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Structure of Amide
When nitrogen is attached to a carbonyl group, the resulting functional group is called amide.
- This organic compound requires a medium for the hydrolysis and produces carboxylic acid along with salt of amine.
- The hydrolysis of amides is a form of chemical reaction in which the amide reacts with the water molecule to break the amide bond.
Hydrolysis
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Hydrolysis is the reaction in which a large molecule is broken down into smaller molecules in the presence of water. In other words, hydrolysis is catalyzed by water.
- Hydroxide (OH⁻) and hydrogen (H⁺) ions are formed when water hydrolyzes.
- Hydrogen ions are produced during acid hydrolysis, while hydroxide ions are produced during bases such as amide hydrolysis.
Hydrolysis of Amide
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Amide is a nitrogen-containing functional group that is present in three different forms: primary, secondary, and tertiary amides.
- The hydrolysis of amide is a challenging process as it usually resists hydrolysis due to the presence of resonance in the amide structure.
- The relationship between activation energy and reaction rate was given by Arrhenius which states that the “higher the activation energy, the lower would be the rate of reaction.’’
- Depending on the structure of the amide, the reaction of hydrolysis of amide yields a carboxylic acid and an amine as by-products.
- Therefore, due to the high activation energy of the amide bond, hydrolysis takes more time.
Types of Amide Hydrolysis
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The hydrolysis of amide is catalyzed in two ways:-
- Acid-catalyzed amide hydrolysis
- Base-catalyzed amide hydrolysis
Acid-catalyzed Amide Hydrolysis
When amide is reacted with water in the presence of water, a carboxylic acid is formed in addition to a salt of ammonia. The reaction proceeds in the following steps:
Protonation of Carbonyl Amide
- Acid-catalyzed amide hydrolysis begins with the protonation of carbonyl oxygen.
- As a result, the carbonyl carbon becomes a stronger electrophile.
Attack of Nucleophile
The next process involves the formation of a tetrahedral intermediate by the attack of a nucleophile on the carbonyl group.
Transfer of Protons
- Subsequently, through the processes of deprotonation of oxygen and protonation of nitrogen, a proton is transferred to the nitrogen atom.
- Now, a positively charged nitrogen group acts as a better-leaving group
Hydrolysis
- The hydrolysis of the amide is thus completed by the formation of a positively charged carboxylic acid derivative.
- This is subsequently deprotonated into the uncharged carboxylic acid.
Base-catalyzed Amide Hydrolysis
When a strong base such as sodium hydroxide (NaOH) or Potassium hydroxide (KOH) is heated with amide in the presence of water, the reaction is called base-catalyzed amide hydrolysis. The overall mechanism of the reaction is as follows:
- The hydroxide ion found in the base acts as a nucleophile, binding to the carbonyl carbon.
- This causes the formation of a tetrahedral intermediate product.
- Furthermore, protons target the amide's NR2 group.
- Thus, the breaking of HNR2 bonds occurs immediately after the attack of an oxonium ion on a carbon atom.
Sample Questions
Ques. What are the roles of amides? (2 marks)
Ans. Amides are the important functional groups present in amino acids. Amino acids are the building blocks of proteins. Therefore, amides play an important role in protein synthesis and metabolism.
Ques. Are amides soluble or non-soluble in water? (2 marks)
Ans. The presence of hydrogen bonds in the amide functional group contributes to their solubility in water. Primary amines are more soluble in water than secondary and tertiary amines due to their simple structure.
Ques. How are amides prepared in the lab? (2 marks)
Ans. The amides can be prepared in three ways:
- From an acyl halide's interaction with a 1° or 2° amine,
- Interaction between an amine and a carboxylic acid, and
- interaction between an amine and an acid anhydride.
Ques. Which can hydrolyze easily: Amide or Ester? (2 marks)
Ans. Hydrolysis of an ester is easier than amide as the amide structure is resonance stabilized. This makes the amide hydrolysis very difficult.
Ques. What are lactams? (1 mark)
Ans. The amides arranged in a cyclic structure are called lactams. These are the antibiotics often called beta-lactams used to prevent bacterial infections.
Ques. What are the important enzymes required for the hydrolysis of amide? (1 mark)
Ans. Deaminase, amidase, acylase, and fatty acylamidase are the four important enzymes that are responsible for amide hydrolysis.
Ques. How do amines differ from amides? (2 marks)
Ans. The ammonia derivatives are called amines whereas amides are derived from carboxylic acids.
- In ammonia, hydrogen is substituted with alkyl or aryl groups.
- On the other hand, the -OH group of carboxylic acid is replaced by -NH2 in the case of amides.
Ques. What is the Hoffman-Bromamide Reaction? (2 marks)
Ans. The reaction in which interconversion of amide into primary amine in the presence of sodium hydroxide or Bromine is called the Hoffman-Bromamide reaction.
Ques. What are the conditions required for amide hydrolysis? (2 marks)
Ans. The hydrolysis of amide is usually challenging but under certain conditions, the result is successfully achieved. The three important requirements are:
- Strong acids,
- High temperature (Around 100 degrees C), and
- Extended reaction time
Ques. Is amide able to undergo reaction with Grignard reagent? (2 marks)
Ques. What are the uses of amide hydrolysis? (2 marks)
- Amines and carboxylic acids synthesis.
- Hydrolysis of peptides and proteins,
- Biosynthesis of several drugs, such as paracetamol, and
- Production of synthetic fibers and plastics.
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