N-(2-hydroxyethyl)chlorofluoroacetamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 甲亚胺酸及其衍生物
• 英文名称: N-(2-hydroxyethyl)chlorofluoroacetamide
• 英文别名: 2-chloro-2-fluoro-N-(2-hydroxyethyl)acetamide
• 化学式: C₄H₇ClFNO₂
• 分子量: 155.556
• InChiKey: NTFUPBUTLMZKRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.37
• 重原子数：
  9.0
• 可旋转键数：
  3.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  49.33
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为产物：
  描述：

  乙醇 、 三氟氯乙烯 、 C.I.酸性橙108 在 sodium ethanolate 作用下， 以 乙醚 为溶剂， 反应 0.08h， 生成 N-(2-hydroxyethyl)chlorofluoroacetamide
  参考文献：
  名称：

  Metabolism of 1,2-Dichloro-1-fluoroethane and 1-Fluoro-1,2,2-trichloroethane:  Electronic Factors Govern the Regioselectivity of Cytochrome P450-Dependent Oxidation

  摘要：

  1,2-Dichloro-1-fluoroethane (HCFC-141) and 1,1,2-trichloro-2-fluoroethane (HCFC-131) were chosen as models to study the regioselectivity of halogenated alkane metabolism. Metabolites in the urine of rats given HCFC-131 ip were the following: inorganic fluoride, chlorofluoroacetic acid, dichloroacetic acid, N-(2-hydroxyethyl)chlorofluoroacetamide, and three unidentified minor metabolites. In vitro incubation of HCFC-131 with either rat liver microsomes from pyridine-treated rats or expressed human cytochrome P450 2E1 isozyme in the presence of NADPH gave fluoride, chlorofluoroacetic acid, and dichloroacetic acid as metabolites. HCFC-141 was biotransformed in rats to inorganic fluoride, chlorofluoroacetic acid, 2-chloro-2-fluoroethanol, and 2-chloro-2-fluoroethyl glucuronide, which were detected in urine. Incubation of HCFC-141 with NADPH-fortified liver microsomes from pyridine-induced rats or expressed human cytochrome P450 2E1 afforded fluoride, chlorofluoroacetaldehyde hydrate, and chloroacetic acid as products. The metabolites identified were consistent with a cytochrome P450-dependent oxidation mechanism. The data also indicated that phosphatidylethanolamine may be a cellular target for chlorofluoroacetyl chloride, a reactive intermediate generated from HCFC-131 by cytochrome P450-dependent oxidation. Chlorofluoroacetic acid given to rats ip was largely recovered in the rat urine, although the formation of inorganic fluoride as a metabolite was observed. The mechanism of defluorination of chlorofluoroacetic acid is not clear. Regioselective oxidation by cytochrome P450 was observed between the two potential oxidizable sites in HCFC-141 and in HCFC-131. Comparison of the observed ratio of oxidation at different sites in in vitro experiments with the calculated activation energies for hydrogen-atom abstraction from these sites indicated that electronic factors are the primary determinant of regioselectivity. In vivo regioselectivity could not be compared with theory since this ratio does not reflect the true regioselectivity due to differences in excretion, reabsorption, secondary metabolism (e.g., fluoride generation from chlorofluoroacetic acid), other routes of fluoride formation, and limitation of the method of detection.

  DOI：

  10.1021/tx950086n

文献信息

• Metabolism of 1,2-Dichloro-1-fluoroethane and 1-Fluoro-1,2,2-trichloroethane:  Electronic Factors Govern the Regioselectivity of Cytochrome P450-Dependent Oxidation
  作者：Hequn Yin、M. W. Anders、Jeffrey P. Jones

  DOI：10.1021/tx950086n

  日期：1996.1.1

  1,2-Dichloro-1-fluoroethane (HCFC-141) and 1,1,2-trichloro-2-fluoroethane (HCFC-131) were chosen as models to study the regioselectivity of halogenated alkane metabolism. Metabolites in the urine of rats given HCFC-131 ip were the following: inorganic fluoride, chlorofluoroacetic acid, dichloroacetic acid, N-(2-hydroxyethyl)chlorofluoroacetamide, and three unidentified minor metabolites. In vitro incubation of HCFC-131 with either rat liver microsomes from pyridine-treated rats or expressed human cytochrome P450 2E1 isozyme in the presence of NADPH gave fluoride, chlorofluoroacetic acid, and dichloroacetic acid as metabolites. HCFC-141 was biotransformed in rats to inorganic fluoride, chlorofluoroacetic acid, 2-chloro-2-fluoroethanol, and 2-chloro-2-fluoroethyl glucuronide, which were detected in urine. Incubation of HCFC-141 with NADPH-fortified liver microsomes from pyridine-induced rats or expressed human cytochrome P450 2E1 afforded fluoride, chlorofluoroacetaldehyde hydrate, and chloroacetic acid as products. The metabolites identified were consistent with a cytochrome P450-dependent oxidation mechanism. The data also indicated that phosphatidylethanolamine may be a cellular target for chlorofluoroacetyl chloride, a reactive intermediate generated from HCFC-131 by cytochrome P450-dependent oxidation. Chlorofluoroacetic acid given to rats ip was largely recovered in the rat urine, although the formation of inorganic fluoride as a metabolite was observed. The mechanism of defluorination of chlorofluoroacetic acid is not clear. Regioselective oxidation by cytochrome P450 was observed between the two potential oxidizable sites in HCFC-141 and in HCFC-131. Comparison of the observed ratio of oxidation at different sites in in vitro experiments with the calculated activation energies for hydrogen-atom abstraction from these sites indicated that electronic factors are the primary determinant of regioselectivity. In vivo regioselectivity could not be compared with theory since this ratio does not reflect the true regioselectivity due to differences in excretion, reabsorption, secondary metabolism (e.g., fluoride generation from chlorofluoroacetic acid), other routes of fluoride formation, and limitation of the method of detection.