What are stereoisomers?

Stereoisomers are a type of isomers. Isomers are molecules that have the same number and
type of atoms (same molecular formula), but the atoms are arranged differently.

Now, there are two main ways this arrangement can differ:

1. Structural isomers – In these, the atoms are connected in a different order. For example,
the atoms may form different chains or branches. This type is called structural (or
constitutional) isomerism.

2. Stereoisomers – In these, the atoms are connected in the same order (same bonding
pattern), but they are arranged differently in space. Imagine two objects that have the
same parts but are twisted or mirrored in different ways — that’s stereoisomerism.

Stereoisomerism does not include differences caused by rotating the whole molecule or rotating
around single bonds — those are just different positions, not different isomers.

There are two main types of stereoisomers:

• Geometrical isomers (also called cis-trans isomers): These occur due to restricted
rotation, usually around a double bond or a ring system.

• Optical isomers (also called enantiomers): These are molecules that are mirror images
of each other and cannot be superimposed, like left and right hands.

Optical Isomerism

Optical isomerism is a type of stereoisomerism. The term "optical" refers to how these
isomers affect plane-polarized light, which is light that vibrates in only one direction.

When a compound shows optical isomerism, it exists in two different forms called
enantiomers. These enantiomers are mirror images of each other, just like your left and right
hands. Although they have the same molecular formula and atom connectivity, they behave
differently when interacting with polarized light.
 • One enantiomer rotates the plane of polarized light to the right (clockwise direction).
This form is called the (+) or dextrorotatory enantiomer.
For example, one optical isomer of the amino acid alanine is known as (+) alanine.
• The other enantiomer rotates the plane of polarized light to the left (anticlockwise
direction). This form is called the (−) or levorotatory enantiomer.
The other isomer of alanine is known as (−) alanine.

If both enantiomers are present in equal amounts, they cancel out each other's effect on light.
This type of mixture is called a racemic mixture or racemate. A racemic mixture is
optically inactive, meaning it does not rotate plane-polarized light.

Origin of Optical Isomers

Optical isomers in organic chemistry usually come from molecules that have a carbon atom
bonded to four different groups. This special carbon atom is called a chiral center or asymmetric
carbon.

Even though two molecules may have the same four groups attached to the central carbon atom,
they can still be different in how those groups are arranged in space. These two different
arrangements are mirror images of each other, but they cannot be superimposed (you cannot
place one over the other and make them match exactly).

Because of this difference in spatial arrangement, these two forms are called optical isomers or
enantiomers. The presence of a chiral carbon is usually the reason why a molecule can exist in
these two distinct mirror-image forms.

Chiral and Achiral Molecules

difference between chiral and achiral molecules lies in symmetry.

 • If a molecule has two or more identical groups attached to the central carbon atom, it
often has a plane of symmetry. This means you can divide the molecule into two equal
halves that are mirror images of each other. Such a molecule is called achiral. It cannot
show optical isomerism.

• On the other hand, if a carbon atom is bonded to four different groups, the molecule has
no plane of symmetry. This means there is no way to split the molecule into two
identical mirror-image halves. Such a molecule is called chiral.

The carbon atom with four different groups attached is known as a chiral center or an
asymmetric carbon.

Only chiral molecules can exist as optical isomers, because they have non-superimposable
mirror images — just like your left and right hands.

The relationship between the enantiomers

Enantiomers are a pair of molecules that are mirror images of each other, but cannot be placed
on top of each other to match exactly. This is what we mean by "non-superimposable mirror
images." Imagine one molecule looking into a mirror — what it would see is the shape of its
enantiomer. Even though both molecules have the same atoms connected in the same order,
the three-dimensional arrangement of these atoms in space is different. Because of this
difference in spatial arrangement, you cannot rotate or flip one enantiomer to make it look
exactly like the other. This is what makes them unique, and it’s why they behave differently in
certain situations, such as when interacting with plane-polarized light or with biological
systems.
If a molecule is achiral (meaning it has a plane of symmetry), then its mirror image is not truly
different from the original. If you imagine the molecule looking into a mirror, the reflection
may look reversed at first, but by simply rotating the mirror image in space, you can line it up
exactly with the original molecule.

In other words, you can superimpose the original molecule and its mirror image — they fit
perfectly on top of each other. Because of this, achiral molecules do not form enantiomers and
do not show optical isomerism.

