trans-2-phenoxy-6-carbethoxytetrahydropyran | 133754-25-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: trans-2-phenoxy-6-carbethoxytetrahydropyran
• 英文别名: ethyl (2R,6S)-6-phenoxyoxane-2-carboxylate
• CAS: 133754-25-3
• 化学式: C₁₄H₁₈O₄
• 分子量: 250.295
• InChiKey: FDUQTOLPGDYPIY-CHWSQXEVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-ethoxy-6-carbethoxytetrahydropyran 、 sodium phenoxide 在 盐酸 作用下， 生成 trans-2-phenoxy-6-carbethoxytetrahydropyran
  参考文献：
  名称：

  Intramolecular general-acid and electrostatic catalysis in acetal hydrolysis. Hydrolysis of 2-(substituted phenoxy)-6-carboxytetrahydropyrans and 2-alkoxy-6-carboxytetrahydropyrans

  摘要：

  Rate constants have been determined for hydrolysis of a series of trans-2-(substituted phenoxy)-6-carboxytetrahydropyrans (e,a) in H2O and 50% dioxane-H2O. The second-order rate constant (k2) for the apparent hydronium ion catalyzed reaction of the anionic species of the p-nitro derivative in 50% dioxane-H2O (50-degrees-C) is 620-fold larger than the second-order rate constant for hydrolysis of 2-(p-nitrophenoxy)tetrahydropyran. The slope (rho) of the Hammett plot of log k2 vs sigma is approximately 0, which supports a mechanism involving intramolecular general-acid catalysis by the un-ionized carboxyl group with proton transfer to the leaving group oxygen. Sizable catalytic effects can therefore be obtained in an intramolecular general-acid-catalyzed reaction when the leaving group is sufficiently good, even though the steric fit is poor and proton transfer may necessarily occur via an intervening water molecule. Intramolecular general-acid-catalyzed ring opening is not a favorable process in the hydrolysis of tetrahydropyranyl acetals; such a mechanism does not occur in the hydrolysis of 2-alkoxy-6-carboxytetrahydropyrans. In the pH-independent decomposition of 2-(p-nitrophenoxy)-6-carboxytetrahydropyran at pH > 6, the neighboring carboxylate anion participates electrostatically in 50% dioxane-H2O and gives a 10-fold rate enhancement. The plot of log k(obsd) vs pH for hydrolysis of 2-(o-carboxyphenoxy)-6-carboxytetrahydropyran is bell shaped, which indicates that the monoanionic species is maximally reactive. The rate enhancement in that reaction in comparison with the hydrolysis of 2-(p-carboxyphenoxy)-6-carboxytetrahydropyran or 2-(p-carboxyphenoxy)tetrahydropyran is a factor of (2-4) x 10(3) in H2O but is 10(4)-10(5) in 50% dioxane-H2O. The o-carboxyl group acts as an intramolecular general acid. However, bifunctional catalysis does not take place in this system. The lack of efficient electrostatic facilitation of these reactions by a neighboring carboxylate anion is most likely due to the energy expenditure required for the 6-carboxylate group to approach the developing oxocarbonium ion closely. There is no chemical support for proposed mechanisms of lysozyme-catalyzed reactions that involve intracomplex general-acid-catalyzed opening of an unstrained hexose ring or large electrostatic stabilization effects by Asp-52.

  DOI：

  10.1021/ja00020a028

文献信息

• Intramolecular general-acid and electrostatic catalysis in acetal hydrolysis. Hydrolysis of 2-(substituted phenoxy)-6-carboxytetrahydropyrans and 2-alkoxy-6-carboxytetrahydropyrans
  作者：Thomas H. Fife、Stuart H. Jaffe、R. Natarajan

  DOI：10.1021/ja00020a028

  日期：1991.9

  Rate constants have been determined for hydrolysis of a series of trans-2-(substituted phenoxy)-6-carboxytetrahydropyrans (e,a) in H2O and 50% dioxane-H2O. The second-order rate constant (k2) for the apparent hydronium ion catalyzed reaction of the anionic species of the p-nitro derivative in 50% dioxane-H2O (50-degrees-C) is 620-fold larger than the second-order rate constant for hydrolysis of 2-(p-nitrophenoxy)tetrahydropyran. The slope (rho) of the Hammett plot of log k2 vs sigma is approximately 0, which supports a mechanism involving intramolecular general-acid catalysis by the un-ionized carboxyl group with proton transfer to the leaving group oxygen. Sizable catalytic effects can therefore be obtained in an intramolecular general-acid-catalyzed reaction when the leaving group is sufficiently good, even though the steric fit is poor and proton transfer may necessarily occur via an intervening water molecule. Intramolecular general-acid-catalyzed ring opening is not a favorable process in the hydrolysis of tetrahydropyranyl acetals; such a mechanism does not occur in the hydrolysis of 2-alkoxy-6-carboxytetrahydropyrans. In the pH-independent decomposition of 2-(p-nitrophenoxy)-6-carboxytetrahydropyran at pH > 6, the neighboring carboxylate anion participates electrostatically in 50% dioxane-H2O and gives a 10-fold rate enhancement. The plot of log k(obsd) vs pH for hydrolysis of 2-(o-carboxyphenoxy)-6-carboxytetrahydropyran is bell shaped, which indicates that the monoanionic species is maximally reactive. The rate enhancement in that reaction in comparison with the hydrolysis of 2-(p-carboxyphenoxy)-6-carboxytetrahydropyran or 2-(p-carboxyphenoxy)tetrahydropyran is a factor of (2-4) x 10(3) in H2O but is 10(4)-10(5) in 50% dioxane-H2O. The o-carboxyl group acts as an intramolecular general acid. However, bifunctional catalysis does not take place in this system. The lack of efficient electrostatic facilitation of these reactions by a neighboring carboxylate anion is most likely due to the energy expenditure required for the 6-carboxylate group to approach the developing oxocarbonium ion closely. There is no chemical support for proposed mechanisms of lysozyme-catalyzed reactions that involve intracomplex general-acid-catalyzed opening of an unstrained hexose ring or large electrostatic stabilization effects by Asp-52.