2-benzyloxy-2-methyl-4H-1,3-benzodioxin-4-one | 52602-18-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 2-benzyloxy-2-methyl-4H-1,3-benzodioxin-4-one
• 英文别名: 2-benzyloxy-2-methyl-benzo[1,3]dioxin-4-one；2-(Benzyloxy)-2-methyl-2H,4H-1,3-benzodioxin-4-one；2-methyl-2-phenylmethoxy-1,3-benzodioxin-4-one
• CAS: 52602-18-3
• 化学式: C₁₆H₁₄O₄
• 分子量: 270.285
• InChiKey: JIVDBAGZANIYPX-UHFFFAOYSA-N

物化性质

• 熔点：
  49-50 °C
• 沸点：
  438.8±45.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-benzyloxy-2-methyl-4H-1,3-benzodioxin-4-one 在 水 作用下， 生成 水杨酸
  参考文献：
  名称：

  Aspirin Prodrugs: Synthesis and Hydrolysis of 2-Benzyloxy-2-methyl-4H-1,3-benzodioxin-4-ones.

  摘要：

  Aspirin is widely used for its analgesic, antiinflammatory and antipyretic properties. Among its disadvantages are the relatively narrow therapeutic margin, its irritancy towards the gastric mucosa, and occasionally patient hypersensitivity towards aspirin. As part of our effort to develop prodrugs without these liabilities eleven new title compounds have been isolated and characterized. These 'superaspirin' candidates were subjected to non-enzymatic hydrolysis for a first rapid screening in vitro. Only 2-(2,6-dimethoxybenzyloxy)-2-methyl-4H-1,3-benzodioxin-4-one (4c) was observed to act as an exclusive aspirin prodrug, while 2-(2-methoxybenzyloxy)-2-methyl-4H-1,3-benzodioxin-4-one (4b) and 2-(2-ethoxybenzyloxy)-2-methyl-4H-1,3- benzodioxin-4-one (4d) were shown to release both aspirin 6 and salicylic acid 7. Subsequently, these three candidates were further characterized by investigation of the pH profile of their hydrolysis rates.

  DOI：

  10.3891/acta.chem.scand.43-0793
• 作为产物：
  描述：

  2-乙酰基苯甲酰氯 、 苯甲醇 以30%的产率得到
  参考文献：
  名称：

  ANKERSEN, MICHAEL;SENNING, ALEXANDER, ACTA. CHEM. SCAND., 43,(1989) N, C. 793-798

  摘要：

  DOI：

文献信息

• Chemical Feasibility Studies Concerning Potential Prodrugs of Acetylsalicylic Acid.
  作者：Asger B. Hansen、Alexander Senning、Xu Jie-Cheng、Ulla Björkroth、Lu Yi-An、Liu Yin-Zeng

  DOI：10.3891/acta.chem.scand.37b-0351

  日期：——

  A rationale is developed for aspirin prodrugs based on non-acidic latentiated derivatives. Knowledge of the gastro-intestinal liabilities and pharmacological profile is required for this approach whereby aspirin is built into a common ortho ester function of the type 2-substituted 2-methyl-4H-1,3-benzodioxin-4-one with latentiated carboxyl and acetoxy groups. Twelve compounds of this type, ten substituted with various alkoxy and aryloxy groups and two with arylthio groups, have been isolated and characterized. A new synthetic route, comprising the reaction of 2-acetoxybenzoyl chloride with TMS derivatives of the corresponding alcohols and phenols, has been devised for the preparation of some of the compounds while others were prepared according to known methods. Subsequently, the prodrug candidates have been subjected to non-enzymatic hydrolysis for a first rapid screening in vitro. Only 2-tert-butoxy-2-methyl-4H-1,3-benzodioxin-4-one is observed to act as a true proaspirin, releasing aspirin, under these conditions, but analogous compounds with tertiary substituents may display the same behavior, and this chemical approach to aspirin modification may offer a viable rationale for aspirin prodrugs with reduced gastric irritancy or for making "superaspirins".
• ANKERSEN, MICHAEL;SENNING, ALEXANDER, ACTA. CHEM. SCAND., 43,(1989) N, C. 793-798
  作者：ANKERSEN, MICHAEL、SENNING, ALEXANDER

  DOI：——

  日期：——
• HANSEN, A. B.;SENNING, A., ACTA CHEM. SCAND., 1983, 37, N 4, 351-359
  作者：HANSEN, A. B.、SENNING, A.

  DOI：——

  日期：——
• Aspirin Prodrugs: Synthesis and Hydrolysis of 2-Benzyloxy-2-methyl-4H-1,3-benzodioxin-4-ones.
  作者：Michael Ankersen、Alexander Senning、Risto S. Laitinen、Otto Dahl

  DOI：10.3891/acta.chem.scand.43-0793

  日期：——

  Aspirin is widely used for its analgesic, antiinflammatory and antipyretic properties. Among its disadvantages are the relatively narrow therapeutic margin, its irritancy towards the gastric mucosa, and occasionally patient hypersensitivity towards aspirin. As part of our effort to develop prodrugs without these liabilities eleven new title compounds have been isolated and characterized. These 'superaspirin' candidates were subjected to non-enzymatic hydrolysis for a first rapid screening in vitro. Only 2-(2,6-dimethoxybenzyloxy)-2-methyl-4H-1,3-benzodioxin-4-one (4c) was observed to act as an exclusive aspirin prodrug, while 2-(2-methoxybenzyloxy)-2-methyl-4H-1,3-benzodioxin-4-one (4b) and 2-(2-ethoxybenzyloxy)-2-methyl-4H-1,3- benzodioxin-4-one (4d) were shown to release both aspirin 6 and salicylic acid 7. Subsequently, these three candidates were further characterized by investigation of the pH profile of their hydrolysis rates.