Example 1: Butan-2-ol (An Optical Isomer Example)

In molecules like butan-2-ol, the asymmetric carbon atom (also called a chiral center) is
the carbon that has four different groups attached to it. In diagrams, this chiral carbon is often
marked with a star (*) to help identify it easily.

To show that a compound like butan-2-ol has optical isomers, it’s important to draw the two
enantiomers properly using 3-dimensional bond notation:

• Use a solid wedge (▲) to show a bond coming out of the plane (towards you).

• Use a dashed wedge (▯ or dashed line) to show a bond going behind the plane (away
from you).

• Draw the other two bonds in the plane of the paper using regular lines.

Start by drawing one isomer, and then draw a mirror line next to it. On the other side of the
mirror, draw the mirror image of the molecule. You don’t have to flip letters or numbers like
you would in a real mirror. However, it's helpful to reverse the positions of large groups, like
the ethyl group, to show the difference clearly.

It doesn’t matter in which order you arrange the four groups around the central carbon in your
first structure — as long as you draw an accurate mirror image, you’ll automatically get the
correct pair of enantiomers.
Example 2: 2-Hydroxypropanoic Acid (Lactic Acid)

In lactic acid (also called 2-hydroxypropanoic acid), there is a chiral center, which is usually
marked with a star (*). This is the carbon atom that is attached to four different groups: a
hydrogen (H), a hydroxyl group (OH), a methyl group (CH₃), and a carboxylic acid group
(COOH).

Because of the chiral center, lactic acid exists as two enantiomers — non-superimposable
mirror images of each other.

When drawing these two enantiomers:

1. Start by drawing one isomer using 3D bond notation (solid wedge, dashed wedge, and
straight lines) to clearly show the arrangement of the four groups around the chiral
carbon.

2. Then draw a mirror line and create the mirror image of the first isomer.

Very important tip:

When drawing the COOH group (the carboxylic acid group) in the mirror image, make sure
to reverse its direction correctly. If you draw it facing the same way as in the original
molecule, there's a high chance that you might attach it incorrectly to the central carbon in the
mirror image.
Example 3: 2-Aminopropanoic Acid (Alanine)

Alanine is a good example of a naturally occurring amino acid that shows optical isomerism.
Its structure is very similar to lactic acid (2-hydroxypropanoic acid), except that the –OH
group is replaced by an –NH₂ group (an amino group).

Like lactic acid, alanine also has a chiral center — a carbon atom bonded to four different
groups:

• A hydrogen atom (H)

• A carboxylic acid group (–COOH)

• An amino group (–NH₂)

• A methyl group (–CH₃)

This allows alanine to exist as two enantiomers — mirror-image forms that cannot be
superimposed.

Which Enantiomer is Found in Nature?

Only one of these two forms is found naturally in proteins: the (+) form of alanine. However,
just by looking at the molecular structure, you cannot tell which one is (+) and which one is
(–).

Scientists have been able to determine which isomer occurs naturally. The naturally occurring
form of alanine has a specific spatial arrangement of its groups around the chiral carbon. This
arrangement is called the L-configuration (with a capital "L"). The other form is called the D-
configuration.

So, natural alanine is often written as L-(+)alanine, which means:

• It has the L-configuration (the arrangement of atoms),

• And it rotates plane-polarized light to the right (clockwise), which is indicated by

the (+) sign.

Important Note on Optical Rotation

Even if another compound has the same arrangement of groups around the chiral center as
alanine (for example, another amino acid), that does not mean it will rotate light in the same
direction. Some amino acids with similar structures are (+), and others are (–). The direction of
rotation depends on the specific 3D arrangement of the atoms and their interactions with
light, which cannot be predicted just by looking at the structure alone.

Biological Importance of Enantiomers

In biological systems, usually only one enantiomer of an optically active substance is active
or useful. This is because the shape and arrangement of the molecule must fit exactly into
specific enzyme active sites — like a key fitting into a lock. The wrong enantiomer may not
fit at all, or may not produce the desired biological effect.

Synthesis in the Laboratory

When chemists synthesize chiral compounds like alanine in the laboratory, they often end up
making a 50:50 mixture of both enantiomers. This is called a racemic mixture or racemate.
Racemic mixtures are optically inactive because the effects of the two enantiomers cancel
each other out.

The two enantiomers are:

Identifying Chiral Centers

To identify chiral centers in molecules, we often use skeletal formulas, which are simplified
versions of structural formulas.

