Convergent Paired Electrosynthesis of β-Nitroalcohols Using an Electrogenerated Base
Authors: Homma Haruka , Hasegawa Ruka , Yokoyama Tomohiro , Tajima Toshiki 
Published: December 2024

Organic electrosynthesis has attracted much attention as an environmentally benign organic synthesis process, because it is a redox process that does not use oxidizing or reducing agents. In organic electrosynthesis, only one of the reactions, oxidation at the anode or reduction at the cathode, is often targeted, and the counter electrode is mostly used only to conduct electric current. In contrast, paired electrosynthesis targets both anodic and cathodic reactions and is attractive from the viewpoint of current efficiency. Furthermore, convergent paired electrosynthesis, which yields a single product by the reaction between active species generated at the anode and cathode, is ideal in terms of product separation. On the other hand, β-nitroalcohols are useful organic synthetic intermediates and synthesized by the Henry reaction of carbonyl compounds with nitroalkanes. With these facts in mind, a convergent paired electrosynthesis of β-nitroalcohols was designed by combining anodic generation of benzaldehydes from benzyl alcohols and cathodic formation of nitromethyl anion from nitromethane (CH3NO2) via an electrogenerated base (EGB).

The first step was to examine the electrolysis conditions for paired electrolysis of benzyl alcohol (1) using an undivided cell. The paired electrolysis of 1 was performed using Bu4PBF4 or Bu4NBF4 as the supporting electrolyte and CH3NO2 as the solvent. As a result, the yield of β-nitroalcohol (3) with the use of Bu4PBF4 was 48%, which was about twice that with the use of Bu4NBF4.

In the paired electrolysis, there are three possible probases (PBs) such as Bu4N+, Bu4P+, and CH3NO2. To verify the PB, linear sweep voltammetry of Bu4NBF4 and Bu4PBF4 was demonstrated in CH3NO2, respectively. Furthermore, linear sweep voltammetry of Bu4NBF4, Bu4PBF4 and CH3NO2 was also demonstrated in CH3CN, respectively. These results suggested that CH3NO2 as the solvent, rather than Bu4NBF4 and Bu4PBF4, is mainly reduced at the cathode. To further validate the EGB that occurs in the reaction system, the electrolysis in 0.1 M Bu4PBF4/CH3NO2 was carried out in the absence of 1 using a divided cell. After the electrolysis, CH3NHOH was detected by TLC and 1H NMR in the cathode chamber. This indicates that CH3NHOH or its precursor derived from CH3NO2 may act as an EGB in this reaction system.

Finally, the paired electrosynthesis of various β-nitroalcohols was carried out using benzyl alcohols having an electron-withdrawing group on the benzene ring. As a result, the corresponding β-nitroalcohols were formed in moderate yields with the exception of p-nitrobenzyl alcohol.

In conclusion, we have successfully demonstrated the paired electrosynthesis of β-nitroalcohols combining anodic generation of benzaldehydes and cathodic formation of nitromethyl anion via an EGB using an undivided cell. This paired electrosynthesis can be applied to the synthesis of various β-nitroalcohols and is expected to make a significant contribution to the synthesis of pharmaceuticals and agrochemicals.

Figure 1