X-ray Diffraction Structures of Regioisomers of N-Methylated Benzimidazole Compounds with Interest for the Design of Amyloid-Avid Probes

Abstract

This work describes the compounds 5-bromo-1-methyl-2-[N-methyl-N-(2′-O-tert-butylcarbonatethyl)-4′-aminophenyl]-1H-benzo[d]imidazole (4) and 6-bromo-1-methyl-2-[N-methyl-N-(2′-O-tert-butylcarbonatethyl)-4′-aminophenyl]-1H-benzo[d]imidazole (5), C₂₂H₂₆BrN₃O₃, which correspond to two regioisomers that were obtained by N-methylation of the corresponding 6-bromobenzimidazole derivative. The structures of these two regioisomers have been confirmed in solution by NMR NOESY experiments, as well as in the solid state using single crystal X-ray diffraction analysis. The structures of 4 and 5 comprise two planar benzimidazole and benzene fragments and a disordered aliphatic chain containing a terminal carbamate group. Compound 4 crystallized in the monoclinic P21/c group with unit cell parameters a = 23.0178(7) Å, b = 7.9106(2) Å, c = 11.9758(3) Å, β = 93.340(2)º, V = 2176.90(10) Å³, Z = 4, D = 1.405 Mg/m³. Compound 5 crystallized in the triclinic P-1 group with unit cell parameters a = 6.7187(3) Å, b = 16.5203(10) Å, c = 21.3544(13) Å, α = 109.279(2)º, β = 94.802(2)º, γ = 98.871(2)º, V = 2187.4(2) Å³, Z = 4, D = 1.398 Mg/m³.

Graphical Abstract

Two regiosomers of benzimidazole derivatives are reported, including the elucidation of their structures in solution by NMR NOESY experiments and in the solid state by X-ray diffraction studies.