Alkylation of 9‐substituted guanine derivatives with α,ω‐dihaloalkanes

Reactions of 9‐substituted guanine derivatives with NaH/1,2‐dibromoethane, 1,3‐dibromopropane, or 1,4‐dibromobutane at room temperature resulted in the isolation of tricyclic 1,N2‐(1,2‐ethano)guanine, 1,N2‐(1,3‐propano)guanine, or 1,N2‐(1,4‐butano)guanine products, respectively. O6‐Haloalkyl and N1‐haloalkyl products were obtained following the use of NaH/1,4‐dibromobutane, higher α,ω‐dibromoalkanes, or α‐bromo‐ω‐fluoroalkanes. Raising the reaction temperature opened the synthetic way toward O6‐guanine‐alkylene‐O6‐guanine and N1‐guanine‐alkylene‐O6‐guanine symmetric and unsymmetric dimers. Protection of the substrate amine group to form N,N‐dialkylformamidine provided the access to N1‐guanine‐alkylene‐N1‐guanine dimers.