Stereochemistry manik 2

Md. Imran Nur ManikLecturer

Department of PharmacyNorthern University Bangladesh

Stereochem-istry

Light that has been passed through a nicol prism or other polarizing medium so that all of the vibrations are in the same plane.

Plane polarized light

non-polarized polarized

OPTICAL ISOMERISMThe polarimeter

If the light appears to have turned to the right turned to the left DEXTROROTATORY LAEVOROTATORY

A Light source produces light vibrating in all directionsB Polarising filter only allows through light vibrating in one directionC Plane polarised light passes through sampleD If substance is optically active it rotates the plane polarised lightE Analysing filter is turned so that light reaches a maximumF Direction of rotation is measured coming towards the observer

A BC D

EF

PolarizationPolarization is a property of certain types of waves that describes the orientation of their oscillations. Electromagnetic waves such as light exhibit polarization; acoustic waves (sound waves) in a gas or liquid do not have polarization because the direction of vibration and direction of propagation are the same.

Plane polarised light: A polarized light vibrating in a single plane perpendicular to the direction of propagation.

Polarimeter: A polarimeter is an instrument used to measure the angle of rotation caused by passing polarized light through an optically active substance.

The property of a substance of rotating the plane of polarized light is called Optical activity and the substance possessing it is said to be Optically active.

The observed rotation of the plane of polarized light (determined with the help of polarimeter) produced by a solution depends on (a) the amount of the substance in tube (b) on the length of the solution examined ; (c) the temperature of the experiment; and (d) the wavelength of the light used.Specific rotation: It is defined as the number of degrees of rotation observed when light passed through 1decimetre (10 centimetres) is of its solution having concentration 1 gram per millilitre.The specific rotation of a given substance can be calculated by the following expression

Where [α]tºD a stands for specific rotation determined at tºC and using D-line of sodium light; αabc is the observed angle of rotation; l is the length of the solution in decimeters ; and c is the concentration of the active compound in grams per milliliter.

Optical IsomerismDefinitionWhen two molecules only differ by the three-dimensional position of the substituents around one or more atoms, they are called optical isomers and this phenomenon is called optical isomerism.

C

Br

HCl

CH3

C

Br

HH3C Cl

* *

The positions of Cl and CH3 around thecarbon differs in the two molecules C

HBr

Cl

C

F

H3C

CH

Cl

Br

C

CH3

FHH

*2

*1 *1

*2

The positions of Cl and Br differ around carbon 1and the positions of CH3 and F differ around

carbon 2 in the two molecules

Chirality• The term ‘Chiral’ and therefore the term ‘Chirality’ comes

from a Greek word Kheir which means hands.• An object is called chiral when its mirror image is

non-superimposable on the original and this phenomenon is called chirality.

• If the mirror image is superimposable then the object is called achiral.

Optical Isomerism Contd.

Chiral center• In chemistry, an atom which is attached to non-identical

substituents and the mirror image is non-superimposable is called a chiral center.


C

Br

HCl

CH3

*

C2H5N

H

CH3

is this a chiral center?

C3H7P

C6H5

CH3

is this a chiral center?Technically, for an atom attached to non-identical substituents, the mirror image should be non-superimposable.But if the mirror image is not stable enough, then practically that atom will not be considered as a chiral center.

Tetrahedral center• In chemistry, an atom which is attached to four substituents

is called a tetrahedral center.• Most commonly, carbons show tetrahedral centers.Chiral carbon• A carbon which is attached to four different substituents is

called a chiral carbon.


C

Br

Cl H

CH3

C

Br

Cl H

H

a tetrahedral carbonbut not a chiral carbon

a tetrahedral carbonand a chiral carbon

Elements of symmetry• Any point, line or plane which divides an object into two equal

parts is referred to as an element of symmetry.Plane of symmetry• The imaginary plane which divides an object into two equal parts

is called a plane of symmetry.• In chemistry, the plane of symmetry is an imaginary plane which

divides a molecule into two parts which are mirror image of each other.


HO

COOH

H

HO H

COOH

Plane of symmetry

Conditions for optical isomerism• Following conditions must be met if a molecule is to have

optical isomers:– The molecule must have at least one chiral carbon.– There should not be any elements of symmetry (specifically

plane of symmetry).– The mirror image of the molecule must not be suporimposable

on the original.• So, what about the following structures….