Let’s first understand how skeletal formulas work:

• Carbon atoms are not shown directly. Instead, each corner (or end) of a line in the
diagram represents a carbon atom.

• Hydrogen atoms attached to carbon are also not shown.

• Other atoms, like oxygen in –OH groups, are shown.

• Every carbon atom is assumed to have 4 bonds. So, if a carbon appears to have fewer
than four visible bonds, the missing ones are hydrogens.

Example: Butan-2-ol

butan-2-ol, a simple alcohol. Its structure contains four carbon atoms, and the –OH group is
attached to the second carbon in the chain.

If we look at its skeletal formula, it may not be obvious at first, but with a bit of analysis, we
can figure it out:

• The second carbon (the one bonded to –OH) also has:

o a hydrogen,

o a methyl group (–CH₃),

o and an ethyl group (–CH₂CH₃).

This carbon is bonded to four different groups, which makes it a chiral center. Because of
this, butan-2-ol exists as optical isomers (enantiomers).

Spot a Chiral Center in a Skeletal Formula:

 1. Locate each carbon and mentally "fill in" the hydrogens needed to make four bonds.

2. Check what is attached to each carbon.

3. If a carbon is bonded to four different groups, it is a chiral center.

Example 4: 2,3-Dimethylpentane

more complex example: 2,3-dimethylpentane. This compound has a straight chain of five
carbon atoms (pentane), with methyl (–CH₃) groups attached to carbon 2 and carbon 3.

Let’s check each labeled carbon:

Carbon 2:

• It is bonded to:

o two methyl groups (identical),

o a hydrogen atom,

o and part of the pentane chain.

Since two of the groups are the same, this carbon does not have four different groups. So, it
is not a chiral center.

Carbon 3:

• It is bonded to:

o a methyl group (–CH₃),

o an ethyl group (–CH₂CH₃),

o a larger hydrocarbon chain,

o and a hydrogen atom.

This carbon has four different groups attached, which means it is a chiral center.
Introducing Ring Structures in Optical Isomerism

When analyzing ring structures, you do not need to check:

• Carbon atoms involved in double bonds.

• Carbon atoms that have only two visible bonds (because the remaining two are
hydrogen atoms, making them not chiral).

Example 1: A Ring with an –OH Group

In the following compound, focus on the carbon with the –OH group attached.

This carbon has:

• An –OH group,
• A hydrogen (not shown in skeletal formula but assumed),
• Two connections to the carbon ring on either side.

To figure out if this carbon is chiral, you need to:

• Trace the ring in both directions starting from the carbon in question.
• See if the two paths give you different groups or identical ones.

In this case:

• Going clockwise: you hit a carbon with a double bond right away.
• Going counter-clockwise: you pass two single-bonded carbons first, then reach a
double bond.

These are not the same, meaning the two hydrocarbon paths are different.

Thus, the carbon with the –OH is bonded to:

 1. –OH group,
2. Hydrogen,
3. One side of the ring,
4. Other side of the ring.

Since all four are different, this carbon is a chiral center.

Example 2: A Similar Molecule, But Symmetrical

Now consider a similar-looking ring compound. Again, look at the carbon with the –OH at
the bottom.

This carbon appears the same as before, but now if you trace the ring in both directions, the
pattern is:

• Exactly the same clockwise and counter-clockwise.

So, this carbon is attached to:

1. –OH group,
2. Hydrogen,
3. A hydrocarbon group (left),
4. An identical hydrocarbon group (right).

Because two of these groups are identical, this carbon does not have four different groups —
so it is not a chiral center.

Additionally, you can see that this molecule has a plane of symmetry running vertically
through the carbon with the –OH group. This symmetry confirms that the molecule is
achiral.
Example 5: Cholesterol

Cholesterol is a complex organic molecule made up of multiple rings and chains, and its
structure includes several carbon atoms that can act as chiral centers. When identifying chiral
centers in such a molecule, we look for carbon atoms that are bonded to four different groups
and lack a plane of symmetry. In the skeletal formula of cholesterol, a few carbon atoms are
marked for clarity, though the numbering used is only for discussion and not part of standard
nomenclature. Out of the nine carbon atoms marked, eight are chiral centers. The exception is
carbon 9, which is not chiral because it is attached to two identical methyl groups, and thus
doesn't have four different substituents. The other marked carbons—such as carbon 1, which
is connected to a hydrogen, a hydroxyl group, and two non-identical ring structures—qualify
as chiral because the four groups around them are all different. Similarly, carbons 2 through 8
(except for 9) also meet the condition for chirality, as each is connected to a hydrogen and three
unique hydrocarbon fragments that differ when traced through the ring system. These
differences in spatial arrangement make them asymmetrical. Even without visible planes of
symmetry, tracing through the molecule shows that the environments on each side of these
carbon atoms are not identical. Hence, these positions are confirmed as chiral centers,
contributing to the molecule’s stereochemical complexity and its biological specificity in
interacting with enzymes and receptors.
SPECIFIC ROTATION

