Acid catalysis decarboxylation

General acid catalysis by anilinium and pyridinium ions has been observed in the decarboxylation of 2,4,6-trihydroxybenzoic acid [246] and 4-aminosalicylic acid [245]. Acetic acid acts as a general catalyst in the reactions of 4-aminosalicylic acid and 2-hydroxyl-l-naphthoic acid [82, 245]. In all of these examples, reaction rates obey the equation... 

Transamination is just one of a wide range of amino acid transformations that are catalyzed by PLP enzymes. The other reactions catalyzed by PLP enzymes at the a-carbon atom of amino acids are decarboxylations, deam-inations, racemizations, and aldol cleavages (Figure 23.12). In addition, PLP enzymes catalyze elimination and replacement reactions at the P-carbon atom (e.g., tryptophan synthetase Section 24.2.11) and the y-carbon atom (e.g., cytathionine P-synthase, Section 24.2.9) of amino acid substrates. Three common features of PLP catalysis underlie these diverse reactions. 

In the realm of homogeneous catalysis we often encounter examples of acid- and base-catalyzed hydration-dehydration and hydrolysis, metal-catalyzed hydrolysis and autoxidation, photocatalytic oxidation and reduction, metal-catalyzed electron transfer, acid-catalyzed decarboxylation, photocatalytic decarboxylation, metal-catalyzed free-radical chain reactions, acid-catalyzed nucleophilic substitutions, and enzymatic catalysis. 

Drug substances having a carboxylic acid group are sometimes susceptible to decarboxylation, as shown in Scheme 42. 4-Aminosalicylic acid is a good example.168 Foscarnet also undergoes decarboxylation under strongly acidic conditions, 169 whereas etodolac is susceptible to decarboxylation by acid catalysis.170... 

Moreover, it is quite certain that the double bond does not migrate before the decarboxylation by three-carbon tautomerism —CH=CH—CH2— —CH2—CH CH— (this usually requires base catalysis but can also occur without a catalyst at temperatures above 200°) the migration occurs only when allied to elimination of carbon dioxide, as is shown by the fact that it takes place also when a9 -dimethyl- 1-cyclohexeneacetic and 2,2-dimethyl-3-butenoic acid are decarboxylated although neither of these acids possesses a vinylic hydrogen atom ... 

Beak and Siegel [8] presented a thorough study of the decarboxylation of 1,3-dimethylorotate and analogs in non-aqueous solvents. The decarboxylation of 1,3-dimethylorotic acid was found to be first order, and slightly faster with the anion 1,3-dimethylorotate than with the acid, indicating a decarboxylation of the carboxylate without general acid catalysis (Fig. 2). 

P-Lactones.—Studies continue on the synthesis and reactions of /3-lactones derived from acid dianions and carbonyl compounds. The decarboxylation of these compounds to sterically hindered olefins, and the steric control of the process by acid catalysis has been described (Scheme 60). ° In the latter case, increasing the acidity of the reaction medium changes the stereochemistry from retention (>98%) to inversion (>98%) of configuration. 

Decarboxylation studies of N-carboxy-2-imidazolidone revealed the poor leaving ability of the imidazolidone anion. Metal ions such as Cu(II) or Mn(II) prevent decarboxylation. The sensitivity of carboxyimidazolidone to specific acid catalysis is probably the most remarkable feature of this compound and could account for the fact that carboxybiotin-enzyme intermediates are unstable. The neutral form however can decarboxylate in a unimolecular pathway via a six-membered transition state. 

Electron-deficient and electron-neutral cinnamic acids undergo decarboxylative coupling with iodobenzenes under palladium catalysis to produce stilbenes... 

Kemp DS, Paul K. Decarboxylation of benzisoxazole-3-carboxyhc acids. Catalysis by extraction of possible relevance to the problem of enzymic mechanism. / Am Chem... 

Bcamples of metal-ion catalysed organic reactions in water where the catalyst acts exclusively as Lewis acid are the hromination of diketones" " and the decarboxylation of oxaloacetate. The latter reaction has been studied in detail. In 1941 it was demonstrated that magnesium(II) ions catalyse this reaction" Later also catalysis by other multivalent metal ions, such as Zn(II), Mn(II), Cu(II), Cd(ir), Fe(II), Pb(II), Fe(III)... 

Electrophilic catalysis is catalysis by an electrophile (Lewis acid) acting as an electron-pair acceptor. For example, metal ions catalyze the decarboxylation of dimethyloxaloacetic acid. ... 

The biologically active form of vitamin Bg is pyridoxal-5-phosphate (PEP), a coenzyme that exists under physiological conditions in two tautomeric forms (Figure 18.25). PLP participates in the catalysis of a wide variety of reactions involving amino acids, including transaminations, a- and /3-decarboxylations, /3- and ") eliminations, racemizations, and aldol reactions (Figure 18.26). Note that these reactions include cleavage of any of the bonds to the amino acid alpha carbon, as well as several bonds in the side chain. The remarkably versatile chemistry of PLP is due to its ability to... 

A few examples have been reported in which no steric parameter is involved in the correlation analysis of cyclodextrin catalysis. Straub and Bender 108) showed that the maximal catalytic rate constant, k2, for the (5-cyclodextrin-catalyzed decarboxylation of substituted phenylcyanoacetic acid anions (J) is correlated simply by the Hammett a parameter. 

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