stereo chemistry
TRANSCRIPT
3 3 2 1 3 2 2 1 2 1 1 2 2 1 1
25
44
5 4 4 4 5 4 4 4 5 3 3 3 3 2.5 2.5
56
100
0
20
40
60
80
100
120
Mua
tan
Form
al
Arah
Elekt
ron
Strukt
ur R
eson
ansi
Hibrid
isasi
Mua
tan
Form
al
Arah
Elekt
ron
Strukt
ur R
eson
ansi
Hibrid
isasi
Basa
Lewis
Efek
Keelek
trone
gatifa
n da
n uk
uran
Efek
Indu
ksi
Efek
Hibrid
isasi
Nama
Gugus
Jeni
s Ika
tan
Hibrid
isasi
Total
Nilai
Konsep
Nila
i
Nilai Rata2 Mahasiswa
Nilai Acuan
Persentase Keberhasilan
66 6762
22
5753
42
25
43 43
35
70 67
48
32
44 44
0
10
20
30
40
50
60
70
80
Mua
tan
Form
al
Stru
ktur
Res
onan
si
Mua
tan
Form
al
Stru
ktur
Res
onan
si
Basa
Lew
is
Efek
Indu
ksi
Nam
a G
ugus
Hib
ridis
asi
Nila
i
Persentase Keberhasilan
OPTICAL ACTIVITYOPTICAL ACTIVITY
PLANE-POLARIZED LIGHT
.
PLANE-POLARIZED LIGHT BEAMPLANE-POLARIZED LIGHT BEAM
unpolarizedbeam
wavelength
=c
frequency ( )
c = speed of light
polarized beam
All sine waves (rays) in the beam aligned in same plane.
Sine wavesare not alignedin the sameplane.
NOT PLANE-POLARIZED
ENDVIEWSIDE
VIEW
singleray orphoton
A beam is a collectionof these rays.
Optically ActiveOptically 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.
Dextrorotatory
Rotates the plane of plane-polarized lightto the right.
(+)- d-
Levorotatory
Rotates the plane of plane-polarized lightto the left.
(-)- l-
TYPES OF OPTICAL ACTIVITYTYPES OF OPTICAL ACTIVITYnew older
new older
[]D = cl
Specific Rotation []D
= observed rotation
c = concentration ( g/mL )
l = length of cell ( dm )
D = yellow light from sodium lamp
t = temperature ( Celsius )
t
Specific rotation calculated in this way is a physicalproperty of an optically active substance.
This equation correctsfor differences in celllength and concentration.
You always get the same
[]D tvalue of
The PolarimeterThe Polarimeter
chemistrynerd
sample cell
polarizer
Na lamp
plane isrotated analyzer
plane-polarizedlight
observedrotation
00000
rotate to null
STEREOISOMERSSTEREOISOMERS
ENANTIOMERS
PASTEUR’S DISCOVERY
Louis Pasteur 1848 Sorbonne, Paris
HOOC CH CH COOH
OH OH
OOC CH CH COO
OH OH
NH4Na ++2-
tartaric acid sodium ammonium tartrate( found in wine must )
Pasteur crystallized thissubstance on a cold day.
(+) (-)Louis Pasteur separated these and gave them to Biot to measure.
Biot’s results :
mirrorimages
Crystals of Sodium Ammonium TartrateCrystals of Sodium Ammonium Tartrate
hemihedral facesPasteur found twodifferent crystals.
EnantiomersEnantiomers
W
CX
ZY
W
CXY
Z
non-superimposable mirror images
Pasteur decided that the molecules that made the crystals,just as the crystals themselves, must be mirror images. Each crystal must contain a single type of enantiomer.
(also called optical isomers)
Pasteur’s hypothesis eventually led to the discoverythat tetravalent carbon atoms are tetrahedral.
