U. Girreser, D. Heber
Mar 1, 2000
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Influential Citations
4
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Journal
Journal Fur Praktische Chemie-chemiker-zeitung
Abstract
The classical Mannich reaction of aromatic methyl ketones with paraformaldehyde and dimethylamine hydrochloride resp. dimethyl(methylene)ammonium chloride has been extended to a few cases of 1-aryl-2-dimethylaminomethyl-prop-2-en-1-ones (ADMP reagents). They have gained remarkable attention in medicinal chemistry, but only more recently their properties as valuable building blocks for ring closure reactions to form either aroyl or dimethylaminomethyl substituted heterocyclic compounds has been evaluated. In this review, a collection of representative examples for their preparation (Scheme 2) and biological effects as well as the synthetic potential for the synthesis of heterocycles (Scheme 3—8) is given. The reaction of 4-hydroxycoumarin delivers with ADMP reagents, via the formation of detectable 3-(2-benzoylallyl)-4-hydroxycoumarins as secondary substitution products, after ring closure 3-benzoyl-3,4-dihy-dro-2H,5H-1-benzopyrano[4,3-b]pyran-5-ones (Scheme 4). The reaction of 4-hydroxy-6-methylpyran-2-one with ADMP reagents is investigated systematically in order to assess its suitability in carbon—carbon bond forming reactions as well as to provide the conditions for subsequent ring closure or intermolecular addition of further nucleophiles to the enone double bond of the intermediate 3-(2-benzoylallyl)-4-hy-droxy-6-methylpyran-2-ones yielding miscellaneous 3-substituted 2-pyrones (Scheme 5 and 8), and their application as building blocks for the combinatorial chemistry. The condensation of ADMP reagents with 2-aminopyridines gives rise to 3-benzoyl-3,4-dihydro-2H-pyrido[1,2-a]pyrimidines (Scheme 6) and the corresponding reaction using amidines affords 5-benzoyl-1,4,5,6-tetrahydropyrimidines (Scheme 7).