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

Submitting author affiliation:
Federal University of Santa Maria, Santa Maria, Brazil

Beilstein Arch. 2021, 202159.

Published 16 Aug 2021

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Herein, we explore the synthetic potential of tetrazolo[1,5-a]pyrimidines to obtain new pyrimidine derivatives by click chemistry and hydrogenation. Click chemistry reactions of the trifluoromethyltetrazolo[1,5-a]pyrimidines with terminal acetylenes produced unprecedented trifluoromethylated triazolylpyrimidines in excellent yields (84-98 %) in which one of them was active against all tested microorganisms, presenting moderate MIC values (62.5-15.62 mg/ml). Hydrogenation was carried out using Pd/C-H2 in MeOH under conventional, photochemical, and pressure (5 bar) conditions. The hydrogenation was an excellent method to obtain 2-amino-6-aryl-4-trifluoromethyl pyrimidines and/or 2-amino-6-aryl-4-trifluoro methyltetrahydro pyrimidines with a preference for 2-aminopyrimidine formation. The photochemical hydrogenation was the fastest and only pathway to reduce aryl-brominated substrate for the product without dehalogenation. Trifluoromethyl-substituted tetrazolo[1,5-a]pyrimidines reacted to 2-amino-6-aryl-4-trifluoromethyl pyrimidine formation in preference to the formation of the corresponding tethaydropyrimidines. However, the hydrogenation of non-trifluoromethylated tetrazolo[1,5-a]pyrimidines showed a preference for tetrahydropyrimidine formation.

Keywords: Pyrimidines; hydrogenation; click chemistry; trifluoromethyl; photochemical reaction

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When a peer-reviewed version of this preprint is available, this information will be updated in the information box above. If no peer-reviewed version is available, please cite this preprint using the following information:

Scapin, E.; Zimmer, G. C.; Vieira, J. C. B.; Rodrigues, C. A. B.; Afonso, C. A. M.; Zanatta, N.; Bonacorso, H. G.; Frizzo, C. P.; Martins, M. A. Beilstein Arch. 2021, 202159. doi:10.3762/bxiv.2021.59.v1

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