Preparation of 6-Monohalo-β-cyclodextrin Derivatives with Selectively Methylated Rims via Diazonium Salts
Abstract
A series of 6-monohalo (Cl, Br, and I) β-cyclodextrinderivativeswith various types of methylations were synthesized via a diazotization/nucleophilicdisplacement reaction from the corresponding methylated cyclodextrinamines. All four starting compounds (6(A)-amino-6(A)-deoxy derivatives of native β-CD, per-6-O-methyl-, per-2,3-O-methyl-, and per-2,3,6-O-methyl-β-CD) were found to have different reactivitiesunder the same reaction conditions.
Unsubstituted and fully per-O-methylatedcyclodextrin amines undergo fast transformation, giving lower yieldsof the monohalogenated product. The selectively methylated cyclodextrinamines react remarkably slower and provide almost complete conversioninto the desired monohalogenated compound.
A pure product was, inseveral cases, successfully isolated with simple purification techniques(extraction and precipitation), allowing large-scale preparations.This new method opens the way for preparing poorly investigated monofunctionalizedselectively methylated cyclodextrins.