Mandelate reaction mechanism

Banerjee and coworkers181-184 have been interested in elucidating the reaction mechanism of the oxidation of mandelic acid and its derivatives by lead tetraacetate [Pb(OAc)4]. 

Gudmundsdottir, A.D., Mandel, S.M., Christman, R., Ault, B., and Krause Bauer, J.A., Solid State Photolysis of Azidoarylke-tones. Book of Abstracts of International Conference on Reactive Intermediates and Reaction Mechanisms, Ascona, Switzerland, 2002, p. 27. 

Varying kinetic dependences on hydroxide ion concentration have been identified in the oxidation of mandelic acid by osmium(vm). Although extensive data are available on osmium-catalysed systems, relatively little is known on the nature of the ion as an independent oxidant. The reaction mechanism may be written as in Scheme 6. The kinetic order is unity with respect to oxidant and organic substrate, indicating an ester intermediate of low thermodynamic stability. The change in order of [OH ] from two to zero on increasing hydroxide ion is not, however, satisfactorily explained. 

Trifluoromethyl-substituted phenylacetic and mandelic acids undergo efficient photodecarboxylation in basic aqueous solution, to give the corresponding trifluoromethyltoluenes or trifluoromethylbenzyl alcohols. This is consistent with formation of benzylic carbanions that subsequently react with water. Quenching studies support a reaction mechanism involving the singlet excited state. 

The study of phosphorus reaction mechanisms is still at a relatively early stage, and many aspects of the course of displacement reactions at chiral phosphorus are not yet completely understood. A recent publication (J. Donohue, N. Mandel, W. B. Famham, R. K. Murray, K. Mislow, and H. P. Benshop, J. Amer. Chenu Soc., 1971, 93, 3792) has demonstrated that a number of earlier correlations are of doubtful validity, and pending clarification anticipated as a result of future work, all of these have been omitted. 

The result of Pezold and Shriner may instructively be compared with the work of Marckwald and McKenzie on the differential rates of saponification of the (—)-menthyl mandelates, and it would be interesting to determine whether the production of optical activity depends here also upon incomplete asymmetric decomposition of the diastereoisomerides of IV. A positive result here would throw further light on the precise reaction mechanism. 

Figure 4.9 Mechanisms of the reactions catalyzed by the enzymes mandelate racemase (a) and muconate lactonizing enzyme (b). The two overall reactions are quite different a change of configuration of a carbon atom for mandelate racemase versus ring closure for the lactonizing enzyme. However, one crucial step (red) in the two reactions is the same addition of a proton (blue) to an intermediate of the substrate (red) from a lysine residue of the enzyme (E) or. In the reverse direction, formation of an intermediate by proton abstraction from the carbon atom adjacent to the carboxylate group.

Although the reaction could proceed via intermediate 14 or 15, the authors favour a mechanism where the formation of 14 is rate-determining because the displacement of the acetate at Pb by carboxylate anions is known to be rapid. The large negative AS (—34 e.u./mol) observed for the oxidation reaction is consistent with formation of the pseudo-cyclic intermediate 14. Also, the small Hammett p value of 0.4 determined for a series of meta- and para-substituted mandelic acids indicates that there is very little charge development on the benzyl carbon in the transition state of the rate-determining step. This is also consistent with the proposed mechanism. 

The pyridinium chlorochromate (PCC) oxidations of pentaamine cobalt(III)-bound and unbound mandelic and lactic acids have been studied and found to proceed at similar rates.Free-energy relationships in the oxidation of aromatic anils by PCC have been studied. Solvent effects in the oxidation of methionine by PCC and pyridinium bromochromate (PBC) have been investigated the reaction leads to the formation of the corresponding sulfoxide and mechanisms have been proposed. The major product of the acid-catalysed oxidation of a range of diols by PBC is the hydroxyaldehyde. The reaction is first order with respect to the diol and exhibits a substantial primary kinetic isotope effect. Proposed acid-dependent and acid-independent mechanisms involve the rapid formation of a chromate ester in a pre-equilibrium step, followed by rate-determining hydride ion transfer via a cyclic intermediate. PBC oxidation of thio acids has been studied. ... 

