Synthesis of 1- and 3-arylcarbonyl derivatives of 5-fluorouracil

4'-Substituted 1-arylcarbonyl-5-fluorouracil derivatives were synthesized from the reaction of the potassium salt of 5-fluorouracil with one equivalent of aryl acid chloride in acetonitrile. 4'-Substituted 3-arylcarbonyl-5-fluorouracil derivatives were synthesized from the reaction of 5-fluorouracil with 3 equivalents of the aryl acid chloride in pyridine and the subsequent hydrolysis of the 1,3-diarylcarbonyl-5-fluorouracil derivatives in situ with a small amount of water. If a large amount of water were used in the second step, the 1,3-diarylcarbonyl-5-fluorouracil precipitated before it hydrolyzed. The melting behaviors of both the 1-arylcarbonyl-5-fluorouracil and 3-arylcarbonyl-5-fluorouracil series suggested that thermal decomposition or rearrangement occurred on heating. The position of the C-6-H absorption in the H-1 nmr spectra of 1-arylcarbonyl-5-fluorouracils was 0.14 to 0.23 ppm farther downfield than that of the corresponding 3-arylcarbonyl-5-fluorouracils while that of the 1,3-diarylcarbonyl-5-fluorouracils was even farther downfield. The Rf values of 1-arylcarbonyI-5-fluorouracils were significantly greater (0.23 to 0.41) than those of the corresponding 3-arylcarbonyl-5-fluorouracils, while that of 1,3-diarylcarbonyl-5-fluorouracil was slightly greater than that of 1-arylcarbonyl-5-fluorouracils.