Green chemistry perspectives on click chemistry approaches for cellulose functionalization: a critical review

Abstract

Cellulose, Earth's most abundant renewable polymer, presents significant opportunities for sustainable materials development due to its inherent biodegradability, biocompatibility, and renewability. However, the efficient and environmentally benign functionalization of cellulose remains a challenge due to its complex structure and limited solubility. Recent advances in click chemistry have offered promising pathways for cellulose modification, enabling the development of functional materials with enhanced properties while potentially addressing sustainability concerns. This review comprehensively examines the application of click chemistry for cellulose functionalization through the lens of green chemistry principles. We systematically assess four traditional click chemistry approaches—azide-alkyne cycloaddition, thiol-ene/yne reaction, Diels-Alder addition, and sulfur (VI) fluoride exchange (SuFEx)—alongside the emerging hydroxyl-yne click chemistry, which enables direct modification of cellulose's native hydroxyl groups. Through critical evaluation using key green chemistry metrics including atom economy, E-factor, process mass intensity, solvent requirements, catalyst usage, energy consumption, and safety profiles, we identify the relative sustainability advantages and limitations of each approach. Our analysis reveals that hydroxyl-yne click chemistry offers significant green chemistry advantages through elimination of preprocessing steps, direct utilization of cellulose's hydroxyl groups, catalyst efficiency, and reduced waste generation. Furthermore, we highlight how these functionalization methods have enabled the development of cellulose-based materials with diverse properties including hydrophobicity, antibacterial activity, self-healing capabilities, and UV protection while maintaining cellulose's inherent biodegradability. This systematic assessment provides valuable guidance for researchers seeking the most sustainable approaches for cellulose functionalization and offers a vision for how these methods can contribute to the development of next-generation renewable materials across multiple industries including packaging, textiles, biomedical applications, and advanced technologies.