Isomer in organic chemistry

7/30/2019 Isomer in organic chemistry

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Isomers

Isomers: different compounds with thesame molecular formula

Constitutional isomers: isomers with adifferent connectivity

Stereoisomers: isomers with the samemolecular formula, the same connectivitybut a different orientation of their atoms in

space that cannot be interconverted byrotation about a single bond


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Isomerism ConstitutionalIsomers and Stereoisomers

Stereoisomers are isomers with the samemolecular formula and same connectivity ofatoms but different arrangement of atomsin space


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Stereochemistryis the chemistry of molecules in three dimension


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HandednessStereochemistry of organic molecules can be

understood, if we understand the meaning ofhandedness

the fundamental reason for this is that ourhands are not identical, rather they are mirror

images


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Although everything has a mirror image, mirror imagesmay or may not be superimposable.

Some molecules are like hands. Left and right hands aremirror images, but they are not identical, orsuperimposable chiral (property of handedness)

The reason for Handedness chirality


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Mirror Image


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Chirality and Nonchirality

Mirror image: the reflection of an object in amirror

Objects that are not superposable on their mirrorimages are said to be chiral, that is, they showhandedness

Objects that are superposable on their mirror

images are said to be achiral, that is, they do notshow handedness. An achiral object has at leastone element of symmetry


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Do these molecules contain a Plane of Symmetry (Mirror Plane)?

Achiral Molecules


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The molecule labeled A and its mirror image labeled B

are not superimposable. No matter how you rotate A andB, all the atoms never align. Thus, CHBrClF is a chiralmolecule, and A and B are different compounds.

A and B are stereoisomersspecifically, they are

enantiomers. A carbon atom with four different groups is a tetrahedral

stereogenic center.

Chiral Molecules


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Chiral vs. AchiralChiral: from the Greek, cheir, hand

an object that is not superposable on its mirrorimage

Achiral: an object that lacks chirality; one thatlacks handedness

an achiral object has at least one element ofsymmetry

plane of symmetry:an imaginary plane passingthrough an object dividing it so that one half is themirror image of the other half

center of symmetry: a point so situated thatidentical components are located on oppositesides and equidistant from that point along theaxis passing through it


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Elements of Symmetry

Symmetry in objects


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Plane of Symmetry or Mirror plane


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C l

C lB r

F F

B r

C l C l

plane of

symmetry

TWO VIEWS OF THE PLANE OF SYMMETRY

side

view

edge

view

FCl

Br


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STEREOGENIC CARBON ATOMS


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Enantiomers


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One of a pair of molecular species that

are mirror images of each other andnot superposable.

They are mirror-image stereoisomers.

Enantiomers


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To draw both enantiomers of a chiral compound such as

2-butanol, use the typical convention for depicting atetrahedron: place two bonds in the plane, one in front ofthe plane on a wedge, and one behind the plane on adash. Then, to form the first enantiomer, arbitrarily place

the four groups

H, OH, CH3 and CH2CH3

on any bondto the stereogenic center. Then draw the mirror image.

Drawing Enantiomers

P i f E i


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Pairs of Enantiomers


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BrFH

Cl Cl

HBrF

H

F

Br

Cl

rotate

this moleculeis chiral note that the fluorine

and bromine have beeninterchanged in theenantiomer

Enantiomers


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Enantiomers

Lactic acid

C

C

HOCH3

H

OHO

C

C

OHH3 CH

O OH

Enantiomers
http://gaia.fc.peachnet.edu/tutor/models/lacticacid.htm


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Enantiomers

3-Chlorocyclohexene

Cl Cl


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Enantiomers

1,2-propanediol

CH3 CHCH 2 OH

OH

C

OH

H

CH2 OHH3 C C

OH

H

HOH2 C CH3


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Enantiomers &Diastereomers


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Enantiomers & Diastereoisomer

Enantiomers: opposite configurations atall stereogenic centers.

Diastereomers: Stereoisomers that arenot mirror images of each other.Different configuration at some

locations.


