stereochemistry manik 3

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.


• 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


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.


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.


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.


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.


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.


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.


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


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 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 (-).



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-.


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-.



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


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.


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.


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 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.


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.


NC C

CH2OH

CHCl2

CH2Cl

Priority 1


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.


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.


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


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)

stereochemistry manik 3

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