stereochemistry manik 2
TRANSCRIPT
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.
Optical Isomerism Contd.
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.
Optical Isomerism Contd.
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.
Optical Isomerism Contd.
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….
Optical Isomerism Contd.
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.
Optical Isomerism Contd.
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.
Optical Isomerism Contd.
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.
Optical Isomerism Contd.
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.
Optical Isomerism Contd.
Optical Isomerism Contd.
• 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.
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).
Optical Isomerism Contd.
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:
Optical Isomerism Contd.
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 Isomerism Contd.
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 (-).
Optical Isomerism Contd.
Optical Isomerism Contd.
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-.
Optical Isomerism Contd.
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-.
Optical Isomerism Contd.
Optical Isomerism Contd.
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
Optical Isomerism Contd.
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.
Optical Isomerism Contd.
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.
Optical Isomerism Contd.
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.
Optical Isomerism Contd.
Br C
F
I
H
Priority 3(atomic number = 9)
Priority 1(atomic number = 53)
Priority 2(atomic number = 35)
Priority 4(atomic number = 1)
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.
Optical Isomerism Contd.
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.
Optical Isomerism Contd.
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.
Optical Isomerism Contd.
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)