ClOH

H3C C

Cl

Br

CH3H3C C

Cl

Br

C2H5

Optical Isomerism Contd.HO OH

HO OH

H3C C C

H

OH

Cl

Br

C

H

OH

CH3

H3C C C

OH

H

Cl

Br

C

H

OH

CH3 CHO

COOH

H

CHO H

COOH

CH

COOH

OH

CHO H

COOHCH

COOH

OH

CH OH

COOH

CHO

COOH

H

CH OH

COOH

Meso compounds• The compounds which have the following criteria are

called meso compounds:– They have one or more chiral carbons.– There is a plane of symmetry.– The mirror image of the molecule is superimposable on the

original.


HO

COOH

H

HO H

COOH

A meso compound

H

COOH

OH

H OH

COOH

H

COOH

HO

HHO

COOH

The mirror imagemolecule 180o rotated mirror

image molecule

Wedge and dash representation• Wedge and dash projection is a method to represent the three-

dimensional (3D) structure of a molecule.• In this method, three types of lines are used to denote bonds:

– Solid lines: Represent atoms/groups in the same plane (the paper).– Wedged lines: Represent atoms/groups which are coming out of the

plane, towards the viewer.– Dashed lines: Represent atoms/groups which are extending away from

the plane, away from the viewer.


CH3

Cl Br

H

CH3

Br

H

Cl

Fischer projection• Fischer projection is an attempt to depict

three-dimensional molecules in two-dimensional paper.• According to this method, the groups bonded by horizontal

bonds are coming towards the viewer and the groups bonded by vertical bonds are going away from the viewer.

• In this projection, the longest chain is drawn vertically with C1 at the top.


C

Br

H F

CH3

C

Br

H F

CH3

Br

H3C H

F

• Types of optical isomerismOptical Isomerism Contd.

Optical iso-mers

Enantiomer

Dextrorotatory Levorotatory

Diastereomers

Erythro Threo

Enantiomer• Enantiomers are those optical isomers which are mirror

images of each other.• Since there can only be one mirror image, there will always

be two and only two molecules which are enantiomers of each other.

• These two enantiomers differ in one property - optical activity. Based on optical activity, the enantiomers are divided into:– Dextrorotatory enantiomer: This is the enantiomer which rotates

the plane of plane-polarized light to the right.– Levorotatory enantiomer: This is the enantiomer which rotates the

plane of plane-polarized light to the left.



• These two compounds fulfill the conditions for optical isomerism.

• They are also mirror images of each other.

• Hence they are enantiomers.

CH3

Br H

Cl

CH3

H Br

Cl

CH3

Br H

C

CH3

H Br

C

F

H Br H Br

F

• So… What about these two structures?

• Are they optical isomers?• Are they enantiomers?

• So, can you tell me among the two structures on the left side, which is dextrorotatory and which is levorotatory?

• Can you tell me, which is R isomer and which is S isomer?

Diastereomers• Optical isomers which are not enantiomers are diastereomers.• Meaning, two optical isomers which are not mirror images of

each other are diastereomers.• For diastereomers to exist, there must be at least two chiral

carbons in the structure.• In diastereomers, the configuration of at least one chiral

carbon will be same.• Diastereomers differ in many physical and chemical

properties.• Two terms ‘erythro’ and ‘threo’ are associated with

diastereomers. Another two terms commonly used are ‘syn’ and ‘anti’.


Optical Isomerism Contd.CH3

CBr H

C

CH3

CH Br

C

F

H Br H Br

F

• These two compounds fulfill the conditions for optical isomerism.

• But they are not mirror images of each other.

• Hence they are not enantiomers, they are diastereomers.

CH3

CBr H

C

CH3

CH Br

C

F

H Br H Br

F

Erythro: When the identical groups on adjacent chiral carbons are on the same side, the diastereomer is called ERYTHRO.Threo: When the identical groups on adjacent chiral carbons are on the opposite sides, the diastereomer is called THREO.

Racemic mixture• A racemic mixture is one in which two enantiomers are present in

the same amount.• Since each enantiomer rotates the plane of the plane-polarized

light by the same degree but in opposite direction, there is no net rotation in racemic mixture.

