Dihalogens Binding and Activation by Imidazoline‐2‐Chalcogenone Model Derivatives: Insight from a Computational Approach

Chalcogenone donors represent a fundamental chemical class of compounds in the treatment of hyperthyroidism; particularly, imidazoline-based systems are associated with the strongest affinity for I₂. Therefore, the reactivity of these types of donors with dihalogens may be insightful to understand the mechanism of action of popular drugs, such as methimazole (1-methyl-4-imidazoline-2-thione, MMI). In this work, the reactivity of 1,3-dimethyl-4-imidazoline-2-chalcogenone (S, Se, Te) with dihalogens X₂ (X = Cl, Br, I) is evaluated for any combination through a systematic computational study. Three different products are found: a linear charge transfer (CT) "spoke" adduct, a "T-shaped" intermediate (TI), and a "T-shaped" hypercoordinate species (TY). The halogen and chalcogen effects are discussed separately as for the solvation effects. Furthermore, only the TY species formed from the reaction between 1,3-dimethyl-4-imidazoline-2-thione and I₂ resulted to be disfavored with respect to the corresponding CT adduct; therefore, this peculiarity is rationalized in the framework of activation strain analysis. Lastly, a possible alternative mechanism involving the formation of a cationic intermediate species is considered.