Question

What happens when ethylamine is made to react with excess formic acid and formaldehyde?

• A. The intermediate is a secondary amine
• B. The final product is a tertiary amine
• C. This reaction is called Eschweiler-Clarke methylation
• D. The mechanism involves reductive amination

Answer 1

Answer: (A), (B), (C), (D)

The correct options are
A The intermediate is a secondary amine
B The final product is a tertiary amine
C This reaction is called Eschweiler-Clarke methylation
D The mechanism involves reductive amination

In the first step, the excess formaldehyde and the primary amine react to give the imine:

Don’t forget, this reaction does happen in the presence of an acid – just like any imine formation. The next step is where the reductive amination happens; but before that, the acid protonates the imine into an iminium. Note how the formate anion acts as a hydride donor!!

But since there is excess $HCHO$ in the flask, the secondary amine will be methylated via an iminium once again to finally yield a tertiary amine. The tertiary amine cannot form an imine and the reaction stops here:

This reaction is called the Eschweiler-Clarke methylation or Eschweiler-Clarke synthesis.