Stereochemistry
Branch of science or chemistry which deals with the study of properties of
molecules on the basis of three dimensional structure
Concept of stereochemistry is based on the Vant Hoff and Le Bels theory,
the four valencies of a carbon are directed towards the four corner of regular
tetrahedron constructed around the carbon atom as the center
Stereochemistry deals with isomerism of compounds having same molecular
formula (structural formula) but different arrangement of atoms or group of
atoms in space
[Cr(H2O)6]3+
CHF2Cl
CF4
Stereochemistry
Isomerism
Structural
Chain
Functional
Stereoisomerism
Conformational
Configurational
Positional
Eclipsed
Staggered
Gauche
Optical
Geomet
rical
Optical Activity and Chirality
Any compound which rotates the plane polarized light is said to be optically active
COOH
COOH
HO
H3C
OH
CH3
d-lactic acid
l-lactic acid
The light which can be vibrate in only one plane.
A carbon atom or center containing four different substituents is called as chiral carbon/
chiral center.
R
R
+
R
2
R
Chiral compound
R
2
R
Chiral compound
R1
R2
R4
R3
R5
Chiral compound
Center of symmetry
Plane of symmetry
CH3
COOH
b
a
d
b
COOH
Elements of
symmetries
Ph
Ha
Hd
Hb
Hd
Hb
Ha
H
CH3
Alternative axis of
symmetry
Axis of symmetry
plane of symmetry
Hb
Ha
Hd
COOH
COOH
H
Ph
Center of symmetry
(a)
H
COOH Ph
Ph
H
Ph
COOH
Plane refle
ction
COOH
COOH
H
Ph
(a)
Enantiomers
O
Disteriomers
R
NH
OH
NH
OH
S - isomer,
beta -blocker
R - isomer,
Contraceptive
Optical Active
compounds
Epimers
CHO
CHO
H
HO
H
* OH
* H
* OH
CH2OH
Epimers
HO
* H
HO
* H
* OH
CH2OH
COOH
H
OH
OH
COOH
plane of symmetry
Same physical and
chemical properties
Enantiomers
Rotate plane polarized light in opposite directions (optical antipodes)
Reacts with different rates with other chiral compounds.
e.g. 1. One isomer is biologically active while other does not.
2. Both enantiomers are reacts different rates with chiral reagents or in presence of chiral
catalyst.
3. Having different solubility in optical solvents.
O
NH
R
O
OH
OH
Et
NH
H
OH
NH
NH
Et
H
OH
S - isomer,
beta -blocker
Isomer rotate plane polarized
light to left (anticlockwise) is
leavo isomer (-)
NH
NH
Et
H
OH
(S,S) -isomer
Tuberculostatic
R - isomer,
Contraceptive
OH
Et
(R,R)-isomer
Cause blindness
Ethambutol
Isomer rotate plane polarized
light towards right (clockwise)
is dextro isomer (+)
The mixtures of equal amounts of enantiomers (d and l form) are optically inactive are
called as racemic mixtures (dl)
They are differ in
their specific
reaction and specific
rotation may have
same or opposite
side
Disteriomers having
different physical
properties such as
m.p., b.p.,
solubility, density,
refractive index, etc
Many of the
chemical
reactions are
similar but few of
them are different
They may have
different energy of
activation,
resulting the
different reaction
rates
Disteriomers
The stereoisomers which are not mirror images of each others are called as
disteriomers
H
HO
OH
HO
H
COOH
(I)
Enantiomers
COOH
COOH
COOH
COOH
OH
HO
OH
OH
HO
COOH
(II)
COOH
COOH
(IV)
(III)
mesoform (inactive)
I and III, I and IV, II and III, II and IV are disteriomers of each others
Epimers
Disteriomers which differs in the configuration at only one
asymmetric carbon atom are called as epimers
CHO
CHO
H
* OH
HO
* H
* OH
CH2OH
Epimers
HO
* H
HO
* H
* OH
CH2OH
Some compounds possesses chiral carbon atoms can show optical inactivity
Reasons
1. Due to internal compensation:
In meso form of the molecule, one half of the
molecule is the mirror image of the other
half; thus if one half of the molecule rotates
the light towards the right, the other half
would rotates it to the same extent towards
the left. Therefore no deflection of the light
is observed due to intrinsic property of the
molecule
COOH
H
OH
OH
COOH
plane of symmetry
2. Due to external compensation:
The external compensation is observed
when the two enantiomers are present in
equal quantities. This mixture is term as
racemic mixture
Absolute configuration of chiral compounds
dl Nomenclature
(obtained by comparing
with glyceraldehyde
Erythro & threo
nomenclature
Absolute or RS
nomenclature
2
1
R (Rectus means
right handed)
Sequence rule
4
R
Clockwise rotation
2
3
4
S
Anticlockwise rotation
S (Sinister means
left handed)
Priority
rule/Sequence rule
Rules used to decide the priority order of the groups of atoms or atoms attached to chiral center
X
Chiral Molecule
1. The atom having highest atomic number (atomic mass) was given highest priority and
the atom with the lowest atomic number has lowest priority.
