CHEM 33 (ORGANIC CHEMISTRY 1)

TRANS FOR FIRST DEPEX

Professors
Sir Edward Gabrielle V. Hilvano (Laboratory LB2A)
Sir Arvin Marasigan (Laboratory LB2B)

Course Content

TOPIC PAGES.

Nomenclature

Structure of Carbon & Resonance 1 - 14

Isomerism 15 - 58

Physical Properties of Organic Compound 59 - 61

Chemical Properties of Organic Compound 62 - 66

Isomerism
-Isomers are different compounds that have the same molecular formula but different
attachment and/or spatial arrangement of atoms.

ISOMERS

Structural or Stereoisomer
Constitutional -same connectivity but
-different connectivity different orientation in space

Chain positional functional conformational geometric optical

I. Structural or Constitutional Isomers

A. Chain Isomers
-same number of C and H but different points of attachment
-exhibited by alkanes
Ex. C4H10 : CH3CH2CH2CH3 CH3CHCH3

CH3

Butane isobutane
CH3
C5H12 : CH3CH2CH2CH2CH3 CH3CHCH2CH3 CH3 CH CH3
CH3 CH3

Pentane isopentane neopentane

B. Position Isomers
-different position of substituents or multiple bonds , same parent chain
Ex. C4H8 : CH2 CHCH2CH3 CH3CH CHCH3

1-butene 2-butene
 C3H7Br : CH3CH2CH2Br CH3CHCH3
Br

1-bromopropane 2-bromopropane

C. Functional Isomers
-different functional groups
Ex. C2H6O : CH3 O CH3 CH3CH2OH

Dimethyl ether Ethanol

C3H6O : CH3CH2CHO CH3COCH3

Propanal 2-propanone
 STEREOISOMERS

Stereoisomers are substances whose atoms have the same connectivities, but have different
arrangement in space.

I. Conformational Isomers (Rotamers or Conformers)

-​ ​compounds represented by different ​conformations

Conformations – refer to the different arrangement of atoms that can be

converted into one another by rotation about single bonds

1. Acyclic Compounds
Acyclic compounds basically exist in three conformations:
a. the ​eclipsed conformation​ where all the bonds on two adjacent atoms coincide with
each other

b. the ​staggered conformation​ where bonds on two adjacent atoms alternate

c. the ​skew conformation​ which represent an infinity or intermediate conformations

 - any conformation in between eclipsed and staggered conformation

Representations

a. Wedge-Dash Notation
- ​most commonly-used notation for straight-chain molecules in organic chemistry
- In this notation, two bonds are drawn in the plane of the page (solid line/sticks), one
bond is drawn coming towards you or out of the page (wedge), and one bond is drawn
going away from you or behind the page (dash).

b. Newman Projection Formula

- used to represent conformations which shows the view of a molecule from one end
directly along the C – C bond axis

The following conventions are used:

Bonds to the back C atom Bonds to the front C atom

Drawing Newman Projections

In this example Newman projection above, the front carbon is attached to the CH​3 on
top and two H’s while the back carbon is attached to the CH​3 on the left and two H’s.
This Newman is in gauche-staggered conformation but we will talk about that later.

Something else that is important to note is the ​dihedral angle.​

​Dihedral angle​ ​- the angle made by four atoms covalently attached to each other.

The dihedral angle is useful to define the energy of the Newman Projection, and
subsequently the stability of different conformations. Again, this will be further
discussed later.

Steps in Drawing Newman Projections (Step-by-Step):

Draw the Newman Projection of 2-butanol.

1. Try to draw the expanded structural formula/bond line structure including all the
H’s first. However, it would be easier if you keep the first and last methyl groups
condensed (write it as CH​3​).

2. Determine which two carbons are being studied. Most of the time, choosing
Carbon 2 and Carbon 3 makes it easier. Draw an eye with an arrow looking
down at the carbon-carbon bond you chose.
 3. Draw 1st carbon in the bond (in this case, carbon 2) as a dot; this represents
that it is in front.

4. Draw 2nd carbon in the bond (in this case, carbon 3) as a circle surrounding the
dot; this represents that it is behind carbon 2.

