5,6-二甲基-1-氧代-2,1,3-苯并恶二唑-1-鎓 | 39132-77-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶二唑类
• 中文名称: 5,6-二甲基-1-氧代-2,1,3-苯并恶二唑-1-鎓
• 英文名称: 5,6-dimethylbenzofuroxane
• 英文别名: 5,6-dimethyl-benzofuroxan；5,6-Dimethyl-1-oxo-2,1lambda~5~,3-benzoxadiazole；5,6-dimethyl-3-oxido-2,1,3-benzoxadiazol-3-ium
• CAS: 39132-77-9
• 化学式: C₈H₈N₂O₂
• 分子量: 164.164
• InChiKey: YNVKVZHZPNWXSW-UHFFFAOYSA-N

物化性质

• 熔点：
  138-139 °C(Solv: ethanol (64-17-5))
• 沸点：
  286.6±43.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  51.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  5,6-二甲基-1-氧代-2,1,3-苯并恶二唑-1-鎓 在 四氢吡咯 、 5%-palladium/activated carbon 、 Clorox 、 氢气 、 potassium hydroxide 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 20.0~60.0 ℃ 、400.01 kPa 条件下， 反应 20.08h， 生成 9,10-bis(dimethoxymethyl)quinoxalino[2,3-c]cinnoline
  参考文献：
  名称：

  喹喔啉[2,3- c ] cinnolines及其5- N-氧化物：甲基取代的喹喔啉[2,3- c ] cinnolines醛缩醛和原酸酯的烷氧基化

  摘要：

  我们报告甲基取代的喹喔啉[2,3- c ] cinnolines的烷氧基化以高收率得到乙缩醛和原酸酯。据报道，该烷氧基化反应的前体以及其他喹喔啉[2,3- c ] cinnoline及其5-氧化物衍生物的途径。这些喹喔啉[2,3- c ]喹啉中的大多数是通过相应的2-氨基-3-（2-硝基苯基）喹喔啉的环化反应制备的，这反过来又是苯并呋喃山氧化物加2-硝基苄基氰化物引起的异常贝鲁特反应的结果。 。提出了这些有趣反应的机械解释。

  DOI：

  10.1021/jo201687x
• 作为产物：
  描述：

  3,4-二甲基乙酰苯胺 在 盐酸 、 sodium azide 、 硫酸 、 硝酸 、 sodium acetate 、 sodium nitrite 作用下， 以 甲苯 为溶剂， 反应 3.17h， 生成 5,6-二甲基-1-氧代-2,1,3-苯并恶二唑-1-鎓
  参考文献：
  名称：

  Hypoxia-Selective Agents Derived from Quinoxaline 1,4-Di-N-oxides

  摘要：

  Hypoxic cells, which are a common feature of solid tumors, but not normal tissues, are resistant to both anticancer drugs and radiation therapy. Thus the identification of drugs with selective toxicity toward hypoxic cells is an important objective in anticancer chemotherapy. The benzotriazine di-N-oxide (SR 4233, Tirapazamine) has been shown to be an efficient and selective cytotoxin for hypoxic cells. Since the bioreductive activation of Tirapazamine is thought to be due to the presence of the 1,4-di-N-oxide moiety, a series of 3-aminoquinoxaline-2-carbonitrile 1,4-di-N-oxides with a range of electron-donating and -withdrawing substituents in the 6- and/or 7- positions has been synthesized and evaluated for toxicity to hypoxic cells. Electrochemical studies of the quinoxaline di-N-oxides and Tirapazamine showed that as the electron-withdrawing nature of the 6(7)-substituent increases, the reduction potential becomes more positive and the compound is more readily reduced. Apart from the unsubstituted 6a and the 6,7-dimethyl derivative 6c, the quinoxaline di-N-oxides have reduction potentials significantly more positive than Tirapazamine (E(pc)-0.90 V). The most potent cytotoxins to cells in culture were the 6,7,-dichloro and 6,7-difluoro derivatives 6i and 6l, which were 30-fold more potent than Tirapazamine. The 6(7)-fluoro and 6(7)-chloro compounds, 6e and 6h, showed the greatest hypoxia selectivity. Four of the compounds, 6e, 6f, 6h and 6i, killed the inner cells of multicellular tumor spheroids in vitro. In vivo Balb/c mice tolerated a dose of these four compounds twice the size of that of Tirapazamine. This study demonstrates that quinoxaline 1,4-di-N-oxides could provide useful hypoxia-selective therapeutic agents.

  DOI：

  10.1021/jm00010a023

文献信息

• Quinoxaline derivatives
  申请人：Research Corporation

  公开号：US04343942A1

  公开（公告）日：1982-08-10

  The synthesis of quinoxaline and benzimidazole-N-oxides and of ester and amide derivatives of 3-hydroxy-2-quinoxalinecarboxylic acid by a novel process consisting of the reaction between a benzofuroxan and an activated methylene-containing compound under basic conditions.

