Reactions of Primary Amine derivatives

imine

Reaction type:  Nucleophilic Addition then Elimination

Summary

• Primary amines, R-NH₂ or ArNH₂, undergo nucleophilic addition with aldehydes or ketones to give carbinolamines which then dehydrate to give substituted imines.
• The reactions are usually carried out in an acidic buffer to activate the C=O and facilitate dehydration but without inhibiting the nucleophile.
• Systems of the general type Z-NH₂ (see table) undergo this type of reaction and can be used as derivatives to aid in the identification of aldehydes and ketones.

Question:
Why can't amine nucleophiles be used in strongly acidic media ? 

Related Reactions

• Formation of Acetals
• Dehydration of Alcohols

NUCLEOPHILIC ADDITION OF A PRIMARY AMINE GIVING AN IMINE.
Step 1: An acid/base reaction. Protonation of the carbonyl activates it and makes it more susceptible to attack by a neutral nucleophilic like the N of a primary amine.
Step 2: Attack of the N nucleophile at the electrophilic C of the C=O group with the electrons from the p bond going to the +ve O.
Step 3: An acid/base reaction. Removal of the proton neutralizes the +ve charge on the N and forms the carbinolamine intermediate.
Step 4: To form the imine we need to dehydrate. However, before -OH leaves it needs to be protonated, so a simple acid/base reaction.
Step 5: Use the electrons of the N to help push out the leaving group, a neutral water molecule, this leaves us with an iminium ion.
Step 6: An acid/base reaction. Deprotonation of the iminium N reveals the imine product and regenerates the acid catalyst.

 

Reaction type:  Nucleophilic Addition then Elimination

Summary

• Aldehydes and ketones react with a range of primary amine derivatives to give substituted imines.
• The derivatives with ammonia are too unstable to be isolated but can be reduced in situ to amines.
• The mechanism of these type of reactions is shown on the previous page.

• Reactions of Primary Amines

Reactions of Secondary Amine Derivatives

enamine

Reaction type:  Nucleophilic Addition then Elimination

Summary

• Secondary amines, R₂NH, react with aldehydes or ketones to give carbinolamines which then dehydrate to give enamines.
• The carbinolamine in these reactions can only eliminate to give a C=C since there is no N-H in the carbinolamine.
• The products are called enamines because they are "alkene amines".
• Enamines are useful reagents in synthetic organic chemistry and biochemical transformations.

• Reaction of Aldehydes and Ketones with Primary Amines
• Dehydration of Alcohols

NUCLEOPHILIC ADDITION OF A SECONDARY AMINE GIVING AN ENAMINE.
Step 1: An acid/base reaction. Protonation of the carbonyl activates it and makes it more susceptible to attack by a neutral nucleophilic like the N of a secondary amine.
Step 2: Attack of the N nucleophile at the electrophilic C of the C=O group with the electrons from the p bond going to the +ve O.
Step 3: An acid/base reaction. Removal of the proton neutralizes the +ve charge on the N and forms the carbinolamine intermediate.
Step 4: To form the enamine we need to dehydrate. However, before -OH leaves it needs to be protonated, so a simple acid/base reaction.
Step 5: Removal of a proton from an adjacent C allows the p bond to form and loss of the leaving group, a neutral water molecule, creating the enamine.