Tartrate sodium ammonium

Tartaric acid is noteworthy for a) the excellent way in which the majority of its salts Crystallise, and h) the frequent occurrence of salts having mixed cations. Examples of the latter are sodium potassium tartrate (or Rochelle salt), C4H40 NaK, used for the preparation of Fehling s solution (p. 525), sodium ammonium tartrate, C4H OaNaNH4, used by Pasteur for his early optical resolution experiments, and potassium antimonyl tartrate (or Tartar Emetic), C4H404K(Sb0). The latter is prepared by boiling a solution of potassium hydrogen tartrate (or cream of tartar ) with antimony trioxide,... 

The optical activity of quartz and certain other materials was first discovered by Jean-Baptiste Biot in 1815 in France, and in 1848 a young chemist in Paris named Louis Pasteur made a related and remarkable discovery. Pasteur noticed that preparations of optically inactive sodium ammonium tartrate contained two visibly different kinds of crystals that were mirror images of each other. Pasteur carefully separated the two types of crystals, dissolved them each in water, and found that each solution was optically active. Even more intriguing, the specific rotations of these two solutions were equal in magnitude and of opposite sign. Because these differences in optical rotation were apparent properties of the dissolved molecules, Pasteur eventually proposed that the molecules themselves were mirror images of each other, just like their respective crystals. Based on this and other related evidence, in 1847 van t Hoff and LeBel proposed the tetrahedral arrangement of valence bonds to carbon. 

L. Pasteur (aged 26) began work on optically active sodium ammonium tartrate. 

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... 

Figure 9.6 Drawings of sodium ammonium tartrate crystals taken from Pasteur s original sketches. One of the crystals is "right-handed" and one is "left-handed."...

Ever since Pasteur s work with enantiomers of sodium ammonium tartrate, the interaction of polarized light has provided a powerful, physical probe of molecular chirality [18]. What we may consider to be conventional circular dichroism (CD) arises from the different absorption of left- and right-circularly polarized light by target molecules of a specific handedness [19, 20]. However, absorption measurements made with randomly oriented samples provide a dichroism difference signal that is typically rather small. The chirally induced asymmetry or dichroism can be expressed as a Kuhn g-factor [21] defined as ... 

The manual separation of the enantiomorphous crystals of sodium ammonium tartrate tetrahydrate (Figure 1) by Pasteur in 1848 (1) is historically significant, because it laid the foundations of modem stereochemistry. This experiment demonstrated for the first time that certain classes of molecules display enan-tiomorphism even when dissolved in solvent. These observations eventually paved the way for the inspired suggestion, made more than two decades later, by van t Hoff (2) and Le Bel (3), of a tetrahedral arrangement of bonds around the carbon atom. 

Figure I. Enantiomorphous crystals of sodium ammonium tartrate -4H20.

Crystals composed of the R and S enantiomers of the same racemic mixture must be related by mirror symmetry in terms of both their internal structure and external shape. Enantiomorphous crystals may be sorted visually only if the crystals develop recognizable hemihedral faces. [Opposite (hid) and (hkl) crystal faces are hemihedral if their surface structures are not related to each other by symmetry other than translation, in which case the crystal structure is polar along a vector joining the two faces. Under such circumstances the hemihedral (hkl) and (hkl) faces may not be morphologically equivalent.] It is well known that Pasteur s discovery of enantiomorphism through die asymmetric shape of die crystals of racemic sodium ammonium tartrate was due in part to a confluence of favorable circumstances. In the cold climate of Paris, Pasteur obtained crystals in the form of conglomerates. These crystals were large and exhibited easily seen hemihedral faces. In contrast, at temperatures above 27°C sodium ammonium tartrate forms a racemic compound. 

Mechanical Separation of Crystals. The first instance of resolution was by L. Pasteur who was able to resolve crystals of sodium ammonium tartrate (which recrystallizes in two distinct, nonsuperimposable forms below 2TC). Although this procedure is rarely used, one might be able to seed a racemic solution resulting in only one... 

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. 

Many substances can rotate the plane of polarization of a ray of plane polarized light. These substances are said to be optically active. The first detailed analysis of this phenomenon was made by Biot, who found not only the rotation of the plane of polarization by various materials (rotatory polarization) but also the variation of the rotation with wavelength (rotatory dispersion). This work was followed up by Pasteur, Biot s student, who separated an optically inactive crystalline material (sodium ammonium tartrate) into two species which were of different crystalline form and were separately optically active. These two species rotated the plane of polarized light equally but in opposite directions and Pasteur recognized that the only difference between them was that the crystal form of one was the mirror image of the other. We know to-day, in molecular terms, that the one necessary and sufficient condition for a substance to exhibit optical activity is that its molecular structure be such that it cannot be superimposed on its image obtained by reflection in a mirror. When this condition is satisfied the molecule exists in two forms, showing equal but opposite optical properties and the two forms are called enantiomers. 

