Nitration aminopyridines

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... 

Nitraminopyridines, mentioned above, are intermediates formed during the nitration of aminopyridines. An example (96) from the quinoline series is shown in Scheme 84. The nitramines undergo acid-catalyzed rearrangement to ring nitro compounds (97). 

Dk yel ndls, mp—decomp at 202° and defgr on rapid heating. Can be prepd by nitration of 4-aminopyridine or 4-nitraminopyridine. 

Note No higher nitrated derivs of aminopyridine were found in Beil or CA through 1956... 

As expected, an amino group facilitates nitration strongly. 2-, 3- and 4-Aminopyridines are nitrated smoothly (H2S04-HN03 at 40-70°C to form mono- (5-, 2- and 3-, respectively) and dinitro- (3,5-, 2,6-and 3,5-, respectively) derivatives (Section 3.2.1.3.2). Alkylamino-, alkoxy- and 3-hydroxy-pyridines react analogously to the corresponding amino compounds. 

On nitration, aminopyridines, such as (41), gave dinitro-derivative (42) (Scheme 30) <95JHC(32)585>. 

The macrocycle 131, containing a 2,6-dipicolyl fragment, has been used as a receptor for malate dianion in aqueous solution <2006CC1227>. 4-Aminopyridine coordinated to Ag(l) and hydrogen-bonded to nitrate forms a high-symmetry three- and four-connected hydrogen-bonded three-dimensional network <2006CC1082>. 

Pyridones, aminopyridines, and diazines with two strongly activating substituents, readily undergo nitration, sulfonation, and halogenation (reactivity approximately that of benzene). 

Acetamido-4-phenylthiazole is nitrated at position 5 of the thiazole ring [232], in contrast to 2-amino-4-phenylthiazole, which is nitrated in the phenyl ring [233], This agrees with existing data on the reactivity of thiazoles during electrophilic substitution. N-(2-Thiazolyl)-2-aminopyridine is nitrated exclusively in the thiazole ring [222],... 

Problem 20.20 Predict and account for the product obtained and conditions used in nitration of 2-aminopyridine. 

Problem 31.11 2-Aminopyridine can be nitrated or sulfonated under much milder conditions than pyridine itself substitution occurs chiefly at the 5-position. Account for these facts. 

Problem 31.12 Because of the difficulty of nitrating pyridine, 3-aminopyridine is most conveniently made via nicotinic acid. Outline the synthesis of 3-aminopyridine from /3-picoline. 

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