2-Amino-4-methyl-5-nitropyridine

To a solution of 10.0 g 2-amino-4-methyl-5-nitropyridine (65.3 mmol) in 90 mL DMF was added 87.0 mL A, lV-dimethylformamide dimethyl acetal (653.0 mmol) in one portion. The deep red reaction mixture was heated at 110°C overnight and then cooled to room temperature and concentrated in vacuo to provide 17.7 g A, A -dimethyl-A -[4-(2-dimethylamino)vinyl)-5-nitropyridin-2-yl]formamidine as a red solid, in a yield of 100%. An analytical sample was purified by recrystallization from benzene, m.p. 149-151°C. 

Initially, most or even all known MALDI matrices were acidic compounds, such as benzoic and cinnamic acid derivatives. However, the acidic medium is not well-suited to keeping noncovalently bound complexes intact. In the 1990s, a couple of groups therefore introduced a number of nonacidic MALDI matrices such as 2-amino-4-methyl-5-nitropyridine, />ara-nitroaniline, or 6-aza-2-thio-thymine. These were shown to be beneficial for MALDI MS of noncovalent complexes—for example, to keep peptide-oligonucleotide complexes or DNA duplexes intact.However, their performance at high molecular... 

Here again the question of reactive species in the acidic medium remains open. It must be noted that bromination of 2-amino-5-methyl-pyridine (pK = 7) and 2-amino-5-nitropyridine (pJC = 2.8) in N sulfuric acid takes place on the free base (443). 

Nitropyridine yields a mixture of 2-, 4- and 6-amino-3-nitropyridines by this method142. An amino group is introduced into the 2-position of l,n-dinitronaphthalenes (.n = 3-8)143 and various 5- and 8-nitroquinolines, such as 8-methyl-5-nitroquinoline and 6-chloro-8-nitroquinoline, have been aminated adjacent to the nitro group144. Pteridines are converted into alkylarnino derivatives by the action of a solution of potassium permanganate in an alkylamine, e.g. equation 51145. 

Nitration of the aminopyridines and their methyl derivatives reveals some interesting facets. The amino group strongly activates the positions ortho and para to itself towards nitration, but reaction proceeds via the N-nitroamines. 4-Aminopyridine undergoes nitration via the iV-nitroamine (65) to yield 4-amino-3-nitropyridine (equation 40). Nitration... 

Rearrangement of the 2-ethoxycarbonylmcthyl-l,4,6-trimethylpyrimi-dinium salt with alcoholic aqueous methylamine gave the respective 2-mcthylaminopyridine-3-carboxylate (94MI2) (Scheme 39a). Similarly, in alkaline medium, even nonquaternized 2-methyl-5-nitropyrimidine gave 2-amino-5-nitropyridine (94MI2) (Scheme 39A). 

Flrotonation first occurs at the 2- or 4-amino group in 2 - and 3,4-diamino-pyridines a second protonation then takes place at the 3-amino group. Replacement of a hydrogen atom by a methyl group on an extranuclear NHj gives rise to a small bathochromic shift for the cation of 3,4-diaminopyridine or 4-amino-3-nitropyridine, but not with the neutral species. ... 

A mixture of 3-hydroxy-6-nitro-2-picoline, dimethylamine, and 30% formalin gives 2-[2-(dimethylamino)ethyl] -3-hydroxy-6-nitropyridine. 2-Amino-methyl-5 hydroxy-6-nitropyridine is prepared similarly from 3-hydroxy-2-nitro-pyridine. ... 

Pure 2-amino-5-bromo-3-nitropyridine, yellow needles, m.p. 210°, may be obtained by recrystallizing the product from ethyl methyl ketone. 

In nitroamine oxides the nitro group may be reduced preferentially but usually both functions are affected. 5-Ethyl-2-methyl-4-nitropyridine A -oxide is converted quantitatively to 4-amino-5-ethyl-2-methylpyridine by hydrogen over 30% palladium on charcoal in ethanolic solution [737]. The outcome of the hydrogenation of a nitroamine oxide may be influenced by reaction conditions [736]. 

C5H4N203 3-hydroxy-2-nitropyridine 15128-82-2 25.00 1.4476 2 4462 C5H6BrN30 2-amino-5-bromo-6-methyl-4-pyrimidinol 6307-35-3 25.00 1.7195 2... 