• Many optically active compounds exist as racemic mixture. e.g. thalidomide, tartaric acid etcetera.

• Racemic mixtures are denoted by symbols like (±) or dl-. e.g. (± tartaric acid).


CH

COOH

OH

CHO H

COOH

L-Tartaric acid(50%)

CHO

COOH

H

CH OH

COOH

D-Tartaric acid(50%)

• Physical properties of meso compounds, racemic mixture and enantiomers

• The chemical properties of enantiomers, meso compounds and racemic mixtures do not vary at all. However the physical properties can vary.

• This is shown with tartaric acid below:


Compound Melting point (°C)Optical rotation

[α]D (degree)

Density (g/mL)

Solubility at 20 °C (g/100 mL

H2O)

(+)-Tartaric acid 168 - 170 +12 1.7598 139.0(-)-Tartaric acid 168 - 170 -12 1.7598 139.0meso-Tartaric acid 146 - 148 0 1.6660 125.0

Racemate of tartaric acid 206 0 1.7880 20.6

Representation of optical isomerism• In general optical isomerism is represented

based on two criteria:• Based on optical activity

– d/l method (old).– (+)/(-) method (modern).

• Based on configuration around chiral carbon.– D/L method (limited use).– R/S method (universal).


Optical isomers based on optical activity• Based on the ability to rotate the plane of the

plane-polarized light, optical isomers are divided into two types.– Dextrorotatory: Rotates the plane to the right. It is

denoted by d- or (+).– Levorotatory: Rotates the plane to the left. It is denoted

by l- or (-).



CH

COOH

OH

CHO H

COOH

This compound is denoted ( )-tartaric acid because it's

specific optical rotation is 12o

On the other hand, it is denotedL-tartaric acid because the OH groupon the carbon before terminal is on the left,it has nothing to do with optical rotation

CHO

COOH

H

CH OH

COOH

This compound is denoted ()-tartaric acid because it's

specific optical rotation is 12o

On the other hand, it is denotedD-tartaric acid because the OH groupon the carbon before terminal is on the right,it has nothing to do with optical rotation

d/l or (+)/(-) denotation is placed on a compound after its optical rotation is measured with a polarimeter. D/L or R/S denotion has nothing to do with it.

D/L configuration• D and L method is used to describe the position of the atoms/groups

around the chiral carbon. It doesn’t tell whether the compound is dextrorotatory or levorotatory.

• This method was proposed by Rosanoff in 1906.• This method uses the two enantiomers of Glyceraldehyde as reference

molecules.

• Any compound which looks like or degrades to D-glyceraldehyde would be denoted by D- and any compound which looks like or degrades to L-glceraldehyde would be denoted by L-.


CHO

C

CH2OH

HO H

This enantiomer is dextrorotatory,Rosanoff designated this molecule

as D-glyceraldehyde

CHO

C

CH2OH

H OH

This enantiomer is levorotatory,Rosanoff designated this molecule

as L-glyceraldehyde

D/L naming method• It can be applied to compounds which are similar to

glyceraldehyde or degrades to glyceraldehyde.• This method is applied to:– Carbohydrates– Derivative of carbohydrates (e.g. some carboxylic acids, aldehydes)– Amino acids

• For this method, first Fischer projection of the compound must be drawn.

• For carbohydrates and its derivatives, the position of the OH group on the highest numbered chiral carbon is looked at. If the OH group is on the left it is termed L- and if it on the right then it is termed D-.



