Proton transfer catalysed

Scheme 18 Proton transfer catalysed by added amines (BNHf in aspartate aminotransferase engineered without lysine-258...

The reaction is clearly acid-catalysed and analysis115 of the variation of the rate-coefficient with acidity (H0) in the range 75-96 % sulphuric acid has indicated that a second proton transfer is taking place. This is because, at these acidities, spectroscopic measurements show that the azoxybenzene is completely protonated, yet the observed first-order rate coefficient increases along the range from 0.016 x 10" 5 to 26.1 x 10 5 sec-1 at 25 °C. For a scheme like... 

The proposed reaction mechanism involves intermolecular nucleophilic addition of the amido ligand to the olefin to produce a zwitterionic intermediate, followed by proton transfer to form a new copper amido complex. Reaction with additional amine (presnmably via coordination to Cn) yields the hydroamination prodnct and regenerates the original copper catalyst (Scheme 2.15). In addition to the NHC complexes 94 and 95, copper amido complexes with the chelating diphosphine l,2-bis-(di-tert-bntylphosphino)-ethane also catalyse the reaction [81, 82]. 

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) ... 

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... 

For this mechanism, values of kr =k 2 = 1.3 x 10lodm3mol-1s-1 are calculated from the experimental value for k in (94), and this means that the proton-transfer steps in (96) are diffusion-controlled in the thermodynamically favourable directions. The hydroxide ion catalysed tautomerisation... 

Figure 16.3 Proton transfers within the active site complex catalysed by Glul78. (From Barynin et al., 2001. Copyright 2005, with permission from Elsevier.)...

If this explanation is correct, the looseness of the proton-transfer part of the mechanism is evidently crucial, both because it is part of every general acid-base catalysed reaction, and more specifically because EM s for reactions... 

The interpretation of formation of homo- (or hetero-) conjugated acid BH+B by proton transfer from the intermediate and the electrophilically catalysed departure of the nucle-ofuge due to this aggregate is common to this and to the dimer mechanism and they can be formulated as essentially the same, and as reflecting different parts of a spectrum of methods for the formation of the second intermediate153. For a given nucleophile, dimer formation increases with increase of concentration, hence the relative importance that reaction via a dimer should increase with increasing nucleophile concentration. 

Since morpholine and piperidine are stereochemically similar but exhibit different pKa values, the difference between their rates in the reactions of the fluoro-substrates in acetonitrile could be also due to a change in mechanism, whereby proton transfer from the intermediate 1 in equation 1 becomes rate-limiting when the reagent is morpholine. The change from an uncatalysed to a base-catalysed reaction with decrease in basicity of the nucleophile is well known in ANS for both primary and secondary amines1 200. 

In contrast, for a proton transfer from a hydrogen-bonded acid occurring by the mechanism in (24), the predicted dependence of kf and on the strength of the catalysing base is quite different. In this case, when the pA bh of the base and the p -value of the hydrogen-bonded acid are closely matched, that is at Ap 0, it would be predicted that the proton in the transition state will be roughly half-transferred and Bronsted exponents a and p of around 0.5 should be observed. 

The reaction of ethyl 2,4,6-trinitrophenyl ether with aniline in dimethyl sulfoxide (DMSO) in the presence of Dabco occurs in two stages via the intermediate (6). Kinetic studies show that proton transfer is rate-limiting both in the formation of the intermediate and in the subsequent acid-catalysed decomposition to give 2,4,6-trinitrodiphenylamine. Phenoxide is a considerably better leaving group than ethoxide so that substitutions of phenyl 2,4,6-trinitrophenyl ethers and phenyl 2,4-dinitronaphthyl ether with aniline occur without the accumulation of intermediates. Both uncatalysed and base-catalysed pathways are involved. ... 

The mechanism of reaction between barbiturate and 1,3-dimethylbarbiturate ions with o-nitro-, j -nitro-, and 2,4-dinitrobenzaldehyde has been explored rate dependence on solvent viscosity is indicative of involvement of a diffusion-controlled proton transfer in the rate-determining step at pH 2-4. Unexpected values of Brpnsted a for the acid-catalysed process have been explained. 

The effect of ring substituents on the rate constants, deuterium kinetic isotope effects and Arrhenius parameters for ene-additions of acetone to 1,1-diphenylsilane have been explained in terms of a mechanism involving fast, reversible formation of a zwitterionic silene-ketone complex, followed by a rate-limiting proton transfer between the a-carbonyl and silenic carbon. A study of the thermal and Lewis acid-catalysed intramolecular ene reactions of allenylsilanes with a variety of... 

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