CHEM 31.

1: Organic Chemistry Laboratory

Dry Lab 2: Stereochemistry
Procedure
Read through the exercise and perform the required activities (constructing models, drawing,
answering questions) as they are asked. When an instruction does not seem to be clear, or when you
have difficulty in constructing or analyzing your model, consult with your laboratory instructor.

Materials:
Each group should provide the following:
13 Spheres: assign a color for each element [7 carbons, 3 oxygen, 1 chlorine, 1 bromine, and 1 fluorine]
1 short white sticks
7 long white sticks
2 coils of springs
2 forks
2 pentagonal pieces of cardboard
1 mirror

A. Chirality, Enantiomerism, Diastereomerism, Optical Activity

Objects that are IDENTICAL are SUPERIMPOSABLE – that is, when we imagine the two
objects “fused” together, all the corresponding parts match exactly. Thus, a sphere is superimposable
on another sphere of the same diameter. A sphere, however, is not superimposable on a cube or on a
sphere of a different diameter.

1. Determine whether each of the following pairs of objects are identical with each other, i.e.,
superimposable or not.
a) Two forks b) your left hand and your right hand

2. View your right hand in front of the mirror.

a) Is the reflection of your right hand superimposable on your left hand?
b) Is your right hand the mirror image of your left hand?

3. Using a mirror, determine whether the following objects are superimposable on their mirror images
or not.
a) a fork b) a pentagon c) your left hand

So far we have examined certain simple relationships between the shapes of pairs of
objects. Two objects may be IDENTICAL or DISTINCT. Distinct objects may be related as mirror
images of each other or not related as mirror images at all.

IDENTICAL: superimposable mirror images

 DISTINCT: non-superimposable

mirror images not mirror images

Molecules can be classified in a similar way. Many molecules are superimposable on their
mirror images, others are not. Those which are related as non-superimposable mirror images are
particularly important in biological systems.

4. A PLANE OF SYMMETRY is an imaginary plane or sheet that divides the object so that one
half is the exact reflection of the other half. Determine whether each of the following has at least
one plane of symmetry or none:
a) a sphere b) a regular tetrahedron c) a shoe

5. Determine whether the objects in no. 4 are superimposable on their mirror images or not.

6. Describe the relationship between the presence of a plane of symmetry in an object and the
object’s superimposability on its mirror image.
Objects which are not superimposable on their mirror images are CHIRAL objects, while
those which are superimposable on their mirror images are ACHIRAL.

There are two alternative methods which may help in the analysis of the shape of an
object to decide whether it is chiral or achiral:

a) Construct the mirror image of the object. If the mirror image is identical to the object, that is,
superimposable, then the object is ACHIRAL. Otherwise, it is chiral.
b) Inspect the object for the presence of a plane of symmetry. If it has a plane of symmetry, then
the object is ACHIRAL. Otherwise, it is chiral.
 The two approaches can be summarized in the following scheme:

Given Model A

Construct model B, the Inspect for the presence of

mirror image of A a plane of symmetry

Are models A and B Does model A have a plane identical? of symmetry?

NO NO
Model A is
CHIRAL
YES YES

Model A is ACHIRAL Model A is ACHIRAL

7. Construct a model of CH4. Is it chiral or achiral? Why?

8. Construct a model of CBrFClH. Is it chiral or achiral? Why?

A chiral molecule such as molecule I below is distinct from its nonsuperimposable mirror
image, molecule II. Construct models for I and II, and verify this relationship.
 I II

(http://plaza.ufl.edu/tmullins/BCH3023/isomers.html)

Molecules such as I and II, which are related as nonsuperimposable mirror images, are called
ENANTIOMERS.

9. a) Are enantiomers chiral?

b) Do enantiomers have the same molecular formula?
c) Does one structural formula represent both members of a pair of enantiomers?

Stereoisomers possess the same molecular and structural formula, but have different spatial
arrangements of their atoms.

10. Are enantiomers stereoisomers?

One of the most important properties of chiral molecules in solution is their effect on plane-
polarized light. Both enantiomers rotate the plane of polarized light. Substances with this property
are said to be optically active. Chiral substances have molecules that are not superimposable on
their mirror images and are optically active. Enantiomers are also known as optical isomers.

