Cracking Meldrum's Acid: Lowering the Temperature
Creators: name: Bollard, Hannah
Publisher: name: The Australian National University
Year: 2023

description: Sucrose fatty-acid mono-esters are valuable surfactants that have many industrial applications in consumer goods and medications. The current industrial syntheses are conducted through trans-esterification protocols, which regularly produces mixtures of sucrose fatty-acid mono-esters and other higher-order esters. The production of sucrose fatty-acid mono-esters through traditional synthetic methodologies was explored within this thesis and found to be inefficient and sometimes unreliable. A reliable and atom economical protocol for accessing esters that accounts for sucrose's own incompatibilities is required. Utilisation of ketenes as a carbonyl source may be one such protocol. Ketenes are highly reactive intermediates that can be produced and reacted under the same reaction conditions, including at a neutral pH. Ketenes therefore present an attractive way to produce sucrose fatty-acid mono-esters if the reaction temperature used to access the ketene intermediate can be kept lower than sucrose's caramelisation point. Meldrum's acid is a common six-membered heterocycle that can access ketenes intermediates through a single-step thermolytic pathway. The key challenge with utilising Meldrum's acid as a ketene source is identifying an analogue with thermolytic compatibility with sucrose and at a temperature lower than that of Meldrum's acid itself. We sought to explore the effects of modifying the C2 and C5 residues of Meldrum's acid on the thermolysis pathway, which is currently unknown to literature. A library of 17 varying C2 substituted Meldrum's acids were prepared. The thermolytic behaviour of these compounds were investigated through thermogravimetric analyses. A constraining effect for the aliphatic Meldrum's acids and an asynchronous hetero-retro-Diels-Alder thermolysis pathway operating for the acetophenone Meldrum's acids were identified. A selection of the aliphatic C2 substituted Meldrum's acids was additionally derivatised at the C5 position to give a library of gem-dialkyl, gem-dialkenyl and gem-dialkynyl Meldrum's acids. Through thermogravimetric analyses, we found the thermolysis temperatures were substantially higher compared to their parent compounds. These derivatives were found to be unsuitable ketene surrogates for esterifying sucrose. The thermolysis results suggest the C5 residue takes precedence over the C2 residue on the thermolysis mechanism, and the C2 residue is the main influence when there is no substitution. A gem-dialkenyl Meldrum's acid afforded a cyclobutanone product through subjection thermolysis, identified by some distinctive mass fragments through GCMS analyses. It was found the same distinctive mass fragments were present in GCMS analyses of the corresponding library of gem-dialkenyl Meldrum's acids, as well as the exact mass of the fragmented C2 ketone residue. Other protocols to access the cyclobutanone and different ketene products were explored. Malonic acids were studied for their capacity to form ketenes through cyclic carbonate and cyclic thiocarbonate intermediates. The synthesised malonic acids were analysed through thermogravimetric analysis experiments. It was found that the two dialkynyl malonic acids decarboxylated readily and possessed a different thermolysis pathway compared to the other analysed malonic acid. This decarboxylation pathway was replicated in thermolysis experiments. The same cyclobutanone product from the gem-dialkenyl Meldrum's acid was also prepared from a malonic acid compound. We were able to demonstrate that cyclic carbonates produced from malonic acids can also form ketene intermediates and the ketene intermediates prepared in this manner can be accessed at lower temperatures than the equivalent Meldrum's acid derivative. Thus, cyclic carbonates may be a possible ketene source for esterifying sucrose.