Dr. Nabila Al-Jaber
STEREOCHEMISTRY IS CHEMISTRY IN SPACE DESCRIBES CHEMISTRY AS A FUNCTION OF TIME
المركبات كيمياء من نوع هي الفراغية الكيمياءكدالة الكيمياء وتصف الفراغ في العضوية
معين تفاعل في كيميائية ظاهرة أي للزمن،الفراغية الكيمياء اساس على شرحها يمكن
CERTAIN MOLECULAR PHENOMENA WERE OBSERVED AND TO EXPLAIN THEM, THE PRINCIPLES OF STEREOCHEMISTRY WERE DEVELOPEDTHE TERM STEREOCHEMISTRY WAS FIRST COINED BY VICTOR MEYER
.
PLANE-POLARIZED LIGHT BEAM
unpolarizedbeam
wavelengthl
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.
الضوئي OpticallyالنشاطActive
Refers to molecules that interact with plane-polarized light
تداخل إلى للمركبات الضوئي النشاط يرجعالستقطب الضوء مستوى مع الجزيئات
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, a
(usually quartz)
a solution of the substance to beexamined is placed inside the cell
a
Dextrorotatory
Rotates the plane of plane-polarized lightto the right.
(+)- d-
Laevorotatory
Rotates the plane of plane-polarized lightto the left.
(-)- l-
TYPES OF OPTICAL ACTIVITYnew older
new older
[a]D = acl
Specific Rotation []D
a = 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
[a]D tvalue of
BIOT’S LAW
POLARIMETER
The instrument used to determine whether asubstance is optically active and to measure thedirection and degree of optical rotation is calleda polarimeter.
POLARIZED LIGHT
and the
Polaroid Film
THE POLAROID FILM WORKS LIKE A NICOL PRISM
polarized light
POLAROID SUNGLASSES
Each eye is polarized in a different plane toeliminate glare.
no lightcan pass
foldfold
Try this with a flexible pair ofclip-on sumglasses (polaroid).
AN EXPERIMENT YOU CAN DO
The Polarimeter
chemist
sample cell
polarizer
Na lamp
plane isrotated analyzer
aaplane-polarizedlight
observedrotation
00000
rotate to null
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 this
substance on a cold day.
(+) (-)Louis Pasteur separated these and gave them to Biot to measure.
Biot’s results :
mirrorimages
Crystals of Sodium Ammonium Tartrate
hemihedral facesPasteur found twodifferent crystals.
THERE IS AN ELEMENT OF SERENDIPITY IN PASTEUR’S DISCOVERY. THE TWO TYPES OF CRYSTALS ARE FORMED ONLY AT THE CONDITIONS WHICH FAVOURED PASTEUR.
TARTARIC ACID IS ALSO KNOWN AS RACEMIC ACID. RACEMUS IN LATIN MEANS ‘ A BUNCH OF GRAPES’
HE MADE THIS DISCOVERY AT THE AGE OF 26.
(SEE REFLECTIONS ON MY LIFE)
Enantiomers
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 laevorotatory
Enantiomers
ALL OTHER PHYSICAL PROPERTIES ARE THE SAME
H COOHH
OH OH
HOOCHOOC H
H COOH
OH OH
H HCOOH
OH OH
HOOC
meso
enantiomers
(as a minor component)
ALSO FOUND
H COOHH
OH OH
HOOCHOOC H
H COOH
OH OH
H HCOOH
OH OH
HOOC
meso
enantiomers
(+)-tartaric acid (-)-tartaric acid
TARTARIC ACIDfrom fermentation of wine
[a]D = 0
meso -tartaric acid
Enantiomers
IF A COMPOUND WITH TWO CHIRALITY CENTRES HAS THE SAME FOUR GROUPS BONDED TO EACH OF THE CHIRALITY CENTRES, ONE OF ITS STEREOISOMERS WILL BE A MESO COMPOUND
THE NEXT IMPORTANT DEVELOPMENT IN STEREOCHEMISTRY WAS THE CONCEPT OF CONFORMATIONAL ANALYSIS (1950).
