On Reuben G. Jones synthesis of 2-hydroxypyrazines
Résumé
In 1949, Reuben G. Jones disclosed an original synthesis of 2-hydroxypyrazines 3 and /or 4 involving a double condensation between 1,2-dicarbonyls and α-aminoamides upon treatment with sodium hydroxide at low temperature. This discovery turned out to be of importance as even today there are no simple alternatives to this preparation. Across the years, it was employed to prepare 2-hydroxypyrazines but some of its limits, notably regioselectivity issues when starting from α-ketoaldehydes 1, certainly hampered a full-fledged generation of pyrazine-containing new chemical entities of potential interest in medicinal chemistry. We will describe here some insights and improvements in the reaction parameters affecting the regioselectivity and yield when starting from phenylglyoxal and two α-aminoamides. We also suggest a mechanism explaining the counterintuitive occurrence of 3,5-substituted-2-hydroxypyrazine 3 as the major reaction product.
Domaines
Chimie
Origine : Fichiers produits par l'(les) auteur(s)