4- Methoxy-5-nitropyrimidine

Methoxy-5-nitropyrimidine is also attacked at a CH position, as indicated by the relatively high upheld shift of one of the ring protons.14,41 The formation of the gem-dimethoxy adduct is thus ruled out. Of the two possible isomeric adducts only the one resulting from attack at the 2-position (17) is formed, as unequivocally shown by the singlet at <5 5.75, which is observed starting from 4-methoxy-5-nitropyrimidine-6-rf.41... 

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... 

The reaction of 2-R-4-methoxy-5-nitropyrimidines 8 with (R0)2P(0)H and EtzN takes place very unusually, "since it leads to the substitution of the 5-NO2 group which is usually inert. a-Complexes are formed rapidly in the reaction and then rearrange to phosphon-ates 10. 

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. 

Methoxy-5-nitropyrimidines react with hydrazine hydrate, being converted into 3-amino-4-nitropyrazoles [546, 547] (Scheme 97). 

In the case of 2-methoxy-5-nitropyrimidine, the adduct that forms predominantly in DMSO solution has been shown to have the structure of 16, as characterized by two doublets of equal intensities in the NMR spectrum.14,41 The presence of a weak singlet has been indicated as evidence for the formation of minor amounts of the gem-dimethoxy isomer,41 although no further confirmation is available. Thus the preferred attack occurs at a position adjacent to the nitro group, located para to an aza group and other than the methoxyl-bearing position. 

The importance of the conjugative effect of the methoxy group can be further illustrated by noting that 2-methoxy-5-nitropyrimidine is attacked at the presumably more hindered 4-position rather than at the 2-position, thus avoiding disruption of conjugation.41 In contrast, position 2 is attacked (adduct 17) when the methoxy substituent is moved to position 4 of the 5-nitropyrimidine system. 

Nitropyrimidine, its 2- and 4-methoxy, and 2,4- and 4,6-dimethoxy derivatives react with acetone in the presence of potassium hydroxide to yield the potassium salts of the anionic adducts 74 and 75, with structures elucidated by spectral ( H-NMR, IR, and UV-visible) methods. The nucleophilic attachment was found to occur only at CH positions, and when there was a choice between 2- and 4(6)-positions, the latter was preferred.125,126 An adduct of the kind corresponding to structure 75 was also obtained by using the conjugate base of acetophenone. The adducts can be converted to the corresponding CH3COCH2- or PhCOCH2-substituted pyrimidines by oxidation, either directly or via the related dihydropyrimidine derivatives.127... 

PMR and UV spectral evidence have been reported322,329 for methoxide addition to 5-nitropyrimidine and its 2- and 4-methoxy derivatives. Methoxide addition to 5-nitropyrimidine in dimethyl sulfoxide gives the C-2... 

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