Substitution and Elimination

Substitution and elimination reactions are at the heart of most of the organic chemistry reactions you will encounter on the MCAT. Having a solid understanding of what these reactions are and how they work will not only allow us to predict what reactions are likely they will help us understand a wide array of other “more complicated” reactions. Since pretty much all of organic chemistry occurs due to electrostatic attraction, electrostatic repulsion, and sterics we will be viewing all of these basic reactions through this lens.


Substitution reactions are aptly named and involve the switching or substitution of one group with another. This occurs because a group or element with a high electronegativity value steals bonding electrons from alkyl chains.

As a result, molecules will have regions that are more positive and other regions that are more negative. Where the electronegative atoms will pull electrons towards them making them more negative while making whatever atom they are bonded to more positive.

Due to this, there are three major organic molecules that undergo substitution reactions: alkyl halides, alcohols, and epoxides.

Here the yellow boxes show the electrophilic carbons that are looking for someone to give them electrons.

Regions with partially positively charges regions are called electrophilic since they have had their electrons stolen and as a result want more electrons. While partially negatively charged regions are called nucleophilic since they have electrons to spare they want to find something positive, a nucleus, to give them to, making them nucleus lovers.

In substitution reactions the electrophilic carbons are swapping out atoms or molecules for better bonding partners.

The atom or molecule that gets left out in the cold is called the leaving group since it will end up leaving the molecule and forging its own way in the world.

Leaving Groups

Not all leaving groups are made equally though and some are much better at tolerating “heartbreak” than others. As a result, these leaving groups are far more reactive and more likely to undergo substitution reactions.

Generally speaking the more stable you are alone the better leaving group you are. There are two major predictive factors that determine the leaving groups stability the first is basicity and the second is size.

As basicity decreases stability increases. This makes sense since the leaving group is totally happy as it is. It doesn’t want to react and pick up a hydrogen from the solution.

Second as size increases stability also increases. This occurs because the extra electrons that the leaving group grabs up have space to stretch out and experience less repulsion from other nearby electrons.