CN115043735B - 一种仲胺与邻二碘苯的反应方法 - Google Patents

一种仲胺与邻二碘苯的反应方法 Download PDF

Info

Publication number
CN115043735B
CN115043735B CN202210813920.XA CN202210813920A CN115043735B CN 115043735 B CN115043735 B CN 115043735B CN 202210813920 A CN202210813920 A CN 202210813920A CN 115043735 B CN115043735 B CN 115043735B
Authority
CN
China
Prior art keywords
nmr
mhz
cdcl
reaction
diiodobenzene
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
CN202210813920.XA
Other languages
English (en)
Other versions
CN115043735A (zh
Inventor
张士磊
祝文静
姜远锐
黄加文
陈鑫
方春辉
胡延维
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.)
Suzhou University
Original Assignee
Suzhou 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 Suzhou University filed Critical Suzhou University
Priority to CN202210813920.XA priority Critical patent/CN115043735B/zh
Publication of CN115043735A publication Critical patent/CN115043735A/zh
Application granted granted Critical
Publication of CN115043735B publication Critical patent/CN115043735B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

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
    • 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
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/80—[b, c]- or [b, d]-condensed
    • 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
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/80—[b, c]- or [b, d]-condensed
    • C07D209/82—Carbazoles; Hydrogenated carbazoles
    • C07D209/86—Carbazoles; Hydrogenated carbazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
    • 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
    • C07D213/24—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 with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
    • 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
    • C07D213/60—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 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
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/68—One oxygen atom attached in position 4
    • 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
    • C07D213/60—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 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
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
    • C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
    • C07D219/02—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with only hydrogen, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
    • C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D223/18—Dibenzazepines; Hydrogenated dibenzazepines
    • C07D223/22—Dibenz [b, f] azepines; Hydrogenated dibenz [b, f] azepines
    • 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
    • C07D231/12—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon 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
    • C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
    • C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
    • C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D257/04—Five-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
    • C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
    • C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
    • C07D279/18—[b, e]-condensed with two six-membered rings
    • C07D279/22—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom
    • 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
    • C07D295/06—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 halogen atoms or nitro radicals
    • C07D295/073—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 halogen atoms or nitro radicals with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/582—Recycling of unreacted starting or intermediate materials

Landscapes

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

Abstract

本发明公开了一种仲胺与邻二碘苯的反应方法，在碱金属氢化物或者格式试剂存在下，将仲胺与邻二碘苯反应，完成仲胺与邻二碘苯的反应。本发明中公开了邻二碘苯在氢化钠作用下与仲胺快速制备芳胺类化合物，这类反应快速、简捷而且温和，是一种快速实现N‑芳基化的新颖方法，反应主产物为2‑碘代芳胺类化合物，易于转化，具有更大的应用价值，尤其是解决了现有技术N‑芳基化方法需要用到高温、金属催化等条件，具有反应时间长、制备成本高、环境污染严重等缺点。

