Acid-catalyzed racemization

In contrast to enzyme- and base-catalyzed DKRs, there are only a few reports of enzyme- and acid-catalyzed DKRs. A plausible explanation is that deactivation of the enzyme can occur under acidic conditions. Also, decomposition of the substrate has 

---

H Frank, W Woiwode, G Nicholson, E Bayer. Determination of the rate of acidic catalyzed racemization of protein amino acids. Liebigs Ann Chem 354, 1981. 

More rigorous evidence supporting the inversion in the transesteiifi-cation of sulfinates was provided by kinetic measurements in which the rate of the acid-catalyzed racemization of (+)-methyl p-toluene-sulflnate 65 in methanol was compared with that of isotopic methoxy-methoxy exchange under exactly the same conditions. 

The beginning of the mechanism forthe acid-catalyzed racemization. 

Compared to the chemo-catalyzed kinetic resolution of alcohols, there are few reports of similar reactions for amines. Building on other work, one elegant example from Berkessel uses bifunctional organocatalysts to enantioselectively hydrolyze a racemic azlactone, and the dynamic kinetic resolution (DKR) is achieved by in-situ acid-catalyzed racemization of the azlactone under mild conditions to give product N-acylarnino esters in, for example, 72% ee and 96% conversion with phenylalanine [6]. 

The small amounts of D-enantiomers in the controls may be attributed to (a) racemization occurring in the caimer-cial preparation of the proteins, (b) acid-catalyzed racemization during the hydrolysis step of our analysis, or both factors. 

P cm 21.8 Show in detail how the enolization mechanism accounts for the following facts (a) the rate constants for acid-catalyzed hydrogen-deuterium exchange and bromination of acetone are identical (b) the rate constants for acid-catalyzed racemization and iodination of phenyl rec- tyl ketone are identical. 

In a comparison of the rates of acid-catalyzed racemization of and lsO exchange in chiral 1-phenylethanol, it was concluded that the departing -OH2 group shields that side of the benzyl carbocation from attack by other solvent molecules.26 The lifetime of the /i-phenylethyl carbocation, which should be similar to that of the fl-hydroxy benzylic carbocation formed in the acid-catalyzed hydrolysis of styrene oxide 32, is therefore too short to allow complete solvent equilibration about the carbocation. 

SCHEME 6.12 Mechanisms of acid-catalyzed racemization of 1-substituted THPC and major by-product d. 

L. C. Schroeter and T. Higuchi, A kinetic study of acid-catalyzed racemization of epinephrine, J. Am. Pharm. Assoc. 47, 426-430 (1958). 

The acid-catalyzed racemization, cis-trans isomerization and oxygen... 

Pretreatment of rats with pentachlorophenol, an inhibitor of sulfation and perhaps of other conjugation reactions, led to a marked decrease in the inversion, suggesting that this chiral inversion of stiripentol is at least in part mediated by an enantioselective conjugation mechanism [160]. Further studies examining the influence of the route of administration demonstrated that this inversion phenomenon was not observed when stiripentol was administered intravenously or intraperitoneally (Fig. 17). Finally, in vitro experiments suggest that stiripentol may undergo partial acid-catalyzed racemization in the rat stomach before absorption from the G1 tract [161]. 

The racemization of chiral tertiary phosphines in many cases is an interesting route to unavailable enantiomers [15]. For example, the thermodynamically controlled pyramidal inversion of tertiary phosphines is useful synthetically. The facile acid-catalyzed racemization of secondary phosphines involves formation of an... 

---