The neutralized diazonium salt of anthranilic acid (I) is treated with sodium diselenide yielding diselenosalicylic acid (II), which is treated with thionyl chloride to give the selenenyl chloride (III). Treatment of (III) with aniline (IV) in the presence of a base affords PZ-51.
A new synthesis of ebselen has been published: The radical reaction of 2-(benzylseleno)-N-phenylbenzamide (I) with triphenyltin hydride (II) and AIBN in refluxing benzene gives N-phenyl-2-(triphenylstannylseleno)benzamide (III), which is treated with dibenzoyl peroxide (IV) in refluxing benzene to yield the diselenide (V). Finally, the diselenide (V) was treated with di-tert-butyl peroxide (VI) in chlorobenzene at 120 C. This reaction cannot be carried out in refluxing benzene due to the extreme insolubility of (V) in benzene.
A new synthesis of ebselen has been reported: The reaction of benzanilide (I) first with lithium diisopropylamide and then with butyllithium in THF gives the dianion (II), which is treated with freshly sublimed selenium to afford the insertion dianion (III). Finally, this compound is cyclized with CuBr2 in the same solvent. This reaction has also been carried out with 77Se in order to obtain labeled ebselen.