Only tetrahedral geometry can lead to mirror imagemolecules:
Square planar, square pyrimidal or trigonal pyramidwill not work:
C
C C
tetrahedralcarbon
C C C
Van’t Hoff andLeBel (1874)
ENANTIOMERS HAVE EQUAL AND OPPOSITE ROTATIONS
W
CX
ZY
W
CXY
Z
(+)-nno (-)-nno
dextrorotatory levorotatory
Enantiomers
ALL OTHER PHYSICAL PROPERTIES ARE THE SAME
H COOHH
OHOH
HOOCHOOC HH COOH
OHOH
H HCOOH
OHOH
HOOC
meso
enantiomers
(as a minor component)ALSO FOUND
more about thiscompound later
H COOHH
OHOH
HOOCHOOC HH COOH
OHOH
H HCOOH
OHOH
HOOC
meso
enantiomers(+)-tartaric acid (-)-tartaric acid
TARTARIC ACIDTARTARIC ACIDfrom fermentation of wine
[]D = 0
meso -tartaric acid
Enantiomers
TARTARIC ACIDTARTARIC ACID
(-) - tartaric acid (+) - tartaric acid
[]D = -12.0o []D = +12.0o
mp 168 - 170o mp 168 - 170o
solubility of 1 g 0.75 mL H2O 1.7 mL methanol 250 mL etherinsoluble CHCl3
solubility of 1 g 0.75 mL H2O 1.7 mL methanol 250 mL etherinsoluble CHCl3
d = 1.758 g/mL d = 1.758 g/mL
meso - tartaric acid
mp 140o
d = 1.666 g/mL
solubility of 1 g 0.94 mL H2O
[]D = 0o
insoluble CHCl3
RACEMIC MIXTURERACEMIC MIXTURE
an equimolar (50/50) mixture of enantiomers
[]D = 0o
the effect of each molecule is cancelled out by its enantiomer
CHIRALITY, SYMMETRY PLANES CHIRALITY, SYMMETRY PLANES AND ENANTIOMERSAND ENANTIOMERS
PLANES OF SYMMETRYPLANES OF SYMMETRY
plane ofsymmetry
mirrorplane
A SYMMETRIC OBJECT HAS A PLANE OF SYMMETRY A SYMMETRIC OBJECT HAS A PLANE OF SYMMETRY - ALSO CALLED A MIRROR PLANE- ALSO CALLED A MIRROR PLANE
IF AN OBJECT HAS A PLANE OF SYMMETRY, IF AN OBJECT HAS A PLANE OF SYMMETRY, ITS MIRROR IMAGE WILL BE IDENTICALITS MIRROR IMAGE WILL BE IDENTICAL
IDENTICAL MIRROR IMAGES WILL SUPERIMPOSESUPERIMPOSE(MATCH EXACTLY WHEN PLACED ON TOP OF EACH OTHER)
CHIRALITYCHIRALITY
no symmetry
CHIRALCHIRALAn object without symmetry is
The mirror imageof a chiral object isdifferent and will notsuperimpose on the original object.
OBJECTS WHICH ARE CHIRALHAVE A SENSE OF “HANDEDNESS”AND EXIST IN TWO FORMS
An object with symmetry is ACHIRALACHIRAL ( not chiral).
The mirror image of an achiral object is identical and will superimpose on the original object.
plane of symmetry
ENANTIOMERSENANTIOMERS
STEREOISOMERS
BrFH
Cl Cl
HBrF
HFBr
Cl
ENANTIOMERSENANTIOMERSnon-superimposable mirror images
rotate
this moleculeis chiral
note that the fluorineand bromine have beeninterchanged in theenantiomer
do interchanges in class
STEREOISOMERSSTEREOISOMERS
ENANTIOMERS are a type of STEREOISOMER
Stereoisomers are the same constitutional isomer,but have a difference in the way they are arrangedin three-dimensional space at one or more of theiratoms.
and remember …...
ENANTIOMERS HAVE EQUAL AND OPPOSITE ROTATIONS
W
CX
ZY
W
CXY
Z
(+)-nno (-)-nno
dextrorotatory levorotatory
Enantiomers
ALL OTHER PHYSICAL PROPERTIES ARE THE SAME
STEREOGENIC CARBON ATOMSSTEREOGENIC CARBON ATOMS
STEREOCENTERSSTEREOCENTERS
One of the ways a molecule can be chiral is to have astereocenter.
A stereocenter is an atom, or a group of atoms, that can potentially cause a molecule to be chiral.
stereocenters - cangive rise to chirality
BrFH
Cl
STEREOGENIC CARBONSSTEREOGENIC CARBONS
A stereogenic carbon is tetrahedral and has four different groups attached.
stereocenterThis is one type of ….
…. others are possible
( called “chiral carbons” in older literature )
HFClBr
ACHIRALACHIRAL
TWO IDENTICAL GROUPS RENDERS ATETRAHEDRAL CARBON ACHIRAL
F
BrClCl
ClClBr
F
The plane of the paper is a plane of symmetry
FClBr
ONE PAIR OF ATOMS ATTACHED TO A TETRAHEDRALCARBON IS IN A PLANE PERPENDICULAR TO THE OTHER PAIR
Look at yourmodel set !
plane 1
plane 2
FClBr
Cl
ClBr
F F
Br
Cl Cl
plane ofsymmetry
TWO VIEWS OF THE PLANE OF SYMMETRY
side view
edgeview
FClBr
Cl
BrClCl
ClClBr
Cl
A CARBON ATOM WITH THREE SIMILARGROUPS IS ALSO ACHIRAL …..
ACHIRALACHIRAL
ClBr
Cl
ClBrBr
Cl Cl
plane ofsymmetry
side view edge view
Cl Cl
CONFIGURATIONCONFIGURATION
ABSOLUTE CONFIGURATION ( R / S )
CONFIGURATIONCONFIGURATION
The three dimensional arrangement of the groups attached to an atom
Stereoisomers differ in the configuration at one ormore of their atoms.
2
CONFIGURATIONCONFIGURATION - relates to the three dimensionalsense of attachment for groups attached to a chiralatom or group of atoms (i.e., attached to a stereocenter).
clockwise counterclockwise
(rectus) (sinister)
view with substituentof lowestpriority inback
1 2
4
3
C C
1
4
3
R S
Enantiomers are assigned a CONFIGURATIONCONFIGURATIONusing the same priority rules we developed for E/Z stereoisomers.
1. Higher atomic number has higher priority.
2. If priority cannot be decided based on the first atom attached move to the next atom, following the path having the highest prioity atom.
