WO2021130057A1 - Dehydrogenation process - Google Patents

Dehydrogenation process Download PDF

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Publication number
WO2021130057A1
WO2021130057A1 PCT/EP2020/086170 EP2020086170W WO2021130057A1 WO 2021130057 A1 WO2021130057 A1 WO 2021130057A1 EP 2020086170 W EP2020086170 W EP 2020086170W WO 2021130057 A1 WO2021130057 A1 WO 2021130057A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
compound
dehydrogenation
mol
equivalent
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.)
Ceased
Application number
PCT/EP2020/086170
Other languages
English (en)
French (fr)
Inventor
Werner Bonrath
Marc-André Mueller
Bettina Wuestenberg
Viktor Zimmermann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
DSM IP Assets BV
Original Assignee
DSM IP Assets BV
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by DSM IP Assets BV filed Critical DSM IP Assets BV
Priority to US17/788,237 priority Critical patent/US12258311B2/en
Priority to JP2022532090A priority patent/JP2023506144A/ja
Priority to BR112022012342A priority patent/BR112022012342A2/pt
Priority to EP20823833.7A priority patent/EP4081505A1/en
Priority to CN202080089217.8A priority patent/CN114829338B/zh
Publication of WO2021130057A1 publication Critical patent/WO2021130057A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C47/00—Compounds having —CHO groups
    • C07C47/20—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms
    • C07C47/225—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms containing rings other than six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
    • C07C403/14—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by doubly-bound oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/002—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by dehydrogenation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated

Definitions

  • the present invention relates to a new compound, which is useful in the process of production of retinal (by dehydrogenation).
  • Retinal is an important compound, which can be used as such or it can be used to produce other derivatives of vitamin A (such as i.e. esters).
  • the goal of the present invention was to find a new and improved process to obtain retinal.
  • the new process uses the compound of formula (I) as starting material.
  • the compound of formula (I) can be in any of the 4 possible isomeric configurations.
  • the compound of formula (I) is a new compound.
  • the compound of formula (I) can be produced easily by processes known from the prior art.
  • the synthesis of the compound of formula (I) is disclosed below.
  • the compound of formula (I) is a very suitable compound in the synthesis of retinal, which is the compound of formula (II)
  • the compound of formula (II) can be in any isomeric configuration.
  • the new dehydrogenation process according to the present invention allows to introduce two double bonds in one step.
  • the present invention also relates to the dehydrogenation (DH) of the following compound of formula (I) to the compound of formula (II) in the presence of at least one oxidative reactant of formula (III) wherein
  • R 1 is CN, Cl or F
  • R 2 is CN, Cl or F
  • R 3 is H, CHs, Cl or F
  • R 4 is H, CHs, Cl or F.
  • Preferred oxidative reactants of formula (III) are those of the following formula (Ilia), (lllb) and (lllc):
  • the present invention relates to a dehydrogenation (DH1 ), which is dehydrogenation (DH), wherein the oxidative reactant is chosen from the group consisting of the compounds of formula (Ilia), (lllb) and (lllc)
  • the present invention relates to a dehydrogenation (DH1 ), which is dehydrogenation (DH), wherein the oxidative reactant is the compound of formula (lllc)
  • the amount of the oxidative reactant of formula (III) used in the process according to the present invention can vary.
  • the amount of the oxidative reactant of formula (III) usually goes from 0.5 mol-equivalent up to 5 mol-equivalent (in relation to compound of formula (I)).
  • the present invention relates to a dehydrogenation (DH2’), which is dehydrogenation (DH) or (DH1), wherein the amount of the oxidative reactant of formula (III) goes from 0.5 mol-equivalent up to 3 mol-equivalent (in relation to compound of formula (I)).
  • the process according to the present invention can also be carried out in the presence of at least one additive compound.
  • This additive compound is usually chosen from the group consisting of triethanolamine, pyridine, butylhydroxyltoluene, hydroquinone and triethoxyamine.
  • the additive compound(s) is (are) added in amount of 0.001 - 1 mol-equivalent (in relation to compound of formula (I)), preferably 0.003- 1 mol-equivalent (in relation to compound of formula (I)).
  • the present invention relates to a dehydrogenation (DH3), which is dehydrogenation (DH), (DH1), (DH2) or (DH2’), wherein the process is carried out in the presence of at least one additive compound.
  • the present invention relates to a dehydrogenation (DH3’), which is dehydrogenation (DH), (DH1), (DH2) or (DH2’), wherein the additive compound is chosen from the group consisting of triethanolamine, pyridine, butylhydroxyltoluene, hydroquinone and triethoxyamine. Therefore, the present invention relates to a dehydrogenation (DH3”), which is dehydrogenation (DH), (DH1 ), (DH2) or (DH2’), wherein the additive compound is added in amount of 0.001 - 1 mol-equivalent (in relation to compound of formula
  • the present invention relates to a dehydrogenation (DH3’”), which is dehydrogenation (DH), (DH1 ), (DH2) or (DH2’), wherein the additive compound is added in amount of 0.003 - 1 mol-equivalent (in relation to compound of formula
  • the reaction is usually carried out in an inert solvent.
  • the solvent is usually an aprotic solvent such as aromatic hydrocarbon (i.e. benzene or toluene), ethyl acetate, THF, 2-methyltetrahydrofuran or 1 , 4-dioxane.
  • the present invention relates to a dehydrogenation (DH4), which is dehydrogenation (DH), (DH1 ), (DH2), (DH2’), (DH3), (DH3’), (DH3”) or (DH3’”), wherein the process is carried out in the presence of at least one inert solvent.
  • the present invention relates to a dehydrogenation (DH4’), which is dehydrogenation (DH4), wherein the solvent is a protic solvent.
  • the present invention relates to a dehydrogenation (DH4”), which is dehydrogenation (DH4), wherein the solvent is chosen from the group consisting of aromatic hydrocarbon (i.e. benzene or toluene), ethyl acetate, THF, 2- methyltetrahydrofuran or 1 , 4-dioxane.
  • DH4 dehydrogenation
  • the solvent is chosen from the group consisting of aromatic hydrocarbon (i.e. benzene or toluene), ethyl acetate, THF, 2- methyltetrahydrofuran or 1 , 4-dioxane.
  • the process according to the present is usually carried out at elevated temperatures.
  • the process according to the present invention is carried out at a temperature of from 0°C - 150 °C, preferably from 30°C - 150°C, more preferred from 60°C - 150°C.
  • the present invention relates to a dehydrogenation (DH5), which is dehydrogenation (DH), (DH1), (DH2), (DH2’), (DH3), (DH3’), (DH3”), (DH3’”), (DH4), (DH4’) or (DH4”), wherein the process is carried out at a temperature of from 0°C - 150 °C.
  • the present invention relates to a dehydrogenation (DH5’), which is dehydrogenation (DH), (DH1), (DH2), (DH2’), (DH3), (DH3’), (DH3”), (DH3’”), (DH4), (DH4’) or (DH4”), wherein the process is carried out at a temperature of from 30°C - 150°C.
  • the present invention relates to a dehydrogenation (DH5”), which is dehydrogenation (DH), (DH1), (DH2), (DH2’), (DH3), (DH3’), (DH3”), (DH3’”), (DH4), (DH4’) or (DH4”), wherein the process is carried out at a temperature of from 60°C - 150°C.
  • the compound of formula (IV) is oxidized to the compound of formula (I):
  • the same reaction conditions as in J. M. Hoover, S. S. Stahl, J. Am. Chem. Soc., 2011, 133, 16901-16910 are used.
  • the temperature is given in °C and all percentages are related to the weight.
  • reaction mixture was heated to 90°C and a solution of DDQ (73 mg, 0.3 mmol, 1.0 eq), in 1.0 ml_ dry toluene was added.
  • DDQ 73 mg, 0.3 mmol, 1.0 eq
  • 1.0 ml_ dry toluene was added.
  • the reaction was stirred at 90°C for 30 min. Subsequently cooled to room temperature and filtered over a glas fibre filter. All volatiles were evaporated under reduced pressure (40°C, 5 mbar) to obtain the product as dark red oil.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
PCT/EP2020/086170 2019-12-23 2020-12-15 Dehydrogenation process Ceased WO2021130057A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
US17/788,237 US12258311B2 (en) 2019-12-23 2020-12-15 Dehydrogenation process
JP2022532090A JP2023506144A (ja) 2019-12-23 2020-12-15 脱水素化方法
BR112022012342A BR112022012342A2 (pt) 2019-12-23 2020-12-15 Processo de desidrogenação
EP20823833.7A EP4081505A1 (en) 2019-12-23 2020-12-15 Dehydrogenation process
CN202080089217.8A CN114829338B (zh) 2019-12-23 2020-12-15 脱氢方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP19219361.3 2019-12-23
EP19219361 2019-12-23

