Continuous flow intensification of ortho-lithiation at ambient conditions
June 19-24, 2016
Ortho-lithiation is an important class of reaction for the synthesis of regiospecifically substituted aromatics and it is an emerging method to prepare phthalides which are common pharmaceutically active compounds.1 This reaction is typically conducted in batch mode under cryogenic temperatures (-78 to -40 ℃)2 to tame the high reactivity of the organolithium intermediates. Scaling up batch cryogenic organolithiation chemistry has traditionally proven to be a significant challenge. This involves the need to handle large quantities of hazardous lithium reagents and excessive costs associated with cryogenic technology at scale. These challenges make ortho-lithiation reaction an ideal candidate in deploying continuous flow processing as a process intensification (PI) technique. Continuous flow processing offers several ‘green’ benefits in the case of ortho-lithiation reaction where the use of highly energy-intensive refrigeration to -78 ℃ may be avoided. This offers the prospect of considerable energy savings at industrial scale, leading to reduced greenhouse gas emissions. It can also achieve high purity product stream so the downstream processing steps may be simplified. This minimizes the amount of solvent used and increases productivity due to higher selectivity. In addition, the use of continuous flow processing lowers the risk of accidental releases arising from the lower inventories of hazardous material.
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Ruili Feng, Sushil Rajan Ramchandani, Balamurugan Ramalingam, Song Wei Benjamin Tan, Chuanzhao li, Soo Khean Teoh, Kamelia Boodhoo, and Paul Sharratt, "Continuous flow intensification of ortho-lithiation at ambient conditions" in "5th International Congress on Green Process Engineering (GPE 2016)", Franco Berruti, Western University, Canada Cedric Briens, Western University, Canada Eds, ECI Symposium Series, (2016). http://dc.engconfintl.org/gpe2016/44