3. Expand multiple bonds by replicating the atoms attached to each end of the bond.
SPECIFICATION OF CONFIGURATIONSPECIFICATION OF CONFIGURATION
SEQUENCE RULESEQUENCE RULECAHN-INGOLD-PRELOG
Cahn-Ingold-Prelog Cahn-Ingold-Prelog RR,,SS-Nomenclature-Nomenclature
Label all substituents at stereocenter, starting at Label all substituents at stereocenter, starting at point of attachment, according to the point of attachment, according to the sequence sequence rulesrules in order of in order of decreasingdecreasing priority: priority: aa, , bb, , cc, , dd (note color scheme). Look down C-(note color scheme). Look down C-d d bond:bond:
aa, , bb, , cc clockwise : clockwise : RR
aa, , bb, , cc counterclockwise : counterclockwise : SS
CC
aa
dd
bb
cc
Naming Enantiomers
RR
Cahn-Ingold-Prelog19661966
2. If same priority at first atom: Go to 2. If same priority at first atom: Go to first first point of difference.point of difference.
1. Order by 1. Order by atomic numberatomic number, i.e. H = 1, , i.e. H = 1, lowest. lowest.
--CCHH22CCHH22SSHH --CCHH22CCHH22SSCCHH33‹‹--CCHH22CCHH33 --CCCCHH33
CCHH33
HH‹‹
--CCHH22CCHH22OOHH --CCHHCCHH33
CCHH33
‹‹ --CCHHCCHH33
DD
‹‹-C-CHH22CCBrBr33
CC
HH
CHCH33
BrBrII
ccaa
bb
dd
NN ::**RR
Sequence Rules
dd
Exception: lone pair, Exception: lone pair,
# “zero”. E.g., amines:# “zero”. E.g., amines:
3. Multiple bonds: Add 3. Multiple bonds: Add double or triple double or triple representationsrepresentations of atoms at the respective of atoms at the respective other endother end of the multiple bond. of the multiple bond.
CC CC CC CC
CC CC
CC CC
HH HH
CC CCHHHH
CCOO
HH OOCCOOCCHH
NNCC CC NN
NN
CCNN
CC
CC CCCC CC
Procedure for Assignment of R, S
Fischer Projection:Fischer Projection: A flat stencil A flat stencil
BrBr HH
CCCCHH33CCHH22CHCH33
HH
BrBr
CCHH33CCHH22CHCH33
HH
BrBr
Eyes in the Eyes in the plane of the plane of the boardboard
Depending on your starting dashed-wedged Depending on your starting dashed-wedged line structure, line structure, severalseveral Fischer projections are Fischer projections are possible for the possible for the samesame molecule. molecule.
Fischer Projections
Rules for handling Fischer projections:Rules for handling Fischer projections:
1. 1. Don’t rotateDon’t rotate. .
2. The 2. The mutualmutual exchangeexchange of any pair gives the of any pair gives the otherother enantiomerenantiomer
BrBr
CHCH33 CCHH22CCHH33
HH CCHH22CCHH33
BrBr
CCHH33
HH HH
CCHH22CCHH33
BrBr
CCHH33
RR RR RR
Therefore: Therefore: TwoTwo exchanges exchanges leaveleave absolute absolute configuration. Example: (2configuration. Example: (2RR)-)-BromobutaneBromobutane
This procedure can be used to readily assign This procedure can be used to readily assign R,S R,S ::
Do Do doubledouble exchanges to place exchanges to place dd on on toptop..
Note: There are three possible arrangements for each, Note: There are three possible arrangements for each, RR or orSS,, e.g.,e.g., R R ::
cc
dd
bb
aa
bb
dd
cc aa
RR
BrBr
bb
dd
ccCHCH33 CHCH22CHCH33
HH
aa
bb
dd
cc
aa RR !! !!
Example:Example:
bb
dd
cc
aa
RRbb
dd
cc
aa
RR
Problem: Problem: Are these two molecules the same Are these two molecules the same or opposite enantiomers? or opposite enantiomers? RR or or SS ? ?
II
FF
HH CHCH33II
FF
HH
CHCH33
Solution:Solution:
II
FF
HH CHCH33
II
FF
HH
CHCH33
II
FF
HH CHCH33dd
aa
bb
cc
dd
aabb
cc
SS
II
FF
HH
CHCH33
aa
bb
cc
dd
dd
aa
bbccSS
Two Stereocenters:Two Stereocenters: The Chlorination of 2- The Chlorination of 2-BromobutaneBromobutane
**
BrBr BrBr
**
ClCl
**ClCl22, , hhνν-HCl-HCl
Generates: Generates:
RR, RS SR, SSRR, RS SR, SS
Four Four stereoisomersstereoisomers
RR SSRR SS and and RS SRRS SR are enantiomer are enantiomer pairspairs
DiastereomersDiastereomers are stereoisomers that are are stereoisomers that are not image-mirror-image-related. not image-mirror-image-related.