CHO

C

CH2OH

HO H

CHO

C

CH2OH

H OH

L-glyceraldehyde D-glyceraldehyde

CHO

2C

1

C3

C4

C5

CH2OH6

HO H

H OH

HO H

HO H

L-glucose

CHO

2C

1

C3

C4

C5

CH2OH6

H OH

HO H

H OH

H OH

D-glucose

CH2OH

2C

1

C3

C4

C5

CH2OH6

HO H

H OH

HO H

HO H

CH2OH

2C

1

C3

C4

C5

CH2OH6

H OH

HO H

H OH

H OH

D-sorbitolL-sorbitolCH2OH

2C

1

C3

C4

C5

COOH6

HO H

H OH

HO H

HO H

CH2OH

2C

1

C3

C4

C5

COOH6

H OH

HO H

H OH

H OH

D-glucoronic acidL-glucoronic acid


L-lactic acid

CH3

C

COOH

HO H

CH3

C

COOH

H OH

D-lactic acidL-erythrose D-erythrose

CHO

C

C

CH2OH

H OH

H OH

CHO

C

C

CH2OH

HO H

HO H

C

C

C

C

C

CH2OH

HO H

H OH

HO H

HO H

L-heptoglucose

C

C

C

C

C

CH2OH

H OH

HO H

H OH

H OH

D-heptoglucose

CHO CHO

HO H H OH

R/S configuration• D/L method of expressing chiral carbon configuration

works on only a few types of compounds.• To express the configuration of chiral carbons in

other compounds, we need another method.• This other method is the R/S method. This method is

universal, meaning that this method works on any compound.

• In R/S method, the configuration of each chiral carbon of the compound is described.


R/S naming method• First, every chiral carbons in the molecule are identified.• Then the configuration in each chiral carbon is determined.• To determine the configuration, the groups attached to the

chiral carbons are assigned priority 1, 2, 3, and 4 according to Cahn-Ingold-Prelog (CIP) rules.

• The group with priority 4 (lowest priority) is sent to the back. Then it is identified which direction follows if one goes from 1 → 2 → 3.

• If the direction is right (clockwise), the chiral carbon is at R (R = rectus, meaning right) configuration.

• If the direction is left (anticlockwise), the chiral carbon is at S (S = sinister, meaning left) configuration.


CIP rules with examples• The group whose first atom (atom connected to

the chiral carbon) has highest atomic number is given priority 1 and so on.


Br C

F

I

H

Priority 3(atomic number = 9)




Anticlockwise direction, steering wheel to the rightSo, it is at R configuration

R-Bromo-fluoro-iodo-methane

• If first atoms are identical, then second atom will be looked at. If the second atoms are also identical, third atom will be looked at and so on.

• If the first atoms are identical, second atoms are also identical, then the group with greater number of high atomic number second atoms is given higher priority.


The number of the chiral carbon is written before the configuration is written

NC C

CH2OH

C2H5

CH3

Priority 1

Priority 2Priority 3

Priority 4(2S)-2-Hydroxymethyl-2-methyl-butyronitrile

• If there is any double or triple bond, then it is considered as two single bonds or three single bonds respectively.

Optical Isomerism Contd.NC C

CH2OH

CHCl2

CH2Cl

Priority 1

Priority 2 Priority 3

Priority 4(2S)-3,3-Dichloro-2-chloromethyl-2-hydroxymethyl-propionitrile

HOOC C

CH2OH

CHCl2

CH2ClPriority 2

Priority 1Priority 3

Priority 4

(2R)-3,3-Dichloro-2-chloromethyl-2-hydroxymethyl-propionic acid

• It is important to note however that Fischer projection is not always reliable, and one should convert the Fischer projection into wedge and dash projection.


C

Br

H F

CH3

C

Br

H F

CH3

Br

H3C H

F

If the configuration is determined from Fischer projection,then this compound is (S)-1-Bromo-1-fluoro-ethane

But actually the configuration is R

C

Br

H F

CH3

CH3

Br

F

H

Now the configuration is R

Br

H3C H

FWhen is looked with the H (4th priority)away from the viewer, it looks like

Fischer projection in wedge and dash projection looks like following

A Simple trick• If the lowest priority group (priority 4 group) is bonded by vertical

bonds, then we can use the Fischer projection to determine R/S configuration directly.

• If the lowest priority group is bonded by horizontal group, then determine the R/S configuration directly. The correct configuration is the opposite of the configuration determined.


Br C

F

I

Cl

Lowest priority group is vertically bonded,just figure out the configuration

Br

C F

I

Cl

Lowest priority group is vertically bonded, figure out the configuration. The opposite of

that configuration is the correct one

S configuration From Fischer projection: S configurationActual: R configuration

• Find the configuration of following structuresOptical Isomerism Contd.

