6-[1,3]dioxolan-2-yl-benzo[1,3]-dioxole-5-carbonitrile | 1805-94-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 6-[1,3]dioxolan-2-yl-benzo[1,3]-dioxole-5-carbonitrile
• 英文别名: 1,3-Benzodioxole-5-carbonitrile, 6-(1,3-dioxolan-2-yl)-；6-(1,3-dioxolan-2-yl)-1,3-benzodioxole-5-carbonitrile
• CAS: 1805-94-3
• 化学式: C₁₁H₉NO₄
• 分子量: 219.197
• InChiKey: PAKFYQWPVDPPCO-UHFFFAOYSA-N

物化性质

• 熔点：
  92-93 °C
• 沸点：
  350.4±42.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  60.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-[1,3]dioxolan-2-yl-benzo[1,3]-dioxole-5-carbonitrile 在 盐酸 作用下， 反应 0.25h， 以100%的产率得到6-formylbenzo[1,3]dioxole-5-carbonitrile
  参考文献：
  名称：

  氧法加宁，酚类苯并[c]菲啶的全合成以及2,3,7,8-和2,3,8,9-四取代的苯并[c]菲啶生物碱的一般合成方法。

  摘要：

  使用锂化甲苯酰胺-苄腈环加成反应，由易得的起始苯甲腈5和甲苯酰胺6合成苯并[c]菲啶生物碱，例如氧硝啶，氧山桂碱，氧鸟嘌呤和酚氧法加宁。偶联反应提供了3-芳基异喹啉酮，其被转化为苯并[c]菲蒽酮。该方法是高效的，并且可用于以克为单位制备各种取代的芳族苯并[c]菲啶化合物。

  DOI：

  10.1248/cpb.54.476
• 作为产物：
  描述：

  胡椒醛 在 溴 、 对甲苯磺酸 、 溶剂黄146 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 23.0h， 生成 6-[1,3]dioxolan-2-yl-benzo[1,3]-dioxole-5-carbonitrile
  参考文献：
  名称：

  Novel 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones: Synthesis and antileishmanial effects against Leishmania amazonensis

  摘要：

  A series of eleven 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones (16-27) was synthesised as part of a study to search for potential new drugs with a leishmanicidal effect. The thiosemicarbazones, ten of which are new compounds, were prepared in good yields (85-98%) by the reaction of 3,4-methylenedioxyde-6-benzaldehydes (6-X-piperonal), previously synthesised for this work by several methodologies, and thiosemicarbazide in ethanol with a few drops of H2SO4. These compounds were evaluated against Leishmania amazonensis promastigotes, and derivatives where X = I (22) and X = CN (23) moieties showed impressive results, having IC50 = 20.74 mu M and 16.40 mu M, respectively. The intracellular amastigotes assays showed IC50 = 22.00 mu M (22) and 17.00 mu M (23), and selectivity index >5.7 and >7.4, respectively, with a lower toxicity compared to pentamidine (positive control, SI = 4.5). The results obtained from the preliminary QSAR study indicated the hydrophobicity (log P) as a fundamental parameter for the 2D-QSAR linear model. A molecular docking study demonstrated that both compounds interact with flavin mononucleotide (FMN), important binding site of NO synthase. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.09.009

文献信息

• A facile synthesis of benzo[c]phenanthridine alkaloids: oxynitidine and oxysanguinarine using lithiated toluamide–benzonitrile cycloaddition
  作者：Thanh Nguyen Le、Seong Gyoung Gang、Won-Jea Cho

  DOI：10.1016/j.tetlet.2004.02.031

  日期：2004.3

  Benzo[c]phenanthridine alkaloids oxynitidine and oxysanguinarine were synthesized from easily available starting benzonitrile 5 and toluamide 6 using toluamide–benzonitrile cycloaddition reaction in six steps. This method is so highly efficient that it could be a more useful way for preparing fully aromatized benzo[c]phenanthridine compounds.

  使用甲苯酰胺-苄腈环加成反应，通过六个步骤，由易于获得的起始苯甲腈5和甲苯酰胺6合成苯并[ c ]菲啶生物碱氧硝啶和氧山桂碱。该方法是如此高效，以至于它是制备完全芳构化的苯并[ c ]菲啶化合物的更有用的方法。
• A Versatile Total Synthesis of Benzo[<i>c</i>]phenanthridine and Protoberberine Alkaloids Using Lithiated Toluamide−Benzonitrile Cycloaddition
  作者：Thanh Nguyen Le、Seong Gyoung Gang、Won-Jea Cho

