Crystallization racemization

The title compound (131)57 has been found to include a wide variety of solvent molecules as guests and form crystalline inclusion crystals.58 In the inclusion crystallizations, racemates or congromerates of 131 were formed depending on the choice of solvent. In the latter case, the inclusion crystals consisting of one enantiomer of 131 were formed preferentially and the optical resolution of 131 could be performed. 

Solubility sol dichloromethane, methanol, benzene insol ether. Form Supplied in white crystals, racemic ( ). 

Table 11. Industrial processes of enantioresolution based on simultaneous crystallization-racemization schemes...

Fig.l4 A combined process consisting of preferential crystallization, racemization and solvent evaporation... 

Experiments were carried out using the D-/L-DOPA (P-(3,4-dihydroxyphenyl) alanine) system with organic acids as the solvents and organic aldehydes as the catalysts for the racemization reaction. Under adequate conditions empirically determined, three rate processes of preferential crystallization, racemization reaction and solvent evaporation proceeded simultaneously at the same rate and the solution composition would then be kept unvaried at the same one as that of initial mixture as shown Figure 14. This process is therefore possible to operate continuously by feeding a conglomerate mixture and by removing the product crystals and the solvents. 

Phenomena of purity drop in racemic resolution by preferential crystallization were surveyed and factors relevant to spontaneous crystallization and their significance were quantitatively summarized. It was empirically concluded that washing of seed crystals would be the best way to prevent such purity drop, although it could not completely suppress the occurrence. With additional experiments on the preparation method of seed crystals, adequate procedures were found. However, recrystallization under these conditions could only prolong the start of purity drop but could not prevent it. A combined process to produce optically pure enantiomers consisting of preferential crystallization, racemization reaction and solvent evaporation steps was proposed. 

I 70% Evapolation Cooling Crystallization Racemic Compound Zone 11... 

To further investigate the effect of DAG composition on MF-TAGs crystallization, racemic and 5 -l,2-speciflc DAGs of palmitic and oleic acid were added to the 2000 MF-TAG at the 0.1 wt% level. These included racemic mixtures of dipalmitin and diolein (PP and OO), sn-, 2 dipalmitin (1,2PP), sn-, 2 diolein (1,200), and sn-l palmitic, 2 oleic (IP, 20). Addition of the DAG standards did not significantly affect the Mettler dropping temperature (P > 0.05) (Table 12). 

Mesotartaric acid crystallizes in plates (IHjO), m.p. 140 C (anhydrous). Very soluble in water. Obtained from the mother-liquors in the preparation of racemic acid or by oxidation of maleic acid. Potassium hydrogen mesotartrale is soluble in water. 

Although Pasteur was unable to provide a structural explanation—that had to wait for van t Hoff and Le Bel a quarter of a century later—he correctly deduced that the enantiomeric quality of the crystals was the result of enantiomeric molecules The rare form of tartanc acid was optically inactive because it contained equal amounts of (+) tartaric acid and (—) tartaric acid It had earlier been called racemic acid (from Latin racemus meaning a bunch of grapes ) a name that subsequently gave rise to our pres ent term for an equal mixture of enantiomers... 

Tartaric acid [526-83-0] (2,3-dihydroxybutanedioic acid, 2,3-dihydroxysuccinic acid), C H O, is a dihydroxy dicarboxyhc acid with two chiral centers. It exists as the dextro- and levorotatory acid the meso form (which is inactive owing to internal compensation), and the racemic mixture (which is commonly known as racemic acid). The commercial product in the United States is the natural, dextrorotatory form, (R-R, R )-tartaric acid (L(+)-tartaric acid) [87-69-4]. This enantiomer occurs in grapes as its acid potassium salt (cream of tartar). In the fermentation of wine (qv), this salt forms deposits in the vats free crystallized tartaric acid was first obtained from such fermentation residues by Scheele in 1769. 

The racemic acid is not a primary product of plant processes but is formed readily from the dextrorotatory acid by heating alone or with strong alkaU or strong acid. The methods by which such racemic compounds can be separated into the optically active modifications were devised by Pasteur and were apphed first to the racemic acid. Racemic acid crystallizes as the dihydrate triclinic prisms. It becomes anhydrous on drying at 110°C... 

