Villsmeier - Haak reaction

The Vilsmeier reaction is another way that we have to attach a formyl group (CO)on a specific molecules. Indeed, Vilsmeier - haack reaction works particularly well for electron rich aromatic rings (perfect, for example, on a pyrrole), in the following example is shown a phenol, that is merely a benzen with an electrodonating group (the hydroxyl group):

vilsmeier-reaction-mechanism

This kind of formylation is carried out using a substituted amide, the most common is doubtless DMF (generally dimethyl formamide) and phosphorous oxichloride (POCl3). Let's try to understand in detail how the reaction actually goes on:

Reaction mechanism

First of all , it's necessary to remember that whatever amides is actually a resonance hybrid. We can't forget the resonance structure with separation of formal charge:

risonanza ammide

this structure is fundamental especially to qualify proteins, but now is important to better explain the following interaction with POCl3, a common chlorinating agent, that is responsible of the conversion of DMF in the corresponding iminium chloride  ion:

iminium-chloride-formation

Iminium chloride is the starting substrate for the next reaction. Even iminium chloride is a resonance hybrid. For him we can write to resonance structures, and in spite of the structure that shows the positive charge on the nitrogen atom is more stable, the second will explain better the last step of the reaction, the electrophilic aromatic substitution:

iminium-chloride-resonance

The iminium chloride takes part in the well-known reaction of Friedel - Kraft, an alkylation:

Friedel kraft cloro imminio

The last part of the reaction is extremely simple The product above can easily lose a chloride ion (good leaving group) to give an iminium ion. Then, the iminium ion can be hydrolized under weak condition to give the desired carbonyl group. If we have used DMF the product is benzaldehyde, considering that contains just one single carbon atom.

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