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WO2017098050A1 - Procédé de production du 6,10,14-triméthylpentadécan-2-one, isophytol et alpha-tocophérol - Google Patents

Procédé de production du 6,10,14-triméthylpentadécan-2-one, isophytol et alpha-tocophérol Download PDF

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Publication number
WO2017098050A1
WO2017098050A1 PCT/EP2016/080664 EP2016080664W WO2017098050A1 WO 2017098050 A1 WO2017098050 A1 WO 2017098050A1 EP 2016080664 W EP2016080664 W EP 2016080664W WO 2017098050 A1 WO2017098050 A1 WO 2017098050A1
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WO
WIPO (PCT)
Prior art keywords
dehydrofarnesylacetone
range
process according
catalyst
mixtures
Prior art date
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Ceased
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PCT/EP2016/080664
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English (en)
Inventor
Werner Bonrath
Jonathan Alan Medlock
Peter Hans RIEBEL
Rene Tobias Stemmler
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DSM IP Assets BV
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DSM IP Assets BV
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Publication of WO2017098050A1 publication Critical patent/WO2017098050A1/fr
Anticipated expiration legal-status Critical
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
    • C07D311/70—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with two hydrocarbon radicals attached in position 2 and elements other than carbon and hydrogen in position 6
    • C07D311/72—3,4-Dihydro derivatives having in position 2 at least one methyl radical and in position 6 one oxygen atom, e.g. tocopherols
    • 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

