The small cage 12,17-dimethyl-5-oxa-1,9,12,17-tetra-azabicyclo[7.5.5]nonadecane (L): its synthesis, characterization, and ‘proton sponge’ behaviour. The crystal structure of the dipicrate salt [H2(L)](picrate)2

Abstract

The synthesis and characterization of the new oxa-azamacrobicycloalkane 12,17-dimethyl-5-oxa-1,9,12,17-tetra-azabicyclo[7.5.5]nonadecane (L) are described. Its basicity behaviour in both aqueous and water–Me₂SO (50:50 mol/mol) solutions has been investigated by potentiometric and spectroscopic (¹H and ¹³C n.m.r.) techniques. In aqueous solution it behaves as a very strong base (proton sponge) in the first protonation step, and as a relatively strong base in the second step (log k₂= 11.21). In the mixed water–Me₂SO solvent both protonation constants have been measured: log k₁= 14.0 and log k₂= 8.2. ¹H N.m.r. experiments indicate that in the monoprotonated species H(L)⁺ the proton is rapidly exchanged with acidic hydrogens on the n.m.r. timescale. ¹H–¹H and ¹H–¹³C two-dimensional n.m.r. experiments allowed the unequivocal assignment for all the ¹H proton and ¹³C resonances of both species H(L)⁺ and H₂(L)²⁺. Crystals of [H₂(L)](picrate)₂ are monoclinic, space group P2₁/n, with a= 12.868(8), b= 17.201(2), c= 16.614(2)Å, β= 110.18(1)°, and Z= 4; final R values of 0.090 (R_w= 0.090) for 3 801 observed reflections. The four basal nitrogen atoms and the apical oxygen atom are located at the apices of a slightly distorted square pyramid. X-Ray analysis shows that protonation occurs on the NCH₃, groups. Each hydrogen atom of the NH⁺CH₃ interacts with the oxygen atom, the 0 ⋯ H distances 2.328(16) and 2.112(18)Å, and with both bridgehead nitrogen atoms, the H ⋯ N distances ranging from 2.32 to 2.34 Å. This arrangement makes the overall structure very stable from the thermodynamic point of view and explains the unusually high basicity of (L) in both first- and second-protonation step.