title: General solution to the synthesis of N-2-substituted 1,2,3-triazoles.
abstract: 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.
authors.affiliation: Department of Chemical Development, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut 06877, USA. xiao-jun.wang@boehringer-ingelheim.com
authors.forename: Xiao-jun
authors.initials: XJ
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Dhileepkumar
authors.initials: D
authors.lastname: Krishnamurthy
authors.forename: Chris H
authors.initials: CH
authors.lastname: Senanayake
authors.forename: Peter
authors.initials: P
authors.lastname: Wipf
mesh_terms: D000478:Alkylation; D008958:Models, Molecular; D015394:Molecular Structure; D055672:Static Electricity; D014230:Triazoles / Q000138:chemical synthesis*
chemical_list: D014230:Triazoles