Publications (1)

Publication Number Publication Date
WO2021130057A1 true WO2021130057A1 (en) 2021-07-01

Family

ID=69005589

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2020/086170 Ceased WO2021130057A1 (en) 2019-12-23 2020-12-15 Dehydrogenation process

Country Status (6)

Country Link
US (1) US12258311B2 (https=)
EP (1) EP4081505A1 (https=)
JP (1) JP2023506144A (https=)
CN (1) CN114829338B (https=)
BR (1) BR112022012342A2 (https=)
WO (1) WO2021130057A1 (https=)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1254613B (de) * 1966-05-17 1967-11-23 Basf Ag Verfahren zur Herstellung von Vitamin A-Aldehyd

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4579415B2 (ja) * 1998-07-06 2010-11-10 ディーシーブイ・インコーポレイテッド・ドゥーイング・ビジネス・アズ・バイオ−テクニカル・リソーシィズ ビタミン製造方法
DE10026750A1 (de) * 1999-06-03 2001-01-18 Sumitomo Chemical Co Verfahren zur Herstellung von Retinin und Zwischenprodukte zur Herstellung desselben
ES2282480T3 (es) * 2001-10-31 2007-10-16 Dsm Ip Assets B.V. Preparacion de retinoides.
CN102276492B (zh) * 2010-06-08 2013-04-10 上海医药工业研究院 阿戈美拉汀中间体及其制备方法
EP2597081A1 (en) * 2011-11-25 2013-05-29 Basf Se Process for preparing 3-substituted 2-alkenals, in particular prenal

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1254613B (de) * 1966-05-17 1967-11-23 Basf Ag Verfahren zur Herstellung von Vitamin A-Aldehyd

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
J. M. HOOVERS. S. STAHL, J. AM. CHEM. SOC., vol. 133, 2011, pages 16901 - 16910

Also Published As

Publication number Publication date
BR112022012342A2 (pt) 2022-09-06
CN114829338A (zh) 2022-07-29
US20230068017A1 (en) 2023-03-02
JP2023506144A (ja) 2023-02-15
EP4081505A1 (en) 2022-11-02
US12258311B2 (en) 2025-03-25
CN114829338B (zh) 2024-05-03

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