Continuous flow intensification of ortho-lithiation at ambient conditions

Conference Dates

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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