Ozone’s Transformative Role in Sustainable Chemistry


Ozone (O3) is a well-known molecule with a dual personality. In the stratosphere, it acts as a crucial shield, absorbing harmful ultraviolet rays and protecting life on Earth. Simultaneously, O3 is one of the most potent oxidants in the chemical world, finding widespread applications in various industrial processes. From the synthesis of active pharmaceuticals to its use in disinfectants and deodorizers, ozone’s versatility is unmatched. The new study led by PhD graduate Danniel Arriaga and Professor Andy Thomas from Texas A&M University, published in the peer-reviewed Journal Nature Chemistry explored a novel approach to harnessing O3 as a constructive reagent for synthetic purposes, rather than its conventional use in deconstructive ozonolysis reactions. This innovative method not only sheds light on the underexplored realm of primary ozonides (POZs) but also introduces a safe and sustainable method for the synthesis of pharmaceutically relevant compounds. Ozone has historically been employed in ozonolysis reactions, primarily used for converting olefins from petroleum feedstocks into various carbonyl products and precursors. While ozonolysis has been a valuable tool for breaking carbon-carbon (C-C) bonds in olefins, the real challenge lies in constructing new bonds, which is the essence of modern synthesis. The ability to use ozone as a constructive reagent for oxidation without C-C cleavage offers a sustainable approach using elemental oxygen and electricity.

The authors proposed an innovative approach involving the primary ozonides (POZs) as synthetic intermediates, aiming to achieve the syn-dihydroxylation of olefins. POZs have been relatively unexplored compared to other ozonolysis intermediates such as Criegee intermediates (CIN) and secondary ozonides (SOZ). They suggested that harnessing POZs could lead to the creation of carbon-oxygen (C-O) bonds without C-C cleavage, resulting in the synthesis of valuable compounds.

To investigate the feasibility of using POZs as synthetic intermediates, the researchers conducted a series of experiments. They evaluated the influence of olefin geometry on the rate of C-C cleavage for different types of POZs, including trans-, terminal-, and cis-olefin-derived POZs. The results indicated that POZs have finite lifetimes at synthetically useful temperatures, which laid the foundation for further chemical reactivity studies. The research team developed a model syn-dihydroxylation strategy, focusing on capturing POZs with nucleophiles to synthesize syn-vicinal glycols. Under controlled conditions, a wide range of functional groups were found to be tolerant of both ozone’s strong oxidizing properties and nucleophilic reactions. This approach offered a sustainable alternative to transition metal-based syntheses, demonstrating its potential for practical applications.

Recognizing the challenges associated with scaling up reactions involving POZs due to their unstable nature, the researchers devised a continuous flow reactor system. This approach not only ensured the safe handling of reactive intermediates at low temperatures but also eliminated peroxide accumulation, making it suitable for large-scale processes. The continuous flow system was successfully applied to the synthesis of pharmaceutically relevant compounds, including guaifenesin and a precursor to ponesimod.

The study led by Danniel Arriaga and Professor Andy Thomas presents a remarkable advancement in the field of chemical engineering by harnessing ozone as a constructive reagent. By exploring the previously underdeveloped primary ozonides (POZs) and introducing a safe and sustainable approach in continuous flow systems, this research paves the way for the development of green and eco-friendly synthetic processes. The findings not only expand our understanding of ozone chemistry but also offer a promising avenue for the synthesis of valuable compounds and pharmaceuticals, reducing the reliance on hazardous transition metals and oxidizing agents. This groundbreaking work underscores the potential of ozone as a versatile and powerful tool in modern organic synthesis, further advancing the field of green chemistry.

Ozone's Transformative Role in Sustainable Chemistry - Advances in Engineering
Image Credit: Nature Chemistry volume 15, pages1262–1266 (2023)

About the author

Andy Thomas
Assistant Professor
Department of Chemistry
Texas A&M University

Our primary research objective is to develop new methods by investigating and harnessing the reactivity of highly unstable intermediates. Essential to improving mechanistic understanding is the development of new strategies that allow us to monitor fleeting intermediates and manipulate their reactivity. To supplement our mechanism driven methodology development, we will develop a new rapid multiple injection NMR (RMI-NMR) system to monitor and control the reactivity of transient species. Representative areas of research interest include the development of new organic transformations; and the development of catalyst-transfer polymerization reactions.


Arriaga DK, Thomas AA. Capturing primary ozonides for a syn-dihydroxylation of olefins. Nat Chem. 2023 Sep;15(9):1262-1266. doi: 10.1038/s41557-023-01247-5.

Go to Nat Chem.

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