The [2.2]cyclophanes are the simplest [2n]cyclophanes that present two benzene rings connected by two ethanediyl linkages. The [2.2]paracyclophane, (1), is considered the most tensioned [2.2]cyclophane, which has face-to-face benzene rings connected by alkane bridges. The structural characteristics of these compounds make possible to investigate the presence of the transannular interactions, which are classified as through-space interactions (π-π interaction between the aromatic rings) or through-bond interactions (σ-π interaction between the benzene rings and the methylene bridges), and how these interactions affect the chemical properties. In this sense, the aim of this work is to investigate the effects of different substituents, as -F, -CN, -C=O, -NH2 and -H+ on the electronic structure and on the chemical properties of 1. All calculations were made by B3PW91/6-31+G(d,p). The geometries indicate that the dihedral angles of the bridges are the most affected by the substituents, independent of their nature (electron-withdraw or electron-donor). The aromaticity was evaluated by using NICS and HOMA criteria. The presence of C=O and the protonation reduce drastically the aromaticity by breaking off the electron delocalization. The NBO, NRT, and NSA analyses showed that the substitution induces the presence the transannular interactions. In addition, the AIM analysis pointed out through-space interactions only in two compounds. In general, it can be concluded that some substituents induces the presence of a large number of through-space interactions with small second-order stabilization energy and the protonation causes a small number of through-space interactions but with large second-order stabilization energy.