Which properties define structural isomers

7. Stereochemistry

In the previous chapters we got to know two types of isomerism (see Chapters 2.2, 2.8, 3.2), the Constitutional isomerism, and the Stereoisomerism :

Stereochemistry is concerned with the geometry (or structure) and handedness (or topography) of molecules, their dynamic aspects, and the relationships between these and the reactivity of the molecule.

We'll get the term here structure define as follows: the type and relative position of atoms in three-dimensional space, which represents a stable molecular system, is called its structure. We often have insight into the structure of a molecule through an X-ray structure analysis. With their help, the structure of a molecule in its crystalline state can be elucidated. After determining the positions of the atoms, one can derive bond lengths and angles as well as other geometric factors.

Examples of stereoisomers we have already encountered:

In this chapter we present another type of stereoisomer that results from the "handedness" of certain molecules. We will see that there are structures that cannot be aligned with your reflection in the mirror, just as your left hand is not aligned with your right. Both structures are therefore different objects, they can have different properties and react in different ways.

7.1 Chiral molecules

Let's consider the Lactic acid molecule, which can exist in two forms:

Mirror plane

Both molecules are related to each other like an object and a mirror image and cannot be brought into alignment. If one wanted to transfer one into the other, one would have to break ties and re-establish them. Pairs of molecules that are mirror images of each other but are not congruent are referred to as Enantiomers. Molecules that can exist in two enantiomeric forms are chiral.

The most important criterion for chirality is that the object and mirror image cannot be brought into congruence, although they have identical connectivity.

Further examples:

In the above examples, all molecules shown contain an atom to which four different substituents are attached. It is referred to as asymmetric atom or Center of chirality.

But many other chiral molecules do not have a center of chirality.
How can chiral structures be distinguished from achiral ones?

It is not always easy to see whether a molecule is chiral or not. It is absolutely foolproof to build models of the molecule and its mirror image and see whether they can be made to coincide. Unfortunately, this procedure is sometimes very time-consuming. But there are two aids that can be used to quickly determine whether a molecule is chiral or not. They are based on the symmetry properties of the molecule.

Due to certain symmetry operations that can be carried out on the molecule, its structure and the position of the atoms in space remain unchanged. We only need to consider two:

the introduction of a Plane of symmetry or one Center of symmetry.

A Plane of symmetry cuts the molecule in such a way that the part of the structure that is on one side of the plane is the mirror image of the part on the other side, e.g .:

A Center of symmetry is a point in a molecule that divides every straight line drawn through it into two equal-sized groups of points on each side with the same neighborhood. There can only ever be one such point, e.g .:

To distinguish a chiral molecule from an achiral one, we just have to remember that chiral molecules must contain neither a center of symmetry nor a plane of symmetry. If one of the two symmetry elements is present in the molecule, it is achiral.

Generalized even further: Molecules with a plane of symmetry or a center of symmetry have two types of so-called rotating mirror axes (pn). Rotary mirror axes consist of a rotary axis (Cn) and a mirror plane perpendicular to the axis of rotation. Chiral molecules may have an axis of rotation but not axis of rotation mirror (pn), where a plane of symmetry = S1 and a center of symmetry = S2 are the same.

Other chiral molecules:

A 1: 1 mixture of enantiomers is referred to as Racemate or racemic mixture

If an enantiomer is brought into equilibrium with its mirror image through some process, one speaks of Racemization i.

E.g. a racemization can occur through a conformational change:

Since this is only a conformational change that requires little energy, the two enantiomeric conformations cannot be separated and obtained in enantiomerically pure form. Succinic acid must therefore be viewed as an achiral molecule.

Against, e.g .:

At Atropisomers they are rotamers in which the rotation around a covalent single bond is restricted by sterically demanding substituents in such a way that conformers can be isolated.

Let's summarize ; Chiral molecules are stereoisomers in which the image and mirror image are not congruent. The two isomers are called enantiomers. Many chiral organic molecules contain a center of chirality, but not others. A chiral molecule has neither a plane of symmetry nor a center of symmetry (in general - no S.n-Symmetry).

7.2 Optical activity

How can we determine which enantiomer is which? And when we know the answer, is there any way to uniquely name an enantiomer and distinguish it from its mirror image?

Enantiomeric molecules are very similar, because they have identical structures ; i.e. identical bond lengths, bond angles, and therefore the same energy content. For this reason Enantiomers have identical physical (melting point, boiling point, etc.) and chemical properties, with the exception of their interaction with other chiral molecules and objects. Nor can they be separated by normal processes (such as crystallization, fractional distillation, various chromatographic methods)

However, if a beam of linearly polarized light is sent through a sample of one of the two enantiomers, the plane of oscillation of the incident light is rotated by a certain amount in one direction (either clockwise or counterclockwise). If you repeat the same experiment with the other enantiomer, the plane of vibration is rotated by exactly the same amount, only in the other direction.