5. Draw the atoms attached to the 1st carbon.

6. Draw the atoms attached to the 2nd carbon.

Done! Take note though, that this is just one (and the most stable: anti-staggered
conformation) Newman projection of 2-butanol. Other conformations will be discussed
later.
 c. Sawhorse Projection Formula
- Carbon-Carbon bond that is compressed in a Newman Projection is fully drawn out

On the left is the the Sawhorse projections for the Newman projections on the right of
2-butanol.

d. Fischer Projection
- Used when dealing with multiple chirality centers
- This will be discussed further in the later part because it involves chirality.

Strains and their Types

Before we proceed to the different types of conformations, it is important to know about strains.

What is a Strain?
- When a molecule is less stable due to electron repulsion or when it is not in its ideal
geometry.
- An increase in molecular potential energy

a. Torsional Strain (Pitzer Strain)

When rotating a molecule, it is the repulsive interaction between bonding electron pairs
as the bonds get close to each other. This is due to electrostatic forces between
electrons in adjacent molecular orbitals.
- ​Caused by the close approach of atoms or groups separated by covalent

bonds which can create a resistance to ​bond rotation and can influence a barrier
to rotation

Sawhorse projections
 Newman projections

b. Steric Strain (van der Waals Strain)

- caused when atoms or groups separated by covalent bonds are forced closer than their
van der Waals radii allow
Anudaw? B ​ asically, steric strain can be thought as the repulsion when ​two bulky
groups become too close to each other and hence there isn’t enough space for
them.

Sawhorse projection Space filling model

This repulsion ​only exists for bulky substituents​, such as methyl or ethyl groups. So in
ethane there is no steric hindrance as the hydrogen atoms are not that bulky.

Don’t worry if you find it difficult to differentiate between steric strain and torsional
strain. Here’s a summarized table for their basic differences:

Steric strain Torsional strain

-​ ​Repulsionbetween two atoms or -​ ​Repulsion

between atoms or groups of
groups of atoms ​when the distance atoms ​when a molecule is rotated
between them is decreased around a sigma bond

-​ ​Cannot​
be lessened by rotating the -​ ​Can​ e lessened by rotating the
b
molecule around a sigma bond molecule around a sigma bond

-​ ​Occurswhen the distance between -​ ​Occurs when bond electrons pass by

bulky groups of a molecule is each other when the molecule is
decreased rotating

c. Angle Strain
 There is a third type of strain, called ​angle strain​, but this type of strain is more common
in cyclic compounds and will be discussed later.

Kinds of Conformations and Conformational Analysis

There exists a maximum of ​four (4) possible conformations based on the differences in
dihedral angles. In the following text, butane (CH​3​CH​2​CH​2​CH​3​) is used as an example to
exhibit these conformations.

Eclipsed syn Eclipsed Gauche-Stagge Anti-Staggered

(fully eclipsed) red

Newman
Projection

Dihedral Angle 0​° 120​° or 240° 60​° or 300° 180​°

Strain Present Steric strain, Torsional strain Steric strain N/A

Torsional strain

Energy 5.68 kcal/mol 3.23 kcal/mol 0.95 kcal/mol 0.00 kcal/mol

​How do we know which conformation of butane is most stable?

In terms of stability,
Anti-staggered > Gauche-staggered > Eclipsed > Eclipsed syn

All of the above conformations is the actual structure of butane. But at any given
moment, most of the molecules are in staggered conformations, the ones with lower
energy and therefore the more stable conformations. ​Generally, the most stable
conformation is the one with the lowest energy.

Therefore, butane will favor its anti-staggered conformation because it is the most stable.

This is better illustrated through the conformational analysis diagram. ​Conformational analysis
show energy changes that a molecule undergoes as groups rotate about single bonds.
Conformational Analysis of Butane

Ethane, the simplest example, has a maximum of two (2) possible conformations.

Eclipsed Staggered

Newman Projection

Dihedral Angle 0​°, 120°, 240°, 360° 60​°, 180°, 300°

Formula: Formula:
180 * (2n + 1) / 3 where n is 180 * (2n) / 3 where n is any
any integer integer

Strain Present Torsional strain N/A (very minimal torsional

strain)

Energy 2.66 kcal/mol 0.00 kcal/mol

Conformational Analysis of Ethane

Because ethane’s staggered conformation has the lowest energy, this is the most stable
conformation of ethane.

