Meso Compounds the Stereoisomers of Tartaric Acid

PROBLEM 5.18 How do you expect the specific rotations of the (2R,3R) and (2S,3S) forms of 2-bromo-3-chlorobutane to be related Answer the same question for the (2R,3R) and (2S,3R) forms. 

PROBLEM 5.19 The Fischer projection formula for glucose (blood sugar, Sec. 16.4, p. 466) is 

Altogether, how many stereoisomers of this sugar are possible  

Actually, the number of isomers predicted by this rule is the maximum number possible. Sometimes, certain structural features reduce the actual number of isomers. In the next section, we examine a case of this type. 

Consider the stereoisomers of 2,3-dichlorobutane. There are two stereogenic centers. 

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Multiple Chiral Centers. The number of stereoisomers increases rapidly with an increase in the number of chiral centers in a molecule. A molecule possessing two chiral atoms should have four optical isomers, that is, four structures consisting of two pairs of enantiomers. However, if a compound has two chiral centers but both centers have the same four substituents attached, the total number of isomers is three rather than four. One isomer of such a compound is not chiral because it is identical with its mirror image it has an internal mirror plane. This is an example of a diaster-eomer. The achiral structure is denoted as a meso compound. Diastereomers have different physical and chemical properties from the optically active enantiomers. Recognition of a plane of symmetry is usually the easiest way to detect a meso compound. The stereoisomers of tartaric acid are examples of compounds with multiple chiral centers (see Fig. 1.14), and one of its isomers is a meso compound. 

Another way to verify that (c) is achiral is to see that it has a plane of symmetry that bisects the molecule in such a way that the top half is the reflection of the bottom half. Thus, even though (c) has two stereocenters, it is achiral. The stereoisomer of tartaric acid represented by (c) or (d) is called a meso compound, defined as an achiral compound that contains two or more stereocenters. 

A meso form with any one of the enantiomers of tartaric acid represents a pair of diastereomers. Although it may not be true for this compound because of the meso form, in general, if you have n stereocenters, there are 2n stereoisomers possible (see Post-Lab question no. 3). 

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. 

Because of the plane of symmetry, the tartaric acid stereoisomer shown in Figure 9.11 must be achiral, despite the fact that it has two chirality j centers. Compounds that are achiral, yet contain chirality centers, are called meso compounds (me-zo). Thus, tartaric acid exists in tliree stereoiso-meric forms two enantiomers and one meso form. 

Some physical properties of the three stereoisomers of tartaric acid and of the racemic mixture are listed in Table 9.3. As indicated, the ( + )- and (-)-tartaric acids have identical melting points, solubilities, and densities. They differ only in the sign of their rotation of plane-polarized light. The meso isomer, by contrast, is diastereomeric with the (+) and (-) forms. As such, it has no mirror-image relationship to ( + )- and (-)-tartaric acids, is a different compound altogether, and has different physical properties. 

More elaborate molecules can also have a plane of symmetry. For example, there are only three stereoisomers of tartaric acid (2,3-dihydroxybutanedioic acid). Two of these are chiral but the third is achiral. In the achiral stereoisomer, the substituents are located with respect to each other in such a way as to generate a plane of symmetry. Compounds that contain two or more stereogenic centers but have a plane of symmetry are called meso forms. Because they are achiral, they do not rotate plane polarized light. Note that the Fischer projection structure of meio-tartaric acid reveals the plane of symmetry. 

The physical properties of the three stereoisomers of tartaric acid are listed in Table 5.1. The meso compound and either one of the enantiomers are diastereomers. Notice that the physical properties of the enantiomers are the same, whereas the physical properties of the diastereomers are different. Also notice that the physical properties of the racemic mixture differ from the physical properties of the enantiomers. 

The figure given below shows a stereoisomer of tartaric acid. Notice that this compound has two chiral (stereogenic) centers. But, there is a plane of symmetry and thus the molecule itself is achiral and optically inactive. Such compounds that contain one or more stereogenic centers, but are achiral, are called meso compounds. Hence, having a stereogenic center or chiral carbon does not always lead to chirality of the entire molecule. 

Stereoisomers of tartaric acid. One pair of enantiomers and one meso compound. The presence of an internal plane of symmetry indicates that the molecule is achiral. 