Specific rotation refers to the amount by which a solution can rotate the plane of polarized
light when the solution has a concentration of 1 gram per milliliter and is measured in a tube
that is 10 centimeters long. This measurement is taken under specific conditions of light
wavelength and temperature. Molecules that are optical isomers and are non-superimposable
mirror images of each other are called enantiomers. Enantiomers always come in pairs—for
example, the two mirror-image forms of lactic acid. These mirror-image molecules share nearly
all physical properties such as melting point, density, solubility, color, and general reactivity.
However, they differ in one important way: how they interact with plane-polarized light. One
enantiomer rotates the plane of polarized light to the right (this is called dextrorotatory, or
(+)), while its mirror image rotates it to the left (levorotatory, or (−)), and both rotate the light
by the same amount, just in opposite directions. Because they are mirror images, their effect
on light is also mirrored. When equal amounts of both enantiomers are mixed, they cancel each
other's effect on polarized light. This kind of mixture is called a racemic mixture or racemic
modification, and it is said to be optically inactive because the rotations from each form
balance out to zero.

● Enantiomers have identical physical properties, except for the direction of rotation of the
plane of polarized light. ● It is reasonable that these molecules, being so similar, can rotate
light by the same amount. ● The molecules are mirror images, and so are their properties: the
mirror image of a clockwise rotation is a counterclockwise rotation and of exactly the same
magnitude. ● Enantiomers have identical properties in all respects except in their interaction
with plane of polarized light. ● Enantiomers have the same melting point density, solubility,
color, and reactivity toward acids and bases. ● They differ, however, in the direction in which
they rotate the plane of polarized light. ● Both rotate the plane of polarized light to exactly the
same extent (same angle) but one rotates the plane to the right (clockwise : called
dextrorotatory), while the other rotates the plane to the left (anticlockwise called levorotatory).
A mixture of equal parts of enantiomers is called a racemic modification. A racemic
modification is optically inactive when enantiomers are mixed together, the rotation caused by
a molecule of one isomer is exactly canceled by an equal and opposite rotation caused by a
molecule of its enantiomer.

DIASTEREOMERS

Each chiral carbon atom in a molecule doubles the number of theoretically pos isomers. Hence,
molecule with n chiral carbon atoms should have 2 stereoisomers. Diastereomers have different
properties. Two diastereomers will have different melting points, boiling points, and
solubilities. They will have different chemical reactivities toward most reagents.
(A) is the mirror image of (B): (C) is the mirror image of (D). Thus the four isomers are two
pairs of enantiomers. Now compare (A) with (C). They are neither superimposable nor are they
mirror images. They are called diastereomers. (A) and (D) are also diastereomers, as are (B)
and (C), and (B) and (D). Stereoisomers that are not mirror images of each other are called
Diastereomers.

Comparison Between Enantiomers and Diastereomers

Feature Enantiomers Diastereomers

Definition Stereoisomers that are non- Stereoisomers that are
superimposable mirror images not mirror images and
of each other. are non-
superimposable.
Chirality Requirement Molecules must contain at least Molecules must contain
one chiral center. two or more chiral
centers.
Mirror Image They are complete mirror They are not mirror
Relationship images. images of each other.
Superimposability Non-superimposable on each Non-superimposable
other. and not mirror images.
Number of Isomers Always occur in pairs. Can be more than two
stereoisomers in a set.
Physical Properties Identical physical properties (e.g., Different physical and
melting point, boiling point, chemical properties
solubility) except optical (melting points, boiling
rotation. points, solubilities,
reactivities, etc.).
Chemical Properties Same chemical behavior in Often exhibit different
achiral environments, but differ chemical reactivities,
 in chiral environments (e.g., even in achiral
enzymes). environments.
Optical Activity Rotate plane-polarized light by May or may not rotate
equal magnitude but opposite plane-polarized light, and
directions. One is dextrorotatory the amount and direction
(+), the other is levorotatory (−). vary.
Racemic Mixture A 1:1 mixture of enantiomers is Racemic mixtures are not
racemic, optically inactive due to possible between
cancellation of rotations. diastereomers.
Separation Methods Difficult to separate by physical Can be separated by
means; require chiral resolving common physical
agents or chromatography with techniques like
chiral stationary phases. crystallization or
distillation.
Biological Activity Often show different biological Can have drastically
activities (e.g., only one different biological
enantiomer may be properties due to
pharmacologically active). different spatial
arrangements.
Example (R)-lactic acid and (S)-lactic acid. Threo- and erythro-
isomers of 2,3-
dibromobutane.