Description

一种仲胺与邻二碘苯的反应方法
技术领域
本发明属于有机合成，具体涉及一种仲胺与邻二碘苯的反应方法。
背景技术
氢化钠是碱金属氢化物的典型代表，它是由Na+和H-组成。2004年，Su等发现在氢化钠可以促进酯交换反应，将化合物与氢化钠在四氢呋喃中回流，经分子内酯交换可得到大环内酯类化合物㈠-Apicularen A。2003年，Blacklock等发现使用催化量的水可以使NaH反应生成高活性的氢氧化钠，可以快速对化合物进行N-甲基化，可有效实现氨基酸及其类似物的甲基化。芳胺类化合物是一种重要的分子骨架，经常被应用于农业、医药、染料、颜料、电子工业等各个领域内。很多生物活性分子都是N-取代芳烃类化合物，如中枢降压药盐酸可乐定、可逆胆碱酯酶抑制剂溴新斯的明、α受体阻断剂酚妥拉明、Ca2+通道拮抗剂苄普地尔等(图 1)。传统N-芳基化一般是由芳基卤代物和胺经Ullmann反应构建[(a) Jourdan F.Ber. Dtsch. Friedrich Jourdan: Xeue Syntheeen von Derivaten dee Hydroacridinsund Aoridins. Chem. Ges., 1885, 18: 1444.(b) Ullmann F, Wenner P. Ber. Dtsch.Chem. Ges, 1900, 33: 2476]，合成方法一般需要金属铜或铜盐或钯催化、高温高压等条件，反应时间长，制备成本高，环境污染严重。后来芳基硼酸作为芳基受体参与N-芳基化反应，也需要过渡金属催化[Patrick Y. S. Lam, et al. New Aryl/Heteroaryl C-N BondCross-coupling Reactions via Arylboronic Acid/Cupric Acetate Arylation.Tetrahedron Letters39 (1998) 2941-2944]。因此寻找绿色高效的C-N键构建方法尤为重要。
发明内容
本发明中公开了邻二碘苯在氢化钠作用下与仲胺快速制备芳胺类化合物，这类反应快速、简捷而且温和，是一种快速实现N-芳基化的新颖方法，反应主产物为2-碘代芳胺类化合物，易于转化，具有更大的应用价值，尤其是解决了现有技术N-芳基化方法需要用到高温、金属催化等条件，具有反应时间长、制备成本高、环境污染严重等缺点。
本发明采用如下技术方案：
一种仲胺与邻二碘苯的反应方法，在碱金属氢化物或者格式试剂存在下，将仲胺与邻二碘苯反应，完成仲胺与邻二碘苯的反应。
一种邻碘代产物的制备方法，在碱金属氢化物或者格式试剂存在下，将仲胺与邻二碘苯反应，得到邻碘代产物。
本发明中，碱金属氢化物为NaH、KH、CaH2、LiH中的一种或几种，格式试剂为i-PrMgBr。
本发明中，反应在溶剂中进行，溶剂优选为DMA、THF、甲苯、CH3CN中的一种或几种；优选为THF、DMA混合溶剂；进一步优选的，THF、DMA的体积比为（3～5）∶1。
本发明中，反应的温度为室温～50℃，优选室温～40℃。
本发明中，仲胺、邻二碘苯、碱金属氢化物的摩尔量比为1∶（1～3）∶（2～5），优选为1∶2∶3。
本发明中，仲胺的化学结构式如下：
邻二碘苯的化学结构式如下：
邻碘代产物的化学结构式如下：
R1、R2独立的选择烷基、取代烷基、芳基、取代芳基、杂环基中的一种；优选的，取代烷基为卤素取代烷基，其中碳原子数为1～10，优选1～5。R1、R2也可以与N组成含氮杂环基团，比如吲哚、吲唑、吡唑、四氮唑、吡啶、咔唑、吖啶类、吩噻嗪等。
R3选自烷基、取代烷基、芳基、取代芳基、杂环基中的一种；优选的，取代烷基为卤素取代烷基，其中碳原子数为1～10，优选1～5；杂环基比如吩噻嗪、咔唑、苯胺基嘧啶、吲哚、吖啶酮、吡唑等基团。
本发明发现，邻二碘苯在碱金属氢化物氢化钠的作用下，能够与胺反应，用于C-N的非金属催化构建。这类反应绿色高效、原子转化率高，不需要过渡金属催化，没有过度偶联的副产物，原料邻二碘苯廉价易得；实验操作简单，放大至克级仍能得到较高的收率；反应主产物为2-碘代化合物，用其他方法难以一步获得；产物易于转化，对复杂药物分子的合成和修饰具有重要意义。
附图说明
图1为现有N-取代芳烃类化合物的化学结构。
图2为二苯胺与邻二碘苯在不同条件下的反应结果。
图3为不同胺化合物与邻二碘苯的反应结果。
图4为吩噻嗪化合物与邻二碘苯的反应结果。
图5为二苯胺与二碘苯衍生物的反应结果。
图6为放大条件下的反应结果。
图7为二碘苯原料制备示意。
具体实施方式
本发明在碱金属氢化物或者格式试剂存在下，将仲胺与邻二碘苯在溶剂中室温反应，得到邻碘代产物。所有原料都为市售产品，具体制备操作以及测试方法为常规技术。
核磁谱图1H NMR、19F NMR和13C NMR均使用Agilent 400 MHz和Bruker 400 MHz仪器测定，样品溶剂均为CDCl3(7.26 ppm)。核磁数据报告包括：化学位移，峰面积积分，偶合常数，峰型等。LR-MS质谱仪为ESI源。TLC薄层色谱板为烟台黄海化工厂生产，在254 nm或365 nm波长下可视化监测，显色剂有KMnO4、碘、磷钼酸和二硝基苯肼，快速柱层析所用硅胶目数为200-300目。所用试剂都为市售分析纯或化学纯，无特殊说明，直接使用。无水溶剂均为重蒸溶剂或市售干燥溶剂（百灵威）。
实施例一
参见图2，改变反应条件（单因素变化），得到不同结果，以第11组为例：室温下，将NaH（1.8 mmol, 3.0 equiv）称量于反应瓶中，悬于无水THF（1.0 mL）中常规搅拌，在搅拌过程中加入二苯胺2a（0.6 mmol, 1.0 equiv，溶于0.5 mL DMA），加完后在室温下搅拌5 min，然后加入邻二碘苯1a（1.2 mmol, 2.0 equiv，溶于1.0 mL THF），室温下搅拌1小时。反应完成后，将反应液加到冰水中淬灭反应，乙酸乙酯萃取3次，合并有机层，饱和NaCl溶液洗涤，无水硫酸钠干燥，过滤，旋干溶剂，加入硅胶粉拌样，快速柱层析分离，得到邻碘芳胺产物3a，收率为72%。
实施例二
室温下，将NaH（1.8 mmol, 3.0 equiv）称量于反应瓶中，悬于无水THF（1.0 mL）中常规搅拌，在搅拌过程中加入仲胺2（0.6 mmol, 1.0 equiv，溶于0.5 mL DMA），加完后在室温下搅拌5 min，然后加入邻二碘苯1（1.2 mmol, 2.0 equiv，溶于1.0 mL THF），常规搅拌反应。反应完成后，将反应液加到冰水中淬灭反应，乙酸乙酯萃取3次，合并有机层，饱和NaCl溶液洗涤，无水硫酸钠干燥，过滤，旋干溶剂，加入硅胶粉拌样，快速柱层析分离，得到邻碘芳胺产品3。
本发明对各类底物具有普适性，参见图3至图5，图中时间为反应时间，收率为分离收率，如无特殊说明，则为常规反应条件；化合物1、化合物2中的取代基与产物3中的取代基一致。参见图3，对于二苯胺、苯萘胺、二苄胺均可取得较高收率（3a-3c）；对于苯氨基吡啶、苯胺基嘧啶、甲基苯胺、甲氨基吡啶类可以取得中等及以上收率（3d-3i）；对于烷基胺类，如二烯丙基胺、哌嗪、氢化异喹啉，可以取得中等收率（3d-3i）；对于氮杂环，如吲哚、吲唑、吡唑、四氮唑、吡啶、咔唑、吖啶类、吩噻嗪等可以取得中等及以上收率（3m-3x）。参见图4，对于吩噻嗪，有强吸电子基氰基存在时可以取得较高收率（3z），-CF3、-Cl 可以取得中等收率（3y、3aa）；对于二苯胺，有吸电子基存在时可以取得较高收率，给电子基存在时收率较低（3ab-3ac）；对于吲哚，甲基、甲氧基、卤素取代时产率相差不大（3ae-3ag），邻位大位阻苯环取代时产率较低（3ah）；对于咔唑类，卤素取代均可得到较高收率（3ai-3aj）。参见图5，吩噻嗪、咔唑、苯胺基嘧啶类、吲哚、吖啶酮、吡唑类与对称性二碘苯反应均可得到中等及以上收率的单一产物（3ak-3ap、3ar-3at、3av、3aw、3bd），与不对称二碘苯反应，得到中等收率的混合产物（3aq、3ax、3ay、3az、3bc），值得注意的是1,2-二碘萘可获得中等的收率（3bb）。
实施例三
进行了放大试验，将投料量放大至克级，该反应为实现工业化生产奠定了基础，参见图6，反应过程与实施例二一致，原料用量放大。
合成例
本发明的原料为市售产品，也可根据常规技术制备，以下给出部分原料的制备方法。
参见图7，对称性邻二碘苯（1b、1c、1d、1e-1i）的制备。
将1,3-苯并间二氧杂环戊烯（100 mmol, 1.0 equiv）置于圆底烧瓶中，加入125mL HOAc:H2O:H2SO4（体积比100:20:1）混合溶剂, 搅拌下依次加入高碘酸（40 mmol, 0.4equiv），I2（80 mmol, 0.8 equiv），加热到70℃磁力搅拌24 h，TLC监测反应。反应完成后，冷却至室温，产物析出，抽滤，用甲醇洗涤，干燥，得到白色固体产物1b，产率65%。
的制备方法与1b相同（原料变化），得白色固体，产率60%。
N2保护下，将碘单质（80 mmol, 2.0 equiv）置于两口瓶中，密闭，换气三次后将1,2,3,4-四甲基苯（40 mmol, 1.0 equiv）溶于50 mL甲醇，注入，后加入高碘酸（16 mmol,0.4 equiv）溶于30 mL甲醇，70℃磁力搅拌过夜，TLC监测反应。反应完成后，将反应液冷却至室温，冰浴下搅拌，产物析出，抽滤，干燥，得白色固体1d，产率为52%。
将苯胺（100 mmol, 1.0 equiv）置于圆底烧瓶中，加入碘（105 mmol, 1.05equiv）、碳酸氢钠（300 mmol, 3.0 equiv），加入500 mL DCM:H2O（0.17 M, 体积比为2:1）的混合溶液，室温下搅拌过夜，TLC监测。反应完全后，用硫代硫酸钠溶液洗涤，DCM萃取三次，合并有机层，饱和NaCl溶液洗涤，无水硫酸钠干燥，过滤，旋干溶剂，直接投下一步。冰水浴下，将取代的邻碘苯胺（100 mmol, 1.0 equiv）悬于盐酸水溶液(250 mL, 4 M)中搅拌30min，之后向反应液中逐滴添加NaNO2水溶液（120 mmol, 1.2 equiv），加完后继续在冰水浴下搅拌30 min，反应液变澄清，然后滴加KI水溶液（150 mmol, 1.5 equiv），加料完毕后，移至室温继续反应3h完成。加水，乙酸乙酯萃取3次，合并有机层，饱和NaCl溶液洗涤，无水硫酸钠干燥，过滤，旋干溶剂，适量硅胶粉拌样，快速柱层析分离（纯PE），最终得到单取代二碘苯产品。
产物核磁。
White solid, yield 72%. 1H NMR (400 MHz, CDCl3) δ 7.91 (dd, J = 7.9,1.2 Hz, 1H), 7.34 (td, J = 7.9, 1.3 Hz, 1H), 7.20 (dd, J = 12.8, 5.5 Hz, 5H),6.95 (t, J = 8.3 Hz, 7H). 13C NMR (101 MHz, CDCl3) δ 149.0, 147.0, 141.0,131.5, 129.9, 129.1, 127.7, 122.2, 122.1, 100.3. LR-MS (ESI): m/z 372.0 [M+H]+.
N-(2-iodophenyl)-N-phenylnaphthalen-2-amine (3b). White solid, yield44%. 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 7.9 Hz, 1H), 7.68 (dd, J = 11.7,8.6 Hz, 2H), 7.52 (d, J = 8.0 Hz, 1H), 7.37 – 7.27 (m, 3H), 7.25 – 7.15 (m,5H), 7.04 – 6.96 (m, 3H), 6.95 – 6.90 (m, 1H). 13C NMR (101 MHz, CDCl3) δ149.1, 147.3, 144.7, 141.1, 134.45, 131.48, 130.0, 129.8, 129.2, 128.8,127.8, 127.7, 127.0, 126.4, 124.4, 123.3, 122.5, 122.5, 118.0, 100.2. LR-MS(ESI): m/z 422.0 [M+H]+.