IMPORTANT!
You must now think that the anti-staggered is the most preferred conformation for
molecules. This is not always true. In ethylene ​glycol, CH​2​(OH)—CH​2​(OH), the
gauche-staggered is shown to be the preferred one. Here, bonded to 2 adjacent carbon
atoms are two polar O​δ-​—H​δ+​ groups.

The two -OH groups tend to interact through H-bonding and for maximum interaction, they
must be at optimum distance from each other, that is, neither too close so that their
electrons overlap, nor too far away so as not to be able to interact anymore. That
corresponds to the gauche-staggered conformation, which is therefore the preferred
conformation of ethylene glycol and of other similar structures.
 2. Cyclic Compounds

Generally, cycloalkanes can adapt two conformations:

a. Planar conformation
b. Non-planar conformation
It is then discovered that the planar conformation utilizes a significant amount of energy so it is
more unstable than its non-planar conformation. The non-planar conformation minimizes ​angle
strain​.

Angle Strain

- the increase in energy associated with a bond angle that has deviated from the preferred
angle
- present in most cycloalkanes

Cyclopropane

- Has the most severe angle strain because of its small bond angles (60°) compared to
the ideal 109.5°
- Also has significant torsional strain because the ring is locked in an eclipsed
conformation (eclipsing H’s) and has no possible way of achieving a staggered
conformation
 - This large amount of strain makes three-membered rings very unstable, highly reactive
and very susceptible to ring-opening reactions. Case in point, epoxides.

Cyclobutane

Bond-line structure Butterfly/puckered conformation

- Less angle strain than cyclopropane
- But more torsional strain because there are four sets of H’s eclipsing rather than just
three
- In order to alleviate this additional torsional strain, cyclobutane adopts a slightly
puckered/butterfly conformation without gaining too much angle strain.

Cyclopentane

Bond-line structure Envelope conformation

- More stable than cyclopropane and cyclobutane because it has less angle and torsional
strains
- The ideal angle of a pentagon in a regular pentagon is 107° which is very close to ideal
tetrahedral angle of 109.5°.
- However, cyclohexane can exhibit an almost stain-free conformation compared to
cyclopentane.

Conformations of Cyclohexane
As exhibited above, the chair and boat/twist boat conformations possess very little angle strain
because the bond angles are fairy close to 109.5°. The significant difference between them can
be seen when comparing torsional strain. The chair conformation has no torsional strain.

In the chair conformation, none of the H’s are eclipsed. All are staggered.
In the boat conformation, however, you have two sources of torsional strain.

Factors contributing to torsional strain in the boat conformation:

a. Eclipsing H atoms
b. Flagpole interactions - steric interactions that occur on the H’s on either side of the ring

In order to alleviate this torsional strain, cyclohexane twists itself from

its boat conformation to a twist boat conformation.

The most energy-consuming and unstable non-planar conformation of

cyclohexane is the half chair conformation. ​The half chair is a "twisted
form" of the chair conformation in which 5 of the carbon atoms are the
same plane.

Conformational Analysis of Cyclohexane

Recall that potential energy is inversely proportional to stability. Therefore, in terms of stability,

Chair > Twist boat > Boat > Half-chair > Planar

Cyclohexane will hence spend the majority of its time in a chair conformation.

Drawing Chair Conformations (Step-by-Step)

A. Drawing the Skeleton of a Chair Conformation

When you are finished drawing a chair, it should contain three sets of parallel lines. If
your chair does not contain three sets of parallel lines, then it has been drawn
incorrectly.

B. Drawing Axial and Equatorial Positions

1. Axial positions: Begin at the right side of the V and and draw a vertical line
pointing up. Then, go around the ring, drawing vertical lines, alternating in
deriction (up, down, up, etc.)

2. Equatorial positions: The equatorial positions are more difficult to draw properly
but by making use of parallel lines, we can minimize mistakes. We saw earlier
that a properly drawn chair skeleton is composed of three pairs of parallel lines:

In between each pair of red lines above, draw two equatorial groups that are
parallel to (but not directly touching) the red lines.

