Regiocontrolled SNAr Reaction on 2,3-Dihalopyridines with NaSMe To Obtain Bromo(methylthio)pyridines as Key Precursors of 3-Halo-2-(hetero)arylthieno[2,3-b]pyridines and Thieno[3,2-b]pyridines

Agathe Begouin; Daniela Peixoto; Maria-João R. P. Queiroz

doi:10.1055/s-0033-1338442

Synthesis, Table of Contents

Synthesis 2013; 45(11): 1489-1496
DOI: 10.1055/s-0033-1338442

paper

Regiocontrolled S_NAr Reaction on 2,3-Dihalopyridines with NaSMe To Obtain Bromo(methylthio)pyridines as Key Precursors of 3-Halo-2-(hetero)arylthieno[2,3-b]pyridines and Thieno[3,2-b]pyridines

Agathe Begouin

Centro de Química, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal Fax: +351(253)604382 Email: mjrpq@quimica.uminho.pt

,

Daniela Peixoto

Centro de Química, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal Fax: +351(253)604382 Email: mjrpq@quimica.uminho.pt

,

Maria-João R. P. Queiroz*

Centro de Química, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal Fax: +351(253)604382 Email: mjrpq@quimica.uminho.pt

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Abstract

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Abstract

The synthesis of 3-halo-2-(hetero)arylthieno[2,3-b]pyridines and 3-halo-2-(hetero)arylthieno[3,2-b]pyridines has been performed through a three-step methodology from 3-bromo-2-chloropyridine or 2-bromo-3-fluoropyridine, respectively. The key step of this methodology is the formation of the required bromo(methylthio)pyridines by a regiocontrolled nucleophilic aromatic substitution (S_NAr) with sodium methanethiolate (NaSMe). Then, the Sonogashira coupling with (hetero)arylalkynes followed by a halocyclization with bromine or iodine, afforded the expected 3-halo-2-(hetero)arylthienopyridines.

Key words

thienopyridines - nucleophilic aromatic substitution - methanethiolate - Sonogashira coupling - halocyclization

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References

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