CN107118143B - 镍催化的三氟甲基芳基硒醚的制备方法 - Google Patents

镍催化的三氟甲基芳基硒醚的制备方法 Download PDF

Info

Publication number
CN107118143B
CN107118143B CN201710487662.XA CN201710487662A CN107118143B CN 107118143 B CN107118143 B CN 107118143B CN 201710487662 A CN201710487662 A CN 201710487662A CN 107118143 B CN107118143 B CN 107118143B
Authority
CN
China
Prior art keywords
bis
diphenylphosphine
nickel
halogenated aryl
aryl hydrocarbon
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.)
Active
Application number
CN201710487662.XA
Other languages
English (en)
Other versions
CN107118143A (zh
Inventor
张成潘
韩家斌
杨炼
董涛
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.)
Wuhan University of Technology WUT
Original Assignee
Wuhan University of Technology WUT
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 Wuhan University of Technology WUT filed Critical Wuhan University of Technology WUT
Priority to CN201710487662.XA priority Critical patent/CN107118143B/zh
Publication of CN107118143A publication Critical patent/CN107118143A/zh
Application granted granted Critical
Publication of CN107118143B publication Critical patent/CN107118143B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C391/00—Compounds containing selenium
    • C07C391/02—Compounds containing selenium having selenium atoms bound to carbon atoms of six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C391/00—Compounds containing selenium
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/325—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
    • C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/91—Dibenzofurans; Hydrogenated dibenzofurans
    • 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
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
    • C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
    • C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D335/10—Dibenzothiopyrans; Hydrogenated dibenzothiopyrans
    • C07D335/12—Thioxanthenes
    • C07D335/14—Thioxanthenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 9
    • C07D335/16—Oxygen atoms, e.g. thioxanthones

Landscapes

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

Abstract

本发明公开了镍催化的三氟甲基芳基硒醚的制备方法。包括以下步骤：将卤代芳烃、三氟甲硒基四甲基铵、镍催化剂与有机膦配体或联吡啶类化合物混合，在零下80至100℃反应5分钟至48小时，分离纯化，得三氟甲基芳基硒醚。所述卤代芳烃包含抗抑郁药吗氯贝胺或用于治疗成人高脂血症的非诺贝特。本发明不仅原料易得、条件温和、反应选择性好、产率高、官能团兼容性好、底物适用范围广(适用于氯代芳烃)，而且对仪器设备要求低、工艺操作简单。

