A Laser Driven Flow Chemistry Platform for Scaling Photochemical Reactions with Visible Light

Abstract

Visible-light-promoted organic reactions can offer increased reactivity and selectivity via unique reaction pathways to address a multitude of practical synthetic problems, yet few practical solutions exist to employ these reactions for multikilogram production. We have developed a simple and versatile continuous stirred tank reactor (CSTR) equipped with a high-intensity laser to drive photochemical reactions at unprecedented rates in continuous flow, achieving kg/day throughput using a 100 mL reactor. Our approach to flow reactor design uses the Beer-Lambert law as a guideline to optimize catalyst concentration and reactor depth for maximum throughput. This laser CSTR platform coupled with the rationale for design can be applied to a breadth of photochemical reactions.

Figure 1

Comparison of CSTRs and PFRs.

Figure 2

(A) C–N coupling reaction used with the optimized conditions. (B) Plot of the initial rates of reaction at several different catalyst concentrations with the proposed exponential relationship shown as a dotted line. (C) Time course plot of the C–N coupling reaction showing the conversion of aryl bromide in red and the solution darkening effect in blue.

Figure 3

(A) Initial rates as a function of catalyst concentration demonstrating a Beer–Lambert law relationship in decarboxylative C–C bond formation. (B) Initial rates as a function of catalyst concentration as another demonstration of the Beer–Lambert law in the anti-Markovnikov addition of carboxylic acids to alkenes.

Figure 4

(A) Correlation between initial rates in the C–N coupling and power density of the laser source where the standard reactor employed was 6.5 cm diameter (167 mL total volume), the large reactor was 8 cm (250 mL total volume), and the small reactor was 5 cm in diameter (100 mL). (B) Example reaction where the rate/power correlation breaks down providing an optimal power density for scale-up.

Figure 5

(A) Optimized reaction conditions determined for 1.85 kg flow reaction. (B) Kinetic time course for the reaction conditions shown in part A in a 100 mL vessel. (C) Levenspiel analysis of the reaction kinetics from part B. (D) Schematic of the CSTR used in the flow reaction.