Preparation of tetraethyl-4-hydroxyphenylmethylene-1,1-bisphosphonate by hydroxy-de-diazoniation of the corresponding diazonium salt of tetraethyl-4-aminophenylmethylene-1,1-bisphosphonate

Bisphosphonates are widely used in diagnosis and therapy of different bone diseases. They are useful agents in osteotic vectorization of antitumor and antiinflammatory drugs because of their potential to accumulate in the inorganic bone matrix hydroxylapatite. Hence, there is great interest in alkyl-bisphosphonates, containing functional groups advantageous for further synthetic modification, as structural units for coupling with the drug. We report on the synthesis of tetraethyl-4-hydroxyphenylmethylene-1,1-bisphosphonate 8 by hydroxy-de-diazoniation of the diazonium salt 7, prepared by diazotation of the corresponding amine tetraethyl-4-aminophenylmethylene-1,1-bisphosphonate 6.