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Zanatta, N.; Mittersteiner, M.; Aquino, E. C.; Budragchaa, T.; Wessjohann, L. A.; Bonacorso, H. G.; Martins, M. A. P.; Synthesis of methylene-bridged trifluoromethyl azoles using 5-(1,2,3-Triazol-1-yl)enones Synthesis 54 439-450 (2022) DOI: 10.1055/s-0040-1719837
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A protocol for synthesizing triazole-containing pyrazolines and pyrazoles selectively using trifluoromethylated 5-(1,2,3-triazol-1-yl)enones as starting materials, is reported. The selectivity of the reaction was controlled by the nature of the hydrazine or derivative used: free hydrazines furnished the 1,5-regiosiomer exclusively in yields up to 98%, whereas protected hydrazines provided the 1,3-regioisomer in yields up to 77%. To demonstrate the synthetic versatility of the triazole-based enone, reactions with other unsymmetrical dinucleophiles (hydroxylamine hydrochloride and S-methyl isothiourea sulfates) allowed the selective preparation of triazole-containing isoxazoline and pyrimidine rings.

Publications

Mittersteiner, M.; Pereira, G. S.; Silva, Y.; Wessjohann, L. A.; Bonacorso, H. G.; Martins, M. A. P.; Zanatta, N.; Substituent-driven selective N-/O-alkylation of 4-(trihalomethyl)pyrimidin-2(1H)-ones using brominated enones J. Org. Chem. 87 4590-4602 (2022) DOI: 10.1021/acs.joc.1c02919
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The selective N- or O-alkylation of 4-(trihalomethyl)-pyrimidin-2(1H)-ones, using 5-bromo enones/enaminones as alkylating agents, is reported. It was found that the selectivity toward the N-or O-regioisomer is driven by the substituent present at the 6-position of the pyrimidine ring, thus enabling the preparation of each isomer as the sole product, in 60−95% yields. Subsequent cyclocondensation of the enaminone moiety with nitrogen dinucleophiles led to pyrimidine−azole conjugates in 55−83% yields.

Publications

Mittersteiner, M.; Pereira, G. S.; Wessjohann, L. A.; Bonacorso, H. G.; Martins, M. A. P.; Zanatta, N.; Chemoselective O-alkylation of 4-(trifluoromethyl)pyrimidin-2(1H)-ones using 4-(iodomethyl)pyrimidines ACS Omega 7 18930-18939 (2022) DOI: 10.1021/acsomega.2c01925
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This study reports two strategies for preparing O-alkyl derivatives of 6-substituted-4-(trifluoromethyl)pyrimidin-(1H)-ones: a linear protocol of alkylation,using a CCC-building block followed by [3 + 3]-type cyclocondensation with 2-methylisothiourea sulfate and a convergent protocol based on direct alkylation, using 4-(iodomethyl)-2-(methylthio)-6-(trihalomethyl)pyrimidines. It was found that thecyclocondensation strategy is not feasible; thus, the direct chemoselective O-alkylationwas performed, and 18 derivatives of the targeted pyrimidines were obtained in 70−98%yields. The structure of the products was unambiguously determined via single crystal X-ray analyses and two-dimensional nuclear magnetic resonance experiments.

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