DiastereomersDiastereomers
I
C
BrCl
F
I
C
ClBrF
1
2
3
4
RR SS
BromochlorofluoroiodomethaneBromochlorofluoroiodomethane
1
32
4
Enantiomers
NUMBER OF NUMBER OF STEREOISOMERS POSSIBLESTEREOISOMERS POSSIBLE
How Many Stereoisomers How Many Stereoisomers Are Possible?Are Possible?
maximum number of stereoisomers = 2n,
where n = number of stereocenters(sterogenic carbons)
sometimes fewerthan this numberwill exist
CH3 C
CH2OH
CH3
CH2 CH CH
CH3
CH3
OH*
*
22 = 4 stereoisomers
R RR SS RS S
CH3
OH
CHCH3 CH3
***
23 = 8 stereoisomers
R R RR R SR S RS R R
R S SS R SS S RS S S
FINDING STEREOCENTERS FINDING STEREOCENTERS (STEREOGENIC CARBONS)(STEREOGENIC CARBONS)
plane( indicates no stereoisomers )
20 = 1 21 = 2 21 = 2
stereoisomers (max) :
O
CH3
O
CH3
O
CH3
**
O
CH3
CH3
O
CH3
CH3
O
CH3CH3
* ***
**
FINDING STEREOCENTERS FINDING STEREOCENTERS (STEREOGENIC CARBONS)(STEREOGENIC CARBONS)
plane( but only if cis )
22 = 4 22 = 4 22 = 4
stereoisomers (max) :
FINDING STEREOCENTERS (CHIRAL CARBONS)FINDING STEREOCENTERS (CHIRAL CARBONS)
CH3
CH3
HO
H
CH3
CH3
CH3
**
**
*
* *
*
n = 8
28 = 256
TYPES OF ISOMERSTYPES OF ISOMERS
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)
MOLECULES WITH MOLECULES WITH TWO STEREOCENTERSTWO STEREOCENTERS
DIASTEREOMERS / MESO
22 = 4 stereoisomers possible
* *1234
HCH3CH3 H
ClBr
CH3 HH CH3
BrCl
HHCH3 CH3
BrCl
CH3CHCHCH3
ClBr
HHCH3 CH3
ClBr
2-Bromo-3-chlorobutane2-Bromo-3-chlorobutane
SRRS
SSRR
When comparing butanes, the comparisons are done best using the eclipsed conformation.
The relationships and planes of symmetry are not easily seen in other conformations.
H CH3
CH3 H
Cl Br
CH3 HH CH3
Br Cl
H HCH3 CH3
Br Cl
CH3CHCHCH3
Cl Br
H HCH3 CH3
Cl Br
enantiomers 1
enantiomers 2
diastereomers
S R RS
S S R R
mirror
2-Bromo-3-chlorobutane2-Bromo-3-chlorobutane
enantiomers-1
enantiomers-2
diastereomers
Models of the Isomers of 2-Bromo-3-chlorobutaneModels of the Isomers of 2-Bromo-3-chlorobutane
Br
Cl
CH3
H
(methyl groups are reduced to a single red atom)
H HCH3 CH3
Cl Cl
CH3CHCHCH3
Cl Cl
H HCH3 CH3
Cl Cl
CH3 HH CH3
Cl Cl
H CH3
CH3 H
Cl Cl
* *
2,3-Dichlorobutane2,3-Dichlorobutane
Now there is the possibility of a plane of symmetry.
The existence of a plane reduces the number of stereoisomers that are possible.
You will not find all 2n (= 4) stereoisomers.
C C
Cl Cl
H HCH3CH3
( Replace the Bromine with a second Chlorine )
(2n = 4)
H HCH3 CH3
Cl Cl
CH3CHCHCH3
Cl Cl
H HCH3 CH3
Cl Cl
CH3 HH CH3
Cl Cl
H CH3
CH3 H
Cl Cl
meso
enantiomers
diastereomers
S R
S S R R
mirror image is identical
2,3-Dichlorobutane2,3-Dichlorobutane
H HCH3 CH3
Cl Cl
HCH3
Cl
HCH3
Cl
plane of symmetry
MESO ISOMERMESO ISOMER
S R
mirror
Meso isomer - has a plane of symmetry and the mirror image is identical to the original molecule.
meso
diastereomers
enantiomers
Cl
CH3
H
Models of the Isomers of 2,3-DichlorobutaneModels of the Isomers of 2,3-Dichlorobutane(methyl groups are reduced to a single red atom)
CONCLUSIONCONCLUSION
When a molecule has 1. multiple stereocenters and2. there is a possibility of an arrangement
with a plane of symmetry you will not always find all of the 2n stereoisomers that are possible.
Some of the stereoisomers may be meso isomers,and their mirror images will be superimposable(identical) - this will eliminate at least one of the possible stereoisomers, and sometimes more.
