High-Productivity Single-Pass Electrochemical Birch Reduction of Naphthalenes in a Continuous Flow Electrochemical Taylor Vortex Reactor

Abstract

We report the development of a single-pass electrochemical Birch reduction carried out in a small footprint electrochemical Taylor vortex reactor with projected productivities of >80 g day –1 (based on 32.2 mmol h –1 ), using a modified version of our previously reported reactor [ Org. Process Res. Dev. 2021 , 25 , 7, 1619–1627], consisting of a static outer electrode and a rapidly rotating cylindrical inner electrode. In this study, we used an aluminum tube as the sacrificial outer electrode and stainless steel as the rotating inner electrode. We have established the viability of using a sacrificial aluminum anode for the electrochemical reduction of naphthalene, and by varying the current, we can switch between high selectivity (>90%) for either the single ring reduction or double ring reduction with >80 g day –1 projected productivity for either product. The concentration of LiBr in solution changes the fluid dynamics of the reaction mixture investigated by computational fluid dynamics, and this affects equilibration time, monitored using Fourier transform infrared spectroscopy. We show that the concentrations of electrolyte (LiBr) and proton source (dimethylurea) can be reduced while maintaining high reaction efficiency. We also report the reduction of 1-aminonaphthalene, which has been used as a precursor to the API Ropinirole. We find that our methodology produces the corresponding dihydronaphthalene with excellent selectivity and 88% isolated yield in an uninterrupted run of >8 h with a projected productivity of >100 g day –1 .

Photoreduction of Anthracenes Catalyzed by peri‐Xanthenoxanthene: a Scalable and Sustainable Birch‐Type Alternative

“…Since electrochemical studies revealed similar reduction potentials for both 9-methyl and 2-methyl anthracenes ðE M=M �À 1=2 ca: À 2 V vs SCE), we could not find any plausible explanation, which does not resemble pure speculation for the unsuccessful transformation of 9 into 9 a. In the case of 9-cyano-anthracene (10) and 9-chloro-anthracene (11), no de-aromatized products could be observed in the presence of PXX, and only the dimeric products were formed under both 405 and 460 nm irradiation conditions (Scheme 2). Notably, both 9-chloro-and 9-cyano-anthracenes absorb throughout the spectral blue window till 460 nm, suggesting that the kinetics of the dimerization is faster than the photoreduction also under this irradiation.…”

“…The loading of photocatalyst (1-10 mol %, entries 23 and 24) and HNTf 2 (0-100 mol %, Table S1 in the Supporting Information) were screened, confirming the optimal PXX concentration at 2 mol % (PXX aggregation is observed at higher loading) [41] and 10 mol % for HNTf 2 . A progressive increase of the yield was observed when solvents with high polarity (CH 3 CN and DMF vs toluene, CH 2 Cl 2 , CHCl 3, and THF) were used (entries [11][12][13][14][15][16][17][18][19][20][21][22], suggesting the formation of a solvent-stabilized polar intermediate (see mechanistic discussion below). Finally, control experiments were performed in the absence of either PXX, light irradiation, or DIPEA, with no dearomatized products being observed (Table 1, entries 8-10).…”

“…However, the applicability of the classical Birch reduction has been limited due to safety, environmental, and technical concerns, and difficulty in its scale-up. [5] In this context, researchers have been recently pursuing sustainable alternatives to the classical Birch reduction protocols, including NH 3 -free variant, [6][7][8][9] electrochemical, [5,10,11] and mechanochemical approaches. [12,13] Recently, catalysts displaying strong reductive photoredox properties (E red < À 2.00 V vs SCE) [14][15][16][17][18] have emerged as alternative tools to trigger reduction reactions and generate radical anions under mild reaction conditions.…”

“…However, the applicability of the classical Birch reduction has been limited due to safety, environmental, and technical concerns, and difficulty in its scale‐up [5] . In this context, researchers have been recently pursuing sustainable alternatives to the classical Birch reduction protocols, including NH 3 ‐free variant, [6–9] electrochemical, [5,10,11] and mechanochemical approaches [12,13] …”

Scaling-up Electroorganic Synthesis Using a Spinning Electrode Electrochemical Reactor in Batch and Flow Mode

“…We envisaged that an electrochemical reactor concept that combines flow processing capabilities with a spinning cylinder electrode design should provide a solution to the aforementioned drawbacks of parallel plate reactors. In particular, an assembly of two concentrical cylindrical electrodes (anode and cathode) in which the central working electrode spins around its axis should provide excellent mixing and thus mass transport, even at very low flow rates, while maintaining a relatively narrow interelectrode gap. , The efficient mixing attained with the system should also enable working with solid suspensions without the risk of clogging the system or the accumulation of particles. Moreover, the fact that the central electrode is spinning should provoke rapid detachment of any gas bubbles from the surface of the electrodes, facilitating their displacement to the reactor headspace and effectively overcoming the issues of gas evolution during electrolysis.…”