EP4255879A1 - Procédé de préparation de frambinone - Google Patents
Procédé de préparation de frambinoneInfo
- Publication number
- EP4255879A1 EP4255879A1 EP21819879.4A EP21819879A EP4255879A1 EP 4255879 A1 EP4255879 A1 EP 4255879A1 EP 21819879 A EP21819879 A EP 21819879A EP 4255879 A1 EP4255879 A1 EP 4255879A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- equal
- frambinone
- compound
- phenol
- acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- NJGBTKGETPDVIK-UHFFFAOYSA-N raspberry ketone Chemical compound CC(=O)CCC1=CC=C(O)C=C1 NJGBTKGETPDVIK-UHFFFAOYSA-N 0.000 title claims abstract description 66
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 15
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims abstract description 104
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 claims abstract description 96
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 104
- 150000001875 compounds Chemical class 0.000 claims description 67
- 238000000034 method Methods 0.000 claims description 36
- 229910052799 carbon Inorganic materials 0.000 claims description 28
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 24
- 238000009833 condensation Methods 0.000 claims description 21
- 230000005494 condensation Effects 0.000 claims description 21
- 238000002360 preparation method Methods 0.000 claims description 14
- BVJSUAQZOZWCKN-UHFFFAOYSA-N p-hydroxybenzyl alcohol Chemical compound OCC1=CC=C(O)C=C1 BVJSUAQZOZWCKN-UHFFFAOYSA-N 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 230000000155 isotopic effect Effects 0.000 claims description 11
- 239000002304 perfume Substances 0.000 claims description 5
- 235000013305 food Nutrition 0.000 claims description 4
- 239000002537 cosmetic Substances 0.000 claims description 3
- 238000009472 formulation Methods 0.000 claims description 3
- 235000013361 beverage Nutrition 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- 238000006243 chemical reaction Methods 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 23
- 239000002585 base Substances 0.000 description 21
- 239000002253 acid Substances 0.000 description 20
- 239000012535 impurity Substances 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 239000003054 catalyst Substances 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 13
- 150000001299 aldehydes Chemical class 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 238000006482 condensation reaction Methods 0.000 description 9
- 229910052751 metal Inorganic materials 0.000 description 8
- -1 2-acetyl-2-hydroxym ethyl ethyl Chemical group 0.000 description 7
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 239000003638 chemical reducing agent Substances 0.000 description 7
- 238000007254 oxidation reaction Methods 0.000 description 7
- 235000011121 sodium hydroxide Nutrition 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000002184 metal Substances 0.000 description 6
- 229910052759 nickel Inorganic materials 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 5
- 150000001298 alcohols Chemical class 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 5
- POILWHVDKZOXJZ-ARJAWSKDSA-M (z)-4-oxopent-2-en-2-olate Chemical compound C\C([O-])=C\C(C)=O POILWHVDKZOXJZ-ARJAWSKDSA-M 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 239000012736 aqueous medium Substances 0.000 description 4
- 230000003851 biochemical process Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 229910017052 cobalt Inorganic materials 0.000 description 4
- 239000010941 cobalt Substances 0.000 description 4
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 4
- XLJKHNWPARRRJB-UHFFFAOYSA-N cobalt(2+) Chemical compound [Co+2] XLJKHNWPARRRJB-UHFFFAOYSA-N 0.000 description 4
- 239000013065 commercial product Substances 0.000 description 4
- 235000013399 edible fruits Nutrition 0.000 description 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 4
- 229910052742 iron Inorganic materials 0.000 description 4
- AQBLLJNPHDIAPN-LNTINUHCSA-K iron(3+);(z)-4-oxopent-2-en-2-olate Chemical compound [Fe+3].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O AQBLLJNPHDIAPN-LNTINUHCSA-K 0.000 description 4
- 229910052697 platinum Inorganic materials 0.000 description 4
- 235000011118 potassium hydroxide Nutrition 0.000 description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 3
- VEQPNABPJHWNSG-UHFFFAOYSA-N Nickel(2+) Chemical class [Ni+2] VEQPNABPJHWNSG-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 239000007868 Raney catalyst Substances 0.000 description 3
- 229910000564 Raney nickel Inorganic materials 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 150000001340 alkali metals Chemical class 0.000 description 3
- 150000001491 aromatic compounds Chemical class 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Chemical compound [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 229910052748 manganese Inorganic materials 0.000 description 3
- 239000011572 manganese Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 230000020477 pH reduction Effects 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 description 3
- 229940031826 phenolate Drugs 0.000 description 3
- 239000012429 reaction media Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 229910052703 rhodium Inorganic materials 0.000 description 3
- 229910052707 ruthenium Inorganic materials 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 229910052723 transition metal Inorganic materials 0.000 description 3
- 150000003624 transition metals Chemical class 0.000 description 3
- LFKXWKGYHQXRQA-FDGPNNRMSA-N (z)-4-hydroxypent-3-en-2-one;iron Chemical compound [Fe].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O LFKXWKGYHQXRQA-FDGPNNRMSA-N 0.000 description 2
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 2
- LVSQXDHWDCMMRJ-UHFFFAOYSA-N 4-hydroxybutan-2-one Chemical compound CC(=O)CCO LVSQXDHWDCMMRJ-UHFFFAOYSA-N 0.000 description 2
- YHXHKYRQLYQUIH-UHFFFAOYSA-N 4-hydroxymandelic acid Chemical compound OC(=O)C(O)C1=CC=C(O)C=C1 YHXHKYRQLYQUIH-UHFFFAOYSA-N 0.000 description 2
- PMMYEEVYMWASQN-UHFFFAOYSA-N 4-hydroxyproline Chemical compound OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 239000005749 Copper compound Substances 0.000 description 2
- JJLJMEJHUUYSSY-UHFFFAOYSA-L Copper hydroxide Chemical compound [OH-].[OH-].[Cu+2] JJLJMEJHUUYSSY-UHFFFAOYSA-L 0.000 description 2
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 2
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 238000004760 accelerator mass spectrometry Methods 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- IADUEWIQBXOCDZ-UHFFFAOYSA-N azetidine-2-carboxylic acid Chemical compound OC(=O)C1CCN1 IADUEWIQBXOCDZ-UHFFFAOYSA-N 0.000 description 2
- FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 description 2
- 150000001720 carbohydrates Chemical group 0.000 description 2
- GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 2
- UFMZWBIQTDUYBN-UHFFFAOYSA-N cobalt dinitrate Chemical compound [Co+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O UFMZWBIQTDUYBN-UHFFFAOYSA-N 0.000 description 2
- ZOTKGJBKKKVBJZ-UHFFFAOYSA-L cobalt(2+);carbonate Chemical compound [Co+2].[O-]C([O-])=O ZOTKGJBKKKVBJZ-UHFFFAOYSA-L 0.000 description 2
- 229910000001 cobalt(II) carbonate Inorganic materials 0.000 description 2
- 239000007859 condensation product Substances 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 150000001880 copper compounds Chemical class 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
- 229910052805 deuterium Inorganic materials 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 2
