Synthesis of methyl 4-oxo-4-(thiophen-2-yl)butanoate

Abstract

The aim of this work is the synthesis of a gama-keto ester derived from thiophene heterocycle, using simple experimental techniques and cheap and commercially available reagents. The synthesis of this compound involve several synthetic transformations, namely the preparation of the acylating reagent followed by the synthesis of a 1,4-dicarbonyl compound by Friedel-Crafts acylation of the thiophene. The students will have contact with several classical reactions in organic chemistry: preparation of an ester using an anhydride as precursor (alcoholysis), nucleophilic substitution (conversion of a carboxylic acid to an acid chloride) and electrophilic aromatic substitution of a heterocycle (Friedel-Crafts acylation). Several experimental techniques will be considered such as heating at reflux in anhydrous conditions, thin layer chromatograpy (TLC), gravity filtration, liquid-liquid extraction. The determination of the structure of all compounds synthesized will be also performed through 1H NMR and IR spectroscopic techniques. The duration of the experiment will be 4 sessions: session 1: preparation of 4-methoxy-4-oxobutanoic acid; session 2: preparation of methyl-4-chloro-4-oxobutanoate; session 3: preparation of methyl 4-oxo-4-(thiophen-2-yl)butanoate and session 4: isolation of methyl 4-oxo-4-(thiophen-2-yl)butanoate through liquid-liquid extraction. The difficulty level of this experiment is medium and the level of study is intermediate.