Green production of 9-aryl-fluoren-9-ols achieved through process intensification of the Grignard reaction using continuous flow at room temperature

In this study, a continuous flow process intensification approach is applied to the Grignard reaction for the kilogram-scale production of 9-aryl-fluoren-9-ols at room temperature and the production efficiency was up to 357 g h(-1). Compared with batch, the yield increased from 45% to >99%, the raw material cost was reduced by 35%, the emission of solid waste was reduced by 64%, and the production period was reduced by 86%. What's more, the continuous flow process demonstrated significantly higher atom efficiency (Ae = 75.8%), reaction mass efficiency (RME = 69.93%), and carbon efficiency (CE = 92.97%) in comparison with the traditional batch synthesis method (Ae = 34.46%, RME = 31.47%, and CE = 41.83%). Moreover, the environmental impact factor (E-factor) of the continuous flow process was impressively reduced by 92.57% compared to the batch process (26.5882 kg kg(-1)), reaching an outstandingly low value of 1.9747 kg kg-1. More importantly, the end to-end synthesis of 9,9'-spirobi[9H-fluorene] (SBF) was realized through a tandem Grignard reaction and Friedel-Crafts reaction, and the theoretical productivity could reach 123 g h(-1), providing a new green production route for diarylfluorene derivatives.