CN105884677A - 一种铁催化苄基氯化镁进行交叉偶联反应的方法 - Google Patents

一种铁催化苄基氯化镁进行交叉偶联反应的方法 Download PDF

Info

Publication number
CN105884677A
CN105884677A CN201610250559.9A CN201610250559A CN105884677A CN 105884677 A CN105884677 A CN 105884677A CN 201610250559 A CN201610250559 A CN 201610250559A CN 105884677 A CN105884677 A CN 105884677A
Authority
CN
China
Prior art keywords
coupling reaction
benzylmagnesium chloride
mol
chloride
out cross
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
Application number
CN201610250559.9A
Other languages
English (en)
Inventor
陈朗秋
戚遐龄
成昌梅
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.)
Xiangtan University
Original Assignee
Xiangtan University
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 Xiangtan University filed Critical Xiangtan University
Priority to CN201610250559.9A priority Critical patent/CN105884677A/zh
Publication of CN105884677A publication Critical patent/CN105884677A/zh
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
    • C07D213/16—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
    • C07D213/127—Preparation from compounds containing pyridine rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)

Abstract

本发明涉及有机合成领域，公开了一种铁催化苄基氯化镁进行交叉偶联反应的方法，该方法包括：在氮气保护下，向烧瓶中加入0.001mol的无水三氯化铁，0.001mol的四甲基乙二胺，无水四氢呋喃10mL，室温搅拌5分钟；然后将0.01mol吡啶氯化物加入其中，随后加入溶于25ml四氢呋喃的苄基氯化镁0.03mol，搅拌6小时，过滤反应液，旋干溶剂，用乙酸乙酯和水以体积比1：1萃取分层，然后将有机相旋干。本发明提供的方法能够高收率地获得产物。