Definitions

  • the present invention is directed to a process for the manufacture of 6, 10, 1 -trimethylpentadecan-2-one ("C18-ketone") comprising the step of hydrogenating a mixture of (3E,5E,9E)-3,4-dehydrofarnesylacetone and (3Z,5E,9E)-3,4-dehydrofarnesylacetone with hydrogen in the presence of a catalyst, whereby the catalyst is capable of preferentially hydrogenating carbon-carbon double bonds over carbon-oxygen double bonds (see Fig. 3).
  • the catalyst comprises a metal selected from the group consisting of palladium, platinum, rhodium, iridium and nickel and mixtures thereof. More preferably the catalyst comprises a metal selected from the group consisting of palladium, platinum and mixtures thereof. Even more preferably the catalyst is a metal selected from the group consisting of palladium, platinum and mixtures thereof. Most preferably the catalyst is palladium.
  • (2E,6E)-Farnesal can be obtained by selective oxidation of (2E,6E)-farnesol (see Fig. 1 ), e.g. by the use of manganese oxide in a solvent with only a small change in the carbon-carbon double bond geometry.
  • oxygen and palladium catalysts as described in Kakiuchi et al, Bull Chem Soc Jpn, 2001 , 165-172 (especially page 168, Table 3, example 11 ) may be used for the selective oxidation of (2E,6E)-farnesol to (2E,6E)-farnesal. This selective oxidation is also an embodiment of the present invention.
  • the (2E,6E)-farnesol may itself be extracted from natural sources or obtained by fermentation or synthesized synthetically and, if needed, separated from (2Z,6E)-, (2E,6Z)- and (2Z,6Z)-farnesol by any method known to the person skilled in the art.
  • the present invention is also directed to a process for the manufacture of isophytol and for the
  • a further object of the present invention is a process for the manufacture of isophytol comprising the following steps: a) selectively oxidizing (2E,6E)-farnesol to (2E,6E)-farnesal according to the process of the present invention;
  • the isophytol may be produced according to a process comprising the following steps which is also an object of the present invention: a) selectively oxidizing (2E,6E)-farnesol to (2E,6E)-farnesal according to the process of the present invention;
  • a further object of the present invention is a process for the manufacture of a-tocopherol and a-tocopheryl acetate, respectively, comprising the following steps: a) selectively oxidizing (2E,6E)-farnesol to (2E,6E)-farnesal according to the process of the present invention; b) converting (2E,6E)-farnesal either by a Wittig reaction or by an aldol condensation with acetone and a base or by a Knoevenagel reaction followed by decarboxylation or by Horner-Wadsworth- Emmons chemistry using a suitable phosphonate to obtain a mixture of (3E,5E,9E)-3,4-dehydrofarnesylacetone and (3Z,5E,9E)-3,4- dehydrofarnesylacetone according to the process of the present invention;
  • the a-tocopherol or its acetate may be produced according to a process comprising the following steps which is also an object of the present invention: a) selectively oxidizing (2E,6E)-farnesol to (2E,6E)-farnesal according to the process of the present invention;
  • the steps d1 ), e1 ), d2) and f) may be carried out according to methods known to the person skilled in the art.
  • the ethynylation e.g. may either be performed with acetylene, ammonia and potassium hydroxide or with ethynyl Grignard.
  • the present invention is directed to a process for the manufacture of 6,10, 14-trimethylpentadecan-2-one ("C18-ketone") comprising the step of hydrogenating a mixture of (3E,5E,9E)-3,4- dehydrofarnesylacetone and (3Z,5E,9E)-3,4-dehydrofarnesylacetone with hydrogen in the presence of a catalyst, whereby the catalyst is capable of preferentially hydrogenating carbon-carbon double bonds over carbon- oxygen double bonds.
  • This process is an important step in the process for the manufacture of isophytol and ⁇ -tocopherol or its acetate.
  • a mixture where the amount of non- (3EZ,5E,9E)-3,4-dehydrofarnesylacetone isomers is up to 49 mol-%, preferably up to 20 mol-%, more preferably up to 10 mol-%, based on the total amount of the mixture, may also be used successfully. More
  • (3E,5E,9Z)-3,4-dehydrofarnesylacetone, (3E, 5Z,9Z)-3,4-dehydrofarnesyl- acetone, (3Z, 5E,9Z)-3,4-dehydrofarnesylacetone and (3Z, 5Z,9Z)-3,4- dehydrofarnesylacetone are only present in traces, i.e. in an amount of less than 0.5 mol-% each, more preferably in an amount of less than 0.1 mol-% each. Most preferably a mixture of (3E,5E,9E)-3,4-dehydrofarnesylacetone and (3Z,5E,9E)-3,4-dehydrofarnesylacetone is used, where neither
  • the catalyst comprises a metal selected from the group consisting of palladium, platinum, rhodium, iridium and nickel and mixtures thereof. More preferably the catalyst comprises a metal selected from the group consisting of palladium, platinum and mixtures thereof. Even more preferably the catalyst is a metal selected from the group consisting of palladium, platinum and mixtures thereof. Most preferably the catalyst is palladium.
  • a support/carrier being selected from the group consisting of carbon, graphite, inorganic oxides, inorganic carbonates, inorganic sulfates, as well as mixtures thereof where the active component (i.e. the metal) is deposited on.
  • Preferred support/carrier materials are carbon, silicon dioxide, aluminum oxide and calcium carbonate, as well as mixtures thereof.
  • An example for such mixtures are silica-alumina-mixtures.
  • the most preferred catalysts according to the present invention are palladium on carbon and palladium on alumina. If the active metal is used on a support/carrier material, the active metal content is preferably in the range of from 0.5 to 20 weight%, more preferably in the range of from 2 to 5 weight%, most preferably in the range of approximately 5 weight%, based on the total weight of active metal and support.
  • the amount of the active component of the catalyst (being preferably a metal selected from the group consisting of palladium, platinum, rhodium, iridium and nickel and mixtures thereof) is preferably in the range of from 0.0001 to 1 weight%, more preferably in the range of from 0.001 to 0.5 weight%, most preferably in the range of from 0.01 to 0.1 weight%, based on the weight of the starting material, the mixture of (3E,5E,9E)-3,4- dehydrofarnesylacetone and (3Z,5E,9E)-3,4-dehydrofarnesylacetone.
  • the hydrogenation reaction is preferably carried out at a temperature in the range of from 10 to 150° C, more preferably at a temperature in the range of from 20 to 100° C, most preferably at a temperature in the range of from 50 to 90 ° C.
  • the hydrogenation reaction is preferably carried out at a hydrogen pressure in the range of from 1 to 25 bar hydrogen absolute, more preferably at a hydrogen pressure in the range of from 2 to 10 bar hydrogen absolute, even more preferably at a hydrogen pressure in the range of from 2 to 6 bar hydrogen absolute, further more preferably at a hydrogen pressure in the range of from 2.5 to 4 bar hydrogen absolute most preferably at a hydrogen pressure of around 3 bar hydrogen absolute.
  • the hydrogenation reaction can be carried without solvent or in the presence of an organic solvent.
  • the reaction is carried out in an organic solvent.
  • the organic solvent is preferably selected from the group consisting of hydrocarbons, halogenated hydrocarbons, alcohols, ethers, esters, amides, nitriles and ketones and mixtures thereof. More preferred are C 4 -Cio
  • Ci -C 4 linear alkyl groups or C 3 -C 4 branched alkyl groups or halogens Ci -C 4 linear alcohols or C 3 -C 4 branched alcohols
  • acyclic and cyclic C 4 -Cio ethers Ci -Cio esters, C 3 -Cio ketones and mixtures thereof.
  • Especially preferred organic solvents are selected from the group consisting of hexane, heptane, toluene, methanol, ethanol, n-propanol, 2-propanol, n- butanol, tetrahydrofuran, 2-methyl-tetrahydrofuran, dioxane, ethyl acetate, isopropyl acetate, acetone, and mixtures thereof.
  • the most preferred solvent is heptane.
  • a mixture of the substrate dehydrofarnesylacetone (200 mg) (either a mixture of (3EZ,5EZ,9E) or (3EZ,5EZ,9EZ) isomers and solvent (2 g) is added to a glass reactor.
  • the catalyst is added and the reactor is sealed.
  • the mixture is purged three times with nitrogen (pressurise to 5 bar, then release) and three times with hydrogen (pressurise to 5 bar, then release).
  • the reactor is heated to the desired temperature and then pressurised with hydrogen to the desired pressure. Stirring is started at 1000 rpm and the hydrogen uptake is recorded. After a total experiment time of 18 hours the reaction mixture is cooled to room temperature, the pressure is released and a sample taken for GC area% analysis.
  • the following catalysts are used: - a 5% Pd/Al 2 0 3 egg-shell catalyst with a BET surface area of 93 m 2 /g and a pore volume of 0.3 ml/g as e.g. commercially available from Evonik under the tradename "5% Pd/Al 2 0 3 E 213 R/D";