11. Determine whether each of the following is optically active or not.

a) CH3CH(NH2)COOH
b) CH3CH2CHClCH3
c) CH3CH2CH2CH3
The rotation of plane polarized light is used to observe experimentally one of the main
differences between a pair of enantiomers. One enantiomer rotates plane-polarized light clockwise
(as seen by observer), the other enantiomer, counterclockwise by the same magnitude.
Conventions used to indicate direction of rotation of the plane polarized light are:
Clockwise (+), dextrorotatory, d
Counterclockwise (–), levorotatory, l
 Alanine, , is a chiral amino acid that has two enantiomers: (+)-alanine
and (-)-alanine. These two are optical isomers.

12) Which enantiomer of alanine rotates the plane of polarized light clockwise?

13) Substances which do not rotate the plane of polarized light are said to be optically inactive.
Determine whether each of the following aqueous solutions are likely to be optically active or
inactive.
a) a solution of ethanol, CH3CH2OH
b) a solution of (+)-alanine
c) a solution of (-)-alanine
d) a solution containing equimolar quantities of (+)-alanine and (-)-alanine

A racemic mixture containing equimolar quantities of a pair of enantiomers is called a

RACEMIC MIXTURE. A racemic mixture is represented as (±) or sometimes dl, e.g., (±)-glucose
or dl-glucose. A racemic mixture is optically inactive.

14) How is the racemic mixture of alanine represented?

In the preceding section, we have seen that if a substance can be shown to be optically
active in solution, then we know it is chiral. However, absence of optical active does not prove that
the substance is achiral, since a racemic mixture may be present. It is therefore also useful to be
able to “detect” molecular chirality directly from molecular shape, if necessary, with the aid of
models.

Two methods have been introduced so far. Another method that allows the detection of
chirality directly from molecular structure (and shape) is described below. This method is useful for
simple organic compounds and easily works even without the aid of models.

15) Construct models of molecules with the following generalized formulas using differently colored
markers for the atoms or groups of atoms H, A, X and B.

H H X
X

H A A
H H H A
H H H B
H
Model I Model II Model III Model IV
16) Construct the mirror image of each model. Which are superimposable on their mirror images?

17) Which model represents a chiral molecule?

18) How many different atoms or groups of atoms must be attached to the central carbon atom in
order to confer chirality to the molecule?

A carbon atom linked to four different groups is asymmetric and known as a tetrahedral
STEREOCENTER. The presence of at least one carbon stereocenter renders chirality to a
molecule.

19) Consider the following structural formulas:

CH3 COOH

H C OH H C Br

COOH COOH
(a) (b)

Match these structural formulas with the generalized formulas given in number (15). Which
of the two contains a stereocenter? Draw the structure and mark the stereocenter with an asterisk.

20) Which of the above is a chiral molecule? Explain your answer.

21)
a) Which of the molecules in number (19) can exist as a pair of enantiomers?
b) Draw the pair of enantiomers.

In the preceding section, you have learned to recognize that the presence of a stereocenter
can confer chirality to a molecule as a whole.

Lactic acid, , for example contains one stereocenter

(marked with *). It is a chiral molecule and therefore can exist as two pure optical isomers, (+)-lactic
acid and (-)-lactic acid.
 Now we will consider molecules with more than one stereocenter. Consider 2,3-
dihydroxybutanoic acid.

22) a) How many stereocenters does it have?

b) Copy the structure and mark the first stereocenter with an asterisk. Encircle the four groups
attached to this stereocenter.
c) Copy the structure and mark the second stereocenter (if any) with an asterisk. Encircle the four
groups attached to this stereocenter.

The molecule 2,3-dihydroxybutanoic acid is an example of a substance with two different

stereocenters.

The flying wedge representation is a two-dimensional representation where a solid wedge

( ) indicates a bond projecting up and out of the plane of the paper while a dashed wedge
( ) indicates a bond projecting into the paper. Thus, in I, –OH and –H are projecting towards you,
the observer, while the –COOH and –CH3 groups are projecting into the paper. (Differentiate H, OH,
COOH and CH3 by using differently colored markers.)

