STEREOCHEMISTRY

-chemistry
-chemistry in
in three
three dimensions-
dimensions-

TEAM TEACHING FTP

 Stereochemistry

Stereochemistry refers to the

3-dimensional properties and reactions of
molecules.
Isomer

• Isomer is different compounds with the same molecular formula

(different of atoms arrangement)
• Type : structural isomers and stereoisomer
• Structural isomers : isomers that differ in which atoms are
bonded to which atoms

• Stereoisomers:isomers that differ in the way the atoms are

orientedin space, butnotin which atoms are bonded to which
atoms (compounds with the same connectivity, different
arrangement in space)
of isomers
CHAINISOMER

POSITIONISOMER
STRUCTURALISOMER

Same molecular formula but

FUNCTIONAL GROUPISOMER
different structural formulae

GEOMETRICAL

ISOMERISM

STEREOISOMER Occurs due to the restricted rotation of C=C

double bonds... two forms - CIS and TRANS

Same molecular formula but atoms

occupy different positions in3- OPTICAL ISOMERISM

dimensionals space.
Occurs when molecules have a chiral centre. Get

two non-superimposable mirror images.

 Structural

isomer
COMPOUNDS HAVE THE SAME MOLECULAR FORMULA

BUT DIFFERENT STRUCTURAL FORMULA

Chain different arrangements of the carbon skeleton

similar chemical properties

slightly different physical properties

more branching = lower boiling point

Positional same carbon skeleton

same functional group

functional group is in a different position

similar chemical properties - slightly different physical properties

 Structural

isomer
COMPOUNDS HAVE THE SAME MOLECULAR FORMULA

BUT DIFFERENT STRUCTURAL FORMULA

Functional Group different functional group

differentchemical properties

differentphysicalproperties
 Structural

isomer
H2
H3C C
C CH2 H2 H2
H2
C C
Butane, mp -0.5 C HO C CH3
H2
1-butanol
H3 C CH3 C4H10 OH
C4H10
CH chain isomer positional isomer
H3 C CH
CH3 C CH3
Isobutane / methylpropane, H2
mp -12C 2-butanol
 Structural

isomer

O
H3 C CH3
Methoxymethane/
dimethy eter

C2H6O
H2 functional isomer
C
HO CH3
ethanol
 Exercise 1

• Draw all the possible isomers of C5H12O !

• Draw all the possible isomersof C6H12O !

 Stereoisomers
• Appear to have same structure in 2D
• In 3D have different structures
• Are non-superimposable mirror images of each other

• With modeling kit build a model: carbon atom with four different colors
attached (use same size bonds!)
• Look at your model in a mirror, build what you see in the mirror.
• Are the two superimposable?Animation(watch Chirality)
 Geometrical

•an example ofstereoisomer isomers

•found in some, but not all, alkenes
•occurs due to the RESTRICTED ROTATION OF C=C bonds
•get twoforms: CIS and TRANS

CIS or Z (zusammen) TRANS or E (entgegen)

Groups/atoms/higher priorityare onthe Groups/atoms/higher priorityare on OPPOSITE SIDES

SAMESIDE of the double bond across the double bond

Isomers - have different physical properties - e.g. boiling points, density

- have similar chemical properties - in most cases

 Assign priority

• Atoms with higher atomic numbers receive higher priorities.

I> Br >Cl> S > F > O > N >13C >12C >2H >1H

F Cl Br I

high priority

2 Br F 2

1 I Cl 1

Z-1-bromo-2-fluoro-1-iodo-2-kloro-etena
 Assign priority

• Incase of ties, use the next atoms along the chain of each
group as tiebreakers.
 Assign priority

• Treat double and triple

bonds as if each were a

bond to a separate atom.

 structure same with
C C
R 2C CR2
R 2C CR2

C C

R C C

R
O O O

C CR2 CN CH2OH CH C COH

H aldehida keton

high priority
 Geometrical

isomers
Cl Cl Cl H

C C

H H H Cl
cis-1,2-Dichloro-ethene trans-1,2-Dichloro-ethene

Cl C2 H5 Cl H

H3C H H3C C2H5

cis-2-Chloro-pent-2-ene trans-2-Chloro-pent-2-ene
 Geometrical

isomers

H H C 2H 5
H

H 3C H

C2 H5 H

H H3C H
H
cis,cis-2,4-heptadiena trans,trans-2,4-heptadiena
 Exercise 2

Give the name for structure in the image below !

