5- -1,3-dialkyluracil

This four-atom replacement was observed in some reactions of uracil derivatives, containing at position 5 a substituent with the CCCN moiety. Treatment of the Z-isomer 5-(2-carbamoylvinyl)-l,3-dialkyluracil with ethanolic sodium ethoxide gave in good yield 3-ethoxycarbonylpyridin-6(lf/)-one (84%) together with 3-A-methylcarbamoyl)pyridin-6-(l7 )-one (10%) (85JOC1513) (Scheme 26). The reaction involves an initial attack of the terminal amino group of the side-chain on position 6 of the uracil molecule. C-6-N-1 bond fission and N-C bond formation yield the pyridin-6(l//)-one. A subsequent attack of the ethoxide ion on the carbonyl groups of the side-chain yields both pyridin-2-one derivatives (Scheme 26). Similar results were obtained with the -isomer. 

Reduction of uracil derivatives. Uracil itself is not reduced by this hydride in THF, DMF, or NH2. However N,Nj-dialkyluracils are reduced in THF in 70-95% yield, possibly because these derivatives are locked in the enone form. Reaction of these uracils with this hydride and then an electrophile results in 5-alkylaled-5,6-dihydro derivatives of uracil (equation I).1... 

Under conditions of the Hilbert-Johnson reaction, the 2,4-dialkoxypyrimidines (29) can furnish the following by-products uracil,13 1-alkyluracil,3-7 1,3-dialkyluracil,19 4-alkoxy-2(lIZ)-pyri-midinone,7 and l-alkyl-4-alkoxy-2(lH)-pyrimidinone.7,20 Thus, for example, 5-chloro-, 5-bromo-, and 5-iodouracil were isolated32- 33 as by-products in the Hilbert-Johnson reaction (in acetonitrile at 20°) of the corresponding 5-halo-2,4-dimethoxypyrimidines and 3,5-di-O-p-toluyl-2-deoxy-D-ribofuranosyl chloride. The formation of 1,3-dimethyluracil and 1,3,5-trimethyluracil as by-products has been observed quite recently19 when the reaction of 2,3,5-tri-O-benzoyl-D-ribofuranosyl chloride with 2,4-dimethoxypyrimidine and 5-methyl-2,4-dimethoxypyrimidine, respectively, was performed in toluene at 70°. 

In contrast with 1,3-unsubstituted uracils, 1,3-disubstituted uracils are susceptible to various nucleophiles and can be regarded as a formylacetate masked with a 1,3-disubstituted urea. In fact, it is documented that 1,3-dialkyluracils in the presence of tetramethylammonium hydroxide behave as an enolate anion of formylacetate (77JOC2574 78JOC3073) (Scheme 134). 

The reaction of ammonia or amines with a suitable carbonyl substituent in a position ortho to a 6-[(7V,7V-dimethylamino)vinyl] group in dialkyluracils yields the corresponding 5-substituted 1,3-dialkylpyrido[4,3-d]py rimidine-2,4(1 //,3//)-diones.518... 

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