Meso compounds
A compound with two or more chiral carbon atoms, but also having a plane of symmetry
is called a meso compound.

These molecules have planes of symmetry dividing them midway between the two chiral
carbon atoms in each. Notice that one half of the molecule is the mirror image of the other,
both the molecules are optically inactive even though which have two chiral centres neither
will rotate the plane polarized light.

Understanding Meso Compounds and Chirality Through Examples

Example 1: Human Body as a Meso Analogy

Although the human body contains chiral elements like hands and feet (which are non-
superimposable mirror images), the body as a whole is achiral because it possesses a plane of
symmetry running vertically from head to toe. This symmetry renders the entire body
superimposable on its mirror image, making it analogous to a meso compound.

• The presence of chiral elements does not necessarily make the entire structure chiral.

Human body = Meso (Achiral) due to internal symmetry.

Example 2: A Meso Molecule with Two Chiral Centers

Consider a molecule like meso-tartaric acid. It contains two chiral centers (asymmetric
carbon atoms), yet the molecule is not optically active. Why? Because it has an internal plane
of symmetry dividing the molecule into two symmetrical halves.

• Both chiral centers have opposite configurations (R and S), which cancel out their
optical activity.

• Molecule is meso (achiral) due to internal mirror plane and equal but opposite
chirality.

Example 3: Molecule with Two Chiral Centers but No Symmetry

Now take a molecule with two chiral centers and no internal plane of symmetry, such as
(2R,3R)-2,3-dibromobutane. Since the molecule lacks symmetry, it cannot be superimposed
on its mirror image and is optically active.

• The molecule and its mirror image are enantiomers.

• Molecule is chiral and not meso.

Example 4: Molecule with Plane of Symmetry but No Chiral Centers

Consider a molecule that appears symmetrical and has a plane of symmetry, such as
ethylenediamine (H₂NCH₂CH₂NH₂). Even though it might look like it has chiral centers (due
to NH₂ substituents), the carbon atoms are not bonded to four different groups, so they are
not chiral centers.

• The molecule has no true chirality centers.

 • Molecule is achiral and not meso, because meso compounds require chiral centers
with symmetry.

Characteristics of Meso Compounds

Feature Meso Compounds

Number of Chiral Must have two or more chiral centers

Centers

Chirality Achiral overall, despite having chiral centers

Optical Activity Optically inactive due to internal cancellation

Plane of Symmetry Always present, dividing molecule into mirror-image halves

Superimposability Superimposable on mirror image

Enantiomeric Pair No true enantiomer; the molecule is identical to its mirror

image

Example Molecules Meso-tartaric acid, meso-2,3-butanediol

In Tartaric acid: The molecule contains two chiral carbons and the number of optical isomers
should be 2n = 22 = 4 but number of optical isomer is reduced to 3 because one molecule has
a plane of symmetry. The stereoisomers of tartaric acid are,
I and II are enantiomers (non-superimposable); III and IV are meso form (superimposable).

Elements of Symmetry

It refers to specific features within a molecule that allow it to show symmetry. These elements
include identity, mirror planes, axes of rotation, and centers of inversion.

Identity Symmetry is the simplest type of symmetry. It involves doing nothing to the
molecule—just leaving it exactly as it is. Every molecule, no matter how complex or simple,
always has this symmetry element. The entire molecule itself acts as the symmetry element in
this case. For example, the molecule CHFClBr (which has four different atoms attached to a
central carbon) still has identity symmetry, even though it may not show any other type of
symmetry. Identity symmetry is usually not marked or shown in diagrams because all
molecules naturally have it by default.

