Water Mediated Chemoselective Synthesis of Novel Spiro Benzoxazinoindoline and Extended Synthesis of Spiro Benzoxazinoindene Derivatives *

Abstract Spirobenzoxazines are a unique class of heterocyclic compounds that combine the structural features of spiro and benzooxazine frameworks, offering enhanced chemical stability and diverse biological activities. Their rigid three‐dimensional structures make them ideal candidates for interacting with biological targets, contributing to their potential in various therapeutic applications, including anticancer, antimicrobial, and enzyme inhibition. However, the development of efficient and sustainable methods for the synthesis of spirobenzoxazines remains a challenge in organic synthesis. In this work, we present a novel and environmentally friendly approach for the synthesis of spirobenzoxazine derivatives. Utilizing water as a green solvent, this methodology offers an efficient and sustainable route for constructing these complex heterocyclic frameworks. By emphasizing eco‐friendly practices, this approach aligns with the principles of green chemistry, providing both high yields and operational simplicity. This advancement not only highlights the potential of spirobenzoxazines in the pharmaceutical and material sciences but also paves the way for future research in sustainable synthetic methodologies.