Nitrogen Heterocyclic Bases as Catalysts for the Selective Synthesis of Symmetric P,P′-Disubstituted Bisphosphonate Esters

Nitrogen heterocyclic bases were investigated as potential catalysts for the selective synthesis of symmetric P,P′-disubstituted partial esters of methylenebisphosphonic acid. The size, presence of oxygen or sulfur donor atoms as well as position and number of nitrogen atoms in the ring were varied systematically to determine the effect of these structural modifications on catalyst selectivity. 1-Methylimidazole and 1H-1,2,3-triazole, which yield exclusively the desired diester product, were shown viable alternatives to 1H-tetrazole for catalyzing the selective coupling of methylenebis- (phosphonic dichloride) with 2 equiv. of alcohol.