Course Code: CHEM 412

Course Title: Advanced stereochemistry and reaction mechanism

Prerequisite (if any): CHEM. 222

Instructor: Dr. KINUTHIA [email protected]

Course Purpose: To enable the students understand advanced stereochemistry using frontier
orbital approach.

Expected Learning Outcomes:

At the end of the semester, the student should be able to:
1. Understand conformational analysis of cyclohexane
2. Differentiate conrotatory and equitorial and axial groups
3. Differentiate HOMO and LUMO frontier orbital approach
4. Understand conrotatory and disrotatory modes of ring closure and opening in Alkenes

Course Content: (Lessons/ Weeks)

Week Content

1 Reporting

2 Review of Stereochemistry: of saturated carbon compounds.

3 Dynamic stereochemistry: Conformational analysis of

cyclohexane: chair and boat forms. Energy profile of chair – chair
inversion.

4 Monosubstituted cyclohexane: Equitorial and axial groups,

relative stabilities.

5 Effect of conformations on reaction rates

6 CAT 1

7 Theory of concerted reactions - using frontier orbital approach

HOMO and LUMO.

8 Electrocyclic reactions: Conrotatory and disrotatory modes of

ring closure and opening using specific examples eg.

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 9 Dimerization of alkenes: allowed and disallowed reactions

10 & 11 Photochemistry. Classical and non-classical carbonium ions

12 CAT 2

14 Revision

15 Exams

Mode of Delivery: Lectures, Class discussions, Reading research

Instructional Material and/ or Equipment: Lecture notes, Whiteboard markers, Textbooks,

Flip Charts, Laptops, Projectors,LCD/Overhead Projector, Handouts

Course Assessment:

CATs: 20%

Assignments: 10%

Final Semester Exam: 70%

Reference Material: (Text Books, Journals and E-materials)

1) Wade L.G, Jr (2006). Organic Chemistry. 6th Ed. Pearson Education

2) Francis A. Carey (2000). Organic Chemistry. 4th Ed. McGraw-Hill, New York,
3) Morrison, R.T. Boyd, R. N. (2002): Organic Chemistry, 6th Ed. Prentice Hall
4) McMurray, J. (2009): Organic chemistry, Volume I, Cengage Learning, USA.
5) Loudon, G. M. (2009): Organic chemistry, Roberts and Co. 5 th Ed, Illustrated.
6) Joseph, M. H. (2005): Organic Chemistry, Cengage Learning, USA.
7) Thomas, S. N. (2006): Organic Chemistry, University Science Books, USA.
8) Solomon, T. W. G. and Craig, B. F. (2009): Organic Chemistry, John Wiley and
Sons.
9) The Journal of Organic Chemistry
10) International Journal of Chemistry

Prepared by Dr. Kinuthia Signature Date

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CHEM. 436- Advanced stereochemistry

Isomerism- different compounds with the same molecular formula.

Do the compounds have the same molecular formulae?

Not isomers
No
Yes
Isomer

Do compounds have the same conectivity?

No Yes
Constitutional Stereoisomers

Can the compounds be interconverted

by rotation about a single bonds?
No Yes

Configurational Conformational

Is the isomerism at a tetrahedral center?

No Yes
Geometric Optical

Are the compounds non-superimposable?

No
Yes
Diastereomers Enantiomers
R and S

Enantiomers
Are two stereoisomers that are related to each other by a reflection i.e. they are mirror reflection
of each other which are non-superimposable e.g. human hands. Left and right hands can’t be
made to coincide point to point, palm to palm in 3-dimensions.

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Two compounds that are enantiomers of each other have the same physical properties except for
the direction in which they rotate plane polarized light and how they interact with different
optical isomers of other compounds.

In 1894, William Thomson coined a word for this property. He defined an object as CHIRAL if
it is not superimposable or its mirror image i.e. a molecule is chiral if its two mirror image
formed are not superposable in 3-dimension.

The opposite of chiral is ACHIRAL- a molecule that is superimposable on its mirror image e.g.
ClF2CH in which two of the atoms attached to C are the same

They may be twisted and turned (so long as no bonds are broken) but they remain non-
superimposable.

They have identical physical and chemical properties except for the direction of rotation of plane
polarized light and toward optically active reagents respectively.

One isomer of an enantiomeric pair may serve as a nourishing food and the other may be useless
e.g. the sugar (+)-glucose plays a unique role in animal metabolism and is the basis of the
fermentation industry, yet (-)- glucose is not.

The experimental facts that led Van’s Hoff and Le Bel to propose that molecules having the same
constitution, could differ in the arrangement of their atoms in space concerned the physical
property of optical activity-is the ability of achiral substance to rotate the plane polarized light and
is measured using polarimeter.

