Efficient Use of 1,2-Dihaloazine Synthons in Transition-Metal-Free Preparation of Diverse Heterocycle-Fused 1,4-Oxazepines

A previously reported condensation reaction of ambiphilic 2‐(1H‐pyrazol‐5‐yl)phenols with various o‐chloro‐substituted nitroaromatic synthons to provide medicinally important tetracyclic pyrazolo[1,5‐d][1,4]oxazepines was extended to more readily available and convenient‐to‐use 1,2‐dihaloazines. Although 4,5‐dichloropyridazin‐3(2H)‐ones and 2,3‐dichloropyrazine are popular bis(electrophilic) partners in various SNAr‐type condensations and also were efficiently used in the reaction reported herein, the facility with which various 3‐bromo‐2‐chloropyridines underwent the same cyclization was unexpected. These reactions are presumed to occur as sequential intermolecular SNAr/Smiles rearrangement/intramolecular SNAr tandem reactions and provide a rare example of the transition‐metal‐free substitution of a bromine atom at the 3‐position of a pyridine ring. Ambiphilic 2‐(1H‐pyrazol‐5‐yl)phenols underwent an efficient condensation reaction with a variety of 1,2‐dihaloazines to afford heterocycle‐fused 1,4‐oxazepines. The reaction is thought to involve sequential SNAr/Smiles rearrangement/SNAr reactions. The participation of 3‐bromo‐2‐chloropyridines in this transition‐metal‐free protocol was unexpected.