1-Chloroethanol. The four atoms/groups attached to chiral carbon are Cl, OH, CH3, and H.
The priority order of substituents according to the atomic number are Cl>O>C>H. Therefore
the priority order of the four atoms/groups is Cl > OH > CH3 > H.
CH3
HO
Cl
Priority rule/Sequence rule
3. The groups having double or triple bonds, instead of considering presence of a single
double bond or a single triple bond, each bond is dublicated in case of a double bond and
triplicated for a triple bond.
2
CH
C C
1
C C
C C
Triple bond replaced by-
CH CH2
H2
CH C
2
C C
double bond replaced by-
In a compound 3-methyl-pent-1-en-4-yne. The group attached to the chiral carbon atom
are -CCH, -CH=CH2, -CH3 and H. The hydrogen is the lowest priority group. The
acetylenic group, the second atoms attached are three carbon whereas in the ethylenic
group the second atoms attached are two carbons and methyl group has three hydrogens
attached as second atoms. Therefore the priority order of the four atoms/groups is CCH >
CH=CH2 > CH3 > H.
According to the rule suggested above the priority order of some groups with unsaturated
bonds can be arranged as follows.
-COOH > -CO- > -COH > -CN > -C=N- > -CC- > -C=C-
4. In case the molecules have two isotopes of the same element attached to
the chiral carbon atom, higher priority is given to the heavier isotope. For
example deuterium would get priority over hydrogen and C-13 would set
priority over C-12.
The symbol R comes from the Latin rectus for right, and S from the Latin sinister for left.
Lowest Priority
group away from
viewer
identify the chirality
center(s)
assign the relative priorities
rotate the low priority group
away
determine the sense of groups 1 ->
3
clockwise = R
To determine the configuration of given
compounds, the molecule is viewed in manner
so that the lowest priority group is placed
furthest (putting behind) from the eye and the
rest three groups (putting in front) are placed
facing the eyes. This can be explaining with
help of example.
CHO
CHO
H
OH
converted to
CH2OH
H
OH
(II)
(Tetrahedral form)
CH2OH
(I)
(Planar structure)
Determination of
R/S configuration
The plane projection diagram of glyceraldehydes
molecule I is converted to the tetrahedral form structure II
places the CH2OH furthest away from the eye. To
determine the R and S configuration of the molecule, the
lowest priority group should occupy the position, furthest
from the eye. Therefore to determine configuration, the
hydrogen atom should be occupy the position occupied
by CH2OH group and hence interchange of the positions
of the groups are required
CHO
HOH 2C
Backside
position
H
OH
Determination of R/S configuration
Fischer suggested some rules to be followed for the interchanging the
groups. The rules are1. One interchange of a pair of substituent group will result in the change
of configuration of the molecule i.e. one enantiomeric form would get
converted to the other enantiomeric form of the molecule by one
interchange of a pair of substituent group.
