Sodium ammonium tartarate crystals

Figure 1.1 The stereostructures of(a) quartz and (b) sodium ammonium tartarate crystals.

Later, Pasteur 15) had arrived at the general stereochemical criterion for a chiral or dissymmetric molecular structure. Thus, the specific rotations of the two sets of sodium ammonium tartrate crystals in solution, isolated from the racemic mixture by hand-picking, were equal in magnitude and opposite in sign, from which Pasteur inferred that enantiomorphism of the dextro- and laevorotatory crystals is reproduced in the microscopic stereochemistry of the (+)- and (—)-tartaric acid molecules. The term dissymmetry or chirality is used when there is no superimposability between the two enantiomers, as seen in Sect. 2.1. 

Splitting Racemic Compounds.—The methods by which racemic compounds may be split into their optically active components are several. The three methods used were all originated by Pasteur. The first method has been referred to and consists of the mechanical separation of the two oppositely hemi-hedral forms in which the salts of a racemic compound crystallize. This method is especially applicable in the case of tartaric acid when the sodium-ammonium salt is used. The crystallization and separation must be carried out under definite conditions. If the racemic acid salt is crystallized below 28° the two forms of crystals are produced and a separation can be accomplished. If, however, the crystallization takes place above 28° the two forms of crystals are not produced but the sodium-ammonium racemate crystallizes in unseparable crystals of one form. That is, above 28° the sodium-ammonium racemate crystallizes as such, while, below 28° the racemate splits into its two isomeric components and equal amouts of the sodium-ammonium dextro tartrate and the sodium-ammonium levo tartrate are formed. The second method for the splitting of a racemic compound into its optically active components consists of the formation of the cinchonine, strychnine, or other similar alkaloid salts. When the cinchonine salt of racemic acid is formed it splits into the... 

The sodium ammonium salt crystallized from racemic tartaric acid has been found to crystallize in the orthorhombic P2j2j2j space group and contains four molecules in the unit cell [28]. This particular crystal class is noncentrosymmetric, and as a result individual crystals will be optically active. In fact, efficient growth of this tartrate salt only takes place if all the (i ,i )-tartrate molecules crystallize in one ensemble of crystals, and if all the (, /S)-tartrate molecules crystallize in another ensemble. When formed below a temperature of 26°C, the preferred molecular packing does not permit the intermingling of the enantiomers to yield a true racemic crystal. The crystallization of sodium ammonium tartrate below 26°C results in a spontaneous resolution of the substance into physically separable enantiomers. Interestingly, a different polymorph forms above 26°C that requires a completely different packing pattern that allows for the formation of a racemic modification of sodium ammonium tartrate. 

Examining crystals of racemic sodium ammonium tartarate under a magnifying glass, Pasteur found that they came in twin forms One half had a particular crystal face oriented to the left and the other half to the right. He was able to sort them with a magnifying glass and tweezers. (As it turns out sodium ammonium tartarate is one of the few chiral salts that crystallize into mirror-image crystals that can be sorted by hand.)... 

When the same experiment, namely crystallization of the non-racemic enantiomeric mixture of sodium-ammonium tartarate, was effectuated at a temperature above 27 °C, the racemic fraction (the racemate) crystallized, because the sodium-ammonium salts of racemic tartaric acid have a racemate like behaviour at around 30 °C. In this case the derivative of tartaric acid (the mixed salt) was suitable for fractioned enantiomeric separation, but only at a lower temperature than 27 °C (influence of temperature). 

Occasionally an optically inactive sample of tartaric acid was obtained Pasteur noticed that the sodium ammonium salt of optically inactive tartaric acid was a mixture of two mirror image crystal forms With microscope and tweezers Pasteur carefully sep arated the two He found that one kind of crystal (m aqueous solution) was dextrorota tory whereas the mirror image crystals rotated the plane of polarized light an equal amount but were levorotatory... 

Little was done after Biot s discovery of optical activity until 1848, when Louis Pasteur began work on a study of crystalline tartaric acid salts derived from wine. On crystallizing a concentrated solution of sodium ammonium tartrate below... 

