3-methyl-10-phenylisolloxazine | 35804-39-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 蝶啶及其衍生物
• 英文名称: 3-methyl-10-phenylisolloxazine
• 英文别名: 3-methyl-10-phenylbenzopteridine-2(1H),4(3H)-dione；10-phenyl-3-methylisoalloxazine；3-methyl-10-phenylisoalloxazine；3-methyl-10-phenyl-10H-benzo[g]pteridine-2,4-dione；3-Methyl-10-phenyl-10H-benzo[g]pteridin-2,4-dion；3-Methyl-10-phenylisoalloxazin；3-Methyl-10-phenyl-10H-benzo[g]pteridine-2,4-dione；3-methyl-10-phenylbenzo[g]pteridine-2,4-dione
• CAS: 35804-39-8
• 化学式: C₁₇H₁₂N₄O₂
• 分子量: 304.308
• InChiKey: KWVXVHQTNVCHDH-UHFFFAOYSA-N

物化性质

• 熔点：
  >300 °C
• 沸点：
  470.2±28.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  65.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-methyl-10-phenylisolloxazine 在 苄基三甲基氢氧化铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-methyl-4-phenyl-3-oxo-3,4-dihydroquinoxaline-2-carboxamide
  参考文献：
  名称：

  黄素（异四恶嗪）的水解产物

  摘要：

  黄酮（I）与Triton B的水解产生了4a-spirohydantoin（II）与III一起作为主要产物，表明氢氧根离子的主要亲核攻击是在I的10a位置引发的。

  DOI：

  10.1016/0040-4039(84)80054-4
• 作为产物：
  描述：

  6-氯-3-甲基尿嘧啶 在 乙酸酐 、 溶剂黄146 、 N,N-二乙基苯胺 作用下， 反应 1.0h， 生成 3-methyl-10-phenylisolloxazine
  参考文献：
  名称：

  Flavins as potential antimalarials. 2. 3-Methyl-10-(substituted-phenyl)flavins

  摘要：

  A series of 3-methyl-10-(substituted-phenyl)flavins was prepared and tested for antimalarial activity against the lethal parasite Plasmodium vinckei in mice. Several of these analogues were found to be effective antimalarial agents. A quantitative structure-activity relationship study was undertaken with 44 analogues and no satisfactory relationship could be established.

  DOI：

  10.1021/jm00110a009
• 作为试剂：
  描述：

  (4-甲基苯基)甲醇 在 3-methyl-10-phenylisolloxazine magnesium(II) perchlorate 、 氧气 作用下， 以 乙腈 为溶剂， 生成 对甲基苯甲醛
  参考文献：
  名称：

  在 Mg2+ 存在下，由黄素类似物（3-甲基-10-苯基异咯嗪和 3-甲基-10-苯基-5-脱氮杂异咯嗪）催化的氧气对 p-甲基苄基醇的光氧化

  摘要：

  黄素类似物（3-甲基-10-苯基异恶嗪和 3-甲基-10-苯基-5-脱氮杂异恶嗪）在乙腈中存在 Mg2+ 离子的情况下，通过氧催化对甲基苯甲醇的光氧化，生成对甲基苯甲醛和过氧化氢λ>360 nm 的可见光照射。

  DOI：

  10.1246/cl.1984.1375

文献信息

• Flavin Activation by Intramolecular Acid Catalysis at N(1) Position
  作者：Seiji Shinkai、Sayuri Kawanabe、Akito Kawase、Toshiro Yamaguchi、Osamu Manabe、Shigeharu Harada、Hideki Nakamura、Nobutami Kasai

  DOI：10.1246/bcsj.61.2095

  日期：1988.6

  In order to assess the effect of intramolecular acid catalysis on the specific flavin reactivities, 3-methyl-10-(2-hydroxyphenyl)isoalloxazine (1(2OH)) and 3-methyl-10-(2-hydroxy-1-naphthyl)isoalloxazine (2(2OH)) were synthesized and the redox properties were compared with those of reference flavins such as 3-methyl-10-(2-methoxyphenyl)isoalloxazine (1(2OMe)) and 3-methyl-10-(2-methoxy-1-naphthyl)isoalloxazine (2(2OMe)). The pKa values for 1(2OH) and 2(2OH) were determined to be 7.7 and 7.0, respectively, which were lower than that of 3-methyl-10-(4-hydroxyphenyl)isoalloxazine (1(4OH): pKa 8.6). It is thus unlikely that 2′-OH and N(1) form a hydrogen bond at the initial state of the reaction (i.e., at the oxidized state). The X-ray crystallographic studies indicated that the phenyl ring makes an angle of 79.7° with the isoalloxazine ring and the 2′-OH group forms a hydrogen bond with methanol included in the crystal lattice. In acetonitrile at 30 °C 1-benzyl-1,4-dihydronicotinamide was not oxidized by 1(2OMe), 1(4OH), and 2(2OMe). On the other hand, the oxidation took place with 1(2OH) and 2(2OH) which have an acidic OH group at the 2′-position of the 10-aryl substituent. The presence of the intramolecular acid catalysis suggests that 2′-OH and N(1) can interact at least at the transition state or at the final state of the reaction (i.e., at the reduced state). In general, the oxidized flavin adopts a “planar” structure which is sterically tense while the reduced flavin adopts a “bent” structure which is sterically relaxed. As the structure of the transition state is more or less similar to the reduced form, the hydrogen-bonding interaction could increase on going from the tense initial state to the relaxed transition state. This is a novel example for acid catalysis in flavin-mediated reactions.