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Two Stereocenters

di

asteromers

entaiomers

entaiomers

Br Cl

H3CH

HCH3

Cl Br

HH3C

CH3

H

Cl Br

HH

3C

HCH

3

Br Cl

HH

3C

HCH

3


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Enantiomers & Diastereomers

For a molecule with 1 stereocenter, 2stereoisomers are possible

For a molecule with 2 stereocenters, amaximum of 4 stereoisomers are possible

For a molecule with n stereocenters, amaximum of 2n stereoisomers are possible

2n-1 pairs of enantiomers


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Enantiomers & Diastereomers


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Enantiomers & Diastereomers2,3-Dihydroxybutanedioic acid (tartaric acid)

two chiral centers; 2n = 4, but only three

stereoisomers exist

Meso compound:an achiral compoundpossessing two or more chiral centers thatalso has chiral isomers

C

C

H OH

COOH

OH

COOH

H

C

C

HHO

COOH

HO

COOH

H

C

C

H OH

COOH

H

COOH

HO

C

C

HHO

COOH

H

COOH

OH

A pair of enantiomersA meso compound

(plane of symmetry)


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Meso compounds

Meso compounds are achiral by virtue of asymmetry plane, but contain a stereogenic

center.

Cl Cl

HH3C

HCH3

Cl Cl

HH3C

HCH3

plane of symmmetry mirror


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Th Th St i f


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The Three Stereoisomers of2,3-dibromobutane

Because one stereoisomer of 2,3-dibromobutane issuperimposable on its mirror image, there are only threestereoisomers, not four.


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NUMBER OFSTEREOISOMERS POSSIBLE


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How Many Stereoisomers ArePossible?

maximum number of stereoisomers

= 2n,

where n= number of stereocenters

(sterogenic carbons)

sometimes fewer

than this number

will exist


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CONFIGURATION

The three dimensional arrangement of the

groups attached to an atom

Stereoisomers differ in the configuration at one ormore of their atoms.


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Cahn-Ingold-Prelog System forNaming Enantiomers R or S


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Ror SEnantiomers


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Manipulation of Chiral Molecules


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R,S Convention

If priority cannot be assigned on the basisof the atoms bonded to the stereocenter,look to the next set of atoms. Priority isassigned at the first point of difference.

CH2 H CH2 CH3 CH2 NH2 CH2 OH

1 6 7 8

Increasing Priority


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Priorities

1. -OH

2. -COOH

3. -CH3

4. -H (R)-(-)-lactic aci

C

HHO COOH

CH3

C

H

CH3

HOOC OH

(S)-(+)-lactic acid


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R and S Assignments in Compo nds


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When a compound has more than one stereogeniccenter, the Rand Sconfiguration must be assigned toeach of them.

Rand SAssignments in Compoundswith Two or More Stereogenic Centers.

One stereoisomer of 2,3-dibromopentaneThe complete name is (2S,3R)-2,3-dibromopentane

Stereoisomerism of Cyclic Compounds


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1,4-dimethylcyclohexane

Neither the cis not trans isomers is optically active

Each has a plane of symmetry


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1,3-dimethylcyclohexane

The trans and cis compounds each have twostereogenic centers

The cis compound has a plane of symmetryand is meso

The trans compound exists as a pair ofenantiomers


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P i f S i


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Properties of Stereoisomers

Enantiomers have identical physical andchemical properties in achiralenvironments

Diastereomers are different compoundsand have different physical andchemical properties

meso tartaric acid, for example, hasdifferent physical and chemical propertiesfrom its enantiomers (see Table 3.1)

Pl P l i d Li ht


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Plane-Polarized Light

Ordinary light:light vibrating in allplanes perpendicular to its direction ofpropagation

Plane-polarized light:light vibrating onlyin parallel planes

Optically active: refers to a compound

that rotates the plane of plane-polarizedlight


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R l ti


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Resolution

Racemic mixture:an equimolar mixtureof two enantiomers

because a racemic mixture contains equalnumbers of dextrorotatory and levorotatorymolecules, its specific rotation is zero

Resolution:the separation of a racemicmixture into its enantiomers

Racemates


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An equal amount of two enantiomers is called a

racemate or a racemic mixture. A racemic mixture isoptically inactive. Because two enantiomers rotateplane-polarized light to an equal extent but in oppositedirections, the rotations cancel, and no rotation isobserved.

Racemates

Specific Rotation


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Specific rotation is a standardized physical constant for

the amount that a chiral compound rotates plane-polarized light. Specific rotation is denoted by thesymbol [ ] and defined using a specific sample tubelength (l, in dm), concentration (cin g/mL), temperature

(250

C) and wavelength (589 nm).