Description

镍催化的三氟甲基芳基硒醚的制备方法
技术领域
本发明属于有机合成领域，具体涉及一种三氟甲基芳基硒醚的制备方法。
背景技术
氟原子具有电负性最大、原子半径与氢原子相当和脂溶性好等特点，将氟原子引入药物分子中，通常能增加原来分子的药理活性、代谢稳定性、提高脂溶性和生物利用度等。上世纪五六十年代，氟非那(Fluphenazine)和5-氟尿嘧啶(5-Fluorouracil)的问世，标志着含氟化合物在药物中开始得到应用。经过数十年的发展，含氟有机物已经在麻醉药、抗精神病药、甾体消炎药、抗感染药、心血管药、抗肿瘤药、酶抑制剂、诊断药等中占据重要地位。据统计，目前上市的药物中有20-30％的医药和35％左右的农药是含有氟元素的。现代医药和农药研究中，利用氟原子或者含氟官能团来调控原来分子的生理活性已成为新药研发的通用准则之一。
近年来，三氟甲硫基(-SCF3)由于具有合适的吸电子性和高亲脂性而受到了广泛的关注，关于构建三氟甲硫基的方法及相关三氟甲硫基化试剂的开发和应用被大量报道(Liang,T.；Neumann,C.N.；Ritter,T.Angew.Chem.,Int.Ed.2013,52,8214)。尽管目前三氟甲硫基化反应的研究已经比较成熟，但是关于三氟甲硒基化反应的研究(-SeCF3)还非常少见。硒是人体必须的微量矿物元素，在动物组织中常以甲硒胺(selenomethionine，简称SeMet)和硒半胱氨酸(selenocysteine，简称SeCys)的形态存在。硒和硫是同一主族的元素，因此三氟甲硒基与三氟甲硫基可能拥有相似的吸电子性和亲脂性。虽然目前没有含三氟甲硒基的药物，但是由于硒被广泛认为具有一定的抗肿瘤作用(Redman,C.；Scott,J.A.；Baines,A.T.；Basye,J.L.；Clark,L.C.；Calley,C.；Roe,D.；Payne,C.M.；Nelson,M.A.CancerLett.1998,125,103)，而且市场上有多种含硒的保健品，因此将含三氟甲硒基的化合物进行生物活性筛选，考察它们在生命科学领域中的应用，是很有研究价值的。
目前芳环上的三氟甲硫基化方法已经很成熟，但是关于向芳烃底物中引入三氟甲硒基的研究还很少。近年来，虽然金属参与的三氟甲硒基化方法取得了一些进展，但是这些方法存在原子经济性较差(Chen,C.；Ouyang,L.；Lin,Q.；Liu,Y.；Hou,C.；Yuan,Y.；Weng,Z.Chem.-Eur.J.2014,20,657–661)、催化剂不易获得、或者底物适用范围窄(Aufiero,M.；Sperger,T.；Tsang,A.-K；Schoenebeck,F.Angew.Chem.Int.Ed.2015,54,10322–10326)等问题。三氟甲硒基四甲基铵([NMe4][SeCF3])是最直接的三氟甲硒基来源，与目前已知的Hg(SeCF3)2、LCuSeCF3、ClSeCF3等相比，它的制备简单，性质稳定。另一方面，镍是一种廉价的偶联反应催化剂，与钯相比，它不仅简单易得，而且活性较高，可以活化很多钯和铜不能反应的惰性化学键如Csp2-Cl键等。因此，在镍催化下，通过[NMe4][SeCF3]对芳基卤代烷(包括芳基碘代烷、芳基溴代烷和芳基氯代烷)进行直接三氟甲硒基化，发展一种温和、高效的制备三氟甲基芳基硒醚的方法，尝试克服已有方法的缺点，具有重要研究意义。
发明内容
本发明的目的旨在提供一种原料易得、条件温和、反应选择性好、产率高、官能团兼容性好、底物适用范围广、仪器设备要求低、操作简单的方法制备三氟甲基芳基硒醚。
为达到上述目的，采用技术方案如下：
一种三氟甲基芳基硒醚的制备方法，包括以下步骤：
将卤代芳烃、三氟甲硒基四甲基铵、镍催化剂与有机膦配体或联吡啶类化合物混合，在零下80至100℃反应5分钟至48小时，分离纯化，得三氟甲基芳基硒醚。
