Question

Briefly compare and contrast the S N 1 and S N 2 mechanisms in terms of kinetics, steric effect, nature of the nucleophile, and the nature of the leaving group.

Answer 1

The Mechanism

• The SN2 reaction is concerted. That is, the SN2 occurs in one step, and both the nucleophile and substrate are involved in the rate determining step. Therefore the rate is dependent on both the concentration of substrate and that of the nucleophile.
• The SN1 reaction proceeds stepwise. The leaving group first leaves, whereupon a carbocation forms that is attacked by the nucleophile.

The Big Barrier – this is the most important thing to understand about each reaction. What’s the one key factor that can prevent this reaction from occurring?

• In the SN2 reaction, the big barrier is steric hindrance. Since the SN2 proceeds through a backside attack, the reaction will only proceed if the empty orbital is accessible. The more groups that are present around the vicinity of the leaving group, the slower the reaction will be. That’s why the rate of reaction proceeds from primary (fastest) > secondary >> tertiary (slowest)
• In the SN1 reaction, the big barrier is carbocation stability. Since the first step of the SN1 reaction is loss of a leaving group to give a carbocation, the rate of the reaction will be proportional to the stability of the carbocation. Carbocation stability increases with increasing substitution of the carbon (tertiary > secondary >> primary) as well as with resonance.

The dependence of rate upon the substrate

• For the SN2, since steric hindrance increases as we go from primary to secondary to tertiary, the rate of reaction proceeds from primary (fastest) > secondary >> tertiary (slowest).
• For the SN1, since carbocation stability increases as we go from primary to secondary to tertiary, the rate of reaction for the SN1 goes from primary (slowest) << secondary < tertiary (fastest)

Remember that SN1 and SN2 reactions only occur for alkyl halides (and related compounds like tosylates and mesylates). If the leaving group is directly attached to an alkene or alkyne, SN1 or SN2 will not occur!

The Nucleophile

• The SN2 tends to proceed with strong nucleophiles; by this, generally means negatively charged nucleophiles such as CH3O(-), CN(-), RS(-), N3(-), HO(-), and others.
• The SN1 tends to proceed with weak nucleophiles – generally neutral compounds such as solvents like CH3OH, H2O, CH3CH2OH, and so on.

The Solvent

• The SN2 reaction is favored by polar aprotic solvents – these are solvents such as acetone, DMSO, acetonitrile, or DMF that are polar enough to dissolve the substrate and nucleophile but do not participate in hydrogen bonding with the nucleophile.
• The SN1 reaction tends to proceed in polar protic solvents such as water, alcohols, and carboxylic acids. These also tend to be the nucleophiles for these reactions as well.

Stereochemistry

• Since the SN2 proceeds through a backside attack, if a stereocenter is present the SN2 reaction will give inversion of stereochemistry.
• By contrast, if the SN1 leads to the formation of a stereocenter, there will be a mixture of retention and inversion since the nucleophile can attack from either face of the flat carbocation.