Electrochemical Synthesis of Pyrazolines and Pyrazoles via [3+2] Dipolar Cycloaddition

Abstract

Pyrazolines and pyrazoles are common and important motifs of pharmaceutical agents and agrochemicals. Herein, the first electrochemical approach for their direct synthesis from easily accessible hydrazones and dipolarophiles up to decagram scale is presented. The application of a biphasic system (aqueous/organic) even allows for the conversion of highly sensitive alkenes, wherein inexpensive sodium iodide is employed in a dual role as supporting electrolyte and mediator. In addition, mechanistic insight into the reaction is given by the isolation of key step intermediates. The relevance of the presented reaction is underlined by the synthesis of commercial herbicide safener mefenpyr‐diethyl in good yields.

Electrochemically enabled oxidative aromatization of pyrazolines

“…As a result of the broad functional group tolerance and previous investigations into biphasic electrochemical reactions involving halogens as mediators, 44 we propose an ionic reaction mechanism (Scheme 5). In the aqueous layer, anodic oxidation of chloride ions initially forms adsorbed or dissolved chlorine.…”

“…Initial reactions were performed using con- ditions based on previous work on the mediated electrochemical synthesis of pyrazolines. 44 Here, graphite electrodes and a biphasic solvent system (ratio of the layers organic/ aqueous 1 : 4), with a sodium halide concentration of 1 M with respect to the aqueous phase was used along with high stirring speed (1000 rpm). The concentration of the test substrate 4a was set to 0.34 mmol (concentrations of pyrazolines are given relative to the organic layer).…”

“…An electrochemical iodide-mediated approach for the synthesis of pyrazolines and pyrazoles from readily available hydrazones gave access to a library of pyrazolines in up to excellent yields. 44 Application of a redox mediator enhances selectivity and suppresses side reactions, e.g. polymerizations or over-oxidations.…”

The Oxidation of Organo‐Boron Compounds Using Electrochemically Generated Peroxodicarbonate

“…[19] In general, electrochemistry can be considered a favorable alternative to conventional chemical processes as it is inherently safe and produces less waste. [19][20][21][22][23] It is already established in numerous applications such as dehydrogenative coupling reactions [34][35][36] and construction of heterocycles such as indazolinones, [37] pyrazoles/pyrazolines, [38] pyrazolidine-3,5-diones, [39,40] and benzoxazoles. [39,[41][42][43] (Para)periodate has recently been established as a highperformance platform oxidizer which can be generated at a boron-doped diamond anode.…”

Electrochemical intramolecular N(sp2)–H/N(sp3)–H coupling for the synthesis of 1H-indazoles

“…12 The electrochemical method emerging as a viable tool has been frequently employed to manipulate chemical bonds, thus minimizing waste emission as well as improving the step and atom economy. 13 In addition, commercially available NH 3 serving as a kind of the most attractive nitrogen donor has rarely been applied in organic transformations. 14,15,19 In particular, in 2017, Xu's group first realized the electrochemical synthesis of phenanthridines by employing molecular NH 3 as the nitrogen donor, in which anodic oxidation of the in situ generated aryl imine by condensation of biaryl aldehydes and NH 3 facilitated the subsequent radical C–H/N–H cyclization process.…”