Computational Study on Hydroxybenzotriazoles as Reagents for Ester Hydrolysis

Kumar, Praveen V and Ganguly, Bishwajit and Bhattacharya, Santanu (2004) Computational Study on Hydroxybenzotriazoles as Reagents for Ester Hydrolysis. In: Journal of Organic Chemistry, 69 (25). pp. 8634-8642.

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Abstract

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°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 $\Delta$$G$$_a_q,$ 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. of electron-donating groups does not significantly enhance the charge accumulation on the oxido atom $(O_7)$ of 1-hydroxybenzotriazoles.

Item Type:	Journal Article
Publication:	Journal of Organic Chemistry
Publisher:	American Chemical Society
Additional Information:	The copyright of this article belongs to American Chemical Society.
Department/Centre:	Division of Chemical Sciences > Organic Chemistry
Date Deposited:	25 Aug 2008
Last Modified:	19 Sep 2010 04:25
URI:	http://eprints.iisc.ac.in/id/eprint/6111

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