Specific Rotation

Discovery of Enantiomers


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Discovery of Enantiomers

There is no doubtthat in dextrotartaric acid thereexists anassymetricarrangement

having anonsuperimposibleimage.

C

C

COO-

Na+

COO-

Na+

H

HO H

OH


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H HCOOH

OH OH

HOOC

meso(as a minor component)

ALSO FOUND

more about this

compound later

H COOHH

OH OH

HOOC

HOOC HH COOH

OH OH

(+)-tartaric acid (-)-tartaric acid

[ ]D = 0

meso-tartaric acid

Tartaric Acid


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DiastereomersThreonine: 2 pairsof enantiomers

COOH

C

C

H

H OHCH3

H2N

COOH

C

C

H

HCH3

NH2

OH

2R, 3S 2S, 3R

2R, 3R 2S, 3S

COOH

C

C

H

HHOH3C

NH2

COOH

C

C

H

HH3C

H2N

HO

2R,3R 2S,3S 2R,3S & 2S,3R

2S,3S 2R,3R 2R,3S & 2S,3R

2R,3S 2S,3R 2R,3R & 2S,3S

2S,3R 2R,3S 2R,3R & 2S,3S


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Enantiomers & DiastereomersFor tartaric acid, the three possiblestereoisomers are one meso compound

and a pair of enantiomers.

Meso compound: an achiral compound

possessing two or more stereocenters.


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Symmetry Plane2R, 3S and 2S, 3Rare identical

Molecule has a planeof symmetryperpendicular to C-Cand is therefore

achira

COOH

C

C

H

HO HCOOH

OH

2R, 3S 2S, 3R

2R, 3R 2S, 3S

COOH

C

C

H

OHHCOOH

OHCOOH

C

C

H

HO HCOOH

HO

COOH

C

C

H

OHCOOH

HO

H


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Symmetry Plane2R, 3S and 2S, 3Rare identical

Molecule has a plane

of symmetryperpendicular to C-Cand is thereforeachira

One mesocompound and apair of enantiomers

COOH

C

C

H

HO HCOOH

OH

2R, 3S 2S, 3R

2R, 3R 2S, 3S

COOH

C

C

H

OHHCOOH

OHCOOH

C

C

H

HO HCOOH

HO

COOH

C

C

H

OHCOOH

HO

H

Mirrorimage is

identical


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H CH3

CH3 H

Cl Br

CH3 H

H CH3

Br Cl

H H

CH3 CH3

Br Cl

H H

CH3 CH3

Cl Br

enantiomers 1

enantiomers 2

diastereomers

S R RS

S S R R

mirror2-Bromo-3-chlorobutane


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H H

CH3 CH3

Cl Cl

H H

CH3 CH3

Cl Cl

CH3 H

H CH3

Cl Cl

H CH3

CH3 H

Cl Cl

meso

enantiomers

diastereomers

S R

S S R R

mirror imageis identical

2,3-Dichlorobutane


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Tartaric Acid(-) - tartaric acid[ ]D = -12.0

o

mp 168 - 170o

solubility of 1 g0.75 mL H2O

1.7 mL methanol

250 mL ether

insoluble CHCl3

d = 1.758 g/mL

(+) - tartaric acid

[ ]D = +12.0o

mp 168 - 170o

solubility of 1 g0.75 mL H2O

1.7 mL methanol

250 mL ether

insoluble CHCl3

d = 1.758 g/mL

meso- tartaric acid

[ ]D = 0o solubility of 1 g

mp 140o 0.94 mL H2O

d = 1.666 g/mL insoluble CHCl3


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Fischer Projections

H OH

CH3


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90

H OH

CH2CH3Fischer Projections

Fischer projection: a two-dimensionalrepresentation showing theconfiguration of a stereocenter

horizontal lines represent bonds projectingforward

vertical lines represent bonds projecting to

the rearthe only atom in the plane of the paper isthe stereocenter

Fischer Projections


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Fischer Projections

(R)-lactic acid

C

COOH

H

OH CH3

COOH

CH3

H OH

How?

