Zinc(II)-Mediated Nitrile–Amidoxime Coupling Gives New Insights into H⁺‑Assisted Generation of 1,2,4-Oxadiazoles

The cyanamides Me₂NCN (<b>1a</b>), OC₄H₈NCN (<b>1b</b>), and PhC­(O)­N­(H)­CN (<b>1c</b>) and the conventional nitriles PhCN (<b>1d</b>) and EtCN (<b>1e</b>) react with 1 equiv of each of the amidoximes R′C­(NOH)­NH₂ (R′ = Me (<b>2a</b>), Ph (<b>2b</b>)) in the presence of 1 equiv of ZnCl₂ producing the complexes [ZnCl₂{H<u>N</u>C­(R)­O<u>N</u>C­(R′)­NH₂}] (R/R′ = NMe₂/Me (<b>3a</b>), NMe₂/Ph (<b>3b</b>), NC₄H₈O/Me (<b>3c</b>), NC₄H₈O/Ph (<b>3d</b>), N­(H)­C­(O)­Ph/Me (<b>3e</b>), N­(H)­C­(O)­Ph/Ph (<b>3f</b>), Ph/Me (<b>3g</b>), Ph/Ph (<b>3h</b>), Et/Ph (<b>3j</b>)) with the chelate ligands originating from the previously unreported zinc­(II)-mediated nitrile–amidoxime coupling. Addition of 1 equiv of <i>p</i>-TolSO₃H to any of one <b>3a</b>–<b>h</b>, <b>3j</b> results in the ligand liberation and formation of the iminium salts [H₂NC­(R)­ONC­(R′)­NH₂]­(<i>p</i>-TolSO₃) ([<b>4a</b>–<b>j</b>]­(<i>p</i>-TolSO₃)), which then at 20–65 °C spontaneously transform to 1,2,4-oxadiazoles (<b>5a</b>–<b>j</b>). As a side reaction, cyanamide derived species [<b>4a</b>–<b>f</b>]­(<i>p</i>-TolSO₃) undergo Tiemann rearrangement to produce the substituted ureas R′NHC­(O)­NH₂ (R′ = Me (<b>6a</b>), Ph (<b>6b</b>)) and RC­(O)­NH₂ (R = NMe₂ (<b>6c</b>), NC₄H₈O (<b>6d</b>), N­(H)­C­(O)­Ph (<b>6e</b>)), whereas phenyl and ethyl cyanide derivatives besides their transformation to the oxadiazoles undergo hydrolysis to the parent amidoxime R′C­(NOH)­NH₂ (R′ = Me (<b>2a</b>), Ph (<b>2b</b>)) and the carboxamides RC­(O)­NH₂ (R = Ph (<b>6f</b>), Et (<b>6g</b>)). All new obtained compounds were characterized by HRESI-MS, IR, ATR-FTIR, ¹H NMR, CP-MAS TOSS ¹³C NMR, elemental analyses (C, H, N), and single crystal X-ray diffraction for seven species (<b>3a</b>–<b>e</b>, [<b>4b</b>]­(<i>p</i>-TolSO₃), and [<b>4d</b>]­(<i>p</i>-TolSO₃)). Two previously unknown heterocycles <b>5c</b> and <b>5e</b> were isolated and characterized by elemental analyses (C, H, N), HRESI-MS, IR, ¹H and ¹³C­{¹H} NMR. The observed conversion of [<b>4a</b>–<b>j</b>]­(<i>p</i>-TolSO₃) to the 1,2,4-oxadiazoles uncovers the mechanism of the previously reported H⁺-assisted generation of these heterocycles (Augustine; et al. J. Org. Chem. 2009, 74, 5640)