Representation of structural formulas

Dash formulas of isopropanol

Bond-line formulas

Free rotation around the single bonds

Condensed formula

Me

HO Et

Three-dimensional formula 1
 H H H
H H
C H C H C
H
H
H H H

a a-1 a-2 a-3

H H H H
H H H H
H H H C
H C C C
C C C H
H H H H
H
H H H
H H H
A A-1 A-2 A-3
d f
e
a c d C e

f a C c
b
a d
d e eclipsed b

e a
C C
f
b
c f b c
d f
e
sawhorse formula staggered e
b a d C
a d d e a
e a d e f b C a
C C c 2
f c
b b c
c f b c
f Newman projection Fischer projection
 Isomers: constitutional isomers
Isomers: different compounds that have the same molecular formula.
Constitutional isomers: same molecular formula but different connectivity.

length of number of
C4H10 chain isomers
C4 2
C5 3
C3H7Cl C6 5
C7 9
C8 18
C9 35
C2H6O C10 75
C15 4347
C20 366 319
C25 36 797 588

Tautomerization: tautomers, a special type of constitutional isomerism, They differ in

the position of a hydrogen and a double bond. They are interconvertible (equilibrium)
Keto-enol tautomers: O O OH O
OH O
C C C C
CH2 C CH3 CH3 C CH3 H3C C CH3 H3C C CH3
H2 H
prop-1-en-2-ol propanon (acetone)
enol forma keto form pentane-2,4-dione pentane-2,4-dione
(>99%) keto form enol form
(24%) (76%) 3
Stereoisomers: have the same constitution, but they differ in the arrangement of their
atoms in space. they can be subdivided to enantiomers and diastereomers
Enantiomers are stereoisomers whose molecules are not superposable mirror images
of each other.
Diastereomers are stereoisomers whose molecules are not mirror images of each other
or every stereoisomer that is not enantiomer.

4
 Isomers
Different compounds with the same molecular formula

CONSTITUTIONAL ISOMERS STEREOISOMERS

The connectivity of the atoms is different same constitution, different arrangement of atoms in space

TAUTOMERS
The same compound can react DIASTEREOMERS ENANTIOMERS
with two different structures
stereoisomers that are not enantiomers nonsuperposable mirror images of each other

Configurational Conformational Conformational Configurational

diastereomers diastereomers enantiomers enantiomers
not interconvertible by single bond rotation interconvertible by interconvertible by not interconvertible by
single bond rotation single bond rotation single bond rotation
conformational isomers of alkanes
chair and boat conformations
Chiral compounds
Central chirality
Achiral Chiral Helical chirality
diastereomers diastereomers Axial chirality
Atropizomerism allenes
Cis-trans isomers compounds with more Twist boat spiro
than one stereogenic centre Gauche conformers compounds
Z - E izomers of alkenes Anti conformers
cis-trans isomerism of condensed bicikloalkanes

5
 Sigma bonds and bond rotation
conformation: temporary molecular shapes that results from rotations of groups about
the single bonds. Each possible structure is called conformer  conformational analysis
conformational stereoisomers: stereoisomers that are interconvertible with one another
by bond rotations about the single bonds.
staggered conformation: dihedral angle between the bonds at each end of the C-C
bonds is 180°, atoms or groups bonded to carbons as far apart as possible
eclipsed conformation: atoms bonded to carbons at each end of a C-C bond are directly
opposed to each other. dihedral angel is 0°.
staggered conformation of ethane

eclipsed conformation of ethane

6
 Potential energy diagram of ethane

E 12
(kJ mol-1)

0

o o o o o o o
0 60 120 180 240 300 360

torsional barrier: 12 KJ mol-1

torsional strain: repulsive interactions called steric hindrance between electron clouds
of bonded groups.

