Reagents for efficient conversion of amines to protected guanidines

Two new guanidinylation reagents, N,N'-bis(ortho-chloro-Cbz)-S-methylisothiourea and N,N'-bis(ortho-bromo-Cbz)-S-methylisothiourea, were compared with the already known N,N'-bis(Boc)-S-methylisothiourea and N,N'-bis(Cbz)-S-methylisothiourea. The new reagents proved to be superior to the known reagents. The reactions with all the new reagents were accelerated by addition of DMAP. N,N'-Bis(ortho-chloro-Cbz)- and N,N'-bis(ortho-bromo-Cbz)guanidines are stable when treated with trifluoroacetic acid and can be converted to guanidines by hydrogenolysis.