(Digital Presentation) Electro-Oxidative Trimerization of Catechol to Hexahydroxytriphenylene Using a Flow Microreactor
Authors: Nakamura Yuto , Sato Yasushi , Shida Naoki , Atobe Mahito 
Published: July 2022

Due to their unique spectroscopic and geometric features, discotic liquid crystals (DLCs) have a variety of possible applications, including optical compensation films for liquid crystal displays, organic semiconductors for electronic devices, organic light-emitting diodes (OLEDs), and organic photovoltaic cells (OPVs).

The most basic molecular structure of DLC is that of a triphenylene core surrounded by alkoxy and acyloxy groups. Even today, triphenylene with 2,3,6,7,10,11-hexaalkoxy and acyloxy groups is considered to be a common structural motif of DLC, and is undergoing rapid development. Until the 1990s, many studies had been reported on the synthesis of these hexasubstituted triphenylenes by trimerization of 1,2-disubstituted benzenes, but these protocols were not practical industrially due to the limitation of substituents, lack of reproducibility, the need for strict temperature control at -80°C, and poor solubility of reagents. Hence, today, the introduction of alkyl or acyl groups into 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) has become a common synthetic strategy for hexasubstituted triphenylene. Therefore, HHTP is an important starting material for the synthesis of various types of hexasubstituted triphenylene.

HHTP was conventionally synthesized by oxidative trimerization of 1,2-dimethoxybenzene followed by demethylation of the resulting hexamethoxytriphenylene. However, this method required the use of at least a stoichiometric amount of sulfuric acid, which generated a large amount of waste acid. Therefore, the development of more efficient methods, such as trimerization of 1,2-dihydroxybenzene (catechol) to HHTP, has been actively studied in recent years. Kobori et al. synthesized HHTP in 70-76% yield by oxidative trimerization of catechol using FeCl3 as an oxidant. However, the HHTP product was contaminated with Fe impurities, which was undesirable for the application of DLC in the display and semiconductor industries. Furthermore, this protocol includes a reduction step of peroxidized HHTP (quinone), which accounts for 40-60% of the total HHTP yields. Some other protocols do not use metal reagents, but they use 60-80 wt% H2SO4 aq., which result in a large amount of waste acid.

On the other hand, we have recently developed an efficient method for aromatic C,C-coupling reactions by electrochemical oxidation in a flow microreactor. In this synthetic method, peroxidation of the products can be avoided by controlling the residence time in the reactor. In addition, electrochemical oxidation can be carried out without the use of oxidants or catalysts. Thus, this synthetic method has many features to overcome the drawbacks of conventional methods.

In this study, we have successfully carried out the electro-oxidative trimerization of catechol in a flow microreactor to synthesize HHTP efficiently without the need for metallic reagents and reduction procedures.

As a result, HHTP was obtained in 20% yield using 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as a solvent. The results showed that the radical cations of catechol, which were generated on the anode surface, proceeds C,C-coupling in HFIP. On the other hand, the yield decreased to 4% or 0% when HFIP/H2O mixed solvents were used. DFT calculation suggested that the proton dissociation equilibrium of catechol intermediate greatly affects the reaction mechanism. We calculated the pK
a values of catechol intermediate in each HFIP/H2O solvent composition, and discussed the effect of H2O contamination on the HHTP yield.

Figure 1