The reaction of di(4-chlorophenyl)disulfide (I) with tetraisopropyl methylenediphosphonate (II) by means of NaH in hot DMF gives tetraisopropyl (4-chlorophenyl)thiomethylenediphosphonate (III), which is finally hydrolyzed with refluxing aqueous 6N HCl.
A synthesis for [benzene-U-14C]-tiludronate has been described: The chlorination of [U-14C]-acetanilide (I) with tetrabutylammonium iodotetrachloride gives the corresponding 4-chloro derivative (II) (along with some of the 2-chloro isomer). The hydrolysis of (II) with concentrated HCl at 60 C yields the chloroaniline (III), which is converted to the corresponding diazonium salt (IV) with NaNO2 and HCl. The reaction of (IV) with ferric thiocyanate affords the labeled 4-chlorophenylthiocyanate (V), which is condensed with the lithium salt of methylenebis(phosphonic acid)tetraisopropyl ester (VI) in THF to yield 4-chlorophenylsulfanylmethylenebis(phosphonic acid)tetraisopropyl ester (VII). Finally, this compound is hydrolyzed with concentrated HCl or aqueous NaOH.