Ozonolysis

Ozonolysis is a widely used reaction in organic synthesis. The reaction was invented by Christian Friedrich Schoenbein in 1840. Alkenes and alkynes are the most common substrates for the ozonolysis reaction. Ozonolysis was an important diagnostic tool for the determination of the position of unsaturation in unknown molecules before the invention and development of spectroscopic techniques for identification and characterization of organic molecules. The reaction was used for structure elucidation work because it provided chemists with smaller and more readily identifiable carbonyl compounds.

Ozonolysis of alkenes

Typically, the ozonolysis reaction involves bubbling ozone into a solution of olefin in an organic solvent. The reaction is rapid and produces an intermediate called ozonide. The ozonide is unstable, and hence not isolated, but can be further reacted with various reagents to give aldehydes, ketones, carboxylic acids, alcohols etc. When the ozonide is treated with mild reducing agents like phosphines and thio compounds (typically dimethyl sulfide or thiourea is used) aldehydes and ketones are produced. Ozonides can be treated with strong reducing agents like sodium borohydride to produce alcohols. Ozonides when treated with oxidizing agents such as oxygen or hydrogen peroxide, they produce carboxylic acids as the products.

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Symmetrical olefins provide 2 molecules of the same product. However, by carefully controlling the work up conditions, the ozonides from symmetrical olefins can be converted into two different products. For example, treating the ozonide with a combination of acetic anhydride and triethylamine gives methyl ester of the carboxylic acid and an aldehyde. Thus, ozonolysis is a versatile reaction.

One of the most important uses of ozonolysis on industrial scale is the production of azelaic and pelargonic acids from oleic acid.

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A bio catalytic alternative for ozonolysis has also been developed. Lyophilized cell cultures of Trametes hirsute produce aldehydes and ketones from olefins. (Sutton, Peter; Whittall, John; (2012). Practical Methods for Biocatalysis and Biotransformations 2. Chichester, West Sussex: John Wiley & Sons, Ltd. pp. 200–202. ISBN9781119991397.)

Ozonolysis of alkynes

Alkynes also undergo ozonolysis but very slowly compared to alkenes. Unlike alkenes, ozonides from alkynes do not need either an oxidizing agent or reducing agent to provide end products. Ozonides from alkynes upon treatment with water provide carboxylic acids are products. Internal alkynes produce two different carboxylic acids while terminal alkynes produce carboxylic acid with one less carbon; the terminal carbon is converted to carbon dioxide.

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Ozonolysis of alkanes

Alkanes get oxidized when treated with ozone. The products formed are alcohols, aldehydes/ketones or carboxylic acids. The rate of oxidative cleavage of alkanes is highest for tertiary C-H bond, followed secondary and primary.

Ozonolysis services at Piramal Pharma Solutions

Piramal provides ozonolysis solutions to various customers for development of ozonolysis process, process safety studies and scale up. A dedicated ozonolysis set up is available both for laboratory scale (5g/h) work and production (up to 3kg/h) work. Efforts are underway to develop ozonolysis reactions in continuous flow micro reactors.

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