Bisulfite-ion-catalyzed degradation of fluorouracil.
5-Fluorouracil (I) reversibly adds bisulfite ion across its greater than C5 equals C6 smaller than bond to form 5-fluoro-5,6-dihydrouracil-6-sulfonate (II). The pH-independent equilibrium constant for this reaction was calculated to be 560 M-1 at ionic strength 1.00 M at 25 degrees. Compound II was observed to be unstable in alkaline solution and reacted to yield uracil-6-sulfonic acid, fluoride ion, and alpha-fluoro-beta-ureidopropionic acid-beta-sulfonate (III), along with I (via a loss of HSO3 minus). In strongly alkaline conditions, i.e., 1 M NaOH, III was observed to undergo a subsequent reaction to produce a compound believed to be alpha-fluoro-beta-ureidoacrylic acid (V) or fluoromalonaldehydic acid (VII). These irreversible degradation reactions of II lead to a complete degradation of I in sodium bisulfite solutions. The similarity of this bisulfite-ion-catalyzed degradation of I to its hydrolytic degradation is discussed.
D002384:Catalysis; D002854:Chromatography, Paper; D005472:Fluorouracil / Q000032:analysis; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013056:Spectrophotometry, Ultraviolet; D013447:Sulfites; D013816:Thermodynamics; D014867:Water
D013447:Sulfites; D014867:Water; D005472:Fluorouracil