Tema 2 QOxENGINY - 2022-23 1

Tema 2: Estereoquímica
1
2. Estereoquímica
2.1. Introducció.
2.2. Convenis per representar estructures 3D en 2D.
2.2.1. Representacions de falques
2.2.2. Representacions de Newman
2.2.3. Projeccions de Fischer
2.3. Isomeria.
2.3.1. Isomeria constitucional.
2.3.2. Isomeria conformacional.
2.3.3. Isomeria configuracional.
2.4. Quiralitat.
2.4.1. Definició.
2.4.2. Centre estereogènic.
2.4.3. Isomeria configuracional en estructures d’1 centre
estereogènic.
2.4.4. Isomeria configuracional en estructures de >1 centre
estereogènic.
2.4.5. Enantio i Diastereoisomeria
2.4.6. Configuració absoluta i relativa
2.4.7. Configuració en alquens
2.5. Puresa enantiòmerica i quantificació.
2.5.1. HPLC.
2.5.2. Activitat òptica: Dextro i levorotatori
2.5.3. Rotació específica i puresa òptica.
2.6. Descriptors D i L
2
2. Estereoquímica
2.1. Introducció.
2.3. Isomeria.
2.4. Quiralitat.
2.4.1. Definició.
estereogènic.
estereogènic.
2.5.1. HPLC.
3
2. Estereoquímica
2.1. Introducció.
4
2. Estereoquímica
2.1. Introducció.
Thalidomide
Sedative Teratogenic
Antiemetic
5
Stereochemistry
2. Estereoquímica
2.1. Introducció.
A carbon with sp3 hybridization has the four substituents around it describing a
geometric figure, a Tetrahedron
Tetrahedron
6
2. Estereoquímica
2.1. Introducció.
2.3. Isomeria.
2.4. Quiralitat.
2.4.1. Definició.
estereogènic.
estereogènic.
2.5.1. HPLC.
7
2. Estereoquímica
Conventions to represent
structures with stereochemical information
3D 2D
8
2. Estereoquímica
A Perspective Representation: (Falca, cuña, wedge)
D A
B
C
B D
C
9
2. Estereoquímica
A tetrahedron can be positioned in many ways in space:
10
2. Estereoquímica
Always retain the spatial orientation around it, substituents may describe a
tetrahedron according to the wedge convention.
11
2. Estereoquímica
Perspective Representation: The Newman Projection
1 s bond referenced
12
dihedral angle (q)
2. Estereoquímica
2.2.3. Projeccions de Fischer The Fischer Projection
In particular, Fischer's projections are most used in

13
carbohydrate and that of Amino acids Chemistry
2. Estereoquímica
Rules:
Choose the main chain
Select the priority carbon (according to nomenclature rules)
Place it at the top of the representation and the rest of the chain aligned vertically.
interpret each carbon from its corresponding appropriate view
B A
FISCHER
A PROJECTION
14
2. Estereoquímica
Examples:
It is worthwhile to draw the main carbon chain describing a zigzag.

15
2. Estereoquímica
2.1. Introducció.
2.3. Isomeria.
2.4. Quiralitat.
2.4.1. Definició.
estereogènic.
estereogènic.
2.5.1. HPLC.
16
2. Estereoquímica
2.3. Isomeria.
ISOMERISM
17
2. Estereoquímica
2.3. Isomeria.
Are the structures in these groups representing exactly the same molecule?
They have the same molecular formula!
molecules with the same molecular

Sometimes, we can find that:
formula are not identical 18
2. Estereoquímica
2.3. Isomeria.
ISOMER:
One of several molecules that have the same atomic composition (molecular
formula) but are not identical and therefore may have different chemical and/or
physical properties
Depending on what differentiates them,

