WO2021056466A1 - Procédé de préparation d'une amine aromatique secondaire - Google Patents

Procédé de préparation d'une amine aromatique secondaire Download PDF

Info

Publication number
WO2021056466A1
WO2021056466A1 PCT/CN2019/108716 CN2019108716W WO2021056466A1 WO 2021056466 A1 WO2021056466 A1 WO 2021056466A1 CN 2019108716 W CN2019108716 W CN 2019108716W WO 2021056466 A1 WO2021056466 A1 WO 2021056466A1
Authority
WO
WIPO (PCT)
Prior art keywords
palladium
alkali metal
ligand
aromatic
aryl
Prior art date
Application number
PCT/CN2019/108716
Other languages
English (en)
Chinese (zh)
Inventor
施继成
周发斌
张力学
卢泽润
徐健辉
陈锐洪
林梦亭
李佩珍
Original Assignee
广东石油化工学院
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 广东石油化工学院 filed Critical 广东石油化工学院
Priority to PCT/CN2019/108716 priority Critical patent/WO2021056466A1/fr
Publication of WO2021056466A1 publication Critical patent/WO2021056466A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/04—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups
    • C07C209/06—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms
    • C07C209/10—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms with formation of amino groups bound to carbon atoms of six-membered aromatic rings or from amines having nitrogen atoms bound to carbon atoms of six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/50—Organo-phosphines

