Chapter 4

Introduction

• Stereochemistry

• It is the systematic study of the three dimensional shapes of molecules and properties that arise from these shapes • The three-dimensional shapes of molecules result from many forces

•

Conformations

are different shapes that a molecule may assume.

•

Conformers

are conformational isomers.

• They are in equilibrium at room temperature.

• They can’t usually be isolated because they interconvert too rapidly

• Alkanes

• have C-C single bonds formed by s sp 3 hybrid orbitals overlap of • Rotation is possible around s bonds because of their cylindrical symmetry => Many Conformers

I. Conformations

A.

Ethane

B.

Propane

C.

Butane

A.

Ethane

• Conformers interconvert rapidly and a structure is an average of conformers • Representing three dimensional conformers in two dimensions is done with standard types of drawings

• Molecular models are three dimensional objects that enable us to visualize conformers

Representing Conformations

There are two representations: • Sawhorse representation • Newman projection

Representing Conformations

•

Sawhorse representations

show molecules at an angle, showing a molecular model – C-C bonds are at an angle to the edge of the page – all C-H bonds are shown •

Newman projections

paper – show how the C-C bond would project end-on onto the Bonds to front carbon are lines going to the center – Bonds to rear carbon are lines going to the edge of the circle

Ethane’s Conformations

• The most stable conformation of ethane has all six C – H bonds away from each other (

staggered

).

• The least stable conformation has all six C –H bonds as close as possible (

eclipsed

) in a Newman projection.

Ethane’s Conformations

• The barrier to rotation between conformations is small (12 kJ/mol; 2.9 kcal/mol) • The

eclipsed

conformers are 12 kJ/mol higher in energy than the

staggered

conformers – energy due to

torsional strain

Ethane’s Conformations

• The

torsional strain

(12 kJ/mol) of the

eclipsed

conformers are due to 3 H-H eclipsing interactions.

• Each H-H interaction contributes 4.0 kJ/mol

B .

Propane

• Propane (C 3 H 8 ) has torsional barrier around the carbon –carbon bonds (14 kJ/mol).

• Eclipsed conformer of propane has two ethane-type H –H interactions and an interaction between C – H and C –C bond

• The

torsional strain

(14 kJ/mol) of the

eclipsed

conformers are due to 2 ethane-type H-H interactions and an interaction between C –H and C–C bond.

• The C–H and C–C bond interaction contributes 6.0 kJ/mol (= 14 – (2 x 4.0))

Practice Problem

: Make a graph of potential energy versus angle of bond rotation for propane, and assign values to the energy maxima

Practice Problem

: Draw Newman projections of the most stable and least stable conformations of bromoethane

C .

Butane

• As the alkane becomes larger, the conformations become more complex.

• Butane has eclipsed and staggered conformers with different energy level around C2-C3:

Butane’s Conformations

•

anti conformation

is the most stable conformation of butane • It has two methyl groups 180° away from each other

Butane’s Conformations

• Rotation around the C2–C3 gives

eclipsed

conformation

Butane’s Conformations

•

gauche conformation

is the staggered conformation with methyl groups 60 ° apart.

• Although it has no eclipsing interactions, it is 3.8 kJ/mol higher in energy than the anti conformation.

• This is due to steric strain .

Butane’s Conformations

• The steric strain conformation (3.8 kJ/mol) of the gauche is due to the repulsive interaction that occurs when atoms are forced together than their atomic radii allow.

Butane’s Conformations

• The least stable

eclipsed

conformation is one in which the methyl groups are too close.

• 19 kJ/mol is due to steric and torsional strain.

For any alkane, the most favorable conformation is: the staggered arrangement on C-C bonds and large substituents arranged anti to one another.

One particular conformer is more stable than another means a large percentage of molecules will be found a in more stable conformation than in a less stable one.

Practice Problem

: Consider 2-methylpropane (isobutane). Sighting along the C2-C1 bond: a. Draw a Newman projection of the most stable conformation b. Draw a Newman projection of the least stable conformation c. Make a graph of energy versus angle of rotation around the C2-C1 bond d. Since a hydrogen-hydrogen eclipsing interaction costs 4.0 kJ/mol and a hydrogen-methyl eclipsing interaction costs 6.0 kJ/mol, assign relative values to the maxima and minima in your graph

Practice Problem

: Sight along the C2-C3 bond of 2,3-dimethyl -butane, and draw a Newman projection of the most stable conformation.