C. Drawing Both Chair Conformations (Ring Flip)

Monosubstituted Cyclohexane
Draw both chair conformations of bromocyclohexane.

1. Draw the chair conformation and place the substituent.

 2. Draw a ring flip and the axial group should become equatorial.

Disubstituted Cyclohexane
Draw both chair conformations of the following compound.

1. Determine the location and configuration of each substituent.

2. Place the substituents on the first chair using the information from step 1.

3. Draw the second chair configuration.

4. Place the substituents on the second chair using the information from step 3.
Stability of the Chair Conformers
Monosubstituted Cyclohexanes
Important things to remember:
- The equatorial position is favored than the axial position.
- Between the two chair conformers, for example, the two structures shown below:

The more stable compound is the one on the right where the methyl group is in the
equatorial position. This is because of a phenomenon called 1,3-diaxial interaction.

1,3-diaxial interaction
- A repulsive and steric interaction between two axial substituents on a
cyclohexane ring
- The numbers 1 and 3 represent the distance between the substituent and each of
the H’s.
Polysubstituted Cyclohexanes
Draw both chair conformations of the following compound.
The chair conformation on the left only has ethyl on the axial position so it is considered more
stable.

II. Geometric Isomers

- Differ in the arrangement of atoms in space due to certain ​geometrical restrictions​ on the
location of certain atoms
- Do not readily interconvert due to the presence of some type of structural rigidity
- Potentially exhibited by ​alkenes​ where rotation is restricted by the pi bond, and by
cycloalkanes​ whose rigidity is brought about by its closed structure

Molecules that only have single bonds do not have geometric isomers.

Cis-Trans Isomers
- Only for disubstituted alkenes and cyclohexanes

A. Alkenes

Consider 1,2-dichloroethene. It has two possible geometric isomers.

● In one, the two chlorine atoms are locked on opposite sides of the double bond. This is
known as the ​trans isomer​. (trans : from latin meaning "across" - as in transatlantic).

● In the other, the two chlorine atoms are locked on the same side of the double bond.
This is know as the ​cis isomer​. (cis : from latin meaning "on this side")

Recognizing Cis-Trans Isomers

Requirements:
1. It should have a Carbon-Carbon double bond or cycloalkane.
2. Do not have the same two groups on one end of the bond. It doesn't matter
whether the left-hand groups are the same as the right-hand ones or not.

Same compound (because you have two same groups on one end of the bond, the two
pinks)

Cis and trans isomers

3. You could have three or multiple groups but by now the words cis and trans are
meaningless. This is where the more sophisticated E-Z notation comes in.
B. Cycloalkanes

When dealing with cycloalkanes, the terms cis and trans are used to signify the relative
spatial relationship of similar substituents:

● cis​ - two groups are on the same side of the ring

● trans​ - two groups are on opposite sides of the ring

While the carbon-carbon single bonds of the rings can rotate partially, there is NO way to
inter-convert between the cis and trans isomers. Cis and trans isomers are unique
compounds with their own unique melting points, boiling points, densities, etc.

In general, if any two sp3 carbons in a ring have two different substituent groups (not
counting other ring atoms) stereoisomerism is possible.

Which is more stable between ​cis​-1,2-Dimethylcyclohexane and

trans-​ 1,2-Dimethylcyclohexane?

Answer: ​trans​-1,2-Dimethylcyclohexane
Why?
 Each stereoisomer of 1,2-dimethylcyclohexane has two conformations.
trans-1,2-dimethylcyclohexane is more stable, because it can adopt a chair conformation
in which both methyl groups are in equatorial positions.

Which is more stable between ​cis​-1,3-Dimethylcyclohexane and

trans-​ 1,3-Dimethylcyclohexane?

Answer: ​cis​-1,3-Dimethylcyclohexane
Why?

cis-1,3-dimethylcyclohexane is more stable, because it can adopt a chair conformation in

which both methyl groups are in equatorial positions.

