Efficient Formylation of Alcohols Using a Core-Shell Magnetic Nanocomposite Via Vilsmeier-Haack Complex Formation.

Introduction: The protection of the hydroxyl group as formamides is a crucial initial step in pharmaceutical synthesis.

Methods: In this study, we investigated the O-formylation of alcohols using dimethylformamide (DMF) in a mixture with a new magnetic nanocomposite Fe₃O₄@Chitosan/POCl_2-x.

Results: The results demonstrate that this core-shell heterogeneous nanocomposite facilitates the formation of alkylformate, yielding products with high efficiency ranging from 79% to 96% within a remarkably short reaction time of 1 to 12 hours at room temperature, depending on the substrate structure. Significantly, the presence of this nanocomposite exhibits remarkable selectivity, favoring the formylation of less hindered benzylic and aliphatic primary alcohols. However, bulkier alcohols and phenols exhibit lower reactivity under these conditions and thiols do not react. The simplicity of the work-up procedure, combined with the magnetic recyclability, makes it reusable and environmentally friendly.

Conclusion: This study highlights the efficacy of this novel magnetic nanocomposite in facilitating formylation reactions, emphasizing its potential for application in pharmaceutical synthesis and bio compounds. This is due to its attributes of non-toxic nature, stability, and significant advantages over conventional methodologies.