Methylation and tautomerism of 1-substituted 5-fluorocytosines.
1. Methylation and thiation of 5-fluorouracil led to 1,3-dimethyl-5-fluoro-4-thiouracil, the amination of which was examined under various conditions. At high dilution, and in the presence of a large excess of NH3, 1,3-dimethyl-5-fluoro-4-thiouracil was converted to 1,3-dimethyl-5-fluorocytosine in 60% yield. 2. Two procedures were employed for methylation of 5-fluoro-1-methylcytosine and 5-fluorocytidine. Treatment of each of these with diazomethane in alcohol-ether gave a complex mixture of products, the major one of which was the desired 3-methyl derivative. By contrast, treatment with methyl iodide in dimethylsulphoxide led exclusively to the 3-methyl derivatives in much better yeilds. 3. Ultraviolet absorption spectra and pKa values are presented for 1-substituted N-methyl-5-fluoro- and 5-bromo-cytosines. The basicity method was applied to determine the tautomeric equilibrium constants of the 1-substituted 5-halogenocytosines. The results show that the proportion of the imino forms of these compounds is of the same order of magnitude as for 1-substituted cytosines, and hence is unlikely to account for the observed mutagenic effects of 1-substituted 5-halogenocytosines.
D000586:Amination; D055598:Chemical Phenomena; D002621:Chemistry; D002849:Chromatography, Gas; D003562:Cytidine / Q000031:analogs & derivatives / Q000138:chemical synthesis; D003596:Cytosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D013058:Mass Spectrometry; D008745:Methylation; D013056:Spectrophotometry, Ultraviolet; D013889:Thiouracil / Q000138:chemical synthesis
D013889:Thiouracil; D003562:Cytidine; D003596:Cytosine