posted on 2024-03-13, 21:08authored byChenguang Liu, Lei Song, Qiong Liu, Weihao Chen, Jinhui Xu, Mu Wang, Yanbin Zhang, Ting Wei Tan, Zhexuan Lei, Lei Cheng, Saif A. Khan, Jie Wu
Although
continuous flow synthesis using microtubing reactors has
provided a wealth of opportunities for homogeneous photochemical synthesis
and has proven particularly beneficial in scaling up processes, employing
continuous flow technology to scale up heterogeneous photoreactions
is challenging due to the issues including handling of solids, poor
light penetration, and commonly lengthy reaction time. Here we present
a solution to these issues by changing the continuous flow mode to
a high-speed circulation flow mode. The high flow rate set in a circulation
flow reactor overcomes solid sedimentation to prevent clogging and
improve the mixing efficiency. We successfully conducted 100 g-scale
C–N and C–S cross-couplings using a heterogeneous photocatalyst
and a nickel catalyst in the flow reactor that significantly outperformed
conventional batch reactors. The photocatalyst was recycled and reused
10 times to achieve a kilogram-scale synthesis without obvious deactivation.
Semicontinuous production was achieved via automated feeding and collection,
and a photopromoted gas/liquid/solid three-phase trifluoromethylation
reaction was employed. A kilogram-scale amount of starting material
was successfully transformed, resulting in a 43.2% yield of trifluridine.
Our study suggests that a circulation flow reactor with high flow
speed will become a crucial tool in the synthetic chemist’s
toolbox because of its simple infrastructure, ease of operation and
automation, significant efficiency improvement compared to conventional
batch reactors, scalability, improved safety, and tolerance of solids.