BASICITY OF C-SUBSTITUTED PYRAZOLES IN THE GAS-PHASE - AN EXPERIMENTAL (ICR) AND THEORETICAL-STUDY

The experimental gas-phase proton affinities (PAs) of 32 N-H and N-methyl pyrazoles have been determined by means of Fourier transform ion cyclotron resonance spectroscopy (FTICR). Together with the previously reported PAs for 12 C-methyl-substituted pyrazoles, they provide a set of 57 data (counting each tautomer separately). The remarkably large spread of PAs, ca. 55 kcal.mol-1, makes this set most suitable for structural analyses. In a few cases, ab initio 6-31G//6-31G protonation energies were calculated and found to be linearly related to the experimental PAs to a very high degree of precision. A simple additive model of substituent effects on PAs (including substitutions at positions 3, 4, and 5) was found to hold, even for very crowded derivatives such as 1,4-dimethyl-3,5-di-tert-butylpyrazole (27). The only significant interaction appears between phenyl groups at positions 3 and 5. The statistically averaged substituent effects on PAs were successfully analyzed in terms of polarizability and field and resonance contributions, according to the Taft-Topsom model. Both positions 3 and 5 behave in a way similar to that of position 2 in the pyridines. From this interesting result it follows that, with the exception of 3-aminopyrazole, the tautomerism of pyrazoles is not very dependent of the nature of the 3(5)-substituent.