Practice Problem

: Draw a Newman projection along the C2-C3 bond of the following conformation of 2,3 dimethylbutane, and calculate a total strain energy

II. Stability of Cycloalkanes

A.

The Baeyer Strain Theory

B.

Heat of Combustion

C.

The Nature of Ring Strain

D.

Cyclopropane: An Orbital View

A.

The Baeyer Strain Theory

•

Baeyer

(1885): since carbon prefers to have bond angles of approximately 109 ° , ring sizes other than five and six may be too exist.

strained

to

•

Angle strain

is the strain introduced in a molecule when a bond angle deviates from the ideal tetrahedral value, 109 °.

• Rings from 3 to 30 C’s do exist, despite Baeyer’s theory.

B.

Heat of Combustion

•

Heat of Combustion (

D

H)

– is the amount of heat released when the compound burns completely with O 2 .

• The more strain energy, the higher less stable the alkane the D H and the

Strain Energy and Heat of Combustion

• • The higher the n ( # CH 2 ), the higher the D H Therefore, one must compare D H/n rather than D H Strain Energy of Cycloalkane = n [ D H/n cycloalkane D H/n reference alkane ]

Baeyer’s theory is not fully correct

• Cyclopropane and cyclobutane are strained as predicted.

• Cyclopentane is more strained than predicted.

• Cyclohexane is strain-free.

Practice Problem

: Figure 4.8 shows that cyclopropane is more strained than cyclohexane by 115 kJ/mol. Which has the higher heat of combustion on a per-gram basis, cyclopropane or cyclohexane?

C.

The Nature of Ring Strain

• Rings larger than 3 atoms are not flat.

• They adopt puckered three-dimensional conformations that allow bond angles to be nearly tetrahedral • Cyclic molecules can assume nonplanar conformations to minimize angle strain and torsional strain by ring puckering • Larger rings have many more possible conformations than smaller rings and are more difficult to analyze

• Cyclopropane has high torsional strain to angle strain).

(in addition • This is because C-H bonds on neighboring atoms are eclipsed .

Summary: Types of Strain

These contribute to the overall energy of a cycloalkane: •

Angle strain

– is caused by expansion or compression of bond angles away from the normal 109 o tetrahedral value •

Torsional strain

– is caused by eclipsing of bonds on neighboring atoms •

Steric strain

– is caused by repulsive interactions between nonbonded atoms in close proximity

Practice Problem

: Each H-H eclipsing interaction in ethane costs about 4.0 kJ/mol. How many such interactions are present interactions are present in cyclopropane? What fraction of the overall 115 kJ/mol (27.5 kcal/mol) strain energy of cyclopropane is due to torsional strain?

Practice Problem

:

cis

-1,2-Dimethylcyclopropane has a larger heat of combustion than

trans

-1,2 dimethylcyclopropane. How can you account for this difference? Which of the two compounds is more stable?

D .

Cyclopropane: An Orbital View

• Cyclopropane was first prepared by reaction of Na with 1,3-dibromopropane:

Cyclopropane

• 3-membered ring must have planar structure • It is symmetrical with C –C–C bond angles of 60° • All C-H bonds are eclipsed

Bent Bonds of Cyclopropane

• Cyclopropane requires that sp 3 based bonds are bent • The orbitals cannot point directly toward each other; they overlap at a slight angle • Cyclopropane bonds are weaker and more reactive

Bent Bonds of Cyclopropane

• Structural analysis of cyclopropane shows that electron density of C-C bond is displaced outward from internuclear axis

III. Conformations of Cycloalkanes

A.

Cyclobutane

B.

Cyclopentane

A.

Cyclobutane

• Cyclobutane has less angle strain than cyclopropane but because of its larger number of ring hydrogens more torsional strain Cyclopropane (115 kJ/mol strain) Cyclobutane (110.4 kJ/mol strain)

Cyclobutane

• Cyclobutane is slightly bent out of plane carbon atom is about 25 ° above - one  The bend

increases

torsional strain angle strain but

decreases

B.

Cyclopentane

• Planar cyclopentane would have no angle strain but very high torsional strain • Actual conformations of cyclopentane are nonplanar ,

reducing

torsional strain • This

increases

angle strain.

