Schmidt Reaction

What is Schmidt Reaction? 

The Schmidt reaction is an important name reaction of organic chemistry. In this reaction azide (conjugate base of hydrazoic acid) reacts with a carbonyl derivative (such as carboxylic acid, aldehyde, ketone) under acidic conditions to give amine or amides with release of nitrogen. It is a rearrangement reaction. That’s why it is also known as Schmidt rearrangement reaction. This reaction is very closely reacted to another name reaction called Curtius rearrangement. 

When Schmidt reaction takes place with carboxylic acid, it gives amine while when it takes place with ketone, it gives amides. Although in Schmidt reactions of both carboxylic acid and ketone, hydrazoic acid is used and nitrogen gets released. 

Schmidt Reaction with Carboxylic Acid –

Carboxylic acid + Hydrazoic acid 🡪 Primary amine + Carbon dioxide + Nitrogen 

Reaction –

[Image will be Uploaded Soon]

Schmidt Reaction with Ketone –

Ketone + Hydrazoic acid 🡪 Amide + Nitrogen 

[Image will be Uploaded Soon]

Schmidt reaction is named after Karl Friedrich Schmidt (1887 - 1971). As Karl Friedrich Schmidt 1st reported the reaction by converting benzophenone and hydrazoic acid to benzanilide in 1924. Although Schmidt reaction for carboxylic acid was not reported until 1991. 

Mechanism of Schmidt Reaction 

First, we are describing here the mechanism of Schmidt reaction with carboxylic acids. Mechanism of this reaction can be understood by following 5 steps –

Step 1. Formation of Acylium Ion – Schmidt reaction with carboxylic acid starts with formation of acylium ion. It is formed by protonation of carboxylic acid with removal of water molecule. Reaction is given below –

[Image will be Uploaded Soon]

Step 2. Acylium Ion Reaction with Hydrazoic Acid – Acylium ion reacts with hydrazoic acid and forms protonated azido ketone. Reaction is given below –

[Image will be Uploaded Soon]

Step 3. Rearrangement of Azido Ketone – Now azido ketone undergoes rearrangement with alkyl group (R) migrating over the C-N bond and with removal of nitrogen gas. Rearrangement of azido ketone forms protonated isocyanate. Reaction is given below –

[Image will be Uploaded Soon]

Step 4. Formation of Carbamate – Water molecule attacks on the protonated isocyanate and forms carbamate. Reaction is given below –

[Image will be Uploaded Soon]

Step 5. Deprotonation of Carbamate and Formation of Amine – Now carbamate undergoes deprotonation and forms carbon dioxide and amine. Reaction is given below –

[Image will be Uploaded Soon]

Mechanism of Schmidt Reaction of Ketones 

Mechanism of Schmidt reaction of ketone can be understood by following steps through Beckmann rearrangement –

Step 1. Activation of Carbonyl Group of Ketone – The carbonyl group of ketone is activated by protonation for nucleophilic addition by the azide. Reaction is given below -

[Image will be Uploaded Soon]

Step 2. Formation of Azidohydrin – Azidohydrin is formed by nucleophilic addition of nucleophile N3- at activated carbon of carbonyl group of ketone. Reaction is given below –

[Image will be Uploaded Soon]

Step 3. Formation of Diazoiminium – Azidohydrin loses water molecules in an elimination reaction to give diazoiminium. Reaction is given below –

[Image will be Uploaded Soon]

Step 4. Formation of Nitrilium Intermediate – One of the alkyl (or aryl) groups migrates from carbon of diazoiminium to nitrogen with loss of nitrogen to give a nitrilium intermediate as in the Beckmann rearrangement. Reaction is given below –

[Image will be Uploaded Soon]

Step 5. Formation of Imidic Acid – Now a water molecule attacks on nitrilium intermediate and converts it into protonated imidic acid. 

Step 6. Formation of Amide – Now imidic acid undergoes loss of proton to arrive at its tautomer of the final amide. Reactions of step 5 and 6 are given below together –

[Image will be Uploaded Soon]

In an alternative mechanism, reaction may occur in a similar manner as Baeyer – Villiger reaction to give protonated amide. 

Schmidt Reaction and Curtius Rearrangement 

Schmidt reaction and Curtius rearrangement are closely related reactions. In Curtius rearrangement reaction acyl azide is produced by the reaction of acid chloride with sodium azide and the acid chloride is formed by the reaction of carboxylic acid with SOCl2 . While in Schmidt reaction acyl azide is produced by reaction of the carboxylic acid with hydrazoic acid as discussed under the section – What is Schmidt Reaction?

For your better understanding we are giving here a brief explanation of Curtius rearrangement. 

Curtius Rearrangement - Theodor Curtius was doing various experiments with acyl azides. During these experiments he discovered that on thermal decomposition of an acyl azide, it gives isocyanate with loss of nitrogen gas. The isocyanate on reaction with alcohols gives carbamate and with water and amines gives primary amine and urea derivatives respectively. The reaction is given below –

[Image will be Uploaded Soon]

Thus, Curtius rearrangement reaction is thermal decomposition of carboxylic azides (such as acyl azide) to give isocyanate. In Curtius rearrangement acyl azide can be prepared by either reaction of acid chlorides or acid anhydrides with sodium azide or trimethyl azide or direct reaction of carboxylic acid with diphenylphosphoryl azide. Reactions are given below –

[Image will be Uploaded Soon]

This ends our coverage on the topic “Schmidt Reaction”. We hope you enjoyed learning and were able to grasp the concepts. We hope after reading this article you will be able to solve problems based on the topic and will not get confused between Curtius Rearrangement and Schmidt Reaction. If you are looking for solutions to NCERT Textbook problems based on this topic, then log on to Vedantu website or download Vedantu Learning App. By doing so, you will be able to access free PDFs of NCERT Solutions as well as Revision notes, Mock Tests and much more.