Straightforward Synthesis of 6-Aryl-2-azido-4-(trifluoromethyl)­pyrimidines and Their Regioselective Copper-Catalyzed Click Cycloaddition to 6-Aryl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-4-(trifluoromethyl)pyrimidines

• Published in: Russian journal of organic chemistry Vol. 59; no. 1; pp. 164 - 173
• Main Authors: Ludwig, F. P., Delevati, M. A., Cargnelutti, R., Cervo, R., Vicenti, J. R. M., Flores, D. C., Flores, A. F. C.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 2023; Springer Nature; Springer Nature B.V
• Subjects: Aromatic compounds; Chemical reactions; Chemical synthesis; Chemistry; Chemistry and Materials Science; Chemistry, Organic; Copper; Cycloaddition; Infrared spectroscopy; Mass spectrometry; NMR; Nuclear magnetic resonance; Organic Chemistry; Physical Sciences; Pyrimidines; Science & Technology; Single crystals; 1,2,3-triazoles; nitrogen heterocycles; 2-azidopyrimidines; 5-aminotetrazole; 1; 2; 3-triazoles
• ISSN: 1070-4280; 1608-3393
• DOI: 10.1134/S1070428023010189

A straightforward one-pot synthesis of 6-aryl-2-azido-4-(trifluoromethyl)pyrimidine derivatives 3 by the [3+3] cyclocondensation of 1,1,1-trifluoro-4-methoxybut-3-en-2-ones [ 1 , F 3 CC(O)CH=C(R 1 )OMe, where R 1 = Ph ( a ), 3,5,5,6,8,8-hexamethyl-5,6,7,8-tetrahydronaphthalen-2-yl ( b ) , 4-PhC 6 H 4 ( c ), 4-FC 6 H 4 ( d ), furan-2-yl ( e ), thiophen-2-yl ( f )] with 2-aminotetrazole monohydrate ( 2 ) under basic conditions is described. Tetrazolo[1,5- a ]pyrimidine is the most probable intermediate product in the reaction, though it has not been identified. Copper-catalyzed click reaction of 3 with phenylacetylene ( 4 ) afforded 6-aryl-2-(4-phenyl-1 H -1,2,3-triazol-1-yl)-4-(trifluoromethyl)pyrimidines 5 . All products were characterized using multinuclear 1 H, 13 C, and 19 F NMR, IR spectroscopy, and electrospray ionization high-resolution mass spectrometry (HRMS). The structures of 2-azido-4-phenyl-6-(trifluoromethyl)pyrimidine ( 3a ), 6-(furan-2-yl)-2-(4-phenyl-1 H -1,2,3-triazol-1-yl)-4-(trifluoromethyl)pyrimidine ( 5e ), and 2-(4-phenyl-1 H -1,2,3-triazol-1-yl)-6-(thiophen-2-yl)-4-(trifluoro­methyl)pyrimidine ( 5f ) have been determined using single-crystal X-ray diffraction.