Properties of enantiomers
 They have identical melting and boiling points.
 They differ when they interact with other chiral substances e.g. enantiomers will rotate
the plane polarized light in an opposite direction.
 Plane polarized light moves in waves in plane perpendicular to the light of propagation.
 When plane polarized light passes thro different enantiomers they rotate light in opposite
direction.

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Polarimeter

Scientific instrument used to measure the angle of rotation caused by passing polarized light thro
optically active substance.

E.g. sucrose + water glucose and fructose. The sample is optically active because it rotates
the plane polarized light.

Optically active
If they rotate plane polarized light, then they are optically active. Those which rotates 50%-50%
(equal quantity) are racemic mixtures/ compounds modifications. They show no rotation of plane
polarized light and are designated as being ±.

Racemic mixture is optically inactive.

Rotation of the plane of polarized light in the clockwise direction is taken as (+)/ dextrorotary
and anticlockwise as (-)-levorotatory (left in Latin).

Calculation of specific rotation

The extent of rotation depends on the compound in the tube i.e. the quantity or the number of
compounds in the molecule.

Specific rotation [∝]𝑇 depends on the wavelength that is employed.

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The polarimeter helps one to determine the optical purity e.g.

[∝]25
𝐷

D- Sodium D line

If you get +13.52o-pure S-2-Butanol

If there is some impurity e.g. a mixture of R and S-butanol, then the value will not be 13.52o.

The rotation of impurity which is pulling it has t be taken care of.

If you get +12, then you have the other enantiomer in the compound.
𝑜𝑏𝑠𝑒𝑟𝑣𝑒𝑑 [∝] +12
Therefore optical purity of S-2-Butanol = [∝]𝑜𝑓 × 100%= × 100% = 90%
𝑝𝑢𝑟𝑒 𝑒𝑛𝑎𝑛𝑡𝑖𝑜𝑚𝑒𝑟 +13.52

Therefore 90% S and 10% R

Example

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Racemic modification
Are equimolar mixtures of two enantiomers e.g. Rand S-same concentration as a mixture
50%/50%. This is designated as (±)-2-Butanol. The rotation caused by a molecule of one isomer
is exactly cancelled by an equal and opposed rotation by a molecule of its enantiomer.

Chiral molecules
A molecule that is not superimposable on its mirror molecule e.g. enantiomers.

Achiral- where the molecule is superimposable on its mirror molecule.

Chiral carbon (asymmetric carbon)

A carbon atom with four different groups attached to it. Any tetrahyde atom with four different
groups attached to it has a chiral centre or asymmetrical centre, BrClFCH e.g. 2-butanol.

Structures

Chiral molecule-not superimposable

The horizontal lines represent bonds coming toward us out of plane of the paper, whereas the
vertical lines represent bonds going away from us behind the plane. The below representation is
referred to as Fischer projection. The stereoisomer can also be represented in 3-dimensional as
follows.

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Diastereomers
They have similar chemical properties but different physical properties like melting and boiling
points, solubilities, densities etc. as a result of their differences in melting points, solubilities.
Molecular shape and polarity, they can be separated by fractional distillation or crystallization or
chromatography.

Let us take 2,3-Dichloropentane with two chiral centers for illustration of diastereomers. Chem
231 notes

Meso compounds

- are superimposable in their mirror images. They are optically inactive although they contain
two or more stereocentres.

-molecules are superimposable on their mirror images even though they contain chiral centers.

-All meso compounds are achiral (superimposable to their mirror images).

-In general, they should contain two or more identical substituted stereocentres.

-They have an internal symmetry plane that divides the compound in half. These two halves
reflect each other by the internal mirror.

-Let us look at the 2,3-Dibromobutane which has two chiral centers

Draw the Structures

We can recognize a meso structure on sight by the fact that one half of the molecule is the mirror
image of the other half.

Compounds with more than one chiral center

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 D C B A

Epimers
Are diastereomers which differ only on one C-atom where you have different configuration e.g.
sugar glucose and mannose differ only in configuration at (-)

Nomenclature
R-S system (Cahn-In gold-Prelog system)

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R-S system was revised by three people, Cahn-In gold-Prelog

The two enantiomers are designated by R-S; R-Rectus (right), S-Sinister (left)

Rules

The four atoms directly attached to the chiral carbon should be numbered according to
decreasing order of atomic number e.g.

Note

If the lowest priority atom is oriented towards you, you don’t need to turn the structure around.
You can leave it as is with the lowest toward you and apply the R/S rule backward e.g.

