Solid state and dynamic solution structures of O-carbamidine amidoximes gives further insight into the mechanism of zinc(II)-mediated generation of 1,2,4-oxadiazoles

• Published in: Journal of molecular structure Vol. 1111; pp. 142 - 150
• Main Authors: Kulish, Kirill I., Novikov, Alexander S., Tolstoy, Peter M., Bolotin, Dmitrii S., Bokach, Nadezhda A., Zolotarev, Andrey A., Kukushkin, Vadim Yu
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05.05.2016
• Subjects: 1,2,4-Oxadiazoles; Bonding; Cations; DFT calculations; Diffraction; Dynamics; Iminium salts; Mathematical analysis; Molecular structure; Solution DNMR; Stabilization; X-ray study; X-rays; Solution DNMR; 1,2,4-Oxadiazoles; Iminium salts; DFT calculations; X-ray study
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2016.01.038

Three new iminium salts [H2NC(R)ONC(R′)NH2](p-TolSO3)·½H2O ([1–3](p-TolSO3)·½H2O; R/R′ = NMe2/PhCH21, NMe2/p-BrC6H42, N(CH2)5/p-BrC6H43) were synthesized via ZnII-mediated amidoxime-cyanamide coupling and their solid structures were studied by X-ray diffraction. Solution structure and conformational changes of [1–3](p-TolSO3)·½H2O were studied by dynamic NMR. The obtained quantitative data were supported by DFT calculations. All the obtained results help to understand the relative stability of the salts [H2NC(R)ONC(R′)NH2](X) (R = NAlk2, Alk, Ar) and give a further insight into the mechanism of ZnII-mediated generation of 1,2,4-oxadiazoles. The electron delocalization and sesquialteral bonds in the [H2NC(NR2)ONC(R′)NH2]+ system was recognized by estimation of values of activation energy barriers (14–18 kcal/mol by DNMR and 16–17 kcal/mol by DFT calculations) for the rotation around the CN bonds for the NR2 groups and inspection of the solid-state X-ray data along with the Wiberg bond indices (intermediate single/double bond order for the CN distances). This electron delocalization is responsible for the stabilization of the positively charged iminium cation. The moderate strength hydrogen bonding between the oxime N atom and the =NH2 group, which is verified from the X-ray, DNMR experiments, and by using quantum chemical calculations, stabilizes the iminium salt, but it is still weak to prevent the heterocyclization. Theoretical calculations of the heterocyclization of [H2NC(R)ONC(R′)NH2]+ to 1,2,4-oxadiazoles demonstrated that it is kinetically hindered to a greater extent for R = NAlk2 and this explains their lower reactivity as compared to the iminium salts with R = Alk, Ar. Solid state and dynamic solution structures of O-carbamidine amidoximes were studied by X-ray diffraction, dynamic NMR, and DFT calculations and the obtained data give an insight into the mechanism of zinc(II)-mediated generation of 1,2,4-oxadiazoles. [Display omitted] •Unstable iminium salts [H2NC(R)ONC(R′)NH2]+ are stabilized when R = NAlk2.•Solid structures were studied by X-ray diffraction.•Solution structures and conformational changes were studied by dynamic NMR.•The structural studies were supported by DFT calculations.•The mechanism of ZnII-mediated generation of 1,2,4-oxadiazoles was studied.