*Article* **Perturbating Intramolecular Hydrogen Bonds through Substituent Effects or Non-Covalent Interactions**

**Al Mokhtar Lamsabhi \*, Otilia Mó and Manuel Yáñez \***

> Departamento de Química (Módulo 13, Facultad de Ciencias) and Institute of Advanced Chemical Sciences (IadChem), Universidad Autónoma de Madrid, Campus de Excelencia UAM-CSIC, Cantoblanco, 28049 Madrid, Spain; otilia.mo@uam.es

**\*** Correspondence: mokhtar.lamsabhi@uam.es (A.M.L.); manuel.yanez@uam.es (M.Y.)

**Abstract:** An analysis of the effects induced by F, Cl, and Br-substituents at the α-position of both, the hydroxyl or the amino group for a series of amino-alcohols, HOCH2(CH2)nCH2NH2 (*n* = 0–5) on the strength and characteristics of their OH···N or NH···O intramolecular hydrogen bonds (IMHBs) was carried out through the use of high-level G4 ab initio calculations. For the parent unsubstituted amino-alcohols, it is found that the strength of the OH···N IMHB goes through a maximum for *n* = 2, as revealed by the use of appropriate isodesmic reactions, natural bond orbital (NBO) analysis and atoms in molecules (AIM), and non-covalent interaction (NCI) procedures. The corresponding infrared (IR) spectra also reflect the same trends. When the α-position to the hydroxyl group is substituted by halogen atoms, the OH···N IMHB significantly reinforces following the trend H < F < Cl < Br. Conversely, when the substitution takes place at the α-position with respect to the amino group, the result is a weakening of the OH···N IMHB. A totally different scenario is found when the amino-alcohols HOCH2(CH2)nCH2NH2 (*n* = 0–3) interact with BeF2. Although the presence of the beryllium derivative dramatically increases the strength of the IMHBs, the possibility for the beryllium atom to interact simultaneously with the O and the N atoms of the amino-alcohol leads to the global minimum of the potential energy surface, with the result that the IMHBs are replaced by two beryllium bonds.

**Keywords:** intramolecular hydrogen bonds; amino-alcohols; α-substitution; beryllium bonds; calculated infrared spectra
