1,5-dimethyl-1H-indole-3-carbonitrile | 128200-46-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1,5-dimethyl-1H-indole-3-carbonitrile
• 英文别名: 1H-Indole-3-carbonitrile, 1,5-dimethyl-；1,5-dimethylindole-3-carbonitrile
• CAS: 128200-46-4
• 化学式: C₁₁H₁₀N₂
• 分子量: 170.214
• InChiKey: HPMXXIBWBXJRDE-UHFFFAOYSA-N

物化性质

• 沸点：
  344.7±22.0 °C(Predicted)
• 密度：
  1.07±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  28.7
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1,5-dimethyl-1H-indole-3-carbonitrile 在 盐酸 、 硼烷 作用下， 反应 24.0h， 生成 3'-(1,5-dimethyl-1H-inden-3-yl)spiro[bicyclo[2.2.2]octane-2,1'-cyclopentan]-3'-ene compound with ethane (1:1)
  参考文献：
  名称：

  Novel 5-HT3 antagonists: indol-3-ylspiro(azabicycloalkane-3,5'(4'H)oxazoles)

  摘要：

  The synthesis and biochemical evaluation of a series of spirofused indole oxazoline 5-HT3 antagonists is described in which the oxazoline ring acts as a bioisosteric replacement for esters and amides. The effect of substitution about the indole ring has shown the steric limitations of the aromatic binding site. Incorporation of a variety of azabicyclic systems within the rigid spirofused framework has allowed the definition of a binding model which incorporates a number of known antagonists and agonists. In this model steric constraints limit substitution around the indole ring although there is some bulk tolerance at the 1- and 2-positions. The importance of constraining the basic nitrogen within an azabicyclic system is underlined by comparison with the monocyclic piperidine. The highest affinity was observed for those compounds in which the basic nitrogen occupies a bridgehead position, the most potent analogue in this group being the azabicyclic [3.3.1] system (pIC50 = 8.95), suggesting lipophilic interactions may play a role in increasing affinity. A suggested model for agonist binding is included in which the basic nitrogens are superimposed and the 5-hydroxyl group of 5-HT is superimposed on the H-bond-accepting atom of the heterocyclic linking group.

  DOI：

  10.1021/jm00084a007
• 作为产物：
  描述：

  2-((((1,5-dimethyl-1H-indol-3-yl)methylene)amino)oxy)-2-methylpropanoic acid 在 四丁基醋酸铵 作用下， 以 甲醇 、 乙腈 为溶剂， 以81%的产率得到1,5-dimethyl-1H-indole-3-carbonitrile
  参考文献：
  名称：

  通过氧化脱羧/N-O裂解从α-亚氨基-含氧酸电合成（杂）芳基腈

  摘要：

  通过 α-亚氨基-含氧酸的电化学氧化脱羧，开发了一种通过亚氨基自由基合成（杂）芳基腈的新方法。该协议为在环境条件下具有广泛的官能团耐受性的腈提供了一种有效的方法，可用于一锅克级合成。

  DOI：

  10.1039/d2cc02986c

文献信息

• Cyanation of indoles with benzyl cyanide as the cyanide anion surrogate
  作者：Lianpeng Zhang、Qiaodong Wen、Jisong Jin、Chen Wang、Ping Lu、Yanguang Wang

  DOI：10.1016/j.tet.2013.03.089

  日期：2013.5

  A copper-mediated direct cyanation of indoles with benzyl cyanide as the cyanide anion surrogate has been achieved. The cascade reaction furnished 3-cyanoindoles under mild reaction conditions in good to excellent yields with various functional groups tolerance.

  已经实现了用苄基氰化物作为氰化物阴离子替代物对吲哚进行铜介导的直接氰化。该级联反应在温和的反应条件下提供了3-氰基吲哚，具有良好的收率和优异的产率，并具有各种官能团耐受性。
• Direct C-2 Carboxylation of 3-Substituted Indoles Using a Combined Brønsted Base Consisting of LiO-<i>t</i> Bu/CsF/18-crown-6
  作者：Masanori Shigeno、Itsuki Tohara、Kanako Nozawa-Kumada、Yoshinori Kondo

  DOI：10.1002/ejoc.202000272

  日期：2020.4.7

  A combination of LiO‐tBu, CsF, and 18‐crown‐6 can be used to carboxylate indole derivatives at the C‐2 position under an ambient CO2 atmosphere. Substrates bearing an electrophilic substituent (i.e. CN, formyl, benzoyl, phenylsulfonyl, phenylsulfinyl, and chloride) at the C‐3 position are smoothly converted into their corresponding carboxylated products with high functional group compatibility.

  LiO-的组合吨卜，CsF和18-冠-6可用于羧酸盐的环境CO下在C-2位的吲哚衍生物2的气氛。在C-3位置带有亲电取代基（例如CN，甲酰基，苯甲酰基，苯磺酰基，苯亚磺酰基和氯化物）的底物可以平滑地转化为具有高官能团相容性的相应羧化产物。
• The palladium-catalyzed cyanation of indole C–H bonds with the combination of NH4HCO3 and DMSO as a safe cyanide source
  作者：Xinyi Ren、Jianbin Chen、Fan Chen、Jiang Cheng

  DOI：10.1039/c1cc11603g

  日期：——

  A palladium-catalyzed cyanation of the 3-position of indole sp2 C–H bonds by the combination of NH4HCO3 and DMSO as the “CN” source was achieved to provide aromatic nitriles in moderate to good yields with excellent regioselectivity. It represents a practical and safe cyanation method.

  实现了通过NH4HCO3和DMSO组合作为“CN”源，钯催化的吲哚3-位sp2 C–H键的氰化反应，以中等至良好的产率得到了具有优异区域选择性的芳香腈。这代表了一种实用且安全的氰化方法。
• Palladium-Catalyzed Direct Cyanation of Indoles with K₄[Fe(CN)₆]
  作者：Guobing Yan、Chunxiang Kuang、Yan Zhang、Jianbo Wang

  DOI：10.1021/ol1000439

  日期：2010.3.5

  Direct cyanation of indole derivatives has been achieved with nontoxic K4[Fe(CN)6] as cyanating agent through Pd-catalyzed C−H bond activation.

  通过无毒的K 4 [Fe（CN）6 ]作为氰化剂，通过Pd催化的CH键活化，可以实现吲哚衍生物的直接氰化。
• Cu-Catalyzed Cyanation of Indoles with Acetonitrile as a Cyano Source
  作者：Mengdi Zhao、Wei Zhang、Zengming Shen

  DOI：10.1021/acs.joc.5b01419

  日期：2015.9.4

  for the synthesis of 3-cyanoindoles has been developed. The Cu/TEMPO/(Me3Si)2 system has been identified to promote highly efficient and selective C–H cyanation of indoles by use of unactivated acetonitrile as a cyano source via a sequential iodination/cyanation process in one pot. This reaction furnishes 3-cyanoindoles in moderate to good yields and tolerates a series of functional groups. Moreover

  已经开发了铜催化的用乙腈对吲哚进行氰化反应以合成3-氰基吲哚的方法。Cu / TEMPO /（Me 3 Si）2系统已被鉴定为通过在一个锅中通过顺序碘化/氰化过程使用未活化的乙腈作为氰源来促进吲哚的高效且选择性的CH氰化。该反应以中等至良好的产率提供3-氰基吲哚并耐受一系列官能团。而且，低成本的铜催化剂和无害的乙腈作为氰基源具有该反应的实用性。