5-nitrospiro[2H-benzimidazole-2,1'-cyclohexane]-1,3-dioxide | 163126-82-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 5-nitrospiro[2H-benzimidazole-2,1'-cyclohexane]-1,3-dioxide
• 英文别名: 2,2-spirocyclohexane-5-nitro-2H-benzimidazole-1,3-dioxide；5-nitrospiro[benzimidazole-2,1'-cyclohexane] 1,3-dioxide；5-nitro-2-spirocyclohexane-2H-benzimidazole-1,3-dioxide；5-nitro-3-oxidospiro[benzimidazol-1-ium-2,1'-cyclohexane] 1-oxide
• CAS: 163126-82-7
• 化学式: C₁₂H₁₃N₃O₄
• 分子量: 263.253
• InChiKey: AUYXGRJVKAVYEZ-UHFFFAOYSA-N

物化性质

• 沸点：
  449.0±48.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  92.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-nitrospiro[2H-benzimidazole-2,1'-cyclohexane]-1,3-dioxide 在 氨 、 potassium carbonate 作用下， 以 氯仿 、 乙腈 为溶剂， 反应 25.0h， 生成 N-methyl-5-nitrospiro[benzimidazole-2,1'-cyclohexan]-4-amine 1-oxide
  参考文献：
  名称：

  Reactions of 5-nitrospiro[benzimidazole-2,1′-cyclohexane] 1,3-dioxide with nucleophiles

  摘要：

  Reactions of 5-nitrospiro[benzimidazole-2,1'-cyclohexane] 1,3-dioxide with aliphatic amines and sodium hydroxide resulted in removal of one N-oxide oxygen atom and formation of 4-alkylamino- or 4-hydroxy-substituted 5-nitrospiro[benzimidazole-2,1'-cyclohexane] 1-oxides, respectively. The title compound reacted with ammonia and methylamine in the presence of MnO2 with conservation of both N-oxide moieties, and the products were 4-amino- and 4-methylamino-5-nitrospiro[benzimidazole-2,1'-cyclohexane] 1,3-dioxides. The reactions with aromatic amines were accompanied by removal of both N-oxide oxygen atoms with formation of N-aryl-5-nitrospiro[benzimidazole-2,1'-cyclohexane]-4-amines. In the reactions of 5-nitrospiro[ benzimidazole-2,1'-cyclohexane] 1,3-dioxide with sodium azide and aromatic amine hydrochlorides nucleophilic replacement of the 5-nitro group by azido or arylamino occurred, in the first case both N-oxide fragments being conserved. The reactions with aromatic amine hydrochlorides afforded N-aryl-5-nitrospiro[benzimidazole-2,1'-cyclohexan]-4-amine 1-oxides. Treatment of 5-nitrospiro[benzimidazole-2,1'-cyclohexane] 1,3-dioxide with sodium cyanide led to the formation of 5-oxo-3,5-dihydrospiro[benzimidazole-2,1'-cyclohexane]-4-carbonitrile 1-oxide.

  DOI：

  10.1134/s1070428012030116
• 作为产物：
  描述：

  spiro[benzimidazole-2,1'-cyclohexane] 1,3-dioxide 在 硝酸 、 溶剂黄146 作用下， 反应 6.0h， 以75%的产率得到5-nitrospiro[2H-benzimidazole-2,1'-cyclohexane]-1,3-dioxide
  参考文献：
  名称：

  通过邻苯二醌二肟与酮的反应合成2 H-苯并咪唑1,3-二氧化物，分离酶抑制剂

  摘要：

  描述了在酸存在下，基于邻苯醌二肟与酮的相互作用，合成新颖的2 H-苯并咪唑1,3-二氧化物。用硝酸在乙酸中硝化这些化合物，得到2 H-苯并咪唑1，3-二氧化物的5-硝基衍生物。