E-Z Isomers (for double bonds)

Although the cis/trans approach can conveniently identify two isomers, it does not apply to all.
Consider the example for the two isomers of 1-bromo-1-chloropropene. Which of the halogens
is cis and which is trans to methyl?
To resolve this problem, IUPAC introduced the E-Z approach which involves prioritization of the
two groups on both ends of the double bond.

Rules for Assigning E or Z

1. The two groups at each end are prioritized separately.

2. The designation ​E (entgegen) is given to the isomer in which the two highest
priority groups are on opposite sides of the bond.
3. The designation ​Z (zussamen) is given to the isomer in which the two highest
priority groups are on the same side of the bond.

E-Z mnemonic:
Z - Zame Side (Same Side); E - Eppesite (Opposite)

Cahn-Ingold-Prelog rules for assigning group priority

1. The groups are compared atom by atom starting with the atom connected to the
site of isomerism. ​The heavier the atom attached, the higher the priority.
2. If they are of the same mass, look at the atoms attached to that previous atom.
The atom with another heavier atom is higher in priority.
3. Move on to the next atom if the tie still hasn’t been broken.
4. If the groups compared only differ in the multiple bonds they contain, the order
of priority is: ​triple bond > double bond > single bond​.

Consider the following compound:

We will now use the Cahn-Ingold-Prelog priority system.
1. Divide the molecule into two.

2. Start with the atom connected directly to the site of isomerism. Which is
heavier?

(Here, we can now eliminate H and give it the least priority because it is lighter than the
other 3 carbon atoms. We now know the group with higher priority in the right side of
the double bond.)

3. Move on to the next atom in the left side.

(Each of the C atom in the left side of the double has different atoms attached. We can
see that the one on the upper left contains an OH group while the one on the lower left
contains a Cl atom.)

4. Determine which is heavier.

O​H​ vs ​Cl
OH = 16.008 g/mol || Cl = 35.45 g/mol
(Cl is heavier.)

5. Assign if it is E or Z.
 (Because the higher priority groups are on the opposite sides from each other, it
is an E isomer. Done!)

More Examples (with Integration to Nomenclature)

Name the following compounds. Specify the configuration of the double bond.
1.

Ans. ​(8Z, 12E)-pentadeca-8,12,14-trienoic acid

(​Why isn’t the 14th carbon with double bond not assigned an E or Z configuration?
Because if we look closely, the 14th carbon with double bond looks like this:

It has 2 H atoms. Because it has the same 2 atoms on one side, it is then not a
geometric isomer; hence, we won’t need to assign whether it is an E or Z. This is true
for all double bonds on the end of a chain.)

2.
 Ans. ​(1E, 4Z)-5-bromo-3,5-dichloro-1-cyclohexylpenta-1,4-dien-1-ol

Exercises​:
Tell whether the following pairs are geometric isomers or not. If they are not, explain why.
1.

Ans. The structures are not isomers because two groups on one carbon are the same. If
their positions relative to the plane of the double bond are interchanged, the same
compound results.

2.

Ans. The two compounds are geometric isomers. The first is ​cis-​ 3,4-dimethylhex-3-ene;
the second is ​trans-​ 3,4-dimethylhex-3-ene.

3.
 Ans. The two structures represent the same compound, cis-1,2-dimethylcyclopentane.

III. Optical Isomers

- Pair of molecules with the same physical properties except on their effect on
plane-polarized light

Chirality
- geometric property of some molecules and ions where a chiral molecule is
non-superimposable to its mirror image

Superimposable vs Non-superimposable

● Superimposable - mirror image is identical to the actual object (e.g. pair of

sunglasses and its mirror image)
● Non-superimposable - mirror image is not identical to the actual object (e.g. pair
of sunglasses with one lens removed and its mirror image; your left hand and
right hand)

Chiral vs Achiral Molecules

● Chiral - molecules that are not superimposable on their mirror images
● Achiral - molecules that are superimposable on their mirror images

Chirality center ​ - tetrahedral carbon bearing four ​different​ groups

The following compound, however, do not have a chirality center.

In this case, the clockwise path and the counterclockwise path are
identical.

Identifying Chirality Centers

Locate all the chirality centers in propoxyphene.