- 238000007210 heterogeneous catalysis Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 150000004679 hydroxides Chemical class 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- PVFSDGKDKFSOTB-UHFFFAOYSA-K iron(3+);triacetate Chemical compound [Fe+3].CC([O-])=O.CC([O-])=O.CC([O-])=O PVFSDGKDKFSOTB-UHFFFAOYSA-K 0.000 description 2
- VCJMYUPGQJHHFU-UHFFFAOYSA-N iron(3+);trinitrate Chemical compound [Fe+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O VCJMYUPGQJHHFU-UHFFFAOYSA-N 0.000 description 2
- LNOZJRCUHSPCDZ-UHFFFAOYSA-L iron(ii) acetate Chemical compound [Fe+2].CC([O-])=O.CC([O-])=O LNOZJRCUHSPCDZ-UHFFFAOYSA-L 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 229920005610 lignin Polymers 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- UPWOEMHINGJHOB-UHFFFAOYSA-N oxo(oxocobaltiooxy)cobalt Chemical compound O=[Co]O[Co]=O UPWOEMHINGJHOB-UHFFFAOYSA-N 0.000 description 2
- VWMVAQHMFFZQGD-UHFFFAOYSA-N p-Hydroxybenzyl acetone Natural products CC(=O)CC1=CC=C(O)C=C1 VWMVAQHMFFZQGD-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- VYXHVRARDIDEHS-QGTKBVGQSA-N (1z,5z)-cycloocta-1,5-diene Chemical compound C\1C\C=C/CC\C=C/1 VYXHVRARDIDEHS-QGTKBVGQSA-N 0.000 description 1
- IWYDHOAUDWTVEP-ZETCQYMHSA-N (S)-mandelic acid Chemical compound OC(=O)[C@@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-ZETCQYMHSA-N 0.000 description 1
- WLIADPFXSACYLS-RQOWECAXSA-N (z)-1,3-dichlorobut-2-ene Chemical compound C\C(Cl)=C\CCl WLIADPFXSACYLS-RQOWECAXSA-N 0.000 description 1
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
- XHZMLDOBAFNUKC-UHFFFAOYSA-N 1-diphenylphosphanylethyl(diphenyl)phosphane;nickel Chemical compound [Ni].C=1C=CC=CC=1P(C=1C=CC=CC=1)C(C)P(C=1C=CC=CC=1)C1=CC=CC=C1 XHZMLDOBAFNUKC-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- TWLSOWAQVSIFIF-UHFFFAOYSA-M 2-hydroxy-2-(2-hydroxyphenyl)acetate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1O TWLSOWAQVSIFIF-UHFFFAOYSA-M 0.000 description 1
- 102100027324 2-hydroxyacyl-CoA lyase 1 Human genes 0.000 description 1
- PCBSXBYCASFXTM-UHFFFAOYSA-N 4-(4-Methoxyphenyl)-2-butanone Chemical compound COC1=CC=C(CCC(C)=O)C=C1 PCBSXBYCASFXTM-UHFFFAOYSA-N 0.000 description 1
- OQWHXHYZFMIILA-UHFFFAOYSA-N 4-acetyloxypyrrolidine-2-carboxylic acid Chemical compound CC(=O)OC1CNC(C(O)=O)C1 OQWHXHYZFMIILA-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- IADUEWIQBXOCDZ-VKHMYHEASA-N Azetidine-2-carboxylic acid Natural products OC(=O)[C@@H]1CCN1 IADUEWIQBXOCDZ-VKHMYHEASA-N 0.000 description 1
- 239000002028 Biomass Substances 0.000 description 1
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
- 229910021580 Cobalt(II) chloride Inorganic materials 0.000 description 1
- 229910021503 Cobalt(II) hydroxide Inorganic materials 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 101001009252 Homo sapiens 2-hydroxyacyl-CoA lyase 1 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N Na2O Inorganic materials [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910021585 Nickel(II) bromide Inorganic materials 0.000 description 1
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 description 1
- 229910021588 Nickel(II) iodide Inorganic materials 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 241001092459 Rubus Species 0.000 description 1
- 240000007651 Rubus glaucus Species 0.000 description 1
- 235000011034 Rubus glaucus Nutrition 0.000 description 1
- 244000235659 Rubus idaeus Species 0.000 description 1
- 235000009122 Rubus idaeus Nutrition 0.000 description 1
- 235000011941 Tilia x europaea Nutrition 0.000 description 1
- 240000001717 Vaccinium macrocarpon Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000012773 agricultural material Substances 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 235000021029 blackberry Nutrition 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 125000005587 carbonate group Chemical group 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- KTVIXTQDYHMGHF-UHFFFAOYSA-L cobalt(2+) sulfate Chemical compound [Co+2].[O-]S([O-])(=O)=O KTVIXTQDYHMGHF-UHFFFAOYSA-L 0.000 description 1
- ZBDSFTZNNQNSQM-UHFFFAOYSA-H cobalt(2+);diphosphate Chemical compound [Co+2].[Co+2].[Co+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O ZBDSFTZNNQNSQM-UHFFFAOYSA-H 0.000 description 1
- TZWGXFOSKIHUPW-UHFFFAOYSA-L cobalt(2+);propanoate Chemical compound [Co+2].CCC([O-])=O.CCC([O-])=O TZWGXFOSKIHUPW-UHFFFAOYSA-L 0.000 description 1
- JAWGVVJVYSANRY-UHFFFAOYSA-N cobalt(3+) Chemical compound [Co+3] JAWGVVJVYSANRY-UHFFFAOYSA-N 0.000 description 1
- ZUKDFIXDKRLHRB-UHFFFAOYSA-K cobalt(3+);triacetate Chemical compound [Co+3].CC([O-])=O.CC([O-])=O.CC([O-])=O ZUKDFIXDKRLHRB-UHFFFAOYSA-K 0.000 description 1
- IVMYJDGYRUAWML-UHFFFAOYSA-N cobalt(II) oxide Inorganic materials [Co]=O IVMYJDGYRUAWML-UHFFFAOYSA-N 0.000 description 1
- 229910000335 cobalt(II) sulfate Inorganic materials 0.000 description 1
- PKSIZOUDEUREFF-UHFFFAOYSA-N cobalt;dihydrate Chemical compound O.O.[Co] PKSIZOUDEUREFF-UHFFFAOYSA-N 0.000 description 1
- 238000004320 controlled atmosphere Methods 0.000 description 1
- RFKZUAOAYVHBOY-UHFFFAOYSA-M copper(1+);acetate Chemical compound [Cu+].CC([O-])=O RFKZUAOAYVHBOY-UHFFFAOYSA-M 0.000 description 1
- RPJAQOVNRDOGAY-UHFFFAOYSA-L copper(1+);sulfite Chemical compound [Cu+].[Cu+].[O-]S([O-])=O RPJAQOVNRDOGAY-UHFFFAOYSA-L 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- JBAKCAZIROEXGK-LNKPDPKZSA-N copper;(z)-4-hydroxypent-3-en-2-one Chemical compound [Cu].C\C(O)=C\C(C)=O JBAKCAZIROEXGK-LNKPDPKZSA-N 0.000 description 1
- ZKXWKVVCCTZOLD-FDGPNNRMSA-N copper;(z)-4-hydroxypent-3-en-2-one Chemical compound [Cu].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O ZKXWKVVCCTZOLD-FDGPNNRMSA-N 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 229910052593 corundum Inorganic materials 0.000 description 1
- 235000021019 cranberries Nutrition 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 229940076286 cupric acetate Drugs 0.000 description 1
- 229960003280 cupric chloride Drugs 0.000 description 1
- 229960004643 cupric oxide Drugs 0.000 description 1
- 229940045803 cuprous chloride Drugs 0.000 description 1
- KRFJLUBVMFXRPN-UHFFFAOYSA-N cuprous oxide Chemical compound [O-2].[Cu+].[Cu+] KRFJLUBVMFXRPN-UHFFFAOYSA-N 0.000 description 1
- 229940112669 cuprous oxide Drugs 0.000 description 1
- 230000000911 decarboxylating effect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- ZMMDPCMYTCRWFF-UHFFFAOYSA-J dicopper;carbonate;dihydroxide Chemical compound [OH-].[OH-].[Cu+2].[Cu+2].[O-]C([O-])=O ZMMDPCMYTCRWFF-UHFFFAOYSA-J 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229960001867 guaiacol Drugs 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- RUTXIHLAWFEWGM-UHFFFAOYSA-H iron(3+) sulfate Chemical compound [Fe+3].[Fe+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O RUTXIHLAWFEWGM-UHFFFAOYSA-H 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- 229910000360 iron(III) sulfate Inorganic materials 0.000 description 1
- 238000002307 isotope ratio mass spectrometry Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 1
- MRELNEQAGSRDBK-UHFFFAOYSA-N lanthanum oxide Inorganic materials [O-2].[O-2].[O-2].[La+3].[La+3] MRELNEQAGSRDBK-UHFFFAOYSA-N 0.000 description 1
- 239000004571 lime Substances 0.000 description 1
- 238000005567 liquid scintillation counting Methods 0.000 description 1
- 239000011656 manganese carbonate Substances 0.000 description 1
- 235000006748 manganese carbonate Nutrition 0.000 description 1
