Tartaric acid salt, crystalline forms

The fact that molecules have a three-dimensional structure and shape was shown by Louis Pasteur in 1848 in some critical experiments on crystalline salts of tartaric acid that formed part of his doctoral studies. Tartaric acid is a naturally occurring compound that is extracted from grape juice and sometimes crystallizes as potassium bitartrate from solution in wine. Pasteur concentrated on the related compound sodium ammonium tartrate. The two forms of tartrate were chemically identical, but a solution of potassium bitartrate would rotate the plane of polarization of plane polarized light to the right whereas a solution of sodium ammonium tartrate would not. Pasteur studied the crystal structures of tartaric acid salts and found the crystallites themselves were chiral, i.e. the facets of the crystals occur in two forms that are mirror images of one another, so that the two crystallite forms cannot be superimposed. In the pure potassium bitartrate, only right-handed facets were... 

An efficient and simple kinetic resolution of the racemic Betti base 387 was achieved via its reaction with acetone in the presence of L-(- -)-tartaric acid. When a suspension of racemic 387 in acetone was treated with L-(- -)-tartaric acid, the (A)-enantiomer formed a crystalline L-tartrate salt 389 this was filtered off, and the (iJ)-enantiomer could be isolated as a naphth[l,2-< ]oxazine derivative 388 from the filtrate (Equation 41). Both enantiomers were obtained in excellent yields and ee s. The enantioseparation is presumed to take place via a kinetically controlled N,0-deketalization of the (3)-naphth[l,2-< ]oxazine derivative <2005JOC8617>. An improved method for the enantioseparation of 387 was developed by the reaction of the ring-chain tautomeric l,3-diphenyl-3,4-dihydro-2//-naphth[2,l-< ][l,3]oxazine (41 X, Y = H) and L-(-f)-tartaric acid, yielding the crystalline 389 in 85% yield <2007SL488>. 

Neutral Tartrate of Lime—2 CaO, H4 010 —occurs in grapes, and mixed with crude tartar also in senna leaves. Neutral tartrate of potassa forms, witli chloride of calcium, a crystalline precipitate—it is the salt obtained in making tartaric acid, Crystals, right rhombic prisms with ootahedral summits soluble in twelve hundred parts of cold water. 

CITRIC ACID. [CAS 77-92-9J. C.tH.,(OH)(COOH),. formula weight 192.12. white crystalline solid, mp 153. decomposes at higher temperatures, sp gr 1.542. Citric acid is soluble In H.O or alcohol and slightly soluble in ether. The compound is a trihasic acid, forming mono-, di-, and Iri- scries of salts and esters. Citric acid may be obtained (I) from some natural products, e.g., the free acid in the juice of citrus and acidic fruits, often in conjunction with malic or tartaric acid the juice of unripe lemons... 

In 1820 Sir John Herschel, in considering the question of the different optical rotation of crystalline substances, suggested that it might be connected with an unsymmetrical form of crystallization. Later, Pasteur in 1848 while studying the salts of tartaric acid recalled this suggestion of Herschel and also a statement by Mitscherlich to the effect that the crystalline form of ordinary tartaric acid which is dextro rotatory is identical with that of racemic acid which is inactive. At that time the tw o tartaric acids just mentioned were the only ones known. 

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. 

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. 

Optical activity involving the ability to rotate the plane of polarized light was first observed by Biot in 1815-1835 in a number of naturally occurring organic compounds, such as turpentine, camphor, sugars, and tartaric acid. Since optically active compounds exhibited this property both in their crystalline form as well as in solutions, it was reasoned that this property is inherent in the molecules. Mitscher-lich in 1844 observed that although tartaric and racemic acids are isomeric, the former and its salt are optically active, while racemic acid is inactive. ... 

In wine, simple salts are dissociated into TH and T ions. The last two tartrates (Figure 1.10) share the property of forming and remaining stable at a pH of over 4.5. On the other hand, in terms of solubility, they differ in that potassium calcium tartrate is highly soluble, whereas the tartromalate is relatively insoluble and crystallizes in needles. The properties of this mixed salt may be used to eliminate malic acid, either partially or totally. Table 1.11 shows the solubility, in water at 20° C, of tartaric acid and the salts that cause the most problems in terms of crystalline deposits in wine. 