按上述方案，所述的卤代芳烃结构式为Ar-X；
其中Ar为苯基、取代苯基、稠环芳基、取代稠环芳基、芳杂环或其衍生基团；X为氯、溴或碘。
按上述方案，所述卤代芳烃包括抗抑郁药吗氯贝胺和用于治疗成人高脂血症的非诺贝特。
按上述方案，卤代芳烃与三氟甲硒基四甲基铵的摩尔比为1：(0.1～10)。
按上述方案，卤代物为碘或溴时，卤代芳烃与三氟甲硒基四甲基铵的摩尔比为1：1.2；卤代物为氯时，卤代芳烃与三氟甲硒基四甲基铵的摩尔比为1：1.5。
按上述方案，有机膦配体为三苯基膦、三(2-甲氧基苯基)膦、三(4-甲氧基苯基)膦、三环己基膦、三乙基膦、三叔丁基磷、1,1'-双(二苯基膦)二茂铁和4,5-双二苯基膦-9,9-二甲基氧杂蒽、1,3-双(二苯基膦)丙烷、1,2-双(二苯基膦)乙烷中的一种；卤代芳烃与有机膦配体的摩尔比为1：(0.1～2)。
按上述方案，联吡啶类化合物为2,2’-联吡啶、4,4’-二甲基-2,2’-联吡啶、4,4’-二甲氧基-2,2’-联吡啶、4,4’-二叔丁基-2,2’-联吡啶和1,10-邻菲咯啉中的一种；其中卤代芳烃与联吡啶类配体的摩尔比为1：(0.05～2)。
当X为碘或溴时，优选联吡啶类化合物为反应的配体；当X为氯时，优选有机膦为反应的配体。
按上述方案，反应中还加入了有机溶剂，所述有机溶剂为乙腈、乙酸乙酯、二氯甲烷、1,2-二氯乙烷、三氯甲烷、四氢呋喃、1,4-二氧六环、乙醚、甲基叔丁基醚、甲苯、二甲苯、苯和砜类溶剂中的任意一种。
优选地，当X为碘或溴时，有机溶剂为四氢呋喃；当X为氯时，有机溶剂为甲苯。
按上述方案，所述的镍催化剂为双-(1,5-环辛二烯)镍、四(三苯基膦)镍、溴化镍、双(二苯基膦)二茂铁二氯化镍、二(三苯基膦)氯化镍中的任意一种；其中卤代芳烃与镍催化剂的摩尔比为1：(0.01～1)。
其中，优选价格低廉、简单易得的双-(1,5-环辛二烯)镍为该反应的催化剂。
按上述方案，三氟甲硒基化反应优选反应温度为0-60℃；优选反应时间为2-12h。
吗氯贝胺三氟甲硒基化类似物的制备方法，包括以下步骤：
将吗氯贝胺、三氟甲硒基四甲基铵、镍催化剂与有机膦配体或联吡啶类化合物混合，在零下80至100℃反应5分钟至48小时，分离纯化，得吗氯贝胺三氟甲硒基化类似物。
非诺贝特三氟甲硒基化类似物的制备方法，包括以下步骤：
将非诺贝特、三氟甲硒基四甲基铵、镍催化剂与有机膦配体或联吡啶类化合物混合，在零下80至100℃反应5分钟至48小时，分离纯化，得非诺贝特三氟甲硒基化类似物。
上述方案所述的三氟甲基芳基硒醚结构通式为：Ar-SeCF3
Ar-SeCF3还包括抗抑郁药吗氯贝胺的三氟甲硒基化类似物、治疗成人高脂血症的非诺贝特的三氟甲硒基化类似物。
本发明相对于现有技术的有益效果如下：
卤代芳烃是一类最常见的有机合成砌块，广泛应用于各种过渡金属参与的有机合成反应中，目前市场上销售的芳基卤代物种类繁多，价格低廉。三氟甲硒基化试剂[NMe4][SeCF3]可采用文献报道的方法非常方便地由TMSCF3，Se8和[Me4N]F合成(Tyrra,W.；Naumann,D.；Yagupolskii,Y.L.J.Fluorine Chem.2003,123,183)，从而保证了试剂的来源。此外，镍在地壳中的含量较为丰富，与钯相比，它的价格便宜、并且活性高。因此，本发明公开的镍催化下三氟甲硒基四甲基铵对芳基卤代物的三氟甲硒基化方法，具有很好的应用前景。
本发明不仅原料易得、条件温和、反应选择性好、产率高、官能团兼容性好、底物适用范围广(适用于氯代芳烃)，而且对仪器设备要求低、工艺操作简单。
抗抑郁药吗氯贝胺的三氟甲硒基化类似物和治疗成人高脂血症的非诺贝特的三氟甲硒基化类似物等类药分子的合成，证实了该方法在合成含三氟甲硒基的农药、医药分子、药物中间体和新材料等方面的巨大潜力。
具体实施方式
