Methyl 1-<(benzyloxy)methyl>-5-(1,3-dioxolan-2-yl)-imidazole-4-carboxylate | 141849-12-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: Methyl 1-<(benzyloxy)methyl>-5-(1,3-dioxolan-2-yl)-imidazole-4-carboxylate
• 英文别名: methyl 5-(1,3-dioxolan-2-yl)-1-(phenylmethoxymethyl)imidazole-4-carboxylate
• CAS: 141849-12-9
• 化学式: C₁₆H₁₈N₂O₅
• 分子量: 318.329
• InChiKey: NZZRHDTWLHMNRR-UHFFFAOYSA-N

物化性质

• 沸点：
  502.3±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)：
  1.89
• 重原子数：
  23.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  71.81
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  Methyl 1-<(benzyloxy)methyl>-5-(1,3-dioxolan-2-yl)-imidazole-4-carboxylate 在 盐酸 、 肼 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 24.5h， 生成 (1H)-Imidazo<4,5-d>pyriddazine-4(5H)-one
  参考文献：
  名称：

  Multifunctionalization of imidazole via sequential halogen-metal exchange: a new route to purine-ring analogs

  摘要：

  A new method for the synthesis of purine-ring analogs based upon the sequential halogen-metal exchange functionalization of 1-[(benzyloxy)methyl]-2,4,5-triiodoimidazole (1) has been developed and is illustrated by the synthesis of (1H)-imidazo[4,5-d]pyridazin-4(5H)-one (2-aza-3-deazahypoxanthine, 8). Treatment of 1 with BuLi followed by quench with PhSSPh afforded the 2-(phenylthio) derivative, which upon treatment with BuLi followed by quench with DMF gave the 5-carboxaldehyde. This aldehyde was converted into its ethylene acetal, which was treated with BuLi followed by quench with ClCO2CH3 to afford a 4-(methoxycarbonyl)imidazole. Removal of the phenylthio group with Al(Hg) and the (benzyloxy)methyl and ethylene acetal protecting groups concomitantly with 3 M HCl afforded methyl 5(4)-formylimidazole-4(5)-carboxylate, which underwent cyclo-condensation with ethanolic NH2NH2 to give target 8. This synthetic approach was found amenable to modification by efficient ''one-pot'' multistep transformations. Thus, treatment of 1 with (a) BuLi, (b) (CH3)3SiCl, (c) BuLi, (d) (CH3)2NN(CH3)CHO, (e) BuLi, and (f) (CH3OCO)2O afforded the N-protected 4-(methoxycarbonyl)-imidazole-5-carboxaldehyde (13) in 25% yield directly from 1. Imidazole 13 was then elaborated to 8 in two steps. 1-Formyl-1,2,2-trimethylhydrazine is a recommended replacement for DMF as a tandem formylating/ortho-metalation directing agent.

  DOI：

  10.1021/jo00040a011
• 作为产物：
  描述：

  1-<(Benzyloxy)methyl>-4,5-diiodo-2-(phenylthio)imidazole 在 吡啶 、 aluminum amalgam 、 正丁基锂 、 对甲苯磺酸 作用下， 以 乙醇 、 苯 为溶剂， 反应 9.0h， 生成 Methyl 1-<(benzyloxy)methyl>-5-(1,3-dioxolan-2-yl)-imidazole-4-carboxylate
  参考文献：
  名称：

  Multifunctionalization of imidazole via sequential halogen-metal exchange: a new route to purine-ring analogs

  摘要：

  A new method for the synthesis of purine-ring analogs based upon the sequential halogen-metal exchange functionalization of 1-[(benzyloxy)methyl]-2,4,5-triiodoimidazole (1) has been developed and is illustrated by the synthesis of (1H)-imidazo[4,5-d]pyridazin-4(5H)-one (2-aza-3-deazahypoxanthine, 8). Treatment of 1 with BuLi followed by quench with PhSSPh afforded the 2-(phenylthio) derivative, which upon treatment with BuLi followed by quench with DMF gave the 5-carboxaldehyde. This aldehyde was converted into its ethylene acetal, which was treated with BuLi followed by quench with ClCO2CH3 to afford a 4-(methoxycarbonyl)imidazole. Removal of the phenylthio group with Al(Hg) and the (benzyloxy)methyl and ethylene acetal protecting groups concomitantly with 3 M HCl afforded methyl 5(4)-formylimidazole-4(5)-carboxylate, which underwent cyclo-condensation with ethanolic NH2NH2 to give target 8. This synthetic approach was found amenable to modification by efficient ''one-pot'' multistep transformations. Thus, treatment of 1 with (a) BuLi, (b) (CH3)3SiCl, (c) BuLi, (d) (CH3)2NN(CH3)CHO, (e) BuLi, and (f) (CH3OCO)2O afforded the N-protected 4-(methoxycarbonyl)-imidazole-5-carboxaldehyde (13) in 25% yield directly from 1. Imidazole 13 was then elaborated to 8 in two steps. 1-Formyl-1,2,2-trimethylhydrazine is a recommended replacement for DMF as a tandem formylating/ortho-metalation directing agent.

  DOI：

  10.1021/jo00040a011