It was the observation of the hemihedral crystals of sodium ammonium tartrate tetrahydrate that enabled Pasteur (1822-1895) to make a decisive step forward in stereochemistry. The problem he encountered was the contamination of the potassium salt of tartaric acid with that of another acid (which Gay-Lussac (1778-1850) called the racemic acid) that made it unsuitable for commercial use. The two acids had the same chemical composition, and Biot showed that whereas tartaric acid and its salts could rotate the plane of polarized light, the racemic acid itself was inactive. In 1848, Pastern-found the solution to this problem.He noticed that crystals of tartaric acid, like its salts, have hemihedral faces, but that the racemic sodium ammonium tartrate exists as two distinct crystals in which the hemihedral faces are mirror images of each other. One of these crystalline forms is identical to the optically active tartrate. In solution, it rotates the plane of polarized light in a dextrorotatory manner, while the other form (a mirror image of the first) is levorotatory, that is in solution it rotates the plane of polarization towards the left (Figure 2.5). 

Tartrates are salts of the diprotic carboxylic acid (+)-tartaric acid (Figure 3.33.1) (or L-tartaric acid). This tartaric acid is the natural occurring form, but the (-)-tartaric acid and the racemate are commercially available as well. The two acid groups have pKa values of 2.93 and 4.43, respectively. The tartaric acid is a crystalline solid, with a high water solubility. Their ammonium and potassium salt has a limited solubility, a fact that in the pharmacopoeia is used for the identification of potassium in 3.27. Potassium. The salts of the other alkali metals are soluble, but salts of most other inorganic cations are sparingly soluble. ... 

This reaction was first reported by Marckwald in 1904. It is the synthesis of chiral L-valeric acid (a-methyl propanoic acid) from the pyrolysis of brucine salt of racemic o -methyl-o -ethylmalonic acid. Therefore, it is generally known as the Marckwald asymmetric synthesis. Occasionally, it is also referred to as the Marckwald method. In this reaction, the brucine salts of racemic a-methyl-a-ethylmalonic acid essentially exist as a pair of diastereomers that are separated by fractional crystallization the one with lower solubility is isolated. Upon pyrolysis of such crystalline salt at 170°C, the corresponding brucine salt of L-valeric acid forms upon decarboxylation, resulting in a 10% e.e. In addition, Marckwald defined the asymmetric synthesis as reactions that produce optically active molecules from symmetrically constituted compounds with the use of optically active materials and exclusion of any analytical processes, such as resolution. However, this work was challenged as not being a trae asymmetric synthesis because the procedure was similar to that of Pasteur. In fact, the If actional crystallization of the diastereomers is a resolution process. This process is used as base for many other preparations of chiral molecules, such as tartaric acid and under its influence, the kinetic resolution and tme asymmetric synthesis have been developed in modem organic synthesis. The asymmetric synthesis has been redefined by Morrison and Mosher as the reaction by which an achiral unit of the substrate is converted into a chiral unit in such a manner that the two resulting stereoisomers are produced in unequal amounts. ... 

Pasteur was convinced that there must be some molecular difference between the two salts, and he made the problem the subject of his first major piece of research. He prepared several salts of tartaric acid and found that in all cases the crystals were asymmetric (Pasteur used the term dissymmetric), and displayed hemihedral faces. Pasteur was tempted to speculate that such asymmetric crystals were typical of optically active materials, and were the manifestation of asymmetry of the molecules. He then found that crystals of the optically inactive sodium ammonium paratartrate also displayed hemihedral faces, but on careful examination he saw that two types of crystal were present, one the mirror image of the other (Figure 10.13). He carefully sorted some of the crystals by hand. Those with right-handed hemihedry gave a solution which was dextrorotatory and identical with a solution of sodium ammonium tartrate. A solution of equal concentration of the crystals with left-handed hemihedry rotated polarised light to an equal extent in the opposite direction. A solution of equal concentrations of each crystalline form was optically inactive. Pasteur thereby demonstrated that paratartaric acid was... 

Note that the resolving agent is recovered unchanged after this procedure and can be reused repeatedly. Because of the need to obtain crystalline adducts which are readily broken down to their components again, the ionic salts formed between amines and acids, either carboxylic or sulphonic, are ideal for resolution. Thus even in the last century very many amines were resolved by formation of salts with, for example, tartaric acid (16) or camphorsulphonic acid (29), while organic acids were resolved with bases such as quinine, cinchonine and the highly toxic alkaloids brucine (36) and strychnine (37). Although reliable resolution methods have now been worked out for... 

By manually separating the two sets, dissolving them in water, and measuring their optical rotation, Pasteur found one of the crystalline forms to be the pure salt of (-l-)-tartaric acid and the other to be the levorotatory form. Remarkably, the chirality of the individual molecules in this rare case had given rise to the macroscopic property of chirality in the crystal. He concluded from his observation that the molecules themselves must be chiral. These findings and others led in 1874 to the first proposal, by van t Hoff and Le Bel independently, that saturated carbon has a tetrahedral bonding arrangement and is not, for example, square planar. (Why is the idea of a planar carbon incompatible with that of a stereocenter )... 

---