Protonation Sites in Conjugated Molecules

Tautomerism Kinetic vs. Thermodynamic Stability Protonation Sites in Conjugated Molecules N/N Alternatives. ... 

Over the past 10-15 years there has been a considerable increase of interest in the question of protonation sites in organic molecules, which contain two or three possible protonation sites in conjugation. 

In conjugated molecules one or other of the possible protonation sites may be more or less favoured by solvation effects and for this reason sites of protonation are often solvent dependent. In some instances, similar stability of two possible cations results in tautomeric equilibria and these too may be solvent dependent. Just as solute-solvent interactions have an effect on the relative stability of two possible cations formed from a conjugated molecule, so in solid salts stability relationships depend on the mode of packing of ions, which determines interactions with the nearest neighbours. Therefore the types of cation observed in solid salts are not necessarily the most stable ones in solution. 

However, several reagents add to the conjugated tt system in a 1,4-manner, a result also called conjugate addition. In these transformations, the nucleophilic part of a reagent attaches itself to the j8-carbon, and the electrophilic part (most commonly, a proton) binds to the carbonyl oxygen. As the resonance forms and the resonance hybrid below illustrate, the j8-carbon in an a,j8-unsaturated carbonyl compound possesses a partial positive charge and is therefore a second electrophilic site in these molecules, in addition to the carbonyl carbon itself (recall Section 17-2). Addition of nucleophiles to the j8-carbon is therefore not a surprising process. 

It is important to emphasize that the presence of two or three basic centres of comparable basicity in a conjugated molecule may lead to protonation processes at all of them. These processes may occur at various rates, but if all the rates are fast, nmr spectra do not enable us to say what are the relative amounts of variously protonated species present at equilibrium. Increasing the acidity of the medium and lowering the temperature in order to observe the resonances of the captured proton may have the effect of shifting the tautomeric equilibria in favour of one or other of the protonation sites. Information on the position of tautomeric equihbria in protonation processes is thus not obt iinable from nmr spectra under the conditions of rapid proton exchange. 

Alternatively, suppose you want to determine which heteroatom in a molecule is protonated first as pH is lowered. Or conversely, you may want to know which is the most acidic proton in a compound (even if it is a hydrocarbon, for example). In such cases, you can obtain optimized geometries for the parent molecule Z and its conjugate acid ZH+ (or conjugate base Z ) for each site of proton attachment or removal. Simply take the differences in total energy (obtained quantum mechanically), E(ZH+)-E(Z) [or E(Z ) E(Z)], and you have a theoretical assessment of the relative gas-phase acidity (basicity). (The electronic energy of a proton is zero because it has no electron.) Of course, these energy differences do not account for solvation, but if the two protonation (or deprotonation) sites are very similar, the vacuum results may suffice. Alternatively, you can turn on implicit (continuum) solvation in your calculation and obtain energies of the simulated solution species. 

Another possible scheme (3.3b) is based on a suggestion that protons transported by the F0 factor and included in H20 molecule in the ATP synthesis differ from one another, and A/ZH is consumed for transforming the / j factor to a conformation making ATP release from the catalytic site easier [26], The second scheme (3.3b) is characterized by its simplicity and conciseness if compared with scheme (3.3a). However, it possesses a serious drawback in that the conjugation idea is completely neglected, no matter if it is energetic or chemical. This contradicts the facts observed and, therefore, may not be accepted. 

Proton transfer from alkane radical cations to alkane molecules results in the transformation of these cations into neutral alkyl radicals (the conjugate bases). The nature of these radicals is determined by the site of proton donation in the alkane radical cation. Information on the site of proton donation in the proton transfer from alkane radical cations to alkane molecules can thus be derived from EPR spectral analysis of the neutral alkyl radicals formed. To aid the reader in appreciating the results that are presented on this matter below and in understanding related spectra from the literature, a section on the characterization of neutral alkyl radicals by EPR spectroscopy in solid systems is included at this point. 

Complexity in the conduction of protons encompasses (1) dissociation of the proton from the acidic site (2) subsequent transfer of the proton to the first hydration shell water molecules (3) separation of the hydrated proton from the conjugate base e.g. the sulfonate anion) and finally (4) diffusion of the protons in the media consisting of confined water and tethered sulfonates within the polymeric matrix. Hence, we will endeavor to discuss the insight from theoretical modeling into these four aspects. 

We used DFT to optimize the geometries of various Hammett bases on cluster models of zeolite Brpnsted sites. For p-fluoronitrobenzene and p-nitrotoluene, two indicators with strengths of ca. -12 for their conjugate acids, we saw no protonation in the energy minimized structures. Similar calculations using the much more strongly basic aniline andogs of these molecules demonstrated proton transfer from the zeolite cluster to the base. We carried out F and experimental NMR studies of these same Hammett indicators adsorbed into zeolites HY and HZSM-5. 

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