An enantiomer that rotates the plane of polarized light clockwise is known as clockwise (dextrorotatory) and arbitrarily calls it (+) - enantiomer. Similarly, the other enantiomer that rotates the plane counterclockwise is the levorotatory or the (-) - enantiomer.

Contains that Polarimeter achiral molecules, the direction remains unchanged, the sample is optically inactive.

The measured rotation is a macroscopic property - the sum of all rotations through the individual molecules. This is known as optical rotation, and a sample giving rise to an optical rotation than optically active.

The value of the observed optical rotation depends on the concentration and structure of the optically active molecule, the length of the measuring cell, the wavelength of the light, the solvent and the temperature. That's why a specific rotation of all things:

 [α]D.25 = specific rotation at 589 nm and 25OC.
& # 945 = observed rotation
 l = Length of the measuring cell in dm (1 dm = 10 cm)
 c = Concentration in g / ml

The specific rotation of an optically active compound is a physical constant that is characteristic of this substance, as well as its melting point, boiling point and density.


Camphor (1.5 g) is dissolved in 10 ml of chloroform (CHCl3) solved. A rotation of +6,645 is measured in a 10 cm cuvette. Calculate the specific rotation value for camphor.

So the (-) enantiomer of camphor rotates the plane counterclockwise with a specific rotation of -44.3O, while the (+) enantiomer increases the level around +44.3O rotates clockwise.

It follows that the optical rotation of a racemate is zero. It is optically inactive.

In order to be able to observe optical activity in a mixture of enantiomers, one of the two enantiomers must be present in excess. With the help of the value of the specific rotation we can calculate the composition of mixtures of two enantiomers:


optical purity = ([& # 945]D-observed / [α]D. x 100%

7.3 Absolute configuration: The R-S-Sequence rules

How can we determine the molecular structure of a pure enantiomer of a chiral compound?

E.g. lactic acid:

Molecules like (+) - and (-) - lactic acid, which are mirror images of each other (i.e. enantiomers), differ in their Topographies (but not in their structures. They have identical structures). They have different spatial arrangements of the substituents around the chiral center, i.e. they have different handedness, or absolute configurations.

Is it possible to determine the absolute configuration of an enantiomer by measuring the specific rotation? Unfortunately not. There is no clear relationship between the sign of the rotation value and the absolute configuration.

In order to clearly name enantiomers, we need a system with which we can specify the handedness of the molecule. Such a system has been developed by Cahn, Ingold (London) and Prelog (ETH Zurich) (CIP nomenclature system).

In the following we will restrict ourselves to the rules that have been developed for stereoisomerism with asymmetric C atoms:

1) assign all four substituents according to decreasing priority (see chapter 3.2) as 1, 2, 3, and 4 (i.e. according to decreasing ordinal number):

2) Next, rotate the molecule so that the substituent with the lowest priority is farthest from the viewer:

3) If you move counterclockwise to go from 1 to 2 to 3, the center of chirality has the absolute configuration S (sinister, Latin, left). If you move clockwise in the other case, the absolute configuration is R (rectus, Latin, right).

The symbol R. or S. is placed in brackets in front of the name of the chiral compound.

Further examples :

For what reasons could we then assign a positive sign of [& # 945] to one stereoisomer of a chiral compound and a negative sign to the other? This assignment is the most direct route through a certain form of the X-ray structure analysis possible, the anomalous dispersion, which determines not only the structure but also the absolute configuration. The absolute configuration of an enantiomer can also be passed through chemical correlation with a structure whose own absolute configuration was determined by X-ray structure analysis.

7.4 Absolute configuration: a historical consideration

7.5 Fischer projections

A Fischer projection (after Emil Fischer, 1852-1919) is a standard method for the two-dimensional mapping of tetrahedral carbon atoms and their substituents. In this representation method, the molecule is drawn as a cross with the chiral carbon at the intersection of the two axes. The horizontal lines represent bonds that are directed towards the viewer, vertical lines point away from him:

In molecules with multiple centers of chirality:

Both spatial arrangements can be
by simply turning it around
merge into each other.
Fischer projection
(spatial representation with ecliptical arrangement)
stable staggered arrangement

7.6 diasteromers; Molecules with multiple centers of chirality

In molecules that have several centers of chirality (asymmetrical carbon atoms), things get more complicated. Several stereoisomers are now possible. As an example, we will first consider the amino acid threonine. Threonine has two centers of chirality, and each of them can either R. or S. be configured:

A simple permutation shows that four stereoisomers should be possible here. The four stereoisomers can also be written using the Fischer projections:

Now an important question is: how do the stereoisomers relate to one another? As a mirror image, or not? It's pretty easy to tell. If we take a closer look at the molecules, we see that we have two pairs of connections: one R, R / S, SPair, and one R, S / S, R-Pair. The R, R Isomer is the mirror image of the S, S-Isomers. And the R, S-Isomer is the mirror image of the S, R-Isomers. So we have two pairs of enantiomers.

However, stereoisomers that do not behave like image and mirror image are diastereomers.

