https://doi.org/10.15255/KUI.2017.020
Published: Kem. Ind. 67 (3-4) (2018) 127–134
Paper reference number: KUI-20/2017
Paper type: Review / History of Chemistry and Chemical Engineering
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Formose Reaction – The Holy Grail of Chemists

N. Raos

Abstract

The formose reaction (FR), the base catalysed condensation of formaldehyde to carbohydrates, was discovered by Butlerov in 1861 and dubbed as a revolutionary discovery, because it presented the first total synthesis of these substances of utmost biological importance. Inspired by the reaction, Baeyer (1870) proposed a mechanism of photosynthesis assuming that the first product is formaldehyde, CH₂O, which further undergoes polymerization into carbohydrates, (CH₂O)_n. However, Butlerov’s methylenitane (formose) turned out not to be a single sugar but a very complex mixture of monosaccharides, polyvalent alchohols, acids, and macromolecular compounds produced by aldol condensation and competitive Cannizzaro reaction. Many attempts have been made in order to optimize the course of the reaction by replacing the original base, Ca(OH)₂, with CaCO₃, PbO, Sr(OH)₂, TlOH, thiazoles, and mineral catalysts, especially borates. It was also proved that the reaction is bettered by addition, as an initiator (cocatalyst), of the first product, glycolaldehyde, HOCH₂CHO, or its phosphate. The application of the reaction was envisaged as a means of commercial production of simple sugars and as part of a life-supporting system in space stations, but its temperature, as well as concentration instabilities were the major obstacles in achieving these goals. In recent years, the reaction has been intensively studied for supporting the theories on the origin of life (especially RNA-world theory), and in studying the chemical processes on comets, meteorites and within interstellar clouds. In the final analysis, FR seemed to be a simple solution to complex problem(s); however, it itself turned out to be a problem of much higher complexity than anyone might have supposed.

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Keywords

history of chemistry, photosynthesis, origin of life, formaldehyde, monosaccharides