雜環胺基甲基吡啶縮胺衍生物暨其配位化學之研究

Synthesis and Reactivity of Picolyl Heterocyclic Amino Aminals and Their Coordination Chemistry

林雅凡(Ya-Fan Lin)

指導教授 ： 陳竹亭

國立臺灣大學/理學院/化學研究所/博士(2008年)

https://doi.org/10.6342/NTU.2008.00649

摘要

在醛與胺的亞胺化反應中，半縮胺被視為其反應中間體，半縮胺在常態下並不穩定，因而不容易被偵測。另一方面，亞胺具高親電子性而容易進行親核加成反應，然而其加成後的產物—縮胺，在溶液的研究也不多見。
本論文的研究成功合成四種雜環胺基甲基吡啶縮胺—APYL1, APYL2, APML1, APML2。這類縮胺對溶液環境的變化十分敏感，因此藉由觀測在不同極性溶劑和酸鹼環境中，以及進行水解與加成反應後，本研究能仔細地了解縮胺的形成與分解，也能觀察到相關的中間體與產物，進一步建立起縮胺、亞胺、與半縮胺之間的反應路徑，並測量相關的平衡常數。
在溶液中，雜環胺基甲基吡啶縮胺與其對應的亞胺呈現平衡狀態；若以含水醇類為溶劑，則可偵測到半縮胺的存在。然而移除醇類溶劑之後，固態縮胺能被分離與鑑定。
所偵測到的半縮胺可以藉由與金屬配位而單離出來，半縮胺配基（CPYL1, CPYL2）之錯合物對中心金屬十分敏感，藉由配位能使錯合物中心金屬被氧化，或使配位基團被氧化。在空氣的條件下，半縮胺（CPYL1, CPML1）與二價鈷離子配位後，中心金屬會被氧化成低自旋之三價鈷錯合物；而與二價銅離子配位後，半縮胺配位基（CPYL1, CPML1）會進一步氧化、水解成羧基配位子（Pca）。
密度泛函理論計算結構優選化與偶極矩計算的結果顯示，亞胺化合物IPYL2，相對於含芳香基團亞胺有更高的親電子性，使其更易於進行親核基加成。同時由結構優選化的計算結果指出：所得到的縮胺產物能形成三組分子內氫鍵，使結構穩定，其中包含一組次甲基氫與氮的作用力，能抑止縮胺進行消去反應。
本研究以1H 和 13C 核磁共振、一維旋轉座標系NOE技術、電灑游離法質譜, 快速原子撞擊質譜、紫外光/可見光吸收光譜、紅外線光譜、X射線繞射等技術，輔以密度泛函理論之結構優選化、單點計算、分子軌域分析、密度泛函核磁共振化學位移計算、及時間相關密度泛函等計算，做為分析鑑定之方法。比較實驗與計算的結果，兩者呈現高度一致性。

關鍵字

縮胺 ； 半縮胺 ； 亞胺 ； 配位化學 ； 密度泛函理論

並列摘要

In the reactions of conventional imine formation via condensation of aldehyde with amine, carbinolamines are considered as the unstable intermediates upon the formation of Schiff bases from amine and carbonyl. Direct observation for carbinolamine under the ambient conditions is rare. On the other hand, imines are well studies and known to be subject to nucleophilic addition. However, the resulting aminals adducts are relatively poorly investigated.
In this dissertation, the synthesis and characterization of a series of 2-picolyl pyridyl (APYL1: N-pyridyl, APYL2: N-6-picolyl) and pyrimidyl amino (APML1: N-pyrimidyl, APML2: N-3,5-dimethylpyrimidyl) aminals are described. We revealed that these aminals are sensitive to the change of the solution conditions. Therefore, we inspected the formation and the decomposition of the aminals with regard to the solvent effect, pH dependence, hydrolysis, and nucleophilic addition. In the reactions of aminal hydrolysis, resulting in the imine products, we have successfully detected the carbinolamine intermediates. In the reactions of nucleophilic additions of aminals, new aminal adducts are derived. The equilibrium between 2-picolyl heterocyclic amino and their corresponding imine are solvent-dependent. Carbinolamine may be observed in wet methanol. However, they reverse to aminal after evaporation and dryness
The DFT calculations for geometry optimization results provide the information about the stability and the reactivity of the 2- picolyl amino heterocyclic aminals. By computing the molecular dipole moment the heterocyclic imine IPYL2 demonstrates higher electrophilicity than aromatic substituted imines. Analysis of the DFT optimized structure indicates that aminals can be stabilized by forming three intramolecular hydrogen bonds. The interaction between methine proton and pyridyl nitrogen could protect aminals against deamination.
The carbinolamine intermediates are stabilized via coordination with metal ions. The 2-picolyl- amino heterocyclic carbinolamine ligands, CPYL1 and CPML1, are susceptible to the metal centers. In the aerobic oxidation, it is found that exposing CoIICPML1b may be oxidized to the CoIIICPML1b’. In the presence of oxidants, bivalent CuIICPML1b undergoes ligand oxidation and hydrolysis to produce Cu(Pca)2, wherein Pca=C5H4NCOO-.
In this work, we have utilized the combination of theoretical calculation and experimental data to characterize structures and analyze results and in most cases they agreed with each other. The experimental techniques are involved in 1H and 13C NMR, 1-D ROESY, ESI-MS, FAB-MS, UV-Vis, IR and X-Ray spectroscopy study. The theoretical results are performed by geometrical optimization, single point calculation, molecular orbital analysis, DFT- NMR calculation, and TD-DFT calculation.

並列關鍵字

Carbinolamine ； Aminal,Schiff Base ； Coordination Chemistry ； Density Functional Theory

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