Synthesis of Arylpropiolic Acids via Carboxylation of Arylacetylenic Grignard Reagents

Abstract

A discovery-based experiment for the synthesis of arylpropiolic acids via carboxylation of arylacetylenic Grignard reagents was developed. This experiment shows the "dual utility" of Grignard reagents. In the synthesis of arylpropiolic acids reported here, we have demonstrated the use of a Grignard reagent as a base in a "Grignard exchange" reaction to form a second Grignard reagent that is used as a nucleophile in a subsequent reaction. In the first step of the synthesis, ethylmagnesium bromide is used as a base to deprotonate an unknown arylacetylene affording the corresponding arylacetylenic Grignard reagent. In the second step of the synthesis, the arylacetylenic Grignard reagent reacts with carbon dioxide to afford the arylpropiolic acid upon acidic workup. Many organic chemistry textbooks show the importance of Grignard reagents as carbon nucleophiles in the formation of new carbon−carbon bonds but rarely show their use as bases. In fact, discussions of Grignard reagents as bases are presented as limitations when considering the choice of solvents for the Grignard reaction. This experiment shows students that Grignard reagents can be used both as a base and as a nucleophile in organic syntheses. Students utilize acid−base extraction to isolate and purify the product. Students use the 1 H NMR spectrum of the product obtained to determine the structure of their assigned unknown arylacetylene.