7
 Conformational isomers of butane
potential energy diagram of butane

anti conformation (I): no torsional strain form steric hindrance, most stable
gauche conformations (III, V): repulsive van der Waals forces, 3.8 KJ mol-1anti
eclipsed conformations (II,IV,VI): van der Waals repulsion

8
 Conformations of cyclohexane
chair conformation: no angle strain (109.5°), 99%

Potential energy diagram of cyclohexane

boat
conformation

9
boat conformation: flagpole interaction (C1C4) twist boat conformation
 Diastereomers
cis-trans isomers of alkenes: cis- and trans-1,2-dichloroethane
Their atoms have different arrangement in space
that is not interconvertible from one to another
(double bond) stereoisomers
they are not mirror images of each other 
diastereomers

cis-trans isomers of disubstituted cycloalkanes

CH3 CH3
CH3 CH3
CH3
CH3 CH3
CH3

trans-1,2-dimethyl- cis-1,2-dimethyl-
cyclohexane cyclohexane
Condensed bicycloalkenes
conformational diastereomers
H H
mirror mirror
CH3 CH3
H

CH3 H3C
H
CH3 CH3 CH3 H3C
trans-decalin cis-decalin
mp. 31 °C mp. -43 °C A enantiomers B C enantiomers D
10
conformational diastereomers
 Enantiomers and chiral molecules
Chiral molecule: not superposable on its mirror image, pair of enantiomers, enantiomeric
cheir (greek word)= hand, chirality means handedness
Achiral: molecules that are superposable on their mirror image.

stereogenic carbon: interchange of

any its two groups will produce a
stereoisomer.
A pair of enantiomers is always possible tetrahedral stereogenic carbon
for molecules that contain one tetrahedral stereogenic center
atom with four different groups attached to it.
A molecule will not be chiral, if it possesses a plane of symmetry

2-chlorobutane
chiral
2-chloropropane
achiral (gauche conformer of butane,
twist boat of cyclohexane are
also chiral) 11
 Nomenclature of enantiomers: The R, S system
Cahn-Ingold-Prelog system or International Union of Pure and Applied Chemistry (IUPAC) rules
1. Each of the four groups attached to the stereogenic centre
is assigned a priority or preference, 1, 2, 3, 4 or a, b, c, d.
The group with the lowest atomic number is given the lowest
priority 4. The group with the next higher atomic number is
given the next higher priority, 3, and so on.
2. When a priority can not be assigned on the basis of atomic
(R) (S) number of the atoms that are directly attached to the stereo-
genic carbon, then the next set of atoms is examined.
2-butanol 3. The model is rotated so that the group with lowest priority
(4) is directed away from us. Trace a path from 1 to 3.
3 If the direction is clockwise, the enantiomer is designated (R).
If the direction is counterclockwise, the enantiomer is desig-
1 4 nated (S).
2 4. Groups containing double or triple bonds are assigned
priorities as if both atoms were duplicated or triplicated
(phantom atom). vinyl > isopropyl,

3 H
-C=CH2 C CH3

CH3

1
4 12
(R) 2
 Importance of chirality

NH2 HOH2C
H
O
OH HO OH
R HO

OH
O
L-amino acid -D-glucopyranose
(S) configuration most natural carbohydrates are D sugar
peptides, proteins

O O CH3

Ph N
H

N O O

NH NH

O O O

(S)-thalidomide (Contergan) 1-methyl-5-phenyl-5-

1957-61 antiemetic for morning sickness and sedative propylbarbituric acid
side-effect: infant malformation, severe fetal limb abnormalities (R): narcotic
(S)-enantiomer is teratogenic, (R)-enantiomer is harmless (S): convulsant
recently: treatment of leprosy, anticancer
13
 Importance of chirality
O
O COOCH3
HO
Ph
OH
HOOC N
H
NH2
NH2
HO

Levodopa or L-dopa aspartam (Asp-Phe-OMe)

treatment for Parkinson's disease non-saccharide sweetener (Nutrasweet)
D-enantiomer has no effect Only the L,L-stereoisomer is sweet

O O

H H H H

(R)-(-)-carvone (S)-(-)-carvone (R)-limonene (S)-limonene

spearmint odour caraway odour orange odour turpentine-like odour
natural product natural product citrus fruit
of spearmint oil of caraway seeds 14
 1. Molecules with centre of chirality
a) Molecules with one stereogenic centre O O
C H C
H
a a H C OH HO C H
d d CH2 OH CH2 OH
c b b c O
D-(+)-glyceraldehide L-(-)-glyceraldehide C H
b) Molecules with more than one R R H C OH
stereogenic centre
HO C H

Types of Chiral Molecules

H C OH
R R
H C OH
1,2-trans-disubstituted cycloalkanes CH2 OH
2. Molecular asymmetry D-(+)-glucose
a) Axial chirality: H H H H
C C C C C C
Y X X Y NO2 NO2
COOH COOH
allenes
1,3-disubstituted allenes
NO2 NO2
COOH COOH
H H H H atropisomers
substituted biphenyls
X X X X

spiro compounds

b) Twist boat

tvistane
c) Helical chirality

M-helicity
left screw right screw (M)- (P)- 15
P-helicity M-helicity P-helicity hexahelicene hexahelicene
conformers of alkenes spirals
 Properties of stereoisomers: optical rotation

Diastereomers have different physical properties: melting points, boiling points, solubilities.
Enantiomers have the same physical properties, and the same rates of reaction with achiral
reagents, different behavior when interacting with other chiral substances or polarized light
Separate enantiomers rotates the plane of the plane-polarized light equal amounts but opposite
direction  optically active compounds, optical rotation.

