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Computational study on hydroxybenzotriazoles as reagents for ester hydrolysis.
V Praveen Kumar1, Bishwajit Ganguly, Santanu Bhattacharya
1Department of Organic Chemistry, Indian Institute of Science, Bangalore, India 560 012.
The Journal of Organic Chemistry
|December 4, 2004
Summary
1-Hydroxybenzotriazole derivatives show esterolytic activity, with compound 4 being the most effective catalyst. Computational studies revealed that while electron-withdrawing groups lower pK(a) and enhance catalytic activity, they also reduce nucleophilicity, leading to only modest improvements.
Area of Science:
- Organic Chemistry
- Computational Chemistry
- Physical Chemistry
Background:
- 1-Hydroxybenzotriazole derivatives are known to exhibit esterolytic activity.
- The deprotonated anionic forms are the reactive species in ester hydrolysis.
- Understanding the nucleophilic character of these compounds is crucial for catalyst design.
Purpose of the Study:
- To investigate the esterolytic activity of 1-hydroxybenzotriazole derivatives.
- To computationally rationalize the nucleophilic character of these compounds.
- To correlate computational predictions with experimental findings.
Main Methods:
- Experimental esterolysis assays using p-nitrophenyl diphenyl phosphate (PNPDPP) and p-nitrophenyl hexanoate (PNPH).
- Ab initio/DFT computational studies including RHF and B3LYP methods with 6-31G and 6-31+G basis sets.
- Calculation of free energy of protonation (fep), free energy of solvation (DeltaG(aq)), pK(a) values, and natural charge analysis.
Main Results:
- Compound 4 demonstrated the highest catalytic activity in hydrolyzing PNPDPP and PNPH.
- Computational results accurately predicted the experimental findings.
- Electron-withdrawing substituents lowered pK(a) and fep, increasing the concentration of active anionic forms, but also decreased charge density on the active oxygen atom.
Conclusions:
- The esterolytic activity of 1-hydroxybenzotriazole derivatives is influenced by a balance between pK(a) and nucleophilicity.
- While substituents can modulate activity, the parent compound and its derivatives show only modest differences in ester cleaving capacity.
- Computational methods provide reliable predictions for catalyst design.