Physical Properties of Diastereomers

We have seen that enantiomers have identical physical properties except for the direction in which they rotate polarized light. Diastereomers, on the other hand, generally have different physical properties. For example, consider the diastereomers of 2-butene (shown next). The symmetry of rranj-2-butene causes the dipole moments of the bonds to cancel. The dipole moments in m-2-butene do not cancel but add together to create a molecular dipole moment. The dipole-dipole attractions of cw-2-butene give it a higher boiling point than rranJ-2-butene. 

Diastereomers that are not geometric isomers also have different physical properties. The two diastereomers of 2,3-dibromosuccinic acid have melting points that differ by nearly 100°C  

Most of the common sugars are diastereomers of glucose. All these diastereomers have different physical properties. For example, glucose and galactose are diastereomeric sugars that differ only in the stereochemistry of one asymmetric carbon atom, C4. 

Because diastereomers have different physical properties, we can separate them by ordinary means such as distillation, recrystallization, and chromatography. As we will see in the next section, the separation of enantiomers is a more difficult process. 

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Summary Fischer Projections andTheir Use 201 Diastereomers 201 Summary Types of Isomers 203 5-12 Stereochemistry of Molecules withTwo or More Asymmetric Carbons 204 5-13 Meso Compounds 205 5-14 Absolute and Relative Configuration 207 5-15 Physical Properties of Diastereomers 208 5-16 Resolution of Enantiomers 209 EssentialTerms 213 Study Problems 215... 

When the absolute structure has been determined, the result must be correlated with some physical property of the crystal, otherwise the result has no use to the chemist. The obvious correlation is with the direction of rotation of the plane of plane-polarized light, that is, whether the compound or crystal is dextrorotatory or levorotatory. Another correlation can be made with crystal appearance this was shown for zinc blende with its matte and shiny faces, and for silica and sodium ammonium tartrate crystals for the disposition of their hemihedral faces. If such data are not available, it may be necessary to list physical properties of diastereomers made with chiral complexing agents. Then, whenever this same compound is encountered by a chemist, its absolute structure is well known. 

A compound with two dissimilar chiral carbon atoms has two possible pairs of enantiomers. The mirror image structures of one enantiomeric pair are diastereomers of those of the other enantiomeric pairs. Diastereomers are stereoisomers that are not mirror images. All physical properties of diastereomers are different including, usually, their rotation of plane polarized light. 

A compound with two similar chiral carbon atoms has one pair of enantiomers and one meso compound. A meso compound has more than one chiral center and is superimposable on its mirror image meso compounds are optically inactive. A meso compound is a diastereomer of each of the enantiomers. Diastereomers are stereoisomers that are not mirror images all physical properties of diastereomers are usually different. 

Physical Properties of DIastereomers Resolution, a Method of Separating Enantiomers from Each Other... 

The physical properties of the three stereoisomers of tartaric acid are listed in Table 4.2. The meso compound and either of the enantiomers are diastereomers. Notice that the physical properties of enantiomers are the same, whereas the physical properties of diastereomers are different. 

The differing physical properties of diastereomers is also the basis for a particularly sensitive method of assessing the optical purity of compounds. Although, in principle, this can be done by measuring the optical rotation, this value is reliable only if the rotation of the pure enantiomer is accurately known. This will never be the case for a newly prepared material and is also often in question for previously prepared compounds. If a derivative is prepared in which a new chiral center is introduced, the two enantiomers will give different diastereomers. Since these will have different physical properties in general, they have different NMR spectra. These spectra are distinguished by somewhat different chemical shifts. A pure... 

Now, consider the physical properties of these stereoisomers. Enantiomers should have many of the same physical properties, such as energy and dipole moment, but diastereomers should not. Obtain the energy of each conformer and use equation (1) to calculate the composition of a large sample of each stereoisomer at 298 K. Then, obtain the dipole moment of each conformer and use equatiori (2) to calculate the dipole moment of a large sample of each stereoisomer at 298 K. Do enantiomers have the same dipole moment Do diastereomers have different dipole moments ... 

