Mandelic acid mixture, racemic

A quasi-racemate or pseudo-racemate is a true racemate like molecular compound formed between optical antipode of different (but related) compounds. The quasi-racemate also has a melting point ciin c resembling the curve of a true racemate but with quasi-racemic compounds the curves are unsymmetrical, because the melting points of the components are different as shown in Fig. (9.3). The curve A represents the melting point of a true-racemate formed by mixing (+) mandelic acid XXII and (-) hexahydromandelic acid XXIII while B represents that of a mixture of (+) XXII and (+) hexa hydro-mandelic acid XXIII. 

To elucidate the metabolic pathway of phenylmalonic acid, the incubation broth of A. bronchisepticus on phenylmalonic acid was examined at the early stage of cultivation. After a one-day incubation period, phenylmalonic acid was recovered in 80% yield. It is worthy of note that the supposed intermediate, mandelic acid, was obtained in 1.4% yield, as shown in Eq. (8). The absolute configuration of this oxidation product was revealed to be S. After 2 days, no metabolite was recovered from the broth. It is highly probable that the intermediary mandelic acid is further oxidized via benzoylformic acid. As the isolated mandelic acid is optically active, the enzyme responsible for the oxidation of the acid is assumed to be S-specific. If this assumption is correct, the enzyme should leave the intact l -enantiomer behind when a racemic mixture of mandelic acid is subjected to the reaction. This expectation was nicely realized by adding the racemate of mandelic acid to a suspension of A. bronchisepticus after a 4-day incubation [4]. 

When the resulting mixture of benzoylformic acid and (i )-mandelic acid was treated with a cell free extract of Streptomyces faecalis IFO 12964 in the presence of NADH,the keto acid can be effectively reduced to (i )-mandelic acid (Fig. 1). Fortunately the presence of A. bronchisepticus and its metabolite had no influence on the reduction of the keto acid. The regeneration of NADH was nicely achieved by coupling the reaction with reduction by formic acid with the aid of formate dehydrogenase. As a whole, the total conversion of racemic mandelic acid to the i -enantiomer proceeded with very high chemical and optical yields. The method is very simple and can be performed in a one-pot procedure [6]. 

Sublimation. Such effects can also be seen in solid-gas interphase. Scheme 30 shows the consequences of fractional sublimation of partially resolved L-mandelic acid (47). The optical purity could be enhanced or reduced, depending on the optical purity of the starting material. Since the eutectic point of mandelic acid is obtained with about a 75 25 enantiomer ratio, such a mixture is more readily sublimed than the racemate or conglomerate. Scheme 30 gives other examples of optical enrichment by sublimation. Phenyl 1-phenyl-1-propyl sulfide in 6% ee affords the sublimed compound in 74% ee, but the residue is... 

The principles outlined above were allied by Marckwald and McKenzie 18 for the partial resolution of a racemic acid with an active alcohol. Thus When df-mandelic acid was heated with less than one equivalent of 1-menthol, the resulting ester contained somewhat more J-menthyl-d-mandelate than f-menthyl-L-mandelate and the unesterified acid contained a corresponding excess of i-mandelic acid. Also, when a mixture of equal amounts of the two diastereoisomeric esters was partially hydrolyzed, the regenerated acid and that still combined in the residual ester contained unequal amounts of the two antipodes. The process has been extended to the resolution of acids and amines through the formation and hydrolysis of amides.89... 

A separation of the racemic mixture of chiral zirconocene compounds into the optically active pure enantiomers is performed using 0-acetyl-(/ )-mandelic acid as chiral auxiliary (Structure 28). Using this enantiomerically pure metallocene in oligomerization experiments confirms the mechanistic hypothesis of stereospecificity predicting the topicity of insertion [69]. 

Biphenyl-bridged bis-Cp titanocene dichloride and dimethyl complexes have been synthesized, and the kinetic resolution of the racemic final mixture of the products has been carried out. A mixture of diastereomers is obtained by treatment of the dimethyl compound with O-acetyl-mandelic acid, while enantiomerically pure products result in the reaction of the dichloro derivative with (i )-binaphthol and 1 equiv. of LiBun (Scheme 661).1050... 

The ephedrine synthesis described by Manske and Johnson (74) and by Skita and Keil (77) in 1929 is founded on a different reaction. If a mixture of o -phenylpropane-a,/S-dione and methylamine, in absolute alcohol is hydrogenated catalytically in the presence of platinum oxide (Manske) or colloidal platinum (Skita), dl-ephedrine, with a little dJr -ephedrine is obtained. The reaction has been further elaborated by Coles, Manske, and Johnson (76), by Skita, Keil and coworkers (78, 79, 262, 263) and by Couturier (265). Manske and Johnson (75) synthesized some ephedrine homologs and resolved racemic ephedrine by means of d-and f-mandelic acid. The pure I form of this acid is prepared easily with the aid of natural ephedrine, as confirmed by Jarowski and Hartung (268). 

Chiral (L-, or D-form) separation from an optical isomer is essential for its commercial use. Preferential crystallization is often used as a separation technique of a chiral from optic isomers, but it is invalid when racemic compounds are formed, as it is in the production of mandelic acid by chemical reaction. However, by using high pressure crystallization, it becomes possible to separate a chiral from Sie mixture in the region of racemic conq)ound formation under atmospheric pressure, when the eutectic conq)ositions shift toward the racemic composition under high pressure. 

Moran and coworkers also combined urea and amide moieties, in this case, in chiral receptors that are recognized chiral hydroxycarboxylates such as lactic or man-delic acid. Receptor 48 combines a hA-chromenylurea with a spirobifluorenone linker in a macrocyclic stmcture and is capable of resolving a racemic mixture of the tetramethylainmonium salt of mandelic acid by thin-layer chromatography. Proton NMR titrations in DMSO-dg gave association constants for lactic acid [(R)-lactic acid K -... 

The diastereomers can be separated by crystallisation. While the marketed products contain the racemic mixture of (RJi)-and (S,S)-enantiomers, their separation may be possible using tartaric acid, its 0,0 -dibenzoyl or 0,0 -di-p-toluoyl derivatives, or mandelic acid. [114,115]... 

Figure 6.4 shows some chemical examples of this. If a racemic mixture of 2-aminobutane is allowed to react with an enantiomerically pure sample of mandelic acid, the two amides that are produced are diastereomers. The two diastereomers can be separated by any conventional method (such as crystallization or chromatography), and subsequent hydrolysis of a pure diastereomer gives enantiomerically pure 2-aminobutane. 

In the search for an improved method for resolution, acetalization of racemic spiroketone with (R)-mandelic acid under catalysis by Sc(OTf)3 (2.2mol%) furnished a chromatographically separable mixture of diastereomers. After hydrolysis, enatiomerically pure spirocyclic intermediates were obtained [154]. 

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