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WO2024011414A1 - Reaction method for secondary amine and o-diiodobenzene - Google Patents

Reaction method for secondary amine and o-diiodobenzene Download PDF

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Publication number
WO2024011414A1
WO2024011414A1 PCT/CN2022/105227 CN2022105227W WO2024011414A1 WO 2024011414 A1 WO2024011414 A1 WO 2024011414A1 CN 2022105227 W CN2022105227 W CN 2022105227W WO 2024011414 A1 WO2024011414 A1 WO 2024011414A1
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nmr
mhz
cdcl
diiodobenzene
reaction
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French (fr)
Chinese (zh)
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张士磊
祝文静
姜远锐
黄加文
陈鑫
方春辉
胡延维
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Suzhou University
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    • 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
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    • 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
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    • 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
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Definitions

  • the invention belongs to organic synthesis, and specifically relates to a reaction method between secondary amine and o-diiodobenzene.
  • Sodium hydride is a typical representative of alkali metal hydride, which is composed of Na + and H - .
  • sodium hydride can promote the transesterification reaction.
  • the compound and sodium hydride were refluxed in tetrahydrofuran, and the macrolide compound (I-Apicularen A) could be obtained through intramolecular transesterification.
  • Blacklock et al. discovered that using a catalytic amount of water can react NaH to generate highly active sodium hydroxide, which can quickly N-methylate compounds and effectively achieve methylation of amino acids and their analogs.
  • Aromatic amine compounds are an important molecular skeleton and are often used in various fields such as agriculture, medicine, dyes, pigments, and electronic industries.
  • Many biologically active molecules are N-substituted aromatic compounds, such as the central antihypertensive drug clonidine hydrochloride, the reversible cholinesterase inhibitor neostigmine bromide, the ⁇ -receptor blocker phentolamine, and Ca 2+ channels
  • the antagonist bepridil and others ( Figure 1).
  • Traditional N-arylation is generally constructed from the Ullmann reaction of aryl halides and amines [(a) Jourdan F. Ber. Dtsch.
  • the invention discloses the rapid preparation of aromatic amine compounds by o-diiodobenzene and secondary amines under the action of sodium hydride.
  • This type of reaction is fast, simple and mild. It is a novel method for quickly realizing N-arylation.
  • the main product of the reaction is It is a 2-iodoaromatic amine compound, which is easy to transform and has greater application value.
  • it solves the problem that the existing N-arylation method requires high temperature, metal catalysis and other conditions, and has long reaction time and preparation cost. High, serious environmental pollution and other shortcomings.
  • the present invention adopts the following technical solution: a reaction method of secondary amine and o-diiodobenzene. In the presence of alkali metal hydride or Grignard reagent, the secondary amine and o-diiodobenzene are reacted to complete the reaction between the secondary amine and o-diiodobenzene. reaction.
  • a method for preparing o-iodo products in the presence of alkali metal hydride or Grignard reagent, reacting secondary amine with o-diiodobenzene to obtain o-iodo products.
  • the alkali metal hydride is one or more of NaH, KH, CaH 2 and LiH
  • the Grignard reagent is i- PrMgBr.
  • the reaction is carried out in a solvent
  • the solvent is preferably one or more of DMA, THF, toluene, and CH 3 CN; it is preferably a mixed solvent of THF and DMA; further preferably, the volume ratio of THF and DMA is ( 3 ⁇ 5):1.
  • the reaction temperature is room temperature to 50°C, preferably room temperature to 40°C.
  • the molar ratio of secondary amine, o-diiodobenzene and alkali metal hydride is 1: (1-3): (2-5), preferably 1:2:3.
  • the chemical structural formula of the secondary amine is as follows: .
  • R 1 and R 2 independently select one of an alkyl group, a substituted alkyl group, an aryl group, a substituted aryl group, and a heterocyclic group; preferably, the substituted alkyl group is a halogen-substituted alkyl group, in which the number of carbon atoms is 1 to 10 , preferably 1 to 5.
  • R 1 and R 2 can also form a nitrogen-containing heterocyclic group with N, such as indole, indazole, pyrazole, tetrazole, pyridine, carbazole, acridine, phenothiazine, etc.
  • R 3 is selected from an alkyl group, a substituted alkyl group, an aryl group, a substituted aryl group, and a heterocyclic group; preferably, the substituted alkyl group is a halogen-substituted alkyl group, in which the number of carbon atoms is 1 to 10, preferably 1 to 10. 5; Heterocyclic groups such as phenothiazine, carbazole, anilinopyrimidine, indole, acridone, pyrazole and other groups.
  • the present invention finds that o-diiodobenzene can react with amines under the action of alkali metal hydride sodium hydride and be used for the non-metal catalytic construction of C-N.
  • This type of reaction is green, efficient, has a high atomic conversion rate, does not require transition metal catalysis, and has no over-coupling by-products.
  • the raw material o-diiodobenzene is cheap and easy to obtain; the experimental operation is simple, and high yields can still be obtained when scaling up to the gram level. ;
  • the main product of the reaction is a 2-iodo compound, which is difficult to obtain in one step by other methods; the product is easy to transform and is of great significance for the synthesis and modification of complex drug molecules.
  • Figure 1 shows the chemical structure of existing N-substituted aromatic hydrocarbons.
  • Figure 2 shows the reaction results of diphenylamine and o-diiodobenzene under different conditions.
  • Figure 3 shows the reaction results of different amine compounds and o-diiodobenzene.
  • Figure 4 shows the reaction results of phenothiazine compounds and o-diiodobenzene.