N, N-dibenzyl-2-iodoaniline (3c). White solid, yield 58%. 1H NMR (400MHz, CDCl3) δ 7.87 (d, J = 7.7 Hz, 1H), 7.33 (d, J = 7.0 Hz, 4H), 7.27 (t, J= 7.0 Hz, 4H), 7.22 (d, J = 8.2 Hz, 2H), 7.15 (d, J = 7.5 Hz, 1H), 6.87 (d, J= 7.8 Hz, 1H), 6.75 (t, J = 7.4 Hz, 1H), 4.12 (s, 4H). 13C NMR (101 MHz,CDCl3) δ 151.6, 140.2, 137.8, 129.0, 128.6, 128.3, 127.2, 125.9, 124.8, 99.9,57.1. LR-MS (ESI): m/z 400.1 [M+H]+.
N-(2-iodophenyl)-N-phenylpyridin-4-amine(3d). Colorless oil, yield31%. 1H NMR (400 MHz, CDCl3) δ 8.26 (dd, J = 5.0, 1.5 Hz, 2H), 7.96 (dd, J =8.0, 1.3 Hz, 1H), 7.42 (td, J = 7.8, 1.4 Hz, 1H), 7.38 – 7.31 (m, 2H), 7.26(d, J = 1.4 Hz, 2H), 7.24 (d, J = 0.9 Hz, 1H), 7.22 – 7.15 (m, 1H), 7.05 (td,J = 7.7, 1.6 Hz, 1H), 6.57 (dd, J = 5.1, 1.5 Hz, 2H). 13C NMR (101 MHz, CDCl3)δ 153.4, 149.6, 146.3, 143.5, 141.2, 131.3, 130.4, 129.7, 129.3, 125.9,125.7, 111.9, 99.9. LR-MS (ESI): m/z 373.0 [M+H]+.
N-(2-iodophenyl)-N-phenylpyridin-2-amine (3e). Colorless oil, yield47%. 1H NMR (400 MHz, CDCl3) δ 8.26 – 8.19 (m, 1H), 7.93 (dd, J = 7.9, 1.4 Hz,1H), 7.44 (ddd, J = 8.9, 7.2, 2.0 Hz, 1H), 7.38 (td, J = 7.7, 1.4 Hz, 1H),7.32 – 7.23 (m, 3H), 7.20 (dd, J = 8.6, 1.1 Hz, 2H), 7.12 – 7.04 (m, 1H),6.98 (td, J = 7.7, 1.6 Hz, 1H), 6.76 (ddd, J = 7.1, 5.0, 0.7 Hz, 1H), 6.65(d, J = 8.4 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 158.0, 148.4, 147.9, 144.9,140.8, 137.4, 131.5, 130.0, 129.2, 128.3, 124.9, 124.2, 116.0, 113.0, 100.7.LR-MS (ESI): m/z 373.0 [M+H]+.
N-(2-iodophenyl)-4,6-dimethyl-N-phenylpyrimidin-2-amine (3f). Whitesolid, yield 74%. 1H NMR (400 MHz, CDCl3) δ 7.90 (d, J = 7.7 Hz, 1H), 7.37–7.19 (m, 6H), 7.08 (d, J = 6.2 Hz, 1H), 6.95 (t, J = 7.2 Hz, 1H), 6.46 (s,1H), 2.24 (s, 6H). 13C NMR (101 MHz, CDCl3) δ 167.5, 161.3, 147.8, 144.0,140.1, 131.1, 129.6, 128.5, 127.8, 125.7, 124.6, 112.3, 101.3, 24.2. LR-MS(ESI): m/z 402.0 [M+H]+.
2-iodo-N-methyl-N-(4-nitrophenyl) aniline (3g). White solid, yield57%. 1H NMR (400 MHz, CDCl3) δ 8.07 (d, J = 9.0 Hz, 2H), 7.99 (d, J = 7.9 Hz,1H), 7.48 (t, J = 7.5 Hz, 1H), 7.26 (d, J = 7.5 Hz, 1H), 7.12 (t, J = 7.6 Hz,1H), 6.44 (d, J = 8.1 Hz, 2H), 3.33 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 153.0,148.0, 140.8, 138.4, 130.7, 129.7, 126.0, 111.6, 99.6, 39.4. LR-MS (ESI): m/z355.0 [M+H]+.
O-(2-iodophenyl)-N-methylpyridin-4-amine (3h). Colorless oil, yield28%. 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 5.8 Hz, 2H), 7.96 (d, J = 7.9 Hz,1H), 7.43 (t, J = 7.5 Hz, 1H), 7.21 (d, J = 7.3 Hz, 1H), 7.06 (t, J = 7.6 Hz,1H), 6.30 (s, 2H), 3.22 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 153.1, 149.9,147.9, 140.7, 130.4, 129.8, 129.5, 107.6, 100.0, 38.3. LR-MS (ESI): m/z 311.0[M+H]+.
iodo-N-methyl-N-(pyridin-2-ylmethyl) aniline (3i). Colorless oil,yield 63%. 1H NMR (400 MHz, CDCl3) δ 8.64 (d, J = 1.3 Hz, 1H), 8.54 – 8.47 (m,1H), 7.86 (m, 2H), 7.33 – 7.28 (m, 1H), 7.26 (dd, J = 7.6, 4.7 Hz, 1H), 7.10(d, J = 7.9 Hz, 1H), 6.88 – 6.77 (m, 1H), 4.12 (s, 2H), 2.62 (s, 3H). 13C NMR(101 MHz, CDCl3) δ 153.5, 150.1, 148.7, 140.2, 136.5, 133.7, 129.2, 126.0,123.4, 122.4, 98.8, 58.4, 41.8. LR-MS (ESI): m/z 325.0 [M+H]+.
N, N-diallyl-2-iodoaniline (3j). pale-yellow oil, yield 48%. 1H NMR(400 MHz, CDCl3) δ 7.86 (dd, J = 7.9, 1.5 Hz, 1H), 7.30 – 7.25 (m, 1H), 7.02(dd, J = 8.0, 1.5 Hz, 1H), 6.79 (td, J = 7.8, 1.5 Hz, 1H), 5.83 (ddt, J =16.4, 10.2, 6.2 Hz, 2H), 5.14 (dddd, J = 19.5, 10.2, 3.1, 1.4 Hz, 4H), 3.63(dt, J = 6.2, 1.2 Hz, 4H). 13C NMR (101 MHz, CDCl3) δ 152.0, 140.1, 135.0,128.6, 125.7, 124.3, 117.9, 100.5, 56.3. LR-MS (ESI): m/z 300.0 [M+H]+.
tert-butyl 4-(2-iodophenyl) piperazine-1-carboxylate(3k). Colorlessoil, yield 13%. 1H NMR (400 MHz, CDCl3) δ 7.85 (dd, J = 7.9, 1.5 Hz, 1H), 7.31(ddd, J = 7.9, 7.4, 1.5 Hz, 1H), 7.00 (dd, J = 8.0, 1.5 Hz, 1H), 6.90 – 6.73(m, 1H), 3.62 (m, 4H), 3.01 – 2.84 (m, 4H), 1.49 (s, 9H). 13C NMR (101 MHz,CDCl3) δ 155.1, 153.3, 140.2, 129.4, 125.8, 121.2, 98.5, 79.9, 52.4, 28.6.LR-MS (ESI): m/z 389.1 [M+H]+.
2-(2-iodophenyl)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (3l). Whitesolid, yield 42%. 1H NMR (400 MHz, CDCl3) δ 7.82 (dd, J = 7.9, 1.2 Hz, 1H),7.24 – 7.05 (m, 9H), 6.89 (t, J = 6.6 Hz, 2H), 6.79 – 6.68 (m, 1H), 5.62 (s,1H), 3.51 – 3.40 (m, 1H), 3.39 – 3.28 (m, 1H), 3.12 (m, 1H), 3.04 – 2.91 (m,1H). 13C NMR (101 MHz, CDCl3) δ 152.3, 142.4, 139.9, 137.9, 135.1, 129.7,128.9, 128.7, 128.6, 127.9, 127.1, 126.4, 125.9, 124.5, 100.5, 65.4, 48.8,29.7. LR-MS (ESI): m/z 412.1 [M+H]+.
1-(2-iodophenyl)-1H-indole (3m). Colorless oil, yield 47%. 1H NMR(400 MHz, CDCl3) δ 8.04 (d, J = 7.9 Hz, 1H), 7.72 (d, J = 6.0 Hz, 1H), 7.50(t, J = 7.5 Hz, 1H), 7.40 (d, J = 7.6 Hz, 1H), 7.21 (d, J = 4.5 Hz, 4H), 7.07(d, J = 7.8 Hz, 1H), 6.72 (d, J = 2.2 Hz, 1H).13C NMR (101 MHz, CDCl3) δ142.2, 140.2, 136.8, 130.0, 129.5, 129.3, 128.7, 128.5, 122.4, 121.1, 120.4,110.8, 103.2, 97.8. LR-MS (ESI): m/z 320.0 [M+H]+.
1-(2-iodophenyl)-1H-indazole (3n). Colorless oil, yield 58%. 1H NMR(400 MHz, CDCl3) δ 8.24 (s, 1H), 8.04 (d, J = 7.9 Hz, 1H), 7.82 (d, J = 8.0Hz, 1H), 7.51 (t, J = 7.5 Hz, 1H), 7.41 (dd, J = 18.5, 7.8 Hz, 2H), 7.23 (dd,J = 14.4, 8.0 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 142.2, 140.4, 140.3, 135.4,130.7, 129.5, 129.3, 127.1, 124.4, 121.5, 121.3, 110.6, 96.8. LR-MS (ESI): m/z 321.0 [M+H]+.
