1.

What are conformations of organic

molecules?
2. What factors cause molecules to have
different conformations?
3. Learn what conformational analysis is
and what information it provides about
the energy of molecules.
Rotation about Carbon-Carbon bonds
• σ bonds are cylindrically symmetrical, rotation on a C-C single
bond can occur without changing the amount of orbital overlap.
• The different spatial arrangement of the atoms that result from
rotation on a single (σ) bond are called conformations.
• A specific conformation is called a conformer.

• There is generally free rotation around carbon-carbon single

bonds. (it can have infinite number of conformations by free C-
C single bond torsional strains rotation but this rotation is limit
by the repulsive interaction - between the electron clouds of C-
H bonds)
Rotation about Carbon-Carbon bonds
the distribution of electrons in a sigma molecular orbital is symmetrical around
the internuclear axis of the C-C bond. Thus, it permits the possibility of free
rotation about the C-C single bond.
 Three different ways to draw
• Perspective formula –
(1) solid lines are used for bonds that lie in the plane of the paper.
(2) Bold lines are used for bonds that are protruding out of the paper.
(3) Dashed lines are used for bonds are extending behind the plane of the
drawing surface

• Sawhorse projection – carbon-carbon bond from an oblique

angle.
• Newman projection – looking down the length of a particular
carbon-carbon bond. H H

H H
H H H
H oblique H
C C H H
H
H H
H H
H H
• There are two conformations of ethane, two extreme
conformations can result – a staggered conformation
and an eclipsed conformation.
• Dihedral (torsion) angle: angle between an atom (group) on the front atom of a
Newman Projection and an atom (group) on the back atom.
• Dihedral angles of ethane:
Staggered conformation: 60⁰ (gauche), 180⁰ (anti), and 300⁰ (-60⁰, gauche)
Eclipsed conformation: 0⁰, 120⁰, and 240⁰ (-120⁰)
 • The electrons in a C-H bond will repel the electrons in another C-
H bond if the bonds get to close to each other.
• The staggered conformation is the most stable conformation of
ethane because the C-H bonds are as far away from each other
as possible.
Energy vs. dihedral angle for ethane

The barrier (Eact) for 120⁰ rotation of ethane (from one staggered conformer to another) is 12 KJ/mol
The eclipsed conformer is the barrier to the rotation.
An H-H eclipsing interaction = 4 KJ/mol
 • Propane has two C-C single bonds and the molecule can rotate
about each of them.
The C-2 – C-3 bond

The C-1 – C-2 bond

• The barrier to C-C rotation for propane is

13 KJ/mol = 1 (CH3-H) + 2 (H-H) eclipsing
interactions
• A CH3-H eclipsing interaction is 5 KJ/mol
• Butane has three C-C single bonds and the molecule can rotate
about each of them.
H
The C-2 – C-3 bond H H

H CH2CH3
The C-1 – C-2 bond The C-3 – C-4 bond
H
• Butane has two different staggered and an eclipsed
conformations
• Steric Strain: repulsive interaction that occurs when two
atoms/groups are closer than their atomic radii

Put on Strain or
Extra ENERGY

• Eclipsed conformations of Butane: rotational barrier of

butane is 25 KJ/mol. A CH3-CH3 eclipsing interaction is 17
KJ/mol.
https://www.youtube.com
/watch?v=dTst62XXJ8g
 STAGGERED CONFORMATION: Anti relationship
• Two bonds are anti when the angle between them is 180°
(substituent opposite each other).
• Most stable of the staggered conformers (C)
Ethane
H H

H H
H H
180° H H
H H
H H
 STAGGERED CONFORMATION: Gauche relationships
• Two bonds are gauche when the angle between them is 60°
(substituent are adjacent each other).
• The 2 gauge conformers (A and E) have the same energy, but
each is less stable than the anti conformer.
Ethane
H 60° H

H H
H H
H H
H H
H H
 ECLIPSED CONFORMATION
• Two bonds/groups are positioned at the same direction; the
angle is 0°.
• There are three types of conformers – B, D, F
• It is the least stable if the bulky groups are on the same sides.
Ethane
HH H

H HH
H
H HH
H
H
• Anti and gauche conformers do not have the same energy
because of steric strain.
• Steric strain is the strain (or extra energy) put on a molecule
when atoms/groups are too close to another, which result in
repulsion between electron clouds of these atoms/groups.