1. Ignore sp​2​- (double bonded) and sp- hybridized (triple bonded) carbons.

2. Ignore CH​2​ and CH​3​ groups.

 3. Identify the remaining carbon atoms bearing four different groups.

Locating chirality centers in a nutshell:

Just look for a carbon with 4 different groups attached! Don’t forget to include the
hidden H atom attached to that carbon in counting if applicable.

Enantiomers
- pairs of stereoisomers which are mirror images of each other (chiral)
- A chiral compound will have exactly one enantiomer, never more and never less. Let’s
practice drawing the enantiomer of chiral compounds.

Drawing Enantiomers

Draw the enantiomer of amphetamine.

3 Ways of Drawing Enantiomers

1. Place a mirror behind the molecule.

 (Here, all wedges become dashes and vice versa.)

2. Place a mirror beside the molecule.

(All dashes remain dashes and all wedges remain wedges.)

3. Place a mirror beneath the molecule.

Drawing enantiomers in a nutshell:

There are 3 ways of drawing enantiomers: placing mirrors (1) behind, (2) beside, and
(3) beneath the molecule. Take note, though, that although they look different, THEY
ARE STILL THE ONE AND THE SAME COMPOUND! Always remember that a
compound with 1 chiral center can only have 1 enantiomer.

Most of the time, it is easier to draw enantiomers simply by just placing the mirror
BEHIND the molecule because you simply redraw the compound and replace the
 wedges with dashes and vice versa. However, this may not be applicable to molecules
without wedges and dashes because their 3d structure is already implied, such as
bicyclic compounds. Hence, in this case, it is easier to place the mirror BESIDE the
molecule.

R and S Configuration
Cahn-Ingold-Prelog System of Configuration
1. Prioritize all four groups connected to the chirality center.
2. If necessary, rotate the molecule so that the fourth priority group is on a dash.
3. Determine whether the sequence 1-2-3 is clockwise or counterclockwise.
a. If it is clockwise, then it is ​R​ (​rectus,​ Latin for right).
b. If it is counter-clockwise, then it is ​S​ (​sinister​, Latin for left).

Designating Configuration of a Chirality Center Using the Cahn-Ingold-Prelog

System

Assign the configuration of the chirality center of this compound.

1. Identify the four atoms directly attached to the chirality center and prioritize by
atomic number.
(​The connected atoms are N, C, C, and H. Because N has the highest atomic number,
it is assigned first priority.)​

2. If two or more atoms are carbon, look at the first point of difference.

(​Oxygen has a higher atomic number than carbon so the carbon containing oxygen will
be assigned 2nd priority. That makes the carbon containing another carbon 3rd and the
hydrogen 4th.)​

3. Redraw the chirality center showing only the priority numbers.

4. If the 4th priority is at the back (dashed line), determine if it is R or S as is. If it is

at front (wedged line), first assume that it is at front and assign if it is R or S.
Then, take the opposite of that (if it is R assuming the 4th priority is at front,
then it is S, and vice versa).
Here, notice that H is at the front.
a. Disregard the 4th priority first (H) and assign configuration to the
1-2-3 sequence only.
 In this case, the 1-2-3 is clockwise, meaning, it is R.

b. Take the opposite of that.

Meaning, the original molecule, has a ​S configuration​.

Note that this is only a shortcut to make things faster and easier. The systematic
version requires rotating the molecule in such a way that the 4th priority group will now
be at the back. If you want to learn about it, please read page 205 of Klein’s “Organic
Chemistry” 2nd ed.

Example (with Integration to Nomenclature)

Name the following compound. Specify the configurations of the chirality centers.

Ans. (2R, 3S, 4R, 5R)-2,3,4,5,6-pentahydroxyhexanal

Polarimetry
Optically active
-solutions of certain organic compounds rotate the plane of plane-polarized light
-the dissolved substance or the solution itself if the plane of vibration changed
-always exist in pairs

Polarimeter
-a device used to measure the rotation of plane-polarized light caused by optically active
compounds
Chiral compounds​ are optically active
Achiral compounds​ are not
Note: enantiomers (nonsuperimposable mirror images) will rotate the plane of plane-polarized
light in equal amounts but in opposite directions

observed rotation ​(α)

-solution of a chiral compound when placed in a polarimeter will be dependent on the number of
molecules that the light encounters as it travels through the solution

T = temperature in °​ C
λ = wavelength of light used
*(+) or (-) refer to the direction that the plane of light is rotated
*no relation between R/S configuration and (+)/(-)

Enantiomer Excess (%ee)

- solution containing both enantiomers in unequal amounts and will be optically active

optically pure or enantiomerically pure

- solution containing a single enantiomer
racemic mixture
- solution containing equal amounts of both enantiomers

Ex.

