Green Synthesis of Alpha-Ketochalcogenoamides

JOSÉ VALDEZ ROJAS; CEBALLOS NOELIA M.; ELIZABETH MOYANO; JOSEFINA JUÁREZ; GUADALUPE GARCÍA GONZALEZ; PENIERES CARRILLO, GUILLERMO

ROSARIO

Workshop; 1st Argentinean Workshop in Environmental Science; 2009

Derived to their wide use as intermediates in organic synthesis, thioamides have attracted attention in the chemistry of the peptides and in the synthesis of many other compounds. A well-known method to obtain these compounds is the Willgerodt-Kindler reaction, which is characterized by the high temperatures and long reaction times that are required and also to the obtained low yields. In its original form, the Willgerodt-Kindler reaction involves the use of either acetophenones or alkylphenylketones which react with elemental sulfur and either primary or secondary amines to give thioamides. In these products the thiocarbonyl group is always at the end of the alkylic chain. Selenoamides are analogue compounds to thiomides and early reports mention that this chalcogenomides have the same activity (i.e. antimalarial) that their sulfur analogues besides to have lower toxicity than thioamides. Also, selenoamides are used as good intermediates for the synthesis of heterocyclic compounds such as selenazoles and selenazines. For their synthesis is necessary to use reagents such as Woollins reagent, NaHSe or LiAlSeH2 and to our knowledge synthetic methodologies for these compounds employing any modification to the Willgerodt-Kindler reaction are not reported. Besides, nowadays alternative energy sources for reaction activation in organic synthesis, as well as other eco-friendly methodologies have been widely used. In this way, we present herein the synthesis of thio(seleno)amides by a modification to the Willgerodt-Kindler reaction, using aromatic ketones 1, elemental sulfur (selenium) and heterocyclic amines 2 in solvent-free conditions using a Mexican bentonitic clay as catalyst, support and reaction media, employing either infrared or microwaves energy. The obtained results are characterized by smaller reaction times and better reaction yields than the original reaction methodology.