3-Chloro-1H-indole-2-carboxaldehydes are obtained in moderate yields by the one-pot reaction of various substituted 2-[(carboxymethyl)amino]benzoic acids (1a−d) using Vilsmeier reagent (DMF/POCl3). The benzfused acyclic diacids analogous to 1a in which nitrogen was replaced by oxygen and sulfur also underwent the reaction smoothly. 3-Chloro-1H-pyrrole-2,4-dicarboxaldehyde was obtained as the only product by the reaction of N-carboxymethyl β-alanine.

One-Pot Synthesis of Heterocyclic beta-Chlorovinyl Aldehydes Using Vilsmeier Reagent.

An unprecedented attack of the azide functionality by iminium species, generated in situ under Vilsmeier conditions, provided a novel route for the construction of nitrogen heterocycles. Thus, the treatment of 2-azidoacetophenones with Vilsmeier reagent under reflux conditions gave 5-aryloxazole-4-carboxaldehydes. One-pot synthesis of oxazole carboxaldehydes from 2-bromoacetophenones by dehaloazidation−Vilsmeier cyclization reaction sequence provided better yields. The susceptibility of the carbonyl group to undergo chloroformylation at room temperature without affecting the azide function was exploited to provide an attractive scheme for the synthesis of α-azido-β-chlorovinyl azides from phenacyl azides. The synthesis of a series of N-aryl 5-chloro-2-(dimethylamino)imidazole-4-carboxaldehydes was accomplished by the Vilsmeier cyclization of N-aryl-2-azidoacetamides. The possible mechanisms for the reactions are also discussed.

Intramolecular Cyclization of Azides by Iminium Species. A Novel Method for the Construction of Nitrogen Heterocycles under Vilsmeier Conditions

Dimerization of substituted 2-aminobenzoic acids under vilsmeier conditions : a novel route to the synthesis of 4-(3h)-quinazolinones

Pyrans and their Benzo Derivatives - Synthesis

This chapter extends the discussion to reactions between the Vilsmeier-Haack reagent (subsequently referred to as the Vilsmeier reagent for brevity) and any other compounds in which a carbon-carbon bond is formed. The discussion thus excludes reactions in which the Vilsmeier reagent acts as a chlorinating agent (for example in the preparation of acid chlorides), or in which it forms carbon-oxygen or carbon-nitrogen bonds, unless these are accompanied by formation of a carbon-carbon bond. For a discussion of the nature of the reagent and of the mechanism of the reaction, the earlier chapter in vol. 49 should be consulted. There are also a number of reviews that deal at length with mechanisms of reactions involving the Vilsmeier reagent, notably those by Jutz and Marson, and hence this chapter will concentrate on applications, with brief mention of mechanisms when necessary.



Wizinger has pointed out that alkenes could react with the Vilsmeier reagent, but his only examples were styrenes where the intermediate carbocation has considerable stability.



Hydrolysis gives the cinnamaldehyde. In principle, any alkene which is not too sterically hindered can undergo this reaction, but the Vilsmeier reagent has low reactivity as an electrophile, and in practice activation is often necessary. The addition depends on the HOMO of the alkene, and anything increasing the HOMO energy will aid reaction, as for example further conjugation (dienes, trienes, etc.) or the presence of an electron-donating substituent. Hence aldehydes and ketones are active in their enol forms, and enol ethers and enamines are good substrates. Indeed, all additions covered by this chapter can be regarded as alkene additions, even those on active methyl groups attached to electron-deficient rings. As with any reaction involving carbocation intermediates, rearrangements are possible; the initial products are sometimes enamines, and this can give rise to polysubstitution. The substrates are grouped into eleven major subsections; references to reviews of particular relevance will be found in the appropriate subsection.


Keywords:

vilsmeier reaction;
non-aromatics;
alkenes;
dienes;
polyenes;
heteroatoms;
substituents;
enamines;
enamides;
alkynes;
aldehydes;
ketones;
imines;
hydrazones;
semicarbazones;
oximes;
carboxylic acids;
anhydrides;
acid chlorides;
esters;
lactones;
amides;
lactams;
imides;
nitriles;
methyl groups;
methylene groups;
adjacent rings;
comparison of methods;
experimental conditions;
experimental procedures;
tabular survey

R. Umarani

Papers

A new method for the preparation of substituted 5,6,7,8-tetrahydro-4H-I-benzopyran and 4H-pyrans by vilsmeier -haack reagent.

A New Method Method for the Preparation of Substituted 5,6,7,8‐ Tetrahydro‐4H‐1‐benzopyran (V) and 4‐Pyrans (III) by Vilsmeier‐Haack Reagent.