Plane of Symmetry
Plane of Symmetry is an imaginary flat surface that divides an object into two equal and
mirror-image halves. If an object has such a plane, it is said to have a plane of symmetry.
Common examples include a person’s body or a hat—both can be split into two matching
halves.

When an object does not have a plane of symmetry, it is called chiral (pronounced ki-ral) or
dissymmetric. In contrast, an object with a plane of symmetry is called achiral.

Chiral objects cannot be superimposed on their mirror images—meaning, you can’t place one
over the other and have all parts line up perfectly. For example, your left hand does not have
a plane of symmetry. Its mirror image is the right hand, and if you try to place them over each
other, the fingers and thumbs don’t match up—they clash. That’s why hands are chiral.

ROTATIONAL SYMMETRY/RADIAL SYMMETRY (Cn)

Rotational Symmetry (also called Radial Symmetry and represented as Cₙ) occurs when an
object can be rotated around a central point and still look exactly the same at certain angles. In
this case, the object matches its original appearance more than once during a full 360° rotation.

The number of times the object looks the same in one full turn (360°) is called its order of
symmetry (n). For example, if an object looks identical 3 times during a full rotation, it has a
C₃ (3-fold) rotational symmetry.

CHIRAL AND ACHIRAL MOLECULES

A molecule (or an object) is said to be chiral or dissymmetric, if it is not superimposable on its

mirror image and the property of non-superimposability is called chirality. On the other hand,
a molecule (or an object) which is superimposable on its mirror image is called achiral (non-
dissymmetric or unsymmetrical). Chiral carbon atom (chiral centre/stereo centre). Carbon atom
bonded to four different atoms or groups is called an asymmetric carbon atom or a chiral atom.
A chiral atom is indicated by an asterisk (*). Note: Isotopes of a particular atom behave as
different groups in stereoisomerism.
If a molecule contains only one chiral centre/atom, then the molecule has to be optically active
(i.e. non superimposable on its mirror image) as it will not contain any element of symmetry.
Molecules containing two or more chiral centers may or may not be chiral (optically active). It
is necessary to distinguish chiral and chiral centre. The word chiral is used for molecule as a
whole which is optically active, whereas chiral centre is for an atom which is attached to form
different atoms/groups. Cholesterol has eight chiral centres

Relationships between Chiral Centers and Chiral Molecules –

The term chiral center refers to an atom in the molecular structure. The term chiral molecule
refers to the entire molecule. - The presence of one chiral center renders the entire molecule
chiral. The presence of two or more chiral centers may or may not result in the molecule being
chiral. In the examples given below the chiral centers are indicated with an asterisk. The
vertical broken line represents a plane of symmetry.

D & L-SYSTEM - The D & L convention, not to be confused with the d (dextro) and l (levo)
descriptors used to designate the direction of specific rotation of chiral compounds, is a
convention used to distinguish between enantiomers of chiral monosaccharides and chiral
alpha-amino acids, based on the molecule drawn as a Fischer projection in a specific
orientation. - The L and D forms of the sugar depends on the orientation of the -H and -OH
groups around the carbon atom adjacent to the terminal primary alcohol carbon (carbon 5 in
glucose) determines whether the sugar belongs to the D or L series. - The D- and L- notation is
based on glyceraldehyde. - When the -OH group on this carbon is on the right, then sugar is
the D-isomer; when it is on the left, then it is the L-isomer.

Most of the monosaccharide occurring in mammals is D sugars, and the enzymes responsible
for their metabolism are specific for this configuration. In solution, glucose is dextrorotatory
hence the alternative name dextrose. - The presence of asymmetric carbon atoms also confers
optical activity on the compound. When a beam of plane- polarized light is passed through a
solution of an optical isomer, it will be rotated either to the right, dextrorotatory (+); or to the
left, levorotatory (-). The direction of rotation is independent of the stereochemistry of the
sugar, so it may be designated D (-), D (+), L (-), or L (+). For example, the naturally occurring
formof fructose is the D (-) isomer.

D-Tagatose is an epimer of D-fructose inverted at C-4

Application of D,L convention to monosaccharides: -

One enantiomer of a chiral monosaccharide is labeled D and the other L. To determine whether
a given enantiomer of a chiral monosaccharide is D or L, use the following procedure. ✔ Step
1: Make sure the acyclic form of the molecule is drawn as a Fischer projection. If the
monosaccharide is an aldose, the aldehyde group must be on top; if it is a ketose, the carbonyl
carbon must be the second carbon from the top.

