1,4-dihydroxy-2,3-bis(3',5'-dimethylpyrazol-1'-yl)benzene | 123834-57-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1,4-dihydroxy-2,3-bis(3',5'-dimethylpyrazol-1'-yl)benzene
• 英文别名: 1,4-dihydroxy-2,3-bis(3,5-dimethylpyrazol-1'-yl)benzene；2,3-bis(3,5-dimethyl-1H-pyrazol-1-yl)benzene-1,4-diol；2,3-Bis(3,5-dimethylpyrazol-1-yl)benzene-1,4-diol
• CAS: 123834-57-1
• 化学式: C₁₆H₁₈N₄O₂
• 分子量: 298.345
• InChiKey: GXEOMTLNPFCXRA-UHFFFAOYSA-N

物化性质

• 沸点：
  513.3±50.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  76.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,4-dihydroxy-2,3-bis(3',5'-dimethylpyrazol-1'-yl)benzene 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以85%的产率得到2,3-bis(3,5-dimethyl-1H-pyrazol-1-yl)cyclohexa-2,5-diene-1,4-dione
  参考文献：
  名称：

  Cytotoxicity and reactivity of a redox active 1,4-quinone-pyrazole compound and its Ru(II)-p-cymene complex

  摘要：

  Quinone based compounds display activation in hypoxia, an environment prevalent in tumours. We have synthesized a bis(pyrazole) based 1,4-quinone compound suitable for metal chelation. The quinone (L2) converted to hydroquinone (H(2)L1) during the complex synthesis leading to [Ru-II(eta(6)-p-cym)(H(2)L1)Cl](PF6) (1). We found from 'FINMR studies that in the methanolic solution L2 stoichiometrically converted to H(2)L1 while oxidizing the methanol to formaldehyde. L2 crystallized in monoclinic space group I2/a while complex 1 crystallizes in P2(1)/c. Cyclic voltammetry of the redox non-innocent L2 showed quasi-reversible (Delta Ep = 67 mV) redox behaviour with E-1/2 at 0.12 V w.r.t. NHE. Complex 1 is stable at pH 7.4 in presence of 4 mM chloride and does not hydrolyse even up to 24 h. L2 showed IC50, values of 155 and 123 mu M against metastatic breast adenocarcinoma (MDA-MB231) and pancreatic carcinoma (MIA PaCa-2) respectively. L2 gets activated by ca. 2.7-fold in hypoxia against MIA PaCa-2 cells. The mechanistic studies showed ROS accumulation and oxidation of NADH to NAD(+), which may be responsible for the cytotoxicity. The reactivity studies showed that conversion to hydroquinone by reaction with NADH or glutathione is irreversible. Complex 1 is not cytotoxic up to 100 mu M in normoxia or hypoxia. Complex 1 displays irreversible redox behavior in cyclic voltammetry displaying two overlapping oxidation peaks at 1.00 and 1.57 V w.r.t. NHE, which may be assigned to the conversion of hydroquinone to quinone and Ru-II -> Ru-III respectively.

  DOI：

  10.1016/j.ica.2019.119361
• 作为产物：
  描述：

  2,3-bis(3,5-dimethyl-1H-pyrazol-1-yl)cyclohexa-2,5-diene-1,4-dione 在 还原型辅酶Ⅰ 作用下， 以 aq. phosphate buffer 、 氘代甲醇 为溶剂， 生成 1,4-dihydroxy-2,3-bis(3',5'-dimethylpyrazol-1'-yl)benzene
  参考文献：
  名称：

  Cytotoxicity and reactivity of a redox active 1,4-quinone-pyrazole compound and its Ru(II)-p-cymene complex

  摘要：

  Quinone based compounds display activation in hypoxia, an environment prevalent in tumours. We have synthesized a bis(pyrazole) based 1,4-quinone compound suitable for metal chelation. The quinone (L2) converted to hydroquinone (H(2)L1) during the complex synthesis leading to [Ru-II(eta(6)-p-cym)(H(2)L1)Cl](PF6) (1). We found from 'FINMR studies that in the methanolic solution L2 stoichiometrically converted to H(2)L1 while oxidizing the methanol to formaldehyde. L2 crystallized in monoclinic space group I2/a while complex 1 crystallizes in P2(1)/c. Cyclic voltammetry of the redox non-innocent L2 showed quasi-reversible (Delta Ep = 67 mV) redox behaviour with E-1/2 at 0.12 V w.r.t. NHE. Complex 1 is stable at pH 7.4 in presence of 4 mM chloride and does not hydrolyse even up to 24 h. L2 showed IC50, values of 155 and 123 mu M against metastatic breast adenocarcinoma (MDA-MB231) and pancreatic carcinoma (MIA PaCa-2) respectively. L2 gets activated by ca. 2.7-fold in hypoxia against MIA PaCa-2 cells. The mechanistic studies showed ROS accumulation and oxidation of NADH to NAD(+), which may be responsible for the cytotoxicity. The reactivity studies showed that conversion to hydroquinone by reaction with NADH or glutathione is irreversible. Complex 1 is not cytotoxic up to 100 mu M in normoxia or hypoxia. Complex 1 displays irreversible redox behavior in cyclic voltammetry displaying two overlapping oxidation peaks at 1.00 and 1.57 V w.r.t. NHE, which may be assigned to the conversion of hydroquinone to quinone and Ru-II -> Ru-III respectively.

  DOI：

  10.1016/j.ica.2019.119361

文献信息

• A hydroquinone based palladium catalyst for room temperature nitro reduction in water
  作者：Alok Kumar、Kallol Purkait、Suman Kr. Dey、Amrita Sarkar、Arindam Mukherjee

  DOI：10.1039/c4ra06547f

  日期：——

  A Pd^II–hydroquinone complex shows efficient catalytic reduction of aromatic nitro compounds in water at room temperature followed by Suzuki–Miyaura coupling.

