Of mandelic acids

It is important to mix the mandelonitrile with hydrochloric acid immediately it has been separated from the water. Standing results in rapid conversion to the acetal of benzaldehyde and mandelonitrile C(H,CH[OCH(CN)C H,] and/or the iso-nitrile the yield of mandelic acid will, in consequence, be reduced. 

The mandelonitrile should be mixed with hydrochloric acid as soon as it is separated from the water. Wood and Lilley (7. Ghent. Soc. 127, 95 (1925)) have found that it undergoes rapid rearrangement to the isonitrilc. Hence if it is allowed to stand long before the hydrolysis, the yield of mandelic acid is reduced. 

The entire amount of the ammonium chloride-mandelic acid mixture may be boiled with the benzene but this gives a supersaturated solution of the acid in the benzene and much difficulty is met in the filtration. The solubility of mandelic acid in hot benzene is approximately i g. in 50 cc. 

A. Ethyl mandelale. To 152 g. (1.0 mole) of mandelic acid and 200 ml. of absolute ethanol in a 1-1. round-bottomed flask f< ui[)ped with a reflux condenser, there is added 100 ml. of abso-liile ethanol containing about 10 g. of anhydrous hydrogen chlo-lidc (Note 1). The solution is heated under reflux on a steam bath for 5 hours, then poured into 11. of ice water in a 3-1. beaker (Note 2). A saturated aqueous solution of sodium bicarbonate is added until the mixture is faintly alkaline (Note 3). It is I lien extracted with two 300-ml. portions of ether in a 2-1. separatory funnel. The ether extracts are washed with a 200-ml. por-lioii of water and dried over 50 g. of anhydrous sodium sulfate. The dried ether solution is concentrated by distillation from a 25()-ml. Claisen flask, and the residue is distilled at reduced pressure. I here is obtained 147-154 g. (82-86%) of ethyl mandel-iilc, l).p. 144-145°/16 mm. The ester may crystallize upon standing for a prolonged period. It melts at 30.5-31.5°. 

I hc objective of the hydrochloric acid treatment is to icmovc small amounts of mandelic acid from the product. If... 

Homatropine (mandelyltropine) being a useful mydriatic it is surprising that of nine esters of mandelic acid tried, none showed mydriatic activity though three were local anaesthetics, two of them being described as good. Only one of the tropic acid esters tried showed local anaesthetic action and that was poor. ... 

It is worth noting that the extractive process can be performed continuously. Thus, the separation of ( )-mandelic acid into its enantiomers was achieved with a liquid particle extractor described by Abe et al. [190-192] using A-docecyl-L-proline as chiral selector. 

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... 

The enantiomerically pure (/ )- and (iS )-ketones are prepared from the corresponding enantiomer of mandelic acid by catalytic hydrogenation, treatment of the resulting hexahydroman-delic acid with ethyllithium, and subsequent introduction of the silyl protecting group33. 

The pH of a 0.010 M aqueous solution of mandelic acid, C6H5CH(OH)COOH, an antiseptic, is 2.95. What is the K, of mandelic acid ... 

Faber and coworkers have reported a DKR of mandelic acid by using a lipase-catalyzed O-acylation followed by a racemization catalyzed by mandelate racemase. However, these two transformations do not take place simultaneously in the same pot. When the sequence was repeated four times, (S)-O-acetylmandelic acid was obtained in 80% isolated yield and >98% ee [57]. 

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... 

The a carbon of mandelic acid is sp hybridized. The corresponding carbons of both a-phenylglycidic acid, 49, and the carbanion intermediate 48 are neither sp hybridized nor sp hybridized, but presumably between these two extremes. It is therefore possible that the a-phenylglycidic acid is restricted to a conformation which resembles a transition state in the racemization process, a transition state which would have much of the character of the intermediate 48, and for which the enzyme would presumably have a high affinity (1). 

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.

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-... 

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... 

The submitters report that when 1 kg. of acetophenone is used yields of 0.98-1.06 kg. of mandelic acid are obtained. 

The use of dissociable diastereomers for enantiomer resolution may be illustrated by the case where racemic mandelic acid is resolved using en-antiomerically pure a-methylbenzylamine. The n and p salts of a-methylbenzyl-amine mandelate have aqueous solubilities of 49.1 and 180 g/L, respectively, at 25°C [153], A more recent example, which focuses on the crystallographic origin of the solubility differences, is provided by the resolution of ( )-mandelic acid with (-)-ephedrine in water or methanol solution [154], In general, the relative solubilities of the n and p salt pairs are strongly influenced by the choice of solvent medium and temperature, which provide considerable flexiblity in optimizing the crystallization conditions and the efficiency of resolution. This process may be facilitated by the development of a full solubility phase diagram. 

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... 

The small Hammett p value of +0.16 observed for a series of related meta- and para-substituted mandelic acids indicates that there is a very small negative charge development on the benzyl carbon in the transition state of the rate-determining step of the pyridine catalysed oxidation of mandelic acid. The large positive AS value (+24 e.u./mol) found for the catalysed reaction led Banetjee and coworkers to conclude that the transition state (Figure 5) is product-like . This conclusion is consistent with the small f n/f D that is observed in this reaction164. The Pb—O bond is shown to rupture in a heterolytic fashion because Partch and Monthony185 have demonstrated that pyridine diverts the reaction from a homolytic to a heterolytic mechanism. 

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

Early synthetic spasmolytics resembled atropine closely, e.g. homatropine (the ester of mandelic acid and tropine (IV)). It may be noted that acetylcholine itself is an ester of a quaternary aminoalcohol and a short-chain organic acid. If the length of the chain is increased, acetylcholine activity decreases and com-... 

Xu MH, Lin J, Hu QS et al (2002) Fluorescent sensors for the enantioselective recognition of mandelic acid signal amplification by dendritic branching. J Am Chem Soc 124 ... 

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