  为了评估分子内酸催化对特定黄素反应性的影响，合成了3-甲基-10-(2-羟基苯基)异黄素（1(2OH)）和3-甲基-10-(2-羟基-1-萘基)异黄素（2(2OH)），并将其氧化还原性质与参考黄素如3-甲基-10-(2-甲氧基苯基)异黄素（1(2OMe)）和3-甲基-10-(2-甲氧基-1-萘基)异黄素（2(2OMe)）进行了比较。1(2OH)和2(2OH)的pKa值分别为7.7和7.0，均低于3-甲基-10-(4-羟基苯基)异黄素（1(4OH)：pKa 8.6）。因此，在反应的初始状态（即氧化状态）下，2′-OH和N(1)形成氢键的可能性较小。X射线晶体学研究表明，苯环与异黄素环之间的夹角为79.7°，而2′-OH基团与晶体格中包含的甲醇形成氢键。在30 °C的乙腈中，1-苯基-1,4-二氢烟酰胺未被1(2OMe)、1(4OH)和2(2OMe)氧化。另一方面，1(2OH)和2(2OH)（在10-芳基取代基的2′位置具有酸性OH基团）发生了氧化。分子内酸催化的存在表明，2′-OH和N(1)至少可以在反应的过渡态或最终状态（即还原状态）下相互作用。一般来说，氧化的黄素采用“平面”结构，立体张力较大，而还原的黄素则采用“弯曲”结构，立体张力较小。由于过渡态的结构或多或少与还原形式相似，因此在从紧张的初始状态转变为放松的过渡状态时，氢键相互作用可能会增强。这是黄素介导反应中酸催化的新颖例子。
• UNUSUAL KINETIC BEHAVIOR OF BIS-FLAVIN FOR<i>N</i>-BENZYL-1,4-DIHYDRONICOTINAMIDE (BNAH) REDUCTION IN AN AQUEOUS SOLUTION
  作者：Yumihiko Yano、Eiichi Ohya

  DOI：10.1246/cl.1983.1281

  日期：1983.8.5

  Several bis-flavins linked at 10,10′-positions of isoalloxazine rings were synthesized. The reactivity of each flavin of a bis-flavin was found to be considerably influenced by another intramolecular flavin moiety, depending on the conformation of the bis-flavin.

  我们合成了几种连接在异咯嗪环 10,10′ 位上的双黄素。研究发现，双黄素中每个黄素的反应活性都会受到分子内另一个黄素分子的很大影响，这取决于双黄素的构象。
• A New and Improved<b><i>N</i></b>-3 Alkylation of 10-Substituted Isoalloxazines Using 1,8-Diazabicyclo[5.4.0]undec-7-ene in Benzene
  作者：Geetanjali、Ram Singh、S. M. S. Chauhan

  DOI：10.1081/scc-120015816

  日期：2003.1.4

  Abstract 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) has been identified as a remarkable base for the alkylation at N-3 position of 10-substituted isoalloxazines with alkyl halides in dry benzene.

  摘要 1,8-二氮杂双环[5.4.0]十一碳-7-烯(DBU) 已被鉴定为在无水苯中用烷基卤在10-取代异恶嗪的N-3 位进行烷基化反应的显着碱。
• Microwave-Assisted Synthesis of 10-Substituted Isoalloxazines in the Presence of Solid Acids
  作者：S. M. S. Chauhan、Ram Singh、Geetanjali

  DOI：10.1081/scc-120017194

  日期：2003.1.5

  Abstract The microwave-enhanced synthesis of 10-substituted isoalloxazines is achieved rapidly (˜4 min) and in good yield (>80–95%) via the cyclocondensation of 2-substituted aminoanilines with alloxan or N-methylalloxan monohydrate in the presence of acidic alumina or montmorillonite clays (KSF and K10).

  摘要 通过 2-取代氨基苯胺与四氧嘧啶或 N-甲基四氧嘧啶一水合物在酸性存在下的环缩合反应，10-取代异咯嗪的微波增强合成可快速（约 4 分钟）且收率良好（>80-95%）。氧化铝或蒙脱石粘土（KSF 和 K10）。
• A new and versatile synthesis of isoalloxazines
  作者：Magoichi Sako、Yutaka Kojima、Kosaku Hirota、Yoshifumi Maki

  DOI：10.1039/c39840001691

  日期：——

  Isoalloxazines (2) were prepared easily by heating of the corresponding 5-anilino-6-(alkyl or aryl amino)pyrimidine-2,4(1H,3H)-diones (1) in dimethylformamide under oxygen.

  通过在氧气下在二甲基甲酰胺中加热相应的5-苯胺基-6-（烷基或芳基氨基）嘧啶-2,4（1 H，3 H）-二酮（1），可以轻松制备异四恶嗪（2）。