The influence of 5-halo substituents on the thermal depyrimidination of the glycosidic bond in 2'-deoxyuridines

Following fusion, 2′-deoxynucleosides undergo thermolytic cleavage of the glycosidic bond to yield the corresponding base, furfuryl alcohol, and water. Purine deoxynucleosides are more readily subject to thermal cleavage of the base than are pyrimidine deoxynucleosides, such as 2′-deoxyuridine. However, when the latter deoxynucleoside is substituted by halogens in the 5-position, the glycosidic bond is weakened and loss of halouracil is competitive with ease of depurination. The reduction in strength of the glycosidic bond is linearly related to the corresponding meta Hammett substituent constant.