SYNTHESIS AND CHARACTERIZATION OF AN AZA-CAGE BEHAVING AS A PROTON SPONGE - CRYSTAL-STRUCTURES OF ITS MONOPROTONATED AND TRIPROTONATED SPECIES

The synthesis and characterization of the new macrobicyclic cage 4,10-dimethyl-1,4,7,10-tetraazabicyclo[5.5.4]hexadecane L is reported. Its basicity behaviour in aqueous solution has been investigated by potentiometric (25-degrees-C, I = 0.15 mol dm-3) and NMR (H-1 and C-13) techniques. It behaves as a very strong base (proton sponge) in the first protonation step, and as a moderate base in the second step (log K2 = 7.8). H-1-H-1 and H-1-C-13 two-dimensional NMR experiments permitted the unequivocal assignment of all H-1 proton and C-13 resonances of both species HL+ and H2L2+. Furthermore NMR experiments indicate that the first protonation involves the bridgehead nitrogens. Crystals of [HL] [ClO4] are orthorhombic, space group P2(1)cn, with a = 9.044(2), b = 12.573(2), c = 16.126(3) angstrom, and Z = 4; final R value of 0.089 (R(w) = 0.086) for 1267 unique observed reflections with / > 3sigma(I). X-Ray analysis shows that protonation occurs on the bridgehead nitrogen N(2) and an overall macrocyclic conformation with the all nitrogen atoms in the endo configuration. The short H(2) ... N(4) [1.69(1) angstrom] and N(2) ... N(4) [2.75(1) angstrom] distances indicate a strong hydrogen bond. H(2) further interacts with the other two tertiary nitrogens: H(2) ... N(1) [2.53(1) angstrom] and H(2) ... N(3) [2.46(1) angstrom]. This arrangement makes the monoprotonated species very stable from the thermodynamic point of view and explains the high basicity of L. Crystals of [H3L] [ClO4]3 are tetragonal, space group P4(3)2(1)2, with a = 8.498(2), b = 8.498(2), c = 32.855(8) angstrom, and Z = 4; final R value of 0.083 (R(w) = 0.093) for 1076 unique observed reflections with I > 3sigma(I). The X-ray analysis shows an overall macrocyclic conformation with two nitrogen atoms in the endo configuration and two in exo configuration.