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Chemistry in Industry : Journal of Chemists and Chemical Engineers of Croatia, Vol. 71 No. 5-6, 2022.

Review article

https://doi.org/10.15255/KUI.2021.070

Renaissance of the Hofmann-Löffler-Freytag Reaction – Development of C–H Functionalisation Strategies Based on Green Chemistry Principles

Gabrijel Zubčić orcid id orcid.org/0000-0003-3264-5826 ; University of Zagreb, Faculty of Pharmacy and Biochemistry, Ante Kovačića 1, 10 000 Zagreb, Croatia
Sofia Shkunnikova orcid id orcid.org/0000-0003-2546-0823 ; University of Zagreb, Faculty of Pharmacy and Biochemistry, Ante Kovačića 1, 10 000 Zagreb, Croatia
Davor Šakić orcid id orcid.org/0000-0002-8871-6622 ; University of Zagreb, Faculty of Pharmacy and Biochemistry, Ante Kovačića 1, 10 000 Zagreb, Croatia
Marijan Marijan ; University of Zagreb, Faculty of Pharmacy and Biochemistry, Ante Kovačića 1, 10 000 Zagreb, Croatia

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Abstract

Increased demand for drugs has promoted the pharmaceutical and chemical industries as the most dynamic industries of the 21st century. By using the Hofmann-Löffler-Freytag (HLF) reaction, the modification of pharmacologically active substances and biologically important compounds can be achieved in an environmentally friendly manner by highly efficient syntheses. This reaction enables the formation of new compounds according to the principles of green chemistry, without expensive metal catalysts. Numerous computational and experimental studies have shown exceptional flexibility and the possibility of optimising this method in order to increase the economy and reduce the amount of waste generated as by-products of synthetic processes. However, the mechanism of this reaction is yet to be elucidated sufficiently, and further experiments are necessary in order to determine the thermodynamic and kinetic parameters that control and guide the HLF reaction. It is necessary to determine the influence of substituents and solvents on 1,5-HAT or 1,6-HAT regioselectivity, and to recognise the mechanism responsible for switching between the radical and ionic mechanism of the reaction.




This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords

Hofmann-Löffler-Freytag reaction; green chemistry; 1,5-HAT; 1,6-HAT; regioselectivity; mechanistic switch

Hrčak ID:

277689

URI

https://hrcak.srce.hr/277689

Publication date:

15.5.2022.

Article data in other languages: croatian

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