Regioselective Bromination of a Thymine–Acridine Conjugate by N-Bromosuccinimide

Abstract

A thymine and acridine conjugate (1), containing a benzylic carbon of thymine and an electron-rich aromatic ring (acridine) within the same molecule, was synthesized. Treatment of 1 with N-bromosuccinimide (NBS) in anhydrous chloroform in the presence of azobisisobutylnitrile produced a dibromo-substituted thymine–acridine conjugate (7) as a major product, in which the bromination was only observed on the acridine ring. Nuclear Overhauser effect (NOE) difference spectroscopy revealed that the actual bromination substitution was on C-2 and C-7 of acridine. Our results suggest that electrophilic aromatic substitution, not the expected benzylic radical reaction, takes place predominantly even when 1 is subjected to the NBS reaction condition, which favors radical processes. In addition, such selectivity is clearly solvent dependent.

Keywords:

• Benzylic substitution
• electrophilic aromatic substitution
• N-bromosuccinimide
• radical reaction

ACKNOWLEDGMENTS

We are grateful for support of this research by University of the Pacific and the National Science Foundation (MRI-0722654). We also thank Mr. Matthew Curtis for carrying out the mass spectrometry measurements.