Pyrazolo[1,5‐a]pyrimidines. A combined multinuclear magnetic resonance (¹H, ¹³C, ¹⁵N, ¹⁹F) and DFT approach to their structural assignment

Abstract

Multinuclear magnetic resonance spectroscopy together with GIAO-DFT calculations allowed establishment of the structure of the products obtained by condensation of 3(5)-amino-4-phenyl-1H-pyrazole and beta-dicarbonyl compounds bearing a trifluoromethyl group. They are 3-phenyl-5-(R)-7-trifluoromethylpyrazolo[1,5-a]pyrimidines.

A systematic approach for the generation and verification of structural hypotheses

“…It is worthy to note that some publications (for example [30] ) devoted to structure elucidation assisted by QM chemical shift prediction frequently do not mention empirical methods at all. In many cases it is seemingly alleged that the QM approach is the unique predictive method for proving or disproving a proposed structure.…”

“…For the purpose of structure determination and confirmation, 1D NMR spectra ( 1 H, 13 C, 15 N and 19 F) in combination with 1 H-13 C gs-HMBC and 1 H-15 N gs-HMBC data were used. The authors [30] derived the two pairs of alternative isomers shown above and the problem was reduced to selection of the correct structure within each of the isomer pairs. For this purpose the authors calculated both the 13 C and 15 N chemical shifts using the GIAO method of DFT approximation for two model compounds:…”

“…Linear regressions of the calculated versus experimental 13 C chemical shifts, the latter assigned for the proposed structures, allowed the authors [30] to confirm configuration 9 as the most preferable [R 2 (9) = 0.998; R 2 (10) = 0.984]. 15 N chemical shift prediction resulted in R 2 (9) = 0.992 and R 2 (10) = 0.991 values for the corresponding model structures and only slightly supports model 9 as the preferred structure.…”

“…The authors [30] synthesized and separated two samples, #1 and #2, with molecular formulae of C 19 H 12 F 3 N 3 (1) and C 17 H 10 F 3 N 3 S (2). For the purpose of structure determination and confirmation, 1D NMR spectra ( 1 H, 13 C, 15 N and 19 F) in combination with 1 H-13 C gs-HMBC and 1 H-15 N gs-HMBC data were used.…”

Synthesis of new bi(pyrazolo[1,5-a]pyrimidinyl)-7-one derivatives from dehydroacetic acid and its analogues as antibacterial agents

“…3-6 5-Amino-1H-pyrazoles like mono-substituted hydrazines have been utilized as active synthons for synthesis of many heterocyclic compounds, e.g., pyrazolo [1,5-a]pyrimidines, pyrazolo [3,4-b]pyridines, etc. [7][8][9][10][11] Large differences in the nucleophilicity of the two nitrogens in 5-amino-1H-pyrazoles, one as endo nitrogen of pyrazole ring and the other as amino group at 5-position,…”