The starting materials for the Kröhnke synthesis are often trivial to prepare, lending to the convenience and broad scope of the method. Preparation of the α-pyridinium methyl ketone salts can be easily achieved by treatment of the corresponding bromomethyl ketone with pyridine. The α,β-unsaturated ketones are often available commercially or can be prepared using a number of known methods. Additionally, Mannich bases can also be utilized as the Michael acceptor for the scheme, further diversifying the scope of starting materials that can be incorporated into the Kröhnke scheme.
The reaction conditions for the Kröhnke synthesis are generally facile and the reactions often proceed in high yields with reaction temperatures generally not exceeding 140 °C. The Kröhnke synthesis is generally performed in either glacial acetic acid or methanol, but it can also be done under aqueous conditions, and more recently under solvent-free conditions.
1,3-dicarbonyl compounds have also been shown to be viable starting materials in place of the α-pyridinium methyl ketone salts. For example, treatment of 1,3-diketone 14 with base in ethanol followed by ammonium acetate, acetic acid, the corresponding enone and a Lewis acid yields 3-acyltriarylpyridines of the form 15. These acyl pyridine are attractive intermediates because they have an electrophilic handle that allows for additional functionality to be incorporated into the molecule. This allows for straightforward construction of complex polyaryl systems, an attractive method for library synthesis of drug targets containing functionalized pyridine moieties.