Tartaric acid salts

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... 

Let s return for a last look at Pasteur s pioneering work. Pasteur took an optically inactive tartaric acid salt and found that he could crystallize from it two optically active forms having what we would now call the 2R,3R and 2S,3S configurations. But what was the optically inactive form he started with It couldn t have been meso-tartaric acid, because meso-tartaric acid is a different chemical compound and can t interconvert with the two chiral enantiomers without breaking and re-forming chemical bonds. 

Pasteur thus made the important deduction that the rotation of polarized light caused by different tartaric acid salt crystals was the property of chiral molecules. The (+)- and ( )-tartaric acids were thought to be related as an object to its mirror image in three dimensions. These tartaric acid salts were dissymmetric and enantiomorphous at the molecular level. It was this dissymmetry that provided the power to rotate the polarized light. 

Extract again with alcoholic tartaric acid and evaporate in a vacuum to dryness. The dry material is the salt (i.e., the tartaric acid salt, the tartrate) of the ergot alkaloids, and is stored in this form because the free basic material is too unstable and decomposes readily in the presence of light, heat, moisture and air. 

R)-(+)-1-(1-Naphthyl)ethylamine is purchased from Aldrich Chemical Company, Inc. The reagent is purified by recrystallization of its tartaric acid salt three times from 94% aqueous methanol followed by treatment with base and distillation of the free amine. 

Section II, 4a. Optical activity and O.K.D. of (+)-tartaric acid salts of poly-2-vinyl pyridine having different stereoregularity have been determined the optical rotation between 578 m/r and 365 mfi of the salt of atactic poly-2-vinyl-pyridine is lower than that of the salt of the isotactic poly-vinyl-pyridine [R. C. Schulz and J. Schwaab Makromol. Chem. 85, 297 (1965)]. 

If used in beverages, tartaric acid must be perfectly pure and guaranteed for food use. One problem that may need to be addressed is that tartaric acid salts, particularly the calcium and magnesium tartrates, have lower solubility than citric acid. Consequently, there is a tendency for unsightly precipitates of insoluble tartrates to form in hard water, and in such conditions it is preferable to use citric acid. 

S-Isomer was prepared the next way. To a solution of 160 parts of dibenzoyl d-tartaric acid in 1600 parts of anhydrous ethanol were added for 15 minutes 80 parts of dl-l-(3-trifluoromethylphenyl)-2-ethylaminopropane. After 15 additional minutes, 90.5 parts of crystalline solid were isolated. When this product was recrystallized from 1300 parts of anhydrous ethanol, there was obtained 70 parts of dibenzoyl d-tartarate acid salt of L-l-(3-trifluoromethylphenyl)-2-ethylaminopropane. This salt was treated with 500 parts of 4 N NaOH. The mixture was extracted with 2x200-part portions of diethyl ether and the ether extract was re-extracted with 100 parts of 4 N hydrodiboric acid. After treatment with 120 parts of 4 N NaOH, the free amine amounting to 25 parts distills at 105°-107°C (17.5 mm.). [a]D25 - 9.6° (c=8% in ethanol). 

Aminomethylbenzylphenylmethylsilane, chiral at the silicon center, has been used as an NMR shift and relaxation reagent.313 Both enantiomers are obtained from the racemic material by fractional crystallization of the (+)-tartaric acid salts.314... 

Southern corn rootworm. The structure of the southern corn rootworm has been defined as 10-methyl 2-tridecanone, XI (Figure 16) (5J3). Alkylation of undecanoic acid with n-propyl bromide was followed by conversion to the diastereomeric amides with either (S)- or (R)-a-methylbenzylamine that had been purified previously by recrystallization of D and L tartaric acid salts, respectively. Recrystallizations of these amides from ethanol (4 was sufficient) gave 32% yields of pure (>99.5%) diastereo-mers (Figure 16). Hydroxyethylation labilized the amides toward hydrolysis. It was convenient to intercept the aminoesters and reduce them with LAH. The resulting carbinols were than carried forward in standard manner to provide the ketones. 

Table 1 Selected (4 )-A-methyl-5-(3-pyridyl)-4-penten-2-amine hemigalactarate salt derivatives and their corresponding melting points. The corresponding D- and L-2,3-diacyl-tartaric acid salt derivatives were previously prepared by Dull (1)...

