Synthesis and characterization of an aza-cage behaving as a ‘proton sponge’. Crystal structures of its mono- and tri-protonated species

Abstract

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 °C, I= 0.15 mol dm^–3) and NMR (¹H and ¹³C) 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). ¹H–¹H and ¹H–¹³C two-dimensional NMR experiments permitted the unequivocal assignment of all ¹H proton and ¹³C 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 P2₁cn, with a= 9.044(2), b= 12.573(2), c= 16.126(3)Å, and Z= 4; final R value of 0.089 (R_w= 0.086) for 1267 unique observed reflections with I > 3σ(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 endoconfiguration. The short H(2)⋯(4)[1.69(1)Å] and N(2)⋯ N(4)[2.75(1)Å] distances indicate a strong hydrogen bond. H(2) further interacts with the other two tertiary nitrogens: H(2)⋯ N(1)[2.53(1)Å] and H(2)⋯ N(3)[2.46(1)Å]. 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 P4₃2₁2, with a= 8.498(2), b= 8.498(2), c= 32.855(8)Å, and Z= 4; final R value of 0.083 (R_w= 0.093) for 1076 unique observed reflections with I > 3σ(I). The X-ray analysis shows an overall macrocyclic conformation with two nitrogen atoms in the endoconfiguration and two in exo configuration.