Dissociative electron attachment induced ring opening in five-membered heterocyclic compounds

Area of Science:

• * Physical Chemistry
• * Organic Chemistry
• * Chemical Physics

Background:

• * Five-membered heterocyclic compounds are prevalent in biological systems and crucial for biochemical processes.
• * Understanding their fundamental fragmentation patterns is essential for various scientific disciplines.
• * Isoxazole, a key five-membered heterocycle, serves as a model for studying such structures.

Purpose of the Study:

• * To investigate the dissociative electron attachment (DEA) fragmentation pathways of isoxazole.
• * To compare the fragmentation of isoxazole with its methylated derivatives and related heterocycles (oxazole, thiazole).
• * To elucidate the dominant DEA-induced ring-opening mechanisms in isoxazole.

Main Methods:

• * Detailed examination of fragmentation patterns using dissociative electron attachment (DEA).
• * Comparative analysis of isoxazole against its methylated derivatives.
• * Comparative analysis of isoxazole against oxazole and thiazole under DEA conditions.

Main Results:

• * The primary DEA pathway in isoxazole involves hydrogen loss at C(3), leading to O-N bond cleavage and ring opening at ~1.5 eV.
• * This dominant hydrogen loss and ring-opening pathway was significantly less pronounced or absent in oxazole and thiazole.
• * Methylated isoxazole derivatives showed comparable fragmentation to isoxazole, indicating the core ring structure's role.

Conclusions:

• * Isoxazole exhibits a unique and dominant DEA-induced ring-opening mechanism via O-N bond cleavage following hydrogen loss.
• * The observed fragmentation behavior is specific to the isoxazole ring system compared to oxazole and thiazole.
• * These findings have significant implications for the pharmaceutical industry, particularly concerning the biotransformation of isoxazole-containing drugs.