Exploring Intermolecular Interactions and Energetics in Crystalline Substituted Thieno[2,3-d]pyrimidines

Abstract

This study explores the synthesis and crystallographic characterization of eight thieno[2,3-d]pyrimidines derivatives. Keeping in mind their practical importance in different biological applications, the understanding of the crystal structure in terms of the existence of various intermolecular interactions is of relevance. The presence of strong N-H⋯N dimers in the crystal structures of five compounds, followed by N-H⋯O and C-H⋯O interactions in the remaining three compounds, due to the presence of the amide and the sulphonamide substituents, is ascertained from crystal packing analysis. In addition, several weak intermolecular interactions, including C-H⋯π/N/S and S⋯C (σ-hole/ π-hole), and S⋯S contacts, contributes towards their additional stability in the crystal. To understand this, the nature and energetics associated with these intermolecular interactions were characterized via Crystal Explorer21.5. Further, the electrostatic complementarity amongst the robust N-H⋯N dimers are evidenced via noticing the large negative and positive molecular surface electrostatic potential (MESP) values across the nitrogen and the hydrogen atoms, respectively. Moreover, carbon-bonding was explicitly described for S⋯C interactions. This implied the participation of the nucleophilic sulphur with electrophilic carbon atom (either mediated through a σ-hole or π-hole on the carbon atom). Besides this, the change in the directionality of these interactions, from the linear to the orthogonal orientation for tetrel interactions was observed and justified through an analysis of the MESP, the deformation density plots and the QTAIM analysis.