Stereochemistry

Handedness Some things have a “handedness,”

that is look at your right and left hand. They look alike, but are not the same. They are mirror images.

Nobel Prize - 2001

Their research deals with the fact that many molecules appear in two forms that are mirror images of each other, just like the left and right hands.

The mirror imageof a chiral object isdifferent and will notsuperimpose on the original object.

Objects which are chiral have a sense of “handedness” and exist in two forms.

Chirality

Mirror Image

HCl Are these two

structures identical?

mirror

Stereoisomers

enantiomersenantiomers

Stereoisomers that are nonidentical mirror images are called enantiomers.enantiomers.

Stereoisomers

Visualize, visualize ….

Visualize, visualize …C C

BrH CC

enantiomer

1..3..5…etc interchanges = enantiomer2..4..6...etc interchanges = original compound

ODD:EVEN:

Visualize, visualize …

Br FH CH3

C C C CCH3

Br F H CH3

F H CH3

CH3 BrF

ENANTIOMER ENANTIOMERSAME

YOU CAN USEINTERCHANGES

Are these identical or are they enantiomers?

Isomers Isomers: different compounds with the

same molecular formula Constitutional isomers: isomers with a

different connectivity Stereoisomers: isomers with the same

molecular formula, the same connectivity but a different orientation of their atoms in space that cannot be interconverted by rotation about a single bond

Chirality Mirror image: the reflection of an object in a

mirror Objects that are not superposable on their

mirror images are said to be chiral, that is, they show handedness

Objects that are superposable on their mirror images are said to be achiral, that is, they do not show handedness. An achiral object has at least one element of symmetry

Chirality A molecule

cannot be chiral if it has a plane of symmetry.

Chirality A plane of symmetry is a plane that

cuts through an object in such a way that one half of the object is an exact mirror image of the other half.

A molecule that has a plane of symmetry must be identical to its mirror image and therefore must be nonchiral, or achiral.

Cl stereocenterThis is one type of ….

…. others are possible

A stereogenic carbon is tetrahedral and has four different groups attached.

Stereogenic Carbons

23ClClBr

BrCl Cl

Elements of Symmetry Plane of symmetry: an imaginary

plane passing through an object dividing it such that one half is the mirror image of the other half

center of symmetry

Elements of Symmetry Center of symmetry: a point so

situated that identical components of the object are located equidistant on opposite sides and equidistant from the point along any axis passing through the point

Two identical groups renders a tetrahedral carbon achiral.

BrClCl

ClClBr

F The plane of the paper is a plane of symmetry

Achiral

BrCl Cl

plane ofsymmetry

side view edge view

Two Views of the Plane of Symmetry

Symmetry Plane

HHCOOH

Symmetry plane No symmetry plane

achiral chiral

CONSTITUTIONAL ISOMERS

Isomers with a differentorder of attachment ofthe atoms in their molecules

STEREOISOMERSIsomers with the same orderof attachment, but a differentconfiguration (3D arrangement)of groups on one or more of the atoms

ISOMERSDifferent compoundswith the same molecular formula

cis/trans ISOMERS

ENANTIOMERSStereoisomers whose molecules are non-superimposible mirrorimages of each other

DIASTEREOMERSStereoisomers whose molecules are not mirror images of each other

each isomer could

double bond or ring

both can apply

have stereoisomers

with a ring

TYPES OF ISOMERISMTYPES OF ISOMERISM(geometric)

Enantiomers Enantiomers: stereoisomers that

are nonsuperposable mirror images; refers to the relationship between pairs of objects

rotate

this moleculeis chiral

note that the fluorineand bromine have beeninterchanged in theenantiomer

do interchanges in class

Enantiomers

Enantiomers Lactic acid

OHH3CH

Enantiomers 1,2-propanediol

CH3CHCH2OHOH

CH2OHH3C C

HOH2C CH3

Enantiomers 3-Chlorocyclohexene

CH3CH2CH2CH2CH2 C CH2CH2CH2CH3

HO CH3

carvone nootkatonespearment oil grapefruit oil

HCH3CCH2

(R)-carvonecaraway and dill seed oils

(S)-carvonespearmint oil

Carvone

LimoneneCH3

HCH3CCH2

(R)-limoneneodor of oranges

(S)-limoneneodor of lemons

Chiral Drugs Most pharmaceutical drugs are

chiral thalidomide

Optically Active Refers to molecules that interact

with plane-polarized light

Jean Baptiste Biot French Physicist - 1815

He discovered that some natural substances (glucose, nicotine, sucrose) rotate the plane of plane-polarized light and that others did not.