  喹啉和苯并咪唑-N-氧化物的合成，以及3-羟基-2-喹啉羧酸的酯和酰胺衍生物的合成，通过一种新颖的过程实现，该过程包括在碱性条件下对苯并呋喃酰胺和含活性亚甲基的化合物进行反应。
• Cu-Catalyzed π-Core Evolution of Benzoxadiazoles with Diaryliodonium Salts for Regioselective Synthesis of Phenazine Scaffolds
  作者：Jinyu Sheng、Ru He、Jie Xue、Chao Wu、Juan Qiao、Chao Chen

  DOI：10.1021/acs.orglett.8b01748

  日期：2018.8.3

  The Cu-catalyzed regioselective synthesis of phenazine N-oxides was realized from benzoxadiazoles and diaryliodonium salts. The process was initiated by the electrophilic arylation of benzoxadiazoles with diaryliodonium salts and followed by benzocyclization reactions. The further reduction of N-oxides in situ to phenazine scaffolds and deviation to organic fluorescent materials were readily accomplished

  由苯并恶二唑和二芳基碘鎓盐实现了铜催化的吩嗪N-氧化物的区域选择性合成。该过程通过苯并恶二唑与二芳基碘鎓盐的亲电芳基化反应开始，然后进行苯并环化反应。容易将原位N-氧化物进一步还原为吩嗪支架并偏离有机荧光材料。
• The reactions of benzofuroxan with carbonyl compounds on the surface of solid catalysts
  作者：Tohru Takabatake、Yumiko Hasegawa、Minoru Hasegawa

  DOI：10.1002/jhet.5570300602

  日期：1993.12

  The cyclocondensations of benzofuroxan 1a with carbonyl compounds were smoothly and efficiently carried out by the adsorption of the components on the surface of silica gel or a molecular sieve to form a 2,3-disubstituted quinoxaline 1,4-dioxide. When the reactions using a molecular sieve 3A (powder) were carried out at 90°, the actual reaction times were reduced to 0.5-2 hours. Although Duerckheimer

  通过将组分吸附在硅胶或分子筛的表面上以形成2，3-二取代的喹喔啉1，4-二氧化物，苯并呋喃喃1a与羰基化合物的环缩反应可以平稳有效地进行。当在90°下使用分子筛3A（粉末）进行反应时，实际反应时间减少到0.5-2小时。尽管Duerckheimer报告了当使5-甲氧基苯并呋喃1e与乙酰乙酸乙酯2j反应时仅分离出7-取代的喹喔啉1,4-二氧化物，但通过我们的方法，它仅生成了6-甲氧基异构体作为反应产物。5-羧基苯并呋喃聚糖1f不与羰基化合物反应。
• Formation and rearrangement of adducts from benzyne and substituted 2,1,3-benzoselenadiazoles
  作者：Martin R. Bryce、Colin D. Reynolds、Peter Hanson、John M. Vernon

  DOI：10.1039/p19810000607

  日期：——

  substituted 2,1,3-benzoselenadiazoles. Some of these adducts rearrange either thermally or photochemically to give 2-(2-pyridyl)phenyl selenocyanates (7), which are reduced to 2-phenylpyridine derivatives (6) or hydrolysed to give ultimately, diselenides (9). The crystal structure of one benzyne adduct (2b) is reported and the mechanism of its rearrangement discussed.

  通过将苯炔加到取代的2,1,3-苯并硒基二唑上，已制备了一系列5-（1,2-苯并硒唑-3-基）戊二烯腈衍生物（2）。这些加合物中的一些通过热或光化学重排得到2-（2-吡啶基）苯基硒氰酸酯（7），将其还原为2-苯基吡啶衍生物（6）或水解得到最终的二硒化物（9）。报告了一种苯并加合物（2b）的晶体结构，并讨论了其重排机理。
• 4-Cyano-2-oxo-1,2,4-oxadiazolo[2,3-<i>a</i>]quinoxaline 5-<i>N</i>-oxides. New synthetic method and reaction with alcohols. Potential cytotoxic activity
  作者：F. J. Martínez Crespo、J. A. Palop、Y. Sainz、S. Narro、V. Senador、M. González、A. López De Ceráin、A. Monge、E. Hamilton、A. J. Barker

  DOI：10.1002/jhet.5570330620

  日期：1996.11

  Several quinoxaline 1,4-di-N-oxides have been shown to be efficient and selective cytotoxins for hypoxic cells. We present now a series of 4-cyano-2-oxo-1,2,4-oxadiazolo[2,3-a]quinoxaline 5-N-oxides 2a-2k. They were prepared starting from 3-amino-2-quinoxalinecarbonitrile 1,4-di-N-oxides 1a-1k and 2-chloroethyl isocyanate in dry dioxane at 100–110°. A reaction mechanism is proposed. The treatment of

  几种喹喔啉1,4-二-N-氧化物已被证明是低氧细胞的有效和选择性细胞毒素。现在我们介绍一系列的4-氰基-2-氧代-1,2,4-恶二唑并[2,3- a ]喹喔啉5 - N-氧化物2a-2k。它们是在干燥的二恶烷中在100–110°下从3-氨基-2-喹喔啉腈1，a-二-N-氧化物1a-1k和2-氯乙基异氰酸酯开始制备的。提出了一种反应机理。用异氰酸苯酯处理1a得到2a。2c与硅胶反应，得到1c。化合物2a-2g将其在乙醇和2-丙醇存在下加热，得到相应的氨基甲酸酯3a-3g和4a-4g。通过加热1d和氯甲酸乙酯的混合物已经获得了化合物2d。当将氨基甲酸酯3b加热至150°时制备化合物2b。喹喔啉在有氧和低氧细胞中均作为细胞毒性剂进行了测试。最有趣的化合物是3g和4g。