  • Figure 5 shows the reaction results of diphenylamine and diiodobenzene derivatives.
  • Figure 6 shows the reaction results under amplified conditions.
  • Figure 7 is a schematic diagram of the preparation of diiodobenzene raw materials.
  • the nuclear magnetic spectra 1 H NMR, 19 F NMR and 13 C NMR were all measured using Agilent 400 MHz and Bruker 400 MHz instruments, and the sample solvent was CDCl 3 (7.26 ppm).
  • NMR data reports include: chemical shifts, peak area integration, coupling constants, peak shapes, etc.
  • the LR-MS mass spectrometer is the ESI source.
  • the TLC thin layer chromatography plate is produced by Yantai Huanghai Chemical Factory. It is visually monitored at a wavelength of 254 nm or 365 nm.
  • the chromogens include KMnO 4 , iodine, phosphomolybdic acid and dinitrophenylhydrazine.
  • the mesh size of silica gel used in flash column chromatography For 200-300 mesh. All reagents used are of commercially available analytical or chemical purity and can be used directly without special instructions. Anhydrous solvents are redistilled solvents or commercially available dry solvents (Bailingwei).
  • Example 1 Refer to Figure 2, change the reaction conditions (single factor change), and obtain different results.
  • reaction solution After the reaction is completed, add the reaction solution to ice water to quench the reaction, extract with ethyl acetate three times, combine the organic layers, wash with saturated NaCl solution, dry over anhydrous sodium sulfate, filter, spin dry the solvent, add silica gel powder to mix the sample, and quickly After column chromatography separation, o-iodoaromatic amine product 3a was obtained with a yield of 72%.
  • Example 2 At room temperature, NaH (1.8 mmol, 3.0 equiv) was weighed into a reaction bottle, suspended in anhydrous THF (1.0 mL) and stirred normally. During the stirring process, secondary amine 2 (0.6 mmol, 1.0 equiv) was added. , dissolved in 0.5 mL DMA), stir at room temperature for 5 min after addition, then add o-diiodobenzene 1 (1.2 mmol, 2.0 equiv, dissolved in 1.0 mL THF), and stir the reaction normally.
  • reaction solution After the reaction is completed, add the reaction solution to ice water to quench the reaction, extract with ethyl acetate three times, combine the organic layers, wash with saturated NaCl solution, dry over anhydrous sodium sulfate, filter, spin dry the solvent, add silica gel powder to mix the sample, and quickly Column chromatography separated to obtain o-iodoaromatic amine product 3 .
  • the present invention has universal applicability to various substrates. See Figures 3 to 5.
  • the time in the figure is the reaction time, and the yield is the isolation yield. Unless otherwise specified, it is the conventional reaction condition; in Compound 1 and Compound 2
  • the substituents are consistent with those in product 3.
  • high yields can be obtained for diphenylamine, benzene naphthylamine, and dibenzylamine ( 3a-3c ); medium and above yields can be obtained for anilinopyridine, anilinopyrimidine, methylaniline, and methylaminopyridine.
  • a higher yield ( 3z ) can be obtained when a strong electron-withdrawing cyano group is present, and -CF 3 and -Cl can achieve a medium yield ( 3y , 3aa ); for diphenylamine, there are Higher yields can be obtained when electron-withdrawing groups exist, and lower yields can be achieved when electron-donating groups exist ( 3ab-3ac ); for indole, there is little difference in yield when methyl, methoxy, and halogen are substituted ( 3ae-3ag ), the yield is lower when the ortho-position large sterically hindered benzene ring is substituted ( 3ah ); for carbazole, halogen substitution can obtain higher yield ( 3ai-3aj ).
  • the reaction of phenothiazine, carbazole, anilinopyrimidines, indole, acridone, pyrazole and symmetric diiodobenzene can obtain a single product with moderate or above yield ( 3ak-3ap , 3ar -3at , 3av , 3aw , 3bd ), react with asymmetric diiodobenzene to obtain mixed products ( 3aq , 3ax , 3ay , 3az , 3bc ) in moderate yields. It is worth noting that 1,2-diiodonaphthalene can be obtained Moderate yield ( 3bb ).
  • Example 3 An amplification test was conducted, and the amount of feed was amplified to the gram level. This reaction laid the foundation for industrial production. See Figure 6. The reaction process was consistent with Example 2, and the amount of raw materials was amplified.
  • Synthesis example The raw materials of the present invention are commercially available products and can also be prepared according to conventional techniques. The preparation methods of some raw materials are given below.
  • the preparation method is the same as 1b (the raw materials are changed), and a white solid is obtained with a yield of 60%.
  • the invention discloses that o-diiodobenzene reacts with secondary amines under the action of sodium hydride to generate o-iodoaromatic amine compounds.
  • This type of reaction is faster, simpler and milder. It does not require transition metal catalysis, has no over-coupling by-products, has good functional group tolerance, and the raw material o-diiodobenzene is cheap and easy to obtain. It is a rapid N-arylation method. Novel approach.
  • the main product of this type of reaction is 2-iodoaromatic amine compounds, which are difficult to obtain in one step by other methods. The product is easy to transform and has important application value.

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Disclosed in the present invention is a reaction method for secondary amine and o-diiodobenzene, comprising: reacting secondary amine with o-diiodobenzene in the presence of an alkali metal hydride or a Grignard reagent to complete the reaction of secondary amine and o-diiodobenzene. Disclosed in the present invention is rapid preparations for arylamine compounds from o-diiodobenzene and secondary amine under the effect of sodium hydride, wherein the reactions are rapid, simple and gentle and are a novel method for rapidly achieving N-arylation. The main products of the reactions are 2-iodo-arylamine compounds, which are easy to convert and have greater value in use. The present invention especially solves the defects of long reaction time, high preparation cost, serious environmental pollution and the like since an N-arylation method in the prior art requires the conditions of high temperature, metal catalysis and the like.

