Aminopyridines, reactions with—continued

A lot of methods are available for the synthesis of this heterocycle, and most of them rely on the formation of the five-membered ring. In this section, only the methodologies of reasonable scope will be reported. The most classical method involves the cyclocondensation of 2-aminopyridine with an a-halo carbonyl compound. Due to the broad availability of the required substrates and the efficiency of this cyclocondensation, it continues to be the method of choice to prepare this heterocycle. New examples highlighting the generality of this reaction are collected in Table 14. 

The use of vinylphosphonium salts in heterocyclic synthesis continues to be exploited. The kinetically controlled reactions of the / -acylvinylphosphonium salts (143) with 2-aminopyridine lead to the salts (144) similar reactions occur with 2-aminopyrimidine and cytosine. Under conditions where thermodynamic control prevails, the salts (145) are formed predominantly, resulting from a Dimroth rearrangement of (144).136... 

Cognate preparation. 3-Aminopyridine. Prepare a cold sodium hypobromite solution from 32 g (10 ml, 0.2 mol) of bromine and 25 g (0.62 mol) of sodium hydroxide in 250 ml of water. Add in one portion 20 g (0.163 mol) of finely powdered nicotinamide (Expt 6.169) and stir vigorously for 15 minutes. Warm the solution in a water bath at 75 °C for 45 minutes. Isolate the crude product by continuous ether extraction (Section 2.22) of the cooled reaction mixture after saturation with sodium chloride. Dry the extract over potassium hydroxide pellets and remove the ether. Crystallise the dark residue from a 4 1 mixture of benzene-light petroleum (b.p. 60-80 °C) with the aid of decolourising charcoal. The yield of almost colourless product, m.p. 63 °C, is 9.3 g (61%). 

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