Guido Bargellini was a disciple of
Hermann Emil Louis Fischer, the German chemist and Nobel laureate famous for the eponymous
Fischer esterification reaction. Bargellini did his post-doctoral lab research in Fischer's laboratory. He spent most of his career as a chemist at the
University of Rome. His interest in
coumarins, a recently isolated compound at the time, led Bargellini to experiment with multi-component reactions (MCRs) between
phenols,
chloroform, and
acetone in a solution of a
sodium hydroxide. He discovered the structure given to the compound produced a
carboxylic acid instead of a phenol as previously thought. In 1894, Link, a German chemist, had published the reaction in
Chemisches Zentralblatt and patented it. However, he wrote the product was either a
ketone or a phenol, specifically he claimed it was a "hydroxyphenyl hydroxyisopropyl keton" or "hydroxyisobutyrylphenol." When Bargellini conducted the same experiment and began testing the product, the chemical properties could not be from a ketone or a phenol. Instead, he was certain it was a carboxylic acid, specifically an "α-phenoxyisobutyric acid." Link himself experimented with reactions in 1900 that proved his original claim was erroneous, yet it was never changed. Since Bargellini correctly identified the product, its structure and properties, then published his results in the
Gazzetta Chimica Italiana, the reaction was named after him. However, the importance of the reaction in organic synthesis and later the pharmaceutical industry has made it important historically. Since the reaction is relatively easy to perform—the reagents being readily available—many other almost identical reactions were named in the decades after. This discovery led the way for new transformation reaction, the presently-established Bargellini-type reactions, that has been of great importance, specifically in the
pharmaceutical industry. It also paved the way for later name reactions, like the
Jocic–Reeve reaction and the
Corey–Link reaction. The Jocic–Reeve and Corey–Link reactions are almost always featured together with the Bargellini reaction in a MCR. The reaction itself has been modified several times to increase efficiency or produce a modified product. The adaptability of the reaction is one of its greatest aspects. No decade has gone by without an important addition or twist of the reaction taking place. In the author's own words, "The first phase in the reaction is probably the formation of
acetonechloroform--(which may, indeed, be used in place of the chloroform), this being then acted on by sodium hydroxide in presence of acetone, yielding
α-hydroxyisobutyric acid, which, with the phenol, gives α-phenoxyisobutyric acid. The chloroform may also be replaced by
bromoform,
bromal,
chloral, or
carbon tetrachloride or
tetrabromide." Most textbooks describe the reaction as a way to make
morpholinones or
piperazinones, but it use extend much farther than that. One hundred years later, the Bargellini reaction itself was used for the
condensation of
coumarins, an ironic twist to the history of the reaction since this was Bargellini's primary compound of interest and his own named reaction produced it. == Reactions and reaction mechanisms ==