R-Substituent vs. exocyclic oxygen: influence on synthesis and crystal packing of R-[1,2,5]oxadiazolo[3,4-c]cinnoline mono- and dioxides†

Abstract

A series of R-[1,2,5]oxadiazolo[3,4-c]cinnoline 5-mono- and 1,5-dioxides containing substituents (R = CH₃, F, Br, CF₃) at different positions were synthesized by an N-nitration–annulation process occurring upon treatment of 3-amino-4-(R-aryl)furazans and 4-amino-3-(R-aryl)furoxans with the HNO₃–H₂SO₄–Ac₂O system. The regioselectivity of the ring closure step was determined for the unsymmetrically substituted R-aryl precursors. Unexpected acylation at position 6 of 7-bromo-[1,2,5]oxadiazolo[3,4-c]cinnoline 5-oxide occurred as a result of the increased duration of the synthesis. The crystal structures of five new compounds were determined by X-ray diffraction analysis, and their crystal packings were compared with each other and with those of previously studied molecules, revealing common motifs regardless of the type or position of the substituent. Specifically, the fluorine derivative forms layers isostructural with those in unsubstituted mono- and dioxides, differing only in their arrangement within the P2₁ and P2₁/c space groups. Two methyl derivatives, on the other hand, exhibit a structure with flat layers. While the crystal environments of different R-substituents are generally distinct, the unsubstituted part of the heterocyclic core tends to form repeating isostructural motifs, such as dimers, chains, and layers. Although substituents disrupt the crystal packing, they still allow for the combination of these motifs in different crystal structures.