Electrochemical Syntheses of Aryl-Substituted Benzothiophenes and Phenanthrenes Using Benzenediazonium Salts as the Aryl Radical Precursors

Abstract

Aryl-substituted benzothiophene and phenanthrene are important structural units in medicinal chemistry and materials science. Although extensive effort has been devoted to prepare these compounds and a variety of approaches have been developed to construct the 2-substituted benzothiophene core structure, environmental-friendly and efficient synthetic means are still desired. Based on our previous electrochemical Minisci-type arylation reaction with aryl diazonium salt as the aryl precursor, as well as the work from König’s group, herein, we described the use of paired electrolysis to achieve 2-aryl benzothiophenes and 9-aryl phenanthrenes employing benzenediazonium salts as the aryl radical precursors. Initially, 2-methylthiobenzendiazonium salt 1a and 4-methylbenzene ethyne 2a were chosen as the model substrates to optimize the reaction conditions by examining solvent, supporting electrolyte, electrode material and current density. After extensive efforts, it was found that an 89% yield of the desired product 3a was afforded in an undivided cell equipped with a graphite felt anode and a Ni plate cathode, using n-Bu₄NBF₄ as the supporting electrolyte and DMSO as the solvent, while operating at a constant current density of 4 mA·cm^-2. Under the optimal conditions, the generality of the electrochemical protocol and substrate scope were then examined. The results showed that both alkyl acetylene and aryl acetylene could be applied in this method, and a series of aryl-substituted benzothiophene derivatives were obtained successfully. Considering the wide range of application of phenanthrene molecules in medicinal chemistry and materials science, we then applied this protocol to the synthesis of phenanthrene derivatives, and succeeded in obtaining the corresponding 9-arylphenanthrene derivatives. Finally, cyclic voltammetric (CV) measurement was conducted to analyze the possible mechanism. It was found that 2-methylthiobenzene diazonium salt 1a gave a significant irreversible reduction peak at -0.4 V vs. Ag/Ag⁺ in CH₃CN, whereas no signal was detected for phenylacetylene 2a in the scanning potential window. In addition, the presence of 2a did not alter the peak potential of 1a, albeit the peak current increased slightly. These results indicate that the reduction of 1a is easier than that of 2a. Based on our CV analysis and previous photocatalytic results, a sequential paired electrolysis mechanism is proposed, that is, the electrochemical reduction of benzodiazonium salt 1a at the cathode produces aryl radical 5a, which is then added to phenylacetylene to produce vinyl radical 6a and sulfonyl radical 7a following an intramolecular cyclization. Finally, the anodic oxidation of 7a, followed by demethylation with DMSO, generates the target product 3a. In summary, we have developed a paired electrolysis method for the syntheses of 2-arylbenzothiophene derivatives and 9-arylphenanthrene derivatives. The protocol features wide substrate scope and functional group tolerance, which further demonstrates that the practicability of aryldiazonium salts as versatile aryl radical sources to generate aryl radicals through electrochemical reduction.

Keywords

Benzothiophenes / Phenanthrenes / Paired electrosynthesis / Aryldiazonium salts / Aryl radicals

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