Most known thiamin diphosphate-dependent reactions (Table 14-2) can be derived from the five halfreactions, a through e, shown in Fig. 14-3. Each halfreaction is an a cleavage which leads to a thiamin- bound enamine (center, Fig. 14-3) The decarboxylation of an a-oxo acid to an aldehyde is represented by step b followed by a in reverse. The most studied enzyme catalyzing a reaction of this type is yeast pyruvate decarboxylase, an enzyme essential to alcoholic fermentation (Fig. 10-3). There are two 250-kDa isoenzyme forms, one an a4 tetramer and one with an ( P)2 quaternary structure. The isolation of ohydroxyethylthiamin diphosphate from reaction mixtures of this enzyme with pyruvate52 provided important verification of the mechanisms of Eqs. 14-14,14-15. Other decarboxylases produce aldehydes in specialized metabolic pathways indolepyruvate decarboxylase126 in the biosynthesis of the plant hormone indoIe-3-acetate and ben-zoylformate decarboxylase in the mandelate pathway of bacterial metabolism (Chapter 25).1243/127... 

The site should also be involved in the forward reaction (by the principle of microscopic reversibility). An interesting phenomenon in this connection is the stereoselectivity observed in the preferential hydrolysis of L(+)-phosphomandelate by liver and kidney alkaline phosphatases (191). It is not stated whether the selectivity originates in the binding or in the rate of hydrolysis, but whatever the mechanism it seems there must be a direct interaction between mandelate and the enzyme. 

The enol form of mandelic acid (101) has been generated by flash photolysis of phenyldiazoacetic acid in aqueous solution.101 The enol forms by hydration of the intermediate carbene (102). The reaction of chloramine-T (TsNClNa O) with methyl p-tolyl sulfide to give the corresponding sulfimide (103) appears to proceed via a nitrene-transfer mechanism in the presence of copper(I) and a second nitrogen ligand (such as acetonitrile).102... 

D KIE of 6.35 has been observed in the oxidation of a-deuteriomandelic acid by pyri-dinium bromochromate to the corresponding oxo acid. The analysis of the D KIE indicated that the reaction involves a symmetric transition state443. The oxidations of phosphinic and phosphorous acids by pyridinium bromochromate exhibits a substantial primary deuterium KIE444. The hydroxyacids, glycolic, lactic, mandelic and malic acids are oxidized by pyridinium hydrobromide perbromide in acetic acid-water mixtures to oxo acids445. The primary KIE in the oxidation of a-deuteriomandelic acid is kn/kn = 5.07, and it does not exhibit a solvent isotope effect. A mechanism involving hydride ion transfer to the oxidant has been proposed445. 

J. A. Gerlt, J. G. Clifton, G. A. Petsko, and G. L. Kenyon, Mechanism of the reaction catalyzed by mandelate racemase structure and mechanistic properties of the... 

The oxidation of a-hydroxy acids by hexamethylenetetramine-bromine (HABR) is first order with respect to each of the hydroxy acids and HABR. The oxidation of o -deuteriomandelic acid exhibited a kinetic isotope effect of kn/ko = 5.91 at 298 K. The rates of oxidation of the substituted mandelic acids show excellent correlation with Brown s er+ values with negative reaction constants. A mechanism involving transfer of a hydride ion from the acid to the oxidant has been postulated.128... 

There is at present no conclusive evidence for either the two-base mechanism or the single-base mechanism. This will probably be shown by a combination of X-ray crystallography and site-directed mutagenesis study, which showed the mechanism of mandelate racemase reactions.42-441... 

Radical mechanisms account for the stoichiometry for reduction of triketohydrindane by N(5)-ethyldihydroflavin and reduction of triphenylmethyl carbonium ion species by dihydroflavin, (24). One-electron reduction of quinone by N(5)-ethyldihydroflavin also has been shown. These results are not surprising since the substrates and flavin support reasonably stable radical states. Radical species also can be established as intermediates in the oxidation of 9-hydroxyfluorene and methyl mandelate by Flox (Equations 28 and 29, respectively). The reactions of Equations 28 and 29 are facile when carried out in... 

Mechanism of action In order to act, methenamine [meth EN a meen] must decompose at an acidic pH of 5.5 or less in the urine, thus producing formaldehyde, which is toxic to most bacteria (Figure 32.5). The reaction is slow, requiring 3 hours to reach 90% decomposition. Methenamine should not be used in patients with indwelling catheters. Bacterial resistance to formaldehyde does not develop. [Note Methenamine is frequently formulated with a weak acid such as mandelic acid, which lowers the pH of the urine thus aiding decomposition of the drug.]... 

In the following reaction sequence, the chirality of mandelic acid is transmitted to a new hydroxy-acid by a sequence of stereochemically controlled reactions. Give mechanisms for the reactions and state whether each is stereospecific or stereoselective. Offer some rationalization for the creation of new stereogenic centres in the first and second reactions. 

Mandel, B. (1976). Neutralization of poliovirus A hypothesis to explain the mechanism and the one-hit character of the neutralization reaction. Virology 69, 500-510. 

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