  DOI：

  10.1016/j.tet.2017.05.078
• 作为试剂：
  描述：

  对苯二酚 在 5-nitrospiro[2H-benzimidazole-2,1'-cyclohexane]-1,3-dioxide 作用下， 以 苯 为溶剂， 反应 4.0h， 以60%的产率得到对苯醌
  参考文献：
  名称：

  Thermal transformations of 2H-benzimidazole 1,3-dioxides

  摘要：

  对由螺[2H-苯并咪唑-2,1′-环己烷] 1,3-二氧化物及其5-硝基衍生物代表的2H-苯并咪唑1,3-二氧化物的热转化进行了研究。加热导致其可逆异构化为螺[3H-[2,1,4]苯并噁二嗪-3,1′-环己烷] 4-氧化物。对2H-苯并咪唑1,3-二氧化物的更长时间加热则导致第一个、然后（在更高温度下）第二个N-氧原子的顺序消除，形成2H-苯并咪唑衍生物，这些衍生物在进一步加热后转化为7,8,9,10-四氢-6H-氮杂环[1,2-a]苯并咪唑。提出了一个过程示意图，以描述获得的实验数据。螺[3H-[2,1,4]苯并噁二嗪-3,1′-环己烷] 4-氧化物在阳光照射下定量转化为2H-苯并咪唑1,3-二氧化物。

  DOI：

  10.1007/s11172-011-0257-x

文献信息

• Synthesis and activity of benzimidazole-1,3-dioxide inhibitors of separase
  作者：Ha T. Do、Nenggang Zhang、Debananda Pati、Scott R. Gilbertson

  DOI：10.1016/j.bmcl.2016.07.080

  日期：2016.9

  other alkyl chains at the C2 moderately improves the effects on the inhibitory activity of those compounds. Modifications on 2H-benzimidazole-1,3-dioxide or the skeleton have variable effect on inhibition of separase enzymatic activity. Density-functional theory (DFT) calculations suggest there may be a correlation between the charges on the oxide moieties on these compounds and their activity in inhibiting

  由于粘蛋白蛋白酶，separase在人癌细胞中的致癌活性，对separase酶活性的调节可能构成靶向抗性，separase过表达的非整倍性肿瘤的新治疗策略。在这里，我们报告了基于铅分子2,2-二甲基-5-硝基-2H-苯并咪唑-1,3-二氧化物（称为Sepin）的修饰，分离酶抑制剂的合成，结构信息和构效关系（SAR） -1，（1）从高通量屏幕中识别。用其他官能团取代C5处的-NO2会降低Separase酶法测定中的抑制活性。两个甲基在C2处被其他烷基链取代可适度改善对这些化合物的抑制活性的影响。对2H-苯并咪唑-1的修饰 3-二氧化物或骨架对Separase酶活性的抑制作用不同。密度泛函理论（DFT）计算表明，这些化合物上的氧化物部分上的电荷与其抑制Separase酶的活性之间可能存在相关性。
• Formation of 2h-benzimidazole-l,3-dioxides by reaction of benzofuroxans with alcohols and alkyl halides in the presence of acids
  作者：V. A. Samsonov、L. B. Volodarskii、V. Shamirzaeva

  DOI：10.1007/bf01169943

  日期：1994.4
• Reaction of 5-nitrospiro[benzimidazole-2,1′-cyclohexane] 1,3-dioxide with electrophilic reagents: Bromine and nitric acid
  作者：V. A. Samsonov、Yu. V. Gatilov、V. A. Savel’ev

