This research investigates the synthesis of novel amide derivatives from 2-hydroxybenzoic acid (salicylic acid) and 2-methoxybenzoic acid using the Schotten-Baumann method, with a focus on optimizing reaction conditions to improve yields while preserving the ortho-substituents. The study examines the preparation of acid chlorides employing oxalyl chloride catalyzed by DMF, followed by amide formation through nucleophilic acylation. Mechanisms, empirical data, and theoretical insights are analyzed, tracing the evolution from traditional aqueous base methods yielding 60-80% to advanced optimizations like controlled temperature, solvent selection, and microwave assistance achieving up to 92% efficiency with reduced by-products. Challenges such as side reactions from the hydroxy group and steric hindrance are mitigated using protective strategies or phase-transfer catalysts. Practical guidelines are offered for selecting optimal protocols based on yield, purity, scalability, and eco-friendliness, recommending the integration of DMF-catalyzed acid chloride formation with biphasic Schotten-Baumann conditions for sustainable amide synthesis in pharmaceutical applications.

Schotten-Baumann reaction, amide synthesis, oxalyl chloride

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