Chemistry Question

Virtual Lab ManualStereochemistry:
From stereocenters to E/Z isomers
Synopsis
Take a deep dive into the world of molecules: discover how they are structured and
understand how their spatial arrangement can make all the difference in their physical and
chemical properties.
Stereochemistry concerns the structure and shape of molecules in three-dimensional space.
The positions and connections of atoms in molecules can affect their properties, that’s why
stereochemistry is crucial in the introduction to organic chemistry
However, using only your imagination to visualize these 3D structures can be tough, especially
if you’ve just started your journey into this topic.
From 2D sketches to 3D molecules
In this simulation, you’ll first be guided through the theory behind isomers and chiral centers,
just to make sure you are familiar with these topics. Then, our friendly Dr. One will move your
attention to 3D structures of stereoisomers and will need your help to solve some tasks.
Here, you’ll be asked to recognize chiral and achiral molecules, rotate them and even break a
couple of bonds (don’t worry, we have good insurance).
As you get used to the 3D visualization, the complexity of the molecules will increase, and
your understanding will be tested through quizzes and tasks.
Prioritize the groups in different enantiomers
Once the concept of stereoisomerism has been introduced, you will learn how to assign the
relative configuration of enantiomers through prioritization rules. This is fundamental to
understanding R and S configurations and by looking at some artistic posters, we’ll be able to
make it less tricky and a bit more intuitive.
Once you grasp the concept, Dr. One will test you using the 2D representation often used in
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the theory books, but we’ll add some feedback and animation depending on your answers.
Identify Cis/Trans or E/Z isomers
The next step will be to distinguish between cis and trans isomers. To do so, a visual game
on the main screen of the laboratory will suggest six different molecules, and you’ll decide
whether they are cis or trans.
Finally, after an introduction to E and Z isomers, you’ll be asked to identify three new
molecules before the final quiz.
Will you be able to understand, apply your knowledge and solve the different quizzes Dr. One
will create during the simulation?
Learning Objectives
At the end of this simulation, you will be able to…
● Identify stereogenic centers in chiral molecules and understand the definition of
enantiomers
● Differentiate between chiral and achiral molecules
● Differentiate between cis/trans and E/Z isomers
● Assign R or S configuration to enantiomers applying Cahn-Ingold-Prelog priority rules
Techniques in Lab
None
Theory
Introduction to stereochemistry
Stereochemistry is a branch of organic chemistry that focuses on the spatial arrangement of
molecules and the main subjects of study are the different isomers of molecules. An isomer
is a chemical compound that has the same molecular formula as another, but different
arrangement of atoms in space. Recognizing the difference between isomers is fundamental
not only for classification but also because they can differ in physical and biological
properties. Isomers can be divided between constitutional isomers and stereoisomers:
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Constitutional isomers have the same atoms (molecular formula) but the bonds that
connect them are different.
Stereoisomers, or spatial isomers, share the same atoms and bonds but are arranged
differently in space. These molecules are defined as chiral.
Stereoisomers can be divided further into two other categories: enantiomers and
diastereomers.
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Figure 1: Stereochemistry scheme.
Stereoisomers
In contrast to more well-known constitutional isomerism, which develops isomers simply by
differentiating the atomic connectivity, stereoisomerism generally maintains equal atomic
connections and orders of building blocks as well as having the same numbers of atoms and
types of elements. The difference between stereoisomers is the spatial disposition of the
atoms, moving the discussion to a three-dimensional level.
Stereoisomerism contains within itself two different kinds of isomers, based on whether one
stereoisomer is a mirror image of the other one or not. Molecules that satisfy the
mirror-image and non-superimposable requirements are defined enantiomers, while the
others are diastereomers.
Enantiomers
When two stereoisomers with a central carbon and four different substituents are mirror
images of each other and non-superimposable, they are classified as enantiomers. This is
equivalent to the right-left hand relationships, where they are identical but cannot be
superimposed.
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The concept of stereoisomers is very close to the one of chirality and the two can be easily
confused. A chiral molecule has a carbon with four different substituents, known as
asymmetric carbon, that has lost any kind of symmetry. Therefore, two chiral molecules can
be distinguished only by their absolute configuration in space. If a molecule has two or more
substituents of the same nature, the molecule is considered achiral.
Remember that stereocenter and chiral center are often used with the same meaning, but
there is a slight difference: while stereocenters don’t necessarily imply four different
substituents, chiral centers do. All chiral centers are stereocenters as enantiomers are a
subgroup of stereoisomers, but the vice-versa is not always true, as diastereomers also have
stereocenters.
Figure 2: Bromoethanol enantiomers.
Priority of stereoisomers
The method to name and distinguish two stereoisomers was created by three chemists: R.S.
Cahn, C. Ingold and V. Prelog. This set of rules, often addressed as Cahn-Ingold-Prelog rules,
distinguishes the enantiomers based on their optical ability to deviate light and is often
referred to as the R/S optical rotation system. By assigning priority to the different groups
connected to the central carbon, a stereoisomer can be classified as S if the arrow from the
highest priority group to the second-highest moves in a counterclockwise direction,
otherwise is classified as R if the arrow moves in a clockwise direction.
Before assigning these configurations, it is necessary to understand that priority is based on
the atomic number of the atoms directly connected to the central carbon. A substituent with
a higher atomic number takes precedence over a substituent with a lower atomic number
and therefore hydrogen has the lowest priority.
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The steps to assign R/S configurations are the following:
1. Assign the priority to the groups based on the atomic numbers of the atoms directly
connected to the central carbon.
2. If two or more of the atoms directly bonded to the carbon are the same, then assign
priority based on the next set of atoms adjacent to the directly-bonded atoms,
repeating the same procedure until there is a difference.
3. If two atoms have substituents of the same priority, a higher priority is assigned to the
atom with more of these substituents.
4. Rotate the molecule in space in a way that the group with the lowest priority is
directed away from you.
5. Assign the configuration S if the groups are arranged in a counterclockwise direction,
R if they are arranged in clockwise order.
Cis and Trans isomers
Enantiomers are allowed free rotations of the bonds, as they are characterized by single
bonds. However, this freedom is taken away when a double bond or a cyclic structure is
introduced in the molecule. In the case of alkenes, for example, all the atoms lie on the
same plane and the structure is rigid, thanks to the double bond. The presence of a double
bond gives importance to the position of the two groups connected to each carbon, whether
they are above or below the double bond. This leads to a special kind of isomerism, part of
the diastereomers, called cis/trans isomers. Having a double bond, however, doesn’t
necessarily imply the presence of an isomer, as some conditions have to be fulfilled:
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The rotation in the molecule must be restricted.
The molecule must present two nonidentical groups on each doubly bonded carbon
atom.
If these conditions are fulfilled and the two nonidentical groups lie on the same side of the
double bond, the isomer is classified as cis; if the two groups are on opposite sides, the
isomer is called trans.
In case three or four nonidentical groups are connected to the carbons forming the double
bond, the cis/trans nomenclature is no more sufficient to describe the structure. It is
required to apply the rules of prioritization of enantiomers to the two ligands on each
carbon: if the groups with the highest priority on the two carbons lie on the same side, the
isomer is described as Z; if they lie on opposite sides, it’s described as E.
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Figure 3: Cis and trans isomers of dichloroethene.
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