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.