A-Methylmandelic acid

Problem 21.6 (a) Suggest a mechanism for the base-catalyzed racemization of the optically active ester, ethyl mandelate, C6H3CHOHCOOC2H5. (b) How do you account for the fact that optically active mandelic acid undergoes racemization in base much more slowly than the ester (Hint See Sec. 18.20.) (c) What would you predict about the rate of base-catalyzed racemization of a-methylmandelic acid, C6HsC(CH3)(OH)COOH ... 

Atrolactic acid is also addressed as 2-hydroxy-2-phenylpropionic acid or a-methylmandelic acid and shown in Figure 1.15. The configuration of atrolactic acid and methods of synthesis and reactions have been described (42). 

Mandelic acid a-Methylmandelic acid a-Cyciopentyimandeiic acid... 

C6H5, —OH, or —H at the chiral centre of the mandelic acid for a methyl group we repeated our tests with DL-a-phenylethanol (III), and DL-2-phenylpropionic acid (VI) (eluant methanol) and with a-methyl-DL-mandelic acid (IV) and DL-lactic acid (V) (eluant methanol or water). Only in the case of a-methylmandelic acid (IV) (eluant methanol) was a weak resolution noticed (maximal 0.5%, optical total enrichment 0.1%). 

The absolute configuration of primary amines containing the chiral centre at the a-position has been correlated with the relative H shifts (upheld or downfield) observed in the NMR spectra of the amides formed with (5 )-0-methylmandelic acid, PhCH(0Me)C02H316. 

About 20 different carboxylic acids have been tested by Dale and Mosher for comparison with MTPA 5. Some of them (mandelic and O-methylmandelic acid) have been partly described in the previous section together with MTPA. Some new and important acids have been added since. Figure 1 shows MPTA and a number of carboxylic acids which can be used in a similar way to Mosher s reagent. 

Various oxidations. An a-oxidase from peas mediates the enantioselective oxidation of hydroxylation of carboxylic acids [to give products of (/f)-configuration]. On the other hand, a-hydroxy acids undergo oxidative decarboxylation, and the process renders methylmandelate as a benzoyl anion equivalent. ... 

The deprotonation of 247 in hexane by t-BuLi/excess 248 at -78°C for 1 h gave the best results (E)-O-methylmandelic acid (250) with greater than 95% ee and the hydroxy ethers (several examples) with high anfi-selectivity, and as well, very good ee. On the basis of control experiments, the authors assume a dynamic thermodynamic resolution as the origin. This mechanism impHes an essentially complete conversion to one epimer 249 of unknown configuration at -78 °C and its stereospecific carbonyl addition. 

The effects of added M + ions, M = Mn, Ni, Cu, or Zn, on rates of aquation and of racemization of [Cr(ox)3] are attributed to their effects on the hydration shell around the complex ion rather than to simple ion-pairing. The markedly different effects of different alkali-metal cations on base hydrolysis of the [Co(NH3)5Br] + cation" and on the cerium(rv) oxidation of methylmandelic acid " may have a similar explanation. Non-electrostatic factors are also important in salt effects on the formate plus chromate and iodide plus bromate reactions." Observed salt effects on rates of hydrolysis of a variety of anions such as [BFi]-, [SiFe] , and [S20 ] ... 

In the reciprocal experiment, the chiral alcohol methylmandelate, (13), is used as a CDA for the study of the enantiomeric purity of acids. Esterification is effected without racemisation with N, N-dicyclohexylcarbodiimide in the presence of the acyl transfer catalyst,... 

Reaction of diclilorocarbene with substituted benzaldehydes affords the corresponding mandelic acids. It might be supposed that this reaction does not involve dichlorocarben but rather its precursor, the trichloromethide ion. Nucleophilic addition of the trichlorc methyl anion to benzaldehyde should yield phenyl trichloromethyl carbinol. In control experiments, however, phenyl trichloromethyl carbinol was not hydrolyzed to mandelic acid under the reaction conditions. It was suggested that the reaction involves dichlorocarbene addition to the benzaldehyde carbonyl to form 2,2-dichloro-3-phenyloxirane followed by rearrangement to a-chlorophenylacetyl chloride which then is hydrolyzed as shown in equation 3.16. Mandelic, 4-methylmandelic, and 4-methoxymandelic acids were produced in 75%, 80%, and 80% yields, respectively [24]. 

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