Fischer Projections


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Fischer Projections

C

COOH

H

OH CH3

COOH

CH3

H OH


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Fischer Projections


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Fischer Projections

1. Orient the stereocenter so that bondsprojecting away from you are vertical andbonds projecting toward you are horizontal

2. Flatten it to two dimensions

(S)-2-Butanol

(3-D formula)

(1) (2)

(S)-2-Butanol

(Fischer projection)

CH3 CH2

HCH3

OH

C

CH3

CH2 CH3

OHH HC OH

CH3

CH2 CH3


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Assigning R,S ConfigurationLowest priority group goes to the top.

View rest of projection.

A curved arrow from highest to lowestpriority groups.

Clockwise - R (rectus)

Counterclockwise - S (sinister)


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Rules of MotionCan rotate 180, but not 90 because

90 disobeys the Fischer projection.

Same groups go in and out of plane

CH3

HO H

COOH

CH3

COOH

HO H180

COOH

H OH

CH3

COOH

CH3

H OH= =


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Rules of MotionCan rotate 180, but not 90 because

90 disobeys the Fischer projection.

Different groups go in and out of planeThis generates an enantiomeric structure

H

H3C COOH

OH

H

OH

H3C COOH

90

COOH

H OH

CH3

COOH

CH3H OH= =

(R)-lactic acid (S)-lactic acid


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Rules of MotionOne group can be held steady and the

others rotated.

H

COOH

HO CH3

same as

CH3

COOH

H OH


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Rules of MotionTo determine if two Fischer projectionsrepresent the same enantiomer carry

out allowed motions.C2H5

CH3

HO H

OH

C2H5

H CH3

H

OH

H3C C2H5

A B C


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C2H5

CH3

HO HOH

C2H5

H CH3

H

OH

H3C C2H5


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Rules of MotionPerform one of the two allowed motionsto place the group with lowest priority

at the top of the Fischer projection.

180H

CH3

OH

CH2C

C not A

CH3HOH

CH2CH3

CH2CH3

HH3C

OH

OH

90

CH3 C2H5OH

A B C


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Priorities1. NH2

2. COOH

3. CH34. H

S - stereochemistry

CH3

H

HOOC NH2

H

CH3

HOOC NH2

CH3

H2N H

HOOC

CH3

H2N H

HOOC

CH3

HOOC NH2

HCH3


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Br Cl BrCl

Cl

Br Br

Cl

enantiomers

enantiomersdiastereomers

cis

trans

1-Bromo-2-chlorocyclohexane

1-Bromo-2-chlorocyclopropane


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ClBr BrCl

Cl

Br Br

Cl

enantiomers

enantiomers

cis

trans

diastereomers

R S SR

R R S S

y p p

1 2 Dib l


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BrB r BrBr

Br

B r B r

Br

mirror image identical

meso

enantiomers

diastereomers

cis

trans

1,2-Dibromocyclopropane

Biological Significance of Stereoisomers


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Structure Properties

Stereochemistry Biological effects

causes

Example

Pasteurs plant mold metabolized (+)-tartaric acid but not (-)-tartaric acid



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Thalidomide

Marketed in 50 countries 1956-1962

Sedative for hysterical pregnant women

Antiemetic to combat morning sickness

Caused thousands of birth defects

N

N

O

O O H

O

Sold as racemic mixture: 1:1 mixture of enantiomers

R enantiomer = antiemetic (not teratogenic)S enantiomer = teratogenic (not antiemetic)

Single-enantiomer drug not useful: quickly racemizes in body

One stereocenter

Teratogen: causes fetal abnormalities



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Another Biological Effect: Odor

Mirror image molecules do not have mirror image effects

enantiomers

(S)-(+)-carvone

O

H

(R)-(-)-carvone

O

H

smells like spearmint smells like caraway



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g gOf Hands, Gloves, and Biology

Why do stereoisomers have different biological properties?Many biological effects involve interaction with a cavity in enzyme or receptor

Good fit to cavity (i.e., strong binding) triggers enzyme or receptor

Most amino acids are chiral, so protein cavity is also chiral

Metaphor: Stereoisomer = left hand or right hand

Protein hole = left glove or right glove

Left hand fits left glove but not right glove

Left hand triggers left protein but not right protein

(R)-carvone triggers spearmint smell receptor but not caraway smell receptor

H2N

O

HR

OH

Enzymes and receptors are proteins; built from amino acids:


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Isomer in organic chemistry