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Geometric IsomerismTwo possible configurations of 1,2-dichloroethane
These two models represent exactly the same molecule. Thesemolecules are not isomers
But what happens if you have a carbon-carbon double bond - asin 1,2-dichloroethene?
These two molecules aren't the same.In one, the two chlorine atoms are locked on opposite sides of the double bond.This is known as the trans isomer. (trans : from latin meaning "across" - as intransatlantic).
In the other, the two chlorine atoms are locked on the same side of the doublebond. This is know as the cis isomer. (cis : from latin meaning "on this side")
Definition
• The isomerism which occurs due to difference of the positions of the
substituents about a double bond or a ring is called geometric
isomerism.
It is also known as cis-trans isomerism.
Conditions for geometric isomerism
• There must be a carbon-carbon double bond in the compounds.
• Each of the carbon of the double bond must be attached to two
different substituents.
• Now…… Are these compounds below geometric isomers?
Geometric Isomerism
C C
H3C
C2H5
H
H
C C
C2H5
H3C
H
H
C C
H3C
H
C2H5
C2H5
H
CH3
C C
H3C
H
C2H5
H
C2H5
CH3
Why does geometric isomerism occur?
• Geometric isomerism occurs because there is no possibility offree rotation about a double bond or a ring.
• As a result, the substituents are fixed in position. They can’tchange position without breaking bond.
• So, the two structures above are separate compounds, andtherefore isomers.
Types of geometric isomers
• There are two methods to denote geometric isomers. Accordingto these two methods there are:
C C
H3C
H
H
CH3
C C
H
H3C
H
CH3
can't rotate about
the double bond into
Cis or Trans isomers E or Z isomers
Geometric Isomerism Contd.
Cis/trans isomerism
• This method of denoting geometric isomerism works best when the
alkene is di-substituted. In fact, it will always work when the alkene is
di-substituted (and other conditions are fulfilled).
• But this method can fail with tri-substituted or tetra-substituted
alkenes.
Cis isomer
• The geometric isomer in which the identical groups on two carbons of
the double bond are on the same side of the double bond is called the
cis isomer.
Trans isomer
• The geometric isomer in which the identical groups on the two
carbons of the double bond are on the opposite sides of the double
bond is called the trans isomer.
• In cases of ring compounds, if the groups are on the same side of the
ring then it is cis and if on the opposite sides then it is trans.
Geometric Isomerism Contd.
• For this cis/trans method of denoting to work, there must be
at least one identical group on each carbon of the double
bond. For example:
C C
H3C
H
CH3
H
C C
C2H5
H
CH3
H
C C
C2H5
H3C
C2H5
H
C C
C2H5
H3C
CH3
C2H5
C C
C2H5
H3C
C3H7
H
Disubstituted Disubstituted Trisubstituted
Tetrasubstituted Trisubstituted
C C
C2H5
H3C
C4H9
C3H7
Tetrasubstituted
Geometric Isomerism Contd.
Cis isomer is less stable than trans isomer
• In cis isomer, two large groups on the separate carbons are always onthe same side. Thus, these two groups are closer to each other and repeleach other. This is called steric strain.
• On the other hand, in trans isomer the two large groups are on theopposite sides. So they are far apart. Hence they don’t repel each other.So, the steric strain is far less.
• This is why cis isomer is less stable than trans isomer.
Geometric Isomerism Contd.
C C
C2H5
H
CH3
H
cis-pentene-2
C C
C2H5
H
H
CH3
trans-pentene-2
large groups are close large groups are far
E/Z isomerism
• E/Z method of denoting geometric isomers is universal.
• This method will not fail even when cis/trans method hasfailed.
• While this method can work on all compounds that havegeometric isomers, it is used for those compounds wherecis/trans method fails.
• According to this method, the groups attached to each carbonof the double bond are analyzed and then given prioritiesaccording to Cahn-Ingold-Prelog (CIP) rules.
• If the group of highest priority on both carbon are on thesame side, then it is Z (Z = Zusammen = Together) isomer, ifthey are on opposite sides, then it is E (E = Entgegen =Opposite) isomer.
Geometric Isomerism Contd.
CIP rules for E/Z naming convention
• Substituents on any one of the two double-bonded carbon
atom is looked at.
• First, the atom which is directly attached to the double bond
carbon is looked at. This is the first atom. The group where
first atom has higher atomic number has higher priority.
Geometric Isomerism Contd.
