Dimethyl Sulfoxide Applications in Organic Synthesis

Dimethyl sulfoxide (DMSO) has transcended its traditional role as a high-polarity aprotic solvent to become a versatile reagent in modern organic synthesis. Its unique combination of nucleophilicity, oxidising power and ability to donate methyl, oxygen and sulphur atoms enables a broad spectrum of transformations. DMSO can act as an oxidant in Kornblum and Swern oxidations, supply methylthiol or methylsulfonyl fragments via radical or electrophilic pathways, and participate in sustainable C–C, C–heteroatom and heterocycle constructions under mild, transition metal-free conditions. The reagent’s low toxicity, high boiling point and compatibility with continuous-flow processes further enhance its appeal for scalable and green chemical manufacture. Recent advances have highlighted DMSO’s multifunctionality in bond-forming reactions ranging from inert C–H activation to cascade annulations, underscoring its global significance for pharmaceutical, agrochemical and materials science applications.

Research from Nature Portfolio

Recent studies have showcased the triple role of DMSO as solvent, synthon and oxidant in one-pot C–H activation protocols. A bimetallic Ag–Cu metal–organic framework catalyses the direct coupling of DMSO with aromatic ketones to afford β-ketoallylic methylsulfonyl derivatives in high yields, demonstrating excellent atom, step and pot economy. Innovations in heterogeneous carbocatalysis have employed graphene oxide to drive solvent-free, three-component annulations of 4-hydroxycoumarin, aldehydes and aromatic amines, yielding chromenoquinolinone frameworks under mild conditions. These approaches illustrate how DMSO’s intrinsic reactivity can be harnessed in concert with advanced catalytic materials to enable streamlined access to value-added molecules.

Dimethyl Sulfoxide Applications in Organic Synthesis publication trend

The graph below shows the total number of articles in dimethyl sulfoxide applications in organic synthesis across all publications each year (not limited to Nature Index journals).

Technical terms

C–H activation: The cleavage and functionalisation of a carbon–hydrogen bond in an organic molecule, often to install new substituents directly on hydrocarbon frameworks.

Atom economy: A measure of the proportion of reactant atoms incorporated into the desired product, reflecting the efficiency and environmental impact of a chemical reaction.

Heteroatom: An atom within an organic molecule that is neither carbon nor hydrogen, commonly introducing unique chemical properties in synthesis.

Metal–Organic Framework (MOF): A porous crystalline material composed of metal nodes coordinated to organic linkers, employed as catalysts or supports in various reactions.

Radical: A highly reactive species containing an unpaired electron, frequently utilised in bond-forming and functionalisation processes.

References

1. DBDMH-Promoted Methylthiolation in DMSO: A Metal-Free Protocol to Methyl Sulfur Compounds with Multifunctional Groups. Molecules (2023).
2. I 2 /DMSO-mediated oxidative C–C and C–heteroatom bond formation: a sustainable approach to chemical synthesis. RSC Advances (2024).
3. β-Ketoallylic methylsulfones synthesis via inert C(sp3)–H bond activation by magnetic Ag–Cu MOF. Scientific Reports (2023).
4. Recent Advances in DMSO-Based Direct Synthesis of Heterocycles. Molecules (2022).
5. One-pot three-component tandem annulation of 4-hydroxycoumarine with aldehyde and aromatic amines using graphene oxide as an efficient catalyst. Scientific Reports (2021).