C2 H5 H H
H

H3 C H

H C2H5

H H3C H
H
 Optical isomer

• samephysical and chemicalproperties

• rotateplane polarizedlight
• isomersdiffer in their reaction to plane-polarised light
•oneisomer rotates light to the right, the other to the left
•rotation of light is measured using apolarimeter

•If the light appears to haveturned to the rightturnedto the left

DEXTROROTATORYLAEVOROTATORY

d or + form l or - form
 Optical isome
Thepolarimeter-an instrument used to measure optical activity.

A B

C D
E

A Light source produces light vibrating in all directions

B Polarising filter only allows through light vibrating in one direction

C Plane polarised light passes through sample

D If substance is optically active it rotates the plane polarised light

E Analysing filter is turned so that light reaches a maximum

F Direction of rotation is measured coming towards the observer

If the light appears to haveturned to the rightturned to the left

DEXTROROTATORYLAEVOROTATORY
Plane-Polarized Light through
an Achiral Compound
Plane-Polarized Light through a
Chiral Compound
 Optical isomer

Occurrenceanotherform ofstereoisomer occurswhen compounds have non-

superimposable mirror images

Optical Isomers

• thetwo different forms are known as optical isomers orenantiomers

• theyoccur when molecules havea chiral centre

• achiral centrecontainsan asymmetric carbon atom

• anasymmetric carbon has four differentatoms(orgroups)

• arrangedtetrahedrallyaround it.
 Chirality

• “Handedness”: Right-hand glove does not fit the left hand.

• An object is chiral if its mirror image is different from the

original object.
 Chirality

chiral achiral

Carbon atom that is bonded to four different groups ischiral

 Stereocenters

• An asymmetric carbon atom is the most common example of

achirality center.

• Chirality centers belong to an even broader group

calledstereocenters.Astereocenter(orstereogenicatom)is any

atomatwhich the interchange of two groups gives a stereoisomer.

 Examples of Chirality
Centers

Asymmetric carbon atoms are examples of chirality centers, which are

examples ofstereocenters.
 Optical isomer

Racemate

• a50-50 mixture of the two enantiomers (d-l) or(±)is a racemic mixture.

• Theopposite optical effects of each isomer cancel each other out

Examples

• Opticalactivity is common in biochemistry andpharmaceuticals

• Mostamino acids exhibit opticalactivity

• manydrugs must be made of one optical isomer to be effective

- need smaller doses (safer and cost effective)

- get reduced side effects

- improved pharmacological activity

 Definitions

• Enantiomers – stereoisomers that arenon-superimposiblemirrorimages; only

properties thatdifferaredirection(+ or -) ofoptical rotation
• Diastereoisomers– stereoisomers that are notmirror images; different
compoundswithdifferentphysical properties
• Racematemixture – mixture that has equal amounts of left- and right-
handed enantiomers of a chiral molecule.
• Meso–a non-optically active member of a set of stereoisomers, at least
two of which are optically active
Enantiomer
 How to draw 3D:
Dash-Wedge Formula

H
• Draw two straight lines about 110
from each other Cl OH
– Bond angle is 109.5

– These represent the bonds in the plane of CH3

the page

• Draw dashed line for the bond that

extends behind the plane of the page

• Draw wedge for bond that extends in

front of the plane of the page
 Cahn–Ingold–Prelog
Priority System

• Enantiomers have different spatial arrangements of the four groups attached

to the asymmetric carbon.

• The two possible spatial arrangements are calledconfigurations.

• Each asymmetric carbon atom is assigned a letter (R)or(S)based on its three-

dimensional configuration.

• Cahn–Ingold–Prelogconvention is the most widely accepted system for

naming the configurations of chirality centers.

 (R) and (S) Configuratio

• Working in 3-D, rotate the molecule so

that the lowest priority group is in

back.

• Draw an arrow from highest (1) to

second highest (2) to lowest (3)

priority group. focus down

/IgnoreGroup 4.

