Dimethyl N-(2-bromoethyl)phosphoramidate | 27839-03-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: Dimethyl N-(2-bromoethyl)phosphoramidate
• 英文别名: 2-bromo-N-dimethoxyphosphorylethanamine
• CAS: 27839-03-8
• 化学式: C₄H₁₁BrNO₃P
• 分子量: 232.014
• InChiKey: XWEZCKKKQXKGAV-UHFFFAOYSA-N

物化性质

• 沸点：
  226.5±42.0 °C(Predicted)
• 密度：
  1.512±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  10
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Dimethyl N-(2-bromoethyl)phosphoramidate 在 lithium bromide 作用下， 以 丁酮 为溶剂， 反应 5.0h， 以69%的产率得到Lithium methyl N-(2-bromoethyl)phosphoramidate
  参考文献：
  名称：

  Decomposition of N-Phosphorylated Nitrogen Mustards: A Mechanistic Investigation

  摘要：

  Lithium methyl N-(2-chloroethyl)phosphoramidate (2b) and lithium methyl N,N-bis(2-chloroethyl)phosphoramidate (2c) were prepared as models of N-phosphorylated mustards used in cancer chemotherapy. The decomposition of those substrates in D2O and in D2O-pyridine-d(5) was studied to elucidate the mechanism of their alkylating reactivity. The products of the decomposition and the variation of the proportions of the products with time were determined, and the results led to the following conclusions. Decomposition of substrates of the type 2 can follow three independent pathways: (i) 1,5-cyclization to a 1,3,2-oxazaphospholidine derivative, followed by fast ring opening via the pH-dependent P-O or P-N bond cleavage; (ii) 1,3-cyclization to a N-phosphorylated aziridinium derivative, followed by the nucleophilic opening of the aziridine ring; (iii) fragmentation to metaphosphate and aziridine species, followed by rapid reactions of those intermediates with nucleophiles. The first pathway deactivates the substrate with respect to the alkylating reactivity. Relative contributions of individual pathways to the decomposition are highly sensitive to the detailed structure of the substrate and to the nucleophilic composition of the reaction medium.

  DOI：

  10.1021/jo00117a039
• 作为产物：
  描述：

  2-溴乙胺氢溴酸盐 、 氯磷酸二甲酯 在 三乙胺 作用下， 以 乙醚 为溶剂， 以56%的产率得到Dimethyl N-(2-bromoethyl)phosphoramidate
  参考文献：
  名称：

  Decomposition of N-Phosphorylated Nitrogen Mustards: A Mechanistic Investigation

  摘要：

  Lithium methyl N-(2-chloroethyl)phosphoramidate (2b) and lithium methyl N,N-bis(2-chloroethyl)phosphoramidate (2c) were prepared as models of N-phosphorylated mustards used in cancer chemotherapy. The decomposition of those substrates in D2O and in D2O-pyridine-d(5) was studied to elucidate the mechanism of their alkylating reactivity. The products of the decomposition and the variation of the proportions of the products with time were determined, and the results led to the following conclusions. Decomposition of substrates of the type 2 can follow three independent pathways: (i) 1,5-cyclization to a 1,3,2-oxazaphospholidine derivative, followed by fast ring opening via the pH-dependent P-O or P-N bond cleavage; (ii) 1,3-cyclization to a N-phosphorylated aziridinium derivative, followed by the nucleophilic opening of the aziridine ring; (iii) fragmentation to metaphosphate and aziridine species, followed by rapid reactions of those intermediates with nucleophiles. The first pathway deactivates the substrate with respect to the alkylating reactivity. Relative contributions of individual pathways to the decomposition are highly sensitive to the detailed structure of the substrate and to the nucleophilic composition of the reaction medium.

  DOI：

  10.1021/jo00117a039

文献信息

• DAVIDOWITZ, B.;MODRO, T. A., S. AFR. J. CHEM., 1982, 35, N 2, 63-66
  作者：DAVIDOWITZ, B.、MODRO, T. A.

  DOI：——

  日期：——
• Decomposition of N-Phosphorylated Nitrogen Mustards: A Mechanistic Investigation
  作者：Charlotte le Roux、Agnes M. Modro、Tomasz A. Modro

  DOI：10.1021/jo00117a039

  日期：1995.6

  Lithium methyl N-(2-chloroethyl)phosphoramidate (2b) and lithium methyl N,N-bis(2-chloroethyl)phosphoramidate (2c) were prepared as models of N-phosphorylated mustards used in cancer chemotherapy. The decomposition of those substrates in D2O and in D2O-pyridine-d(5) was studied to elucidate the mechanism of their alkylating reactivity. The products of the decomposition and the variation of the proportions of the products with time were determined, and the results led to the following conclusions. Decomposition of substrates of the type 2 can follow three independent pathways: (i) 1,5-cyclization to a 1,3,2-oxazaphospholidine derivative, followed by fast ring opening via the pH-dependent P-O or P-N bond cleavage; (ii) 1,3-cyclization to a N-phosphorylated aziridinium derivative, followed by the nucleophilic opening of the aziridine ring; (iii) fragmentation to metaphosphate and aziridine species, followed by rapid reactions of those intermediates with nucleophiles. The first pathway deactivates the substrate with respect to the alkylating reactivity. Relative contributions of individual pathways to the decomposition are highly sensitive to the detailed structure of the substrate and to the nucleophilic composition of the reaction medium.