isomers can be classified into different types
Constitution Configuration
Conformation
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2. Estereoquímica
2.3. Isomeria.
CONSTITUTION:
It is the way in which atoms are connected
Constitutional isomers of pentane
20
2. Estereoquímica
2.3. Isomeria.
CONFORMATION
It is the way in which atoms of a molecule are distributed based on degrees of freedom
Ex: turns around s bond
Different conformations of the same molecule q
Newman Projections
1 s bond referenced
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dihedral angle (q)
2. Estereoquímica
2.3. Isomeria.
CONFORMATION:
We can make turns of different degrees around s bonds.
This will generate different conformations.
For the same bond with carbon sp3 atoms on both sides, we can generate:
3 different staggered conformations and 3 different eclipsed conformations.
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2. Estereoquímica
2.3. Isomeria.
CONFORMATION:
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2. Estereoquímica
2.3. Isomeria.
CONFIGURATION:
It is the way atoms are distributed around a subspace of the molecule and
that it does not vary by rotating s bonds
X and Y centers have DIFFERENT CONFIGURACIONS
DOUBLE BONDS may also have different configurations
24
Isomer classification chart 2. Estereoquímica
2.3. Isomeria.
25
2. Estereoquímica
2.1. Introducció.
2.3. Isomeria.
2.4. Quiralitat.
2.4.1. Definició.
estereogènic.
estereogènic.
2.5.1. HPLC.
26
2. Estereoquímica
2.4. Quiralitat.
2.4.1. Definició.
estereogènic.
estereogènic.
CHIRALITY
27
2. Estereoquímica
2.4. Quiralitat.
2.4.1. Definició.
CHIRAL:
Any structure that its:
MIRROR IMAGE is
NON SUPERIMPOSABLE
We will understand it better with some examples of everyday life....
28
2. Estereoquímica
2.4. Quiralitat.
2.4.1. Definició.
Chirality
Any structure that its mirror image is NON SUPERIMPOSABLE
χειρ (kheir)
29
2. Estereoquímica
2.4. Quiralitat.
2.4.1. Definició.
which of
these objects is chiral?
30
2. Estereoquímica
2.4. Quiralitat.
2.4.1. Definició.
Chiral
Not chiral
Chiral
Not chiral
31
2. Estereoquímica
2.4. Quiralitat.
sp3 carbon atoms CAN GENERATE ALSO CHIRAL STRUCTURES: A≠B≠C=D

superimposable = NOT CHIRAL
A≠B≠C≠D
not superimposable = CHIRAL
A sp3 carbon with a CHIRAL environment is call:

STEREOGENIC CENTER
ALWAYS must be a carbon atom with all 4 different substituents! 32
2. Estereoquímica
2.4. Quiralitat.
Any sp3 carbon atom with at least two equal substituents presents an internal plane
of symmetry and because of this, is not an stereogenic center, NOT CHIRAL.
In the same way, a MOLECULE with an internal plane of symmetry can’t be CHIRAL
Symmetry plane
33
2. Estereoquímica
2.4. Quiralitat.
2.4.3. Isomeria configuracional en estructures d’1 centre estereogènic.
How many different structures do you identify among these 4

representations?
A B C D
34
2. Estereoquímica
2.4. Quiralitat.
If we try to draw all the possible structures for a sp3 carbon bonded to 4 different
substituents, ONLY TWO DIFFERENT STRUCTURES can be given:
A B C D
TWO CONFIGURATIONS are so obtained. Move them, rotate them and you will check, only
2 are different
That is what we call an ASYMMETRIC CARBON or STEREOGENIC CENTER.
And we also say that it is CHIRAL.
35
2. Estereoquímica
2.4. Quiralitat.
How many different structures do you identify among these 8

representations?
36
2. Estereoquímica
2.4. Quiralitat.
Within each group, the only difference is the orientation in space.

Remember: for a carbon with 4 DIFFERENT SUBSTITUENTS,
ONLY 2 DIFFERENT CONFIGURATIONS CAN BE GENERATED 37
2. Estereoquímica
2.4. Quiralitat.
This… or this ??
To know if we deal with one or other configuration

an agreement to describe them is needed.
But ... how we can describe, that is ... how can we name them?
The 2 possible configurations can be R or S.