Keep one group fixed and rotate the other three molecules such that the group of the lowest
atomic number comes to the bottom (in our case H). if we keep Cl fixed

2.when two atoms have same atomic number and are isotopes, the isotope with greater atomic
weight gets the priority e.g. ethanol-1-di (deuterium)

Draw the Structure

3.one that if the decision priority between the two rules in two groups cannot be reached, use
next atoms in the group e.g.

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4.when there is multiple bonds e.g.

Assignment

Write all the stereoisomers of Isoleucine and tartaric acid. Name them using R-S nomenclature

Geometric isomerism
Trans-E- opposite, German (entgegen)

Cis-Z-same, German (Zusummen)

Examples. 2-butene

Differ from one another only in the way atoms are oriented in space (but are alike with respect to
which atoms are attached). They belong to the stereoisomers.

They are not mirror images of each other and hence are not enantiomers.

Note

Geometric isomers cannot exist if either carbon carries two identical groups e.g.

2-methyl-2-butene and 1-butene

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 No geometric isomerism

In cases where each doubly bonded carbon has different substituents, we arrange these
substituents on each carbon in their Cahn-Ingold-Prelog sequence.

We take the group of higher priority on each carbon and tell whether they are on the same side or
opposite sides of the molecule, we use the letter Z for the same side and E for the opposite sides.

a-(E)-1,2-Dibromoethene: b-(Z)-1,2-Dibromoethene

Conformational isomers of ethane and butane

Different arrangements of atoms that can be converted into one another by rotation about single
bonds are called conformation or are different spatial arrangements of a molecule that are
generated by rotation about single bonds.

Conformational analysis of ethane

Ethane is the simplest HC that can have distinct conformation.

Some commonly used representations of eclipsed conformation and staggered conformation.

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Different conformations of the same molecule are sometimes called conformers or rotamers.

Staggered and eclipsed forms are portrayed in various ways- sawhorse, wedge and dash and
Newman projection.

In Newman projection we sight down C-C bond and represent the front C by a point and back C
by a circle. Each C-has three substituents that are placed symmetrically around it.

The structural feature that the figures above illustrate is the spatial relationship between atoms an
adjacent C-atoms. Each H-C-C-H unit in ethane is characterized by a torsion angle or dihedral
angle, which is the angle between H-C-C plane and the C-C-H planar. This angle is easily seen in
a Newman projection of ethane as the angle between C-H bonds of adjacent C.

Eclipsed bonds are characterized by a torsion angle of 0o. When the torsion angle is approximately
60o, we say the spatial relationship is Gauche, and when it is 180 o we say it is anti. Staggered
conformation have only gauche or anti relationships between bonds on adjacent atoms.

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Staggered is more stable than the eclipsed. The measured difference in potential energy between
them is 12 Kj/mol (2.9Kcal/mol).

The destabilization that comes from the eclipsed bands an adjacent atom is called torsional strain.
The total strain of all of the spatially dependent features is often called steric strain.
There are in infinite number of conformations of ethane differing by only increments in their
torsion angles.

Three equivalent eclipsed conformations and three equivalent staggered conformations occur
during 360o rotation, eclipsed appear at the highest point on the curve (PE max) the staggered ones
at the lowest (PE minima).

The region that lies between a torsion of the angle 60 o and 180o tracks the conversion of one
staggered conformation of ethane to the next one. Both staggered conformation are equivalent and
equal in energy, but for one staggered to get to the next, it must first pass through an eclipsed
conformation and needs to gain 12 KJ/mol of energy to reach it. This is the activation
energy(Eact).

Conformational of butane
Unlike ethane in which the staggered conformations are equivalent, two different staggered
conformations occur in butane.

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The rotation is about the bound between the middle two Cs (CH 3CH2-CH2CH3). The methyl
groups are gauche to each other in one, anti in the other. Both are free of torsional strain.

Beside torsional strains there is van der Waals strains or steric hindrance due to van der Waals
(or steric) between the methyl groups.

The point of maximum potential energy lies some 25Kj/mol (6.1Kcal/mol) above the anti-
conformation.

Assignment

Sketch a potential energy diagram for rotation around a C-C bond in CH3CH2CH3. Clearly identify
each potential energy maximum and minimum with a structural formula that shows the
conformation of C3H8 at that point. Does your diagram closely resemble that of C2H6 or C4H10.

Interconversion of conformational isomers involves rotation about single bonds.

The other kind of stereoisomers differ from one another in configuration about a chiral centre e.g.
CH3CH2-CH2CH2CH2CH3.

CHYCLOALKANES

Commonly encountered in natural products, such as steroids. Cyclopentanes and cyclohexane

are the common. They are rings of carbon atoms with –CH2- units.
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PERICYCLIC REACTIONS

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