WO2021056466A1 - 二级芳香胺的制备方法 - Google Patents

二级芳香胺的制备方法 Download PDF

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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
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palladium
alkali metal
ligand
aromatic
aryl
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PCT/CN2019/108716
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French (fr)
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施继成
周发斌
张力学
卢泽润
徐健辉
陈锐洪
林梦亭
李佩珍
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广东石油化工学院
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    • 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

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  • 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.

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Abstract

钯催化的(拟)卤代芳烃或(拟)卤代杂环芳烃与一级(杂环)芳香胺发生C-N偶联反应制备二级芳香胺的方法，用于促进反应的碱为碱金属羧酸盐或碱金属碳酸氢盐。

Description

二级芳香胺的制备方法 技术领域
本发明涉及经过Buchwald-Hartwig胺化反应来制备二级芳香胺的方法，属于精细化工领域。
背景技术
二级(杂环)芳香胺常用于药物、农药和有机光电材料的制备中，是一种重要的精细化学品。Hartwig和Buchwald率先开展钯催化的(拟)卤代芳烃的胺化反应，亦称为Buchwald-Hartwig胺化反应。由于其反应条件温和选择性高，钯催化的(拟)卤代芳烃和(拟)卤代杂环芳烃与芳香胺和杂环芳香胺发生C-N偶联反应业已成为制备二级(杂环)芳香胺不可替代的方法。碱是Buchwald-Hartwig胺化反应必要反应组分，对反应的影响很大。目前，碱金属碳酸、磷酸和叔丁氧盐常用于钯催化的C-N偶联反应(David S.Surry and S.L.Buchwald.,Chem.Sci.,2011,2,27.)。为了提供反应效率和/或增加官能团的容忍性，近几年开始探索应用碱金属苯酚盐和有机碱作为碱来促进反应的报道(E.P.K.Olsen,et al.,Angew.Chem.Int.Ed.,2017,56,10569；A.T.Brusoe,et al.,J.Am.Chem.Soc.,2015,137,8460；J.M.Dennis,White,N.A.,Liu,R.Y.,and Buchwald,S.L.,J.Am.Chem.Soc.,2018,140(13),4721)。曾有报道锗化物与胺在醋酸钠作用下发生钯催化的的C-N偶联反应的报道(Zhang,Qiang,et al.,Synlett,2016,27(13),1945)，但未见到比碱金属苯酚盐更弱的碱金属羧酸盐和碱金属碳酸氢盐用于钯催化的(拟)卤代芳烃和(拟)卤代杂环芳烃与芳香胺和杂环芳香胺发生C-N偶联反应。
本发明提供碱金属羧酸盐和碱金属碳酸氢盐作为碱来促进钯催化的C-N偶联反应的方法，具有以下优点：
(1)由于碱金属羧酸盐和碱金属碳酸氢盐的碱性更弱，进而进一步增大了这个反应对碱敏感的官能团的底物的应用范围；
(2)对于邻位带硝基(拟)卤代芳烃这类底物具有高活性，且不会如使用苯酚盐作为碱可能形成相应的芳醚类副产物；
(3)在重要而又挑战的五元杂环芳香胺如2-氨基恶唑或2-氨基噻唑与(拟)卤代芳烃的偶联反应中，有时具有更高的活性；
(4)长链羧酸碱金属盐甚至会加速反应；
(5)应用碱金属羧酸盐作为碱，提供了在反应体系中添加羧酸来与底物或产物中的氮原子形成氢键，从而抑制了这些氮原子与钯中心配位这些毒化催化剂的行为，进而提高催化效率；
(6)碱金属羧酸盐和碱金属碳酸氢的价格低于相应的碱金属苯酚盐和有机碱。
发明内容