以下实施例进一步阐述本发明的技术方案，但不作为对本发明保护范围的限制。
本发明以芳基碘代烷为原料合成的三氟甲基芳基硒醚，其典型结构如下所示，但不作为对本发明保护范围的限制。
本发明以芳基溴代烷为原料合成的三氟甲基芳基硒醚，其典型结构如下所示，但不作为对本发明保护范围的限制。
本发明以芳基氯为原料合成的三氟甲基芳基硒醚，其典型结构如下所示，但不作为对本发明保护范围的限制。
实施例1：
室温下，100mL氮气保护的反应瓶中，加入4-碘苯甲醚(4.68g，20mmol)、四甲基三氟甲硒基铵(5.33g，24mmol)、2,2’-联吡啶(0.31g，2mmol)和双-(1，5-环辛二烯)镍(0.28g，1mmol)，然后用注射器加入四氢呋喃(50mL)，室温下反应2小时。将反应液旋干，残留物用硅胶柱层析(洗脱剂为正己烷)，即得4-三氟甲硒基苯甲醚(4.69g，92％)。
1H NMR(400MHz,CDCl3)δ7.66(d,J＝8.8Hz,2H),6.91(d,J＝8.8Hz,2H),3.83(s,3H)；19F NMR(376MHz,CDCl3)δ-37.2(s,3F)；13C NMR(100MHz,CDCl3)δ161.4,138.9,122.5(q,J＝333.0Hz),115.2,112.9,55.3.
实施例2：
室温下，100mL氮气保护的反应瓶中，加入4-碘苯乙酮(4.92g，20mmol)、四甲基三氟甲硒基铵(5.33g，24mmol)、2,2’-联吡啶(0.31g，2mmol)和四(三苯基膦)镍(1.11g，1mmol)，然后用注射器加入四氢呋喃(50mL)，室温下反应2小时。将反应液旋干，残留物用硅胶柱层析(洗脱剂为石油醚：乙酸乙酯＝20：1(v/v))，即得4-三氟甲硒基苯乙酮(3.47g，65％)。
1H NMR(400MHz,CDCl3)δ7.95(d,J＝8.3Hz,2H),7.83(d,J＝8.2Hz,2H),2.62(s,3H)；19F NMR(376MHz,CDCl3)δ-35.2(s,3F)；13C NMR(100MHz,CDCl3)δ197.2,138.2,136.6,129.1,128.2,122.3(q,J＝332.9Hz),26.6.
实施例3：
零下80摄氏度下，100mL氮气保护的反应瓶中，加入4-碘苯甲酸乙酯(5.52g，20mmol)、四甲基三氟甲硒基铵(5.33g，24mmol)、2,2’-联吡啶(0.31g，2mmol)和双-(1，5-环辛二烯)镍(0.28g，1mmol)，然后用注射器加入四氢呋喃(50mL)，0℃下反应2小时。将反应液旋干，残留物用硅胶柱层析(洗脱剂为石油醚：乙酸乙酯＝20：1(v/v))，即得4-三氟甲硒基苯甲酸乙酯(4.16g，70％)。
1H NMR(400MHz，CDCl3)δ8.04(d，J＝8.4Hz，2H)，7.80(d，J＝8.2Hz，2H)，4.39(q，J＝7.0Hz,2H),1.40(t,J＝7.1Hz,3H)；19F NMR(376MHz,CDCl3)δ-35.3(s,3F)；13C NMR(126MHz,CDCl3)δ165.7,136.4,132.2,130.4,127.9,122.4(q,J＝332.4Hz),61.4,14.2.IR(KBr):2985,2937,2909,2875,2856,1724,1594,1567,1478,1466,1447,1396,1369,1302,1284,1273,1179,1130,1098,1066,1015,964,853,784,759,739,690cm-1.HRMS-EIcalcd.for C10H9F3O2 74Se:291.9779；Found:291.9780.
实施例4：