38
2. Estereoquímica
2.4. Quiralitat.
NOMENCLATURE FOR STEROGENIC CENTERS :

CAHN-INGOLD-PRELOG PRIORITY RULES
(SEQUENCE, CIP)
39
1st) Rank the 4 substituents from most priority to less,

Priority is assigned following the ATOMIC NUMBER
40
1st) Rank the 4 substituents from most priority to less,

Priority is assigned following the ATOMIC NUMBER
≡
41
Once a priority has been assigned:

2nd) We will have to "position ourselves" in the opposite side to the least priority
substituent in such a way that the other 3 substituents would be like a tripod
pointing towards us. Once placed in this way, we will imagine that we are
pointing the three substituents in order of priority, this will describe a circular
path. If we describe the trajectory clockwise (time) we will say that the
configuration is R, on the contrary if it is anti-clockwise it will be S.
42
MOLECULES WITH 1 STEREOGENIC CENTER

Nr of stereoisomers: 2n= 21 = 2
Are mirror images

ENANTIOMERS: Configurational isomers
Are NOT superimposable
43
2. Estereoquímica
2.4. Quiralitat.
2.4.4. Isomeria configuracional en estructures de >1 centre estereogènic.
MOLECULES WITH >1 STEREOGENIC CENTER

Nr of stereoisomers: 2n
EXAMPLE:
This structure has 2 stereogenic centers (*) : (22 = 4 stereoisomers)
2-bromo-3-methyl-2-phenylpentan-3-ol
44
4 possible stereoisomers of 2-bromo-3-methyl-2-phenylpentan-3-ol:
45
The reflection of a R center has configuration S and vice versa
configurational isomers, they are mirror images and are not

superimposable. 46
configurational isomers, they are mirror images and are not

superimposable. 47
configurational isomers they are neither mirror image and are nor
superimposable. 48
superimposable. 49
superimposable. 50
superimposable. 51
2. Estereoquímica
2.4. Quiralitat.
MOLECULES WITH >1 STEREOGENIC CENTER

ENANTIOMERS: Those configurational isomers that, among them, are a

mirror image and are not superimposable. Same physical properties (except
one, see below)
DIASTEREOMERS: Those configurational isomers that are neither mirror

image and nor not superimposable. Different physical properties.
52
2. Estereoquímica
2.4. Quiralitat.
Relative & Absolute Configurations
Are the
Same molecule
Meso FORM
ABSOLUTE CONFIGURATIONS
53
Relative & Absolute Configurations
RELATIVE CONFIGURATIONS 54
2. Estereoquímica
2.4. Quiralitat.
C=C Double bond configurations: ZiE
55
2. Estereoquímica
2.1. Introducció.
2.3. Isomeria.
2.4. Quiralitat.
2.4.1. Definició.
estereogènic.
estereogènic.
2.5.1. HPLC.
56
2. Estereoquímica
2.5.1. HPLC.
High Performance Liquid Chromatography (HPLC):
RACEMIC MIXTURE or RACEMATE

Is a mixture composed by
50% of each enantiomer
57
1.6. Enantiomeric Purity Determination
High Performance Liquid Chromatography (HPLC):
58
2. Estereoquímica
OPTICAL ACTIVITY
A property of the substances whose molecules are chiral.
We say that a compound has optical activity when is able to rotate the plane from a beam
of polarized light.
POLARIMETER
Enantiomers will rotate light in the same absolute value but opposite sign
2. Estereoquímica
T
The Optical Activity is quantified as Specific Rotation [a] :
l
...Where:
a = Observed rotation: Rotation angle measured with a polarimeter ( in degrees and sign)
l = path length of light through the cuvette (in dm)
c= concentration of the analyzed solution (in g/mL)
Convention:
example: = + 225 (c 1.0, MeOH)

Two enantiomers of the same molecule present

the same rotation but opposite sign
If we have a mixture of 2 enantiomers of the same molecule two things can

happen:
=0
a) If the mixture is 50%, the mixture will not exhibit optical activity, this mixture is
a RACEMATE or RACEMIC MIXTURE.
b) If one predominates over the other, we will see a certain deflection and if we
know the specific rotation of each of the 2 pure enantiomers, we can know the
% of the enantiomer in the mixture (OPTICAL PURITY):
Example:
a 74% Optical Purity of dextrorotatory enantiomer means:
100-74= 26, 26/2= 13

87% of dextrorotatory enantiomer
13% of levorotatory enantiomer
The enantiomer that ROTATES the light to the RIGHT is DEXTROROTATORY
The enantiomer that ROTATES the light to the LEFT is LEVOROTATORY
It is very important to know that:
SPECIFIC ROTATION SIGN is not assigned to R, S CONFIGURATIONS
In other words:
the R enantiomer can be Dextrorotatory or either Levorotatory

the S enantiomer can be Dextrorotatory or either Levorotatory
To know the sign, you must ALWAYS use the polarimeter!