Description

一种仲胺与邻二碘苯的反应方法A kind of reaction method of secondary amine and o-diiodobenzene 技术领域Technical field

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。The invention belongs to organic synthesis, and specifically relates to a reaction method between secondary amine and o-diiodobenzene.

背景技术Background technique

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、Ca 2+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 Hydroacridins und 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 Bond Cross-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。 Sodium hydride is a typical representative of alkali metal hydride, which is composed of Na + and H - . In 2004, Su et al. found that sodium hydride can promote the transesterification reaction. The compound and sodium hydride were refluxed in tetrahydrofuran, and the macrolide compound (I-Apicularen A) could be obtained through intramolecular transesterification. In 2003, Blacklock et al. discovered that using a catalytic amount of water can react NaH to generate highly active sodium hydroxide, which can quickly N-methylate compounds and effectively achieve methylation of amino acids and their analogs. Aromatic amine compounds are an important molecular skeleton and are often used in various fields such as agriculture, medicine, dyes, pigments, and electronic industries. Many biologically active molecules are N-substituted aromatic compounds, such as the central antihypertensive drug clonidine hydrochloride, the reversible cholinesterase inhibitor neostigmine bromide, the α-receptor blocker phentolamine, and Ca 2+ channels The antagonist bepridil and others (Figure 1). Traditional N-arylation is generally constructed from the Ullmann reaction of aryl halides and amines [(a) Jourdan F. Ber. Dtsch. Friedrich Jourdan: Xeue Syntheeen von Derivaten dee Hydroacridins und Aoridins. Chem. Ges ., 1885 , 18 : 1444.(b) Ullmann F, Wenner P. Ber. Dtsch. Chem. Ges , 1900 , 33 : 2476], the synthesis method generally requires metal copper or copper salt or palladium catalysis, high temperature and high pressure and other conditions, long reaction time, preparation The cost is high and the environmental pollution is serious. Later, arylboronic acids participated in N-arylation reactions as aryl acceptors, which also required transition metal catalysis [Patrick YS Lam, et al. New Aryl/Heteroaryl CN Bond Cross-coupling Reactions via Arylboronic Acid/Cupric Acetate Arylation. Tetrahedron Letters39 ( 1998 ) 2941-2944]. Therefore, it is particularly important to find green and efficient CN bond construction methods.

技术问题technical problem

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。The invention discloses the rapid preparation of aromatic amine compounds by o-diiodobenzene and secondary amines under the action of sodium hydride. This type of reaction is fast, simple and mild. It is a novel method for quickly realizing N-arylation. The main product of the reaction is It is a 2-iodoaromatic amine compound, which is easy to transform and has greater application value. In particular, it solves the problem that the existing N-arylation method requires high temperature, metal catalysis and other conditions, and has long reaction time and preparation cost. High, serious environmental pollution and other shortcomings.

技术解决方案Technical solutions

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。The present invention adopts the following technical solution: a reaction method of secondary amine and o-diiodobenzene. In the presence of alkali metal hydride or Grignard reagent, the secondary amine and o-diiodobenzene are reacted to complete the reaction between the secondary amine and o-diiodobenzene. reaction.

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。A method for preparing o-iodo products, in the presence of alkali metal hydride or Grignard reagent, reacting secondary amine with o-diiodobenzene to obtain o-iodo products.

本发明中，碱金属氢化物为NaH、KH、CaH 2、LiH中的一种或几种，格式试剂为 i-PrMgBr。 In the present invention, the alkali metal hydride is one or more of NaH, KH, CaH 2 and LiH, and the Grignard reagent is i- PrMgBr.

本发明中，反应在溶剂中进行，溶剂优选为DMA、THF、甲苯、CH 3CN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。 In the present invention, the reaction is carried out in a solvent, and the solvent is preferably one or more of DMA, THF, toluene, and CH 3 CN; it is preferably a mixed solvent of THF and DMA; further preferably, the volume ratio of THF and DMA is ( 3～5):1.

本发明中，反应的温度为室温～50℃，优选室温～40℃。In the present invention, the reaction temperature is room temperature to 50°C, preferably room temperature to 40°C.

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。In the present invention, the molar ratio of secondary amine, o-diiodobenzene and alkali metal hydride is 1: (1-3): (2-5), preferably 1:2:3.

本发明中，仲胺的化学结构式如下： 。 In the present invention, the chemical structural formula of the secondary amine is as follows: .

邻二碘苯的化学结构式如下： 。 The chemical structural formula of o-diiodobenzene is as follows: .

邻碘代产物的化学结构式如下： 。 The chemical structural formula of o-iodinated products is as follows: .

R 1、R 2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。R 1、R 2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。 R 1 and R 2 independently select one of an alkyl group, a substituted alkyl group, an aryl group, a substituted aryl group, and a heterocyclic group; preferably, the substituted alkyl group is a halogen-substituted alkyl group, in which the number of carbon atoms is 1 to 10 , preferably 1 to 5. R 1 and R 2 can also form a nitrogen-containing heterocyclic group with N, such as indole, indazole, pyrazole, tetrazole, pyridine, carbazole, acridine, phenothiazine, etc.

R 3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。 R 3 is selected from an alkyl group, a substituted alkyl group, an aryl group, a substituted aryl group, and a heterocyclic group; preferably, the substituted alkyl group is a halogen-substituted alkyl group, in which the number of carbon atoms is 1 to 10, preferably 1 to 10. 5; Heterocyclic groups such as phenothiazine, carbazole, anilinopyrimidine, indole, acridone, pyrazole and other groups.

