The gas-phase basicity (GB) of the flexible polyfunctional N(1),N(1)-dimethyl-N(2)-beta-(2-pyridylethyl)formamidine (1) containing two potential basic sites (the ring N-aza and the chain N-imino) is obtained from proton-transfer equilibrium constant measurements, using Fourier-transform ion-cyclotron resonance mass spectrometry. Comparison of the experimental GB obtained for 1 with those reported for model amidines and azines indicates that the chain N-imino in the amidine group is the favored site of protonation. Semiempirical (AM1) and ab initio calculations (HF, MP2, and DFT), performed for 1 and its protonated forms, confirm this interpretation. These results are in contrast to those found previously for N(1),N(1)-dimethyl-N(2)-azinylformamidines (containing the amidine function directly linked to the azinyl ring), in which the ring N-aza is the most basic site in the gas phase. The separation of the two potential basic sites in 1 by the ethylene chain interrupts the resonance conjugation between the two functions and changes their relative basicities and, thus, the preferable site of protonation. It also increases the chelation effect against the proton and the gas-phase basicity of 1 in such a magnitude that consequently 1 may be classified as a superbase (GB = 241.1 kcal mol(-)(1)). A transition state corresponding to the internal transfer of the proton (ITP) between the ring N-aza and the chain N-imino in 1 is investigated at the DFT(B3LYP)/6-31G level. The energy barrier calculated for the ITP between the two basic sites is small and vanishes when zero-point vibrational terms and thermal corrections are applied to obtain the enthalpy or Gibbs energy of activation for the proton transfer. Additional calculations at the DFT(MPW1K)/6-31G level confirm this behavior. This indicates that the quantum-chemical ITP in 1 has a single-well character. The proton is located on the N-imino site, and the H-bond is formed with the N-aza site.
epoc ABSTRACT: Tautomeric and basicity center preferences for isolated neutral and monoprotonated histamine were studied by means of ab initio calculations (HF, MP2 and DFT). The polarizable continuum model (PCM) was applied to the study of the variations of the tautomeric and basicity center preferences in histamine on going from the gas phase to aqueous solution. Twelve solvents of different polarities (from n-heptane to water) were chosen and calculations were performed for geometries optimized at the HF/6-31G* level. In low-polarity solvents and in the gas phase the protonation site is identical. A change of the preferred site of protonation takes place in solvents containing heteroatoms (except tetrachloromethane). Under the same conditions, a variation of the tautomeric preference in the monocation occurs. The ring N 2 -protonated form (ImH þ )-favored in gas phase-is also preferred in non-polar solvents (n-heptane, benzene, tetrachloromethane). The ImH þ form becomes less important in more polar solvents. In such a case, the chain N 3 -protonated form (AmH þ -T 1 ) predominates. For the neutral histamine, solvation has a relatively small influence on the relative energies (variations are less than 1 kcal mol À1 ), and does not change the tautomeric preference (HA-T 2 ). Calculated basicity parameters were compared with those obtained experimentally in the gas phase and in aqueous solution. In the gas phase, the experimental ('macroscopic') basicity parameter (PA) is close to the 'microscopic' PA calculated for the gauche conformation. In aqueous solution, the microscopic pK a order is similar to that of the E prot calculated for the trans conformation. In the solid state, both forms of histamine (neutral and monoprotonated) prefer the trans conformation. Some exceptions occur for complexes with metals.
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