Optical Activity

incidentpolarizedlight

transmittedlight (rotated)

sample cell

angle ofrotation,

(usually quartz)

a solution of the substance to beexamined is placed inside the cell

Plane Polarized Light Ordinary light: consists of waves vibrating

in all planes perpendicular to its direction of propagation

Plane polarized light: consists of waves vibrating only in one plane

Plane polarized light is an equal mixture of left and right-circularly polarized light. These two forms are nonsuperposable mirror images and, therefore, enantiomers.

Plane-Polarized Light Beam

unpolarizedbeam

wavelength

frequency ( n )

c = speed of light

polarized beam

Sine wavesare not alignedin the sameplane.

NOT PLANE-POLARIZED

ENDVIEWSIDE

Plane Polarized Light Because of its handedness, circularly

polarized light reacts one way with a stereocenter with R-handedness, and differently with its enantiomer

The net effect of the interaction of plane polarized light with a chiral compound is that the plane of polarization is rotated

Polarimeter: a device for measuring the extent of rotation of plane polarized light

Optical Activity optical activity - ability of certain molecules

to rotate plane polarized light

detected using a polarimeter

Polarimeter

l(dam)

sample cell

Na vapor lamp

polarizer analyzer

Polarimeter

Optical Activity Observed rotation: the number of

degrees, , through which a compound rotates the plane of polarized light

Dextrorotatory (+): rotation of the plane of polarized light to the right

Levorotatory (-): rotation of the plane of polarized light to the left

Optical Activity Specific rotation:

Observed rotation of the plane of polarized light when a sample is placed in a tube 1.0 dam in length and at a concentration of 1g/mL.

= observed rotation

c = concentration ( g/mL )

l = length of cell ( dm )

D = yellow light from sodium lamp

T = temperature ( Celsius )

Optical Activity For a pair of enantiomers, the

value of the specific rotation of each is the same, but opposite in sign

[]25D -13.52 +13.52D

(R)-(-)-2-Butanol(S)-(+)-2-Butanol

CH3CH3CH2H

H3C CH2CH3H

Discovery of EnantiomersLouis Pasteur Recrystallized

tartaric acid Two different kinds

of crystals that were mirror images.

Each type of crystal rotated light in opposite directions.

Discovery of Enantiomers“There is no

doubt that in dextro tartaric acid there exists an assymetric arrangement having a nonsuperimposible image.”

CCCOO-Na+

COO-Na+

H COOHH

OHOHHOOC

HOOC HH COOHOHOH

H HCOOH

OHOHHOOC

enantiomers

(as a minor component)ALSO FOUND

more about thiscompound later

H COOHH

OHOHHOOC

HOOC HH COOHOHOH

H HCOOH

OHOHHOOC

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

[]D = 0

meso -tartaric acid

Tartaric Acid

R,S Convention Priority rules (Cahn, Ingold, Prelog)

Each atom bonded to the stereocenter is assigned a priority, based on atomic number. The higher the atomic number, the higher the priority

Increasing Priority

H CH3 NH2 OH SH Cl Br I1 6 7 8 16 17 35 53

R,S Convention If priority cannot be assigned on the

basis of the atoms bonded to the stereocenter, look to the next set of atoms. Priority is assigned at the first point of difference.

CH2 H CH2 CH3 CH2 NH2 CH2 OH1 6 7 8

Increasing Priority

R,S Convention Atoms participating in a double or

triple bond are considered to be bonded to an equivalent number of similar atoms by single bonds

Naming Enantiomers1. Locate the stereocenter2. Assign a priority to each

substituent from 1 (highest) to 4 (lowest)

3. Orient the molecule so that the group of lowest priority (4) is directed away from you

Naming Enantiomers4. Read the three groups projecting

toward you in order from highest (1) to lowest priority (3)

5. If reading is clockwise, configuration is R (from the Latin rectus). If it is counterclockwise, configuration is S (from the Latin sinister).

