Substitution reactions

A nucleophilic substitution reaction occurs when a nucleophile (link to nucleophile post) reacts with the substrate to replace the leaving group. This reaction can occur via two pathways – Sn1 or Sn2. We’ll start with Sn1.

The Sn1 reaction occurs in two steps, the first is the removal of the leaving group from the substrate, and the second is the addition of the nucleophile to the carbocation.

Formation of the carbocation

Nucleophilic attack

The formation of the carbocation is the rate-determining step, (the slow step that determines the overall rate of the reaction), and as it relies only on the concentration of the substrate, the kinetics are first order – hence Sn1.

In order for an Sn1 reaction to occur, the carbocation formed in step one must be stable enough for the leaving group to leave without causing a reverse reaction. Carbocation stability depends on the number of alkyl side groups attached to the positively charged carbon – the more substituents, the more stable the carbocation is:

In order to create a carbocation at all, the leaving group must be good enough to detach from the substrate on its own.

By going through a planar intermediate, Sn1 reactions lose any stereochemistry, as the nucleophile is free to attack from either face of the carbocation. The product of an Sn1 reaction will always be a racemic mixture.

The Sn2 reaction occurs in a single, concerted step, the rate of which depends on both the nucleophile and substrate concentrations.

The nucleophile attacks the substrate from the opposite side to the leaving group, (backside attack), pushing the leaving group away. This results in an inversion of stereochemistry, known as an umbrella inversion or Walden inversion. Of course, if you start with a racemic mixture, you’ll end up with one.

Because it is like an umbrella being blown inside out in the wind

Sn2 reactions must go through a 5 membered transition state, which is crowded and unpleasant for the central carbon. This transition state can only form provided the substrate is not bulky, and the nucleophile is also small. If there are too many atoms around the central carbon, the nucleophile simply won’t fit.

Now you know all you need to in order to distinguish between Sn1 and Sn2 reactions.

  1. Is the leaving group a very good leaving group? If no, it cannot be Sn1
  2. Is the nucleophile a good nucleophile? If no, it cannot be Sn2.
  3. Will the removal of the leaving group from a stable carbocation? If no, it cannot be Sn1.
  4. Is the substrate sterically hindered? If yes, it cannot be Sn2.
  5. Has there been inversion of stereochemistry? Yes? Sn2.

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Filed under Biomed, Chem 2, Organic Chemistry

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