第一方面，本发明提供一种在碱金属羧酸盐或碱金属碳酸氢促进下、在钯催化的(拟)卤代芳烃或(拟)卤代杂环芳烃与(杂环)芳香胺发生C-N偶联制备二级芳香胺的方法，可由下面反应方程式显示如下：
Figure PCTCN2019108716-appb-000001
其中，
Ar和Ar’代表通常定义的具有芳香性化合物的取代基，可以是单个芳香环，也可以是多个芳香环，甚至这些芳香环可以与其它芳香环稠合，这里指的芳香环中可以带有N、O或S杂原子，这些芳香环上可以带1-5个含有0-25个碳原子的取代基，这些取代基可以带有1-15个N、O、S、F或Cl原子、也可以相互之间连接成环；
X为I、Br、Cl原子，或者是OR 1基团，这里的R 1代表甲磺酰基、苯磺酰基、对甲苯磺酰基或三氟甲磺酰基；
且X直接与Ar中的芳香环相连。
第二方面，根据第一方面，钯催化剂由钯源和膦配体或氮杂环卡宾配体组成(钯与配体的比例为1:0到1:5)。
第三方面，根据第一、二方面，钯源为一般用于钯催化的C-N偶联反应的钯化合物，包括醋酸钯、氯化钯、乙酰丙酮钯、二苯基亚甲基丙酮钯、四(三苯基膦)钯、二乙腈氯化钯、1,5-环辛二烯氯化钯、二聚烯丙基氯化钯、二聚甲基烯丙 基氯化钯、2-氨基联苯-2-基氯化钯，或其它对于那些本领域技术人员来说熟知的钯源；
第四方面，根据第一、二方面，配体为膦配体或氮杂环卡宾：
膦配体具有通式I的结构
Figure PCTCN2019108716-appb-000002
其中，R 2、R 3和R 4各自独立地选自1-30个碳原子的烷基、芳基、二茂铁基或吡喃糖苷基，这些芳基和吡喃糖苷基可以含有O、N或S原子以及1-6个含1-20个碳原子的烷基和芳基取代基。
氮杂环卡宾具有通式II-1、II-2或II-3的结构
Figure PCTCN2019108716-appb-000003
其中，R 5和R 6各自独立地选自(1-30)个碳原子的烷基、芳基、二茂铁基或吡喃糖苷基，这些芳基和吡喃糖苷基可以含有O、N或S原子以及1-6个含1-20个碳原子的烷基和芳基取代基。
第五方面，根据第四方面，膦配体和氮杂环卡宾配体可以选自以下结构的配体：
Figure PCTCN2019108716-appb-000004
Figure PCTCN2019108716-appb-000005
第六方面，根据上述方面，钯源甚至可以是具有膦配体或氮杂环卡宾配体事先与钯配位形成的化合物，包括以下结构的钯化合物：
Figure PCTCN2019108716-appb-000006
第七方面，本发明提供的方法需要在反应介质中进行，反应介质可以是苯、甲苯、二甲苯、四氢呋喃、2-甲基四氢呋喃、乙二醇二甲醚、叔丁基甲基醚、甲醇、乙醇、丙醇、丁醇、异丙醇、叔丁醇、丙酮、乙腈、甲酸、乙酸、丙酸、丁酸、水，或它们的混合物；
第八方面，本发明提供的方法使用的碱是碱金属碳酸氢盐或碱金属羧酸盐，碱金属碳酸氢盐包括碳酸氢铯、碳酸氢钾、碳酸氢钠和碳酸氢锂，而碱金属羧酸盐MO 2CR 7，这里M为碱金属，R 7为H或1到15个碳原子的烷基或芳基。
第九方面，本发明提供的方法中，钯催化剂与底物的比例为1:10到1:100000。
本发明提供的方法的操作步骤包括，可以将用作催化剂的钯源与配体先在于室温到120℃的温度下处理5到60分钟，再加入到反应体系中，在20-180℃下反应5分钟到24小时，反应压力一般为1到50个大气压。
具体实施方法
下文提供了具体的实施方法进一步说明本发明，但本发明不仅仅限于以下的实施方式。
实施例1.
化合物N-(2-乙氧酰基苯基)-2-氨基噁唑的合成：
Figure PCTCN2019108716-appb-000007
在压力管中,在氮气氛围下,将2-氯苯甲酸乙酯(184mg,1.0mmol)、2-氨基噁唑(101mg,1.2mmol)、醋酸钾(128mg,1.3mmol)、2mol％的催化剂和75uL的十二烷(作为GC分析的内标)溶于2.0mL无水溶剂中。将该管密封并置于100℃中,反应12小时。加入二氯甲烷并硅藻土助滤，用气相色谱分析。通过(石油醚/乙酸乙酯)柱层析分离产物N-(2-乙氧酰基苯基)-2-氨基噁唑222.8mg，收率96％。
Figure PCTCN2019108716-appb-000008
a[(TPhos)Pd(all)Cl]：([(2,6-双(2,4,6-三异丙基苯基)苯基)-二环己基膦]-烯丙基-氯化钯)。 bE.P.K.Olsen,et.al.,Angew.Chem.Int.Ed.,2017,56,10569。
文献中，应用苯酚钠为碱，由于其碱性较强，在较强的碱存在下酯会发生副反应只能得到的成环的产物。表明更弱的碱如醋酸钾能容忍更多种类的官能团。
实施例2-5.
Figure PCTCN2019108716-appb-000009