• Clockwise = (R), Counterclockwise =

(S)
 Assign Priority to each Group on Asymmetric Center

I I 1
rotate
Cl F 4 H Cl 2
H F3
focus down C-4 bond
 Exercise 3

Identify the configuration of the compound below !

OH

CH2CH3
H3CH2CH2C
H
 Exercise 3

3
1 CH2CH3
OH
rotate
C 3 2
C 4
2 CH2CH3 CH3CH2CH2 H
CH3CH2CH2
H OH
4 1

Clockwise(R)

When rotating to put the lowest priority group in the back, keep one group in place and

rotate the other three.

 Exercise 4

Identify the configuration of the image below !

CH3

CH3CH2CH=CH H
CH2CH2CH2CH3
Configuration in Cyclic

Compounds
 Enantiomer 2-
butanol

CH3 H3 C

C2 H 5 C C2 H5
OH HO
H H

enantiomer
 CH3 2 3
C2 H5 CH3
C2H5 C (R)-2-butanol
OH
H
OH
1
clockwise

H3C 3 2
H3 C C2 H5
C2 H5 (S)-2-butanol
HO
H
OH
1
counterclockwise
 Enantiomers
nonsuperimposible
mirrorimages

mirror plane

OH OH

H H
CH3 H3C COOH
HOOC

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

from muscle tissue from milk
+13,5o -13.5o
 Properties of

Enantiomers

• Same boiling point, melting point, and density.

• Same refractive index.
• Rotate the plane of polarized light in the same magnitude, but in
opposite directions.
• Different interaction with other chiral molecules:
– Active site of enzymes is selective for a specific enantiomer.
– Taste buds and scent receptors are also chiral. Enantiomers may have
different smells.
– Different metabolismreaction
 Diastereomers

• Molecules with two or more chiral carbons.

• Stereoisomers that arenotmirror images.

 Diastereomers

H OH H OH
3 3
2
2 CO2H CO2H
H Br Br H
(2S,3S) (2S,3R)
same stereochemistry at C 2 (S)
opposite stereochemistry at C 3
 Diastereomers

Fischer Projections with 2 Chiral Centers

CO2H CO2H
2 2
H OH H OH

3 3
Br H H Br

CH3 CH3
(2S,3S) (2S,3R)
 Properties ofDiastereomers

• Diastereomershave different physical properties, so they can

be easily separated.

• Enantiomers differ only in reaction with other chiral

molecules and the direction in which polarized light is

rotated.

• Enantiomers are difficult to separate.

• Convert enantiomers intodiastereomersto be able to separate

them.
 Exercise 5

Identify the molecules below,

EnantiomersorDiastereomers?
H CH2CH3

Br CH3 H CH3

CH2CH3 Br

CH3

HO H
CH3 H NH2

H
H OH
H3C NH2

CH3
 2-bromo-3-chlorobutane
H H

H3C * * CH3

Br Cl

CH3 CH3 CH3 CH3

R S R S
Br C H H C Br Br C H H C Br

R S S R
H C Cl Cl C H Cl C H H C Cl

CH3 CH3 CH3 CH3

A B C D
• A & B : enantiomer • C& D : enantiomer
• A& C :diastereomer • A & D :diastereomer
• B & C :diastereomer • B & D :diastereomer
 Exercise 6 :
2,3,4-trichlorohexane
Howmany stereoisomers?

Cl

* * *

Cl Cl
 Exercise :
2,3,4-trichlorohexane

CH3 CH3 CH3 CH3

Maximum number of
stereoisomers = 2n, S H Cl Cl H R H Cl Cl H
n = # asymmetric
centers
S H Cl Cl H R H Cl Cl H
RH Cl Cl H S Cl H H Cl
CH2CH3 CH2CH3 CH2CH3 CH2CH3

CH3 CH3 CH3 CH3

H Cl Cl H Cl H H Cl
n = 3; 2n= 8 Cl H H Cl H Cl Cl H
H Cl Cl H H Cl Cl H
CH2CH3 CH2CH3 CH2CH3 CH2CH3
 Racemic Products

If optically inactive reagents combine to form a chiral molecule, a

racemic mixture is formed.