✔ Step 2: Number the carbon atoms starting at the top.

✔ Step 3: Locate the carbon atom that bears the second highest number, which is known as the
penultimate carbon. If the hydroxy group on the penultimate carbon is on the right of the carbon
chain, assign the label D to he compound; if it is on the left of the carbon chain, assign the label
L.
SEQUENCE RULES

Sequence Rule 1. If the four atoms attached to the chiral center are all different priority depends
on atomic number, with the atom of higher atomic number getting higher priority. If two atoms
are isotopes of the same element, the atom of highet mass number has the higher priority. For
example, in chloroiodomethanesulfonic acid the sequence is I. CI, a-deuterioethyl bromide it
is Br, C, D, H.

Sequence Rule 2.

If the relative priority of two groups cannot be decided by Rule 1, it shall be determined by a
similar comparison of the next atoms in the groups (and so on, if necessary, working outward
from the chiral center). That is to say, if two atoms attached to the chiral center are the same,
we compare the atoms attached to each of these first atoms. For example, take sec-butyl
chloride, in which two of the atoms attached to the chiral center are themselves carbon In CH,
the second atoms are H, H, H in C 2H5 they are C, H, H. Since carbon has a higher atomic
number than hydrogen,C2H5 has the higher priority. A complete sequence of priority for sec-
butyl chloride is there fore Cl,C 2H5 CH3 H.
Specification of configuration:

R and S Now, a further problem arises. How can we specify a particular configuration in some
simpler, more convenient way than by always having to draw its picture? The most generally
useful way yet suggested is the use of the prefixes R and S. According to a procedure proposed
by R. S. Cahn, Sir Christopher Ingold, and V. Prelog, two steps are involved.

Step 1. Following a set of sequence rules, we assign a sequence of priority to the four atoms or
groups of atoms that is, the four ligands-attached to the chiral center. In the case of CHCIBrl,
for example, the four atoms attached to the chiral center are all different and priority depends
simply on atomic number, the atom of higher number having higher priority. Thus I. Br, Cl, H.

Step 2. We visualize the molecule oriented so that the ligand of lowest priority is directed away
from us, and observe the arrangement of the remaining ligands. It in proceeding from the ligand
of highest priority to the ligand of second priority and thence to the third, our eye travels in a
clockwise direction, the configuration specified R (Latin: rectus, right); if counterclockwise,
the configuration is specified S (Latin: sinister left). Thus configurations I and II are viewed
like this:
and are specified R and S, respectively. A complete name for an optically active compound
reveals-if they are known both configuration and direction of rotation, as, for example, (S)-(+)-
sec butyl chloride. A racemic modification can be specified by the prefix RS, as, for example,
(RS)-sec-butyl chloride. We must not, of course, confuse the direction of optical rotation of a
compound a physical property of a real substance, like melting point or boiling point-with the
direction in which our eye happens to travel when we imagine a molecule held in an arbitrary
manner. So far as we are concerned, unless we happen to know what has been established
experimentally for a specific compound, we have no idea whether (+) or (-) rotation is
associated with the R or the S configuration.

Racemic Mixture & Racemization RACEMIC MIXTURE

A racemic mixture is a 1:1 mix of two enantiomers (Each of a pair of molecules that are mirror
images of each other). - No matter how many molecules are in a mixture, it is racemic if there
are equal numbers of the two enantiomers. - The racemic mixture produces a net optical rotation
- of plane polarized light - of zero degrees. This is because the mixture contains equal amounts
- equimolar mixture - of both enantiomers that have opposite rotations. - A racemic mixture is
a solution containing equal amounts of a pair of enantiomers.

