Reactivity of trifluoromethyl-tetrazolo[1,5-a]pyrimidines in click chemistry and hydrogenation

We explored the synthetic potential of tetrazolo[1,5-a]pyrimidines to obtain new pyrimidine derivatives via click chemistry and hydrogenation. Click chemistry reactions of trifluoromethyl-tetrazolo[1,5-a]pyrimidines with terminal acetylenes produced unprecedented trifluoromethylated triazolylpyrimidines at excellent yields (84-98 %), and one of them was active against all tested microorganisms, with moderate minimum inhibitory concentration values (62.5-15.62 mu g/mL). Hydrogenation was performed using Pd/C-H2 in MeOH under conventional, photochemical, and pressure (5 bar) conditions. Hydrogenation was an excellent method for obtaining 2amino-6-aryl-4-trifluoromethylpyrimidines and/or 2-amino-6-aryl-4-trifluoromethyltetrahydropyrimidines with a preference for 2-aminopyrimidine formation. Photochemical hydrogenation was the only pathway for reducing aryl-brominated substrates without dehalogenation. The reduction of trifluoromethyl-substituted tetrazolo[1,5a]pyrimidines furnished 2-amino-6-aryl-4-trifluoromethylpyrimidines instead of the corresponding tetrahydropyrimidines. However, the hydrogenation of non-trifluoromethylated tetrazolo[1,5-a]pyrimidines showed a preference for tetrahydropyrimidine formation.

Automated summary

In this study, the synthetic potential of tetrazolo[1,5-a]pyrimidines to obtain new pyrimidine derivatives was explored via click chemistry and hydrogenation. Click chemistry reactions produced unprecedented trifluoromethylated triazolylpyrimidines with excellent yields. Hydrogenation reactions resulted in the formation of different pyrimidine compounds, with a preference for 2-aminopyrimidine formation. Photochemical hydrogenation was effective in reducing aryl-brominated substrates without dehalogenation.