How Do We Understand Hoffmann’s Bromamide Reaction Mechanism?
In this article, we will learn about the following concepts -
Hoffmann Bromamide Reaction Mechanism- An introduction
What is Hoffmann Bromamide Reaction Mechanism?
Example of the Mechanism
Steps of Hoffmann Bromamide Reaction Mechanism
Application of the Mechanism
Limitations of the Mechanism
Key learning from the chapter
Frequently asked questions
Hoffmann’s bromamide degradation reaction
As the name of the reaction suggests, Hoffmann's bromamide degradation reaction was given by August Wilhelm Von Hoffmann. It is also known as the Hoffmann Rearrangement Reaction. This reaction is used to form primary amines. Let’s understand the name of the reaction first so that it will be easy for you to remember the reaction.
Hoffmann – Named after the German Chemist August Wilhelm Von Hoffmann.
Bromamide – Bromine molecule and amide are used in the reaction.
Degradation – One less Carbon atom you get in the product than reactant after the reaction. Thus, degradation of carbon takes place.
In Hoffmann bromamide degradation reaction, an amide reacts with bromine and an aqueous solution of sodium hydroxide which produces primary amine. This is a degradation reaction as the primary amine in the product has one carbon lesser than primary amide (in the reactant).
Hoffmann bromamide degradation reaction can be written as follows –
R-CO-NH2 + Br2 + 4NaOH → R-NH2 + Na2CO3 + 2NaBr + 2H2O
(General amide) (Bromine) (Sodium Hydroxide)
In other words, Hoffmann reaction can be written as follows –
Primary amide Br2+NaOH→ Primary amine
Secondary and tertiary amides don’t show Hoffmann bromamide reactions. Only one unit or molecule of bromine is used in the reaction.
Example of Hoffmann bromamide degradation reaction
1. Preparation of aniline
2. Preparation of methylamine
Hoffmann Bromamide Degradation Reaction Mechanism
Hoffmann bromamide reaction mechanism can be explained in the following steps –
Step 1: In this step primary amide reacts with sodium hydroxide. Hydroxide ion(anion) of NaOH attacks on a group of primary amides which results in deprotonation of primary amides and forms water and negatively charged primary amide ions.
Step 2: In this step while reacting with primary amide ion, one atom of bromine molecule develops partially positive charge while another atom develops partially negative charge due to negatively charged primary amine. It results in the formation of R-CO-NHBr (bromamide) and elimination of Br- .
Step 3: In this step, another molecule of sodium hydroxide reacts with R-CO-NHBr and another water molecule is eliminated and R-CO-NBr is left behind.
Step 4: In this step, R (alkyl or aryl group) gets detached from bromamide anion as R- which results in OC-NBr. Its rate determines the step.
Step 5:In this step R- attacks on the nitrogen atom of O=C=NBr and isocyanate is formed. Now alkyl or aryl groups are attached directly to nitrogen atoms.
Step 6: In isocyanate, a carbon atom is attached with two highly electronegative elements (oxygen and nitrogen), so it develops a partially positive charge. In this step, isocyanate reacts with water molecules, and the removal of carbon dioxide molecules takes place. Which finally results in the formation of primary amine.
Applications of Hoffmann bromamide degradation reaction
Some of the applications of the mechanism are discussed below-
It is used to produce primary aromatic and aliphatic amines.
It is used in the preparation of aniline.
It is used in the preparation of anthranilic acid and phthalimide.
3-Aminopyridine is produced by this reaction from nicotinic acid.
Hoffmann reaction does not change the symmetrical structure of -phenyl propanamide.
Limitations of Hoffmann bromamide reaction
No theory is perfect and comes with its own set of limitations. The essential step is to identify and learn about the limitations for further rework. The limitation of the Hoffmann Bromamide Reaction Mechanism is are as follows-
Secondary and tertiary amides can’t be used in the Hoffmann bromamide reaction to produce primary amines.
Conclusion:
This article focuses on Hoffmann Bromamide Reaction, its mechanism, uses/applications, and limitations to help you grasp the concept easily. The proper understanding of concepts is a crucial part of learning.
FAQs on Hoffmann Bromamide Reaction Mechanism?
1. What is the Hoffmann Bromamide Reaction? Provide an example.
The Hoffmann Bromamide Reaction is a method in organic chemistry used to convert a primary amide into a primary amine containing one less carbon atom. This transformation is achieved by treating the amide with bromine in an aqueous or ethanolic solution of a strong base, such as sodium hydroxide (NaOH).