Whereas peroxyacetic acid oxidizes 2,6-dichloroaniline to 2,6-dichlo-ronitrosobenzene [/5J], peroxytrifluoroacetic acid carries the oxidation to the nitro compound. Refluxing 2,6-dichloroaniline with peroxytrifluoroacetic acid, which is prepared in situ from 90% hydrogen peroxide and trifluoroacetic anhydride in dichioromethane, gives 2,6-dichloronitroben-zene in 89-92% crude yields and 59-73% pure yields [290. 2-Amino-4-methylpyridine treated with 30% hydrogen peroxide in fuming sulfuric acid at 10-25 °C for 50 h yields 68% of 4-methyl-2-nitropyridine [203]. 

Structural studies presented by Chibata and by Kamiya included similar total syntheses of eritadenine, each consisting of the condensation of 4-amino-6-chloro-5-nitropyridine with 4-amino-4-deoxy-2,3-C)-isopropyli-dene-D-erythromic acid, followed by catalytic reduction of the ni-tro group and imidazole ring closure by formic acid or its amide. This can be exemplified by Kamiya s procedure (400) shown in Scheme 83. Soon improved syntheses were reported from both laboratories by Kawazu et al. (401) and Kamiya et al. (402), each starting from adenine and methyl 2,3-0-isopropylidene-5-0-tosyl-)8-D-ribofuranoside or d-erythronolactone acetonide, respectively (Schemes 84 and 85). Kamiya... 

Boron Reagents. The Suzuki coupling with methylboronic acid and 2-chloro-3-nitropyridine gives the 2-methyl product 249 (Scheme 91) in high yield. 3-Amino-2-chloropyridine reacts less readily and 2-chloropyridine failed to react. 

Chloro- and bromoaminopyridines are oxidized by persulfuric acid at 0° to their nitro derivatives thus, 3-chloro-, and 3-bromo-4-aminopyridine are converted to the respective 3-halo-4-nitropyridines. However, 4-araino-3-iodo-pyridine is not oxidized under these conditions. 4-Amino-2,3,5,6-tetrafluoro-pyridine is difficult to oxidize and requires refluxing peroxytrifiuoroacetic acid for 22 hours in order to yield the 4-nitro derivative. Potassium bromate has been used to oxidize S-amino-3-methyl-2-pyridone, but the product was not a nitro compound instead 3-hydroxy-6-methyl-2-aza-l,4-benzoquinone-4-(2,6-di-hydroxy-5-methyl-3-pyridyl)imine (IX-S7) was obtained. ... 

Catalytic reductions of substituted pyridinecarboxylic acids continue to play an important role in some syntheses of pyridoxol. Thus 4-carbethoxy-6-chloro-5-cyano-2-methyl-3-nitropyridine (X-132) is reduced over Raney Nickel in water to 3-amino-5-aminomethyl-4-carboxy-2-methylpyridine-4,5-lactam (X-133). - ... 

Halo-4-nitropyridines and their A -oxides react at the C-nitro group when treated with bases or alkoxides to give XII-357 or MI-358 (X = Cl, Br, I). However, 3-fluoro-4-nitropyTidine and its 1-oxide form 4-nitro-3-pyridinols and 4-nitro-3-alkoxypyridines, respectivelyThe 3-alkoxy-4-nitropyridine-l-oxides have been converted to 3,4-dialkoxypyridine-l-oxides. Because of this marked reactivity of the 3-fluoro substituent, these studies have been extended to 3-fluoro-5-methyl-4-nitropyridine-l-oxide, 3-fluoro-2-methyl-4-nitropyri-dine-l-oxide, and 2,6-dimethyl-3-fluoro-4-nitropyridine-l-oxide. Several of these fluoronitropyridines have been extensively studied as potential reagents for formation of amino acid derivatives. 2-Fluoro-3,5-dinitropyridine, a typical example, is hydrolyzed by hot water and reacts with hot alcohols to form 2-alkoxy-3,5-dinitropyridines and reacts with amino acids and their derivatives to give well-defined products. The reactions of a number of fluoronitropyridines and their N-oxides have been summarized by Talik and Talik and the relative reactivities toward simple nucleophiles have been observed, as shown on p. 689. 

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