Mandelic acid indications

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. 

In our laboratory we have been investigating the mechanism of action of mandelic acid racemase from Pseudomonas putida (101), which catalyzes the racemization of either D or L-mandelic acid, 47. Evidence from kinetic and isotopic exchange studies indicates that the racemization proceeds via an... 

In the flask are placed 240 g. (2 moles) of acetophenone and 1 1. of glacial acetic acid. The thermometer is adjusted so that it extends considerably below the surface of the solution, and chlorine is admitted at such a rate that the temperature does not exceed 60° (Note 1). Chlorination is continued until an excess of the halogen has been absorbed. This requires about five hours completion of the reaction is indicated by the development of a yellow color. The reaction mixture is poured over 6 1. of crushed ice in a 2-gal. jar. The mixture is stirred several times (Note 2) and allowed to stand until the ice has melted. The dichloroacetophenone, which separates as a heavy lachrymatory oil, is removed. The yield is 340-370 g. (90-97 per cent of the theoretical amount). This product, containing only a few per cent of water and acetic acid, is pure enough for the preparation of mandelic acid. It may be purified by adding about 100 cc. of benzene, removing the... 

However, the formation of intermediate 14 requires at least two steps, (i) a proton transfer and (ii) the formation of the cyclic intermediate. If formation of the intermediate, 14, is rate-determining, the carboxy hydrogen must be lost in a pre-equilibrium step because no deuterium kinetic isotope effect is observed for this reaction (Scheme 34). Alternatively, the mandelic acid could displace an acetate ligand in a slow step and the proton could be transferred to the acetate ion in a fast, subsequent step (Scheme 35). Unfortunately, the results do not indicate which step in the formation of the cyclic intermediate, 14, is rate-determining. 

None of the chemical methods (e.g., mandelic acid or methanol test) gives a perfect indication of weather resistance. Most of them only measure partial qualities of the photochemical reactivity [1.58]. 

As would be anticipated for a carboxylic acid, mandelic acid is known to exhibit a pH strong dependence in its aqueous solubility. This pH dependence was calculated using the solubility module of the ACD PhysChem computational program (version 6.0, Advanced Chemistry Development, Toronto, Canada), and these results are plotted in Figure 1. The results indicate that mandelic acid will be freely soluble in basic solution, which would be interpreted to imply that the sodium salt would be freely soluble as well. 

Even more interesting is the addition of the (.S )-cnantiomcr of 2-amino-1-butanol, which itself forms a salt with (R)-mandelic acid. This salt has almost inhnite solubility. With this additive, the resolution of alaninol with (W)-mandelic acid results in the crystallization of an almost diastereoiso-merically pure salt, without incorporation of 2-amino-l-butanol. On use of this method enantiopure (R)-alaninol can be obtained after an additional recrystallization, without the need to separate the alaninol from the 2-amino-l-butanol. We call this procedure reverse Dutch Resolution, to indicate that the family mix remains in solution. Most likely in this case stereoselective nucleation inhibition plays a role by suppressing the nucleation of the (.S )-alaninol-(A )-mandclic acid diastereoisomer. 

The chirality of 22 was observed by diastereomeric encapsulation of R-mandelic acid. The observation of two diastereomers in the H-NMR evidenced that the racemization of P- 22 to M- 22, which requires the cleavage of at least two Pd - N bonds, did not take place on the NMR timescale. Notably, diastereomers were not observed when racemic mandelic acid was employed, indicating a rapid guest exchange of R- and S-mandelic acid on the NMR timescale. Modest chiral induction was obtained in a 3 2 diastereomeric ratio upon encapsulation of the chiral guest (S)-l-acetoxyethylbenzene. 

An example of tests for chirality is provided by studies of mandelic acid crystals (Figure 14.23). These crystals are polar and noncentrosymmetric, space group T 2i, but no hemihedral faees develop and therefore there are no external indications that allow one to distinguish the two ends of its polar axis b. Other techniques have to be used. In order to differentiate between the two ends of the hexagonally-shaped crystals (which were shown, by X-ray diffraction studies to have the c axis along the unique axis of the crystal). The directions of the a and b axes with respect to crystal habit were also established by X-ray diffraction studies. 

Ethyl benzene distributes to the adipose tissues. It is metabolized to mandelic acid (64%) and phenyl-glyoxylic acid (25%). The percentage of metabolites may vary according to the route of exposure with mandelic acid formation being favored with inhalation. The primary route of excretion is via the urine. Experimental evidence indicates that the percutaneous absorption rate of ethyl benzene is 37 pgcm... 

The oxidation of the p-chloro derivative in perchlorate medium does indicate the existence of a stable precursor complex. Both the slope and intercept of the l/fc bs versus 1 /[subst] plot exhibit a dependence on acidity, implying the involvement of a protonated species either in the formation of the precursor complex or in the electron transfer reaction. The relative rates for the oxidation of the substituted mandelic acids are CH3O- NO2 > -Cl = -CH3 > -H. The oxidation of the p-methoxy derivative is characterized by 50% lower AH and negative AS, suggesting a different mechanism operating for the oxidation of this substrate. 

These results indicate that the mother liquor of saturated mandelic acid solution may coexist with both L-form crystals and the racemic crystals, when feed C was pressurized in the vessel for crystallization. The coexistence of the chiral and the racemic indicates that the conqx)sition of the solution was the eutectic. So, the solubility and the L-form connposition of mandelic acid in the mother liquor represents the eutectic points of mandelic acid under pressure (see the arrow from point C in Fig.5). 

Fig. 3 Quininium (l )-mandelate with oxygen atoms (red, indicated with 0 ) and nitrogen atoms (magenta, indicated with N ). Mandelic acid is the entity containing 02 6 and 027. (View this art in color at www.dekker.com.)...

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. 

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