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

La présente invention concerne un procédé de production du 6,10,14-triméthylpentadécan-2-one ("cétone en C18") comprenant l'étape consistant à hydrogéner un mélange de (3E,5E,9E)-3,4-déshydrofarnésylacétone et de (3Z,5E,9E)-3,4-déshydrofarnésylacétone avec de l'hydrogène en présence d'un catalyseur, le catalyseur pouvant hydrogéner de préférence les liaisons doubles carbone-carbone par rapport aux liaisons doubles carbone-oxygène. Le catalyseur comprend de préférence un métal choisi dans le groupe constitué par le palladium, le platine, le rhodium, l'iridium et le nickel, et des mélanges de ceux-ci. L'invention concerne également un procédé de préparation du (2E,6E)-farnésal par oxydation sélective du (2E,6E)-farnésol et un procédé de fabrication d'un mélange de (3E,5E,9E)-3,4-déshydrofarnésylacétone et de (3Z,5E,9E)-3,4-déshydrofarnésylacétone à partir du (2E,6E)-farnésal.
PCT/EP2016/080664 2015-12-11 2016-12-12 Procédé de production du 6,10,14-triméthylpentadécan-2-one, isophytol et alpha-tocophérol Ceased WO2017098050A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EPEP15199585.9 2015-12-11
EP15199585 2015-12-11

Publications (1)

Publication Number Publication Date
WO2017098050A1 true WO2017098050A1 (fr) 2017-06-15

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PCT/EP2016/080664 Ceased WO2017098050A1 (fr) 2015-12-11 2016-12-12 Procédé de production du 6,10,14-triméthylpentadécan-2-one, isophytol et alpha-tocophérol

