Mandelic acids, oxidation

Analyses of alloys or ores for hafnium by plasma emission atomic absorption spectroscopy, optical emission spectroscopy (qv), mass spectrometry (qv), x-ray spectroscopy (see X-ray technology), and neutron activation are possible without prior separation of hafnium (19). Alternatively, the combined hafnium and zirconium content can be separated from the sample by fusing the sample with sodium hydroxide, separating silica if present, and precipitating with mandelic acid from a dilute hydrochloric acid solution (20). The precipitate is ignited to oxide which is analy2ed by x-ray or emission spectroscopy to determine the relative proportion of each oxide. 

The (ZZ-ephedrine was resolved into its components by the use of d-and Z-mandelic acids. In 1921 Neuberg and Hirsch showed that benz-aldehyde was reduced by yeast, fermenting in suerose or glueose solution to benzyl aleohol and a phenylpropanolone, which proved to be Z-Ph. CHOH. CO. CH3. This ean be simultaneously, or consecutively, eondensed with methylamine and then eonverted to Z-ephedrine by reduction, e.g., with aluminium amalgam in moist ether, or by hydrogen in presenee of platinic oxide as catalyst (Knoll, Hildebrant and Klavehn ). 

Ethyl benzoylformate has been prepared by the direct esterification of the acid 1 and by the action of oxides of nitrogen on an alcoholic suspension of indigo.2 The acid has been prepared by many different reactions but the most practical are the hydrolysis of benzoyl cyanide,3 the oxidation of acetophenone 4 and the oxidation of mandelic acid.5... 

Procedure. The solution (20-30 mL) may contain 0.05-0.2 g Zr, and should possess a hydrochloric acid content of about 20 per cent by volume. Add 50 mL of 16 per cent aqueous mandelic acid solution and dilute to lOOmL. Raise the temperature slowly to 85 °C and maintain this temperature for 20 minutes. Filter off the resulting precipitate through a quantitative filter paper, wash it with a hot solution containing 2 per cent hydrochloric acid and 5 per cent mandelic acid. Ignite the filter and precipitate to the oxide in the usual manner a temperature of 900-1000 °C is satisfactory. Weigh as Zr02. 

Bakore and Narain obtained the following kinetics for the oxidations by chromic acid of lactic, malic and mandelic acids... 

Kemp and Waters found a primary kinetic isotope effect of 8.7 for oxidation of C-deuterated mandelic acid and noted a large difference in rate between the oxidations of mandelic acid k at 24.4 °C = 1.7 l.mole . sec ) and a-hydroxy-isobutyric acid ( 2 at 24.4 °C = 5.6 x 10 l.mole . sec ) — a difference not reproduced for the oxidation of these compounds by the one-equivalent reagent, manganic sulphate. The various data are fully in accord with a Westheimer-type mechanism, viz. 

Fig. I. Isotope effect for acid permanganate oxidation of mandelic acid. Temperature = 26.2 °C [MnO -] = 1.4x10- M [H SO ] = 1.69 M.

The kinetics of the initial stages of the oxidation of some a-hydroxy-carboxylic such as lactic, malic and mandelic acids by chromic acid have been studied by Bakore and Narain . The initial reaction resembles the oxidation of a secondary alcohol to ketone. The authors concluded that the rate determining step involves C-H bond rupture at the a-carbon atom. The rate of oxidation of these acids is reduced to one-half by the addition of manganous ions, when the concentration of the latter is commensurable with that of the acids. 

Benzoylformic acid can be prepared by the oxidation of acetophenone with potassium permanganate in alkaline solution,1 by the oxidation of mandelic acid with potassium perman-... 

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]. 

TABLE 15. The activation parameters for the oxidation of mandelic acid" by Pb(OAc)4 in benzene and in benzene-pyridine... 

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. 

FIGURE 5. The transition state for the pyridine-catalysed oxidation of mandelic acid with lead tetraacetate... 

Toniolo reported the carbonylation of aromatic aldehydes containing electron-donating substituents with a Pd/PPh3 catalyst system in the presence of HC1 to give phenylacetic acid derivatives [64]. No activity was observed in the absence of PPI13 or HC1, and high yields could be achieved with alkanols as solvent (e.g., EtOH). It is believed that the mechanism involves HC1 addition to the aldehyde, with the resultant chlorohydrin being subject to oxidative addition to Pd, CO insertion, and alcoholysis. Upon Cl -o- OR substitution with the formed mandelic acid derivative, a second carbonylation takes place,... 

