2-bromo-5-iodo-3-methylthiophene | 157925-12-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 2-bromo-5-iodo-3-methylthiophene
• 英文别名: 2-Brom-5-jod-3-methyl-thiophen
• CAS: 157925-12-7
• 化学式: C₅H₄BrIS
• 分子量: 302.961
• InChiKey: POTNJSFIXFBSTP-UHFFFAOYSA-N

物化性质

• 沸点：
  258.5±40.0 °C(Predicted)
• 密度：
  2.270±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  28.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-bromo-5-iodo-3-methylthiophene 在 盐酸 、 sodium hydroxide 、 正丁基锂 、 sodium methylate 、 potassium carbonate 、 copper(II) oxide 作用下， 以 乙醚 、 二丁醚 、 水 、 异丙醇 为溶剂， 反应 105.0h， 生成
  参考文献：
  名称：

  The synthesis of novel GABA uptake inhibitors. Part 2. Synthesis of 5-hydroxytiagabine, a human metabolite of the GABA reuptake inhibitor tiagabine

  摘要：

  (R)-1-(4-(2,5-Dihydro-3-methyl-5-oxothien-2-ylidene)-4-(3-methyl-2-thienyl)butyl)-3- piperidinecarboxylic acid (5-hydroxytiagabine) 13, has been prepared in 8 steps from 2-bromo-3-methylthiophene 3. Key steps are Grignard reactions, displacement of heteroaromatic chlorine with methoxy, and simultaneously demethylation and opening of a hydroxymethylcyclopropane with bromotrimethylsilane. An alternative approach involving acylation of 2-lithio-3-methylthiophene 17a was found less satisfying. A metalloporphyrin assisted hydroxylation of tiagabine 1 also yielded the target metabolite. The structure of 5-hydroxytiagabine was confirmed by NMR-data including COSY, ROESY, HMQC and HMBC experiments.

  DOI：

  10.1016/s0040-4020(01)85345-x
• 作为产物：
  描述：

  3-甲基噻吩 在 (2,2'-bipyridine)nickel(II) dibromide 甲醇 、 四丁基溴化铵 、 tetrabutylammonium tetrafluoroborate 、 溴 、 zinc dibromide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-bromo-5-iodo-3-methylthiophene
  参考文献：
  名称：

  New and efficient access to 3-substituted 2,5-dibromothiophenes. Consecutive nickel-catalyzed electrochemical conversion to thienylzinc species

  摘要：

  我们已经通过电化学方法和一种原创的溴化程序实现了3取代噻吩锌试剂的逐步合成。对于几个化合物，3-溴噻吩是起始底物，它根据最近开发的电化学程序进行了功能化。在锌盐存在下，对得到的3取代2,5-二溴噻吩进行镍催化的电化学还原，使得单噻吩锌物种以良好的产率形成。关于该反应的选择性，我们在电化学合成有规聚噻吩的背景下进行了讨论。

  DOI：

  10.1039/b006748m

文献信息

• Synthesis and pharmacological evaluation of ( Z )-9-(Heteroarylmethylene)-7-azatricyclo[4.3.1.0 3,7 ]decanes: thiophene analogues as potent norepinephrine transporter inhibitors
  作者：Jia Zhou、Thomas Kläß、Ao Zhang、Kenneth M Johnson、Cheng Z Wang、Yanping Ye、Alan P Kozikowski

  DOI：10.1016/s0960-894x(03)00786-8

  日期：2003.10

  at norepinephrine transporters (NET), we have introduced both five- and six-membered heteroaromatic moieties such as substituted pyridyl, pyrazinyl, pyrimidyl, thiazolyl, and mono- or disubstituted thienyl groups into conformationally constrained, tricyclic tropane analogues. A number of (Z)-9-(heteroarylmethylene)-7-azatricyclo[4.3.1.0(3,7)]decanes were synthesized, and their abilities to block dopamine

  为了进一步探索某些对烷的结构活性关系（SAR），并深入了解去甲肾上腺素转运蛋白（NET）的高活性和选择性所需要的结构特征，我们引入了五元和六元杂芳族部分，例如取代的吡啶基，吡嗪基，嘧啶基，噻唑基和单或二取代的噻吩基成构象约束的三环托烷类似物。合成了许多（Z）-9-（杂芳基亚甲基）-7-氮杂三环[4.3.1.0（3,7）]癸烷，并评估了它们各自转运蛋白阻断多巴胺，5-羟色胺和去甲肾上腺素再摄取的能力。发现五元或六元含氮芳族化合物太碱性，无法显示出较高的NET活性，
• Steinkopf; Jacob, Justus Liebigs Annalen der Chemie, 1935, vol. 515, p. 273,277
  作者：Steinkopf、Jacob

  DOI：——

  日期：——
• New and efficient access to 3-substituted 2,5-dibromothiophenes. Consecutive nickel-catalyzed electrochemical conversion to thienylzinc species
  作者：Mohamed Mellah、Eric Labbe´、Jean Yves Ne´de´lec、Jacques Pe´richon

  DOI：10.1039/b006748m

  日期：——

  We have achieved the stepwise synthesis of 3-substituted thienylzinc reagents using both electrochemical methods and an original bromination procedure. For several compounds 3-bromothiophene was the starting substrate, which was functionalized according to recently developed electrochemical procedures. The nickel-catalyzed electrochemical reduction of the resulting 3-substituted 2,5-dibromothiophenes in the presence of zinc salts allowed the formation of monothienylzinc species in good yields. The selectivity of this reaction is discussed within the context of the electrochemical synthesis of regioregular polythiophenes.

  我们已经通过电化学方法和一种原创的溴化程序实现了3取代噻吩锌试剂的逐步合成。对于几个化合物，3-溴噻吩是起始底物，它根据最近开发的电化学程序进行了功能化。在锌盐存在下，对得到的3取代2,5-二溴噻吩进行镍催化的电化学还原，使得单噻吩锌物种以良好的产率形成。关于该反应的选择性，我们在电化学合成有规聚噻吩的背景下进行了讨论。
• The synthesis of novel GABA uptake inhibitors. Part 2. Synthesis of 5-hydroxytiagabine, a human metabolite of the GABA reuptake inhibitor tiagabine
  作者：Knud E. Andersen、Mikael Begtrup、Mukund S. Chorghade、Elaine C. Lee、Jesper Lau、Behrend F. Lundt、Hans Petersen、Per O. Sørensen、Henning Thøgersen

  DOI：10.1016/s0040-4020(01)85345-x

  日期：1994.1

  (R)-1-(4-(2,5-Dihydro-3-methyl-5-oxothien-2-ylidene)-4-(3-methyl-2-thienyl)butyl)-3- piperidinecarboxylic acid (5-hydroxytiagabine) 13, has been prepared in 8 steps from 2-bromo-3-methylthiophene 3. Key steps are Grignard reactions, displacement of heteroaromatic chlorine with methoxy, and simultaneously demethylation and opening of a hydroxymethylcyclopropane with bromotrimethylsilane. An alternative approach involving acylation of 2-lithio-3-methylthiophene 17a was found less satisfying. A metalloporphyrin assisted hydroxylation of tiagabine 1 also yielded the target metabolite. The structure of 5-hydroxytiagabine was confirmed by NMR-data including COSY, ROESY, HMQC and HMBC experiments.