- 229910000016 manganese(II) carbonate Inorganic materials 0.000 description 1
- XMWCXZJXESXBBY-UHFFFAOYSA-L manganese(ii) carbonate Chemical compound [Mn+2].[O-]C([O-])=O XMWCXZJXESXBBY-UHFFFAOYSA-L 0.000 description 1
- AHSBSUVHXDIAEY-UHFFFAOYSA-K manganese(iii) acetate Chemical compound [Mn+3].CC([O-])=O.CC([O-])=O.CC([O-])=O AHSBSUVHXDIAEY-UHFFFAOYSA-K 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 150000002815 nickel Chemical class 0.000 description 1
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
- LGQLOGILCSXPEA-UHFFFAOYSA-L nickel sulfate Chemical compound [Ni+2].[O-]S([O-])(=O)=O LGQLOGILCSXPEA-UHFFFAOYSA-L 0.000 description 1
- BMGNSKKZFQMGDH-FDGPNNRMSA-L nickel(2+);(z)-4-oxopent-2-en-2-olate Chemical compound [Ni+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O BMGNSKKZFQMGDH-FDGPNNRMSA-L 0.000 description 1
- 229910000008 nickel(II) carbonate Inorganic materials 0.000 description 1
- 229910021508 nickel(II) hydroxide Inorganic materials 0.000 description 1
- 229910000363 nickel(II) sulfate Inorganic materials 0.000 description 1
- ZULUUIKRFGGGTL-UHFFFAOYSA-L nickel(ii) carbonate Chemical compound [Ni+2].[O-]C([O-])=O ZULUUIKRFGGGTL-UHFFFAOYSA-L 0.000 description 1
- BFDHFSHZJLFAMC-UHFFFAOYSA-L nickel(ii) hydroxide Chemical compound [OH-].[OH-].[Ni+2] BFDHFSHZJLFAMC-UHFFFAOYSA-L 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- MOOYVEVEDVVKGD-UHFFFAOYSA-N oxaldehydic acid;hydrate Chemical compound O.OC(=O)C=O MOOYVEVEDVVKGD-UHFFFAOYSA-N 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- KTUFCUMIWABKDW-UHFFFAOYSA-N oxo(oxolanthaniooxy)lanthanum Chemical compound O=[La]O[La]=O KTUFCUMIWABKDW-UHFFFAOYSA-N 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical class O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- NOTVAPJNGZMVSD-UHFFFAOYSA-N potassium monoxide Inorganic materials [K]O[K] NOTVAPJNGZMVSD-UHFFFAOYSA-N 0.000 description 1
- VLJNHYLEOZPXFW-UHFFFAOYSA-N pyrrolidine-2-carboxamide Chemical compound NC(=O)C1CCCN1 VLJNHYLEOZPXFW-UHFFFAOYSA-N 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 235000021013 raspberries Nutrition 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000007655 standard test method Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000011269 tar Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- DZLNHFMRPBPULJ-UHFFFAOYSA-N thioproline Chemical compound OC(=O)C1CSCN1 DZLNHFMRPBPULJ-UHFFFAOYSA-N 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 229910001845 yogo sapphire Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/367—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in singly bound form
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
- A23L27/20—Synthetic spices, flavouring agents or condiments
- A23L27/204—Aromatic compounds
-
- 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
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/32—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen
- C07C45/37—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of >C—O—functional groups to >C=O groups
- C07C45/39—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of >C—O—functional groups to >C=O groups being a secondary hydroxyl group
-
- 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
- C07C45/62—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 hydrogenation of carbon-to-carbon double or triple bonds
-
- 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
- C07C45/72—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 by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
- C07C45/74—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 by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups combined with dehydration
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/353—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by isomerisation; by change of size of the carbon skeleton
Definitions
- the present invention relates to a process for the preparation of frambinone comprising a step of condensation of phenol and glyoxylic acid.
- Frambinone or 4-(4-hydroxyphenyl)-2-butanone, is the main aromatic compound of raspberries, but also present in cranberries or blackberries.
- Frambinone is used in perfumery, cosmetics or in the food industry to give a fruity smell.
- This natural aromatic compound can be extracted from fruits at the rate of 1 to 4 mg per kilogram of raspberry. Given the very low abundance of this aromatic compound in the fruit, synthetic processes have been developed, in particular:
- the present invention aims at the manufacture of frambinone by a new access route using non-toxic and less expensive starting materials.
- the method allows the manufacture of a new compound: natural frambinone, the method advantageously uses reagents of natural origin.
- the method advantageously uses milder operating conditions, in particular in terms of temperature or pressure, than the methods of the prior art.
- a first object of the present invention relates to a process for the preparation of frambinone comprising a stage (a) of condensation of phenol and glyoxylic acid.
- the present invention also relates to frambinone which can be obtained according to the method of the present invention.
- the present invention also relates to frambinone whose carbon content of biosourced origin is greater than or equal to 50% and strictly less than 100%.
- the present invention relates to frambinone whose 13 C isotopic deviation is between -27%o and -15%o, preferably whose carbon content of biosourced origin is greater than or equal to 50%.
- the present invention also relates to the use of frambinone according to the present invention as a flavor or perfume.
- the present invention relates to a composition comprising frambinone according to the present invention.
- biosourced origin refers to a product which is composed, entirely or mainly, of biological products, or renewable agricultural materials (including vegetable, animal and marine materials) or forestry.
- carbon of bio-based origin or “bio-based carbon” refers to carbons of renewable origin such as agricultural, plant, animal, fungal, micro-organisms, marine or forest living in a natural environment in balance with the atmosphere.
- Bio-based carbon content is typically assessed using carbon-14 dating (also called carbon dating or radiocarbon dating).
- biobased carbon content refers to the molar ratio of biobased carbon to total carbon of the compound or product.
- Bio-based carbon content can preferably be measured by a method of measuring the decay process of 14 C (carbon-14), in disintegrations per minute per gram of carbon (or 10 dpm/gC), by liquid scintillation counting , preferably according to the ASTM D6866-16 Standard Test Method. Said American standard ASTM D6866 test would be equivalent to ISO 16620-2. According to said ASTM D6866 standard, the test method can preferably use AMS (Accelerator Mass Spectrometry) techniques with IRMS 13 C (Isotope Ratio Mass Spectrometry) to quantify the bio-based content of a given product.
- AMS Accelelerator Mass Spectrometry
- Hydrogen and carbon atoms naturally co-exist with their stable isotopes: deuterium and 13 C respectively.
- the quantity and the D/H and 13 C/ 12 C ratios are influenced by several factors such as, in particular, the environment for natural products.
- the isotopic fingerprint of a product gives information on the origin of the product in particular the natural or fossil origin.
- the 2 H-SNIF-NMR method measures the deuterium/hydrogen ratio of each site of a molecule.
