One-pot synthesis of 5-nitropyridines by the cyclocondensation of nitroacetone, triethyl orthoformate and enamines

NitropyridineS. 9*. Synthesis of substituted 3-amino-5-nitropyridines

“…Sodium azide (0.43g, 6.6 mmol) was added by portions with stirring to a mixture of the corresponding 3-acetylpyridine (6 mmol) [10,11] in 3 ml conc. H 2 SO 4 .…”

“…In these cases the reaction product needed to be purified by chromatography. 2-Methyl-5-nitro-4,6-diphenylnicotinic acid (10). A mixture of ethyl 2-methyl-5-nitro-4,6-diphenylnicotinate [26] (1.45 g, 4 mmol), ethanol (10 ml), KOH (1.12 g, 20 mmol) in water (2 ml) was boiled for 3-4 h, diluted with water and acidified with conc.…”

“…3-Amino-5-nitropyridines 2a,b were obtained by the Schmidt reaction starting from 3-acetyl-5-nitropyridines 1a,b by a one-stage synthesis which we had developed earlier [10,11]: N Ac O 2 N Me R N NH 2 R Me O 2 N 1. NaN 3 , H 2 SO 4 2.…”

“…3-Amino-5-nitropyridines 2a,b were obtained by the Schmidt reaction starting from 3-acetyl-5-nitropyridines 1a,b by a one-stage synthesis which we had developed earlier [10,11] In the synthesis of 3-amino-4,6-dimethyl-5-nitropyridine (4) from the previously known nicotinamide 3a we successfully used the classical Hofmann reaction (NaOBr) [12]. Under these conditions the nitronicotinamides 3b,c and 7a,c, which are insoluble in aqueous alkali, did not rearrange to the corresponding 3-amino-5-nitropyridines.…”

Synthesis of pyridines by cyclocondensation of acetyl and benzoyl pyruvates with enamines

“…In one variant of the Hantzsch synthesis for the preparation of pyridines condensation of ethyl ethoxymethyleneacetoacetate (or other products of the reaction of β-dicarbonyl compounds with ethyl orthoformate) with enamines of β-dicarbonyl compounds is used [3]. We have previously successfully used a one-pot variant of this synthesis using methylene-activated nitroacetone and nitroacetophenone [4,5].…”