Examining intermolecular interactions in crystal structures of amide-substituted 2-aminopyrimidine derivatives

Abstract

A systematic structural investigation of acetylated 2-aminopyrimidine derivatives was conducted to understand the balance between hydrogen and halogen bonds in supramolecular assembly. The 2-aminopyrimidine derivatives were grouped into three series to examine the effects of alkyl chain length, chain nature, and halogen substitution on supramolecular assembly. A total of twenty-one new crystal structures across these targets indicate that steric effects (alkyl chain length), the nature of the carbon chain, and halogen-atom substitution did not influence the assembly, with primary bonding motifs remaining largely consistent within each series. Notably, the study demonstrated that hydrogen bonds could be replaced by halogen bonds without disrupting overall crystal assembly when the halogen bond donor was sufficiently strong. Analysis of bond directionality illustrated that halogen bonds are more directional than hydrogen bonds, with hydrogen bond angles ranging from 126° to 166°, chlorine halogen bonds from 170° to 175°, and bromine halogen bonds from 168° to 177°. These findings highlight the potential of halogen bonds as reliable alternatives to hydrogen bonding in crystal engineering and expand possibilities for designing molecular structures with tailored noncovalent interactions.