Synthesis of a Novel Bisphosphonic Acid Alkene Monomer

Abstract

The convenient, scaleable synthesis of a novel ⟨-fluorinated bisphosphonic acid, incorporating a tethered acrylamide monomer, [1-fluoro-1-phosphono-7-(prop-2-enamido)heptyl]phosphonic acid (1), is described. The α–fluorine substituent offers the advantage (compared to an α–hydroxy) of compatibility with basic conditions in tetraester intermediates (avoiding phosphonate-phosphate rearrangement) while maintaining a phosphonic acidity that mimics that of pyrophosphoric acid. Sodio tetraisopropyl methylenebis(phosphonate) was monoalkylated with 1,6-dibromohexane and fluorinated with Selectfluor. An ω-nitrogen atom was introduced into the tether via incorporation of a phthalimide group, which as a UV-visible chromophore facilitated purification. Subsequent removal of the ester (HCl) and phthalimide (hydrazine) groups yielded ⟨–F, ω-aminohexyl methylenebis(phosphonic acid), which was reacted with acryloyl chloride at pH 8-9, then treated with HCl to give 1.

Keywords:

• Bisphosphonate
• conjugate
• fluorination
• polymerization monomer

ACKNOWLEDGMENT

We thank Kerr-Sybron Corporation for support of this research.