Definitions

  • the invention relates to a method for preparing secondary aromatic amines through Buchwald-Hartwig amination reaction, and belongs to the field of fine chemicals.
  • Secondary (heterocyclic) aromatic amines are often used in the preparation of drugs, pesticides and organic photoelectric materials, and are an important fine chemical. Hartwig and Buchwald pioneered the palladium-catalyzed (pseudo) haloaromatic amination reaction, also known as the Buchwald-Hartwig amination reaction. Due to its mild reaction conditions and high selectivity, palladium-catalyzed (pseudo) halogenated aromatic hydrocarbons and (pseudo) halogenated heterocyclic aromatic hydrocarbons have CN coupling reactions with aromatic amines and heterocyclic aromatic amines, which have become the preparation of secondary (heterocyclic) aromatics. Amine is an irreplaceable method.
  • Alkali is an essential component of the Buchwald-Hartwig amination reaction and has a great influence on the reaction.
  • alkali metal carbonic acid, phosphoric acid and tert-butoxy salt are commonly used in palladium-catalyzed C-N coupling reactions (David S. Surry and S. L. Buchwald., Chem. Sci., 2011, 2, 27.).
  • the present invention provides a method for using alkali metal carboxylates and alkali metal bicarbonates as bases to promote palladium-catalyzed C-N coupling reactions, which has the following advantages:
  • alkali metal carboxylates as bases provides that carboxylic acids are added to the reaction system to form hydrogen bonds with the nitrogen atoms in the substrate or product, thereby inhibiting the coordination of these nitrogen atoms with the palladium center of these poisoning catalysts. Behavior, thereby improving the catalytic efficiency;
  • the present invention provides a palladium-catalyzed (pseudo) halogenated aromatic hydrocarbon or (pseudo) halogenated heterocyclic aromatic hydrocarbon and (heterocyclic) aromatic amine promoted by alkali metal carboxylate or alkali metal hydrogen carbonate.
  • the method of CN coupling to prepare secondary aromatic amine can be shown by the following reaction equation:
  • Ar and Ar' represent the commonly defined substituents of aromatic compounds, which can be a single aromatic ring or multiple aromatic rings, and even these aromatic rings can be condensed with other aromatic rings.
  • the aromatic ring referred to here can contain There are N, O or S heteroatoms, these aromatic rings can have 1-5 substituents containing 0-25 carbon atoms, and these substituents can have 1-15 N, O, S, F or Cl atoms , Can also be connected to each other to form a ring;
  • X is an I, Br, Cl atom, or an OR 1 group, where R 1 represents a methanesulfonyl, benzenesulfonyl, p-toluenesulfonyl or trifluoromethanesulfonyl group;
  • the palladium catalyst is composed of a palladium source and a phosphine ligand or a nitrogen heterocyclic carbene ligand (the ratio of palladium to ligand is 1:0 to 1:5).
  • the palladium source is a palladium compound commonly used in palladium-catalyzed CN coupling reactions, including palladium acetate, palladium chloride, palladium acetylacetonate, palladium diphenylmethylene acetone, and palladium (Triphenylphosphine) Palladium, Diacetonitrile Palladium Chloride, 1,5-Cyclooctadiene Palladium Chloride, Dipolyallyl Palladium Chloride, Dipolymethylallyl Palladium Chloride, 2-Amino Bis Phen-2-ylpalladium chloride, or other sources of palladium well known to those skilled in the art;
  • a palladium compound commonly used in palladium-catalyzed CN coupling reactions including palladium acetate, palladium chloride, palladium acetylacetonate, palladium diphenylmethylene acetone, and palladium (Triphenylphosphine) Pal
  • the ligand is a phosphine ligand or an azacyclic carbene:
  • the phosphine ligand has the structure of general formula I
  • R 2 , R 3 and R 4 are each independently selected from alkyl, aryl, ferrocene or pyranosidyl groups of 1 to 30 carbon atoms, and these aryl and pyranosidyl groups may contain O, N or S atoms and 1-6 alkyl and aryl substituents containing 1-20 carbon atoms.
  • the nitrogen heterocyclic carbene has the structure of general formula II-1, II-2 or II-3
  • R 5 and R 6 are each independently selected from (1-30) carbon atom alkyl, aryl, ferrocene or pyranosidyl, these aryl and pyranosidyl may contain O, N Or S atoms and 1-6 alkyl and aryl substituents containing 1-20 carbon atoms.
  • the phosphine ligand and the nitrogen heterocyclic carbene ligand may be selected from ligands of the following structures:
  • the palladium source may even be a compound formed by pre-coordination with palladium with a phosphine ligand or nitrogen heterocyclic carbene ligand, including a palladium compound with the following structure:
  • the method provided by the present invention needs to be carried out in a reaction medium.
  • the reaction medium can be benzene, toluene, xylene, tetrahydrofuran, 2-methyltetrahydrofuran, ethylene glycol dimethyl ether, tert-butyl methyl ether, methanol, ethanol , Propanol, butanol, isopropanol, tert-butanol, acetone, acetonitrile, formic acid, acetic acid, propionic acid, butyric acid, water, or mixtures thereof;
  • the base used in the method provided by the present invention is an alkali metal bicarbonate or an alkali metal carboxylate.
  • the alkali metal bicarbonate includes cesium bicarbonate, potassium bicarbonate, sodium bicarbonate and lithium bicarbonate, and the alkali metal bicarbonate includes cesium bicarbonate, potassium bicarbonate, sodium bicarbonate, and lithium bicarbonate.
  • Carboxylate MO 2 CR 7 where M is an alkali metal, and R 7 is H or an alkyl or aryl group of 1 to 15 carbon atoms.
  • the ratio of the palladium catalyst to the substrate is 1:10 to 1:100,000.
  • the operation steps of the method provided by the present invention include that the palladium source and ligand used as a catalyst can be treated at a temperature of room temperature to 120°C for 5 to 60 minutes, then added to the reaction system, and reacted at 20-180°C. From 5 minutes to 24 hours, the reaction pressure is generally 1 to 50 atmospheres.
  • aryl halide (1.0mmol), amine (1.2mmol), alkali (1.3mmol), 0.5mmol% [(TPhos)Pd(all)Cl] and 75uL of 12 Alkane (as an internal standard for GC analysis) was dissolved in 2.0 mL tert-butanol with or without acetic acid (1.0 mmol).
  • the tube was sealed and placed at 100°C to react for 6 hours. Add dichloromethane and celite to aid filtration. It was analyzed by gas chromatography, and the product was separated by (petroleum ether/ethyl acetate) column chromatography.
  • aryl halide 1.0mmol
  • amine 1.2mmol
  • potassium acetate 1.3mmol
  • 0.5mmol% [(TPhos)Pd(all)Cl] and 75uL ten Dioxane was dissolved in 2.0 mL of anhydrous solvent.
  • the tube was sealed and placed at 100°C for 12 hours of reaction.
  • aryl halide 1.0mmol
  • amine 1.2mmol
  • potassium bicarbonate 1.3mmol
  • 0.5mmol% [(TPhos)Pd(all)Cl] 75uL
  • Dodecane (as an internal standard for GC analysis) was dissolved in 2.0 mL of anhydrous solvent. The tube was sealed and placed at 100°C for 12 hours of reaction. Add dichloromethane and celite to aid filtration, analyze by gas chromatography, and separate the product by (petroleum ether/ethyl acetate) column chromatography.
  • aryl halide 1.0mmol
  • amine 1.2mmol
  • bicarbonate 1.3mmol
  • 0.5mmol% [(TPhos)Pd(all)Cl] 75uL
  • Dodecane (as an internal standard for GC analysis) was dissolved in 2.0 mL of solvent. The tube was sealed and placed at 100°C for 12 hours of reaction. Add dichloromethane and celite to aid filtration, analyze by gas chromatography, and separate the product by (petroleum ether/ethyl acetate) column chromatography.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