有益效果beneficial effects

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。The present invention finds that o-diiodobenzene can react with amines under the action of alkali metal hydride sodium hydride and be used for the non-metal catalytic construction of C-N. This type of reaction is green, efficient, has a high atomic conversion rate, does not require transition metal catalysis, and has no over-coupling by-products. The raw material o-diiodobenzene is cheap and easy to obtain; the experimental operation is simple, and high yields can still be obtained when scaling up to the gram level. ; The main product of the reaction is a 2-iodo compound, which is difficult to obtain in one step by other methods; the product is easy to transform and is of great significance for the synthesis and modification of complex drug molecules.

附图说明Description of drawings

图1为现有N-取代芳烃类化合物的化学结构。Figure 1 shows the chemical structure of existing N-substituted aromatic hydrocarbons.

图2为二苯胺与邻二碘苯在不同条件下的反应结果。Figure 2 shows the reaction results of diphenylamine and o-diiodobenzene under different conditions.

图3为不同胺化合物与邻二碘苯的反应结果。Figure 3 shows the reaction results of different amine compounds and o-diiodobenzene.

图4为吩噻嗪化合物与邻二碘苯的反应结果。Figure 4 shows the reaction results of phenothiazine compounds and o-diiodobenzene.

图5为二苯胺与二碘苯衍生物的反应结果。Figure 5 shows the reaction results of diphenylamine and diiodobenzene derivatives.

图6为放大条件下的反应结果。Figure 6 shows the reaction results under amplified conditions.

图7为二碘苯原料制备示意。Figure 7 is a schematic diagram of the preparation of diiodobenzene raw materials.

本发明的实施方式Embodiments of the invention

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。In the present invention, in the presence of alkali metal hydride or Grignard reagent, secondary amine and o-diiodobenzene are reacted in a solvent at room temperature to obtain o-iodo products. All raw materials are commercially available products, and specific preparation operations and testing methods are conventional techniques.

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CDCl 3(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KMnO 4、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）。 The nuclear magnetic spectra 1 H NMR, 19 F NMR and 13 C NMR were all measured using Agilent 400 MHz and Bruker 400 MHz instruments, and the sample solvent was CDCl 3 (7.26 ppm). NMR data reports include: chemical shifts, peak area integration, coupling constants, peak shapes, etc. The LR-MS mass spectrometer is the ESI source. The TLC thin layer chromatography plate is produced by Yantai Huanghai Chemical Factory. It is visually monitored at a wavelength of 254 nm or 365 nm. The chromogens include KMnO 4 , iodine, phosphomolybdic acid and dinitrophenylhydrazine. The mesh size of silica gel used in flash column chromatography For 200-300 mesh. All reagents used are of commercially available analytical or chemical purity and can be used directly without special instructions. Anhydrous solvents are redistilled solvents or commercially available dry solvents (Bailingwei).

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%。 Example 1: Refer to Figure 2, change the reaction conditions (single factor change), and obtain different results. Take Group 11 as an example: at room temperature, weigh NaH (1.8 mmol, 3.0 equiv) in a reaction bottle, and suspend in Add diphenylamine 2a (0.6 mmol, 1.0 equiv, dissolved in 0.5 mL DMA) in water THF (1.0 mL) with normal stirring. After the addition, stir at room temperature for 5 min, then add o-diiodobenzene 1a ( 1.2 mmol, 2.0 equiv, dissolved in 1.0 mL THF), stir at room temperature for 1 hour. After the reaction is completed, add the reaction solution to ice water to quench the reaction, extract with ethyl acetate three times, combine the organic layers, wash with saturated NaCl solution, dry over anhydrous sodium sulfate, filter, spin dry the solvent, add silica gel powder to mix the sample, and quickly After column chromatography separation, o-iodoaromatic amine product 3a was obtained with a yield of 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。 Example 2: At room temperature, NaH (1.8 mmol, 3.0 equiv) was weighed into a reaction bottle, suspended in anhydrous THF (1.0 mL) and stirred normally. During the stirring process, secondary amine 2 (0.6 mmol, 1.0 equiv) was added. , dissolved in 0.5 mL DMA), stir at room temperature for 5 min after addition, then add o-diiodobenzene 1 (1.2 mmol, 2.0 equiv, dissolved in 1.0 mL THF), and stir the reaction normally. After the reaction is completed, add the reaction solution to ice water to quench the reaction, extract with ethyl acetate three times, combine the organic layers, wash with saturated NaCl solution, dry over anhydrous sodium sulfate, filter, spin dry the solvent, add silica gel powder to mix the sample, and quickly Column chromatography separated to obtain o-iodoaromatic amine product 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），-CF 3、-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）。 The present invention has universal applicability to various substrates. See Figures 3 to 5. The time in the figure is the reaction time, and the yield is the isolation yield. Unless otherwise specified, it is the conventional reaction condition; in Compound 1 and Compound 2 The substituents are consistent with those in product 3. Referring to Figure 3, high yields can be obtained for diphenylamine, benzene naphthylamine, and dibenzylamine ( 3a-3c ); medium and above yields can be obtained for anilinopyridine, anilinopyrimidine, methylaniline, and methylaminopyridine. Yield ( 3d-3i ); for alkylamines, such as diallylamine, piperazine, and hydrogenated isoquinoline, moderate yields ( 3d-3i ) can be obtained; for nitrogen heterocycles, such as indole, indole Azoles, pyrazoles, tetrazole, pyridine, carbazole, acridines, phenothiazines, etc. can achieve moderate and above yields ( 3m-3x ). Referring to Figure 4, for phenothiazine, a higher yield ( 3z ) can be obtained when a strong electron-withdrawing cyano group is present, and -CF 3 and -Cl can achieve a medium yield ( 3y , 3aa ); for diphenylamine, there are Higher yields can be obtained when electron-withdrawing groups exist, and lower yields can be achieved when electron-donating groups exist ( 3ab-3ac ); for indole, there is little difference in yield when methyl, methoxy, and halogen are substituted ( 3ae-3ag ), the yield is lower when the ortho-position large sterically hindered benzene ring is substituted ( 3ah ); for carbazole, halogen substitution can obtain higher yield ( 3ai-3aj ). Referring to Figure 5, the reaction of phenothiazine, carbazole, anilinopyrimidines, indole, acridone, pyrazole and symmetric diiodobenzene can obtain a single product with moderate or above yield ( 3ak-3ap , 3ar -3at , 3av , 3aw , 3bd ), react with asymmetric diiodobenzene to obtain mixed products ( 3aq , 3ax , 3ay , 3az , 3bc ) in moderate yields. It is worth noting that 1,2-diiodonaphthalene can be obtained Moderate yield ( 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。Example 3: An amplification test was conducted, and the amount of feed was amplified to the gram level. This reaction laid the foundation for industrial production. See Figure 6. The reaction process was consistent with Example 2, and the amount of raw materials was amplified.

