N-acetyl-4′-amino-4-nitrodiphenylmethane | 6665-60-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-acetyl-4′-amino-4-nitrodiphenylmethane
• 英文别名: N'-acetyl-4'-amino-4-nitrodiphenylmethane；4-Acetylamino-4'-nitro-diphenylmethan；4-Nitro-4'-acetylamino-diphenylmethan；4-Acetamino-4'-nitro-diphenylmethan；4-Nitro-4'-acetamino-diphenylmethan；4-Nitro-4'-acetaminodiphenylmethan；N-[4-[(4-nitrophenyl)methyl]phenyl]acetamide
• CAS: 6665-60-7
• 化学式: C₁₅H₁₄N₂O₃
• 分子量: 270.288
• InChiKey: RKUQIGNXRBKWNX-UHFFFAOYSA-N

物化性质

• 熔点：
  162 °C
• 沸点：
  506.8±38.0 °C(Predicted)
• 密度：
  1.264±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-acetyl-4′-amino-4-nitrodiphenylmethane 在 盐酸 、 sodium carbonate 作用下， 以 乙醇 、 水 为溶剂， 反应 3.0h， 以90%的产率得到4-(4-硝基苄基)苯胺
  参考文献：
  名称：

  合成方法获得4,4'-亚甲基二苯基二异氰酸酯的氨基酸加合物

  摘要：

  4,4'-亚甲基二苯基二异氰酸酯（MDI）是化学工业中最重要的异氰酸酯。暴露于MDI后，肺部过敏和哮喘是主要的损害类型。MDI的白蛋白加合物可能与致敏反应的病因有关。因此，必须有敏感的和特定的生物标记物，例如血液蛋白加合物，以监测暴露于异氰酸酯的人。为了发现体内存在的血液蛋白与新的异氰酸酯加合物，需要新的合成标准品。为此，我们开发了五种方法来获得MDI的氨基酸加合物。我们合成并分离了天冬氨酸，谷氨酸，半胱氨酸和缬氨酸的MDI加合物。新的加合物通过LC-MS / MS和NMR进行表征。我们合成了相应的同位素标记的MDI加合物，以开发使用LC-MS / MS的分析方法。异氰酸酯的谷胱甘肽加合物是将反应性异氰酸酯转移到远离原始暴露部位的较远部位的一种重要方式。因此，我们使用了MDI的N-乙酰基-半胱氨酸加成物：N-乙酰基-S [[[4-（4-氨基苄基）苯基]氨基甲酰基]-半胱氨酸（MDI-AcCys）和N-乙酰基-S

  DOI：

  10.1021/tx300347e
• 作为产物：
  描述：

  N-乙酰基-4,4'-二氨基二苯基甲烷 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以80%的产率得到N-acetyl-4′-amino-4-nitrodiphenylmethane
  参考文献：
  名称：

  Synthesis and Quantification of DNA Adducts of 4,4‘-Methylenedianiline

  摘要：

  4,4'-Methylenedianiline (MDA) is used as a hardener in the manufacture of plastics and polyurethanes. MDA has been classified as a carcinogen in animals and is a suspected human carcinogen. Assuming that MDA would yield similar DNA adducts to other arylamines, we synthesized the following C-8 guanine adducts: N'-acetyl-N-(deoxyguanosin-8-yl)-MDA, N-(deoxyguanosin-8-yl)-MDA, N-(deoxyguanosin-8-yl)-4MA, and their corresponding 3'-monophosphate derivatives. We developed methods to identify these adducts of MDA in liver DNA using P-32-postlabeling, HPLC, and GC-MS techniques. Liver DNA was obtained from rats treated with radiolabeled MDA (1.11 and 116.5 mu mol/kg body weight). The total radioactivity bound to the DNA corresponded to 0.06 and 2.7 adducts per 10(7) nucleotides [covalent binding index (CBI=(mu mol of adduct per mol of nucleotide)/(mmol of compound per kg body weight)) of 1.05 and 2.3]. This DNA-binding potency is in the range of weakly genotoxic compounds. The liver DNA was analyzed for the presence of the synthesized adducts by the following methods: (I) HPLC analysis of nucleotides and purines after enzymatic and acid hydrolysis, and (II) P-32-postlabeling after enzymatic hydrolysis. The major adducts found in vivo did not correspond to the synthesized standards. Further work was carried out to determine the structure of the unidentified adducts. It was possible to release MDA and MDA-d(4) from DNA of rats dosed with MDA and/or MDA-d(4) and from the synthesized adducts using strong base hydrolysis. Liver of two female Wistar rats given 500 mu mol/kg MDA . 2HCl was hydrolyzed in 0.1 M NaOH overnight at 110 degrees C. GC-MS analysis of the heptafluorobutyric anhydride derivatized dichloromethane extracts detected 428+/-40 fmol of MDA/mg of DNA. In the control animals no MDA was found. The experiment was repeated with livers from animals dosed 500 mu mol/kg MDA-d(4) . 2HCl. In these rats 488+/-19 fmol MDA-d(4) was found to be bound at liver DNA. Taking into account a 68% yield of the method, the CBI found in these cases was 0.82 and 1.0, respectively.