If we look again at a pair of diastereomers, we can determine something else important:

Diastereomers have different structures (or geometries). That is, if we consider each corresponding bond length, bond angle, and torsion angle, we can see that the diastereomers differ in at least one of these values. This also means that diastereomers should have different energy contents, which further means that in contrast to enantiomers, diastereomeric molecules must have different physical and chemical properties.

They can be separated e.g. by fractional distillation or crystallization or by chromatographic methods. They differ in their melting and boiling points and in their density, just like constitutional isomers, and show different specific rotation values.

The same stereochemical relationship applies to systems in which such centers are separated by one or more atoms.

e.g .:

7.7 Meso connections

How many stereoisomers can one expect if both centers are equally substituted?

e.g. tartaric acid:

Both spatial arrangements can be
by simply turning it around
merge into each other.
Fischer projection
(spatial representation with ecliptical arrangement)
stable staggered arrangement

For the first pair of stereoisomers, the R, R- and S, S-Stereoisomers, it can be clearly seen that it is a pair of enantiomers. However, if you take a closer look at the second pair, you can see that the image (S, R) and mirror image (R, S) to be brought to cover. Both molecules are therefore identical!

The 2R, 3S-Isomer of tartaric acid is achiral and therefore not optically active, although it contains two centers of chirality. A compound that contains two (or more) centers of chirality, but is congruent with their mirror image, is known as Meso connection. All meso connections have a mirror plane, which maps one chiral center onto the other.

It should be emphasized again that there are only two criteria for chirality: 1) Can the molecule be made to coincide with its mirror image? If not, is it chiral, or 2) Does the molecule contain a center or plane of symmetry? If not, it's chiral.

A few more examples:

7.8 Relative configuration

Diastereomers have different ones relative configurations. The relative configuration is the relationship between the absolute configuration (or handedness) of the two contained chiral centers.


You can see the relative configuration with the help of the Erythro / Threo nomenclature describe.

It must be a molecule that contains two equally substituted (i.e. two identical substituents) centers of chirality. The molecule should be written in a Fischer projection:


The erythro / threo Nomenclature is often not suitable because many diastereomers do not meet these criteria. In such cases, the relative configuration can only be changed with the R / S Nomenclature must be specified.

7.9 More than two centers of chirality: even more stereoisomers

What structural diversity can we expect from a compound with three centers of chirality? We can solve this problem again by permuting the various possibilities. Let us mark the three centers one after the other R. or S., the following possible stereoisomers result:


so, a total of eight stereoisomers. They can be assigned to the following four pairs of enantiomers:

picture R-R-R R-R-S R-S-S R-S-R
Mirror image S-S-S S-S-R S-R-R S-R-S

The number of possible stereoisomers decreases when mesoforms and certain cyclic systems occur. In general, a connection with n Centers of chirality maximum2n May have stereoisomers. With larger systems, of course, there are fantastic structural possibilities.

7.10 Separation of enantiomers

The formation of a chiral molecule from achiral starting materials often results in a racemic mixture.The question now arises of how to obtain pure enantiomers of a chiral compound.

One possible method is to start from the racemate and separate the enantiomers from one another. This process is known as Resolution.

But enantiomers have identical physical and chemical properties, with the exception of their interaction with other chiral molecules and phenomena. Diastereomers, on the other hand, have different physical and chemical properties and can be separated by fractional crystallization, distillation or chromatography.

For example, the reaction of the racemate would result XR, S with an optically active, chiral compound YS. two optically active diastereomers:

Below we see how naproxen (a so-called "non-steroidal anti-inflammatory drug" such as ibuprofen) is broken down into the enantiomers in this way. The racemate is first treated with a glucose derivative (which can be obtained from nature in an optically pure form), whereby the two diastereomeric salts are formed:

The (S) -isomer crystallizes out as a salt with the amine on standing and can be filtered off from the mother liquor with the (R) -isomer. When treating the salt with aqueous carbonate solution, the amine can be extracted and (S) -naproxen is crystallized as the sodium salt.

The cleavage of a racemic amine with an enantiomerically pure acid is also possible. There are many other ways in which the formation of diastereomers can be used for resolution.

7.11 Chirality in Nature

We just noticed that diastereomers have different physical properties and can be separated by fractional crystallization, distillation, or chromatography. They also have different chemical properties, which can mean different reactivities towards (chiral) reagents or can lead to different products after a reaction.

We have also noticed that enantiomers have identical physical and chemical properties except for their interaction with other chiral molecules and phenomains. Almost all chiral Biomolecules come in optically pure forms. This means that enantiomeric molecules can show different properties in nature (compared to their properties in the laboratory).

e.g .:

Why do such stereoisomers have different biological properties? In order to exert their biological effect, the molecules must form complexes with other biomolecules (proteins or DNA, e.g.). The biomolecules are chiral! A chiral molecule has to match its specific receptor (like a hand to a glove!). For example, in the following figure we can show a specific interaction between the receptor for adrenaline and the two adrenaline stereoisomers:

Only one of the two diastereomer complexes is stable because only in one complex does each substituent exactly match its binding site.