Aldehydes reactions with chloromethyleneiminium salts

The Vilsmeier-Haack reaction, as depicted in Scheme 1, is an important method for synthesizing aldehyde derivatives. Numerous other transformations of iminium salts into products other than aldehydes have been achieved, and these additional transformations add considerable scope and versatility to the Vilsmeier-Haack reaction. The Vilsmeier-Haack reaction is not restricted to carbon nucleophiles oxygen and nitrogen nucleophiles also react with chloromethyleneiminium salts. 

The Vilsmeier-Haack reaction of electron-rich carbocyclic aromatic compounds (Ar—H) with chloromethyleneiminium salt (1) gives aldehyde derivatives (Ar—CHO), generally in good yield. The intermediate iminium salt (cf. salt 5 Scheme 1) can be treated with hydroxylamine to obtain nitrile derivatives (Ar—CN). Benzene and naphthalene are not sufTiciently electron rich to participate in the Vilsmeier-Haack reaction, but polycyclic hydrocarbons, such as anthracene, do react. Benzene and naphthalene derivatives that possess an electron-releasing substituent (—OMe,—SMe,—NMe2, etc.) af-... 

The classical Vilsmeier-Haack reaction - involves electrophilic substitution of a suitable carbon nucleophile with a chloromethyleneiminium salt, for example salt (1). Suitable carbon nucleophiles are generally electron-rich aromatic compounds such as V,N-dimethylaniline (2), alkene derivatives such as styrene (3) or activated methyl or methylene compounds such as 2,4,6-trinitrotoluene (4 Scheme I). These compounds (2-4) react with salt (1) giving, after loss of hydrogen chloride, the corresponding im-inium salts (5-7). Hydrolysis of iminium salt (5) affords aldehyde derivative (8) and this transformation (Ar—H - Ar—CHO) is the well-known Vilsmeier-Haack formylation reaction. Hydrolysis of iminium... 

Vilsmeier acylation of pyrroles, formylation with dimethylformamide/phosphoryl chloride in particnlar, is a generally applicable process. The actual electrophilic species is an Al,Al-diaIkyl-chloromethyleneiminium cation (the chloride is available commercially as a solid). " Here again, the presence of a large pyrrole-A-substituent perturbs the intrinsic a-selectivity, formylation of A-tritylpyrrole favonring the P-position by 2.8 1 and trifluoroacetylation of this pyrrole giving only the 3-ketone " the nse of bulky iV-silyl substituents allows P-acylation with the possibility of subsequent removal of the N-snbstituent." The final intermediate in a Vilsmeier reaction is an iminium salt requiring hydrolysis to prodnce the isolated product aldehyde. When a secondary lactam is used, hydrolysis does not take place and a cyclic imine is obtained." ... 

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