THEN 3D STEREOCHEMISTRY BECAME TIME DEPENDENT
(TEMPORAL) AND MARKED THE ADVENT OF DYNAMIC STEREOCHEMISTRY
MOLECULAR SYMMETRY AND CHIRALITY
STEREOCHEMISTRY IS PRIMARILY CONCERNED WITH MOLECULAR GEOMETRY AND MOLECULAR GEOMETRY IS BEST EXPLAINED IN TERMS OF SYMMETRY
SYMMETRY OPERATION AND ELEMENTS OF SYMMETRY
• AXIS OF SYMMETRY,
• PLANE OF SYMMETRY (σv, σh & σd)
• CENTRE OF SYMMETRY
plane ofsymmetry
A SYMMETRIC OBJECT HAS A PLANE OF SYMMETRY - ALSO CALLED A MIRROR PLANE
Mirror Plane
no symmetry
CHIRALAn 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
STEREOCENTERS
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 CARBONS
A stereogenic carbon is tetrahedral and has four different groups attached.
stereocenter
( called “chiral carbons” in older literature )
HFClBr
Cl
ClBrBr
Cl Cl
plane ofsymmetry
side view edge view
Cl Cl
PRESENT ACHIRAL
MOLECULES Sn AXIS
ABSENT CHIRAL, DISSYMMETRIC
NO Cn
ASYMMETRIC
CONFIGURATION
ABSOLUTE CONFIGURATION ( R / S )
CONFIGURATION
The three dimensional arrangement of the groups attached to an atom
المركزية بالذرة المرتبطة المجموعات أو للذرات األبعاد ثالثي الترتيب
Stereoisomers differ in the configuration at one ormore of their atoms.
مجموعة أو ذرة في اختالفها عند الفراغية هيئتها في المركبات تختلف
2
CONFIGURATION - 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 CONFIGURATIONusing 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 CONFIGURATION
SEQUENCE RULE
CAHN-INGOLD-PRELOG
I
C
BrCl
F
I
C
ClBrF
1
2
3
4
R S
Bromochlorofluoroiodomethane
1
32
4
Enantiomers
How Many Stereoisomers 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
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 ISOMERISM(geometric)
IMPORTANCE OF STEREOCHEMISTRY
AN ACHIRAL REAGENT REACTS IDENTICALLY WITH BOTH ENANTIOMERS.
AN ACHIRAL SOCK FITS ON EITHER FOOT
A CHIRAL REAGENT REACTS DIFFERENTLY WITH EACH ENANTIOMERS
A CHIRAL SHOE FITS ON ONLY ONE FOOT
RECEPTORS ARE PROTEINS THAT BIND PARTICULAR MOLECULES
BECAUSE A RECEPTOR WILL RECOGNISE ONLY ONE OF A PAIR OF ENANTIOMERS, ENANTIOMERS CAN HAVE DIFFERENT PHYSIOLOGICAL PROPERTIES.
RECEPTORS LOCATED ON THE EXTERIOR OF NERVE CELLS IN THE NOSE ARE ABLE TO PERCIEVE AND DIFFERENTIATE THE ESTIMATED 10000 SMELLS TO WHICH THEY ARE EXPOSED.
(R)-(-)-CARVONE IS FOUND IN SPEARMINT OIL AND (S)-(+)- CARVONE IS FOUND IN CARAWAY SEED OIL. EACH HAS A DIFFERENT SMELL AS IT FITS INTO DIFFERENT RECEPTORS.
CH3O
C
CH2H3C
(R)-(-) CARVONE
CH3O
C
CH2H3C
(S)-(+) CARVONE
ABOUT HALF THE COMMERCIALLY AVAILABLE DRUGS HAVE ONE OR MORE CHIRALITY CENTRES.
SYNTHETIC DRUGS ARE RACEMIC MIXTURES.
THEY ARE MARKETED AS SUCH BECAUSE OF THE HIGH COST OF SEPARATION.
