3,4-dimethoxy-2-nitrobenzonitrile | 1175636-14-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3,4-dimethoxy-2-nitrobenzonitrile
• CAS: 1175636-14-2
• 化学式: C₉H₈N₂O₄
• 分子量: 208.174
• InChiKey: PPXIMMALSMXMBD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  88.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,4-dimethoxy-2-nitrobenzonitrile 在 吡啶 、 palladium on activated charcoal 、 氢气 、 zinc(II) chloride 作用下， 以 乙酸乙酯 、 氯苯 为溶剂， 反应 23.0h， 生成 (S)-3,5-dichloro-N-(6-(4-isopropyl-4,5-dihydrooxazol-2-yl)-2,3-dimethoxyphenyl)benzenesulfonamide
  参考文献：
  名称：

  Selective Activation/Coupling of Polyhalogenated Nucleophiles in Ni/Cr-Mediated Reactions: Synthesis of C1–C19 Building Block of Halichondrin Bs

  摘要：

  The C1-C19 building block 46 of halichondrin Bs was synthesized via a selective activation/coupling of beta-bromoenone 34 with aldehyde 35 in a Ni/Cr-mediated reaction. The first phase of study was a method development to effect a coupling of a naked vinylogous anion with an aldehyde. The study with the coupling of 9 + 10 -> 11 revealed: (1) beta-bromoenone 9b is a better nucleophile than the corresponding beta-iodo- and beta-chloroenones 9a,c; (2) (Me)(2)Phen(OMe)(2)center dot NiCl2 13b is a better Ni-catalyst than (Me)(2)Phen(H)(2)center dot NiCl2 13a; and (3) a low Ni-catalyst loading, for example, 0.05-0.1 mol % Ni-catalyst against 10 mol % Cr-catalyst, is crucial for an effective coupling. The second phase of study was a method development to realize a selective activation/coupling of polyhalogenated nucleophiles such as 34. The competition experiment of 10 + 9b over 10 + 31a-c revealed: (1) (Me)(2)Phen(OMe)(2)center dot NiCl2 13b is more effective than (Me)(2)Phen(H)(2)center dot NiCl2 13a for the required selective activation/coupling; (2) a low Ni-catalyst loading, for example, 0.05-0.1 mol % Ni-catalyst against 10 mol % Cr-catalyst, is crucial for discriminating beta-bromoenone 9b from the three types of vinyl iodides 31a-c. The third phase of study was an application of the developed method to execute the proposed coupling of 34 + 35 -> 36. For this application, a polyether-type Ni-catalyst 37c, readily soluble in the reaction medium, was introduced to achieve the selective activation/coupling with higher efficiency. With use of ion-exchange resin-based device, the coupling product 36 was transformed to the C1-C19 building block 46 of halichondrin Bs without purification/separation of the intermediates.

  DOI：

  10.1021/jacs.5b03498
• 作为产物：
  描述：

  4-羟基-3-甲氧基-2-硝基苯甲醛 在 ammonium hydroxide 、 碘 、 sodium hydride 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 3,4-dimethoxy-2-nitrobenzonitrile
  参考文献：
  名称：

  Selective Activation/Coupling of Polyhalogenated Nucleophiles in Ni/Cr-Mediated Reactions: Synthesis of C1–C19 Building Block of Halichondrin Bs

  摘要：

  The C1-C19 building block 46 of halichondrin Bs was synthesized via a selective activation/coupling of beta-bromoenone 34 with aldehyde 35 in a Ni/Cr-mediated reaction. The first phase of study was a method development to effect a coupling of a naked vinylogous anion with an aldehyde. The study with the coupling of 9 + 10 -> 11 revealed: (1) beta-bromoenone 9b is a better nucleophile than the corresponding beta-iodo- and beta-chloroenones 9a,c; (2) (Me)(2)Phen(OMe)(2)center dot NiCl2 13b is a better Ni-catalyst than (Me)(2)Phen(H)(2)center dot NiCl2 13a; and (3) a low Ni-catalyst loading, for example, 0.05-0.1 mol % Ni-catalyst against 10 mol % Cr-catalyst, is crucial for an effective coupling. The second phase of study was a method development to realize a selective activation/coupling of polyhalogenated nucleophiles such as 34. The competition experiment of 10 + 9b over 10 + 31a-c revealed: (1) (Me)(2)Phen(OMe)(2)center dot NiCl2 13b is more effective than (Me)(2)Phen(H)(2)center dot NiCl2 13a for the required selective activation/coupling; (2) a low Ni-catalyst loading, for example, 0.05-0.1 mol % Ni-catalyst against 10 mol % Cr-catalyst, is crucial for discriminating beta-bromoenone 9b from the three types of vinyl iodides 31a-c. The third phase of study was an application of the developed method to execute the proposed coupling of 34 + 35 -> 36. For this application, a polyether-type Ni-catalyst 37c, readily soluble in the reaction medium, was introduced to achieve the selective activation/coupling with higher efficiency. With use of ion-exchange resin-based device, the coupling product 36 was transformed to the C1-C19 building block 46 of halichondrin Bs without purification/separation of the intermediates.

