Stable, aromatic, and electrophilic azepinium ions: Design using quantum chemical methods

Area of Science:

• Organic Chemistry
• Theoretical Chemistry
• Computational Chemistry

Background:

• Cyclic nitrenium ions with five- and six-membered rings are known, but seven-membered azepinium ions are rare.
• The stability of azepinium ions is linked to their 6π electron aromaticity.
• Limited theoretical and experimental studies exist for azepinium ions, though related diazepinium ions appear in drug metabolism.

Purpose of the Study:

• To investigate the stability, aromaticity, and electrophilicity of various azepinium ion derivatives.
• To explore the impact of substituents and ring fusion on azepinium ion properties using quantum chemical analysis.

Main Methods:

• Quantum chemical analysis was employed to study azepinium ion derivatives.
• Calculations focused on estimating singlet-triplet energy differences (ΔE_S-T), Nucleus-Independent Chemical Shift (NICS(1)) values, and electrophilicity parameters (HIA, FIA, ω).

Main Results:

• Some designed azepinium ions exhibited singlet-triplet energy differences favoring the singlet state (ΔE_S-T ~50 kcal/mol).
• π-donating groups at the 2nd position enhanced singlet-triplet energy differences, while most substituents decreased NICS(1) values.
• Ring fusion with five-membered heterocyclic rings generally increased aromaticity and stability; electrophilicity can be modulated via substituents.

Conclusions:

• Azepinium ions, despite their rarity, exhibit tunable stability and aromaticity.
• Quantum chemical calculations provide insights into structure-property relationships for azepinium ions.
• The findings suggest potential for fine-tuning azepinium ion chemical properties through molecular design.