室温下，100mL氮气保护的反应瓶中，加入6-碘吲哚(4.86g，20mmol)、四甲基三氟甲硒基铵(5.33g，24mmol)、2,2’-联吡啶(0.37g，2.4mmol)和双-(1，5-环辛二烯)镍(0.56g，2mmol)，然后用注射器加入四氢呋喃(50mL)，室温下反应2小时。将反应液旋干，残留物用硅胶柱层析(洗脱剂为石油醚：乙酸乙酯＝5：1(v/v))，即得4-三氟甲硒基苯甲醚(5.23g，99％)。
1H NMR(500MHz,CDCl3)δ8.22(br,1H),8.06(s,1H),7.53(d,J＝8.3Hz,1H),7.35(d,J＝8.2Hz,1H),7.22(s,1H),6.58(s,1H)；19F NMR(471MHz,CDCl3)δ-37.1(s,3F)；13C NMR(126MHz,CDCl3)δ136.5,130.8,130.5,129.0,125.4,122.7(q,J＝333.4Hz),112.5,112.0,103.0.
实施例5：
室温下，100mL氮气保护的反应瓶中，加入4-碘-N-2-(4-吗啉基)乙基苯甲酰胺(7.20g，20mmol)、四甲基三氟甲硒基铵(5.33g，24mmol)、2,2’-联吡啶(0.31g，2mmol)和双-(1，5-环辛二烯)镍(0.28g，1mmol)，然后用注射器加入四氢呋喃(50mL)，室温下反应2小时。将反应液旋干，残留物用硅胶柱层析(洗脱剂为二氯甲烷：甲醇＝20：1(v/v))，即得4-三氟甲硒基-N-2-(4-吗啉基)乙基苯甲酰胺(6.99g，92％)。
1H NMR(500MHz,acetone-d6)δ7.94(d,J＝8.2Hz,2H),7.87(d,J＝8.1Hz,2H),7.81(s,1H),3.60(t,J＝4.4Hz,4H),3.53(q,J＝6.4Hz,2H),2.56(t,J＝6.4Hz,2H),2.46(m,4H)；19F NMR(471MHz,acetone-d6)δ-37.0(s,3F)；13C NMR(126MHz,acetone-d6)δ166.4,138.1,137.6,129.3,126.2(q,J＝1.8Hz),123.8(q,J＝331.6Hz),67.5,58.3,54.5,37.5.
实施例6：
室温下，100mL氮气保护的反应瓶中，加入4-溴联苯(4.66g，20mmol)、四甲基三氟甲硒基铵(5.33g，24mmol)、2,2’-联吡啶(0.31g，2mmol)和双-(1，5-环辛二烯)镍(0.56g，2mmol)，然后用注射器加入四氢呋喃(50mL)，室温下反应2小时。将反应液旋干，残留物用硅胶柱层析(洗脱剂为正己烷)，即得4-三氟甲硒基联苯(5.72g，95％)。
1H NMR(500MHz,CDCl3)δ7.82(d,J＝7.9Hz,2H),7.64-7.58(m,4H),7.48(t,J＝7.3Hz,2H),7.41(t,J＝7.2Hz,1H)；19F NMR(471MHz,CDCl3)δ-36.0(s,3F)；13C NMR(126MHz,CDCl3)δ143.3,139.8,137.4,128.9,128.2,128.1,127.2,122.6(q,J＝332.4Hz),121.3.
实施例7：
室温下，100mL氮气保护的反应瓶中，加入4-溴苯甲砜(4.70g，20mmol)、四甲基三氟甲硒基铵(5.33g，24mmol)、2,2’-联吡啶(0.31g，2mmol)和双-(1，5-环辛二烯)镍(0.56g，2mmol)，然后用注射器加入四氢呋喃(50mL)，室温下反应2小时。将反应液旋干，残留物用硅胶柱层析(洗脱剂为石油醚：乙酸乙酯＝2：1(v/v))，即得4-三氟甲硒基苯甲砜(5.88g，97％)。
M.p.:68-70℃.1H NMR(500MHz,CDCl3)δ7.97-7.91(m,4H),3.08(s,3H)；19F NMR(471MHz,CDCl3)δ-34.8(s,3F)；13C NMR(126MHz,CDCl3)δ142.2,137.1,129.3,128.3,122.2(q,J＝333.3Hz),44.3.