  DOI：10.1134/s1070428013080198

  日期：2013.8

  Reactions of 5-nitrospiro[benzimidazole-2,1'-cyclohexane] 1,3-dioxide with bromine and nitric acid lead to the electrophilic substitution of the hydrogen atom in the meta-position with respect to the nitro group. At thebromination the primarily formed 4-bromo-6-nitrospiro[benzimidazole-2,1'-cyclohexane] 1,3-dioxide when kept in the solution loses an oxygen atom forming 4-bromo-6-nitrospiro[benzimidazole-2,1'-cyclohexane] 1-oxide and an isomerization product, 8-bromo-6-nitrospiro[3H-[2,1,4]benzoxadiazine-3,1'-cyclohexane] 4-oxide. The latter exposed to light turns into 4-bromo-6-nitrospiro[benzimidazole-2,1'-cyclohexane] 1,3-dioxide. The reaction of the initial 1,3-dioxide with nitric acid afforded 4,6-dinitrospiro[benzimidazole-2,1'-cyclohexan]-7-ol 1-oxide whose heating in o-dichlorobenzene resulted in 3,5-dinitro-1,8-diazatricyclo[7.5.0.0(2,7)] tetradeca-2(7),3,5,8-tetraen-6-ol.
• Synthesis of 2H-benzimidazole 1,3-dioxides, separase inhibitors, by reaction of o-benzoquinone dioximes with ketones
  作者：Elena Chugunova、Vladimir Samsonov、Nurgali Akylbekov、Dmitrii Mazhukin

  DOI：10.1016/j.tet.2017.05.078

  日期：2017.7

  The synthesis of novel 2H-benzimidazole 1,3-dioxides on the basis of o-benzoquinone dioximes interaction with ketones in the presence of acids is described. Nitration of these compounds by nitric acid in acetic acid yields the 5-nitro derivatives of 2H-benzimidazole 1,3-dioxide.

  描述了在酸存在下，基于邻苯醌二肟与酮的相互作用，合成新颖的2 H-苯并咪唑1,3-二氧化物。用硝酸在乙酸中硝化这些化合物，得到2 H-苯并咪唑1，3-二氧化物的5-硝基衍生物。
• Thermal transformations of 2H-benzimidazole 1,3-dioxides
  作者：V. A. Samsonov、I. Yu. Bagryanskaya、Yu. V. Gatilov、V. A. Savel’ev

  DOI：10.1007/s11172-011-0257-x

  日期：2011.8

  Thermal transformations of 2H-benzimidazole 1,3-dioxides represented by spiro[2H-benz-imidazole-2,1′-cyclohexane] 1,3-dioxide and its 5-nitro derivative were studied. Their heating resulted in reversible isomerization to spiro[3H-[2,1,4]benzoxadiazine-3,1′-cyclohexane] 4-oxides. More prolonged heating of 2H-benzimidazole 1,3-dioxides caused sequential elimination of the first and then (at higher temperature) the second N-oxide oxygen atom to form 2H-benzimidazole derivatives, which upon further heating were transformed to 7,8,9,10-tetrahydro-6H-azepino[1,2-a]benzimidazoles. A scheme of the process was suggested, which described the experimental data obtained. Spiro[3H-[2,1,4]benzoxadiazine-3,1′-cyclohexane] 4-oxides on exposure to the sunlight were quantitatively transformed to 2H-benzimidazole 1,3-dioxides.

  对由螺[2H-苯并咪唑-2,1′-环己烷] 1,3-二氧化物及其5-硝基衍生物代表的2H-苯并咪唑1,3-二氧化物的热转化进行了研究。加热导致其可逆异构化为螺[3H-[2,1,4]苯并噁二嗪-3,1′-环己烷] 4-氧化物。对2H-苯并咪唑1,3-二氧化物的更长时间加热则导致第一个、然后（在更高温度下）第二个N-氧原子的顺序消除，形成2H-苯并咪唑衍生物，这些衍生物在进一步加热后转化为7,8,9,10-四氢-6H-氮杂环[1,2-a]苯并咪唑。提出了一个过程示意图，以描述获得的实验数据。螺[3H-[2,1,4]苯并噁二嗪-3,1′-环己烷] 4-氧化物在阳光照射下定量转化为2H-苯并咪唑1,3-二氧化物。