Abstracts
Curtius rearrangement of 10 with diphenylphosphoryl azide (DPPA) gave aniline 11 in 65% yield after flash chromatography.
Diazonium salt 12 was obtained by treatment of 11 with NaNO2. Without separation, iodide 13 was prepared, in a one-pot fashion,
by addition of NaI to the reaction mixture. Although Pd-catalyzed carbonylation reaction of both 12 and 13 led to the final acid 15,
the yields for these reactions were low (below 1%). Conversion of iodide 13 to cyanide 14 with Zn(14CN)2 was found to be a robust
reaction with much higher yield (88%). Hydrolysis of 14 gave the acid 15. Preparative HPLC purification of 15 was used to achieve an
excellent radiochemical purity of 99.4%.
In summary, either an unlabeled alkyl acid or an aromatic acid can efficiently be converted to its [14C] labeled counterpart with
only the last two steps involving handling of radio-chemicals.
Acknowledgements: The authors wish to thank Dr. David J. Schenk for analytical support. J.Z.H. gratefully acknowledges Dr. Lee
J. Silverberg for help in the preparation of this manuscript.
References
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SURVEY OF DIFFERENT TRITIUM-LABELLING METHODS USED AT RC TRITEC
¨
CHRISTIAN MEISTERHANS, STEFAN C. NUCKEL, AND ALBERT ZELLER
RC TRITEC AG, Speicherstrasse 60a, CH-9053 Teufen, Switzerland
Abstract: The radiosynthesis group of RC TRITEC is specialised in custom tritium synthesis and therefore has gained a lot of
experience in a large variety of different tritium-labelling methods. We present a survey of the projects carried out in the past years
focusing on the diverse characteristics and popularities of the different methods. All applied reaction types have been classified into
different groups of tritium-labelling methods. These groups are illustrated and discussed with regard to specific activities,
regioselective labelling, tritium efficiency, possible labelling candidates and precursors. The varying popularities of the different
methods used at RC TRITEC in the past years are statistically analyzed.
Keywords: tritium chemistry; tritiation; tritide; tritium-labelling, tritiated
Introduction: Radioisotopically labelled organic compounds are irreplaceable tools for research and development especially in the
pharmaceutical and agrochemical industry as well as in academic research. Among the most widely used radioisotopes C-14 and
H-3, the latter, tritium, is very much favoured for early applications in the R&D process. From a synthetic viewpoint it is relatively easy
to introduce tritium into organic compounds, this allows fast and cost efficient labelling which is of great importance in the fast-
paced early development. Beside tritium chemistry’s nature of a low-threshold labelling approach the high specific activity of tritium
at 29 Ci/milliatom allows the use of such labelled compounds for binding studies, imaging techniques, and many other applications
that require highest sensitivities. In contrast, C-14-labelling usually requires multi step syntheses, therefore this time and cost
consuming labelling approach is used predominantly for later phases in development.
In this article we present a survey over different methods that are used in tritium chemistry and in special at our facility at RC
TRITEC. We would like to offer the researcher the ability to pick out the most suitable tritiation method for his labelling candidate.
Classification of tritium chemistry
There are numerous ways to bring some systematic order to the world of tritium chemistry. Evans1 has categorised the different
preparations of tritium-labelled compounds into isotope exchange reactions, direct chemical synthesis, biochemical methods and
recoil labelling (hot-atom reactions). After three decades of advances in tritium chemistry with the introduction of numerous new
reagents and methods, Saljoughian and Williams2 ordered the methods in two groups: ‘Hydrogen Isotope Exchange Labeling’ and
J. Label Compd. Radiopharm 2010, 53 239–268
Copyright r 2010 John Wiley & Sons, Ltd.