  DOI：10.1021/jo035836+

  日期：2004.4.1

  A new versatile synthesis of benzo[c]phenanthridine and protoberberine alkaloids using lithiated toluamide−benzonitrile cycloaddition was carried out. The coupling reaction between benzonitrile 6 with o-toluamides (8a−c) afforded 3-arylisoquinolines (9a−c) that were transformed to the protoberberines (11a−c) or benzo[c]phenanthridines (14a−c). These compounds were synthesized by ring closure of the

  利用锂化的甲苯胺-苄腈环加成法进行了苯并[ c ]菲啶和原小ber碱生物碱的新型通用合成。苄腈6与邻甲苯甲酰胺（8a - c）之间的偶联反应提供了3-芳基异喹啉（9a - c），该3-芳基异喹啉（9a - c）转化为原小ber碱（11a - c）或苯并[ c ]菲啶（14a - c）。这些化合物是通过在3-芳基异喹啉酮（9a - c）。合成了几种取代的苯并[ c ]菲啶生物碱，例如氧山桂碱，氧鸟嘌呤和氧可尼丁，以及原小ber碱，例如8-氧代黄嘌呤，8-氧代伪小ber碱和8-氧代葡多酚。
• Reaction of benzocyclobutenoxides with nitriles: Synthesis of hypecumine and other 3-substituted isoquinolines
  作者：John J. Fitzgerald、Forrest E. Michael、R.A. Olofson

  DOI：10.1016/0040-4039(94)88462-5

  日期：1994.12

  Treatment of benzocyclobuten-2-ols with MeLi affords o-tolualdehyde anions which in the presence of nitriles cyclize to 3-substituted isoquinolines. Examples include the synthesis of the alkaloid hypecumine from the precursors, 14 and 19 (1:1), in 50% yield.

  用MeLi处理苯并环丁烯-2-醇可得到邻甲苯甲醛阴离子，在腈存在下，它们可环化为3-取代的异喹啉。实例包括从前体14和19（1：1）以50％的收率合成生物碱hypercumine 。
• Novel 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones: Synthesis and antileishmanial effects against Leishmania amazonensis
  作者：Jorge Luiz R. de Melos、Eduardo Caio Torres-Santos、Viviane dos S. Faiões、Catarina de Nigris Del Cistia、Carlos Maurício R. Sant'Anna、Cláudio Eduardo Rodrigues-Santos、Aurea Echevarria

  DOI：10.1016/j.ejmech.2015.09.009

  日期：2015.10

  A series of eleven 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones (16-27) was synthesised as part of a study to search for potential new drugs with a leishmanicidal effect. The thiosemicarbazones, ten of which are new compounds, were prepared in good yields (85-98%) by the reaction of 3,4-methylenedioxyde-6-benzaldehydes (6-X-piperonal), previously synthesised for this work by several methodologies, and thiosemicarbazide in ethanol with a few drops of H2SO4. These compounds were evaluated against Leishmania amazonensis promastigotes, and derivatives where X = I (22) and X = CN (23) moieties showed impressive results, having IC50 = 20.74 mu M and 16.40 mu M, respectively. The intracellular amastigotes assays showed IC50 = 22.00 mu M (22) and 17.00 mu M (23), and selectivity index >5.7 and >7.4, respectively, with a lower toxicity compared to pentamidine (positive control, SI = 4.5). The results obtained from the preliminary QSAR study indicated the hydrophobicity (log P) as a fundamental parameter for the 2D-QSAR linear model. A molecular docking study demonstrated that both compounds interact with flavin mononucleotide (FMN), important binding site of NO synthase. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Total Synthesis of Oxyfagaronine, Phenolic Benzo[c]phenanthridine and General Synthetic Way of 2,3,7,8- and 2,3,8,9-Tetrasubstituted Benzo[c]phenanthridine Alkaloids
  作者：Thanh Nguyen Le、Won-Jea Cho

  DOI：10.1248/cpb.54.476

  日期：——

  Benzo[c]phenanthridine alkaloids such as oxynitidine, oxysanguinarine, oxyavicine and phenolic oxyfagaronine were synthesized from easily available starting benzonitriles 5 and toluamides 6 using a lithiated toluamide-benzonitrile cycloaddition reaction. The coupling reaction provided 3-arylisoquinolinones that were transformed to the benzo[c]phenanthridones. This method is highly efficient and could

  使用锂化甲苯酰胺-苄腈环加成反应，由易得的起始苯甲腈5和甲苯酰胺6合成苯并[c]菲啶生物碱，例如氧硝啶，氧山桂碱，氧鸟嘌呤和酚氧法加宁。偶联反应提供了3-芳基异喹啉酮，其被转化为苯并[c]菲蒽酮。该方法是高效的，并且可用于以克为单位制备各种取代的芳族苯并[c]菲啶化合物。