Abstract
A series of disubstituted 1H-pyrazoles with methyl (1), amino (2), and nitro (3) groups, as well as ester (a) or amide (b) groups in positions 3 and 5 was synthesized, and annular tautomerism was investigated using X-ray, theoretical calculations, NMR, and FT-IR methods. The X-ray experiment in the crystal state showed for the compounds with methyl (1a, 1b) and amino (2b) groups the tautomer with ester or amide groups at position 3 (tautomer 3), but for those with a nitro group (3b, 4), tautomer 5. Similar results were obtained in solution by NMR NOE experiments in CDCl3, DMSO-d6, and CD3OD solvents. However, tautomer equilibrium was observed for 2b in DMSO. The FT-IR spectra in chloroform and acetonitrile showed equilibria, which can be ascribed to conformational changes of the cis/trans arrangement of the ester/amide group and pyrazole ring. Theoretical analysis using the M06-2X/6-311++G(d,p) method (in vacuo, chloroform, acetonitrile, and water) and measurement of aromaticity (NICS) showed dependence on internal hydrogen bonds, the influence of the environment, and the effect of the substituent. These factors, pyrazole aromaticity and intra- and inter-molecular interactions, seem to have a considerable influence on the choice of tautomer.
Highlights
Pyrazole is a five-membered aromatic heterocycle with two adjacent nitrogen atoms, classified as azole
We present a study on the annular tautomerism of 3(5)-disubstituted-1H-pyrazoles, with an ester/amide bond and methyl, amine, and nitro substituents (Figure 2)
The general concept, which arose from the presented studies, indicated that the tendency to adopt a given tautomer is connected with the substituents at the pyrazole ring
Summary
Pyrazole is a five-membered aromatic heterocycle with two adjacent nitrogen atoms, classified as azole. It was found that the observed conformational preferences were clearly related to the presence of intramolecular interactions formed within the studied residue [29] This shows that the N-unsubstituted 1H-pyrazole moiety is able to create a specific type of hydrogen interaction and, association, which can be crucial for biological properties, or even broader for materials science. And2019, inter-molecular interactions can be important factors, the position of the hydrogen atom of 17 at the pyrazole nitrogen atom, and the conformation of the carbonyl linkage are considered. Assuming that intraand inter-molecular interactions can be important factors, the position of the hydrogen atom at the pyrazole nitrogen atom, and the conformation of the carbonyl linkage are considered
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