N-亚硝基-2-羟基吗啉 | 67587-52-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 中文名称: N-亚硝基-2-羟基吗啉
• 英文名称: N-nitroso-2-hydroxymorpholine
• 英文别名: 4-nitrosomorpholin-2-ol
• CAS: 67587-52-4
• 化学式: C₄H₈N₂O₃
• mdl: MFCD01713311
• 分子量: 132.119
• InChiKey: NIRHEGBBHNJANV-UHFFFAOYSA-N

物化性质

• 沸点：
  311.9±37.0 °C(Predicted)
• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  62.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-亚硝基-2-羟基吗啉 在 glucose 6-phosphate dehydrogenase Sprague-Dawley rat liver microsomes 、 氧气 、 烟酰胺腺嘌呤双核苷酸磷酸盐 作用下， 以 phosphate buffer 为溶剂， 反应 0.33h， 生成 草酸醛 、 羟乙醛
  参考文献：
  名称：

  微粒体介导的N-亚硝基二乙醇胺（NDELA）（一种潜在的致癌物）的氧化。

  摘要：

  N-亚硝基二乙醇胺（NDELA），一种在环境上普遍存在的强致癌物，在2-羟乙基链的α（与N相邻）和β位均经历竞争性大鼠肝微粒体介导的氧化。前一种过程是α-羟基化，是通过形成乙醇醛（确定为其2,4-二硝基苯基hydr DNP）来检测的，该醛被认为是由相应的α-羟基亚硝胺的分解而产生的，α-羟基亚硝胺也是2的祖先。羟乙基重氮离子。这一发现反驳了先前发表的工作，该工作指出NDELA不会发生α-羟基化。在β位置发生竞争性微粒体氧化，生成半缩醛N-亚硝基-2-羟基吗啉（NHMOR）的速率为α-羟基化的1.5倍。乙醇醛在该系统中被氧化为乙二醛，其转化率是NDELA转化为乙醇醛的39倍。NHMOR在C-3或C-5处分别产生乙二醛或乙醛的α-羟基化反应的发生率分别是NDELA的α-羟基化反应的3-6倍。乙二醇（2-羟乙基重氮离子的水解产物）显示出微粒体介导氧化为乙二醛的作用。乙基-2-羟乙基亚硝胺（NEE

  DOI：

  10.1021/tx000267b
• 作为产物：
  描述：

  二乙醇亚硝胺 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 以91%的产率得到N-亚硝基-2-羟基吗啉
  参考文献：
  名称：

  高反应性，多功能α，β-环氧-和α-乙酰氧基-亚硝胺的合成

  摘要：

  通过环完成了两个α-羟基亚硝胺的反应性乙酸酯，反式-3-乙酰氧基-2-羟基-N-亚硝基吗啉3和N-（1-乙酰氧基-2-羟基乙基）-N-亚硝基乙醇胺12的合成。打开由乙烯亚硝胺的二甲基二环氧乙烷氧化制得的相应的环氧化物NEMOR和10。

  DOI：

  10.1016/s0040-4039(97)10868-1

文献信息

• Probing the Mechanism of the Carcinogenic Activation of <i>N</i>-Nitrosodiethanolamine with Deuterium Isotope Effects:  In Vivo Induction of DNA Single-Strand Breaks and Related in Vitro Assays
  作者：Richard N. Loeppky、Anne Fuchs、Christine Janzowski、Christina Humberd、Petra Goelzer、Heiko Schneider、Gerhard Eisenbrand

  DOI：10.1021/tx9801716

  日期：1998.12.1

  A series of bioassays, including in vivo induction of DNA single-strand breaks (SSB) and cytotoxicity in cytochrome P450 2E1-transfected cells, were utilized with N-nitrosodiethanolamine (NDELA), its deuterated isotopomers (alpha-D(4)NDELA and beta-D(4)NDELA), N-nitroso-2-hydroxymorpholine (NHMOR), and two of its deuterated isotopomers (2-D-NHMOR and 5,5-D-2-NHMOR) to probe the mechanism of carcinogenic activation of NDELA and the role of its metabolite NHMOR. DNA samples, taken from the livers of male Wistar rats 4 h after the administration of NDELA, exhibited dose-dependent DNA SSB levels over the range of 0.08-0.75 mmol/kg (body weight), with the greatest SSB level at the highest dose. Deuterium isotope effects on DNA SSB levels were inversely dependent on dose: alpha-D(4)NDELA, 3.22-1.37; and beta-D(4)NDELA, 1.38-0.79, At the lowest dose of 0.15 mmol/kg (body weight), 5,5-D-2-NHMOR gave an isotope effect for DNA SSB of 2.8 while that for 2-D-NHMOR was 0.7, NDELA and beta-D(4)NDELA were equally cytotoxic to human P450 2E1-transfected V79 Chinese hamster cells, while alpha-D(4)NDELA was not. Significant DNA SSR levels were observed in these cells for NDELA and beta-D(4)NDELA but not for alpha-D(4)NDELA. A kinetic deuterium isotope effect of 2.6 NDELA to NHMOR, while k(II)/k(D) for alpha-D(4)NDELA was 1.05, These data provide the first definitive evidence fur the activation of NDELA by a pathway involving the scission of the alpha-CH bond and are consistent with P450 2E1-mediated alpha-hydroxylation of NDELA producing the corresponding reactive alpha-hydroxynitrosamine.
• In Vitro DNA Deamination by α-Nitrosaminoaldehydes Determined by GC/MS-SIM Quantitation
  作者：Misun Park、Richard N. Loeppky

