3-(3,4-dimethoxyphenyl)propyl isocyanate | 72584-71-5

• 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-(3,4-dimethoxyphenyl)propyl isocyanate
• 英文别名: 4-(3-Isocyanatopropyl)-1,2-dimethoxybenzene
• CAS: 72584-71-5
• 化学式: C₁₂H₁₅NO₃
• 分子量: 221.256
• InChiKey: GFRNEWUSCKERHA-UHFFFAOYSA-N

物化性质

• 沸点：
  322.2±32.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  47.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(3,4-dimethoxyphenyl)propyl isocyanate 在 四氯化锡 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 17.0h， 生成 7,8-dimethoxy-2,3,4,5-tetrahydro-1H-2-benzazepin-1-one
  参考文献：
  名称：

  Synthesis of Erythrina and Related Alkaloids Part XLIV. Total Synthesis of Homoerythrinan Alkaloids, Schelhammericine and 3-Epischelhammericine.

  摘要：

  描述了两种同红藻碱（homerythrinan alkaloids），即施尔哈默碱（schelhammericine）和3-去施尔哈默碱（3-epischelhammericine）的总合成。将一个二氧基吡咯苯并氮烯（dioxopyrrolobenzazepine）与1-甲氧基-3-三甲基硅氧基丁二烯进行光环加成，得到了线性和立体特异性的环丁烷衍生物，该衍生物通过利用TBAF诱导的1,3-阴离子重排转化为同红藻衍生物。最终产物在几步反应中转化为目标碱类。

  DOI：

  10.1248/cpb.44.500
• 作为产物：
  描述：

  4-(3,4-二甲氧苯基)丁酸 在 sodium azide 、 三乙胺 作用下， 以 水 、 丙酮 、 甲苯 为溶剂， 反应 2.5h， 生成 3-(3,4-dimethoxyphenyl)propyl isocyanate
  参考文献：
  名称：

  Synthesis of Erythrina and Related Alkaloids Part XLIV. Total Synthesis of Homoerythrinan Alkaloids, Schelhammericine and 3-Epischelhammericine.

  摘要：

  描述了两种同红藻碱（homerythrinan alkaloids），即施尔哈默碱（schelhammericine）和3-去施尔哈默碱（3-epischelhammericine）的总合成。将一个二氧基吡咯苯并氮烯（dioxopyrrolobenzazepine）与1-甲氧基-3-三甲基硅氧基丁二烯进行光环加成，得到了线性和立体特异性的环丁烷衍生物，该衍生物通过利用TBAF诱导的1,3-阴离子重排转化为同红藻衍生物。最终产物在几步反应中转化为目标碱类。

  DOI：

  10.1248/cpb.44.500

文献信息

• Synthesis of 3,4-Dihydroisoquinolin-1-ones from<i>N</i>-Boc-(β-Arylethyl)carbamates via Isocyanate Intermediates
  作者：Jinkyung In、Soonho Hwang、Changhun Kim、Jae Hong Seo、Sanghee Kim

  DOI：10.1002/ejoc.201201408

  日期：2013.2

  reaction conditions for the regioselective synthesis of isoquinolin-1-ones and related fused-ring heterocycles from N-Boc-protected (β-arylethyl)carbamates are described. The reactions involved the use of Tf2O and 2-chloropyridine and isocyanates are likely to be key intermediates. The method was extended to substrates bearing less nucleophilic aryl moieties by using Lewis acid additives, such as BF3·Et2O

  描述了从 N-Boc 保护的 (β-芳基乙基) 氨基甲酸酯区域选择性合成异喹啉-1-酮和相关稠环杂环的温和反应条件。涉及使用 Tf2O 和 2-氯吡啶和异氰酸酯的反应可能是关键中间体。通过使用路易斯酸添加剂，如 BF3·Et2O，该方法扩展到带有较少亲核芳基部分的底物，以增强异氰酸酯中间体的 Friedel-Crafts 型环化。该方法允许以良好的产率和高区域选择性合成各种取代的异喹啉-1-酮、β-咔啉、噻吩稠环系统和四氢苯并氮杂-1-酮。
• The Discovery of Capsazepine, the First Competitive Antagonist of the Sensory Neuron Excitants Capsaicin and Resiniferatoxin
  作者：Christopher S. J. Walpole、Stuart Bevan、Guenter Bovermann、Johann J. Boelsterli、Robin Breckenridge、John W. Davies、Glyn A. Hughes、Iain James、Lukas Oberer、Janet Winter、Roger Wrigglesworth

  DOI：10.1021/jm00039a006

  日期：1994.6.1

  Capsaicin and resiniferatoxin are natural products which act specifically on a subset of primary afferent sensory neurons to open a novel cation-selective ion channel in the plasma membrane. These sensory neurons are involved in nociception, and so, these agents are targets for the design of a novel class of analgesics. Although synthetic agonists at the capsaicin receptor have been described previously, competitive antagonists at this receptor would be interesting and novel pharmacological agents. Structure-activity relationships for capsaicin agonists have previously been rationalized, by ourselves and others, by dividing the capsaicin molecule into three regions-the A (aromatic ring)-, B (amide bond)-, and C (hydrophobic side chain)-regions. In this study, the effects on biological activity of conformational constraint of the A-region with respect to the B-region are discussed. Conformational constraint was achieved by the introduction of saturated ring systems of different sizes. The resulting compounds provided agonists of comparable potency to unconstrained analogues as well as a moderately potent antagonist, capsazepine. This compound is the first competitive antagonist of capsaicin and resiniferatoxin to be described and is active in various systems, in vitro and in vivo. It has recently attracted considerable interest as a tool for dissecting the mechanisms by which capsaicin analogues evoke their effects. NMR spectroscopy and X-ray crystallography experiments, as well as molecular modeling techniques, were used to study the conformational behavior of a representative constrained agonist and antagonist. The conformation of the saturated ring contraint in the two cases was found to differ markedly, dramatically affecting the relative disposition of the A-ring and B-region pharmacophores. In agonist structures, the A- and B-regions were virtually coplanar in contrast to those in the antagonist, in which they were approximately orthogonal. A rationale for agonist and antagonist activity at the capsaicin receptor is proposed, based on the consideration of these conformational differences.