实施例8：
室温下，100mL氮气保护的反应瓶中，加入6-氯喹啉(3.27g，20mmol)、四甲基三氟甲硒基铵(6.66g，30mmol)、1,1'-双(二苯基膦)二茂铁(2.22g，4mmol)和双-(1，5-环辛二烯)镍(0.55g，2mmol)，然后用注射器加入甲苯(50mL)，50℃下反应12小时。将反应液旋干，残留物用硅胶柱层析(洗脱剂为石油醚：乙酸乙酯＝10：1(v/v))，即得6-三氟甲硒基喹啉(5.26g，95％)。
1H NMR(500MHz,CDCl3)δ8.99(d,J＝4.0Hz,1H),8.26(s,1H),8.17(d,J＝8.3Hz,1H),8.11(d,J＝8.9Hz,1H),7.99(d,J＝8.7Hz,1H),7.47(dd,J＝8.2,4.1Hz,1H)；19F NMR(471MHz,CDCl3)δ-35.6(s,3F)；13C NMR(126MHz,CDCl3)δ152.0,148.3,137.2,136.4,136.1,130.8,128.6,122.5(q,J＝333.3Hz),122.0,120.7(q,J＝1.8Hz).
实施例9：
室温下，100mL氮气保护的反应瓶中，加入5-氯吲哚-2-羧酸乙酯(4.47g，20mmol)、四甲基三氟甲硒基铵(6.66g，30mmol)、1,1'-双(二苯基膦)二茂铁(3.33g，6mmol)和双-(1，5-环辛二烯)镍(0.83g，3mmol)，然后用注射器加入甲苯(50mL)，50℃下反应12小时。将反应液旋干，残留物用硅胶柱层析(洗脱剂为正己烷：二氯甲烷＝1：1(v/v))，即得5-三氟甲硒基吲哚-2-羧酸乙酯(5.71g，85％)。
M.p.:264-266℃.1H NMR(500MHz,acetone-d6)δ11.28(s,1H),8.20(s,1H),7.67-7.62(m,2H),7.29(s,1H),4.38(q,J＝7.0Hz,2H),1.38(t,J＝7.0Hz,3H)；19F NMR(471MHz,acetone-d6)δ-38.3(s,3F)；13C NMR(126MHz,acetone-d6)δ161.9,139.0,133.6,133.4,130.4,129.4,123.9(q,J＝332.4Hz),114.7,113.7,108.8,61.6,14.6.
实施例10：
室温下，100mL氮气保护的反应瓶中，加入2-甲基-2-(4-(4-氯苯甲酰基)苯氧基)丙酸异丙酯(7.22g，20mmol)、四甲基三氟甲硒基铵(6.66g，30mmol)、1,1'-双(二苯基膦)二茂铁(4.44g，8mmol)和双-(1，5-环辛二烯)镍(1.10g，4mmol)，然后用注射器加入甲苯(50mL)，50℃下反应12小时。将反应液旋干，残留物用硅胶柱层析(洗脱剂为正己烷：二氯甲烷＝1：2(v/v))，即得2-甲基-2-(4-(4-三氟甲硒基苯甲酰基)苯氧基)丙酸异丙酯(7.38g，78％)。
1H NMR(500MHz,CDCl3)δ7.83(d,J＝8.1Hz,2H),7.76(d,J＝8.7Hz,2H),7.73(d,J＝8.1Hz,2H),6.87(d,J＝8.7Hz,2H),5.08(m,1H),1.66(s,6H),1.20(d,J＝6.2Hz,6H)；19FNMR(471 MHz,CDCl3)δ-35.2(s,3F)；13C NMR(126 MHz,CDCl3)δ194.4,173.0,160.0,139.7,136.3,132.1,130.4,129.8,126.7,122.4(q,J＝333.4 Hz),117.2,79.4,69.3,25.3,21.5.

