Proton transfer pathway

Basaric, N. Wan, P. Competing excited state intramolecular proton transfer pathways from phenol to anthracene moieties. J. Org. Chem. 2006, 71, 2677-2686. 

The other extreme case, i.e. wholly intramolecular proton transfer— pathway (b), is seen in the Et3N catalysed conversion of the optically active substrate (28) into (29) ... 

Shu X, Leiderman P, Gepshtein R, Smith NR, Kallio K, Huppert D, Remington S J (2007) An alternative excited-state proton transfer pathway in green fluorescent protein variant S205V. Protein Sci 16 2703-2710... 

Figure 13.9 (a) The structure of the four subunits of the CcO from R. sphaeroides (b) a more detailed view of the redox-active cofactors and amino acid residues in the proton transfer pathways (dotted arrows). (From Namslauer and Brzezinski, 2004. Copyright 2004, with permission from Elsevier.)... 

Superoxide anion formed in situ in a solution exposed to air (i.e. with only a small concentration of O2) has been used as an EGB to generate nitroalkane anions that may add to activated alkenes or to carbonyl compounds [130, 131]. An example is shown in Scheme 33. The reaction is catalytic since the product anion can act as a base toward the nitroalkane. Using the nitroalkane as the solvent favors the proton transfer pathway over the competing addition of the product anion to a second molecule of activated alkene, a pathway that may lead to polymerization [130]. In some cases, better yields of the Michael addition product were obtained if a stoichiometric amount of the anion was formed ex situ (with O2 as the PB), and the activated alkene added subsequently ]130, 132]. 

However, if there is no other exothermic pathway available, all the intermediate can do is revert to reactants. In such a situation, the more favorable the addition process is, the more internal energy is in the intermediate and the faster the reverse dissociation will occur. The better the addition is thermochemically, the worse it is kinetically. For the proton transfer pathway (6b), the neutral methanol product can carry off the excess energy as translational energy (and capture some of it in the newly formed OH bond) and the reaction proceeds. 

We can, however, form alkoxide ions that are monosolvated by a single alcohol group, via the Riveros reaction [Equation (7)]. When the monosolvated methoxide is reacted with acrylonitrile, the addition process reaction (8a), is the major pathway, because there is a molecule of solvent available to carry off the excess energy. The proton transfer pathway, reaction (8b), becomes endothermic, because the methoxide-methanol hydrogen bond, at about 29 kcal/mol, must be broken in order to yield the products. Thus, one can observe either the unique gas phase mechanism in the gas phase, reaction (6b), or the solution phase mechanism in the gas phase, reaction (8a), and the only difference is in the presence of the first molecule of solvent. 

The experimental barrier for the forward reaction is only around 13 kcal/mol (2). While this discrepancy is not alarming (it is in fact rather normal for the present method) it might still indicate a problem in the model. A third possible problem of the reaction scheme in Fig. 8 is that two different proton transfer pathways are being used rather than one. This is not necessarily a problem either but it is rather unusual. For these reasons an alternative model was also investigated, and this is described below. 

A. Proton Transfer Pathways within Protein Molecules. 379... 

---