1,3-bis(4-methoxybenzyl)-4,5-bis(4-methylphenyl)-1H-imidazol-3-ium chloride | 1428619-79-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1,3-bis(4-methoxybenzyl)-4,5-bis(4-methylphenyl)-1H-imidazol-3-ium chloride
• CAS: 1428619-79-7
• 化学式: C₃₃H₃₃N₂O₂*Cl
• 分子量: 525.09
• InChiKey: ZRTFLGXNDNAQAR-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  3.84
• 重原子数：
  38.0
• 可旋转键数：
  8.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  27.27
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  1,3-bis(4-methoxybenzyl)-4,5-bis(4-methylphenyl)-1H-imidazol-3-ium chloride 、 silver(I) acetate 以 二氯甲烷 为溶剂， 反应 48.0h， 以56%的产率得到1,3-bis(4-methoxylbenzyl)-4,5-bis(4-methylphenyl)-1H-imidazole-2-ylidene silver(I) acetate
  参考文献：
  名称：

  Synthesis and biological evaluation of N-heterocyclic carbene–silver(I) acetate complexes derived from 4,5-ditolyl-imidazole

  摘要：

  From the reaction of 1,2-bis-(4-methylphenyl) ethane-1,2-dione with formamide, symmetrically substituted 4,5-bis-(4-methylphenyl)-1H-imidazole (1) was synthesised and further reacted with p-benzyl substituted halides to give the symmetrically substituted N-heterocyclic carbene (NHC) precursors 1a-e.The NHC precursors were then reacted with silver(I) acetate to yield NHC-silver(I) acetate complexes 1,3-bis-(benzyl)-4,5-bis-(4-methylphenyl)-imidazole-2-ylidene silver(I) acetate (2a), 1,3-bis-(4-methylbenzyl)-4,5-bis-(4-methylphenyl)-imidazole-2-ylidene silver(I) acetate (2b), 1,3-bis-(4-methoxylbenzyl)-4, 5-bis-(4-methylphenyl)-imidazole-2-ylidene silver(I) acetate (2c), 1,3-bis-(4-methoxycarbonylbenzyl)-4, 5-bis-(4-methylphenyl)-imidazole-2-ylidene silver(I) acetate (2d) and 1,3-bis-(4-cyanobenzyl)-4,5-bis-(4-methylphenyl)-imidazole-2-ylidene silver(I) acetate (2e).Two NHC-silver acetate complexes 2a and 2e were characterised by single crystal X-ray diffraction. The preliminary in vitro antibacterial activity of the NHC-silver complexes 2a-e was investigated against Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Escherichia coli using the qualitative Kirby-Bauer disk-diffusion method. The areas of clearance determined for the maximum dose (4.3 mu M) range between 1 mm and 7 mm for MSSA and 0 mmand 7 mm for E. coli. All of the newly synthesised silver(I) acetate complexes were tested for their cytotoxicity by MTT based in vitro tests on the human renal cancer cell line Caki-1 and human breast cancer cell line MCF-7 in order to determine their IC50 values. The NHC-silver complexes 2a-e were found to have IC50 values of 3.0 (+/-0.6), 0.51 (+/-0.07), 4.2 (+/-1.2), 9.0 (+/-0.6), 26 (+/-2) mu M, against the renal cancer cell-line Caki-1 and IC50 values of 2.3 (+/-0.4), 1.4 (+/-0.2), 3.0 (+/-0.5), 3.4 (+/-1.2) and 14 (+/-2) mu M against the breast cancer cell line MCF-7, respectively. Compared to our lead compound SBC3 (1,3-bisbenzyl-4,5-bisphenyl-imidazole-2-ylium silver(I) acetate) (IC50 value = 14 (+/-1) mu M against Caki-1 and 5.8 (+/-0.6) mu M against MCF-7) these values represent improved cytotoxicity against both cell lines, especially for the silver complexes 2a and 2b. These two compounds are not only more active than SBC3 but also exhibit in the case of 2b a 7 times higher biological activity than cisplatin (IC50 value = 3.3 mu M) against Caki-1. (C) 2012 Elsevier B. V. All rights reserved.