Description

一种铁催化苄基氯化镁进行交叉偶联反应的方法
技术领域
本发明涉及有机合成领域，具体地，涉及一种铁催化苄基氯化镁进行交叉偶联反应的方法。
背景技术
2-苄基吡啶类衍生物因在医药等领域中的重要应用价值而引起人们的高度的重视，如2-(1,2-二苯基乙基)吡啶-3-胺类系列化合物对于治疗老年痴呆很有疗效，吡美诺在抗心律失常方面有显著药效等。
近年来，被报道的2-苄基吡啶类化合物合成方法有很多，Hirohisa报道的钴催化2-氯吡啶与芳基格式试剂的偶联反应，Liu报道的钯催化2-吡啶醋酸钾盐与芳基卤代物(或芳基三氟甲磺酸酯)的脱羧偶联反应，Alice报道的钯催化二氯吡啶与苄基硼烷化合物的Suzuki-Miyaura交叉偶联反应，Knochel报道的用氯化锌，三氟甲磺酸钪(或三氟化硼乙醚溶液)促进钯催化2-甲基吡啶与芳基溴的偶联反应等等。
综合以上几种2-苄基吡啶类化合物的合成方法来看，由于钯催化剂高昂的成本，所以用钴催化2-氯吡啶和芳基格式试剂的偶联应该是一种相对简单且成本低的制备方法，但由于钴催化剂效率不算特别高，在此的研究基础上，考虑到铁化合物廉价、无毒和环境友好的优点，我们最终以三氯化铁为催化剂，用苄基氯化镁和2-氯吡啶及其衍生物为原料，研究了配体、溶剂、温度等因素的影响，最高得到了接近定量的偶联反应收率。
发明内容
本发明提供了一种铁催化苄基氯化镁进行交叉偶联反应的方法，该方法包括：在氮气保护下，向烧瓶中加入0.001mol的无水三氯化铁，0.001mol的四甲基乙二胺，无水四氢呋喃10mL，室温搅拌5分钟；然后将0.01mol吡啶氯化物加入其中，随后加入溶于25ml四氢呋喃的苄基氯化镁0.03mol，搅拌6小时，过滤反应液，旋干溶剂，用乙酸乙酯和水以体积比1：1萃取分层，然后将有机相旋干。
本发明提供的方法能够实现高收率地获得产物。
具体实施方式
本发明提供了一种铁催化苄基氯化镁进行交叉偶联反应的方法，该方法包括：在氮气保护下，向烧瓶中加入0.001mol的无水三氯化铁，0.001mol的四甲基乙二胺，无水四氢呋喃10mL，室温搅拌5分钟；然后将0.01mol吡啶氯化物加入其中，随后加入溶于25ml四氢呋喃的苄基氯化镁0.03mol，搅拌6小时，过滤反应液，旋干溶剂，用乙酸乙酯和水以体积比1：1萃取分层，然后将有机相旋干。
本发明首先确定以三氯化铁为催化剂，以2-氯吡啶与苄基氯化镁的偶联为模板反应，选择不同溶剂、温度和配体，来观察不同因素对偶联反应的影响。
本发明提供的上述方法能够实现高收率地获得产物。
以下将通过实施例对本发明进行详细描述。
实施例1：溶剂对铁催化偶联反应的影响
首先制备格式试剂苄基氯化镁，所以选取合适的溶剂来引发格式反应显得格外重要，于是我们选取了四个格式试剂制备最常用的溶剂在常温的条件下来进行偶联反应，最终结果如表1所示，通过观察可以发现，偶联在不同溶剂里的转化率有着较大差别，其中N-甲基吡咯烷酮和乙醚反应效率较为低下，原因可能是由于格式试剂制备时自身偶联严重，相比较而言，四氢呋喃和二氧六环作溶剂时偶联反应的产率要高一些，其中又以四氢呋喃作溶剂时产率最高，达到了64％。
表1
编号 溶剂 收率(％)
1 THF 64
2 Et2O 40
3 NMP 33
4 1,4-二氧六环 53
实施例2：温度对铁催化偶联反应的影响
确定了四氢呋喃为最优溶剂之后，我们测试了零度，室温，溶剂回流温度三个不同程度对偶联反应的影响，结果如表2所示，可以看出，反应转化率并没有随着温度的升高而升高，而是在室温时达到了相对较高的转化率。
表2
编号 温度(℃) 收率(％)
1 0 41
2 25 64
3 70 59
实施例3：配体对铁催化偶联反应的影响
考察不同配体对偶联反应的影响，如表3所示，发现在使用碳配体1，5-环辛二烯和烯丙苯时，都对反应产生了抑制作用，这可能是配体与催化剂生成络合物之后，对铁离子的束缚过大，从而抑制了铁催化剂与2-氯吡啶的氧化加成，同样包括二茂铁，四苯基卟啉氯化铁，以及1,1'-双(二苯基膦)二茂铁可能都存在这样的问题，导致反应收率较低。而在使用氮配体时，除了三乙烯二胺与1，10-邻菲罗啉之外其它配体都是促进反应的进行，特别是使用四甲基乙二胺做配体时，产率高达98％。
表3
编号 配体 收率(％)
1 1,5-环辛二烯 48
2 二茂铁 30
3 烯丙苯 30
4 1，1-双(二苯基磷)二茂铁 20
5 四苯基卟啉氯化铁 0
6 三乙烯二胺 54
7 1,10-菲罗琳 55
8 1,4-二甲基哌嗪 81
9 2,2-联吡啶 79
10 四甲基乙二胺 98
11 1,8-二氮杂二环十一碳-7-烯 87
从上述实施例的结果可以看出：采用本发明的方法能够获得高的产物收率。
以上详细描述了本发明的优选实施方式，但是，本发明并不限于上述实施方式中的具体细节，在本发明的技术构思范围内，可以对本发明的技术方案进行多种简单变型，这些简单变型均属于本发明的保护范围。
另外需要说明的是，在上述具体实施方式中所描述的各个具体技术特征，在不矛盾的情况下，可以通过任何合适的方式进行组合，为了避免不必要的重复，本发明对各种可能的组合方式不再另行说明。
此外，本发明的各种不同的实施方式之间也可以进行任意组合，只要其不违背本发明的思想，其同样应当视为本发明所公开的内容。