2n = the maximumnumber
PHYSICAL PROPERTIES OF PHYSICAL PROPERTIES OF ENANTIOMERS, DIASTEREOMERSENANTIOMERS, DIASTEREOMERS AND MESO COMPOUNDSAND MESO COMPOUNDS
ENANTIOMERS HAVE EQUAL AND OPPOSITE ROTATIONS
W
CX
ZY
W
CXY
Z
(+)-nno (-)-nno
dextrorotatory levorotatory
Enantiomers
ALL OTHER PHYSICAL PROPERTIES ARE THE SAME
REMEMBER :
IN CONTRAST :DIASTEREOMERS MAY HAVE DIFFERENT ROTATIONS
AND ALSO DIFFERENT PHYSICAL PROPERTIES
H COOHH
OHOH
HOOCHOOC HH COOH
OHOH
H HCOOH
OHOH
HOOC
meso
enantiomers
H COOHH
OHOH
HOOCHOOC HH COOH
OHOH
H HCOOH
OHOH
HOOC
meso
enantiomers(+)-tartaric acid (-)-tartaric acid
TARTARIC ACIDTARTARIC ACIDfrom fermentation of wine
meso -tartaric acid
Enantiomers
Diastereomers
HAS THREESTEREOISOMERS
TARTARIC ACIDTARTARIC ACID
(-) - tartaric acid (+) - tartaric acid
[]D = -12.0o []D = +12.0o
mp 168 - 170o mp 168 - 170o
solubility of 1 g 0.75 mL H2O 1.7 mL methanol 250 mL etherinsoluble CHCl3
solubility of 1 g 0.75 mL H2O 1.7 mL methanol 250 mL etherinsoluble CHCl3
d = 1.758 g/mL d = 1.758 g/mL
Enantiomers
meso - tartaric acid
mp 140o
d = 1.666 g/mL
solubility of 1 g 0.94 mL H2O
[]D = 0o
insoluble CHCl3
D
astereo
ers
i
m
CISCIS / / TRANSTRANS RINGS RINGS
DIASTEREOMERS
ClBr BrCl
Cl
Br Br
Cl
enantiomers
enantiomers
cis
trans
diastereomers
1-Bromo-2-chlorocyclopropane1-Bromo-2-chlorocyclopropanenote that the cis/trans isomers are also diastereomersnote that the cis/trans isomers are also diastereomers
R S SR
R R S S
BrBr BrBr
Br
Br Br
Br
mirror image identical
meso
enantiomers
diastereomers
1,2-Dibromocyclopropane1,2-Dibromocyclopropane
cis
trans
DISUBSTITUTED CYCLOHEXANESDISUBSTITUTED CYCLOHEXANES
USING PLANAR RINGS FOR STEREOCHEMICAL ANALYSIS
Br Cl BrCl
Cl
Br Br
Cl
1-Bromo-2-chlorocyclohexane1-Bromo-2-chlorocyclohexane
enantiomers
enantiomersdiastereomers
cis
trans
cyclohexanes may be analyzed using planar rings
Cl Cl ClCl
Cl
Cl Cl
Cl
1,2-dichlorocyclohexane1,2-dichlorocyclohexane
cis
trans
meso
enantiomers
diastereomers
mirror image identical
Cl Cl Cl Cl Cl Cl
cis (meso) trans (enantiomers)
DOT NOTATION CAN ALSO BE USEDDOT NOTATION CAN ALSO BE USED
plane of symmetryis readily seen
ClCl
Cl Cl Cl Cl Cl Cl1,1-dichloro
1,2-dichloro
cis trans
meso enantiomers
Cl
Cl
1,3-dichloro
cis trans
meso enantiomers
Cl
Cl
Cl
Cl
DOTS MAKE FIGURING CYCLIC ISOMERS EASYDOTS MAKE FIGURING CYCLIC ISOMERS EASYIsomers of Dichlorocyclohexane
1,4-dichloro
ClCl
ClCl
cis
trans both meso
INTERCHANGING GROUPSINTERCHANGING GROUPS
SOLVING A PROBLEM
INTERCHANGESINTERCHANGES
C
CH3
BrF
H
C
CH3
FBr
H
enantiomer
ONE STEREOCENTER
1..3..5…etc interchanges = enantiomer
2..4..6...etc interchanges = original compound
ODD:
EVEN:
C C
CH3
BrF
H CH3
H
FBr
PROBLEM: ARE THESE IDENTICALPROBLEM: ARE THESE IDENTICAL OR ARE THEY ENANTIOMERS?OR ARE THEY ENANTIOMERS?
C C C C
CH3
BrF
H CH3
Br
FH CH3
H
BrF
H
CH3 BrF
ENANTIOMER ENANTIOMERSAME
12
3
YOU CAN USEINTERCHANGES
AN EASIER WAY IS TO DETERMINE THE AN EASIER WAY IS TO DETERMINE THE ABSOLUTE CONFIGURATION OF EACH MOLECULEABSOLUTE CONFIGURATION OF EACH MOLECULE
C C
CH3
BrF
H CH3
H
FBr
Br
FCH3
H
R
TIP HYDROGENTIP HYDROGENBACKWARDSBACKWARDS
CH3
FBr
H
S
ENANTIOMERS
ROTATE TOROTATE TOTHE RIGHTTHE RIGHT
1
3
2 23
1
H HCH3 CH3
ClCl
CH3CHCHCH3
ClCl
H HCH3 CH3
ClCl
CH3 HH CH3
ClCl
H CH3CH3 H
ClCl
MORE THAN ONE STEREOCENTERMORE THAN ONE STEREOCENTER
To form an enantiomer you must interchange all of the stereocenters.
enantiomertwo stereocenterstwo interchanges
If a compound has more than one stereocenter,and you only interchange one of them, you will form a distereomer.
