N-(Pivaloyloxy)-2-(acetylamino)fluorene | 153524-18-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: N-(Pivaloyloxy)-2-(acetylamino)fluorene
• 英文别名: [acetyl(9H-fluoren-2-yl)amino] 2,2-dimethylpropanoate
• CAS: 153524-18-6
• 化学式: C₂₀H₂₁NO₃
• 分子量: 323.392
• InChiKey: OPQUPQPNJLYMJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  谷胱甘肽 、 N-(Pivaloyloxy)-2-(acetylamino)fluorene 在 sodium perchlorate 作用下， 以 乙腈 为溶剂， 生成 4-乙酰氨基联苯 、 4-(N-acetylamino)-4'-(glutathion-S-yl)biphenyl 、 4-(N-acetylamino)-3-(glutathion-S-yl)biphenyl 、 (E)-4-(4-acetylamino)-2-(glutathion-S-yl)-1-phenyl-3,5-cyclohexadien-1-ol 、 (Z)-4-(4-acetylamino)-2-(glutathion-S-yl)-1-phenyl-3,5-cyclohexadien-1-ol
  参考文献：
  名称：

  谷胱甘肽与N-芳基异羟肟酸致癌酯的反应

  摘要：

  N-(磺基氧基)-N-乙酰基-2-氨基芴 (1a) 和 N-(磺基氧基)-N-乙酰基-4-氨基联苯 (1b) 水解产生的氮莠离子 7a 和 7b 被谷胱甘肽阴离子 (GS -) 选择性比率 kgs-/ks 分别为 8200 ± 600 M-1 和 300 ± 15 M-1。由于在我们的反应条件下这两种离子的 ks 都是已知的，因此可以计算 kgs−。对于 7a，kgs− 是 6.3 × 108 M-1 s-1，对于 7b，kgs− 是 1.8 × 109 M-1 s-1。在生理条件下（50-100 μM GS-），两种离子都不会被 GS- 有效捕获。本研究中分离出的一些 GSH 加合物（1a 中的 4 个，1b 中的 11 和 12 个）并非来自氮离子捕获。它们来自于喹诺亚胺 8a 和 8b 的 GS 捕获，它们是 H2O 捕获 7a 和 7b 的初始产物。该反应在生理 GS 浓度下非常有效，并可能导致体内

  DOI：

  10.1021/ja9534563
• 作为产物：
  描述：

  羟基乙酰氨基芴 、 三甲基乙酰氯 在 N-乙基吗啉 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以80%的产率得到N-(Pivaloyloxy)-2-(acetylamino)fluorene
  参考文献：
  名称：

  Nucleophilic aromatic substitution on ester derivatives of carcinogenic N-arylhydroxamic acids by aniline and N,N-dimethylaniline

  摘要：

  Decomposition of N-(pivaloyloxy)-2-(acetylamino)fluorene (1b) and N-(sulfonatooxy)-4-(acetylamino)-biphenyl (2a) in MeOH occurs predominately via N-0 bond cleavage to yield oxazoles (5, 6, 23), methoxy adducts (7,8,24,25,26), and rearrangement products (10b,11b,28). Minor ester methanolysis paths lead to the N-arylhydroxamic acids (9, 27). In the presence of 0.1 M aniline (3), 1b yields a number of adducts (14-18) identical to those previously obtained from the reaction of 3 with N-(sulfonatooxy)-2-(acetylamino)fluorene (1a). This occurs with no change in the rate constant for decomposition of 1b. At 0.1 M 3 all solvolysis products of 1b, except the rearrangement products 10 band 11b, are reduced below detectable levels. Similar results were obtained for 2a, which yields the adducts 30-35 in the presence of 3 and 36-38 in the presence of N,N-dimethylaniline (4). These results are consistent with a mechanism (Scheme V) in which the N-O bond heterolysis leads to a tight ion pair that can undergo internal return to yield the rearrangement products or diffusional separation to yield the free ion. The free nitrenium ion can be trapped by solvent or added nucleophiles. Both the N-acetyl-N-(4-biphenylyl)nitrenium ion (45) and the N-acetyl-N-(2-fluorenyl)nitrenium ion (48) react slowly enough with the solvent to undergo selective reaction with strong nucleophiles. Since 1a, 1b, and 2a span the reactivity range of the ester derivatives of the common N-arylhydroxamic acids which undergo N-O bond heterolysis in H2O, it appears that all of the carcinogenic esters will react with simple aromatic amines via an S(N)1 mechanism.