Two compounds are diastereomers when they contain more than one chiral center. If the number of dissymmetric centers is given by N, then the number of possible diastereomers is given by 2N. Of these 2 v diastereomers, each will be characterized by its mirror image, so that the number of enantiomers is given by 2NI2. Whereas the physical properties of enantiomers in an achiral environment are necessarily identical, the physical properties (including solubility) of diastereomers are normally different. The differences arise since there is no structural requirement that the crystal lattices of different diastereomers be the same. For instance, the solubility of an (SS )-diastereomer could differ substantially from that of the (/ S)-diastereomer. However, it should be remembered that the solubility of the (SS)-diastereomer must be exactly identical to that of the (I 7 )-diastereomer, since these compounds are enantiomers of each other. At the same time, the solubilities of the (SI )-diastereomer and the (I S)-diastereomer must also be identical. 

The first example of the deliberate separation of optically active molecules is appropriate as an example of physical separation in the clearest sense of the term. The molecules are referred to as optically active because polarized light interacts differently with right- and left-handed molecules. In the case of simple diastereomers the RR and SS forms are enantiomers while the RS and SR forms are not. The separation of the latter and former was first done under a microscope using crossed polarizers and the crystals which were seen were separated from those that caused little or no rotation of plane-polarized light by hand using tweezers. A truly physical separation of chemical species using a physical property of chemical origin ... 

Comparison of physical properties of compound 41 (in Scheme 2) with the corresponding product from vertine showed that both compounds were diastereomers as predicted (24). There were significant differences in the NMR and IR spectra, and the melting point of 41 (84-85°) was depressed (77-92°) on admixture with the corresponding derivative from vertine. 

For convenience, a phase diagram of a pair of diastereomeric crystals is ordinarily studied in detail, and the mechanism of the diastereomeric resolution is interpreted in terms of the thermodynamic and physical properties of the bulk of the diastereomeric crystals.4,7-10 Such studies reveal the importance for diastereomeric resolution of the type of mixture of diastereomers in a target system. There are three types of diastereomer mixtures an eutectic mixture, a 1 1 addition compound, and a solid solution. To achieve successful resolution, it is essential that the mixture of the diastereomeric crystals of a target racemate with a resolving agent be an eutectic mixture. The classic studies are thoroughly reviewed by Collet and co-workers.4,12... 

The physical properties of meso compounds, diastereomers and racemic mixtures differ from each other and from the properties of enantiomers. 

Diastereomers are not miiror images of each other, and as such, their physical properties are different, including optical rotation. Figure 5.12 compares the physical properties of the three stereoisomers of tartaric acid, consisting of a meso compound that is a diastereomer of a pair of enantiomers. 

The physical properties of A and B differ from their diastereomer C. The physical properties of a racemic mixture of A and B (last column) can also differ from either enantiomer and diastereomer C. C is an achiral meso compound, so it is optically inactive [a] - 0. 

Diastereomers are optical isomers that are not related as an object and its mirror image. Unlike enantiomers, the physical and chemical properties of diastereomers can differ and it is not unusual for them to have different melting and boiling points, refractive indices, solubilities, etc. Their optical rotations can differ in both sign and magnitude. 

All stereoisomers that are not enantiomers are termed diastereomers. For example, in a molecule containing two or more stereogenic centres any pair of stereoisomers that are not enantiomers are diastereomers. In other words, a pair of diastereomers share the same configuration at one or more, but not all, of their stereogenic centres and, unlike enantiomers, they have different physical properties. Two diastereomers that differ in configuration at only one of a number of stereogenic centres are called epimers, and their interconversion epimerization. 

As pointed out previously, all of the amino acids prepared in this section are racemic. To obtain an enantiopure amino acid requires separation of the enantiomers via resolution. As discussed in Chapter 9 (Section 9.2), the physical properties of enantiomers are identical except for specific rotation. Because separation methods rely on differences in physical properties, this is a problem. It is overcome if the racemic amino acid mixture reacts with a reagent that has a stereogenic center. The resulting product will be a mixture of diastereomers, which have different physical properties and may be separated. 