Now, let us consider another similar molecule, tartaric acid, where there are two chiral carbons. In tartaric acid, four isomeric forms are theoretically expected (2 = 4). However, because one half of the tartaric acid molecule is a mirror image of the other half, we get a meso structure. This means this compound and its mirror image are superimposable, i.e. they are the same compound. Thus, instead of four, we obtain only three stereoisomers for tartaric acid. 

Fischer projections are especially useful in the case of compounds with more than one chirality center. For example, it is easy to see the plane of symmetry in meso-tartaric acid. As was the case with regular structures, interchanging any two groups in a Fischer projection results in inversion of configuration at the chirality center. Thus, interchanging the H and OH on the lower chirality center of weso-tartaric acid inverts the configuration at that chirality center, resulting in the (27 ,3R)-stereoisomer, (-i-)-tartaric acid. It is also easy to see that this stereoisomer does not have a plane of symmetry. 

We can now return to the original question How many stereoisomers are there of tartaric acid The answer is three one meso compound and one pair of enantiomers. Note that the meso compound is a diastereomer of each of the other stereoisomers. 

In general, the maximum number of optically active isomers is given by 2n where n represents the number of asymmetric carbon atoms. Thus for a compound where n = 1, as in lactic acid, there would be two stereoisomers, one the dextro and the other the laevo. For a compound with two asymmetric carbon atoms, there would be 22 = 4 stereoisomers. But if the two asymmetric carbon atoms carry exactly identical groups, as in tartaric acid, the number would be fewer than four and we know that it exists in three forms, the d the 1 and the meso. 

This is essentially the same as the tartaric acid example, without the conformational complication. Thus, there are two chiral centres, and the groups around each centre are the same. Again, we get only three stereoisomers rather than four, since the cis compound is an optically inactive meso compound. There is a plane of symmetry in this molecule, and it is easy to see that one chiral centre is mirrored by the other, so that we lose optical activity. 

We can draw these three stereoisomers as Fischer projections, reversing the configurations at both centres to get the enantiomeric stereoisomers, whilst the Fischer projection for the third isomer, the meso compound, is characterized immediately by a plane of symmetry. For (-l-)-tartaric acid, the configuration is 2R, >R), and for (—)-tartaric acid it is (2S,3S). For both chiral centres, the group of lowest priority is hydrogen, which is on a horizontal line. In fact, this is the case in almost all Fischer projections, since, by convention, the vertical... 

The two glyceraldehyde isomers of 4-13 are identical in all physical properties except that they rotate the plane of polarized light in opposite directions and form enantiomorphous crystals. When more than one asymmetric center is present in a low-molecular-weight species, however, stereoisomers are formed which are not mirror images of each other and which may differ in many physical properties. An example of a compound with two asymmetric carbons (a diastereomer) is tartaric acid, 4-16, which can exist in two optically active forms (d and L, mp 170 C), an optically inactive form (meso, mp 140 C), and as an optically inactive mixture (dl racemic, mp 206°C). 

Tartaric acid has three stereoisomers because each of its two asymmetric carbons has the same set of four substituents. The meso compound and the pair of enantiomers are named as shown. 

So tartaric acid can exist as two diastereoisomers, one with two enantiomers and the other achiral (a meso compound). It s worth noting that the formula stating that a compound with n stereogenic centres has 2 diastereoisomers has worked but not the formula that states there are 2 stereoisomers. In general, it s safer not to count up total stereoisomers but to work out first how many diastereoisomers there are, and then to decide whether or not each one is chiral, and therefore whether or not it has a pair of enantiomers. 

Only three stereoisomers exist for tartaric acid because it has two equivalent chiral centers. Two of the stereoisomers are enantiomers. The third has a plane of symmetry, is optically inactive, and is called a meso compound, i.e., meso-x.zxx.znc acid. 

Compounds containing several chiral centers can exist in different stereoi-someric forms. Various stereoisomers usually possess different physicochemical properties, except for isomers that are enantiomers (the remaining isomers with different properties are diastereoisomers). If a molecule contains two identical chiral centers (as in, e.g., 2,3-butanediol, 2,3-dichlorobutane, or tartaric acid), it can occur in the meso form that is not optically active, or in the form of two optically active enantiomers. If a molecule contains two different chiral centers, then it exists as two enantiomeric pairs that are diastereoisomeric with respect to each other (Figure 2.12). 

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