Preparation of trimethylsilyl ethers of 3?azetidinols. Scope and Limitations
Abstract
Preparation of the trimethylsilyl ethers of 1?alkyl?3?azetidinols from non?hindered primary amines and epichlorohydrin by conversion of the intermediate 1?(alkylamino)?3?chloro?2?propanols to their trimethylsilyl ethers by either N?(trimethylsilyl)acetamide or by 1?(trimethylsilyl)imidazole followed by ring closure in acetonitrile is described. This sequence of reactions fails for aromatic amines, but appears to be general for all primary aliphatic amines, although the condensation of hindered amines with epichlorohydrin occurs slowly. Several novel azetidinols, in which the N?alkyl substituent itself contains a second heterocyclic system, are reported. In addition, the pKA's of several m. and p?substituted 1?benzylazetidinols correlates well with the Hammett equation. Copyright © 1988 Journal of Heterocyclic Chemistry