Electrosynthesis of 3,3′,5,5’-Tetramethyl-2,2′-biphenol in Flow

Abstract

Abstract3,3′,5,5’-Tetramethyl-2,2′-biphenol is well known as an outstanding building block for ligands in transition-metal catalysis and is therefore of particular industrial interest. The electro-organic method is a powerful, sustainable, and efficient alternative to conventional synthetic approaches to obtain symmetric and non-symmetric biphenols. Here, we report the successive scale-up of the dehydrogenative anodic homocoupling of 2,4-dimethylphenol (4) from laboratory scale to the technically relevant scale in highly modular narrow gap flow electrolysis cells. The electrosynthesis was optimized in a manner that allows it to be easily adopted to different scales such as laboratory, semitechnical and technical scale. This includes not only the synthesis itself and its optimization but also a work-up strategy of the desired biphenols for larger scale. Furthermore, the challenges such as side reactions, heat development and gas evolution that arose during optimization are also discussed in detail. We have succeeded in obtaining yields of up to 62% of the desired biphenol.

Developments in the Dehydrogenative Electrochemical Synthesis of 3,3′,5,5′‐Tetramethyl‐2,2′‐biphenol

“…The reaction was then transferred to the semitechnical scale by using the 4 cm×12 cm flow electrolysis cell. Here, the previously optimized electrolysis conditions could be applied almost unchanged and a similar yield of 58 % of 2 could be obtained (Scheme 5: B) [60] …”

“…Therefore, the cooling temperature was decreased to 0 °C. Altogether, the electrolysis conditions were largely maintained with minor modifications and an overall yield of 59 % for 2 could be achieved (Figure 2: 9 and Scheme 5: C) [60] …”

“…Here, the supporting electrolyte MeBu 3 NO 3 SOMe proved to be most suitable. Through optimization, an increased yield of 62 % of 2 could be achieved [60] . With the aim of developing a universal method, which is also suitable for other phenols, the anode material was changed from glassy carbon to BDD.…”

“…Reprinted from ref. [60]. B) Schematic depiction of a continuous cascade process.…”

“… Electrolysis conditions for the dehydrogenative C−C homocoupling of 1 with MeBu 3 NO 3 SOMe as a supporting electrolyte for scale‐up in A) a 2 cm×6 cm flow electrolysis cell (flow rate: 2.24 mL min −1 , 10 °C), B) a 4 cm×12 cm flow electrolysis cell (flow rate: 8.95 mL min −1 , 10 °C), and C) an EUT pilot cell (flow rate: 38.8 mL min −1 , 0 °C) [60] …”