Preparative Methods the most convenient preparation of (/ ,/ )-stilbenediamine is described in Organic Syntheses." Condensation of benzil and cyclohexanone in the presence of ammonium acetate and acetic acid (eq 1) produces a spirocyclic 2//-imidazole (mp 105-106 °C). Reduction with Lithium in THF/NH3 followed by an ethanol quench and hydrolysis with aqueous HCl (eq 2) affords the racemic diamine as a pale yellow solid (mp 81-82 °C). Resolution is achieved by multiple recrystallizations of the tartaric acid salts ifom water/ethanol. The sulfonamides are prepared by reaction of the enantiomeri-cally pure diamine with the appropriate anhydride or sulfonyl chloride in CH2CI2 in the presence of Triethylamine and a catalytic amount of 4-Dimethylaminopyridine (eq 3). 

Preparative Methods (i) preparation of racemic DPEN and its optical resolution Reaction of benzil and cyclohexanone in the presence of ammonium acetate and acetic acid at reflux temperature gives a cyclic bis-imine (1) (eq 1). Stereoselective reduction of the bis-imine with lithium in THF-liquid ammonia at —78 °C followed by addition of ethanol, then hydrolysis with hydrochloric acid and neutralization with sodium hydroxide produces the racemic diamine (2). Recrystallization of the l-tartaric acid salt from a 1 1 water-ethanol mixture followed by neutralization with sodium hydroxide, recrystallization from hexane results in (5,5)-DPEN (3) as colorless crystals. 

Racemic bupivacaine hydrochloride (38, Marcaine) is currently used as an epidural anesthetic during labor and as a local anesthetic in minor operations. Clinical studies have shown that ei o-bupivacaine (41) is less car-diotoxic in man, making it significantly safer than the racemate (67). Separation of the enantiomers was readily achieved using 0.25 eq of D-tartaric acid. This resulted in the isolation of a 2 1 (S)-bupivacaine o-tartaric acid salt (39) in 98% de, leaving the (J2)-bupivacaine... 

Today, we would describe Pasteur s work by saying that he had discovered the phenomenon of enantiomerism. The enantiomeric tartaric acid salts that Pasteur separated are physically identical in all respects except for their interaction with plane-polarized light. They have the same melting point, the same boiling point, the same solubilities, and the same spectroscopic properties. 

Louis Pasteur deduced in 1848 that the handedness of molecular structure is responsible for optical activity. He sorted the chiral crystals of tartaric acid salts into left-handed and right-handed forms, and discovered that the solutions showed equal and opposite optical activity. 

A molecule that cannot be superimposed on its mirror image is said to be chiral. When a carbon atom is bonded to four different atoms or groups of atoms, it is called a chiral carbon. Two stereoisomers that are nonsuperimposable mirror images of one another are a pair of enantiomers. As mentioned in Section 17.3, the chemical and physical properties of enantiomers are identical, with the exception that they rotate plane-polarized light to the same degree but in opposite directions. This is exactly the phenomenon that Pasteur observed with the mirror-image crystals of tartaric acid salts. 

When Louis Pasteur measured the specific rotation of the mixture of left- and right-handed tartaric acid salt crystals, he observed that it was optically inactive. The reason was that the mixture contained equal amounts of the (+) enantiomer and the (-) enantiomer. A mixture of equal amounts of a pair of enantiomers is called a racemic mixture, or simply a racemate. The prefix ( ) is used to designate a racemic mixture. Consider the following situation ... 

The initial asymmetric synthesis (see Scheme 5.2) of pyrrolidine acid 3 suffered from a chiral HPLC bottleneck. As a result, chiral salt resolution was investigated. The rapid discovery of a crystalline di-p-toluoyl-D-tartaric acid salt provided the necessary means to resolve and purify the desired diastereomer. Using 0.65 equivalent of the acid in methyl (cr(-butyl ether (MTBE), the crystallized salt was shown to be a 92 8 ratio of (3S,4R) (3R,4S) diastereomers. The resolved tartaric acid salts were then recrystalhzed from n-butanol to ratios of >99 1 in a 42% overall yield on a 2-kg scale. Further improvements were made in the preparation of the azomethine ylide precursor 38. In step 1, using dimethyl sulfoxide (DMSO) as the solvent, the reaction temperature of trimethylsilylmethylation of tert-butylamine was lowered from 200°C used in the original synthesis to 80°C. In step 2, substituting n-butanol in place of methanol reduced the amount of oligomerization observed and increased the yield to 69%. Overall, these improvements allowed for the preparation of pyrrolidine acid 3 in 22% overall yield in 99% ee from cinnamate 39 (Scheme... 

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