COOH

H C OH

H C OH

CH3

I
23)
a) Make a model of this molecule whose three dimensional structure is given above in flying wedge
representation. Copy structure I.
b) Construct a second model, II. Draw a flying wedge representation of II, related to I as mirror image.
c) Are I and II chiral?
d) What kind of stereoisomers do they represent?
 A compound that contains two different stereocenters can exist as four optically active
stereoisomers. Construct the models of the other two stereoisomers of 2,3-dihydroxybutanoic acid, III and
IV. The flying wedge representations of the four stereoisomers are given below:

COOH COOH COOH COOH

H C OH HO C H HO C H H C OH

H C OH HO C H H C OH HO C H

CH3 CH3 CH3 CH3

I II III IV
All of the above stereoisomers of 2,3-dihydroxybutanoic acid are optical isomers. Some
pairs are related as non-superimposable mirror images (enantiomers). Other, called
DIASTEREOMERS, are also nonsuperimposable and are not related as mirror images.

24) What is the relationship between

a) I and II b) III and IV c) I and IV d) II and IV
25) What is the relationship between
b) I and III b) II and III

26) The constitutional formula of tetrose is shown below

H C CH(OH)CH(OH)CH2OH

a) Using the flying wedge representation, draw all the stereoisomers of tetrose. Label each
stereoisomer I, II, and so on. Mark the stereocenters using asterisks.
b) Identify enantiomers.
c) Identify diastereomers.

B. Conformational Isomers
Atoms within molecules can vibrate and are free to rotate about single bonds. This rotation may
result in the atom taking different positions relative to the rest of the molecule. Molecular structures that
are interconvertible by simple bond formations are called CONFORMATIONAL ISOMERS or
CONFORMERS.

Open Chain Compounds

27) Construct a model of ethane CH3CH3. Rotate the C–C single bond.
a) Is there a change in the relative positions of the different atoms?
b) Does the ethane molecule have more than one conformation?

Rotation about the C–C bond changes the shape of the molecule while rotation about the C–H
bond has no effect. Atoms can rotate “freely” about single bonds as opposed to double bonds (e.g., C=C,
C=N), which have restricted rotation. The ethane molecule can adopt an infinite number of conformations
according to the relative positions of the hydrogen atoms. These conformations can be interconverted by
rotating about the C–C single bond. The two extreme conformations of ethane, the ECLIPSED and
STAGGERED can be seen by viewing long the C–C axis. Examine these conformations using your model.

28) In which of the two conformations are the hydrogen atoms farthest apart from each other?

Conformation Representation

Sawhorse projection Newman projection

Eclipsed

Staggered

The conformation in which the atoms are farthest apart normally has the lowest potential
energy and is referred to as the preferred conformation. Molecules are continuously and rapidly
changing from one conformation to another, but they spend most of their time in the preferred
conformation.

The changes in potential energy of ethane as one methyl group moves relative to the other
about the carbon-carbon single bond can be shown diagrammatically in the figure below. The
dihedral angle (or rotation angle, Φ) is illustrated as:
 The difference in the potential energy of the staggered and eclipse conformers of ethane
is 3 kcal/mol. Because this energy is readily attained at room temperature, different conformations
of ethane cannot be isolated. An energy barrier greater than 15-20 kcal/mol is required to be able
to isolate different conformations at room temperature.

29) Draw the Newman and sawhorse representations of the conformation of ethane with the
highest potential energy.

30) Draw the Newman and sawhorse representations of the conformation of ethane with the
lowest potential energy.

31) Which of these conformations is the preferred conformation of ethane?

32) Construct a model of chloroethane, CH 3CH2Cl. Remember that these models do not actually
show the relative sizes of different atoms. View the model along the carbon-carbon axis and
draw the sawhorse and Newman projections of the preferred conformation.

33) Do all chloroethane molecules spend all of their time in this preferred conformation?

34) What is the preferred conformation called?