It was the optical resolution of [Co(en)2(NH3)Cl]2+ that firmly established Werner s theory and which initiated the study of the optical activity of complex ions. The realization that some octahedral complexes are chiral evidently did not occur to Werner until several years after he published his theory of coordination. He then realized that the demonstration of this property would furnish an almost irrefutable argument in favor of his theory, and he and his students devoted several years to attempts to effect such resolution. Had he but known it, the problem could have been easily solved, for cis-[Co(en)2(N02)2]X (X = Cl, Br) crystallizes in hemihedral crystals which can be separated mechanically, just as Pasteur separated the optical isomers of sodium ammonium tartrate. 

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. 

FIGURE 2 The stereostructures of quartz and sodium ammonium tartrate crystals. 

Since Pasteur separated crystalline sodium ammonium tartrate manually in 1848, many researchers have worked on the subject of enantiomeric separation. In 1939 Henderson and Rule fully separated derivatives of camphor by column chromatography using lactose as a stationary phase material [1]. Gil-Av et al. [2] were able to separate amino acid derivatives on a polysiloxane-based stationary phase by gas chromatography (GC) in 1966. Since then many approaches for a successful distinction between enantiomers have been developed for capillary GC and liquid chromatography [3]. It is still a current topic for researchers searching for chiral separation with SciFinder [4] results in 812 hits and searching for chiral recognition leads to 285 hits for the year 2003 only. 

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. 

It was Pasteur, in the middle of the 19th century, who first recognized the breaking of chiral symmetry in life. By crystallizing optically inactive sodium anmonium racemates, he separated two enantiomers of sodium ammonium tartrates, with opposite optical activities, by means of their asymmetric crystalline shapes [2], Since the activity was observed even in solution, it was concluded that optical activity is due to the molecular asymmetry or chirality, not due to the crystalline symmetry. Because two enantiomers with different chiralities are identical in every chemical and physical property except for optical activity, in 1860 Pasteur stated that artificial products have no molecular asymmetry and continued that the molecular asymmetry of natural organic products establishes the only well-marked line of demarcation that can at present be drawn between the chemistry of dead matter and the chemistry... 

Chirality, in its many and varied manifestations, is ubiquitous a concept rooted in mathematics, it permeates all branches of the natural sciences.1 In 1848, Louis Pasteur announced his epochal discovery of a causal relationship between the handedness of hemihedral sodium ammonium tartrate crystals and the sense of optical rotation of the tartrates in solution.2 This discovery, which marks the beginning of modem stereochemistry, connected enantiomorphism on the macroscopic scale to enantiomorphism on the molecular scale and thus led to Pasteur s recognition that the optical activity of the tartrates is a manifestation of dissymetrie moleculaire, 3 that is, of molecular chirality. 

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. 

Louis Pasteur was the first scientist to study the effect of molecular chirality on the crystal structure of organic compoimds [23], finding that the resolved enantiomers of sodium ammonium tartrate could be obtained in a crystalline form that featured nonsuperimposable hemihedral facets (see Fig. 9.1). Pasteur was quite surprised to learn that when he conducted the crystallization of racemic sodium ammonium tartrate at temperatures below 28 °C, he also obtained crystals of that contained nonsuperimposable hemihedral facets. He was able to manually separate the left-handed crystals from the right-handed ones, and foimd that these separated forms were optically active upon dissolution. More surprising was the discovery that when the crystallization was conducted at temperatures exceeding 28 °C, he obtained crystals having different morphologies that did not contain the hemihedral crystal facets (also illustrated in Fig. 9.1). Later workers established that this was a case of crystal polymorphism. 

FIGURE 9.1 Crystals of sodium ammonium tartrate, obtained under conditions yielding the hemihedral facets (darkened crystal faces) distinctive of the chiral crystalline forms. Also shown is the crystal morphology of racemic sodium ammonium tartrate. 

R. Kuroda, S.M. Mason, Crystal structures of dextrorotatory and racemic sodium ammonium tartrate, J. Chem. Soc., Dalton Trans. B50 (1994) 59-68. 

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