Effect of Substituents on the Intramolecular n→π* Interaction in 3-[2-(Dimethylamino) phenyl] propanal: A Computational Study

n→π* non-covalent interaction (NCI) and hydrogen bond have similarity in terms of delocalization of the electron density between the two orbitals involved in the interaction. Hydrogen bond (X-H···Y) involves delocalization of the lone pair electrons (n) on the Y atom into the σ* orbital of the X-H bond. In contrast, the n→π* interaction deals with delocalizing the lone pair electrons (n) on the N, O, or S atom into the π* orbital of a C═O group or aromatic ring. Herein, we have shown a resemblance of this weak n→π* interaction with the relatively stronger hydrogen bond in terms of folding the side chains in flexible molecules. This work reports the study of folding of the flexible side-chain in 3-[2-(dimethylamino) phenyl] propanal (DMAPhP) through a N···C═O n→π* interaction using various computational approaches such as NBO, QTAIM, and NCI analyses. The folding of the molecule by the n→π* interaction observed in this study is found to be similar to that present in the secondary structures of peptides or proteins through hydrogen bonding interactions. Interestingly, the stabilization of the global minimum conformer of DMAPhP by the n→π* interaction demonstrates the importance of this NCI in providing conformational preferences in molecular systems. Another important finding of this study is that the theoretical redshift obtained in the C═O stretching frequency of the most stable conformer of the DMAPhP is contributed mostly by the n→π* interaction as the C═O group is not involved in hyperconjugation with any neighboring heteroatom, which is a common phenomenon in any ester or amide. We have also demonstrated here that the strength of the intramolecular n→π* interaction can be modulated by varying the electronic substituents at the para position of the donor group involved in the interaction.