ORGANIC CHEMISTRY II

Hydrolysis of Amides

 

Reaction type:  Nucleophilic Acyl Substitution

Summary

• Amides hydrolyse to the parent carboxylic acid and the appropriate amine.
• The mechanisms are similar to those of esters.
• Reagents : Strong acid (e.g. H₂SO₄) / heat (preferred) or strong base (e.g. NaOH) / heat.

Related Reactions

• Hydrolysis of Esters

Reaction under ACIDIC conditions:

• Note that the acid catalysed mechanism is analogous to the acid catalysed hydrolysis of esters.
• The mechanism shown below proceeds via protonation of the carbonyl not the amide N (see step 1).
• The mechanism is an example of the less reactive system type. 

 
 

MECHANISM OF THE ACID CATALYSED  HYDROLYSIS OF AMIDES

	Step 1: An acid/base reaction. Since we only have a weak nucleophile and a poor electrophile we need to activate the amide. Protonation of the amide carbonyl makes it more electrophilic. Step 2: The water O functions as the nucleophile attacking the electrophilic C in the C=O, with the electrons moving towards the oxonium ion, creating the tetrahedral intermediate.  Step 3: An acid/base reaction. Deprotonate the oxygen that came from the water molecule to neutralise the charge. Step 4: An acid/base reaction. Need to make the -NH2 leave, but need to convert it into a good leaving group first by protonation. Step 5: Use the electrons of an adjacent oxygen to help  "push out" the leaving group, a neutral ammonia molecule. Step 6: An acid/base reaction. Deprotonation of the oxonium  ion reveals the carbonyl in the carboxylic acid product and regenerates the acid catalyst.

Amine compounds Primary amines

Primary amine-containing-NH2 bound to the hydrocarbon chains or rings. You can think of amines as derivatives of ammonia, NH3. In primary amines, one of the hydrogen is replaced by hydrocarbons.

Example 1: Write the structural formula of ethylamine.

In this case, an ethyl group attached to the-NH2.

This name (ethylamine) there is no problem as long as there is no unambiguous meaning of the location-NH2. But it is like you have a 3-carbon chain in this case-NH 2 can be at either end or the middle.

Example 2: Write the structural formula for 2-aminopropane.


Indicate the name of the three carbon chain attached to the amino carbon into two. Amino-NH2 show.

Ethylamine (example 1) can also be called aminoethane.




Secondary and Tertiary Amine

In two of the secondary amine hydrogen atoms in ammonia is replaced by hydrocarbons. and three hydrogen replaced by a tertiary amine.

Example 1: Write the structural formula for dimethylamine.

In this case the two hydrogen atoms replaced by methyl groups.



Example 2: Write the structural formula for trimethylamine.

Here are three hydrogens in ammonia are replaced by methyl groups.