# Reaction of amines with diethyl oxalate (Hofmann amine separation method)

Why does only one molecule of secondary amine react with diethyl oxalate and two molecules of primary amine react with diethyl oxalate?

I feel secondary amine also should have reacted similar to primary amine.

From JEE-Main 2015:

### Reaction with diethyl oxalate

1°, 2°, and 3° amines can be distinguished by their reactions with diethyl oxalate. Primary (1°) amines react with diethyl oxalate forming N,N-oxamide, which is a solid.

Secondary (2°) amines react with diethyl oxalate forming oxamic ester, which is a liquid.

Tertiary (3°) amines do not react with diethyl oxalate.

• Probably a steric issue. Seems reasonable.
– Zhe
Jan 10 '18 at 3:47
• You may want to look at the Hinsberg test for distinguishing between amines. Jul 21 '18 at 21:51
• @Zhe: From this site, I looked at structutr of oxamic ester, which was different from the one given in this post. As, the -OR and -NR2 groups are on opposite sides, hence I think steric reason aren't reasonable. Jul 21 '20 at 3:59
• The second reaction has a typo: it should be $\ce{CONR2}$. Jul 22 '20 at 16:26
• Tetra-substituted oxamide or N,N,N',N'-tetraalkyloxamide can be prepared by the action of oxalyl chloride on secondary amines.(see here) Jul 23 '20 at 5:39

## 2 Answers

When a 1° amine attacks to a carboxyl group, The structure below (left) is generated which lowers the energy level of the intermediate such that the second amine can easily react with the other carboxyl group.

It is clear that 2° amines (right) don't have such proton for hydrogen bonding with the oxygen. Why the second 2° amine doesn't attack to the other carboxyl at all is maybe due to the decreased partial positive charge of the amide (less electronegativity of nitrogen) toward the carboxyl.

Finally, 3° amines don't have even a leaving proton to substitute with the ethoxide.

The tetrahedral intermediate in the primary amine attack case would have an intramolecular hydrogen bond to stabilize. In the secondary amine case, no such H-bond is available.