Claims (1)

1.一种铁催化苄基氯化镁进行交叉偶联反应的方法，该方法包括：在氮气保护下，向烧瓶中加入0.001mol的无水三氯化铁，0.001mol的四甲基乙二胺，无水四氢呋喃10mL，室温搅拌5分钟；然后将0.01mol吡啶氯化物加入其中，随后加入溶于25ml四氢呋喃的苄基氯化镁0.03mol，搅拌6小时，过滤反应液，旋干溶剂，用乙酸乙酯和水以体积比1：1萃取分层，然后将有机相旋干。
CN201610250559.9A 2016-04-21 2016-04-21 一种铁催化苄基氯化镁进行交叉偶联反应的方法 Pending CN105884677A (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610250559.9A CN105884677A (zh) 2016-04-21 2016-04-21 一种铁催化苄基氯化镁进行交叉偶联反应的方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610250559.9A CN105884677A (zh) 2016-04-21 2016-04-21 一种铁催化苄基氯化镁进行交叉偶联反应的方法

Publications (1)

Publication Number Publication Date
CN105884677A true CN105884677A (zh) 2016-08-24

Family

ID=56704352

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610250559.9A Pending CN105884677A (zh) 2016-04-21 2016-04-21 一种铁催化苄基氯化镁进行交叉偶联反应的方法

Country Status (1)

Country Link
CN (1) CN105884677A (zh)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108129284A (zh) * 2018-01-13 2018-06-08 中国烟草总公司郑州烟草研究院 一种基于ɑ-紫罗兰酮的新型合成香料及其制备方法
CN108164401A (zh) * 2018-01-13 2018-06-15 中国烟草总公司郑州烟草研究院 一种新型紫罗兰酮类香料及其制备方法
CN114478361A (zh) * 2022-01-24 2022-05-13 浙江工业大学 无金属催化的利用偶联反应制备氮杂芳烃类化合物的方法
CN114478361B (zh) * 2022-01-24 2024-06-07 浙江工业大学 无金属催化的利用偶联反应制备氮杂芳烃类化合物的方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101508625A (zh) * 2009-03-31 2009-08-19 四川大学 钴盐催化的芳卤与卤代烷直接交叉偶联合成烷基取代苯的方法
CN102395564A (zh) * 2009-04-17 2012-03-28 石原产业株式会社 2-卤代-6-取代-4-三氟甲基吡啶的生产方法
WO2012056003A1 (en) * 2010-10-28 2012-05-03 Syngenta Participations Ag Novel microbicides

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101508625A (zh) * 2009-03-31 2009-08-19 四川大学 钴盐催化的芳卤与卤代烷直接交叉偶联合成烷基取代苯的方法
CN102395564A (zh) * 2009-04-17 2012-03-28 石原产业株式会社 2-卤代-6-取代-4-三氟甲基吡啶的生产方法
WO2012056003A1 (en) * 2010-10-28 2012-05-03 Syngenta Participations Ag Novel microbicides

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HIROHISA O.ET AL.: "Cobalt-catalyzed Cross-coupling Reaction of Chloropyridines with Grignard Reagents", 《CHEMISTRY LETTERS》 *
胡跃飞主编: "《现代有机合成试剂.2.还原反应试剂》", 31 July 2011, 化学工业出版社 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108129284A (zh) * 2018-01-13 2018-06-08 中国烟草总公司郑州烟草研究院 一种基于ɑ-紫罗兰酮的新型合成香料及其制备方法
CN108164401A (zh) * 2018-01-13 2018-06-15 中国烟草总公司郑州烟草研究院 一种新型紫罗兰酮类香料及其制备方法
CN114478361A (zh) * 2022-01-24 2022-05-13 浙江工业大学 无金属催化的利用偶联反应制备氮杂芳烃类化合物的方法
CN114478361B (zh) * 2022-01-24 2024-06-07 浙江工业大学 无金属催化的利用偶联反应制备氮杂芳烃类化合物的方法