L'invention concerne un procédé de préparation d'une amine aromatique secondaire par la mise en oeuvre d'une réaction de couplage C-N entre des hydrocarbures aromatiques (pseudo)halogénés catalysés par du palladium ou des hydrocarbures aromatiques hétérocycliques (pseudo)halogénés et une amine aromatique (hétérocyclique) primaire. Un alcali pour favoriser la réaction est un carboxylate de métal alcalin ou un hydrocarbonate de métal alcalin.
PCT/CN2019/108716 2019-09-27 2019-09-27 Procédé de préparation d'une amine aromatique secondaire WO2021056466A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/CN2019/108716 WO2021056466A1 (fr) 2019-09-27 2019-09-27 Procédé de préparation d'une amine aromatique secondaire

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2019/108716 WO2021056466A1 (fr) 2019-09-27 2019-09-27 Procédé de préparation d'une amine aromatique secondaire

Publications (1)

Publication Number Publication Date
WO2021056466A1 true WO2021056466A1 (fr) 2021-04-01

Family

ID=75165376

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2019/108716 WO2021056466A1 (fr) 2019-09-27 2019-09-27 Procédé de préparation d'une amine aromatique secondaire

Country Status (1)

Country Link
WO (1) WO2021056466A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103418438A (zh) * 2013-08-22 2013-12-04 上海化工研究院 一种氮杂卡宾类钯催化剂及其制备方法和应用
CN108929317A (zh) * 2018-10-25 2018-12-04 瑞阳制药有限公司 一锅法制备Delamanid高纯度中间体的方法
CN110156832A (zh) * 2019-05-29 2019-08-23 东莞市均成高新材料有限公司 双缩醛基苯基膦、它们的制备方法及在偶联反应中的用途
WO2019170163A1 (fr) * 2018-03-07 2019-09-12 东莞市均成高新材料有限公司 Ligands de triarylphosphine, leur procédé de préparation et leur utilisation dans la catalyse de réactions de couplage

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103418438A (zh) * 2013-08-22 2013-12-04 上海化工研究院 一种氮杂卡宾类钯催化剂及其制备方法和应用
WO2019170163A1 (fr) * 2018-03-07 2019-09-12 东莞市均成高新材料有限公司 Ligands de triarylphosphine, leur procédé de préparation et leur utilisation dans la catalyse de réactions de couplage
CN108929317A (zh) * 2018-10-25 2018-12-04 瑞阳制药有限公司 一锅法制备Delamanid高纯度中间体的方法
CN110156832A (zh) * 2019-05-29 2019-08-23 东莞市均成高新材料有限公司 双缩醛基苯基膦、它们的制备方法及在偶联反应中的用途

