Related Experiment Videos
Modeling of protonation processes in acetohydroxamic acid
Munoz-Caro1, Nino, Senent
1Departamento de Quimica, Facultad de CyTA y Ciencias Quimicas, Universidad de Burgos, Misael Banuelos, 09001 Burgos, Spain.
The Journal of Organic Chemistry
|May 18, 2000
Summary
This theoretical study reveals acetohydroxamic acid's amide form is more stable. Protonation preferentially occurs at the carbonyl oxygen, yielding a more stable species than nitrogen protonation.
Area of Science:
- Computational Chemistry
- Quantum Chemistry
- Molecular Modeling
Background:
- Acetohydroxamic acid is a compound with potential pharmaceutical applications.
- Understanding its tautomeric equilibria and protonation behavior is crucial for its chemical and biological activity.
- Previous studies have explored aspects of its structure and reactivity, but a comprehensive theoretical investigation of its protonation energetics was lacking.
Purpose of the Study:
- To theoretically investigate the tautomeric stability of acetohydroxamic acid.
- To characterize the protonation sites and determine the protonation energies (proton affinities) of acetohydroxamic acid.
- To quantify the gas-phase basicity and analyze the thermodynamic stability of different protonated forms.
Main Methods:
- Ab initio computational methodology was employed, specifically the MP2(FC)/cc-pdVZ level of theory.
- A three-dimensional conformational study was performed on the most stable tautomer.
- Electrostatic potential distribution was analyzed to identify potential electrophilic attack sites.
- A statistical model was developed to quantify gas-phase basicity (DeltaG).
Main Results:
- The amide tautomer of acetohydroxamic acid is found to be more stable than the imidic tautomer by less than 1.0 kcal mol(-1).
- Intramolecular hydrogen bonding was characterized in the amide form.
- The carbonyl oxygen and nitrogen atoms were identified as the primary protonation sites.
- Proton affinities were calculated as 203.4 kcal mol(-1) for carbonyl oxygen protonation and 194.5 kcal mol(-1) for nitrogen protonation.
- The carbonyl oxygen protonated form is thermodynamically more stable (by 8.3 kcal mol(-1) at 298.15 K and 1 atm) due to enthalpic contributions.
Conclusions:
- Acetohydroxamic acid predominantly exists in its amide tautomeric form.
- Protonation at the carbonyl oxygen is energetically favored over protonation at the nitrogen atom.
- The theoretical findings provide valuable insights into the chemical reactivity and acid-base properties of acetohydroxamic acid.