EXAMPLE:
Which enantiomer of epinephrine is the Dextrorotatory?
WITHOUT THE VALUE OF THE SPECIFIC ROTATION, WE CAN NOT KNOW!

EXEMPLE:
On the other hand,

If we know that the enantiomer R has a specific rotation [a]TD= -50 (LEVO)
Then, because they are ENANTIOMERS!!! :

We can assure the S enantiomer must have [a]TD= +50 (DEXTRO)
2. Estereoquímica
2.1. Introducció.
2.3. Isomeria.
2.4. Quiralitat.
2.4.1. Definició.
estereogènic.
estereogènic.
2.5.1. HPLC.
66
2. Estereoquímica
WACHT OUT !!: D & L DESCRIPTORS
(-)-D-ribosa (+)-L-ribosa
CARBOHYDRATES, EXAMPLE:
(+)-D-glucose (-)-L-glucose
AMINO ACIDS EXAMPLE:
dextrorotatory levorotatory
levorotatory dextrorotatory
70

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Tema 2: Estereoquímica

A Perspective Representation: (Falca, cuña, wedge)

A tetrahedron can be positioned in many ways in space:

Perspective Representation: The Newman Projection

In particular, Fischer's projections are most used in

It is worthwhile to draw the main carbon chain describing a zigzag.

molecules with the same molecular

Depending on what differentiates them,

Constitutional isomers of pentane

Different conformations of the same molecule q

DOUBLE BONDS may also have different configurations

We will understand it better with some examples of everyday life....

Any structure that its mirror image is NON SUPERIMPOSABLE

sp3 carbon atoms CAN GENERATE ALSO CHIRAL STRUCTURES: A≠B≠C=D

A sp3 carbon with a CHIRAL environment is call:

How many different structures do you identify among these 4

How many different structures do you identify among these 8

Within each group, the only difference is the orientation in space.

To know if we deal with one or other configuration

The 2 possible configurations can be R or S.

NOMENCLATURE FOR STEROGENIC CENTERS :

1st) Rank the 4 substituents from most priority to less,

1st) Rank the 4 substituents from most priority to less,

Once a priority has been assigned:

MOLECULES WITH 1 STEREOGENIC CENTER

Are mirror images

MOLECULES WITH >1 STEREOGENIC CENTER

4 possible stereoisomers of 2-bromo-3-methyl-2-phenylpentan-3-ol:

The reflection of a R center has configuration S and vice versa

configurational isomers, they are mirror images and are not

The reflection of a R center has configuration S and vice versa

configurational isomers, they are mirror images and are not

The reflection of a R center has configuration S and vice versa

The reflection of a R center has configuration S and vice versa

The reflection of a R center has configuration S and vice versa

The reflection of a R center has configuration S and vice versa

MOLECULES WITH >1 STEREOGENIC CENTER

ENANTIOMERS: Those configurational isomers that, among them, are a

DIASTEREOMERS: Those configurational isomers that are neither mirror

Relative & Absolute Configurations

C=C Double bond configurations: ZiE

High Performance Liquid Chromatography (HPLC):

RACEMIC MIXTURE or RACEMATE

example: = + 225 (c 1.0, MeOH)

Two enantiomers of the same molecule present

If we have a mixture of 2 enantiomers of the same molecule two things can

100-74= 26, 26/2= 13

The enantiomer that ROTATES the light to the RIGHT is DEXTROROTATORY

The enantiomer that ROTATES the light to the LEFT is LEVOROTATORY

It is very important to know that:

SPECIFIC ROTATION SIGN is not assigned to R, S CONFIGURATIONS

the R enantiomer can be Dextrorotatory or either Levorotatory

To know the sign, you must ALWAYS use the polarimeter!

Which enantiomer of epinephrine is the Dextrorotatory?

WITHOUT THE VALUE OF THE SPECIFIC ROTATION, WE CAN NOT KNOW!

On the other hand,

Then, because they are ENANTIOMERS!!! :

AMINO ACIDS EXAMPLE:

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