BROMINATION OF CYTOSINE DERIVATIVES

The reactions of cytosine (6a), 5-bromocytosine (8a), cytidine (6b), 5-bromocytidine(8b), 1-methylcytosine (18a), 5-bromo-1-methylcytosine (8c), 1, Ar4-dimethylcytosine (18b), 5-bromo-1, N4-dimethylcytosine (18c), 5-bromo-1, 3-dimethylcytosine (38), 5-methylcytosine (39), N5-dimethylcytosine(40), and 1, 4, 4-trimethylcytosine (41) with bromine or N-bromosuccinimide in aqueous or methanolic solutions have been studied. Product analyses and UV spectral changes observed at different pHs strongly support an addition-elimination mechanism. Thisis further substantiated by the synthesis and characterization of the previously unavailable bromohydrin intermediates, 5-bromo-6-hydroxy-5, 6-dihydro and the corresponding-6-methoxy derivatives of 6a, 8a, 6b, 8b, 8c, 18a, 18b, 18c, 38, 39, 40, and 41.The final products of bromination were 5-bromocytosine (8) or 5-bromouracil (3) derivatives. The former resulted from direct dehydration of the bromohydrins and the latter from deamination prior to dehydration.From the UV spectra of these new 5, 6-dihydrocytosine compounds and the related cyclobutyl dimers and bisulfite adducts, a scheme for calculation of the UV absorption maxima of hydrocytosine derivatives was deduced. The empirical values for bathochromicshifts due to substituents distinct and characteristic for amino (Xmal 239 nm, e ˜ 10 000) and imino (Xmax 227 nm, c ˜5000) forms are given. © 1979, American Chemical Society. All rights reserved.