4- Nitropyridine 1-oxides, reactions

Halo-4-nitropyridine-1 -oxide, reaction with alkoxides,... 

Little success has attended attempts to form Reissert compounds from pyridine 1-oxidesbut 3-nitropyridine 1-oxide does react with benzoyl chloride and silver cyanide to give a small amount of a cyano-3-nitropyridine, a reaction recalling that of 1-methoxypyridinium salts described above 5. ... 

The ortho indirect deactivating effect of the two methyl groups in 2,6-dimethyl-4-nitropyridine 1-oxide (163) necessitates a much higher temperature (about 195°, 24 hr) for nucleophilic displacement of the nitro group by chloride (12iV HCl) or bromide ions N HBr) than is required for the same reaction with 4-nitropyridine 1-oxide (110°). With 5-, 6-, or 8-methyl-4-chloroquinolines, Badey observed 2-7-fold decreases in the rate of piperidino-dechlorination relative to that of the des-methyl parent (cf. Tables VII and XI, pp. 276 and 338, respectively). 

However, attempts to prepare 3-iiitro-l,8-iiaphthyridiiie (11) by the Skraup reaction—heating of 2-amino-5-nitropyridine with glycerol in the presence of an oxidant— were not successful (74YZ1328). 

The reaction of 4-methoxy-3-nitropyridines 129 with guanidine under similar conditions results in 3-aminopyrido[3,4-e]-l,2,4-triazine 1-oxides 130 (76MI). 

Use of some pyridinium oxides in this reaction was also described and the formed azaphenoxathiin /V-oxides can be easily converted to their mother heterocycles (80JHC989, 87JHC211). When 3-chloro-4-nitropyridine 1-oxide (271) was used, small amounts of products of Smiles rearrangement were... 

Alkylzinc halides have also been prepared under microwave irradiation. The Reformatsky reagents (2-t-butoxy-2-oxoethyl)zinc bromide and [(2-dibenzylamino)-2-oxoethyl]zinc bromide were synthesized from the corresponding bromides via reaction with zinc in THF (Scheme 5) [24], The oxidative addition was executed at 100 °C in 5 min. The obtained reagents were subsequently used in Negishi reactions on 2-bromopyridine, 3-bromopyridine, 2-bromo-5-nitropyridine, and 2-bromo-5-trifluoromethyl-pyridine using Pd(PPh3)4 as a catalyst (Scheme 5). 

It had been shown previously 7 ) that 4-nitropyridine-N-oxides 7 a—d are photo-reduced (> 300 nm) in ethanol solution to the corresponding 4-hydroxylamino-pyridine-N-oxides 2 a—d. Presence of oxygen was found to alter the course of the reaction. 

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]. 

Jawdosiuk et al.220 have treated 4-chloro- and 4-nitropyridine N-oxides (145) with substituted phenylacetonitrile. This is in agreement with the well-known activating effect of N-oxides toward SNAr reactions the results show that nitro is a better leaving group than chloro. 

Al-Jallo and Al-Biaty24 prepared 4-phenyl-2-oxo-2H-pyrido[l,2-c<]-pyrimidines from 2-aminopyridines and ethyl phenylpropiolate. When the reactions were carried out in deuterium oxide, the 3-deuterated derivatives were obtained. 2-Amino-5-nitropyridine failed to react. 

On treatment of a solution of the pyrido[l,2-a]pyrimidinium salt (16) with potassium permanganate in 2 N sulfuric acid, 11% 2-aminopyridine, 1% 4-oxo-4H-pyrido[l,2-a]pyrimidine, and traces of 2-nitropyridine were isolated from the reaction mixture.9 When 2,4-dimethylpyrido[l,2-a]-pyrimidinium iodide was oxidized with aqueous potassium permanganate at 50-60°C, 2-acetamidopyridine was obtained in 65% yield.2... 

Selective silylation of ribonucleosides.2 Only the 5 -hydroxyl group of ribonucleo-sides is silylated by reaction with the reagent in THF in the presence of silver nitrate. On addition of pyridine to the reaction, 2, 5 -disilyl derivatives are formed in 80-90% yield. The actual reagent may be r-butyldimethylsilyl nitrate. Highly selective 3, 5 -disilylation can be achieved in the presence of several silver salts (AgN03, AgC104, and AgOAc) in the presence of either DABCO or 4-nitropyridine N-oxide. 

Other nucleophilic chlorinations have included reactions of hydrogen chloride, phosphoryl chloride, and acetyl chloride with 4-nitropyridine 1-oxide to form 4-chloropyridine 1-oxide (86JHC177 87MI1 91TI697). 

Dimethyl-4-nitropyridine-N-oxide-dimethyl sulfate adduct (220 g, 0.75 mole) was dissolved in methanol (1.0 Itr) and the solution heated to reflux. A solution of ammonium persulfate (140 gm) in water (200 ml) was added dropwise over 4 hours after which reflux was continued for 4 hours. Methanol was distilled off under reduced pressure and the residue was basified to pH 10 by addition of caustic lye (105 ml). The mixture was extracted with dichloromethane (2 times 400 ml). The dichloromethane layer was dried over sodium sulfate and filtered. The product was used as its solution in dichloromethane for the next reaction. 

To prepare 2-aminopyridine by treatment of pyridine with potassium amide in liquid ammonia at —33 °C and using permanganate as oxidant was not successful. No reaction takes place under these conditions. The aromaticity of the pyridine ring is too high to allow nucleophilic amide addition. It was surprisingly observed that treatment of a solution of 3-nitropyridine in liquid ammonia (thus without the presence of potassium amide) with potassium permanganate, gave after work-up a mixture of... 

Site specificity was found to be considerably higher in oxidative amino-dehydrogenation reactions with derivatives of 3-nitropyridine. 2-R-3-nitropyridine (R = C1, OMe) when treated with liquid ammonia and permanganate gives a reasonable yield of 6-amino-2-R-3-nitropyridine (R = C1, OMe) 6-R-3-nitropyridine yields 2-amino-6-R-3-nitropyridine (R = C1, OMe) (Scheme 4) (91LAC875). The corresponding 4-amino compounds are only obtained in small amounts. A similar observation was made on the low temperature oxidative amination of 2-amino-5-R-3-nitropyridines (R = H, Cl, Br). 

All these amination reactions show exclusive SNH substitution. There is hardly any indication for the formation of 3-nitropyridines, in which the chloro or methoxy group was replaced by an amino group, even when these leaving groups are present at the reactive a-position of the pyridine ring. It seems to be a characteristic feature of the oxidative amination... 

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