H HC H 3 C H 3
C l C l
C H 3 C H C H C H 3
C l C l
H HC H 3 C H 3
C l C l
C H 3 HH C H 3
C l C l
H C H 3
C H 3 H
C l C l
two stereocentersone interchange
diastereomer
HCH3
Cl
IF HYDROGEN IS NOT IN BACK - REVERSE YOUR RESULT !
REDUCTIO AD NUMERAE (reduce to a set of numbers)
F
1
23= S ( after reversal )
1
23
4
2
14
3
COPING TECHNIQUESCOPING TECHNIQUES
= S
twointerchanges
THERE IS NO SINGLE CORRECT METHODTO SOLVE A STEREOCHEMICAL PROBLEM
USE WHATEVER METHOD WORKS BEST FOR YOU
THERE ARE MANY METHODSTHERE ARE MANY METHODS THAT LEAD TO A SOLUTIONTHAT LEAD TO A SOLUTION
RELATIONSHIPSRELATIONSHIPSAMONG STEREOISOMERSAMONG STEREOISOMERS
Two Stereoisomers
Enantiomers
Diastereomers
not mirror images
nonsuperimposable mirror images
COMPARING TWO STEREOISOMERSCOMPARING TWO STEREOISOMERS
molecule has one or more stereocenters
has an enantiomer is meso
is chiral is achiral
mirror imagesuperimposes
no yes
plane of symmetry
optically active
optically inactive
no plane of symmetry
DETERMINING CHIRALITY / OPTICAL ACTIVITYDETERMINING CHIRALITY / OPTICAL ACTIVITY
FISCHER PROJECTIONSFISCHER PROJECTIONS
CHO
HOCH2 HOH
OHH
CHO
CH2OHH
CH2OH
CHO
OH
EVOLUTION OF THEEVOLUTION OF THEFISCHER PROJECTIONFISCHER PROJECTION
Substituents willstick out towardyou like prongs
Fischer Projection
Main chain bendsaway from you
“Sawhorse” Projection
Orient themain chainvertically withthe mostoxidized groupat the top.
ORIENTATION OFTHE MAIN CHAINAND THE SUBSTITUENTSIN A FISCHERPROJECTION
continuation of the main chain
CH3
OHH
OHH
OHH
CH3
OH
OH
OH
H
H
H
CH3 CH2OH CH
C
OH
O
CHO COOH
CO
HC
O
OH
INCREASING OXIDATION STATEINCREASING OXIDATION STATE
increasing oxidation state
In the Fisher projection the main chain is orientedwith the most highly oxidized group at the top.
C=O on carbon-2 increasesthe priority of C-OH
H HCH3 CH3
Cl Br
CH3
CH3
H
H
Cl
Br
Cl
CH3
Br
CH3
main chain in red
orient main chain vertically
convert toFischerProjection
rotate 90o
Br
Cl
CH3
H
H
CHO
OH
OH
CH2OH
CHO
HO
HO
CH2OH
CHO
OH
OH
CH2OH
CH2OH
HO
HO
CH3
Mirror images (enantiomers)are created by switching substituents to the other side.
This is equivalent to turningthe molecule over like apancake.
OPERATIONS WITH FISCHER PROJECTIONSOPERATIONS WITH FISCHER PROJECTIONS
All stereocenters must beswitched to get an enantiomer (the mirror inverts them all).
CHO
OH
HO
CH2OH
diastereomers
enantiomers
If you switch only some of the stereocenters,not all of them, you get a diastereomer.
Rotation by 180o in the planeof the paper does not changethe molecule.
No other angle of rotationis allowed.
180o
OPERATIONS WITH FISCHER PROJECTIONSOPERATIONS WITH FISCHER PROJECTIONS
CHO
OH
OH
CH2OH
CH2OH
HO
HO
CHO
.
Rotation can be used for comparisons …..
3
A
Does A have an enantiomer A* ?
CH3
Br
Br
CH
CH
1) reflect
A* 3
Br
Br
CH3
HC
2) rotate
3
Br
Br
CH3
3) compare
NO !
CH3
Br
Br
CH3
A The molecule did not have an enantiomer because itwas not chiral.
It had a plane of symmetry,rendering it a meso molecule.
THE MOLECULE WAS MESO !THE MOLECULE WAS MESO !
plane of symmetry
CHO
OH
HO
OH
HO
CH2OH
CHO
OH
OH
OH
OH
CH2OH
CHO
HO
HO
HO
HO
CH2OH
CHO
HO
OH
OH
OH
CH2OH
CHO
OH
HO
HO
OH
CH2OH
CHO
OH
OH
HO
OH
CH2OH
CHO
OH
OH
OH
HO
CH2OH
CHO
HO
HO
OH
OH
CH2OH
CHO
OH
HO
OH
OH
CH2OH
ENANTIOMERSENANTIOMERS
DIASTEROMERSDIASTEROMERS
all stereocentershave been inverted
only some stereocentershave been inverted
HOME STUDYCan you find all 16(2n = 16) stereo-isomers? Group them as pairs ofenantiomers. Donot repeat any!