A young Louis Pasteur observed that many salts of tartaric acid formed chiral crystals (which he knew was related to their ability to rotate the plane of polarization of plane-polarized light). He succeeded in solving the mystery of racemic acid when he found that the sodium ammonium salt of racemic acid could be crystallized to produce a crystal conglomerate. After physical separation of the macroscopic enantiomers with a dissecting needle, Pasteur... 

Through luck, in 1848, Louis Pasteur was able to separate or resolve racemic tartaric acid into its (+) and (—) forms by crystallization. Two enantiomers of the sodium ammonium salt of tartaric acid give rise to two distinctly different types of chiral crystal that can then be separated easily. However, only a very few organic compounds crystallize into separate crystals (of two enantiomeric forms) that are visibly chiral as are the crystals of the sodium ammonium salt of tartaric acid. Therefore, Pasteur s method of separation of enantiomers is not generally applicable to the separation of enantiomers. 

The crystallization procedure employed by Pasteur for his classical resolution of ( )-tartaric acid (Section 5-1C) has been successful only in a very few cases. This procedure depends on the formation of individual crystals of each enantiomer. Thus if the crystallization of sodium ammonium tartrate is carried out below 27°, the usual racemate salt does not form a mixture of crystals of the (+) and (—) salts forms instead. The two different kinds of crystals, which are related as an object to its mirror image, can be separated manually with the aid of a microscope and subsequently may be converted to the tartaric acid enantiomers by strong acid. A variation on this method of resolution is the seeding of a saturated solution of a racemic mixture with crystals of one pure enantiomer in the hope of causing crystallization of just that one enantiomer, thereby leaving the other in solution. Unfortunately, very few practical resolutions have been achieved in this way. 

In 1848, the French scientist Louis Pasteur prepared the sodium ammonium salt of racemic tartaric acid and allowed it to crystallize in large crystals which are visually distinctive from hemihedral forms.4 By discriminating the asymmetric faces of the crystals, he picked out the two kinds of crystals mechanically with a pair of tweezers and a loupe. Finally he obtained two piles of crystals, one of (+) and one of (-)-sodium ammonium tartrate. This was the first separation of optically active compounds from their racemate. 

Figure 35, Top Enantiomorphous crystals of sodium ammonium tartrate. Hemihedral facets are marked by an h. Bottom (+)-(2R,3R)-tartaric acid (left) and (-)-(2S,35)-tartaric acid (right).

This conclusion stemmed from his initial work on tartaric acid where he observed that naturally occurring materials rotated the plane of polarized light whereas synthetic materials did not. He noticed that the crystals of sodium ammonium tartrate came in two asymmetric forms that were mirror images of one another. By painstakingly sorting the crystals by hand he found that solutions of one form rotated polarized light clockwise, while the other form rotated light counterclockwise. Pasteur correctly deduced the molecule in question was asymmetric and could exist in two forms that differed only by their handedness or chirality. 

On studying the sodium-ammonium salt of ordinary tartaric acid (dextro tartaric acid), to see if there was any indication of unsymmetrical crystalline form with which to connect the optical activity, according to the suggestion of Herschel, Pasteur observed that the crystals possessed hemi-hedral facets. These gave to the crystals an unsymmetrical form. He then turned his attention to the second known tartaric acid, viz., racemic acid, which is optically inactive. His expectation was that in this acid no such unsymmetrical form would exist as it did not possess optical activity. But to his surprise he found, in the crystals of the sodium-ammonium salt, the same hemi-hedral facets that he had just found in the salts of the active acid. On closer examination. 

Thus from a study of the crystalline sodium-ammonium salt of racemic acid and of dextro tartaric acid Pasteur showed, conclusively, the relationship of these two acids to each other and also discovered the existence of a third isomer optically active but of opposite direction to the ordinary tartaric acid already known. Racemic acid, therefore, is optically inactive because it consists of equal molecules of the ordinary dextro tartaric acid and the newly discovered levo tartaric acid. Also racemic acid can be resolved into its optically isomeric components by mechanically separating the two forms of crystals of the sodium-ammonium salt. The two active forms of tartaric acid, when mixed in equal molecular amounts, yield the inactive or racemic acid. Later, Pasteur prepared the fourth variety of tartaric acid, viz., meso-tartaric acid, by heating the cinchonine salt of dextro tartaric acid. This new acid proved to be inactive like racemic acid, but, unlike it, was unable to be resolved into optically active components. Its relation to the other three forms of tartaric acid was unexplained by Pasteur. 