H3C C

CH2OH

OH

C

Br

Cl

CH3

(2R, 3S)-3-Bromo-3-chloro-2-methyl-butane-1,2-diol

Cl

CHOOC CH3

H

(2S)-2-Chloro-propionic acid

COOH

CH OH

CH3(R)-Lactic acid

CHO

C

C

C

C

CH2OH

H OH

HO H

H OH

H OH

(2R, 3S, 4R, 5R)-Pentahydroxyhexanal

CHO

C

C

C

C

CH2OH

HO H

H OH

HO H

HO H

(2S, 3R, 4S, 5S)-Pentahydroxyhexanal

The stereoisomers of aldohexoses• Monosaccharides which contain six carbons and a aldehyde group are

called aldohexoses.• Aldohexose contains 4 chiral carbons, so a total of 24=16 stereoisomers are

there.

CHO

C

C

C

C

CH2OH

HO H

H OH

HO H

HO H

CHO

C

C

C

C

CH2OH

H OH

HO H

H OH

H OH

CHO

C

C

C

C

CH2OH

H OH

H OH

H OH

H OH

CHO

C

C

C

C

CH2OH

HO H

HO H

HO H

HO H

CHO

C

C

C

C

CH2OH

HO H

H OH

H OH

H OH

CHO

C

C

C

C

CH2OH

H OH

HO H

HO H

HO H

CHO

C

C

C

C

CH2OH

H OH

H OH

HO H

HO H

CHO

C

C

C

C

CH2OH

HO H

HO H

H OH

H OH

CHO

C

C

C

C

CH2OH

HO H

HO H

H OH

HO H

CHO

C

C

C

C

CH2OH

H OH

H OH

HO H

H OH

CHO

C

C

C

C

CH2OH

HO H

H OH

HO H

H OH

CHO

C

C

C

C

CH2OH

H OH

HO H

H OH

HO H

CHO

C

C

C

C

CH2OH

HO H

H OH

H OH

HO H

CHO

C

C

C

C

CH2OH

H OH

HO H

HO H

H OH

CHO

C

C

C

C

CH2OH

H OH

H OH

H OH

HO H

CHO

C

C

C

C

CH2OH

HO H

HO H

HO H

H OH

D-glucose(+53o)

L-glucose (-53o)

D-mannose (+14o)

L-mannose (-14o)

D-allose (+14o)

L-allose (-14o)

D-altrose (+33o)

L-altrose (-33o)

D-gulose (-20o)

L-gulose (+20o)

D-iodose (+15o)

L-iodose (-15o)

D-galactose (+80o)

L-galactose (-80o)

D-talose (+21o)

L-talose (-21o)

The stereoisomers of aldohexoses Contd.CHO

C

C

C

C

CH2OH

HO H

H OH

HO H

HO H

CHO

C

C

C

C

CH2OH

H OH

HO H

H OH

H OH

CHO

C

C

C

C

CH2OH

H OH

H OH

H OH

H OH

CHO

C

C

C

C

CH2OH

HO H

HO H

HO H

HO H

CHO

C

C

C

C

CH2OH

HO H

H OH

H OH

H OH

CHO

C

C

C

C

CH2OH

H OH

HO H

HO H

HO H

CHO

C

C

C

C

CH2OH

H OH

H OH

HO H

HO H

CHO

C

C

C

C

CH2OH

HO H

HO H

H OH

H OH

CHO

C

C

C

C

CH2OH

HO H

HO H

H OH

HO H

CHO

C

C

C

C

CH2OH

H OH

H OH

HO H

H OH

CHO

C

C

C

C

CH2OH

HO H

H OH

HO H

H OH

CHO

C

C

C

C

CH2OH

H OH

HO H

H OH

HO H

CHO

C

C

C

C

CH2OH

HO H

H OH

H OH

HO H

CHO

C

C

C

C

CH2OH

H OH

HO H

HO H

H OH

CHO

C

C

C

C

CH2OH

H OH

H OH

H OH

HO H

CHO

C

C

C

C

CH2OH

HO H

HO H

HO H

H OH

D-glucose (+53o)

L-glucose (-53o)

D-mannose (+14o)

L-mannose (-14o)

D-allose (+14o)

L-allose (-14o)

D-altrose (+33o)

L-altrose (-33o)

D-gulose (-20o)

L-gulose (+20o)

D-iodose (+15o)

L-iodose (-15o)

D-galactose (+80o)

L-galactose (-80o)

D-talose (+21o)

L-talose (-21o)

Health & Medicine

Stereochemistry manik 2