BNQ10204

SEM I (2022/2023)

CHAPTER 2: STEREOCHEMISTRY

PREPARED BY: DR NADIRUL HASRAF MAT NAYAN

REVISED & DELIVERED BY: ASSOC. PROF. DR NOOR AKHMAZILLAH MOHD FAUZI

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 OUTLINE

2.0 Introduction
2.1 Stereoisomers
2.2 Enantiomers
2.3 Diastereomers
2.4 Meso compounds 2
 2.0 Introduction to Stereochemistry

 Theterm “stereochemistry” is derived from the Greek

“stereos” meaning solid—it refers to chemistry in three
dimensions.
 The
three-dimensional (3D) structure of a molecule can
greatly affect its physical and chemical properties.
 3D structure is critical in biochemistry.
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2.0: Introduction (Organization of Isomers)

Isomers are compounds with

DIFFERENT physical and chemical
properties but the SAME molecular
formula
There are two (2)
classifications of isomers

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2.0: Introduction (Organization of Isomers)

Constitutional/structural isomers have:

i. different IUPAC names
ii. same or different functional groups
iii. different physical properties
iv. different chemical properties

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2.0: Introduction (Isomers)
• C–C bonds that are constrained in a
cyclic structure cannot freely rotate.
• Although the two molecules below have
the same connectivity, they are NOT
identical.
• With rings and C=C double bonds, cis and
trans notation is used to distinguish
between stereoisomers.
i. Cis—identical groups are positioned
on the SAME side of a ring. Cis- Trans-
1,2-Dimethylcyclohexane 1,2-Dimethylcyclohexane
ii. Trans—identical groups are
positioned on OPPOSITE sides of a
ring.

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 2.1 Stereoisomers

 Stereoisomers that DIFFER IN THE WAY THE ATOMS ARE

ORIENTED IN SPACE, but not in which atoms are
bonded to which atoms.
 Recall that conformational isomers are related solely
by rotations about single bonds.
 Beyond cis and trans isomers, there are many other
important stereoisomers.
 To identify such stereoisomers, we must be able to
identify CHIRAL molecules.
 A CHIRAL object is NOT identical to its mirror image.
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How to determine type of isomers?

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2.1 Stereoisomers (Chirality)

 A CHIRAL object is NOT identical to its mirror

image.
 Chirality is important in molecules.
 Chirality most often results when a carbon
atom is bonded to 4 unique groups of atoms.
 If two molecules are mirror images, they will
have many similar properties, but because they
are not identical, their pharmacology may be
very different.
 Rotation about single bonds can determine
whether a molecule is chiral or achiral.
 If a molecule and its mirror image are rapidly
interconverting conformational isomers, then
the molecule is effectively achiral. 9
 ……Chiral

 The molecule labeled A and its mirror image labeled B are not superimposable
(cHIRAL- NOT IDENTICAL).
 No matter how you rotate A and B, all the atoms never align.
 Thus, CHBrClF is a chiral molecule, and A and B are different compounds.
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 A and B are stereoisomers—specifically, they are enantiomers (mirror image).
 ….Chiral

o A molecule or object that is superimposable on its mirror image

is said to be achiral.
o No matter how all atoms are rotates, it will stay align. 11
o Both of compound are same compound and achiral
2.1 Stereoisomers (Plane of symmetry)

 When an atom such as carbon

forms a tetrahedral center with
four different groups attached to
it, it is called a chiral center (aka
stereocenter or stereogenic
center)
 A carbon atom with four different
groups is a tetrahedral
stereogenic center.
 A PLANE OF SYMMETRY is a mirror
plane that cuts the molecule in
half, so that one half of the
molecule is a reflection of the 12
other half.
 2.1 Stereoisomers (Stereogenic centers)

 Achiral molecules usually contain a plane of

 Always omit from consideration all C atoms
To locate a stereogenic center, examine each
tetrahedral carbon atom in a molecule, and look
at the four groups (not the four atoms) bonded to
it.
symmetry but chiral molecules do not.
 With ONE stereogenic center, a molecule will
ALWAYS be chiral.
 With TWO or more stereogenic centers, a
molecule MAY OR MAY NOT be chiral.
that cannot be tetrahedral stereogenic
centers. These include:
 CH2 and CH3 groups
 Any sp or sp2 hybridized C
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• Tetrahedral stereocenters can be found in cyclics and acylic compounds.
• While larger organic molecules can have two, three, or even hundreds of
stereogenic centers.