- the 13 C-SNIF-NMR method measures the 13 C/ 12 C ratio of each site of a molecule.
- the D/H ratios are measured by comparison with tetramethylurea (TMU), the international reference standard.
- TMU tetramethylurea
- the measurements can be carried out in dioxane or in a dioxane/benzene mixture.
- the average 13 C isotopic deviation ( ⁇ 13 C) is measured by isotopic ratio mass spectrometry (IRMS) compared to PDB (pee bee belemnite), the international reference standard.
- the process for preparing frambinone comprises a step (a) of condensation of phenol and glyoxylic acid and can be represented according to the following diagram:
- Step (a) of condensation of phenol and glyoxylic acid allows the formation of 2-hydroxy-2-(4-hydroxyphenyl)acetic acid (Compound I).
- Step (a) can be carried out according to any process for the condensation of an aromatic derivative with glyoxylic acid, in particular as described in particular in WO 09/077383 or WO 2015/071431.
- the phenol can be a biobased phenol or a non-biobased phenol.
- phenol having a biobased carbon content greater than 50% is also called “biobased phenol”.
- the biobased phenol according to the invention may have a biobased carbon content greater than 60%, preferably between 75% and 100%, more preferably between 90% and 100%, more preferably between 95% and 100%, more preferably between 98 % and 100%, and more preferably between 99% and 100%.
- Biobased phenol is a commercial product. It can be obtained in a natural way from natural resources such as lignin in particular by different methods, charcoal oil, from vegetable oil or saccharide residues.
- biochemical processes are known. Mention may be made, by way of example, of US 2013/0232852 which describes a process for the biorefining of lignin biomass. Mention may also be made of EP 2639295 which describes a biochemical process for the production of phenol from saccharides.
- biobased phenol Given the biosourced origin of phenol, it may contain certain impurities.
- the nature of the impurities contained in biobased phenol is different from those contained in phenol of fossil origin. Furthermore, these impurities may be specific depending on the origin of the phenol and its method of preparation.
- phenol of biobased origin has a purity greater than or equal to 99%.
- the content of total impurities in the biobased phenol is less than or equal to 1%, and greater than or equal to 0.5%.
- the content of each impurity in the biobased phenol is between 0.005 and 0.1%, preferably between 0.01 and 0.08%.
- the biosourced phenol has an average isotopic deviation ⁇ 13 C of between -33%o and -20%o, preferably between -30%o and -25%o, very preferably between -30%o and -27% y.
- the glyoxylic acid can be a bio-based glyoxylic acid or a non-bio-based glyoxylic acid.
- glyoxylic acid having a biobased carbon content greater than 50% is also called “biobased glyoxylic acid”.
- the biobased glyoxylic acid according to the invention may have a biobased carbon content greater than 60%, preferably between 75% and 100%, more preferably between 90% and 100%, more preferably between 95% and 100%, more preferably between 98% and 100%, and more preferably between 99% and 100%.
- Bio-based and non-bio-based glyoxylic acid can be purchased from several producers. Certain processes for the production of biobased glyoxylic acid are described in the prior art. In particular, different biochemical processes are available. For example, US 5219745 describes an industrially advantageous process for the biochemical production of glyoxylic acid.
- bio-based glyoxylic acid can be produced by well-known industrial methods (see for example “Glyoxylic Acid” in Ullmann's Encyclopedia of Industrial Chemistry, G. MATTIODA and Y. CHRISTIDIS, Vol.17 p.89-92, 2012) from bio-based raw materials, such as bio-based ethanol, or bio-based glycerol or bio-based ethylene glycol.
- bio-based glyoxylic acid Given the biosourced origin of glyoxylic acid, it may contain certain impurities. The nature of the impurities contained in bio-based glyoxylic acid is different from those contained in fossil-based glyoxylic acid. Furthermore, these impurities may be specific depending on the origin of the glyoxylic acid and its preparation process.
- the biosourced glyoxylic acid used in the context of the present invention generally has an average 13 C isotopic deviation of between -33 and -7%o, preferably comprised between -31%o and -9%o, preferentially comprised between -30%o and -10%o, and very preferentially comprised between -31 and -25%o.
- the biosourced glyoxylic acid used in the context of the present invention generally has an average 13 C isotopic deviation of between -7 and -3%o, preferably between -6%o and -5% y.
- condensation reaction of phenol with glyoxylic acid allows the synthesis of the corresponding condensation product, which is a para-hydroxymandelic acid.
- This condensation step can give rise to certain impurities, namely an ortho-hydroxymandelic acid (Compound II) and a dimandelic derivative (Compound III).
- Other phenol impurities may react during the condensation step.
- the compound (I) obtained at the end of step (a) has a carbon content of biosourced origin greater than or equal to 50%, preferably greater than or equal to 70%.
- the molar ratio between phenol and glyoxylic acid can be between 1.0 and 4.0, preferably between 1.2 and 2.2.
- the condensation reaction can be carried out in a cascade of stirred reactors. According to a variant, the reaction is carried out in a plug-flow reactor, optionally comprising a heat exchanger. Such an embodiment is for example described in application WO 09/077383.
- the condensation reaction between phenol and glyoxylic acid can be carried out in water, in the presence of an alkali metal, said reaction being carried out in a plug flow reaction. It can also be carried out in a tubular reactor.
- the condensation reaction can advantageously be catalyzed by a quaternary ammonium hydroxide, according to the reaction described in patent application EP 0 578 550.
- the phenol is reacted with glyoxylic acid in the presence of a base, preferably an inorganic base or an organic base, more preferably an alkali metal, and even more preferably in the presence NaOH, KOH, lime or K2CO3.
- a base preferably an inorganic base or an organic base, more preferably an alkali metal, and even more preferably in the presence NaOH, KOH, lime or K2CO3.
- sodium hydroxide may be preferred.
- the alkali metal hydroxide can be used in solution.
- the alkali metal hydroxide solution can have a concentration between 10% and 50% by weight.
- the quantity of alkali metal hydroxide introduced into the reaction medium takes into account the quantity necessary to salify the hydroxyl function of the phenol and the carboxylic function of the glyoxylic acid.
- the phenol is in the phenolate form and the condensation product is a mandelate compound.
- the amount of alkali metal hydroxide is between 80% and 120% of the
- the phenolate reacts with glyoxylic acid to form the corresponding para-mandelate.
- reaction steps for preparing the glyoxylate and the phenolate can be carried out according to two distinct steps.
- the glyoxylic acid is brought into direct contact with the phenolate in the presence of the base.
- a possible variant consists in carrying out the reaction in the presence of a catalyst of the dicarboxylic acid type, preferably oxalic acid, as described in international patent application WO 99/65853.
- the quantity of catalyst used expressed by the ratio between the number of moles of catalyst and the number of moles of glyoxylic acid, can be advantageously chosen between 0.5% and 2.5% and preferably between 1% and 2% .
- the phenol and the alkaline agent are mixed together before the phenol is brought into contact with the glyoxylic acid.
- the method according to the invention may comprise a first step of bringing the phenol into contact with an alkali metal hydroxide in aqueous solution, followed by bringing the resulting solution into contact with glyoxylic acid.
- This embodiment advantageously makes it possible to better control the reaction temperature, because the salification reaction of glyoxylic acid is exothermic.
- the method according to the invention comprises in a first step bringing glyoxylic acid into contact with an alkali metal hydroxide in aqueous solution, followed by bringing the resulting solution into contact with phenol .
- the process according to the invention comprises, on the one hand, bringing the phenol into contact with the alkaline agent in aqueous solution, and, on the other hand, bringing the glyoxylic acid with the alkaline agent in aqueous solution, followed by bringing the two resulting solutions into contact.