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。Synthesis example: The raw materials of the present invention are commercially available products and can also be prepared according to conventional techniques. The preparation methods of some raw materials are given below.

参见图7，对称性邻二碘苯（1b、1c、1d、1e-1i）的制备。See Figure 7 for the preparation of symmetric o-diiodobenzene (1b, 1c, 1d, 1e-1i).

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125 mL HOAc:H 2O:H 2SO 4（体积比100:20:1）混合溶剂, 搅拌下依次加入高碘酸（40 mmol, 0.4 equiv），I 2（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%。 Place 1,3-benzodioxole (100 mmol, 1.0 equiv) in a round-bottomed flask, and add 125 mL HOAc:H 2 O:H 2 SO 4 (volume ratio 100:20:1) Mix the solvents, add periodic acid (40 mmol, 0.4 equiv) and I 2 (80 mmol, 0.8 equiv) in sequence while stirring, heat to 70°C and stir magnetically for 24 hours, and monitor the reaction with TLC. After the reaction is completed, the product is cooled to room temperature and the product is precipitated, filtered with suction, washed with methanol, and dried to obtain a white solid product 1b with a yield of 65%.

的制备方法与 1b相同（原料变化），得白色固体，产率60%。 The preparation method is the same as 1b (the raw materials are changed), and a white solid is obtained with a yield of 60%.

N 2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%。 Under N 2 protection, place iodine element (80 mmol, 2.0 equiv) in a two-necked bottle, seal it, and after ventilating three times, dissolve 1,2,3,4-tetramethylbenzene (40 mmol, 1.0 equiv) in 50 mL of methanol, inject, then add periodic acid (16 mmol, 0.4 equiv) dissolved in 30 mL of methanol, stir magnetically at 70°C overnight, and monitor the reaction with TLC. After the reaction is completed, the reaction solution is cooled to room temperature, stirred in an ice bath, and the product is precipitated, filtered, and dried to obtain a white solid 1d with a yield of 52%.

将苯胺（100 mmol, 1.0 equiv）置于圆底烧瓶中，加入碘（105 mmol, 1.05 equiv）、碳酸氢钠（300 mmol, 3.0 equiv），加入500 mL DCM:H 2O（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30 min，之后向反应液中逐滴添加NaNO 2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。 Place aniline (100 mmol, 1.0 equiv) in a round-bottomed flask, add iodine (105 mmol, 1.05 equiv), sodium bicarbonate (300 mmol, 3.0 equiv), and add 500 mL DCM:H 2 O (0.17 M, volume The mixed solution (ratio 2:1) was stirred at room temperature overnight and monitored by TLC. After the reaction is complete, wash with sodium thiosulfate solution, extract with DCM three times, combine the organic layers, wash with saturated NaCl solution, dry with anhydrous sodium sulfate, filter, spin dry the solvent, and add directly to the next step. Under an ice-water bath, the substituted o-iodoaniline (100 mmol, 1.0 equiv) was suspended in aqueous hydrochloric acid solution (250 mL, 4 M) and stirred for 30 min, and then NaNO 2 aqueous solution (120 mmol, 1.2 equiv) was added dropwise to the reaction solution. ), after the addition, continue stirring in an ice-water bath for 30 min. The reaction solution becomes clear, and then add KI aqueous solution (150 mmol, 1.5 equiv) dropwise. After the addition is complete, move to room temperature and continue the reaction for 3 h to complete. Add water, extract with ethyl acetate three times, combine the organic layers, wash with saturated NaCl solution, dry with anhydrous sodium sulfate, filter, spin dry the solvent, mix an appropriate amount of silica gel powder with the sample, and separate by flash column chromatography (pure PE) to finally obtain the monosubstituted Diiodobenzene products.

产物核磁。Product NMR.

White solid, yield 72%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 72%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCL 3 ) Δ 149.0, 141.0, 131.5, 129.1, 127.7, 122.2, 122.1 , 100.3. LR-MS (ESI): m/z 372.0 [M+H] + .

White solid, yield 44%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) δ 149.1, 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] +。 White solid, yield 44%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) δ 149.1, 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] + .

White solid, yield 58%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 58%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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, yield 31%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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-4-amine(3d). Colorless oil, yield 31%. 1 H NMR (400 MHz, CDCl 3 ) 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), 13 _ _ _ C NMR (101 MHz, CDCl 3 ) 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] + .

