Baeyer‐Villiger oxidation tuned to chemoselective conversion of non‐activated [18F]fluorobenzaldehydes to [18F]fluorophenols |
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Authors: | Johannes Ermert Johnny Castillo Melen Swen Humpert Daniel Modemann Dominik Krupp Isabel Kern Sabrina Kreft Heinz H Coenen |
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Institution: | Johannes Ermert,Johnny Castillo Meleán,Swen Humpert,Daniel Modemann,Dominik Krupp,Isabel Kern,Sabrina Kreft,Heinz H. Coenen |
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Abstract: | A reaction pathway via oxidation of 18F]fluorobenzaldehydes offers a very useful tool for the no‐carrier‐added radiosynthesis of 18F]fluorophenols, a structural motive of several potential radiopharmaceuticals. A considerably improved chemoselectivity of the Baeyer‐Villiger oxidation (BVO) towards phenols was achieved, employing 2,2,2‐trifluoroethanol as reaction solvent in combination with Oxone or m‐CPBA as oxidation agent. The studies showed the necessity of H2SO4 addition, which appears to have a dual effect, acting as catalyst and desiccant. For example, 2‐18F]fluorophenol was obtained with a RCY of 97% under optimised conditions of 80°C and 30‐minute reaction time. The changed performance of the BVO, which is in agreement with known reaction mechanisms via Criegee intermediates, provided the best results with regard to radiochemical yield (RCY) and chemoselectivity, i.e. formation of 18F]fluorophenols rather than 18F]fluorobenzoic acids. Thus, after a long history of the BVO, the new modification now allows an almost specific formation of phenols, even from electron‐deficient benzaldehydes. Further, the applicability of the tuned, chemoselective BVO to the n.c.a. level and to more complex compounds was demonstrated for the products n.c.a. 4‐18F]fluorophenol (RCY 95%; relating to 4‐18F]fluorobenzaldehyde) and 4‐18F]fluoro‐m‐tyramine (RCY 32%; relating to 18F]fluoride), respectively. |
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Keywords: | fluorine‐18 18F‐labelling [18F]fluorophenol [18F]fluorobenzaldehyde 4‐[18F]fluoro‐m‐tyramine Baeyer‐Villiger oxidation |
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