Collect. Czech. Chem. Commun. 2001, 66, 507-516

A Facile Synthesis of Azetidin-2-ylphosphonic Acid and Its 1-Alkyl Derivatives

Miroslav Otmar*, Lucie Poláková, Milena Masojídková and Antonín Holý

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic


Treatment of racemic diisopropyl [1,3-bis(mesyloxy)propyl]phosphonate with allyl-, benzyl-, 2-hydroxyethyl-, or propylamine gave the corresponding diisopropyl [(3-(alkylamino)-1-(mesyloxy)propyl]phosphonates. Heating of their toluene solution with aqueous potassium carbonate effected a cyclization to diisopropyl (1-alkylazetidin-2-yl)phosphonates. In the 1-benzyl- and [1-(2-hydroxyethyl)azetidin-2-yl]phosphonate, the isopropyl ester groups were removed by treatment with bromotrimethylsilane which gave 1-benzyl- and [1-(2-hydroxyethyl)azetidin-2-yl]phosphonic acid. Following hydrogenolysis of the benzyl group afforded azetidin-2-ylphosphonic acid.

Keywords: Phosphonates; Phosphonopeptides; Azetidines; Aminophosphonates; Amino acids analogs; Cyclizations; Hydrolysis.

References: 14 live references.