Page - (000027) - in Biomedical Chemistry: Current Trends and Developments

mechanisms can be used to understand the equivalent biological transformations. 1.1.4.1 Nucleophilic Substitution Reactions Nucleophilic substitution reactions occur when a group attached to an sp3 carbon is substituted for a more nucleophilic one. These reactions may follow two similar mechanisms ‒ bimolecular and unimolecular ‒ but with very different implications for biological systems in terms of stereochemistry. 1.1.4.1.1 SN2 – Bimolecular Nucleophilic Substitution This type of mechanism (Scheme 1.1.5) is called a bimolecular nucleophilic substitution (SN2) since the determining step involves the reaction of two species, the nucleophile and the substrate (electrophile species). Scheme 1.1.5: General reaction for an SN2 reaction mechanism. The following happens in one concerted step: a nucleophile (N) attacks the carbon atom as a more electronegative group (X) leaves, with inversion of stereochemistry through an unstable transition state. Note that N can be a neutral protic nucleophile that deprotonates after the substitution. This type of mechanism is typical of primary alkyl halides substitutions. One reaction often performed in a laboratory is an O- methylation using methyl iodide. The oxygen atom (of an alcohol, for example) acts as nucleophile substituting the iodide which is a very good leaving group. 1.1.4.1.2 SN1 ‒ Unimolecular Nucleophilic Substitution Reactions