2clockwise counterclockwise

(rectus) (sinister)

view with substituentof lowestpriority inback

R, S Convention

Enantiomers

Bromochlorofluoroiodomethane

Priorities1. -OH2. -COOH3. -CH3

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

HHO COOH

HOOC OH

(S)-(+)-lactic acid

You try it!1. Br2. COOH3. CH3

Diastereoisomer Enantiomers: opposite

configurations at all stereogenic centers.

Diastereomers: Stereoisomers that are not mirror images of each other. Different configuration at some locations.

Diastereoisomer Stereoisomers

that are not mirror images of each other. Different configuration at some locations.

COOHCC

H OHCH3

Two Stereocenters

diasteromers

entaiomers

Diastereomers Threonine: 2 pairs

of enantiomers

COOHCC

H OHCH3

COOHCC

2R, 3S 2S, 3R

2R, 3R 2S, 3S

COOHCC

HHOH3C

COOHCC

2R,3R 2S,3S 2R,3S & 2S,3R2S,3S 2R,3R 2R,3S & 2S,3R2R,3S 2S,3R 2R,3R & 2S,3S2S,3R 2R,3S 2R,3R & 2S,3S

Enantiomers & Diastereomers For a molecule with 1 stereocenter, 2

stereoisomers are possible For a molecule with 2 stereocenters,

a maximum of 4 stereoisomers are possible

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

2n-1 pairs of enantiomers

Enantiomers & Diastereomers For tartaric acid, the three possible

stereoisomers are one meso compound and a pair of enantiomers.

Meso compound: an achiral compound possessing two or more stereocenters.

Symmetry Plane 2R, 3S and 2S, 3R

are identical Molecule has a

plane of symmetry perpendicular to C-C and is therefore achira

COOHCC

HO HCOOH

2R, 3S 2S, 3R

2R, 3R 2S, 3S

COOHCC

OHHCOOH

OHCOOHCC

HO HCOOH

COOHCC

OHCOOH

Symmetry Plane 2R, 3S and 2S, 3R

are identical Molecule has a

plane of symmetry perpendicular to C-C and is therefore achira

One meso compound and a pair of enantiomers

COOHCC

HO HCOOH

2R, 3S 2S, 3R

2R, 3R 2S, 3S

COOHCC

OHHCOOH

OHCOOHCC

HO HCOOH

COOHCC

OHCOOH

Mirror image is identical

H CH3CH3 H

CH3 HH CH3

H HCH3 CH3

CH3CHCHCH3

H HCH3 CH3

enantiomers 1

enantiomers 2

diastereomers

S R RS

S S R R

mirror

2-Bromo-3-chlorobutane

H HCH3 CH3

CH3CHCHCH3

H HCH3 CH3

CH3 HH CH3

Cl Clmeso

enantiomers

diastereomers

S S R R

mirror image is identical

2,3-Dichlorobutane

Meso Meso compounds are achiral by virtue

of a symmetry plane, but contain a stereogenic center.

plane of symmmetry mirror

Racemic Mixture Racemic mixture (d,l;): an

equimolar mixture (50:50) of two enantiomers because a racemic mixture contains

equal numbers of dextrorotatory and levorotatory molecules, its specific activity is zero.

Properties of Stereoisomers Enantiomers have identical physical

(except for ) and chemical properties.

Diastereomers are different compounds and have different physical and chemical properties

Meso-tartaric acid, for example, has different physical and chemical properties from its enantiomers

Tartaric Acid(-) - tartaric acid

[]D = -12.0o

mp 168 - 170o

solubility of 1 g 0.75 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 g 0.75 mL H2O

1.7 mL methanol 250 mL ether

insoluble CHCl3 d = 1.758 g/mL

meso - tartaric acid[]D = 0o solubility of 1 gmp 140o 0.94 mL H2Od = 1.666 g/mL insoluble CHCl3

CH2CH3Fischer Projections Fischer projection: a two-

dimensional representation showing the configuration of a stereocenter horizontal lines represent bonds

projecting forward vertical lines represent bonds

projecting to the rear the only atom in the plane of the paper

is the stereocenter

Fischer Projections

(R)-lactic acid

HOH CH3

Fischer Projections

HOH CH3

Fischer Projections

Fischer Projections1. Orient the stereocenter so that bonds

projecting away from you are vertical and bonds projecting toward you are horizontal

2. Flatten it to two dimensions

(S)-2-Butanol (3-D formula)

(1) (2)

(S)-2-Butanol (Fischer projection)

