Nitropyridines. 7*. Synthesis of nitropyridines from nitro-malonic dialdehyde

Abstract

Cyclocondensation of sodium nitromalone dialdehyde with different enamines gave 3-acetyl (benzoyl, cyano, cyclopropanoyl, carbethoxy)-2-methyl(phenyl)-5-nitropyridines. With the aim of increasing the yield of pyridines we have activated the nitromalonic dialdehyde through acylation of its enol form.Aliphatic nitro compounds are widely used in the synthesis of nitropyridines unavailable by direct nitration of pyridines and by other known methods [2][3][4][5]. Nitromalone dialdehyde is one of the most available of the nitro ketones used but examples of nitropyridines obtained in this way are few [6][7][8][9][10].The aim of this work was to synthesize 5-nitropyridines by cyclocondensation of nitromalone dialdehyde with different enamines.Analysis of the experimental work has shown that an activated form of the nitromalone dialdehyde is most efficiently used in the cyclocondensation. With this in view, tosylation and acetylation of its enol form have been carried out [9,10]. We have checked both variants of the acylation of nitromalone dialdehyde in the synthesis of nitropyridines experimentally and found that use of acetic anhydride for elimination of a molecule of water from the sodium malone dialdehyde monohydrate salt with simultaneous acetylation is more H O CHO O 2 N Ac 2 O, Py H OAc CHO O 2 N X R N H 2 N X R O 2 N O _ 1a, 2a-d, 3a,b,e,f4a, 5a-d, 6a,b,e,f 1, 4 R = H, 2, 5 R = Me, 3, 6 R = Ph a X = COPh, b X = CN, c X = COMe, d X = , e X = NO 2 , f X = CO 2 Et Na +

Nitropyridines 11. *Recyclization of quaternary nitropyridinium salts into substituted nitroanilines

“…A mixture of the corresponding pyridine (5-nitro-2-(phenylethynyl)pyridine [1], 3-acyl-2-methyl-5-nitropyridine [16], 3-acetyl-2,6-dimethyl-5-nitropyridine [17], 2,6-dimethyl-3-nitropyridine [18], or 2-methyl-4-nitropyridine [19]) (5 mmol), and dimethyl sulfate (1.9 g, 15 mmol) was heated (reaction conditions are shown in Table 1). The reaction mixture was cooled, washed with dry ether (3×10 ml), and the ether decanted.…”

Synthesis of New Structural Analogues of Natural Integrastatins with a Basic Epoxybenzo[7,8]oxocine Skeleton: Combined Experimental and Computational Study

“…Next we synthesized 3-acetyl-5-nitro-2-methylpyridine (5f) to find out the effect of other acceptor groups (e.g., the nitro group in the 5th position of 3-acetyl-2-methylpyridine) on the possibility of cyclization. 20 Pyridines 1-(2methyl-5-nitro-6-phenylpyridin-3-yl)ethan-1-one (5g), 1-[4-(furan-2-yl)-2-methyl-5-nitro-6-phenylpyridin-3-yl]ethan-1-one (5h), and 1-(2,6-dimethyl-5-nitropyridin-3yl)ethan-1-one (5i) were synthesized by a multicomponent reaction according to the described methods. [21][22][23] Then there was a verification of the cyclization of three 5-nitropyridines with salicylaldehyde to epoxybenzooxocins under acid catalysis conditions at reflux in 2-propanol (Scheme 6, method A).…”

“…19 1-(2-Methyl-5-nitropyridin-3-yl)ethan-1-one ( 5f ) was synthesized according to a published procedure. 20 1-(2-Methyl-5-nitro-6-phenylpyridin-3-yl)ethan-1-one ( 5g ) was synthesized according to a published procedure. 22 1-(2,6-Dimethyl-5-nitropyridin-3-yl)ethan-1-one ( 5i ) was synthesized according to a published procedure.…”

“…J = 17.2 Hz, 1 H, H-14ª), 3.62 (dd, 2 J = 17.1 Hz, 3 J = 5.6 Hz, 1 H, H-14b), 5.37 (d, 3 J = 5.5 Hz, 1 H, H-15), 6.72 (d, 3 J = 7.7 Hz, 1 H, H-4), 6.86 (td, 3 J = 7.5 Hz, 4 J = 1.0 Hz, 1 H, H-2), 7.03 (dd, 3 J = 7.7 Hz, 4 J = 1.4 Hz, 1 H, H-1), 7.09 (td, 3 J = 7.7 Hz, 4 J = 1.5 Hz, 1 H, H-3), 7.50 (s, 1 H, H-7) 13. C NMR(20 MHz, CCl 4 ):  = 22.7, 26.0, 28.0, 31.5, 32.4, 34.7, 38.3, 69.3, 96.3, 116.5, 120.5, 125.2, 128.3, 129.3, 133.4, 136.0, 148.6, 151.0, 154.9, 162.8. MS (EI): m/z (I rel , %) = 307.04 ([M] + , 100), 292.03 (15), 264.02 (58), 147.05 (16).…”