Pyridine 3-nitropyridine from

The mechanism of the formation of 3-nitropyridine from pyridine on reaction with dinitrogen pentaoxide in the presence of sulfur dioxide has been partially elucidated,... 

Oxadiazolo[3,4-c]pyridine, 3(l)-oxo-synthesis from 4-azido-3-nitropyridines, 6, 730... 

Acylation with acetyl chloride (giving 94) or protonation permits rapid displacement of the nitro group from 4-nitropyridine A-oxide by the weakly nucleophilic chloride Pyridine A-oxide... 

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). 

C. 2,3-Diamino-5-bronto pyridine (Note 8). A 100-ml. flask fitted with a reflux condenser is charged with 10.9 g. (0.05 mole) of 2-amino-5-bromo-3-nitropyridine, 30 g. of reduced iron, 40 ml. of 95% ethanol, 10 ml. of water, and 0.5 ml. of concentrated hydrochloric acid (Notes 9 and 10). The mixture is heated on a steam bath (Note 11) for 1 hour, and at the end of this period the iron is removed by filtration and is washed three times with 10-ml. portions of hot 95% ethanol. The filtrate and washings are evaporated to dryness, and the dark residue is recrystallized from 50 ml. of water, 1 g. of activated carbon being used and the mixture being filtered while hot. The charcoal is washed with hot ethanol to avoid losses. 2,3-Diamino-5-bromopyridine crystallizes as colorless needles, m.p. 163°. The yield is 6.5-7.1 g. (69-76%). 

Many pyridine derivatives difficult to make directly from pyridine are readily accessible starting from pyridine A7-oxide, made by oxidation of pyiidine with hydiogen peroxide in acetic acid. As but one example, the nitration of pyndine A7-oxide gives 4-nitropyridine IV-oxide in high yield. Reduction of the >-oxide to the parent pyridine nucleus is readily effected by hydrogenation or reagents, such as PCli or Iriphenyl phosphine. 

As shown in the previous section, N-alkyl nitroanilines 23 are obtained in the reaction of pyridone 1 with ketones 22 in the presence of amines. In this case, amines are introduced as the dialkylamino substituents. On the contrary, different reactivity is observed when ammonia is used instead of amines. The TCRT reaction proceeds to afford 2,3-dialkyl-5-nitropyridines 24 upon treatment of pyridone 1 with ketones 22 in the presence of ammonia (Table 2) [42,43]. The C4 - C5 - C6 unit is derived from pyridone 1, the C2 - C3 unit is derived from ketone, and the ring nitrogen (Nl) is from ammonia, namely the new ring consists of three components. As electrophilic nitration of pyridines is quite difficult, the present TCRT will be an alternative method for preparation of nitropyridine derivatives. 

Attack of the electrophile at the C2 or C4 position results in an intermediate cation with partial positive charge on the electronegative nitrogen atom. This is clearly not energetically favourable when compared to C3 substitution, where no partial positive charge resides on nitrogen. In fact the product of C3 substitution, nitropyridine 5.15, can be isolated from the exhaustive nitration of pyridine, but only in poor yield. 

For instance, 4-nitropyridine 5.20 can be prepared from pyridine in three steps by this methodology. 

Heterocyclic compounds are more difficult to nitrate. For example, from quinoline 11% of mononitroquinoline was obtained at 95-100°C, while at 155-160°C 10-12% of dinitroquinoline could be obtained from pyridine 6% of nitropyridine was obtained at 115-120°C. 

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