Studies of hydrogen isotope scrambling during the dehalogenation of aromatic chloro-compounds with deuterium gas over palladium catalysts |
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Authors: | William JS Lockley Niccolò A E Venanzi Georgie J Crane |
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Institution: | 1. Department of Chemistry, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford, UK;2. Department of Chemistry, University College London, London, UK |
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Abstract: | Catalytic dehalogenation of aromatic halides using isotopic hydrogen gas is an important strategy for labelling pharmaceuticals, biochemicals, environmental agents and so forth. To extend, improve and further understand this process, studies have been carried out on the scrambling of deuterium isotope with protium during the catalytic deuterodehalogenation of model aryl chlorides using deuterium gas and a palladium on carbon catalyst in tetrahydrofuran solution. The degree of scrambling was greatest with electron-rich chloroarene rings. The tetrahydrofuran solvent and the triethylamine base were not the source of the undesired protium; instead, it arose, substantially, from the water content of the catalyst, though other sources of protium may also be present on the catalyst. Replacement of the Pd/C catalyst with one prepared in situ by reduction of palladium trifluoroacetate with deuterium gas and dispersed upon micronised polytetrafluoroethylene led to much reduced scrambling (typically 0–6% compared with up to 40% for palladium on carbon) and to high atom% abundance, regiospecific labelling. The improved catalytic system now enables efficient polydeuteration via the dehalogenation of polyhalogenated precursors, making the procedure viable for the preparation of MS internal standards and, potentially, for high specific activity tritium labelling. |
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Keywords: | catalysis halogen exchange isotope scrambling mechanism palladium palladium trifluoroacetate PTFE reductive dehalogenation |
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