Taming tosyl azide: the development of a scalable continuous diazo transfer process

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Deadman, Benjamin J.
O'Mahony, Rosella M.
Lynch, Denis
Crowley, Daniel C.
Collins, Stuart G.
Maguire, Anita R.
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Royal Society of Chemistry
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Heat and shock sensitive tosyl azide was generated and used on demand in a telescoped diazo transfer process. Small quantities of tosyl azide were accessed in a 'one pot' batch procedure using shelf stable, readily available reagents. For large scale diazo transfer reactions tosyl azide was generated and used in a telescoped flow process, to mitigate the risks associated with handling potentially explosive reagents on scale. The in situ formed tosyl azide was used to rapidly perform diazo transfer to a range of acceptors, including beta-ketoesters, beta-ketoamides, malonate esters and beta-ketosulfones. An effective in-line quench of sulfonyl azides was also developed, whereby a sacrificial acceptor molecule ensured complete consumption of any residual hazardous diazo transfer reagent. The telescoped diazo transfer process with in-line quenching was used to safely prepare over 21 g of an alpha-diazocarbonyl in > 98% purity without any column chromatography.
Continuous flow synthesis , C-H insertion , Alpha-diazocarbonyl compounds , Hetero-Wolff rearrangement , Beta-oxo sulfoxides , Organic synthesis , Carbene insertion
Deadman, B. J., O'Mahony, R. M., Lynch, D., Crowley, D. C., Collins, S. G. and Maguire, A. R. (2016) 'Taming tosyl azide: the development of a scalable continuous diazo transfer process', Organic & Biomolecular Chemistry, 14(13), pp. 3423-3431. doi: 10.1039/c6ob00246c
© The Royal Society of Chemistry 2016