2-Acetylpyridine (Avocado),
thiophene-2-carboxaldehyde (Acros),
25 % aqueous ammonia solution (Merck),
Potassium hydroxide pellets (Prolabo),
absolute ethanol (Carlo-Erba).

To a solution of 2-acetylpyridine (4.84 g, 40 mmol, 2 equiv.) in ethanol (100 ml), are added thiophene-2-carboxaldehyde (2.24 g, 20 mmol, 1 equiv.), potassium hydroxide (3.08 g, 55 mmol, 2.75 equiv.) and ammonia solution (58 ml). The resulting mixture is stirred at room temperature for 15 hours. The resulting pale yellow precipitate is filtered off and successively washed with water (4×25 ml) and cold 50% ethanol (25 ml). The yellow product is first air dried for 48 hours and then in a dessicator over phosphorus pentoxide. The yield is 2.40 g (38 %).

This method for the synthesis of 4’-(het)aryl terpyridine is a very simple one pot procedure which allows preparation of variously substituted terpyridine derivatives. The products so obtained are generally sufficiently pure to be used as ligands in coordination chemistry. The first step is an aldol reaction between 2-acetylpyridine and the aldehyde, followed by a Michaël addition of a second equivalent of 2-acetylpyridine yielding a 1,5-diketo derivative. The latter undergoes ring closure upon reaction with ammonia to form the central pyridine ring.

mp 206-211°C (dec.); ¹H NMR (250 MHz, CDCl₃) ppm = 8.73 (2H, dd, J= 4.8, 1.9), 8.70 (2H, s), 8.62 (2H, d, J= 7.9), 7.87 (2H, ddd, J= 7.9, 7.6, 1.9), 7.78 (1H, dd, J= 3.6, 1.2), 7.46 (1H, dd, J= 5.0, 1.2), 7.35 (2H, ddd, J= 7.9, 1.9, 0.9), 7.13 (1H, dd, J= 5.0, 3.6).

Wang, J.; Hanan, G.S. Synlett 2005, 8, 1251

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