Electronegative atoms, proton transfer

As the atom (A) to which H is bonded becomes more electronegative the polarization H—A becomes more pronounced and H is more easily lost as H An alternative approach to the same conclusion is based on the equation for proton transfer especially with regard to the flow of electrons as shown by curved arrows... 

This proton transfer step produces an intermediate that is very similar to a bromo-nium ion (a three-membered ring with a positive charge on an electronegative atom). Just as a bromonium ion can be attacked by water, similarly, a protonated epoxide can also be attacked by water ... 

Favorable proton transfers between electronegative atoms such as O, N, and S are extremely fast. The bimolecular rate constants are generally diffusion-controlled, being 1010 to 10" s-1 A/-1 (Table 4.2). For example, the rate constant for the transfer of a proton from H30+ to imidazole, a favorable transfer since imidazole is a stronger base than H20, is 1.5 X 1010 s 1 M l (Table 4.3). The rate constant for the reverse reaction, the transfer of a proton from the imidazolium ion to water, may be calculated from the difference in their p a s by using the following equations ... 

These are found from comparing the rates of a reaction in H20 and D20. They are usually a result of proton transfers between electronegative atoms accompanying the bond making and breaking steps between the heavier atoms in reactions such as the following ... 

The reaction dimensions that have so far been found necessary (though this list will doubtless increase as more families of reaction are analyzed by NBT) are bond formation/breaking, proton transfer, geometry change, and proton transfer (between electronegative atoms). The use of proton transfer between... 

Proton transfer between electronegative atoms can be treated as a simple reaction dimension. This is known to be only an approximation but appears to be quite permissible if the reaction includes geometry change or heavy atom bond forming. 

The rate of enolate-carbonyl equilibration " is dependent on the forward and backward rates of proton exchange. Proton exchange from a carbon-based acid is known to be slower than that of a more electronegative atom donor (in particular, O and N atoms) . For a series of closely related molecules usually the more acidic a given molecule is, the faster the rate of proton transfer (high kreu note that thermodynamic and kinetic parameters are not related). For example, benzocyclobutanone (10) is less acidic and the rate of deprotonation is substantially slower (10 times) than the related benzocyclopentanone (12) due to its enolate (11) having unfavourable anti-aromatic character. Deprotonation of the simplest cyclobutanone (13) clearly does not lead to an unfavourable anti-aromatic enolate (14) . By assuming the internal strain of 14 is similar to that of 11, cyclobutanone (13) is evidently 10 " times more acidic than benzocyclopentanone (12). By the same vain, the more acidic propanone (15) has a faster rate of deprotonation (10 times) than the less acidic ethyl acetate (16) . ... 

In the detailed description of proton-transfer reactions, especially of rapid proton transfers between electronegative atoms, it should always be specified whether the term is used to refer to the overall process (including the more-or-less ENCOUNTER-CONTROLLED formation of a hydrogen-bonded complex and the separation of the products [see microscopic diffusion control]) or just to the proton-transfer event (including solvent rearrangement) by itself. 

All elimination routes are improved by this swap of oxygen for carbon (Fig. 4.29). The ElcB proton transfer step now creates a very stable oxyanion, an anion on a very electronegative oxygen atom. The slow step of the El, loss of the leaving group, is also sped up because the oxygen lone pair can stabilize the carbocation formed. All routes have formed a very strong C=0 bond. The primary determinant at this point, since all routes are reasonable, is the pH of the reaction medium. The ElcB is found in base because the oxyanion is basic (pA"abH is about 12 to 16). The El is found in acid because the lone pair stabilized carbocation is just a protonated carbonyl (pA a is near -7). The E2 is found in more neutral media. 

The rate-limiting step in proton transfer between electronegative atoms is either /c, the diffusion-controlled encounter of the acid-base pair for thermodynamically favourable transfers or the diffusion-controlled dissociation of the acid-base pair, for thermodynamically unfavourable transfers (Figure 1). The rate-limiting step is rarely the proton transfer within the encounter complex. Eigen plots are predominantly observed in reactions in which proton transfer occurs to or from heteroatoms in reactive intermediates. 

Most enzyme kinetic studies assume that proton transfer is fast compared with catalysis, but this is also not necessarily so. It has long been known that bimolecular rate constants for proton transfer between electronegative atoms follow an Eigen curve , with the rate in the thermodynamically favourable direction being dilfusion controlled (10 ° M s at ambient temperature) and in the thermodynamically unfavourable direction being s ... 

The invocation of general base catalysts on the enzyme to transfer protons from amide or serine/threonine hydroxyl seems unnecessary kinetic barriers to proton transfer from electronegative atoms are small, the difficulty in creating a reasonable N-nucleophile from a primary amide lying largely in the unfavourable tautomeric equilibrium. 

The prototropic tautomerism of compounds containing an amidine moiety has been studied extensively.41-43 However, the data obtained on this type of equilibrium are rather qualitative and have not been explored systematically. The difficulties encountered in this work stem primarily from the common experience that proton transfer between electronegative atoms, such as nitrogen, is very fast.43,44... 

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