Synthesis of tetraethyl (2-benzyl-3-oxoisoindolyl-1,1-diyl)-bisphosphonate and its properties

Abstract

The reaction of o-phthalyl chloride with sodium diethylphosphite affords a cyclic bisphosphonate, 3,3-bis(diethylphosphono)-1(3H)-isobenzofuranone. The reaction of 1(3H)-isobenzofuranone with potassium carbonate proceeds through the ring opening and elimination of one phosphonate group to give acyclic α-ketophosphonate. At the same time, the reaction of bisphosphonate with the concentrated hydrochloric acid does not lead to the ring opening but gives bisphosphonic acid in a good yield. 3,3-Bis(diethylphosphono)-1(3H)-isobenzofuranone reacts with benzylamine in the presence of triethylamine with the replacement of endocyclic oxygen atom by benzylamino group, which leads to the formation of the corresponding bisphosphonate phthalimide, the first representative of a new type of bisphosphonates and phosphorus heterocycles.