Colorless oil, yield 47%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 Colorless oil, yield 47%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

White solid, yield 74%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 74%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

White solid, yield 57%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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/z 355.0 [M+H] +。 White solid, yield 57%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.07 (d, J = 9.0 Hz, 2H), 7.99 (d, J = 7.9 Hz, 1H), 7.48 (t, J = 7.5 Hz 13 C NMR _ (101 MHz, CDCl 3 ) 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/z 355.0 [M+H] + .

O- (2-iodophenyl)-N-methylpyridin-4-amine (3h).Colorless oil, yield 28%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 O- (2-iodophenyl)-N-methylpyridin-4-amine (3h). Colorless oil, yield 28%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

Colorless oil, yield 63%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 Colorless oil, yield 63%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

pale-yellow oil, yield 48%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 pale-yellow oil, yield 48%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

Colorless oil, yield 13%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 Colorless oil, yield 13%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz , CDCl 3 ) 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] + .

White solid, yield 42%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 42%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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, CDCl 3) 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, CDCl 3) δ 142.2, 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-indole (3m). Colorless oil, yield 47%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) δ 142.2, 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] + .

Colorless oil, yield 58%. 1H NMR (400 MHz, CDCl 3) δ 8.24 (s, 1H), 8.04 (d, J = 7.9 Hz, 1H), 7.82 (d, J = 8.0 Hz, 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, CDCl 3) 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] +。 Colorless oil, yield 58%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.24 (s, 1H), 8.04 (d, J = 7.9 Hz, 1H), 7.82 (d, J = 8.0 Hz, 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

White solid, yield 45%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 45%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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, CDCl 3) 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, CDCl 3) 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)-5-phenyl-1H-tetrazole (3p). White solid, yield 15%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

Colorless oil, yield 54%. 1H NMR (400 MHz, CDCl 3) 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, 0.9 Hz, 1H), 6.91 (d, J = 6.0 Hz, 2H). 13C NMR (101 MHz, CDCl 3) 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] +。 Colorless oil, yield 54%. 1 H NMR (400 MHz, CDCl 3 ) 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, 0.9 Hz, 1H), 6.91 (d, J = 6.0 Hz, 2H). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

White solid, yield 90%. Mp. 130 – 131 °C. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 90%. Mp. 130 – 131 °C. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

White solid, yield 34%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 34%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz , CDCl 3 ) 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] + .

Colorless oil, yield 83%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 Colorless oil, yield 83%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

White solid, yield 67%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 67%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) δ 178.3, 142.0, 141.6, 141.3, 133.7, 131.5, 131.3, 131.1, 127.7, 122.1, 122.0, 11 6.3, 100.7. LR-MS (ESI): m/z 398.0 [M+H] + .

White solid, yield 75%.. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 75%.. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

White solid, yield 43%. 1H NMR (400 MHz, CDCl 3) δ 8.14 (dd, J = 8.0, 1.3 Hz, 1H), 7.61 (td, J = 7.6, 1.4 Hz, 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, CDCl 3) 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] +。 White solid, yield 43%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.14 (dd, J = 8.0, 1.3 Hz, 1H), 7.61 (td, J = 7.6, 1.4 Hz, 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) . 13 C NMR (101 MHz, CDCl 3 ) 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] + .

White solid, yield 56%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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/z 403.0 [M+H] + 。 White solid, yield 56%. 1 H NMR (400 MHz, CDCl 3 ) 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). , 129.7, 127.3, 126.5, 123.3, 118.7, 118.4, 116.4, 115.3, 102.1. LR-MS (ESI): m/z 403.0 [M+H] + .

White solid, yield 67%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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, CDCl 3) δ -63.06. LR-MS (ESI): m/z 470.0 [M+H] +。 White solid, yield 67%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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. 19 F NMR (377 MHz, CDCl 3 ) δ -63.06. LR-MS (ESI): m/z 470.0 [M+H] + .

White solid, yield 93%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) δ 142.5, 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] +。 White solid, yield 93%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) δ 142.5, 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] + .

White solid, yield 39%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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/z 435.9 [M+H] +。 White solid, yield 39%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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/Z 435.9 [m + H] + .

White solid，yield 68%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 68%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

White solid, yield 38%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 38%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

White solid, yield 33%. 1H NMR (400 MHz, CDCl 3) 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 (101 MHz, CDCl 3) 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。 White solid, yield 33%. 1 H NMR (400 MHz, CDCl 3 ) 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 ( 13 _ C NMR (101 MHz, CDCl 3 ) 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.

Colorless oil, yield 36%. 1H NMR (400 MHz, CDCl 3) 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 = 7.4 Hz, 1H), 7.02 (d, J = 2.6 Hz, 1H), 6.94 (d, J = 6.9 Hz, 1H), 6.69 (d, J = 2.6 Hz, 1H), 1.95 (s, 3H). 13C NMR (101 MHz, CDCl 3) 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] +。 Colorless oil, yield 36%. 1 H NMR (400 MHz, CDCl 3 ) 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 = 7.4 Hz, 1H), 7.02 (d, J = 2.6 Hz, 1H), 6.94 (d, J = 6.9 Hz , 1H), 6.69 (d, J = 2.6 Hz, 1H), 1.95 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

Colorless oil, yield 27%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) δ 154.7, 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] +。 Colorless oil, yield 27%. 1 H NMR (400 MHz, CDCl 3 ) 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) . 13 C NMR (101 MHz, CDCl 3 ) δ 154.7, 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] + .

Colorless oil, yield 38%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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, CDCl 3) δ -120.12. LR-MS (ESI): m/z 338.0 [M+H] +。 Colorless oil, yield 38%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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. 19 F NMR (377 MHz, CDCl 3 ) δ -120.12. LR-MS (ESI): m/z 338.0 [M+H] + .