- These optional steps of bringing glyoxylic acid into contact with an alkali metal hydroxide in aqueous solution and/or bringing phenol into contact with the alkaline agent can be carried out at a temperature between 10°C and 40°C , for example at 15°C or at 35°C.
- the reaction mixture obtained may have a viscosity at 20° C. of between 0.5 mPa.s and 50 mPa.s and more preferably between 1.5 mPa.s and 3 mPa.s. According to the invention, this mixture is introduced into at least one reactor, in which the condensation reaction takes place.
- the phenol is reacted with the glyoxylic acid in the absence of any added acid compound or base compound. This embodiment is further described in document WO 2015/071431.
- This condensation step can be carried out in an aqueous medium.
- the concentration of the phenol can preferably be between 0.5 and 1.5 mol/liter and more particularly approximately 1 mol/liter.
- Glyoxylic acid can be used in aqueous solution with a concentration ranging for example between 15% and 70% by weight. Commercial solutions are preferably used, the concentration of which is approximately 50% by weight.
- the phenol is reacted with glyoxylic acid without any solvent, and the glyoxylic acid is glyoxylic acid monohydrate.
- glyoxylic acid is glyoxylic acid monohydrate.
- the phenol is reacted with glyoxylic acid in the presence of a catalyst chosen from the group consisting of complexes of transition metals with oxygenated ligands.
- Said catalyst is preferably chosen from the group consisting of iron(II) acetate (Fe(OAc)2), iron(III) acetate (Fe(OAc)3), copper(II) acetate (Cu(OAc)2) , iron (II) acetylacetonate (Fe (acac) 2), iron (III) acetylacetonate (Fe (acac) 3), cupper (II) acetylacetonate (Cu (acac) 2), cupper (III) acetylacetonate (Cu (acac) )3), and a transition metal complex having a glyoxylate ligand.
- This embodiment is further described in document WO 2015/071431.
- the operating conditions of the reaction can be fixed according to the reagents and the type of reactor or sequence of reactor used.
- the reaction temperature can be between 10°C and 90°C. According to one embodiment, the reaction temperature can be between 10°C and 20°C. According to another embodiment, the temperature may be between 30°C and 40°C. In addition, the temperature may vary during the reaction. For example, the reaction can be carried out at a temperature between 10°C and 20°C for a certain time, and the temperature can then be raised to between 30°C and 50°C for a finishing phase.
- the reaction can be carried out at atmospheric pressure, optionally under a controlled atmosphere of inert gases, preferably nitrogen or, optionally, rare gases, in particular argon. Nitrogen is preferentially chosen.
- the total residence time of the reagents in continuous mode and the operating or cycle time in batch mode can vary widely, for example from a few minutes to several hours, or even several days, in particular depending on the operating conditions, in particular depending on the reaction temperature.
- the total residence time of the reagents can be between 10 hours and 100 hours.
- the total residence time of the reagents can be between 30 minutes and 30 hours.
- the condensation compound obtained can be separated from the reaction mixture by conventional separation techniques, in particular by crystallization or by extraction using an appropriate organic solvent.
- a neutralization step can be carried out.
- the reaction mixture obtained after the condensation reaction can be used in its existing form.
- the phenol generally being in excess relative to the glyoxylic acid, the unreacted phenol fraction is advantageously recovered from a recycling loop, for example by distillation of the water/phenol azeotrope. This excess reduces the likelihood of forming dimandelic acid type compounds (i.e. compounds resulting from the condensation of two molecules of glyoxylic acid with one molecule of guaiacol).
- Unreacted phenol can be recovered by acidification, as described in WO 2014/016146.
- the process for preparing frambinone may also comprise a step (b) of decarboxylating oxidation of the compound of formula (I) obtained at the end of step (a) to form a compound of formula (IV).
- Step (b) is a step in which compound (I) is oxidized to form compound (IV) according to the following scheme, carbon dioxide is released:
- the compounds (II) and (III) obtained at the end of step (a) can also be oxidized under the same conditions to form the compounds (V) and (VI).
- step (a) The impurities contained in the biobased phenol which may have reacted during step (a) are also likely to be oxidized under the conditions of step (b).
- the oxidation can be carried out under an oxidizing atmosphere, such as O2 or under air.
- the reaction medium is an alkaline aqueous medium, preferably an inorganic base and more preferably sodium or potassium hydroxide, so as to form the corresponding phenate, and to capture the released CO2, in carbonate form.
- the reaction can be carried out continuously or discontinuously, for example in a medium strongly diluted in water.
- a catalyst for this oxidation reaction can be chosen from catalysts comprising at least one metallic element chosen from the group formed by copper, nickel, cobalt, iron, manganese and any mixture thereof.
- inorganic or organic copper compounds mention may in particular be made, as copper compounds, of cuprous and cupric bromide; cuprous iodide; cuprous and cupric chloride; basic cupric carbonate; cuprous and cupric nitrate; cuprous and cupric sulphate; cuprous sulfite; cuprous and cupric oxide; cupric hydroxide; cuprous and cupric acetate; and cupric trifluoromethyl sulfonate.
- nickel (II) halides such as nickel (II) chloride, bromide or iodide; nickel(II) sulfate; nickel(II) carbonate; nickel (II) hydroxide; salts of organic acids containing from 1 to 18 carbon atoms, such as in particular acetate or propionate; nickel (II) complexes, such as nickel (II) acetylacetonate, nickel (II) dichlorobis (triphenylphosphine) or nickel (II) dibromobis (bipyridine); and nickel(0) complexes, such as nickel(0)bis(cycloocta-1,5-diene) or nickel(0) bisdiphenylphosphinoethane.
- nickel (II) halides such as nickel (II) chloride, bromide or iodide
- nickel(II) sulfate nickel(II) carbonate
- nickel (II) hydroxide such as in particular acetate or prop
- cobalt-based compounds mention may in particular be made of cobalt (II) and (III) halides, such as cobalt (II) chloride, bromide or iodide or cobalt chloride, bromide or iodide (III); cobalt (II) sulfate and cobalt (III); cobalt(II) carbonate, basic cobalt(II) carbonate; cobalt(II) orthophosphate; cobalt(II) nitrate; cobalt (II) and cobalt (III) oxide; cobalt(II) hydroxide and cobalt
- cobalt (II) and (III) halides such as cobalt (II) chloride, bromide or iodide or cobalt chloride, bromide or iodide (III); cobalt (II) sulfate and cobalt (III); cobalt(II) carbonate, basic cobalt(II)
- salts of organic acids comprising from 1 to 18 carbon atoms such as in particular cobalt(II) and cobalt(III) acetate or cobalt(II) propionate; cobalt (II) complexes, such as hexaminecobalt (II) or (III) chloride, hexaminecobalt (II) or (III) sulfate, pentaminecobalt (III) chloride or triethylenediaminecobalt (III) chloride ).
- catalytic systems based on iron generally in the form of oxides, hydroxides or salts, such as chloride, bromide, iodide or fluoride of iron (II) and iron (III ); iron (II) and iron (III) sulfate; iron (II) and iron (III) nitrate; or iron(II) oxide and iron(III).
- the reaction can also use manganese-based catalytic systems such as manganese(II) carbonate, manganese(III) acetate.
- the oxidation reaction can be catalyzed, for example, by a catalytic system comprising two metallic elements chosen from the group formed by copper, nickel, cobalt, iron, manganese and any mixture thereof.
- a catalytic system comprising two metallic elements chosen from the group formed by copper, nickel, cobalt, iron, manganese and any mixture thereof.