The procedures in this chapter are chosen to study (a) separating diastereomers by chromatography (Sec. 7.2), (b) converting one diastereomer into another (Sec. 7.3), (c) evaluating some chemical and physical properties of enantiomers (Sec. 7.4), and (d) resolving a racemate (Sec. 7.6). A description of the technique of polarimetry is given in Section 7.5 to support this last study. 

A common chemical means of resolving organic compounds is to treat the racemic mixture with a chiral resolving agent that converts the mixture of enantiomers into a pair of diastereomers. The diastereomers are separated based on differences in their physical properties each diastereomer is then converted to a pure stereoisomer, uncontaminated by its enantiomer. 

While compounds which are enantiomers have identical chemical and physical properties and equal and opposite optical rotation, compounds which are diastereomeric with each other can have completely different chemical and physical properties and optical rotations. This feature provides the basis for the resolution of chiral compounds. In this procedure a racemic mixture is derivatised by reaction with an enantiomerically pure compound which leads to a mixture of two diastereomers. These can be separated by crystallisation or chromatography as a result of their different properties and the pure enantiomers of the starting compound obtained by cleavage of each diastereomer separately. In the synthesis of the chiral phosphines (section 1.7) the phosphine oxide (37) is obtained by resolution of the starting material (34) via the diastereomeric esters (35) and (36). A further important application of the differing properties of diastereomers is in the determination of e.e. by derivatisation with an enantiomerically pure compound followed by chromatographic or NMR analysis (see section 3.4.1). 

The physical properties of A and B differ from their diastereomer C. 

The physical properties of a racemic mixture of A and B (last column) can also differ from either enantiomer and diastereomer C. 

The relationship between the 2R,3R and the 2S,3S stereoisomers is that they are nonsuperimposahle mirror images of each other they are enantiomers. Similarly, the 2R,3S and the 2S,3R stereoisomers are enantiomers of each other. The relationship between the 2R,3R and the 2R,3S stereoisomers is that they are diastereomers. Diastereomers are stereoisomers that are not mirror images. Diastereomers generally have different, albeit similar, physical properties. Of the four stereoisomers of threonine, only the 2S,3R stereoisomer occurs naturally and is an essential human nutrient [29]. 

There are many synthetic techniques for stereoselective synthesis and because of the importance much research is currently devoted to expanding these techniques. Omeprazole, marketed as Prilosec , was the first proton pump inhibitor and is used as a treatment for gastric ulcers. It is a racemic mixture. The S enantiomer has better pharmacokinetics and pharmacodynamics than the racemic mixture and therefore higher efficacy in controlling acid secretion [38]. The S enantiomer is called esomeprazole and is marketed as Nexium . Nexium has annual sales of 8.4 billion [39]. The chiral center is at the sulfur and the enantiomers can be separated by derivatizing with a R-(-) mandelic acid chiral auxiliary to form two diastereomers. Unlike enantiomers, diastereomers have different physical properties. The diastereomers can be separated by HPLC and then the chiral auxiliary removed to afford each of the omeprazole enantiomers. Alternatively, the sulfide precursor can be asymmetrically oxidized to form esomeprazole in 99.99% enantiomeric excess (ee) [40]. Enantiomeric excess means the excess amount of one enantiomer over the racemic mixture. If something is 80% ee that means that 20% is a racemic mixture and the other 80% is excess of that enantiomer. In this example, for 100 g, there are 90 g of the predominant enantiomer and 10 g of the lesser enantiomer in other words, 20 g is a racemic mix (lOg of each enantiomer) and 80g is excess enantiomer. 

The formation of diasteriomers by itself does not guarantee that a separation can be obtained it merely establishes that a separation may be possible using a conventional (achiral) separation system. A useful separation depends on the differences in physical properties of the diastereomers, the extent to which these differences affect the relative distribution of the diasteromers in a biphasic separation system, and the chromatographic efficiency of the separation system. 

Be sure that you understand the meanings of enantiomer and diastereomer, and how physical properties of molecules relate to those stereoisomeric relationships, before you answer this question about anomers. 

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