Nitration pyridinones

An alternative method for the synthesis of amrinone from 3-cyano-5-(4-piridyl)-2(l//)-pyridinone (17.2.2) is based on it s acidic hydrolysis to the corresponding acid, 3-carboxy-5-(4-piridyl)-2(l//)-pyridinone (17.2.5), nitration of which with nitrous acid in the presence of sulfuric acid forms 3-nitro-5-(4-piridyl)-2(l//)-pyridinone (17.2.6). Reducing the nitro group of this product with hydrogen gives the desired amrinone (17.2.4) [19, 20]. 

Pyridinones and quinolinones undergo electrophilic attack at the (3 -position (12,13) fairly easily and disubstitution is well known in the pyridine series. Pyridinones are more easily halogenated than benzene, but the highly acidic conditions used for nitration and sulfonation makes these less easy reactions. Electrophiles also attack at the oxygen (14), but this is considered as a substituent reaction and therefore will be dealt with in Chapter 2.06. 

The similarities in rates of nitration of uracils and 1,3-dimethyluracil suggest that they are all nitrated in the dioxo forms the rate for 2,4-dimethoxypyrimidine is slower by a factor of about 10. 2(l/f)-Pyrimidinone and its 1-methyl derivative also react as the free base the rates are much lower than those of the corresponding uracil and 100 times slower than for 3-methyl-2(l/f)-pyridinone. These results reflect the deactivating effect of a second annular nitrogen and the presence of only one 0X0 function <7lJCS(B)l>. 

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