Claims (7)

1.一种三氟甲基芳基硒醚的制备方法，其特征在于包括以下步骤：
将卤代芳烃、三氟甲硒基四甲基铵、镍催化剂与有机膦配体或联吡啶类化合物混合，在零下80至100℃反应5分钟至48小时，分离纯化，得三氟甲基芳基硒醚；
所述的卤代芳烃结构式为Ar-X；
其中Ar为苯基、取代苯基、稠环芳基或取代稠环芳基；X为氯、溴或碘；
所述有机膦配体为三苯基膦、三(2-甲氧基苯基)膦、三(4-甲氧基苯基)膦、三环己基膦、三乙基膦、三叔丁基磷、1,1'-双(二苯基膦)二茂铁和4,5-双二苯基膦-9,9-二甲基氧杂蒽、1,3-双(二苯基膦)丙烷、1,2-双(二苯基膦)乙烷中的一种；卤代芳烃与有机膦配体的摩尔比为1：(0.1～2)；
联吡啶类化合物为2,2’-联吡啶、4,4’-二甲基-2,2’-联吡啶、4,4’-二甲氧基-2,2’-联吡啶、4,4’-二叔丁基-2,2’-联吡啶和1,10-邻菲咯啉中的一种；其中卤代芳烃与联吡啶类化合物的摩尔比为1：(0.05～2)；
所述镍催化剂为双-(1，5-环辛二烯)镍或四(三苯基膦)镍。
2.如权利要求1所述三氟甲基芳基硒醚的制备方法，其特征在于所述卤代芳烃包括抗抑郁药吗氯贝胺和用于治疗成人高脂血症的非诺贝特。
3.如权利要求1所述三氟甲基芳基硒醚的制备方法，其特征在于卤代芳烃与三氟甲硒基四甲基铵的摩尔比为1：(0.1～10)。
4.如权利要求1所述三氟甲基芳基硒醚的制备方法，其特征在于反应中还加入了有机溶剂，所述有机溶剂为乙腈、乙酸乙酯、二氯甲烷、1,2-二氯乙烷、三氯甲烷、四氢呋喃、1,4-二氧六环、乙醚、甲基叔丁基醚、甲苯、二甲苯、苯和砜类溶剂中的任意一种。
5.如权利要求1所述三氟甲基芳基硒醚的制备方法，其特征在于卤代芳烃与镍催化剂的摩尔比为1：(0.01～1)。
6.吗氯贝胺三氟甲硒基化类似物的制备方法，包括以下步骤：
将吗氯贝胺、三氟甲硒基四甲基铵、镍催化剂与有机膦配体或联吡啶类化合物混合，在零下80至100℃反应5分钟至48小时，分离纯化，得吗氯贝胺三氟甲硒基化类似物；
所述有机膦配体为三苯基膦、三(2-甲氧基苯基)膦、三(4-甲氧基苯基)膦、三环己基膦、三乙基膦、三叔丁基磷、1,1'-双(二苯基膦)二茂铁和4,5-双二苯基膦-9,9-二甲基氧杂蒽、1,3-双(二苯基膦)丙烷、1,2-双(二苯基膦)乙烷中的一种；卤代芳烃与有机膦配体的摩尔比为1：(0.1～2)；
联吡啶类化合物为2,2’-联吡啶、4,4’-二甲基-2,2’-联吡啶、4,4’-二甲氧基-2,2’-联吡啶、4,4’-二叔丁基-2,2’-联吡啶和1,10-邻菲咯啉中的一种；其中卤代芳烃与联吡啶类化合物的摩尔比为1：(0.05～2)；
所述镍催化剂为双-(1，5-环辛二烯)镍或四(三苯基膦)镍。
7.非诺贝特三氟甲硒基化类似物的制备方法，包括以下步骤：
将非诺贝特、三氟甲硒基四甲基铵、镍催化剂与有机膦配体或联吡啶类化合物混合，在零下80至100℃反应5分钟至48小时，分离纯化，得非诺贝特三氟甲硒基化类似物；
所述有机膦配体为三苯基膦、三(2-甲氧基苯基)膦、三(4-甲氧基苯基)膦、三环己基膦、三乙基膦、三叔丁基磷、1,1'-双(二苯基膦)二茂铁和4,5-双二苯基膦-9,9-二甲基氧杂蒽、1,3-双(二苯基膦)丙烷、1,2-双(二苯基膦)乙烷中的一种；卤代芳烃与有机膦配体的摩尔比为1：(0.1～2)；
联吡啶类化合物为2,2’-联吡啶、4,4’-二甲基-2,2’-联吡啶、4,4’-二甲氧基-2,2’-联吡啶、4,4’-二叔丁基-2,2’-联吡啶和1,10-邻菲咯啉中的一种；其中卤代芳烃与联吡啶类化合物的摩尔比为1：(0.05～2)；
所述镍催化剂为双-(1，5-环辛二烯)镍或四(三苯基膦)镍。
CN201710487662.XA 2017-06-23 2017-06-23 镍催化的三氟甲基芳基硒醚的制备方法 Active CN107118143B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201710487662.XA CN107118143B (zh) 2017-06-23 2017-06-23 镍催化的三氟甲基芳基硒醚的制备方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201710487662.XA CN107118143B (zh) 2017-06-23 2017-06-23 镍催化的三氟甲基芳基硒醚的制备方法

