Category Archives: Biomed

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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Elimination reactions

Read the post on substitution reactions first, as many of the concepts follow on…

In an elimination reaction, fragments of a molecule are removed from adjacent atoms and replaced with a double bond. There are two mechanisms for an elimination, E1 and E2.

E1

The E1 reaction starts in the same way as an Sn1 reaction: the removal of the leaving group to form a carbocation. The nucleophile can now either attach to the carbocation and reaction becomes a substitution, or it may act as a base and take one of the hydrogens attached to an adjacent carbon. If this occurs, the elimination product is formed.

 

 

 

E1 reactions will occur under similar conditions to Sn1: they must form a stable carbocation and have a good leaving group.

 

 

 

E2:

 

E2 reactions are bimolecular eliminations, with the elimination occurring in a single step

 

 

An E2 reaction requires the nucleophile to act as a base and taken a proton from a carbon. Alkyl hydrogens are not very acidic, so this reaction requires a strong base to occur.

 

In order to distinguish E1 from E2, you need to ask the same questions for Sn1 and Sn2, the only difference is that a strong base is required for E2.

 

Zaitzev’s rule:

 

There are situations where it is possible to get two elimination products, just as in addition reactions it is possible to place the hydrogen on two difference carbons. For elimination reactions, the most substituted product will be the major product, as the more substituted an alkene is, the most stable it is.

 

Image from wikipedia

 

Links:

 

http://www.chemguide.co.uk/mechanisms/elimmenu.html#top

 

http://www.physchem.co.za/OB12-mat/organic3.htm

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Filed under Biomed, Chem 2, Organic Chemistry