Amide coupling with an activating reagent

Reaction class

Acylation

Typical conditions

A carbodiimide or a uronium or phosphonium salt, with a tertiary amine base, at room temperature.

Mass balance

balanced — the co-products are written out, not dropped

Mechanism

Amide coupling through an active ester, 4 steps

Conditions are what the literature ordinarily uses, recorded so you can see whether yours are in the usual range. They are not a procedure and they are not scaled to your flask.

The reagent turns the acid into something an amine will attack, and then it is an ordinary acyl substitution: attack, tetrahedral intermediate, collapse, proton transfer.

1. 1The reagent turns the acid into an active ester
2. 2The amine attacks the activated carbonyl
3. 3The carbonyl comes back and the activating group goes
4. 4A base takes the proton

This is the pathway taught for the class, not a record of what was observed. On the platform it is drawn on the structures you supply, with the curly arrows on the atoms that actually move.