(2-iodophenyl)-3,5-diphenyl-1H-pyrazole (3o). White solid, yield 45%.1H NMR (400 MHz, CDCl3) δ 8.00 – 7.95 (m, 2H), 7.92 (d, J = 7.6 Hz, 1H), 7.51– 7.36 (m, 5H), 7.29 (m, 5H), 7.13 (ddd, J = 8.8, 6.7, 2.5 Hz, 1H), 6.92 (s,1H). 13C NMR (101 MHz, CDCl3) δ 152.2, 145.6, 143.2, 140.0, 133.1, 130.6,130.0, 129.8, 129.1, 128.7, 128.5, 128.4, 128.1, 126.0, 104.0, 98.0. LR-MS(ESI): m/z 423.0 [M+H]+.
1-(2-iodophenyl)-5-phenyl-1H-tetrazole (3p). White solid, yield 15%.1H NMR (400 MHz, CDCl3) δ 8.02 (dd, J = 8.0, 1.3 Hz, 1H), 7.56 (ddd, J = 8.6,5.5, 1.4 Hz, 3H), 7.50 – 7.41 (m, 2H), 7.40 – 7.30 (m, 3H). 13C NMR (101 MHz,CDCl3) δ 154.1, 140.7, 137.8, 132.6, 131.6, 129.9, 129.2, 128.8, 128.5,123.5, 96.4. LR-MS (ESI): m/z 349.0 [M+H]+.
1-(2-iodophenyl) pyridin-4(1H)-one (3q). Colorless oil, yield 54%. 1HNMR (400 MHz, CDCl3) δ 8.37 (d, J = 6.0 Hz, 2H), 8.00 (d, J = 7.9 Hz, 1H),7.63 (d, J = 7.7 Hz, 1H), 7.40 (t, J = 7.6 Hz, 1H), 7.10 (td, J = 7.5, 0.9Hz, 1H), 6.91 (d, J = 6.0 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 149.7, 148.6,140.9, 136.1, 135.3, 131.1, 129.7, 121.2, 107.7. LR-MS (ESI): m/z 298.0 [M+H]+.
9-(2-iodophenyl)-9H-carbazole (3r). White solid, yield 90%. Mp. 130 –131 °C. 1H NMR (400 MHz, CDCl3) δ 8.15 (dd, J = 20.2, 7.7 Hz, 3H), 7.58 (t, J= 7.4 Hz, 1H), 7.43 (dd, J = 14.6, 7.5 Hz, 3H), 7.30 (dd, J = 15.7, 8.0 Hz,3H), 7.05 (d, J = 8.0 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 140.8, 140.6, 140.5,130.8, 130.5, 129.9, 126.1, 123.4, 120.5, 120.1, 110.3, 99.4. LR-MS (ESI): m/z 370.0 [M+H]+.
5-(2-iodophenyl)-10,11-dihydro-5H-dibenzo [b, f] azepine (3s). Whitesolid, yield 34%. 1H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 7.9 Hz, 1H), 7.62 –7.45 (m, 2H), 7.11 (d, J = 6.6 Hz, 3H), 6.92 (t, J = 7.4 Hz, 2H), 6.81 (t, J= 7.2 Hz, 2H), 6.43 (d, J = 8.4 Hz, 2H), 3.26 (s, 4H). 13C NMR (101 MHz,CDCl3) δ 148.4, 144.4, 141.8, 133.4, 133.0, 130.6, 129.9, 128.7, 126.3,121.2, 120.5, 101.9, 37.2. LR-MS (ESI): m/z 398.0 [M+H]+.
7-(2-iodophenyl)-7H-benzo[c]carbazole (3t). Colorless oil, yield 83%.1H NMR (400 MHz, CDCl3) δ 8.85 (dd, J = 8.2, 4.3 Hz, 1H), 8.64 (dd, J = 6.3,3.9 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 8.1 Hz, 1H), 7.80 (d, J =8.8 Hz, 1H), 7.72 (ddd, J = 8.3, 5.6, 2.8 Hz, 1H), 7.61 – 7.37 (m, 5H), 7.27– 7.21 (m, 1H), 7.20 (dd, J = 8.2, 2.5 Hz, 1H), 7.16 – 7.10 (m, 1H). 13C NMR(101 MHz, CDCl3) δ 140.6, 140.2, 139.9, 138.5, 130.9, 130.7, 130.0, 129.9,129.6, 129.4, 127.6, 127.1, 124.6, 124.0, 123.6, 123.3, 122.2, 120.9, 115.7,112.0, 110.8, 99.6. LR-MS (ESI): m/z 420.0 [M+H]+.
10-(2-iodophenyl) acridin-9(10H)-one (3u). White solid, yield 67%. 1HNMR (400 MHz, CDCl3) δ 8.61 (d, J = 8.0 Hz, 2H), 8.18 (d, J = 7.9 Hz, 1H),7.69 (t, J = 7.6 Hz, 1H), 7.60 – 7.50 (m, 2H), 7.44 (d, J = 6.9 Hz, 1H), 7.35(dd, J = 12.2, 4.6 Hz, 1H), 7.31 (t, J = 7.5 Hz, 2H), 6.62 (d, J = 8.6 Hz,2H). 13C NMR (101 MHz, CDCl3) δ 178.3, 142.0, 141.6, 141.3, 133.7, 131.5,131.3, 131.1, 127.7, 122.1, 122.0, 116.3, 100.7. LR-MS (ESI): m/z 398.0 [M+H]+.
10-(2-iodophenyl)-9,9-dimethyl-9,10-dihydroacridine (3v). Whitesolid, yield 75%.. 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 7.9 Hz, 1H), 7.66(t, J = 7.6 Hz, 1H), 7.56 (dd, J = 7.2, 1.7 Hz, 2H), 7.43 (d, J = 7.7 Hz,1H), 7.29 (d, J = 8.6 Hz, 1H), 7.13 – 6.95 (m, 4H), 6.23 – 6.08 (m, 2H), 1.89(s, 3H), 1.75 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 143.4, 141.5, 139.2, 132.9,130.9, 130.0, 129.8, 126.7, 126.0, 121.0, 113.6, 102.9, 36.0, 34.6, 31.10.LR-MS (ESI): m/z 412.1 [M+H]+.
10-(2-iodophenyl)-10H-phenothiazine (3w). White solid, yield 43%. 1HNMR (400 MHz, CDCl3) δ 8.14 (dd, J = 8.0, 1.3 Hz, 1H), 7.61 (td, J = 7.6, 1.4Hz, 1H), 7.49 (dd, J = 7.8, 1.5 Hz, 1H), 7.21 (td, J = 7.8, 1.6 Hz, 1H), 7.05– 6.96 (m, 2H), 6.87 – 6.77 (m, 4H), 6.13 – 5.96 (m, 2H). 13C NMR (101 MHz,CDCl3) δ 142.6, 142.0, 141.7, 133.2, 130.5, 130.1, 126.9, 126.7, 122.7,119.5, 115.37, 102.7. LR-MS (ESI): m/z 402.0 [M+H]+.
10-(2-iodophenyl)-10H-benzo[b]pyrido[2,3-e][1,4]thiazine (3x). Whitesolid, yield 56%. 1H NMR (400 MHz, CDCl3) δ 8.06 (dd, J = 8.0, 1.3 Hz, 1H),7.75 (dd, J = 4.9, 1.6 Hz, 1H), 7.57 (td, J = 7.6, 1.4 Hz, 1H), 7.47 (dd, J =7.8, 1.6 Hz, 1H), 7.24 – 7.11 (m, 2H), 7.02 – 6.94 (m, 1H), 6.91 – 6.78 (m,2H), 6.68 (dd, J = 7.5, 4.9 Hz, 1H), 6.04 – 5.89 (m, 1H). 13C NMR (101 MHz,CDCl3) δ 152.7, 145.0, 142.30, 141.7, 140.7, 133.9, 133.2, 129.8, 129.7,127.3, 126.5, 123.3, 118.7, 118.4, 116.4, 115.3, 102.1. LR-MS (ESI): m/z403.0 [M+H]+
10-(2-iodophenyl)-3-(trifluoromethyl)-10H-phenothiazine (3y). Whitesolid, yield 67%. 1H NMR (400 MHz, CDCl3) δ 8.13 (d, J = 8.0 Hz, 1H), 7.61 (t,J = 7.6 Hz, 1H), 7.46 (d, J = 7.7 Hz, 1H), 7.24 – 7.19 (m, 1H), 7.07 – 6.98(m, 2H), 6.95 (dd, J = 5.8, 3.3 Hz, 1H), 6.86 – 6.77 (m, 2H), 6.14 (s, 1H),6.03 – 5.91 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 142.5, 142.0, 141.9, 141.4,132.9, 130.9, 130.7, 129.3 (q，J = 272 Hz), 127.45, 126.79 (d, J = 5.0 Hz),125.25, 124.60 (d, J = 1.2 Hz), 123.41, 122.55, 119.35 (q, J = 3.9 Hz),118.69, 115.81, 111.43 (q, J = 4.1 Hz), 102.14. 19F NMR (377 MHz, CDCl3) δ -63.06. LR-MS (ESI): m/z 470.0 [M+H]+.