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2.2 Enantiomer

 Two compounds that are NON-

SUPERIMPOSABLE mirror images are
called enantiomers.
 The physical and chemical
properties of enantiomers are
IDENTICAL, except
1) the direction of rotation of the
plane of plane polarized light
2) how they react with optically
active reagents.
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2.2 Enantiomer (Drawing Enantiomers)

HOW TO DRAW THIS ENANTIOMER?

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2.2 Enantiomer (Drawing Enantiomers)

1 2

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3 4

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 2.2 Enantiomer
(Identification of Stereogenic Centre of Enantiomers)

✓ Stereogenic centers may

also occur at carbon atoms
that are part of a ring.

✓ To find stereogenic centers

on ring carbons, always
draw the rings as flat
polygons, and look for
tetrahedral carbons that are
bonded to four different
groups 19
 2.3 Diastereomers

 Diastereomers are
stereoisomers that are not
mirror images of each other
and are non-
superimposable on one
another.
 Stereoisomers with two or
more stereocenters can be
diastereomers.
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 Example: Cis-1,2-dichloroethene and trans-1,2-dichloroethene

▪ These have the same molecular formula and the same connectivity, but they are different
molecules (chlorine atoms are on opposite sides).
▪ Also, they are not mirror images of each other.
▪ Cis-1,2-dichloroethene and trans-1,2-dichloroethene, are diastereomers.

▪ Since diastereomers have DIFFERENT PHYSICAL PROPERTIES they can often be separated
by common laboratory techniques such as fractional distillation, crystallization, and simple
chromatography.
▪ Enantiomers cannot be separated by these methods in an achiral environment. 21
 2.4 Meso Compound

❑ Meso compounds ARE ACHIRAL COMPOUNDS THAT HAS MULTIPLE CHIRAL CENTERS. It
is superimposed on its mirror image and is optically inactive despite its stereocenters.
❑ A meso compound should contain two or more identical substituted stereocenters.
❑ Also, it has an internal symmetry plane that divides the compound in half. These two
halves reflect each other by the internal mirror. The stereochemistry of stereocenters
should "cancel out".
❑ When there an internal plane that splits the compound into two symmetrical sides,
the stereochemistry of both left and right side should be opposite to each other, and
therefore, result in optically inactive. Cyclic compounds may also be meso. 22
• Single bonds or sp3-orbitals is that
we can rotate the substituted
groups that attached to a
stereocenter around to recognize
the internal plane. As the
molecule is rotated, its
stereochemistry does not change.

• Even when the whole molecule

rotated by 180 degree. Both
molecules below are still meso.

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 EXAMPLE: Stereoisomers of 2,3-dibromobutane
•Compound C contains a plane of symmetry, and
is achiral (identical to its mirror image).

•A meso compound is an achiral compound

that contains tetrahedral stereogenic centers.
C is a meso compound.

•Meso compounds generally contain a plane of

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symmetry so that they possess two identical

halves.

•Because one stereoisomer of 2,3-dibromobutane

is superimposable on its mirror image, there are
only three stereoisomers, not four.

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▪ Meso compounds can exist in many different forms such as pentane, butane, heptane, and
even cyclobutane.
▪ They do not necessarily have to be two stereocenters, but can have more 25
 Summary and Conclusions
✓ A variety of isomers types were examined in this chapter.

✓ A molecule is chiral if it has an enantiomers. If it does not, it is achiral.

✓ Enantiomers and diastereomers are types of configurational isomers.

✓ Enantiomers are mirror images of each other, while diastereomers are not.

✓ A tetrahedral atom bonded to four different substituents is called a

stereocenter.

✓ Meso compounds, although having tetrahedral stereocenters, are overall

achiral as a result of an internal plane of symmetry.

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End of Chapter

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