Proton transfer steps

Turning the argument around reactions that do not involve proton transfer steps will only experience a significant effect of the Lewis acids if a direct interaction exists between catalyst and reactant. The conventional Diels-Alder reaction is a representative of this class of reactions. As long as monodentate reactants are used, the effects of Lewis acids on this reaction do not exceed the magnitude expected for simple salt effects, i.e. there are no indications for a direct interaction between Lewis-acid and substrate. 

The mechanism includes two single electron transfers (steps 1 and 3) and two proton transfers (steps 2 and 4) Experimental evidence indicates that step 2 is rate determining and it is believed that the observed trans stereochemistry reflects the dis tribution of the two stereoisomeric alkenyl radical intermediates formed in this step... 

Group I metals—sodium is the one usually employed—in liquid ammonia as the solvent convert alkynes to trans alkenes The reaction proceeds by a four step sequence in which electron transfer and proton transfer steps alternate... 

The mechanism of enolization involves two separate proton transfer steps rather than a one step process m which a proton jumps from carbon to oxygen It is relatively slow m neutral media The rate of enolization is catalyzed by acids as shown by the mechanism m Figure 18 1 In aqueous acid a hydronium ion transfers a proton to the carbonyl oxygen m step 1 and a water molecule acts as a Brpnsted base to remove a proton from the a car bon atom m step 2 The second step is slower than the first The first step involves proton transfer between oxygens and the second is a proton transfer from carbon to oxygen... 

Step 4 Proton transfer steps yield an alcohol and a carboxylate anion... 

Step 2 Enzyme catalyzed proton transfer steps cause migration of the double bond converting the mine formed m step 1 to an isomeric mine... 

Step 4 Proton transfer steps to yield ethanol and benzoate ion... 

Nitriles are susceptible to nucleophilic addition. In their hydrolysis, water adds to the carbon-nitrogen triple bond. In a series of proton-transfer steps, an anide is produced ... 

Challis and Rzepa (1975) observed kinetic deuterium isotope effects in the azo coupling of 2-methyl-4,6-di-tert-butylindole (12.139) and its anion. The origin of this effect must also be attributed to steric hindrance of the proton transfer step in the substitution proper, since 2-deuterated methylindole and unsubstituted indole (Binks and Ridd, 1957) do not give isotope effects. 

Rate parameters [(da/df), A, E measured for dehydroxylations are frequently sensitive to the availability of water vapour in the vicinity of the reactant and this accounts for the apparent variations in kinetic data sometimes found between different reports concerned with the same reaction. Water adsorbed on product adjoining the reaction interface could be expected to participate in the reversible proton transfer step, the precursor to water elimination. Despite this influence of PH2o on reaction rate, we are aware of no reported instance of S—T behaviour in dehydroxylations. 

FIGURE 5.8. A downhill trajectory for the proton transfer step in the catalytic reaction of trypsin. The trajectory moves on the actual ground state potential, from the top of the barrier to the relaxed enzyme-substrate complex. 1, 2, and 3 designate different points along the trajectory, whose respective configurations are depicted in the upper part of the figure. The time reversal of this trajectory corresponds to a very rare fluctuation that leads to a proton transfer from Ser 195 to His 57. 

Exercise 8.1. Find a1 a2, and H12 for the proton transfer step by using the above experimental information and Program 2.B. 

On the basis of the examples given above, it is reasonable to suggest that the underlying principles for optimization of the overall reaction rate with respect to the choice of metal ion are similar. That is, there are basically three states along the reaction pathway which determine the most suitable choice of metal ion. These are (1) the reactant state with bound metal and substrate before the proton transfer step, (2) the intermediately created free OH nucleophile and, (3) the subsequent transition state associated with... 

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 ... 

Kovacs, G., Ujaque, G. and Lledos, A. (2008) The Reaction Mechanism of the Hydroamination of Alkenes Catalyzed by Gold(I)-Phosphine The Role of the Counterion and the N-Nucleophile Substituents in the Proton-Transfer Step. Journal of the American Chemical Society, 130, 853-864. 

Only three steps of the proposed mechanism (Fig. 18.20) could not be carried out individually under stoichiometric conditions. At pH 7 and the potential-dependent part of the catalytic wave (>150 mV vs. NHE), the —30 mV/pH dependence of the turnover frequency was observed for both Ee/Cu and Cu-free (Fe-only) forms of catalysts 2, and therefore it requires two reversible electron transfer steps prior to the turnover-determining step (TDS) and one proton transfer step either prior to the TDS or as the TDS. Under these conditions, the resting state of the catalyst was determined to be ferric-aqua/Cu which was in a rapid equilibrium with the fully reduced ferrous-aqua/Cu form (the Fe - and potentials were measured to be within < 20 mV of each other, as they are in cytochrome c oxidase, resulting in a two-electron redox equilibrium). This first redox equilibrium is biased toward the catalytically inactive fully oxidized state at potentials >0.1 V, and therefore it controls the molar fraction of the catalytically active metalloporphyrin. The fully reduced ferrous-aqua/Cu form is also in a rapid equilibrium with the catalytically active 5-coordinate ferrous porphyrin. As a result of these two equilibria, at 150 mV (vs. NHE), only <0.1%... 

Calculating rate constants for the formation and breakdown of tetrahedral intermediates is possible provided the corresponding equilibrium constant is known. The mechanism must be known or postulated these mechanisms often involve proton transfer steps. 

Acid and base catalysis of a chemical reaction involves the assistance by acid or base of a particular proton-transfer step in the reaction. Many enzyme catalysed reactions involve proton transfer from an oxygen or nitrogen centre at some stage in the mechanism, and often the role of the enzyme is to facilitate a proton transfer by acid or base catalysis. Proton transfer at one site in the substrate assists formation and/or rupture of chemical bonds at another site in the substrate. To understand these complex processes, it is necessary to understand the individual proton-transfer steps. The fundamental theory of simple proton transfers between oxygen and nitrogen acids and... 

When the acids HA and BH are of similar acidity (ApAT ca 0) the interpretation of the kinetic behaviour is less straightforward. It is usual to interpret the reaction by the mechanism in (8). The intermediates Ix and I2 are assumed to be hydrogen-bonded complexes, so that the proton-transfer step... 

ApA < 1. In Fig. 2 the region of curvature is much broader and extends beyond — 4 < ApA < + 4. One explanation for the poor agreement between the predictions in Fig. 3 and the behaviour observed for ionisation of acetic acid is that in the region around ApA = 0, the proton-transfer step in mechanism (8) is kinetically significant. In order to test this hypothesis and attempt to fit (9) and (10) to experimental data, it is necessary to assume values for the rate coefficients for the formation and breakdown of the hydrogen-bonded complexes in mechanism (8) and to propose a suitable relationship between the rate coefficients of the proton-transfer step and the equilibrium constant for the reaction. There are various ways in which the latter can be achieved. Experimental data for proton-transfer reactions are usually fitted quite well by the Bronsted relation (17). In (17), GB is a... 

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