Keto-enol tautomerism decarboxylation

Keto-acids, decarboxylation, 286 Keto-enol tautomerism, 201, 219, 225 carbanions in, 278 catalysis of, 277... 

It has been established that zinc-catalysed decarboxylation of (3-keto-acids involves a preliminary metal-promoted keto-enol tautomerism, as shown.272... 

Covey and Leussing have subsequently carried out detailed studies of the zinc(IT)-catalyzed decarboxylation of oxaloacetate. Two processes are observed using stopped flow techniques an initial absorbance increase being complete in about 30 s and a subsequent absorbance decrease being complete after 15 to 30 min. The first process is due to metal ion-promoted keto-enol tautomerism and the second to catalyzed decarboxylation. The subsequent protonation of the zinc pyruvate intermediate is rapid and unobservable. The rate constant for the decarboxylation... 

The mushroom tyrosinase-catalyzed oxidative decarboxylation of 3,4-dihydroxyphenyl mandelic acid (111, R = H) and a-(3,4-dihydroxyphenyl) lactic acid (111, R = Me) proceeds via the quinone methide intermediate 112. The coupled dienone-phenol rearrangement and keto-enol tautomerism transforms the quinone methide 112 into 1-acyl-3,4-dihydroxyphenyl compounds 113 (equation 48) . ... 

P-Keto acids, decarboxylation, 762—763, 768, 838, 840-841, 850 Keto-enol isomerism, 355, 705—707 Keto-enol tautomerism. See Keto-enol isomerism P-Keto esters acidity of, 831 alkylation of, 839-841, 850 Michael addition of, 846—847 nomenclature of, 832 preparation of... 

Covey and Leussing have subsequently carried out detailed studies of the zinc(IT)-catalyzed decarboxylation of oxaloacetate. Two processes are observed using stopped flow techniques an initial absorbance increase being complete in about 30 s and a subsequent absorbance decrease being complete after 15 to 30 min. T e first process is due to metal ion-promoted keto-enol tautomerism and the second to catalyzed decarboxylation. The subsequent protonation of the zinc pyruvate intermediate is rapid and unobservable. The rate constant for the decarboxylation ofZn(oxac)(.etois 7.42 x 10 s at 25 °Cand I = 0.1 M compared with the rate constant 31 x 10 s previously reported at 37 °C (Table 24). Detailed studies of the copper(II)-promoted decarboxylation have also been published. The reaction scheme in this case is summarized in Scheme 27. The release of CO is biphasic as is also the rate of H uptake in the step where pyruvate is formed. Only about 20% of the oxac in the system undergoes decarboxylation within the first 30 s. The remaining 80% is present as Cu(oxac)e ci which does not decarboxylate. The slow rate of CO2 evolution arises from the decarboxylation of a residual level of Cu(oxac)keio which is replenished by reketonization of Cu(oxac)e o,. For the decarboxylation Cu oxac)keto — CO2+ Cu(pyruvate)enoiate) = 0.17 s at 25 °C and / = 0.1 M so that the copper(II) complex decarboxy-lates some 23 times faster than the zinc complex. 

Indeed, heating 101 to >200°C leads to decarboxylation with formation of enol 102, which then tautomerizes to give 2,5-dimethyl-3-pentanone (103). (Keto-enol tautomerism was discussed in Chapter 10, Section 10.4.5.) Note that loss of CO2 results in forming a C=C unit between the C=0 carbon and the a-carbon in 101. Decarboxylation is slightly more difficult (requires a somewhat higher reaction temperature) for P-keto acids than for 1,3-dicarboxylic acids, but it is still a very facile reaction at 200°C. Claisen condensation products can therefore potentially be converted to a ketone via decarboxylation. 

FIGURE 19.61 Hydrolysis and decarboxylation of a diester is shown. The mechanism of decarboxylation has a six-memhered ring transition state.The initially formed enol is not isolahle. It undergoes keto-enol tautomerization to give the carboxylic acid. 

Here too there is an enol that tautomerizes to the product. The mechanism is illustrated for the case of p-keto acids,475 but it is likely that malonic acids, a-cyano acids, a-nitro acids, and p,y-unsaturated acids476 behave similarly, since similar six-membered transition states can be written for them. Some a,p-unsaturated acids are also decarboxylated by this mechanism by isomerizing to the p,7-isomers before they actually decarboxylate.477 Evidence is that 36 and similar bicyclic p-keto acids resist decarboxylation.47" In such compounds the... 

P-Diacids are unstable to heat. They decarboxylate (lose CO2), resulting in cleavage of a carbon-carbon bond and formation of a carboxylic acid. Decarboxylation is not a general reaction of all carboxylic acids. It occurs with P-diacids, however, because CO2 can be eliminated through a cyclic, six-atom transition state. This forms an enol of a carboxylic acid, which in turn tautomerizes to the more stable keto form. 

A p-keto acid such as 49 will also undergo decarboxylation. The temperature required for decarboxylation is usually a bit higher than that required for dicarboxylic acids such as 50. In general, however, heating either 49 or 50 to 200-300°C will lead to decarboxylation. An example heats 2-benzyl-3-oxohexanoic acid (55) to 275 C to form enol 56, which tautomerizes to ketone 57, l-phenyl-3-hexanone. Remember that the enol is not isolated, so heating 55 will give 57 as the isolated product. This reaction is drawn a second time to show the transformation of 55 to 57, with loss of the COOH unit. Note that heating a P-keto acid leads to a ketone product. 

In the decarboxylation reaction, the carbonyl oxygen of the keto group acts as a base and removes the acidic hydrogen of the carboxylic acid group. Notice the nicely organized six-membered ring transition state for this reaction (Fig. 19.58). Carbon dioxide is lost and an enol is initially formed. Normal tautomerization of the enol to the more stable ketone gives the final product. 

Decarboxylation, or loss of CO2, is not a typical reaction of carboxylic acids under ordinary conditions. However, j8-ketoacids are unusually prone to decarboxylation for two reasons. First, the Lewis basic oxygen of the 3-keto function is ideally positioned to bond with the carboxy hydrogen by means of a cyclic six-atom transition state. Second, this transition state has aromatic character (Section 15-3), because three electron pairs shift around the cyclic six-atom array. The species formed in decarboxylation are CO2 and an enol, which tautomerizes rapidly to the final ketone product. 

The decarboxylation of acetoacetic acid, a P-keto acid, occurs by way of a cyclic transition state in which a proton is transferred from the carboxylate atom to the carbonyl oxygen to give an enol that rapidly tautomerizes to give acetone. 

The mechanism of the decarboxylation reaction is shown below. The enolate picks up a proton from an acidic group at the enzyme active site and tautomerizes to the keto form. 

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