Diastereomers - Chemistry LibreTexts
relationship between absolute configuration (R or S) and the direction of each center is either R or S there are four possible combinations: RR, RS, SS, SR. (RR,SS,RS, SR). *Note: This is only the maximum number of stereoisomers possible not the actual number, it may be less due to meso compounds. * Remember. In essence, this was the birth of stereochemistry. The SS stereoisomer is a diastereomer of both the RS and SR stereoisomers. are equal and opposite, there is no a priori relationship between the optical rotations of diastereomers.
This is one of the primary reason drugs are expensive. When scientists synthesize drugs in the lab, what results is a mixture of diastereomers, molecules with the same connectivity but different stereocenter configurations. The more chiral centers there are in the molecule, the more diastereomers will result. In fact, for a molecule with n chiral centers, there are 2n diastereomers.
Check this for a molecule with three stereocenters. Thus there are a total of 8 possibilities, or 2. It turns out that it is relatively easy to separate the molecules into groups as follows: But now comes the hard part. It's very difficult to separate enantiomers. You will be separating enantiomers in the lab and if you don't agree with me now, you will after that!
Stereochemistry and Chirality Text
Up until about fifteen years ago, the FDA didn't enforce the current rule that drugs could only be sold in their enantiomerically effective form. Thalidomide came very close to being sold in the US in its teratogenic form. The sad story of the thalidomide babies born in Europe was one of the reasons that this rule was established. Note that vitamins, however, are not subjected to the same scrutiny as drugs.
Pure enantiomers have the property that they rotate plane polarized light. This is convienient for scientists, because it allows us to recognize pure enantiomers when we have them.meso compounds
We take a solution of the enantiomer and shine plane polarized light through it. Then we measure the rotation of that light when it comes out on the other side of the solution. The two enantiomers rotate plane polarized light in opposite directions by the same amount of degrees.
This quarter, you will do an experiment in which you measure the rotation of plane polarized light by an enantiomer that you make. Hopefully, it will rotate. In any case, however, remember thatwhether a molecule is R or S has absolutely nothing to do with the direction in which it rotates plane polarized light.
If you have equal amounts of both enantiomers a racemic mixture, or racemate then the two enantiomers will rotate light in opposite directions, cancelling each other out. If at the end of the lab your solution has no net rotation, then you probably didn't separate the enantiomers properly.
In case you hadn't made the connection yet, chirality in this context means the exact same thing that it meant back in section 1. There, we discussed it in very mathematical, group theoretical terms. We said that the defining property of chiral molecules was that they do not possess an improper rotation axis. Of course, the same must be true for the molecules above. A useful fact to remember is that an S1 axis is the same as a mirror plane and an S2 axis is the same as a center of inversion.
If a molecule has either a mirror plane or a center of inversion, then it is not chiral. For molecules having more than one carbon, it is often useful to use Newman projections to determine whether or not the molecule is chiral.
If any conformer of the molecule has a mirror plane or a center of inversion, then the molecule is not chiral. For example, consider 1,2-dichloro-1,2-dibromoethane. Looking at the Newman projection taken along the central C-C bond, we can see that the molecule possesses a center of inversion and therefore is not chiral, despite the fact that it has two stereocenters where a stereocenter is a carbon with four different substituents attached.
Such compounds are called meso compounds. Diastereomers Molecules with more than one stereocenter have many different isomers. Say we have two stereocenters.
Only a pair of molecules with opposite chirality at both carbons can constitute an enantiomeric pair. However, RR and RS have a different relationship. They are called diastereomers. Diastereomers are molecules with opposite chirality at some of the carbons and the same chirality at other carbons. A molecule with 3 stereocenters has 8 stereoisomers: There are 4 pairs of enantiomers.
Other combinations are diastereomers. In general, a molecule with n stereocenters has 2n stereoisomers.
Enantiomers have exactly the same physical properties: They differ only in their reactivity with other chiral molecules such as the receptors in your nose; you might expect enantiomers to have different fragrances. On the other hand, diastereomers have different physical properties.
In the lab, you will synthesize a racemic mixture of a chiral molecule. Separating the two enantiomers that you make will be the challenging part, because the fact that they have the same physical properties makes them difficult to pull apart.
The trick that chemists use is to add another stereocenter to the molecule, thereby creating two diastereomers out of two enantiomers. Where you had a racemic solution of R and S, you now have a solution of two diastereomers: Then, after the diastereomers are separated based on their different physical properties in this case, their different solubilitiesthe extra stereocenter is removed, and you're left with two different solutions of R and S.
This trick is used constantly in the laboratory synthesis of naturally occuring chiral molecules. This may give rise to some chiral centers in which case the molecule is called "prochiral", but the molecules are always created in a racemic mixture, because the double bond can picks up the hydrogens from top or bottom with equal liklihood. The compound that Pasteur examined contained two chiral carbon atoms. In general, a compound that contains n chiral atoms can exist in 2n stereoisomeric forms.
These stereosiomers may be sub-divided into two groups, enantiomers and diastereomers. Diastereomers If a compound contains two chiral atoms, it may exist in four stereoisomeric forms.
Since the configuration at each chiral carbon may be either R or S, there are four stereochemical possibilities: The RR and SS stereoisomers are enantiomers. The RS and SR stereoisomers are also enantiomers. Figure 1 should make things a bit clearer. It shows sawhorse projections of the four stereoisomers of 2-chlorofluorobutane. Figure 1 Ride 'em Cowboy The enantiomeric pairs are shown in matching colors in the figure. Notice that the configurations at C-2 and C-3 of one enantiomer are reversed in the other.
For diastereomers the configurations are opposite at only one of the two chiral centers. So what is the definition of diastereomers? Diastereomers are stereosiomers that are not enantiomers. Exercise 1 A compound that contains 3 chiral atoms may exist in eight stereoisomeric forms. If one of them is designated RRR, what are the designations for the other seven? What are the other three groups?
Absolute Configuration: R-S Sequence Rules
Enter the group with priority 1 in the first box, priority 3 in the second box, and priority 4 in the third box. Exercise 3 What are the four groups attached to C-3 in 2-chlorofluorobutane? Enter the group with priority 1 in the first box, priority 2 in the second box, etc. Unlike enantiomers, diastereomers have different physical properties.
They have different melting points, boiling points, densities, etc. While the optical rotations of enantiomers are equal and opposite, there is no a priori relationship between the optical rotations of diastereomers.
This should be apparent from the structures and optical rotations of the four stereoisomers of the amino acid threonine shown in Figure 2. The naturally occuring stereoisomer of threonine is enclosed in the box within the box. Exercise 5 What are the four groups attached to C-3 in threonine?