Colorless oil, yield 20%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 Colorless oil, yield 20%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

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). 13C NMR (101 MHz, CDCl 3) 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] +。 White solid, yield 55%. 1 H 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). 13 C NMR (101 MHz, CDCl 3 ) 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, 12 0.7, 120.6, 113.0 , 111.7, 110.4, 99.1. LR-MS (ESI): m/z 447.9 [M+H] + .

White solid, yield 91%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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/z 495.9 [M+H] +。 White solid, yield 91%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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/z 495.9 [M+H] + .

White solid，yield 43%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 43%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

White solid，yield 47%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 47%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

White solid, yield 55%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 55%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

White solid, yield 39%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 39%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

White solid, yield 36%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 36%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

White solid, yield 33%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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, CDCl 3) δ -62.58 (s), -62.79 (s). LR-MS (ESI): m/z 438.0 [M+H] +。 White solid, yield 33%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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, 19 F NMR (377 MHz, CDCl 3 ) δ -62.58 (s), -62.79 (s). LR-MS (ESI): m/z 438.0 [M+H] + .

White solid, yield 78%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 78%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

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 (101 MHz, 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/z 458.1 [M+H] +。 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 (101 MHz, CDCl3) δ LR- MS (ESI): m/z 458.1 [M+ H] + .

White solid, yield 58%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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/z 446.0 [M+H] +。 White solid, yield 58%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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/z 446.0 [M+H] + .

White solid, yield 57%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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. 19F NMR (377 MHz, CDCl 3) δ -62.28 (s). LR-MS (ESI): m/z 470.0 [M+H] +。 White solid, yield 57%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) δ 167.8, 161.0, 151.4, 143.6, 137.2 (d, J 19 _ _ _ F NMR (377 MHz, CDCl 3 ) δ -62.28 (s). LR-MS (ESI): m/z 470.0 [M+H] + .

Colorless oil, yield 45%. 1H NMR (400 MHz, CDCl 3) 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). 13C NMR (101 MHz, CDCl 3) 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/z 348.0 [M+H] +。 Colorless oil, yield 45%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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/z 348.0 [M+H] + .

Colorless oil, yield 25%. 1H NMR (400 MHz, CDCl 3) 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). 13C NMR (101 MHz, CDCl 3) 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] +。 Colorless oil, yield 25%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

Colorless oil, yield 28%. 1H NMR (400 MHz, CDCl 3) 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, 0.8 Hz, 0.7H), 1.40 (s, 6H), 1.35 (s, 9H). 13C NMR (101 MHz, CDCl 3) 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] +。 Colorless oil, yield 28%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.02 (d, J = 2.1 Hz, 0.7H), 7.93 (d, J = 8.4 Hz, 1H), 7.75 – 7.69 (m, 1.4 H), 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 13 C _ NMR (101 MHz, CDCl 3 ) 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, 12 1.09, 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 compound with 10-(2-iodo-5-(trifluoromethyl) phenyl) acridin-9(10H)-one (1:1) (3ax). White solid, yield 42%. 1H NMR (400 MHz, CDCl 3) δ 8.59 (ddd, J = 8.1, 5.7, 1.6 Hz, 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, CDCl 3) δ 178.2, 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 = 3.9 Hz), 115.84, 101.26. 19F NMR (377 MHz, CDCl 3) δ -62.60, -62.64. LR-MS (ESI): m/z 466.0 [M+H] +。 10- (2-iodo-4-(trifluoromethyl) phenyl) acridin-9(10H)-one compound with 10-(2-iodo-5-(trifluoromethyl) phenyl) acridin-9(10H)-one (1:1 ) (3ax). White solid, yield 42%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.59 (ddd, J = 8.1, 5.7, 1.6 Hz, 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). 13 C NMR (101 MHz, CDCl 3 ) δ 178.2, 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 = 3.9 Hz ), 115.84, 101.26. 19 F NMR (377 MHz, CDCl 3 ) δ -62.60, -62.64. LR-MS (ESI): m/z 466.0 [M+H] + .

White solid, yield 39%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 39%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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 ] + .

White solid, yield 59%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 59%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

yield 52% 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 yield 52% 1 H NMR (400 MHz, CDCl 3 ) 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, 2.6 H), 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

White solid, yield 46%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 46%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCl 3 ) 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] + .

White solid, yield 31%. 1H NMR (400 MHz, CDCl 3) 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, CDCl 3) 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] +。 White solid, yield 31%. 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (101 MHz, CDCL 3 ) Δ 152.1, 148.7, 145.7, 137.0, 130.1, 128.8, 128.5, 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。The invention discloses that o-diiodobenzene reacts with secondary amines under the action of sodium hydride to generate o-iodoaromatic amine compounds. This type of reaction is faster, simpler and milder. It does not require transition metal catalysis, has no over-coupling by-products, has good functional group tolerance, and the raw material o-diiodobenzene is cheap and easy to obtain. It is a rapid N-arylation method. Novel approach. The main product of this type of reaction is 2-iodoaromatic amine compounds, which are difficult to obtain in one step by other methods. The product is easy to transform and has important application value.