在压力管中,在氮气氛围下,将2-氯硝基苯(1.0mmol)、2-氨基硝基苯(1.2mmol)、碱(1.3mmol)、1mol％的[(TPhos)Pd(all)Cl]和75uL的十二烷(作为GC分析的内标)溶于2.0mL叔丁醇中。将该管密封并置于100℃中,反应12小时。加入二氯甲烷并硅藻土助滤，用气相色谱分析。通过(石油醚/乙酸乙酯)柱层析分离得到产物和副产物2-硝基苯基苯醚。
Figure PCTCN2019108716-appb-000010
从实施例2到5可以明显看出，应用醋酸钠和醋酸钾作为碱可以到58-81％预期的产物，而应用碳酸钾为碱则只得到8％的产物，而应用苯酚钠为碱则只得到副产物。
实施例6-14.
Figure PCTCN2019108716-appb-000011
在压力管中,在氮气氛围下,将2-氯苯甲醚(143mg,1.0mmol)、2-氨基噁唑(101mg,1.2mmol)、碱(1.3mmol)、0.5mmol％[(TPhos)Pd(all)Cl]和75uL的十二烷(作为GC分析的内标)溶于2.0mL无水溶剂中。将该管密封并置于100℃中,反应12小时。加入二氯甲烷并硅藻土助滤。用气相色谱分析，通过(石油醚/乙酸乙酯)柱层析分离产物N-(2-甲氧基)-2-氨基噁唑。
实施例 碱 溶剂 收率(％)
6 KHCO 3 t-BuOH 99
7 KOAc t-BuOH 88
8 K 2CO 3 t-BuOH 83
9 KHCO 3 甲苯 96
10 KOAc 甲苯 66
11 K 2CO 3 甲苯 53
12 KHCO 3 THF 99
13 KOAc THF 97
14 K 2CO 3 THF 90
从实施例6到14可以明显看出，应用碳酸氢钾和醋酸钾作为碱在所得到产物的量，明显高于以碳酸钾为碱的量。
实施例15-17.
Figure PCTCN2019108716-appb-000012
在压力管中,在氮气氛围下,将2-(2-氯苯基)-苯基乙炔(1.0mmol)、2-氰基苯胺(1.2mmol)、碱(1.3mmol)、0.5mmol％[(TPhos)Pd(all)Cl]和75uL的十二烷(作为GC分析的内标)溶于2.0mL叔丁醇中。将该管密封并置于100℃中,反应1小时。加入二氯甲烷并硅藻土助滤。用气相色谱分析，通过(石油醚/乙酸乙酯)柱层析分离产物N-(2-苯乙炔基)-2-氰基苯胺。
实施例 碱 收率(％)
15 异辛酸钾 95
16 NaOPh 32
17 K 2CO 3 63
从实施例15到17可以明显看出，应用长链羧酸钾作为碱，在较短的时间内得到产物的量明显高于常用的苯酚钠和碳酸钾。
实施例18-21.
在压力管中,在氮气氛围下,将芳基卤化物(1.0mmol)、胺(1.2mmol)、碱(1.3mmol)、0.5mmol％[(TPhos)Pd(all)Cl]和75uL的十二烷(作为GC分析的内标)溶于2.0mL叔丁醇中，添加或不添加醋酸(1.0mmol)。将该管密封并置于100℃中,反应6小时。加入二氯甲烷并硅藻土助滤。用气相色谱分析，通过(石油醚/乙酸乙酯)柱层析分离产物。
Figure PCTCN2019108716-appb-000013
从实施例18到21可以明显看出，额外再添加1当量的醋酸，在相同的时间内得到产物的量明显增加。
实施例22-33.
在压力管中，在氮气氛围下,将芳基卤化物(1.0mmol)、胺(1.2mmol)、醋酸钾(1.3mmol)、0.5mmol％[(TPhos)Pd(all)Cl]和75uL的十二烷(作为GC分析的内标)溶于2.0mL无水溶剂中。将该管密封并置于100℃中,反应12小时。加入二氯甲烷并硅藻土助滤，用气相色谱分析，通过(石油醚/乙酸乙酯)柱层析分离产物。
Figure PCTCN2019108716-appb-000014
实施例34-47.
在压力管中，在氮气氛围下,将芳基卤化物(1.0mmol)、胺(1.2mmol)、碳酸氢钾(1.3mmol)、0.5mmol％[(TPhos)Pd(all)Cl]和75uL的十二烷(作为GC分析的内标)溶于2.0mL无水溶剂中。将该管密封并置于100℃中,反应12小时。加入二氯甲烷并硅藻土助滤，用气相色谱分析，通过(石油醚/乙酸乙酯)柱层析分离产物。
Figure PCTCN2019108716-appb-000015
实施例48-68.
在压力管中,在氮气氛围下,将芳基卤化物(1.0mmol)、胺(1.2mmol)、碳酸氢盐(1.3mmol)、0.5mmol％[(TPhos)Pd(all)Cl]和75uL的十二烷(作为GC分析的内标)溶于2.0mL溶剂中。将该管密封并置于100℃中,反应12小时。加入二氯甲烷并硅藻土助滤，用气相色谱分析，通过(石油醚/乙酸乙酯)柱层 析分离产物。
Figure PCTCN2019108716-appb-000016
Figure PCTCN2019108716-appb-000017