  DOI：10.1021/tx990126d

  日期：2000.2.1

  The deamination of DNA bases by three alpha-nitrosaminoaldehydes, butylethanalnitrosamine, methylethanalnitrosamine, and N-nitroso-2-hydroxymorpholine (NHMOR), the direct metabolite of potent animal carcinogen N-nitrosodiethanolamine, was demonstrated by a set of in vitro experiments. The deamination of guanine, adenine, and cytosine bases in nucleotides, oligonucleotides, and calf thymus DNA gave xanthine, hypoxanthine, and uracil, respectively. The order of relative reactivities of the bases was as listed above. Deamination of cytosine to uracil was detected by the reaction of P-32-labeled oligonucleotide ([5'-P-32]CGAT) followed by enzymatic hydrolysis. Quantitative analysis of deamination of guanine and adenine in calf thymus DNA was performed by a gas chromatography/mass spectrometry-selected ion monitoring method. Both the extent and the rate of the deamination reactions which occur by transnitrosation from the alpha-nitrosaminoaldehyde to the base were determined for formation of xanthine and hypoxanthine. The deamination of guanine by NHMOR remained significant at low substrate levels.
• Acid-catalyzed rearrangements of N-nitrosodehydromorpholine
  作者：Richard N. Loeppky、Heping Xiong

  DOI：10.1021/jo00122a036

  日期：1995.9

  N-Nitrosodehydromorpholine, a potential metabolic intermediate in the carcinogenic activation of N-nitrosodiethanolamine, and N-nitrosomorpholine, was prepared from the hemiacetal N-nitroso-2-hydroxymorpholine (2) by tosylation and in situ base-catalyzed elimination. The attempted acid-catalyzed hydration of 3 gives neither 2 nor the unstable alpha-hydroxynitrosamine, N-nitroso-3-hydroxymorpholine (4). The product of this transformation is N-(2-hydroxyethyl)-2-oximinoethanamide (5) as confirmed by an X-ray crystallographic determination. Treatment of 3 with gaseous HCl in CH2Cl2 gives 1-aza-4-oxa-3-oximinocyclohexene (6), which rearranges to 5 upon treatment with aqueous acid. The initial rearrangement was proven to be intermolecular by means of a crossover experiment employing (NO)-N-15 and C-5-D-2 isotopomers of 3.
• The synthesis of highly reactive, multi-functional α,β-epoxy- and α-acetoxy-nitrosamines
  作者：Misun Park、Feng Gu、Richard N. Loeppky

  DOI：10.1016/s0040-4039(97)10868-1

  日期：1998.3

  oline 3 and N-(1-acetoxy-2-hydroxyethyl)-N-nitrosoethanolamine12, of two α-hydroxynitrosamines has been accomplished through the ring opening of the corresponding epoxides, NEMOR and 10 which were prepared by dimethyldioxirane oxidation of the vinyl nitrosamines.

  通过环完成了两个α-羟基亚硝胺的反应性乙酸酯，反式-3-乙酰氧基-2-羟基-N-亚硝基吗啉3和N-（1-乙酰氧基-2-羟基乙基）-N-亚硝基乙醇胺12的合成。打开由乙烯亚硝胺的二甲基二环氧乙烷氧化制得的相应的环氧化物NEMOR和10。
• Microsome-Mediated Oxidation of <i>N</i>-Nitrosodiethanolamine (NDELA), a Bident Carcinogen
  作者：Richard N. Loeppky、Petra Goelzer

  DOI：10.1021/tx000267b

  日期：2002.4.1

  N-Nitrosodiethanolamine (NDELA), an environmentally prevalent, potent carcinogen, undergoes competitive rat liver microsome-mediated oxidation at both the alpha (adjacent to N)- and beta-positions of the 2-hydroxyethyl chains. The former process, alpha-hydroxylation, is detected by the formation of glycolaldehyde (determined as its 2,4-dinitrophenylhydrazone DNP) that is assumed to arise from the decomposition

  N-亚硝基二乙醇胺（NDELA），一种在环境上普遍存在的强致癌物，在2-羟乙基链的α（与N相邻）和β位均经历竞争性大鼠肝微粒体介导的氧化。前一种过程是α-羟基化，是通过形成乙醇醛（确定为其2,4-二硝基苯基hydr DNP）来检测的，该醛被认为是由相应的α-羟基亚硝胺的分解而产生的，α-羟基亚硝胺也是2的祖先。羟乙基重氮离子。这一发现反驳了先前发表的工作，该工作指出NDELA不会发生α-羟基化。在β位置发生竞争性微粒体氧化，生成半缩醛N-亚硝基-2-羟基吗啉（NHMOR）的速率为α-羟基化的1.5倍。乙醇醛在该系统中被氧化为乙二醛，其转化率是NDELA转化为乙醇醛的39倍。NHMOR在C-3或C-5处分别产生乙二醛或乙醛的α-羟基化反应的发生率分别是NDELA的α-羟基化反应的3-6倍。乙二醇（2-羟乙基重氮离子的水解产物）显示出微粒体介导氧化为乙二醛的作用。乙基-2-羟乙基亚硝胺（NEE