99% 1%
%ee = (0.99)(-23.1) + (0.01)(23.1)
=0

Diastereomers
- stereoisomers that are NOT mirror images of one another
- According to these definitions, we can understand why cis-trans isomers are said to be
diastereomers, rather than enantiomers.
- An important difference between enantiomers and diastereomers is that enantiomers
have the same physical properties, while diastereomers have different physical
properties.

A molecule has 2​n​ (where n = no. of chiral centers) stereoisomers.

Consider the compound with 2 chiral centers below.

It has 2​2​ = 4 stereoisomers.

● The 1st stereoisomer has a 1R, 2S configuration. Therefore, its enantiomer has a 1S, 2R
configuration.
● The 3rd stereoisomer (1R, 2R) is NOT a mirror image of the 1st stereoisomer (1R, 2S),
so they are diastereomers with respect to each other.
● The same goes for the 4th stereoisomer. The 4th stereoisomer (1S, 2S) is NOT a mirror
image of the 1st stereoisomer (1R, 2S). Hence, they are also diastereomers with respect
to each other.
● However, the 3rd diastereomer (1R, 2R) and the 4th diastereomer (1S, 2S) are indeed
mirror images to one another so they are enantiomers with respect to each other.

You should be able to recognize between diastereomers and enantiomers right now.

How many stereoisomers does cholesterol have? How many diastereomers and enantiomers
does one stereoisomer have?
● No. of chiral centers = 8
● No of stereoisomers = 2​n​ = 2​8​ = 256
● One stereoisomer will have exactly 1 enantiomer and 254 diastereomers.

Determining the Stereoisomeric Relationship Between Compounds

Identify whether the pair of compounds is enantiomers or diastereomers.

1. Compare the configuration of each chirality center.

(​Two of the chirality centers have opposite configurations.)​

(​One of the chirality centers, though, have the same configuration.)​

 2. If only some of the chirality centers have opposite configuration, then the
compounds are diastereomers. If all chirality centers have opposite
configuration, then the compounds are enantiomers.

(​Since one of the chirality centers have the same configuration, they are
diastereomers.​ )

Meso Compounds (Mesomers)

- compounds that exhibit ​reflectional symmetry​ even though it has chirality centers; it
becomes an achiral compound
- will have fewer than 2​n​ stereoisomers

Identifying Meso Compounds

Draw all possible stereoisomers of 1,3-dimethylcyclopentane.

Since this compound has 2 chirality centers, we expect 2​2​ = 4 stereoisomers.

The first two are a pair of enantiomers because they lack reflectional symmetry.

The next pair, however, are the same compound. They represent two drawings of the
same compound (a meso compound).
 This molecular family is therefore comprised of only three stereoisomers—a pair of
enantiomers and one meso compound:

Identifying meso compounds in a nutshell:

Draw a plane that separates the compound into two groups. Does it have reflectional
symmetry (meaning, the groups are exactly the same: naka-wedge both, or naka-dash
both)? If yes, it is a meso compound.

Also, it is important to remember, therefore, that because of reflectional symmetry, ​cis

compounds are considered achiral while trans compounds are considered chiral.

Fischer Projection
- used when dealing with compounds bearing multiple chirality centers

Horizontal lines: wedged

Vertical lines: dashed

- Useful for analyzing sugars

- Useful for quickly comparing the relationship between stereoisomers
 *(see note)

NOTE: higher MP, if and only if branching makes the molecule

become more symmetric; otherwise, branching lowers MP
CORRECTION: B > C > A > D

REASON: higher branching, lower MP

(if molecule does not become symmetric)