DRUGS FROM NATURAL SOURCES ARE SINGLE ENANTIOMERS.
ONE ENANTIOMER MAY BE MORE POTENT AND THE OTHER MAY HAVE SIDE EFFECTS.
SOMETIMES SEPARATION IS NOT DONE TO AVOID OVERDOSAGE.
(S)-(-)-KETAMINE IS FOUR TIMES MORE POTENT THAN (R)-(-)-KETAMINE AND HAS LESS SIDE EFFECTS.
THE ACTIVE INGREDIENT OF IBUPROFEN IS THE (S)-(+)-ISOMER.
OCONHCH3
THE STEREOCHEMISTRY OF REACTIONS ARE VERY IMPORTANT.
A REGIOSELECTIVE REACTION FORMS MORE OF ONE CONSTITUTIONAL ISOMER THAN THE OTHER.
A B + C MORE ‘B’ IS FORMED THAN ‘C’, WHERE B AND C ARE CONSTITUTIONAL ISOMERS.
A STEREOSELECTIVE REACTION FORMS MORE OF ONE STEREOISOMER THAN THE OTHER.
A B + C MORE ‘B’ IS FORMED THAN ‘C’, WHERE B AND C ARE STEREOISOMERS.
IN A STEREOSPECIFIC REACTION, EACH STEREOISOMERIC REACTANT FORMS A DIFFERENT STEREOISOMERIC PRODUCT OR A DIFFERENT SET OF STEREOISOMERIC PRODUCTS.
A B
C D
‘A’ AND ‘C’ ARE STEREOISOMERS
‘B’ AND ‘D’ ARE STEREOISOMERS
A STEREOSPECIFIC REACTION IS ALSO STEREOSELECTIVE. A STEREOSELECTIVE REACTION IS NOT NECESSARILY STEREOSPECIFIC
ALL THE REACTIONS THAT OCCUR IN BIOLOGICAL SYSTEMS ARE CATALYSED BY ENZYMES.
AN ENZYME CATALYSED REACTION FORMS ONLY ONE STEREOISOMER BECAUSE AN ENZYME POSSESSES A CHIRAL BINDING SITE.
THEY ARE COMPLETELY STEREOSELECTIVE.
THE ENZYME FUMARASE, WHICH CATALYSES THE ADDITION OF WATER TO FUMARATE, FORMS ONLY (S)-MALATE. COO-
-OOCH2COH
HC C
H
-OOC
COO-
H
+ H2Ofumarase
fumarate (S)-malate
ENZYME CATALYSIS IS STEREOSPECIFIC. AN ENZYME CATALYSES THE REACTION OF ONLY ONE STEREOISOMER.
FUMARASE CATALYSE THE ADDITION OF WATER TO FUMARATE BUT NOT TO MALEATE
C C
-OOC
H
COO-
H
+ H2Ofumarase
maleate
no reaction
AN ENZYME CAN DIFFERENTIATE STEREOISOMERS BECAUSE OF THE CHIRAL BINDING SITE
FISCHER PROJECTIONS
CHO
HOCH2 HOH
OHH
CHO
CH2OHH
CH2OH
CHO
OH
EVOLUTION OF THEFISCHER 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 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
DETERMINATION OF R / S CONFIGURATIONIN 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 AGILEWHY BOTHER INTERCHANGING? JUST REVERSE YOUR RESULT!
H comingtoward you
Same moleculeas on previousslide. S reverse R
Same resultas before.
THE SIMPLEST WAY OF ASSIGNING (R S) CONFIGURATION WAS GIVEN BY EPLING (1982)
1. FIX THE PRIORITY
2. TRACE A SEMICIRCLE JOINING a b c IGNORING d.
3. CLOCKWISE IS ‘R’ AND ANTICLOCKWISE ‘S’ IF ‘d’ IS VERTICAL (TOP OR BOTTOM)
4. IF ‘d’ IS ON THE HORIZONTAL LINE REVERSE THE NOTATION.