Vilsmeier–Haack formylation: practice and mechanism
The Vilsmeier reagent (from POCl₃ and DMF) is a mild electrophile. The electron-rich heteroaromatic is formylated at C2: hydrolysis gives an aldehyde (–CHO).
Example
POCl₃ and DMF form the Vilsmeier reagent, a chloroiminium ion. The electron-rich heteroaromatic attacks it at C2. Aqueous workup hydrolyses the iminium ion to the aldehyde: a 2-formyl heteroaromatic forms.
Mechanism step by step
- 1
DMF attacks POCl₃, giving the chloroiminium ion (CH=N⁺(CH₃)₂ with Cl), the Vilsmeier reagent.
- 2
The electron-rich ring attacks the iminium carbon at C2; after loss of H⁺ and Cl⁻ an aryl iminium salt forms.
- 3
Aqueous workup hydrolyses the iminium ion to the aldehyde; dimethylamine is released.
Practice tasks
Which product forms, which reagent is needed? After each answer you see the explanation.
Which main product forms?
Typical mistakes
- Attack at C3 is less favourable: the σ-complex there has only two resonance forms, at C2 three. Five-membered heteroaromatics therefore react at C2 (or C5).
- The pyrrole N–H is weakly acidic, but under these conditions the electron-rich ring reacts at carbon (C2), not at nitrogen.
- The dimethylaminomethyl group is the product of the Mannich reaction (HCHO, Me₂NH). In the Vilsmeier reaction the iminium ion is hydrolysed to the aldehyde.
Often confused with: Acylation of furan, thiophene and pyrrole
Frequently asked questions
How reactive are the five-membered heteroaromatics?
Pyrrole > furan > thiophene > benzene. The heteroatom pushes its lone pair into the ring; N donates most easily, S least (poorer orbital overlap). Pyrrole polymerises with strong acids, hence mild conditions.
Which substrates are suitable?
Only electron-rich arenes: pyrrole, furan, thiophene, indole, dimethylaniline, anisole derivatives. Benzene itself does not react; the electrophile is too weak.