- the teachings of WO 2008/148760 can be applied for the preparation of the compound
- the condensation compound (IV) obtained at the end of step (a) reacts with the base (preferably sodium hydroxide) so as to salify the phenate function of the condensation compound. Then, oxidation in an oxidizing medium (preferably in air) produces a compound of formula (IV) and CO2 (trapped in the form of carbonate). At the end of the oxidation reaction, a compound of formula (IV) is obtained in salified form, that is to say with a hydroxyl group in salified (ionic) form, and various impurities, including tars, are obtained.
- the acidification of the compound of formula (IV) in salified form in the reaction medium is carried out using a strong acid, for example sulfuric acid.
- the oxidation reaction can be carried out in the absence of any added acid compound or basic compound. This embodiment is further described in document WO 2015/071431.
- the compound (IV) obtained at the end of step (b) has a carbon content of biosourced origin greater than or equal to 50%, preferably greater than or equal to 70%, preferably greater than or equal 75% and less than or equal to 100%.
- the process for preparing frambinone may comprise a step (c) of condensation of the compound of formula (IV), obtained at the end of step (b), with acetone to form a compound of formula (VII) .
- Step (c) is a condensation of the compound of formula (IV) obtained at the end of step (b) with acetone, followed by dehydration, to form a compound of formula (VII).
- the acetone used in step (c) is a biosourced acetone.
- the bio-based acetone has a bio-based carbon content of between 75% and 100%, more preferably between 90% and 100%, more preferably between 95% and 100%, more preferably between 98% and 100%, and more preferably between 99 % and 100%.
- Bio-based acetone is a commercial product. It can be obtained naturally from natural resources such as by fermentation of sugars from corn residues, residues from the sugar industry in particular. Several biochemical processes are known, as described in Jones, DT and Woods, D R. (1986) Microbiol. Rev. 50: 484-524, or EP 2875139. Given the biosourced origin of acetone and its production process, it may contain certain impurities, such as in particular methanol, isopropanol, aldehydes. These impurities can be specific depending on the origin of the acetone.
- the biosourced acetone used in the context of the present invention generally has an average 13 C isotopic deviation of between -10%o and -2%o, preferably of between -8%o and -4%o.
- biobased acetone The nature of the impurities contained in biobased acetone is different from those contained in acetone of fossil origin. Moreover, these impurities can be specific depending on the origin of the acetone and its preparation process. In general, acetone of biosourced origin has a purity greater than or equal to 99%. In general, the content of total impurities in biosourced acetone is less than or equal to 1%, and greater than or equal to 0.5%. Generally, the content of each impurity in bio-based acetone is between 0.005 and 0.1%, preferably between 0.01 and 0.08%.
- step (c) is carried out in the presence of at least 1 equivalent of acetone, preferably of at most 5 equivalents of acetone, for example 2 equivalents of acetone.
- Step (c) can be carried out in the presence of a base or an acid.
- step (c) is carried out in the presence of a base.
- the base can be present in a catalytic quantity.
- step (c) is carried out in the presence of 1 base equivalent.
- the quantity of bases is less than or equal to 2 equivalents.
- the base used can be an inorganic base, such as KOH, NaOH.
- the base can be in aqueous solution at a concentration of between 10% and 50% by weight, preferably between 15% and 25% by weight.
- the base used can also be a basic solid of an alkali metal, alkaline earth, rare earths or transition metals such as oxides, hydroxides, carbonates, or hydrooxycarbonates, preferably chosen from the group consisting of Li2 ⁇ , Na2O, Al2O3, K2O, CS2O, BaO, MgO, BaCCL, CeCh, La2O3.
- the base used can also be an anion exchange resin having basic properties.
- the reaction is maintained at a temperature comprised between 10°C and 60°C, preferably comprised between 20°C and 50°C, preferentially comprised between 25°C and 40°C.
- the reaction is generally carried out in a solvent, preferably chosen from water, acetone, alcohols, or mixtures thereof.
- the alcohol is chosen from methanol, ethanol, isopropanol. This embodiment is described in particular in document CN 1097729.
- step (c) is carried out in the presence of an acid.
- Step (c) can be carried out in a mixture comprising water, an alcohol, preferably ethanol, acetone and an acid or with an acid in catalytic quantity.
- the amount of acid is generally less than or equal to 1 equivalent, relative to the amount of compound of formula (IV), preferably less than or equal to 0.8 equivalents, preferably less than or equal to 0.5 equivalents.
- the amount of acid is greater than or equal to 0.01 equivalents, preferably greater than or equal to 0.1 equivalents.
- the solvent for step (c) can be chosen from water, acetone, alcohols, acetic acid or mixtures thereof.
- the reaction is carried out in a water/acid mixture, in general the volume of water relative to the volume of acid is between 1:1 and 5:1.
- the acid used can also be a resin cation exchanger with acidic properties.
- the reaction is maintained at a temperature comprised between 10°C and 60°C, preferably comprised between 20°C and 50°C, preferentially comprised between 25°C and 40°C.
- the acid is generally a strong acid, preferably the acid is chosen from acids having a pKa of less than or equal to 2, such as sulfuric acid, triflic acid, hydrochloric acid, hydrobromic acid.
- step (c) can be carried out in the presence of an amino acid, preferably chosen from proline, azetidine-2-carboxylic acid, piperidine-2-carboxylic acid, 4-hydroxypyrrolidine-2- carboxylic acid, pyrrolidine-2-carboxamide, thiazolidine-4-carboxylic acid, 4-acetoxypyrrolidine-2-carboxylic acid.
- the amount of amino acid is generally between 15% by volume and 40% by volume.
- the solvent is generally a mixture of DMSO and acetone.
- the compound (VII) obtained at the end of step (c) has a carbon content of biosourced origin greater than or equal to 50%, preferably greater than or equal to 70%, preferably greater than or equal to 75 % and less than or equal to 100%.
- the compound (VII) obtained at the end of step (c) is recovered in salified form.
- the process for preparing frambinone may comprise a stage (d) of hydrogenation of the compound of formula (VII) obtained at the end of stage (c), in protonated or salified form.
- Stage (d) is a stage of hydrogenation of the compound of formula (VII) obtained at the end of stage (d) to form frambinone (VIII). live. (Wine)
- step (d) is carried out in the presence of a reducing agent with or without heterogeneous catalysis.
- step (d) is carried out in the presence of a metal-based catalyst, preferably chosen from catalysts based on Pd, Pt, Ni, Ru, Rh, such as Pd/C, Pt/Alumina or Raney Nickel.
- a metal-based catalyst preferably chosen from catalysts based on Pd, Pt, Ni, Ru, Rh, such as Pd/C, Pt/Alumina or Raney Nickel.
- the amount of catalyst is generally greater than or equal to 0.1% by weight, preferably greater than or equal to 0.5% by weight, and less than or equal to 25% by weight, preferably less than or equal to 20% by weight.
- Stage (d) is generally carried out in the presence of a reducing agent
- the reducing agent can be chosen from dihydrogen, phosphite and hypophosphite derivatives such as than described in Org. Biomol. Chem., 2015, 13, 7879-7906.
- the reducing agent can be chosen from HCO 2 (NH 4 ), NaH 2 PO 2 , Na 2 HPO 3 , HCO 2 H.
- the amount of reducing agent is generally greater than or equal to 1 equivalent relative to the amount of compound of formula (VII), preferably greater than or equal to 1.5 equivalents, and less than or equal to 10 equivalents, preferably less than or equal to 7 equivalents, very preferably less than or equal to 5 equivalents.
- the solvent can be chosen from the group consisting of water, alcohols, or acetic acid and their mixtures, in particular the solvent can be water, methanol, ethanol, isopropanol , acetic acid or mixtures thereof.
- step (d) can be carried out in the presence of a base, preferably a strong base, very preferably a non-nucleophilic strong base.