  DOI：

  10.1021/jacs.5b03498

文献信息

• Chromium-mediated coupling and application to the synthesis of halichondrins
  申请人：President and Fellows of Harvard College

  公开号：US10344038B2

  公开（公告）日：2019-07-09

  The present invention provides unified synthesis of the CI-CI 9 building blocks of halichondrins and analogs thereof using selective coupling of poly-halogenated nucleophiles in chromium-mediated coupling reactions. The present invention also provides a practical and efficient synthesis of C20-C38 building blocks of halichondrins and analogs thereof. Also provided herein are general methods of selective activation and coupling of poly-halogenated analogs with an aldehyde. The provided coupling reactions are selective for halo-enone and halo-acetylenic ketal over vinyl halide and halide attached to a sp hydridized carbon. The provided efficient selective coupling reactions can allow easy access to the CI-CI 9 building blocks and C20-C38 building blocks of halichondrins and analogs thereof with limited or no purification or separation of the intermediates.

  本发明提供了在铬介导的偶联反应中利用多卤代亲核物的选择性偶联来统一合成卤代姜黄素及其类似物的 CI-CI 9 结构单元。本发明还提供了一种实用高效的卤代龙毒素及其类似物的 C20-C38 结构单元的合成方法。本发明还提供了选择性活化多卤代类似物并将其与醛偶联的一般方法。所提供的偶联反应对卤代烯酮和卤代乙炔缩酮具有选择性，而对乙烯基卤化物和连接到 sp 水化物碳上的卤化物则没有选择性。所提供的高效选择性偶联反应可以方便地获得卤代烯酮及其类似物的 CI-CI 9 结构单元和 C20-C38 结构单元，中间产物的纯化或分离程度有限或根本不需要。
• [EN] CHROMIUM-MEDIATED COUPLING AND APPLICATION TO THE SYNTHESIS OF HALICHONDRINS<br/>[FR] COUPLAGE INDUIT PAR CHROME ET APPLICATION À LA SYNTHÈSE D'HALICHONDRINES
  申请人：HARVARD COLLEGE

  公开号：WO2016176560A8

  公开（公告）日：2017-06-22
• CHROMIUM-MEDIATED COUPLING AND APPLICATION TO THE SYNTHESIS OF HALICHONDRINS
  申请人：President and Fellows of Harvard College

  公开号：US20200031843A1

  公开（公告）日：2020-01-30

  The present invention provides unified synthesis of the C1-C19 building blocks of halichondrins and analogs thereof using selective coupling of poly-halogenated nucleophiles in chromium-mediated coupling reactions. The present invention also provides a practical and efficient synthesis of C20-C38 building blocks of halichondrins and analogs thereof. Also provided herein are general methods of selective activation and coupling of poly-halogenated analogs with an aldehyde. The provided coupling reactions are selective for halo-enone and halo-acetylenic ketal over vinyl halide and halide attached to a sp hybridized carbon. The provided efficient selective coupling reactions can allow easy access to the C1-C19 building blocks and C20-C38 building blocks of halichondrins and analogs thereof with limited or no purification or separation of the intermediates.
• Selective Activation/Coupling of Polyhalogenated Nucleophiles in Ni/Cr-Mediated Reactions: Synthesis of C1–C19 Building Block of Halichondrin Bs
  作者：Wuming Yan、Zhanjie Li、Yoshito Kishi

  DOI：10.1021/jacs.5b03498

  日期：2015.5.20

  The C1-C19 building block 46 of halichondrin Bs was synthesized via a selective activation/coupling of beta-bromoenone 34 with aldehyde 35 in a Ni/Cr-mediated reaction. The first phase of study was a method development to effect a coupling of a naked vinylogous anion with an aldehyde. The study with the coupling of 9 + 10 -> 11 revealed: (1) beta-bromoenone 9b is a better nucleophile than the corresponding beta-iodo- and beta-chloroenones 9a,c; (2) (Me)(2)Phen(OMe)(2)center dot NiCl2 13b is a better Ni-catalyst than (Me)(2)Phen(H)(2)center dot NiCl2 13a; and (3) a low Ni-catalyst loading, for example, 0.05-0.1 mol % Ni-catalyst against 10 mol % Cr-catalyst, is crucial for an effective coupling. The second phase of study was a method development to realize a selective activation/coupling of polyhalogenated nucleophiles such as 34. The competition experiment of 10 + 9b over 10 + 31a-c revealed: (1) (Me)(2)Phen(OMe)(2)center dot NiCl2 13b is more effective than (Me)(2)Phen(H)(2)center dot NiCl2 13a for the required selective activation/coupling; (2) a low Ni-catalyst loading, for example, 0.05-0.1 mol % Ni-catalyst against 10 mol % Cr-catalyst, is crucial for discriminating beta-bromoenone 9b from the three types of vinyl iodides 31a-c. The third phase of study was an application of the developed method to execute the proposed coupling of 34 + 35 -> 36. For this application, a polyether-type Ni-catalyst 37c, readily soluble in the reaction medium, was introduced to achieve the selective activation/coupling with higher efficiency. With use of ion-exchange resin-based device, the coupling product 36 was transformed to the C1-C19 building block 46 of halichondrin Bs without purification/separation of the intermediates.