General solution to the synthesis of N-2-substituted 1,2,3-triazoles.
The regioselective N-alkylation of 1,2,3-triazoles 1-6 was studied. Good to excellent N-2 selectivity and high chemical yields for N-2-substituted 4,5-dibromotriazoles 7 were obtained with 4,5-dibromo- and 4-bromo-5-trimethylsilyl-1,2,3-triazoles. These building blocks can be readily converted to 2-mono-, 2,4-di-, and 2,4,5-polysubstituted triazoles 10-15, providing a general, protective, group-free method for the synthesis of N-2-substituted triazoles. Observed regioselectivities can be rationalized by a combination of Frontier Molecular Orbital, steric, and electrostatic directing effects on the heterocyclic scaffolds.
Wang
Xiao-jun
XJ
Department of Chemical Development, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut 06877, USA. xiao-jun.wang@boehringer-ingelheim.com
Zhang
Li
L
Krishnamurthy
Dhileepkumar
D
Senanayake
Chris H
CH
Wipf
Peter
P
D000478:Alkylation; D008958:Models, Molecular; D015394:Molecular Structure; D055672:Static Electricity; D014230:Triazoles / Q000138:chemical synthesis*
D014230:Triazoles