Similar Documents

Publication Publication Date Title
Hartwig et al. Iridium-catalyzed allylic substitution
Wolfe et al. Simple, efficient catalyst system for the palladium-catalyzed amination of aryl chlorides, bromides, and triflates
Li et al. Room temperature and solvent-free iridium-catalyzed selective alkylation of anilines with alcohols
Pujala et al. Zinc tetrafluoroborate hydrate as a mild catalyst for epoxide ring opening with amines: scope and limitations of metal tetrafluoroborates and applications in the synthesis of antihypertensive drugs (RS)/(R)/(S)-metoprolols
Yuan et al. Asymmetric catalytic Mannich-type reaction of hydrazones with difluoroenoxysilanes using imidazoline-anchored phosphine ligand–zinc (II) complexes
Yu et al. A highly efficient Mukaiyama–Mannich reaction of N-Boc isatin ketimines and other active cyclic ketimines using difluoroenol silyl ethers catalyzed by Ph 3 PAuOTf
Matsumoto et al. Catalytic imine–imine cross-coupling reactions
Yang et al. Enantioselective carbene insertion into the N–H bond of benzophenone imine
Okamoto Synthetic Reactions Using Low‐valent Titanium Reagents Derived from Ti (OR) 4 or CpTiX3 (X= O‐i‐Pr or Cl) in the Presence of Me3SiCl and Mg
Weng et al. Organocatalytic Michael Reaction of Nitroenamine Derivatives with Aldehydes: Short and Efficient Asymmetric Synthesis of (−)‐Oseltamivir
CN107602320B (zh) 一种基于镍催化制备三取代烯烃的合成方法
Hao et al. Cobalt (ii)/(imidazoline–oxazoline)-catalyzed enantioselective Michael addition of 2-acetyl azaarenes to β-CF 3-β-disubstituted nitroalkenes
Lu et al. Highly enantioselective catalytic alkynylation of ketones–A convenient approach to optically active propargylic alcohols
CN110294689B (zh) 一种钌金属配合物催化伯胺脱氢制备腈类化合物的方法
WO2016119349A1 (fr) Procédé de préparation de composés sulfonylurées et formate de sulfonamide
Yoo et al. Ir-Catalyzed C–H Amidation Using Carbamoyl Azides for the Syntheses of Unsymmetrical Ureas
Isa et al. Palladium-catalyzed amination of 2, 3, 3-trifluoroallyl esters: synthesis of trifluoromethylenamines via an intramolecular fluorine shift and CF 3 group construction
Gallego et al. Rh (I)-catalyzed enantioselective intramolecular hydroarylation of unactivated ketones with aryl pinacolboronic esters
Yiğit et al. Active ruthenium (II)-NHC complexes for alkylation of amines with alcohols using solvent-free conditions
Mohite et al. O-benzoylhydroxylamines: A versatile electrophilic aminating reagent for transition metal-catalyzed C–N bond-forming reactions
WO2021056466A1 (fr) Procédé de préparation d'une amine aromatique secondaire
Avidan-Shlomovich et al. Synthetic and mechanistic study of the catalytic enantioselective preparation of primary β-amino ketones from enones and a fluorinated Gabriel reagent
WO2024011921A1 (fr) Procédé de synthèse d'un dérivé d'indolone contenant une structure de buténamine
JPWO2008111371A1 (ja) ホスホロアミド化合物及びその製造方法、配位子、錯体、触媒、及び光学活性アルコールの製造方法
CN103748065B (zh) 2－烯基胺化合物的制造方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19946279

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 19946279

Country of ref document: EP

Kind code of ref document: A1

122 Ep: pct application non-entry in european phase

Ref document number: 19946279

Country of ref document: EP

Kind code of ref document: A1