(E)-2-Chloro-3-(dichloromethyl)-4-oxobutenoic acid | 115340-67-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (E)-2-Chloro-3-(dichloromethyl)-4-oxobutenoic acid
• 英文别名: (E)-2-Chloro-3-dichloromethyl-4-oxo-butenoic acid；E 2-chloro-3-dichloromethyl-4-oxo-butenoic acid；(E)-2,4,4-trichloro-3-formylbut-2-enoic acid
• CAS: 115340-67-5
• 化学式: C₅H₃Cl₃O₃
• 分子量: 217.436
• InChiKey: BYYQBAWEAGLGPF-NSCUHMNNSA-N

物化性质

• 沸点：
  317.1±42.0 °C(Predicted)
• 密度：
  1.662±0.06 g/cm3(Predicted)
• 溶解度：
  In water, 2,265 mg/L at 25 °C (est)
• 蒸汽压力：
  2.25X10-4 at 25 °C (est)
• 解离常数：
  pKa = 2.00 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

毒理性

• 非人类毒性摘录

/遗传毒性/ 最近在氯化饮用水中识别出的氯化丁烯酸的诱变活性通过沙门氏菌微体试验和SOS色测试验进行了测定。使用了沙门氏菌伤寒测试菌株TA97、TA98和TA100，有和无S9混合物。在SOS色测试验中，使用大肠杆菌PQ37作为指示生物，有和无代谢激活。此外，通过小鼠腹腔注射处理的微核试验，研究了极其强效的Ames试验诱变剂(Z)-2-氯-3-(二氯甲基)-4-氧代丁烯酸（MX，开放形式）。沙门氏菌试验和SOS色测试验的结果显示，MX是所测试化合物中最强的诱变剂。还原形式的MX，(Z)-2-氯-3-(二氯甲基)-4-羟基丁-2-烯酸（red-MX），以及MX的几何异构体，(E)-2-氯-3-(二氯甲基)-4-氧代丁烯酸（EMX）也能诱导突变。然而，由于EMX的溶液中大约含有5%的MX，其大部分活性可能归因于MX。EMX的氧化形式，(E)-2-氯-3-(二氯甲基)-丁二酸（ox-EMX），仅在SOS色测试验中略有活性。所有这些化合物都是直接作用的诱变剂，在有代谢激活（S9混合物）的情况下，它们不会产生诱变性。MX的氧化形式，(Z)-2-氯-3-(二氯甲基)-丁二酸（ox-MX），在所测试的剂量水平下不具有诱变性。MX没有在小鼠骨髓中诱导微核。

/GENOTOXICITY/ The mutagenic activities of the chlorinated butenoic acids recently identified in chlorinated drinking waters were determined by the Salmonella microsome assay and by the SOS chromotest. The Salmonella typhimurium tester strains TA97, TA98 and TA100 were used without and with S9 mix. In the SOS chromotest Escherichia coli PQ37 was used as an indicator organism with and without metabolic activation. In addition, the extremely potent Ames test mutagen (Z)-2-chloro-3-(dichloromethyl)-4-oxobutenoic acid (MX, in the open form), was studied by the micronucleus test with mice using intraperitoneal treatment. The results of the Salmonella assay and the SOS chromotest showed that MX was by far the most potent mutagen of the compounds tested. Mutations were also induced by the reduced form of MX, (Z)-2-chloro-3-(dichloromethyl)-4-hydroxybut-2-enoic acid (red-MX), and by the geometric isomer of MX, (E)-2-chloro-3-(dichloromethyl)-4-oxobutenoic acid (EMX). However, since the solution of EMX contained approximately 5% MX, most of its activity might be attributable to MX. The oxidised form of EMX, (E)-2-chloro-3-(dichloromethyl)-butenedioic acid (ox-EMX), was marginally active in the SOS chromotest only. All these compounds were directly acting mutagens and in the presence of metabolic activation (S9 mix) they did not generate mutagenicity. The oxidized form of MX, (Z)-2-chloro-3-(dichloromethyl)-butenedioic acid (ox-MX), was not mutagenic at the dose levels tested. MX did not induce micronuclei in the bone marrow of mice.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

遗传毒性：通过 Ames 致突变性实验，测定了来自芬兰26个地区的自来水中的致突变剂3-氯-4-(二氯甲基)-5-羟基-2(5H)-呋喃酮（MX）及其几何异构体E-2-氯-3-(二氯甲基)-4-氧代丁烯酸（E-MX）的浓度。在用消毒剂处理过的23个自来水样本中，TA100菌株呈阳性反应。除了3个边缘活性的提取物外，所有表现出致突变性的提取物中均检测到了MX和E-MX。MX占观察到的致突变性的15-57%（平均为33%）。E-MX的浓度略低于相应的MX浓度。致突变性与MX和E-MX的浓度之间存在线性相关性，MX的相关系数为0.894，E-MX的相关系数为0.910。

/GENOTOXICITY/ The Ames mutagenicity and the concentration of the strong Ames mutagen 3-chloro-4-(dichloro-methyl)-5-hydroxy-2(5H)-furanone (MX) and its geometric isomer E-2-chloro-3-(dichloromethyl)-4-oxobutenoic acid (E-MX) ... were determined in XAD extracts of tap water collected from 26 localities in Finland. The 23 tap waters treated with disinfectants gave a positive response in strain TA100. MX and E-MX were detected in all extracts exhibiting mutagenicity with the exception of 3 extracts of marginal activity. MX accounted for 15-57% (average 33%) of the observed mutagenicity. The concentration of E-MX was slightly lower than the corresponding concentration of MX. Linear correlations were observed between mutagenicity and concentration of MX and E-MX, with correlation coefficients of 0.894 for MX and 0.910 for E-MX.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

