2-(chloromethyl)-3,7,8-trimethylpyrimido<4,5-g>quinazoline-4,5,9,10(3H,8H)-tetrone | 143430-54-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-(chloromethyl)-3,7,8-trimethylpyrimido<4,5-g>quinazoline-4,5,9,10(3H,8H)-tetrone
• 英文别名: 2-(Chloromethyl)-3,7,8-trimethylpyrimido[4,5-g]quinazoline-4,5,9,10-tetrone
• CAS: 143430-54-0
• 化学式: C₁₄H₁₁ClN₄O₄
• 分子量: 334.719
• InChiKey: RCRSHXOKTWQQES-UHFFFAOYSA-N

物化性质

• 沸点：
  481.2±55.0 °C(Predicted)
• 密度：
  1.67±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  99.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(chloromethyl)-3,7,8-trimethylpyrimido<4,5-g>quinazoline-4,5,9,10(3H,8H)-tetrone 在 sodium dithionite 、 水 作用下， 以 氯仿 、 二甲基亚砜 为溶剂， 生成 2,3,7,8-tetramethylpyrimido<4,5-g>quinazoline-4,5,9,10(3H,8H)tetrone
  参考文献：
  名称：

  Design of pyrimido[4,5-g]quinazoline-based anthraquinone mimics. Structure-activity relationship for quinone methide formation and the influence of internal hydrogen bonds on quinone methide fate

  摘要：

  Pyrimido[4,5-g]quinazolinequinone derivatives were synthesized as a anthraquinone-like reductive alkylating agents. Like many naturally-occurring antibiotics, these quinone derivatives are designed to afford an alkylating quinone methide species upon reduction and leaving-group elimination. Kinetic studies of pyrimido[4,5-g]quinazoline hydroquinones provided evidence of quinone methide intermediate able to trap nucleophiles (alkylation) and protons (ketonization). The rate of quinone methide formation is determined by the hydroquinone free energy. Thus, a linear free energy relationship for quinone methide formation was obtained by plotting rates of quinone methide formation as the log versus the quinone reduction potential. The pyrimido[4,5-g]quinazoline quinone methides fall on this free energy plot, showing that these species are formed by the same mechanism as the other structurally-diverse quinone methides previously studied in this research group. Internal hydrogen bonds present in pyrimido[4,5-g]quinazoline derivatives influence the fate of the quinone methide species as well as the rate of hydroquinone oxidation in the presence of oxygen Such hydrogen bonds stabilize the hydroquinone species, thereby resulting in slow rates of hydroquinone oxidation to quinone in alkaline aerobic buffer. Stabilization of the hydroquinone also results in substantial nucleophile trapping by the quinone methide. Without internal hydrogen bonds, hydroquinone oxidations are rapid and the quinone methide traps only electrophiles.

  DOI：

  10.1021/jo00047a017
• 作为产物：
  描述：

  2,5-Dimethoxy-1,4-benzoldicarbonitril 在 palladium on activated charcoal 吡啶 、 sodium hydroxide 、 ammonium cerium(IV) nitrate 、 硫酸 、 氢气 、 双氧水 、 硝酸 、 乙酸酐 、 sodium nitrite 作用下， 以 甲醇 、 乙醇 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 100.0 ℃ 、344.73 kPa 条件下， 反应 16.83h， 生成 2-(chloromethyl)-3,7,8-trimethylpyrimido<4,5-g>quinazoline-4,5,9,10(3H,8H)-tetrone
  参考文献：
  名称：

  Design of pyrimido[4,5-g]quinazoline-based anthraquinone mimics. Structure-activity relationship for quinone methide formation and the influence of internal hydrogen bonds on quinone methide fate

  摘要：

  Pyrimido[4,5-g]quinazolinequinone derivatives were synthesized as a anthraquinone-like reductive alkylating agents. Like many naturally-occurring antibiotics, these quinone derivatives are designed to afford an alkylating quinone methide species upon reduction and leaving-group elimination. Kinetic studies of pyrimido[4,5-g]quinazoline hydroquinones provided evidence of quinone methide intermediate able to trap nucleophiles (alkylation) and protons (ketonization). The rate of quinone methide formation is determined by the hydroquinone free energy. Thus, a linear free energy relationship for quinone methide formation was obtained by plotting rates of quinone methide formation as the log versus the quinone reduction potential. The pyrimido[4,5-g]quinazoline quinone methides fall on this free energy plot, showing that these species are formed by the same mechanism as the other structurally-diverse quinone methides previously studied in this research group. Internal hydrogen bonds present in pyrimido[4,5-g]quinazoline derivatives influence the fate of the quinone methide species as well as the rate of hydroquinone oxidation in the presence of oxygen Such hydrogen bonds stabilize the hydroquinone species, thereby resulting in slow rates of hydroquinone oxidation to quinone in alkaline aerobic buffer. Stabilization of the hydroquinone also results in substantial nucleophile trapping by the quinone methide. Without internal hydrogen bonds, hydroquinone oxidations are rapid and the quinone methide traps only electrophiles.

  DOI：

  10.1021/jo00047a017

文献信息

• US5639881A
  申请人：——

  公开号：US5639881A

  公开（公告）日：1997-06-17
• Design of pyrimido[4,5-g]quinazoline-based anthraquinone mimics. Structure-activity relationship for quinone methide formation and the influence of internal hydrogen bonds on quinone methide fate
  作者：Robert H. Lemus、Edward B. Skibo

  DOI：10.1021/jo00047a017

  日期：1992.10

  Pyrimido[4,5-g]quinazolinequinone derivatives were synthesized as a anthraquinone-like reductive alkylating agents. Like many naturally-occurring antibiotics, these quinone derivatives are designed to afford an alkylating quinone methide species upon reduction and leaving-group elimination. Kinetic studies of pyrimido[4,5-g]quinazoline hydroquinones provided evidence of quinone methide intermediate able to trap nucleophiles (alkylation) and protons (ketonization). The rate of quinone methide formation is determined by the hydroquinone free energy. Thus, a linear free energy relationship for quinone methide formation was obtained by plotting rates of quinone methide formation as the log versus the quinone reduction potential. The pyrimido[4,5-g]quinazoline quinone methides fall on this free energy plot, showing that these species are formed by the same mechanism as the other structurally-diverse quinone methides previously studied in this research group. Internal hydrogen bonds present in pyrimido[4,5-g]quinazoline derivatives influence the fate of the quinone methide species as well as the rate of hydroquinone oxidation in the presence of oxygen Such hydrogen bonds stabilize the hydroquinone species, thereby resulting in slow rates of hydroquinone oxidation to quinone in alkaline aerobic buffer. Stabilization of the hydroquinone also results in substantial nucleophile trapping by the quinone methide. Without internal hydrogen bonds, hydroquinone oxidations are rapid and the quinone methide traps only electrophiles.