10-(2-iodophenyl)-10H-phenothiazine-4-carbonitrile (3z). White solid,yield 93%. 1H NMR (400 MHz, CDCl3) δ 8.15 (dd, J = 8.0, 1.4 Hz, 1H), 7.64 (td,J = 7.7, 1.4 Hz, 1H), 7.43 (dd, J = 7.8, 1.5 Hz, 1H), 7.29 – 7.26 (m, 1H),7.01 (dt, J = 16.8, 4.7 Hz, 2H), 6.96 – 6.90 (m, 1H), 6.87 – 6.80 (m, 2H),6.08 (d, J = 1.4 Hz, 1H), 5.99 – 5.92 (m, 1H). 13C NMR (101 MHz, CDCl3) δ142.5, 142.1, 141.4, 140.8, 132.6, 131.1, 130.8, 127.6, 126.9, 126.7, 126.1,123.6, 118.9, 117.9, 117.2, 115.8, 110.2, 101.9. LR-MS (ESI): m/z 427.0 [M+H]+.
3-chloro-10-(2-iodophenyl)-10H-phenothiazine (3aa). White solid,yield 39%. 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 7.9 Hz, 1H), 7.62 (t, J =7.6 Hz, 1H), 7.46 (d, J = 7.7 Hz, 1H), 7.23 (t, J = 7.7 Hz, 1H), 6.99 (dd, J= 5.8, 3.3 Hz, 1H), 6.90 (d, J = 8.2 Hz, 1H), 6.83 (dd, J = 5.6, 3.8 Hz, 2H),6.78 (dd, J = 8.2, 1.8 Hz, 1H), 6.08 – 5.91 (m, 2H). 13C NMR (101 MHz, CDCl3)δ 143.2, 142.0，141. 9, 141.5, 132.9, 132.7, 130.7, 130.5, 127.3, 127.2,126.8, 123.2, 122.5, 119.4, 118.2, 115.7, 115.6, 102.2. LR-MS (ESI): m/z435.9 [M+H]+.
2,6-dichloro-N-(2-iodophenyl)-N-phenylaniline (3ab). White solid，yield 68%. 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 7.9 Hz, 1H), 7.38 (d, J =8.0 Hz, 2H), 7.29 (s, 1H), 7.23 (d, J = 8.0 Hz, 2H), 7.17 (t, J = 8.0 Hz,1H), 7.00 (dd, J = 8.0, 1.0 Hz, 1H), 6.96 (t, J = 7.3 Hz, 1H), 6.83 (t, J =7.6 Hz, 1H), 6.68 (d, J = 8.0 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 146.5,145.7, 141.8, 141.3, 136.5, 129.9, 129.13, 129.08, 127.9, 127.7, 126.1,121.7, 120.6, 95.3. LR-MS (ESI): m/z 439.9 [M+H]+.
2-iodo-N, N-di-p-tolylaniline (3ac). White solid, yield 38%. 1H NMR(400 MHz, CDCl3) δ 7.92 (d, J = 7.9 Hz, 1H), 7.35 (m, 1H), 7.20 (dd, J = 7.9,1.1 Hz, 1H), 7.05 (d, J = 8.3 Hz, 4H), 6.94 (m, 1H), 6.87 (d, J = 8.4 Hz,4H), 2.31 (s, 6H).13C NMR (101 MHz, CDCl3) δ 149.4, 145.0, 141.0, 131.4,131.2, 129.8, 129.7, 127.3, 122.3, 100.2, 20.9. LR-MS (ESI): m/z 400.1 [M+H]+.
N-(2-iodophenyl)-3,4-dimethyl-N-phenylaniline (3ad). White solid,yield 33%. 1H NMR (400 MHz, CDCl3) δ 7.93 (dd, J = 7.9, 1.4 Hz, 1H), 7.37 (td,J = 7.7, 1.4 Hz, 1H), 7.25 – 7.20 (m, 3H), 7.02 (d, J = 8.1 Hz, 1H), 6.97 –6.89 (m, 4H), 6.87 – 6.76 (m, 2H), 2.23 (s, 3H), 2.19 (s, 3H). 13C NMR (101MHz, CDCl3) δ 149.3, 147.5, 144.8, 141.0, 137.40, 131.40, 130.90, 130.3,129.8, 129.1, 127.5, 124.4, 121.4, 121.3, 120.7, 100.3, 20.1, 19.2.
1-(2-iodophenyl)-7-methyl-1H-indole (3ae). Colorless oil, yield 36%.1H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 7.9 Hz, 1H), 7.57 (d, J = 7.8 Hz, 1H),7.45 (d, J = 3.9 Hz, 2H), 7.20 (dt, J = 8.3, 4.4 Hz, 1H), 7.09 (t, J = 7.4Hz, 1H), 7.02 (d, J = 2.6 Hz, 1H), 6.94 (d, J = 6.9 Hz, 1H), 6.69 (d, J = 2.6Hz, 1H), 1.95 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 144.4, 139.1, 135.4, 130.3,130.2, 129.4, 129.2, 128.6, 124.8, 121.7, 120.6, 119.22, 103.4, 100.4, 18.8.LR-MS (ESI): m/z 334.0 [M+H]+.
1-(2-iodophenyl)-5-methoxy-1H-indole (3af). Colorless oil, yield 27%.1H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 7.9 Hz, 1H), 7.48 (t, J = 7.5 Hz, 1H),7.38 (d, J = 7.5 Hz, 1H), 7.17 (d, J = 7.3 Hz, 3H), 6.95 (d, J = 8.8 Hz, 1H),6.89 – 6.78 (m, 1H), 6.63 (s, 1H), 3.88 (s, 3H). 13C NMR (101 MHz, CDCl3) δ154.7, 142.3, 140.3, 132.1, 129.9, 129.5, 129.3, 129.2, 129.0, 112.6, 111.6,102.9, 102.7, 97.7, 56.0. LR-MS (ESI): m/z 350.0 [M+H]+.
5-fluoro-1-(2-iodophenyl)-1H-indole (3ag). Colorless oil, yield 38%.1H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 8.0 Hz, 1H), 7.62 (dd, J = 8.6, 5.3 Hz,1H), 7.51 (t, J = 7.6 Hz, 1H), 7.39 (d, J = 7.6 Hz, 1H), 7.20 (dd, J = 12.7,5.5 Hz, 2H), 6.96 (td, J = 9.2, 2.2 Hz, 1H), 6.75 (dd, J = 9.7, 1.9 Hz, 1H),6.69 (s, 1H). 13C NMR (101 MHz, CDCl3) δ 160.3(d, J = 240 Hz), 141.8, 140.4,136.9 (d, J = 12.1 Hz), 130.3, 129.3 (dd, J = 27.0, 8.1 Hz), 124.9, 121.8 (d,J = 10.0 Hz), 109.3, 109.0, 103.3, 97.6, 97.4, 97.1. 19F NMR (377 MHz, CDCl3)δ -120.12. LR-MS (ESI): m/z 338.0 [M+H]+.
1-(2-iodophenyl)-2-phenyl-1H-indole(3ah). Colorless oil, yield 20%.1H NMR (400 MHz, CDCl3) δ 7.95 (dd, J = 8.0, 1.3 Hz, 1H), 7.70 (ddd, J = 4.5,2.2, 0.5 Hz, 1H), 7.38 (td, J = 7.7, 1.4 Hz, 1H), 7.31 (ddd, J = 8.4, 3.5,2.3 Hz, 2H), 7.26 – 7.23 (m, 2H), 7.21 (dt, J = 5.9, 1.7 Hz, 2H), 7.17 (dt, J= 10.7, 3.4 Hz, 2H), 7.14 – 7.08 (m, 1H), 6.97 – 6.90 (m, 1H), 6.83 (s, 1H).13C NMR (101 MHz, CDCl3) δ 141.7, 141.0, 140.2, 138.7, 132.5, 131.0, 130.0,129.4, 128.9, 128.40, 128.35, 127.6, 122.5, 120.9, 120.7, 111.3, 103.6,100.0. LR-MS (ESI): m/z 396.0 [M+H]+.
3-bromo-9-(2-iodophenyl)-9H-carbazole (3ai). White solid, yield 55%.1H NMR (400 MHz, DMSO) δ 8.27 (s, 1H), 8.11 (d, J = 7.8 Hz, 2H), 7.58 (t, J =7.5 Hz, 1H), 7.48 (d, J = 8.6 Hz, 1H), 7.43 (t, J = 7.5 Hz, 2H), 7.31 (dd, J= 13.2, 6.8 Hz, 2H), 7.02 (d, J = 8.1 Hz, 1H), 6.91 (d, J = 8.6 Hz, 1H). 13CNMR (101 MHz, CDCl3) δ 141.1, 140.6, 139.9, 139.4, 130.7, 130.6, 129.9,128.7, 126.8, 125.1, 123.3, 122.2, 120.7, 120.6, 113.0, 111.7, 110.4, 99.1.LR-MS (ESI): m/z 447.9 [M+H]+.
3-iodo-9-(2-iodophenyl)-9H-carbazole(3aj). White solid, yield 91%. 1HNMR (400 MHz, CDCl3) δ 8.47 (s, 1H), 8.16 – 8.06 (m, 2H), 7.65 (dd, J = 8.5,1.6 Hz, 1H), 7.57 (td, J = 7.6, 1.3 Hz, 1H), 7.46 – 7.38 (m, 2H), 7.36 – 7.27(m, 2H), 7.02 (d, J = 8.2 Hz, 1H), 6.82(d, J = 4 Hz,1H). 13C NMR (101 MHz,CDCl3) δ 140.9, 140.7, 139.99, 139.96, 134.4, 130.8, 130.7, 130.0, 129.4,126.9, 125.9, 122.1, 120.7, 120.6, 112.4, 110.4, 99.2, 82.9. LR-MS (ESI): m/z495.9 [M+H]+.
