Exercise 5 INTRODUCTION TO STEREOCHEMISTRY

I. Introduction

Stereochemistry is concerned with the shapes of molecules and how the differences in shapes can effect the properties and reactions of compounds. Subtle differences in molecular shape have far reaching consequences and it is probably the field of molecular biology that a full awareness of molecular shapes has emerged. A knowledge of the molecular shapes of such vital compounds as sugars, amino acids, and proteins is essential in understanding their reactions and properties.

Molecular structures are so frequently represented in two dimensions that

we often experience considerable difficulty in thinking about molecules in three dimensions. The purpose of this exercise is to persuade you to think in three dimensions.

II. Chirality, Enantiomerism, Diastereomerism and Optical Activity.

Objects which are IDENTICAL are SUPERIMPOSABLE that is, when we imagine the two objects are used 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 nor on a sphere of a different diamter.

1. Determine whether each of the following pairs of objects are identical with

each other, i.e. superimposable

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, decide whether the following objects are superimposable on

their mirror images.

a) a fork b) a pentagon c. your left hand

4. A PLANE OF SYMMETRY is an imaginary plane or sheet that divides the objects so that one half is exactly a reflection of the other half. Determine whether each of the following has at least one plane of symmetry.

a) a sphere b) a regular tetrahedron c) a shoe

5. Determine whether the objects in number four 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 objects 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.

7. Look at the model of CH4. Is it chiral or achiral? Why?

8. Look at the model of CBrFClH. Is it chiral or achiral? Why?

Non superimposable mirror images are called ENANTIOMERS.

9. a) Are entiomers chiral?

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

enantiomers?

10. Are enantiomers stereoisomers? One of the most important property of chiral molecules 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 containing molecules which are not superimposable on their mirror images are optically active. Enantiomers are also known as optical isomers.

11. Determine whether each of the following are optically active.

a) CH3CH(NH2)COOH b) CH3CH2CHClCH3 c) CH3CH2CH2CH3

The rotation of the 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 the observer), the other enantiomer, counterclockwise by the same amount. Coventions used to indicate the direction of rotation of the plane of polarization are:

Clockwise (+), dextrorotatory, d Counterclockwise ( - ) levorotatory, l

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

13. Which of the following are aqueous solutions likely to be optically 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 mixture containing equimolar quantities of a pair of enantiomers is called a RACEMIC MIXTURE

14. How is the racemic mixture of alanine represented?

15. Examine the models for the presence of a plane of symmetry. Which of them

has at least one plane of symmetry?

16. Which are superimposable on their mirror image?

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?

Consider the following structural formula:

19. Which is a chiral molecule?

20. Which can exist as a pair of enantiomers? Draw the pair of enantiomers.

21. a) How many chiral centers? d) Mark the chiral centers with an asterisk. e) Copy the structure and encircle the four groups which are attached to

each chiral carbon

NH2 NH2

CH3

CH3 CH3

CH3 NH2

PH2

NH2

PH2

OHCH3

H

OH

CH3 COOH CH3 CH2Br

Cl

Cl

CH3CH3

CH3

CH3

Now we will consider molecules with more than one chiral center. Consider

2,3 dihydroxybutanoic acid.

The flying wedge representation of 2,3 dihydroxybutanoic acid is

shown below.

22. a) Draw the flying wedge representation of its mirror image (II).

d) Are I and II chiral?

A compound which contains two different chiral centers can exist as four optically active stereoisomers. The flying wedge representation of the four stereoisomeric 2,3 dihydroxybutanoic acid are given below.

I II III IV Some are related as enantiomers while others, called DIASTEREOMERS

are not related as mirror images at all.

23. What is the relationship between: a) I and II b) III and IV c. I and IV d. II and IV

24. What is the relationship between:

a) I and III b) II and III

OHOHO

OH H H

CH3

OHH

COOH

OHH

CH3

OHH

COOH

OHH

CH3

H

H

OH

OH

COOH

CH3

OH

H

H

OH

COOH

CH3

H

OH

OH

H

COOH

CH3

CONFORMATIONS. Atoms within the molecules can vibrate and are free

to rotate about the single bond. 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 rotations are called CONFORMATIONS.

OPEN CHAIN COMPOUNDS Look at the model of ethane. Rotate the C C single bond.

25. a) Is there a change in the relative positions of the different atoms as the C C bond is rotated?

e) Does the ethane molecule have more than one conformation?

Ethane can adopt an infinite number of conformations but the two extreme conformations are eclipsed and staggered.

Newman Projection:

Eclipsed Staggered Sawhorse Projection

Eclipsed Staggered

26. In which extreme conformation are the hydrogens farthest apart from each

other?

27. Draw the Newman and Sawhorse representation of ethane with the highest potential energy.

HH

HH

HH

H

HH

H

H H

28. Draw the Newman and Sawhorse representation of ethane with the lowest potential energy.

29. Which is the preferred conformation of ethane?

Look at the model of chloroethane

30. Do all chloroethane molecules spend all of their time in this preferred

conformation?

31. What is the preferred conformation called? RING COMPOUNDS Look at the model of cyclohexane. Rotate the carbon atoms and examine

the different conformations

32. Are there any conformation in which all carbon atoms of the ring are in one plane?

The two extreme conformations of cyclohexane are referred to as chair

and boat:

Chair boat Put your model 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 hydrogens along the C2 C3 and C5 C6 bonds.

33. Does flipping of carbon 4 result in a change in conformation?

34. In which conformations are the hydrogens farthest apart?

35. Which is the preferred conformarion?

Compare your models with the Newman Projections below by looking

through the C2 C3 and C5 C6 bonds at the same time.

I II

36. Which is the eclipsed conformation? Which is the staggered? In the chair condormation, there are two conformation of the hydrogen

atoms. Bonds that are oriented vertically are called axials bonds while the rest known as equatorial bonds.

37. Mark the axial bonds. Hold carbon atoms 1, 2, 3, 4, 5, and 6 firmly and flip up

carbon 4. What conformation results?

38. Then holding carbons 2, 3, 4, 5, and 6 firmly, flip down carbon 1. What conformarion results?

39. Did you break any bonds?

40. What is the orientation of the marked bondsnow?

41. Make a sketch of the final conformation showing the marked bonds.

Now with the equatorial bonds marked, reverse the process and rotate the

bonds to reform the chair conformation with the axial bonds marked. This overall process of one chair conformation changing to another chair conformations is called RING INVERSION.

42. Represent the process using the symbol to indicate that the two chair conformations are in dynamic equilibrium.

43. Construct a model of methycyclohexane with the methyl attached ac\xially.

Make the ring undergo inversion and complete the following:

44. a) In which chair conformation a or e, is the methyl froup farthest from the

neighboring hydrogen atom? b) In which chair conformation a or e does the methyl group have greater

room? c) Which is the preferred conformation of mthylcyclohexane, a or e?

45. Make a general statement about the preferred conformation of

monosubstituted cyclohexanes.

CH3