Pyrazoles protonation, calculated

All of the azoles showed a linear variation of these values except the pyrazoles, which belong to a parallel line 4.5 pK units apart. Fully optimized INDO geometries have been calculated for 12 azoles, as well as their cations and anions, both isolated and specifically solvated by five water molecules166. Evaluation of the protonation and deprotonation energies of the solvated molecules indicates a behaviour similar to that found experimentally in solution. In particular, the difference between pyrazoles (and indazoles) and all the other azoles is a consequence of the protonation of the nitrogen contiguous to NH, that is due to a difference in basicity. 

A density functional theory computational approach has been used " to investigate the [1,5]-hydrogen shift in (z)-penta-l,3-diene. Ab initio calculations of the activation barriers to proton transfer in nitrogen derivatives have been computed and these values used to show that the proton transfer in pyrazole is formally a... 

Treatment of 348 with Na[EIBEt3] has also been reported, affording initially the Pt(II) formyl complex anion [Tp PtMe C(0)H ] (355 ), as determined by 1EI and 13C NMR spectroscopic data that again reveal a chiral metal center. At 193 K two formyl environments (2 1 ratio) are apparent, which coalesce at 201 K. These are attributed to restricted rotation about the Pt—C linkage, and AG for conversion of the minor to major isomer was calculated at 8.8 kcal mol-1.120 Protonation of 355 affords exclusively the Pt(IV) formyl complex Tp PtMe C(0)H H (356), with no evidence for protonation of either pyrazole or the formyl, or... 

The acid-base properties of 4-nitroso-5-aminopyrazoles 50 have been studied. In particular, protonation sites have been determined where salts 51 are formed [66], The effects produced on II, 13C, and 15N chemical shifts by protonation and by hydrogen-bonding solvents on five azoles (imidazole, 4,5-dimethylimidazole, pyra-zole, 3,5-dimethyl-pyrazole, and 4,5-dihydro-3-methyl-2//-benz[g]indazole) have been determined experimentally. Phase effects on the 13C chemical shifts of the C-4 atom of pyrazole were discussed, based both on empirical models and on GIAO calculations of absolute shieldings in different complexes. The special case of the chemical shifts of pyrazoles in the solid state, where they form multiple N-H N hydrogen bonds, was also studied theoretically [88],... 

Consider for instance, 1 //-pyrazole (87). It is known that proton transfer between both nitrogen atoms (leading to tautomerism) occurs in the gas phase, in solution and, in some cases, in the solid state (depending on the substituents on the carbon atoms). Is the process an intramolecular 1,2-shift Theoretical calculations show that this is a very high-energy process, almost forbidden [91] (214 kJ mol 1 at the B3LYP/6-31G level). Then, the logical conclusion is that proton transfer in azoles involves solvent molecules (solution) or other azole molecules (solid state). 

We studied, at the B3LYP/6-31+G theoretical level, four monomers and 12 NH-pyrazole cyclamers, C-unsubstituted or bearing fluoro, chloro and bromo substituents at positions 3 and 5 [100], Two mechanisms of proton transfer, stepwise and synchronous, were calculated for dimers, trimers, and tetramers. The set of values of energies and geometries thus obtained provide useful insights about the dynamics of NH-pyrazoles in the solid state. It has been shown that pyrazole cyclamers exist not only in condensed phases but in the gas phase as well [101], thus our gas-phase calculations will provide information about the solid state. 

We have published some papers concerning some less common heterocycles such as 1,2,4-diazaphospholes 257 and 258 [203], Using X-ray crystallography, CPMAS NMR, and GIAO-type calculations we have found that 257 is a cyclic dimer with localized N-H protons (similar to pyrazole dimers) while 258 is probably a tetramer (similar to pyrazole tetramers) showing ISSPT (intramolelecular solid state proton transfer). This prediction was only partly true because 258 crystallizes in two cyclic dimers, both presenting proton disorder [204] (Fig. 8). 

AMI semiempirical calculations have shown that, as far as tautomerism is concerned, there is a structural relationship between jS-dicarbonyl compounds and NH-pyrazoles, and in a wide variety of NH-pyrazoles studied " the most stable tautomer was found to be that having the largest single-bond character between the C(3)—C(4) bond. The problem of proton transfer in NH-pyrazole crystals has been subjected to a detailed theoretical study, while a study of the tautomerism of 2-aryl and 2-heteroaryl derivatives of benzimidazole has indicated that tautomerism takes place by the intermolecular relay of protons between stacked molecules. The first report of the stable co-existence of two different histidine tautomers in one peptide crystal structure has appeared. Ab initio calculations have been used to study the tautomerism of both histamine and pyrazolo[3,4-i/]pyridazine in the gas phase and in aqueous solution, and a theoretical study of the NH tautomerism in free-base porphyrin has been undertaken. ... 

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