Synthesis of specifically labeled (S)-nicotine-5-3H and (S)-cotinine-5-3H BY carrier free tritiolysis of the corresponding 5-bromo derivatives

The synthesis of high specific activity tritium labeled (S)-nicotine and (S)-cotinine has been achieved. (S)-5-Bromonornicotine of high enantiomeric purity was converted to the corresponding (S)-5-bromonicotine by reductive amination with formaldehyde and sodium borohydride. Tritiolysis of this intermediate with carrier free tritium in the presence of triethylamine using 10% Pd/C catalyst provided (S)-nicotine-5- H with a specific activity of 32 Ci/mmol in ethanol solvent and 28 Ci/mmol in tetrahydrofuran solvent. Similarly, tritiation of (S)-5-bromocotinine, obtained by oxidation of (S)-5-bromocotinine, obtained by oxidation of (S)-5-bromonicotine with bromine followed by reduction of the intermediate (S)-3′, 3′, 5-tribromonicotine with zinc dust, yielded the corresponding (S)-cotinine-5- H (22.8 Ci/mmol). All reactions proceeded in good to excellent yields.