RESOLUTION OF RACEMIC MIXTURES –

The separation of a racemic mixture into the individual enantiomerically pure enantiomers is
called resolution. - Since enantiomers have identical physical properties, such as solubility,
boiling point and melting point, they cannot be resolved by common physical techniques such
as direct crystallization, distillation or basic chromatography. - The main difficulty in a process
of resolution is that d or (+) and l or (–) forms have identical physical and chemical properties,
so they cannot be separated by ordinary methods. However, the following methods can be used
for this purpose. (i) Mechanical separation: ▪ If the d or (+) and l or (–) forms of a substance
exits in well-defined crystalline forms, the separation can be done by hand picking with the
help of magnifying lens and a pair of tweezers. ▪ For example, the d and l forms of sodium
ammonium tartarate can be separated by this method. ▪ The method has very limited application
and applies to only few crystalline constituents having different shape. (ii) Biochemical
separation: ▪ In this method, the resolution is done by the use of microorganisms. ▪ When
certain bacteria or moulds are added to a solution of a racemic mixture, they decompose one
of the optically active forms more rapidly than the other. ▪ For example, when the mould,
racemic ammonium tartarate, the mould completely decomposes the d form white l form is left
practically unaffected. The main drawback of the method is that half of the material is destroyed
during resolution. The process is very slow and only small amounts of the materials can be
separated. (iii) Chemical separation: ▪ This is probably the best method of resolution. The
racemic mixture is made to combine with another optically active compound and the resulting
solubility in various solvents. ▪ By fractional crystallization from a suitable solvent, they can
be separated. ▪ For example, the racemic mixture of lactic acid is allowed to combine with the
optically active base (-) strachnine or (+) brucine. –

Example of Resolution of Racemic Mixtures (i) (S)-1-Phenylethylamine combines with a

racemic mixture of lactic acid to form diastereomeric salts. The diastereomers are separated by
fractional crystallization.

After the separation process, each of the diastereomers is subsequently treated with a strong
acid such as hydrochloric acid to regenerate the corresponding enantiomer of lactic acid
Note that the lactic acid would be soluble in the organic layer, while the ammonium salt would
be in the water layer. o Since enantiomerically pure compounds are very expensive, it is usually
necessary to recover and reuse the chiral amine. This is achieved by treating the (S)-1-
phenylethyl ammonium chloride salt with a base such as sodium hydroxide to regenerate and
recover the chiral amine.

RACEMIZATION

Racemization is the conversion of an enantiomerically pure mixture (one where only one
enantiomer is present) into a mixture where more than one of the enantiomers are present. (Or)
Conversion of an optically active substance to a raceme. - Optically active carbonyl compounds
of the type −CHC=O , in which the alpha carbon is asymmetric, are racemized by both acids
and bases

The racemization of an optically active secondary halide with the chiral carbon carrying the
halogen (e.g., 2- chlorobutane) may occur in the solution and, usually, the more polar and better
ionizing the solvent is, the more readily the substance is racemized. Ionization of the halide by
an SN1 process probably is responsible, and this certainly would be promoted by polar
solvents. All indications are that an alkyl carbocation once dissociated from its accompanying
anion is planar; and, when such an ion recombines with the anion, it has equal probability of
forming the D and L enantiomers:

Asymmetric Synthesis

If one could prepare 2-hydroxypropanenitrile from ethanal and hydrogen cyanide in the
absence of any chiral reagent and produce an excess of one enantiomer over the other, this
would constitute an absolute asymmetric synthesis - that is, creation of preferential chirality
(optical activity) in a symmetrical environment from symmetrical reagents:

This obviously is unlikely for the given example because there is no reason for cyanide ion to
have anything other than an exactly equal chance of attacking above or below the plane of the
ethanal molecule, producing equal numbers of molecules of the enantiomers, 21 and 22 .
However, when a chiral center is created through reaction with a dissymmetric (chiral) reagent,
we should not expect an exactly 1:1 mixture of the two possible isomers. For example, in an
aldol-type addition (Section 18-8E) of a chiral ester to a prochiral ketone the two configurations
at the new chiral center in the products 23 and 24 are not equally favored. That is to say,
asymmetric synthesis is achieved by the influence of one chiral center (R∗) on the development
of the second:
You will notice that the reaction products 23 and 24 are diastereomers, not enantiomers.
Asymmetric synthesis can be achieved only when the possible transition states for reaction are
diastereomeric because they then will have different energies and will lead to products at
different rates. The larger the energy difference between diastereomeric transition states, the
more stereochemical preference there will be for one chirality over the other. The degree of
stereochemical control displayed by the first chiral center usually depends on how close it is to
the second - the more widely separated they are, the less steric control there is. Another factor
is the degree of electronic control. If all the groups are very much the same electrically and
sterically, not much stereochemical control is to be expected. Even when the chiral centers are
close neighbors, asymmetric induction is seldom 100% efficient in simple molecules. In
biochemical systems, however, asymmetric synthesis is highly efficient. The stereospecificity
of living organisms is imperative to their efficiency.