Hydrodehalogenation of Aromatic Halides with Isotopically Labeled Sodium Borohydride Catalyzed by Metal Salts
Radiolabeling has become an effective and efficient way of observing the travel patterns or metabolic breakdown of different compounds in a living organism, whether it be an organ such as the liver or an entire body. This method does have its drawbacks though. The obvious concern of radioactivity is present but there is another problem of compound preparation. The incorporation of the radioactive label ideally is in the last step of the chemical synthesis and the reagent, which is providing the radioactive atom(s), is efficiently used to minimize the generation of radioactive waste. Tritium comes in very small quantities when it is shipped. This project was concerned with developing a newer, more efficient method for substituting a tritium atom in place of a halide on an aromatic ring. These more efficient conditions for this type of hydrodehalogenation of aromatic systems will enable a chemist to effectively radiolabel compounds using the three different hydrogen isotopes of borohydride. In order to develop these conditions reduction reactions were done using sodium borohydride in a palladium-catalyzed system. Several methods were considered and tested to find the highest yield. The starting material was synthesized from 5-bromoindole and [2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile] (BOC-On). The tert-butoxycarbonyl group (Boc) was placed on the 5-bromoindole to prevent the indole amine hydrogen from scrambling with the isotopic hydrogens of the reducing agent. Indole and indoline standards were also synthesized. These were used to identify the products after reduction had occurred. The standards and starting material were confirmed with TLC, 1H NMR, mass spectrometry and infrared spectroscopy. The reduction reactions were monitored with a Varian 5500 HPLC. The results showed that the optimized reaction conditions, mentioned later, gave a +90% yield.