2. Two interchange of two pairs of substituent groups result in no change
in the enantiomeric form. The configuration of the molecule is retained.
e.g. Glyceraldehyde (I) molecule. The structure (I) can be changed such
that H atom occupies the position farthest from the eye i.e. it should be
occupied the position of CH2OH group. Two interchanges of two pairs of
substituent groups would be required to retain the configuration.
OH
CHO
1st interchnage
H
OH
HOCH2
between H
CH2 OH and CH2OH
(I)
CHO
OH
H
OH
2nd interchange
between OH
and CHO
HOCH2
CHO
H
H
HOCH2
CHO
'R'
To assign the configuration of the molecule, arrow is to be drawn starting
from the highest priority order group OH, going to the next CHO, and
then to the next i.e. to CH2OH. Thus the configuration of glyceraldehyde
molecule is R.
Fischers Plane Projection Diagram
Tetrahydral molecule can be represented with the help of a dashed wedge
line formula. Out of the four bonds, one bond projected towards the
viewer, the other away from viewer and rest two are lie on the plane of the
paper. The heavy wedged bond is drawn to represent the bond towards the
viewer, a dashed bond projected away from the viewer and normal bonds
lying on the plane of paper.
plane containing chiral carbon
above the plane
CHO
H
HO
CH2OH
tetrahedral form
title as suggested
by Fischer
away to viewer
H
OHC
OH
CH2OH towards viewer
below the plane
title form
CHO
H
vertical line
OH
CH2OH
horizontal line
planar structure
Fischer suggested the tilting of the tetrahedral form of the molecule in a
manner that if the chiral carbon atom is held on a line drawn on the paper,
two groups are lie above the plane of paper and the other two groups
would lie below the plane of paper. Fischer then represented the title form
of molecule on a cross with the groups above the plane of paper
represented on horizontal line of the cross and the group lying below the
plane of paper in the title form is represented on the vertical line of the
cross. Out of the two groups present below the plane of paper in title
form, the group away from the viewer is placed at the upper end of the
vertical line and the group towards the viewer on the lower end of the
vertical line.
Determination of R/S configuration
The configuration of the molecule does not change by
rotating it through 1800 within the plane of the paper about
an axis perpendicular to the paper. But rotation of the same
molecule by 900 or 2700 will leads to an enantiomeric
mirror image form.
Br
Br
H3 C
C2 H5
CH3
H
180
CH3
Br
'R'
Rotation
H
C2 H5
C2 H5
C2 H5
1st interchange
H
of H and Et
CH3
Br
C2 H5
C2 H5
2nd interchange
of H and Br
Br
CH3
H
Br
CH3
H
'R'
Determination of R/S configuration
Rotation by 90 degree:
Br
Br
H3 C
C2 H5
CH3
H
90
'R'
Rotation
CH3
H
C2 H5
Br
C2 H5
CH3
1st interchange
of H and Et
C2 H5
Br
H
C2 H5
C2 H5
2nd interchange
of Me and Et
H3C
Br
H
CH3
Br
H
'S'
Molecules with more than one chiral atom
The total number of optical isomers containing n number of chiral
carbon atoms is 2n. Fischers projection diagram of a molecule with
more than one chiral carbon atom always represented in eclipsed
conformational form of the molecule.
e.g. erythreose molecule.
CHO
H
OH
OH
CH2OH
Fischer plane projection dia.
H
H
OH
OH
CHO
CH2OH
Eclipsed conformation
Molecules with more than one chiral atom
Fischer then represented the title form of molecule on a cross with the groups above the
plane of paper represented on horizontal line of the cross and the group lying below the
plane of paper in the title form is represented on the vertical line of the cross. The
configuration of each chiral carbon atom is worked out separately. First working out the
configuration of carbon atom C2, the steps adopted are as follows.
CHO
H
OH
OH
CH2 OH
CHO
CHO
H
R
H
Erythreose
OH
of H and R
OH
CHO
1st interchange
R
OH
CHO
2nd interchange
of R and OH
HO
R = -CHOH-CH2OH
R
H
CHO
H
HO
R
'R'
Working out the configuration of carbon atom C3, the steps adopted are as follows.
