Synthesis and Tautomerism of Substituted Pyrazolo[4,3-c]pyrazoles
| Authors | |
|---|---|
| Year of publication | 2013 |
| Type | Article in Periodical |
| Magazine / Source | European Journal of Organic Chemistry |
| MU Faculty or unit | |
| Citation | |
| Web | DOI: 10.1002/ejoc.201300606 |
| Doi | http://dx.doi.org/10.1002/ejoc.201300606 |
| Field | Organic chemistry |
| Keywords | NMR chemical shift; synthesis of pyrazolo[4.3-c]pyrazoles; stability of tautomers; regioisomers; low-temperature NMR; X-ray diffraction; DFT calculations |
| Attached files | |
| Description | Fused five-membered nitrogen heterocycles comprise a very important group of compounds frequently utilized in pharmaceutical applications. In this study, we report the first systematic synthesis of substituted pyrazolo[4,3-c]pyrazoles and three regio-isomers of their N-methyl derivatives. All compounds were fully characterized by using NMR spectroscopy in solution and selected compounds also by X-ray diffraction in the solid state. 1H, 13C, and 15N NMR data for all isomers were interpreted by DFT calculations of nuclear shielding constants and indirect spin-spin coupling constants. The N-methyl isomers were used in the following steps as model compounds to investigate a potential N1-H/N4-H, N2-H/N4-H, and N1-H/N5-H tautomerism of 3,6-substituted pyrazolo[4,3-c]pyrazoles by using low-temperature NMR spectroscopy. All bases were shown to occur predominantly in the N1-H/N4-H tautomeric form and the structure of minor form was governed by the substituents at positions 3 and 6. Stabilities of individual tautomeric forms are calculated by DFT methods and discussed. A relationship between the tautomeric populations and the ratios among N-methyl isomers obtained upon methylation of selected base in solution is investigated. |
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