Pyrrole, acylation Vilsmeier-Haack reactions

Another acylation procedure uses iminium salts rather than acyl halides. The Vilsmeier-Haack reaction is a well-known process illustrated by reaction of pyrrole with the POCI3 complex of N,N-dimethylacetamide (207, which can decompose to a chloroiminium salt). The acylation reaction gave 208, which was converted to 2-acetylpyrrole by hydrolysis with aqueous sodium acetate.A synthetic example is taken from Lai s synthesis of indole analogs of mycophenolic acid,l in which 209 reacted with POCI3 and DMF to give a 77% yield of the aldehyde 210. 

As is the case with pyrroles, C-alkylation of indoles results in mixtures of products. Formylation and acylation, however, occur more readily. The Vilsmeier-Haack reaction furnishes indole-3-carbaldehyde heating with acetic anhydride produces 3-acetylindole. In the Houben-Hoesch acylation, substitution takes place in the 3-position. 

Thiophene is also readily acylated under both Friedel-Crafts and Vilsmeier-Haack conditions and similarly to pyrrole and furan gives 2-acylated products. An almost quantitative conversion of thiophene into its 2-benzoyl derivative is obtained by reaction with 2-benzoyloxypyridine and trifluoroacetic acid. The attempted preparation of 2-benzoylthiophene under standard Friedel-Crafts conditions, however, failed (80S139). 

Pyrrole, 2-acetyl-1 -(2-hydroxyethyl)-5-nitro-cydization, 4, 74 ipso substitution, 4, 243 Pyrrole, 2-acetyl-1-methyl-dipole moment, 4, 194 photocydization reactions with 2,3-dimethylbut-2-ene, 4, 269 Pyrrole, 3-acetyl-4-methyl-Vilsmeier-Haack formylation, 4, 222 Pyrrole, 2-acetyl-3-nitro-reduction, 4, 297 Pyrrole, acyl-basicity, 4, 207 isomerization, 4, 208 oximes... 

Reactions of Pyrroles. 1,3-Di-t-butylpyrrole forms the first stable protonated pyrrole, the salt (104). Electrophilic substitution of pyrrole with MeaC or Me FC in the gas phase occurs mainly at the j3-position, as does nitration and Friedel-Crafts acylation of l-phenylsulphonylpyrrole2 Pyrrole-2,5-dialdehyde has been prepared by Vilsmeier-Haack formylation of the ester (105), followed by hydrolysis. A similar method has been used to convert the di-acetal (106) into pyrrole-2,3,5-tricarbaldehyde. AT-Benzoyl-pyrrole reacts with benzene in the presence of palladium(II) acetate to yield a mixture of l-benzoyl-2,5-diphenylpyrrole, the bipyrrolyl (107), and compound (108). Treating lithiated A-methylpyrrole with nickel(II) chloride results in the polypyrrolyls (109 = 0-4). 2-Aryl-1-methylpyrroles are obtained by cross-coupling of l-methylpyrrol-2-ylmagnesium bromide with aryl halides in the presence of palladium(0)-phosphine complexes. ... 

Alkylation of pyrroles proves to be problematic because the usual Lewis acid catalysts initiate polymerization. The Vilsmeier-Haack formylation, however, leads to the formation of pyrrole-2-carbaldehyde in good yield. The Houben-Hoesch acylation (reaction with nitriles in the presence of hydrogen chloride) provides 2-acylpyrroles ... 

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