CHO
OH
OH
CH2 OH
Erythreose
R
H
CH2 OH
H
OH
OH
1st interchange
CH2 OH
HOCH2
of H and CH2OH
R
H
2nd interchange
HO
OH
of CH2OH and OH
R = -CHOH-CHO
R
CH2OH
H
R
H
HO
CH2 OH
'R'
The configuration at C2 and C3 are R & respectively.
Other Optical active compounds
Compounds with tervalent chiral atoms (other than carbon):
Atoms with pyramidal geometry or bonding mild be gives optical activity if three
different atoms or groups are present and lone pair is serves as fourth groups. But
it is optically inactive because of pyramidal inversion which is rapid oscillation of
the unshared pair of electrons from one side of X, Y and Z plane to other i.e. 2 x
1011 inversion per second.
Y
X
N
X
z
(Pyramidal inversion)
z
Y
The inversion is less in substituted amines and amides. Two types of nitrogen
atom invert slowly as nitrogen in three membered ring and nitrogen connected to
another atom bearing lone pair of electrons. In some molecules in which nitrogen
atom is at a bridgehead, pyramidal inversion is prevented.
mirror
Cl
Cl
N
CH3
Cl
H3C
CH3
N
CH3
Cl
CH3
H3C
(cis)
(trans)
The phosphorous, arsenic and antimony resolved slowly. Sulfur exists in
pyramidal geometry in sulfoxides, sulfinic esters, sulfonium, sulfonium salts and
O
O
sulfites.
CH
3
As
H3C
Ph
Et
Me
R
RO
O
S
R'
OR'
OR'
R''
S+ X
R'
R
Optical activity of other compounds
Restricted rotation giving rise to perpendicular
dissymmetric planes:
There are certain compounds which are optically active
without containing any asymmetric center because of its
structure in which two perpendicular planes neither of
which can be bisected by a plane of symmetry. The
geometry or structure of molecule is-
A
B
A
B
e.g. Biphenyls, allenes, spiranes, etc.
Prochiral relationship:
When chiral center is produced after the substitution reaction in the
original center or assembly is known as prochiral center.
e.g. 1,3-Propane diol. If -H hydrogen atom undergoes deuteration in
presence of suitable catalyst forming two identical compound is optically
inactive. The protons at C2 is symmetric are called as homotopic ligands.
HO
H D
H H
OH
HO
OH
HO
H
OH
replace beta H
replace alpha-H
by D
by D
HO
Optically inactive
C2 substitution
OH
pro-R hydrogen
H D
beta-H substitution
OH
HO
H
HO
OH
C1/C3 substitution
pro-S hydrogen D
H
alpha-H substitution
Replacement of one proton at C1 by D produces the chiral center at C1 as
these protons are non-equivalent (isotopes). As substitution either takes
place at H or H produces different stereoisomers.
Hence, this proton is known as heterotopic proton or heterotopic ligand.
As they produces enantiomers are known as enatiomeric ligands or if they
produces disteromers are known as disteriotopic ligands. Thus the C1 and
C3 are prochiral centers. In above example, the enatiotropic groups are
equivalent in all chemical aspects except towards chiral reagents. The
replacement of H produces S configuration in product so the H is called
as pro-S hydrogen and replacement of H produces the product having R
configuration, H is called as pro-R hydrogen
Prochiral faces
There are two faces for the chiral carbons as Si-face and Re-face. In
Si-face we obtained S configuration in prochiral carbon. In Re-face
we obtained R configuration in prochiral carbon. E.g. Reduction of
deutarated acetaldehyde.
We can distinguish these two products by asymmetric reaction. In
above example, there is formation of only R-1-deutarated ethanol
indicates that attack of H takes from Si face only.
CH3
HO
D
'R'
H2/Si face
attack from
backside
H3C
H2/Re face
D
attack from
frontside
CH3
D
D
HO
'S'
