Tautomerism in pyridazin-3(2H)-one: a theoretical study using implicit/explicit solvation models

Area of Science:

• Computational Chemistry
• Organic Chemistry
• Physical Chemistry

Background:

• Pyridazin-3(2H)-one and pyridazin-3-ol exist as tautomers.
• Understanding their interconversion is crucial for predicting chemical behavior.

Purpose of the Study:

• To theoretically investigate the tautomeric conversion of pyridazin-3(2H)-one to pyridazin-3-ol.
• To compare the energetics of different reaction mechanisms and solvent effects.

Main Methods:

• Density Functional Theory (DFT) calculations at the B3LYP/6-311++G** level.
• Analysis of two distinct hydrogen transfer mechanisms: direct transfer and dimer-mediated double transfer.
• Evaluation of implicit, explicit, and combined solvation models using polar protic and aprotic solvents.

Main Results:

• Direct hydrogen transfer via TS12 exhibits a high activation energy (42.64 kcal/mol) due to strain in the four-membered transition state.
• Dimer-mediated double hydrogen transfer via TS1122 requires significantly lower activation energy (14.66 kcal/mol).
• Solvation studies indicate that protic polar solvents are necessary to reduce the activation energy for the direct transfer mechanism.

Conclusions:

• The dimer-mediated mechanism is kinetically favored over direct hydrogen transfer.
• Protic polar solvents play a critical role in facilitating the direct tautomeric conversion by lowering the activation energy barrier.