Chemistry 3719 - Dr. Peter Norris
Nucleophilic Substitution Reactions

Nucleophilic Substitution reactions are transformations in which nucleophilic reagents displace a leaving group in an electrophilic substrate. The substrate will usually be an alcohol (or some derivative thereof) or an alkyl halide.  There are two possible mechanisms to be considered here, the SN1 in which the leaving group comes off before the nucleophile bonds (i.e. a stepwise mechanism), and the SN2 in which the bond making and bond breaking steps occur at the same time (concerted mechanism).  The following series of graphics may help you visualize the events occurring during these different mechanisms.

Nucleophilic Substitution Unimolecular (SN1) - So far in 3719 this type of reaction most often occurs with tertiaryalcohols which are capable of generating a tertiary carbocation when the leaving group is lost. We use an acid such as HCl, HBr and HI so that water behaves as the leaving group and Cl -, Br - or I - as the nucleophile.

Overall Reaction:
Mechanism
Using t-butanol reacting with HBr as an example, the first step of the reaction is a protonation of the alcohol's OH group. It is important to note that this is not the SN1 yet, it is a very fast acid-base reaction that sets up the substitution reaction.
The actual substitution reaction begins when the leaving group breaks away to generate a 3o cation. This is the slowest step in the mechanism and is therefore defined as the rate-determining step. Since the R.D.S. only involves one species (the protonated alcohol) this reaction is said to be unimolecular, i.e. SN1.



The unstable carbocation (unstable since it only has 6 electrons) is then able to react with the elecrton-rich nucleophile (in this case the Br - from HBr) and regain the stable octet configuration. This reaction is very fast (low activation barrier) and leads to the alkyl halide product.



Overall, the reaction results in nucleophilic substitution of a leaving group by a nucleophile on an electrophilic carbon. In this case the R.D.S. is known to be unimolecular and is therefore defined as SN1. The SN1 is classified as a stepwise mechanism. The following animation puts the mechanistic events in sequence:

Nucleophilic Substitution Bimolecular (SN2) - So far in 3719 this type of reaction most often occurs with primary alcohols which are not capable of generating a decent carbocation when the leaving group is lost, instead the bond making and bond breaking events occur simultanously (i.e. a concerted pathway). We use an acid such as HCl, HBr and HI so that water behaves as the leaving group and Cl -, Br - or I - as the nucleophile.

Overall Reaction
Mechanism
Using ethanol and HBr as a typical example, the first step in the alcohol to alkyl halide conversion is an acid-base reaction to form a good leaving group (H2O). Notice again that this step is a prelude to the substitution reaction.

sn2b

The sustitution step occurs when the nucleophile (Br - in this case) begins to bond to the electrophilic carbon at the same time that the leaving group (in this case H2O) begins to break away. The system passes through a transition state which is depicted using partial bonds. Note there are no intermediates such as carbocations formed here. This step is rate determining and is bimolecular, therefore SN2.

sn2c

The complete breaking of the C-O bond and the complete formation of the C-Br bond leads to the alkyl halide product.

Overall, the reaction results in nucleophilic substitution of a leaving group by a nucleophile on an electrophilic carbon. In this case the R.D.S. is known to be bimolecular and is therefore defined as SN2. The SN2 is classified as a concerted mechanism.

sn2d
The following animation puts the mechanistic events in sequence:

sn2
Most alcohol substrates have the option of either SN2 or SN1 and the path taken depends on structure. At this point tertiary alcohols will follow the SN1 pathway (decent carbocation, stepwise mechanism), and primary alcohols will follow the alternate SN2 pathway (concerted mechanism).
Peter Norris, Ph.D.