When there is some constraint in a molecule that restricts the free rotation of
substituted groups, they become fi xed in space relative to each other. In these cases, the position of the groups must be described with respect to a reference plane.
There are two circumstances where these isomers arise.
1 Double bonded molecules
The double bond consists of one sigma (σ) bond and one pi (π) bond, with the π bond forming by sideways overlap of two p orbitals. Free rotation around this is not possible as it would push the p orbitals out of position, and the π bond would break. The reference plane is perpendicular to the sigma bonds and passes through the double bond.
2 Cyclic molecules
Cycloalkanes contain a ring of carbon atoms that restricts rotation. The bond angles are strained from the tetrahedral angles in the parent alkane. For example, in cyclopropane the carbon atoms form a triangle with bond angles of 60°, and in cyclobutane the atoms form a puckered square with approximate angles of 90°. The reference plane is the plane of the ring.
When the molecule contains two or more different groups attached to the double bond or to the ring, these can be arranged to give two different isomers. The simplest examples, involving only two different substituents, form what are known as cis and trans isomers.
C X Y X
Y C
Y
X X
Y
C C
X Y
X Y
X Y
Y X trans isomer cis isomer
trans isomer cis isomer
Cis refers to the isomer that has the same groups on the same side of the double bond or ring, while trans is the isomer that has the same groups on opposite sides, or across the reference plane. These prefi xes are given in italics before the name of the compound.
Cis–trans isomerism plays an important role in the chemistry of vision, as light causes a photochemical transformation between the isomers of the pigment rhodopsin.
Cis–trans isomerism is a concern in the margarine industry, where partial hydrogenation of fats leads to the production of trans fats, associated with some negative health effects. A widely used chemotherapy drug used in the treatment of cancer is cis-platin, the activity of which is dependent on its stereochemistry.
Stereoisomers differ from each other in the spatial arrangement of their atoms.
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Organic chemistry
10
C CH3
H H3C
H
C C
CH3
H H
H3C C
trans-but-2-ene cis-but-2-ene
C H
H C CH3
H C
H3C
H
C H
H C H
CH3 C
H3C
H
C Cl
H
C H
H C Cl
H C
H
H
C Cl
H
C H
H H C Cl C
H
H
trans-1,2-dimethylcyclopropane cis-1,2-dimethylcyclopropane
trans-1,3-dichlorocyclobutane cis-1,3-dichlorocyclobutane
Note from the example of 1,3-dichlorocyclobutane above, the substituted groups do not have to be on adjacent carbon atoms; it is their position relative to the plane of the ring that defi nes the isomer.
Worked example
Draw and name the cis–trans isomers of butenedioic acid.
Solution
As the carboxylic acid groups must be in the terminal positions and cannot be attached to a double bond, the condensed structural formula must be
Molecular graphics of the geometric isomers of 1,2-dibromoethene. The atoms are shown as colour-coded cylinders, with carbon in yellow, hydrogen in white, and bromine in red. The cis form is on the left and the trans form on the right. The molecule cannot alternate between the two forms as there is restricted rotation about the carbon–carbon double bond.
517
HOOC–CH=CH–COOH. To identify the geometric isomers, we need to represent the geometry of the molecule.
C
COOH
H HOOC
H C
trans-butenedioic acid cis-butenedioic acid
C
COOH
H H
HOOC C
There are, however, many cases in alkenes where the cis–trans designation breaks down.
This happens when the carbon atoms of the double bond are bonded to more than two different substituents. Consider, for example, 1-bromo-2-methylbut-1-ene.
C CH3
C2H5 H
Br C
As all the groups attached to the double bond are different, there are no ‘same groups’
to position relative to the reference plane. For these cases, a more comprehensive naming system has been developed, known as E/Z isomers.
E/Z isomerism is based on the so-called Cahn–Ingold–Prelog rules of priority, which are applied in turn to the groups on each end of the double bond.
C CH3
1) apply priority rules to these groups
2) apply priority rules to these groups
C2H5 H
Br C
The priority rules get complicated in many cases, but for our purposes can be summarized as follows:
• Rule 1: Look at the atom bonded to the carbon of the double bond. The atom with the higher atomic number has the higher priority.
• Rule 2: If the atoms are the same, for example if they are both carbon atoms, apply the same rule to the next bonded atom. This means that longer hydrocarbon chains have higher priority.
C3H7 > C2H5 > CH3 > H and Br > Cl > F
Next we compare the positions of the highest priority groups on the two carbons of the double bond.
• If the two highest priority groups are on the same side of the double bond then the isomer is ‘Z’.
• If the two highest priority groups are on the opposite side of the double bond, they are labelled as ‘E’.
When we apply these rules to the example above, we fi nd:
1 Br has the higher priority of the two groups attached to the left-hand carbon and 2 C2H5 has the higher priority of the two groups attached to the right-hand carbon.
You will not be able to demonstrate the presence of stereoisomers using a condensed formula of the compound. It is essential in this topic that you use the full structural formula or stereochemical formula to show the differences between the isomers.
CHALLENGE YOURSELF
9 Cis–trans isomerism can occur in inorganic as well as in organic compounds.
Think about why it can occur in square planar or octahedral complexes, but not in tetrahedral molecules.
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Organic chemistry
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As the two highest priority groups are on the same side, this is the Z isomer. If they were on opposite sides it would be the E isomer.
C
This process may sound more complicated than it really is, but becomes clearer with examples.
Worked example
Draw and name, using the E/Z convention, the two stereoisomers of 3-methylpent-2-ene.
Solution
Draw out the full structural formula, identifying the two groups attached to each carbon of the double bond.
C
Apply the priority rules in turn to the groups on each carbon of the double bond.
Draw the isomers with the highest priority groups on the same side (Z) and opposite sides (E) of the double bond.
C2H5 We can see that the E/Z convention has wider application than cis–trans, and is therefore being used increasingly in both organic and inorganic nomenclature.
Cis and trans and E/Z isomers may have some different physical properties depending on the infl uence of the substituted groups on polarity and the shape or symmetry of the molecules. Boiling points, melting points, and solubility data are therefore reported separately for each isomer.
To remember which way round the E/Z classifi cation is applied, it may help to think ‘Z’ is on the ‘zame’ side.
Often the E designation is trans and the Z designation is cis. But this is not always the case, as we can see in this example, where the E isomer is the cis form. So when asked for E/Z nomenclature, make sure you work it out from the priority rules, not from a possible cis–trans approach.
The E/Z notation is derived from German words. Z derives from zusammen meaning ‘together’ and E derives from entgegen meaning ‘opposite’.
CHALLENGE YOURSELF
10 Cis-butenedioic acid forms intramolecular hydrogen bonds at the expense of intermolecular hydrogen bonds. Consider what impact this may have on the physical properties and acid strength of the two isomers.
Differences in the properties of the cis and trans isomers of butenedioic acid become very evident when examples of their roles in biology are compared. They are given distinct non-IUPAC names. Fumaric acid (trans) is an intermediate in the Krebs cycle, an essential part of the reactions of aerobic respiration for energy release in cells. By contrast, maleic acid (cis) is an inhibitor of reactions that interconvert amino acids, for example in the human liver. Their different biological activities are a consequence of their different shapes affecting their binding to enzymes, the biological catalysts that control all these reactions. More details on enzyme activity are given in Chapter 13, Option B – Biochemistry.