Kumar V Praveen, Ganguly Bishwajit, Bhattacharya Santanu
Department of Organic Chemistry, Indian Institute of Science, Bangalore, India 560 012.
J Org Chem. 2004 Dec 10;69(25):8634-42. doi: 10.1021/jo049539w.
1-Hydroxybenzotriazole (1) and several of its derivatives (2-5) demonstrate potent esterolytic activity toward activated esters such as p-nitrophenyl diphenyl phosphate (PNPDPP) and p-nitrophenyl hexanoate (PNPH) in cationic micelles at pH 8.2 and 25 degrees C. The deprotonated anionic forms of such reagents act as reactive species in the hydrolysis of ester. To rationalize the origin of their nucleophilic character, a detailed ab initio/DFT computational study has been performed on 1-5 along with additional hydroxybenzotriazole derivatives (6-13). The geometries of 1-hydroxybenzotriazoles (1-13) and their corresponding bases are discussed in detail. All calculations were carried out using different methods, i.e., restricted Hartree-Fock (RHF) and hybrid ab initio/DFT (B3LYP) using 6-31G and 6-31+G basis sets. Free energy of protonation ("fep") of the 1-hydroxybenzotriazoles (1-13), free energy of solvation DeltaG(aq), and the corresponding pK(a) values have been calculated. Solvation-free energies were calculated using density functional theory and the polarizable continuum model. In addition, to examine the reliability of calculated fep, benzaldehyde oxime (14) and 2-methyl propionaldehyde oxime (15) have been computed as reference systems using different methods and basis sets, the experimental feps of which are known. Our experimental finding shows that the compound 4 is the most effective catalyst for the hydrolytic cleavages of PNPDPP and PNPH. This has been predicted from our calculated fep, pK(a), and natural charge analysis results as well. In general, the introduction of electron-withdrawing substituents on 1-hydroxybenzotriazoles facilitates the lowering of pK(a) and fep. As the pK(a) values are lowered, a greater percentage of such hydroxybenzotriazoles remain in their deprotonated, anionic forms at pH 8.2. Since the anionic forms are nucleophilic, pK(a) lowering should enhance their ester cleaving capacity. However, such substitution also decreases the charge density on the catalytically active oxido atom (O(7)). Taking these two factors together, the derivatives are only modestly better nucleophiles in comparison to the parent 1-hydroxybenzotriazole. Interestingly, the introduction of electron-donating groups does not significantly enhance the charge accumulation on the oxido atom (O(7)) of 1-hydroxybenzotriazoles.
1-羟基苯并三唑（1）及其几种衍生物（2 - 5）在pH 8.2和25℃的阳离子胶束中，对诸如对硝基苯基二苯基磷酸酯（PNPDPP）和对硝基苯基己酸酯（PNPH）等活性酯表现出强大的酯解活性。这些试剂的去质子化阴离子形式在酯的水解中充当活性物种。为了阐明它们亲核特性的来源，对1 - 5以及其他羟基苯并三唑衍生物（6 - 13）进行了详细的从头算/密度泛函理论（DFT）计算研究。详细讨论了1-羟基苯并三唑（1 - 13）及其相应碱的几何结构。所有计算均使用不同方法进行，即使用6 - 31G和6 - 31 + G基组的受限Hartree - Fock（RHF）和混合从头算/DFT（B3LYP）方法。计算了1-羟基苯并三唑（1 - 13）的质子化自由能（“fep”）、溶剂化自由能ΔG(aq)以及相应的pK(a)值。使用密度泛函理论和可极化连续介质模型计算了无溶剂化能。此外，为了检验计算得到的fep的可靠性，已使用不同方法和基组将苯甲醛肟（14）和2-甲基丙醛肟（15）作为参考体系进行了计算，其实验fep是已知的。我们的实验发现表明，化合物4是PNPDPP和PNPH水解裂解最有效的催化剂。这也已从我们计算得到的fep、pK(a)和自然电荷分析结果中预测出来。一般来说，在1-羟基苯并三唑上引入吸电子取代基有助于降低pK(a)和fep。随着pK(a)值降低，在pH 8.2时，此类羟基苯并三唑以去质子化阴离子形式存在的比例更大。由于阴离子形式具有亲核性，pK(a)降低应会增强它们的酯裂解能力。然而，这种取代也会降低催化活性氧化原子（O(7)）上的电荷密度。综合考虑这两个因素，与母体1-羟基苯并三唑相比，这些衍生物只是适度更好的亲核试剂。有趣的是，引入供电子基团并不会显著增强1-羟基苯并三唑氧化原子（O(7)）上的电荷积累。