Similar Documents

Publication Publication Date Title
Wang et al. Ligand-promoted palladium-catalyzed aerobic oxidation reactions
Du et al. A Versatile Ruthenium (II)–NNC Complex Catalyst for Transfer Hydrogenation of Ketones and Oppenauer‐Type Oxidation of Alcohols
Liu et al. Oxygen-promoted PdCl 2-catalyzed ligand-free Suzuki reaction in aqueous media
Wickham et al. Transition metal (Ni, Cu, Pd)-catalyzed alkene dicarbofunctionalization reactions
Huang et al. Iron-catalyzed oxidative radical cross-coupling/cyclization between phenols and olefins.
Moselage et al. Cobalt-catalyzed C–H activation
Nieto et al. Transfer Hydrogenation in Water via a Ruthenium Catalyst with OH Groups near the Metal Center on a bipy Scaffold
He et al. Mn-catalyzed three-component reactions of imines/nitriles, Grignard reagents, and tetrahydrofuran: an expedient access to 1, 5-amino/keto alcohols
Russell et al. Iron-catalyzed intermolecular [2π+ 2π] cycloaddition
Varela et al. Construction of pyridine rings by metal-mediated [2+ 2+ 2] cycloaddition
Serrano et al. Synthesis and Characterization of Imine-Palladacycles Containing Imidate “Pseudohalide” Ligands: Efficient Suzuki–Miyaura Cross-Coupling Precatalysts and Their Activation To Give Pd0L n Species (L= Phosphine)
Grohmann et al. An iron (II) complex of a diamine-bridged bis-N-heterocyclic carbene
Xu et al. Rhodium (III)-Catalyzed cascade [5+ 1] annulation/5-exo-cyclization initiated by C–H activation: 1, 6-Diynes as one-carbon reaction partners
Guo et al. Palladium, iridium and ruthenium complexes with acyclic imino-N-heterocyclic carbenes and their application in aqua-phase Suzuki–Miyaura cross-coupling reaction and transfer hydrogenation
Manikandan et al. Ruthenium (II) carbonyl complexes containing pyridoxal thiosemicarbazone and trans-bis (triphenylphosphine/arsine): Synthesis, structure and their recyclable catalysis of nitriles to amides and synthesis of imidazolines
Arumugam et al. Palladium (II) complexes containing ONO tridentate hydrazone for Suzuki–Miyaura coupling of aryl chlorides in aqueous-organic media
You et al. Cooperative effects of lanthanides when associated with palladium in novel, 3D Pd/Ln coordination polymers. Sustainable applications as water-stable, heterogeneous catalysts in carbon–carbon cross-coupling reactions
Kumar et al. Bifunctional nickel precatalysts of amido-functionalized N-heterocyclic carbenes for base-free Michael reaction under ambient conditions
Hwang et al. Single-electron-transfer strategy for reductive radical cyclization: Fe (CO) 5 and phenanthroline system
Sun et al. Rhodium (III)-Catalyzed Oxidative Allylic C–H Indolylation via Nucleophilic Cyclization
Wang et al. Nickel-catalyzed carbonylative Negishi cross-coupling reactions
Wooten et al. Insight into substrate binding in Shibasaki’s Li3 (thf) n (binolate) 3Ln complexes and implications in catalysis
CN105884677A (zh) 一种铁催化苄基氯化镁进行交叉偶联反应的方法
Tanabe et al. Synthesis and reactivity of ruthenium complexes bearing arsenic-containing arsenic-nitrogen-arsenic-type pincer ligand
Li et al. Efficient palladium (II)-catalyzed homocoupling of thiazole-4-carboxylic or oxazole-4-carboxylic derivatives

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
WD01 Invention patent application deemed withdrawn after publication
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20160824