Lewis Acid-Catalyzed Synthesis of Alkoxymethylhalides for Multipurpose Mixed Acetals; Scope and Limitations

Abstract: The work describes a detailed account of the Lewis acid-catalyzed preparation of structurally variant alkoxymethyl halides. A series of Lewis acids with different halogenating agents are evaluated for the cleavage of bis-alkoxymethanes, where several readily available Lewis acids were found to exhibit high catalytic potential. SOCl2 with MgCl2 was found to be one of the best combinations for the facile and efficient preparation of structurally diverse alkoxymethyl halides under solvent-free conditions. The efficacy of the methodology was established to obtain a wide range of mixed acetals through alkoxymethylation of phosphorus, sulfur, nitrogen, and oxygen containing nucleophiles. The present procedure has significant advantages including simplicity, generality, rapidity, and availability of reagents.