The amide hydrolysis you have just met is much faster in base because base (in this case hydroxide) deprotonates the intermediate and makes it more reactive. The same is true for many other base-catalysed processes: often it is the nucleophile that is made more reactive by deprotonation to form an anion. For example, ester hydrolysis is faster at higher pH because the higher the pH the more hydroxide there is to act as a nucleophile.

We can plot this on a graph of rate vs. pH:

The rate equation at high pH is second order, as you expect, and depends on the concentration of hydroxide and the concentration of the ester. Notice, though, that below pH₇ the rate starts to increase again as the concentration of [H⁺] increases. This is because ester hydrolysis is also acid catalysed, as you saw in Chapter 10. At acidic pH, a new mechanism takes over in which protonation of the carbonyl group accelerates attack of weakly nucleophilic water.

The reaction is still bimolecular but the rate constant is different: we can represent the two processes by two rate equations, labelling the rate constants ka and kb with the suffixes ‘a’ for acid and ‘b’ for base to show more clearly what we mean: rate of ester hydrolysis in acid (pH < 7) solution = ka[MeCO₂R][H₃O⁺] rate of ester hydrolysis in basic (pH > 7) solution = kb[MeCO₂R][HO−] This is typical acid–base catalysis, known as ‘specifi c acid–base catalysis’ because the specifi c acid and base involved are H+ (or H₃O₊) and OH−. The form of the pH dependence of the rate tells us that there is a choice of two mechanisms—the one that is faster is the one that is observed. You met a reaction in Chapter 11 whose rate has a very different pH dependence: imine formation. To remind you, here is the mechanism again. We pointed out in Chapter 11 that

the reaction is acid catalysed because acid is needed to help water leave. But too much acid is a problem because it protonates the starting amine and slows the reaction down.

For these reasons, the pH–rate profile for imine formation looks like this: there is a maxi mum rate around pH 6, and either side the reaction goes more slowly.

The difference now is that at low pH, the rate-determining step changes from being the dehydration step (which can then go very fast because of the high concentration of acid) to being the addition step, which is slowed down by protonation of the amine. Whereas a reaction will always go by the fastest of the available mechanisms, it is also bound to go at the rate of the slowest step in that mechanism.

●Multistep reaction rates The overall rate of a multistep reaction is decided by:

• the fastest of the available mechanisms

• the slowest of the possible rate-determining steps.

Catalysis by weak bases

In Chapter 10 we used pyridine as a catalyst in carbonyl substitution reactions, even though it is only a weak base. Catalysis by pyridine involves two mechanisms, and is discussed on p. 200. Acetate ion is another weak base which can catalyse the formation of esters from anhydrides:

The problem is, it is far too weak a base (acetic acid has a pKa of 5) to deprotonate the alcohol (pKa 15), so it can’t be forming alkoxide (in the way that hydroxide would for example). But what it can do is to remove the proton from the alcohol as the reaction occurs.

مواضيع ذات صلة

Protons on saturated carbon atoms Chemical shifts are related to the electronegativity of substituents

Regions of the proton NMR spectrum

Integration tells us the number of hydrogen atoms in each peak

The differences between carbon and proton NMR

Kinetic versus thermodynamic products

What does third-order kinetics mean

Rate equations

Catalysis

Reaction intermediates

Why some reactions are done at low temperature

The route from reactants to products: the transition state

How fast do reactions go? Activation energies