This dissertation describes the density functional theory (DFT) computational modelling of reactions between organolithium nucleophiles and various substituted quinoxalines. These reactions result in the functionalisation of the C (sp2)–H bond, thus substituting the sigma-hydrogen. The reactions are known as nucleophilic substitution of hydrogen (SNH) and are used by experimental chemists to form new C–C bonds. The SNH reactions are very important in various industries, e.g. in designing and manufacturing of pharmaceuticals. Quinoxaline is widely used in medicinal chemistry due to its various biological activities; these reactions play a crucial role in the synthesis of new classes of compounds. The reactions of 2-phenyl- (A), 2-butyl- (B), and 6-nitro-2-phenyl- (C) quinoxaline with lithiofuran (a) and lithiothiophene (b) involves a direct (1) nucleophilic attack on an activated electron-deficient system, leading to the intermediate sigma^H-complex. This is followed by hydrolysis (2), where an sp2-type nitrogen is changed to an sp3 while forming Li---OH as a by-product. The presence of Li---OH then allows the departure of an sigma-proton via oxidation reaction, concomitantly forming H2O2 as the second by-product. All approaches to functionalise the C(sp2)–H bond involve elimination of a proton, and an oxidant is needed for the departure of the sigma-hydrogen. Although the sequence of steps and mechanisms of these C–H transformations are the same, various factors have shown to affect the reactions differently. The theoretical study of this catalytic-free transformation, shows that the formation of sigma^H-adducts is not easily reversible, and that their formation is spontaneous. The reaction does not just require an oxidant to eliminate the sigma-hydrogen with the pair of electrons, but rather requires the presence of water for hydrolysis prior to oxidation. We must stress the crucial role of the oxidant since the key problem of the SNH reactions is associated with the elimination of sigma-hydrogen. However, the main objective of this study is to present a correct and complete mechanistic picture of oxidative nucleophilic substitution of hydrogen (ONSH). Previous reports indicated that the presence of an electron donating/withdrawing group on the quinoxaline ring had a significant influence on the yield and selectivity. This is between reactions A+a, A+b, and B+a. These experimental observations correlated well with the modelling results when the potential energy surfaces (PES) of the reactions were compared. / Dissertation (MSc)--University of Pretoria, 2020. / National Research Foundation (NRF) / Chemistry / MSc / Unrestricted