H OH HO H
C C
(+)-tartaric acid (-)-tartaric acid
COOH HOOC o
o HO OH mp: 170 C
mp: 170 C H H
o
[]D = + 12
o C C []D = - 12
COOH HOOC

x z

z
ordinary light polarizator plane-polarized plane-polarized light
light left and right cicularly-
polarized light
α
x  αD 
x
cl
= rotation of the plane-polarized
sample light (degree)
z z
c= concentration of the solution (g  cm–3)
l= the length of tube (dm) 16
[]D = specific rotation
 Reacemic mixture and separation of enantiomers
There is no necessary correlation exists between the (R) and (S) designation and the direction of
rotation of plane-polarized light.
Equimolar mixture of two enantiomers is called racemic mixture or racemate.

(-) (+)

separation of enantiomers (resolution):

1) Acid-base reaction: racemic form is reacted with a single enantiomer of some other
compound, which converts the racemic mixture into a mixture of diastereomers which can
be separated by conventional means.

General acid-base reaction between a carboxylic acid and an amine:

17
Acid-base reaction between racemic lactic acid and an achiral amine (methyamine)

18
 Acid-base reaction between racemic lactic acid and an optically active amine

The resultant R,R and S,R salts are diastereomers, which have diffrent physical properties and
hence they can be separated. After seapration, the salts can be hydrolysed to afford (R) and
(S)-lactic acids. 19
2) Kinetic resolution: resolution by enzymes

O
enzyme
OH solvent OAc OH
rac-2-butanol (R)-2-butyl-acetate (S)-2-butanol

3) Separation wih High Performance Liquid Chomatography (HPLC) using optically active
stationary phase; a chromatographyic technique

20
 Molecules with more than one stereogenic centre

The total number of stereoisomers will not exceed 2n, where n is equal to the number of tetra-
hedral stereogenic centres.

21
 Meso compounds

Meso compounds: achiral even though they contains tetrahedral carbon atoms with four different
substituents. superposable on its mirror image (plane of symmetry)

(2S,3R) (2R,3S) (2R,3R) (2S,3S)

meso

22
 Possible isomers of tartaric acid

enantiomers
diastereomers diastereomers
H OH
HO COOH HOOC HOOC
C C H
C OH R
H S S
mirror
R C H R H
H S C
C
HO COOH HOOC OH HOOC OH

COOH COOH COOH

HO C H HO C H H C OH
H C OH HO C H HO C H
COOH COOH COOH

(2S,3S) or (-) (2R,3S) or meso (2R,3R) or (+)

mp: 168-170oC mp: 159-160oC mp: 168-170oC
 20= -12o  20= 0o  20= +12o
D D D
20
racemic or ()-tartaric acid mp: 205-206oC  D = 0o
23
Molecule with two stereogenic carbon atoms and no plane of symmetry (no meso compounds)
22 = 4  four possible isomers or two pairs of enantiomers

COOH COOH COOH COOH COOH

CHOH HO C H H C OH H C OH HO C H
CHBr H C Br Br C H H C Br Br C H
COOH COOH COOH COOH COOH

enantiomers enantiomers
diastereomers

Molecule with two stereogenic carbon atoms and a pseudo stereogenic carbon: C-2 and C-4 are
stereogenic centres, C-3 does not have four different groups in A and B. Although C-3 has two
two different groups due to the different configurations of C-2 and C-4 in C and D, they are not
optically active since C-2 and C-4 cancel each other.
A B C pseudo stereogenic D
centre
1 COOH COOH COOH COOH COOH
R S R R
2 CHOH H C OH HO C H H C OH H C OH
3 CHOH H C OH HO C H H C OH HO C H
4 CHOH HO C H H C OH H C OH H C OH
R S S S
5 COOH COOH COOH COOH COOH
24
enantiomers optically inacive isomers