Selective deuteration of N-heterocyclic aromatics is important for pharmaceutical
purposes and for studying reaction mechanisms. As part of this thesis, six carboxamides
were synthesized from diazine carboxylic acids. The synthesized amides were subjected
to deuteration using directed ortho-metalation. This was achieved using lithium 2,2,6,6
tetramethylpiperidide and employing heavy water as an inexpensive, safe, and
environmentally friendly deuterium source. After optimizing the protocol, four substrates
were selectively deuterated with high deuterium incorporation, while one substrate
exhibited lower regioselectivity. In addition to the deuterated compounds, we isolated
dimers of the starting amides as side products of the metalation. Several factors
influencing the efficiency of deuteration and dimer formation were investigated. Our
method stands out by using heavy water as the deuterium source and simple reagents,
avoiding the precious metals typically used in such processes. The synthesized
isotopically labelled amides could be further transformed and used in the syntheses of
high-value deuterated molecules in the future.
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