1

Lecture 5

(2) Geometrical isomerism

Geometrical isomerism which results from restricted rotation about double

bond or cycle e.g. 2-butene CH3CH=CHCH3 exists in two geometrical

isomers, cis-form (when the two methyl groups are on the same side) and

trans- form (when the two methyl groups are on opposite sides)

cis-2-butene trans-2-butene

Fumaric acid

COOH

Maleic acid

COOH

COOHCOOH

Fumaric acid

COOH

Maleic acid

COOH

COOHCOOH

The restricted rotation about the double bond makes it possible to isolate the

two geometrical (cis- , trans-) isomers.

Geometrical isomerism cannot exist if either carbon atoms carry identical

groups. Thus:

a a a a

dc cd

2

Geometrical isomers are diastereomers and thus possess different physical

properties.

The E-Z system of labeling alkene diastereomers:

It is difficult to use the cis-trans system for trisubstituted or

tetrasubstituted alkenes. E.g. how would we distinguish?

E Z

and

Cl

Br

CH3

H

Br

Cl

CH3

H

E Z

and

Cl

Br

CH3

H

Br

Cl

CH3

H

For such compounds the E-Z system is used: the two groups attached to each

carbon of the double bond are arranged in the order of their priorities

according to sequence rules explained before. We then take the group of

higher priority on one carbon and compare with the group of higher priority

on the other carbon. If the two groups of higher priority are on the same side

of the double bond the alkene is labeled Z (German: Zusammen = together).

If the two groups of the higher priority are on opposite sides of the double

bond, the alkene is designated E (German: Entgegen = opposite).

OH

Vitamine A

E

E,E-heptadieneE,Z-heptadiene

ZE

E

3

Geometrical isomerism in cyclic compounds:

Rings having at least two substituents at different carbon atoms give

rise to geometrical isomers. The “rigid” ring plays the same role as double

bond in alkenes: the substituents may be arranged on the same side of the

ring or on opposite sides of it.

Illustrations are:

CH3

H

CH3

H

H

CH3

CH3

H

CH3

H

CH3

H

CH3

H

H

CH3

HO2CCO2H

CO2H

CO2H

Cis

Trans

4

(3)CONFORMATIONS (ROTATIONAL

ISOMERS)

They are different forms of spatial arrangement of atoms in a molecule of a

given constitution and configuration as a result of either rotation around

single bonds or flipping or inversion of cyclohexane without affecting the

constitution or the configuration of this compound. These forms (of the same

molecule) are called conformations (or rotomers or conformer s). For

example, the molecule of ethane

(CH3-CH3) show free rotation around single bond and the Newman

projection for its conformations (eclipsed and staggered) are outlined as

such:

H H

H

H

HH

H H

H

HH

H

60°

Staggered Eclipsed

These Newman projections are obtained by viewing the molecule along the

bonding line of the two carbon atoms with the carbon atom nearer to the eye

being designated by equal space radii and the carbon atom further from the

eye by a circle with three equal space radial extensions. The rotation around

the C-C bond will change the dihedral angle (Ǿ)

Y

X

Y

X

5

In the staggered (anti-periplanar) conformation, the hydrogen atoms of

ethane are as far apart as possible (with dihedral angle Ǿ = 60° or 180°), while in the eclipsed (syn-periplanar) conformation, the hydrogens are as

close together as possible (with dihedral angle Ǿ= 0°).

The difference between eclipsed and staggered conformers is in the energy

level between them (i.e.) there is an energy barrier between them. In case of

ethane the energy barrier between its conformers is much too small to the

extent that they are readily interconvertible and hence neither can be

isolated.

However, the staggered conformation is the preferred form (i.e.) its ratio

is greater than that of the eclipsed form. It should be noted that molecules in

its normal condition will exist largely in the conformation of the lowest

energy content.

etc

fully eclipsed Gauche, skewpartially eclipsed fully staggered

(anti)

ClH

Cl

Cl

Cl

HH

Cl

HH

H

H

H

Cl

H H

HH

H

Cl

H H

Cl

Hetc

fully eclipsed Gauche, skewpartially eclipsed fully staggered

(anti)

ClH

Cl

Cl

Cl

HH

Cl

HH

H

H

H

Cl

H H

HH

H

Cl

H H

Cl

H

H

HH

H

H CH3

HH

CH3CH3CH3

H

Rotation

Eclipsed

Rotation Rotation

CH3

H H

HH

CH3

Staggeredmore stable

H

CH3H

CH3H

H

partial eclipsedLess stablehigh energy

Q: Draw all conformations of butane? rotation around single bond

60 60 60

Gauche (skew)

A B C D

6

In case of ethylene glycol or ethylene chlorhydrin, the most stable conformer

is the gauche (Ǿ= 60°), due to the high stabilization induced by intramolecular hydrogen bond.

