Breaking through tradition! Continuous flow+anthracene cerium synergistic catalysis brings a green and efficient new solution for benzyl oxidation reaction

The scientific research team of Sichuan University of Light Chemical Technology and the Shanghai Institute of Organic Chemistry of the Chinese Academy of Sciences published a blockbuster research achievement in the first issue of the Journal of Chemistry in 2023- they developed an anthracene cerium synergistic catalytic system based on a continuous flow microreactor, successfully overcome many problems in the traditional benzyl oxidation reaction, and provided a new idea for green organic synthesis.

Core breakthrough: Achieving efficient conversion under mild conditions

The traditional benzyl oxidation reaction relies on expensive and complex metal catalysts, and requires high temperatures and strong oxidants, resulting in low reaction efficiency and poor safety. The new plan proposed by the research team has achieved three key breakthroughs:

1. Collaborative catalytic system significantly improves efficiency

The study selected 9,10-dibromoanthracene (DBA) as an organic photocatalyst, combined with cerium alcohol complex (Ce (NO3) ③· 6H ₂ O as cerium source and trichloroethanol as hydrogen atom transfer catalyst), to construct an anthracene cerium synergistic catalytic system. Through ligand to metal charge transfer (LMCT) and hydrogen atom transfer (HAT) mechanisms, under visible light (400nm LED) irradiation, excited state DBA can rapidly promote the regeneration of Ce (III) into Ce (IV), significantly accelerating the catalytic cycle.

Experimental data shows that with only 2mol% DBA as a co catalyst, the yield of ethylbenzene benzyl oxidation reaction can soar from 14% catalyzed by cerium alone to 92%, and the yield can reach 8.4mmol/h, far exceeding traditional catalytic systems (such as TBADT catalysis at only 0.3mmol/h and iron catalysis at 1.1mmol/h).

2. Continuous flow technology, balancing security and scale

The team innovatively combined the collaborative catalytic system with a continuous flow microreactor to build a reaction system consisting of four major units: transport, reaction, back pressure, and product collection. The gas-liquid two-phase mixing in the microreactor is efficient, the light efficiency is improved, and the reactor volume is small (total volume 5.4mL), which can reduce the unit load of hazardous reactants and greatly improve the safety of aerobic oxidation reactions.

More importantly, the system can flexibly control the reaction by adjusting the flow rate: under the conditions of liquid flow rate of 2mL/min and oxygen flow rate of 8mL/min, the reaction retention time only needs 1.8min to complete the conversion, with a maximum yield of 8.7mmol/h; And the system is easy to scale up, laying the foundation for continuous industrial production.
3. Mild conditions and strong universality

The entire reaction is carried out at room temperature and 0.8MPa oxygen pressure, without the need for high temperature and pressure. The oxidant only uses environmentally friendly oxygen, which has high atomic economy and low waste emissions. Meanwhile, the system exhibits excellent compatibility with various alkyl aromatic substrates:

-Whether it is ethylbenzene with electron donating groups such as methoxy, or substrates containing electron withdrawing groups such as boronic acid esters and acetyl, the target aromatic ketone can be obtained with a yield of about 90%;

-Highly efficient oxidation can also be achieved for substrates with special structures such as xylene, cyclic fluorene, and phthalein substituted with benzyl phenyl groups, with yields ranging from 58% to 86%;

-The reaction exhibits high chemical selectivity, and no benzoic acid byproduct was detected from the C-C bond cleavage at the benzyl position.

Figure 1 Diagram of Continuous Flow Photoelectrochemical Reactor Device

Mechanism Unveiled: Dual Cycle Driven Reaction Efficiently Conducted

To elucidate the core mechanism of synergistic catalysis, the team proposed a dual cycle model of "organic photocatalyst cycle+cerium catalytic cycle" through experiments such as UV Vis absorption spectroscopy, fluorescence emission spectroscopy, and cyclic voltammetry

1. Cerium catalytic cycle: Ce (IV) - alcohol complexes undergo LMCT cleavage under visible light to generate trichloroethoxy radicals, which are then activated by HAT to form benzyl radicals via C-H bonds at the benzyl position. The latter are captured by oxygen and reduced to form acetophenone, while Ce (IV) is converted to Ce (III);

2. Organic photocatalyst cycling: The ground state DBA absorbs photons and transitions to an excited state, where it is oxidized by oxygen or peroxide species to form DBA radical cations. Subsequently, Ce (III) is oxidized to Ce (IV) through single electron transfer (SET), returning to the ground state and completing the cycle.

The synergistic effect of dual cycles has solved the bottleneck of slow Ce (III) regeneration in traditional cerium catalysis, achieving a qualitative leap in reaction efficiency.

Application prospects: opening up new paths for green synthesis

Aromatic ketones are key structural units in drugs and bioactive molecules (such as antidepressants and anti-inflammatory intermediates). The catalytic system developed in this study has the advantages of being inexpensive, efficient, green, and easy to scale up. It is expected to be applied in the future for:

-Large scale green synthesis of pharmaceutical intermediates, reducing production costs and pollution;

-In the field of fine chemical engineering, achieve targeted preparation of various functionalized aromatic ketones;

-Expand to other C (sp ³) - H bond functionalization reactions to promote the development of photocatalytic synthesis technology.

This study not only provides a new solution for the benzyl oxidation reaction, but also demonstrates the enormous potential of combining continuous flow technology with synergistic catalysis, injecting new impetus into the development of organic synthesis towards a "greener, more efficient, and safer" direction. I believe that with further optimization of technology, this system will play an important role in fields such as medicine and chemical engineering, and help upgrade the sustainable chemical industry.

(Original link: Journal of Chemistry)（ http://sioc-journal.cn )， DOI: 10.6023/A23030099）
Zhejiang Brillis has profound expertise in the field of continuous flow photochemistry, with technological innovation and industrial implementation capabilities as its core advantages. Its continuous kettle type photoreactor combines the advantages of continuous flow and kettle type reaction, overcomes the difficulties of solid-liquid system reaction, increases the light utilization rate by more than 2 times, and the mixing uniformity exceeds 98%.