In ethane, energy differences between various conformations are mainly due to electronic
interactions between the electron pairs in the C–H bonds. In chloroethane, there are electronic
interactions between the C–H bonds and with the C–Cl bonds. Also, interactions between the larger
chlorine atom and hydrogen atoms are greater than any hydrogen-hydrogen interactions.

35) Construct a model of 1,2-dibromoethane, BrCH2CH2Br. Examine possible conformations of this

molecule. Which of the following interactions will be the greatest?
a) hydrogen-hydrogen interactions
 b) hydrogen-bromine interactions
c) bromine-bromine interactions

Ring Compounds

Many important organic molecules contain rings of atoms, for example, sucrose,
chlorophyll, nicotine, etc. Rings range in size from three-membered like cyclopropane to those
containing more than 30 atoms. However, most cyclic compounds are made up of 5- or 6membered
rings. In this exercise, only cyclohexane and its monosubstituted derivatives will be considered.

Construct a model of the cyclohexane molecule (C 6H12).

Rotate the carbon atoms and examine different conformations.

36) Are there any conformations in which all carbon atoms of the ring are in one plane? (Note: Be
careful not to distort models.)

The two extreme conformations of cyclohexane are referred to as the CHAIR and BOAT
conformations.

chair boat

Manipulate your models carefully to get the chair and boat conformations. Be sure you can
differentiate the two extreme conformations. If in doubt, consult your laboratory instructor.

Put your models carefully in the chair conformation. Look at the relative positions of the
hydrogen atoms along the axes, C2–C3 and C5– C6. Hold carbons 2, 3, 5 and 6 firmly in one hand,
then without moving carbon 1, flip carbon 4 up (or down) without breaking any bond. Again look at
the relative positions of the hydrogen atoms along C 2–C3 and C5– C6 bonds.
 37) Does the flipping of carbon 4 result in a change in conformation?

38) In which conformation are the hydrogen atoms farthest apart?

39) Which is the preferred conformation? Give reasons for your answer. Compare your models with the
Newman projections below by looking through C 2–C3 and C5–C6 bonds at the same time.

I II

40) Which is the eclipsed conformation? The staggered conformation? Which is the boat conformation?
The chair conformation?

In the chair conformation, notice that there are two orientations for the C–H bonds. Bonds that are
oriented vertically are known as AXIAL bonds; the rest are known as EQUATORIAL bonds. The axial
bonds alternate above and below the ring carbons while the equatorial bonds point away from the ring.
The drawings below are meant to show the general orientations of equatorial and axial bonds. They do
not represent specific compounds.

equatorial bonds only axial bonds only axial and equatorial bonds

Use white sticks for the axial bonds. Let these be the marked bonds. Hold carbon atoms 1, 2, 3, 5
and 6 firmly and flip carbon 4 up.

41) What is the conformation results?

42) Then holding carbons 2, 3, 4, 5 and 6 firmly, flip carbon 1 down. What conformation results?

43) Did you break any bonds?

44) What is the orientation of the marked bonds now?

45) Make a sketch of the final conformation (include marked bonds).
Now, with the equatorial bonds marked by the white sticks, reverse the process and rotate
the bonds to reform the chair conformation such that the axial positions are now marked. This
overall process of one chair conformation changing to another chair conformation is known as RING
INVERSION or ring flipping and is a very rapid process. The cyclohexane ring inverts approximately
10 times a second at room temperature.

46) Represent ring inversion and indicate that the two chair conformations are in dynamic equilibrium. The
symbol is the usual way of indicating that a dynamic equilibrium exists, in this case, between the two
conformations.

47) Consider methylcyclohexane. Construct the model of methylcyclohexane with the methyl attached axially.
Make the ring undergo inversion. Complete the following:

48) Methylcyclohexane can exist in two chair conformations, one with the methyl group on an axial position
(a-methylcyclohexane) and the other with the methyl group on an equatorial position (emethylcyclohexane).
a) In which chair conformation, a or e, is the methyl group farthest away from the neighboring hydrogen
atoms?
b) In which chair conformation, a or e, does the methyl group have greater room?
c) Which is the preferred chair conformation of methylcyclohexane, a or e?

49-50) Make a general statement about the preferred conformation of monosubstituted cyclohexane.