COOH
OH
OH
OH
OH
COOH
FURTHER HOME STUDY
Find all of the stereoisomers for this compound. Group allenantiomers in pairs. Are there any meso stereoisomers?
Will you find 16 (24 = 16)stereoisomers? Why orwhy not?
DETERMINATION OF DETERMINATION OF R / S CONFIGURATIONR / S CONFIGURATIONIN FISCHER PROJECTIONSIN FISCHER PROJECTIONS
H
CH2OH
CHO
OH
PLACE THE PRIORITY=4 GROUP IN ONE OF THE VERTICALPOSITIONS, THEN LOOK AT THE OTHER THREE
H
OH
OHC CH2OH1
2
3
4
1
2 3
4
R
alternatively:
H
CH2OH
CHO
OH1
2
3
4 HOCH2 CHO
OH2
1
4
3
H
R
#4 at top position
#4 at bottom position
BOTH IN BACKSAME RESULT
H
CH2OH
CHO
OH 1
2
3
4
FOR THE MENTALLY AGILEFOR THE MENTALLY AGILEWHY BOTHER INTERCHANGING? JUST REVERSE YOUR RESULT!
H comingtoward you
Same moleculeas on previousslide. S reverse R
Same resultas before.
CH2OH
CH2OH
H
CHO
OH1
2
3
4
H
CH2OH
CHO1
2
3
4
HO
CYCLIC ROTATION OF GROUPS IN A CYCLIC ROTATION OF GROUPS IN A FISCHER PROJECTIONFISCHER PROJECTIONYOU MAY FIX ONE GROUP AND THEN ROTATE THE OTHER THREE
H
CHO
OH1
3
4
2
Any of the fourgroups may be fixed.
This rotation does notchange the molecule.
R configurationfixed
fixed
rotate
OTHER EXAMPLESOTHER EXAMPLES
diastereomers
3- Chloro-2-butanol3- Chloro-2-butanol
OH
CH3
Cl
CH3
HO
CH3
Cl
CH3
HO
CH3
Cl
CH3
OH
CH3
Cl
CH3
enantiomers-1 enantiomers-2
2,3-Dichlorobutane2,3-Dichlorobutane
meso
diastereomers
Cl
CH3
Cl
CH3
Cl
CH3
Cl
CH3
Cl
CH3
Cl
CH3
Cl
CH3
Cl
CH3
enantiomers
STEREOCENTERS OTHER THANSTEREOCENTERS OTHER THAN STEREOGENIC CARBONSTEREOGENIC CARBON
STEREOGENIC CARBONS are not the only possible stereocenters in a molecule.
TETRAHEDRAL ATOMSTETRAHEDRAL ATOMSNON-CARBON STEREOCENTERSNON-CARBON STEREOCENTERS
Any atom which is tetrahedral with four differentgroups has the potential to be stereogenic.
CH3
Si H
CH2CH3
CH3
P H
CH2CH3
+N
CH2CH3
CH2CH2CH3
CH3+
PYRIMIDAL ATOMS WITH AN PYRIMIDAL ATOMS WITH AN UNSHARED PAIRUNSHARED PAIR
P
CH2CH3
CH3
.. ..N
CH2CH3
CH2PhCH3
....S
F
ClO- +
If the atoms do not invert (see next slide) thesemolecules will be chiral.
Pyrimidal atoms can be stereocenters.
N
H
CH2CH3CH3
..
..
N
CH2CH3HCH3
..
INVERSION OF SMALL AMINES INVERSION OF SMALL AMINES
Small amines (those with H, CH3, or CH2CH3 groups) exhibit fast inversion rates:
INVERSION OF SMALL AMINES INVERSION OF SMALL AMINES
With larger groups, the rate of inversion slows.
If fast inversion occurs, a pyrimidal nitrogen will not be an active stereocenter.
..
N
CH3CH2
H CH3
..
..N
HCH2CH3CH3
..
When there is no inversion, an amine with three different groups attached will be a stereocenter.
SR RACEMIC MIXTURE
OF ENANTIOMERS
If the groups are large enough, inversion stops completely.
: = priority 4
In acid solution, fast inversion may occur if one of the attached groups is a hydrogen atom (H).
A CHIRAL AMINE IN ACID SOLUTIONA CHIRAL AMINE IN ACID SOLUTION
..N
CH2CH2CH3
H
..
....N
CH2CH2CH3
H
H+H+
HCH2CH2CH3N
-H+
Removal of a different hydrogen (blue) from the ammonium ion than the one added (red), causes a change (inversion)of configuration.
+
amine 1 ammonium ion amine 2
PROTON EXCHANGE
SS
RR
BICYCLIC AMINES ARE USUALLY RIGID BICYCLIC AMINES ARE USUALLY RIGID ..... and they do not invert
The nitrogen is rigidly held inthe bicyclic rings and cannotinvert.
N
NTröger’s base
[]D = 287o
The rings cannot invert.
NCH3
..
CH3
H
*
* *
*
*
*
NOTE: Without the exo methyl groupthere would be a plane of symmetryand the molecule would be meso.
AZIRIDINES DO NOT INVERTAZIRIDINES DO NOT INVERT
Aziridine = a three-membered ring containing a nitrogen atom.