- a base preferably a strong base, very preferably a non-nucleophilic strong base.
- the base can be chosen from tertiary amines, such as triethylamine.
- Step (d) is generally carried out at a temperature greater than or equal to 25°C, preferably greater than or equal to 30°C, preferably greater than 40°C, very preferably greater than 50°C.
- the temperature of step (d) is less than or equal to 190°C, preferably less than or equal to 175°C, very preferably less than or equal to 150°C.
- step (d) is carried out at a temperature of between 25°C and 100°C.
- Step (d) can be carried out at atmospheric pressure, alternatively step (d) can be carried out under autogenous pressure.
- step (d) can be carried out by biochemical transformation, in particular transformation of the compound of formula (VII) into frambinone of formula (VIII) can be carried out via a microorganism having an ene activity -reductase, as described in particular in GB2416769 or in Journal of Molecular Catalysis B: Enzymatic (1998), 4(5-6), 289-293.
- steps (c) and (d) can be carried out without isolation of the compound of formula (VII).
- steps (c) and (d) can be carried out according to a “one-pot” process.
- steps (c) and (d) can be carried out without isolation of the compound of formula (VII) and can be carried out by heterogeneous catalysis, in particular in the presence of a resin, preferably an acid resin. This embodiment is described in particular in ACS Omega 2020, 5, 14291-14296.
- steps (c) and (d) can be carried out without isolation of the compound of formula (VII) and can be carried out by acid catalysis, in the presence of a reducing agent and a metal-based catalyst.
- the metal-based catalyst is chosen from catalysts based on Pd, Pt, Ni, Ru, Rh, such as Pd/C or Raney Nickel.
- the reducing agent is generally chosen from NaHzPCh, HCO2H, NaHPCb.
- the catalyst is generally a strong acid such as hydrochloric acid, sulfuric acid.
- the solvent can be chosen from the group consisting of water, alcohols, or acetic acid and their mixtures, in particular the solvent can be water, methanol, ethanol, isopropanol , acetic acid or mixtures thereof.
- the compound (VIII) obtained at the end of step (d) has a carbon content of biosourced origin greater than or equal to 50%, preferably greater than or equal to 70%, preferably greater than or equal to 75 % and less than or equal to 100%.
- the present invention relates to a process for the preparation of frambinone from 4-hydroxybenzyl alcohol and acetone.
- the preparation process can be represented by the following diagram:
- 4-Hydroxybenzyl alcohol is a commercial product, in particular the commercial product can be adapted for use in the food industry.
- 4-Hydroxybenzyl alcohol can be of biobased or non-biobased origin.
- 4-hydroxybenzyl alcohol can also be obtained by reduction of the aldehyde (IV) obtained at the end of step (b).
- the 4-hydroxybenzyl alcohol has a carbon content of biosourced origin greater than or equal to 60%, preferably greater than or equal to 70%, preferably greater than or equal to 75% and less than or equal to 100%.
- the acetone can be of biobased origin, as described previously in step (c).
- the condensation reaction of the compound of formula (IX) and acetone is carried out in a basic medium.
- the base used can be a base chosen from NaOH, KOH, K3PO4.
- the amount of base is generally greater than or equal to 1 equivalent, preferably greater than or equal to 1.1 equivalents, preferably greater than or equal to 1.5 equivalents relative to the compound of formula (IX).
- the amount of base is less than or equal to 5 equivalents, preferably less than or equal to 4, very preferably less than or equal to 3 equivalent equivalents with respect to the compound of formula (IX).
- the condensation reaction of the compound of formula (IX) and acetone is carried out in the presence of a metal-based catalyst, preferably chosen from catalysts based on Pd, Pt, Ni, Ru, Rh, such as Pd/C or Raney Nickel.
- a metal-based catalyst preferably chosen from catalysts based on Pd, Pt, Ni, Ru, Rh, such as Pd/C or Raney Nickel.
- the amount of catalyst is generally greater than or equal to 0.1% by weight, preferably greater than or equal to 0.5% by weight, and less than or equal to 25% by weight, preferably less than or equal to 20% by weight.
- the solvent can be chosen from the group consisting of water, alcohols, acetone, dioxane and their mixtures, in particular the solvent can be water, methanol, ethanol, isopropanol, acetone, dioxane or mixtures thereof.
- a third aspect of the present invention refers to a frambinone capable of being obtained according to the process of the invention, in particular to a biosourced frambinone capable of being obtained by the process of the invention.
- the compound (VIII) obtained at the end of the condensation step of the compound of formula (IX) and acetone has a carbon content of biosourced origin greater than or equal to 50%, preferably greater than or equal to to 70%, preferably greater than or equal to 75% and less than or equal to 100%.
- a fourth aspect of the present invention covers a frambinone whose carbon content of biosourced origin is greater than or equal to 50%, preferably greater than or equal to 75% and strictly less than 100%.
- the present invention also covers a frambinone characterized in that the average isotopic deviation 13 C is between -27%o and -15%o, preferably between -23%o and -15%o, preferably between -22%o o and -15%o, preferably between -23%o and -18%o, preferably between -22%o and -18%o, very preferably between -21%o and -19%o.
- the frambinone of the present invention has a carbon content of biobased origin greater than or equal to 50%, preferably greater than or equal to 75%.
- the frambinone of the present invention has a carbon content of biosourced origin less than or equal to 110%, preferably less than or equal to 105%, preferentially less than or equal to 103%, preferentially less than or equal to 100% and very preferably strictly less than 100%.
- all the carbon atoms of the frambinone according to the present invention are of biobased origin, in particular the 10 carbon atoms of the frambinone of the present invention are of biobased origin.
- Preferably 9 carbon atoms of frambinone are of biosourced origin, preferably 8 carbon atoms, preferably 7 carbon atoms, preferably 6 carbon atoms are of biosourced origin.
- frambinone may have a (D/H) 3 /(D/H) 2 ratio of less than or equal to 1.10, preferably less than or equal to 1.00, very preferably less than or equal to 0.90 and very preferably less than or equal to 0.80.
- frambinone may have a (D/H) 3 /(D/H) 2 ratio greater than or equal to 0.10, preferably greater than or equal to 0.20 very preferably greater than or equal to 0.30 and very preferably greater than or equal to 0.40.
- frambinone may have a (D/H)S/(D/H)4 ratio of less than or equal to 1.10, preferably less than or equal to 10, very preferably less than or equal to 0.90 and very preferably less than or equal to 0.85.
- frambinone may have a ratio (D/H)S/(D/H)4 greater than or equal to 0.10, preferably greater than or equal to 0.20 very preferably greater than or equal to 0.30 and very preferably greater than or equal to 0.40.
- the frambinone of the present invention has a (D/H) 3 /(D/H) 2 ratio of less than or equal to 1.10, preferably less than or equal to 1.00, very preferably less than or equal to 0.90 and very preferably less than or equal to 0.80 and a ratio (D/H)S/(D/H)4 less than or equal to 1.10, preferably less than or equal to 10, very preferably less than or equal to 0.90 and very preferably less than or equal to 0.85.
- frambinone has a (D/H) 3 /(D/H) 2 ratio greater than or equal to 0.10, preferably greater than or equal to 0.20, very preferably greater than or equal to 0.30 and very preferably greater than or equal to 0.40 and a ratio (D/H)s/(D/H)4 greater than or equal to 0.10, preferably greater than or equal to 0.20 very preferably greater than or equal to 0.30 and very preferably greater than or equal to 0.40.
- the organoleptic properties of a flavoring substance can depend on the presence and the quantity of certain impurities. This is why the manufacturing process is essential for the flavor of the final compound.
