Proton acids on neutral compounds

The pyrazole/pyridine-iV-oxide (which measures the HB acidity of the pyrazole NH) and the pyrazole/3,4-dinitrophenol (which measures the HB basicity of pyrazole N2 lone pair) equilibrium constants were determined for several N/f-pyrazoles in cyclohexane by UV spectroscopy 87CR(C)567 . The correlation between these equilibrium constants and the thermodynamic p s is excellent, allowing the indirect determination of p/f s of very lipophilic pyrazoles pATa of 1-(1-adamantyl)pyrazole = 3.12. The equilibrium constants, Afpj.o (in dm moF ) pertaining to equilibrium (AH -I- OPy AH - - OPy, AH = N/f-pyrazole, = pyridine iV-oxide) have been measured for pyrazole, 3(5)-methylpyrazole, 4-methylpyrazole, 3,5-dimethylpyrazole, 3,4,5-trimethylpyrazole, 4-bromopyrazole, and 3,5-dimethyl-4-bromopyrazole) 90JOC2230 . These values allow the determination of a 2 values (HB acidity parameter) it shows that pyrazole is as acidic as trifluoroethanol as far as HB acidity is concerned. 

The p/faS corresponding to the mono- and diprotonation of betaines of the azolate-triphenyl-pyridinium class have been determined. In the case of the 3-methylpyrazole derivative (76 ), the p/fa values corresponding to both equilibria are pAfa(l) = —2.50 and pK 2)= 11.42 87BSF604 . Assuming a Hammett relationship Ap/fa = a -I- these p/faS indicate that the triphenylpyridinium substituent has 7 = 0.67 + 0.12. 

The basicity of simple 4,5-dihydropyrazoles (A -pyrazolines) has been discussed on the basis of protonation at N-1 in the case of 1-unsubstituted, 1-methyl, and 1-phenyl derivatives 2000JP0372 . The pA values of 15 4,5-dihydropyrazoles substituted at N-1 by /i-nitrophenyl, 2,4-dinitrophenyl, and 2,4,6-trinitrophenyl groups were determined. After examining some linear free energy relationships, to discuss these values further, DFT calculations, including temperature effects, were carried out on the parent compounds (no C-substituents) for the 1-unsubstituted, 1-methyl, 1-phenyl, l-/)-nitrophenyl, and 1-(2,4,6-trinitrophenyl) series. These calculations predicted an inversion of N-1 and N-2 basicities between 1-phenyl- and l-(/ -nitrophenyl)-4,5-dihydropyrazoles. Since there were no experimental data for the protonation of 4,5-dihydropyrazoles in the gas phase, chemical ionization mass spectrometry was used to try to determine the structure of protonated 1-methyl- and l,3-dimethyl-5-phenyl-4,5-dihydropyrazoles. The substituent effects and protonation sites of 1-phenyl-3-methyl-5-A-benzylideneaminopyrazoles were studied by NMR and ab initio (6-31G ) MO calculations 1996J(P2)2383 . 

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