An environmentally benign way to synthesize 2-thiocyano-1,3-dicarbonyl compounds with high antifungal activity: a key role of solvent?

Organic & Biomolecular Chemistry Pub Date: 2023-04-06 DOI: 10.1039/D3OB00474K

Abstract

The introduction of thiocyano groups into organic molecules is important for the preparation of many active ingredients and synthetic intermediates. A commonly used and attractive strategy is the nucleophilic substitution of halogens with the SCN anion or oxidative thiocyanation using an excess amount of external oxidants. A sustainable alternative to stoichiometric reagents is electrochemistry based on anodic oxidation of the SCN anion and other intermediates. Electrochemical thiocyanation of various organic compounds, carried out in the usual non-acidic organic solvents, is well known. Here, we present an electrochemical thiocyanation of 1,3-dicarbonyl compounds in which high efficiency was only achieved using AcOH as the solvent. Electrolysis proceeds in an undivided cell under constant current conditions without any additional halogen-containing electrolytes. Ammonium thiocyanate was used as the source of the SCN group and the electrolyte. Electrochemical thiocyanation of 1,3-dicarbonyl compounds begins with the generation of (SCN)2 from the thiocyanate anion, followed by the addition of thiocyanogen to the double bond of the enol tautomer of 1,3-dicarbonyl compounds, which finally gives the products. A variety of thiocyanated 1,3-dicarbonyl compounds bearing different functional groups were obtained in 37–82% yields and were shown to exhibit high antifungal activity.

Graphical abstract: An environmentally benign way to synthesize 2-thiocyano-1,3-dicarbonyl compounds with high antifungal activity: a key role of solvent
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