Dynamic Effects in Nucleophilic Substitution Reactions



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In order to rationally optimize a reaction, it is necessary to have a thorough understanding of its mechanism. Consequently, great effort has been made to elucidate a variety of reaction mechanisms. However, the fundamental ideas needed to understand reaction mechanisms are not yet fully developed. Throughout the literature, one encounters numerous examples of experimental observations that are not explainable by conventional mechanistic ideas and methods. The research described in this dissertation employs a unique approach towards the identification and analysis of systems whose observations cannot be explained by conventional transition state theory (TST).

The nucleophilic substitution of 4,4-dichloro-but-3-en-2-one by sodium-para-tolyl-thiolate was explored. It was deduced that the reaction was concerted and consequently, the product selectivity observed in the reaction cannot be explained by TST. Dynamic effects play a major role in the observed selectivity and this is further supported by the results of dynamic trajectory simulations.

Using computational studies, the ethanolysis of symmetric aryl carbonates was also shown to be concerted, provided that the substrate possesses good leaving groups. Furthermore, extensive precedence has been set by Gutthrie, Santos, Schelgel, and others, detailing concerted substitutions at acyl carbon.

The Fujiwara hydroarylation is thought to occur by either a C-H activation mechanism or an electrophilic aromatic substitution (EAS). The KIEs associated with this reaction have been determined and provide strong support for the latter. Computational studies also displayed fair agreement with experimentally determined KIEs, further supporting the EAS mechanism.

Isotopic perturbation of equilibria is invaluable in helping to determine whether a structure exists as a single structure or whether it is a time average of two equilibrating structures. The bromonium cation of tetramethylethylene and hydrogen pthalate have been wrongly reported as existing as equilibrating structures. The time averaged geometries have been determined in each case, via a variety of methods and the myth of equilibrating structures in the above cases has been debunked.