Anodic Trimerization of Catechol to Hexahydroxytriphenylene Using a Flow Microreactor

Abstract

The unique spectroscopic and geometric features of discotic liquid crystals (DLCs) give rise to a variety of applications, for example, optical compensating films in the liquid crystal display industry, organic semiconductors in electronic devices, organic light-emitting diodes (OLEDs), organic photovoltaic solar cells (OPVs) and so on. The most basic molecular structure of DLCs consists of triphenylene core surrounded by alkoxy or acyloxy groups. Even today, 2,3,6,7,10,11-hexaalkoxy- and acyloxy-substituted triphenylenes are seen as a common structure motif of DLCs, and achieving rapid development. Until 1990s, many studies had been reported on the synthesis of these hexasubstituted triphenylenes by the trimerization of 1,2-disubstituted benzenes, however, those protocols were not practical for industrial use, because of the limited scope of substituents, lack of reproducibility, requirement of strict temperature control at -80℃, or poor solubility of the reagents. As a result of these difficulties, today’s common synthetic strategy for hexasubstituted triphenylenes is to introduce alkyl and acyl groups into 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP). Therefore, HHTP is an important starting material in the preparation of various types of hexasubstituted triphenylenes. HHTP was classically synthesized by the oxidative cyclotrimerization of 1,2-dimethoxybenzene followed by demethylation of resulting hexamethoxy-triphenylene. However, in the demethylation procedure, at least the stoichiometric amount of hydrohalic acid was used, and a large amount of waste acid was produced. Therefore, the development of more efficient method like a trimerization of 1,2-dihydroxybenzene (catechol) to HHTP has been studied vigorously in recent years. Kobori et al. synthesized HHTP by oxidative trimerization of catechol using FeCl3 as an oxidant in 70-76% yield. However, the contamination of Fe impurity into HHTP product is unfavorable in the application of DLCs to display and semiconductor industry. In addition, this protocol involves a reduction process of over-oxidized HHTP (quinones), which accounts for 40-60% of the total HHTP yield. Some other protocols do not use metal reagents, however, the use of 60-80wt% H2SO4 aq. results in the generation of an enormous amount of waste acid. On the other hand, recently, we have developed an efficient method for aromatic C,C-coupling reaction using electrochemical oxidation in a flow microreactor. Using this synthetic method, over-oxidation of the product can be avoidable by the control of residence time in the reactor. In addition, electrochemical oxidation was conducted without any oxidants or catalysts. Thus, this synthetic method possesses many characteristics designed to overcome the disadvantages of conventional methods. Under these backgrounds, in the present work, we have demonstrated the electro-oxidative trimerization of catechol in a flow microreactor in order to synthesize HHTP efficiently without the use of metal reagents nor reduction procedure. As a result, HHTP was obtained as a main product in the yield of 40-47% using 50-200mM trifluoromethanesulfonic acid solution in the mixed solvent of 70%(v/v) water and 30%(v/v) 2,3,6,7,10,11-hexafluoro-2-propanol(HFIP). The result indicates that C,C-coupling of catechol intermediate proceeded predominantly to produce HHTP, and this mechanism was supported by DFT calculation. Figure 1