Membrane-based TBADT recovery as a strategy to increase the sustainability of continuous-flow photocatalytic HAT transformations

Abstract

Photocatalytic hydrogen atom transfer (HAT) processes have been the object of numerous studies showcasing the potential of the homogeneous photocatalyst tetrabutylammonium decatungstate (TBADT) for the functionalization of C(sp³)-H bonds. However, to translate these studies into large-scale industrial processes, careful considerations of catalyst loading, cost, and removal are required. This work presents organic solvent nanofiltration (OSN) as an answer to reduce TBADT consumption, increase its turnover number and lower its concentration in the product solution, thus enabling large-scale photocatalytic HAT-based transformations. The operating parameters for a suitable membrane for TBADT recovery in acetonitrile were optimized. Continuous photocatalytic C(sp³)-H alkylation and amination reactions were carried out with in-line TBADT recovery via two OSN steps. Promisingly, the observed product yields for the reactions with in-line catalyst recycling are comparable to those of reactions performed with pristine TBADT, therefore highlighting that not only catalyst recovery (>99%, TON > 8400) is a possibility, but also that it does not happen at the expense of reaction performance.

Fig. 1. Overview detailing the importance of in-line TBADT recovery.

a Photocatalytic Hydrogen Atom Transfer enables both early- and late-stage functionalization of hydroalkanes and biologically active compounds. b Small-scale versus large-scale synthetic organic chemistry requires different approaches: catalyst lifetime and cost are only relevant on a process chemistry level. c TBADT is a high molecular weight molecule resulting in a large mass fraction and thus high associated cost when discarded. This warrants the need for catalyst recycling. d We disclose a general and efficient approach for decatungstate recycling using in-line nanofiltration.

Fig. 2. C(sp³)–H alkylation with in-line TBADT recovery via nanofiltration.

a TBADT-catalyzed C(sp³)–H alkylation investigated in the present work. b flow chart of the multi-stage nanofiltration-based continuous-flow system employed for the recovery of TBADT. EWG electron withdrawing group, BPR back pressure regulator.

Fig. 3. OSN performance investigation with a photocatalytic hydroalkylation reaction.

a Results of the nanofiltration experiment of the reacted mixture (Stage 1): concentration of TBADT in the retentate (R) and permeate (P); permeate flux; catalyst and product recovery. b Results of the nanofiltration experiment of the retentate solution from Stage 1 (Stage 2): concentration of TBADT in the retentate and permeate; permeate flux; catalyst and product recovery. c Summary of the overall recovery process for the two NF stages.

Fig. 4. Results of the in-line catalyst recovery experiment.

Data about turnover number and measured reaction yield, residual TBADT concentration in the permeate solution, and permeate flux is included. The equilibration phase of the experiment is reported with a shaded background.

Fig. 5. Practicality investigations of the nanofiltration process.

a Fraction yield and TON in permeate of a 60-h run of C(sp³)–H alkylation executed with in-line TBADT recovery. The equilibration phase of the experiment is reported with a shaded background. b Fraction yield and TON in permeate of a 27-h run of C(sp³)–H amination executed with in-line TBADT recovery. The equilibration phase of the experiment is reported with a shaded background. c Preliminary investigations of the recovery of other commercially available photocatalysts with nanofiltration. For more experimental details see Supplementary Information.

Fig. 6. Scope of the photocatalytic C(sp³)–H alkylation executed with in-line TBADT recovery.

^a Reaction conditions for single run without catalyst recycling: alkene (0.1 M), H-donor (10 equiv), TBADT (1 mol%) in CH₃CN (5 mL). Irradiation source: λ = 365 nm (150 W), residence time: 5 min (see the Supplementary Information for additional details). Isolated yields are given in parentheses. ^b The yield was determined by ¹H-NMR using 1,2,4,5-tetramethylbenzene as external standard. ^c 1.2 mol% TBADT.