DFT and X‐Ray Structural Studies of N(7)‐Tetramethylbenzyl/Pentamethylbenzyl Theophylline Derivatives and Their Catalytic Applications

ABSTRACT Theophylline, a naturally occurring xanthine derivative with well‐established pharmaceutical applications, has recently emerged as an attractive scaffold in coordination chemistry and catalysis because of its unique heterocyclic structure and donor properties. In this study, two novel N(7)‐substituted theophylline derivatives, namely 1,3‐dimethyl‐7‐((2,3,5,6‐tetramethyl)benzyl)‐3,7‐dihydro‐1 H ‐purine‐2,6‐dione and 1,3‐dimethyl‐7‐((2,3,4,5,6‐pentamethyl)benzyl)‐3,7‐dihydro‐1 H ‐purine‐2,6‐dione, were synthesized and comprehensively characterized by spectroscopic methods, single‐crystal x‐ray diffraction analysis, and density functional theory (DFT) calculations. Structural and theoretical investigations were carried out to evaluate their electronic features, coordination behavior, and potential interaction sites. For the first time, these theophylline‐based heterocyclic compounds were employed as ligand‐like components in in situ generated palladium catalytic systems for C─H bond activation reactions. The catalytic results demonstrated that the N(7)‐substituted theophylline framework effectively stabilizes palladium intermediates and promotes selective C─H functionalization under mild reaction conditions. DFT studies further revealed that the nitrogen donor centers of the theophylline scaffold play an important role in tuning the electronic properties and reactivity of the palladium species. In addition, frontier molecular orbital analyses, including HOMO–LUMO energy levels and orbital localizations, provided insight into the possible coordination and interaction regions of the molecules. These findings establish N(7)‐substituted theophylline derivatives as a new class of ligand‐like scaffolds for Pd‐catalyzed C─H activation.