Cyclopentane

• Four carbon atoms are in a plane  The fifth carbon atom is above or below the plane – looks like an envelope  Most of the H’s are nearly staggered  This

increases

strain angle strain but

decreases

torsional

Practice Problem

: How many H-H eclipsing interactions would be present if cyclopentane were planar? Assuming an energy cost of 4.0 kJ/mol or each eclipsing interaction, how much torsional strain would planar cyclopentane have? How much of this strain is relieved by puckering if the measured total strain of cyclopentane is 26.0 kJ/mol?

Practice Problem

: Two conformations

cis

-1,3-Dimethylcyclobu -tane are shown. What is the difference between them, and which do you think is likely to be more stable?

IV. Conformations of Cyclohexanes

A.

Overview

B.

Axial and Equatorial Bonds in Cyclohexane

C.

Conformational Mobility of Cyclohexane

IV. Conformations of Cyclohexanes

D.

Monosubstituted Cyclohexanes

E.

Disubstituted Cyclohexanes

F.

Boat Cyclohexane

A.

Cyclohexane: Overview

• Substituted cyclohexanes occur widely in nature • The cyclohexane ring is free of angle strain and torsional strain

Cyclohexane

Cyclohexane has a

chair conformation:

 The conformation has alternating atoms in a common plane and tetrahedral angles (109 o ) between all carbons  All neighboring C-H bonds are staggered  The ring is strain-free , with neither angle strain nor torsional strain

How to Draw Cyclohexane

B.

Axial and Equatorial Bonds in Cyclohexane

• The chair conformation has two kinds of positions for substituents on the ring: • •

axial

positions and

equatorial

positions

Chair Cyclohexane

• Chair cyclohexane has six perpendicular to the ring (parallel to the ring axis) and six

equatorial axial

hydrogens hydrogens near the plane of the ring

Axial and Equatorial Positions

• Each carbon atom in cyclohexane has one axial one equatorial hydrogen and • Each face of the ring has three axial equatorial and three hydrogens in an alternating arrangement

Drawing the Axial and Equatorial Hydrogens

C .

Conformational Mobility of Cyclohexane

•

Conformational mobility

: Chair conformations readily interconvert, resulting in the exchange of axial and equatorial positions by a

ring-flip

Ring-flip

• A chair cyclohexane can be ring-flipped by keeping the middle four carbon atoms in place while folding the two ends in opposite directions. • An axial substituent in one chair form becomes equatorial substituent an in the ring-flipped chair form, and vice-versa.

Bromocyclohexane

• When bromocyclohexane ring flips, the bromine’s position goes from equatorial to axial and so on • At room temperature the ring-flip is very fast and the structure is seen as the weighted average

Practice Problem

: Draw two different chair conformations of cyclohexanol (hydroxycyclohexane), showing all hydrogen atoms. Identify each position as axial or equatorial.

Practice Problem

: Draw two different chair conformations of

trans

-1,4-dimethylcyclohexane, and label all positions as axial or equatorial.

Practice Problem

: Identify each of the colored positions – red, blue, and green – as axial or equatorial. Then carry out a ring-flip, and show the new positions occupied by each color.

D .

Monosubstituted Cyclohexanes

• The two conformers of a monosubstituted cyclohexane are not equal in energy • A substituent is always equatorial more stable in an position than in axial position

• The equatorial conformer of methyl cyclohexane is more stable than the axial by 7.6 kJ/mol.

Energy and Equilibrium

The relative amounts of the two conformers depend on their difference in energy D

E =



RT ln K

•

R

is the gas constant [8.315 J/(K•mol)] •

T

is the Kelvin temperature •

K

is the equilibrium constant between isomers

1,3-diaxial interactions

• Difference between axial and equatorial conformers is due to steric strain caused by

1,3-diaxial interactions

• Hydrogen atoms of the axial methyl group on C1 are too close to the axial hydrogens three carbons away on C3 and C5, resulting in 7.6 kJ/mol of steric strain

Relationship to Gauche Butane Interactions

• Gauche butane is less stable than anti butane by 3.8 kJ/mol because of steric interference between hydrogen atoms on the two methyl groups • The four-carbon fragment of axial methylcyclohexane and gauche butane have the same steric interaction (2 x 3.8 kJ/mol)

In general, equatorial positions give more stable isomer

The exact amount of 1,3-diaxial steric strain in a specific compound depends on the nature and size of the substituent.