 COOH COOH Racemic
R S Mixtures
H OH HO H

R S
HO H H OH

COOH COOH

Racemic mixture (racemate) : 50/50 mixture of enantiomers

(R, R) Tartaric acid (S,S) Tartaricacid (+/-) Tartaric acid

o
mp( C) 168 – 170 168 – 170 210– 212

[α] (degree) -12 +12 0

ρ(g/mL) 1.7598 1.7598 1.7723

The mixture may have different boiling point (b. p.) and melting point (m.
p.) from the enantiomers
 Biological Activity

(R)(+) Thalidomide (S)(-) Thalidomide

O O H O O H
H N N
H
N O N O

O O
a sedative and hypnotic a teratogen
 Biological Activity

-(p-isobutylphenyl)propionic acid

H H CH3
CH3 CO 2H HO 2C
(S)(+) ibuprofen (R)(-) ibuprofen
anti-inflammatory 80-90% metabolized to (S)(+)
 Bromination
Transis formedexclusively
NoMesois formed (cis)

Br2

Br Br Br Br
R R S S
racemic mixture

Meso– a non-optically active member of a set ofstereoisomers, at least two of

which are opticallyactive
 H H

H3C C* C* CH3

Cl Cl
2,3-Dichloro-butane
mirror plane
CH3 CH3 CH3 CH3
R S R S
Cl C H H C Cl Cl C H H C Cl
R S S R
H C Cl Cl C H Cl C H H C Cl

CH3 CH3 CH3 CH3

enantiomer, chiral identik, achiral, meso

(stereomers having simetry/ mirror plane)
3stereomers: 2 enantiomers, 1mesocompound
 MesoCompound

Internal Plane of Symmetry

Optically Inactive

COOH
COOH

HO H
H OH
mirror
plane HO H
H OH

COOH
COOH
rotate 180o
 Reactions
thatGenerate
ChiralityCenters
Hydrogenation,syn

CH3 CH3 H H
H2, Pt/C
CH3 CH3
CH2CH3 CH2CH3 CH2CH3 CH2CH3

CH2CH3 product is meso

H CH3
H CH3
CH2CH3
 BrominationsOften Generate Asymmetric Centers

CH3 CH3 Br2 CH3 CH3 CH3 CH3

H H H H
H H Br Br Br Br
S S R R
racemic mixture

CH3 CH3 Br CH3 CH3

H Br2 H
H H H
H CH3 Br CH3 Br Br
S R
meso
 Exercise 7

• Identify the compounds below, chiral or achiral?

– 1-chlorobutane
– 3-chloro-2-butanol
– 4-bromo-1-chlorocyclohexene
– 1,3-dimethylbenzena
• Draw the R and S-isomers the structures below !
– 3-phenyl-2-butanol
– 2-amino-3-hydroxybutanoic acid
• Find the stereoisomers of 2-bromo-3-chloro-4-flouropentane !

60
 KUIS

1. Isomergeometriterbagidalambentukisomerapasaja?
a.Jelaskansingkatmasiang-masingperbedaaannya
b.Jelaskansingkatsifatfisikdariisomer-
isomergeometritersebut(boillingpointdandensitasny)

Poin= 20
 mirror plane
Poin15
OH OH

H H
CH3 H3C COOH
HOOC

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

from muscle tissue from milk
+13,5o -13.5o

2 PERNYATAAN B ATAU S

a Titikdidih(S)as.laktatlebihtinggidaripada(R)as.laktat

b Titiklebur(S)as.laktatlebihtinggidaripada(R)as.laktat

c Densitas(R)as.laktatsamadengan(S)as.laktat

d sisiaktifenzimtertentudapatmengenalienantiomer

(S)as.laktatdan(R)as.laktatsebagaisenyawayangsamasehinggadapatdikatalisolehenzimyan

gsama.

e Pasanganenantiomertertentumemberikanresponyangberbedaterhadappersepsirasadanar

oma
 Poin= 15

3.Berikutadalah2,3,4-trichlorohexane

a. Maximum number of
stereoisomers = ?
b. Gambarkanmacamstereoisomersn
ya CH3 CH3
S H Cl Cl H R H
S H Cl Cl H R H
RH Cl Cl H S Cl
CH2CH3 CH2CH3

CH3 CH3
H Cl Cl H Cl
Cl H H Cl H
H Cl Cl H H