Amines Vilsmeier-Haack reaction

The reaction with disubstituted formamides and phosphorus oxychloride, called the Vilsmeier or the Vilsmeier-Haack reaction,is the most common method for the formylation of aromatic rings. However, it is applicable only to active substrates, such as amines and phenols. An intramolecular version is also known.Aromatic hydrocarbons and heterocycles can also be formylated, but only if they are much more active than benzene (e.g., azulenes, ferrocenes). Though A-phenyl-A-methyl-formamide is a common reagent, other arylalkyl amides and dialkyl amides are also used. Phosgene (COCI2) has been used in place of POCI3. The reaction has also been carried out with other amides to give ketones (actually an example of 11-14),... 

A rare example of the Vilsmeier- Haack reaction succeeding with a primary amine is provided by 4-amino-3-methyltriazole (33), which, when heated... 

A variation of the Vilsmeier-Haack reaction uses a formamide such as 211 with benzene (or another aromatic compound) to give the aromatic aldehyde (benzaldehyde) and the amine precursor to the formamide (N-methylaniline in this case). A solvent-free Vilsmeier reaction has been reported using microwave irradiation on silica gel. 39... 

TL5981>. The proposed mechanism involves the oxidation of the amine to an imine, tautomerization to an enamine, and a sequence of nucleophilic attacks on the pyridazine rings followed by oxidation steps. The oxidant of choice is (bispyridine)silver permanganate <1982TL1847>, which is easily prepared, mild in action, and is soluble in organic media. If R1 = H in the product 77, electrophilic substitution (e.g., bromination, nitration, Mannich, and Vilsmeier-Haack-Arnold reactions) occurs at this position. 

Reaction of A -acylamino acids with the Vilsmeier-Haack reagent leads to 2-alkyl-4-[(Af,Af-dimethylamino)methylene]-5(47i)-oxazolones 814. The reactivity of these compounds with various nucleophiles has been studied. Primary alkylamines undergo amine exchange with 814 to afford 2-alkyl-4-[(alkylamino)methylene]-5(4/i)-oxazolones 815 (Scheme 7.250). ° ... 

The reaction of 5-acetyl-,V-ethyl-2-(pyrrolidin-l-yl)pyrimidin-4-amine with the Vilsmeier-Haack reagent leads to cyclization followed by formylation in the 6-position of the resulting pyrido[2,3-c/]pyrimidin-5(8/7)-one, thus representing one of the few examples of electrophilic attack at a ring carbon.184-185... 

Vilsmeier-Haack-type reaction provided the C ring of the Aspidosperma skeleton, and elaboration of the E ring was achieved by the addition of a radical generated from the xanthate derivative of the primary alcohol to give nonacyclic compound 111. The final steps for the completion of the total synthesis consisted of the formation of a lactone ring, which was achieved by oxidation of the tertiary amine with potassium ferricyanide,... 

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