Chiral nematic Hquid crystals are sometimes referred to as spontaneously twisted nematics, and hence a special case of the nematic phase. The essential requirement for the chiral nematic stmcture is a chiral center that acts to bias the director of the Hquid crystal with a spontaneous cumulative twist. An ordinary nematic Hquid crystal can be converted into a chiral nematic by adding an optically active compound (4). In many cases the inverse of the pitch is directiy proportional to the molar concentration of the optically active compound. Racemic mixtures (1 1 mixtures of both isomers) of optically active mesogens form nematic rather than chiral nematic phases. Because of their twist encumbrance, chiral nematic Hquid crystals generally are more viscous than nematics (6). 

Crystallization Method. Such methods as mechanical separation, preferential crystallisation, and substitution crystallisation procedures are included in this category. The preferential crystallisation method is the most popular. The general procedure is to inoculate a saturated solution of the racemic mixture with a seed of the desired enantiomer. Resolutions by this method have been reported for histidine (43), glutamic acid (44), DOPA (45), threonine (46), A/-acetyl phenylalanine (47), and others. In the case of glutamic acid, the method had been used for industrial manufacture (48). 

The initial product is recrystalLized and filtered. The filtrate contains a 65% yield (99% ee) of the R-isomer. The crystals ate racemic (32% yield 8%... 

In the United States and some European countries, beet-sugar-waste molasses, or Stefen s waste, has been used as raw material for MSG production. The 2-pyrrohdinone-5-carboxyhc acid [98-79-3] contained ia beet sugar as by-product, is hydrolyzed at weakly alkaline pH, and moderate temperature (eg, pH 10.5—11.5, at 85°C for 2 h) to avoid racemization (14). The pH of the hydrolyzate is adjusted to 3.2 with a mineral acid to precipitate crystals of L-glutamic acid. The L-glutamic acid crystals obtained are transformed to MSG as described above. 

The hydrochloride addition salt of the above reaction product was prepared in customary fashion, that is, by reaction with hydrochloric acid, followed by fractional crystallization from a mixture of alcohol and ether. The two possible racemic forms were obtained thereby. The difficultly soluble racemate had a melting point of 169° to 170°C and the more readily soluble racemate had a boiling point of 145° to 148°C. 

The following is taken from U.S. Patent 3,061,517. Sixteen grams of racemic 3-(2-pYridyl)-3-p-bromophenyl-N,N,-dimethylpropylamine and 9,7 grams of d-phenylsuccinic acid are dissolved in 150 ml of absolute alcohol and kept at room temperature until crystallization is effected. The crystals are filtered, washed with absolute ethyl alcohol, and recrystallized from the same solvent using 5 ml thereof per gram of solid. Three subsequent crystallizations from 80% alcohol give d-3-(2-pYridYl)-3-p-bromophenYl-N,N-dimethylpropYlamine-d-phenylsuccinate MP 152°-154°C 91 (concentration, 1% in dimethylformamide). 

Two mols, for example, 270 grams, of racemic a-methylphenethylamine base are reacted with one mol (150 grams) of d-tartaric acid, thereby forming dl-a-methylphenethylamine d-tartrate, a neutral salt. The neutral salt thus obtained is fully dissolved by the addition of sufficient, say about 1 liter, of absolute ethanol, and heating to about the boiling point. The solution is then allowed to cool to room temperature with occasional stirring to effect crystallization. The crystals are filtered off and will be found to contain a preponderance of the levo enantiomorph. 

From the ethanolic filtrates upon addition of 130 ml of about 4 N ethanolic hydrochloric acid and cooiing, there was obtained 55 grams of white crystals melting at 176.5° to 178°C and a second crop of 10 grams melting at 171.5° to 174.5°C. This is the di racemate dihydrochloride. 

At present moment, no generally feasible method exists for the large-scale production of optically pure products. Although for the separation of virtually every racemic mixture an analytical method is available (gas chromatography, liquid chromatography or capillary electrophoresis), this is not the case for the separation of racemic mixtures on an industrial scale. The most widely applied method for the separation of racemic mixtures is diastereomeric salt crystallization [1]. However, this usually requires many steps, making the process complicated and inducing considerable losses of valuable product. In order to avoid the problems associated with diastereomeric salt crystallization, membrane-based processes may be considered as a viable alternative. 

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