10-(2-iodo-3,4,5,6-tetramethylphenyl)-10H-phenothiazine-1-carbonitrile(3ak). White solid，yield 43%. 1H NMR (400 MHz, CDCl3) δ 6.94 (dd,J = 7.9, 1.6 Hz, 1H), 6.88 (d, J = 7.9 Hz, 1H), 6.86 – 6.79 (m, 1H), 6.80 –6.72 (m, 2H), 5.89 (d, J = 1.5 Hz, 1H), 5.84 – 5.77 (m, 1H), 2.61 (s, 3H),2.42 (s, 3H), 2.30 (s, 3H), 2.20 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 141.4,140.9, 139.5, 138.1, 137.3, 136.9, 135.7, 127.8, 126.6, 126.42, 126.39,125.8, 123.2, 119.6, 117.3, 116.6, 115.2, 110.3, 107.0, 27.8, 18.7, 17.2,17.1. LR-MS (ESI): m/z 483.0 [M+H]+.
10-(2-iodo-4,5-dimethylphenyl)-10H-phenothiazine-1-carbonitrile(3al). White solid，yield 47%. 1H NMR (400 MHz, CDCl3) δ 7.87 (s, 1H), 7.16 (s,1H), 6.99 (dd, J = 7.9, 1.5 Hz, 1H), 6.94 (d, J = 7.9 Hz, 1H), 6.91 – 6.87(m, 1H), 6.85 – 6.77 (m, 2H), 6.10 (d, J = 1.5 Hz, 1H), 6.02 – 5.97 (m, 1H),2.35 (s, 3H), 2.31 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 142.8, 142.3, 141.0,140.5, 140.3, 139.0, 132.9, 127.3, 126.8, 126.7, 126.6, 126.0, 123.4, 119.1,117.7, 117.4, 116.0, 110.2, 97.6, 19.9, 19.3. LR-MS (ESI): m/z 455.0 [M+H]+.
10-(6-iodobenzo[d] [1,3] dioxol-5-yl)-10H-phenothiazine-1-carbonitrile (3am). White solid, yield 55%. 1H NMR (400 MHz, CDCl3) δ 7.06 –6.99 (m, 2H), 6.97 (d, J = 7.8 Hz, 1H), 6.92 (dd, J = 7.3, 1.7 Hz, 1H), 6.87(td, J = 7.7, 1.8 Hz, 1H), 6.84 – 6.78 (m, 3H), 6.36 (s, 1H), 6.24 (dd, J =8.1, 1.2 Hz, 1H), 6.13 (s, 2H). 13C NMR (101 MHz, CDCl3) δ 150.0, 148.3,145.0, 143.2, 133.1, 127.7, 126.9, 126.7, 125.8, 124.2, 123.4, 119.1, 118.1,117.7, 116.2, 111.1, 110.31, 110.27, 102.3. LR-MS (ESI): m/z 471.0 [M+H]+.
9-(6-iodobenzo[d] [1,3] dioxol-5-yl)-9H-carbazole(3an). White solid,yield 39%.1H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 7.7 Hz, 2H), 7.40 (ddd, J =18.0, 12.5, 4.5 Hz, 4H), 7.29 (dd, J = 10.7, 4.0 Hz, 2H), 7.01 (dd, J = 3.7,1.0 Hz, 3H), 6.11 (s, 2H). 13C NMR (101 MHz, CDCl3) δ 148.8, 147.1, 141.4,131.5, 126.0, 123.3, 121.0, 120.4, 119.9, 109.9, 109.06, 108.6, 102.0. LR-MS(ESI): m/z 414.0 [M+H]+.
8-(2-iodo-4,5-dimethylphenyl)-9H-carbazole(3ao). White solid, yield36%. 1H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 7.7 Hz, 2H), 7.86 (s, 1H), 7.40(ddd, J = 8.3, 7.2, 1.2 Hz, 2H), 7.31 – 7.26 (m, 2H), 7.19 (s, 1H), 7.05 (d,J = 8.1 Hz, 2H), 2.37 (s, 3H), 2.28 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 141.0,140.9, 139.8, 138.9, 137.9, 131.4, 126.0, 123.3, 120.5, 119.9, 110.33, 95.2,19.61, 19.31. LR-MS (ESI): m/z 398.0 [M+H]+.
9-(2-iodo-4-(trifluoromethyl) phenyl)-9H-carbazole compound with 9-(2-iodo-5-(trifluoromethyl) phenyl)-9H-carbazole (7:5) (3ap). White solid,yield 33%. 1H NMR (400 MHz, CDCl3) δ 8.39 (s, 1.4H), 8.27 (d, J = 8.3 Hz, 1H),8.18 (d, J = 7.7 Hz, 4.8H), 7.85 (dd, J = 8.1, 1.4 Hz, 1.4H), 7.71 (d, J =1.6 Hz, 1H), 7.56 (d, J = 8.2 Hz, 1.4H), 7.53 (dd, J = 8.4, 1.8 Hz, 1H), 7.46– 7.39 (m, 4.8H), 7.34 (t, J = 7.5 Hz, 4.8H), 7.03 (dd, J = 8.1, 4.4 Hz,4.8H). 13C NMR (101 MHz, CDCl3) δ 144.2, 141.6, 141.5, 140.5, 140.4, 137.8 (d,J = 3.7 Hz), 132.5 (q, J = 250 Hz), 131.1, 127.6 (d, J = 3.8 Hz), 127.0 (d, J= 3.7 Hz), 126.33 (d, J = 2.8 Hz), 124.18, 123.66 (d, J = 2.7 Hz), 121.46,120.7, 120.6, 110.2, 110.1, 104.1, 99.3. 19F NMR (377 MHz, CDCl3) δ -62.58(s), -62.79 (s). LR-MS (ESI): m/z 438.0 [M+H]+.
N-(2-iodo-4,5-dimethylphenyl)-4,6-dimethyl-N-phenylpyrimidin-2-amine(3aq). White solid, yield 78%. 1H NMR (400 MHz, CDCl3) δ 7.65 (s, 1H), 7.36 –7.22 (m, 4H), 7.12 – 7.03 (m, 1H), 6.99 (s, 1H), 6.44 (s, 1H), 2.24 (s, 6H),2.21 (s, 3H), 2.13 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 167.4, 161.4, 145.2,144.2, 140.5, 138.3, 136.8, 131.7, 128.4, 125.7, 124.2, 112.0, 97.2, 24.2,19.6, 19.1. LR-MS (ESI): m/z 430.1 [M+H]+.
N-(2-iodo-3,4,5,6-tetramethylphenyl)-4,6-dimethyl-N-phenylpyrimidin-2-amine (3ar). White solid, yield 80%. 1H NMR (400 MHz, CDCl3) δ 7.31 (d, J =8 Hz, 2H), 7.23 – 7.16 (m, 2H), 6.98 (q, J = 7.6 Hz, 1H), 6.44 (s, 1H), 2.53(s, 3H), 2.32 (s, 3H), 2.24 (s, 6H), 2.18 (s, 3H), 2.07 (s, 3H). 13C NMR (101MHz, CDCl3) δ 167.3, 160.9, 142.9, 142.6, 138.2, 136.4, 135.0, 134.6, 128.0,123.7, 122.9, 112.1, 108.3, 27.7, 24.2, 18.5, 17.1, 17.0. LR-MS (ESI): m/z458.1 [M+H]+。
White solid, yield 58%.1H NMR (400 MHz, CDCl3) δ 7.38 – 7.26 (m, 5H),7.15 – 7.07 (m, 1H), 6.77 (s, 1H), 6.49 (s, 1H), 5.99 (s, 2H), 2.29 (s, 6H).13C NMR (101 MHz, CDCl3) δ 167.4, 161.4, 149.1, 146.9, 143.8, 141.3, 128.9,128.5, 125.4, 124.3, 118.3, 112.2, 111.3, 102.2, 89.9, 24.2. LR-MS (ESI): m/z446.0 [M+H]+.
N-(2-iodo-4-(trifluoromethyl)phenyl)-4,6-dimethyl-N-phenylpyrimidin-2-amine(3at). White solid, yield 57%. 1H NMR (400 MHz, CDCl3) δ 8.16 (d, J =1.4 Hz, 1H), 7.61 (dd, J = 8.3, 1.6 Hz, 1H), 7.35 – 7.26 (m, 5H), 7.18 – 7.12(m, 1H), 6.54 (s, 1H), 2.28 (s, 6H). 13C NMR (101 MHz, CDCl3) δ 167.8, 161.0,151.4, 143.6, 137.2 (d, J = 3.8 Hz), 131.1, 129.3(d, J = 33 Hz), 128.8, 126.6(d, J = 3.5 Hz), 126.0, 125.0, 123.1(d, J = 273 Hz), 112.9, 100.8, 24.1. 19FNMR (377 MHz, CDCl3) δ -62.28 (s). LR-MS (ESI): m/z 470.0 [M+H]+.
1-(2-iodo-4,5-dimethylphenyl)-1H-indole (3au). Colorless oil, yield45%.1H NMR (400 MHz, CDCl3) δ 7.74 (s, 1H), 7.71 – 7.60 (m, 1H), 7.18 – 7.10(m, 4H), 7.06 – 6.99 (m, 1H), 6.64 (s, 1H), 2.29 (s, 3H), 2.23 (s, 3H). 13CNMR (101 MHz, CDCl3) δ 140.5, 139.7, 139.2, 138.2, 136.9, 130.3, 128.8,128.4, 122.2, 121.0, 120.2, 110.9, 102.8, 93.6, 19.5, 19.2. LR-MS (ESI): m/z348.0 [M+H]+.
