Hoffmann Bromamide Reaction

Hoffmann Bromamide Reaction is named after the famous chemist August Wilhelm Von Hoffmann. If an amide is treated with Bromine in an aqueous or ethanolic solution of sodium hydroxide, the formation of amine takes place. It is used to synthesize primary aromatic and aliphatic amines.

In this article, we will explore the Hoffmann Bromamide Reaction, its mechanism, its applications, examples, and limitations in detail.

What is Hoffmann Bromamide Reaction?

Hoffmann Bromamide Reaction involves the strategic use of alkali as a strong base to attack an amide. This attack triggers deprotonation and the generation of an anion. The reaction unfolds by heating a primary amide with a halogen, a strong base, and water. The primary amine that results is entirely free from contamination. No secondary or tertiary amines are present in the Hoffmann Bromamide Reaction. This is a significant characteristic of the reaction. Hoffman Bromamide Reaction is also called Hoffman Bromamide Degradation Reaction.

R-C=O-NH₂ + Br₂ + 4KOH → R-NH₂ + K₂CO₃ + 2KBr + 2H₂O

Related read: Chemical Reactions of Alcohols, Phenols, and Ethers

Hoffmann Bromamide Reaction Mechanism

General equation of Hoffmann Bromamide reaction is

RCONH₂ + Br₂ + 4 NaOH ——> RNH₂ + Na₂CO₃ + 2 NaBr + 2 H₂O

Step 1: Hydroxide Ion Attack on Amide

RCONH₂ + OH⁻ → RCONH⁻ + H₂O

The process initiates with the strong base’s hydroxide ion (OH-) attacking the amide. The interaction causes the amide to lose a proton. This forms water and the amide’s anion.

Step 2: Anion Attack on Bromine

RCONH⁻ + Br₂ → RCONHBr + Br^–

The anion formed in the previous step attacks the diatomic bromine. This happens in an alpha substitution reaction. This results in the formation of N-bromamide and a bromide anion. This forms an unstable intermediate compound.

Step 3: Base Attack on N-Bromamide

RCONHBr + OH⁻ → RCONBr⁻ + H₂O

The base attacks the N-bromamide again. This leads to its deprotonation and the creation of bromamide anion.

Step 4: Rearrangement of Bromamide Anion

RCONBr⁻ → R-NC≡O + Br⁻

The bromamide anion rearranges, causing the alkyl or aryl group bonded with the carbonyl carbon to bond with nitrogen. Simultaneously, the bromide anion departs, resulting in the formation of an isocyanate.

Step 5: Addition of Water to Isocyanate

R-NC≡O + H₂O → RNHCOOH

The isocyanate undergoes a nucleophilic addition reaction when water is added. This reaction forms carbamic acid.

Step 6: Loss of Carbon Dioxide

RNHCOOH → RNH₂ + CO₂

Carbamic acid loses carbon dioxide and undergoes decarboxylation. This gives rise to a negatively charged nitrogen bonded to hydrogen and the alkyl or aryl group.

Read More,

• Carboxylic acids
• Methods of preparation of Carboxylic acids

Examples of Hoffmann Bromamide Reaction

Some examples of Hoffmann Bromamide Reaction

Preparation of Aniline

The preparation of Aniline from the Hoffmann Bromamide reaction is shown below,

CH₃CONHPh + 3Br₂ + 6NaOH → C₆H₅NH₂ + CH₃COONa + 3NaBr + 3H₂O

Preparation of Methylamine

The preparation of Methylamine from the Hoffmann Bromamide reaction is shown below,

CH₃CONH₂ + 3Br₂ + 6NaOH → CH₃NH₂ + CH₃COONa + 3NaBr + 3H₂O

Hoffmann Bromamide Reaction Applications

Hoffmann Bromamide Reaction finds extensive applications in organic synthesis. Some important applications include,

Preparation of Aniline: The reaction is used to make aniline. Aniline is a crucial compound in making dyes and medicine.

3-Aminopyridine Synthesis: Hoffmann Bromamide Reaction plays an important role in synthesizing 3-aminopyridine from nicotinic acid.

Anthranilic Acid and Phthalimide Preparation: The reaction is used to prepare anthranilic acid and phthalimide. These compounds have various applications in the chemical industry.

Production of Primary Aromatic and Aliphatic Amines: The Hoffmann Bromamide Reaction is used in industry to produce primary aromatic and aliphatic amines.

Limitations of Hoffmann Bromamide Reaction

Hoffmann Bromamide Reaction is an important organic reaction, however, it does have limitations that are,

Limited to Primary Amides: The Hoffmann bromamide reaction is limited to primary amides. It can only convert primary amides to primary amines. It is not effective for secondary or tertiary amides.

Formation of Side Products: The Hoffmann bromamide reaction can form unwanted side products. These products include alkenes or alkynes in some cases.

Strong Reaction Conditions: The Hoffmann bromamide reaction requires strong conditions. These conditions include bromine and sodium hydroxide. These conditions can be hazardous and may not be suitable for all substrates.

Sample Questions on Hoffmann Bromamide Reaction

Some questions on Hoffmann Bromamide Reaction are,

1. What is Hoffmann Bromamide Reaction?

Hoffmann Bromamide Reaction is,

RCONH₂ + Br₂ + 4 NaOH ——> RNH₂ + Na₂CO₃ + 2 NaBr + 2 H₂O

2. What is Importance of Hoffmann Bromamide Reaction?

• Hoffmann Bromamide Reaction is used for the preparation of aniline.

• Hoffman Bromamide Reaction produces primary aromatic and aliphatic amines.

Hoffmann Bromamide Reaction – FAQs

1. What Is Hoffmann Bromamide Reaction in Chemistry?

Hoffmann Bromamide Reaction is a chemical reaction that is used to perform primary amine.

2. What is Other Name of Hoffmann Bromamide Reaction

Hoffmann Bromamide Reaction is also called Hoffmann Degradation.

3. What is Intermediate Compound in Hoffmann Bromamide Reaction?

Intermediate compound in the Hoffmann Bromamide Reaction is the Bromamide Anion (RCONBr⁻).

4. What are Reagents in the Hoffmann Bromamide Reaction?

Hoffmann Bromamide Reaction uses specific reagents for the process. These reagents are a primary amide (RCONH₂), Bromine (Br₂), a strong base (usually sodium hydroxide, NaOH), and water (H₂O).

5. What is an Example of a Hofmann Reaction?

Some example of Hoffamm Reaction are,

CH₃CONHPh + 3Br₂ + 6NaOH → C₆H₅NH₂ + CH₃COONa + 3NaBr + 3H₂O

6. What is the Name Reaction of Amide to Amine?

Name Reaction of Amide to Amine is Hofmann’s Bromamide Reaction.

7. What Is Mechanism Of Hoffmann Bromamide Reaction?

Mechanism of Hoffmann Bromamide reactions includes the following steps,

1. Hydroxide Ion Attack on Amide
2. Anion Attack on Bromine
3. Base Attack on N-Bromamide
4. Rearrangement of Bromamide Anion
5. Addition of Water to Isocyanate
6. Loss of Carbon Dioxide