Abstract
Imidazole-1-sulfonyl azide and salts thereof are valuable reagents for diazo-transfer reactions, most particularly conversion of primary amines to azides. The parent reagent and its HCl salt present stability and detonation risks, but the hydrogen sulfate salt is significantly more stable. An updated procedure for the large-scale synthesis of this salt avoids isolation or concentration of the parent compound or HCl salt and will facilitate the use of hydrogen sulfate salt as the reagent of choice for diazo transfer.
Highlights
Cavender and Shiner first reported the use of trifluoromethanesulfonyl azide (TfN3) as an organic-soluble diazotransfer reagent more than 40 years ago.[10]
Due to the product being readily storable, we felt most laboratories would not benefit from subgram production, so the smallest scale we evaluated used 1.0 g of sodium azide, which yielded 2.1 g of 1-H2SO4 (51%)
The method described above allows for synthesis, crystallization, and isolation of the shelf-stable salt 1H2SO4
Summary
We found that 1 could be generated as a safely diluted solution at 2 M in acetonitrile and, following partitioning with saturated aqueous NaHCO3 and extraction into EtOAc, 1-H2SO4 could be precipitated directly from the organic layer, thereby avoiding 1HCl (Scheme 2). Different EtOAc/MeCN ratios were evaluated as the reaction solvent system (Table 1, Method B), with aqueous wash/partition workup, but no additional organic extraction employed. We felt an evaluation of 15 g of sodium azide could be safely duplicated in most laboratory environments, yielding 46.0 g of 1-H2SO4 (73%) These reactions are reliable and reproducible, and the synthesis of 1-H2SO4 was safely conducted to provide tens of grams of this valuable reagent. Use of 1-H2SO4 to duplicate literature reactions which had previously been conducted utilizing 1-HCl yielded comparable results, verifying its ability as a diazo-transfer reagent (see Supporting Information)
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