5- Nitropyrimidines, adduct formation with

The delicate balance between adduct formation at position 2 or at position 4 is shown in the amino-dehydrogenation of 4-methoxy-5-nitropyrimidine. The course of the amination is found to temperature dependent. Treatment with liquid ammonia/permanganate at —60° to —70 °C gave 2-amino-4-methoxy-5-nitropyrimidine, while at +20 °C 6-amino-4-methoxy-5-nitropyrimidine is obtained (Scheme 18) (83JOC1354). This result indicates that at low temperature the C-2 adduct is the kinetically favored one and at room temperature the C-4 adduct is thermodynamically favored. 

In summary, both 2- and 4-methoxy-5-nitropyrimidines undergo attack at a CH position rather than at the COMe position. A major factor for this behavior is believed to be the COMe bond-strengthening effect of the conjugation of the methoxy substituent with the ring. This is especially evident in the formation of adduct 16 resulting from attack of the reagent at the more hindered position 4 relative to position 2.41... 

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