C C
C
Br
C2H5
H
H3C
H H
Atomic number = 35
Atomic number = 12Bromine gets
priority soC C
C2H5
Br
C2H5
H
Priority 2
Priority 1
• If, both groups are attached by the same first atom,then the atomic number of the second atom (atomattached to first atom) is looked at.
• Similarly, if the second atoms are also same, thirdatoms are looked at.
Geometric Isomerism Contd.
C C
C
C
C2H5
H
C
H H
Atomic number = 12
Atomic number = 16
Oxygen gets
priority soC C
C2H5
HOH2C
C2H5
H
Priority 2
Priority 1
O
H H
H
H
H
H
• If the first atoms of two groups have the same higher atomic number
substituents, one with more such substituent is given higher priority.
Geometric Isomerism Contd.
C C
C
C
C2H5
H
C
H H
Atomic number = 12
Atomic number = 1
Carbon gets
priority soC C
C3H7
C2H5
C2H5
H
Priority 1
Priority 2
C
H H
H
C
H H
H HH
H
H
C C
CH2
HC
C2H5
H
One higher atomic number substituent
Two gets
priority soC C
ClH2C
Cl2HC
C2H5
H
Priority 2
Priority 1Cl Cl
Cl
Two higher atomic number substituent
• If there is any double bond or triple bond within the group, it isconsidered at two or three single bonds respectively. So:
• Exemplary:
• If there is a phenyl group attached to first atom, then it is thought thatFirst atom is attached to three carbons.
Geometric Isomerism Contd.
C C
CH2
C
C2H5
H
first atom is attached to one O and two H
Two gets
priority soC C
HOH2C
OHC
C2H5
H
Priority 2
Priority 1O H
HO
First atom is attached to two O and one H
C
O
H C
O O
Hmeans
• Example of E and Z isomers:
• Z isomer is not always cis and E isomer is not always trans
Geometric Isomerism Contd.
C C
C2H5
H3C
C2H5
H
Priority 1
Priority 2
Priority 1
Priority 2
Z-3-methylhexene-3
C C
C2H5
H3C
H
C2H5
Priority 1
Priority 2
Priority 2
Priority 1
E-3-methylhexene-3
C C
C2H5
Br
C2H5
H
Priority 1
Priority 2 Priority 1
Priority 2
E-3-bromohexene-3[cis-bromohexene-3]
C C
C2H5
Br
H
C2H5
Priority 1
Priority 2 Priority 2
Priority 1
Z-3-bromohexene-3[trans-bromohexene-3]
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 denoted
L-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 group
on 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 theatoms/groups around the chiral carbon. It doesn’t tell whetherthe compound is dextrorotatory or levorotatory.
• This method was proposed by Rosanoff in 1906.
• This method uses the two enantiomers of Glyceraldehyde asreference molecules.
• Any compound which looks like or degrades to D-glyceraldehydewould be denoted by D- and any compound which looks like ordegrades 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 toglyceraldehyde 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 compoundmust be drawn.
• For carbohydrates and its derivatives, the position of theOH group on the highest numbered chiral carbon islooked 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-sorbitol
CH2OH
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 carbonconfiguration works on only a few types ofcompounds.
• To express the configuration of chiral carbons inother compounds, we need another method.
• This other method is the R/S method. This methodis universal, meaning that this method works onany compound.
• In R/S method, the configuration of each chiralcarbon of the compound is described.
Optical Isomerism Contd.
R/S naming method
1. First, every chiral carbons in the molecule are identified.
2. Then the configuration in each chiral carbon isdetermined.
3. To determine the configuration, the groups attached tothe chiral carbons are assigned priority 1, 2, 3, and 4according to Cahn-Ingold-Prelog (CIP) rules.
4. The group with priority 4 (lowest priority) is sent to theback. Then it is identified which direction follows if onegoes from 1 → 2 → 3.
5. If the direction is right (clockwise), the chiral carbon is atR (R = rectus, meaning right) configuration.
6. If the direction is left (anticlockwise), the chiral carbon isat 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 right
So, it is at R configuration
R-Bromo-fluoro-iodo-methane
• If first atoms are identical, then second atom will belooked at. If the second atoms are also identical, thirdatom will be looked at and so on.
• If the first atoms are identical, second atoms are alsoidentical, then the group with greater number of highatomic 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
CH2Cl
Priority 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
H3CH
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
H3CH
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 structures
Optical 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)