3.5- dimethoxy-2-nitropyridine

Figure 1 Rate profiles for the nitration of (a) 2,6-dimethoxypyridine (x = 3) and (b) 2,6-dimethoxy-3-nitropyridine ( = 5.5)...

Most nitrations of pyridines take place on the A-protonated species, and this includes the conversion of 2,6-dimethoxypyridine to the 3-nitro derivative. However, the further nitration of 2,6-dimethoxy-3-nitropyridine to the 3,5-dinitro derivative occurs on the free base. The introduction of the first nitro group reduces the basicity such that sufficient free base is now present for the reaction to take place through this minority species. 2,6-Dihalopyridines also undergo nitration as free base. 

Dichloropyridine is mononitrated at C(3> as the free base, whilst the mononitration of 2,6-dimethoxypyridine goes through the cation. The subsequent nitration of 2,6-dimethoxy-3-nitropyridine involves the free base. In these examples the ring nitrogen atom is deactivating by a factor of 20-2001248. 

Nitration of 3,5-dimethoxypyridine and 3,5-dimethoxy-2-nitropyridine takes place at the 6 position as expected. For the former compound the rate-acidity profile shows reaction to clearly occur on the conjugate acid, whereas the latter only has a small increase in rate coefficient between H0 — 7.8 and —9.0, suggesting reaction on the free base. Correction of the observed rate coefficients as before gives a rate-acidity profile similar to that of 3,5-dimethoxypyridine showing that the reaction takes place upon the free base of the nitro compound. The corrected... 

For one compound (3,5-dimethoxy-2-nitropyridine 1-oxide), the UV method could not be used since the dinitro product precipitated from solution even at the concentrations used in UV spectroscopy. The kinetics were therefore followed by NMR [67JCS(B)1213]. 

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