Taming tosyl azide: the development of a scalable continuous diazo transfer process
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
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 β-ketoesters, β-ketoamides, malonate esters and β-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 α-diazocarbonyl in >98% purity without any column chromatography.
Date Issued
2016-04-07
Date Acceptance
2016-02-26
Citation
Organic & Biomolecular Chemistry, 2016, 14 (13), pp.3423-3431
ISSN
1477-0539
Publisher
Royal Society of Chemistry
Start Page
3423
End Page
3431
Journal / Book Title
Organic & Biomolecular Chemistry
Volume
14
Issue
13
Copyright Statement
© The Author(s) 2016. Organic & Biomolecular Chemistry is © The Royal Society of Chemistry 2016.
Subjects
Organic Chemistry
0304 Medicinal And Biomolecular Chemistry
0305 Organic Chemistry
1115 Pharmacology And Pharmaceutical Sciences
Publication Status
Published
Date Publish Online
2016-03-01