Green dithioester synthesis reaction developed for a brighter tomorrow

Dithioesters are sulfur-containing compounds with versatile applications in biomedicine and polymer science and have shown potential as antimicrobial molecules and agrochemicals. Modern synthesis methods, however, are inefficient, unsafe and/or require high temperatures to generate these compounds, limiting their practicality.

Dithioesters are similar to carboxylate esters, which are organic compounds derived from a carboxylic acid and an alcohol, but the oxygen atoms of the ester group in dithioesters are replaced by sulfur atoms. This exchange results in molecules with unique characteristics compared to carboxylate esters that are often used as intermediates for the organic synthesis of other molecules.

Dithioesters are additionally used as chain transfer agents that can control both polymer length and architecture of large polymer molecules, which are critical for materials science. Biomedical researchers have also speculated that dithioesters may be capable of releasing hydrogen sulfide (H₂S) gas in the presence of the amino acid cysteine, which mediates vasodilation in blood vessels and the scavenging of reactive oxygen species in the cell.

Given the potential applications of dithioesters, a group of researchers from Jinan University and China Three Gorges University developed a new dithioester synthesis reaction that avoids many of the pitfalls of conventional synthesis reactions, including toxicity and high energy requirements.

The team published their paper on January 30 in Polyoxometalates, published by Tsinghua University Press.

“The current raw materials and procedures for the synthesis of disulfides are all facing significant limitations. The use of thiols, organic compounds that contain a sulfur atom bonded to a hydrogen atom and well known for their malodor and toxicity, or the highly flammable and explosive carbon disulfide, made up of one carbon and two sulfur atoms, poses serious operational hazards. Furthermore, certain protocols necessitate the presynthesis of specialized intermediates, leading to multistep procedures and cumbersome handling.  Therefore, the development of efficient and green synthetic methods for dithioesters remains a central challenge in this field,” said Shang-Fu Yuan, professor Chemistry and Materials Science at Jinan University in Guangzhou, China and co-author of the research paper.

The synthesis of dithioesters depends on the construction of a core carbon and two sulfur atom scaffold. In their previous work, the researchers developed metal chalcogenide supertetrahedral clusters, T4-CdCu, capable of using light to catalyze, or drive, chemical reactions. By creating lithium bromide (LiBr)-mediated dispersion conditions, the team was able to create a synergistic photocatalytic system that integrates single-electron transfer (SET) from T4-CdCu and hydrogen atom transfer (HAT) mediated by tetrabutylammonium decatungstate (TBADT), to synthesize benzyl thioesters from elemental sulfur, benzyl chlorides and aldehydes. However, in this synthesis reaction, TBADT functions as the HAT catalyst to generate acyl radicals that do not react with elemental sulfur (S₈) to form thioacyl radicals, or highly reactive, sulfur-centered reactive intermediates in organic chemistry, which are key intermediates in the formation of dithioesters.

“In contrast, amines have been shown to react with S₈ under alkaline conditions to … facilitate the conversion of carbon-oxygen bonds into carbon-sulfur bonds. On this basis, we anticipated that the T4-CdCu photocatalyst, under NH₂CHO, rather than LiBr, dispersion conditions, would promote the formation of acylthio radicals, key intermediates necessary for dithioester synthesis,” said Yuan.

Further, the team hypothesized that photoexcited T4-CdCu* species, which exist in a charge-transfer state, could react with alkyl bromide to deliver intermediates that then react with S₈ to produce corresponding alkylthio radicals. Ultimately, coupling between the alkylthio radicals and the corresponding acylthio radicals generates the final dithioester compound using only readily available sulfide powder (S₈), alkyl bromides and aromatic aldehydes as precursor molecules.

This method eliminates many of the hurdles associated with conventional dithioester synthesis methods, including avoiding highly toxic sulfur compounds, eliminating the need for specialized reagents with specific chemical groups attached to the molecule before synthesis, and room-temperature reaction conditions.

“This study pioneers a sustainable photocatalytic approach for dithioester synthesis through cooperative SET and HAT catalysis using economical and environmentally friendly feedstocks. We anticipate that this strategy will inspire the development of additional novel sulfur-containing compounds through photocatalysis,” said Yuan.

Pei-Lin Ou,, Hong-Tao Gao, Chao-Li Chen, Hao Ma, Bingzhe Wang and Tao Wu from the State Key Laboratory of Bioactive Molecules and Druggability Assessment at the Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules in the Discovery of Innovative Drugs in the College of Chemistry and Materials Science and the Guangdong Provincial Key Laboratory of Supramolecular Coordination Chemistry at Jinan University in Guangzhou, China; Rui Zhou from the State Key Laboratory of Bioactive Molecules and Druggability Assessment at the Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules in the Discovery of Innovative Drugs in the College of Chemistry and Materials Science and the  Guangdong Provincial Key Laboratory of Supramolecular Coordination Chemistry, and the Department of Developmental and Regenerative Biology at Jinan University; and Dong-Sheng Li from the College of Materials and Chemical Engineering at Hubei Provincial Collaborative Innovation Center for New Energy Microgrid in the Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials at China Three Gorges University in Yichang, China also contributed to this research.

This research was supported by the Science and Technology Project in Guangzhou (No. 202102070001).

DOI Link:

https://doi.org/10.26599/POM.2026.9140111

About Polyoxometalates

Polyoxometalates (ISSN 2957-9821) is a peer-reviewed (single-blind), open-access and interdisciplinary journal, sponsored by Tsinghua University. Polyoxometalates publishes original high-quality research papers and significant review articles that focus on cutting-edge advancements in Polyoxometalates, and clusters of metals, metal oxides and chalcogenides. Rapid review to ensure quick publication is a key feature of Polyoxometalates. The journal is indexed by ESCI (IF 2025 = 10.4, Top 3), Scopus (CiteScore 2025 = 17.6, Top 3), Ei Compendex, CAS, and DOAJ. For details about Polyoxometalates, please visit: https://www.sciopen.com/journal/2957-9821.