Fig. 11.12. Metabolic scheme for reaction of benzyl cyanide (11.80) to mandelonitrile (11.81) as a crossroads to benzoic acid (11.83) via oxidative denitrilation, and to mandelic acid (11.82) as a minor metabolite produced by hydrolysis of the CN group [118][122]...

There are a few data in the literature to suggest that the hydrolysis of aliphatic nitriles occurs in mammals, but only as a minor or even undetectable pathway in competition with oxidative denitrilation. For example, benzyl cyanide (11.80, Fig. 11.12) undergoes cytochrome P450 catalyzed hydroxy-lation to mandelonitrile (11.81), from which cyanide and benzaldehyde are produced, the latter being oxidized to benzoic acid (11.83) [118]. However, a careful metabolic study of mandelonitrile has shown that, in the rat, this pathway accounts for ca. 90% and not 100% of the dose [122], Only ca. 10% of orally administered benzyl cyanide was converted to mandelic acid (11.82, Fig. 11.12) by hydrolysis of the CN group. 

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]. 

As shown in Eq. (9), optically pure (i )-mandelic acid was obtained in 47% yield, as well as 44% of benzoylformic acid. Benzoic acid was also isolated, although in very low yield, probably as a result of oxidative decarboxylation of benzoylformic acid. 

The present reaction was proven to occur even when the microorganism had been grown on peptone as the sole carbon source. These results lead to the conclusion that this enzyme system is produced constitutively. In the case of man-delate-pathway enzymes in Pseudomonas putida, (S)-mandelate dehydrogenase was shown to be produced in the presence of an inducer (mandelic acid or benzoylformic acid) [5]. Thus, the expression of the present oxidizing enzyme of A. bronchisepticus is different from that of R putida. 

J )-Mandelic acid 3 is a useful chiral synthon for the production of pharmaceuticals such as semi-synthetic penecillins, cephalosporins and antiobesity agents and many methods have been reported for the preparation of the optically pure material. A method to deracemize the racemate which is readily available on a large scale was developed by Ohta et al. using a combination of two biotransformations. The method consists of enantioselective oxidation of (S)-... 

Cerium(IV) oxidations of organic substrates are often catalysed by transition metal ions. The oxidation of formaldehyde to formic acid by cerium(IV) has been shown to be catalysed by iridium(III). The observed kinetics can be explained in terms of an outer-sphere association of the oxidant, substrate, and catalyst in a pre-equilibrium, followed by electron transfer, to generate Ce "(S)Ir", where S is the hydrated form of formaldehyde H2C(OH)2- This is followed by electron transfer from S to Ir(IV) and loss of H+ to generate the H2C(0H)0 radical, which is then oxidized by Ce(IV) in a fast step to the products. Ir(III) catalyses the A -bromobenzamide oxidation of mandelic acid and A -bromosuccinimide oxidation of cycloheptanol in acidic solutions. ... 

Scheme 6.27 Typical P-alkoxy alcohols obtained from the highly regioselective alcoholysis of styrene oxides catalyzed by thiourea 9 and mandelic acid 20 in a cooperative organocatalytic system.

Under optimized conditions regarding the choice of Br0nsted acid (mandelic acid 20), stoichiometry (1 1 ratio 9 and mandelic acid 20), solvent (the respective alcohol neat conditions), temperature (rt or 50°C), and catalyst loading (lmol% 9 and lmol% mandelic acid 20) electron-rich and electron-deficient styrene oxides underwent alcoholysis with simple aliphatic, stericaUy demanding as well as unsaturated and acid-labile alcohols. The completely regioselective (>99%) alcoholysis was reported to produce the corresponding P-aUcoxy alcohols 1-10 in moderate (41%) to good (89%) yields without noticeable decomposition or polymerization reactions of acid-labile substrates (Scheme 6.27). Notably, aU uncatalyzed reference experiments showed no conversion even after two weeks under otherwise identical conditions. 

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