For example, when Acetamide (CH₃CONH₂) is treated with bromine and NaOH, it degrades to form Methylamine (CH₃NH₂):
CH₃CONH₂ + Br₂ + 4NaOH → CH₃NH₂ + Na₂CO₃ + 2NaBr + 2H₂O
2. What does 'degradation' signify in the name 'Hoffmann Bromamide Degradation Reaction'?
The term 'degradation' refers to the shortening of the carbon chain during the reaction. The final product, a primary amine, has exactly one carbon atom less than the starting primary amide. This is because the carbonyl carbon (C=O) of the amide group is removed from the molecule and eliminated in the form of a carbonate ion (CO₃²⁻) during the reaction mechanism.
3. What are the key reagents required for the Hoffmann Bromamide Reaction?
To carry out the Hoffmann Bromamide Reaction, the following key reagents are essential:
- A primary amide (R-CONH₂): This is the starting material or substrate.
- Bromine (Br₂): This acts as the brominating agent.
- A strong aqueous base: Typically, Sodium Hydroxide (NaOH) or Potassium Hydroxide (KOH) is used to facilitate the reaction.
4. Can you explain the step-by-step mechanism of the Hoffmann Bromamide Reaction?
The Hoffmann Bromamide Reaction mechanism proceeds through several key steps:
- Step 1: Deprotonation. A hydroxide ion (OH⁻) from the base removes a proton from the nitrogen of the amide, creating an anion.
- Step 2: Bromination. The amide anion attacks a bromine molecule to form an N-bromoamide intermediate.
- Step 3: Second Deprotonation. Another hydroxide ion removes the remaining proton from the nitrogen, forming a bromoamide anion.
- Step 4: Rearrangement. The alkyl or aryl group (R) attached to the carbonyl carbon migrates to the nitrogen atom, simultaneously displacing the bromide ion. This is the rate-determining step and results in the formation of an isocyanate (R-N=C=O) intermediate.
- Step 5: Hydrolysis. The isocyanate is hydrolysed by water, which leads to the formation of an unstable carbamic acid. This acid quickly decarboxylates (loses CO₂) to yield the final primary amine (R-NH₂).
5. What is the rate-determining step in the Hoffmann Bromamide Reaction mechanism?
The rate-determining step, or the slowest step of the reaction, is the rearrangement of the bromoamide anion. This is the crucial intramolecular step where the alkyl or aryl group migrates from the carbonyl carbon to the nitrogen atom, leading to the formation of the isocyanate. The overall speed of the Hoffmann reaction depends on how quickly this rearrangement occurs.
6. What is the primary intermediate formed during the Hoffmann rearrangement?
The primary and most significant intermediate formed during the Hoffmann rearrangement is an isocyanate (R-N=C=O). This molecule is the direct result of the migration of the alkyl/aryl group. The subsequent hydrolysis of this isocyanate is what ultimately leads to the formation of the final primary amine product.
7. Why can't secondary or tertiary amides undergo the Hoffmann Bromamide Reaction?
Secondary (R-CONHR') and tertiary (R-CONR'R'') amides cannot undergo this reaction because the mechanism requires the presence of two acidic hydrogen atoms on the amide's nitrogen atom. These two hydrogens are removed in two separate deprotonation steps by the base. Since secondary amides have only one hydrogen on the nitrogen and tertiary amides have none, the reaction cannot proceed beyond the initial steps, making the reaction specific to primary amides only.
8. What are some important applications of the Hoffmann Bromamide Reaction?
This reaction is highly useful in organic synthesis for several purposes:
- Synthesis of Primary Amines: It is a classic and reliable method for preparing primary aliphatic and aromatic amines.
- Step-down Reaction: As it reduces the carbon chain by one atom, it is used to descend a homologous series.
- Preparation of Aniline: Aniline, an important industrial chemical, can be synthesised from benzamide using this reaction.
- Synthesis of Anthranilic Acid: This reaction is used commercially to convert phthalimide into anthranilic acid, a precursor for dyes and pigments.
9. How is the Hoffmann Bromamide Reaction different from the Hofmann Elimination Reaction?
Despite both being named after August Wilhelm von Hofmann, these are two distinct reactions:
- Hoffmann Bromamide Reaction: This is a degradation reaction that converts a primary amide into a primary amine with one less carbon. Its key feature is an intramolecular rearrangement to form an isocyanate intermediate.
- Hofmann Elimination Reaction: This is an elimination reaction used to convert a quaternary ammonium salt into an alkene by heating it with a base like silver oxide (Ag₂O). It is known for producing the least substituted alkene (the 'Hofmann product') as the major product.
