Hoffmann Bromamide Reaction Mechanism

Introduction

August Wilhelm von Hoffmann discovered the Hoffmann bromamide reaction mechanism. It is also known as Hoffmann bromamide degradation or Rearrangement as the amine formed is one carbon less than the reagent used in the reaction. This reaction is used to form the primary amine and aromatic amines from amide. The reaction is performed in presence of bromine and strong base sodium hydroxide or potassium hydroxide. This reaction gives the highest yield of the amine and aromatic amines but to get the best yield of an aliphatic amine, the amide should be of less than eight carbon atoms. The product forms from this reaction are primary amine that is free from contamination of secondary and tertiary amines.

Hoffmann Bromamide Reaction Mechanism- An Introduction

In this reaction, the amide is treated with bromine and an aqueous solution of strong base i.e., sodium and potassium hydroxide. On heating, the amide is attacked by the hydroxide group and then bromide is attached to the amide and by hydrolysis, the primary amine is formed in this reaction. The other products are sodium carbonate, sodium bromide, and water. The amine formed by this reaction always carries one carbon less than the parent amide. This reaction is also known as Hoffman bromamide degradation as the amide is reduced to an amine with less carbon.

$$\mathrm{R-CO-NH_2+Br_2+4NaOH\rightarrow R-NH_2+NaCO_3+2NaBr+2H_2O\ \:\:Amide\:\:\:\:\:\:\:\:\:\:\:\:\:\:\:\:\:\:\:\:Primary Amine}$$

Example of The mechanism

The Hoffman Bromamide Reaction mechanism is shown in many reactions. Here are some examples of this reaction.

Facts Hoffman Bromamide Reaction
Reaction named after	August Wilhelm Von Hoffman
Reaction type	Rearrangement Reaction, Degradation reaction.
Reagent Used	Amides
Product formed	Primary Amines
Mediators	Bromine and an aqueous solution of a strong base.
Steps of Hoffmann Bromamide Reactions	Bromination of nitrogen, removal of hydrogen molecules, rearrangement of anion, and then hydrolysis.

• Formation of methyl amine from acetamide: In this reaction, the acetamide is treated in the presence of bromine and sodium hydroxide, the acetamide is degraded to methyl amine, and other products formed are sodium carbonate, sodium bromide, and water.

• Formation of aniline from Benzamide: Aniline is also prepared by the Hoffman bromamide reaction. In this reaction, the benzamide is reacted with bromine and potassium hydroxide to form aniline and potassium carbonate and potassium bromide, and water.

Steps of Hoffmann Bromamide Reaction Mechanism

The steps of this reaction are as follows −

• In the first step, the amide reacts with the hydroxide group, and one hydrogen is released from the amine group to form a water molecule. The removal of hydrogen generates a negative charge on the nitrogen.

• The second step is the reaction polar generates in the bromine and the positive moiety of bromine gets attached to the nitrogen of amide and forms R-CO-NHBr.

• Again, the deprotonation of amide happens and the hydrogen attached to the amide group is removed and a negative charge is generated on nitrogen and forms bromamide anion R-CO-N^- Br.

• Now, the negative charge of nitrogen tries to form a bond with carbon, and in this phase, oxygen pulls its electron and gives it back to carbon. By this, the Alkyl group detached from the carbon and formed CO-N-Br and R-.

• The alkyl group with a negative charge attacks the nitrogen and gets attached to nitrogen and bromine gets removed from the nitrogen atom and forms isocyanate C⁺ O-NR.

• There is a stereochemistry in the rearrangement of the alkyl group, the alkyl group does not detach from the amine but remains attached to the reagent in some way intramolecularly or we can say via a bridge transition state.

• In the next step, a water molecule attacks the carbon and gets attached to it, and the hydrogen of the water molecule attacks the nitrogen atom and gets attached to it.

• Again, the second hydrogen of the water molecule is also attached to the nitrogen.

• Now, carbon has two oxygen and due to thermodynamic enthalpy, the carbon forms carbon dioxide and is released from the nitrogen of the amine group and forms the product alkyl amine, sodium carbonate, and water.

Hoffman Bromamide Reaction Mechanism

Application of Hoffman Bromamide Reaction

There are various applications of the Hoffman Bromide reaction. Some are mentioned below −

• Hoffman reaction is used to prepare anthranilic acid from phthalic anhydride and urea. The intermediate product form is phthalimide, which when reacted with potassium hydroxide and bromine forms anthranilic acid.

• This reaction is used in the preparation of primary amine and aryl amines.

• By Hoffmann degradation, the isoazole-4,5 carboxamide forms an isocyanate group which is then converted into uracil by reacting with the carboxyl group.

• Nicotinamide is converted into 3-aminopyridine through the Hoffman Bromamide Reaction. In this reaction, the nicotinamide is heated in presence of bromine in the presence of aqueous sodium hydroxide at 70oC. The product formed by 3-aminopyridine is hygroscopic if it is collected in a suction filter.

Conclusion

The Hoffmann Bromamide reaction mechanism is the reaction through which we can prepare primary amine and aryl amines. In this mechanism, the amide is reacted with a strong base in presence of bromine. In the reaction the amine prepared was not contaminated by the other secondary and tertiary amine. In this reaction the amide was reacted with a strong base and released water then after reaction with bromine, it forms sodium hypobromite that after rearrangement forms isocyanate as intermediate. This isocyanate by hydrolysis includes the primary amine and carbonate of the base.

FAQs

1. In the Hoffmann bromide reaction mechanism how many bromine atoms are used?

In the overall reaction of Hoffman bromamide reaction, only one bromine is used that forms N-bromamide R-CO-NHBr.

2. Why is the Hoffmann Bromamide reaction mechanism also known as Hoffman rearrangement?

In this reaction mechanism, the alkyl group attached to the amide group changes its position from a carboxyl group to a nitrogen atom to form the N-alkyl Isocyanate R-N=C=O that later after hydrolysis forms carbamic acid which converts into the final product of amine. That is why this reaction is also known as Hoffman rearrangement.

3. Name a few similar reactions that are similar to Hoffman’s bromamide degradation reaction.

There are a few reactions that follow the same route of forming amine from amides these are Lossen, Curtius, and Schmidt Rearrangement, in these reactions the carboxylic acid groups change into isocyanate groups to form amines from amides.

4. What are the uses of Anthranilic acid prepared by the Hoffman reaction?

The Anthranilic acid prepared from the phthalic acid and urea is used commercially in the preparation of dyes, and synthesis of saccharin. The esters of anthranilic acid are used in preparing perfumes, as medicines, and as inhibitors of corrosion.

5. In the Hoffman degradation reaction, the addition of water molecule to isocyanate to form carbamic acid is which type of reaction?

The addition of water molecules to the isocyanate groups in the Hoffman bromamide degradation reaction is a nucleophilic addition reaction.