Double the value to arrive at the amount of strain in a monosubstiuted cyclohexane

Practice Problem

: How can you account for the fact (Table 4.2) that an axial

tert

-butyl substituent has much larger 1,3-diaxial interactions than isopropyl, but isopropyl is fairly similar to ethyl and methyl? Use molecular models to help with your answer.

Practice Problem

: Why do you suppose an axial cyano substituent causes practically no 1,3-diaxial steric strain (0.4 kJ/mol). Use molecular models to help with your answer.

Practice Problem

: Look at Figure 4.18 and estimate the percentages of axial and equatorial conformers present at equilibrium in bromocyclohexane

E .

Disubstituted Cyclohexanes

• In disubstituted cyclohexanes the steric effects of both substituents must be taken into account in both conformations before deciding which conformation is favored.

• There are two isomers of 1,2 dimethylcyclohexane: •

cis

•

trans

Conformational Analysis of 1,2-dimethylcyclohexane

cis-1,2-Dimethylcyclohexane

• In the cis isomer, both methyl groups are on the same face of the ring, and compound can exist in two chair conformations • Consider the sum of all interactions • In cis-1,2, both conformations are equal in energy

trans-1,2-Dimethylcyclohexane

• • • • Methyl groups are on opposite faces of the ring One trans conformation diaxial interactions has both methyl groups equatorial and only a gauche butane interaction between methyls (3.8 kJ/mol) and no 1,3 The ring-flipped conformation both methyl groups axial with four 1,3-diaxial interactions has • Steric strain of 4 conformation  3.8 kJ/mol = 15.2 kJ/mol makes the diaxial conformation 11.4 kJ/mol less favorable than the diequatorial

trans

-1,2-dimethylcyclohexane will exist almost exclusively (>99%) in the diequatorial conformation

Conformational Analysis of 1-Bromo-4-t-butylcyclohexane

• The large amount of steric strain caused by an axial

tert

-butyl group holds the cyclohexane ring in a single conformation. • This allows chemists to study chemical reactivity of immobile cyclohexane rings.

Axial and Equatorial Relationships among substituents

Practice Problem

: Draw the most stable chair conformation of the following molecules, and estimate the amount strain in each: a.

trans

-1-Chloro-3-methylcyclohexane b.

cis

-1-Ethyl-2-methylcyclohexane c.

cis

-1-Bromo-4-ethylcyclohexane d.

cis

-1-tert-Butyl-4-ethylcyclohexane

Practice Problem

: Name the following compound, identify each substituent as axial or equatorial, and tell whether the conformation shown is the more stable or less stable chair form (yellow-green = Cl)

F .

Boat Cyclohexane

• Cyclohexane can also be in a

boat conformation

– It is also free of angle strain – It is less stable than chair cyclohexane due to steric and torsional strain – ~29 kJ/mol (7.0 kcal/mol) less stable than chair

• C-2, 3, 5, 6 are in a plane • H on C-1 and C-4 approach each other closely enough to produce considerable steric strain • Four eclipsed H-pairs on C- 2, 3, 5, 6 produce torsional strain

• Boat cyclohexane is ~29 kJ/mol less stable than chair cyclohexane. • This value is reduced to about 23 kJ/mol by twisting slightly, thereby relieving some torsional strain: Twist boat conformation

Practice Problem

:

trans

-1,3-Di-

tert

-butylcyclohexane is one of the few molecules that exists largely in a twist-boat conformation. Draw both a chair conformation and the likely twist-boat conformation, and then explain why the twist boat form is favored.

V. Conformations of Polycyclic Molecules

A.

Overview

A.

Overview

• Decalin consists of two cyclohexane rings joined to share two carbon atoms (the

bridgehead

carbons , C1 and C6) and a common bond

Decalin has two isomeric forms:

cis

fused or

trans

fused

• In

cis

-decalin hydrogen atoms at the bridgehead carbons are on the same face of the rings • In

trans

-decalin , the bridgehead hydrogens are on opposite faces • Both compounds can be represented using chair cyclohexane conformations • Flips and rotations do not interconvert cis and trans

• Polycyclic compounds are common, and many valuable substances have fused-ring structures.

• Like decalin, norborane is a bicycloalkane.

• It has a conformationally locked boat cyclohexane ring in which carbons 1 and 4 are joined by an additional CH 2 group.

• Substituted norboranes, such as camphor, are found widely in nature.

Practice Problem

: Which isomer is more stable,

cis

-decalin or

trans

-decalin? Explain.

Chapter 4