Publications (2)

Publication Number Publication Date
CN107118143A CN107118143A (zh) 2017-09-01
CN107118143B true CN107118143B (zh) 2019-05-24

Family

ID=59718787

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201710487662.XA Active CN107118143B (zh) 2017-06-23 2017-06-23 镍催化的三氟甲基芳基硒醚的制备方法

Country Status (1)

Country Link
CN (1) CN107118143B (zh)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110003069A (zh) * 2018-01-04 2019-07-12 深圳福山生物科技有限公司 一种含硒化合物及其用途
CN109053536B (zh) * 2018-08-27 2022-01-04 武汉理工大学 富电子芳烃或芳杂烃的三氟甲硒基化方法
CN109705012B (zh) * 2019-01-25 2022-04-05 西北师范大学 一种2,5-二芳基五元杂环芳烃的制备方法
CN111018765B (zh) * 2019-12-27 2020-12-22 武汉理工大学 一种醇的直接三氟甲硒基化方法
CN114875433B (zh) * 2022-04-24 2024-03-19 台州学院 一种多氟芳基硒醚衍生物的制备方法

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Fundamental Studies and Development of Nickel-Catalyzed Trifluoromethylthiolation of Aryl Chlorides: Active Catalytic Species and Key Roles of Ligand and Traceless MeCN Additive Revealed;Guoyin Yin et al.;《Journal of the American Chemical Society》;20150319;第137卷;第4168页Table1及其底部的反应条件
Highly Efficient C-SeCF3 Coupling of Aryl Iodides Enabled by an Air-Stable Dinuclear Pd1 Catalyst;Marialuisa Aufiero et al;《Angew.Chem.Int.Ed》;20150824;第54卷(第35期);第10324页左栏Scheme1
Nickel-Catalyzed Synthesis of Aryl Trifluoromethyl Sulfides at Room Temperature;Cheng-Pan Zhang et al.;《Journal of the American Chemical Society》;20111207;第134卷;第184页左栏Table2

Also Published As

Publication number Publication date
CN107118143A (zh) 2017-09-01

Similar Documents

Publication Publication Date Title
CN107118143B (zh) 镍催化的三氟甲基芳基硒醚的制备方法
Jones et al. Nickel phosphite/phosphine-catalyzed C–S cross-coupling of aryl chlorides and thiols
Hadei et al. The First Negishi Cross-Coupling Reaction of Two Alkyl Centers Utilizing a Pd− N-Heterocyclic Carbene (NHC) Catalyst
Lee et al. An improved catalyst system for the Pd-catalyzed fluorination of (hetero) aryl triflates
Gallop et al. Sonogashira couplings catalyzed by collaborative (N-heterocyclic carbene)-copper and-palladium complexes
Hornillos et al. Catalytic direct cross-coupling of organolithium compounds with aryl chlorides
Zhang et al. Palladium difluorocarbene involved catalytic coupling with terminal alkynes
Torres et al. Labile N-heterocyclic carbene complexes of iridium
Syu et al. Preparation of functional benzofurans, benzothiophenes, and indoles using ester, thioester, and amide via intramolecular wittig reactions
Lin et al. Iron-catalyzed cross-coupling reactions between arylzinc reagents and alkyl halides bearing β-fluorines
CN103415495B (zh) 环聚亚芳基化合物及其制备方法
CN108610225A (zh) 一种过渡金属催化硝基芳烃与末端芳基炔烃交叉偶联制备芳香炔烃的方法
Xia et al. Rh (I)-Catalyzed Cross-Coupling of α-Diazoesters with Arylsiloxanes
CN106957207A (zh) 2‑芳基（烯基）‑乙烯基磺酰氟化合物的制备方法
Inoue et al. Trapping of transient organolithium compounds
Shi et al. Selective Synthesis of Diaryl Sulfoxides and m-Arylthio Sulfones from Arylsulfinic Acids and Arenes via BF3-Promoted C–S Bond Formation
Huan et al. Visible light-induced photoredox construction of trifluoromethylated quaternary carbon centers from trifluoromethylated tertiary bromides
Casey et al. Furan Forming Reactions of cis-2-Alken-4-yn-1-ones
Si et al. Development and application of trifluoromethoxylating reagents
Li et al. Palladium-catalyzed remote hydro-oxygenation of internal alkenes: an efficient access to primary alcohols
Gao et al. Base-promoted synthesis of vinyl sulfides from sulfonium triflates
Lu et al. Fe-Catalyzed Three-Component Coupling Reaction of α, β, γ, δ-Unsaturated Carbonyl Compounds and Conjugate Dienes with Alkylsilyl Peroxides and Nucleophiles
CN108997178B (zh) 一种β-碘代烯基砜类化合物的合成方法
CN113979897A (zh) 一种γ-芳基烯丙基磺酰氟化合物及其制备方法与应用
CN110294730B (zh) 一种二氟甲基硫化黄酮类化合物及其制备方法

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant