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The addition of hydroxylamine to the halogenated uracils
Author(s) -
Priest John H.,
Scheffler Julie E.,
Sander Eugene G.
Publication year - 1980
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570170106
Subject(s) - hydroxylamine , chemistry , uracil , reaction rate constant , kinetics , solvent , medicinal chemistry , catalysis , base (topology) , tris , inorganic chemistry , organic chemistry , dna , mathematical analysis , biochemistry , physics , mathematics , quantum mechanics
Hydroxylamine adds reversibly to C‐6 of uracil bases via a multistep mechanism. Equilibrium constants measured at several p H values, 25°, μ = 3.0 M are: uracil, 0.25 M −1 ; 5‐iodouracil, 0.30 M −1 , 5‐bromouracil, 0.24 M −1 , 5‐chlorouracil, 0.06 M −1 and 5‐fluorouracil, 5.11 M −1 . The kinetics of hydroxylamine addition to both 5‐bromo‐and 5‐iodouracil are complex. At low hydroxylamine buffer concentrations, the rate constants are second‐order with respect to hydroxylamine buffer but at higher concentration a first‐order dependence is approached. Hydroxylamine elimination from 5‐iodo‐6‐hydroxylamino‐5,6‐dihydrouracil is subject to general base catalysis by tris(hydroxy‐methyl)aminomethane but at higher concentrations the rate constants are not proportional to the concentration of general base. This reaction is subject to solvent effects where increasing ethanol concentration depresses the rate when measured at constant p H. These kinetics can be rationalized in terms of a multistep reaction pathway in which hydroxylamine addition to C‐6 of the halogenated uracil precedes general acid catalyzed proton transfer to C‐5 yielding the final 6‐hydroxylaminodihydropyrimidine product.