  一种Pd^II-对苯二酚配合物在室温下在水中显示出高效催化还原芳香族硝基化合物，随后进行Suzuki-Miyaura偶联反应。
• Intramolecular Valence and Spin Interaction in<i>meso</i>and<i>rac</i>Diastereomers of a<i>p</i>-Quinonoid-Bridged Diruthenium Complex
  作者：Doyel Kumbhakar、Biprajit Sarkar、Somnath Maji、Shaikh M. Mobin、Jan Fiedler、Francisco A. Urbanos、Reyes Jiménez-Aparicio、Wolfgang Kaim、Goutam Kumar Lahiri

  DOI：10.1021/ja807043s

  日期：2008.12.24

  (L(2-))-bridged Ru(IV)Ru(III)} situation nor with an Ru(III)(mu-L(*-))Ru(III)} three-spin arrangement with up-down-up spin configuration in the ground state, which would result in metal-centered spin through antiferromagnetic coupling between the adjacent individual spins. Only the Ru(III)(mu-L(*-))Ru(III)} situation, with up-up-down spin configuration, leads to ligand-centered resulting spin through

  配合物 meso- 和 rac-[(acac)2Ru(mu-L)Ru(acac)2]n, 1 和 2，其中 L(2-) = 1,4-dioxido-2,3-bis(3, 5-二甲基吡唑-1'-基）苯和 acac- = 2,4-pentanedionato，在可接近的氧化还原状态（n = 0, +, -, 2-)。由于空间干扰，中性化合物包含严重扭曲的 L(2-) 桥接配体，在对苯二酚二价阴离子的平面和邻位吡唑基取代基的平面之间具有 43-48 度的二面角。内消旋异构体和外消旋异构体之间的差异在氧化还原电位（外消旋形式 2 更容易氧化和还原）和氧化态的吸收光谱方面相当显着。磁化率和 EPR 测量证实了中性物质的 Ru(III)(mu-L(2-))Ru(III)} 构型，显示自旋-自旋的 J 值为 -37 和 -21 cm(-1) ca之间的相互作用。7.75 A 分离的金属中心分别位于 1
• Reaction of pyrazole addition to quinones
  作者：Paloma Ballesteros、Rosa M. Claramunt、Consuelo Escolastico、M. Dolores Santa Maria、Jose Elguero

  DOI：10.1021/jo00032a048

  日期：1992.3

  The reactions of pyrazole, 4-nitropyrazole, 3,5-dimethylpyrazole, and 4-chloro-3,5-dimethylpyrazole with 1,4-benzoquinone in dioxane have been analyzed. Mono- and 2,3-bis-adducts were obtained and only in the case of pyrazole was a 2,5-bis(pyrazol-1-yl)-1,4-dihydroxybenzene formed. Further oxidation of the mono- and bis-adducts with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) afforded the quinones, which in turn added 1 mol of azole (pyrazole and imidazole) to yield tetrapyrazolylquinols. Nitration of the 2,3-bis(pyrazol-1-yl)- and 2,3-bis(3,5-dimethylpyrazol-1-yl)-1,4-dihydroxybenzenes has been performed to prepare the corresponding 4-nitropyrazolyl derivatives.
• Catalán, Javier; Fabero, Fernando; Soledad Guijarro, Journal of the American Chemical Society, 1990, vol. 112, # 2, p. 747 - 759
  作者：Catalán, Javier、Fabero, Fernando、Soledad Guijarro、Claramunt, Rosa M.、Dolores Santa María、De la Concepción Foces-Foces、Cano, Felix Hernández、Elguero, José、Sastre, Roberto

  DOI：——

  日期：——
• Cytotoxicity and reactivity of a redox active 1,4-quinone-pyrazole compound and its Ru(II)-p-cymene complex
  作者：Kallol Purkait、Arindam Mukherjee

  DOI：10.1016/j.ica.2019.119361

  日期：2020.3

  Quinone based compounds display activation in hypoxia, an environment prevalent in tumours. We have synthesized a bis(pyrazole) based 1,4-quinone compound suitable for metal chelation. The quinone (L2) converted to hydroquinone (H(2)L1) during the complex synthesis leading to [Ru-II(eta(6)-p-cym)(H(2)L1)Cl](PF6) (1). We found from 'FINMR studies that in the methanolic solution L2 stoichiometrically converted to H(2)L1 while oxidizing the methanol to formaldehyde. L2 crystallized in monoclinic space group I2/a while complex 1 crystallizes in P2(1)/c. Cyclic voltammetry of the redox non-innocent L2 showed quasi-reversible (Delta Ep = 67 mV) redox behaviour with E-1/2 at 0.12 V w.r.t. NHE. Complex 1 is stable at pH 7.4 in presence of 4 mM chloride and does not hydrolyse even up to 24 h. L2 showed IC50, values of 155 and 123 mu M against metastatic breast adenocarcinoma (MDA-MB231) and pancreatic carcinoma (MIA PaCa-2) respectively. L2 gets activated by ca. 2.7-fold in hypoxia against MIA PaCa-2 cells. The mechanistic studies showed ROS accumulation and oxidation of NADH to NAD(+), which may be responsible for the cytotoxicity. The reactivity studies showed that conversion to hydroquinone by reaction with NADH or glutathione is irreversible. Complex 1 is not cytotoxic up to 100 mu M in normoxia or hypoxia. Complex 1 displays irreversible redox behavior in cyclic voltammetry displaying two overlapping oxidation peaks at 1.00 and 1.57 V w.r.t. NHE, which may be assigned to the conversion of hydroquinone to quinone and Ru-II -> Ru-III respectively.