Schmidt Reaction refers to an organic chemical reaction wherein azides are reacted with the carbonyl group of a compound to give rise to amines or amides. This reaction was first reported by Karl Friedrich Schmidt in 1924.
Schmidt Reaction Examples
The Schmidt Reaction can be employed to either get amides by reacting the azide with a ketone, or to get an amine by reacting the azide with a carboxylic acid.
Schmidt Reaction for Carboxylic Acids
The chemical reaction wherein amines can be produced from an azide and a carboxylic acid can be illustrated as follows:
Schmidt Reaction for Ketones
Another example of the Schmidt Reaction is when an amide is produced from the chemical reaction between an azide and a ketone. This reaction can be illustrated as follows:
The Schmidt reaction can be used to prepare benzanilide from benzophenone and hydrogen azide. This is an example of the preparation of an amide from a ketone and an azide.
Schmidt Reaction Mechanism
As discussed earlier, the schmidt reaction can be used to produce either amides or amines. For each of these products, a different functional group is required (ketones and carboxylic acids respectively). Therefore, the mechanisms for each of these reactions are detailed below.
Schmidt Reaction Mechanism for Producing Amines
- This mechanism begins with the formation of an acylium ion from the protonation of the carboxylic acid followed by the removal of water.
- This acylium ion is now reacted with hydrazoic acid, leading to the formation of a protonated azido ketone.
- Now, the protonated azido ketone and the R group undergo a rearrangement reaction, resulting in the migration of the carbon-nitrogen bond and the removal of dinitrogen leading to the formation of a protonated isocyanate.
- Now, a carbamate is formed when water is introduced to attack the protonated isocyanate.
- The carbamate is now deprotonated. The subsequent removal of CO2 yields the required amine.
This mechanism can be illustrated as follows:
Schmidt Reaction Mechanism for Producing Amides
- This Mechanism begins with the protonation of the ketone, leading to the formation of an O-H bond.
- The subsequent nucleophilic addition of the azide leads to the formation of an intermediate.
- Water is now removed from this intermediate via an elimination reaction, forming a temporary imine.
- An alkyl group which was a part of the original ketone now migrates from the carbon to the nitrogen belonging to the imine. This results in the elimination of dinitrogen.
- Now, water is used to attack the resulting compound, and the subsequent deprotonation yields a tautomer of the required amide.
- The relocation of a proton belonging to the tautomer of the amide gives the final amide product.
The Schmidt Reaction mechanism for producing amides from ketones is illustrated above.