Nitropyridines. 2. Hantzsch Synthesis of Nitro- and Dinitropyridines

Abstract

The interaction of α,β-unsaturated nitro ketones and various enamines leads to the synthesis of 5-nitro-1,4-dihydropyridines containing acetyl, amide, benzoyl, ester, and cyano groups in position 3, and also unsymmetrical 3,5-dinitro-1,4-dihydropyridines. Aromatization of the nitrodihydropyridines was carried out with sodium nitrite in acetic acid.The synthesis of nitropyridines by the Hantzsch reaction is effected by the cyclocondensation of α,β-unsaturated nitro ketones (condensation products of aromatic aldehydes with nitroacetone and nitroacetophenone) with various enamines.The availability of nitroacetone and nitroacetopheone enables them to be considered as valuable raw materials in the synthesis of nitropyridines [2], possessing potential biological activity.Nitroacetone [3,4] and nitroacetophenone [5] used in the work were obtained by the condensation of nitromethane with acetaldehyde and benzaldehyde (the Anri reaction). The nitroalcohols obtained were oxidized with sodium dichromate.The condensation of nitroacetophenone with aromatic aldehydes proceeds readily and the corresponding nitrochalcones 1 are formed in preparative yield [6].Nitroacetone may interact with aromatic aldehydes at both the methyl and the methylene group. Under alkaline catalysis conditions the aldol condensation product is formed only at the methyl group. To obtain condensation products at the methylene group a less reactive Schiff's base of the aromatic aldehyde is used. In this way condensation products at the methylene group are formed in good yield only in the reaction of nitroacetone with Schiff's bases of an aromatic aldehyde containing an acceptor group in the nucleus [7], the yield of 2-nitro-1-phenyl-1-buten-3-one 1a was only 26%. Because of the low yield of chalcone 1a, the cyclocondensation of benzylideneacetoacetic ester with the enamine of nitroacetone 2f was used for the synthesis of nitrodihydropyridine 3d (variant B) (Scheme 1).The condensation of benzylidenenitroacetone 1a with aminocrotonic ester (variant A) in acetic acid at room temperature and an equimolar ratio of initial reactants leads to nitrodihydropyridine 3d in 56% yield. On condensation by variant B under analogous conditions pyridine 3d is formed with a yield of 40%. We also note that the enamine of nitroacetone 2f [8], obtained by the transamination of 2-dimethylamino-1-nitro-1-propene _______ * For Part 1 see [1]. __________________________________________________________________________________________

Construction of 3,5-dinitrated 1,4-dihydropyridines modifiable at 1,4-positions by a reaction of β-formyl-β-nitroenamines with aldehydes

“…With 4-arylated dinitro-DHPs in hand, we carried out preliminary studies on the oxidative conversion of 4-substituted DHPs to 4-substituted-3,5-dinitropyridines, which are not easily accessible by other methods. 13 As shown in Scheme 6, treatment of 4-anisyl DHP 3Bb with excess amount of NaNO 2 in chloroform under oxygen atmosphere at 80 C for 24 h to afford the desired product 7 in a promising isolated yield of 68%. The obtained 4-arylated-3,5-dinitropyridines are useful synthetic intermediates for functional materials.…”

“…13 As shown in Scheme 6, treatment of 4--anisyl DHP 3Bb with excess amount of NaNO 2 in chloroform under oxygen atmosphere at 80 °C for 24 h to afford the desired product 7 in a promising isolated yield of 68%. The obtained 4--arylated--3,5--dinitropyridines are useful synthetic intermediates for functional materials.…”

α‐Substituted Chalcones: A Key Review

“…Results revealed that pyrroles unsubstituted at positions 2 and 5 are the most active. Similarly, 1,4‐dihydropyridines were also prepared from α‐nitrochalcones as shown in reaction 8, Figure 31 [137] . Aromatization of the obtained nitrodihydropyridines was carried out with sodium nitrite in acetic acid to give pyridines.…”

Synthesis and Biological Activity of 4-(Pyridin-3-yl)-2-hydroxy-4-oxobut-2-enoic Acid Derivatives

“…Aiming to expand a number of promising quinoxaline and oxazine derivatives and to study their pharmacological activities, we synthesized similar compounds using the example of 1-(5-nitropyridin-3-yl)ethan-1-one derivative. 1-[4-(furan-2-yl)-2-methyl-5-nitro-6-phenylpyridin-3-yl]ethan-1-one 18 (3) was chosen as an initial object for our study. The presence of pyridine core and pharmacophore functions such as nitro group and furan ring, as well as reactive acetyl group in the molecule of 5-nitro-6-phenylpyridine 3 opens the way to its modification.…”