1-(6-iodobenzo[d] [1,3] dioxol-5-yl)-1H-indole (3av). Colorless oil,yield 25%. 1H NMR (400 MHz, CDCl3) δ 7.71 (dd, J = 6.5, 1.6 Hz, 1H), 7.40 (s,1H), 7.25 – 7.16 (m, 2H), 7.15 (d, J = 3.2 Hz, 1H), 7.07 (d, J = 7.8 Hz, 1H),6.89 (d, J = 3.1 Hz, 1H), 6.69 (s, 1H), 6.10 (dd, J = 5.1, 1.2 Hz, 2H). 13CNMR (101 MHz, CDCl3) δ 148.9, 148.7, 136.9, 135.8, 128.8, 128.4, 122.4,121.1, 120.3, 118.4, 110.7, 109.9, 103.1, 102.6, 86.7. LR-MS (ESI): m/z 364.0[M+H]+.
1-(4-(tert-butyl)-2-iodophenyl)-1H-indole compound with 1-(5-(tert-butyl)-2-iodophenyl)-1H-indole (10:7) (3aw). Colorless oil, yield 28%.1H NMR(400 MHz, CDCl3) δ 8.02 (d, J = 2.1 Hz, 0.7H), 7.93 (d, J = 8.4 Hz, 1H), 7.75– 7.69 (m, 1.4H), 7.50 (dd, J = 8.2, 2.2 Hz, 0.7H), 7.42 (d, J = 2.4 Hz, 1H),7.32 (d, J = 8.2 Hz, 0.7H), 7.24 (d, J = 2.9 Hz, 1.4H), 7.23 – 7.21 (m,1.4H), 7.21 – 7.17 (m, 3.4H), 7.09 (dd, J = 3.0, 1.4 Hz, 1H), 7.08 (dd, J =2.0, 1.0 Hz, 0.7H), 6.72 (dd, J = 3.2, 0.8 Hz, 1H), 6.70 (dd, J = 3.2, 0.8Hz, 0.7H), 1.40 (s, 6H), 1.35 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 153.6,153.3, 141.8, 139.7, 139.5, 137.3, 136.9, 136.8, 128.8, 128.5, 127.4, 126.8,126.5, 122.4, 122.3, 121.09, 121.03, 120.30, 120.26, 110.91, 110.89, 103.0,97.8, 93.5, 34.93, 34.85, 31.4, 31.3 LR-MS (ESI): m/z 376.1 [M+H]+.
10-(2-iodo-4-(trifluoromethyl) phenyl) acridin-9(10H)-one compoundwith 10-(2-iodo-5-(trifluoromethyl) phenyl) acridin-9(10H)-one (1:1) (3ax).White solid, yield 42%.1H NMR (400 MHz, CDCl3) δ 8.59 (ddd, J = 8.1, 5.7, 1.6Hz, 3H), 8.43 (d, J = 1.4 Hz, 0.5H), 8.01 (d, J = 8.3 Hz, 1H), 7.99 – 7.91(m, 1H), 7.88 (t, J = 7.8 Hz, 0.5H), 7.70 (s, 0.5H), 7.61 (t, J = 8.0 Hz,1H), 7.56 (dd, J = 7.1, 1.4 Hz, 2H), 7.54 – 7.48 (m, 2H), 7.37 – 7.27 (m,3H), 6.72 – 6.63 (m, 2H), 6.55 (d, J = 8.6 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ178.2, 144.8, 142.9, 142.8, 142.4, 141.5, 139.8, 138.7, 134.1, 134.0, 133.70(d, J = 5.1 Hz), 132.2, 132.1, 131.9, 131.1, 128.5 (d, J = 3.3 Hz), 127.95,127.69 (d, J = 3.2 Hz), 122.17 (dd, J = 26.8, 12.4 Hz), 116.43 (d, J = 3.9Hz), 115.84, 101.26. 19F NMR (377 MHz, CDCl3) δ -62.60, -62.64. LR-MS (ESI):m/z 466.0 [M+H]+.
10-(4-(tert-butyl)-2-iodophenyl) acridin-9(10H)-onecompound with 10-(5-(tert-butyl)-2-iodophenyl) acridin-9(10H)-one (2:1) (3ay). White solid,yield 39%.1H NMR (400 MHz, CDCl3) δ 8.65 – 8.56 (m, 3H), 8.13 (d, J = 2.1 Hz,0.5H), 8.04 (d, J = 8.4 Hz, 1H), 7.67 (dd, J = 8.2, 2.2 Hz, 0.5H), 7.53(dddd, J = 8.6, 7.0, 3.2, 1.7 Hz, 3H), 7.43 (d, J = 2.3 Hz, 1H), 7.38 (dd, J= 8.4, 2.3 Hz, 1H), 7.33 (d, J = 8.7 Hz, 1H), 7.28 (dt, J = 5.8, 2.3 Hz, 3H),6.64 (t, J = 8.3 Hz, 3H), 1.44 (s, 4.5H), 1.35 (s, 9H). 13C NMR (101 MHz,CDCl3) δ 195.5, 161.31, 161.26, 154,5, 154.4, 152.6, 150.2, 139.6, 138.0,137.2, 132.65, 132.60, 132.2, 132.0, 131.9, 129.9, 128.3, 127.2, 124.4,120.9, 119.2, 116.6, 116.3, 89.9, 86.2, 34.9, 34.5, 31.4, 31.2. LR-MS (ESI):m/z 454.1 [M+H]+.
10-(6-iodobenzo[d] [1,3] dioxol-5-yl) acridin-9(10H)-one(3az). Whitesolid, yield 59%. 1H NMR (400 MHz, CDCl3) δ 8.72 – 8.50 (m, 2H), 7.68 – 7.45(m, 3H), 7.38 – 7.27 (m, 2H), 6.88 (s, 1H), 6.75 (d, J = 8.6 Hz, 2H), 6.16(d, J = 4.0 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 178.3, 150.4, 149.5, 142.1,134.6, 133.8, 127.6, 122.2, 122.0, 119.5, 116.3, 111.0, 103.0, 89.6. LR-MS(ESI): m/z 442.0 [M+H]+.
1-(1-iodonaphthalen-2-yl)-3,5-diphenyl-1H-pyrazole compound with 1-(2-iodonaphthalen-1-yl)-3,5-diphenyl-1H-pyrazole (10:3)(3ba) yield 52% 1H NMR(400 MHz, CDCl3) δ 8.24 – 8.17 (m, 1H), 8.03 – 7.91 (m, 2.6H), 7.84 – 7.74(m, 2.6H), 7.62 – 7.48 (m, 2.6H), 7.45 – 7.38 (m, 4.2H), 7.36 – 7.28 (m,1.3H), 7.29 – 7.23 (m, 2H), 7.21 – 7.15 (m, 3.6H), 7.15 – 7.08 (m, 1H), 7.01(s, 0.3H), 6.93 (s, 1H). 13C NMR (101 MHz, CDCl3) δ 152.7, 152.2, 145.8,142.1, 139.8, 135.3, 135.2, 133.6, 133.5, 133.4, 133.1, 132.8, 130.8, 130.0,129.9, 128.7, 128.6, 128.5, 128.4, 128.24, 128.17, 128.1, 128.0, 127.2,126.5, 126.07, 126.02, 123.6, 104.5, 103.9, 103.8. LR-MS (ESI): m/z 473.1 [M+H]+.
1-(4-(tert-butyl)-2-iodophenyl)-3,5-diphenyl-1H-pyrazole compoundwith 1-(5-(tert-butyl)-2-iodophenyl)-3,5-diphenyl-1H-pyrazole (2:1) (3bb).White solid, yield 46%.1H NMR (400 MHz, CDCl3) δ 7.94 (dd, J = 10.7, 3.6 Hz,2.7H), 7.87 (d, J = 2.0 Hz, 0.5H), 7.77 (d, J = 8.4 Hz, 1H), 7.45 – 7.36 (m,3.5H), 7.36 – 7.31 (m, 2.5H), 7.24 (dt, J = 10.1, 3.6 Hz, 7H), 7.11 (dd, J =8.4, 2.4 Hz, 1.5H), 6.87 (d, J = 6.6 Hz, 1.5H), 1.30 (s, 4.5H), 1.20 (s, 9H).13C NMR (101 MHz, CDCl3) δ 154.2, 152.8, 152.02, 151.97, 145.6, 142.6, 140.6,139.5, 137.0, 133.2, 130.14, 130.08, 129.0, 128.70, 128.68, 128.5, 128.4,128.3, 128.0, 127.7, 127.3, 126.3, 126.02, 125.98, 103.8, 97.9, 93.6, 34.8,34.7, 31.2, 31.0. LR-MS (ESI): m/z 479.1 [M+H]+.
1-(6-iodobenzo[d] [1,3] dioxol-5-yl)-3,5-diphenyl-1H-pyrazole (3bc).White solid, yield 31%.1H NMR (400 MHz, CDCl3) δ 7.98 – 7.90 (m, 2H), 7.44 (t,J = 7.5 Hz, 2H), 7.38 – 7.29 (m, 6H), 6.94 (s, 1H), 6.86 (s, 1H), 6.05 (s,2H). 13C NMR (101 MHz, CDCl3) δ 152.1, 149.1, 148.7, 145.7, 137.0, 133.1,130.1, 128.8, 128.6, 128.5, 128.4, 128.2, 126.0, 118.3, 110.2, 103.9, 102.7,87.4. LR-MS (ESI): m/z 467.0 [M+H]+.
本发明公开了邻二碘苯在氢化钠作用下，与仲胺反应生成邻碘芳胺化合物。这类反应更加快速、简捷而且温和，不需要过渡金属催化，没有过度偶联的副产物，官能团耐受性好，原料邻二碘苯廉价易得，是一种快速实现N-芳基化的新颖方法。此类反应主产物为2-碘代芳胺类化合物，用其他方法难以一步获得，产物易于转化，具有重要的应用价值。

