2,6-Bis(2-phenyl-4,5,6,7-tetrahydrobenzopyrazol-3-yl)pyridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2,6-Bis(2-phenyl-4,5,6,7-tetrahydrobenzopyrazol-3-yl)pyridine
• 英文别名: 2-Phenyl-3-[6-(2-phenyl-4,5,6,7-tetrahydroindazol-3-yl)pyridin-2-yl]-4,5,6,7-tetrahydroindazole
• 化学式: C₃₁H₂₉N₅
• 分子量: 471.605
• InChiKey: LYKOWUCFMZVGSK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  36
• 可旋转键数：
  4
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  48.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2,6-Bis<(2-oxocyclohexanyl)carbonyl>pyridine 、 苯肼 以 氯仿 为溶剂， 以48%的产率得到2,6-Bis(2-phenyl-4,5,6,7-tetrahydrobenzopyrazol-3-yl)pyridine
  参考文献：
  名称：

  Chelation-Controlled Regioselectivity in the Synthesis of Substituted Pyrazolylpyridine Ligands. 2. Tridentates

  摘要：

  A new, more reliable synthesis of tetraketone 4 was found. With (t)BuNHNH(2), PhNHNH(2), and 4-hydrazinobenzoic acid, it condensed to give mostly in,in-disubstituted derivatives (7ii-9ii) of the parent, C-linked 2,6-bis(pyrazol-3-yl)pyridine 5, along with some in,out materials. MeNHNH(2) also provided some out,out isomer (6oo). This same derivative was also produced by NaH-mediated methylation of 5 with CH3I, presumably via a Na+ chelate that disallowed access to the inner pyrazole nitrogens, and was able, as a tridentate, to solubilize solid sodium picrate (NaPic) into CDCl3, with H-1-NMR detection of the complex. In contrast, the bidentate in,out isomer did not solubilize NaPic. Similarly, ethyl bromoacetate produced 10oo and it also solubilized NaPic. Previously reported alkylations of 5 had also given out,out products that bound alkali metal ions. 10oo was hydrolyzed to the disalt 13oo. In the presence of ZnCl2, 1 reacted with PhNHNH(2) to give the out,out derivative 8oo, presumably through a metal-mediated activation of the inner carbonyls of 1. Though 8oo also solubilized NaPic, a better NMR spectrum was obtained by treatment with CF3COOD, which indicated multidentate binding of D+. The same phenomenon was also observed with the out,out diester 1 loo, which was obtained by the nucleophilic aromatic substitution by 5 of ethyl 4-fluorobenzoate, presumably via a Kf chelate that also disallowed in substitution. A mono-out-substituted product 12 was also isolated from this reaction. Apart from mechanistic arguments and the ability or inability to dissolve NaPic, the aromatic H-1-NMR regions were diagnostic of the regiochemistries: In all cases, the pyridine H-3/5 doublet lay upfield of the H-4 triplet for in,in. isomers and downfield for out,out isomers, while in,out isomers showed one doublet on either side of the triplet. The binding of Na+ or D+ by the out,out isomers resulted in shifts of the H-3/5 doublets to upfield positions. The deuteration of in,in isomers did not. This situation was analogous to that of the bidentates reported in the accompanying paper and was similarly interpreted in conformational terms, with support from MM2 calculations: Like terpyridine, the imino nitrogens of the out,out materials prefer anti orientations due to electronic and steric repulsions (calculated Delta G(syn-anti) > 2.7 kcal/mol between rotamers about each pyridine-pyrazole bond in 6oo and 7oo and about the out-substituted pyrazole-pyridine bonds of 6io and 7io), but they are forced into syn orientations upon binding Na+ or D+. This induces a shielding interaction between the pyridine H-3/5 and neighboring CH2 groups. This same shielding is present in any conformation of the in,in products and of the in-substituted side of in,out isomers, which are much closer in energy (/Delta G(syn-anti)/ less than or equal to 0.4 kcal/mol for any ring-ring bond in 6ii and 7ii and for the in-substituted pyrazole-pyridine bonds of 6io and 7io).

  DOI：

  10.1021/jo00086a029

文献信息

• Chelation-Controlled Regioselectivity in the Synthesis of Substituted Pyrazolylpyridine Ligands. 2. Tridentates
  作者：Patrick van der Valk、Pierre G. Potvin

  DOI：10.1021/jo00086a029

  日期：1994.4

  A new, more reliable synthesis of tetraketone 4 was found. With (t)BuNHNH(2), PhNHNH(2), and 4-hydrazinobenzoic acid, it condensed to give mostly in,in-disubstituted derivatives (7ii-9ii) of the parent, C-linked 2,6-bis(pyrazol-3-yl)pyridine 5, along with some in,out materials. MeNHNH(2) also provided some out,out isomer (6oo). This same derivative was also produced by NaH-mediated methylation of 5 with CH3I, presumably via a Na+ chelate that disallowed access to the inner pyrazole nitrogens, and was able, as a tridentate, to solubilize solid sodium picrate (NaPic) into CDCl3, with H-1-NMR detection of the complex. In contrast, the bidentate in,out isomer did not solubilize NaPic. Similarly, ethyl bromoacetate produced 10oo and it also solubilized NaPic. Previously reported alkylations of 5 had also given out,out products that bound alkali metal ions. 10oo was hydrolyzed to the disalt 13oo. In the presence of ZnCl2, 1 reacted with PhNHNH(2) to give the out,out derivative 8oo, presumably through a metal-mediated activation of the inner carbonyls of 1. Though 8oo also solubilized NaPic, a better NMR spectrum was obtained by treatment with CF3COOD, which indicated multidentate binding of D+. The same phenomenon was also observed with the out,out diester 1 loo, which was obtained by the nucleophilic aromatic substitution by 5 of ethyl 4-fluorobenzoate, presumably via a Kf chelate that also disallowed in substitution. A mono-out-substituted product 12 was also isolated from this reaction. Apart from mechanistic arguments and the ability or inability to dissolve NaPic, the aromatic H-1-NMR regions were diagnostic of the regiochemistries: In all cases, the pyridine H-3/5 doublet lay upfield of the H-4 triplet for in,in. isomers and downfield for out,out isomers, while in,out isomers showed one doublet on either side of the triplet. The binding of Na+ or D+ by the out,out isomers resulted in shifts of the H-3/5 doublets to upfield positions. The deuteration of in,in isomers did not. This situation was analogous to that of the bidentates reported in the accompanying paper and was similarly interpreted in conformational terms, with support from MM2 calculations: Like terpyridine, the imino nitrogens of the out,out materials prefer anti orientations due to electronic and steric repulsions (calculated Delta G(syn-anti) > 2.7 kcal/mol between rotamers about each pyridine-pyrazole bond in 6oo and 7oo and about the out-substituted pyrazole-pyridine bonds of 6io and 7io), but they are forced into syn orientations upon binding Na+ or D+. This induces a shielding interaction between the pyridine H-3/5 and neighboring CH2 groups. This same shielding is present in any conformation of the in,in products and of the in-substituted side of in,out isomers, which are much closer in energy (/Delta G(syn-anti)/ less than or equal to 0.4 kcal/mol for any ring-ring bond in 6ii and 7ii and for the in-substituted pyrazole-pyridine bonds of 6io and 7io).