遗传毒性... 强致突变剂3-氯-4-(二氯甲基)-5-羟基-2(5H)-呋喃酮(MX)及其几何异构体E-2-氯-3-(二氯甲基)-4-氧代丁烯酸(E-MX)已被发现在氯化饮水中存在。MX约占整体突变活性的30%，而E-MX仅占几个百分点。MX和E-MX在水中的稳定性较差，会发生pH依赖的异构化（MX与E-MX之间达到平衡）和水解降解。... MX类似物3-氯-4-(二氯甲基)-2(5H)-呋喃酮(红-MX)和2-氯-3-(二氯甲基)-2-丁二酸(氧-MX)也已在氯化水中被识别。然而，这些化合物的相对较低的致突变性表明，它们对氯化水整体致突变性的贡献仅为中等程度。

/GENOTOXICITY/ ... The strong Ames mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2 (5H)-furanone (MX) and its geometric isomer E-2-chloro-3-(dichloromethyl)-4-oxobutenoic acid (E-MX) have been shown to be present in chlorinated drinking waters. MX accounts for approximately 30% and E-MX for a few percent of the overall mutagenicity. MX and E-MX are unstable in water and undergo both pH dependent isomerization (MX in equilibrium E-MX) and hydrolytic degradation. ... The MX analogues 3-chloro-4-(dichloromethyl)-2 (5H)-furanone (red-MX) and 2-chloro-3-(dichloromethyl)-2-butenedioic acid (ox-MX) have also been identified in chlorinated water. However, the relatively low mutagenicity of these compounds suggests that their contribution to the overall mutagenicity of chlorinated water is of only moderate significance.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

遗传毒性/ 对几种氯代丁烯酸进行了突变活性测试...在 Salmonella typhimurium 测试菌株 TA98、TA100 和 TA104 中进行了测定... 不加 S9 混合液。调查结果显示，(Z)-2-氯-3-(二氯甲基)-4-氧代丁烯酸（MX，开链形式）是所测试化合物中最强的诱变剂。然而，许多与 MX 结构相似的化合物也能诱导大量突变。总的来说，除了丁二酸外，所有化合物在碱基对替换菌株（TA100、TA104）和移码突变菌株 TA98 的测试中都具有诱变性，其中在 TA100 菌株中观察到的诱变反应最强。当 MX 和 2-氯-3-(氯甲基)-4-氧代丁烯酸（CMCF，开链形式）中的醛基被二氯甲基取代时，TA98 和 TA104 菌株的诱变反应发生了变化。/得出/结论，由于这种取代，发生了移码突变。TA104 诱变性的增加表明腺嘌呤可能是这类化合物的靶点。进一步支持这种可能性的证据是一些氯代丁烯酸可以识别出的改性腺嘌呤加合物的存在。

/GENOTOXICITY/ The mutagenic activities of several chlorinated butenoic acids ...were determined /in/ ... the Salmonella typhimurium tester strains TA98, TA100, and TA104 ... without S9 mix. The results from the investigation showed that (Z)-2-chloro-3-(dichloromethyl)-4-oxobutenoic acid (MX, in the open form) was the most potent mutagen of the compounds tested. However, a significant number of mutations was also induced by compounds with structural similarities to MX. In general, all the compounds, except the butenedioic acids, were mutagenic in the assays for both base-pair substitution strains (TA100, TA104) and for the frameshift strain TA98, with the highest mutagenic response observed in strain TA100. When the aldehyde group of MX and of 2-chloro-3-(chloromethyl)-4-oxobutenoic acid (CMCF, in the open form) was replaced by a dichloromethyl group, the mutagenic response in strains TA98 and TA104 changed. /It was/ concluded that a frame-shift mutation occurred because of the replacement. The increase of the TA104 mutagenicity suggested that adenosine could be the target for these types of compounds. Further evidence for such possibility were the modified adenosine adducts /that could be identified/ for some chlorinated butenoic acids.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为产物：
  描述：

  L-酪氨酸 生成 (E)-2-Chloro-3-(dichloromethyl)-4-oxobutenoic acid
  参考文献：
  名称：

  HORTH, H., AQUA, 38,(1989) N, C. 80-100

  摘要：

  DOI：

文献信息

• Possible reaction pathways for the formation of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX)
  作者：Vivi-Ann Långvik、Osmo Hormi

  DOI：10.1016/0045-6535(94)90329-8

  日期：1994.3

  Three compounds, 3,4,5-trimethoxybenzaldehyde (I), 1-dichloromethyl-3,4,5-trimethoxy-benzene (II) and 3,4,5-trimethoxyphenylacetic acid (III) were treated with aqueous chlorine at pH 2. Aqueous chlorination of the three compounds increased the formation of MX (3-chloro-4-dichloromethyl-5(2H)-hydroxy-furanone) and E-MX (E 2-chloro-3-dichloromethyl-4-oxo-butenoic acid) in the order I > II > III. By H-1-NMR spectroscopy and gas chromatography it was shown that II hydrolizes readily to I in water. It is known that III is converted to II in chlorination reactions. We suggest that the (formed) aldehyde group remains intact during the formation of MX and E-MX from these three compounds. They could thus form MX and E-MX, via similar mechanisms. This suggested mechanism may also occur when phenolic precursor structures present in humic material are treated with chlorine in the process of drinking water production.
• HORTH, H., AQUA, 38,(1989) N, C. 80-100
  作者：HORTH, H.

  DOI：——

  日期：——