- the frambinone of the present invention exhibits satisfactory organoleptic properties. It should be noted that the organoleptic profile of the frambinone of the present invention is equivalent to the organoleptic profile of the frambinone extracted from fruits.
- the present invention covers the use of frambinone according to the present invention or of frambinone obtained according to the process of the invention as flavoring or perfume.
- the present invention also covers a composition comprising frambinone according to the invention preferably chosen from the group consisting of food products, beverages, cosmetic formulations, pharmaceutical formulations and perfumes.
- Example 1 Phenol is condensed with a 50% by weight solution of glyoxylic acid at 30° C. in the presence of NaOH. The compound of formula (I) was obtained with a yield of 60%.
- the compound of formula (I) obtained in Example 1 is oxidized in the presence of a metal catalyst (metal content 8% by weight) and heated to 75° C. with bubbling of air under pressure. Autogenous (6-8bars) in an alkaline aqueous medium.
- the compound of formula (IV) is obtained after acidification with ELSCM with a yield of 95%.
- Example 2 The compound of formula (IV) obtained in Example 2 is condensed with acetone (4 equivalents) in acetic acid, in the presence of sulfuric acid (0.5 equivalent) at 50°C.
- the compound of formula (VII) is obtained with a selectivity of 87%.
- Example 2 The compound of formula (IV) obtained in Example 2 is condensed with acetone (8.6 equivalents), in the presence of 10% aqueous sodium hydroxide (2.2 equivalents) at 20°C.
- the compound of formula (VII) is obtained with a selectivity of 94%.
- Example 2 The compound of formula (IV) obtained in Example 2 is condensed with acetone (4 equivalents), in the presence of glycine (0.3 equivalent) and NaHCOs (0.1 equivalent) in DMSO at 58°C.
- the compound of formula (VII) is obtained with a selectivity of 83%.
- Example 3 The compound of formula (VII) obtained in Example 3 is reduced in the presence of NaEhPC EbO (4 equivalents), Pd/C (20% by weight) in a solvent composed of water and ethanol (mixture 1: 1).
- the frambinone of formula (VII) is obtained with a selectivity of 81%.
- Example 4b The compound of formula (VII) obtained in Example 3 is reduced in the presence of Na HPCL, 5 H2O (4 equivalents), Pd/C (20% by weight) in a solvent composed of water and ethanol ( 1:1 mixture). The frambinone of formula (VII) is obtained with a selectivity of 91%.
- Example 4c The compound of formula (VII) obtained in Example 3 is reduced in the presence of HCO2H (4 equivalents), Pd/C (20% by weight) in a solvent composed of water and ethanol (mixture 1 : 1). The frambinone of formula (VII) is obtained with a selectivity of 78%.
- the frambinone obtained of formula (VII) has 10 carbon atoms of biosourced origin and an isotopic deviation of between -22%o and -18%o.
- the organoleptic profile of the frambinone of the present invention is equivalent to the organoleptic profile of the frambinone extracted from fruits.
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Application Number | Priority Date | Filing Date | Title |
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FR2012448A FR3116819B1 (fr) | 2020-12-01 | 2020-12-01 | Procédé de préparation de frambinone |
PCT/EP2021/083815 WO2022117670A1 (fr) | 2020-12-01 | 2021-12-01 | Procédé de préparation de frambinone |
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EP4255879A1 true EP4255879A1 (fr) | 2023-10-11 |
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EP21819879.4A Pending EP4255879A1 (fr) | 2020-12-01 | 2021-12-01 | Procédé de préparation de frambinone |
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US (1) | US20230416182A1 (fr) |
EP (1) | EP4255879A1 (fr) |
CN (1) | CN116615407A (fr) |
AU (1) | AU2021391841A1 (fr) |
FR (1) | FR3116819B1 (fr) |
WO (1) | WO2022117670A1 (fr) |
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FR1227595A (fr) | 1958-07-03 | 1960-08-22 | Dragoco Gerberding Co Gmbh | Procédé de préparation de 1-(4-hydroxyphényl)-butanone-3 et parfum contenant ledit produit |
FR2221433A1 (en) | 1972-09-15 | 1974-10-11 | Shell Int Research | Hydroxy phenyl substd ketones - useful as flavourings and aromatising agents |
JPH01242549A (ja) | 1988-03-24 | 1989-09-27 | Denki Kagaku Kogyo Kk | 4−(4−ヒドロキシフエニル)−2−ブタノンの製造方法 |
US5219745A (en) | 1989-10-16 | 1993-06-15 | E. I. Du Pont De Nemours And Company | Production of glyoxylic acid from glycolic acid |
FR2693458B1 (fr) | 1992-07-10 | 1994-12-09 | Rhone Poulenc Chimie | Procédé de para-hydroxyalkylation de composés aromatiques hydroxylés. |
CN1036455C (zh) | 1993-12-18 | 1997-11-19 | 江阴市顾山香料厂 | 对羟基苯基丁酮的合成方法 |
FR2779718B1 (fr) | 1998-06-16 | 2000-12-29 | Rhodia Chimie Sa | Procede de preparation de composes p-hydroxymandeliques eventuellement substitues et derives |
GB2416769A (en) | 2004-07-28 | 2006-02-08 | Danisco | Biosynthesis of raspberry ketone |
FR2917085B1 (fr) | 2007-06-06 | 2009-07-17 | Rhodia Recherches & Tech | Procede de preparation d'un aldehyde hydroxyaromatique. |
FR2925047B1 (fr) | 2007-12-18 | 2010-01-01 | Rhodia Operations | Procede de preparation de composes p-hydroxymandeliques eventuellement substitues et derives. |
CA2719274C (fr) * | 2008-03-26 | 2015-12-29 | Council Of Scientific & Industrial Research | Procede de preparation de 4-(4-hydroxyphenyl)butan-2-one utilisant un catalyseur acide solide a base d'argile |
EP2639295B1 (fr) | 2010-11-10 | 2017-06-28 | Green Phenol Development Co., Ltd. | Transformant de bactérie corynéforme ainsi que procédé de fabrication de phénol mettant en oeuvre ce transformant |
US20130232852A1 (en) | 2012-03-09 | 2013-09-12 | Thesis Chemistry, Llc | Method for tiered production of biobased chemicals and biofuels from lignin |
GB2505638B (en) | 2012-07-23 | 2016-01-06 | Green Biologics Ltd | Continuous culture |
FR2993881B1 (fr) | 2012-07-26 | 2014-08-15 | Rhodia Operations | Procede de preparation d'alkoxyphenol et d'alkoxyhydroxybenzaldehyde |
FR3013351B1 (fr) | 2013-11-15 | 2016-01-01 | Rhodia Operations | Procede de preparation de compose aromatique mandelique et de compose aldehyde aromatique |
CN104193607B (zh) | 2014-09-10 | 2016-01-20 | 曹仪山 | 一种覆盆子酮的合成方法 |
CN104355977B (zh) | 2014-11-06 | 2016-03-02 | 南京林业大学 | 一种覆盆子酮的合成工艺 |
CN104496778B (zh) | 2014-12-11 | 2017-06-16 | 南京林业大学 | 一种固体酸碱催化合成覆盆子酮的方法 |
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- 2021-12-01 AU AU2021391841A patent/AU2021391841A1/en active Pending
- 2021-12-01 US US18/252,823 patent/US20230416182A1/en active Pending
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CN116615407A (zh) | 2023-08-18 |
AU2021391841A1 (en) | 2023-06-08 |
US20230416182A1 (en) | 2023-12-28 |
FR3116819B1 (fr) | 2023-11-17 |
FR3116819A1 (fr) | 2022-06-03 |
WO2022117670A1 (fr) | 2022-06-09 |
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