Claims (1)

1.一种仲胺与邻二碘苯的反应方法，其特征在于，在碱金属氢化物存在下，将仲胺与邻二碘苯反应，完成仲胺与邻二碘苯的反应；碱金属氢化物为NaH；反应在溶剂中进行；溶剂为DMA、THF混合溶剂；反应的温度为室温～50℃；仲胺、邻二碘苯、碱金属氢化物的摩尔量比为1∶（1～3）∶（2～5）；邻二碘苯的化学结构式如下：
；
R3为氢；
仲胺的化学结构式及对应的反应时间如下：
。
CN202210813920.XA 2022-07-12 2022-07-12 一种仲胺与邻二碘苯的反应方法 Active CN115043735B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202210813920.XA CN115043735B (zh) 2022-07-12 2022-07-12 一种仲胺与邻二碘苯的反应方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202210813920.XA CN115043735B (zh) 2022-07-12 2022-07-12 一种仲胺与邻二碘苯的反应方法

Publications (2)

Publication Number Publication Date
CN115043735A CN115043735A (zh) 2022-09-13
CN115043735B true CN115043735B (zh) 2024-07-05

Family

ID=83165917

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202210813920.XA Active CN115043735B (zh) 2022-07-12 2022-07-12 一种仲胺与邻二碘苯的反应方法

Country Status (1)

Country Link
CN (1) CN115043735B (zh)

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10167292B2 (en) * 2015-08-04 2019-01-01 Catalyst Therapeutics Pty Ltd. Benzodiazepines as bromodomain inhibitors
KR20180079694A (ko) * 2017-01-02 2018-07-11 (주)피엔에이치테크 유기발광 화합물 및 이를 포함하는 유기전계발광소자
KR102418331B1 (ko) * 2017-09-25 2022-07-08 삼성디스플레이 주식회사 함규소 화합물 및 이를 포함하는 유기 전계 발광 소자
CN111925391A (zh) * 2020-08-05 2020-11-13 西北工业大学 含三苯基（氧）膦的有机长余辉材料及制备方法和使用方法
KR20220055202A (ko) * 2020-10-26 2022-05-03 덕산네오룩스 주식회사 유기전기소자용 화합물, 이를 이용한 유기전기소자 및 그 전자 장치
CN112979400B (zh) * 2021-02-21 2023-06-06 苏州大学 一种在碱金属氢化物作用下制备2-碘代芳醚的方法
CN113683559B (zh) * 2021-08-18 2023-01-31 苏州大学 一种制备杂环邻碘硫醚的方法
CN114105775A (zh) * 2021-11-30 2022-03-01 武汉工程大学 一种带有末端双键的取代碘苯的制备方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
A simple method for N-arylation of secondary amides/amines through a NaH-initiated aryne generation strategy;Yuanrui Jiang，et al.;Org. Chem. Front.,;20231003;第11卷(第1期);12–20 *

Also Published As

Publication number Publication date
CN115043735A (zh) 2022-09-13

Similar Documents

Publication Publication Date Title
US3894029A (en) Production of camptothecin and camptothecin-like compounds
Wang et al. Visible-light induced decarboxylative C2-alkylation of benzothiazoles with carboxylic acids under metal-free conditions
JP2021536471A (ja) メチル６−（２，４−ジクロロフェニル）−５−［４−［（３ｓ）−１−（３−フルオロプロピル）ピロリジン−３−イル］オキシフェニル］−８，９−ジヒドロ−７ｈ−ベンゾ［７］アンヌレン−２−カルボキシレートの塩およびその製造方法
PL184942B1 (pl) Nowe podstawione aminopirazole i pośrednie aminopirazole
NZ517900A (en) Phenylpiperazines useful as serotonin reuptake inhibitors
Knight et al. Synthesis of 3-aminoBODIPY dyes via copper-catalyzed vicarious nucleophilic substitution of 2-halogeno derivatives
ISHII et al. Studies on the Chemical Constituents of Rutaceous Plants. LV. The Development of a Versatile Method for the Synthesis of Antitumor Active Benzo [c] phenanthridine Alkaloids.(5). A New Method for Quaternization of the Benzo [c] phenanthridine Nucleus
CN115043735B (zh) 一种仲胺与邻二碘苯的反应方法
Caliendo et al. Synthesis of new 1, 2, 3-benzotriazin-4-one-arylpiperazine derivatives as 5-HT1A serotonin receptor ligands
TW202216642A (zh) 生產氘化芳香族化合物的方法、氘化反應組成物、氘化芳香族化合物以及電子裝置
CN109879788B (zh) 一种制备n-取代吲哚衍生物的方法
CN111471046A (zh) 一种咔唑吲哚醌衍生物及其制备方法和应用
JP2731853B2 (ja) トリ低級アルカノイルオキシホウ素の製造法
CN113735752B (zh) 一种基于取代碘苯制备异硫脲化合物的方法
WO2024011414A1 (zh) 一种仲胺与邻二碘苯的反应方法
CZ294957B6 (cs) Způsob přípravy substituované imidazopyridinové sloučeniny
CN112979529B (zh) 一种芳香胺吲哚萘醌衍生物及其制备方法
WO2014121671A1 (zh) 一种（+）-三环羟内酯制备方法
CN116253675B (zh) 一种n-取代-2-哌啶酮的合成方法
Musmar et al. The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 10. Synthesis and structure determination of naphtho [1′, 2′: 4, 5] thieno [3, 2‐a]‐4, 7‐phenanthroline
CN110437227A (zh) 一种具有多环桥环骨架的多取代四氢异喹啉及其制备方法
AU2019337018A1 (en) Method of producing tetracyclic compound
Reddy et al. CuI-catalyzed amination of Tröger's base halides: a convenient method for synthesis of unsymmetrical Tröger's bases
Glamkowski et al. Synthesis of 1, 2‐dihydroindolo [1, 7‐AB][1, 5] benzodiazepines and related structures. A new heterocyclic ring system
CN100383144C (zh) 一种奥氮平的中间体及其制备与应用

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