NCH3O
CH3
H
..N
CH3
H
OCH3
:
trans cis
This amine does not invert even at 200o
The transition state would be planar, requiring a 120o angle.
diastereomers
**
*
*
STEREOCENTERS THAT DO NOTSTEREOCENTERS THAT DO NOTINVOLVE A STEREOGENIC ATOMINVOLVE A STEREOGENIC ATOM
NOT ALL STEREOCENTERS ARE ATOMSNOT ALL STEREOCENTERS ARE ATOMS
Sometimes a group of atoms (none of which is astereocenter itself) can confer chirality.
C C CH
CH3Cl
FC C C
H
H3CCl
F
The allene group (C=C=C) is a stereocenter. An allene is chiral when four different groups areattached ..... try it with any two groups the same!
Also notice that this group is a stereocenter, andit has no stereogenic (chiral) carbon atoms.
remember thatan allene has atwist in the center
C C CH
C H 3C l
FC C C
H
H 3 CC l
FC C C
H
C H 3C l
FC C C
H
H 3 CC l
FC C C
H
C H 3C l
FC C C
H
H 3 CC l
FC C C
H
C H 3C l
FC C C
H
H 3 CC l
F
The allene group is just like a stretched outtetrahedral carbon.
remember thetwist
COMPARISON OF THE ALLENE AND COMPARISON OF THE ALLENE AND STEREOGENIC CARBON STEREOCENTERSSTEREOGENIC CARBON STEREOCENTERS
both ends areperpendicular
SPIRO COMPOUNDS CAN ALSO BE CHIRALSPIRO COMPOUNDS CAN ALSO BE CHIRAL
FCl
CH3
H H
H3C
ClF
CH3
HCl
F H3C
H Cl
F
enantiomers
enantiomers
C H 3
HC l
F H 3 C
H C l
F
HEPTIHELICENEHEPTIHELICENE
coronene heptihelicene(completely planar)
(makes a helix which is chiral)heptihelicene has an enantiomer
has no enantiomer
has no stereocenters - all sp2 atoms
seven ringsoverlapcompare:
helices may be right- or left-handed
six rings joinperfectly
H
H
H
H
transtrans - CYCLOOCTENE - CYCLOOCTENE
This molecule has no stereocenters,but it is chiral.
enantiomers
( Remember that this is the smallest ring which can contain a trans double bond.)
The enantiomers have either a right-handed or a left-handed twist.
SUMMARYSUMMARY
It doesn’t even matter whether there are any other stereocenters present that we recognize as the usual sources of chirality (including allenes, spiro rings, etc.)
The entire molecule can be chiral (it can be its own stereocenter).
Stereogenic Carbon Atoms (or P, or N, or S atoms) are not required to be present for a molecule to be chiral !
THERE IS NO REQUIREMENT FOR ATOMICTHERE IS NO REQUIREMENT FOR ATOMICSTEREOCENTERS FOR A MOLECULE TO BE CHIRALSTEREOCENTERS FOR A MOLECULE TO BE CHIRAL
A chiral molecule needs only to have no symmetry of any kind.
The only definitive test for chirality is to take the mirror image of the molecule and check if it willsuperimpose :
chiral = mirror image doesnt superimposeachiral = mirror image does superimpose
It doesn’t matter if you recognize any stereocentersor not ! The entire molecule can be chiral !
TESTING FOR CHIRALITYTESTING FOR CHIRALITY
A compound can have stereocenters and not be chiral.
meso compounds are an example
BrBr
CH3
CH3
HH
COOH
OH
OH
COOH
STEREOCENTERS give a molecule the possibility of being chiral, but they do not assure it; a plane of symmetry is possible.
NOTE ALSO THATNOTE ALSO THAT
S
RR
S
The handedness of the chiral herbicide metolachlor.The handedness of the chiral herbicide metolachlor.
Enantiomers and Physiological Activity
Drugs: Enantiomers Act Very Differently
H2NOH
O
O
H2N H
S
Bitter Sweet
Asparagine
NH2
HO
O
O
NH2H
R
Cl
Cl
OOH
O
CH3H
R
Cl
Cl
OHO
O
H3C H
S
Active Inactive
Dichlorprop
(Herbicide)
HO
HOH2CHN
HO H
OH
CH2OHHN
OHH
RS
BronchodilatorAntagonist
Albuterol
Enantiomer Recognition
In nature: Enzymes, receptorsIn nature: Enzymes, receptors
Synthetic: Enantiomerically pure reagents and catalystsSynthetic: Enantiomerically pure reagents and catalysts
Enantioselectivity:Generating One Enantiomer from
Achiral Material
A A “handed” “handed” reagentreagentor catalyst can or catalyst can telltellthe differencethe difference
Which?Which?
Nevertheless, we still Nevertheless, we still need a chiral auxiliaryneed a chiral auxiliary to generate to generate a new stereocenter selectively. What generated the a new stereocenter selectively. What generated the “first” enantiomer?“first” enantiomer?
Amplification of Chirality from Extremely Low to Greater than 99.5% ee by Asymmetric AutocatalysisItaru Sato, Hiroki Urabe, Saori Ishiguro,Takanori Shibata, and Kenso Soai*
Angew. Chem. Int. Ed. 2003, 42, 315