Aminations according to Class of Compounds

An enormous amount of work has been carried out on the amination of alkylpyridines, and the work has been well documented (42OR91 54CRV449 62HC(14,3)1 67MI1 74MI1). This section will cover the more recently reported aminopyridines. The amination products of some alkylpyridines are listed in Table V. 

Arylpyridines can also be aminated. For example, 2-phenylpyridine was aminated in DMA with sodium amide to give 6-amino-2-phenylpyridine in 87% yield (72KGS1642). The yield was a function of reaction time and temperature prolonged heating decreased the yield, and the optimum temperature was in the range 130-140°C (73MI1). 

Pyridine rings containing electron-donating substituents are deactivated toward the Chichibabin reaction relative to pyridine. Pozharskii et al. have studied the amination of the three isomeric aminopyridines. Treatment of an aminopyridine results in evolution of ammonia and formation of the sodium salt of the heterocycle. The sodium salt of 2-aminopyridine (88) was readily aminated at 160-180°C, forming 2,6-diaminopyridine (65) in 70-80% yield. 

Attempts to aminate the sodium salts of 3- and 4-aminopyridine (111 and 112) led to resin formation. Quantum mechanical calculations have been useful to explain the disparity in reactivity of the aminopyridines. Position 6 of 88 has a considerable positive charge however, the 2- and 6-positions of 111 and 112 have acquired excess negative charge, making them unsuitable substrates for amination. 

Pozharskii continued the investigation with dialkylaminopyridines (73CHE1119). Amination of 2-dimethylaminopyridine resulted in formation of 2,6-diaminopyridine (65). No significant amount of 2-amino-6-dimethyl-aminopyridine was found, suggesting that the dimethylamino moiety is displaced prior to amination. It is interesting to find that 4-dimethylaminopyri-dine was aminated to 2-amino-4-dimethylaminopyridine since it represents 

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