  DOI：

  10.1021/jo00079a028

文献信息

• Nucleophilic aromatic substitution on ester derivatives of carcinogenic N-arylhydroxamic acids by aniline and N,N-dimethylaniline
  作者：Michael Novak、Kanchugarakoppal S. Rangappa、Rebecca K. Manitsas

  DOI：10.1021/jo00079a028

  日期：1993.12

  Decomposition of N-(pivaloyloxy)-2-(acetylamino)fluorene (1b) and N-(sulfonatooxy)-4-(acetylamino)-biphenyl (2a) in MeOH occurs predominately via N-0 bond cleavage to yield oxazoles (5, 6, 23), methoxy adducts (7,8,24,25,26), and rearrangement products (10b,11b,28). Minor ester methanolysis paths lead to the N-arylhydroxamic acids (9, 27). In the presence of 0.1 M aniline (3), 1b yields a number of adducts (14-18) identical to those previously obtained from the reaction of 3 with N-(sulfonatooxy)-2-(acetylamino)fluorene (1a). This occurs with no change in the rate constant for decomposition of 1b. At 0.1 M 3 all solvolysis products of 1b, except the rearrangement products 10 band 11b, are reduced below detectable levels. Similar results were obtained for 2a, which yields the adducts 30-35 in the presence of 3 and 36-38 in the presence of N,N-dimethylaniline (4). These results are consistent with a mechanism (Scheme V) in which the N-O bond heterolysis leads to a tight ion pair that can undergo internal return to yield the rearrangement products or diffusional separation to yield the free ion. The free nitrenium ion can be trapped by solvent or added nucleophiles. Both the N-acetyl-N-(4-biphenylyl)nitrenium ion (45) and the N-acetyl-N-(2-fluorenyl)nitrenium ion (48) react slowly enough with the solvent to undergo selective reaction with strong nucleophiles. Since 1a, 1b, and 2a span the reactivity range of the ester derivatives of the common N-arylhydroxamic acids which undergo N-O bond heterolysis in H2O, it appears that all of the carcinogenic esters will react with simple aromatic amines via an S(N)1 mechanism.
• Reactions of Glutathione with Carcinogenic Esters of <i>N</i>-Arylhydroxamic Acids
  作者：Michael Novak、Jing Lin

  DOI：10.1021/ja9534563

  日期：1996.1.1

  this study (4 from 1a, 11 and 12 from 1b) are not derived from nitrenium ion trapping. They arise from GS- trapping of the quinol imines 8a and 8b, which are the initial products of trapping of 7a and 7b by H2O. This reaction is very efficient at physiological GS- concentrations and could lead to significant GSH depletion in vivo. Although it has been known for some time that quinol imines such as

  N-(磺基氧基)-N-乙酰基-2-氨基芴 (1a) 和 N-(磺基氧基)-N-乙酰基-4-氨基联苯 (1b) 水解产生的氮莠离子 7a 和 7b 被谷胱甘肽阴离子 (GS -) 选择性比率 kgs-/ks 分别为 8200 ± 600 M-1 和 300 ± 15 M-1。由于在我们的反应条件下这两种离子的 ks 都是已知的，因此可以计算 kgs−。对于 7a，kgs− 是 6.3 × 108 M-1 s-1，对于 7b，kgs− 是 1.8 × 109 M-1 s-1。在生理条件下（50-100 μM GS-），两种离子都不会被 GS- 有效捕获。本研究中分离出的一些 GSH 加合物（1a 中的 4 个，1b 中的 11 和 12 个）并非来自氮离子捕获。它们来自于喹诺亚胺 8a 和 8b 的 GS 捕获，它们是 H2O 捕获 7a 和 7b 的初始产物。该反应在生理 GS 浓度下非常有效，并可能导致体内