CH3CH2H

CH2CH3

OHH HC OH

CH2CH3

Assigning R,S Configuration Lowest priority group goes to the

top. View rest of projection. A curved arrow from highest to

lowest priority groups. Clockwise - R (rectus) Counterclockwise - S (sinister)

Assigning R,S Configuration

OHH3C COOH

s-lactic acid

Rules of Motion Can rotate 180°, but not 90°

because 90° disobeys the Fischer projection. Same groups go in and out of plane

CH3HO H

COOHHO H

180COOH

H OH= =

Rules of Motion Can rotate 180°, but not 90°

because 90° disobeys the Fischer projection. Different groups go in and out of

plane This generates an enantiomeric

structureH

H3C COOH

OHH3C COOH

90COOH

H OH= =

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

Rules of Motion One group can be held steady and

the others rotated.

COOHHO CH3same as

COOHH OH

Rules of Motion To determine if two Fischer

projections represent the same enantiomer carry out allowed motions. C2H5

HO HOH

OHH3C C2H5

Rules of Motion By performing two allowed

movements on B, we are able to generate projection A. Therefore, they are identical.

HOCH2CH3

CH2CH3

HHOCH3

CH2CH3CH3

CH3CH2

HO HOH

OHH3C C2H5

Rules of Motion Perform one of the two allowed

motions to place the group with lowest priority at the top of the Fischer projection.

OHCH2CH3

C not A

CH3HOH

CH2CH3

HH3COH

HO HOH

OHH3C C2H5

Priorities1. NH2

2. COOH3. CH3

S - stereochemistry

HHOOC NH2

HOOC NH2

Stereochemistry of Reactions

CH3CH2CH CH2ether

CH3CH2CHCH3

achiral chiral

Addition of HBr

CCH3CH2

CH3CH2 CCH3

CH3CH2CH CH2etherH Br

CH3CH2 CCH3

Addition of Br2 Cis

Racemic mixture Achiral bromonium ion

C CH H

CH3 CH3Br

C CH H

CH3 CH3

Br2C C

CH3 CH3

CH3 CH3Br

Addition of Br2

Symmetry plane, therefore meso Models are superimposible

CH3Br2C C

Addition of Br2

Addition of HBr to a Chiral Alkene

CH3 H HBrC CH3

CH3 H HBr-

CH3 H Br H

CH3 H BrH

2S,4R 2R,4R

Addition of HBr to a Chiral Alkene Chiral intermediate is not attacked

equally from top and bottom because of steric reasons. Therefore, a mixture of product is formed in unequal amounts.

Chirality in Substituted Cyclohexanes Symmetry plane No stereogenic centers 1,4-disubstituted Only cis & trans diastereomers

1,3-disubstituted Cis Symmetry plane Meso compound

1,3-disubstituted Trans No symmetry plane Therefore enantiomers

1,2-disubstituted Trans Enantiomers

1,2-disubstituted Cis Meso

Br Cl BrCl

enantiomers

enantiomersdiastereomers

1-Bromo-2-chlorocyclohexane

ClBr BrCl

enantiomers

diastereomers

R S SR

R R S S

1-Bromo-2-chlorocyclopropane

BrBr BrBr

mirror image identical

enantiomers

diastereomers

1,2-Dibromocyclopropane

(S)-ibuprofen

Stereochemistry

Documents

Transcript of Stereochemistry

CYCLIC STEREOCHEMISTRY

9. Stereochemistry

Stereochemistry: an introduction

Lecture 13 - Stereochemistry

Chapter 4: Stereochemistry

Topic 5F Stereochemistry

stereochemistry withans

INTRODUCTION TO STEREOCHEMISTRY · Introduction to Stereochemistry Stereochemistry and Medicine 14 •Stereochemistry is particularly of practical concern to pharmaceutical chemists

Introduction to stereochemistry

more on stereochemistry

Basic Stereochemistry

Stereochemistry manik 1

Overview of Stereochemistry · Overview of Stereochemistry Stereochemistry and Medicine 7 Stereochemistry is particularly of practical concern to pharmaceutical chemists. It is a

Stereochemistry (1).ppt

questions on stereochemistry

Drug Stereochemistry

Stereochemistry (2)

IMPORTANCE OF STEREOCHEMISTRY

Stereochemistry lecture

Stereochemistry Tutorial Chemistry