Synthesis, NMR, and X-ray crystallographic analysis of C-hydrazino-C-carboxycarboranes:: Versatile ligands for the preparation of BNCT and BNCS agents and 99mTc radiopharmaceuticals

Protected hydrazine derivatives of ortho-, meta-, and para-carboranes were synthesized in good to excellent yields by reacting the mono-lithio salts of the respective carboranes with di-tert-butyl azodicarboxylate (DBAD). Subsequent deprotonation of the remaining carborane CH group, followed by the addition Of CO2(g), resulted in the formation of bifunctional C-hydrazino-C carboxycarboranes in good to excellent overall yields. Crystal structures of the monosubstituted ortho-carborane, 1-[(N,N'((tert-butyloxy)carbonyl)hydrazino)]-1,2-dicarba-closo-dodecaborane (8) [a = 21.213(6) Angstrom, b = 10.498(3) Angstrom, c = 9.866(2) Angstrom, alpha = gamma = 90degrees, beta = 90.529(4)degrees] and the bifunctional paracarborane 1 -[(N,N'((tert-butyloxy)carbonyl)hyd razino)]-1,12-dicarba-c/oso-dodecaborane-12-carboxylic acid (3) [a = 12.744(10) Angstrom, b = 12.875(9) Angstrom, c = 14.767(9) Angstrom, alpha = beta = gamma = 90degrees] were obtained. Intermolecular hydrogen bonding was a dominant packing feature in both structures. The reported compounds represent a unique class of bifunctional carboranes that can be used in peptidomimetic research and as synthons to prepare novel radiopharmaceuticals and boron neutron capture therapy/boron neutron capture synovectomy (BNCT/BNCS) agents.