Claims (9)

  1. 本发明提供一种在碱金属羧酸盐或碱金属碳酸氢促进下、在钯催化的(拟)卤代芳烃或(拟)卤代杂环芳烃与一级(杂环)芳香胺发生C-N偶联制备二级芳香胺的方法，可由下面反应方程式显示如下：
    Figure PCTCN2019108716-appb-100001
    其中，
    Ar和Ar’代表通常定义的具有芳香性化合物的取代基，可以是单个芳香环，也可以是多个芳香环，甚至这些芳香环可以与其它芳香环稠合，这里指的芳香环中可以带有N、O或S杂原子，这些芳香环上可以带1-5个含有0-25个碳原子的取代基，这些取代基可以带有1-15个N、O、S、F或Cl原子、也可以相互之间连接成环；
    X为I、Br、Cl原子，或者是OR 1基团，这里的R 1代表甲磺酰基、苯磺酰基、对甲苯磺酰基或三氟甲磺酰基；
    且X直接与Ar中的芳香环相连。
  2. 根据权利要求1，钯催化剂由钯源和膦配体或氮杂环卡宾配体组成(钯与配体的比例为1:0到1:5)。
  3. 根据权利要求1和2，钯源为一般用于钯催化的C-N偶联反应的钯化合物，包括醋酸钯、氯化钯、乙酰丙酮钯、二苯基亚甲基丙酮钯、四(三苯基膦)钯、二乙腈氯化钯、1,5-环辛二烯氯化钯、二聚烯丙基氯化钯、二聚甲基烯丙基氯化钯、2-氨基联苯-2-基氯化钯，或其它对于那些本领域技术人员来说熟知的钯源；
  4. 根据权利要求1和2，配体为膦配体或氮杂环卡宾：
    膦配体具有通式I的结构
    Figure PCTCN2019108716-appb-100002
    其中，R 2、R 3和R 4各自独立地选自1-30个碳原子的烷基、芳基、二茂铁基或吡喃糖苷基，这些芳基和吡喃糖苷基可以含有O、N或S原子以及1-6个含1-20个碳原子的烷基和芳基取代基。
    氮杂环卡宾具有通式II-1、II-2或II-3的结构
    Figure PCTCN2019108716-appb-100003
    其中，R 5和R 6各自独立地选自1-30个碳原子的烷基、芳基、二茂铁基或吡喃糖苷基，这些芳基和吡喃糖苷基可以含有O、N或S原子以及1-6个含1-20个碳原子的烷基和芳基取代基。
  5. 根据权利要求4，膦配体和氮杂环卡宾配体可以选自以下结构的配体：
    Figure PCTCN2019108716-appb-100004
    Figure PCTCN2019108716-appb-100005
  6. 根据上述权利要求，本发明中的钯源甚至可以是具有膦配体或氮杂环卡宾配体事先与钯配位形成的化合物，包括以下结构的钯化合物：
    Figure PCTCN2019108716-appb-100006
  7. 本发明提供的方法需要在反应介质中进行，反应介质可以是苯、甲苯、二甲苯、四氢呋喃、2-甲基四氢呋喃、乙二醇二甲醚、叔丁基甲基醚、甲醇、乙醇、丙醇、丁醇、异丙醇、叔丁醇、丙酮、乙腈、甲酸、乙酸、丙酸、丁酸、水，或它们的混合物；
  8. 本发明提供的方法使用的碱是碱金属碳酸氢盐或碱金属羧酸盐，碱金属碳酸氢盐包括碳酸氢铯、碳酸氢钾、碳酸氢钠和碳酸氢锂，而碱金属羧酸盐MO 2CR 7，这里M为碱金属，R 7为H或1到15个碳原子的烷基或芳基。
  9. 本发明提供的方法中，钯催化剂与底物的比例为1:10到1:100000。
    本发明提供的方法的操作步骤包括，可以将用作催化剂的钯源与配体先在 于室温到120℃的温度下处理5到60分钟，再加入到反应体系中，在20-180℃下反应5分钟到24小时，反应压力一般为1到50个大气压。
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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 (zh) * 2018-03-07 2019-09-12 东莞市均成高新材料有限公司 三联芳单膦配体、它们的制备方法和在催化偶联反应中的用途

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 (zh) * 2018-03-07 2019-09-12 东莞市均成高新材料有限公司 三联芳单膦配体、它们的制备方法和在催化偶联反应中的用途
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

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