F F

B D

Butane
~ SUMMARY
• The most stable confirmation of unbranched alkanes has anti
relationships between carbons (extended carbon chain)
~ SUMMARY
• Angle Strain: strain due to deforming (changing) a bond
angle from its ideal value (Baeyer Strain Theory)

Reduced overlap of orbital when

bond angle deformed
• Cyclic compounds twist and bend in order to attain a
structure to minimizes the three different kinds of strain
that can be destabilize a cyclic compound:
1. Angle strain – induced in a molecule when the bond
angles are different from the ideal tetrahedral bond
angle of 109.5° .
2. Torsion strain – cause by repulsion between the
bonding electrons of one substituent and the
bonding electrons of a nearby substituent.
3. Steric strain – caused by atoms or groups of atoms
approaching each other too closely.
 • Compound with 5 and 6-membered rings were more stable than 3 and 4-
membered rings – due to angle strain (in cycloalkane).
• Angle strain results when bond angles deviate from the ideal 109.5° bond
angle.
Small Rings: Cyclopropane & Cyclobutane
• Bonding in Cyclopropane: reduced overlap of the sp3-hybridized
orbitals

• Bonding in Cyclobutane: reduced angle and torsion strain relative to

cyclopropane
Cyclopentane
• Planar conformation is strain free according to Baeyer;
however there is considerable torsional strain (10 H-H
eclipsing interactions)
• Envelope and half-chair conformations relieve/reduce
much of the torsional strain
• Six-membered rings – most commonly found.
• Two types of conformations of cyclohexane:
1. Boat – less stable because some of the bonds are eclipsed, giving it a
torsional strain.
2. Chair – most stable because it is free of strain.
• The chair conformation of cyclohexane is free of strain.
• All bond angles are 111° (minimal angle strain), which is
very close to the ideal bond angle of 109.5° and all the
adjacent bond (H-H interactions) are staggered.
• Cyclohexane also can exist in a boat conformation.
• Not stable – some of the bond are eclipsed, giving it torsional
strain.
• Cyclohexane rapidly interconverts between two stable
chair conformations because of the ease of rotation about
its C-C bonds – called as ring flip.
• Methylcyclohexane has two not equivalent chair conformers.
• The methyl substituent that are equatorial in one chair conformer
and one are axial in the other.

Less Steric Hindrance

• Axial position – C-1 carbon is gauche to the C-3 and C-5
• Interacting substituent are on 1,3-position, this unfavorable
steric interaction are called 1,3-diaxial interaction.
• The larger the substituent on a cyclohexane ring, the more the
equatorial substituted conformer will be favored
Keq = [equatorial conformer] / [axial conformer]
• Example: 1,4-dimethylcyclohexane 1
4
• Two types: cis isomer and trans isomer
H H
1 4
ring-flip
H CH 3 H 3C H
4 1

CH 3 cis-1,4-dimethylcyclohexane CH 3

Equatorial H CH 3
1 4
ring-flip H H
H 3C CH 3
4 1
More stable Less stable
H CH 3
trans-1,4-dim ethylcyclohexane
• Example: 1,3-dimethylcyclohexane
• Cis-isomer is more stable.

(More stable) Cis-1,3-dimethylcyclohexane

Trans-1,3-dimethylcyclohexane
• Example: 1-tert-Butyl-3-Methylcyclohexane
• If a trans-isomer is given, the more stable conformer is where the
larger group is on the equatorial position.
 Stereochemistry is the study of how the
geometry affects the properties of molecules
and how they react.
&

The study of the spatial arrangements of atoms

in molecules and complexes.
• Isomers - nonidentical compounds/different molecules
having the same molecular formula

(Structural isomers) (Spatial isomers)

• Constitutional isomers – have the same molecular
formula but connected differently (different in
structural arrangement).
• Example: C2H6O - ethanol and dimethyl ether.
• Stereoisomers – differ in the way their atoms are
arranged in space.
• Two kind of stereoisomers , cis – trans isomers and
isomers that contain chirality center.
 CONSTITUTIONAL ISOMERS
• They have the same molecular formula but their
atoms are linked differently.
 Diastereomers

• Result from restricted rotation caused by a double bond

or by a cyclic structure.
• Cis isomer – substituent in the same side of double bond.
• Trans isomer – substituent in opposite sides of double
bond
Stereochemical Notations
 CH3(CH2)6CH2 CH2(CH2)6CO2H
C C
H H
• cis and trans are useful when substituents are identical
or analogous (oleic acid has a cis double bond)
• cis and trans are ambiguous when analogies are not
obvious
• If one of the C atom is attached to two methyl groups,
the alkene do not have any isomers.
• If there are two different groups on one or both carbons,
the cis-trans nomenclature cannot be used.
• Example: 1-bromo-2-chloropropene

What is needed:
1. A systematic body of rules for ranking substituents
2. A new set of stereochemical symbols other than cis
and trans
• Look at the substituents on both carbon atoms in C=C
bond and categorize them into low and high priority.

