Studies on the 1,4-oxazepine ring formation reaction using the molecular orbital method

Area of Science:

• Organic Chemistry
• Computational Chemistry
• Chemical Kinetics

Background:

• 1,8-naphthyridine derivatives are important heterocyclic compounds.
• Understanding their reaction mechanisms, particularly oxazepine formation, is crucial for synthetic chemistry.

Purpose of the Study:

• To investigate the 1,4-oxazepine formation reactions of 1,8-naphthyridine derivatives.
• To computationally predict reaction pathways and products using molecular orbital methods.
• To compare computational predictions with experimental findings.

Main Methods:

• Utilized semiempirical Molecular Orbital (MO) method (AM1).
• Employed ab initio Molecular Orbital (MO) method (Gaussian 94).
• Calculated energies of molecules and transition states along reaction paths.

Main Results:

• Computational models successfully predicted experimental products for 1,8-naphthyridine derivatives 1-3.
• Calculations for derivative 4 indicated a different oxazepine product than initially expected.
• The predicted novel oxazepine for derivative 4 was confirmed through subsequent experimental studies.

Conclusions:

• Molecular orbital calculations are reliable for predicting reaction outcomes in 1,8-naphthyridine chemistry.
• The study identified a new pathway for oxazepine formation with derivative 4.
• Computational chemistry serves as a valuable tool for guiding and verifying experimental organic synthesis.