O

H

H- Bond O H- Bond

HH

OH

H

Cl

H

H

H H

H

HO

H

H- Bond O H- Bond

HH

OH

H

Cl

H

H

H H

H

H

7

Lecture 6

Cyclohexane

All C-C-C bond angles in the hypothetical planer form of cyclohexane

are 120° a value considerably larger than the tetrahedral angle of 109.5°. So

cyclohexane can be twisted into a number of nonplanar, or puckered,

conformations; (The chair and boat). The most stable of which is the chair

conformation in which all C-C-C bond singles are 109.5°, and C-H bonds on

adjacent carbons are staggered (gauche) with respect to one another. The

boat conformation is considerably less stable than the chair conformation

because of two factors;

1- Four sets of eclipsed hydrogen interaction along C-C bonds labeled

2-3 and 5-6

2- One set of “flagpole” interactions between hydrogens on carbon 1

and carbon 4.

The difference in potential energy between chair and boat conformations

is approximately 7 Kcal/mole that is, the interconversion of chair and

boat conformations by twisting or flipping about a C-C bonds need high

energy. This large difference in the potential energy between chair and

boat conformations means that at room temperature, chair conformation

make up more than 99.99% of the equilibrium mixture. For cyclohexane,

the two

equivalent chair

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conformations can be interconvert by twisting (flipping) first to a boat

and then to the other chair

aa

aa

ae

a

e

a

a

e

a

e

ea

ee

ee

ea

e

ae

chairChair

1

234

5 6

aa

aa

ae

a

e

a

a

e

a

e

ea

ee

ee

ea

e

ae

chairChair

1

234

5 6

Equatorial and axial bonds of cyclohexane:

When we look more closely at all the atoms constituting cyclohexane, we

see that the 12 hydrogen atoms do not occupy equivalent positions. In chair

conformation six hydrogen atoms are perpendicular to the molecular plane

and parallel to each other are called Axial bonds (a) and the other six

hydrogen atoms extend outward from the ring are called Equatorial bonds

(e). Each carbon atom of the cyclohexane ring posses’ one axial bond and

one equatorial bond directed toward opposite sides of the molecular plane.

That is, there are three axial bonds and three equatorial bonds in each side of

the ring.

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1, 3-Diaxial interactions in cyclohexane:

The chair conformation of cyclohexane is very stable, but it suffer from

little steric-repulsion (or opposition interactions) induced by the atoms or

groups present in the axial bonds in each side. This numbering do not refer

to the relationship between any two axial bonds in each side of the ring

which have the 1, 3-position i.e. 1,3 & 3,5& 5,1& 2,4& 4,6& and 6,2. That

is, groups or atoms occupy axial bonds will be suffered from

1,3- diaxial interaction. However, groups or atoms which occupy

equatorial bonds have not any interactions (since they are oriented outside

the ring which means that they are very far from any steric repulsion).

Indeed, when one chair is converted to the other ( by flipping or twisting the

ring), a change occurs in the relative orientations in space of the hydrogen

atoms attached to each carbon. A hydrogen atom Axial in one chair becomes

in the other vice versa. In non substituted cyclohexane, where the two chairs

are readily interconvertible and so they are equal energy; and each hydrogen

will be axial half of the time and equatorial the other half of the time.

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As mentioned above, the boat form of cyclohexane has very low population

(0.01%) in its equilibrium with the other two chair conformations. This

means that it has no existence but it may be a transient of flipping process.

a

a

aa

a

a

e

e

ee

e

e

a axial suffer from 1,3- diaxialinteraction that will decrease stability

if bulky groups

e equatorial with no relation between them

11

Conformations of Monosubstituted Cyclohexane:

When a substituent group replaces one hydrogen atom of

cyclohexane, the difference between equatorial and axial positions can

become significant. For example, the methyl group of methylcyclohexane

rapidly interconvert between the equatorial and axial positions but is

energetically more favorable in equatorial position.

Measurements show that, at equilibrium the methyl group is 95 %

equatorial conformation

and 5 % axial conformation

It is clear that the t-butyl group [C(CH3)3], because of its large size, is

far more stable in the e-than in the a-position. Thus almost only the e-form is

present and consequently this position is “locked” alternatively, the t-butyl

group is referred to as an “anchor”, or anchoring group and the molecule is

said to be conformotionally “Biased”.

12

CH3

CH3

Less than 0.01%

CH3

Greater than 99.99%

CCH3

CCH3

H3C

CH3

CH3

axialless stable

equatorialmore stable

95%