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109651118A (zh) * 2018-12-25 2019-04-19 万华化学集团股份有限公司 一种植酮的制备方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4005147A (en) * 1971-10-13 1977-01-25 Badische Anilin- & Soda-Fabrik Aktiengesellschaft Production of α,β-unsaturated ketones
JPS5414906A (en) * 1977-07-06 1979-02-03 Kuraray Co Ltd Preparation of phytone or isophytol
US5955636A (en) * 1996-07-05 1999-09-21 Kuraray Co., Ltd. Process for producing 6-methyl-3-hepten-2-one and 6-methyl-2-heptanone analogues, and process for producing phyton or isophytol
WO2014096098A1 (fr) * 2012-12-18 2014-06-26 Dsm Ip Assets B.V. (6r,10r)-6,10,14-triméthylpentadécan-2-one préparée à partir de 6,10,14-triméthylpentadéca-5,9,13-trién-2-one ou de 6,10,14-triméthylpentadéca-5, 9-dién-2-one
CN104387221A (zh) * 2014-11-24 2015-03-04 深圳万乐药业有限公司 一种培维a酸脱羧体杂质的合成方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4005147A (en) * 1971-10-13 1977-01-25 Badische Anilin- & Soda-Fabrik Aktiengesellschaft Production of α,β-unsaturated ketones
JPS5414906A (en) * 1977-07-06 1979-02-03 Kuraray Co Ltd Preparation of phytone or isophytol
US5955636A (en) * 1996-07-05 1999-09-21 Kuraray Co., Ltd. Process for producing 6-methyl-3-hepten-2-one and 6-methyl-2-heptanone analogues, and process for producing phyton or isophytol
WO2014096098A1 (fr) * 2012-12-18 2014-06-26 Dsm Ip Assets B.V. (6r,10r)-6,10,14-triméthylpentadécan-2-one préparée à partir de 6,10,14-triméthylpentadéca-5,9,13-trién-2-one ou de 6,10,14-triméthylpentadéca-5, 9-dién-2-one
CN104387221A (zh) * 2014-11-24 2015-03-04 深圳万乐药业有限公司 一种培维a酸脱羧体杂质的合成方法

Non-Patent Citations (6)

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Title
DATABASE WPI Week 197911, 1979 Derwent World Patents Index; AN 1979-20563B, XP002766181 *
KAKIUCHI, N. ET AL.: "Pd(II)-hydrotalcite-catalyzed selective oxidation of alcohols using molecular oxygen", BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, vol. 74, no. 1, 2001, pages 165 - 172, XP009171442, ISSN: 0009-2673, DOI: 10.1246/BCSJ.74.165 *
NAVES, Y.-R.: "Etudes sur les matières végétales volatiles XCII. Sur la farnésylidène-acétone", HELVETICA CHIMICA ACTA, vol. 32, no. 5, 1949, pages 1802 - 1805, XP055337115, ISSN: 0018-019X, DOI: 10.1002/hlca.19490320556 *
SARYCHEVA, I.K. ET AL.: "New synthesis of 2,6,10,14-tetramethyl-15-hexadecen-14-ol, isophytol", ZHURNAL OBSHCHEI KHIMII, vol. 28, 1958, pages 647 - 651, XP009193141 *
TAKAJO, S. ET AL.: "Membrane properties of sodium 2- and 6-(poly)prenyl-substituted polyprenyl phosphates", NEW JOURNAL OF CHEMISTRY, vol. 25, no. 7, 2001, pages 917 - 929, XP055336851, ISSN: 1144-0546, DOI: 10.1039/b101802g *
ZOBRIST, F. ET AL.: "Zur Kenntnis der Sesquiterpene. 86. Mitteilung. Die Cyclisation von Farnesyliden-aceton", HELVETICA CHIMICA ACTA, vol. 32, no. 4, 1949, pages 1192 - 1197, XP055336924, ISSN: 0018-019X, DOI: 10.1002/hlca.19490320405 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109651118A (zh) * 2018-12-25 2019-04-19 万华化学集团股份有限公司 一种植酮的制备方法

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