  DOI：

  10.1016/j.ica.2012.10.029
• 作为产物：
  描述：

  4,4'-二甲基联苯甲酰 在 sodium hydrogen sulfate 、 nitrosomethane 、 potassium carbonate 、 sodium hydroxide 作用下， 以 水 、 乙腈 为溶剂， 反应 48.0h， 生成 1,3-bis(4-methoxybenzyl)-4,5-bis(4-methylphenyl)-1H-imidazol-3-ium chloride
  参考文献：
  名称：

  Synthesis and biological evaluation of N-heterocyclic carbene–silver(I) acetate complexes derived from 4,5-ditolyl-imidazole

  摘要：

  From the reaction of 1,2-bis-(4-methylphenyl) ethane-1,2-dione with formamide, symmetrically substituted 4,5-bis-(4-methylphenyl)-1H-imidazole (1) was synthesised and further reacted with p-benzyl substituted halides to give the symmetrically substituted N-heterocyclic carbene (NHC) precursors 1a-e.The NHC precursors were then reacted with silver(I) acetate to yield NHC-silver(I) acetate complexes 1,3-bis-(benzyl)-4,5-bis-(4-methylphenyl)-imidazole-2-ylidene silver(I) acetate (2a), 1,3-bis-(4-methylbenzyl)-4,5-bis-(4-methylphenyl)-imidazole-2-ylidene silver(I) acetate (2b), 1,3-bis-(4-methoxylbenzyl)-4, 5-bis-(4-methylphenyl)-imidazole-2-ylidene silver(I) acetate (2c), 1,3-bis-(4-methoxycarbonylbenzyl)-4, 5-bis-(4-methylphenyl)-imidazole-2-ylidene silver(I) acetate (2d) and 1,3-bis-(4-cyanobenzyl)-4,5-bis-(4-methylphenyl)-imidazole-2-ylidene silver(I) acetate (2e).Two NHC-silver acetate complexes 2a and 2e were characterised by single crystal X-ray diffraction. The preliminary in vitro antibacterial activity of the NHC-silver complexes 2a-e was investigated against Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Escherichia coli using the qualitative Kirby-Bauer disk-diffusion method. The areas of clearance determined for the maximum dose (4.3 mu M) range between 1 mm and 7 mm for MSSA and 0 mmand 7 mm for E. coli. All of the newly synthesised silver(I) acetate complexes were tested for their cytotoxicity by MTT based in vitro tests on the human renal cancer cell line Caki-1 and human breast cancer cell line MCF-7 in order to determine their IC50 values. The NHC-silver complexes 2a-e were found to have IC50 values of 3.0 (+/-0.6), 0.51 (+/-0.07), 4.2 (+/-1.2), 9.0 (+/-0.6), 26 (+/-2) mu M, against the renal cancer cell-line Caki-1 and IC50 values of 2.3 (+/-0.4), 1.4 (+/-0.2), 3.0 (+/-0.5), 3.4 (+/-1.2) and 14 (+/-2) mu M against the breast cancer cell line MCF-7, respectively. Compared to our lead compound SBC3 (1,3-bisbenzyl-4,5-bisphenyl-imidazole-2-ylium silver(I) acetate) (IC50 value = 14 (+/-1) mu M against Caki-1 and 5.8 (+/-0.6) mu M against MCF-7) these values represent improved cytotoxicity against both cell lines, especially for the silver complexes 2a and 2b. These two compounds are not only more active than SBC3 but also exhibit in the case of 2b a 7 times higher biological activity than cisplatin (IC50 value = 3.3 mu M) against Caki-1. (C) 2012 Elsevier B. V. All rights reserved.

  DOI：

  10.1016/j.ica.2012.10.029