Halogen-lithium exchange reaction using an integrated glass microfluidic device: an optimized synthetic approach

Zeibi Shirejini, S ; Sharif University of Technology | 2017

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  1. Type of Document: Article
  2. DOI: 10.1021/acs.oprd.6b00307
  3. Publisher: American Chemical Society , 2017
  4. Abstract:
  5. A telescoped approach was developed for the efficient synthesis of methoxybenzene through the generation of an unstable intermediate reagent, based on the Br-Li exchange reaction of p-bromoanisole and n-BuLi, followed by its reaction with water. In the first stage, p-methoxyphenyllithium was synthesized and consumed immediately in the second stage. For this purpose, an integrated glass microfluidic device was fabricated using laser ablation followed by the thermal fusion bonding method. The impact of various parameters, including solvent, reaction time, molar ratio, concentration of reagents, and flow rates were investigated to achieve the highest yield of the desired product, leading to an optimized condition for the synthetic approach. It was found that the yield varies significantly with change in solvent composition. While p-bromoanisole does not react with n-BuLi in pure n-hexane, the existence of a small amount of THF (or 2-MeTHF) in n-hexane facilitates p-bromoanisole reaction with n-BuLi. Moreover, the reaction is complete within 1 s by the yield of 95% using the microfluidic device, whereas in a batch system, the best result is obtained in 1 min by the yield of 49%. In addition, the optimal molar ratio of n-BuLi to p-bromoanisole was found to be 1.2. Furthermore, the higher flow rates of the reagents result in a higher yield of the desired product. Finally, under the optimized condition, the generated p-methoxyphenyllithium, by the Br-Li exchange reaction of p-bromoanisole and n-BuLi, was reacted with various electrophiles using the microfluidic device. © 2017 American Chemical Society
  6. Keywords:
  7. Integrated glass microfluidic device ; Organometallic compound ; Fluidic devices ; Glass ; Glass bonding ; Halogen compounds ; Hexane ; Laser ablation ; Lithium ; Microfluidics ; Organometallics ; Reaction intermediates ; Reaction rates ; Butyllithium ; Glass microfluidic devices ; Halogen-lithium exchange reaction ; Methoxybenzene ; Organometallic compounds ; Chemical reactions
  8. Source: Organic Process Research and Development ; Volume 21, Issue 3 , 2017 , Pages 292-303 ; 10836160 (ISSN)
  9. URL: https://pubs.acs.org/doi/10.1021/acs.oprd.6b00307