Year: 2026
Type: article
Abstract: The Butlerov, or formose, reaction is the transformation of formaldehyde into a complex mixture of sugars in the presence of calcium hydroxide, eventually leading to sugar degradation with the formation of a tar, difficult to analyse. Its intricate mechanism has long captivated researchers, not only for its potential in sugar synthesis for food applications but also for its relevance to prebiotic chemistry. The autocatalytic formation of glycolaldehyde from the retro-aldol reaction of tetroses was proposed by Breslow in 1959 and has been discussed in most of the literature; however, the mechanism has recently been set under discussion. This study aims to explore the reaction pathway by starting from the first-principles automatic generation of reaction products and density functional theory (DFT) free energy calculations. The kinetics of the obtained chemical network were simulated and compared with experimental results. No derivatizing agents were employed for sugar identification to avoid biased detection based on their reactivity. Our results are in accordance with recent literature showing that C7 branched ketoses are formed mainly and, in addition, that the autocatalytic mechanism is not needed to explain the results. The model was also tested by using different sugars as initiators, showing agreement with published data. The Butlerov reaction, relevant to prebiotic chemistry, has become a matter of debate, with questions arising regarding the applicability of the generally accepted mechanism involving the Breslow autocatalytic cycle. Here, the authors integrate first-principles reaction prediction, density functional theory free energy calculations, and automated synthesis with real-time monitoring to map the entire reaction, showing that C7 branched ketoses constitute the main product and that the proposed Breslow autocatalytic cycle does not have a substantial impact on the mechanism, in favour of recent literature.
Source: Communications Chemistry
Authors: Dhanalakshmi Vadivel, Daniele Dondi
Institution: University of Pavia
Language: English
Subfield: Astronomy and Astrophysics
Field: Physics and Astronomy
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,690
OpenAlex ID: W7166523349