Need help preparing for the Organic Chemistry section of the MCAT? MedSchoolCoach expert, Ken Tao, will teach everything you need to know about SN2 for nucleophilic substitution. Watch this video to get all the MCAT study tips you need to do well on this section of the exam!
SN2: A ‘Concerted’ Reaction
Bimolecular nucleophilic substitution reactions, or SN2 reactions for short, are single-step reactions in which a nucleophile replaces (substitutes) for an existing leaving group of lesser nucleophilicity, through attack on an adjacent electrophilic center. The ‘bimolecular’ portion of the name stems from the fact that the reaction kinetics of such reactions are second order, meaning they depend on the concentrations of two individual reactants species: The nucleophile and the substrate.
All SN2 reactions occur in a single, concerted step. This means that both nucleophilic attack and removal of the leaving group happen in the same step and proceed through the formation of only a single intermediate. As the nucleophile attacks the electrophilic center adjacent to the leaving group, the bond to the leaving group is broken. We can expect this property to have a lot of consequences for the stereochemistry of products, rates of reaction and what reactants and substrates are suitable for such reactions.
Mechanism of SN2 Reactions
The primary driving force behind all SN2 reactions is nucleophilic attack by a sufficiently strong nucleophile. In fact, strength of the attacking nucleophile is highly predictive of the reaction rate of an SN2 reaction. The stronger the nucleophile, the higher the reaction rate. Of special importance is the directionality of this attack: Since in SN2, the leaving group is still bound during the attack, most potential avenues for attack upon the electrophilic center are strongly sterically hindered. This forces a situation where the nucleophilic attack takes place on the side opposite the leaving group in 3-dimensional space. This is the so-called backside attack.
A pentameric transition state (‡) is formed in which all 5 ligands are briefly bound. Keep in mind that transition states are extremely high energy states, in fact the highest energy state on a reaction coordinate is conventionally called the transition state. This means that its existence is very transient before decaying to a more energetically favorable configuration, that of our products. Despite its brief lifetime, the molecular geometry of this transition state has important implications for the stereochemistry of the product.
The benefit of understanding the transition state is that it makes obvious why an inversion of stereochemistry occurs. We can observe our bromine substituent in the reagents facing right, and the location of both iodine and bromine in the pentameric transition state. As bromine leaves, the remaining iodine is now on the opposite side of the new tetrahedral arrangement around the central carbon.
If we use Cahn-Ingold-Prelog (CIP) rules to assign priority to each substituent, we notice that our initial alkyl halide, we notice that it was in the R configuration before the reaction. Analyzing our product the same way, we find an S configuration. This inversion of stereochemistry is something you can expect to see happening in SN2 reactions, and often a criterion by which we can suspect that an SN2 mechanism may be at work in a particular reaction.
Summary of SN2 reactions
Now we have enough information to summarize SN2 reactions. First of all, their kinetics are second order, as presented in equation 1. Both the concentration of the nucleophile and electrophile matter.
rate = k[Nu:][Electrophile]
Equation 1. Rate of an SN2 reaction
Next, all SN2 reactions occur in a single concerted step and result in an inversion of absolute stereochemistry between reactants and products, with the very rare exception of higher priority CIP groups being present outside the nucleophile and leaving group.
And finally, we need to conclude our discussion by mentioning the viability of different reactants and solvents in an SN2 reaction. In terms of reactants, methyl alkyl halides, primary alkyl halides and secondary alkyl halides can all undergo SN2 - however, methyl and primary alkyl halides react fastest by far. Tertiary alkyl halides are not viable at all. As a general pattern, the fewer substituents any reactant has, the more readily it will undergo an SN2 reaction.
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