  DOI：

  10.1021/tx950194+

文献信息

• Synthesis and Quantification of DNA Adducts of 4,4‘-Methylenedianiline
  作者：Dietrich Schütze、Peter Sagelsdorff、Ovnair Sepai、Gabriele Sabbioni

  DOI：10.1021/tx950194+

  日期：1996.1.1

  4,4'-Methylenedianiline (MDA) is used as a hardener in the manufacture of plastics and polyurethanes. MDA has been classified as a carcinogen in animals and is a suspected human carcinogen. Assuming that MDA would yield similar DNA adducts to other arylamines, we synthesized the following C-8 guanine adducts: N'-acetyl-N-(deoxyguanosin-8-yl)-MDA, N-(deoxyguanosin-8-yl)-MDA, N-(deoxyguanosin-8-yl)-4MA, and their corresponding 3'-monophosphate derivatives. We developed methods to identify these adducts of MDA in liver DNA using P-32-postlabeling, HPLC, and GC-MS techniques. Liver DNA was obtained from rats treated with radiolabeled MDA (1.11 and 116.5 mu mol/kg body weight). The total radioactivity bound to the DNA corresponded to 0.06 and 2.7 adducts per 10(7) nucleotides [covalent binding index (CBI=(mu mol of adduct per mol of nucleotide)/(mmol of compound per kg body weight)) of 1.05 and 2.3]. This DNA-binding potency is in the range of weakly genotoxic compounds. The liver DNA was analyzed for the presence of the synthesized adducts by the following methods: (I) HPLC analysis of nucleotides and purines after enzymatic and acid hydrolysis, and (II) P-32-postlabeling after enzymatic hydrolysis. The major adducts found in vivo did not correspond to the synthesized standards. Further work was carried out to determine the structure of the unidentified adducts. It was possible to release MDA and MDA-d(4) from DNA of rats dosed with MDA and/or MDA-d(4) and from the synthesized adducts using strong base hydrolysis. Liver of two female Wistar rats given 500 mu mol/kg MDA . 2HCl was hydrolyzed in 0.1 M NaOH overnight at 110 degrees C. GC-MS analysis of the heptafluorobutyric anhydride derivatized dichloromethane extracts detected 428+/-40 fmol of MDA/mg of DNA. In the control animals no MDA was found. The experiment was repeated with livers from animals dosed 500 mu mol/kg MDA-d(4) . 2HCl. In these rats 488+/-19 fmol MDA-d(4) was found to be bound at liver DNA. Taking into account a 68% yield of the method, the CBI found in these cases was 0.82 and 1.0, respectively.
• Synthetic Approaches To Obtain Amino Acid Adducts of 4,4′-Methylenediphenyl Diisocyanate
  作者：Gabriele Sabbioni、Nagaraju Dongari、Siegfried Schneider、Anoop Kumar

  DOI：10.1021/tx300347e

  日期：2012.12.17

  obtain amino acid adducts of MDI. We synthesized and isolated MDI adducts of aspartic acid, glutamic acid, cysteine, and valine. The new adducts were characterized by LC-MS/MS and NMR. We synthesized the corresponding isotope-labeled MDI adducts to develop analytical methods using LC-MS/MS. Glutathione adducts of isocyanates are an important way of transportation of the reactive isocyanates to distant

  4,4'-亚甲基二苯基二异氰酸酯（MDI）是化学工业中最重要的异氰酸酯。暴露于MDI后，肺部过敏和哮喘是主要的损害类型。MDI的白蛋白加合物可能与致敏反应的病因有关。因此，必须有敏感的和特定的生物标记物，例如血液蛋白加合物，以监测暴露于异氰酸酯的人。为了发现体内存在的血液蛋白与新的异氰酸酯加合物，需要新的合成标准品。为此，我们开发了五种方法来获得MDI的氨基酸加合物。我们合成并分离了天冬氨酸，谷氨酸，半胱氨酸和缬氨酸的MDI加合物。新的加合物通过LC-MS / MS和NMR进行表征。我们合成了相应的同位素标记的MDI加合物，以开发使用LC-MS / MS的分析方法。异氰酸酯的谷胱甘肽加合物是将反应性异氰酸酯转移到远离原始暴露部位的较远部位的一种重要方式。因此，我们使用了MDI的N-乙酰基-半胱氨酸加成物：N-乙酰基-S [[[4-（4-氨基苄基）苯基]氨基甲酰基]-半胱氨酸（MDI-AcCys）和N-乙酰基-S