Claims (10)

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。A reaction method for secondary amine and o-diiodobenzene, which is characterized in that in the presence of alkali metal hydride or Grignard reagent, the secondary amine and o-diiodobenzene are reacted to complete the reaction between the secondary amine and o-diiodobenzene. 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。A method for preparing o-iodo products, in the presence of alkali metal hydride or Grignard reagent, reacting secondary amine with o-diiodobenzene to obtain o-iodo products. 根据权利要求1或者2所述的方法，其特征在于，碱金属氢化物为NaH、KH、CaH 2、LiH中的一种或几种，格式试剂为 i-PrMgBr。 The method according to claim 1 or 2, characterized in that the alkali metal hydride is one or more of NaH, KH, CaH 2 and LiH, and the Grignard reagent is i- PrMgBr. 根据权利要求1或者2所述的方法，其特征在于，反应在溶剂中进行。The method according to claim 1 or 2, characterized in that the reaction is carried out in a solvent. 根据权利要求4所述的方法，其特征在于，溶剂为DMA、THF、甲苯、CH 3CN中的一种或几种。 The method according to claim 4, characterized in that the solvent is one or more of DMA, THF, toluene and CH 3 CN. 根据权利要求1或者2所述的方法，其特征在于，反应的温度为室温～50℃，时间为0.55小时。The method according to claim 1 or 2, characterized in that the reaction temperature is room temperature to 50°C, and the reaction time is 0.55 hours. 根据权利要求1或者2所述的方法，其特征在于，仲胺、邻二碘苯、碱金属氢化物的摩尔量比为1∶（1～3）∶（2～5）。The method according to claim 1 or 2, characterized in that the molar ratio of secondary amine, o-diiodobenzene and alkali metal hydride is 1: (1-3): (2-5). 根据权利要求1或者2所述的方法，其特征在于，仲胺的化学结构式如下：The method according to claim 1 or 2, characterized in that the chemical structural formula of the secondary amine is as follows: 邻二碘苯的化学结构式如下：The chemical structural formula of o-diiodobenzene is as follows: 邻碘代产物的化学结构式如下：The chemical structural formula of o-iodinated products is as follows: R 1、R 2 、R 3独立的选择烷基、取代烷基、芳基、取代芳基、杂环基中的一种；或者R 1、R 2与N组成含氮杂环基团。 R 1 , R 2 , and R 3 independently select one of alkyl, substituted alkyl, aryl, substituted aryl, and heterocyclic groups; or R 1 , R 2 and N form a nitrogen-containing heterocyclic group. 根据权利要求8所述的方法，其特征在于，取代烷基为卤素取代烷基，杂环基为吩噻嗪、咔唑、苯胺基嘧啶、吲哚、吖啶酮或吡唑基团。The method according to claim 8, wherein the substituted alkyl group is a halogen-substituted alkyl group, and the heterocyclic group is a phenothiazine, carbazole, anilinopyrimidine, indole, acridone or pyrazole group. 碱金属氢化物或者格式试剂在仲胺与邻二碘苯反应中的应用。Application of alkali metal hydrides or Grignard reagents in the reaction of secondary amines with o-diiodobenzene.
PCT/CN2022/105227 2022-07-12 2022-07-12 Reaction method for secondary amine and o-diiodobenzene Ceased WO2024011414A1 (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1518534A (en) * 2001-04-24 2004-08-04 麻省理工学院 Copper-catalyzed carbon-heteroatom and carbon-carbon bond formation
CN113735752A (en) * 2021-08-18 2021-12-03 上海药坦药物研究开发有限公司 Method for preparing isothiourea compound based on substituted iodobenzene
CN113735777A (en) * 2021-08-18 2021-12-03 上海药坦药物研究开发有限公司 Method for preparing cyclic thiourea compound
CN113735751A (en) * 2021-08-18 2021-12-03 上海药坦药物研究开发有限公司 Method for preparing aryl isothiourea

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1518534A (en) * 2001-04-24 2004-08-04 麻省理工学院 Copper-catalyzed carbon-heteroatom and carbon-carbon bond formation
CN113735752A (en) * 2021-08-18 2021-12-03 上海药坦药物研究开发有限公司 Method for preparing isothiourea compound based on substituted iodobenzene
CN113735777A (en) * 2021-08-18 2021-12-03 上海药坦药物研究开发有限公司 Method for preparing cyclic thiourea compound
CN113735751A (en) * 2021-08-18 2021-12-03 上海药坦药物研究开发有限公司 Method for preparing aryl isothiourea

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
"Master's Thesis", 1 May 2008, SUZHOU UNIVERSITY, CN, article XUE, FEI: "The Research on Reactions of C-N Bond Formation", pages: 1 - 51, XP009552018 *
BARKER, TIMOTHY J. ET AL.: "Titanium-Mediated Amination of Grignard Reagents Using Primary and Secondary Amines", ANGEWANDTE CHEMIE, INTERNATIONAL EDITION, vol. 50, no. 36, 18 July 2011 (2011-07-18), pages 8325 - 8328, XP072086344, ISSN: 1433-7851, DOI: 10.1002/anie.201103700 *
FAN GUANG-GAO, JIANG BO-WEN, SANG WEI, CHENG HUA, ZHANG RUI, YU BAO-YI, YUAN YE, CHEN CHENG, VERPOORT FRANCIS: "Metal-Free Synthesis of Heteroaryl Amines or Their Hydrochlorides via an External-Base-Free and Solvent-Free C–N Coupling Protocol", THE JOURNAL OF ORGANIC CHEMISTRY, AMERICAN CHEMICAL SOCIETY, vol. 86, no. 21, 5 November 2021 (2021-11-05), pages 14627 - 14639, XP093129219, ISSN: 0022-3263, DOI: 10.1021/acs.joc.1c01467 *
PAIN A.J.: "MECHANISMS AND MODELS FOR COPPER MEDIATED NUCLEOPHILIC AROMATIC SUBSTITUTION. 2. A SINGLE CATALYTIC SPECIES FROM THREE DIFFERENT OXIDATION STATES OF COPPER IN AN ULLMANN SYNTHESIS OF TRIARYLAMINES.", JOURNAL OF THE CHEMICAL SOCIETY, vol. 109, 1 January 1987 (1987-01-01), pages 1496 - 1502, XP000913833, ISSN: 0368-1769, DOI: 10.1021/ja00239a032 *

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