Enolization is catalysed by acids and bases

Enolization is, in fact, quite a slow process in neutral solution, even in D2O, and we would catalyse it with acid or base if we really wanted it to happen. In the acid-catalysed reaction, the molecule is first protonated on oxygen and then loses the C-H proton in a second step. We shall use a different example here to show that aldehydes form enols too. 

This is a better mechanism for enolization than those we have been drawing because it shows that something (here a water molecule) must actually be removing the proton from carbon. Though this reaction will occur faster than the uncatalysed enolization, the equilibrium is not changed and we still cannot detect the enol spectroscopically. 

In the base-catalysed reaction the C-H proton is removed first by the base, say, a hydroxide ion, and the proton added to the oxygen atom in a second step. 

This is a good mechanism too because it shows that something must remove the proton from carbon and something (here a water molecule—we can t, of course, have protons in basic solution) must put the proton on the oxygen atom. The concentration of free protons in water is vanishingly small (Chapter 8). 

Notice that both of these reactions are genuinely catalytic. You get the proton back again at the end of the acid-catalysed mechanism. 

Notice that both of these reactions are genuinely catalytic. You get the proton back again (in the form of HjO ) at the end of the acid-catalysed mechanism, and you get the hydroxide ion back again at the end of the base-catalysed mechanism. 

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We have established that the formation of enols is catalysed by acids and bases. The reverse of this reaction—the formation of ketone, from enol—must therefore also be catalysed by the same acids and bases. If you prepare simple enols in the strict absence of acid or base they have a reasonable lifetime. A famous example is the preparation of the simplest enol, vinyl alcohol, by heating ethane-1,2-diol (glycol—antifreeze) to very high temperatures (900 °C) at low pressure. Water is lost and the enol of acetaldehyde is formed. It survives long enough for its proton NMR spectrum to be run, but gives acetaldehyde slowly. 

In the last chapter you saw that many ketones have a nucleophilic alter ego known as an enol tautomer. Formation of the enol tautomer is catalysed by acid or by base, and because the ketone and enol are in equilibrium, enolization in the presence of D2O can lead to replacement of the protons in the a positions of ketones by deuterium atoms. This is what happens to pentan-3-one in acidic D2O ... 

Ah initio methods have been used to compare enzyme-catalysed enolization mechanisms.130 Acid- and base-catalysed stepwise mechanisms have been compared with the concerted reaction the latter is favoured by several hydrogen-bonding interactions. 

Enolisation.— The isomerisation of androst-5-ene-3,17-dione (314) into the 4-ene-3,17-dione (316) proceeds through the enol (315), and is subject to rate-controlling removal of 4-H, whether catalysed by acid, base, or enzyme. Isotopic labelling of 4/5-H has indicated differing stereoselectivities in hydrogen removal according... 

Intramolecular aldol reaction of (14) to give (16), promoted by lyate ion, has been found to proceed by rate-determining deprotonative formation of enolate intermediate (15) the intramolecular addition (/cc) occurs more rapidly than reprotonation of (15) by H2O or D2O ( hoh or A dod), c/ hoh = 35. However, when the reaction is catalysed by high concentrations of 3-substituted quinuclidine buffers, the enolate addition is rate determining and competitive with reprotonation of (15) k-Q /k (lmol ) increases from 7 to 450 as the acidity of the buffer acid increases from p/(bh = 11-5 to 7.5. The unexpectedly small Marcus intrinsic value for addition of (15) to the carbonyl group has been attributed to favourable interactions between the soft-soft acid-base pair. 

A system of parallel reactions as shown in Fig. 5.3-9 was studied by Paul et at. (1992). The reactions are an acid-base neutralization and a base-catalysed hydrolysis of product (C). The labile compound (Q is in solution in an organic solvent, and aqueous NaOH is added to raise the pH from 2 to 7. Enolization occurs under basic conditions and is accompanied by irreversible decomposition (ring opening), which is not shown in the figure. The system was studied in the laboratory using the 6-Iitre reactor shown in Fig. 5.3-10. 

Studies of relative rates, activation parameters, kinetic isotope, and solvent isotope effects, and correlation of rates with an acidity function, have elucidated the mechanisms of cyclization of diacetyl aromatics (23-26) promoted by tetramethyl-ammonium hydroxide in DMSO.32 Rate-determining base-catalysed enolate anion formation from (24-26) is followed by relatively rigid intramolecular nucleophilic attack and dehydration whereas the cyclization step is rate determining for (23). 

Acid-catalysed hydrogen-deuterium exchange in norcamphor has also been investigated by Werstiuk and Banerjee (1977) (DOAc—D20—DC1 medium). It was observed that exo-deuteron addition to the enol is also preferred, but with a slightly smaller selectivity (x 190). This would mean that, if torsional factors cause preferential base-catalysed exo-exchange, they also occur for acid-catalysed keto-enol tautomerism. However, the absence of important torsional strain effects on the rate constants of acid-catalysed enolisation of cyclic and bicyclic ketones contradicts this assumption. 

The halogenation of ketones is also general acid catalysed. The mechanism usually consists of a rapid pre-equilibrium protonation of the carbonyl group followed by a slow proton transfer from carbon to the base catalyst [41]. The enol thus produced reacts rapidly with halogen. The overall mechanism is similar to mechanism (7) described earlier and the observed rate coefficient is a product of the equilibrium constant for protonation of the carbonyl group and the rate coefficient for the proton transfer from carbon, and therefore does not refer to a single proton transfer step. 

Compound 61 yes this compound is chiral, but remember that 61 is an enol and is readily converted to the more stable ketone 64, which is not chiral. Any reversion to 61 from the ketone by base-catalysed enolization via the enolate, or acid-catalysed enolization, will produce both 61 and its enantiomer. 

Step of a general acid-catalysed reaction is general base catalysed. There is a simple relationship between values of the Bronsted coefficients a and p for the forward and reverse reactions respectively, and this may be derived using the example of enolisation of acetone (Equation 36). The equilibrium constant for the formation of enolate ion is given by the equation (= so that the Bronsted relationships... 

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