Mechanical Separation This is the method by which Pasteur proved that racemic acid was actually a mixture of (+)- and (—(-tartaric acids.In the case of racemic sodium ammonium tartrate, the enantiomers crystallize... 

The first resolution was, of course, the one Pasteur carried out with his hand lens and tweezers (Sec. 4.6). But this method can almost never be used, since racemic modifications seldom form mixtures of crystals recognizable as mirror images. Indeed, even sodium ammonium tartrate does not, unless it crystallizes at a temperature below 28 . Thus partial credit for Pasteur s discovery has been given to the cool Parisian climate— and, of course, to the availability of tartaric acid from the winemakers of France. 

Tartaric acid, HOOCCHOHCHOHCOOH, has played a key role in the development of stereochemistry, and particularly the stereochemistry of the carbohydrates. In 1848 Louis Pasteur, using a hand lens and a pair of tweezers, laboriously separated a quantity of the sodium ammonium salt of racemic tartaric acid into two piles of mirror-image crystals and, in thus carrying out the first resolution of a racemic modification, was led to the discovery of enantiomerism. Almost exactly 100 years later, in 1949, Bijvoet, using x-ray diffraction—and also laboriously—determined the actual arrangement m space of the atoms oY the sodium rubidium salt of (-f )-tartaric acid, and thus made the first determination of the absolute configuration of an optically active substance. 

Resolution can be thought of as the converse of racemization (Section 2.4). One starts with a 50 50 mixture of both enantiomers and separates this mixture into the individual enantiomers. Of course, for some purposes one may only want one enantiomer, and recovery of the second enantiomer can be painstaking. Since enantiomers have identical properties, including solubility, separation of enantiomers by recrystallization is quite rare. It was, however, such a crystallization by Pasteur in 1848 that opened up the field of resolution. Pasteur s key observation was that two distinct but related types of crystal were obtained from an aqueous solution of the sodium ammonium salt of racemic tartaric acid. The two types of crystal were related as object and non-superimposable mirror image, and one type was identical to the dextrorotatory crystals of sodium ammonium tartrate obtained from (+)-tartaric acid, itself obtained as a by-product of wine-making. 

Pasteur was only 26 years old at the time and was unknown in scientific circles. He was concerned about the accuracy of his observations because a few years earlier, the well-known German organic chemist Eilhardt Mitscherlich had reported that crystals of the same salt were all identical. Pasteur immediately reported his findings to Jean-Baptiste Biot and repeated the experiment with Biot present. Biot was convinced that Pasteur had successfully separated the enantiomers of sodium ammonium tartrate. Pasteur s experiment also created a new chemical term. Tartaric acid is obtained from grapes, so it was also called racemic acid (racemus is Latin for a bunch of grapes ). When Pasteur found that tartaric acid was actually a mixture of enantiomers, he called it a racemic mixture. Separation of enantiomers is called the resolution of a racemic mixture. 

Racemic acid is of considerable historical interest as it was the first inactive substance to be resolved into optically active compounds. The remarkable discovery was made by Pasteur in 1848 in an investigation of the crystalline structure of the salts of racemic acid. It was found that two kinds of crystals, which differed slightly in the relative position of the faces they contained, were formed when a solution of the sodium ammonium salt of racemic acid was allowed to crystallize spontaneously. The relation in form which the two kinds of crystals bear to each other, is that of an object and its reflection in a mirror. Pasteur separated the two kinds of crystals and examined the solutions of each in polarized light. He found that one solution was dextro-rotatory and the other was levo-rotatory. From the two salts two acids were isolated one was ordinary d-tartaric acid, the other a new acid which was levo-rotatory. When equal weights of the two acids were mixed and recrystallized, inactive racemic acid was obtained. 

It was shown later that if the crystals of sodium ammonium racemate are deposited from solution at a temperature above 28°, crystals of but one kind are obtained. These differ in form and content of water of crystallization from the crystals of the corresponding salts of d-tartaric and Z-tartaric acids, which are obtained when the temperature is below 28°. 

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