• E isomer: higher ranked substituents on opposite sides

• Z isomer: higher ranked substituents on same side
Rule 1: Consider the atomic number of the atoms bonded
directly to a specific sp2 carbon.
Rule 2: If there is a tie, consider the atoms attached to the tie.
Higher priority is for atoms that have a higher
molecular weight.
Rule 3: Multiple bonds are treated as attachment of
multiple single bonds.
A C=C double bond is considered as two C-C bonds,
so a higher priority will be given to atoms with
multiple bonds.
Rule 4: Rank the priorities by mass number in isotopes.
Isotopes with higher mass number have a higher
priority.
• Chiral compounds have
nonsuperimposable mirror images
(image is not the same as itself).
• Achiral compounds have
superimposable mirror images

 The isomers should have

one asymmetric carbon.
• Asymmetric carbon is a carbon atom that is bonded to four
different groups.
• Example: 4-octanol – bonded to H, OH, CH2CH2CH3 and
CH2CH2CH2CH3.
• An asymmetric carbon is also known as a chirality center.
• Atom other than carbon, such as N and
P also can be chirality centers.
 Chemist draw enantiomers using either perspective formulas
or Fischer projections

When a molecule is
represented with Fischer
projection formula,
Erythro isomer is the
one which has two like
(or similar) groups on the
same side and Threo is
one in which two like (or
similar) groups are on the
opposite side.
• A stereocenter (stereogenic center) is an atom at which
the interchange of two groups produces a stereoisomer.
• Therefore, both asymmetric carbons produces an
enantiomer and convert a cis isomer to trans isomers are
stereocenters.
• A compound with more than one chiral carbons/
asymmetric carbons have a maximum of 2n stereoisomers.
EXAMPLE: 3-chloro-2-butanol have two stereocenters.
• Hence, there are 4 stereoisomers or two pairs of
enantiomers.

• 1 & 2 and 3 & 4 are enantiomers.

• 1 & 3 and 2 & 4 are diastereoisomers.  (perhaps Cis-,Trans
or E-,Z-…)
 Non Enantiomer

Different Structural Different

Arrangement Arrangement in Space

Diastereomers

Diastereomers
• One pair of enantiomer has 2 stereoisomers, we
need to name them.
Rules R,S system of nomenclature
• Rank the groups (atoms) bonded to the chirality center
Rules R,S system of nomenclature
• Orient the lowest priority (no. 4) away.
 Clockwise = R configuration
 Counterclockwise = S configuration

• The notation is determined

from the Perspective Formulas
or Fischer Projections.
Rules R,S system of nomenclature
• The four substituents around the chiral carbon must be
first ranked in order of decreasing order
 a highest priority
 b second-highest priority
 c third-highest priority
 d lowest priority

• When the molecule is positioned with the lowest-

priority substituent away from the viewer, the
remaining three substituents will be arranged in either
a clockwise or counterclockwise directions.
1. Rank the groups bonded to the asymmetric carbon
1

2
3
2. If the group (or atom) with the lowest priority is bonded by
hatched wedge, draw an arrow from the group with the
highest priority to second highest priority.

(S)-2-bromobutane
3. If necessary, rotate the molecule so that the lowest
priority group (or atom) is bonded by a hatched wedge

4. You can draw group 1 to group 2, passing group 4, but never 3

5. Flip entire molecule 180 degrees
1. Rank the groups (or atom) that are bonded to the asymmetric
carbon and draw an arrow with the highest priority to the lowest
priority
Cl

CH3CH2 CH2CH2CH3 (R)-3-chlorohexane

2. If the lowest priority is on a horizontal bond, the naming is

opposite to the direction of the arrow.
CH3

H OH (S)-2-butanol

CH2CH3
3. The arrow can go from group 1 to 2, passing group 4, but not
group 3
2
CO2H

H CH3 (S)-lactic acid

4 3

OH
1