Imidazolidinethiones: Underexplored organocatalysts that show promise in catalyzing prebiotic and modern organic reactions

Project Information

SImCat

Grant agreement ID: 101024710

DOI

10.3030/101024710

Project closed

EC signature date 12 April 2021

Start date 15 June 2021

End date 14 April 2023

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 149 239,20

EU contribution

€ 149 239,20

Coordinated by

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Germany

Periodic Reporting for period 1 - SImCat (Imidazolidinethiones: Underexplored organocatalysts that show promise in catalyzing prebiotic and modern organic reactions)

Reporting period: 2021-06-15 to 2023-04-14

Summary of the context and overall objectives of the project

Many chemical reactions are too slow to be productive and need catalysis to be more efficient. There are several methods to promote such intrinsically slow chemical reactions. Utilising so-called organocatalysts to boost chemical reactions provides an optimum of benefits, in particular when comparing the aspects of costs, energy efficiency, waste production, and negative environmental impacts to alternative methods such as heating and/or the use of metal-based catalysts. “Organo” in the word organocatalyst indicates that these molecules are comprised of chemical elements such as carbon, hydrogen, nitrogen, oxygen, and/or sulphur. The word part “catalyst” refers to the characteristic feature of these molecules, that is, that they enhance the rate of chemical transformations. Imidazolidine-4-thiones (ITO) are cyclic secondary amines and a class of organocatalysts, which have only been used in a few chemical transformations so far, possibly because they are not well understood. Importantly, imidazolidine-4-thiones may provide insight into the origins of life. This is because they can assemble from simple molecular building blocks that may have feasibly formed on the early Earth and could have catalysed prebiotic reactions that may have led to the generation of increasingly complex organic molecules on our planet. Therefore, it is of interest to garner a deeper understanding of imidazolidine-4-thiones and investigate their reactivity. This allowed us to better understand the role they played on the early Earth and gain insight on how to efficiently use them in reaction transformations.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In the SImCat project, we studied in detail the pathway of the organocatalytic reactions using imidazolidine-4-thiones. During our investigation, we discovered a new type of organocatalyst, namely 4-(alkylthio)-2,5-dihydro-1H-imidazoles (TIMs). We systematically modified the TIM structure to gain a broad understanding of how those structural variations could affect the catalysed reactions. We used chemical kinetics to determine how strongly TIM organocatalysts activate reactants for carbon-carbon bond-forming reactions. To do so, we monitored the reactions of TIM-derived compounds with reference compounds. These reference compounds or the TIM derived compounds are coloured when dissolved in organic solvents (see photo). After mixing solutions of the TIM derived reactants with solutions of the reference compounds, we traced the disappearance of colour by using photometric methods. The results of these measurements and a subsequent mathematical treatment of the data enabled us to determine how reactive the TIM derivatives are. In total, 15 ITO- and TIM-derived organic compounds were synthesised and analysed through this method. The characterisation of their reactivities now provides a broad overview of their scope in organocatalytic reactions and will make it easier for researchers to beneficially employ them in future organic synthesis.
Results of the SImCat project have led to one publication in a peer-reviewed journal and were presented at four international conferences by poster contributions and oral communications.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Excitingly, we have discovered and now classified a new type of organocatalyst which will be further investigated and utilised by the greater scientific community. This catalyst can promote the investigated prebiotic reaction, that is, the α-cyanomethylation of aliphatic aldehydes, under mild conditions without the need for elevated temperatures. The organocatalyst works even more efficiently when the reaction mixture is irradiated by light, which may arise from the sun in a natural environment or an LED light source. As TIM catalysts can be assembled from cheap, easily obtainable feedstock, they represent affordable, green organocatalysts for future exploration.

Colourful Reference Compounds