5- Nitropyrimidines reaction with enamines

A great number of N-substituted 4-hydroxy-3-nitro-l,8-naphthyridin-2 (IH)-ones are obtained by reaction of N-substituted azaisatoic anhydrides with ethyl nitroacetate carbanion (Section II,A,4,a). A very specific method, more recently developed, is that of the inverse Diels-Alder method, involving the reactions of enamines with 5-nitropyrimidine (Section II,A,4,b). 

S-Unsaturated hydrazones such as (12) have been shown to behave as 1 -aza-1, 3-dienes in Diels-Alder addition reactions with a range of dienophiles such as maleic anhydride (Scheme 2). The dimethylamino substituent in the cycloadducts (e.g. 13) may be cleaved by treatment with zinc and acetic acid, but no conditions have so far been found to cleave the N-N bond without reducing the C-C double bond 5-Nitropyrimidine undergoes inverse Diels-Alder cycloaddition with electron-rich dienophiles such as enamines and ketene N,N- and 0,0-acetals (Scheme 3). ... 

Extension of this work by reacting 5-nitropyrimidine with 0,0-ketene acetals and with other cyclic and non-cyclic enamines showed that also with these electron-rich dienophiles the addition is regioselective and gives rise to the formation of 2-mono- or 2,3-disubstituted 5-nitropyridines (Scheme 30). Thus, reaction of 5-nitropyrimidine with the cyclic N,S-ketene acetals 4,5-dihydro-1 -methyl-2-methylthiopyrrole and 4,5,6,7-tetrahydro-1 -methyl-2-methylthioazepine gives in low yields 2,3-dihydro-1-methyl-5-nitropyr-olo[2,3-h]pyridine and the 5,6,7,8-tetrahydro-9-methyl-3-nitropyrido [2,3-Z)]azepine, respectively (89T2693) (Scheme 30). 

Pyrimidines are expected to be much less reactive in cycloadditions of this type than triazines and tetrazines. Normally, the presence of electron-withdrawing substituents on the pyrimidine ring is essential. The best results are obtained with a nitro group in position 5. Reaction of 5-nitropyrimidine with various enamines affords fused nitropyridines (82TL3965 89T2693) (Scheme 59). The mechanism (89T2693) is in agreement with the usual expectations. 

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