The use of immobilised crown ethers as in-situ protecting groups for organic synthesis within flow reactors

Wild, Peter Gareth

Abstract

Organic synthesis often requires one functional group of a bifunctionalised compound to be rendered temporarily inert to allow the selective reaction of another moiety. While protecting groups are used to remove the problem of the functional group incompatibility, they also raise other issues such as increasing the length of the synthetic pathway (by at least two steps – protection and deprotection), generally leading to an increase in cost and a decrease in yield. The protecting group is often selected based upon the deprotection conditions, leading to the requirement for orthogonal protecting groups. Crown ethers are commonly associated with the complexation of metal ions, but the 18-crown-6 species also readily bind ammonium ions with complexation occurring via hydrogen bonding. As discussed in Chapter 1, crown ethers have previously been employed for N-protection in this way, to successfully facilitate the reaction of bifunctional compounds, though they have exhibited very little selectivity and reaction control. Isolation of the desired product from the resulting reaction mixture has also proven to be problematic.Over recent years there has been a large increase in the volume of organic protocols conducted in micro and continuous flow reactors. Utilising the high surface to volume ratio obtained under these reaction conditions, greater reaction control of many common and specialised organic syntheses has been reported. Building upon literature precedent, the work herein reports the immobilisation of an 18-crown-6 ether derivativeonto a solid-support and its incorporation into a continuous flow reactor to enable sequestration of the primary amine salt of a bi-functionalised compound. This effectively affords a non-covalent N-protection strategy allowing the selective reaction of the remaining moiety. The desired product is subsequently recovered as the free amine by a simple process of decomplexation using an organic base.

Citation

Wild, P. G. (2008). The use of immobilised crown ethers as in-situ protecting groups for organic synthesis within flow reactors. (Thesis). University of Hull. Retrieved from https://hull-repository.worktribe.com/output/4208618

• Thesis Type: Thesis
• Deposit Date: Aug 15, 2011
• Publicly Available Date: Feb 22, 2023
• Keywords: Chemistry
• Public URL: https://hull-repository.worktribe.com/output/4208618
• Additional Information: Department of Chemistry, The University of Hull
• Award Date: Aug 1, 2008