Enolization acid-catalysed mechanism

Fig. Acid-catalysed mechanism for keto-enol tautomerism.

An H acidity function scale has been constructed for methoxide ion in methanol and its mixtures with DMSO (10-80%, v/v) using the dissociation of 11 amides (114) as the anchors for the scale.The degradation pathways of the anti-flammatory and analgesic lomoxicam (115), which contains an amide bond, have been examined recently. In acid, cleavage of the amide bond was the main reaction path and in alkaline and neutral solution the proton shift of the enolic hydroxyl initiated the major degradation pathway. The mechanism of hydrolysis of some A-nitrobenzamides (116) in strong acid follow an -1 mechanism with O-protonation but, in more moderate acid, they exhibit a neutral water-catalysed mechanism. /V-Methyl-/V-nitroacetamide (117) shows only the neutral water-catalysed process. Nitrourea follows an, 4-1 acid-catalysed mechanism. ... 

The aza-Payne rearrangement and its use as a synthetically valuable equilibration process has been reviewed. Unusual diazadioxabicyclo[2.2.2]octanes (352) have been obtained by the acid-catalysed rearrangement of A -quinazolinonyl- and A -phthalimido-aziridines derived from 3-phenylcyclohex-2-enol. ° A probable mechanism is outlined in Scheme 108. A-Acyl-2,2-dimethylaziridines have been isomerized by sodium iodide into three isomers whose yields appear to depend... 

The intermediacy of enols or enolate anions may be demonstrated by hydrogen exchange reactions (see Section 4.11.2). Both acid-catalysed and base-catalysed tautomerism mechanisms involve removal... 

Two mechanisms are shown above. The base-catalysed mechanism proceeds through the enolate anion. The acid-catalysed process would be formulated as involving an enol intermediate. Note that the terminal hydrogens in pentan-3-one are not exchanged, since they do not participate in the... 

A related mechanism can be drawn for acid-catalysed halogenation. Again, the halogen concentration does not figure in the rate equation, and the rate of enolization controls the rate of reaction. 

For acid-catalysed aldol condensations (which are less frequent), the homogeneous mechanism [371] can again be accepted. The enol form of the hydrogen donor interacts with the protonated form of the hydrogen acceptor, viz. 

Assess this evidence in terms of structure 2, show that the claim to have prepared 2 as a stable enol is specious, and, on the basis of mechanism, devise a structure for the product from the acid-catalysed hydroysis of 1 (the molecular formula C14H16O3 for the product is correct). 

Current understanding of the reaction suggests that an unprecedented mechanism is operating. Unlike in classical Lewis acid catalysed reactions [28], the metal complex does not activate the carbonyl moiety but is understood to enhance the degree of enolisation and thus create the necessary nucleophilic enol structure for reaction with the fluorinating agent [29]. 

On the other hand, in view of important analogies in kinetic behaviour between enol ketonisation and enol ether hydrolysis, the HA [HA,] terms cannot correspond to a concerted mechanism. Lienhard and Wang (1969) and this author (Dubois and Toullec, 1969b Toullec and Dubois, 1974) have pointed out that the rate-limiting step of enol ketonisation is closely similar to that of enol ether hydrolysis if the two-step mechanism for acid-catalysed enolisation is valid. The two reactions occur by rate-limiting proton transfer to the double bond with formation of either a hydroxycarbenium ion (19) or an alkoxycarbenium ion (20). However, in the latter reaction, in contrast to the... 

The elimination is even easier in acid solution and acid-catalysed aldol reactions commonly give unsaturated products instead of aldols. In this simple example with a symmetrical cyclic ketone, the enone is formed in good yield in acid or base. We shall use the acid-catalysed reaction to illustrate the mechanism. First the ketone is enolized under acid catalysis as you saw in Chapter 21. 

The mechanism involves acid-catalysed conversion of the keto form of the cyclic p-diketone into the enol form, which is able to attack the protonated enone. The mechanistic detail is precisely analogous to the attack of an enolate shown above the only difference is that both reactants are... 

The mechanism in the frame shows the enol of acetyl CoA attacking the reactive ketone. In nature the enolization is catalysed by a basic carboxylate group (Asp) and an acidic histidine, both part of the enzyme, so that even this easy reaction goes faster. 

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. 

Reactions involving Enols or Enolic Derivatives.—A review of the structure and reactivity of alkali-metal enolates includes some steroidal reactions. A study of the mechanism of isomerization of androst-5-en-17/3-ol-3-one to testosterone indicated that the acid-catalysed process proceeds through rate-determining enolization whereas the base-catalysed reaction proceeds through rate-determining protonation of an enolate ion. Bromination of the 4,4,6-trimethyl-A -3-oxo-compounds (111)—(113) gave the 2a-bromo-derivatives, each of which showed anomalous o.r.d. curves. Bromination at C-2 was favoured for the... 

The kinetics and mechanism of the acid-catalysed reactions of methylated trioses have been determined and the results were shown to be in good agreement with quantum mechanical calculations of charge distributions in substrates and intermediates. The same group has studied the kinetics and mechanism of acid-base-catalysed enolization of glycolaldehyde and methoxyacetaldehyde by polarography. Deuterium incorporation was used to establish the mechanism. ... 

At lower acidities and high oxidant concentrations, however, the rate became zero-order in oxidant and first-order in hydrogen ion, the limiting rate constant being similar to that for the acid-catalysed enolization of cyclohexanone. The mechanism... 

Study of structure-activity relationships in nucleophilic vinylic substitution reactions (S nV) that proceed by the addition-elimination mechanism has been furthered by the study of acid-catalysed breakdown of alkoxide and thiolate ion adducts of benzylidene Meldrum s acid (36a), methoxybenzylidene Meldrum s acid (36b), and thiomethoxybenzylidene Meldrum s acid (36c). Catalysis of alkoxide or thiolate expulsion is in competition with protonation of the a-carbon or one of the carbonyl oxygens to form an enolate. The positive Ag values for H+-catalysed RO and RS departure imply an imbalanced transition state in which proton transfer leads C-O or C-S bond cleavage. The pA values of the various adducts are much lower than for Meldrum s acid, in view of the stabilizing influence of OR, SR, and OMe groups on the carbanion. 

---