (ja) | 2004-12-02 |
US20040186042A1 (en) | 2004-09-23 |
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